Original publications
Latest Research
Selected research with implications for clinical practice. Click a headline to read the original journal article.
- Methylphenidate and behavior therapy improve classroom outcomes in children with ADHD
JAMA Pediatrics
Crossover trial: 255 children began treatment. Methylphenidate increased academic productivity by 22% and quiz scores by 3.9 points; both medication and behavioral support reduced rule violations. Four tested accommodations showed no clear benefit. Summer-program setting limits generalization to everyday classrooms; this does not establish that all individualized accommodations are ineffective. - Tumor Treating Fields delay deterioration in selected quality-of-life measures in pancreatic cancer
JAMA Network Open
PANOVA-3 secondary analysis, 571 randomized patients with unresectable locally advanced pancreatic cancer: global-health deterioration-free survival was 7.1 vs 5.7 months with Tumor Treating Fields plus chemotherapy versus chemotherapy alone (HR 0.77). Open-label patient-reported outcomes and incomplete follow-up questionnaires limit interpretation; opioid-use analysis was post hoc. - Risk-stratified penicillin-allergy alerts are associated with greater cephalosporin use
JAMA Network Open
Before-and-after study of 26,903 patients with penicillin-allergy labels: cephalosporin use increased 17.8% in hospital and 35.4% in operating rooms after risk-stratified alerts. No anaphylaxis was identified by the study surveillance method. Nonrandomized single-system study; delayed allergic reactions and long-term clinical outcomes were not assessed. - Clinician training and assigned text reminders show no clear HPV vaccination benefit
JAMA Network Open
Text & Talk randomized trial across 30 Florida clinics and 7,234 children: vaccine initiation and completion did not differ by assigned training or texting strategy. Higher uptake among actual text recipients was an as-treated association, not the randomized result. Delivery problems and activity in control clinics may have diluted effects. - A fluid tau marker shows promise for detecting advanced chronic traumatic encephalopathy
JAMA
Case-control biomarker study of 229 participants, including only 11 with CTE: plasma eMTBR-tau243 distinguished advanced CTE from controls but not early-stage disease. It was also elevated in Alzheimer disease and some genetic tauopathies. Small selected samples; clinical diagnostic utility requires prospective validation. - Extended-release opioids after arthroplasty are associated with more persistent opioid use
Anesthesiology
Ontario cohort of 258,624 patients: a new extended-release opioid prescription was associated with persistent opioid use (adjusted OR 1.08), readmission and emergency visits. Observational findings with mixed health-service outcomes; causation is unproven. Abstract reviewed. - An invasive strategy does not significantly reduce the primary outcome in cognitively impaired older adults with NSTEMI
Age and Ageing
Prespecified SENIOR-RITA subgroup: among 909 cognitively impaired patients, cardiovascular death or nonfatal MI occurred in 26.8% versus 29.6% (HR 0.85, 95% CI 0.66–1.10). No treatment-by-cognition interaction; the nonfatal MI reduction is exploratory. Abstract and relevant full-text sections reviewed. - Izalontamab brengitecan improves survival in previously treated advanced esophageal squamous cancer
JAMA
PANKU-Esophagus01: open-label phase 3 trial in China, 497 patients after PD-1/PD-L1 inhibitor plus platinum therapy. Median overall survival was 9.79 vs 7.20 months (HR 0.63). Grade ≥3 treatment-related adverse events were more frequent (85.1% vs 59.3%). Interim analysis; publisher abstract reviewed. - Cefazolin causes fewer adverse-event discontinuations and less acute kidney injury in MSSA bacteraemia
JAMA Network Open
Bayesian meta-analysis of CloCeBa and SNAP: 1,579 evaluable patients for 90-day mortality. Cefazolin versus cloxacillin/flucloxacillin reduced adverse-event discontinuation (OR 0.25) and AKI (OR 0.54). Mortality OR 0.84 (95% credible interval 0.59–1.28); survival superiority is not established. Only two open-label trials; original methods and results reviewed. - Biomarker-guided antibiotics fail to establish noninferiority in very preterm infants
JAMA Network Open
