LWCT, MKFA, GSQA, CCH, AAQC
03/01/2022
10:30:00 pm (CEST)
2021 REBELEM - RECOVERY RS, CPAP vs HFNO vs Conventional Oxygen Therapy in COVID-19.pdf
CAREFUL WITH CPAP AE = Hemodynamic instability, Pneumothorax, Pneumomediastinum
X, 2021, UK ➩ mc, ol, adap RCT / 1272 / ? ➩ *P* adults C19, ARF *I* 3arms: conven + HFNO + CPAP *C* 1:1:1 *O* (p) ‘intub+MM30’ (s) incid (intub+MM30) +
TTI + dMV + ttMM + MM + incidICUadm + LOS
MKFA, SGQA, CCH, LWCT, AAH, AAQC
04/01/2022
10:30:00 pm (CEST)
2021 NEJMjw - New Surviving Sepsis Guidelines (CCM)
1. RINGER LACT better than NS (SSF 0.9)
2. discharge: PTSD, anxiety, depression, others phy
3. Dynamic update (fluids immediate, assess quantity + vasopressors peripherical (w_fluids ok)
2021 REBELEM - RECOVERY RS, CPAP vs HFNO vs Conventional Oxygen Therapy in COVID-19
Discussion:
1. CPAP more AE though (neumo -thorax -medias, HD instability)
2. HFNO > CPAP to reduce adverse events (i.e awake prone positioning, patient nutrition, etc).
CCH, GSQA, MKFA, AAQC
08/01/2022
10:30:00 pm (CEST)
2021 UNIVADIS - Triglicéridos elevados en hombres de peso normal con apnea obstructiva del sueño (NSS).pdf
NSS, 2021, AUS ➩ OBS PROS / 753 / ? ➩ *P* saos *I* 3groups with P.Ab, (mor + in AP/HIPO, desat) polisomnogr *C* no *O* CORRELATION TG↑ - saos - PAb<95
Look for OSA even if slim
More attention to men
JJFM, AAH, JCAS, HAQC, AAQC
12/01/2022
10:30:00 pm (CEST)
NEJM Notable Articles of 2021.pdf
Eric J. Rubin letter
Ingenuity: Infection with the endosymbiont Wolbachia pipientis bacteria made these mosquitoes resistant to dengue;
two practice-changing articles that addressed the use of race in the estimation of kidney function
New Creatinine- and Cystatin C–Based Equations to Estimate GFR without Race
2021, NEJM, USA ➩ validDatSet / 4050 / x ➩ *P* people *I* new equation *C* no *O* more accurate
Molnupiravir for Oral Treatment of Covid-19
in Nonhospitalized Patients
➩ disminución de incidencia MM u H+ 29d
2021, NEJM, x ➩ dbRCT / 1433 / x ➩ *P* unvax, mild-mod C19, lab confirmed, ONE rf for sC19 *I* 5d after symptoms MOLNUPIRAVIR 800mg BID x 5d *C* placebo (717)*O* efficacy (H+ OR MM 29) + safety (advEve)
CCH, JJFM, HIBN, JCAS, GSQA, MKFA, AAQC
13/01/2022
10:30:00 pm (CEST)
NEJM Notable Articles of 2021.pdf
Molnupiravir — A Step toward Orally Bioavailable Therapies for Covid-19
➩ MM 29 + H+ (PRIMARY)
➩ 7%molnu VS 10%placebo (primary endpoint)
➩ 72h critical time
➩ avoid pregnancy & breasfeeding
➩ One death oc- curred in the treatment group, and nine among placebo recipients.
HAQC, AAQC
14/01/2022
10:30:00 pm (CEST)
2021 NEJMjw - Another Monoclonal Therapy Option for Early COVID-19 (NEJM).pdf
2021, NEJM, ? ➩ RCT / 583 / by January 2021 ➩ *P* C19, adults, 1rf, <5d *I* 500mg sotrovimab *C* placebo *O* ↓85% rr (1% vs 7%) hospitalzation + MM29
Mini-Cog
➩ 6 versions
➩ dementia - cognitive impairment
AAH, HAQC, GSQA, CCH, AAQC
17/01/2022
10:30:00 pm (CEST)
2022 JAMA - COVID-19 Therapeutics for Nonhospitalized Pxs (Gandhi) [Viewpoint].pdf
➩ sotro 10d (mild-mod)
➩ 1st. nirmatrelvir-rito 2nd. sotrovimab 3rd. remdesivir 4th. molnupiravir
➩ nirmatrelvir-rito = 5 days (adults, >12yo, >40Kg, hrProgress)
➩ nirma-rito:
- AVOID absolute:
amiodarone
RMP
rivaroxaban
-AVOID relative:
calcineurin (-)
-stop:
statins
➩ REMDESIVIR = in 7 days
➩ Molnupiravir = in 5 days (3days IMPORTANT, see Ed.), genotoxicity??
2022 BMJ - Covid-19. WHO recommends baricitinib + sotrovimab to treat pxs (Kmietowicz) [News].pdf
Baricitinib = critical and severe C19 ➩ + CORTICOIDS
Sotrobimab = mild-mod symC19
AVOID: plasma, ivermec, hydroxi
AAH, CCH, AAQC
18/01/2022
10:30:00 pm (CEST)
2022 NEJM - Comparative Effectiveness of mRNA C-19 Vaccines [Quick take]
2021, NEJM, USA ➩ observ RETRO / 219 842 / 6m (1st phase), 3m (2nd phase) ➩ *P* wo_prevC19 + alfa (1st ph) + delta (2nd ph) *I* pfizer *C* moderna *O* (AsymptomaticC19, Sympt C19, Hospi C19, ICU admiss, MM): a) both effective SYMP C19 & H+ b) >r with Pfizer than Moderda
2022 JAMA - COVID-19 Therapeutics for Nonhospitalized Pxs (Gandhi) [Viewpoint].pdf
Avoid Molnupiravir in PREGNANCY
Sotrovimab: ok in Omicron (active) - NOT bamla/etesev NOT casiri/imdevi
AAH, ±MKFA, AAQC
19/01/2022
10:30:00 pm (CEST)
2022 JAMA - COVID-19 Therapeutics for Nonhospitalized Pxs (Gandhi) [Viewpoint].pdf
➩ THOMAS LEE (NEJM Catalyst)
Fauci documentary (VIH, vision)
➩ MICHAEL (Harvard)
Sprint - marathon
Organization framework
Burnout
—-
Scattered now, organized later
Interact with each other
Case notes and procedures
Peer accountability or group scrunity
➩ MAYO (Amy)
Cure, connect and transform
Use capabilities that we did not have in the past: AI, tech, big data, new partnerships (analysts, industry, etc).
—-
Why - is change medicine
Opportunities for clinicians to get engaged
Learn how to be part of this new creation
➩ BROWN U (Ashish)
“We have made massive progress”
Monoclonal Atbs, vaccines, oral therapeutics
Omicron
—-
Broader context? Yes - community leaders, profound role in society, right medicine - right disease.
Physician leadership has to change (methodology, training)
Communicate effectively
Essential for society
➩ Teamwork is imp
➩ Use of current technology
MKFA, GSQA, AAQC
20/01/2022
10:30:00 pm (CEST)
2021 CC - Equilibrating SSC guidelines with individualized care (Vincent) [ed].pdf
➩ Heterogeneity, Evidence based medicine is not "cookbook" medicine. (SACKETT)
➩ Timing ICU admission = availabitly in the ward + bed + physio status&reserve
➩ ATB in SepsShock REALLY URGENT - IF less urgent, THINK MORE
2022 MEDPAGE - Controversial Doc Resigns From Medical School (Fiore) [r].pdf
➩ pxs 13% of all math+ = MM 28%
➩ Not first time = HAT (hidro, ascor, thiam)
➩ 38% of pxs received only 1 / 4 math+ = MM25%
➩ Vincent Rhodes, vice-pres EVMS: aware
AAH, MKFA, CCH, AAQC
21/01/2022
10:30:00 pm (CEST)
2021 CC - Equilibrating SSC guidelines with individualized care (Vincent) [ed].pdf
➩ Timing ICU admission = availabitly in the ward + bed + physio status&reserve
➩ ATB in SepsShock REALLY URGENT - IF less urgent, THINK MORE
JJFM, AAQC
24/01/2022
10:30:00 pm (CEST)
2022 LANCET - Aspirin in patients admitted to hospital w_ C-19. a R, C, open-label, platform trial (RECOVERY) [R].pdf
2022, LANCET, UK ➩ ii,ol,RCT / 14892 (7361 vs 7541) / Nov2020 - Mar2021 ➩ *P* C19, hospit, c/s INTUB wo_HH *I* ASA 150mg daily until DISCH *C* usual care *O* (p) MM28 = (s) DIS hosp28 (+) (sub) all (-)
JJFM, AAH, MKFA, CCH, ±GSQA, AAQC
25/01/2022
10:30:00 pm (BO Time)
2021 WHO - Update on Omicron.pdf
➩ Vaccines ok for omicron (severe, critical, death)
➩ Reinfection risk w_omicron
➩ RT-PCR for Omicron, not clear RAPID TEST, yet
2021 NEJMjw - Sodium, Potassium, and Cardiovascular Disease (Year in review).pdf
➩ ↓Na = >benefit w_ORwo_HTA
➩ K careful in CKD, not SO MUCH the rest
➩ K ingestion OK => 1 fewer CV event in 100
➩ CHINESE study = salt-substitute = ↓stroke, MACE, MM
2021 NEJMjw - Use Of Medications That Might Raise Blood Pressure (JAMA).pdf
➩ 30/12/2021 ➩ REFRESH
MKFA, CCH, SGQA, JJFM, AAQC
28/01/2022
10:30:00 pm (BO Time)
2022 MEDPAGE - Which fully vaccinated adults are most at risk of severe C-19 (Walker).pdf
2022, MMWR, USA ➩ OBS / 1228k (465 HCFacilities) / Dic 2020 - Oct 2021 ➩ P⃣ >18y + fully PRIMARY vax I⃣ rf: (8) >65, lung, liver, kidney, heart, neurol, diabetes, immunosup C⃣ none O⃣ sOC = H+ ARF (+) NIV (+) ICU + MM
➩ 3/6 MORE FREQUENT: liver, lung, kidney
➩ >4/8 = 60% ARF or ICU
➩ >4/8 = 80% DIED
➩ >4/8 = 20% NON SEVERE
NO link w_ sex, race, ethnicity
NO link w_primary vax TIMEPOINT
MKFA, AAH, SGQA, AAQC
29/01/2022
10:30:00 pm (BO Time)
2021 NEJM Evidence – Molnupiravir. Is It Time to Move In or Move Out (Castillo Almeida) [Ed].pdf
MOVe-OUT:
2021, NEJM, USA ➩ dbRCT / 302 / ? ➩ P⃣ nonH+ + mild-mod + <7d SYMP I⃣ molnu 200, 400, 800 BID x 5d C⃣ placebo O⃣ H+orMM_29 (+)
➩ (+)OC = 3 vs 5%
➩ >60a + sevILLN = more benefit (4 vs 21%)
➩ <5d SYMP = 4 vs 12%
MOVe-IN:
2021, NEJM, USA ➩ dbRCT / 304 / ? ➩ P⃣ pxsH + mild-mod + <7d I⃣ molnu 200, 400, 800 BID x 5d C⃣ placebo O⃣ recovery29d (-)
➩ <5d SYMP = no effect
➩ insufficient LUNG PARENC PENETRATION
———
CORTICOIDS dangerous early:
1. delayed VIRAL CLEARANXCE
2. (-)effect on immune RESP
JJFM, AAH, MKFA, AAQC
31/01/2022
10:30:00 pm (BO Time)
2022 MEDPAGE - Don't Expect Much From C-19 Vax in This Px Group (Ann Rheum Dis).pdf
1. Delta: vax ↓ in ANCA-assoc vascultitis (AAV) W_RTX
2. RTX = rituximab
3. 2022, ARD, DE ➩ RCT / 21 / ? ➩ P⃣ AAV a) cortic + others b) wo_RTX c) w_RTX I⃣ 3rd dose C⃣ no placebo O⃣ neutralizing ACTIV (NA) = b) noRTX: NA>40% + MOST >90% c) yesRTX: detectable Acs 2/8 + NA 1/8
4. AR = in general popul and NO SEVERE
2022 JAMA - Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Pxs W_ Acute Hypoxemic Respiratory Failure + C-19 (Perkins) [RCT].pdf
1. CPAP>HFNC>CONV (opposite for AR)
2. RECOVERY-RS: 2022, JAMA, UK, JERSEY ➩ parG, adap RCT / 1273 (1260) / April2020 - May2021 (fu June2021) ➩ P⃣ C19, hypARF I⃣ CPAP, HFNO, CONV C⃣ 1:1:1 O⃣ pOC: intub OR MM30 / 36% CPAP, 44% HFNO, 45% CONV
3. AE = 34%CPAP, 21% HFNO, 14% CONV
4. AbsDIFF = -8% (CPAP vs CONV)5. Crossover = 15% CPAP, 11% HFNO, 24% CONV
ARVC, CCH, SGQA, PICL, AAH, AAQC
01/02/2022
10:30:00 pm (BO Time)
2022 UNIVADIS - COVID-19. subcutaneous casirivimab + imdevimab reduce symptomatic disease risk in PCR-positive people (JAMA).pdf
1. 2022, JAMA, USA, ROM, MOLDOVA ➩ dbRCT / 314 / ? ➩ P⃣ C19(+), ASYMP (>12a) I⃣ casiri+imdeb 600mg SC 1 dose C⃣ placebo O⃣ PROG to SYMPT 14d ➩ 29% vs 42%
2. Viral load: 489 vs 812 (p=0,001)
3. Not action to OMICRON
4. SERONEGATIVE + UNVAX
5. LIMIT: sample size, young, duration 28d mark
2022 JAMA - Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Pxs W_ Acute Hypoxemic Respiratory Failure + C-19 (Perkins) [RCT].pdf
1. LIMIT: underpower in CPAP vs CONV
2. LIMIT: early termination
3. Subgroup analy (CPAP vs CONV): a) <50 b) male c) FiO2 >0.6 d) BMI ≤35
4. (s)OC: (7) : indiv compon p(OC) 1.INTUB30 2. MM30 3. INTUB rate 4. ICUadmi 5. d_invMV 6. tte (intub + M) 7. icu- + h-LOS 8. icu-MM + hMM
AAH, JJFM, MKFA, AAQC
02/02/2022
10:30:00 pm (BO Time)
2022 JAMA - Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Pxs W_ Acute Hypoxemic Respiratory Failure + C-19 (Perkins) [RCT].pdf
1. hypARF = SpO2 ≤94% + FiO2 ≥40%
2. ex = PREG + invMV <1h + planned withdrawal TTO
3. 1:1:1 or 1:1
4. 90% power, 0.05 stats
–––––
1. TO stipulate specific criteria: PROBLEMS a. equipoise b. acceptability c. recruitment, d. geeralizability
2. RECOVERY-RS = pivotal for C19
3. HiFlo-Covid ➩ Colomb, HFNO vs CONV ➩ ↓nINTUB + ttCR4. HENIVOT ➩ helmet vs HFNO ➩ NO DIFF fdResSupp
ABFL, JJFM, MKFA, AAQC
03/02/2022
10:30:00 pm (BO Time)
2020 JAMA - Prone Positioning for Acute Respiratory Distress Syndrome (ARDS) (Hadaya) [Px Page].pdf
1. SEDATED + awake
2. Compression + flow + prevention + ↑blood return & ↓constriction + >drainage
3. Blood return to right chambers
4. Improves RESP STATUS + SYMPTOMS
2022 ICM - Effect of proning + recruitment on physio-anatomical variables in C-19 pneumonia (Gurjar) [Let].pdf
1. Rossi et al study
2. ok recruitment at 4th week. Days from symptom onset 18±8
3. Supine 5: LVdys + EVLV influence?
4. Prone 5: time of prone enough? (not appropriate)
5. Shock & HD instabilty known? (during RM and proning) ➩ recruitment due to CO
6. lung collapse not always detrimental??
2021 ICM - Mechanisms of oxygenation responses to proning and recruitment in C-19 pneumonia (Rossi) [r].pdf
1. 2021, ICM, IT (Parma) ➩ intPROS / 25 / Mar2020 - Jan 2021 ➩ P⃣ C19 pneum + 1-3w since ADM I⃣ CT + gasEX + ∆∆mech = supine (5), prone (5), and recruitment (35) C⃣ no O⃣ >consolidation 3rdw ➩ PF changes ↑65% in prone ➩ venous admixture & PF ratio SIMILAR supine-5 and prone-5
2. Consolidated tissue = Non aerated tissue35.
3. Atelectatic tissue = non aerated tissue5 − non aerated tissue35,
CCH, SGQA, AAQC
05/02/2022
10:30:00 pm (BO Time)
2022 IM - COVID prolongado es menos probable en las personas vacunadas (Kuodi) [News].pdf
1. Comparison VAX vs n-VAX by SYMPTOMS (post-COVID - LONGcovid)
2. MedRxIv, 2022, IL ➩ onlineSURVEY / 950 (637, 67%) / mar2020 - nov2021 ➩ P⃣ vax 2doses Pfizer + infection I⃣ survey of SYMPTOMS longC19 C⃣ unvVAX O⃣ SYMP (fatigue 22%, cephalea 20%, weakness 13%, mialgias 10%) VAX: <SYMP (64%, 54%, 57%, 68%)
2022 ICUmmp - Optimal Respiratory Support for C-19 Pxs (JAMA).pdf
1. YES: ↓need invMV NO: ↓MM
2. CPAP = 1ST LINE therapy
3. PostHoc = CPAP vs HFNO ↓10% pOC
4. AE = 34%, 21%, 14% (CPAP, HFNO, CONV respect)
AAH, JMCM, JCAS, CCH, AAQC
07/02/2022
10:30:00 pm (BO Time)
2022 CC - Vitamina C improves microvascular reactivity and peripheral tissue perfusion in SS• (Lavillegrand) [R].pdf
1. 2022, CC, FR ➩ pros n-RCT / 30 / 6m ➩ P⃣ icu SS• I⃣ vitC: 40mg/Kg x30m C⃣ subgroups: w_defVitC & wo_defVitC O⃣ CLINICS: mottling, finger-tip, CRT, temp. MOLECULAR: transdermal iontophoresis = microvascular reactivity ➩ ↑all
2. ↑MICROvas REACT w_&wo_VITCdefiiciency
3. HAS NEVER BEEN STUDIED before ➩ iN VIVO
4. PLEIOTROPIC effect: a. antiox b. ↓proinflamm gene express c. immune restoration d. ↓ COAG gene express
AAH, CCH, MKFA, AAQC
08/02/2022
10:30:00 pm (BO Time)
2021 NEJMe - Acetazolamide to Prevent Adverse Altitude Effects in COPD and Healthy (Furian) [R].pdf
1. 2022, NEJM, centralASIA ➩ db, pd, RCT / T1: 176 - T2: 345 / T1: May2017-Aug2018 – T2: May2018-Aug2019 ➩ P⃣ T1: COPD + adults (18-75yo) T2: HEALTHY + >40yo T1+T2= living <800m I⃣ T1+T2 = Acetazolamide 375mg/d 24h BEFORE trip to 3100m (2-day-stay) C⃣ placebo O⃣ T1: ARAHE + symp requir INTERV T2: inciAMS ➩ (+) prevents both oc (T1 and T2)
2. T1: p<0.001 T2: p<0.035
3. COPD criteria = a. FEV1 40-80% of predicted (postBRONCHO) b. FEV1/forcedVitCap <0.7 c. SpO2≥92% d. PaCO2 <45% ➩ altitude 760m (GOLD criteria)4. Stationary cycling to EXHAUSTION D1 + D3
AAH, JCAS, MKFA, ±GSQA, AAQC
09/02/2022
10:30:00 pm (BO Time)
2021 NEJMe - Acetazolamide to Prevent Adverse Altitude Effects in COPD and Healthy (Furian) [R].pdf
1. trial 1 (COPD) = NNT 3.7 – trial 2 (healthy >40yo) 10
2. TRIAL 1: intention to treat ➩ 76% vs 49% (placebo VS acetazolamide) –– per-protocol analysis ➩ 73% vs 46% (pla VS aceta) = BOTH p<0.001
3. TRIAL 2: intention to treat ➩ 32% vs 22% (placebo VS acetazolamide) p = 0.035 –– per-protocol analysis ➩ 32% vs ? (pla VS aceta) p =0.0324. SEvere hypox 🔝 frequent BOTH TRIALS = 44% VS 16% (placebo VS aceta ➩ trial 1) [95%CI 0.16 - 0.55] + 31 vs 7% (placebo VS aceta ➩ trial 2) [95%CI 0.13 - 0.43]
CCH, SGQA, AAQC
10/02/2022
10:30:00 pm (BO Time)
2021 NEJMe - Acetazolamide to Prevent Adverse Altitude Effects in COPD and Healthy (Furian) [R].pdf
1. Trial 1 = 5 sOC, trial 2 = 7 sOC
2. Trial 1 ➩ SpO2 <85% time in bed < with acetazolamide
3. sOC = clinical exam + ABG + spirometry + resp sleep studies ➩ IN BOTH TRIALS
2022 NEJMjw - Risk for ASCVD in Individuals Wo_ Coronary Artery Calcium (Circulation).pdf
1. 2021, CIRCULATION, MULTIethnic ➩ cohort / 3416 / fu: 16y ➩ P⃣ multiethnic participants I⃣ CAC=coronary artery calcium + ASCVD rf C⃣ no O⃣ ASCVD events: CHD, stroke, both ➩ if CAC=0 BUT hypert (HR 1.6), DM (HR 2), smoking (HR 2) = ↑r ASCVD
2. Statins could be considered in this scenario
3. Familiy history PREMA ASCVD = women
AAH, JREC, SGQA, HIBN, JCAS, AAQC
11/02/2022
10:30:00 pm (BO Time)
2022 MEDPAGE - Warning Labels on Sugary Drinks. Do They Work (PLOS Med).pdf
1. 2022, PLOS MED, USA ➩ RCT / 325 / Jan-Mar 2020 ➩ P⃣ parents of children (2-12yo) I⃣ warning labels in sugary beverages packages: IMAGES (diabet foot + unhealthy heart) C⃣ bar codes in packages O⃣ SELL 45% (warning) vs 28% (barcode) (p=0.002) ➩ 52Cal (warning) vs 82Cal (barcode) (p=0.003)
2. Barcode = NO warning label
3. Reactins to the warning labels ➩ QUITE EFFECTIVE (p<0.05)
4. another study to COMPARE images vs legends
2022 ICUmmp - Intravenous Vitamin C Administration for SS° (CC)
1. 2022, CC, ? ➩ RCT / 40 / ? ➩ P⃣ SS• I⃣ vitC 25mg/Kg every 6h C⃣ placebo O⃣ pOC = vasopress REQUIR sOC (4) = SOFA, ICULOS, H+LOS, MM ➩ not significant difference in pOC
2. ICU LOS < w_vitC ➩ vit C (4d) VS plac (7)
3. MM, H+LOS.. not big difference
AAH, GSQA, CCH, JJFM, JCAS, AAQC
12/02/2022
10:30:00 pm (BO Time)
2016 ROB - The Risk Of Bias In Non-randomized Studies – of Interventions (ROBINS-I) assessment tool (AC Sterne)
2019 Rob - Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) OFFICIAL (Higgins)
HAQC, AAH, MKFA, AAQC
14/02/2022
10:30:00 pm (BO Time)
2022 MEDPAGE - Does Omicron pose as much of a blood clot threat (DAmbrosio) [br].pdf
1. < clot w_Omicron? ➩ less severe DIS + VAX + coagul strategies + limited to upper AIRWAYS
2. Monitorization: D dimer - if EXTREMELY ↑ = antiCOAG tto
3. clots IN SITU - NOT moving clots (broken and travel to lungs)
4. High-risk of CLOTS = elderly, ♡ DIS, CA, immobility, S or sevINF
2022 CC - Gut microbiota plays a pivotal role in opioid-induced adverse effects in gastrointestinal system (Xu) [let].pdf
1. Opiods can INDUCE ➩ GI DYS
2. Antagonist of opioids can REVERT the ‘’protective lung effect’ of OPIOIDS
3. LOOK UP adverse effects of opioidANTAG
4. GUT MICROB DYSBIOSIS ➩ 1. edema, 2. microb METABOLITES … ∑dysmot + intAbsorDYS
5. 5-HT ➩ IS MODULATED by opioids ∑ if DYS = GI DISORD
±HAQC, AAH, ARVC, MKFA, ±JREC, CCH, AAQC
15/02/2022
10:30:00 pm (BO Time)
2021 NEJMjw - A Focus on the Adrenal Gland (Year In Review).pdf
1. 2020, AIM, USA ➩ OBS, retro? / >1000 / ? ➩ P⃣ HTA I⃣ PREVALENCE C⃣ no O⃣ 16% = HTA S1 / ±22% HTA S2 or rHTA
2. Adrenal incidentaloma (>1cm?) = ask for CORTISOL ∑ 20% ↑ (±>3 ug/dL)
??SUBCLINIC’ = ↑MM
3. 2021, AIM, USA ➩ OBS (retro?) / 270k / ? ➩ P⃣ veterans rHTA tto I⃣ ARR? C⃣ NO O⃣ underdiagnosis (<2% were screened for ↑ALDOS)
4. MA ➩ ARR = S 10-100%, E 70-100%
2022 JAMA - Evaluation of Adiposity and Cognitive Function in Adult (Anand) [R].pdf
1. 2022, JAMA, CANADA+POLAND ➩ crossSec / 9189 / CAHHM (Jan2014 - Dec2018) PURE-MIN (Jan2010 - Dec2018) = 4y - 8y ➩ P⃣ free of CV DIS (30-75y) I⃣ body fat (BF) + visAdipTiss (VAT) C⃣ no O⃣ cognitive scores ➩ ↓ w_ gral and visceral FAT (ADJUTED: CVr, CereVasInj, EducLevel)
2. VasBrainInju = ↑ hiperint of white matter OR sileBrainInfarc
AAH, ARVC, MKFA, GSQA, CCH, JREC, AAQC
16/02/2022
10:30:00 pm (BO Time)
2022 JAMA - Evaluation of Adiposity and Cognitive Function in Adult (Anand) [R].pdf
1. Body fart % (bioelImpeAnal), visceAdipTiss vol (MRI), MRI of the brain (➩ vasBrainInju), CVrf (IHRS), cogniAssess (DSST + MoCA)
2. DSST = digital symbol substit test
3. MoCA = Montreal Cog Assess
4. STROBE ➩ guidelines to report OBS studies (applied here)
5. CORREL w_↓ COGN tests
6. Fazekas score for BRAIN (standarized) - measures 15mm OBJETIVE
➩ HWMH = FAZEKAS ≥4
7. T1 image is in L4-L5 ➩ great S for fat
8. Turbo echo = faster
2021 ROB - Revised Cochrane risk-of-bias tool for cluster-randomized trials (RoB 2 CRT) TEMPLATE FOR COMPLETION
1. Domains appraisal
2. 2020 JAMA - Systemic Corticosteroids + MM in CIpxs w_C19, online (Sterne) [MA] .pdf
AAH, ±SGQA, AAQC
17/02/2022
10:30:00 pm (BO Time)
2022 JAMA - The First 2 Years of C19 (Nuzzo) [Viewpoint].pdf
1. Pandemic ↑poverty (75 million)
2. Should CREATE urgency to iNVEST IN + MANTAIN: a. resilient HealSys, b.test+survei, c.publicTrust, d. equity, e. StrongGlobaInstit
3. Inadequate testing capabilies PERSIST now.
4. Uneven access to testing = surveillance BIASES
5.risk-mitigation behaviors = PREVENTION
6. 2021, ?, US ➩ survey, 1305, ? ➩ HIGH LEVELS OF DISTRUST (52% CDC, 37% FDA, 41% STATEhealDep)
7. 7% people of LIC have 1st vax dose
AAH, ARVC, MKFA, GSQA, CCH, JREC, AAQC
23/02/2022
10:30:00 pm (BE Time)
2022 NEJMjw - Remdesivir for Treating Non-Hospitalized Pxs w_ C-19 (NEJM).pdf
1. 2022, NEJM, USA ➩ RCT / >1200pxs / ? ➩ P⃣ unVAX + 1rf for sC19 I⃣ remdesiv (200, 100, 100 QD) C⃣ placebo O⃣ <Hospit (0.7% vs 5.3) [PINETREE]
2. Difficult to implement ➩ already-stressed HC sys
2022 NEJM - Effectiveness of Homologous or Heterologous C19 Boosters in Veterans (Mayr) [corr].pdf
1. 2022, NEJM, USA ➩ MATCHED CONTROL / 4.8M / ? (veterans db) ➩ P⃣ veterans + c19 dx LAB + VAX 1st dose I⃣ booster HETER C⃣ HOMOL O⃣ ↓incid of C19 w_mRNAvax booster after J&J (0.49 95%CI 0.4-0.6)
2. With mRNA primed NO MATERIAL DIFERENCE WAS NOTED (homo vs heter)
3. IgG antiBOD were the LOWEST w_J&J BOOSTER (homol)
ABFL, AAH, ±HIFS, AAQC
24/02/2022
10:30:00 pm (BE Time)
2022 NEJMjw - Allopurinol Is Safe for Pxs w_ Gout + CKD (AIM).pdf
1. 2022, AIM, UK ➩ retroCOHORT / >5000 / 5Y ➩ P⃣ gout + CKD I⃣ w_allopurinol (initiator) C⃣ wo_allopurinol (noninitiator) O⃣ ↓MM5y (5% vs 6%), target urate levels <1y (dose escalation ±300mg =)
2. RCTs (2 previous) ➩ NO beneficial effect on RENAL FUNCTION in pxs WO_GOUT
2022 NEJM - Medical Conditions and High-Altitude Travel (Luks) [r].pdf
1. Hypobaric hypoxia IMP physiological phenomenon
2. UNACCLIMATIZED lowlanders might have problems in ALT ➩ brain, heart, lungs, kidney, blood (5)
3. Unacclimatized NUMBER is UNKNOWN
4. Cerebral blood flow (CBF) + HR + CO ➩ ↑abruptly in MINUTES
HIBN, AAH, MKFA, CCH, AAQC
25/02/2022
10:30:00 pm (BE Time)
2022 JAMA - Effect of Sleep Extension on Objectively Assessed Energy Intake in Overweight in Real-life Settings (tasali) [R].pdf
1. 2022, JAMA, USA ➩ sc, pg, RCT / 80 / 6y (1m fu) ➩ P⃣ overweight (21-40yo) + sleep time <6,5h (habitual sleep) I⃣ extension 1.2h C⃣ habitual sleep O⃣ pOC ↓ energy intake sOC ↓weight + energy balance + free-fat mass
2. Intake >100Kcal/d ➩ 4.5Kg ↑ in 3y
3. Adequate SLEEP DURATION ➩ ↓weight (observational studies)
4. REDUCTION of 270Kcal/d (energy intake) w_extended sleep
5. Energy intake = ingesta de energía =
6. PREVENTION for obesity + weight loss programs
2022 NEJM - Medical Conditions and High-Altitude Travel (Luks) [r].pdf
1. Ascent abouve 2000m = RISK (particularly 2500)
2. Lungs: ventilation + pulmonary artery pressure ➩ ↑ in mins ➩ up and down + progressive, respectively ➩ both PEAK in weeks
3. Time + degree of exertion = risk of events
AAH, CCH, AAQC
02/03/2022
10:30:00 pm (BE Time)
2022 JAMA - Association of COVID-19 Incidence and MM Rates With School Reopening in Brazil d_C19 (Lichard) [R].pdf
1. 2022, JAMA, BR (saoPao) ➩ crossSEcc OBS + 643 MUNIC / 18761 school (repoen: >8500school/ 129 muni VS n-reopen: <10mil/ 514 munic) / Oct - Dec 2020 ➩ P⃣ school students I⃣ open schools C⃣ non-open school O⃣ cases + deaths ➩ both = WHEN MOBILITY IS ALREADY HIGH
2. Figures: trend of ➩ MATCHED SAMPLES + DIFERENCE IN DIFFERENCES STIMATOR (Callaway and Sant’Anna estimator)3. REALITY depends on local contexts, ➩ income levels, school infrastructure, senior population share, and local disease activity.
AAH, JCAS, AAQC
03/03/2022
10:30:00 pm (BE Time)
2022 HEALIO - Anger, emotional upset associated w_ stroke (EHJ).pdf
1. 2022, EHJ, IR ➩ case-control / 13462 / ? ➩ P⃣ pxs w_stroke I⃣ “cases”: stroke day (1h of symptom onset) C⃣ “control”: previous stroke day O⃣ Anger, emotional upset ⬄ stroke ➩ a. 9.2% overall b. all types of Stroke (ische + hemorr) c. heavy physical exertion = 5.3% icHH
2. Controlled ➩ region, CVD, rf, CVmed, timeORday symp
3. exposure to both triggers were not additive
2022 JAMA - Proactive vs Reactive Machine Learning in Health Care (Luo) [VP].pdf
1. Machine learning (ML) reactive VS proactive
2. ML level 2 NEEDS improvement (pandemic = highly dynamic situation)
3. REACTIVE = human expert input workflow
4. PROACTIVE = 2 levels (engineering automatization + upstream data collection)
AAH, CCH, SGQA, AAQC
04/03/2022
10:30:00 pm (BE Time)
2021 LANCET - Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure (Ehrmann) [R].pdf
1. 2022, LANCET, CANADA + FR, IR, MX, USA, ES ➩ prosPriori(setUp+defined)CollabMeta-trial (6 ol_supRCT) / 1126 (i567 vs c559) / Apr2020 - Jan2021 ➩ P⃣ sevC19 + hfnc I⃣ APP = awake prone posit C⃣ SOC = standard of care O⃣ pOC (comp): TTO FAILURE = intubated OR MM28 ➩ ↓pOC
2. Incidence ADVERSE EVENTS ➩ low + similar in both (i vs c) = SAFE INTERV3. IMPROVES: SpO2/FiO2, RR, ROX (Sp/Fi OVER RR)
AAH, JMCM, AAQC
05/03/2022
10:30:00 pm (BE Time)
2021 LANCET - Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure (Ehrmann) [R].pdf
1. sOC: intub, MM, LOS, WEANING, tTF, ttI, tTD, d_MV, MM iMV, preDEF safety, PHYSIO response, ROX
2. Most of the time APP possible
3. 28 days, why? numeric + stats + convenient
2022 ICUmmp - Learning from Medical Errors (Joya-Ramirez) .pdf
1. 4/10 patients ar harmed due to MED ERR
2. Errors ➩ AFFECTS not only PXS but also PHYSICIANS (emotional burden ➩ anger, guilt, remorse)
3. SYSTEM reestructuration is NEEDED to allow LEARNING FROM ERROR
AAH, AAQC
07/03/2022
10:30:00 pm (BE Time)
2022 HEALIO - Resistance exercise superior to aerobic exercise for sleep (Schaffer) [r].pdf
1. 2022, ?, USA ➩ RCT / 406 (aerobic 101, resistance 102, comined 101, none 102) / 1y ➩ P⃣ overwORobese + HTA S1 + hR CVD I⃣ TIME MATCHED exercise ➩ 3x/w for 60min/session C⃣ 3 groups O⃣ pOC = Pittsburgh Sleep Quality Index (PSQI), duration (hj, efficency (asleep/bed), latency (time to fall asleep), disturbances (# and freq) ➩ 🔝 is RESISTANCE
2. 94% completed INT + 84 exercise ahderence
3. Resistance exercises might improve CV health indirectly? ➩ motivation
2022 ICUmmp - Learning from Medical Errors (Joya-Ramirez) .pdf
1. Use medical error as an oppotunity to learn
2. Strategiers to learn:
a. debriefing
b. education on px safety
c. simulation of clin scenarios
d. constructive feedback
e. mentorship
f. peer support
3. CRUCIAL ➩ request help when NEEDED
4. Kroll 2008: supervisors must ENSURE a. trainee confidence b. trainee appropriate level of RESPONSABILITY of errors
AAH, EACQ, MKFA, AAQC
08/03/2022
10:30:00 pm (BE Time)
2022 HEALIO - Resistance exercise superior to aerobic exercise for sleep (Schaffer) [r].pdf
1. PSQI ➩ resistance exer ↑ sleep duration in 40min
2. LATENCY ➩ ↓3min : resistance group
3. EFFICIENTY: ↑ IN RESISTANCE exer (p=0.0005)
2022 PSYADV - Computerized Adaptive Test May Help Assess Suicide Risk (PLOS ONE).pdf
1. 2022, PLOS ONE, USA ➩ prosOBS / 305 / 6m - 1y ➩ P⃣ veterans I⃣ ASSESSMENT: CAT-SS = computar Adapt Test Suic Scale C⃣ no O⃣ PREDICTION or suicide risk➩ 10 points of change ↑ 50-77% LIKELIHOOD
2. “AI could be involved in its development”
3. “pressing” public health problem of suicide
2022 MEDPAGE - Treating a Messiah (Ahmed).pdf
1. Respectful connection
2. Nice narrative about an experience
3. Sharing phychiatric rotation anecdotes
4. Contrast about where to withdraw samples ➩ ER or Psychiatry5. Similar schizophrenia case with AAH, the px had to meet someone mythical.
MAL, AAH, SGQA, JCAS, XARS, MKFA, AAQC
10/03/2022
10:30:00 pm (BE Time)
2022 WHO - WHO prequalifies first monoclonal antibody - tocilizumab – to treat C-19 [News].pdf
1. WHO prequalifications are a global reference
2. Roche: originator company in collaboration
3. Toci = C19 severe-critically ill (considering INFLAMMATORY STATES, high pcr >7.5) ➩ rapid deterior + ↑O2 needs + sign inflamm response
4. 500-600USD every dose?
