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

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).

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)

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