Randomized trial of 283 infants born at 25–31 weeks: survival without major morbidity was 53% with biomarker-guided treatment versus 55% with universal antibiotics. Noninferiority was not demonstrated. No early-onset sepsis occurred, leaving safety in infected infants uncertain; major infection risk factors were excluded. Original results and limitations reviewed. - Intensive HABIT-ILE therapy improves motor function in preschool children with bilateral cerebral palsy
JAMA Network Open
Small randomized trial with 49 children analyzed: 50 hours of HABIT-ILE over two weeks improved GMFM-66 at three months versus usual motor activities (adjusted difference 4.33 logits). Specialized setting and short follow-up limit generalizability and conclusions about durability. Original results and limitations reviewed. - Celiac disease is associated with a higher risk of eating disorders
JAMA Network Open
Swedish cohort: 37,853 patients with biopsy-confirmed celiac disease and 185,159 reference individuals; adjusted hazard ratio for eating disorders 1.39 (95% CI 1.27–1.53). Detection bias and residual confounding prevent causal interpretation. - Earlier surgery is associated with better survival in stage I non-small-cell lung cancer
JAMA Network Open
US retrospective cohort of 157,894 patients; propensity-matched analysis included 112,772. Five-year overall survival was 74.1% with surgery within four weeks versus 69.9% later. Selection and residual confounding prevent a causal claim or a universal four-week deadline. - Gut microbiome diversity at engraftment does not predict non-relapse mortality in a transplant study
Nature Medicine
BMT CTN 1801 companion study: 2,575 stool samples from 304 allogeneic-transplant recipients. The primary association between engraftment microbiome diversity and one-year non-relapse mortality was not detected (P=0.314). Regimen-related microbiome differences were exploratory; this does not test a microbiome-directed treatment. - Guanfacine does not show a significant adjusted delirium benefit in an ICU pilot trial
Crit Care Med
Single-centre feasibility RCT of 100 surgical/trauma ICU patients: an unadjusted difference in delirium/coma-free days was not significant after prespecified adjustment. Length of stay and ventilation duration did not differ; efficacy needs a definitive trial. Abstract reviewed. - Targeting normocapnia shows no mortality advantage over mild hypercapnia in an ARDS emulation
Crit Care Med
Target-trial emulation, 584 patients: 90-day in-hospital mortality was 28.8% in both groups. Normocapnia required higher respiratory rates. This was not a randomized comparison of carbon-dioxide targets; residual confounding remains possible. Abstract reviewed. - A computational TROP2 score may predict benefit from datopotamab deruxtecan in lung cancer
Nature Medicine
Retrospective biomarker analyses of TROPION trials: TROP2 membrane-ratio status was associated with differential progression-free survival on datopotamab deruxtecan versus docetaxel (interaction P=0.0098). This is a candidate treatment-selection marker, not prospective proof of biomarker-guided care. Abstract and relevant full-text sections reviewed. - JAK inhibition shows preliminary responses in thymoma-associated immune dysregulation
NEJM
NEJM research correspondence: four severely affected patients treated with JAK1/2 inhibitors had clinical and biomarker responses. Uncontrolled observations cannot establish efficacy or safety; only the publisher’s short abstract was accessible. - More extensive lung cavities and prolonged cough are associated with household TB infection
Chest
Peruvian cohort with 3,109 index patients and 12,767 household contacts: greater cavitation and longer cough were associated with infection in child contacts. Associations with incident TB disease were uncertain. Author abstract in PubMed reviewed; publisher page blocked. - Adding intismeran to pembrolizumab improves recurrence-free survival after melanoma resection
NEJM
INTerpath-001 phase 3 RCT, 1,137 patients with resected stage IIB–IV melanoma: 24-month recurrence-free survival was 82.2% versus 70.0%. Grade ≥3 adverse events occurred in 23.6% versus 20.3%; overall-survival benefit is not established here. Abstract reviewed. - Aspirin fails to establish noninferiority for clot prevention after hip or knee replacement
NEJM
PEPPER randomized 18,883 patients; the primary per-protocol analysis included 15,317. Aspirin did not meet noninferiority versus rivaroxaban or warfarin for death or symptomatic VTE. The anticoagulants also did not establish safety noninferiority versus aspirin; superiority is not demonstrated by these findings. Abstract reviewed. - Withholding ACE inhibitors or ARBs on surgery morning reduces hypotension in older adults