5. QUALITY, efficacy and safety
2021 LANCET - Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure (Ehrmann) [R].pdf
1. UNDERESTIMATION in I due to: intention-to-treat ➩ some controls moved to I
2. LIMITATION of DECISION-MAKING mediated by physicians: intubation refraining (better RespPar in I) OR lower intub threshold (in C)
3. APP ➩ longer DURATION in MX = hypothesis generating ➩ better ourcomes
4. APP = appeared SAFE + favour effect on OC
5. OC = treatment failure: intub OR MM28
6. Meta-trial ↓time to reach conclusions
XARS, AAH, CCH, AAQC
12/03/2022
10:30:00 pm (BE Time)
2022 JAMA - Masks Cut Secondary SARS-CoV-2 Infections by Half (kuehn) [News].pdf
1. 2022, EID, ? ➩ retros ⏤ 431cases/966contacts ⏤ Oct2020-Feb2021 ➩ P⃣ C19 (“tests”) I⃣ mask use (yes/no) C⃣ no O⃣ No infected persons ➩ infRATE ↑26% (both unmasked or INFECTED unmasked) VS ↓13% (both masked)
2. Duration: 26% of contacts (≥2h) w_INFECTED VS 14% less time (<2h)
3. Symptoms DID NOT affect RATES of contacts.
2022 JAMA - COVID-19 linked with incresed incidence of youth diabetes (kuehn) [News]
1. 2022, MMWR, USA (CDC) ➩ retros / 2db = IQVIA 1.7M +HealthVerity (HV) 900k / Mar2020 - Feb2021 ➩ P⃣ children + adolescent I⃣ IQVIA (4groups = C19, n19, ARI, nARI) + HV (2groups = C19, nC19) C⃣ NA O⃣ new-onset DIABETES ➩ IQVIA —> C19 166% > nC19 ; C19 116% > ARI ➩ HV —> C19 31% > nC19
2. ARI = acure respiratory infection PRE pandemic
3. C19 virus ATTACKS pancreCells (ACE2r)? ↑GLU may be the trigger? Prediabetes to DIAB progress?
XARS, MKFA, AAH, AAQC
14/03/2022
10:30:00 pm (BE Time)
2022 NEJMjw - Masks Work … If You Wear'Em (MMWR).pdf
1. 2022, MMWR, USA ➩ case-control ⏤ 652 (cases) 1176 (control) ⏤ Feb - Dec2021 ➩ P⃣ adults I⃣ mask use (cloth, surgical, respirator) C⃣ controls O⃣ C19 ➩ ↑ cloth ~ Qx ↓ respir
2. higher proportion of cases were unvaccinated
3. IRONIC ➩ published when masks are LESS used
2022 PSYADV - Emoji Use Helps Avoid Remote Dropout, Study of GitHub Software Developers Suggests (Plos ONE).pdf
1. emoji user worked MORE hours/day - twice the number of days VS non-users (2019)
2. Emojis reflects the EMOTIONAL STATUS of working developers
3. nonemoji USERS = 3x ↑lk DROP OUT
JCAS, XARS, AAH, AAQC
16/03/2022
10:30:00 pm (BE Time)
2022 BMJ - Effect of sedation w_inhaled anaesthetics on cognitive + psychiatric OC in CIpxs (Cuninghame) [sr PROT] .pdf
1. INHALED ANESTH ➩ ↓lung inflamm + ↓tEXT + ↓LOS ICU, COMPARED to IV + ↑O2
2. Short supply of IV promoted the use of INHALED ones
3. ADV EVE of long-tem use INHAL ➩
a. dose-depen resp DEPRESSION
b. ↓TA
c. Malignant HYPERTHERMIA
d. Diab INSIPIDUS
e. Hepatitis
4. ICU delirium ➩ ASSOCIATED ↑MM, prolMV + H+, ↑costs
5. INHALE SEDATIVES safety and efficacy will be ASSESSED
6. LONG-TERM COGNITIVE DISABILITES ➩ 10% - 58% incidence
➩ P⃣ x I⃣ x C⃣ x O⃣ x will be used for this sr
PICL, AAH, MKFA, JMCM, AAQC
17/03/2022
10:30:00 pm (BE Time) Differed to 00h00 BE
2022 NEJMjw - How Useful Is Vaccination After COVID-19 Infection (NEJM).pdf
1. 2022, NEJM, UK ➩ pros ⏤ >35k ⏤ Dec2020 to Sep2021 ➩ P⃣ asymp HCworkers I⃣ prev C19 YES C⃣ prev C19 nO O⃣
a. YES (9K): UNVAX: rRE-INF = ↓86% than others ➩ 1y AFTER ↓70%
b. YES (9K): VAX: with 1 or 2 Pfizer: rRE-INF = ↓ ≥90%
c. NO (26k): with 2 Pfizer ➩ rRE-INF = ↓85% ➩ 6-7m AFTER (2nd dose) ↓50%
2. UK STUDY ➩ extending VAX interval >6w ➩ NO CHANGE
3. 2022, NEJM, ISR ➩ retro ⏤ 150k ⏤ Aug2020 to May2021 ➩ P⃣ recovC19 I⃣ UNVAX 66k vs VAX 83k C⃣ NO O⃣ *RE-INF*
a. UNVAX: 2168 RE-INF (Nov2021) ➩ 10.2/100k
b. VAX: 354 RE-INF ➩ 2.5/100k
4. ISR study ➩ est VAX EFFECTIV = 82% ➩ 2 VAX postINF DID NOT APPEAR TO CONFER MORE PROTECTION than a single dose.
5. NO DATA on ADVEFF from VAX in prev INF
6. NO description (speculation) on variant on the study dates
2022 UNIVADIS - COVID-19 pneumonia, methylprednisolone pulse therapy added to dexamethasone shows no benefit (CROI).pdf
1. 2022, ?, IT ➩ mc_dbRCT ⏤ >300 (151 methyl vs 150 placebo)⏤ ? ➩ P⃣ pneumonia C19 WITH SOC (dexa in both groups) I⃣ methyl 1g x 3d C⃣ placebo O⃣ a. pOC:hLOS = randozima - dischage wo_needSuppO2; b. sOC: allMM, iMVfreeSS, SAFETY
➩ NO DIFF within 28D
2. NO DIFF: admICU w_INTUB or DD + overallMM
3. Included pxs w_PaFi 100-300
JCAS, AAH, CCH, MKFA, SGQA, AAQC
18/03/2022
10:30:00 pm (BE Time)
2022 PSYADV - Fluid + Fixed Cognitive Decline Are Interrelated (Sci Adv).pdf
1. 2022 SCIEN ADVANC ➩ 2 longitudinal STUDIES: VCAP (Virginia Cog Aging Projec) + BETULA (Betula Project)
2. IF ↓fluid ability ➩ ↓crystallized ability OR litte gain
3. Multivariate growth curve modeling
4. Vascular DYS + cortical ATROPHY = might explain 2
5. Age might influence this changes
2022 JCEM - Approach to the Pxs w_ Moderate Hypertriglyceridemia (subramaniam) (R).pdf
1. ↑TG ➩ ↑rACVD
2. TG high acceptable = 150
3. Step-wise RECOMM ➩
a. secondary contirbutors (DM)
b. pxs CHAR (lifestyle: weight + alcohol)
c. Statin and non-stat
4 General clasiff: 4 levels (mild <200, mod 200-500, mod-sev 500-1k, sev >1k)
EACQ, ±JCAS, CCH, SGQA, MKFA, AAQC
19/03/2022
10:30:00 pm (BE Time)
2020 JAMA - Infection, Antibiotics+Patient Outcomes in the ICU (yin) [ed].pdf
1. 3 studies: EPIC I, II, III ➩ COMPARISONS
2. MM and prevalence has not changed in 3 decades (33% in EPIC II)
3. Gram-negative bacteria MOST FREQUENT
4. 2 REPORTS of WHO ➩ 60 in development + 50 ATBS + 10 BIOLOGICS ➩ FEW TARGET MRGneg BAC
5. HIGH USE OF ATBS ➩ prophylaxis 28%, empiric 51%, postive cultures (35%)
6. EFFORTS to DC: a. procalcit b. atb stewarship c. computerized decision support system
MKFA, CCH
21/03/2022
10:30:00 pm (BE Time)
Plastic bronchitis (Maqsood 2022).pdf
1. Plastic bronchitis ➩ might present as ARF or AIRWAY OBSTRUCTION
2. Associated with: congenital heart disease, thorac-duct trauma, sickle, others.
3. Bronchoscopy was relevant in this case - MAINLY histopathology
2022 JAMA - Artificial Intelligence in Medical Imaging—Learning From Past Mistakes in Mammography (Elmore) [vp].pdf
1. CAD = computer-aided detection
2. CAD did not IMPROVE radiologist accuracy IN 2 DECADES!!!
3. 1998, FDA cleared CA found that CAD
SGQA, AAQC
28/03/2022
11:30:00 pm (BE Time)
2022 LANCET - The pandemic + the great awakening in the mm of hypoxaemic ARF (Shekar) [comm].pdf
1. APP = awake prone positioning
2. srMA (Li) ➩ NO ↗️ MM + ICU admiss YES ↘️INTUB
3. NEED of resource-allocation: beds + staffing
4. APP ➩ ↗️ O2 + HOMOGENEISA tPP + ↘️ lung compression + ↗️ VQ matching
5. Where to APP? icu better to AVOID risks6. Limitations to better clinical trials = absence of grade def of hypARF + agreed TRIGGER for IMV + develop CORE OC measures
MAL, AAH, EACQ, AAQC
29/03/2022
06:30:00 pm (BO Time)
2022 JAMA - Artificial Intelligence in Medical Imaging—Learning From Past Mistakes in Mammography (Elmore) [vp].pdf
1. ∆ = TO PREVENT repeating HISTORY
2. ∆ automation bias ➩ DIFF computer ALGORITHM vs PHYSICIAN JUDGEMENT (-) if presented prior to INDEPENDENT assessment
3. ∆ reimbursement AI tech ➩ FDA clearance: small reader studies + noninferiority
4. ∆ improve AI ALGORITHMS + software based on AI
4. EACQ: Types ➩ supervised, non-superv, reinforcement (error due to overtraining)
5. TO PREVENT repeating HISTORY: ↓ legal responsability ➩ optimize MammograQualStandAct
2022 NEJMjw - Validation of the Erasmus Respiratory Insufficiency Score in pxs w_GBS (AN).pdf
1. 2022, AN, [ASIA, NA, EUR] ⏤ prosValidation / 1023 (19coun, 155H+) / ? ⏤ P⃣ GBS I⃣ EGRIS application C⃣ no O⃣ PREDICTION ➩ NothAme + EUR (9 VS 21 not calibrated) good prediction when CALIBRATED ➩ Asia NO (17% vs 21%)
2. GBS = Guillain-BArre syndrome, EGRIS ERASMUS GBS RESP insuff score
MAL, AAH, ±MKFA, AAQC
30/03/2022
10:30:00 pm (BO Time)
2022 JAMA - Once Viewed as a Promising C-19 Tto, Convalescent Plasma Falls Out of Favor (Rubin).pdf
1. CP• = convals plas
2. C. Lane (NIAID): there was a preconceived notion of efficay
3. Lane: it is NOT a uniform product - FDA mesured only abs TO THE SPIKE of 1 variant
4. 2000, JAMA-PNAS, JMV, Wuhan ⏤ ↓ viral load + SYMP ↗️
5. FDA ➩ expanded access program (EAP) ➩ Schulman comment “multiple, large clin trials COULD HAVE BEEN CONDUCTED”
6. Dec2020: SAFETY ➩ serious AdvEve <1%
7: MA in JAMA net: 8RCTs, >2k ➩ 1231/2341 breathing WO_MV
8. UK TRIAL: almost 12k ➩ 5% w_iMV (usual care VS usuaCare+CP•) ➩ DID NOT ↗️ SS or progVENTI
9. K. Schulman (Stanford): “turned into panic, not into science”
10. IMP: optimal dose + timing of tto + which pxs (2500pxs “Schulman”)
11. pre print paper ➩ 1228pxs, 8d onset-SYMP, ↓ H28 in 54%
12. HIGH TITER OF CP ⭐️13. in OUTPXS ➩ PAXLOVID (nilmatrelvir-ritonavir) + REMDESIVIR
AAH, CCH, AAQC
31/03/2022
11:30:00 pm (BE Time)
2022 MEDPAGE - FDA Greenlights Second COVID Booster for Select Groups (Walker) [r].pdf
1. Second booster OK for FDA (EUA) (>50yo)
2. Moderate to sever immunocompr CONDITIONS (solid organ transpla) + adults for Moderna + >12yo for Pfizer
3. Waning ummunity + risk of SEvERE diseases
4. Studies ➩ ISRAEL: 700k ADULTS, NO safety concerns
5. FDA ➩ 1/3 50-65 SIGNIF MEDICAL COMORB
6. Immunogenicity ➩ ISRAEL: olSTUDY, Pfizer or Moderna (Delta, Omicron)
7. VRBPAC on Apr6 ➩ if 2nd booster works for other populations
2022 NEJMjw - Gut Viruses Might Influence Our Cognition (Cell Host Microbe).pdf
1. 2022, CHM, ? ⏤ obserINT / 942 / ? ⏤ P⃣ HUMANS, mice, flies I⃣ 1. Examined GUT BACTERIA + VIRUSES 2. Caudovirales transplant to MICE 3. Caudovirales phages to FLIES C⃣ NO O⃣ Cognitive tests ➩ humans = executive function + memory ➩ mice = brain up-regulation of genes ➩ flies = cognitive tests ➩ ALL ↗️
2. The IMPORTANCE of human microbiome GROWS
3. BACTERIOPHAGES in gut can INFLUENCE human cognition
05/04/2022
11:15:00 pm (BE Time)
2022 NEJM - Medical Conditions and High-Altitude Travel (Luks) [r].pdf
1. Prophylaxis only for known clinical conditions
2. Rule of thumb ➩ acclimatization only 1 RCT
3. Rule of thumb = above 3k m, stop every 500m (sleep/night) ➩ 3-4 days REST included (same altitude 2 conseq nights)
4. DESCENT = best option when a. AMS worsens b. AMS fails to improve
5. AMS = acute mountain sickness
2022 MEDPAGE - Persistent Brain Fog After Mild C19 Infection Tied to CSF Markers (AAN).pdf
1. 2022, AAN, USA ➩ OBS ⏤ 13+5 ⏤ 10m (after first C19 SYMP) ➩ P⃣ adults, postC19 I⃣ OBS: pxs w_COGNITIVE SYMP C⃣ pxs wo_COG SYMP O⃣ CSF 10m: ↑ CRP (p=0.004), ↑ Amyloid A (p=0.001) ➩ trends↑ IP10, IL8, VEGF-C, VEGFR-1
2. Some CSF markers ➩ showed SPECIFICITY FOR C19 (early-onset COGNITIVE CHANGES)
3. IMMUNOVASCULAR DYSREGULATION: brain inflammation + SARS-CoV-2 (alter homeostasis)
4. PATHOLOGY RESEARCH ➩ disruption of BRAIN small blood VESSELS ➩ protein leak
5. EXECUTIVE FUNCTION DISORDER: a. DIFF retrieving names-words. b. DIFF holding onto + manipul info c. SLOW processing speed
6. AAN chair: “first step toward UNDERSTANDING … one of the GREATEST QUESTIONS … post-C19 ”
LFMC, HACQ, AAQC
LFMC, AAH, MKFA, HIBN, AAQC
06/04/2022
11:15:00 pm (BE Time)
2022 NEJM - Medical Conditions and High-Altitude Travel (Luks) [r].pdf
1. HACE = high altitude cerebral edema
2. HACE has neurologic features (global encephalopathy: altered mental status, ataxia, BOTH ⏤ ↓ COMMON focalization) ≠ HAPE, AMS, HAH, CSA
3. COMMON >2500m ➩ HAH, AMS ⏤ UNSUAL ➩ <3500m HACE, <3000m HAPE ⏤ VERY COMMON >2500m ➩ CSA
4. AFTER ASCENT: AMS onset 1-2d ⏤ HAPE onset 2-4d
5. TTO ➩ HAH stop, rest, NSAIDSs, dexa ➩ IF PERSISTENT = descend OR O2
2022 EPA - Air Cleaners, HVAC Filters, and Coronavirus (COVID-19).pdf
1. 2022, EPA, USA ➩ AIR CLEANER: NOT ENOUGH ALONE (abcdef needed = CDC best practices)
2. EPA = United States environmental protection agency
3. Small airborne particles are REMOVED ➩ particles size IS IMPORTANT
4. 0.1-1um are small and needed to be removed⏤ 0.3um are removed by most filters. ➩ verify THE FILTERING CAPACITY (consider particle size, space size)
5. HEPA UNIT = (HEPA = High Efficiency Particlate Air) high CADR for smoke (CADR = Clean Air Delivery Rate)
6. LARGE BUILDINGS requires PROFESSIONAL INTERPRETATION OF technical guidelines
ALAC, AAQC
02/04/2022
11:15:00 pm (BE Time)
BMJ - What is grade (EBM).pdf
1. Grading of recommendations, assessment, development and evaluations
2. 4 levels of evidence: certainty in evidence = quality of evidence (very low, low, moderate, high)
3. Very low = tEFF ‘probably mark≠’ eEFF ⏤ low = tEFF ‘might be mark≠’ eEFF ⏤ moderate (believe that) = tEFF ‘probably close to’ eEFF ⏤ high (lot of confidence) = tEFF ‘’similar to’ eEFF
4. tEFF = true effect ⏤ eEFF = estimated effect5. Domains: ROB, imprecision, inconsistency, indirectness, publication bias
MKFA, ±SGQA, AAQC
04/04/2022
11:15:00 pm (BE Time)
2022 NEJM - Medical Conditions and High-Altitude Travel (Luks) [r].pdf
1. Altitute agravation determinants in pxs w_UNDERLYIN DIS ➩ time (longer stay) + degree of exertion
2. W_unilateral absence of PUL ART ➩ HAPE at 1500m
3. 25-43% of travelers to hALT ➩ ACUTE MOUNTAIN SICKNESS
4. 37% of = ➩ hALT headache
5. INCIDENCES OF: hALT cerebral edema + hALT ∆edema = low BUT FATAL
2022 NEJMjw - Hazards of aspirin + heparin during acute stroke thrombectomy (LANCET).pdf
1. 2022, LANCET, NL ➩ ol.mc.RCT ⏤ 628 ⏤ Jan2018-2021 ➩ P⃣ adults + acute iS (anterior circ) ≥2 NIHSS I⃣ 2 goups: ASA (300mg) + unHEPAR (bolus 5000 + a. 1250 IU/h x 6h b. 500 IU/h x 6h) C⃣ 2 groups: no ASA + no HEPAR O⃣ pOC: modRankin90 ⏤ safOC: sICH ➩ both I have worse sOC (stopped early) + wo_benefic on FUNC OC
2. MOD RANKIN SCALE = funcional scale to assess DISABILITY (0-6 points, no SYMP to DEATH)
3. NIHSS = over 42, level of LOC, LOC quest, LOC comm, best GAZE, visual, facial palsy, mortor arm, motor leg, limb ataxia, sensory, best LANGUAge, DYSARTHRIA, extingtion & inattention
4. MR CLEAN-MED
07/04/2022
11:15:00 pm (BE Time)
2014 CEREBRAL CORTEX - Boosting Vocabulary Learning By Verbal Cueing During Sleep (schreiner) [R].pdf
1. Hypothesis ➩ CUED Dutch words ↗️ MEMORY compared ➩ NON CUED words
2. Memory cues = odors, sounds
3. VERBAL CUEING failed to ↗️ MEMORY d_active + pasive WAKING
4. EEG ➩ 🔝 verbal CUEING (nonREM):
- PRONOUNCED frontal (-) ERP
- ↑ frequ FRONTAL SLOW WAVES
- ↑ THETA POWER ➩ right frontal + left parietal
5. ERP = event-related potential
2022 NEJM - Medical Conditions and High-Altitude Travel (Luks) [r].pdf
1. ↓ Pbar, to 3500 is 82-88% ➩ HEALTHY (24 -48h after ASCENT)
2. Who requere FURTHER ATTENTION before the intended trip ?
- r_sevHYPOX OR iDO2
- r_iVENTIL response
- r_probl ➩ ∆VASC response
- r_compi ➩ UNDERLYING CONDITIONS
3. CONTRAind ➩ > 2500 m
• obstr + restri ➩ CYST<30% ➩ ↑ PAP
• ♡ Ø IAM unANG 0sick
• † (seis + CVabn)
4. mPAP >20 + rightHF OR both ➩ PREDISPOSE to HAPE OR WORSENING righ♡func
LFMC, HIBN, MKFA, AAH, AAQC
LFMC, AAH, CCH, GSQA, AAQC
08/04/2022
11:15:00 pm (BE Time)
2019 ICM - Plateau and driving pressure in the presence of spontaneous breathing (bellani) [cr].pdf
1. Pplat ESTIMATION is unreliable d_ SPONT EFFORT ➩ STABLE inspHOLD UNACHIEVABLE ➩ ignored without Pes.
2. Pes = esophageal manometry ⏤ Paw = airway pressure
3. inspHOLD d_ (+)press breath wo_sponEFFORT ➩ slight ↓insPRESS (PRESS from static∆VOL)
4 inspHOLD d_(+)PRESS
breath with spontaneous efort ➩ ↑ Paw = Pplat.
5. THIS is a TRUE Pplat that refects the size of the VT + (hidden) spontEFFORT
2022 NEJM - Medical Conditions and High-Altitude Travel (Luks) [r].pdf
1. PREDICTION RULES: pulmonary-function TESTS + ABG + CP exercise testing + hyp ALT stimulation test ➩ rHYPOXEMIA (O2 yes or no)
2. Related to the 4 questions ➩ affirmative = 1 or more ⏤ negative = all ➩ former: further evaluat OR cancel trip / latter: disease-specific planning
3. TOLERANCE in resourceful settings ➩ ski-resort community COLORADO
4. low risks ➩ EXACERBATIONS are IMP ➩ asthma, Afib, migraine, IBD ➩ check your DEVICES (hypobaric hypoxia + extremely cold temperatures)
MKFA, HIBN, ±SGQA, JJFM, AAQC
09/04/2022
11:15:00 pm (BE Time)
2022 NEJM - Medical Conditions and High-Altitude Travel (Luks) [r].pdf
1. Migraine ➩ COULD INCREASE with highALT
2. Anemia ➩ PROPORTIONAL to severity + no Hb level PRECLUDES TRAVEL ➩ consider IRON (infusion)
3. ACS
- uncomplicated ➩ DELAY 4w
- complicated ➩ DELAY 3 month
4. C19 ➩ AFTER (+) test (wo_symp) = 2 w after ⏤ AFTER (+) symp resolution (w_symp) = 2 w after
5. PASP>60 mmHg o NYHA III o IV ➩ AVOID TRAVEL
6. COPD & EPID ➩ SpO2, GRADED exposure
7. Consider kidney + liver adjustments + drug-drug interac + travel insura
8. acetazol + dorzolam ➩ AVOID COMBINATION
META JOURNAL REVIEW of the week
1. Four dx criteria for CSA of altitude: a.Recent ascent to hALT (>2500m), remember exceptions at 1500m b. Sleepiness, awakening with sob, snoring, witnessed apneas, insomnia (DIFF i_ OR m_SLEEP, freqAWAK…ings, nonRESTORATIVE sleep) c. SYMP ➩ hALT period breathing or PSG w_recurrent CENTRAL APNEAS or HYPOPNEAS d_NREM (≥5/h) d. NOT better explained by ANOTHER sleep DISORDER, medical OR neuro DISOR, MEDs (narcotics), substance use DISOR
HIBN, AAQC
10/04/2022
11:15:00 pm (BE Time)
2014 CeCo - Boosting Vocabulary Learning By Verbal Cueing During Sleep (schreiner) [R].pdf
CW = cued words
UW = uncued words
1. Animal studies ➩ birds: sound learning IMP for development ➩ MAMAL ≠ BIRDS mechanisms of memory consolidation
2. SLEEP = IMP role in MEMORY CONSOLIDATION
3. ODORS + SOUNDS + MELODIES ➩ benefits ASSOCIATED MEMORY CUES consolidation ➩ HYPPOCAMPAL celss in rodents
4. RESULTS:
Sleep group ➩
- CW 105.14 ± 2.64%
- UW 95.43 ± 2.07%
Sleep control ➩
- CW 93.55 ± 2.37
- UW 92.80 ± 3.10%
Active awake
- CW 85.53 ± 2.8
- UW 84.2 ± 2.16%
Passive awake
- CW 79.86 ± 4.58
- UW 81.25 ± 2.09%
5. Sleep architecture NOT altered by cueing
6. ALL accompanied by distinct NEURONAL activities which involve sleep-specific slow oscillatory mechanisms.
7. Verbal CUEING ➩ efficient and effortless tool to ↗️ foreign vocabulary learning.
LFMC, AAH, MKFA, AAQC
13/04/2022
11:15:00 pm (BE Time)
2022 NEJM - Effect of Early Treatment w_ Ivermectin among pxs w_ C19 (Reis) [R].pdf
1. nCIpxs ➩ IN: >18yo, outpatients w_clincC19 7d after ONSET + ≥1 hrCRI for PROG of C19
2. hrFACTORs ➩ ≥50yo, DM, HTA in too, CVD, ∆ DIS, smoking, OBESI (BMI>30), transpl, CKD (stage IV) or DIAL, immunoSUPRESSIV (≥ 10,g prednisone), CA <6m, chemotherapy ➩ DM, HTA, OBES, AGE
3. RAPID antigen test was used
4. PROMIS GLOBAL-10 = patient-reported OC measumente info system ➩ SYMP + FUNCTION + hrQOL ➩ 5-20
5. SETTING ➩ 12 clinical sites
6. RANDOM + INTERV ➩ text message used + block random + stratif (≥< 50yo) + randomized ASSIGNMENTS unaware (trial team, site staff, pxs)
7. OC measures ➩ pOC composite: H+28 afterRAND OR ED visit28 (for worsen C19, >6h) afterRAND ⏤ capacity limitation CONSIDERED ⏤ there was an EVENT-ADJUDICATION committee to JUDGE the REASON of H+ or observ ED (IF RELATED TO C19)
8. sOC ➩ viral CLEAR d3, d7 ⏤ anyCauseH+ ⏤ ttH+ ⏤ EDvisit >6h ⏤ ttCLINrecov ⏤ anyCauMM ⏤ MV ⏤ dMV ⏤ hrQOL ⏤ adherence to regimen ⏤ AdvReac
2022 ICUmmp - HFNO alone versus HFNO alternated w_ NIV FLORALI-IM Study (LANCET).pdf
1. 2022, LANCET, FR-IT ➩ RCT ⏤ 29 ICUs ⏤ ? ➩ P⃣ adults, CIpxs immunocomp I⃣ HFNO C⃣ HFNO + NIV O⃣ MM28 ➩ THE SAME (36 vs 35%) ➩ sOC (+) discomfort with HFNO
2. IN ➩ adults + immunosupp + ARF: RR≥25, PF ≤300 on HFNO, NIV or O2 ≥10L/min
3. EX ➩ PaCO2 > 50 + strong BENEF from NIV: CLD, CPE, postOP + sevSHOCK + GCS ≤12 + urgINTUB + DNI + contraInd NIV
LFMC, AAH, MKFA, AAQC
11/04/2022
11:15:00 pm (BE Time)
2022 NEJM - Effect of Early Treatment w_ Ivermectin among pxs w_ C19 (Reis) [R].pdf
1. 2022, NEJM, BR ➩ db,adap,RCT ⏤ 3515 (679 VS 679) ⏤ Mar-Aug2021 ➩ P⃣ adults, sC19 + 1rf PROGRESSION I⃣ ivermec 400ug/Kg x3d C⃣ placebo O⃣ composed pOC: H+28 C19 or ED long stay >6h in 28d ➩ NO CHANGE
2. IVER indications: onchocerc, strongyl, ectopara
3. IN VITRO: good for virus ➩ HIV, dengue, Zika, yellos fev, West Nile, Hendra, chikun, Semliki, Sindbis, Avan
4. 60 RCTs REGIST ➩ 31 REPORT ➩ small, withdrawn
5. IDEAL drug/med ➩ inexp, widely available, effective
HIBN, AAQC
12/04/2022
11:15:00 pm (BE Time)
2022 UNIVADIS - Nueva variante de la COVID-19, XE, descubierta en el Reino Unido (NEWS).pdf
1. XE new variant = recombinant = Omicron + subVAR BA.2
2. potientially + contagious than BA.2
3. 637 cases ➩ UK: 1st case Jan19, 2022
4. XA, XB, XC, XD none VOC ➩ now we have XE
5. WHO Mar29 ➩ high transmisibility of XE = now 70% of cases in USA
6. Predominant VARIANT currently ➩ BA.2
2022 JAMA - Thromboinflammation and Antithrombotics in COVID-19 (Connors) [ed] .pdf
1. RECOVERY ➩ 2022, LANCET, UK-IND-NEP ➩ RCT ⏤ 14892 ⏤ ? ➩ P⃣ nCIpxs I⃣ ASA+usuaCare C⃣ usualCare alone O⃣ MM28 ➩ equal (17& in both) ➩ rHH ↑ (1.6 VS 1%)
2. ACTIV-4a ➩ 2022, JAMA, USA-BR-IT-ES ➩ RCT ⏤ 562 ⏤ ? ➩ P⃣ nCIpxs I⃣ heparin C⃣ hparin + P2Y12 (-) (tica 63, clopi 37%) O⃣ OSfd21 ➩ FUTILITY in both ➩ majBLED in group control (6 VS 2 particip)
3. REMAP-CAP ➩ 2022, JAMA, UK ➩ RCT ⏤ 565, 455, 529 ⏤ ? ➩ P⃣ CIpxs I⃣ ASA ⏤ 1of3 P2Y12 (clopi, tica, prasu) C⃣ open control O⃣ OSfd21 ➩ no diff (7d) ➩ sOC: SS iH+MM + OSfd 14d in bot ➩ rHH ↑ 2.1 vs 0.4%
4. US ACTIV-4B ➩ 2021, JAMA, USA ➩ RCT ⏤ 657 ⏤ ? ➩ P⃣ nCIpxs I⃣ ASA 81mg C⃣ placebo O⃣ EFFICACY ➩ equal to placebo ➩ sOC: prophy OR therap-DOSEapaixaban SIMILAR TO placebo ➩ APIXABAN ↑ HH
Thursday 14/04/2022
11:15:00 pm (BE Time)
CCH, AAQC
ECG refresher module
Friday 15/04/2022 11:15:00 pm (BE Time)
LFMC, HIBN, ±GSQA, AAQC
Intestinal Tuberculosis (Oñate 2022).pdf
1. 36F, ED, abd pain + fever + cough
2. CT miliary pattern of ∆ nodules + subdia free air
3. six perforations in terminal ileum PANEL A
4. necrotizing granulomatous inflamation PANEL B
5. Completed 9m of antiTBC
6. ILEOCECAL infflammation usually MISDIAGNOSED ➩ appendicitys OR IBD (Intestinal TBC)
2022 HEALIO - Sotrovimab no longer authorized to treat C19 in areas w_ high BA.2 frequency (CDC).pdf
1. Sotrovimab (500mg) NOT for Omicron subvariant BA.2 (Mar25, FDA statement)
2. CDC data: >50% BA.2 in several states as of Mar19, 2022 (NY, NJ, MASS, CONNEC…)
3. Remain authorized + approved ➩ nirmatlervir, remdesivir, molnupiravir, bebtelovimab FOR ‘MILD-MOD C19 + hr PROG to sC19’
2022 NEJM - Effect of Early Treatment w_ Ivermectin among pxs w_ C19 (Reis) [R].pdf
1. Adverse effects were graded ➩ Division of AIDS table for Grading sev f Adult and Pedia AdvEven2. Aug5, 2021 ➩ data and safety monit COMMITTEE stopped ERROLLMENT because the PLANNED sample size had been REACHED3. Adapted apporached to sample-size were applied4. MIN clinical utility 37.5% ivermectin FOR 80& power (type I error 0.05) ➩ pairwise compar 15% of pxs in placebo5. Superiority + futility threshold ➩ through 200k simulations6. Intention-to-treat (all randomized) + modified ITT (tto or place at least 24h BEFORE pOC) + per-protocol (100% adherence ASSIGNED REGIMEN)7. Bayesian approach for sOC
Saturday 16/04/2022 11:30:00 pm (BE Time)
LFMC, SGQA, AAQC
2022 ICUmmp - Sepsis in critical care effective antimicrobial strategies in ICU (Nair) [r].pdf
1. SEPSIS implies ↑ COSTS + ↑ MM ➩ nosocomial S
2. Majority FROM COMMUNITY
3. MM 6m ➩ 60% in SS•
4. S is HETEROGENOUS ➩ DIFF phenotypes and endotypes
5. MRSA INDEPENDENTLY associated ↑ MM in ICU
6. rf_MRSA: priorH MRSA ⏤ atbs IV ⏤ recurreSKIN INF ⏤ invasive devices ⏤ HD ⏤ H+ 90d
7. MM30 is ↑ : w_MDR, comord (cirrh, immunos, vasc Disea), have received ATBS , chemo, wound care, dial, surg 30d8. DELAY of 6h in DX S• = 7.6^% ↑ MM 9. MA ➩ IMPACT delay ATB appropi = ↓ tto FAILURE + ↓MM + ↓ COST
Monday 18/04/2022 11:15:00 pm (BE Time)
LFMC, AAH, AAQC
2022 ICUmmp - Sepsis in critical care effective antimicrobial strategies in ICU (Nair) [r].pdf
1. Several markers of HOST RESPONSE ➩ PCT, CRP, sol RECEP mueloid1, PROadrenomedul, UPAr, IL6 ➩ sepsis
2. rf_MDR ➩ prior colonisation (1y) + local prevalence + broad spectr atb 90d + selec digest DECONTAM + TYPE (comm, nosoc) + travel highly endemic + H+ abroad <90d
3. EMPIRIC ATB CHOICE ➩ rf related w_ATB resis: comobidites, recent healthcare, immunosupress, type (commun, nosoc), selection pressure prior ATB, colonisati by RESISt, LOCAL epidemio and INF prev measures
4. DOSE ➩ based on:
- pk/pd - MIC - volume of distribution
- ARC - RENAL OR LIVER failure (metabolism)
- phiysiochemical (hydro/lypoph). - organ support - site of iNF
5. INITIAL LARGE BOLUS = 1.5 x standard dose (DDB 2019)
2022 HEALIO - FDA authorizes first breath test for C19 (FDA) [r].pdf
1. FDA OK 1st BREATH TEST for C19 ➩ EUA
2. InspectIR systems ➩ DX IN 3 min
3. Jeff Shuren ➩ another example of INNOVATION w_DX tests
4. 2400 w_ & wo_SYMP C19 ➩ S 91.2% ⏤ E 99.3% ⏤ NPV 99.6% ➩ SIMILAR FOR omicron
5. PRINCIPLE ➩ chromatography gas mass-spectrometry
6. It is NOT the sole BASIS FOR TTO ➩ ∑we need: - MOLECULAR TESTING ( IF positive) - PRETEST PROBAB (if negative) = recent expos, history and sign&symp
7. We expect 64k for this month
Tuesday 19/04/2022 11:15:00 pm (BE Time)
LFMC, SGQA, AAQC
2022 ICUmmp - Sepsis in critical care effective antimicrobial strategies in ICU (Nair) [r].pdf
1. 5th generation Cephal – cephal/beta-lac + bLac(-) ➩ NEW ATB
2. cephal/Blact(-) ➩ cetazid-avibac, ceftoloane-tazo, imi-relebactam, mero-vaborbactam, cefiderocol
3. R-P. aeruginosa ➩ effective: cefto-tazo, cefta-avi, imi-relebac
4. Carbap-R Enterobac (CRE) ➩ effective: cefta-avi, imi-rele, mero-vabor
5. Metalo-B-lact ➩ cefta-avi, cefiderocol
6. BLEE, K. pneumoniae carbapenemases, CRE ➩ MERO-VABOR
7. MRSA ➩ vanco, line, telavancin, teicoplanin, streptogramins
8. CEFTOBIPROLE ➩ 5th generation ➩ MSSA, P. aerug, Enterobac ⏤ LIMITED EFFICACY: MRSA, ESBL (not used in USA)
9. ATS/IDSA 2019 ➩ ‘sPNEU r_ICU’ + NO rf_MRSA or _P. aerug = b-lact+macrolide OR b-lact+fluoroqui respir
9.1 Prior studies ➩ macrolide was a good option (antiinflamat) BUT
9.2 Recent sr ➩ NO DIFF OC (b-lac+macrol VS b-lac+fluoroqu) (Vardakas, 2017)
10. NOT monotherapy IF ➩ dosing + safety is NOT stablished
11. ATS/IDA 2019 ➩ ‘empiric MRSA’ AND/OR ‘Pseudomona coverage’ = CAP w_rf for these pathogens ➩ FOLLOWED BY DE-ESCALATION if CULTURES wo_these organisms.
2022 JAMA - Vaccine Booster Dose Appears to reduce Omicron H+ (Abbasi) [new].pdf
1. C19 sev (WHO def) ➩ lower for VAX vs UNVAX2. VAX (2 or 3 does) : (BMJ) - 76% effective ‘prog_iMV OR MM’ (∞) - 45% effective ‘=’ (∆ OR Ω)
Wednesday 20/04/2022 11:15:00 pm (BE Time)
LFMC, MKFA, AAQC
2022 ICUmmp - Sepsis in critical care effective antimicrobial strategies in ICU (Nair) [r].pdf
1. P. aeruginosa ➩ anti-pseu b-lact (cefe, imi, mero, pip-tazo) + cipro O levo ➩ ANOTHER combination: ‘anti-pseudo b-lact’ + aminogly + ‘quinol (anti-pneumoc) OR macrolide’
2. MRSA ➩ vanco OR linezolid
3. 2016 ATS/IDSA VAP GL➩ empiric coverage BASED ON a. MDR rf b. local atbgram ➩ cover MSSA and G(-) [pip-tazo, cefe. imi, mero, cetol/tazo]
4. MDR rf for VAP = IV atbs 90 + SS• at VAP dx + ARDS pre-VAP + H+ 5d (past 90d) + RRT pre-VAP
5. IF “VAP + 1rf R (MRD) + ‘local preval G(-) resistan to a SINGLE ANTI-PSEUMONAL is unknown’ OR ‘ >10% G(-) isolates’ ” = 2 anti-pseudom from DIFF CLASSES
6. IF “VAP + 1rf R (MDR) = EMPIRIC TTO ➩ aminogly OR anti-pseudom quinol (high-dose cipro OR levo) + anti-pseud b-lact (cefe, cefta, cefto/tazo, imi, mero, cefta/avi, imi/rele, pip/tazo) Ej. pip/tazo + amika Ej. levo + cefta Ej. pip/taz + levo
7. MDR G(-) ➩ new combina = cefta-avi AND cefto-tazo
Thursday 21/04/2022 11:30:00 pm (BE Time)
LFMC, AAQC
2022 ICUmmp - Sepsis in critical care effective antimicrobial strategies in ICU (Nair) [r].pdf
1. G (-) (BLEE + K. Ppneumo carbap + Enterobac carpe-R) ➩ mero-vabor
2. SS in VAP ➩ imi-relebactam
3. MRSA COVERAGE ➩ should include: ‘rf for R’ + ‘local PREVAL MRSA unknown’ OR ’10-20% S. aureus isolates’ ➩ LINE or VANCO
4. De-escalation + ↓ No ATB + STOP therapy if NOT INF + ↓ duration = RECOMMENDED ➩ ↗️ MM, ↓ secINF, ↓ R
5. VAP tto duration = 8 days
6. Non-responsive pxs ➩ inhabled colistin OR aminoglyc + IV ATB
7. HAP GL = VAP ➩ except MRD rf are: prior ATB use 90d + ↑rMM
8. intraABD inf + S• and SS• = polymicrobial (aerobin and anaerobic) ➩ EMPIRICAL TTO ➩ G(-) + ANaerobic (b-lac/b-lac inhib OR carbapenem) ➩ COMMON is Enterococcus ➩ IF B-lactams R = glycop, oxazolidinones or carbap.
9. Fungal INF w_candia ➩ EMPIRICAL TTO = azoles OR echinocandins (severely ill).
2022 JAMA - Vaccine Booster Dose Appears to reduce Omicron H+ (Abbasi) [new].pdf
1. 2022, BMJ, USA ➩ RCT / >11k / Mar2021-Jan2022 ➩ P⃣ C19 I⃣ odds of vax C⃣ control O⃣ vax effectiveness ➩ DETERMINED BY whole-genome sequencing OR CLASSIFIED BY predominat variant ➩ 2 DOSIS ⏤ 85% ∞∆ (study); 65% Ω (Dec2021-Jan2022); 86% 3 vax Ω ➩ WHO CPS = vax 2-3 doses = 76% prevPROG -iMV or -MM (∞) = 45% prevPROG -iMV or -MM (∆ Ω)
2. CPS = clinical progression scale ➩
3. 2022, LANCET, USA ➩ obser ⏤ 300M (167M Pfizer, 132M Moderna) ⏤ Dec2020-June2021 ➩ P⃣ vax 2 types I⃣ SURVEILLANCE (new v-safe sys + VAERS) C⃣ no O⃣ AdvReac ➩ >340k = 92% NONSERIOUS, 6.6% SERIOUS wo_death, 1.3% DEATHS ➩ most common SERIOUS = shortness of breath, fever, fatigue and headache4. VAERS = VAccine adverse event reporting sys5. Most common causes of DEATH in this study = ♡dis, C19 (death certif and autopsy = 18% of <4500 deaths) ➩ NO unusual patterns
Friday 22/04/2022 11:15:00 pm (BE Time)
LFMC, ±SGQA, AAQC
2022 JAMA - Bizarre Wide-Complex Tachycardia 60 M w_Severe Chest Pain (Chuang).pdf
1. 60M, sChestPain d_18h, ED (126bpm, 36bpm, 126/77)
2. Wide-complex tachycardia with a bizarre QRS-T (ST deviation)
3. V4-5 = 1:1 AV ➩ TRIANGULAR or LAMBDA shaped QRS-ST ECG = OMINOUS SIGN OF STEMI
4. CorArt = complete oclussion LADA
5. Complicated w_poly ventr tachyarr + CardS• ➩ deceased
2022 ICUmmp - Sepsis in critical care effective antimicrobial strategies in ICU (Nair) [r].pdf
1. RISK FACTORS ➩ identify risk factors for MDR (local microbiol, atbs 90, 5H+ 90, prior COL or INF MRSA or Pseudo), MRSA, fungi.
2. PREVALENCE ➩ Bacterias (G-)m,
3. APPROPRIATE TTO = ↓MM, ↓LOS, ↓cost ➩ CORRECT dose (often higher), augmented renal clearance (ARC), Vol distrin, CO, penetration ➩ Prompt ATB TTO ➩ source control4. STEWARSHIP ➩ PCT, PCR… ➩ in CAP, HAP, VAP = NEVER only single agent5. cIAI = POLYMICROBIAL (G-, anae, enteroc) ➩ TTO b-lac/b-lactASA inhibitor OR carbapenem (Candida targeted)
Saturday 23/04/2022 11:15:00 pm (BE Time)
LFMC, MKFA, ±SGQA, AAQC
2021 UNIVADIS - Idiopathic pulmonary fibrosis. pirfenidone improves OS, PFS in meta-analysis (BMJ).pdf
1. 2021, BMJ, ? ➩ MA ⏤ 9 RCT (1011 pirf, 912 control) ⏤ ? ➩ P⃣ pxs IPF I⃣ pirfenidone C⃣ control O⃣ pOC: OS + PFS ➩ PROLONGS pOC (49% OS ⏤ 15% PFS)
2. IPF = idiopathic pulmonary fibrosis; OS = overall SS; PFS = progression-free SS
3. MA WHERE? PubMed, Medl, Cochr, Emb
4. WHY? 2-43/100k + SS 3-5y aft_DX
5. AdvEve ➩ 4x PIRFE (naus, rash, dysp, vomit, photsen)
6. LIMIT ➩ small numb + subgroup or senst ANALY diff + heteroge + potential selec bias.
2022 NEJM - Nirmatrelvir for hR C-19 Outpxs (Hammond) [vid]
1. 2022, NEJM, ? ➩ ph2-3, dbRCT ⏤ 2246 (1120 VS 1126) ⏤ ➩ P⃣ mild-mod symptoms, unVAX, hR C19 outPxs, confirmed C19 I⃣ Nirma 300 + Rito 100 C⃣ placebo O⃣ pOC (composite): H+ OR all-causeMM 28 (TTO ≤3d aft_sympOnset) ➩ POSITIVE ↓
2. Nilmatrelvir = has shown promise in preliminary studies
3. DOSIS: Nirma+Rito every 12h x 5d ➩ beginning ≤5d af_sympOnset
4. pOC: mod_ITT = 1379 ➩ Nirma (5 H+, 0 MM) ⏤ placebo (44 H+ , 9 MM) ➩ ↓89% RR (Nirma)
5. sOC: H+ OR all-causeMM 28d (TTO ≤5d aft_sympOnset) ➩ ↓ 88% RR (Nirma)6. AdvEve: dysgeusia + diarrhea ➩ dys (5.6%), diarr (3.1%) [nirma] ⏤ dys (0.3%), diare (1.6%) [placebo]
Monday 25/04/2022 11:15:00 pm (BE Time)
LFMC, MKFA, ±SGQA, AAQC
2022 JAMA - Association of Subcutaneous or IV Casirivimab + Imdevimab w_Clinical OC in COVID-19 (McCreary) [R].pdf
1. 2Q (1) sc casirivimab + imdemivab is ≈ w_ better 28d clinOC vs nTTO (2) casirivimab + imdemivab SC = IV (Clin + stat).
2. pOC:
- 28d adj_rR ➩ H+ OR MM (question 1)
- 28d adj_rD ➩ + DIFF of H+/MM (question 2)
sOC:
- 28d adj_rR
- DIFF of Hº + MM + ‘EDadm & Hº’ + AdvEve rates
4. ∆var = 100% in pxs
5. Q1 ➩ nTTO = 28d ƒ-up was ON the day aft_(+)C19test ⏤ TTO = 28d ƒ-up ON the day of mAB tto
6. EHR ancillary clinical SYS aggregated in a ‘clinical data warehouse’.
Tuesday 26/04/2022 11:15:00 pm (BE Time)
MKFA, ±SGQA, AAQC
2022 NEJMjw - Observations from ID+Beyond; Should We Prescribe Nirmatrelvirr (Paxlovid) to Low-Risk COVID-19 Pxs (HIV+ID).pdf
1. Paul Sax ➩ views for or against PAXLOVID (Nirma/r) for lowR C19 sevOC
2. ok for hR
2022 NEJMjw - New Insights into Ivermectin+Convalescent Plasma for Outpatients w_ C19 (NEJM).pdf
1. 2022, NEJM, BR ➩ RCT ⏤ >1300 ⏤ Mar-Aug2021 ➩ P⃣ outpxs: C19 SYMP ≤7d + 1rf_PROGsDIS I⃣ IVER 400ug/Kg/d x 3d C⃣ pla O⃣ pOC H+ OR ED obs >6h ➩ iver <15% vs pla 16% = NO DIFF ➩ others: viral clear, H+, LOS H+, SYMP score
2. 2022, NEJM, USA ➩ RCT ⏤ >1200 ⏤ Jun2020-Oct2021 ➩ P⃣ C19 outpxs ≤8d SYMP regardless rfDP I⃣ hTITER ConvPlas C⃣ plac (plasma) O⃣ H+ ➩ I 3% vs C 6% = RR ↓ 54% (53/54 unvax + 1 part vax)
3. rfDP = risk factor for disease progression
4. plac= placebo
5. IVER ➩ nope ⏤ ConvPlas ➩ early + last resource (if unavailable: Nirma/r + remde + mAbs) + immunosupp
Wednesday 27/04/2022 11:15:00 pm (BE Time)
LFMC, JCAS, AAQC
2022 JAMA - Association of Subcutaneous or IV Casirivimab + Imdevimab w_Clinical OC in COVID-19 (McCreary) [R].pdf
1. n = 1959 ➩ mild-mod C19.
2. FIRST analysis ➩ 969pxs SC vs 4353 nTTO (28d ƒ-up) ➩ Matched: 652pxs SC vs 1304 nTTO
3. SECOND analysis ➩ 969 SC vs 1216 IV ➩ SAME SITES: 721 SC vs 441 IV
2022 NEJMjw - Deprescribing Proton-Pump Inhibitors (Gastroenterology).pdf
1. PPI = 🔝 10 prescribed (USA)
2. Long-term indications are LIMITED
3. GL = expert opinion (mainly) ➩ SUPPORTED by literature review
4. ONLY DEFINITE IND ➩ CHRONIC USE (>8w = 2m) = GERD + Barret + eosinophilic e + Zollinger-Ellis + hr NSAIDs + IPF (possibly)
5. PPIs can be TAPRED or STOPPED ABRUPTLY ➩ in EITHER case = REBOUND SYMP ➩ TTO: PPIs on demand, H2 block, antiACIDS
6. AVOID high dosis = BID or DOUBLE-DOSE PPIS (can be stepped down to once-
7. PPIs should be STOPPED ➩ LACK OF INDICATION instead of AdvEve (observational vs RCT)8. No longer than 3y = safe ➩ (RCTs? Many years of chronic use… when AdvEve?)
Thursday 28/04/2022 11:15:00 pm (BE Time)
LFMC, AAQC
2022 NEJMjw - Beta-Blockers+Alzheimer Disease (Brain).pdf
1. 2022, BRAIN, DANISH ➩ retro ⏤ >69k ⏤ ? ➩ P⃣ HTA under BB I⃣ PERMEABILITY high, mod, low BBB C⃣ no O⃣ ƒ-up 9.8y: rAD + rDEM (all-cause) + rMM
2. rAD = ↓ w_HIGH BBB P (vs low) ➩ remained w_SENSIT ANALYSES
3. rDEM (all-cause) = SIMILAR (low, mod, high)
4. rMM = ↑ w_MOD & HIGH (vs low) BBB P aft_ADJUSTMENT for covariates (rfAD)
5. last OC may be explained by UNMEASURED ↑ COMORB BURDEN
GLOSSARY: BBB = brain-blood barrier; P = PERMEABILITY; AD = Alzheimer disease
2022 NEJMjw - Does Home Monitoring w_ Pulse Oximetry Improve C19 OC (NEJM).pdf
1. 2022, NEJM, ? ➩ RCT ⏤ 1217 ⏤ ? ➩ P⃣ C19 I⃣ standard home monit (SHM) + SpO2 C⃣ SHM O⃣ “Hº + MM” ➩ SIMILAR2. ALSO similar = MV or suppl O2 ⏤ > telephone encount (combined group)3. NO rf_sDP TAKEN ➩ this might change results4. 78% reported 1 SpO2 AT LEAST (mean 10reading/px)
Friday 29/04/2022 11:15:00 pm (BE Time)
AAH, LFMC, AAQC
2022 JAMA - Association of Subcutaneous or IV Casirivimab + Imdevimab w_Clinical OC in COVID-19 (McCreary) [R].pdf
1. SocioDemo + clinCharac compared SC vs noTTO use SD DIFF.
2. Control for imbalances 2groups w_ propensity score method = logistic regresion model ➩ measured preTTO variables: a. presumed BIOL relevance, b. 0.10 OR > of SD DIFF, c. other selection criteria.
3. Matched + nonmatched adjusted analyses: linear models w_ mAb receip, specifying binomial distribution + log link.
Saturday 30/04/2022 11:15:00 pm (BE Time)
LFMC, AAQC
2022 JAMA - Air Quality+Brain Health (Slomski) [persp].pdf
1. Lots of modifiable rf for DEM ➩ air pollution is ONE
2. If associated w_COGdecl ➩ inconsistent results
3. ?, PLOS Med, US ➩ ? ⏤ ? ⏤ 10y ➩ P⃣ older women I⃣ cognitive abilities in AIR POLLUTED environ C⃣ ? O⃣ neuroDEG + neurDEVE DISOR
4. WHIMS-ECHO = >2k, 74-92yo ➩ cognitive function + episodic memory, 2008-2018 (10y) annually (telephone) ➩ estimated the contaminants (PM2.5 _ vehicles, gases_plants and steel mills, industrial processe, fuel combustion, forest fires ➩ if ↗️ air quality in 10y = COGstatus + epiMemory = EQUIVALENT TO 1.6y YOUNGER
5. PM2.5 = fine particule matter
Monday 02/05/2022 23h15 (BE Time)
LFMC, AAH, AAQC
2022 ICM - Less pharmacotherapy is more in delirium (Chou) [r].pdf
1. Lack of EB data for Delirium
2. Incidence ➩ Hº + CIpxs = 32% ➩ MV pxs = 80% ➩ elderly = 30-60% Hº + 70% ICU
3. DEF DELIRIUM (5 items) = acute onset + fluctuating MENTAL STATUS + inattention + disorganized thinking + altered CONSCIOSNESS
4. Medication is used in 86% (retrospective study)
5. ICU requires ➩ SED, IMMOB, ISOL, UNCOMFORTABLE int, sleep DEPRIVATION ➩ contribute DELIRIUM
6. INNEFECTIVE? Nonpharmacological = TIME, PX LOAD = ADDITIONAL DEDICATED TEAM MEMBERS
7. NON-PHARMA int = reorientation + cognition + mobility + sensorium + sleep + agency and independence + nutri&hydration
2022 JAMA - COMET-ICE, Sotrovimab on Hº or MM hrPxs w_Mild to Mod C19 (Gupta) [RCT].pdf
1. 5 sOC
2. Viral load was determined ➩ RT-PCR
3. Prespecified explorer OC = Hº LOS + ICU LOS + MV29 + rtPCR29
4. AdvEve = Hº + MM (regardless of C19) ➩ infusion-related reactions + Ab Depend Enhance
5. Ab DEPEND ENHANCEMENT = ↘️ virulence by mAb ➩ independently assessed
6. SamS = <1500 (<700) ➩ POW 90% ➩ EFF 37.5% ➩ 0.05 ➩ AssuPROG ➩ 10% vs 16% (SOTRO vs PLA) ➩ RR29 0.75
7. Intention-to-treat vs per-protocol ANALY
8. InterimANALY ➩ <600 EFF + < 880 SAF ➩ a center + committee ➩ study stopped
Tuesday 03/05/2022 23h15 (BE Time)
LFMC, AAH, AAQC
2022 JAMA - COMET-ICE, Sotrovimab on Hº or MM hrPxs w_Mild to Mod C19 (Gupta) [RCT].pdf
1. IMP to have SC for disadvantaged neighborhoods + LMIC
2. SC easier to administer = ↓ No appointment times
3. LIMITATIONS:
a. UNABLE to determine SYMP sev OR vax status ➩ controls = perhaps asymptomatic ∑ ↓r Hº ➩ tend to bias results against mAb
b. Immortal time bias ➩ OC assessment start point (tto: day of tto ⏤ control: day of pos test) ➩ HOWEVER: sensitivity analysis = likely small
c. Prioritization of tto to vulnerable groups (after Sep 2021) due to shortages ➩ non treated w_more comord ➩ HOWEVER: propensity match = BALANCED matched vs non matched
d. Fully vax = DIFF in SC vs IV ➩ ≠ fully protected (UNKNOWN vax type, 3rd primary series, time from last vax)
e. NOT DURING Ω
f. Mean TIME symptoms onset = 6d (better earlier BUT real-life is DIFF)4. Administering TOO faster in real-world settings is logistically challenging, ✩ 5. ttTTO windows IMP ➩ as novel, oral, antiviral MEDS are available
Thursday 05/05/2022 23h15 (BE Time)
LFMC, AAH, AAQC
2022 JAMA - COMET-ICE, Sotrovimab on Hº or MM hrPxs w_Mild to Mod C19 (Gupta) [RCT].pdf
1. Crossed boundaries = EFFICACY
2. Interim = by center + commite
3. 4 🔝common predefined rf: OBESITY, >55yo, DM w_MED, sASTHMA. ⏤ 🔝common SYMP: cough, headache, myalgia, and fatigue.
4. pOC = a-cH° (lasting > 24h for aILL management) or any-cMM29
5. sOC = a-cED, H° OR MM, sev-critC19, prog sC19 OR cC19 D29.
6. postHOC ➩ "allPROG events for RELATIONSHIP w_C19" ➩ Hº SOTRO pxs: 3 ∆∆_≈_C19 ⏤ 3 Hº_not≈_C19 (1 sINT_OBSTRUCTION, 1 non-small cellLung_CA, 1 DIABfoot ULCER)
Friday 06/05/2022 23h15 (BE Time)
LFMC, AAH, AAQC
2022 JAMA - COMET-ICE, Sotrovimab on Hº or MM hrPxs w_Mild to Mod C19 (Gupta) [RCT] FINAL
1. SOTRO ➩ preven MORE sCOMPL C19 + prevent NEED OF Hº
2. In a previous publication (same study, previous analysis 2021) ➩ 3 clinical sOC were already positive
3. ↗️ virus neutraization ➩ BUT MODESTLY ➩ not a strong predictor = rtPCR from nasopharynx DOES NOT SHOW the viral activity in the LUNG + abscence of replication-competent virus
4. LIMITATIONS ➩ chagengin to determine PX or DIS char assoc w_C19 progres + difficult to find RARE AdvEve + efficacy of SOTRO is unknown for VOC after the study
2022 NEJMjw - Are Monoclonal Antibodies Beneficial for pxs H+ w_C19 (LANCET).pdf
1. 2022, LANCET, UK ➩ RCT ⏤ 9785 (127 H+)⏤ ? ➩ P⃣ C19 Hº I⃣ usual care (UC) + ‘casi+imde 4g each’ C⃣ UC O⃣ pOC = MM28 ➩ efficacy OK = SERONEGATIVE
2. 62yo, 8% prev VAX
3. SUBGROUPS = «UC+combin» (N<4850: 34% seroNEG) VS «UC» (N<4950: 31% seroNEG) ➩ H+dis MORE LIKELY seronegative w_CASI+IMDE (64% VS 58%)
4. AdvEve ➩ yes ONLY 7 (none fatal)
5. In SEROPOSITIVE ➩ even worse?
Saturday 07/05/2022 23h15 (BE Time)
CARE, AAH, ±SGQA, AAQC
2021 NEJM - MOVe-OUT, Molnupiravir for Oral TTO of C19 in nHº pxs (Bernal) [RCT].pdf
1. EX:
a. ANTICIPATED need_Hº f_C19 (next 48h)
b. DIAL (eGFR <30)
c. pregnancy
d. sNEUTRO ↓ (N<500)
e. PLT < 100k
f. VAX
2. PROHIBITED ➩ mAb + REMDES
3. RANDOMIZATION:
a. Ratio 1:1
b. Block of four (stratified ≤3d VS >3d)
c. Blinding ➩ until 7m ƒ-up VISIT
2022 HEALTHEXEC - Long COVID-19 impacts 30% of infected pxs (Baxter) [r].pdf
PASC = post-acute sequelae C19 ⏤ TS = taste and smell ⏤ QUALmc = quality of medical care
1. 2022, JGIM, USA (UCLA, Medicaid) ➩ cohort QUESTIONN ⏤ >1k ⏤ Apr2020 - Feb2021 ➩ P⃣ pxs past INF or Hº I⃣ Q_D60 OR D90 C⃣ NO O⃣ pOC: IMPACT + rf for PASC ➩ 309 developed longC19 = 30%
2. WEAKNESSES
- pxs autodefined (rated) SYMP = SUBJECTIVE
- # of SYMP ➩ LIMITED
- COMOBID info ➩ LIMITED
3. FREQUENT SYMP ➩ Fatigue (31%), soB (15%), LOSS of TS, RARE: fever & rash
4. LESS LIKELY ➩ Medicaid pxs + Organ transplant
5. MORE LIKELY ➩ px Hº history, DM, hBMI
6. UNICENTER STUDY = ↘️ variation in QUALmc
7. NOT ≈ longC19 ➩ ethnicity, older age, socioeco status
8. CONTRADICTORY ➩ “men > women” in UCLA study = develop longC199. CAREFUL with exacerbations + emergORchroCond
Tuesday 10/05/2022 00h15 (BE Time)
LFMC, AAH, ±SGQA, AAQC
2022 NEJMjw - Second Booster for C19 vax. Early Results (NEJM).pdf
1. 2 observational in ISRAEL ➩ together makes 1M PEOPLE ➩ Jan-Mar2022
2. ↘️ infection roughly 50% with 4th dose by 4w (compared to 3rd dose recipient)
3. Effect had disappeared by 8w ➩ peak at 6w
4. Editorial point out ➩ tradeoffs + detriments (too-frequent boosting)
2021 NEJM - MOVe-OUT, Molnupiravir for Oral TTO of C19 in nHº pxs (Bernal) [RCT].pdf
DILI = drug-induced liver injury
1. Oversight: consent ok, sponsor = DESIGN, safety oversight = sponsor + committee.
2. Assessments: report of S&S ➩ not present, mild, mod, sev (by participants) ➩ D29 ➩ list of 15
3. DX ➩ quantification = Nasopharyngeal swabs ⏤ genotyping = next-gen sequencing ➩ when? D1, 3, 5, 10, 15 and 29
4. AdvEve ➩ when? d_tto + for 14D aft_tto ➩ who? Investigator
5. pOC EFF = “any-c_Hº OR MM29” (mod-ITT) ➩ criteria mod_ITT = at least 1 dose MOLNU o PLA + not Hº before 1st dose
6. pOC SAF = AdvEve incidence (random + 1dose i OR c)
7. POSTBASELINE EVALUATION = PLT <50k + DILI
Wednesday 11/05/2022 00h15 (BE Time)
LFMC, AAH, ±SGQA, ±MKFA, AAQC
2022 NEJMjw - Similar Mortality in pxs Resuscitated with Normal Saline or Balanced Crystalloid (NEJM).pdf
1. 2022, NEJM, AUS+NZ ➩ mc_RCT ⏤ >5k ⏤ ? ➩ P⃣ CIpxs I⃣ normal saline (NS) C⃣ Plasmalyte O⃣ ⚯ function + MM90 ➩ SIMILAR
2. NS ➩ Chlorhide ↑ + pH ↓
3. 2 OBS STUDIES:
a. 2018, NEJM, ? ➩ RCT ⏤ ? ⏤ ? ➩ Balanced VS NS ➩↓ MM + ↓ ⚯ injuries w_BALANCED (although DIFF were smal) ➩ “PROMPTED to change practice”
b. 2021, JAMA, BR ➩ mcRCT ➩ did NOT confirm these results
4. TBI ➩ NS is the one :)
2021 NEJM - MOVe-OUT, Molnupiravir for Oral TTO of C19 in nHº pxs (Bernal) [RCT].pdf
CPS = Clinical Progression Scale
1. sOC EFF = WHO CPS + px’s report (D29)
2. improvement = reduction ➩ progression = worsenig
3. RESOLUTION = #D rand-1st (3D consec resolution or allev) ➩ PROGRESSION = #D rand-1st (2D consec worsening)
4. INTERIM <800 (54%) vs TOTAL >1400 (100%)
5. EXCEPT sex (women ↑ in MOLNU), ALL WERE SIMILAR
6. RISK FACTORS ➩ obesity (74%), >60yo (17%), DM (16%)
7. Recent or previous INF (not vax) = 20% of all
8. ✖ sequence data available ➩ 26% pxs (interim) + 45% pxs (all)9. ✔ BASELINE sequence data available ➩ most common = ∆, µ, ∂
Thursday 12/05/2022 00h15 (BE Time)
LFMC, AAH, AAQC
Update previous JRs
Insights, wrap-up deets, structure proposals
2021 NEJM - MOVe-OUT, Molnupiravir for Oral TTO of C19 in nHº pxs (Bernal) [RCT].pdf
1. Exceptions ➩ 1 pxs = not confirmed SS29 (mITT) = (+)pOC ⏤ 2 pxs = not confirmed SS29 = (-)pOC (alive D29)
2. EFFICACY (mITT) ➩ interim (i) vs all (a) ➩ (i) = pOC 7 vs 14% ⏤ (a) = pOC 7 vs 10% (molnu vs pla)
3. SPEC SUPPORTING ANALY ➩ only for C19 ‘Hº OR MM’ = 6 VS 9% (molnu vs pla)
4. POST HOC ➩ sex (female predominant) = in women pOC 2.8%points ↓ MOLNU
5. Time-to-event ANAL ➩ same results
6. RATE pOC 31% ↓ MOLNU
7. MM 1 interv vs 9 control⏤ RISK of MM 89%↓ molnu
8. PREspecified subgroup ➩ ↓ Molnu (CI substantial uncertainty about the magnitude)
9. DIFF RISK ➩ favored PLA:
- VIRUS nucleocapsid ab (baseline);
- low viral load (baseline) - diabetes (baseline); •••• 😳 - Asian only, Black only, Native American only, or mixed Black–Native American–White; and patients en- rolled in the Asia-Pacific region 10. VARIANT OC available only in 56%11. CLINICAL PROG ➩ PEAK = D5 ➩ largestDIFF = D10, D15 ➩ S&S = (+) resolution MORE LIKELY (molnu) = (-) progression LESS LIKELY (molnu)12. Likelihood = probability = cuantitative - numeric - precise ⏤ possibility = general = qualitative - imprecise
Friday 13/05/2022 00h15 (BE Time)
LFMC, AAH, AAQC
2021 NEJM - MOVe-OUT, Molnupiravir for Oral TTO of C19 in nHº pxs (Bernal) [RCT].pdf
1. EXPLORATORY OC = eOC ➩ 77% had RNA ➩ only 88% tested D5 ➩ still ongoing samples ➩ viral load ↓ MOLNU on D3, 5, 10
2. SAFETY = SIMILAR in both groups ➩ 30 vs 33% ➩ related to trial 8 vs 8.4% ➩ NO DEATH related to regimen ➩ 3 deaths in PLA + 1 death in INT = D29
3. AdvEve = C19 pneum + diarrhea + bacte pneum + worsening C19 ➩ AdvEve RELATED TO REGIMEN = diarrhea, nausea, dizziness ➩ PLT <50k = ONE in each group
4. PREVIOUS studies = PLA incid_pOC = 3-7% ⏤ CURRENT = PLA incid_pOC = 14% interim + 10% all-random ➩ current study has ↑ r_DP
2022 UNIVADIS - Drug regulators investigating reports of rebound COVID after PAXLOVID (WHO).pdf
PAX = Paxlovid = nirmatrelvir - ritonavir ⏤ Bloomberg = news agency ⏤ NIAID = National Institute of Allergy and Infectious Diseases
1. Drug regulators reports of REBOUND after TTO w_PAX.
2. WHO <2w ago "strong" recomm f_TTO in mild/mod C19
3. PAX for 5d af_SYMPon ➩ ↓ «Hº or MM» 80% w_hi_’rf_sDP’
4. Bloomberg: US government researchers WORKING ON ➩ howOFTEN + WHY C19 levels rebound w_PAX completion
5. NIAID ➩ data collection is “a priority” + “a pretty urgent thing for us to get a handle on.” 6. Phase 2/3 EPIC-PEP ➩ PAX = FAILED to sig↓_r of household transmission.
Saturday 14/05/2022 23h15 (BE Time)
AAH, AAQC
2021 NEJMe - MOVe-IN, randomized Trial of Molnupiravir or PLA in pxs Hº w_C19 (arribas) [RCT]
1. PCR used ⏤ RNA error rates evaluated ⏤ No of nucleotide changes
2. NHC in plasma + NHC-TP intracellularly —> Cmax + AUC
3. GLUCOCOR = 67% ⏤ NOT REMDES (bef/at) = 76% ⏤ ≥1rf s_C19 = 74%(+freq_rf >60yo 41%, OBES 40%)
4. FREQUENCY ➩ 1.r_ sC19 = more frequent in MOLNU800 ⏤ 2. r_sC19 = ‘MOLNU 800 (78%), 400 (77%)’ VS ‘MOLNU 200 (69%) or PLA (72%)’
MB - IL-6 Inhibitors Improve Overall SS OC in sC19 (EJIM).pdf
1. 2022, EJIM, MEDLINE+SCOPUS ➩ rctMA ⏤ 11 studies (<7500pxs) ⏤ incep-Oct2021 ➩ P⃣ C19 I⃣ IL6(-) C⃣ SOC O⃣ OS = OVERALL SURVIVAL ➩ ↗️ = ↓ rMM by 75% ➩ MM i24% vs c30%
2. sOC ➩ ↘️ INTUB ↗️ Hº disch
3. ANALYSES ➩ Kaplan-Meier + cox proportional hazard regression + sensitivity cumulative 2-stage-MA + meta-regression analysis
4. AdvEve = secondary INF
Monday 16/05/2022 23h15 (BE Time)
LFMC, MKFA, ±AAH, ±SFQA, AAQC
2021 NEJMe - MOVe-IN, randomized Trial of Molnupiravir or PLA in pxs Hº w_C19 (arribas) [RCT]
1. NO MOLNU dose effect AdvEve relation
2. AdvEve ➩ MOLNU 56% VS pla 61% ➩ Difficult to determine in PLA (out of trial setting) ➩ PLT ↓ not reported MOLNU ➩ Abnormal test = >PLA ➩ GLUCOCOR = similar in both groups = ‘more freq use’ appeared in SEVERE AdvEve
3. DEATHS ➩ 16 = 14 molnu vs 2 pla ➩ MOST occurred = comorb, >60yo, sC19 baseline, S&S for >5d [in general 10-12 vs 2]
4. ThomboEmbol events ➩ no DIFF
5. EFFICACY ➩ Xtime recovery = 9D = 29D (82 -85%) ➩ POST-HOC = no signal of TTO EFF: >60yo + wo_REMDE or GLU (bef/at rand) + (-)Ab virus + ≤5d S&Son ➩
6. EXCEPTION ➩ molnu 2/14 MM29 were IMPUTED (SS was unknown)
7. NO DIFFERENCE ➩ all-c_MM29 + clinical scales (WHO, pulm, pulm+)
2022 MEDPAGE - What Paxlovid Rebound Could Mean for pxs (Hutto) [r].pdf
1. Paxlovid rebound ➩ couple of days after the 5-day cycle ➩ RESISTANCE may be occurring ➩ high rate
2. It might need to be extended (duration)
3. Trials are needed + eMed is performing a study (ongoing) in home patients
4. “It is NOT the MAJORITY, not even close to the majority” Michael Mina
5. Pxs can test after TTO ➩ if ASYMP = continue isolating ➩ if SYMP = another course or monoclonals
Tuesday 17/05/2022 23h15 (BE Time)
LFMC, MKFA, AAH, AAQC
2021 NEJMe - MOVe-IN, randomized Trial of Molnupiravir or PLA in pxs Hº w_C19 (arribas) [RCT]
1. Next-generation sequencing ➩ RNA error after TTO >MOLNU 800mg, <PLA.
2. Mean error rates per 10k nucleotides w_allele freq ≥2% = i5.9 vs c2.8
3. No clear difference in RNA viral load reduction FROM BASELINE ↔ MOLNU + PLA
4. NHC: N-hydroxycytidine = Molnu active form ➩ NHC plasmatic = 89.9%
5. At ⬆️dose (800mg) = ⬆️Cmax. Dose dependent
6. Long term toxicity = UNKNOWN > pharmacovigilance needed
7. ↑AdvEve of MM was reported _MOLNU than PLAC (NOT associated w_the medication)
8. Older + comorbidities + sC19 appeared associated w_C19 complications.
9. MM in MOVE-IN = 5% ➩ was ↓ COMPARED TO similars:
- 2 analyses in Hº, nCIpxs = 12 + 26%
- Clinical trial w_similar design = 11 (remdesivir) + 15% (pla)
2022 MEDSCAPE - Exercise, Good Sleep Help Maintain Weight Loss in Obesity (Maccall) [r]
ECO = European Congress on Obesity ⏤ TIC = taken into consideration ⏤ BW = body weight ⏤ PSQI = Pittsburgh sleep quality index questionnaire
1. ECO 2022 ➩ “…variables that impact regain of weight lost” (Signe Torekov, Denmark) ➩ Sleep Q + d_ should be TIC
2. Christopher Kline (Pittsburg, Pennsylvania) ➩ sleep would mantain weight loss ➩ his 2021 study = TIMING OF SLEEP + MORNING WAKE TIME = strongest predictors of weight loss… NOT THE DURATION
3. Ihuoma Eneli (Columbus, Ohio) ➩ d_ + Q = need to be TIC ➩ in OBESITY = diet + physAct + SLEEP = key behavior
4. S-LITE ➩ RCT – 195 - ? ➩ obese ƒ ‘8w, 800cal/d’ ➩ ↓ 12% BW ➩ THEN randomized: †12m PLA injection †3mg LIRAGLUT †4exercise sess/w †LIRAGLU & exercise ➩ PSQI for Q (✂ 5p) + accelerometers for d_ (✂ 6h) ➩ ®
- Low-calorie Q&d_ ➩ ↗️ (PSQI = by 0.8p) + (D_ = by 17min)
Wednesday 18/05/2022 23h15 (BE Time)
LFMC, AAH, AAQC
2021 NEJMe - MOVe-IN, randomized Trial of Molnupiravir or PLA in pxs Hº w_C19 (arribas) [RCT]
1. pOC (of efficacy = sustained recovery) similar in both ➩ even in subgroups w_ REMDE or GLUCO
2. sOC (all-c_MM) similar in both ➩ 2pxs withdrawn = were imputed as having died
3. In vitro = yes mutagenicity ➩ in Vitro = no mutag... mammals inferred from rodents ➩ humans? Pharmacovigilance will say
4. Immunomod ≠ nonimmuno IN TERMS OF SS of Hº pxs ➩ [Immunomod ARE glucocor, toci, bari, Nanak, otilimab ⏤ NONimmuno = molnu] ➩ no conclusive EVIDENCE on IMPROVEMENT
5. Timing of TTO initiation might be IMP ➩ sooner better ➩ for antivirals
6. TIME OF VIRAL REPLICATION ➩ in upper respiratory tract ➩ peak = 7 day ➩ duration 9 to 10 days
7. VIRAL EFFECT vs HOST INFLAMMATORY RESPONSE ➩ inflammatory response predominates since d10
8. CURRENT STUDY ➩ started 10 or fewer days of S&S
9. OTHER STUDIES ➩ clinical + virology EFFIC of CONVALES and MONOCLONALS ➩ works in outPXS at VERY EARLY DISEASE (2-4 DAYS), not in inPXS.
10. +: NOT dose-limiting side effects ➩ -: NO signal of clinical benefit ➩ perhaps DELATY IN INITiation WAS THE reason???
Thursday 19/05/2022 23h15 (BE Time)
(postponed to 1h later ➩ Fri 00h15 BE)
LFMC, AAH, AAQC
15-min REFRESH:
Yesterday, last Thursday
1. 2021 NEJMe - MOVe-IN, randomized Trial of Molnupiravir or PLA in pxs Hº w_C19 (arribas) [RCT]
2. 2021 NEJM - MOVe-OUT, Molnupiravir for Oral TTO of C19 in nHº pxs (Bernal) [RCT].pdf
2022 NEJMjw - Is a Fourth Dose of COVID-19 mRNA Vaccine Needed (NEJM).pdf
dº = dose
1. Bar-On et al, 2022 (NEJM Apr5) ⏤ Magen et al, 2022 (NEJM Apr13) ⏤ Offit et al, 2022 (NEJM Apr13)
2. 2 retro IS = px >60yo: ↓’r_INF + sDIS’ → in the SHORT TERM
3. Bar-On ➩ 2022, NEJM, IS ➩ obs ⏤ 1.2M ⏤ ? ➩ P⃣ volunteers I⃣ 4rd dose (623k) C⃣ 3rd dose (629k) + internal control O⃣ pOC = rates of sC19 (>30bpm, <94%, <300):
- «w4-6» 4th dose = 3.5-4.3x ↓ (than 3rd dº) + 2.3-2.8x ↓ (than internal control)
- «w4-8» 4th dº = 2-1.1x ↓ (than 3rd dº) + 1.8-1x ↓ (than internal control)
4. Magen ➩ 2022, NEJM, IS ➩ obs ⏤ 182k ⏤ ? ➩ P⃣ >60yo I⃣ 4th dº C⃣ 3rd dº O⃣ pOC = relative EFFECTIVENESS:
- 45% against C19 virus
- 55% against sympC19
- 68% against C19-related Hº
- 62% against sC19
- 74% against C19 death
5. Transient but POSSIBLY larger effect on sDIS ➩ none were RANDOMIZED ➩ DIFF ↔ groups HARD TO GET = masking, indoor gatherings, meds like mAb, antiVIR = none COMPARED THESE MEASURES
6. RE- dosing = NEITHER sustainable NOR immunologically wise (editorialist)
2022 NEJMcr - A 56-Year-Old Man with Myalgias, Fever+Bradycardia (Paras) [cr].pdf
PCP = Primary care physician ⏤ NAVODI = nausea, vomiting, diarrhea
1. 56yo M, 1m (myalgias + fever) ➩ 4w ago = myalgias + arthralgias (worse in shoulders, prox. arms and upper back) ➩ T 38.2, chills + diaphoresis
2. Naproxen ➩ ‘URG care’ next D = 37.2, 72, 175/95, 100% aa ➩ normal PhyExam
3. C19 (-) ➩ SYMP abated af_3d ➩ 38.3 + fatigue ➩ stopped -OL
4. 3w later ➩ mDYSP w_ “coughing fits” ➩ 2nd ‘URG care’ = 37.2, 59, 138/75, 98% aa ➩ Fatigued, rest PhyExam OK ➩ C19 (-) again, urianalysis + Xray OK
5. NEXT D ➩ PCP = 1m of “stabbing” back pain ↔ shoulders ➩ not relieved w_naproxen OR heat ➩ 36.7, 48, 122/72, 100%aa ➩ tenderness on left thoracic paraspinal area, rest OK ➩ Xray T spine OK
6. ED ➩ systems rev = 40-50bpm, baseline 80-90bpm + ←H dysuria (chronic prostatitis) + pain ← wrist&knee (gout) ➩ NO weight loss, sweats, pulpit, dyspnea, dizziness, lighthea, chest discom, joint swell, rash, headache, focalization, NAVODI, rectal bleeding.
7. Med ←H ➩ …
Friday 20/05/2022 23h15 (BE Time)
LFMC, AAH, AAOR, AAQC
15-min REFRESH: yesterday, last Friday
2022 NEJMjw - Is a Fourth Dose of COVID-19 mRNA Vaccine Needed (NEJM).pdf
2022 NEJMcr - A 56-Year-Old Man with Myalgias, Fever+Bradycardia (Paras) [cr].pdf
2021 NEJM - MOVe-OUT, Molnupiravir for Oral TTO of C19 in nHº pxs (Bernal) [RCT].pdf
2022 UNIVADIS - Drug regulators investigating reports of rebound COVID after PAXLOVID (WHO).pdf
2022 NEJMcr - A 56-Year-Old Man with Myalgias, Fever+Bradycardia (Paras) [cr].pdf
LTPA = left thoracic paraesternal area – LIA = left infraescapular area
1. H+ = sickle cell trait, HTA mLVH, palp, unprovPE, OSA, ↑ uricemia, latent TBC, malaria, chronic HepB, H. Py, colonic schistose, prostat, ↓ PLT
2. DENTAL PROCEDURE = 2y before
3. MED = așa, metoprolol, losart, sildenaf ➩ 2vax C19 (last 7m ←) ➩ no AdvRea
4. ORIGIN ➩ Central Africa + USA 20y, NOT returned to Africa (>5y), working in UNIVERSITY ➩ lived w_flia BOSTON ➩ VISITS wooded areas ➩ ANIMALS, contact tick, not bitten, scratched by cats ➩ -OL stopped 1 month ago
5. FLIA ➩ Atherosclerotic coronary DIS (rf_CVD)
6. EXAM ➩ ↓ HR, ↑ SpO2, obesity I, tenderness LIA, nontender hemorrhoid
7. LAB DATA ➩ ↓ Hb, ↓LEU (6m ←), NEUTRO ↓ , crea ↑ , D-dimer ↑ , ESR ↑ , C-RP ↑ , hsTROP T ↑ . Hemocult (-)
8. ECG ➩ 1st-D + 2nd-D AV block (2:1) w_rBBB ⏤ alternating w_sinusR 3rd-D AV block ⏤ JUNCTIONAL ESCAPE rhythm w_IV conduction delay
9. CT ➩ wo_PE ; CEFTRIA, NAPROX, ACETAM, OXYCO = administered
10. TTE ➩ normal BIventr SYST function ➩ mild DIAST mitral + tricuspid regurgitation = AV block ➩ no vegetations
11. INT-∂ Mycobacterium TBC (+) ➩ cardio CT = epicardial fat + thickened interatrial septum ABUTTING non coronary sinus of AORTIC valve (↑ radiodensity on delayed imaging) = INFLAMMATORY CHANGES = MAY INDICATE evolving ABSCESS.