BMJ
Multicentre RCT, 2,036 patients aged 60–80 years; 2,012 completed follow-up. Perioperative hypotension occurred in 31.2% after withholding versus 45.5% after continuing treatment. No significant difference in 30-day complications or mortality. Applies to the studied non-cardiac-surgery population. Abstract reviewed. - Trevogrumab limits lean-mass loss during semaglutide treatment
The Lancet
COURAGE phase 2 RCT, 975 participants: trevogrumab reduced lean-mass loss with semaglutide. Adding garetosmab further improved body composition but had unfavorable safety and tolerability, including 32% discontinuation in the combination group. Functional benefit remains unproven. Abstract reviewed. - Clomipramine shows strong OCD efficacy but poorer tolerability than SSRIs
Lancet Psychiatry
Network meta-analysis of 52 trials and 7,316 participants: clomipramine had the largest estimated efficacy but more adverse-event discontinuation in adults. Several between-drug comparisons, especially in children, had low or very-low certainty. Abstract reviewed. - Lung-function decline persists in some adults with cystic fibrosis despite triple therapy
Lancet Respir Med
French prospective cohort of 2,321 adults on elexacaftor–tezacaftor–ivacaftor: initial FEV1 improvement was followed by a mean 0.70 percentage-point annual decline; 31.8% declined by more than 1.5 points/year. Observational findings support continued monitoring, not a causal comparison of add-on therapies. Abstract reviewed. - SOFA-2 underpredicts ICU mortality in older patients in external validation
Crit Care Med
Single-centre MIMIC-IV cohort of 64,015 patients: overall AUROC 0.77, falling to 0.72 at age ≥75 versus 0.85 at ages 18–44. Calibration and discrimination varied by age and language; this does not establish effects on clinical decisions. Abstract reviewed. - Early-pregnancy doxycycline use is associated with higher pregnancy-loss risk
Ann Intern Med
Observational active-comparator cohorts: doxycycline versus amoxicillin for respiratory infection was associated with adjusted pregnancy-loss risk ratios of 1.54 and 1.40 in two databases. Residual confounding and misclassification remain possible; causation is not established. Abstract reviewed. - An integrated high-sensitivity troponin pathway is associated with shorter emergency stays
JAMA Netw Open
Before-and-after study, 16,094 encounters: mean ED stay fell from 6.18 to 5.64 hours. Workflow changes and temporal confounding prevent attributing the improvement solely to the assay. - Risovalisib shows activity in PIK3CA-mutated ovarian clear-cell cancer
Lancet Oncol
Single-arm phase 2 study: objective response in 35% of 84 efficacy-evaluable patients. Severe rash and hyperglycaemia were important toxicities; no randomized comparator. Abstract reviewed. - A digital parenting programme reduces reported sexual violence in adolescent girls
Lancet
Cluster randomized trial, 2,396 caregiver-adolescent pairs in Tanzania: reported sexual violence decreased among girls, without a demonstrated effect among boys; maltreatment decreased overall. Abstract reviewed. - Oliceridine provides noninferior ICU analgesia to remifentanil
Intensive Care Med
CO-ROAM randomized trial, 307 patients: noninferior time in target analgesic range, with fewer respiratory-depression events. No demonstrated improvement in ventilation duration, ICU stay or 28-day mortality. Abstract reviewed. - Bepranemab fails to slow clinical decline in early Alzheimer disease
Lancet Neurol
Phase 2 randomized trial, 466 participants: neither dose improved the primary CDR-SB endpoint at 80 weeks. Biomarker and secondary cognitive findings remain hypothesis-generating. Abstract reviewed. - Talking with Voices therapy improves recovery in people with distressing voices
Lancet Psychiatry
Talking with Voices-II randomized trial, 309 participants: personal recovery improved at eight months, with a smaller benefit at 14 months. Comparator was usual care, not an active psychological intervention. Abstract reviewed. - Long-term antidepressant response differs between drugs, but evidence remains uncertain
Lancet Psychiatry
Network meta-analysis, 115 trials and 30,428 participants: escitalopram, duloxetine and agomelatine favored sustained response versus fluoxetine in the principal analysis. Substantial risk of bias limits confidence in rankings. Abstract reviewed. - Brepocitinib improves cutaneous sarcoidosis in a small phase 2 trial
JAMA Dermatol