12. AV block = pathologic DELAY or INTERRUPTION of electrical impulses: sinus TO ventricles ➩ causes: fibrosis + isch ♡DIS
13. Subacute fever → IMP for myocarditis + inf. Endocarditis
14. MYOCARDITIS ➩ inflammation of MYOCARDIUM, can involve CONDUCTION SYSTEM (arrhythmias: AV block included) ➩ ≤3m acute ⏤ >3m subacute or chronic ➩ ‘fatigue + chest pain’ TO HF, arrhyt or sudden death
15. INF ENDOCARDITIS ➩ INF endocardium w_heart valves (often) ➩ ‘fever + fatigue + symptoms INF distant sites + HF + arrhyth’ ➩ usually ABSCESS
16. TTE = modestly sensitive for VEGETATIONS = limited sensitivity for AORTIC ABSCESS
Monday 23/05/2022 23h15 (BE Time)
AAH, AAQC
15-min REFRESH: yesterday, last Monday
2021 NEJMe - MOVe-IN, randomized Trial of Molnupiravir or PLA in pxs Hº w_C19 (arribas) [RCT]
2022 MEDPAGE - What Paxlovid Rebound Could Mean for pxs (Hutto) [r].pdf
2022 NEJMcr - A 56-Year-Old Man with Myalgias, Fever+Bradycardia (Paras) [cr].pdf
2022 NEJM - Protection by a Fourth Dose of BNT162b2 against Omicron in Israel (Bar-On) [R] .pdf
2022 NEJMcr - A 56-Year-Old Man with Myalgias, Fever+Bradycardia (Paras) [cr].pdf
EGP = Eosinophilic granulomatosis with polyangiitis ⏤ GP = granulomatosis with poliangiitis ⏤ PM = polymyositis ⏤ SLD = scleroderma ⏤ ♡ SARC = cardiac sarcoidosis
1. EVOLUTION
D5: Hepatits B (+) ➩ ’surface Ag and DNA’ for HepB (-) ➩ C-RP 189.5 ➩ 8-beat run non sustained VT ➩ MRI = edema (hyper intensity of central fibrous T1)
D6: accelerated junctional rhythm, VR70-80. ‘Perfil ENA + C19’ (-)
D7: IgM Toxo, Borrelia, brucella, mycoplasma, microfilaria… (-). anti-DNA abs (1:20). C-RP 51.6 ➩ PET intense FDG in interatrial septum + anterior mediastinal lymph node
2. DIFF DX ➩ general appraisal = SYMP + ♡ conduction abnormality + myocardial injury = more likely MYOCARDITIS ➩ TOXIN? Aside -OL no epidemilogic clues + a toxin does not cause SUBACUTE FEVER + no allergies (we rule out allergic reactions to meds) = ∑narrow dx to IMMUNE-MEDIATED or INF process
3. IMMUNE-MEDIATED ➩ NO intestinal illness or asthma + normal examination (muccocutenous, skin, musculskele, eye, lungs) ➩ NO eosinofilia + normal thyropronin and calcium. ➩ NO serology for vasculitis or arthritis + normal renal, urinalysis, chest Xray ➩ ∑ ALL THESE DATA MAKE UNLIKELY (IBD, THYROT, EGP, GP, PM, SLD, SLE, ♡ SARC) ➩ Chagas = NO, cause no trips to Central or South America ➩ AGE = not consistent w_Kawasaki ➩ NO vax related myocarditis because of 7m interval (too long) ➩ GIANT-CELL MYOCARDITIS? Possible BUT usually involves: ‘clinically significant VT’ + ‘HF’
2022 NEJM - Protection by a Fourth Dose of BNT162b2 against Omicron in Israel (Bar-On) [R] .pdf1. CASES vs sC19 ➩ cases = week 3-4 = adj rate ratio: 2.1-2 (compared w_3rd dose) ⏤ 1.9-1.8 (compared w_internal) = adj rate DIFF: 175-170 vs 142-137 (3rd dose and internal, respectively) ➩ sC19 = week 6 = adj rate ratio: 4.3 & 2.8 (3rd dose & internal, respectively) = adj. rate DIFF: 4.2 & 2.4 (3rd dose & internal, respectively)2. RESULTS ➩ Distributions of covariates’ are SIMILAR to INTERNAL CONTROL ➩ 80yo people = more in 3rd dose ➩ Jewish = more in 4th dose ➩ 111K vs 42k in CONFIRMED (3rd vs 4th doses) ⏤ >1200 vs >350 in sC19 (3rd vs 4th doses)
Tuesday 24/05/2022 23h15 (BE Time)
LFMC, MKFA, AAQC
Improving notes APPRAISAL:
- 3 bottom lines from very wrap-up
- Header and footer from the wrap-up points
- Recall ⓘ-brief in blue/yellow
15-min REFRESH: yesterday, last Tuesday
2021 NEJMe - MOVe-IN, randomized Trial of Molnupiravir or PLA in pxs Hº w_C19 (arribas) [RCT]
2022 MEDSCAPE - Exercise, Good Sleep Help Maintain Weight Loss in Obesity (Maccall) [r]
2022 NEJMcr - A 56-Year-Old Man with Myalgias, Fever+Bradycardia (Paras) [cr].pdf
2022 NEJM - Protection by a Fourth Dose of BNT162b2 against Omicron in Israel (Bar-On) [R] .pdf
2022 NEJM - Protection by a Fourth Dose of BNT162b2 against Omicron in Israel (Bar-On) [R] .pdf
inter = internal control group ⏤ …
Protection Conferred by the Fourth Dose
1. UNADJUSTED RATE ➩ confirmed: <200, >350, <400 (/100k, 4th-3rd-inter) ➩ sC19: 1.5, <4, >4 (/100k, 4th-3rd-inter)
2. 4th week (CONFIRMED):
* ADJ RATE ➩ 2 (4th vs 3rd), <2 (4th vs inter)
* ADJ RATE (aft_rounding) ➩>150 vs <350 vs >300 (/100k) (4th, 3rd, inter)
* ADJ RATE DIFF ➩ ↓ >150 (4th vs 3rd), ↓ <150 (4th vs inter)
3. 5th week (CONFIRMED) ➩ RATE RATIO started to ↓
4. 8th week
* ADJ RATE RATIO: SIMILAR ‘4th vs controlS’
* RATE RATIO: 3rd vs 4th = 1.1 ⏤ inter vs 4th = 1The rate ratios comparing the control groups
Thursday 26/05/2022 23h15 (BE Time)
LFMC, AAH, AAQC
2022 NEJMcr - A 56-Year-Old Man with Myalgias, Fever+Bradycardia (Paras) [cr].pdf
1. INF. MYOCARDITIS ➩ VIRAL is the most common ➩ think on epidemiological clues ➩ in px = PROSTATITIS = suggests G(-): C. trachomatis or M. tuberculosis (not tto for latent + (+)test ) ➩ -OL = ↑r bartonella, aeromonas, Listeria m, pneumonocoo ➩ WHIPPLE’s DIS: age + sex + Hist arthalgias ➩ CATS: toxocar, B. henselae, T. gondii. ➩ OUTDOOR (swimming, fishing, hiking): L. monocyt, Borrelia burg…, Rickettsia, blastomyces, lestospira, aeromonas ➩ CENTRAL AFRICA: brucela, schistosome, C. burnetii, Wuchereria bancrofti, or Taenia solium. ➩ ∑ M. Tuberculosis, L. Monocytogenes, pneumoncoco = possible causes
2. TTO ➩ responds to doxycycline NOT to ceftriaxona = L. Monocytogenes = LISTERIOSIS
3. Endomyocardial biopsy MAY CONFIRM, but MICROBIAL CELL-FREE DNA was done ( plasma is used, ≠fetal abnor & cancer dx) = 42 cell-free DNA molecules/ µL (ref. <10) = 95%SEN, 98-99% SPE
4. MGM ➩ ampi + genta = REGIMEN of choice ➩ BUT:
- NOT RESISTANCE over time (in vitro)
- Predilection in: immunocompromised + pregnant
- RCTs? NO
- Retrospective: correlate tto w_OC
- Small studies: GENTA = NOT LARGE benefit + toxic effects
- MONALISA: 870pxs, 2009-2013, ampi or penicillin, trim-sulfa, genta ➩ independently CORRELATE WITH ‘BETTER SURVIVAL’. ➩ amoxi+genta (i) VS amoxi for 3d (c) = ↗️ SS ➩ DEXA = not advantageous in CNS
- Ampi VS penicilline ➩ AMPI is preferred
- ALTENATIVES: Bactrim, bactrim+genta, vanco, mero (failure reported with the last 2)
- DOXYCYCLINE = NOT PREFERRED but PARTIALLY treats listeriosis ➩ DURATION ➩ healthy (uncomplicated bacteremia) = 2w ➩ immunocomp = 3-4w ➩ visceral INF, SEEDING of deep sites, endocarditis = 6-8w
- GENTA ➩ 1-2w (careful monitoring of RENAL FUNCTION)
2022 NEJM - Heterologous C19 Booster Vaccinations (Atmar) [Quick Take]
1. 2022, NEJM, USA ➩ ph1-2_mc_ol_nRCT ⏤ >450 (150 each group) ⏤ ? ➩ P⃣ adults, VAX (12w earlier) wo_INF I⃣ HOMOL vs HETERO (Pfizer, Moderna, J&J) C⃣ NO O⃣ ‘SAF + IMMUNO (reactor + humoral) 15 & 29’ booster
2. REACTIONS ➩ injection site pain = 85, 81, >70% (Pfi, Mod, J&J) ⏤ MALAISE = 71, 73, 71 (=) MYALGIA 61% Moderna ⏤ HEADACHE 53% Moderna ➩ ∑ NO SAFETY CONCENS 28D
3. D15 ➩ binding Abs ↑ w_booster (3 types_vax) TO ‘WILD VIRUS + PSEUDOVIRUS’
4. HETEROLOGOUS and HOMOLOGOUS were SIMILAR IN INCRESE OF neutralizing abs ➩ J&J WITH less INCREASE
5. T CELL RESPONSES ➩ increase in all EXCEPT ‘homologous in J&J’ (although good response to PRIMARY DOSE)
6. HOMOL + HETEROL are similar in SAFE + IMMUNOGENIC
Friday 27/05/2022 23h15 (BE Time)
AAH, AAQC
2022 NEJMcr - A 56-Year-Old Man with Myalgias, Fever+Bradycardia (Paras) [cr].pdf
Dr. Leslie T. Cooper: Myocarditis due to L. monocy…
1. L. Monocytogenes (1979) ➩ rare condition = <10 cases of listeria
2. PRODOME: fever, tachypnea ‘←weeks’ ♡ involvement (AMI, AV block, VT, ‘intracav+ intramyo’ masses, HF)
3. If SYSTEMIC INF = can mimic a sepsis-mediated myocardial depression (impairedLVF + ↑ TROP)
4. IMAGES = CR, MRI, PET = focal inflammation (w_fever + systINFLAMM)
5. NONSPECIFIC = ↑ VSR, C-RP, WCB (immature forms) ➩ in HEART VALVES common to isolate listeria.
6. CONFIRMATION = blood or tissue CULTURE (less common: histologic examination G(+) rods)
7. COMPLICATIONS = aneurysms may form in regions of abscess (myocardial) ➩ associated r_TromboEMB
8. ↓ inflammatory MARKER levels (6w), AV blocks continued (intermittent w_compete AV block), dual-chamber pacemaker (at 4w: palpitation + atrial tachycardia = tto w_metoprolol).
FINAL DX: Regional myocarditis due to infection with Listeria monocytogenes.
2022 LANCET - When+which pxs should receive remdesivir (Garcia) [comm].pdf
1. Multiple RCTs evaluated efficacy of anti-viral, -inflammat, -thrombotic
2. DIFF and OVERLAPPING pathophys PHENOTYPES = viral pneum, hyperinflamm response, thrombEve, orgaPneum, HF, co-INF (bacterial or fungal) ➩ most appropriate TTO can vary among pxs
3. SOLIDARITY final: 2022, LANCET, 35c ➩ RCT ⏤ >14k ⏤ ? ➩ P⃣ C19 I⃣ lopi, HCQ, IFN ß1a, remde C⃣ own control group O⃣ Remde: ↓MM nonVenti + prog ‘’MV or MM’ [m- itT population]
4. REMDE: Not ↗️ in MV pxs ➩ REASON: hyperinflammation, thrombosis, co-INF are causes of ‘ICU + needMV’
5. AUTHORS DO NOT RULE OUT: if high viral load = might benefit WHEN early ICU admission
6. LIMITATION: no data since SYMP onset to REMDE use, viral load, viral antigen (might prove ‘suitably integral’)
7. PINETREE + ACTT-1 = show the same ➩ COMMON DENOMINATOR = high viral component (initial stage) ➩ IMMUNOCOMPROMISED might have ↑ viral loads for MONTHS (consider this)
8. NEGATIVE STUDIES = due to ≠ clinical phenotypes ➩ China RCT = 11days (SYMPonset to remde) + 19% undetectable viral RNA
9. TURNING POINTS in EPIDEMIO = variants (not reflected in Solidarity) ➩ ∆ = quick H+ for younger ➩ ∆Ω, not VAX = not considered for Solidarity
10. STRENGHT = large number of pxs ➩ LIMITATION = absence of concordance w_reality (variants + vax) ➩ ∑ when + which pxs debate will CONTINUE
Saturday 28/05/2022 23h15 (BE Time)
JMCM, JCAS, AAQC
2022 LANCET - Explaining the unexplained hepatitis in children (WHO, CDC, JIMHICR, UKHSA, MMWR).pdf
UK Health Security Agency = UKHSA
1. >300, ±20c, majority UK (163 as of May3) ⏤ NOT DUE TO hepatitis A-E ⏤ 20children = required transplants + severe have died
2. It is looking for CAUSES ➩ Adenoviruses 70% (WHO on May10)
3. HYPOTHESES ➩ a. New adenovirus (causing severe liver DIS) b. Lack of exposure to pathogens d_C19 pandemic = ↑ SUSCEPTIBILITY to adenovirus INF c. Massive wave of adenovirus due to RELAXATION OF RESTRICTIONS (pandemic) d. Expositions (coINF, toxin, drug, environmental)
4. Subtype 41 = UKHSA + Alabama (Oct2021 - Feb2022) ➩ causes MILD-MOD GI SYMP ➩ excludes = ‘liver & plasma negatie’ + ‘low concentrations’ = PRECLUDING PERFOMANCE OF WHOLE-GENOME sequencing
5. PERHAPS NOT REPORTED YET ➩ still being recorded (Scotland) + pending clasif (England)
6. C19 related? ➩ FEW (+) + NONE (Alabama) (UMBRELLA MSID???)
7. FOCUS on EARLY IDENTIFICATION (while: ID causes, children unwellness, transplantation?)
2022 NEJMjw - Remdesivir for pxs Hospitalized w_ C19 (THE LANCET).pdf
1. SOLIDARITY: 2022, LANCET, 35c ➩ RCT ⏤ >8k ⏤ Mar2020-Jan2021 ➩ P⃣ C19 Hº I⃣ REMDE C⃣ PLA O⃣ pOC: MM±progVENTI ➩ ↗️ wo_MV
2. A preliminary version was published on 2021
3. Px wo VENTIL ➩ MM = REMDES 12% vs 14% (p=0.02)4. Pxs w_VENTIL ➩ MM = REMDES 42% vs 39%
Monday 30/05/2022 23h15 (BE Time)
LFMC, JCAS, AAH, AAQC
15-min REFRESH: yesterday, last Monday
2022 NEJMcr - A 56-Year-Old Man with Myalgias, Fever+Bradycardia (Paras) [cr].pdf
2022 NEJM - Protection by a Fourth Dose of BNT162b2 against Omicron in Israel (Bar-On) [R] .pdf
2022 NEJM - Fourth Dose of BNT162b2 mRNA Covid-19 vaccine in a Nationwide Setting (Magen) [R].pdf
priA+ = primary analysis
RESULTS
1. >258k (total eligible) DIVIDED into matched YES vs NO ➩ yes matched = >210k were assigned into 4TH DOSE and CONTROL ➩ Control received pxs from TOTAL eligible + not vax before Feb18 (see Fig 1)
2. DIFF WERE NOTED on: age, sex, popul sector and H+admiss = prev_3y = in matched vs unmatched
3. DIFFICULTIES in FINDING MATCHES on: >80yo + numerous H+admiss
4.
5. Relative VAX effectiveness (relatEFF) of 4th dose (%)
6. PCR for C19 = TRANSIENTLY <frequent in 4th dose vs control ➩ not seen d_ƒ-up period
7. Cumulative incidence for 5pOC (Fig 2) ➩ curves DIVERGE at D7 aft_4th dose ➩ D5-6 small DIFFs ➩ aft_D7 relatEFFEC: ↑until a stable estimate of 50% by D14
8. SENSITIVITY ANALYSES: delayed by 7D ⏤ parametric model used
- relatEFF PCR-confirmed INF = SIMILAR TO priA+ (sizeEstim + trajectories)
- relaEFF C19 MM = not possible to compare DUE TO broad CI
- dailyVAX PCR-confiemd = SIMILAR TO priA+
DISCUSSION
Thursday 02/06/2022 23h15 (BE Time)
LFMC, AAQC
15-min REFRESH: yesterday, last Thursday
2022 NEJMcr - A 56-Year-Old Man with Myalgias, Fever+Bradycardia (Paras) [cr].pdf
2022 NEJM - Heterologous C19 Booster Vaccinations (Atmar) [Quick Take]
2022 NEJMr - Fluids in the ICU_ Are Balanced Electrolyte Solutions Better than Normal Saline.pdf
eAbsDIFF = estimated absolute difference ⏤ BMES = balanced multi electrolyte solution
1. 77to, M, T 38.5, HR 130, BP 80/50, LEU 16k, URIANALY >50wbc/f, >3 leuko esterasa
2. Balanced vs Saline? ➩ WORSE PX OC = Albumin + HES ➩ NS: concerns ↑r ‘AKI + MM’
3. 2022, NEJM, AUS+NZ ➩ db, mcRCT ⏤ >5k ⏤ Sep2017-Dec2020 ➩ P⃣ ICU pxs I⃣ BALANCED C⃣ NS O⃣ pOC: MM90 ⏤ sOC: newRRT, maxCREA ➩ = ‘’THE SAME’
4. CONTEXT INTERPRETATION: consider LIMITATIONS + EVIDENCE ➩
- Failure to meet the initial target px recruitment (eAbsDIFF)
- mixed type of solutions (I w_500mL NS, C w_500ml BMES)
- Cross-over BETWEEN GROUPS aft_randomization = >NS in BMES group (more compatibility of meds w_NS)
5. srMA: 2022 NEJMe = BMES ↓ MM (high probability)
6. DO NOT RUPPORT SUPERIORITY of BMES over NS… but NOT enough to OVERTURN pre-existing evidente (POTENTIAL BENEFIT of BMES)
Similar Mortality in Patients Resuscitated with Normal Saline or Balanced Crystalloid
1. SMART = 2018 NEJM, Nashville, Vanderbilt = ↓ MM ↓⚯ injuries (favors BMES) = NOT CONFIRMED by BR study (JAMA 2021)
2. ‘↑Cl + ↓pH’ in NS (not relevant) ➩ rest EQUAL ➩ SEPSIS subgroup = SIMILAR RESULTS
2022 NEJM - Fourth Dose of BNT162b2 mRNA Covid-19 vaccine in a Nationwide Setting (Magen) [R].pdf
1. LIMITATIONS: short ƒ-up + confounding factors (OBS study) “small DIFF” aft_HEALTHY VAX BIAS + tradeoff ‘minimization of bias VS generalizability of results’ + misclassification (PCR test DIFF) “↑ sevOC = ↓ missclassification”
2. CONCERNS: variantes + EMA ‘too frequently = weaker immune response?’ + apparently EFFECTIVE agains Ω (real-world study) + better “less frequently? Or combination?” 3. 4th dose VAX (Pfizer) ↗️ PROTECTION: INF, SYMP, Hº, sC19, MM ⏤ 4m earlier ⏤ ≥60yo
Saturday 04/06/2022 23h15 (BE Time)
LFMC, AAQC, MKFA
❗️15-min REFRESH: last Saturday
2022 LANCET - Explaining the unexplained hepatitis in children (WHO, CDC, JIMHICR, UKHSA, MMWR).pdf
2022 NEJMjw - Remdesivir for pxs Hospitalized w_ C19 (THE LANCET).pdf
2022 CMI - From hydroxychloroquine to ivermectin how unproven “cures” can go viral (FT) [comm].pdf
1. BIAS OF IVER studies ➩ heterogeneity + imbalanced allocation + selected doses + uncontrolled intervention
2. Poor results with STUDIES in HCQ, combined or alone + IVER ➩ DESPITE scientific evidence, still used
3. Colombian + Argentina studies ➩ RCTs = nonSIG ↓ 2d SYMP REOLU + NO EFFECTS on MM + NO effect on Hº prev ➩ WHO GL says AGAINST.
4. AdvEve IVER = INTERACTIONS w_anticoag + GI symptoms + ↓ AP + ALLERGIES + dizziness + ataxia + seizures
5. New studies: TOGETHER (halted due to futility) ⏤ ongoing: ‘PRINCIPLE + ACTIV-6’
6. FLCCC paper WAS REJECTED ➩ inappropriate REPORT OF MORTALITY
7. CONCERNS: vicious progression of ANTI-SCIENCE
Monday 06.06.22 at 23h15 BE
JJFM, ±AAH, AAQC
❗️REFRESH: yesterday, last Monday
2022 CMI - From hydroxychloroquine to ivermectin how unproven “cures” can go viral (FT) [comm].pdf
2022 NEJM - Fourth Dose of BNT162b2 mRNA Covid-19 vaccine in a Nationwide Setting (Magen) [R].pdf
2022 NEJMcr - A 57-Year-Old Man w_Persistent Cough and Pulmonary Opacities (Knipe) [cr].pdf
PAN = polyartheritis nodosa
1. PX ➩ 57yoM, pCOUGH, 🫁 opacities, fever, weight loss, ➩ (Alba) 3m ← fever + green sputum w_cough = 37.3ºC + 89% aa21%
2. PAN ➩ 7y← = fevers, arthargias, 🫃🏽 pain, testic pain ➩ TTO = cyclophos + prednisone (maintenance) + methotrexate weekly ➩ prednisone escalated (5m ← current admiss) ➩ now = oxycodone ↑ (pain + physician direction)
3. CT (w_contrast) thorax + abd + pelvis = ‘abd+ pelvis’ OK ➩ THORAX = mild centrilobular emphysema + small 🫁 nodules = similar to 6y ago ➩ + thickening of bronchial wall + secretions (right bronchi, trachea) + hiatal hernia
4. Xray = patchy + confluent opacities (right mid and lower 🫁 )
5. NORMAL = mycobacterium TBC + protein electrophoresis (Ig G) + electrolytes + LIP-AMIL + LDH + tropT ♡ + 🫃🏽liver + ⚯
2022 NEJMjw - Is Thunderstorm Asthma a Real Thing (JACI)
THUNDERSTORM ASTHMA = TA; ASTHMA = ASTH
1. Yes, it carries ↑r for exacerbations in susceptible pxs
2. Who triggers it? wind + humidity + lightning ➩ ruptures grass pollen + mold spores —> breaks AEROSOLIZED PARTICLES
3. Why the name? Australia, 228, w_ALLERGIC RHINITIS + self-reported TA.
4. ASSOCIATED w_TA = sensitivity to rye grass pollen + lower 🫁 function, peripheral eosinophilia >300/µL, ↑ fractionalExhal NO, worse Asthma control
5. EXCESS rHº = grass pollen allergy + FEV1 <90%
6. Commenter sees it in USA (late spring & early summer storms)
7. The MORE allergic inflamm, the HIGHER r TA ↔ the BETTER controlled ASTH, the LESS chance of exacerb
8. TTO ➩ NAEPP>GINA ➩ allergic ASTH: be WARY of seasonal spring thunderstorms
Tuesday 07.06.22 at 18h15 BO (postponed to 1h later ➩ Wed 00h15 BE)
CARE, LFMC, AAQC
❗️REFRESH: yesterday + last Tuesday
2022 NEJMcr - A 57-Year-Old Man w_Persistent Cough and Pulmonary Opacities (Knipe) [cr].pdf
2022 NEJMjw - Is Thunderstorm Asthma a Real Thing (JACI)
2022 NEJMcr - A 57-Year-Old Man w_Persistent Cough and Pulmonary Opacities (Knipe) [cr].pdf
1. NEGATIVES = crytococoos + legionella urine test + Pneumocystis jirovecii
2. POSTIVES = SPUTUM (flora normal + Candida albicans)
3. PhyExam (Alba) = crackles + wheezing of right 🫁
4. LAB DATA: LEU = ↑, less ↑, ↑, ↑ (3m, 1m, 8d, now)
5. TTO ➩ Vanco, cefepime, levo,
6. NEXT SEVERAL DAYS = fever + SpO2 normal
7. D5 ➩ discharge + levo x 14d = cough and constitutional symptoms ABATED PARTIALLY ➩ PCP: fluticasona-salmeterol, albuterol PRN
8. 6w after discharge (5w before admission) ➩ nonproductive cough + rhinorrhea ➩ several days later = pxs w_brown sputum + similar symp + cough + dyspnea + 38.4ºC + 89% + xRay (patchy opacities ↑ - ↓ right)
9. 2nd Hº ➩ normal: electrolytes, liver + renal functions ➩ TTO = Vancom, cefepime, azithro + prednisone + inhaled: albuterol & ipratropium ➩ sputum culture = to previous ➩ discharged + levo 7d
10. 8D before current admission ➩ ED = 37.2ºC, 94%, crakles (both bases + right middle), NO wheezes
shown in Table 1. |
2022 UTD - Approach to the patient with abnormal liver biochemical and function tests > COMMON LIVER BIOCHEMICAL AND FUNCTION TESTS (online)
1. LDH = cytoplasmatic enzyme in tissues + 5 isoEnz in serum (can be separated w_electropho)
2. Slowest migrating band is in LIVER
3. NOT AS SENSITIVE as AST, ALT + poor DX specificity (EVEN w_isoEnz) + MImarker (past)
4. USEFUL as marker of hemolysis5. Differentiates ISCH vs VIRAL hepatitis
Wednesday 08.06.22 at 23h15 BE
AAQC
❗️REFRESH: yesterday, last Wednesday
2022 NEJM - Fourth Dose of BNT162b2 mRNA Covid-19 vaccine in a Nationwide Setting (Magen) [R].pdf
2022 MEDPAGE - Did Pulse-Ox Levels Lead to COVID Therapy Delays for People of Color (JAMA).pdf
1. SpO2 overestimated for minority groups (JAMAim)
2. Minority groups = Black and hispanic pxs = delayed eligibility for C19 therapies
3. Compared to white = SpO2 ↑ estimated SpO2 (1.7, 1.2, 1.1% - Asian, Black, non-Black Hispanic)
4. Recognition of eligibility for C19 TTO: Black = HR 0.71 ⏤ nBlack Hisp = HR 0.77 ⏤ Asian = 0.97 ➩ 24% unRECOG C19 eligibility TTO (55% Black, 27% Hispanic)
5. An overestimation of SpO2 ↔ underappreciation of clinical risk (as presented by these calculators)
6. Ocult hypoxemia = SaO2 88% w_ SpO2 92-96% = (%) 3.7, 3.7, 2.8, 1.7 (Asian, Black, nB Hisp, white)
7. Overall = (%) 30.2, 28.5, 29.8, 17.2 (Asian, Black, nB Hisp, white)8. Editorial (same date) = known design flaw = “market pressure” into account = clinicians should “lower the threshold + more ABGs”9. Not generalizable to: healthy + less ill…delays = No frequent measurements
Thursday 09.06.22 at 23h15 BE
±SGQA, AAQC
❗️REFRESH: yesterday + last Thursday
2022 NEJMr - Fluids in the ICU_ Are Balanced Electrolyte Solutions Better than Normal Saline.pdf
2022 NEJM - Fourth Dose of BNT162b2 mRNA Covid-19 vaccine in a Nationwide Setting (Magen) [R].pdf
2022 NEJMcr - A 57-Year-Old Man w_Persistent Cough and Pulmonary Opacities (Knipe) [cr].pdf
Dr. Harvey Barnes: A chest radiograph (Fig. 2A)
RSV = respiratory syncytial virus; GM = galactomannan; rSYS = review of systems; (…) = ongoing; PAN = polyartheritis nodosa
1. Xray = multifocal reticulonodular + patchy opacities (right lower lobe)
2. CT chest wo_contrast = multifocal clustered, centrilobular nodules + opacities (←🫁 mid, low) + lymphadenopathy (not in previous)
3. Again admitted ➩ anti DNA cytoplasmic (-) + C3,C4 (normal) + Legionella (-)
4. 3rd Hº day ➩ biopsy (broncho + transbronch):
- BAL rMIDlobe= cloudy = N 48%, L 2%, E 0% = gram: N + G(+) cocci; stain acid-fast (-) = culture: normal, Candida
- BAL tests NEGATIVE: ⓘ, Aden- , parainfluenza- , respiratory syncytial virus, metapneumo-, P. jirovecii, histoplasma Ag, and blastomyces Ag.
- ITF ∂ for M. TBC ⊖
- D3 home, ƒ-up 3w
5. After DISCH (D4): BAL test GM ⊕
6. Readmitted
- SYMP: dysp- (…) ➕ cough w_ thick white sputum ➕ 39.3°C (persistent)
- rSYST: diffuse chrArthralgias (notable) ➕ bitter taste (mouth)➕intermDysphagia.
- ⊖: chest 😩, edema, orthopnea, nausea, vomiting, jaundice, rash
- NO known current sick contacts.
- 5 kg < 1y⏳
7. HISTORY
- DIS: PAN ➕ DVP ➕ GERD ➕ pancreatitis (choledocholithiasis) ➕ HTA ➕ dysLIPID ➕ DM ➕ osteopenia ➕ chrNeuropathic 😩
- MEDS: ASA ➕pred- ➕ MTX➕ bactrim ➕ folates ➕metformin ➕ atenolol ➕ simvastatin ➕ pregabalin ➕ oxycodone PRN ➕ inhFluti–salme ➕ albuterol PRN ➕ Lisinopril (pancreatic inflammation) ➩ NO OTHER AdvRea
- White European ancestry
- LIFE: New England, w_wife
- WORK: machine shop (solvents, fuels, sulfur USED… BUT no known EXPOSURE)
- EXPOSURE: ⊖ (mold, pets, asbestos)
- VAX: influenza ✔ pneumococcal ✔
- TRIPS: USA ✔ Caribbean ✔
- TOXIC: smoked 1.5 packs/d x30y (quit few w←) ➕ marijuana ➕ -OL rarely
- FAMILY: ⊖ (autoimm-, 🫁 ) ➕ father† colorectal CA ➕ mother† ST• (had esophageal CA) ➕ 3 adult children healthy. The temperature was 36.6°C, the heart rate
Saturday 11.06.22 at 23h15 BE
CCH, AAQC
❗️REFRESH: last one and last Saturday
2022 CMI - From hydroxychloroquine to ivermectin how unproven “cures” can go viral (FT) [comm].pdf
JJFM - 2022 MEDPAGE - Faust Files. Preventing the Next Uvalde (Hutto) [Video]
1. WHAT WORKS
* Prevention violence + suicide METHODS
* Gun control use + policies ➩ would stop (2y evidence)
* Most kids ➩ parents’ gun
* Pediatricians + families talk
* Structural Changes = ↓ isolation + community cohesion + vacant lots (↓ depression, anxiety, stress-related conditions)
* Not only policy
2. Black, hispanic, women ➩ avoid demonizing (2nd ammendment) ➩ appropriate tto, signs of danger
3. Pointless = arm every teacher, take every gun ➩ BALONEY (nonsense)
4. What are the community support that are in place
5. C19 - Politicized ➩ nonjudgmental, space for people to move
6. Word, language, hope
7. HELPful and HOPEful TO THINk AS A society - each provider alone makes a DIFF, all together more, SCHOOL teachers, military
8. INTERCULTURALIDAD = SIMILAR concept in BO
2022 PSYADV - Lidocaine Infusions Beneficial for Refractory Chronic Migraine (RAPM)
1. LIDOCAINE as an option of migraine TTO ➩ REFRACTORY CHRONIC MIGRAINE
2. DOSIS: 1 mg/min ➩ titrated to 4 mg/min MAX ➩ based on: daily plasma levels, PAINresp, and tolerability.
3. In Regional Anesthesia & Pain Medicine
4. 832 admission ➩ 609 admissions ➩ pOC change in headache pain
5. H+ = PAIN RATING 7 to 1
6. postDISCH = remained below baseline (5.5)
7. PostDISCH = 27 TO 23 DAYS
Monday 13.06.22 at 23h15 BE
ARAA, LFMC, AAQC
❗️REFRESH: yesterday, last Monday
2022 NEJMcr - A 57-Year-Old Man w_Persistent Cough and Pulmonary Opacities (Knipe) [cr].pdf
2022 NEJMjw - Is Thunderstorm Asthma a Real Thing (JACI)
2022 NEJMcr - A 57-Year-Old Man w_Persistent Cough and Pulmonary Opacities (Knipe) [cr].pdf
1. 36.6ºC, ♡ 75bpm, 135/69, 🫁 28bpm, 91% (6L)
2. PHY = cushingoid + ↑ 🫁 + RALES ← 🫁 base + rhonchi ins&esp + insp wheezing 🫁 ←
3. Xray = progression of RETICULONODULAR opacities + patchy opacities ← 🫁 & left ↓ 🫁
4. TESTS = ⊖ ➩ electrolytes, amyl-lipase, proBNP , and tropT ♡, ⚯ LIVER, Legionella
5. BAL = culture enteroccus + C. albicans & glabrata = NO mycobac in sputum ➩ Cytologic: inflammation + columnar cells + macrophages
6. VORICONAZOLE (empirical tto) + stop methotrexate
7. D2 ➩ 37.9ºC , 91% (5L) ➩ CT contrast (PE) ➩ CT = centrilobular pulm nodules + tree-in-bud + patchy ground-glass + mucus plugging (lower lobes)
8. SPUTUM = cultivo, GRAM (+) (-) ↑ N
9. D3 ➩ 36.9ºC, 96% (3L)
10. PAN (medium-vessel vasculitis) = affect many organs (⚯ , skin, nerves, muscles 🫃🏽 ) BUT not 🫁
11. MYCOPLASMA? ➩ NOT typical bacterial pneumonia ➩ BUT we should THINK in atypical ➩ mycoplasma (patchy reticulonodular, ground-glass, centrilobular nodules, tree-in-bud nodules) ➩ LEVO did not ↗️ the SYMP ➩ ∑ LESS LIKELY
12. IMAGES reviewed
13. NOCARDIA = slow-growing modAcidFast 🫁 + 🧠 ➩ rf = HIV, CA, DM ➩ NODULES supper lobes (single or multiple) typically ➩ BAL-fluid cultures ⊖ = ∑ nocardiosis UNLIKELY
14. ASPERGILLUS ➩ BAL ⊕GM = aspergillosis ➩ GM recognizes POLYSACH fungal cell (81% SPECIFIC), cross-reaching Ag (fusarium or penicillium) ➩ FALSE POSITIVE = fungal colonization + food aspiration + contamined BAL fluid or blood + ATB (pip-tazo) ➩ affect IMMUNOSUPPRESSED ➩ imaging = multiple CAVITARY NODULES + angioinvasive + nodules w_”halo” of ground glass (HEMORRHAGE around) ➩ GM posit BUT Xray NOT COMPATIBLE
Tuesday 14.06.22 at 23h15 BE
AAH, MKFA, PICL, AAQC
❗️REFRESH: yesterday, last tuesday
2022 NEJMcr - A 57-Year-Old Man w_Persistent Cough and Pulmonary Opacities (Knipe) [cr].pdf
2022 UTD - Approach to the patient with abnormal liver biochemical and function tests > COMMON LIVER BIOCHEMICAL AND FUNCTION TESTS (online)
2022 NEJM - Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults (Hammod) [RCT]
pOC = ‘Hº or MM28’
1. RESULTS ➩ 343 sites + I⃣ >1K C⃣ >1k ➩ safety (D 34)= >2100pxs ➩ long-term ƒ-up = NONE
2. NOT mAb ➩ at randomization (94%) ➩ BEFORE trial = 3 in Nilmatrel + 1 in PLA
3. TTO ➩ within 3 days aft_OnsetSYMP = drug or PLA
4. EFFICACY (TTO within 3D aft_symp onset)
* planINTERIManaly ➩ pOC = nirmatrel (0.77%) VS PLA (7%) ➩ DIFF %points -6 ➩ relRisk↓ 89%
* FinalANALY ➩ pOC = nirmatrel (0.72%) vs PLA (6.5%)
* Kaplan-Meier ➩ nirmatrel (0.72) vs PLA (6.53%) ➩ DIFF %points -6 ➩ relRisk↓ 89%
5. MM AdvEve ➩ 9pxs (PLA) + 0pxs (INT)
6. Secondary ANALY ➩ (5D aft_symp onset) ➩ final ANALY = pOC = nirmatrel (0.77%) vs PLA (6%) (p<0.001) relRisk ↓ 88%
* WITH mAb = pOC = 1% (nirmatrel) vs 6% (pLA)
7. Subgroup ANALY ➩ consistent (age, sex, BMI, viral load, coexisting condition, etc.)
2022 MEDPAGE - FDA Severely Limits Use of J&J COVID Shot (Walker) [r].pdf
1. LIMITED TO CERTAIN ADULTS ➩ whom mRNA vaccines not accessible or clinically appropriate + would not get vaccinated if not for the J&J vaccine
2. FDA + CDC paused ➩ April 2021 (15 cases) ➩ March 2022 (60 cases + 9 deaths)
3. 3.2/M TTS CASES + 0.5/M TTS DEATH of vax administered
4. HIGH RISK ➩ women 30-49 years (8 cases/M)
5. Causes? NOT KNOWN
6. Consequences? Long-term + debilitating
Wednesday 15.06.22 at 23h15 BE
AAQC
❗️REFRESH: yesterday, last wednesday
2022 MEDPAGE - Did Pulse-Ox Levels Lead to COVID Therapy Delays for People of Color (JAMA).pdf
2022 MB - Vitamin D, Omega-3s, + Exercise May Reduce Cancer Risk in Older Adults (FA).pdf
1. DO-HEALTH: 2022, FA, 5 EUR ▶ db_RCT ➖ >2k ➖ 3y ▶ P⃣ ≥70yo I⃣ vitD3 + w3 + homeExerc C⃣ pla O⃣ r_anyInvCA ➩ ↗️ combination OR w3+exercise (NOT FOR: GI, breast) ➩ 61% ↓
2. 8 TTO groups: all together + doubles + alone + placebo
3. W3 = 1g/d ➩ D3 = 2000 UI/d ➩ EXERCISE = mod-intense
4. PROSTATE CA ➩ W3 alone OR w3+exer
2022 NEJMjw - Even Mild C19 Can Lead to Substantial Brain Changes (NATURE).pdf
1. 2022, NATURE, UK ▶ longitudinal ➖ >400 I⃣ + >380 C⃣ ➖ 2020-Jul2021 (first 18m of pandemic) ▶ P⃣ mild C19 I⃣ 2MRI (1st d_18m, 2nd 141d after ⊕) C⃣ PLA O⃣ MRI changes:
- ↓ gray matter thickness in ORBITOFRONTAL CORTEX + PARAHIPPOCAMPAL GYRUS
- Damage in regions CONNECTED to the OLFACTORY CORTEX
- ↓ global brain size
- Greater COGNITIVE DECLINE
2. CONCERNS ➩ progress to dementia? + durability of changes? + contribute to long-COVID?
3. THIS changes were not SEEN in non-COVID pneumonias
Thursday 16.06.22 at 23h59 BE
AAH, AAQC
❗️REFRESH: yesterday, last thursday
2022 NEJMcr - A 57-Year-Old Man w_Persistent Cough and Pulmonary Opacities (Knipe) [cr].pdf
2022 NEJMcr - A 57-Year-Old Man w_Persistent Cough and Pulmonary Opacities (Knipe) [cr]
1. P. jirovecci ➩ opportunistic ➩ pxs receive BACTRIM to ↓r P.jirov + nocardia ➩ Xray = bilateral interstitial infiltrate + ground-glass (often CAVITATE + CYSTIC) ➩ BAL ⊖
2. Candida (⚯ 🫃🏽) ➩ COLONIZATION = BAL fluid growth ➩ Histologic confirmation (rarely performed) ➩ bilateral nodules + consolidation + centrilobular nodules + tree-in-bud modularity ➩ CASE: colonization (bronchos + sputum) + 1,3ßDglucan ⊕
3. 1,3ßDglucan ➩ less SPECIFIC for ASPERGILLUS ➩ present in CELL WALL of yeasts + molds (P. jiro..candida..fusarium…acremonium) ➩ FALSE POSITIVE = in presence of cellulose membrane (HD, IGIV, ALB, QX gauze)
4. MYCOBACTERIAL ➩ Xray consistent ➩ TBC? No active contact + cultures ⊖ ➩ CONSIDER nonTBC = bronchiectasis
5. VIRUS ➩ VSR, INFLUENZA, paraI, ADENO = diffuse centrilobular + tree-in-bud NODULAR pattern ➩ BAL virus studies ⊖
6. INTERSTITIAL 🫁 DIS
- ILD (no fibrotic changes) ➩ can cause centrilobular nodules ➩ HYPERSENSITIVY pneumonitis = waxing+ waning + imagen: partially consistent = centrilobular nod ✔ , tree-in-bud nodularity ✖ ➩ PX: no air trapping + environmental exposure; BAL = NO lymphocytosis (character of HYPERSENSITIVITY)
- SARCOIDOSIS (granulomatous reaction) ➩ 🫁 skin, joints, 👁 MOST affected ➩ PX = perilymphatic nodules ✖ hiliar lymphadenopathy ✖
- ORGNIZING PNEUMONIA (inflmmatory reaction 🫁 + CAUSES: INF, concentivopathies, CA, meds, CRYPto ) ➩ PX: waxing+waning ✔ peripheral+peribronchovasular nodular consolidations ✖ ➩ 🚬 related = dyspnea ✔ FEVER+COUGH ✖
- BRONCHIOLITIS-ASSOCIATED ILD (BAI) ➩ NO ➩ air trapping + ground-glass opacities ARE COMMON ➩ PXS has centrilobular nodules (LESS COMMON for BAI
- LYMPHOCITIS INTERSTITIAL PNEUMONIA ➩ associated to Sjogren + HIV-1 + cysts ➩ Follicular bronchiolitis (= characteristics) = centrilobular nodules + tree-in-bud ✔ ➩ PX: fever + cough (NOT COMPATIBLE)
- DIFFUSE PANBRONCHIOLITIS ➩ rarely in non Asian ancestry ➩ px = WHITE European ancestry
Friday 17.06.22 at 23h15 BE
ARAA, AAQC
❗️REFRESH: yesterday, last Friday
2022 NEJMcr - A 57-Year-Old Man w_Persistent Cough and Pulmonary Opacities (Knipe) [cr]
2022 NEJMcr - A 57-Year-Old Man w_Persistent Cough and Pulmonary Opacities (Knipe) [cr]
1. Drug-related toxic effect ➩ cyclophos + methotre = pxs ➩ 🫁 effects of CYCLO rare ➩ when acutePNEUMONITIS = 6m of TTO 🆚 chronic pneumonitis = fibrosis ➩ METO = diffuse pneumonitis = 1y of TTO
2. CA ➩ always think with OPACITIES ➩ PRIMARY 🫁 CA = discrete NODULES + lymphadenopathy
3. LymphomGranulomatosis = rare + ↔Epstein-Barr (context of METHOT) ➩ image = single + multiple NODULES that can CAVITATE in PERIbronchovascular distribution
4. TUMOR embolization = NODULES in random distribution
5. LYMPHANGIticCA..osis = nodules in PERLYMPHATIC distribution
6. RECURRENT ASPIRATION = silent + even in absence of reflux ➩ centrilobular nodules ✔ tree-in-bud ✔ ➩ PX: secretion in aw + mucus plugging + hiatal hernia + esophagus residual contrast + GERD + mouth BITTER taste + waning-waxing + BAL w_acute infammation + BAL w_squamous cells, candida, bacteria ▶ ∑ INFECTIOUS + ASPIRATION BRONCHIOLITIS
7. APPRAISAL ▶ microbiologic al ⊖ except FUNGAL markers ➕ clinical + radio = diffuse aspiration bronchiolitis
8. PATHOLOGICAL discussion = BIOPSY video assisted ➩ multifocal organizing pneumonia + giant cells + PERI bronchiolar histiovytes + intraluminal polypoid structures + aspirated food particles + microabcess formation + organizing fibrosis ➩ NO vasculitis ➩ ⊖ stains
9. ADDITIONAL IMAGING ➩ VIDEO-FLUOROSCOPIC swallowing examination w_speech-language pathologist = mod pharyngeal DYSPHAGIA + DELAYED swallowing initiation + trace silent aspiration ➩ BARIUM-swallow = normal esophageal motility ➩ in PRONE a small contrast aspirated into TRACHEA + righBRONCH ➩ mod GE reflux to carina WHEN prone-supine
10. DISCUSSION OF mm ➩ under appreciated CAUSE OF 🫁 DIS ➩ HALF adults ASPIRATE w_orophar contents while ASPLEEP ➩ rf = ↓ loConsciousness + abnormal swallowing mechs + ↑ GEReflux + imp_cough reflex ➩ PX opioid use = imp: LOConsc + GE motility ➕ can suppress cough ➩ TTO = ATB for aspiration + gastric acidity suppression + nonopijoid tto + dietary + iifestyle + head of bed elevated (↓ occurrence GER) w_MATRESS WEDGE ▶ all ok (SYMP, O2, inflaMARKERS, 🫁 function, CT)
Monday 20.06.22 at 23h15 BE
LFMC, MKFA,AAH, AAQC
❗️REFRESH: last one and same day last week
2022 NEJMcr - A 57-Year-Old Man w_Persistent Cough and Pulmonary Opacities (Knipe) [cr].pdf
2022 HEALIO - Fauci tests positive, is experiencing mild C19 symptoms, NIAID says (Gallagher) [r].pdf
1. Fauci (+) ➩ Antigen
2. CONTACTS ➩ Joe Biden + NONE senior officials
3. Isolate + work from home
4. NIAID ➩ “omicron will ultimately find just about everybody”
2022 NEJMjw - Radiographic Abnormalities Can Persist After Hospitalization in Some C19 pxs (Radiology).pdf
1. R, 2022, ENGLAND ▶ descriptive ➕ 80 ➕ spring 2020 ▶ P⃣ post C19 I⃣ ƒ-up 3m + 1y C⃣ NO O⃣ Imaging characteristics: CT ➩ 80% normal or better (1y) ➩ Fibrosis 10%
2. Ground-glass opacities (50%) + curvilinear bands (40%) = 3 months
3. Rx abnormalities at 3m = 56%
4. Pxs characteristics = 94% w_O2 (40% i and niMV) ➩ H+ LOS 8 dys
5. METHODS ▶ selection bias = most SS were healthy to complete the f-up ▶ LIMITATION = lack of control group
6. This info avoids UNNECESSARY workups
Monday 20.06.22 at 23h15 BE
LFMC, MKFA,AAH, AAQC
❗️REFRESH: last one and same day last week
2022 NEJMcr - A 57-Year-Old Man w_Persistent Cough and Pulmonary Opacities (Knipe) [cr].pdf
2022 NEJMjw - Are Four Doses of Pfizer-BioNTech SARS-CoV-2 Vaccine Better than Three (BMJ).pdf
1. BMJ, 2022, IS ▶ retrospective + case-control ➕ <98k (30% received 4th dose) ➕ 2022 ▶ P⃣ past VAX 4dose I⃣ 4th dose C⃣ matching O⃣ waning: sDIS ≥10w ➩ relative effectiveness 72%
2. PEAK of relative effectiveness (RE) (4th over 3rd) = 65% = 3rd WEEK
3. FALL of RE = 22%. = 10w f-up
4. 4th DOSE recipients = were more chronically ill ▶ ∑ confounders analysis: time of 1st test + month of receipt 3rd dose + comorbidities + immnosuppressive.
2022 JAMA - I-TECH, Efficacy of Ivermectin TTO on Disease Progression Among Adults W_ Mild to Moderate C19+Comorbidities (lim) [R].pdf
1. AdvEve = Terminology Criteria V5.0
2. Subgroup analyses ➩ vaxC19 + age + clinical stage + d_DIS + comorbidities
3. D5 = blood sampling + xRay
4. Power = 462pxs ➩ 80%5. CLINICALLY IMPORTANT = ↓ 50% pOC OR 9% rate DIFF I⃣ 🆚 C⃣
Wednesday 22.06.22 at 23h15 BE
AAQC
❗️REFRESH: yesterday and last Wednesday
2022 MB - Vitamin D, Omega-3s, + Exercise May Reduce Cancer Risk in Older Adults (FA).pdf
2022 NEJMjw - Even Mild C19 Can Lead to Substantial Brain Changes (NATURE).pdf
2022 MEDPAGE - More Inflammatory Foods, More Fecal Incontinence (CGH).pdf
FECAL INCONTINENCE = FI; CGH = Clinical Gastroenterology and Hepatology; NM = neuromuscular
1. 🧓🏼women, proINFLA diet = ↑ rFI
2. NHS = Nurses’ Health Study
3. 2022, CGH, USA ▶ RETRO ➕ >57K ➕ 2006-2012 ▶ P⃣ 🧓🏼 women I⃣ proINFLA diet (30-55yo) C⃣ others O⃣ rFI ➩ ↑ when proINFLA diet
4. ADJUSTED ➩ PROinflamm diet scores in HIGHEST QUINTILE = 17% ↑r FI compared to LOWEST QUINTILE ➩ in both SOLID & LIQUID stool incontinence
5. SECONDARY ANALYSES ➩ DIFF even MORE pronounced in sFI (weekly) = overall (HR 1.25) + solid (HR 1.29) + liquid (HR 1.27)
6. Ƒ-up done w_questionnaries
7. Food PROinflammatory effect:
8. Men?… We cannot establish a cause and effect
9. ⤹work = fiber intake ↔ ↓r liquid but NOT solid stool incontinence
10. Low-grade INFLAMMATION occurs w_many chrDIS (HTA, DM2, CVD)
11. chrDIS ↔ Western diet consumption (processed meats, refined grains, simple sugars)
12. IN ▶ no FI at baseline
13. EX ▶ ⤹ colorectalCA ± IBD ± immobility
14. EDIP score = empirical dietary inflammatory pattern score = validated energy-adjusted = ↑ EDIP (⊕ PROinflammatory)
15. Fiber intake was ↑ ‘w’_least PROinflamm EDIP score diet’ as was daily -ol consumption
Friday 24.06.22at 23h15 BE
AAH, MKFA, AAQC
❗️REFRESH: yesterday and last Friday
022 NEJMcr - A 57-Year-Old Man w_Persistent Cough and Pulmonary Opacities (Knipe) [cr]
2022 NEJM - EPIC-HR, oral Nirmatrelvir for hr, nHº Adults (Hammod) [RCT].pdf
1. Baseline + D5 (>1.5k) ➩ ADJUSTMENT baseline, serology, geoRegion = ↓ D5 of viral load (0.8log10/mL, p<0.001) IF given <3D aft_SYMPonset = ↓ D5 of viral load (0.7…, p<0.001) IF given <5D aft_SYMPonset
2. If mAb used = similar results on EFFICACY ➩ ↓ VIRAL LOAD at D5 (0.7log10/mL)
3. Subgroup analyses = same efficacy regardless baseline viral load + serology
4. SAFETY ➩ incidence = similar in I⃣ and C⃣ (23% vs 24%) ➩ the most frequently reported (by investigator): dysgeusia (6% vs 0.3%), diarrhea (3% vs. 2%), fibrin D-dimer increase (2% vs. 3%), ALT ↑ (1.5% vs. 2.4%), headache (1.4% vs. 1.3%), creatinine renal clearance ↓ (1.4% vs. 1.6%), nausea (1.4% vs. 1.7%), and vomiting (1.1% vs. 0.8%) ➩ ALL NONSERIOUS
5. AdvEve ➩ diff ↔ I⃣ and C⃣ = 7.8% vs 3.8% ➩ ATRIBUTTED TO disgeusia (4.5%) and diarrhea (1.3%), both vs 0.2% in placebo ➩ ONLY 1% of NIRMA-RITO reported AdvEve. (Grade 1 and 2) ➩ grade 3 and 4 were similar and lower in I⃣ and C⃣
6. Most frequent SERIOUS AdvEve = C19 pneumonia (0.5 vs 3.3%), C19 (0.2 vs 0.7%), ↓ renal CREA clear (0.2 vs 0,3%) = NONE related to NIRMA or PLA
7. D34 ➩ NO serious AdvEve resulted in DEATH ➩ 13 deaths among PLA = C19-related.
8. Discontinuation of the drug or PLA (order of frequency) ➩ C19 pneumonia, nausea, ↓ ⚯ CREA CLAR, vomiting, C19, ← GFR, pneumonia, pneumonitis, ↓ WBC and dyspepsia
9. MOST AdvEve were MILD TO MOD.
10. PLANNED INTERIM ➩ relRisk ↓ 89% of pOC ▶ FULL ➩ relRsk↓ 89% (D3 aft_sympOn) 88% (D5 =) ▶ SUBGROUP ➩ same, regardless counfounders.
11. ADDITIONAL (D3 had already ↓) VIRAL LOAD ↓ at D5 by a FACTOR OF 10, as compared with placebo.
12. Nirma+rito TARGETS AN essential protein (conserved across coronas) ➩ inhibit of Mpro may RETAIN ACTIVITY against FUTURE VARIANTS
Saturday 25.06.22at 23h15 BE
AAQC, LFMC
❗️REFRESH: last one and last Friday
2022 NEJMcr - A 57-Year-Old Man w_Persistent Cough and Pulmonary Opacities (Knipe) [cr]
2022 MEDPAGE - Less Fluid Not Better for SS° (NEJM)
1. CLASSIC: NEJM, 2022, DN, NOR, SWE, SWIT, IT, CR, UK, BE ▶ int_mcRCT ➕ >1.5k ➕ Nov2018-Nov2021 ▶ P⃣ 31 ICUs, ADULTS I⃣ RESTRICTIVE fluid therapy (ft) C⃣ STANDARD ft O⃣ pOC: MM90 ➩ SIMILAR (did NOT ↓ pOC)
2. IN ▶ conf OR sus INF + lact ≥1.8 + vasopressor or inotropic
3. EX ▶ SS• >12h ± life-threatening bleeding ± acute burns ≥10% ± pregnancy
4. RESTRICTIVE FLUIDS = small boluses only: severe ↓ perf (MAP<50, mottling knee, UO <0.1 in 2h) + replace losses + dehydration + electrolyte
5. sOC: SS ‘ICUdisch or 90’ = SIMILAR I⃣ 42% and C⃣ 42%
6. AdvEve ▶ SIMILAR 29 vs 31% I⃣ 🆚 C⃣
7. DIFF in volume ↔ GROUP = 2L
8. POWER of 7%-point DIFF = not feasible = due to standard group also treated w_conservative fluid strategy
9. LIMITATIONS ▶ not blinded + lack of data on co-int + HD factors + free receipt of fluid (before enrollment)
Monday 27.06.22 at 23h15 BE
MKFA, AAQC
❗️REFRESH: last one and same day last week
2022 HEALIO - Fauci tests positive, is experiencing mild C19 symptoms, NIAID says (Gallagher) [r].pdf
2022 NEJMjw - Radiographic Abnormalities Can Persist After Hospitalization in Some C19 pxs (Radiology).pdf
2022 NEJMjw - Are Four Doses of Pfizer-BioNTech SARS-CoV-2 Vaccine Better than Three (BMJ).pdf
2022 JAMA - I-TECH, Efficacy of Ivermectin TTO on Disease Progression Among Adults W_ Mild to Moderate C19+Comorbidities (lim) [R].pdf
2022 NEJMcr - A 57-Year-Old Man w_Persistent Cough and Pulmonary Opacities (Knipe) [cr]
2022 JAMA - I-TECH, Efficacy of Ivermectin TTO on Disease Progression Among Adults W_ Mild to Moderate C19+Comorbidities (lim) [R].pdf
1. SAMPLE SIZE ➩ calculated: superiority + pOC measure ➩ expected rate = 17.5% in control ➩
2. Clinically important ➩ 50%↓ pOC ± ratDIFF 9% I⃣ 🆚 C⃣
3. Power 80% = 462pxs ⏤ significance 5%
4. 500pxs (250 each group) ➩ last f-up Oct2021
5. Many excluded due to dengue, symp>7d, ⊖ C19 rtPCR, ACS, withdrew consent.
6. mITT = primary = 241 I⃣ 🆚 249 C⃣ ➩ 96% COMPLETED 5 DOSES
7. 62 yo + 54% women + 52% fully VAX + Malaysia well represented + comobidities (HTA 75%, DM 53%, DYS 38%, 🐷 24%)
8. SYMP ➩ 5D = cough, fever, runny nose ➩ 2/3 mod DIS ➩ MARKERS: NLration + CRP were similar ➩ Meds were similar
9. SENSITIVITY ➩ SIMILAR
2022 WHO - Clinical management of C19 (Who) [GL]
AMR = ANTImicrobial resistance
1. Mild:
* when suspected or confirmed C19 = ISOLATION
* TTO ➩ antipyretics (fever), painkiller (pain) + nutrition + rehydration
* NDSAIDs not CONTRAINDICATED
* ATBS only if needed = careful with AMR
2. MOD
* Isolation = not require ER or Hº
* Location decided CASE-BY-CASE depending on: clinical presentation + supportive care + rf_sD + home conditions (vulnerable persons)
* If high RISK of deterioration BETTER HOSPITAL for isolation
* Pulse oximetry can be used at home (equipment, personnel, ability to interpret and knowledge about implementation)
Tuesday 28.06.22at 23h15 BE
AAH, LFMC, AAQC
❗️REFRESH: yesterday + last Tuesda
2022 JAMA - I-TECH, Efficacy of Ivermectin TTO on Disease Progression Among Adults W_ Mild to Moderate C19+Comorbidities (lim) [R].pdf
2022 WHO - Clinical management of C19 (Who) [GL]
2022 NEJMjw - Intracerebral Hemorrhage GL 2022 Key New Aspects (Stroke).pdf
CVT = cerebral venous thrombosis; ICH = intracerebral hemorrhage; 4FPC = 4-factor prothrombin complex concentrate; FFP: Fresh frozen plasma
1. MM90 = 15-40% ➩ ICH ➩ due to: age, antiCOAG, EFFECTS on poor and minority communities
2. IMAGES ➩ CTA + venography = to exclude MACROVASCULAR causes or CVT, in pxs with: ‘lobar sICH+<70yo’ ± ‘deep/post fossa sICH+<45yo’ ± ’= 45-70yo wo_HTA’ (CLASS I)
3. PROCEDURE ➩ sICH + NOT detectable parenchymalHH = catheter intra-arterial digital subtraction angiography ➩ to EXCLUDE MACROVACULAR causes (CLASS I)
4. IMAGES ➩ MRI + MRIangio = sICH + ⊖CTA/venography ➩ to establish nonMACROVASCULAR causes (CLASS IIA)
5. ↓ HTA IN sICH ➩ TITRATE CAREFULLY ➩ ENSURE continuous smooth and sustained control (CLASS IIA)
6. sICH + mild-mod + SBP 150-220 ➩ AIM 130-150 (target, 140) ➩ SAFE and may ↗️ fOC
7. ANTIDOTE ELECTION ➩ AntiCOAG (vit K antagonist) + INR ≥2 ➩ sICH ➩ 4FPC is PREFERABLE to FFP to CORRECT INR + limiting of HEMATOMA EXPANSION (CLASS I)
8. TRANSFUSION ➩ NO platelet TRANSFUSION when sICH w_ASA ➩ UNLESS emergency Qx (CLASS III)
9. TEAMWORK ➩ sICH ➩ PROVIDE CARE in specialized inpx UNIT (e.g. stroke) w_ MULTIdisciplinary TEAM to ↗️ OC (CLASS I)
10. EMBOLISM ➩ sICH not AMBULATORY, UNFRAX heparin ± LMWH ➩ ↓ PE
11. SCORES ➩ Baseline severity score should NOT be the only predictor for PROGNOSIS + limiting TTO ➩ sICH
2022 JAMA - I-TECH, Efficacy of Ivermectin TTO on Disease Progression Among Adults W_ Mild to Moderate C19+Comorbidities (lim) [R].pdf
1. pOC = progression to SD ➩ 22% iver+SOC, 17% SOC (p=0.25) ➩ iTT in sensitivity ANALYSIS was SIMILAR
2. sOC = 5 ➩ PROG sD at enrollment (2.4 vs 2d) ➕ MV (1.7 vs 4%) ➕ ICU admiss (2.5 VS 3.2%) ➕ 28H MM (1.2 VS 4%) ➕ Hº LOS (4 VS 4)
3. D5 ➩ SYMP resolution (comparable in both)➕ Xray WO_changes or w_RESOL (similar) ➕ DIS complication (no DIFF) ➕ HIGHEST O2 requirement (similar)
Wednesday 29.06.22 at 23h15 BE
CCH, LFMC, AAQC
❗️REFRESH: yesterday and last Wednesday
2022 MEDPAGE - More Inflammatory Foods, More Fecal Incontinence (CGH).pdf
2022 JAMA - I-TECH, Efficacy of Ivermectin TTO on Disease Progression Among Adults W_ Mild to Moderate C19+Comorbidities (lim) [R].pdf
CFR = case fatality rate
1. SUBGROUP analyses ➩ prog to sDIS = 18 vs 9% ( I⃣ 🆚 C⃣ ) ➩ post hoc = fully vax controls had ↓ rate of sDIS (p=0.002)
2. AdvEve (55) ➩ in 44pxs (9%) = 33 IVER w_diarrhea ➩ 5 SAE = 4 I⃣ (2MI, 1sANEMIA, 1hypoSHOCK secDIarrhea) + 1 C⃣ (infEPIG arterial bleeding) ➩ 6 pxs DISCONTINUED iver
3. DEATH ➩ sC19 pneumonia (69%) + 4pxs nosocomialS• (control)
4. SIMILAR RESULTS AS IVERCOR-COVID19 (AR) BMC InfDis
5. Prior RCT were for outpxs, this one INPXS ➩ clearly defined criteria TO ASCERTAIN PROGRESSION
6. CFR was 1% (current study), 2.7% (another study w_hrCohort) ➩ MA (8 RCT) = CFR 3.8% = NO effect on SS
7. PHARMACOKINETICS ➩ we need high doses = 0.2 - 0.6 m/Kg/d x 5d for FAVORABLE results = this study (0.4 mg/Kg/d) ➩ Safe and well TOLERATED DOSE = 120mg of Iver
8. LIMITATIONS ➩ a. Open-label = underreporting AdvEve in C⃣ + overestimating AdvEve in I⃣ b. MM not studied c. Older pxs might have generalized results.
22 NEJMjw - Autonomic Dysfunction After C19 (JACC)
1. 2022, JACC, ? ▶ case-report ➕ 1 center (24) ➕ ±6m ▶ P⃣ past C19 ⊕ + palpitations + ↑ FC minimal OR positional change + exertion intolerance I⃣ head-up tilt table test C⃣ control O⃣ ORTHOSTATIC INTOLERANCE on the tilt-table test ➩ almost all had it (23/24)
2. POTS = postural orthostatic tachycardia syndrome + AND dysregulation ➩ both are PURPORTED MECHS
3. 20 of 24 were WOMEN ➩ raises attention4. Nitroglycerin administration made ALL be with orthostatic intolerance. 5. We KNOW little about this condition
Thursday 30.06.22 at 23h59 BE
AAH, LFMC, AAQC
❗️REFRESH: yesterday and last Thursday
2022 JAMA - I-TECH, Efficacy of Ivermectin TTO on Disease Progression Among Adults W_ Mild to Moderate C19+Comorbidities (lim) [R].pdf
2022 NEJMjw - Autonomic Dysfunction After C19 (JACC)
2022 NEJM - EPIC-HR, oral Nirmatrelvir for hr, nHº Adults (Hammod) [RCT].pdf
CM = concomitant medication
1. EPIC-HR was in outPXS ⏤ EPIC-SR was in inPXS
2. DRUG INTERACTION ➩ mm w_ dose ↓ CM ➕ use alternative CM ➕ ↑ monitoring for AdvEve or CM drug levels ➕ temporary DC of CM ➕ avoidance of coadministration
3. DOSES ➩ short duration = rito 100mg x 5d ➩ long-term use = rito 600mg (HIV) ➩ CAREFUL w_nirma+rito and CERTAIN CONTRAINDICATED drugs
4. STRENGTHS ➩ geographic generalizability ➕ relatively common demo+clin char = CVD, 🐷, DM (12% of world in 2017 was ≥60yo)
5. EFFECTS ➩
6. Nirma-rito ➩ ↓ p_sD + viral LOAD
2022 HEALIO - 55% of pxs have persistent symptoms 2 years after C19 infection (Welsh) [r]
mMRC = modified British Medical Research Council;
1. 2022, LANCETrm, CH (Beijng) ▶ ambidirec, long, COHORT ➕ >1.1k ➕ Jan-May2020 ▶ P⃣ PAST C19 pxs I⃣ ƒ-up 6m, 12m, 24m C⃣ control wo_C19 O⃣ long-C19 symptoms (measured health OC) ➩ fatigue ± muscle weakness (52% of pxs at 6m and 2y)
2. Measured health OC = how measured? USING 6-MIN WALKING ➕ LABS ➕ Questionnaries (SYMP, mental health, hrQOL, return to WORK and HCuse after DISCH)
3.
4. 6-MIN walk ↓ 89% at 2y
5. LongC19 🆚 non-longC19 ➩ MORE: mobility problems (OR 4) ± pain or discomfort (OR 4) ± anxiety or depression (OR 7)
6. SS 🆚 non-SS ➩ MORE problems w_usual activity ➕ pain or discomfort ➕ anxiety or depression = all at 2y
7. sC19 w_🫁 support 🆚 controls ➩ lung diffusion impairment (65 vs 36%) ➕ reduced residual volume *(62 vs 20%) ➕ ↓ total 🫁 capacity (39 vs 6%) ➩ *has the highest DIFF8. REHABILITATION PROGRAMS would be IMPORTANT
Monday 04.07.22 at 23h15 BE
EACQ, MKFA, AAQC
❗️REFRESH: last one and same day last week
2022 JAMA - I-TECH, Efficacy of Ivermectin TTO on Disease Progression Among Adults W_ Mild to Moderate C19+Comorbidities (lim) [R].pdf
2022 WHO - Clinical management of C19 (Who) [GL]
2017 UNI - Beneficios del desarrollo de la telemedicina en América Latina.pdf
1. Impact of Telemedicine in DX and TTO
2. 60000M text messages daily = potential of access to healthcare and diagnosis
3. CEPAL = international scale + public politics together develop initiatives in Telemedicine
4. Real time information ➩ to HELP in the DECISION making process ➩ BENEFIT for population = better informed, better taken care, with the capability of influencing and deciding on his/her own disease
5. Comment EAQC = development of a vital sign machine + further info in a database
2020 JAMA - Association of Electronic Health Record Use W_ Physician Fatigue + Efficiency (Khairat) [R].pdf
1. 2020, JAMA, USA ▶ cross-sectional, SIMULATION-based ➕ 25 ICU physicians (4 px cases)➕ March-April 2018 ▶ P⃣ ICU physician I⃣ simulation of EHR (eye-tracking glasses) C⃣ no O⃣ pOC = fatigue + efficiency
2. FATIGUE = measured through continuous eye pupil data (PUPILLOMETRY) ➩ lower scores = GREATER FATIGUE ➩ ALL experienced it at least ONCE ➕ 80% experienced it within 1st 22min of EHR use
3. EFFICIENCY = task completion time (p=0.007) + mouse clicks (p=0.003) + EHR screen visits (p=0.01)
4. CARRYOVER ASSOCIATION across px cases = if fatigued in 1 case, they were less efficient in the subsequent px case
Tuesday 05.07.22 at 23h15 BE
LFMC, MKFA, AAQC
❗️REFRESH: yesterday + last Tuesday
2022 NEJMjw - Intracerebral Hemorrhage GL 2022 Key New Aspects (Stroke).pdf
2022 JAMA - I-TECH, Efficacy of Ivermectin TTO on Disease Progression Among Adults W_ Mild to Moderate C19+Comorbidities (lim) [R].pdf
2022 NEJM - CLASSIC, restriction of Intravenous Fluid in ICU pxs W_ septic shock (Meyhoff) [RCT]
CS = Circulatory support;
OC MEASURES
1. pOC = MM90 aft RANDOM
2. sOC ➩
* sAdvEve ICU (🧠, 🫀, 🫃🏽, limb) ± sAKI (new episode) ➩ mKDIGO S3 ➕ mUO
* sAdvReac to 💉 FLUIDS
* dALIVE wo_LIFE SUPPORT (CS, MV, RRT) at D90
* dALIVE + ooH at D90
3. simplMM score in ICU ➩ based on age + coexisting conditions + acuteDIS markers = 24h ⤹ RANDOM (scale 0-42) ➩ ↑ scores = ↑ predicted 90MM
4. 99.4% were analyzed ➩ >750 each group ➩ well balanced ➩ pxs were REPRESENTATIVE of their ICU (EXCEPT for 🫁 INF in fewer trial)
5. 90D trial ➩ pxs remained in the ICU for 5D (median) [3-9 restrictive] [3-10 standard]
6. DISCONTINUED fluid protocols ➩ 10% restrictive ⏤ 7% standard
2022 NEJM - Intravenous Fluids in Septic Shock — More or Less (Mclntyre) [ed].pdf
hRESTR = highly restrictive
1. British cholera 1931: William O’Shaughnessy ➕ Scottish GP: Thomas Latta = which fluids, how much, targets?
2. FEAST trial ➩ ↑SS = fluid-restrictive approach (children sINF)
3. sr (ICM 2017, Silversides, EF) ➩ restrictive ± activeFluidRemoval = CIchildren + adults ➩ 11 RCT, >2k pxs ➩ restrictive-fluids ± active-fluid-removal = ↑💨-freeD ➕ ↓📌 LOS ▶ BUT NOT ↓MM ➩ rigorous and adequately powered trials ARE NEEDED
4. CLASSIC ▶ intRCT, MM90, >1550pxs (SS• <12h ⤹screen) ➩ restrictive 🆚 standard ➩ stratified: SITE + ✖✔CA (metas ± hemato) ➩ 💧 = 3L ⤹RANDOM ➩ ⏳enroll = 3h ‘aft_📌admiss’ ➩ median bet-groupDIFF = 2L ➩ NO DIFF MM90 pOC + sOC
- restrictive = 250 or 500ml for s↓PERF (lact, MAP, mottling, UO)
- standard = no limit↑ + SSC 2016
5. Clinical OC did NOT differ? ▶ raises ADDITIONAL QUESTIONS:
- Magnitude of effect = EFFICACY I⃣ ➕ NATURE C⃣
- ↔ TTO in a BROADLY similar manner = absence of therapeutic signal
- «When the I⃣ is a drug or device, the use of a PLA or SHAM allows valid inferences of causality» ➩ BUT when I⃣ = mm strategy ∑ MORE COMPLEX
- Small ↔group 💧DIFF = pxs in standard also TTO as conservative ➩ ∑ detection 7-%-pointDIFF MM90 = INFEASIBLE
- SUPERIORITY ➩ usual-care thought to be ↗️
- Is usual care the same? ➩ no = 💧fluid < other NAL & intNAL studies (ICM 2015, Angus srMA of ARISE + ProCESS + ProMISe ➕ ICM 2015, Boulain prosMc 19FR ICUs ➕ CCM 2018, Silversides deresuscitation of iatrogenic overload and ↓ MM in CIpxs)6. CLASSIC hRESTR = safe + NEW ❓(how much, threshold&targets, when to use, vaosactives, removal…???) ➩ challenge CONVENTIONAL WISDOM ➩ ultimate GOAL of ↓ MM ➕ ↗️ f + QOL (SSpxs)
Friday 08.07.22 at 23h15 BE
JCAS, ±LFMC, AAQC
❗️REFRESH: yesterday and last Friday
2022 NEJMjw - Another Look at Proning in Nonintubated Hospitalized pxs W_ C19 (JAMA)
2022 NEJMjw - Optimizing Remdesivir's Use for C19 Infection vs. Inflammation (JAC)
2022 NEJM - CLASSIC, restriction of Intravenous Fluid in ICU pxs W_ septic shock (Meyhoff) [RCT]
1. pOC ➩ MM90: 42% I⃣ 🆚 42% C⃣ ➩ consistent: sensitivity + per-protocol ➩ heterogeneity NOT SIG.
2. pOC ➩ sAdvEve: 29% I⃣ 🆚 31% C⃣ ➩ AdvEve 💉 admin: 4 🆚 4%
3. sOC ➩ NoD_alive wo_LIFEsupp + NoD_alive & ooHº = 90d
4. 95%CI at D90: ↑ or ↓ ≥5% WAS UNLIKELY
5. OTHER STUDIES ➩ srMA = no DIFF ↔ groups in MM = 621 pxs ➩ observational = suggested HARM from ↑ fluid volumes = BIAS: indication + time-dependent
6. STRENGHTS ➩
- Completeness: char + OC = similar to other trials
- Fluid volumes: within the ranges of other trials (ICU)
- Generalizability: Europe = 31 ICUs (univ&non-univ) in 8 EUR countries
- Pilot trial: before this trial (to assess feasibility + design for the staff in the centers)
7. LIMITATIONS ➩
- Aware
- Not collected data
- Some fluids received
- Protocol violations
- Given outside the volumes
- Power to detect DIFF in OC and subgroup analyses
- THE GOAL Diff 7% points MM90 may be LARGE
Wednesday 13.07.22 at 23h15 BE
AAQC
2022 JAMA - Association of Music Interventions With Health-Related Quality of Life (mccrary) [srMA].pdf
SMD = standardized mean difference
1. ↑ HRQOL = BETTER mental + physical HRQOL
2. IN ➩ RCT, nRCT (music making & listening), no restriction in controls, music w_HRQOL as pOC ± sOC, SF-36 -12 reported (if not, data to calculate).