BEACON phase 2 randomized trial, 31 participants: 69% receiving 45 mg achieved clear or almost-clear disease at 16 weeks versus none on placebo. Small, short study; long-term efficacy and safety remain uncertain. Abstract reviewed. - Off-pump CABG shows no significant primary-outcome advantage in frail patients
Circulation
FRAGILE randomized trial, 508 prefrail or frail patients: the 30-day composite occurred in 10.9% with off-pump versus 16.0% with on-pump surgery, a nonsignificant difference. This does not establish equivalence. Abstract reviewed. - A seven-item rule may help identify patients at very low risk of acute aortic syndrome
Eur Heart J
ARC retrospective derivation and external validation: high sensitivity across two validation cohorts, but one estimate had wide uncertainty. Prospective clinical utility needs confirmation; not a stand-alone instruction to withhold testing. Abstract reviewed. - Inpatient ibuprofen use is associated with higher AKI risk in vulnerable patients
JAMA Netw Open
Observational cohort, 78,656 patients: adjusted AKI rate ratio 1.22 versus oxycodone. Associations were stronger after surgery and in critical illness; no excess was detected in the defined low-risk subgroup. Residual confounding remains possible. - A blood RNA marker shows promise for detecting early ovarian cancer
Nature Medicine
Biomarker study of 506 individuals: extracellular-vesicle Tu-stroma discriminated tubal precursor lesions and ovarian cancer from controls. Selected case–control comparisons can overestimate screening performance; prospective real-world validation and clinical utility are unproven. Abstract and relevant full-text sections reviewed. - Hypoglycaemia is associated with impaired cognition during the following hour
Diabetes Care
190 adults with type 1 diabetes underwent continuous glucose monitoring and smartphone cognitive testing over 15 days. Recent hypoglycaemia was associated with worse performance, mainly within one hour. Observational results do not define a universally safe return-to-driving interval. Author abstract in PubMed reviewed; publisher page blocked. - Postoperative digital monitoring is associated with fewer readmissions
Anesthesiology
Meta-analysis of 38 studies (30 randomized, eight observational; 7,494 patients): readmissions were less frequent (RR 0.85), with benefit concentrated in interventions involving active clinician review. Heterogeneity was substantial and evidence certainty low to very low. Abstract reviewed. - Resistance exercise limits lean-mass loss and improves strength during tirzepatide treatment
Nat Med
Randomized trial, 120 adults: three resistance sessions weekly preserved about 1.09 kg more lean tissue over 40 weeks and improved strength despite similar weight loss. Lean-mass loss was reduced, not eliminated. - Azetukalner reduces drug-resistant focal seizures in X-TOLE2
JAMA Neurol
X-TOLE2 phase 3 randomized trial, 374 adults: median seizure-frequency reductions were 53.2% with 25 mg and 34.5% with 15 mg versus 10.4% with placebo over 12 weeks. Longer-term outcomes remain important. - Pulse methylprednisolone improves visual-response rates after ethambutol optic neuropathy
Ophthalmology
Single-centre randomized trial, 100 patients: at least two-line visual improvement at six months occurred in 72% versus 46%. Mean final visual acuity did not differ significantly. Preliminary findings require larger confirmation. Abstract reviewed. - Efinopegdutide improves MASH resolution in a phase 2b trial
Lancet
Phase 2b trial, 386 randomized adults with MASH and F2-F3 fibrosis: histological MASH resolution favored efinopegdutide; fibrosis improvement was significant at 4 and 7 mg. Clinical liver-outcome benefit remains unproven. Abstract reviewed. - Pharmacist stewardship modestly increases deprescribing, but the effect is not sustained
JAMA Intern Med
Cluster randomized trial, 4,827 older inpatients: adjusted deprescribing increased by 5.3 percentage points. The gain was not sustained after active stewardship ended; inpatient adverse events were similar. Abstract reviewed. - CAR T-cell therapy shows promise in refractory stiff person syndrome
JAMA Neurol
Single-arm phase 2 study, 26 treated patients: walking and disability measures improved without a control group. Cytokine-release syndrome occurred in 92%, although reported cases were low grade. Long-term follow-up is ongoing. - The inforatio technique improves healing of selected diabetic foot ulcers
JAMA Netw Open