3. MCS + PCS ➩ include 8 sub scales:
* Physical functioning (PCS)
* Role physical (PCS)
* Bodily pain (PCS)
* General health (PCS)
* Vitality (MCS)
* Social functioning (MCS)
* Role-emotional (MSC)
* Mental health (MSC)
4. EX ➩ observational + cross-sectional ➕ other music-related activities (songwriting)
5. PRE-POST CHANGES ➩ music ↔ ↗️ MCS (p<0.001) + PCS (p=0.02) ➕ SMD 0.25 (MCS) vs 0.15 (PCS) ➩ MCS: greater in mod-high QUALITY
6. MCS score was THE SAME after excluding gospel music
7. DOSE ➩ no changes ↔ MCS or PCS
8. HETEROGENEITY ➩ none
9. Small study or PUBLICATION BIAS ➩ none10. Imprecision = wide CI
Friday 01.07.22at 23h15 BE
LFMC, ±SGQA, AAQC
❗️REFRESH: yesterday and last Friday
2022 NEJM - EPIC-HR, oral Nirmatrelvir for hr, nHº Adults (Hammod) [RCT].pdf
2022 NEJMjw - Another Look at Proning in Nonintubated Hospitalized pxs W_ C19 (JAMA)
1. 2022, JAMAim, USA ▶ non-R, CONTROLLED ➕ 501 ➕ ? ▶ P⃣ C19 mild-mod (nonINTUB) I⃣ awake prone positioning C⃣ control (usual care) O⃣ ↓ O2 ➩ SIMILAR MM + pINTUB + LOS
2. GL2021 ➩ recommends awake prone positioning ➩ BASED on limited evidence
3. 1st 5d ➩ 4h I⃣ 🆚 0h C⃣
4. D5 ➩ WORSE OC for O2 support in I⃣ ➩ NOT present: days 0-4 ➕ 14-18,
5. CONFOUNDERS ➩ delayed ‘THERAPIES ± DX TESTING’
6. AdvOC ➩ not DIFF by day 14
7. HARM ➩ IS UNLIKELY
2022 NEJMjw - Optimizing Remdesivir's Use for C19 Infection vs. Inflammation (JAC)
Viral load = VL
1. JACH, 2022, ES ▶ COHORT ➕ >1.3K ➕ Mar2020-Apr2021 ▶ P⃣ C19 w_REMD I⃣ viral load + CRP C⃣ no O⃣ MM28 + pMV ➩ ↗️ LOW inflammation + hVIRAL LOAD
2. MAX BENEFIT OF REMDESIVIR ➩ 5-7 d of C19 symp
3. CUT-OFFS ➩ PCR cycle threshold <25 + CPR <38mg/L
4. March 2020: dexa + toci were used (Hº protocol) ➕ July2020: remdesivir
5. ALL PXS received CORTICOIDS ➩
- TOCI 74%
- Remde 63%
- Toci + remde 56%
6. PXS in GLUCO+TOCI ➩ MM28 = aHR 0.48 hVL ➕ 0.12 hVL + <5d SYMP ➕ 0.13 low-grade INFLAMM
7. PXS in GLUCO+TOCI ➩ pMV = 0.32 w_hVL
8. 1ST STUDY to measure PCR (viral load) and CRP (inflammation) for Remdesivir
Friday 15.07.22 at 23h15 BE
MKFA, AAQC
❗️REFRESH: yesterday and last Friday
2022 NEJM - CLASSIC, restriction of Intravenous Fluid in ICU pxs W_ septic shock (Meyhoff) [RCT]
2022 NEJM - Targeted Therapy in Melanoma (Rokhzan) [img clinical].pdf
51yo man, dermato = ⤹36m growth of multiple skin tumors + 6m weight ↓ & 🫃🏽😩 ➩ cachectic + masses in axillae, inguinal, abdominal
CT + MRI ➩ metastases dispersed in the body
BIOPSY ➩ chest-wall mass = metastatic MELANOMA
TTO ➩ a. Ipilimumab + nivolumab ➩ BRAF ⊖ = dabrafenib ➕ MEK ⊖ = trametinib
TIME
2 weeks = mass ↓ size
6 weeks = CT w_metastases regression (except right axila = Qx removed)
12 weeks = even smaller
15 months = transitioned to hospice care
2022 MEDPAGE - Lower Long COVID Risk Tied to More Vaccine Doses (JAMA).pdf
1. 2022, JAMA, IT ▶︎ OBS ➕ >2.5k ➕ 2y (Mar2020 - Apr2022) ▶︎ P⃣ HC workers (outpatients) I⃣ vax (1, 2, 3 doses) register by surveys C⃣ unvax O⃣ Long-C19 symptoms ➩ ↓r pOC ↔ ↑VAX
2. LongC19 = symptoms >4w
3. Prevalence ➩ 42% unvax, 30% 1 dose, 17% 2 doses, 16% 3 doses.
4. LINGERING SYMPT more common d_1st wave ➩ NOT sigAssociation w_ INF
5. VARIANTS ➩ not associated to OC
6. Al-Aly “the most optimal strategy is to avoid infection or reinfection in the first place.”
7. «Older + ↑ BMI + allergies + COPD» = PERSISTEN C19 SYMP
8. ODDS of longC19 (compared to unvax WOMEN + no allergies + no comorb) =
9. ⏳INF ↔ 2ndVAX = not TIED TO longC19
10. LIMITATION ➩ SYMP auto-reported
Monday 18.07.22 at 23h15 BE
AAQC MKFA
2022 NEJMcp - Pulmonary embolism (kahn) [CP].pdf
1. 41yo M, ED, ⤹ 3w: breathlessness ➩ ATB for pneumonia? ➩ dull pain on ←back ➩ VS: HR88, BP149/86, RR18, T37, SpO2 95%aa ➩ PhEx: legs ok. ➩ COMP:
CREA ok
TROPONIN ok
Xray ok
2. PE likelihood >15% by physician ➕ Wells 0 ➕ D-dimer 2560 ng/mL
3. OCCURS ➩ embolic venous thrombi in branch 🫁 vasculature + develop in 🦵🏼± pelvis + 1/2 of DVT —> embolize 🫁
4. INCIDENCE ➩ 1/1000 +
5. CAUSE OF DEATH ➩ 20% of TTO die within 90D BUT IT IS due to: CA, S•, illness leading to Hº, surgeries
6. MM ➩ unDX PE in <5% ➩ RECOVERY ↔ ‘complications = ‘bleeding (antiCOAG) + recurrent VTE + chrTEPHyper + long-term phychoDIstress
7. LIMITATIONS 1 YEAR ➩ functional + exercise + hrQOL
8. Minority = benefits of CT
9. Initial TTO ➩ guided by ‘hr, ir, lr’ PE ➩ lrPE mm at home
10. TTO duration ➩ 3m with antiCOAG for acutePE ➩ decision to continue INDEFINITELY = ⚖️recurVTE 🆚 ↑r BLEEDing = PX prefences
11. FOLLOW UP ➩ focus on: dyspnea ± functLIMIT (postPE syndr OR chrTEPHyp)
2022 MEDPAGE - Should Young+Healthy pxs Take Paxlovid (Adalja) [r].pdf
1. PAXLOVID was game-changing ➩ EUA (Pfizer, Paxlovid) Dec2021
2. ACTIVE INGREDENT ➩ nirmatrelvir = blocks protease enzyme of C19 VIRUS ➩ ritonavir = pharmacological BOOSTER of nirma
3. Start TTO ➩ earlier = better = <5D following SYMPonset
4. AIM of Paxlovid ➩ ↓ likelihood of sC19 (hr groups) ➩ not for lower-risk groups
5. PAX for VACCINATED = YES, if older high-risk pxs = NOT for the rest
6. EUA mentions EXPLICITLY ➩ PAX is targeted EXCLUSIVELY for r sD + symptomatic ➩ PAX FAILEDt o show significant benefit in lower-risk pxs
7. AdvEve ➩ alteration of taste and diarrhea
8. IMP (great interest) ➩ SYMP duration + contagiousness + long-t SYMP r ➩ but PAX does not have DATA.
Tuesday 19.07.22 at 23h15 BE
MKFA, LFMC,
±SGQA, AAQC
❗️REFRESH: yesterday + last Tuesday
2022 NEJMcp - Pulmonary embolism (kahn) [CP].pdf
2022 NEJMcp - Pulmonary embolism (kahn) [CP].pdf
PERC = PE Rule-Out criteria
1. Challenge = when to test?
2. SYMP ➩ 😅 + dys🫁 + chest pain + dizziness + cough + diaphoresis + fever + hemophtysis
3. MA ➩ rf = ⤹ dys 🫁 + immobilization + recent SX + CA + HEMOPTYSIS + ⤹ VTE + sync = ↑ likelihood PE
4. When NO response to TTO for another 🫁 condition = think of PE (test)
5. EPIDEMIO ➩ NorthAmer (NA) 🆚 EUR = EUR is ⊕ FREQUENT (4X) ➩ NA 1/20 tested for PE (ED)
6. GL ➩ do not stipulate who will be tested
7. Qualitative research = physician norms + local cuture = MAJOR DRIVERS to test for PE
8. Noninvasive tests w_CLINICAL PROBABILITY = safe TO ↓ CT scans ➩ 30-40% will undergo DX imaging
9. RULE OUT PE ➩ physician implicit sense (<15%) + PERC = rule out wo_further IMAGING ➩ PERC use limited when ‘implicit estimation OVERstimates the probability of PE’
10. LOW scores [Wells score (≤4) + revised Geneva (≤10, scale 0-22)+ simplified Geneva (≤4, scale 0-9)] + NORMAL D-dimer (see cut-off)= SAFELY rule out PE (SE 98-99%, SP 37-40%)
11. OLDER DATA ➩ D-dimer < 500ng/mL = rule out PE wo_CONSIDERATION of CLINICAL rf ➩ NEED TO BE CONFIRMED for current assays
Wednesday 20.07.22 at 23h15 BE
AAQC
❗️REFRESH: yesterday + last Wednesday
2022 JAMA - Association of Music Interventions With Health-Related Quality of Life (mccrary) [srMA].pdf
2022 MEDPAGE - CDC Updates Testing Recommendations for Unknown Hepatitis in Kids (Walker) [r].pdf
UASH = Unknown acute severe hepatitis in kids
1. CDC ➩ attempts to decipher the origin in kids ➩ released detailed RECOMM
2. CLINICIANS ➩ continue TEST for ADENOVIRUS + collect 🩸 🫁 🐒🔬
3. PARAMETERS to test:
- Ehylenediaminetetraacetic acid > blood
- In 🫁 > 🥢🤤BAL
- Sample 💩 BETTER THAN 🐒swab
- Tissue 🥊 if BIOPSY indicated
- PCR is preferred in 🩸 ALTHOUGH not available
- 109 reported cases ➩ 90% 🧒🏼 hospitalized ➕ 14% req_transplant = all still under INVESTIG
- HYPOTHESIS ➩ other possible causes + contributing factors
- WORLDWIDE ➩ 348 probable cases UASH ➩ 21 countries + 7.4% req_transplant = WHO report
- ADENOVIRUS ➩ seems coincidental RATHER THAN causal = ‘cause NOT DETECTED in liver tissues (although in blood samples)
2022 NEJMjw - Are Four Doses of Pfizer-BioNTech SARS-CoV-2 Vaccine Better than Three (BMJ).pdf
1. 2022, BMJ, IS ▶︎ retros_case-con ➕ 97500 ➕ ❓ ▶︎ P⃣ vax > 60yo (large HC service) I⃣ 4th dose C⃣ 3rd dose O⃣ effectiveness ➩ 65% until 3w + waned ≥10w
2. Expectations dashed due to: waning vax-induced immunity + new variants
3. 29% received the 4th vax (more chronically ill THAN those of the 3 doses)
4. STATS ▶︎ matched for confounders (1st test + month of 3rd dose ) + adjusted (comorbidities + immunosuppressive cond)
5. VAX effectiveness ▶︎ 4 🆚 3 doses = 65% d_3rd week ➩ fell quickly to 22% end of 10w ➩ sC19 WS PREVENTED with 72% REL EFFEC throughout ƒ-up
6. Longer intervals provide better immunity (short ones are allowed in IS)
7. POTENTIAL solutions ▶︎ Modified booster?
Saturday 23.07.22 at 23h15 BE
ALAC, AAQC
❗️ REFRESH: last one and last Friday
2022 NEJM - LOVIT, Intravenous Vitamin C in Adults w_S• In the ICU (Lamontagne) [RCT].pdf
2022 NEJMjw - Clinical Decision Support for Pneumonia [AJRCC
2022 NEJMcp - Pulmonary embolism (kahn) [CP]
1. Newer APPROACHES ▶︎ D-dimer threshold adjustments to rule out = VALIDATED for cutoff 500ng/ml = adjusted for age (Se97-99%; Sp 42-47%) + to YEARS algor (Se96-98%; Sp54-61%) + to Wells score (Se93-97%; Sp61-67%)
2. IMAGING ▶︎ careful w_radiation ➩ CT 🆚 SPECT (↓ lung & breast-tissue radiation in YOUNGER) ▶︎ CT false (+) 5% ▶︎ after 3m of (-)CT = 1.2% VenousThrom ▶︎ SPECT dx performance NOT well stablished
3. mm ▶︎ 1st. Risk of stratification (↑ - ↓) ➩ massive + submassive NOT DICTATE therapy4. hR ▶︎ 5% of pxs = Sø ± endHYPOperf ± ↓ AP (S <90, ↓S >40mmHg not by S•)± 📈 ± ⚡️▶︎ OBS STUDY = do immediate REperfusion BY ruling-out contraIND (🧠 meta, 🩸 diso, ⤹ Sg) ▶︎ 💉 sysThrombolysis ➩ options: tenecteplase, alteplase 0.6mg/Kd, alteplase 100mg d_1-2h. (INSUFFICIENT to know which to support) ▶︎ ED = tenecteplase BOLUS ➖🧓🏼+ lowW = tenecteplase WEIGHT-BASED ▶︎ alterTTO = Sg thECTOMY + Cath-direc thLYSIS ▶︎ addTTO = inoTROPES + EcLS5. iR ▶︎ echo OR CT of ‘r🫀strain’ ± ↑🫀 bioMARKERS ± both ▶︎ sysThromLYSIS ✖︎ ▶︎ RCT ➩ tenecte + heparin = ↓ rHD_descomp 3%points + ↑r 🩸9%points ▶︎ TTO = antiCOAG + closely monitoring (1 in 20) ➩ no GL for door-to-needle ⏳ ▶︎ EXPERT = lmwh for IMMEDIATE antiCOAG ▶︎ NOT YET STUDIES = riva & apix 🆚 lmwh
Monday 25.07.22 at 23h15 BE
MKFA, ALAC, AAQC
❗️REFRESH: last one and same day last week
2022 NEJMcp - Pulmonary embolism (kahn) [CP].pdf
2022 MEDPAGE - Should Young+Healthy pxs Take Paxlovid (Adalja) [r].pdf
2022 NEJMcd - Substitute Decision Making in End-of-Life Care (caulley vs gillick)
1. 70♀ ICU, dyspnea, fatigue, fevers ➕ T2D uncontrolled➕ neighbor & close friend ➕LABS = ↑ WBC ⏤ Xray = blat opacities ➕ DX = H1N1 ➕ SSØ ➩ ARDS, AKI ➩ DETERIORATION 🫁(MV, ↓ PF) ⚯ (DYA)
2. WISHES ▶︎ not written + no designated surrogate ▶︎ CLOSE FRIEND 10y (px did. Not want life-sust measure if sCI + not RESUSCITATION) 🆚 BROTHER (reluctant to consider DNR) 20y wo_CONTACT
3. DNR ▶︎ CPR would be INEFFECTIVE = ▶︎ TECHNICAL COMPONENT ➕ VALUES COMPONENT ▶︎ shared decision making: ENTIRE CARE TEAM & interested PARTIES ▶︎ FUTILITY = avoid the term (current ) = “distanasia” ➩ Texas allows to withdraw life-sustaining
4. WHAT THE PX WOULD WANT = written OR judgment of a surrogate OR others (ministers, friends, neighbors)
5. DEFINITIONS: critical illness + life-sustaining measures ➩ favored withholding TTO (CPR included)
6. SURROGAGE ▶︎ brother is disqualified (due to his LACK OF CONTACT) ➩ SOCIAL WORKER may be helpful to ADRESS guilt or anger (for the brother to endorse DNR)7. AHA ▶︎ “clinicians should not hesitate to withdraw support on ethical grounds when functional survival is highly unlikely”
Tuesday 26.07.22 at 23h15 BE
ALAC, AAH,LFMC, AAQC
❗️REFRESH: yesterday + last Tuesday
2022 NEJMcp - Pulmonary embolism (kahn) [CP].pdf
2022 ICUmmp - Understanding carbon dioxide in resuscitation (Zimmerman) [r].pdf
1. CO2 measurement aim ▶︎ assess resuscitation efficacy
2. AIM ▶︎ current knowledge + future research
3. EPIDEMIO ▶︎ MB & MM = USA 450K 🆚 EU 400k ▶︎ GL = call use of CO2 for CPR
4. PHYSIO ▶︎ CO2 = 70% mitochondria + 23% mitoch-Hb + 7% plasma ▶︎ dissolved CO2 = tranported to 🫁 (PmvCO2, 🫁 artery) ▶︎ If NORMAL CO + 🫁 physio = VQ match is ok ▶︎ PACO2 = ±40mmHg ▶︎ CO2 diff gradient = 5mmHg
5. MEASUREMENT ▶︎ PetCO2 is evaluates INDIRECTLY PACO2 ➩ PetCO2 is “<5mmHg below” (∆CO2 🫁) PACO2 (PaCO2 also in healthy)
6. Changes CO ▶︎ changes ‘a, v, A’ CO2 levels
7. ↓ CO ▶︎ LESS EFFECTIVE CO2 REMOVAL (CO2 accumulates in tissues and venous 🩸 ) = ↓ flow (peripheral & 🫁) ➩ ↓ 🫁 perfusion PRESSURES = mismatch V/Q
8. CA ▶︎ no-flow state = NO organ perfusion ➩ release of cellular by-products = CO2 + lactate + H = resp&metab acidosis = NO CHANGES in CO2 (initially)
9. QUALITY OF CPR ▶︎ achieve 25% of n_CO = converting NO-FLOW to LOW-FLOW ➩ compressions _ ppVentil
10. LOW FLOW ▶︎ ↑ PmvCO2 ➕ decoupling PetCO2 (↓) - PaCO2 (↑) due to POOR ALVEOLAR Q
11. CPR PERFORMANCE + OC ▶︎ change in CO2 = CO2 pressure in SYST & 🫁 & ALVEOLAR (reflected by PetCO2)
2022 NEJMcd - Substitute Decision Making in End-of-Life Care (caulley vs gillick)
CONTINUE FULL RESUSCITATION MEASURES
1. Highest priority to FAMILY MEMBERS ▶︎ legal justification + moral ground = to the brother ▶︎ IMP & deepest commitments ARE OFTEN TO FLIA (choose the best for px) = most likely affected
2. STEPWISE HIERARCHY ▶︎ 1st. pxs’ advance directive 2nd. Substituted judgement 3rd. Pxs’ best interest ➩ 2nd IN PRACTICE can be DIFFICULT
3. DECISION CHANGES ▶︎ preferences EVOLVE with their clinical situation ➕ people change their minds ➕ hold onto life at all costs = WHEN CONFRONTED with real possibility of DEATH
4. BEFORE any advance directive rigidly followed ➩ FLIA & PHYS can participe in RESUS decisions (brief intubation) = the discussion of px with neighbor can be taken only as a comment
Saturday 30.07.22 at 23h15 BE
GATL, MKFA, AAQC
❗️ REFRESH: previous JR&JC same topic
Saturday 09.07.22 at 15h00 BE > EACQ, AAQC
Wednesday 13.07.22 at 23h15 BE > AAQC
2022 JAMA - Association of Music Interventions With Health-Related Quality of Life (mccrary) [srMA].pdf
TAU = treatment as usual alone MOD-Q = “the true effect is probably close to the estimated effect”, LOW-Q = (ie, “the true effect might be markedly different from the estimated effect”; 2022 = current study = ‘pre-post and vs TAU’; SMD = standard mean difference
1. PRE-POST changes ▶︎ ↗️ MCS+PCS from pre I⃣ ▶︎ mod-Q evidence
2. MUSIC + TTO 🆚 TAU ▶︎ I⃣ ↑MCS scores (3.7 points, p=0.03) ➩ ↑MCS scores DID NOT VARY w_: quality OR type ➕ NO heterogeneous OR smallStud &publication BIASES ▶︎ MINIMALLY affected by indStudyBIASES ▶︎ LIMITED by wide CI ▶︎ MOD-Q evidence
3. Music LISTENING 🆚 MEDITATION ▶︎ NO DIFF MCS or PCS (3 studies) ▶︎ NO heterog OR smallStud & publication BIASES. ▶︎ LIMITED by small # studies + wide CI ▶︎ LOW-Q evidence
4. Graphs analyses ➩ discussion of RECOVERY reports regarding SAMPLE SIZE, TIME OF STUDY, and other variables
5. HRQOL ↔ music in CONTEXT ▶︎ MCS ‘pre-post I⃣ and vs TAU’ exceeded the THRESHOLD (3 points DIFF) ➩ PCS did NOT EXCEED.
6. WEIGHT LOSS study (Obes Rev. 2014) ▶︎ pxs w_obesity ➩ MCS changes (2022) similar to PCS changes (2014)
7. RESISTANCE study (Health Promot Perspect. 2019) ▶︎ SMD in MCS & PCS (2022) smaller than DIFF MCS & PCS (2019) ➩ elderly pxs & volunteers 🆚 controls
8. MIXED MODES OF EXERCISE study (J Phys Ther Sci. 2015) ▶︎ SMD in MCS & PCS (2022) smaller than DIFF MCS & PCS (2015) ➩ knee osteoarthritis 🆚 inactive OR psycho-educational CONTROLS
Thursday 21.07.22 at 23h15 BE
ALAC, AAQC
❗️REFRESH: last one and same day last week
2022 NEJMcp - Pulmonary embolism (kahn) [CP].pdf
2022 MEDPAGE - Should Young+Healthy pxs Take Paxlovid (Adalja) [r].pdf
2022 ISICEMc - ICU nutrition: practical consideration
1. ICU, if cannot eat 60% start EN within 48 h
2. CI: upper active GI 🩸, uncontrolled Sø,🫃🏽 ischemia, obstruction, Sg planned, residual vol >500mL/6h, ACS, h_OPfistula, intestine not usable (9)
3. NOT ↑ MM by 💉 route (PN) = SAME SAFETY as EN = Expense is high with PN
4. On D4, be on target = ESPEN GL (cal + prot) ➩ MA + r = D3-7 use supplementary nutrition (PN)
5. Prof. Ismaer (Vienna) paper = nutrition in ICU is bad = takes 14d to get to the target
6. Pieroni (Bologna) = C19, pxs are not WELL fed
7. DeWaele = they only achieved 70-75% prot + cal in C19 pxs
8. We are UNDERFEEDING - not OVERfeeding
9. TARGET for every px (we need to have a plan):
- 1.3g /Kg of protein/day (PROT)
- Body composition analysis (PROT)
- CAL = individualization is IMP
* nonMV: 20-25% Kcal/Kg/d
* MV: indirect calorimetry
* NON intentionals = glucose, propofol ➩ measure every 24 h
10. Susman + Singer (TelAviv) = dosing of CAL ↔ PROT ↔ OC
11. MET + NUT needs ➩
12. BE (Waele) + USA (Wishmeyer) + TelAviv = METABOLISM ↔ WBC + T + min/vol + ICU LOS + height… albumin… = NOT CRP = the hyperinflamation does not dictate the basal energy
13. Min 8:45 ➩ basal energy expenditure = med 23Kcal/Kg/d for BMI 30 (peak at 12, for BE) + peak at day 14 (USA) ⏤ the hyperMETAB IS LATER ON ➩ MEASURE the status every day
14. hBMI make the equationS not good
15. “20-25Kcal/Kg/d” = 30% fit there = 70% do not fit there ESPECIALLY hBMI (analogy with ANTIfungals)
16. WIN APPROACH (to avoid errors)
* Invest ➩ dietitians, nurses, doctor for nutri
* ESPEN Protocol
* 48h in EN = do not WASTE time
17. VITAMIN + trace elements + monitor GLU + REfeeding (if PO4 <0.65 STOP 1d to give PO4)
18. postICU ➩ CVC, 60% of oral intake19. TO READ: * NEJM 2014 - in the acute phase of critical illness
Friday 22.07.22 at 23h15 BE
GATL, EACQ, AAQC
❗️REFRESH: yesterday + last Friday
2022 NEJM - Targeted Therapy in Melanoma (Rokhzan) [img clinical].pdf
2022 MEDPAGE - Lower Long COVID Risk Tied to More Vaccine Doses (JAMA).pdf
2022 NEJM - LOVIT, Intravenous Vitamin C in Adults w_S• In the ICU (Lamontagne) [RCT].pdf
1. pOC ▶︎ ‘MM or pOD’ 28 (vp + iMV + nRRT) ➩ ↘️ I⃣ (p=0,01) ➩ RR 1.15 ➩ best case-worst case SIMILAR
2. sOC ▶︎ D wo_OD to 28d (CI -7.23 to 2.37)➕ MM 28d (CI 0.98 to 1.4) & 6m ➕ QOL6m ➕ OFail 2,3,4,7,10,14, 28 ➕ lactate ➕ inflammation (IL1ß & TNFå) ➕ endothelial injury (thrombomod & angiopoietin2) d3 & d7 ➩ NO DIFF ➩
3. QOL ▶︎ EQ-5D-5L = the European Quality of Life–5 Dimension 5-Level = mobility, personal care, usual activities, pain or disco, anxiety or depre
4. OF ▶︎ SOFA (6 systems) ⏤ APACHE II ▶︎ severity
5. AdvEfe ▶︎ AKI3 + homely + ↓GLU + serious = all reported
6. DATE ▶︎ Nov2018 - July2021
7. PXS ▶︎ total 872 ➩ 8 error + 1 withdrew consent = 863 pANALY (±430 each group)
8. CHARACTERISTICS = similar ➩ STAY = 6d ICU + 16d H+ ➩ C19 similar in both groups
2022 NEJMjw - Clinical Decision Support for Pneumonia [AJRCC]
ePNa = electronic pneumonia clinical decision support tool, BL= BASELINE
1. 2022, AJRCCM, USA ▶︎ prosOBS ➕ ±7K ➕ 2m interval in 2017 - 2018 ▶︎ P⃣ ED pxs I⃣ ePNa BEFORE and AFTER C⃣ ✖︎ O⃣ Discharge + MM30
2. 4 scenarios ▶︎ ED ➕ ICU ➕ H+ ward admission ➕ outpatients
3. RESULTS:
- ED = ↗️ (discharges and all-cause MM30) after ePNa
- ICU = ↗️ sev-adj MM30 after ePNa (p=0.01)
- H+ ward admiss = SIMILAR MM30 (p=0.09)
- OUTpxs = SIMILAR MM30
4. BL CHAR ▶︎ different❓ = might have driven some of the benefit
5. SHOWS PROMISE ▶︎ IF these results can be replicated at other institutions.
Monday 01.08.22 at 23h15 BE
MKFA, AAQC
❗️REFRESH: last one and same day last week
2022 NEJMcd - Substitute Decision Making in End-of-Life Care (caulley vs gillick)
2022 JAMA - Association of Music Interventions With Health-Related Quality of Life (mccrary) [srMA].pdf
2022 NEJM - CLASSIC, restriction of Intravenous Fluid in ICU pxs W_ septic shock (Meyhoff) [RCT]
1. CLASSIC ▶ NEJM, 2022, DEN, NOR, SW, SWIT, IT, CR, UK, BE (8 sites) ▶ 2. INT_stra_pg_ol_RCT ➕ >1.5k (31 ICU: I⃣ 770 🆚 C⃣ 784) ➕ Nov2018-Nov2021 ▶ P⃣ SS• I⃣ restrictive (≥1L of fluids) C⃣ standard O⃣ pOC: MM90 ▶ sOC: days alive wo_LIFEsupp + day alive and ooH
IN ▶ adults (≥18yo), ICU, SSø (suspORconf INF, lact≥2, vpORiono infusion, 1L 💉 solution before), <12h shock
3. EX ▶ SS• >12h, pregnant, no consent, life-threatBleed, burn >10%
4. CLASSIC trial (revisited) ▶︎ SSø ▶︎ restrictive vs standard fluid volume
5. Restrictive ▶︎ given only in response to SPECIFIC clinical parameters
6. Median FLUID VOL ▶︎ after 90 days = I⃣ 1798 🆚 C⃣ 3811 ➩ standard doubled the restrictive
7. DEATH 90D ▶︎ 42.3 I⃣ 🆚 42.1 C⃣ (P=0.96)
8. sOC ▶︎ ≥1 sAdvEve = 29 🆚 31% ➩ dALIVE wo_LifeSupp = 77 🆚 77 ➩ dALIVE+outOfH+ = 21 🆚 33
2022 MEDPAGE - Should Young and Healthy Pxs Take Paxlovid (Adalja) [News].pdf
1. EUA in Dec2021 for unVAX hr_sDP
2. Recents studies ➩ …
3. Recalled: Monday 18.07.22 at 23h15 BE
Tuesday 02.08.22 at 23h15 BE
AAH, AAQC
❗️REFRESH: yesterday + last Tuesday
2022 ICUmmp - Understanding carbon dioxide in resuscitation (Zimmerman) [r].pdf
2022 NEJMcd - Substitute Decision Making in End-of-Life Care (caulley vs gillick)
2022 NIH - Q&A, C19, Vaccines, + Myocarditis (News)
1. NHLBI: National Health, Lung and Blood Institute
2. Americans Vaccinated >590M doses ➩ Dec2022 and Jun2022
3. VAX is by FAR less likely to cause MYOCARDITIS than COVID-19
4. TW w_Jerome Fleg = program officer NHLBI
SYMP = chest 😩 ➕ fever ➕ fatigue ➕ shortnessOFbreath ➕ ↑📈 pulse ➩ can have SERIOUS COMPLICATIONS = 🫀failure + Sø + MM
5. TTO ▶︎ 💉 fluids + steroids + tto for 📈 🫀(pump)
6. EPIDEMIO ▶︎ UNCOMMON COMPLICATION ▶︎ 40 per 1M in ⊕ cases ➕ 226 per 100k in Hº
7. JCC 2020, Ho et al ▶︎ 70% male, age 56 = 51 pxs ➩ rf for sC19 illness = hBP, DM, 🐷
8. USUALLY it is mild = with ret and supportive TTO is ENOUGH
9. AGES MORE COMPROMISED ▶︎ 16-29 ➕ after 2nd dose = because STRONG immune response to the VAX
10. All VAX have side effects ▶︎ MYOCARDITIS was linked with other VAX = influenza, smallpox, shingles
11. YOUR chance of getting myocarditis after getting a C19 vax IS LESS than the chance of being STRUCK BY LIGHTING during your lifetime. Klamer et al. 2022, Cordero et al. 2022
12. MUSIC INT may present a ↑ attractive and effective nonPHARMA ALT to other healthINT.
Wednesday 03.08.22 at 23h15 BE
AAH, CCH,
±GSQA, AAQC
❗️REFRESH: yesterday + last Wednesday
2022 NEJMcd - Substitute Decision Making in End-of-Life Care (caulley vs gillick)
2022 NIH - Q&A, C19, Vaccines, + Myocarditis (News)
1. Benefits of VAX outweigh the VERY SMALL RISK of vax-related myocarditis
2. MYOCARDITIS IN VAX ▶︎ < 20 per 1M C19 vax ➩ Pfizer + Moderna
3. SYMP ▶︎ 95% just mild symptoms
4. SEVERE ▶︎ 1 out of 100 cases (life-threatening) ▶︎ ANALYSIS ➩ 627 of vax-myo = 626 FULLY recovered and 1 MM ▶︎ more severe in OLDER + OTHER HEALTH CONDITIONS
5. CONSEQUENCES ▶︎ long-lasting 🫀 damage or DEATH ▶︎ ANALYSIS ➩ 400pxs w_C19-related myo = 15% DIED (within 6m)
6. WHY TESTING VAX did not show r_MYO? ▶︎ because the studies were not LARGE ENOUGH to detect VERY RARE complications
7. C19-VAX-rel myocarditis ▶︎ 16-29yo = 7x - 8x MORE COMMON (myo) after C19 INF
8. CDC ▶︎ recommends VAX since 6m
9. FACTORS to think about VAX CHILDREN ▶︎ rates of C19 INF ➕child’s overall health ➕ parents’ assessments of RISKS
10. MMWR 2022 ▶︎ in teenaged BOY = rMYO in 2-5x AFTER C19inf than C19vax
11, STUDY ▶︎ ENGLAND = 12-17yo = VAX prevented 4,5k + 300 ICU Hº + 36 MM = in summer 2021
12. HILDREN myo_C19vax ▶︎ BENEFITS ➩ ↓r_of: Hº + ICU admission + NEED ventilator (compared to myo_C19inf) ▶︎ preprint
2022 JAMA - Association of Music Interventions With Health-Related Quality of Life (mccrary) [srMA].pdf
TAU = treatment as usual
1. REFRESH OF THE STUDY ▶︎ srMA ➕<800 pxs ➕ up to
2. MA 26 studies ▶︎ music INT in mental HRQOL ▶︎ 8 studies = ↗️ clinically sig changes to MENTAL HRQOL (SMALLER in physical) ▶︎ general guide
3. HETEROGENEITY ▶︎ populations & geo location ➕ MUSIC types & doses ➕ TAU control group ▶︎ no statistical heterogeneity or BIAS (small study or publication)
4. MUSIC interventions ↔ MCS scores ▶︎ are within the range (low end) OF scores with STABLISHED non-pharma/med , pharma/med, health INT
5. SIMILAR TO prior sr ▶︎ uptake and adherence ➩ persist w_non-pharma MED INT (weight loss, exercise
Thursday 04.08.22 at 23h15 BE
MKFA, AAQC
❗️REFRESH: yesterday + last Thursday
2022 NEJMcd - Substitute Decision Making in End-of-Life Care (caulley vs gillick)
2022 ICUmmp - Understanding carbon dioxide in resuscitation (Zimmerman) [r]
OHCA = out of H+ cardiac arrest
1. CO = 5L/min (healthy) ➩ CO ‘1L↓’ = PetCO2 ‘4-6mmHg↓’
2. PetCO2 = effective surrogate of 🫁Q ▶︎ ‘Quant waveform capnography d_resus’ ↔ CO + 🫀Perf
3. srMA ▶︎ achieved (PetCO2 36±10 mmHg) 🆚 not achieved ROSC (PetCO2 13±8 mmHg), p=0.001 ➩ NaHCO3 + Vmin + ResusProtoc NO↔ w_PetCO2 changes
4. AHA + ERC ▶︎ recommend QuantWavef capnography in CPR to OPTIMISE: ‘chest compressions’ + ‘indentify ROSC’
5. Arterial CO2 was studied during or after ROSC
6. pCO2 determine ➩ Venus + arterial acidosis
7. Acidosis: Venus>arterial
8. ↑ acidosis d_CPR ➩ failure of CPR
9. Study ▶︎ 136 OHCA: ROSC in less profound acidosis (6.85 vs. 6.96, p=0.009)
10. PaCO2 + lactate were ↓ in px who achieved ROSC
11. PaCO2 < 80, lactate close to 10 ➩ achieved ROSC.
12. PaCO2 d_CPR may be an ischemia severity marker
13. < acidosis + < PaCO2 related to scope of ROSC
14. ↑ ∆ PaCO2 - PetCO2 (AaDCO2) related to CPR failure
15. mc study ▶︎ ↑ AaDCO2 dur_ or post_CPR in OHCA ➩ failure for sustained 16. ROSCAaDCO2 > 33.5 dur_ CPR ➩ ROSC not reached.
Monday 08.08.22 at 23h15 BE
MKFA, AAQC
❗️REFRESH: last one and same day last week
2022 NEJM - CLASSIC, restriction of Intravenous Fluid in ICU pxs W_ septic shock (Meyhoff) [RCT]
2022 MEDPAGE - Should Young and Healthy Pxs Take Paxlovid (Adalja) [News].pdf
2021 JAMA - Association of Social Support With Brain Volume and vuln = vulnerability, FS = Framingham study, SNI = Berkman-Syme Social Network Index,
1. CEREBRAL VOL ▶︎ 🧠 structure ↔ cogn ➩ ↑ cognResilience = ↓ß values ▶︎ 2. MRI = total cerebral VOL (measure of early ADRD vuln)
MRI + neuroPsy = same day
3. FS MRI QUANTIFICATION ▶︎ a. imaging param&sequences, b. Mesurement protocols, c. Segmentation methods, d. Reliability, e. Reproducibility ▶︎ VOL measures CORRECTED for head size (ratio 🧠vol/ total 💀vol * 100)
4. SOCIAL SUPPORTS ▶︎ SNI = self-report = MEASURES: a. social network size, b. type, c. frequency of SOCIAL SUPPORT (provided by respondent)
5. SNI ▶︎ 5Q: current situation (none, little, some, most, all OF THE TIME) = forms: listening ➕ advice ➕ love-affection ➕ emotional support ➕sufficient contact
6. PRIMARY analysis ▶︎ dichotomous: higher level (most, all OF THE TIME) 🆚 lower level (none, a little, some OF THE TIME)
7. OVARIATES ▶︎ parsimoniously assessed char + SELECTED COVARIATES A PRIORI (to maximize comparability)
Common rf for ADRD: age, sex, educaAttainment
Age squared: nonlinear age & 🧠VOL
Interval: years FROM social support to ‘’MRI & neuroPsy’
Depressive SYMP: by CentEpidemoiStud-Depress scale = cutoff 16
Educational attainment: 3-level variable (NO, SOME, COLLEGE graduate)
DNA genotype: apolipoprotein ε4 carrier status.
8. ↓ p value = directly proportional modification ➩ vol 🆚 cog
9. ↑ p value = no MODIFICATION ➩ vol 🆚 cog
Thursday 11.08.22 at 23h59 BE
AAH, AAQC
❗️REFRESH: yesterday + last Thursday
2022 ICUmmp - Understanding carbon dioxide in resuscitation (Zimmerman) [r]
2022 JAMA - Association of Music Interventions With Health-Related Quality of Life (mccrary) [srMA]
1. N = >2.1k ➩ 164 original ➕ 2007 offspring
2. Samples and availability of SocSupp = OTHER COHORTS (community-based)
3. >65yo ➩ no CollDeg (45%), HTA (63%), CVD (22%)
4. Compared to YOUNGER ➩ OLDER < 🧠 VOL + global CogFunc
5. Age groups ▶︎ NO DIFF by APOLIP E4 + DEPRESIIVE symp
6. Time interval: neuroPsy ↔ MRI = 0.8y ➩ associations varied by DOMAIN
7. SocSupp INTERACTIONS ▶︎ listener AVAILABILITY ↔ TOTAL 🧠 VOL ➩ in identifying GLOBAL COG
8. ↑ 🆚 ↓ listener availability ▶︎ CogPerf ➕ 🧠 VOL
9. INTERACTIONS were ABSENT ▶︎ 4 SocSupp domains: advice + love-affection + emotional support + sufficient contact
10. LISTENER AVAILABILITY ▶︎ present in <65yo, p=0.02 (not in ≥65yo, p=0.61)
11. SocSupp + CogResil ▶︎ ↑ listener AVAILABILITY modify ‘🧠 vol ↔ GlobCogScore’, p<0.001 ➩ most evident in YOUNGER
12. <65yo + ↓ listAvail ➩ ↓🧠VOL ↔ ↓GlogCogPerf, p=0.01
13. <65yo + ↓ listAvail ➩ «1SDU ↓ 🧠 VOL = 0.17SDU ↓ CogPerf»
14. <65yo + ↑ listAvail ➩ «1SDU ↓ 🧠 VOL = 0.01SDU ↓ CogPerf»
15. SENSITIVITY ANALY ▶︎ persisted with 5-level socSupp variable
16. The decrease in global cognition with lower cerebral volumes was more pronounced for participants with low listener availability than for those with high listener availability.
2022 ICUmmp - Understanding carbon dioxide in resuscitation (Zimmerman) [r]
Post-OHCA in ICU ▶︎ ↓ PaCO2 ↔ POORER prog ▶︎ rel ↑ CO2 ↔ IMPROVED cerebralFunction ➩ due to hypocapnia 🧠 effects ▶︎ HYPERcapnia ↔ ↑ MM
During + immediaPostREsus ▶︎ ↑ PaCO2 ↔ POORER PROGLater POSTresuss ➩ ↓ PaCO2 ↔ POORER PROG
Wednesday 17.08.22 at 23h15 BE
AAH, MKFA,EACQ, AAQC
2022 NEJM - LOVIT, Intravenous Vitamin C in Adults w_S• In the ICU (Lamontagne) [RCT]
1. pOC ➩ MM or pOD 28
2. pOD ➩ use of VP or iMV or nRRT
3. sOC ➩ D_wo_OD, MM 28D + 6m ➕ QOL 6m ➕ SOFA ➕ BIOMARKERS (lactate, IL1ß, TNFalfa, thrombomodulin, angiopo2) at D3 + D7 ➕ OD D2,3,4,7,10,14, 28 ➕ APACHE
4. POTENTIAL AdvEve VIT C ➩ S3 AKI ➕ acute hemolysis ➕ hypoglycemia
5 .PRIMARY ANALYSIS = ITT ➩ superiority of Vit C ▶︎ SECONDARY = MM28 in 2 models (unadjusted + adjusted) ▶︎ DATA AND SAFETY MONITORING = 2 planned interim analyses ▶︎ SUBGROUP = age, sex, frailty, severity, SS•, baseline VitC
6. Points missing to write down - we continue tomorrow
7 .Deeper understanding of STATS + SUBGROUP analysis
8. We see ALBIOS to compare deets
Thursday 18.08.22 at 23h59 BE
AAH, AAQC
2012 NEJM - BEST TRIP, a Trial of ICP Monitoring in TBI (Chesnut) [R]
BEST:TRIP = Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure
w_bSPEC_TTO: with brain specifi treatment
1. BEST:TRIP:
2012, NEJM, BO+EC ▶︎ mc_pg_RCT ➕ >300pxs ➕ Sept2008-Oct2011 ▶︎ P⃣ sTBI >13yo I⃣ pressure-monitoring C⃣ imaging-clinical examination O⃣ pOC: composite ‘tSS, iCONS, funcSTATUS 3m&6m + neuroPsychoSTATUS 6m ➩ NO DIFF
2. IN: ≥13yo ➕ GCS 3-8 (M 1-5 if MV) ➕ GCS that drops (3-8) within48h a_injury
3. EX: GCS 3 ⏤ ↔ fixed & dilated PUPILS ⏤ unsurvivable injury ⏤ complete list (SUP)
4. sOC: LOS ICU (total ICU days & No ICU days w_bSPEC_TTO) ➕ systCOMPLI > pos hoc sOC: H+ LOS + days VM + tto hDOSE barbituratees OR decomprCraniec + therapIntensity
5. bSPEC_TTO = tto for icHTA = hyperOSM + pressors + hyperventi = EX: ventilation, sedation, analgesia
6. EPIDEMIO:
monitoring ICP: widely recog BUT incomplete acceptance
GL showed inadecuate efficacy evidence (call for RCT + ethical issue)
Ethical constraint ELIMINATED: intensivists in LA manage sTBI wo_MONITORS
7. EBM:
RCTs are lacking
few HQ, pros_case-control OR cohort conducted
8. THEORY: monitoring-based mm, confounding factors:
involvement of intensivists
development of neuroCC (subspecialty)
improvements in RESUS (trauma)
myriad developments in mm TBI d_preH ED care, ED care, rehabilitation
improvements monit&mm ICU
9. ClinOC table 2 analysis
Friday 19.08.22 at 23h15 BE
AAH, MKFA, AAQC
❗️REFRESH: yesterday + last Friday
2012 NEJM - BEST TRIP, a Trial of ICP Monitoring in TBI (Chesnut) [R]
2012 NEJM - BEST TRIP, a Trial of ICP Monitoring in TBI (Chesnut) [R]
1. BEST:TRIP trial
2. METHODS:
- Study design = type, stratification (site, severity, age), recruitment (3 BO H+… later 1 BO + 2 EC), staff (intensivists, 24-h CT, neuroSx, hVOL trauma pxs)
- Eligibility = screen (all pxs w_TBI), IN, EX, consent.