Randomized trial, 100 analyzed patients with noninfected Wagner grade 1 ulcers: wound-bed punch incisions plus standard care achieved closure in 49% versus 27.5% by 20 weeks. Applicability to infected or deeper ulcers is unproven. - A clinician-led initiative is associated with a modest reduction in low-value care
JAMA Intern Med
Controlled quality-improvement study involving approximately 4.5 million patients: selected low-value services decreased by 1.1 percentage points, without a demonstrated spending reduction. Observational association. Abstract reviewed. - Survodutide meets cardiovascular safety noninferiority in adults with obesity
The Lancet
SYNCHRONIZE-CVOT phase 3 trial, 5,530 randomized: cardiovascular composite events occurred in 3.7% versus 4.1% (HR 0.89, 95% CI 0.67–1.18). Noninferiority was established, not cardiovascular superiority. Gastrointestinal treatment discontinuation was more frequent. Abstract reviewed. - ANGPTL4 inhibition lowers triglycerides in a phase 2b trial
NEJM
TYDAL-TIMI 78 randomized 236 adults: MAR001 reduced triglycerides by 39–45 percentage points versus placebo at 12 weeks. This is a lipid endpoint; prevention of cardiovascular events and long-term safety remain unproven. Abstract reviewed. - Single-pill combinations with team-based care substantially improve blood-pressure control
JAMA
CATCH cluster trial, 1706 participants: systolic BP fell about 10 mmHg more at 18 months. Multicomponent intervention; benefit cannot be attributed to the pill alone. Abstract reviewed. - Adding low-voltage ablation does not clearly reduce persistent AF recurrence
JAMA
COAST-AF, 508 participants: recurrence 49.4% versus 57.5%; HR 0.82 (95% CI 0.65–1.04). Overall primary outcome was negative. Abstract reviewed. - Dapagliflozin improves the chronic eGFR slope after heart transplantation
Circulation
DAPARHT, 430 recipients: chronic eGFR slope difference 1.7 mL/min/1.73 m²/year over 12 months. Surrogate endpoint; prevention of kidney failure was not established. Abstract reviewed. - Intravenous iron modestly improves exercise capacity in HFpEF
Circulation
IRONMET-HFpEF, 65 participants: peak oxygen uptake improved by 1.1 mL/kg/min versus placebo at 12 weeks, without clear KCCQ benefit. Small trial, not clinical-event evidence. Abstract reviewed. - Retatrutide improves knee pain and weight in people with obesity
NEJM
TRIUMPH-4 and TRIUMPH-1-OA: pain improved alongside substantial weight loss. Gastrointestinal adverse effects were common; serious adverse events were more frequent with active treatment. Abstract reviewed. - A community and EMS intervention package does not improve favourable cardiac-arrest survival
NEJM
RACE-CARS, 55 clusters and 22459 patients: neurologically favourable survival 9.0% versus 9.4%. Tests an implementation package, not the effectiveness of CPR itself. Abstract reviewed. - Left bundle-branch pacing reduces a composite of death, heart failure and pacing cardiomyopathy
NEJM
OptimPacing, 702 randomised: composite-outcome HR 0.41. Trial stopped early; isolated mortality benefit was not established. Abstract reviewed. - Obinutuzumab beta improves short-term response in active lupus
Lancet Rheumatol
Phase 2 randomized trial, 123 patients: SRI-4 response at week 12 was 52% versus 34%. Predominantly Han Chinese population; confirmation and longer-term safety assessment are needed. Abstract reviewed. - An initial invasive strategy does not improve long-term survival in advanced CKD with stable coronary disease
Circulation
ISCHEMIA-CKD EXTEND, 777 participants, median eight-year follow-up: mortality 57.4% versus 56.8%; HR 1.05. Abstract reviewed. - Pelacarsen lowers lipoprotein(a) without reducing cardiovascular events
NEJM
Lp(a)HORIZON, 8350 randomised: cardiovascular events 12.3% versus 12.1%; HR 1.02 over median 4.7 years despite substantial lipoprotein(a) lowering. Abstract reviewed. - Ziltivekimab does not reduce cardiovascular events despite suppressing inflammation
NEJM
ZEUS, 6376 participants with ASCVD, CKD and raised hsCRP: events 17.6% versus 17.7%. Serious infections were more frequent with treatment. Abstract reviewed. - Stopping statins meets a noninferiority margin despite more events in older adults
NEJM
STREAM, 1880 adults aged at least 70 receiving primary prevention: composite events 12.7% versus 9.2%. Meeting the prespecified noninferiority margin does not establish equal safety. Abstract reviewed. - Intensive blood-pressure lowering shows no clear cardiovascular benefit in type 2 diabetes
NEJM