- Group ASSIGN + INT = computer, stratification:
* Site = ✔︎
* Severity = ‘GCS 3-5 or M 1-2’ 🆚 ‘GCS 6-8 or M 3-5’
* Age = <40yo 🆚 ≥40yo (block 2-4)
- Group ASSIGN + INT = protocol: 3CT (baseline, 48h, 5-7d) + suppCare (MV, sed, analg), mm (agressive for nonNEURO) + intraPAREN monitoring (goal ICP <20) w_GL sTBI, drainage CSF required ventriculOSTOMY, image-clin examination (followed the protocol: 3 original H+), in absence of MASS requiring Sx (icHTA was tto w_ a. hyperosmolar therapies, b. mild hyperVENTI, c. optional ventricular drainage, continuing edema (hDOSE barbiturates), additional tto (if neuroworsening, PERSISedema, PERSISicHTA)
3. Kaplan-Meier SURVIVAL plot
Saturday 20.08.22 at 23h15 BE
AAQC
❗️REFRESH: yesterday + last Saturday
2012 NEJM - BEST TRIP, a Trial of ICP Monitoring in TBI (Chesnut) [R]
❗️WEEK REFRESH APPROACH
Analysis for topic of the week:
Nuestra metodología de *lunes* consiste en:
➩ 10 min = refresh (día y semana previa)
➩ 30 min = *statistical analysis* de los JC
➩ 5 min = artículo de *novedad o urgente*
➩ 15 min = prolongación _según prioridades_
Nuestra metodología de *martes* consiste en:
➩ 10 min = refresh (día y semana previa)
➩ 30 min = *review article* programado
➩ 20 min = *último JC revisado*
Nuestra metodología de *miércoles* consiste en:
➩ 10 min = refresh (día y semana previa)
➩ 30 min = *clinical case article* programado
➩ 5 min = artículo de *novedad o urgente*
➩ 15 min = prolongación _según prioridades_
Nuestra metodología de *jueves* consiste en:
➩ 10 min = refresh (día y semana previa)
➩ 35 min = *artículos de novedad o urgentes*
➩ 15 min = prolongación _según prioridades_
Nuestra metodología de *viernes* consiste en:
➩ 10 min = refresh (día y semana previa)
➩ 30 min = *clinical case article* programado
➩ 20 min = *review article* programado
Nuestra metodología de *sábado* consiste en:
➩ 30 min = *refresh* de toda la *semana*
➩ 15 min = *JC sabatino* de la semana previa
2022 JAMA - Association of Music Interventions With Health-Related Quality of Life (mccrary) [srMA]
MCS: mental component summary,
1. DISCUSSION:
a. targeted research (for insights into MECHS of music INTERV w_(+) QOL)
b. DIFF absence (types & doses) = intriguing (NOT definite) = due to divers_Popula&Interv
c. Broad CI in R = ±reflect divers_inter
d. 2021 alys = MechsMusic are COMPLEX & SPECIFIC to distinct settings (∑ targetetStudy needed)
e. Other analy = Identify PhysiolMECHS to easy target research & generalize
2. LIMITATIONS:
a. Broad IN = limited to particular scenarios ≠ MA needed for EVEN gralQuantSynth
b. SMD = prone to Bias + interpret w_caution (similar ES_C in MCS - additional confidence)
c. Only SF-36 or SF-12 = skewed subsets of musInterv (BUT: statHomogen + absenceApparentPubl + smallStudBiases + broadPsychoRigor_SF36&12) d. This subset ‘not representative’? OR SF36-12 do NOT completCapture the IMPACT of musiOnHRQOL
Monday 22.08.22 at 23h15 BE
AAH, AAQC
❗️REFRESH: last one and same day last week
2022 JAMA - Association of Music Interventions With Health-Related Quality of Life (mccrary) [srMA]
2022 LANCET - RECOVERY Baricitinib in pxs admitted to hospital W_ C19 [RCT]
2022 NEJM - LOVIT, Intravenous Vitamin C in Adults w_S• In the ICU (Lamontagne) [RCT]
estEff = estimates of the effect
1. MA vs RCT
2. MA (LANCET, 2022 - Baricitinib): type of analysis
intention-to-treat: compared I⃣ to C⃣
OBS: unstratified random - Baric were slightly OLDER ➩ following the plan for IMBALANCES, estEff were ADJUSTED FOR AGE
Adjustment ➩ <70, ≥70 to <80, ≥80
Sensitivity: wo_adjustment, w_furtherAdj for other predefined subgroups
3. RCT (NEJM, 2022 - VitC):
Previous studies: similar population ➩ rMM28øpOD in C⃣ = 50%
Power = 80% to DETECT betGroupDIFF of 10%points w_0,05 (two-sided type I error)
Sample: 400 per group = to account for WITHDRAWAL (consent) and LOSS (follow-up)
C19: pxs w_sC19 would participate (ethics comm) + sample size was inflated (to include #intended pxs wo_C19)
2022 HEALIO - AF a risk factor for dementia in adults younger than 70 years (Salvaryn) [r]
DEM = dementia
1. 2022, JAHA, IT (Modena) ▶︎ srMA ➕ 1.6M (6 studies) ➕ ? ▶︎ P⃣ adults w_AF I⃣ no History of AF vs historyAF or DxAF_baseline C⃣ - O⃣ dementia ➩ IT IS ASSOCIATED (RR=1.5, 95%CI 1-2.26)
2. Age affected = 65-70yo
3. R: 3 reported incidence OVERALL demential at all ages + early-onset dementia ➩ Dx was identified = HºDISCH, admissREC, a_confDX
4. Adjustments = stroke + vascularDemen = RISK REMAINED (RR=1.38, 95%CI 0.91-2.11)
5. AF + early-onsetDEM strengthened at OLDER AGES = <65 (1.06), <67 (1.81), <70 (2.13)
6. 95%CI for <65 = 0.54-2.06
7. Findings were CONSISTENT with AF + dementiaRisk = supports by other studies (AF therapy in DEM preventioN)
Tuesday 23.08.22 at 23h15 BE
AAH, AAQC
❗️REFRESH: yesterday + last Tuesday
2022 LANCET - RECOVERY Baricitinib in pxs admitted to hospital W_ C19 [RCT]
2022 NEJM - LOVIT, Intravenous Vitamin C in Adults w_S• In the ICU (Lamontagne) [RCT]
2022 NEJMcp - Pulmonary embolism (kahn) [CP]
D-d: D-dimer, VTE: venous thromboembolism
1. Decision to test = ASSESS likelihood of PR (≥15% vs <15%)
- <15% = very unlikely = see PERC
• if (+) CHOOSE ‘strategy & combination w_D-dimer’ =
• if (-) PE RULED OUT
- ≥15% = CHOOSE ‘strategy & combination w_D-dimer’
2. CHOOSE ‘strategy & combination w_D-d’:
- Above vs below THRESHOLD
- ABOVE: options 1, 2, 3 (above) OR D-d a, b, c (at or above)
- BELOW: options 1, 2, 3, 4 AND D-d a, b, c
3. Option 1 = wells score (neg ≤4 ) ➖ option 2 = revGeneva (neg ≤10) ➖ option 3 = simGeneva (neg ≤4) –– option 4 = ‘(-) YEARS & D-d <1000ng/mL’ OR ‘(+) YEARS & D-d <500ng/mL’
4. Option a = D-d (neg: <manufRecomm_cutoff) ➖ option b = D-d (neg: <ageAdjustedCutoff) ➖ option c = D-d (neg: <1000ng/mL)
5. If ABOVE = CT angio OR ventil-perfSPECT
6. TTO = DOAC 1st line = do NOT necessitate monitoring (RCT) = as EFFECTIVE as VitK_antag (rRECURR VTE)
7. DOAC comparison is lacking = ∑ CHOICE OF AGENT guided by PHARMA properties + pxs charac + pxs prefer
8. CA: apixaban + edoxaban + rivaroxaban ARE safe&eff (as alternatives to LMWH)
9. RISK of AdvEve
- hrPE: Sø, eoHYPO, hypoTA, CA
- irPE: rHEART strain (image), ‘highTROP_or_BNP_or_both’
- lrPE: the rest
10. One decision tool: NO Hestia OR simpPESI OR implicitAssess (wo_IV med or O2, homeSupp, NOTr_imminBleed) = then DECIDE if SUITABLE for dischange
Wednesday 24.08.22 at 23h15 BE
AAH, MKFA, AAQC
❗️REFRESH: yesterday + last Wednesday
2022 NEJMcp - Pulmonary embolism (kahn) [CP]
2012 NEJM - BEST TRIP, a Trial of ICP Monitoring in TBI (Chesnut) [R]
bsTTO = brain-specific treatment
1. PostHoc_secOC: HºLOS + #D_w_MV + tto highDose barbiturates OR decomprCraniec + therapIntensi
2. Analys on INTERV: duration of therapy = #d from INJURIY until last bsTTO
3. Analys on SURVIVORS: pxs >1d a_last_bsTTO
4. All bsTTO were integrated (summing per hour)
5. Oversight: U.Washington ethics OKed ➖ authors = accuracy + completeness + fidelity ➖ Integra (company) donated catheters + support ➖ Integra had NO ROLE on design + conduct + analysis + writing
6. S. participants
- Last f-up May2012
- Stopped when SAMPLE SIZE was attained
- Before RANDOM were EX 39% of 528 (elegible)
- After RANDOM, 92% were followed for 6m OR until MM
- Few violations
- Baseline characteristics SIMILAR
- Primary cause TBI = traffic incidence
- Transport by ambulance (1st H+) = 45%
- Median time: to arrival 1h (direct) ➖ 2.7h (transfers) –– injury-arrival 3.1h
- No INFO of preH+ INT
7. Initial INJURY
- GCS dropped = 24%
- GCS motor = 4 at RANDOM = 49% localizBrainInj = 0 followingCommands = nonReact Pupil 44%
- AbbreInjScal (0-6, higher is worse) = median 5 = 82% had ≥4
- CT = grade III diffuse injury 43% + mass lesions reqSx 33%
- MesencephaCIst COMPRESSED in 85%
- MidLin shifted >5mm in 36%
8. grade III diffuse injury = ‘swelling + compressBasaCist’ wo_MASS or MidLineSHIF>5mm
Thursday 25.08.22 at 23h59 BE
AAH, MKFA, AAQC
❗️REFRESH: yesterday + last Thursday
2012 NEJM - BEST TRIP, a Trial of ICP Monitoring in TBI (Chesnut) [R]kkq
2022 CNBC - Monkeypox cases jumped 20% in the last week to 35,000 across 92 countries, WHO says (Kimball) [news]
MSM: men who have sex with men
1. Kepoints
- INCREASED from 7.5K to 35k > 92count (WHO)
- Nearly all in Europe + Americas > MSM
- VAX are limited > supplies + data (effectiveness)
2. Deaths = 12 reported
3. Jynneos (US) = Danish company = supply is limited and data is SPARSE
4. AGAIN a problem of EQUITABLE ACCESS (poorest will be left behind)
5. VAX > vaccinated breakthrough cases after exposure STILL FALLING ILL + vax as preventive is not working (becoming infected).
6. VAX administration > after (↓r sD) OR before exposure (↓r INF)
7. MOST IMPORTANT = precautions MSM (#sexual partners + avoid group/casual sex)
8. Study > 1980 > smallpox VAX = effectiveness 85% (prevent monkeypox) > Jynneos approved US 2019 > not 100% EFFECTIVE
9. MUTATIONS were observed (not YET clear for BEHAVIOR of the pathogen) > could infect other species
10. A dog was infected by a couple > Paris
11. IMP > MANAGE waste properly TO AVOID ANIMALS INF (history: rodents + small mammals)
2022 JAMA - Pharmacists Allowed to Prescribe C19 Antiviral (rubin) [news].pdf
LIC = lower income countr, HCP = health care providers, ttt= test to treat, EHR = electronic health record, PHR= printed health record, L&K = liver and kidney
1. FDA allowed pharmacists to prescribe paxlovid under EUA
2. Paxlovid must be taken w_in 5d of sympt onset ➩ prescrip from pharmacists could expand px access (Cavazzoni, FDA)
3. Allowing pharmacists to prescribe will improve access in communities w_fewer physicians (IDSA president)
4. Recent study = where they live causes NOT to receive PAX
5. Barriers to TTO in LIC + color + communities w_<HCP
6. Concern to RELAX prescribStandards could ‘JEOPARDIZE pxs safety' + ‘undermine collabCare’ + ‘prevent Phys to careProcess adverseInteractions’ (ACP president)
7. PAX authorized = ≥12 w_hrProg_sD (age, obes, CA, chrDIS like T1or2D), or hrPxs mild-mod C19 Hº FOR OTHER REASONS
8. IF +C19 > 1st HCP or tttSITE (FDArecomm)9. IF pharmacist prescrip > provide: EHR or PHR <1yo (labs: L&K prob + allMeds: interactions)
Friday 26.08.22 at 23h15 BE
AAH, AAQC
❗️REFRESH: yesterday + last Friday
2012 NEJM - BEST TRIP, a Trial of ICP Monitoring in TBI (Chesnut) [R]
NEJMcps 2019 - Repetition (strohbehn)
ILD: interstitial lung disease, OL = alcohol
1. CASE: 60yo man + ED + 3 historical points:
- 2-day H: dyspnea (wosenExer) + cough (prod of nonbloody)
- Prev. month: dysphagia (progressive, to solid&liqu) + weighLoss (4.5kg)
- 10y before: weighLoss (84 to 48.5Kg)
2. PROBLEMS: dysp&coug + subAcutDysph + weigLoss + subtCrhWeighLoss > oropharyn OR esoph DIS
3. ESOPH MOTI DISOR (achalasia): px's difficulty in swallowing (sol&liq) RATHER THAN encroachment EsophLumen (CA or stricture)
4. RESTRICTED NUTR INTA: recent weigh loss > due to AnyCauseDisph OR catabolEffect (ObstrucCA)
5. LINK dysph + dysp > Dysp (predispAspir = pneumon OR cahrILD > Sclerodermi = affects lung&esoph > ErosEsoph_or_Bronc CA_or_INF = invade LUMEN (fistula = tracheoEsoph or bronchoEso)
6. 10y WeigLoss:
- prob due to contrained CaloricIntake (disphagia) >
- Malabs + reduced accessTo OR interestIn FOOD = MORE LIKELY than catabolic process (CA, TBC)
- UNCLEAR: relation w_ ‘2d dysn+cough’ AND ‘1m dysph’
7. CASE: medicalH
- cataractEx + intraOc lens IMPLANTATION + coron-art angioplasty w_stent (14y before)
- NO: med, envirExposures, receTrav, sexAct, noChil
- FosterHome, hisBrother and him were healthy (childhood)
- Alone in Michigan w_dog + no travel OUT USA
- SMOKING = 40pack-year 14y BEFORE this admission (he quit)
- OL = no ➖ NO DRUGS
- Maintenance MECH
- FEVER + FATIGUE (both subjective) = NO: chills, nighSwea, AdbPain, EarSatie, Anorex
2022 NEJMcp - Pulmonary embolism (kahn) [CP]
rf = risk factors = Sx w_gral Anesth >30min + confinement to bed Hº ≥3d w_acuteIlln + majTraum_or_Fract), PE = pulmonary embolism, RVD = right ventricule dysf
1. NO DOACs, YES vitK antag:
- AdvKid OR liver DIS
- AntiphospoSynd (triple-positive = lupusAnticoag, anticardiolipin, B2-Glyco I abs)
- veryHighAbsTiters
- H of artThrom
2. NO DOACs, NO vitK antag, YES LMWH:
- pregWomen: ‘vitK antag + DOACs’ = CROSS THE PLACENTA + related to ADVpregOCs
3. DURATION:
- At least 3m = ↓r: furthEmbol, thromExte, earRecurr VTE, MM
- Depends on = recVTE VS rBleed + px preferences
- If MAJOR transient (reversible) rf > long-term r VTE is LOW > antiCOAG can be stopped a_3m
- If PE large OR w_modRVD OR w_persResidualSYMP > extend to 6m
- if activeCA OR antiphosSYNDR OR prevEpis_unprovVTE > undefinite TTO (long-term r of recurrence is HIGH)
Monday 29.08.22 at 23h15 BE
AAH, MKFA, AAQC
❗️REFRESH: last one and same day last week
2022 LANCET - RECOVERY Baricitinib in pxs admitted to hospital W_ C19 [RCT]
2022 NEJM - LOVIT, Intravenous Vitamin C in Adults w_S• In the ICU (Lamontagne) [RCT]
2022 HEALIO - AF a risk factor for dementia in adults younger than 70 years (Salvaryn) [r]
2022 NEJM - LOVIT, Intravenous Vitamin C in Adults w_S• In the ICU (Lamontagne) [RCT]
GLMM: Generalized linear mixed model, GEE: Generalized estimating equation,
1. pANLY: itt > to assess SUPERIORITY of vitC > they estimated RR and 95%CI for pOC in GLMM (with binomial DISTRIBUTION + log-link function)
2. sANLY: pOC > ADJUTED to prespecified baseline CHARs:
- age, sex, APACHE II, baseline GLUCOCOR, time_fromICUadmis_toRandomiz (GENERALIZED ESTIMATING EQUATIONS)
3. Appraisal of GLM images
4. GEE is a method for modeling longitudinal or clustered data. It is usually used with non-normal data such as binary or count data. The name refers to a set of equations that are solved to obtain parameter estimates (ie, model coefficients).
Tuesday 30.08.22 at 23h15 BE
AAH, FG,MKFA, AAQC
❗️REFRESH: last Tuesday
2022 NEJMcp - Pulmonary embolism (kahn) [CP]
2022 NEJMcp - Pulmonary embolism (kahn) [CP]
1. Unprovoked OR weakly provoked PE = minorTrians_rf = estrogen ther, minor Qx, minorLegInju
2. REGARDING POINT 1 > r_EmbEve a_stopping ACs: (BMJ 2019, srMA)
- 1y = 10% recurrVTE + 0.4% fatalPE
- 10y = 36% recurrVTE + 1.5% fatalPE (3x ↑ )
3. >r VTE&PE in men
4. Duration: (AIM 2021, srMA)
- Extended AC prevent recurrVTE BETTER THAN shorter AC
- MA (14RCT, 13coh): rMAJOR_bleed > extended AC > DOAC vs VITKant > 1.12 vs 1.74
5. rBLEED is higher: older pxs + creaCLEAR <50, H bleed, antiPLT, anemia (<10g/dL).
2022 LANCET - RECOVERY Baricitinib in pxs admitted to hospital W_ C19 [RCT]
1. Concomitant use of Toci > discretion of PHYS
2. PLATFORM TRIAL > FACTORIAL design: colchi + ASA + dymethyFuma + casiriImdeb + empagli
3. Making: NOT MASKED (allocated TTO), MASKED (OC)
4. FORM: discharged, had died, 28d a_random > other C19 TTO + durAdmiss + respORrenaSUPP + newCardArrhyth + Thromb + clinSignBleed + nC19 INF + VITALstatus > 28D
5. OC (next JR)
Wednesday 31.08.22 at 23h15 BE
AAQC
❗️REFRESH: yesterday + last Wednesday
2012 NEJM - BEST TRIP, a Trial of ICP Monitoring in TBI (Chesnut) [R]
NEJMcps 2019 - Repetition (strohbehn)
CIDP= chronic inflammatory demyelinating polyneuropathy
1. ChronicIntesIsch > ↓ foodIntak > modulateEating to avoid intAngi
2. Tobacco > esophageal squamous-cell CA
3. Midwest (residence) > HISTOPLASMA CAPSULATUM > asympPneumon + lymphad (ITIS)
4. MECHANIC > chem + solvne + fumes = ALL TOXIC
5. VITAL SIGNS: T 37.6, HR 104, BP 101/72, SpO2 85 (21%), 94 (4L cannula) > MENTAL: alert and oriented
6. Exam > bitemporal wasting + cough + clearing of secretion + hoarse + hypophonic voice
7. LUNG: normal, rhonci bibasal
8. CV: normal + ABD: normal + NEURO: weakness of muscles (both sides of the fce), minipal PALATAL elevation > REFLEXES: absence TRI, patellar, achilles > STRENGTH proxi + distal > MUSCLES not tender
9. Bulbar weakness > dysphagia + dysphonia + facialWeakness >> 3 points: cranial neurons + neuromuscJunct + muscle
10. Facial weakness: both sides > VII dysf >
11. Palatal weakness + facial weakne + diff managing secretions = OROPHARYNG cause of dysph
12. Pneumonitis ≠ NM RESPfail > dysnea + hypoxemia + insEff normal = pneumonitis > Ronchi = alveolar DIS
13. Diffuse symmetric arefl = demielinating DISORD (CIDP)
14. DIFFs:
- NM DISR = oculopharynDISOR persist for m_OR_y BEFORE peripheral weakness.
- ALS = insidious + affectRespFun + weightLoss (typicall: muscle wasting + fascicu + uppMotNeuron)
- Multifoca NEURO signs = systSymp + weighLoss = PARANEO SYND
- Hereditary = X0link spinobulbar atrophy + myoDystro + bodyMyos (w_bulbar weakness + w_limb weakn)
2022 HEALIO - Increased alcohol consumption associated W_ higher cancer risk (JAMA)
-ol: alcohol, BW: body weight
1. 2022, JAMA, KR ➖ retrosSelf-rep + 4.5M + 2009-2011 ➖ PICO:
- P: population
- I: surveys (-ol consumption & all CA types)
- C: no
- O: pOC = newlyDX -ol-related CA = neck, esopha, colorec, liver, laryn, ♀breastCA >> DIRECTLY correlated >> if_↓-ol = ↓r_CA ➖ sOC = all_NewlyDX_CA EXCEPT thyroid
2. CA: second cause MM (>9.5M_2018) >> 3rd a_tobac&↑BW
3.-ol consumption: causes 7 CA types
4. PaucityRese_CA incidence w_changes in drinking habits (Jung Eun Yoo)
5. One cohort: assoc ‘↓-ol = rCA ‘
6. ∑: assoc ‘↓vs STOP vs ↑: -ol’ –– ‘-ol associated & allCAtypes’
7. Categories: nondrinker, sustainer, increaser, quitter, reducer
8. F-up: from1y a_2011 (inciCA ø MM ø endStud_Dec2018: whichever 1st) >> median <6.5y
9. Stop: <30% mild + <10% mod + <9% heavy
10. Comparisons:
- same drinking vs ↑drinking = latter: ↑r ‘-olCA & allCA’
- no drink vs start to drink (mild, mod, heav) = latter: aHR 1.03, 1.1, 1.34 for ‘-olCA & allCA’
- same drinking vs mild drinker who quit = ↓-olCA (0.96)
- same drinking vs stopped = latter: ↑incid allCA in mod (1.07) ø heav (1.07) drinking levels >> DISSAPEARED when remained -ol_free over time.
- same heavy drinking vs heavy to mod = ↓r -olCA 0.91 & allCA 0.96
- same heavy drinking vs heavy to mild = ↓r -olCA 0.92 & allCA 0.92
11. Implications:
- LIMIT = underreporting + unavailability of long-term habits info + lack of pertinent info (reasons to ↓ø STOP & d_drinking)
- PREVENTION OF CA = drinking cessation & reduction
- Support from Editorial
- Further studies = examine longer intervalsBetwAsses
Thursday 01.09.22 at 23h59 BE
AAH, EMCC, FG, CCC, JMBR, SBH, AAQC
❗️REFRESH: yesterday + last Thursday
2022 CNBC - Monkeypox cases jumped 20% in the last week to 35,000 across 92 countries, WHO says (Kimball) [news]
2022 JAMA - Pharmacists Allowed to Prescribe C19 Antiviral (rubin) [news].pdf
2022 MB - FDA Clears At-Home Visual Acuity Testing System (FDA)
VDAP = Visibility Digital Acuity Product,
1. FDA clears VDAP
2. VDAP = at-home online visual acuity test w_ or wo_correction
3. AGE = 22-40yo >> self-test at home
4. Touchscreen mobile device PAIRED w_computer >> presents VISUAL STIMULI (block letters ø symbols... like a usual one)
5. Study: prosRCT = safe+effect (ETDRS test)
6. test = 6min = BENEFITS ON TIME (90% prescrip in 24h + most in 2h)
7. Does NOT replace an eye health exam
2021 JAMA - What Is an Aerosol-Generating Procedure (Klompas) [vp]
1. Aerosol generating proced = ↑transmission r of C19 (respPathog)
2. MV, extubation, intub, tracheos, nebul... (AAH)
3. Aerosol particles = small + light ENOUGH TO remain suspended
4. How far? beyond 6ft
5. Protection? N95 + isolation rooms (≥12 air changes/h) + negative air flow
6. NO consensus in which
7. Intub + NIV + tracheo + CPR + bronchos + sputumInduc (WHO) >> why? associa w_greater rINF
8. POSSIBLE aero-generProc = HFO + nebuliza >> why possible? associ w_INF were EQUIVOCAL
9. Other SOCIETIES declaration of aeroGenProc:
- NG tube + thoracent + esophagasduo
- colon + cardCath + exercToleTes
- pulmoFuncTest + percutGasTub +faciSx + 2nd stage labor + other
ALL based on therorGrounds - NOT formalQual + epidemiolStud
10. NONE APPEAR in WHO or CDC list
ME MANAGEMENT
01:05:07Round: 3 25:45:20 Urgent 2Round: 2 26:15:55 Urgent 1Round: 1 13:06:43 Refresh yesterday
Friday 02.09.22 at 23h15 BE
MKFA, AAACC,AAH, AAQC
❗️REFRESH: yesterday + last Friday
NEJMcps 2019 - Repetition (strohbehn)
2022 NEJMcp - Pulmonary embolism (kahn) [CP]
NEJMcps 2019 - Repetition (strohbehn)
1. LABS:
WBC 11,8 * BUN 20 ast/alt 36
Hb 12.9 CREA 0.7 BT 1
MCV 97.1 Ca 8.8/9.1c DB 0.3 *
PLT 289k Mg 2.1 FAL 270*
Na 143 P 3.3 PT 15.5*
K 4.1 Protein 6.7 INR 1.2*
Cl 104 Albumin 3.6 Lactate 1.6*
2. protein gap = MONOCLONAL GAMMOPATHY (Protein - Alb)
3. FAL ↑ = bony DIS + hepatobil DIS
4. CT = proxEsoph dilatation = distal stricture + CA + esopha + achalas + pseudoachal >> INF or INFLAMM >> dysphagia = aspirPneum
5. Bulbar weakness + ↑FAL + DISTAL esophDYSF + pulmonaryFindings = infiltrative process = GRANULOM DIS + NEOPLASTIC DIS
6. TEAM DISCUSSION:
- ATB selection discussion
- overuse of ATB (number and duration)
- aspiration pneumonia ‘NEJM 2019 review’
- algorithm (community- and hospital-acquired)
- culture times and follow up
- appropriate use of ATB in aspiration pneumonia
TIME MANAGEMENT
01:17:37
Round: 2 01:04:16 Clinical case + discussionRound: 1 13:20:75 Refresh
Saturday 03.09.22 at 23h15 BE
MKFA, AAH,AAACC, AAQC
WEEK WRAP-UPS REVIEW
2022 NEJM - LOVIT, Intravenous Vitamin C in Adults w_S• In the ICU (Lamontagne) [RCT]
2022 LANCET - RECOVERY Baricitinib in pxs admitted to hospital W_ C19 [RCT]
2022 NEJMcp - Pulmonary embolism (kahn) [CP]
NEJMcps 2019 - Repetition (strohbehn)
2022 HEALIO - Increased alcohol consumption associated W_ higher cancer risk (JAMA)
TIME MANAGEMENT
50:29:48
Round: 1 50:29:48 Refresh
Monday 05.09.22 at 23h15 BE
AAACC, MKFA, JBO, AAH, AAQC
❗️REFRESH: last one and same day last week
2022 NEJM - LOVIT, Intravenous Vitamin C in Adults w_S• In the ICU (Lamontagne) [RCT] –– Monday, Aug29 2022
2022 NEJMqt - Lower Glycemic Criteria for Gestational Diabetes Diagnosis | NEJM
1. 2022, NEJM, ? ➖ RCT + >4k + ? ➖ PICO:
* P: Gestation 24-32
* I: lowThreshold
* C: highThreshold
* O: large-for-gestational-age infant >> noDIFF
2. sOC: (infant) birth weight + gestational age at birth + preterm birth + composite:SeriouHealtOC ➖ (maternal) SeriousHealOC ➩ NO DIFF
3. Threshold: lower = fasting ≥92, 1h ≥180, 2h ≥153 🆚 higher = fasting ≥99, 2h ≥162
4. R: overall ➩ Dx GestDM in LOWER (15.3) was 2.5x as likely as HIGHER (6.1)
5. Neonatal ↓GLU = HIGHER IN lower threshold (10.7)
6. sOC = Labor induction (↑ in lowerThr) + TTO (↑ in lowerThr) + visits to H+ (↑ in lowerThr)
2022 NEJMstat - The Problem of Multiple Comparisons
1. We can reject the H0 when it is true
2. Reject H0 = gray part (0.05)
3. False positive = type 1 error, i.e. astrological sign & fractures
4. How much error you are willing to accept? That is 0.05 = alfa
5. If we test 5, 10, 100, or more… problems!
6. The more test we perform, the most likely it becomes to get a FALSE POSITIVE result
7. Alfa INFLATION = alfa increases in proportion to # of tests we perform
8. Family-wise error rate (FWER) = 1 false positive in a family of of hypothesis tests
9. FWER = 1-(1-alfa)^number of tests = if 5 tests at alfa 0.05, there is >20% chance of observing >1 positive results.
10. Methods to correct for multiple comparisons = Bonferroni, Sidak, Holm’s, Tukey’s (each has CONSIDERATIONS and APPLICATIONS)
TIME MANAGEMENT
01:07:41
Round: 2 01:01:12 StatsRound: 1 06:56:69 Refresh
Monday 12.09.22 at 23h15 BE
AAH, JBO, AAQC
❗️REFRESH: last one and same day last week
2022 NEJMqt - Lower Glycemic Criteria for Gestational Diabetes Diagnosis | NEJM
2022 NEJMstat - The Problem of Multiple Comparisons
2022 NEJMjw - Laying Some Spurious C19 Treatments to Rest (NEJM)
1. BS: 2022, NEJM, ? ➖ dbRCT, 2X3 + >1,4K + Dec2020-Jan2022 ➖ PICO:
- P: C19 pxs (proven), overwe or obese, C19symp_5Dbefore_enroll
- I: iverm, metf, fluvox
- C: control
- O: pOC (composite) = hypoxe ± ER visit ± H+ ± MM >> NO BENEFIT
2. Rigurous trial >> for MILD-MOD C19
3. Iver = antipara –– metf = hypoglu –– fluvoxa = SSRI (antidepre)
4. why were them used? IN VITRO + MODELING DATA + FLAWED CLINICAL STUDIES (supported their use)
5. METFORMIN = ↓r for ER visits
6. NO EFFECT ON symp + side effects
7. USING THEM precludes use of proven effective C19 TTO + diverts THE SUPPLY FOR their legitimate uses.
TIME MANAGEMENT
01:07:49
Round: 3 18:03:45 UrgentRound: 2 39:15:25 STATSRound: 1 10:31:27 review
Wednesday 14.09.22 at 23h15 BE
AAH, MKFA, JBO, AAQC
❗️REFRESH: last one and same day last week
NEJMcps 2019 - Repetition (strohbehn)
2022 ICM - Intracranial pressure pulse morphology, the missing link (Brasil) [corr]
NEJMcps 2019 - Repetition (strohbehn)
1. Myotonic dystrophy = EMG (discharges) + SouthBlotAnal (CTG in DMPK…)
2. Type 1 = 26y – type 2 = 34 y
3. Delay in Dx = type1 (7.3y) + type2 (14.4y)
4. Guidelines = NO (for genetic testing) >> testing is DECISION MADE (w_medical geneticist)
5. Multorgan problem = interdisci care
6. TTO = Na-blockClass I antiarr + antiEPILI + antiDEPRE + CaChannelBlock >> NO largeRCT
7. IMP = training in strength and skill >> life-span NORMAL (TYPE 1)
8. Classic &congen = cardiopulmCOMPL >> ↓life span >> cardioverter-defibril is NEEDED (cardiacDeath + niMV)
9. DYSPHAGIA can lead to W↓ from catabol, malnutri, both
10. Progressive DYSPHAGA = unrecog & unreport (cognImpair + sociallyIsola) –– until ↓W + Strength
11. Our px = hypernasality + impaiLarynElev + facialWeakn
12. IF isolatedBulWeakn wo_CNS ø cranNeuroPATHIES ø NMjunctDISOR = MUSCLE
13. Also in older (even wo_ weakness in arm and legs + HANDGRIP)
14. Like many other inherited disorders, myotonic dystrophy has a
late-onset form that can be insidious and partially expressed.
2022 NEJM - Time to Stop Using Ineffective C19 Drugs (Abdool) [ed]
1. EBM best evidence currently available (safety + efficacy)
2. Rushed use of medication during eraly c19
3.COUL NOT BE REPLPICTED the evidence behind the MEDS -- ∑ even so, physicians are RELUCTANT (MAINLY iver + fluvoxa)
4. COVID-OUT (Bramante 2022), RCT, 3 DRUGS (iver + metf + fluvox) = 1323outPxs = no ↓HYPOxemia + EDvisits ø MM >> STRENGHT = 30-85y (hr_pSD due to overW or Obe) >> LIMIT = lr_SD not taken
5. Secondary analysis >> METFORMIN = ↓composite (ED visit + Hº + MM in overWøOBE) = WE NEED FURTHER INVEST
6. PAST EVIDENCE:
- 2020 (UNavailab or equivo)
- many data (MA, trial of the 3 drugs)
- COMBINED ANALY = a. OADs (3M w_DM_C19 in 24 observ) b. trial 110pxs >> METFORMIN before HºADMI WAS gooood (but NOT in-hospital) >> pOC: MM
- MA = fluvoxami (>2k, outpxs, nonseve, C19) in 3 trial = NO GOOD >> incidenHº ± MV ± MM
- MA = IVERM (>2k, sev & nonSev) = NO goood >> MV + HºAdmin + d_Hº + clinSeverity + MM >> NO EFFECT TO THE DOSE
7. WHO = barometer of EBM (quality of evidence) >> COVID-OUT not included (Metformin nOT MENTIONED) >> DESPITE THAT = increase of condicene + degree of certainty OF NOT USEFULNESS (iver + fluvox) in SevDis
8. «There are no evidence based grounds to continue prescribing ivermectin and fluvoxamine »
9. SIDE EFFECTS + THERAPEUTIC BENEFIT + DRUG SHORTAGES
10. «Hence, it is important to have relIable evidence of nonefficacy and to have journals publish such studies.»