OPTIMAL-DIABETES, 9476 participants: systolic targets below 120 versus 140 mmHg; events 6.0% versus 6.7%, HR 0.90 (95% CI 0.77–1.06). Abstract reviewed. - Intensive blood-pressure control reduces cardiovascular events after ischaemic stroke
NEJM
OPTIMAL-STROKE, 4368 participants: events 10.9% versus 13.5%, HR 0.79. Adverse kidney outcomes were more frequent with intensive treatment. Abstract reviewed. - Prehospital extracorporeal support is associated with better cardiac-arrest survival
NEJM
OnScene, nonrandomised study of 231 patients aged 50 or younger: discharge survival 40% versus 20%. Selection, confounding and specialised resources limit causal interpretation. Abstract reviewed. - Cangrelor provides faster platelet inhibition but fails clinical noninferiority in cardiogenic shock
Lancet
DAPT-SHOCK-AMI, 605 participants: 30-day death/MI/stroke approximately 38% versus 41% with crushed ticagrelor. Prespecified clinical noninferiority was not demonstrated. Abstract reviewed. - An initial invasive strategy does not improve long-term overall survival in stable coronary disease
JAMA
ISCHEMIA-EXTEND, 5179 participants, median nine-year follow-up: mortality HR 0.97. Does not cover excluded groups such as significant left-main disease or unacceptable angina. Abstract reviewed. - Systemic inflammatory markers are associated with bronchiectasis severity and exacerbations
Am J Respir Crit Care Med
EMBARC-BRIDGE observational study, 487 patients: a systemic neutrophil-endothelial inflammatory signature was associated with severity and severe exacerbations. Not yet a validated treatment-selection test. Abstract reviewed. - Ulinastatin does not reduce 28-day mortality in sepsis
Chest
ADJUST, 347 randomised and 335 analysed: mortality 23.6% versus 22.9%; adverse events were more frequent with ulinastatin. Abstract reviewed. - Ganaplacide–lumefantrine achieves high malaria cure rates in children in a phase 2 trial
Lancet Infect Dis
KALUMI phase 2: approximately 99% PCR-corrected response with both regimens. Vomiting and hypokalaemia were more frequent with investigational treatment; further evidence is needed. Abstract reviewed. - Individualised blood-pressure targets during cardiac surgery show no clear outcome benefit
Anesthesiology
OPTIPAM, 172 participants: death/AKI/neurological outcome 32% versus 29%. Stopped early after a bleeding imbalance; target adherence was limited. Abstract reviewed. - A pre-COPD score predicts future airflow obstruction across three cohorts
Am J Respir Crit Care Med
Derivation and validation across three cohorts: discrimination ranged from 0.76 to 0.88 using smoking, symptoms and spirometry. Score-guided intervention has not been shown to improve outcomes. Abstract reviewed. - Seladelpar increases alkaline-phosphatase normalisation in primary biliary cholangitis
J Hepatol
IDEAL, 96 participants with mildly elevated ALP: normalisation 75.4% versus 16.1% at 12 months. Biochemical benefit does not establish improved survival or fewer transplants. Abstract reviewed. - Paravertebral blockade does not outperform epidural analgesia for chronic post-thoracotomy pain
BMJ
TOPIC2, 770 randomised: six-month chronic pain 22% versus 16%, without a statistically clear difference. Paravertebral blockade caused less hypotension; epidural provided better early pain relief. Abstract reviewed. - Smartwatch hypertension detection shows useful specificity but misses some cases
Nature
Prospective evaluation in 196 participants: sensitivity 65.8%, specificity 90% against ambulatory BP monitoring. Screening signal, not a replacement for diagnostic BP measurement. Abstract reviewed. - Missing newborn vitamin K is associated with greater intracranial bleeding risk
JAMA
Observational cohort of approximately 5.24 million newborns: intracranial bleeding 33 versus 13.2 per 10000; adjusted risk ratio 2.43. Association, not a new randomised trial. Abstract reviewed. - Laryngeal masks reduce respiratory adverse events during paediatric adenotonsillectomy
BMJ
Randomised trial of 400 children: respiratory events 22.5% versus 57.5% with tracheal tubes. Composite included severe cough; experienced teams and selected patients limit generalisability. Abstract reviewed. - Shockwave therapy may improve short-term frozen-shoulder pain
BMJ
Network meta-analysis of 189 trials and 12988 participants: moderate-certainty short-term pain benefit, with substantial trial bias and uncertain long-term outcomes. Abstract reviewed. - Dialysis preparation does not clearly improve quality-adjusted survival over conservative kidney care
Lancet
Prepare for Kidney Care, 445 predominantly older, frail or multimorbid participants, median age 82: no statistically clear QALY difference. This does not prove equivalence. Abstract reviewed. - Imipenem–cilastatin–funobactam meets mortality noninferiority in hospital-acquired pneumonia
Lancet Infect Dis
450 participants: 14-day mortality 3.0% versus 2.7% with imipenem–cilastatin–relebactam. Low event rates and a 10-percentage-point noninferiority margin warrant caution. Abstract reviewed. - Mobile addiction and HIV services do not improve primary treatment-uptake outcomes
JAMA Psychiatry
HPTN 094, 409 people who inject drugs: no clear primary PrEP/MOUD uptake benefit. Fewer deaths in a secondary analysis are hypothesis-generating. Abstract reviewed. - Adding hydralazine–isosorbide dinitrate shows no clear benefit in contemporary-treated HFrEF
Eur Heart J
H-HeFT, 592 predominantly White participants: primary events 30.6% versus 30.5%; HR 0.90 (95% CI 0.67–1.21). Do not generalise to every population or established indication. Abstract reviewed. - Plozasiran lowers triglycerides and reduces pancreatitis events
NEJM
SHASTA-3/4, 757 participants: substantial triglyceride lowering; pooled pancreatitis rate approximately 1 versus 5 per 100 patient-years. Pancreatitis was a pooled secondary outcome. Abstract reviewed. - Chemogenetic neuromodulation shows an early seizure-reduction signal
NEJM correspondence
Uncontrolled three-patient report: mean seizure reduction 92.6%. Experimental evidence, not established treatment. Short publisher abstract reviewed. - Adding fusion shows no clear disability benefit across lumbar spondylolisthesis subgroups
Ann Intern Med
Target-trial emulation, 2252 adults: 12-month disability and reoperation outcomes did not clearly differ. Observational evidence with residual confounding; not a new randomized comparison. Abstract reviewed. - About half with persistent long COVID improve by three years
Ann Intern Med
RECOVER-Adult cohort, 1019 people with likely long COVID at 12 months: 50.1% crossed below the research-index threshold at two consecutive visits by 36 months; 26.9% reached an index of zero. Improvement is not necessarily complete recovery. Publisher abstract reviewed. - TAVR reduces death-or-heart-failure events in selected patients with moderate aortic stenosis
NEJM
PROGRESS randomized trial, 744 patients: two-year death or heart-failure events 16.7% versus 23.9%. Benefit was driven by fewer heart-failure events; mortality alone was not lower. Publisher abstract reviewed. - Simpler antithrombotic regimens meet noninferiority criteria after uncomplicated left atrial appendage closure
JAMA
SIMPLAAFY randomized trial, 1857 patients: aspirin alone or three months of reduced-dose anticoagulation followed by aspirin met noninferiority criteria versus dual antiplatelet therapy for the six-month composite outcome. Applies to selected patients after successful uncomplicated closure, not all patients with AF. Publisher-deposited abstract reviewed. - Povorcitinib improves facial repigmentation in nonsegmental vitiligo
Nature Medicine
STOP-V1 and STOP-V2 randomized trials, 916 participants: F-VASI75 at 52 weeks was 18.9% with povorcitinib versus 6.8% and 3.1% with placebo. Acne was more frequent; longer-term safety remains important. Publisher abstract reviewed. - Preoperative botensilimab–balstilimab shows pathological responses in a small colon cancer trial
Nature Medicine
UNICORN: 56 patients in four sequential nonrandomized cohorts. Major pathological response with combination therapy occurred in 36% of pMMR and 100% of dMMR cases (14 per cohort). Surrogate endpoint; comparative survival benefit is unproven. Publisher abstract and methods reviewed. - Surgery is associated with lower mortality than SABR in operable early lung cancer
J Clin Oncol
Registry target-trial emulation, 12546 eligible patients: adjusted three-year all-cause mortality 30.3% after SABR versus 21.6% after surgery. Residual confounding remains; cancer-specific mortality difference was not statistically clear. Publisher abstract reviewed. - Toripalimab added to FOLFIRINOX improves event-free survival in pancreatic cancer
J Clin Oncol
Open-label phase 2 randomized trial, 392 borderline-resectable/locally advanced cases: median EFS 11.1 versus 9.6 months(HR 0.74); overall survival advantage not established(HR 0.81, 95%CI 0.63–1.03). Resection rates similar. Publisher abstract reviewed. - Caring Contacts shows no added benefit for suicidal outcomes over enhanced usual care