11. AMERICAN BOARD OF IM = “There aren’t always right answers, but some answers are clearly wrong.”
TIME MANAGEMENT
01:18:18Round: 4 00:00:60 CommentsRound: 3 38:59:07 UrgentRound: 2 26:44:55 Clinical caseRound: 1 12:34:02 Refresh
Thursday 15.09.22 at 23h59 BE
MIMC, AAH, AAQC
❗️REFRESH: last one and same day last week
2022 NEJMqt - Lower Glycemic Criteria for Gestational Diabetes Diagnosis | NEJM
2022 NEJMstat - The Problem of Multiple Comparisons
2022 NEJMjw - A Better Treatment Option for Drug-Resistant Tuberculosis (NEJM)
1. 2022, NEJM, SA ➖ RCT + 181 + X ➖ PICO:
- P: drug-resMycobacTuberc
- I: BPL (BEDAQUILINE + PRETOMANID + LINEZOLID) 1200-26
- C: BNP 1200-9 BPL 600-26, BPL 600-9
- O: efficacy + safety (LESS TOXICITY) >> BPL 600-26 [efficacy 91%, AdvEve a) PeripherNeuro 24% b) Myelosuppre 2%]
2. NEJM 2020: usually BPL 1200mg-26 = cure rate >90% >> significant TOXICITY due to Linezolid
3. Current study with HIV = 20%
4. Analysis = intention-to-treat5. R: BPL 1200-26 (93%), 1200-9 (89%), 600-26 (91%), 600-9 (84%) 6. AdvEve: PeriphNeuro = 38, 24, 24, 13%, respectively >> Mielosuppresion = 22, 15, 2, 7%, respectively7. Limitation = small size >> HOWEVER, similar results to previous (beda+line+levo AND 2 other FOR 6months, BLUE JOURNAL)8. WHO: adapter THIS REGIMEN as an alternative to LENGTHIER TTO (>14yo w_MDRtbc)
Friday 16.09.22 at 23h15 BE
MIMC, AAH, JBO, MKFA, GSQA, AAQC
❗️REFRESH: last one and same day last week
NEJMcps 2019 - Repetition (strohbehn)
2022 ICM - Intracranial pressure pulse morphology, the missing link (Brasil) [corr]
NEJMcps 2019 - Repetition (strohbehn)
All notes and paper re-assessed
Notes corrections available here
1. Mnemonics:
1.1 Bulbar weakness: DDD
1.2 Anatomical alterations: lungs, oropha, esoph
1.3 No peripheral neural compromise
2. Resources
2.1 Sanford Guidelines
2.2 Aspiration pneumonia (NEJM 2017, Mandell et al.)
2.3 Genetic principles
3. Take-aways
3.1 Cataracts at young age
3.2 Disphagia (broad but meaningful)
3.3 Repeated physical examination
3..4 Outining the case impacts positively
TIME MANAGEMENT
01:05:49Round: 3 00:05:45 oommentsRound: 2 50:15:25 review and appraisalRound: 1 10:31:27 review
Monday 19.09.22 at 23h15 BE
ALAC, JBO, AAH,XARS, GSQA,MIMC, AAQC
❗️REFRESH: last one and same day last week
2022 NEJMjw - Laying Some Spurious C19 Treatments to Rest (NEJM)
2022 NEJM - Blood-Pressure Targets in Comatose Survivors of cardiac arrest (Kjaergaard) [RCT]
1. Previous study = 6m MM H+ coma = 33%
2. Sample size: NO interaction w_O2 INT
3. >700 ot >800 >> power 0.8 or 0.9 >> MM 28% and 38% (p=0.05)
4. two-sided alpha level = p
5. 800 = PLANNED >> f-up 3m a_enrollment
6. Global type I error = 0.05 = correction 0.0471
7. MEAN betw-group DIFF ‘BP + NE + VP-INO’ for 2-48h = REPEATED-MEASURES VARIANCE
8. pOC + sOC (2: all_c_MM90 + ttRRT) = ADJUSTED proportional-hazards model
- cox = hazard model = cox hazard model = cox proportional hazard
- SS + one other PREDICTOR
- TIME
Monday 26.09.22 at 23h15 BE
AAH, AAACC,JBO, MIMC, AAQC
❗️REFRESH: last one and same day last week
2022 NEJM - Blood-Pressure Targets in Comatose Survivors of cardiac arrest (Kjaergaard) [RCT]
2020 JIC - Automated pupillometry to assess CAR (Quispe-Cornejo) [R]
1. Median = IQR (25-75) = numeric — count = % = categorical
2. Wilcoxon rank test = continuous => comparisons
3. Correlation = Pearson
4. Prediction = ROC = receiver operating characteristic curves
2022 LANCET - RECOVERY Baricitinib in pxs admitted to hospital W_ C19 [RCT]
1. Protocol = samples sizes not estimated
2. Recruitment stopped Dec2021, w_>8k, MM28 13%, 90% power w_2-sided significance level of 1%
3. Steering committee + individual = masked to OC
4. pOC = MM28: all studies of JAKinhib
5. all with equal risk (#MM among pxs w_JAK) = variance was calculated OR observed - expected (o-e)
6. RECOVERY = age-adjustedMM ➖ other trials = SE >> 2x2 contingency tables used (calculated MM)
7. ALL RESULTS COMBINED >> log of MM rate ratio calculated = using sum of all trials of ‘o-e’ (S) and ‘v’ (V) >> inverse-variance weighted average S/V
8. SUCH MA DOES NOT make assumptions on HETEROGENEITY
2022 NEJMjw - Another Look at Proning in Nonintubated Hospitalized pxs W_ C19 (JAMA)
1. 2022, JAMAim, ? ➖ nRT, controlled + 501 + ? ➖ PICO:
– P: C19 nonINTUB pxs
– I: prone (4 hours daily)
– C: control (usual care)
– O: pOC = O2 supp (WORSE 5D) ––
sOC = MM, progINTUB, LOS (SIMILAR) 2. GL 2021 >> recommended prone in awake nonINTUB >> limited evid + extrapolation from ICU MV ARDS pxs
3. pOC was SIMILAR (not present) D 0-4 and D14 or D28 (not persisted)
4. HARM not proven >> p
TIME MANAGEMENT
01:17:08
Round: 3 03:47:80 urgentARTRound: 2 01:02:18 JC statsRound: 1 11:02:07 Refresh
Tuesday 27.09.22 at 23h15 BE
JBO, MKFA, AAQC
❗️REFRESH: last one and same day last week
2022 NEJMcp - Pulmonary embolism (kahn) [CP]
2022 NEJMcp - Pulmonary embolism (kahn) [CP]
ChrTEPH: Chronic tromboembolic pulmonary hypertension, ACCP: ACCHEST PHY, ASH: Am. Society of Hematology, ESC: European Society of Cardiology, Sh-t: short-term, APS: antiphospholipid syndrome
1. CA = detected 5.2% a_1y of DX of unprovoked PE
2. SCREENING >> ‘extensive’ detects MORE CA than ‘limited’ >>OC uncertain
3. How to do it? guided by MEDICAL H, PHYSexam, Labs, Xray, age-&sex-specific CA screening
4. After PE, we need evaluation? yes, 3-6m, to evaluate DYSNEA or FUNCTlimita >> to define ‘POST PE SYNDR’ or ‘ChrTEPH’
5. If AC indefinite = reassess anually OR more often >> discontinue? yes, if: r_BLEED ↑ +majorBleed occurs + px prefers to stop
6. GL = ACCP + ASH + ESC >> RECOMM_strength is different in SOME TOPICS >> ACCP + ASH = stop AC at 3m IF 1stPE by ‘weakTRANSIENT_rf’ 🆚 ESC = indefinite AC by the same cause >> NEJM: “ACCP + ASH + consider influence r_of_recurrence + pxPreference”
7. GL RECOMM:
a. Home VS H+ (low_r) = the 3 say home = ACCP w_conditions (AC, care, circums) ➖ ESC some conditions (care + AC)
b. subSeg PE = ESC: no data ➖ ACCP: low (surveill+US both legs) VS high (AC if_pxs H+ + immo + CA + preg + unprovPE) ➖ ASH: sh-t_AC only if_CA
c. Choice AC = ALL 3: DOACs instead VitK + vitK antag in APS ➖ IF renalIMP do vitK antag (ASH, ESC) ➖ IF liverDIS do SAME (ASH) ➖ IF preg-lact do SAME (ESC)
2020 JIC - Automated pupillometry to assess CAR (Quispe-Cornejo) [R]
1. TCD + CAR = BP w_AL (hydrostatPressInflu) + brain flow veloc (BFV) by TCD in MCA + digitalized by a machine + removal of artifacts + script + Pearson (Mxa) = >0.3 is impaired and <0.3 is intact
2. 123px + 92 pu >> icu MM 9% >> 56% S•
3. PrimarySiteINF = abdominal (48%) –– then resp (21%)
4. Gram (-) most prevalent (50%)
5. COMBOR = renal + heart + obesity
6. CAR & PU = 20% SEDATED + 48% analg >> 55% w_impCAR = NPI 4.3 & PUPILsize 3.7mm
TIME MANAGEMENT
01:02:39
Round: 3 10:52:01 LAST JC
Round: 2 42:40:87 ReviewRound: 1 11:57:05 Refresh
Wednesday 28.09.22 at 23h15 BE
JBO, MKFA, AAQC
❗️REFRESH: last one and same day last week
2019 NEJMcps - Repetition (strohbehn)
2022 NEJM - Time to Stop Using Ineffective C19 Drugs (Abdool) [ed]
2022 NEJMcd - Screening for Atrial Fibrillation in Asymptomatic Older Adults [cd]
1. 75yo man –– HTA + DM2
2. H: NO HF, S†, CAD, PAD, OSA, hyperTHY, PulmDIS
3. HABITS: no -ol, tocacco, ilicit
4. HTA: lisi + HCT –– DM: metf + lowCarbs + exer
5. MEDS no changes
6. wo_chestPain, palp, dysp, angina, edema, claud –– all activities ok (walks wo_rest)
7. PhyExam: unremarkable (normal VS, cardioPulm, vascu)
8. Wife died = Afib w_ischS† complications
9. YES:
- VARIABLES: age + HTA + DM + CHA2DS2-VASC 4
- Scenario: If Afib = ↑r compli+MM >> start AC
- symp = asymp FOR RISK OF ’S† + MM’ from Afib
10. Preval of Afib (≥30s ) in asymp is detected in 3-32% (depending on the SCREENING METHOD) >> if DETECTED AC is initiated (in 5y follow-up 90% still w_AC)
11. EVIDENCE: Does DOAC reduce S† + MM???
- STROKESTOP: 75-76yo + RCT + I: ECG for 30s BID x14d + C: yes >> all Afib received AC ➖ 5y f-up: ‘signif, modest’ EP (composite: isch OR hemorr S† ± systEMBOL ± H+ for bleeding ± any_cause_MM) ➖ NNT = 91
- LOOP: 75yo + RCT + loop recorder (39 months) + control + Afib detected in 32% + AC initiated (≥6min of Afib) ➖ 64.5m f-up: primary EP (S† OR systTE) 4.5 int 🆚 5.6% in control (p=0.11, underpowered) ➖ at 6y only 16% of all were assessed for pOC (long-term lacking) ➖ control had 12% w_Afib (higher than expected) ➖ NO serious bleeding
- SAFER: RCT, 120K, 70yo, ECG, pOC = ischS† + expected for 2026
- GL: European, Canadian, Australian = SCREENING in asympPXS ≥65 ➖ PXS should be screened w_intermitent ECG >> IF ≥30 SEC of AFIB = we AC
2022 MEDPAGE - New Guidance on managing HyperGLU in Hº Pxs (JCEM)
1. 15 recomm from ENDO SOCIETY CPG
2. Topics : prandial insulin + noninsulin + preoperative GLU measures + insulin correction + DM education
3. University of Pittsbutg >> updated from 2012
4. Continuous GLU monitoring: USE alongside confirmatory bedsite POC blood GLU >> IT IS SOC IN OUTPXS, in inpxs NOT CLEAR but NOW recommended >> why? too many visits in the room + a lot of finger sticks use
5. INSULIN PUMPS: CONTINUE using them if APPROPRIATE mental + physical capacities –– why basal bolus insulin is used in H+ instead? not FDA approved - BUT NOW it is recommended to continue its use
6. EDUCATION: it is important PRIOR TO DISCHARGE –– why is it IMP? ↓r of RE-admission + better GLU control IN 3-6m f_DISCH >> DISCHARGE-PLANNING PROCESS
TIME MANAGEMENT
01:22:27
Round: 4 02:51:81 COMMENTSRound: 3 25:12:40 urgARTRound: 2 31:50:34 Clinical caseRound: 1 22:33:39 Refresh
Thursday 29.09.22 at 23h59 BE
MKFA, AAH, MIMC, AAQC
❗️REFRESH: last one and same day last week
2022 NEJMjw - A Better Treatment Option for Drug-Resistant Tuberculosis (NEJM)
2022 LANCET - Early treatment to prevent progression of SARS-CoV-2 (Cohen) [comm]
sDP: severe disease progression,
1. C19 cases to May2022 = >520M = 6M MM
2. 2022, LANCETrm, ? ➖ dbRCT + >900 (>450 each group) + ? ➖ PICO: P = C19 unvax / I = tixagevimab & cilgavimab 600mg, IM, within 7d onset / C = placebo / O = pOC‘sC19 ø MM’ >> ↓50.5%.
3. R: pOC = I 4% 🆚 C 9%
4. Mean age. = 46yo = diff from other studies w_elderly&comorb
5. 2022, NEJM, Levin: C19 INF = 83% over 56m, unvax.
6. Tixa-Cilga = has a mutation in the FC portion = extends HALF-LIFE >> LONGER DURATION + perhaps PREV of reINF (when early use)
7. Study 5 (Levin): ONGOING to define DURATION of PREV
8. IN VITRO: tixa-cilga + bebtelo = NEUTRALIZATION activity >> FDA EUA
9. Tixa-Cilga: preEXPOS prophy of C19 at ‘hr + unlikely response to VAX’
10. Bebtelo: early TTO at sDP.
11. GREATEST rf_sDP = older w_comorb + host defense defects + pregnancy >> HELP promptly and decide the best
12. MOST POPULAR TTO = paxlovid (5d within 5d SYMonset).
13. Molnupiravir: FDA EUA = 30% protection of sDP >> orals are NOT affected by MUTATION in viralPROT + not HCP required + cornerston of USA government test to treat programme
14. Some DIFFICULTY predicting who has responded to VAX + who will have sDP
15. When UNABLE TO clear viralINF = DANGER of new variants
16. A respiratory INF will NOT BE THE SAME >> other pathogens + better tto + time of tto + mm still ongoing
2022 JAMA - Preventive Medication for C19 Infection (malani) [pp]
1. When to give?
- NOT TTO for C19
- NOT for INF C19
- NOT for close contact w_C19
- YES a_2w (at least) of C19vax
2. Who to give?
- Dec2021 = US FDA EUA ok
- Eligible: adults&child≥12yo(40Kg) + mod-sevIMMUNO↓ (medCOND ø IMMUNOSUPmeds) AND inadequaIMM resp Ø unable to be VAX (H of SEVEREreactions)
3. Where and how?
- 2 separate IM doses d_single session
- AdvRea surveillance ≥1h
- IF ongoing protection C19 = give every 6m
- In USA: ask your doctor, it is FREE
4. How EFFECTIVE?
- lasts 6m (a_administration)
- Duration of PROTECTION ongoing (Levin?)
- Potential problem: emerging variants COULD INTERFERE w_its effectiveness
5. Possible side effects?
- IM med: pain + soreness + swelling + bruising + bleeding + INF (siteInject)
- Allergic reactions = possible w_shortBreath + chestPain + hives + wheeze + swelling face, lips, mouth, tongue
- IF severe Reaction to C19vax = HIGHrisk to tixa-cilga
- CARDIAC EVENTS? rare ONLY if underlying cardiac rf
6. What if C19 symp while tixa-cilga?
- test SOOON
- may be ELIGIBLE for TTO (contact your doctor)
TIME MANAGEMENT
01:02:39
Round: 3 10:52:01 LAST JCRound: 2 42:40:87 ReviewRound: 1 11:57:05 Refresh
Friday 30.09.22 at 23h15 BE
AAQC
❗️REFRESH: last one and same day last week
NEJMcps 2019 - Repetition (strohbehn)
2022 NEJMcd - Screening for Atrial Fibrillation in Asymptomatic Older Adults [cd]
UC: usual care, AC: anticoagulation, earlyDET: early detection, HC: healthcare, pvc: premature ventricular complexes, screening-DET: screening detected
DEFER SCREENING (John Mandrola)
1. Reasons to avoid:
- LOOP trial: 2021, LANCET, ? ➖RCT ✚ >6k ✚ ? ➖PICO: •P = “persons” •I = loop rec, •C = UC, •O: pOC = S† ø systEMBOL >> a_ ‘5y ƒ-up + ↑3x Afib_detection + AC in “I” = NO DIFF in pOC (p=0.11) >> sOC: anyC_MM = SIMILAR
- Px fits in LOOP
- Reliable measure (LOOP) and NO net benefit >> unlikely «less robust devices» will
2. Uncertainty on TTO of Afib ∑ against enhan_screen (¢subCLIN ø short_d_)
3. BASIC PREMISE: earlyDET ≈ effec_therapy
- colon ≈ Sx offers a POTENTIAL CURE
4. In Afib w_HC visit ≈ ok AC >> threshold of the burden of Afib to AC is unknown in subCLIN
5. Potential harms even MORE salient
- physical + emotional
- physical = bleeding (AC) + arrhy (pvc ≈ complications from WORKUP)
- emotional = anxiety
- modern-day car_MONITOR ≈ NO ref_STANDARDS (like for brady ø pvc)
6. His RECOMM: grieve your wife + not ignore NEW_SYMP + KEEP monitoring wo_devices + soooon 2 trials: NOAH & ARTESiA (both on AC in screening-DET_Afib)
2022 NEJMcp - Pulmonary embolism (kahn) [CP]
insOF: instead of, wADJ: weight adjusted, ALT: alternative, GI_CA: gastrointestinal cancer, ltAC: long-term anticoagulation, sympPE: symptomatic PE, stAC: short-term anticoagulation, CA: cancer,
1. Last session GL in Table 2
2. Table 2:
a. AC f_CA≈PE 🟰 ACCP: DOAC insOF LMWH (most pxs) ✚ ASH: DOAC insOF LMWH f_3-6m ✚ ESC: wADJ_LMWH f_6m insOF vitK_antag –– edoxa ø rivaroxa as ALT to LMWH in GI_CA >> ACCP&ASH say DOAC, ESC say LMWH
b. Incident_asympPE 🟰ACCP: ltAC (as in sympPE) ✚ ASH: stAC insOF obs (CA) ✚ ESC: ltAC (CA)
TIME MANAGEMENT
01:11:59
Round: 3 19:15:35 Review, PE
Round: 2 06:13:10 RefreshRound: 1 46:31:27 Clinical case
Monday 03.10.22 at 23h15 BE
AAH, MKFA, AAACC, MIMC, JBO, GSQA
❗️REFRESH: last Monday JR
2020 JIC - Automated pupillometry to assess CAR (Quispe-Cornejo) [R]
2022 LANCET - RECOVERY Baricitinib in pxs admitted to hospital W_ C19 [RCT]
2022 NEJMjw - Another Look at Proning in Nonintubated Hospitalized pxs W_ C19 (JAMA)
2022 NEJM - Blood-Pressure Targets in Comatose Survivors of cardiac arrest (Kjaergaard) [RCT]
1. DID NOT correct for multiplicity >> efficacy in other OC: points estimates + 95%CI >> ∑intervals CANNOT be hypothesis test
2. To SS >> Kaplan-Meier
3. SUBGROUPS:
- sex, age, site, status (COPD, HTA, renal), shockable rhythm, STEMI.
- HTA = use of antiHTA
- renal DIS = RRT + GFR<30
4. MoCA = LOWEST value (score) assigned to the ‘missing + deceased’
TIME MANAGEMENT
01:10:47
Round: 2 01:01:31 JC + urgART
Round: 1 09:15:33 Refresh
Tuesday 04.10.22 at 23h15 BE
MKFA, AAH, MIMC, AAQC
❗️REFRESH: last Tuesday JR
2022 NEJMcp - Pulmonary embolism (kahn) [CP]
2020 JIC - Automated pupillometry to assess CAR (Quispe-Cornejo) [R]
2022 MB - Helmet May Be Better Than Facemask in CPAP for C19 ARF (Chest)
sc: single center,
1. BS: 2022, CHEST, ARG –– pros_sc_Cohor + >100pxs (55 vs 57) + Jun2020-Sep2021 –– PICO: P=ARF C19 ICU, I= helmet vs facemask, C=no, O= endotrIntub + inciHypoxemia >> HELMET is better (p=0.017 + 0.005)
2. Oronasal = double-limb circuit >> helmet = single-limb circuit
3. Who decided to receive helmet or facemask? pxs
4. BEFORE CPAP = PaFi in helmet (96mmHg) vs facemask (101mmHg) p=0.25
5. HR was adjusted to SOFA + PaFi at inclusion >> for ENDOintub (pOC)
6. ‘SpO2/FiO2 ratio ↑ + RR ↓’ in HELMET (variance for repeated measures)
7. ‘inH+ MM ↓’ helmet (18 vs 35%, p=0.015)
8. LIMIT: nonRCT + small sample >> even so = POSSIBLE CLINICAL BENEFIT >> WE NEED FURTHER RCTs
TIME MANAGEMENT
01:08:32
Round: 3 10:59:14 JC by ISICEM chat
Round: 2 38:33:71 urgARTRound: 1 18:59:21 Refresh
Wednesday 05.10.22 at 23h15 BE
AAQC
❗️REFRESH: last Wednesday JR
2022 NEJMcd - Screening for Atrial Fibrillation in Asymptomatic Older Adults [cd]
Blood Pressure and Oxygen Targets after Cardiac Arrest https://www.youtube.com/watch?v=ILrOYo-aS7Y
BOX trial: 2022, NEJM, DK ➖ db_ii_2cen_RCT2x2fd + 789 px + Mar2017-Dec2021 ➖ PICO
- P: ohCA in ICU
- I: map63 (ol_INT: liberal vs restrictive O2 –– subordinate random Tº a_24h)
- C: map77
- O: pOC = all_cauMM90 Ø H+DISCH(cpc 3-4)90 >> NO DIFF
• IN: ≥18yo + ohCA (cardiac cause), ≤20min chestCompr + remainedComa (no response to verbalComm)
• EX: unwitnessAsys + susp_acIC_BLEEDorST
• sOC: NSE 48h + allCau_MM + MoCA_3m + mRankin_3m + CPC_3m >> NO DIFF
TIME MANAGEMENT
01:08:32
Round: 3 10:59:14 JC by ISICEM chatRound: 2 38:33:71 urgARTRound: 1 18:59:21 Refresh
Thursday 06.10.22 at 23h15 BE
AAH, MKFA, AAACC, GSQA, AAQC
❗️REFRESH: last Thursday JR
2022 LANCET - Early treatment to prevent progression of SARS-CoV-2 (Cohen) [comm]
2022 JAMA - Preventive Medication for C19 Infection (malani) [pp]
2022 HEALIO - Healthy habits in midlife may help delay onset of cognitive decline (Herpen) [News]
1. Healthy habits are IMP to avoid Alz and Dem
2. Brain Week 2022 presenter explains
3. Gary Small = chair of Psy in Hackensa Univ. >> how to forestall effects of Alz?
4. Used Jeanne Calment (FR, died 1997, at 122) >> other elderly (JAP, IT, COSTA RICA) = 80-90 yo
5. FACTORS TO IMPROVE: nongenetic factors = excercise, diet, mental activ, socail intera
6. Older who were motivate to make better and healthier choices (↓memory concerns + ↑cogFunct)
7. Technology ≠ poorer memory + ↓CogAbilities >> TECH can imp COGfunct w_ONLINE GAMES (cited by Small)
8. To improve LEARNIN + VISUAL + MEMOR >> stationary cycling >> better visual MEM and executeFunc
TIME MANAGEMENT
01:20:17
Round: 3 27:30:44 uARTRound: 2 33:34:20 Clinical caseRound: 1 19:13:08 Refresh
Monday 10.10.22 at 23h15 BE
AAACC, AAH, MKFA, MIMC, AAQC
❗️REFRESH: last Monday JR
2020 JIC - Automated pupillometry to assess CAR (Quispe-Cornejo) [R]
2022 LANCET - RECOVERY Baricitinib in pxs admitted to hospital W_ C19 [RCT]
2022 NEJMjw - Another Look at Proning in Nonintubated Hospitalized pxs W_ C19 (JAMA)
The Case of the Missing Data | NEJM Evidence
1. Types of missing data: missing data completely at random, md at random, md not random
2. MD completely at random = prob. not related to other variables
3. MD at random = prob. related to some other known variable
4. MD not at random = prob. Depends on the actual values of MD
5. Can we fix these MD? The are many stat aproaches to handle it such as last observation carried forward, single imputation, mean imputation, etc
GSQA 2022 HEALIO - Despite recommendations, statin use ‘not ubiquitous’ in CKD w_ ASCVD (ClinCar) [News]
1. GOULD: 2022, CC, USA (Mount Sinai) ➖ prosp + >3.3k + 2y ➖ PICO: P=adultsCKD+ASCVD I=observ high-inte_STATIN + ‘EZET and/or inhPCSK9’ C=no, O= LDL goal ≤70 >> NO INCREASE
2. KDIGO 2013 + ACC/AHA 2018 = statin for aduts w_NON-DIALY-DEPEND ‘CKD + ASCVD’
3. WHO recomm high-inten STATINS? ACC/AHA
4. use of high-inten stati + ezetimi REMAIN LOW
5. Intensified statins = 20% ➖ LDL ≤70 =30%
6. 3 cohorts: PCSK9inh = 554 –– LDL≥100 wo_pcsk9inh = >1.8k –– LDL 70-99 wo_PCSK9inh = >2.6k
7. RESULTS: stable over 2y >> S2 statin 85 & 83, S3 83 & 80, S4-5 88 & 79 at baseline and 2y, respectively.
8. eGFR <60 = INTENSIF in 22%, DESCALATION 10%, WO_CHANGES 62%
9. STATIN + EZET = ↑3 to 5% >> discontinuation of statins at 2y was ↑ in lower eGFR
10. In CKD PXS it is IMPORTANT TO intensify statins and associate w_ezetim and/or PCSK9 inh
TIME MANAGEMENT
01:48:58
Round: 5 10:03:32 Q&A
Round: 4 45:09:60 uART
Round: 3 25:48:64 STAT
Round: 2 07:31:68 commentsRound: 1 20:25:34 Refresh
Tuesday 11.10.22 at 23h15 BE
AAQC
❗️REFRESH: last Tuesday JR
2022 NEJMcp - Pulmonary embolism (kahn) [CP]
2020 JIC - Automated pupillometry to assess CAR (Quispe-Cornejo) [R]
NEJMjw - Timing of Anticoagulants in Stroke Related to Afib (Circulation)
1. 2022, CIRCULATION, Sweden (34cen) ➖ RCT + 888 + 4y ➖ PICO:
- P: ischS† w_Afib (27% w_OralAC + AF was known in HALF)
- I: DOAC early (4d)
- C: DOAC late (5-10d)
- O: pOC = comb: recIschS† + sICH + allcMM90 >> not stat sup
2. Before: EARLY AC was concerning due to HEMORR TRANSF in S†
3. CI was within nonINF range
4. Some clinicians wondered if EARLY DOAC would be ok
5. 3pxs = HHtransfor within 28d (asymp) 🆚0pxs = HHtrasn (SYMP)
6. DOACs are safe in early phase in MILD S† >> UNKNOWN in large S†
TIME MANAGEMENT
Wednesday 12.10.22 at 23h15 BE
MKFA, MIMC, AAQC
❗️REFRESH: last Wednesday JR
2022 NEJMcd - Screening for Atrial Fibrillation in Asymptomatic Older Adults [cd]
2022 JAMA - Screening for Atrial Fibrillation—Refining the Target (Kalscheur) [ed]
UC: usual care, H-R: health-related, ILR: implantable loop recorder, ICD: implantable cardioverter-defibrilator
1. Morbidity, MM, H-R expenditures with Afib cannot be UNDERESTIMATED
2. There is an ≈: Afib & r_S†
3. 2018 USPSTF 🟰 ‘insufficiente evidence to ASSESS THE BALANCE benef-harm w_ECG for screening’ ✚ ‘ECG may not detect more Afib than UC (pulse palpation)’ ✚ ‘>50yo wo_dx ø Afib_symp + wo_H of TIAøS† = evidence insufficient to balance benef-harm of screening…’
4. sr 🟰USPSTF recognizes ADEQUATE evidence “INTERMITTENT screen + continuos screen = may identify Afib MORE EFFECTIVELY than UC” BUT unclear benefits of broad AF screening (harmful: AC + early rhythm control)
5. 2019 USPSTF 🟰 abd aortAneu screening NOT FOR ALL but: ‘hr_subset men 65-75yo + prev_smoked’ ✚ Lung CA = low-dose CT in 50-80yo + 20 pack-year + H¤tly smoke Ø quit within past 15y ➩ PERHAPS (Afib) will fail to demonstrate merit in targeted screening
6. NEW USPSTF notes 🟰’optimal screen + effect of TTO’ is LIMITED (Why? diff approaches in a. optimal screen b. deriving S† r c. TTO thresholds)
7. APPROACHES 🟰binary screening (present ø absent) ✚ current practice = measure r in ‘ORDINAL STRAT scores’ HOWEVER… IDENTIFYING pxs ‘w_ ø wo_Afib + S† r’ w_ a number is MISALIGNED w_remarkable I2 ➩ ∑ it is BETTER to assess THE BURDEN of Afib
8. LOOP ➩ 6k + ➩ randomized ILR vs UC ➩
2021, LANCET, ? ➖ RCT + 6K + 5y (ƒ-up) ➖ PICO:
- P = older + wo_Afib + CHA2DS2VASc 4
- I = ILR (if Afib >6min = AC)
- C = UC
- O = pOC S†øsysArtEmbol >> NO DIFF (4.5 vs 5.6%) >> Afib was ↑ in ILR (32 vs 12% = 3-fold ↑) + 30% AC in ILR w_Afib >> majBLEED 4.3 VS 3.5% (p>0.05)
9. ASSERT ➩ interpret carefully (6min threshold) because of this study >> 2012, NEJM, ? ➖ RCT + >2.5k + 3.5y ➖ PICO:
- P = ≥65yo w_HTA wo_H_Afib w_dualChamb PMK ø ICD
- I = ECG (monitored atrial tachyarrhy (at) burden = episode>6min w_atrialRate > 190bpm)
- C = UC
- O = ischS† ø sysEmbol >> 3m = 10% w_subcl_ at ≈ 2.5-fold ↑ pOC >> 3.5y = episodes LONGER THAN 24h = greatest ↑r S† >> ∑ tto might be IMP in this context (incindentally found subclArrhth)
10. soon ARTESIA = pros_mc_db_RCT + pxs w_’subclAfib (PMK, ICD, cardiac monitor) + rf for S†’ + TTO randomized to apixa vs ASA >> IF apixa is beneficial MORE LIGHT we would have for TTO subcl_Afib
11. USPSTF = data supporting improved yield w_intensiScreen >> STROKE-STOP ➩ 2021, LANCET, Sweden ➖ mc_pg unMask_RCT + >7k + <7y ➖ PICO:
- P = 75-76yo
- I = self-applied handheld ECG recorder (2w)
- C = UC
- O = compos: ischøhhS† + HH for BLEED + allC_MM + sysEmbol >> FEWER in I• >> NO DIFF in individual components
TIME MANAGEMENT
59:55:89
Round: 3 00:35:53 comment
Round: 2 38:22:18 review
Round: 1 20:58:17 Refresh
Friday 14.10.22 at 23h15 BE
AAH, MKFA, AAQC
❗️REFRESH: last Friday JR
2022 NEJMcd - Screening for Atrial Fibrillation in Asymptomatic Older Adults [cd]
2022 NEJMcp - Pulmonary embolism (kahn) [CP]
2022 JAMA - Screening for Atrial Fibrillation—Refining the Target (Kalscheur) [ed]
1. DESPITE USPSTF = screening will continue OUTSIDE physician encounters
2. Apple Heart ➩ 2019, NEJM, ? ➖ prosObs + 420k + ? ➖ PICO:
- P = mass enrollment
- I = SMARTWATCH (photoplethysmo)
- C = no
- O = Afib >>
OBS: to use photoplet I• would need to be MORE TARGETED + ACCURACY algorith WOULD REQUIRE continuous improvement >> DEEP LEARNING (to identify hrAfib) may help to refine POPULATION of Afib
3. More screening = MORE COSTS beyond monetary (in-person visits, wearable monitors, telehealth) AND would ↑disparities in care.
4. Benefits of screening is not only S† PREVENTION >> USPSTF notes = behavior + lifestyle MODIF are IMP >> PXS w_Afib WOULD BENEFIT from TTO MODIFIAB rf (obesity, HTA, -ol, sleep apnea, smok, DM)
5. Afib affect pxs + HCsys
6. UNTARGETED, ONETIME screening w_ INTENTION TO START AC (prophy) IN PXS ↑r events = NO EVIDENCE OF BENEFIT vs UC
7. Practicioners find INCIDENTALLY dysrhyt (an ECG artifact) = IN asymp WILL BE A CHALLENGE
8. MEANS of translating EBR (↓ ‘symp + l-t HC use’) into language our pxs CAN understand SO THAT we can extend to clinPract.
9. USPSTF gives us VALUABLE OPPORTUNITIES for DISCOVERY (Afib risk estim + evolving evidence) WITH THE OBJECTIVE of ↑targete screen & measure IMPAC OF TTO
TIME MANAGEMENT
01:27:19
Round: 3 04:02:08 commentsRound: 2 01:11:35 Clinical caseRound: 1 11:42:04 Refresh
Monday 17.10.22 at 23h15 BE
AAH, MKFA, AAQC
❗️REFRESH: last Monday JR
The Case of the Missing Data | NEJM Evidence
2022 HEALIO - Despite recommendations, statin use ‘not ubiquitous’ in CKD w_ ASCVD (ClinCar) [News]
How to Handle Missing Data: Complete cases & Imputation
TIME MANAGEMENT
01:58:53
Round: 2 01:41:94 Appraisal of last & current STATs Round: 1 19:17:65 Refresh
Tuesday 18.10.22 at 23h15 BE
MKFA, CCC, AAACC, AAQC
❗️REFRESH: last Tuesday JR
NEJMjw - Timing of Anticoagulants in Stroke Related to Afib (Circulation)
2022 NEJMcp - Pulmonary embolism (kahn) [CP]
insOF: instead of, pTTO: primary TTO, ext-phaseAC: extended phase anticoagulation, hBLEEDr: high bleeding risk, chro: chronic, ir: intermediate risk, E&S: efficacy and safety
TIME MANAGEMENT
01:30:34Round: 4 00:17:48 CommentsRound: 3 33:03:35 Review contentRound: 2 39:51:97 Review tableRound: 1 17:21:20 Refresh
Wednesday 19.10.22 at 23h15 BE
AAQC
❗️REFRESH: last Wednesday JR
2022 JAMA - Screening for Atrial Fibrillation—Refining the Target (Kalscheur) [ed]
2021 LANCET - Population screening for atrial fibrillation to prevent stroke (Lowres) [com]
2022 MEDPAGE - FDA Says Young Kids Can Now Get Omicron Boosters Too (Hein) [New]
E&S: efficacy and safety;
TIME MANAGEMENT
01:27:47Round: 2 01:16:42 Clinical case + uARTRound: 1 11:04:97 Refresh
Thursday 20.10.22 at 23h15 BE
AAQC
❗️REFRESH: last Thursday JR
2022 HEALIO - Healthy habits in midlife may help delay onset of cognitive decline (Herpen) [News]
2022 LANCET - Waking up to the importance of sleep [ed].pdf
PCP: primary care physician; DEM: dementia; CBT: cognitive behavioral therapy; MB: morbidity; HCP: health-care professionals; PM: policy makers
11. Much less attention: physicians + HCP + PM
2022 NEJMjw - How Long Does C19–Associated Smell+Taste Dysfunction Last (JAMA2x, BMJ)
SoT: Smell or taste;
TIME MANAGEMENT
01:40:29Round: 3 18:51:91 smell and taste C19Round: 2 01:10:41 Sleep articleRound: 1 10:56:23 Refresh
Thursday 27.10.22 at 23h15 BE
GMC, ARAA, AAQC
❗️REFRESH: last Thursday JR
2022 LANCET - Waking up to the importance of sleep [ed].pdf
2022 NEJMjw - How Long Does C19–Associated Smell+Taste Dysfunction Last (JAMA2x, BMJ)
2022 NEJMjw - Procalcitonin-Guided Therapy Can Improve ATBS Stewardship in Acute Pancreatitis (LANCET)
NEJMjw - Two-Day Course of Antibiotics for COPD Exacerbation (Ther Adv Respir Dis)
TNSA: Tunisia;
TIME MANAGEMENT
01:10:53
Round: 3 01:59:95 Comments
Round: 2 58:12:47 uARTRound: 1 10:41:48 Refresh
Friday 28.10.22 at 23h15 BE
GMC, AAH, AAQC
❗️REFRESH: last Friday JR
2022 JAMA - Screening for Atrial Fibrillation—Refining the Target (Kalscheur) [ed]
2019 NEJMcd - S GL (chen) [cd]
TIME MANAGEMENT
01:44:59
Round: 4 25:33:49 Clinical case discussion
Round: 3 16:36:75 comment srMARound: 2 52:10:87 Clinical CaseRound: 1 10:38:25 Refresh
Thursday 03.11. 22 at 23h15 BE
MJAC, GMC, AAQC
❗️REFRESH: last Thursday JR
2022 NEJMjw - Procalcitonin-Guided Therapy Can Improve ATBS Stewardship in Acute Pancreatitis (LANCET)
NEJMjw - Two-Day Course of Antibiotics for COPD Exacerbation (Ther Adv Respir Dis)
2022 MEDSCAPE - New COVID Variant Gaining Traction in US (O'Mary) [r].pdf
NY: New York, NJ: New Jersey
BQ.1 + descendants = EMERGING C19 ➩ 1 in 10 cases (US)… according to CDC
1 month ago = <1%
Fauci ➩ “when this type of variants = you look at the RATE of ↑ as a relative proportion. (troublesome doubling time)
Potential mutations
USA currently most known subvariant = Ω BA.5 = 68% of INF
Monoclonal abs might NOT BE as effective for BQ.1 + BQ.1.1 (descendant) [both predominantly in NY and NJ = 20% of INF] ➩ REASON OF CONCERN!!!
Double reason: DOUBLING TIME + ELUDE monoclonal Abs
The booster shots ➩ STILL 1st line of protection (BECAUSE IT IS a variant from Ω)
ENCOURAGING NEWS = BA.5 sub-lineage = we will have CROSS-PROTECTION
2022 NEJMjw - Are Bronchodilators Effective in Symptomatic Smokers w_Normal Spirometry (NEJM).pdf
TIME MANAGEMENT
01:12:03
Round: 3 00:36:27 Comment
Round: 2 01:00:31 uART 1 and 2
Round: 1 10:55:35 Refresh
Monday 07.11. 22 at 22h45 BE
ALAC
2022 CO - Inotrope and vasopressor use in cardiogenic shock: what, when and why? (Hu) [r]
CS → Low cardiac output that leads to end-organ hypoperfusion. Stages from A to E (SCAI, standard and px info). SHOCK-trial: less MM w/ urgent revasc in AMI-CS. Mainstay tt: vasopressors+inotropes (expert consensus). NA 1st line vasopressor (a1 vasopression B1 cardiac contractility). Ad→more MM (OptimaCC trial). Vasopressin/phenyleohrine: no cardiac contractility (good for LVOTO). Vasopressin: good for RVDisfx. Dopamina contraindicated: increased arritmias + 28d MM. Dobutamine: + inotropic and reduce afterload. Careful in post-AMI (more oxygen demand + arrythmias). CAPITAL DOREMI trial: No diff dobuta*milrinone.
2022 CO - Antimicrobial stewardship (Lanckohr) [r]
AMS→ actions to promote responsible use of atb: audit and feedback (interdisciplinary expertise in infection mgmt), restriction and preapproval (drug use after specialist authorization; generally less accepted), surveillance of resistance and antimicrobial use. AMS does not increase MM, reduce costs, atb prescription. Antimicrobial de-escalation: no neg impact of patient. Antimicrobial duration: Shorter is better (5-7 days in most situations). PROGRESS-trial: use of PCT for atb discontinuation.
Tuesday 08.11. 22 at 23h15 BE
ALAC
2022 CO - Ressuscitation guideline highlights (Olasveengen) [r]
High quality CPR optimizing education & training to lay & professional rescuers. ILCOR 2015: telecommunication (some CPR better than no CPR). New techniques not validated yet: Positive-pressure ventilation? Head-up CPR? IO access second line if IV access not possible. Transport during maneuvres decrease CPR quality → even w/ mechanical compressions (exception ECPR).
2022 CO - Update on SA bacteremia (Tabah) [r]
SAB leading cause Sepsis+SS. MRSA SAB increased during COVID-19 pandemic. MM decreased since 1991. Malignancy is a risk factor for SAB (++nosocomial) w/ MM~43% at 6m. Persisting SAB: 2-7d w/ +ve HC. TT MRSA SAB: daptomycin or vancomycin 1st line? (low evidence) → Davis et al. role of combination dapto+B-lact; Johnson et al. combination dapto+ceftaroline for persisting MRSA SAB despite vanco?
Wednesday 09.11. 22 at 22h45 BE
ALAC
2022 JCIS - The many faces of cryptogenic pneumonia (Kloth) [r]
Organizing pneumonia: interstitial pneumonia w/ acute/subacute clinical course & histological pattern compatible w/ acute lung injury. Secondary (to recent infection, p.e) vs. primary (cryptogenic). HRCT typical COP: sharply delineated from surrounding parenchyma w/ lobular pattern next to bronchovasc structures; no parenchymal destruction; bipulmonary spto shaped infiltrates w/ rounded/flat consolidations + GGO; parenchymal consolidation + air bronchogram. ++ 50-60yo, W=M, ++ smokers. Stx ~flu, lasting weeks, no improve/ w/ atb. Triad: Stx~resp infection no atb response + typical image + histology. BAL: lympos w/ reduced CD4/CD8. GS = biopsy (Masson Bodies).
2022 AIC - Loop diuretics in ICU ptx w/fluid overload (Wichmann) [SRMA]
Fluid overload (FO) common in ICU (ressuscitation, AKI w/ oliguria, capillary leak). Sodium overload w/ fluids diff to excrete by kidneys = water retention. FO is RF for IAP, AKI and inc MM. Furosemide predominant diuretic. SRMA: 10 trials → 6 trials: loop diuretic vs. placebo (1), no diuretics (3) or SOC (2). No MM diff in 28-90d (low certainty), no plasma creat diff (low certainty). No diff in resolution of fluid overload (very low certainty).
Tuesday 22.11. 22 at 23h15 BE
ALAC
ICME 2022 - Pathophysiology of fluid administration in critically ill patients (Messina) [r]
Fluids are commonly administrated, but heterogeneous administration. Shock tt: fluids +- vasopressors obj improve DO2. Fluids increase venous return → increase SV → increase CO → increase DO2 (effect not linear). SSC: initial fluid resuscitation 30ml/kg. Fluids only when patient is fluid responsive → benefit reduces after a few hours of resuscitation. Response should be analized in multimodal fashion: real time responses to increase in systemic blood flow and/or perfusion pressure → peripheral perfusion (CRT), ScvO2, venous-arterial pCO2. Hyperlactacidemia may not be good marker (hyperadrenergism/liver dysfunction). MAP is not a good marker of SV increase (depends on vessels elastance → more response in hypovolemic shock, less in septic). Rate of infusion dictates difference in fluid responsiveness. Large RCT 16ml/min vs 5.5ml/min → no diff MM BUT rates smaller than FC.
Monday 28.11.22 at 21h15 BO
AAQC, AAACC, MKFA
❗️REFRESH: last Monday JR
JIM 2022 - How to integrate hemodynamic variables during resuscitation of septic shock? (Teboul) [r]
2022 MEDPAGE - Did My Strong COVID Vax Reaction Give Me Better Immunity (Fiore) [r].pdf
2022 HEALIO - Non-nutritive sweeteners alter microbiome composition, glycemia in healthy adults (Cell) [r].pdf
TIME MANAGEMENT
01:35:57
Round: 3 05:33:38 Comments
Round: 2 00:00:09 JR 2 articlesRound: 1 01:30:23 Refresh
1. A JR is an academic session where we go through some articles previously codified/labeled, for 45-60 min.
2. The articles are selected during the session based on the participants interests and backgrounds.
3. Its purpose is to understand and discuss relevant content elements applying systematized note-taking methodologies.
4. We generate discussion and recall pivotal concepts about different topics, all pertinent to our clinical practice.
5. We write down the key points of every session and publish them on our website.
6. In the following session we briefly recall the key-points from the previous JR, applying the 'reinforcing technique’.
7. Check out our calendar and see you in the DISCORD server.
Notes to navigation