JAMA Netw Open
CARE randomized trial, 709 American Indian/Alaska Native adults with active suicidality: no significant added benefit on suicidal outcomes; only 64% provided 12-month follow-up. Findings specific to this intervention and active comparator. Publisher abstract reviewed. - Hospital delirium is associated with greater subsequent dementia risk
JAMA Neurol
Mayo longitudinal cohort, 3501 previously nondemented hospitalized adults: 75 had documented delirium; adjusted dementia HR 5.39. Observational association, sparse delirium detection and residual confounding; does not show delirium causes dementia. Publisher abstract reviewed. - Continued mammography shows no clear reduction in advanced second breast cancers in older survivors
JAMA Intern Med
Observational cohort, 9888 older survivors(mean age 81): advanced second cancers 1.65% versus 2.15%, HR 0.76(95%CI 0.46–1.26). Low event rates and imprecision; no proof surveillance is universally unnecessary. Publisher abstract reviewed. - Child developmental scores are similar after maternal COVID-19 mRNA vaccination
JAMA Pediatr
Prospective cohort, 217 matched pairs: ASQ-3 scores met prespecified equivalence limits at 18–30 months. Observational, questionnaire-based developmental assessment; does not establish all long-term outcomes. Publisher abstract reviewed. - Bicarbonate may reduce dialysis initiation without a clear survival benefit in ICU acidosis
Intensive Care Med
Bayesian meta-analysis of 4 RCTs/1544 patients: mortality RR 0.94(95%CrI 0.73–1.22), RRT initiation RR 0.74(0.59–0.98). Search ended 2 April 2026, so this synthesis excludes subsequently published trials and is not a complete November evidence summary. Publisher abstract reviewed. - CT-guided PCI meets noninferiority criteria against intravascular ultrasound guidance
NEJM
P4 randomized trial, 1105 selected patients: 12-month target-vessel failure 4.1% versus 4.6%; risk difference −0.42 percentage points (95% CI −2.82 to 1.99), within the 4.5-point noninferiority margin. Superiority was not established. Publisher abstract reviewed. - Anticoagulant monotherapy reduces two-year net adverse events in AF patients with a coronary stent placed at least one year earlier
NEJM
ADAPT AF-DES extended follow-up: NOAC monotherapy versus a NOAC plus clopidogrel in patients with atrial fibrillation and a coronary stent placed at least one year earlier. Fewer net adverse clinical events at two years. Only the short publisher abstract was accessible; event rates, individual components and detailed safety could not be reviewed. - TAVR reduces one-year major clinical events in selected patients with severe pure aortic regurgitation
Circulation
SEASON-AR: open-label randomized trial, 210 patients at 18 Chinese centres who could not readily undergo surgery or persistently declined it. TAVR plus medical therapy versus medical therapy alone: death, disabling stroke or heart-failure rehospitalization 8.3% versus 24.8% at one year (HR 0.31, 95% CI 0.14–0.66), driven mainly by fewer heart-failure admissions. More major/life-threatening bleeding and pacemaker implantation. Publisher-deposited abstract reviewed through Crossref; full text unavailable. - Early drug treatment of patent ductus arteriosus may increase mortality in preterm infants
Lancet Child Adolesc Health
Bayesian meta-analysis of 10 trials, 2,365 infants; overall mortality RR 1.23 (95% credible interval 1.00–1.54), without compensatory bronchopulmonary dysplasia benefit. Subgroup estimates remain uncertain. Abstract reviewed. - Oral orforglipron reduces weight in Japanese adults with obesity
Lancet Diabetes Endocrinol
ATTAIN-J; 238 participants, 72 weeks; weight change −5.9% to −8.7% versus −0.6% with placebo. Gastrointestinal adverse effects; no cardiovascular-outcome assessment. Abstract reviewed. - Methylphenidate reduces fatigue in selected patients with haematological cancer
J Clin Oncol
152-person crossover trial; FACIT-F improvement 5 points greater than placebo over 6 weeks; more adverse events (57% versus 40%). Patients receiving recent chemotherapy were excluded. Abstract reviewed. - Self-directed lifestyle support fails the weight-loss endpoint in obstructive sleep apnoea
Am J Respir Crit Care Med
POWER; 696 participants; −1.1 kg between-group difference did not meet prespecified significance threshold of 0.025. Sleep-related quality-of-life improvement was small. Abstract reviewed. - Adult-onset type 1 diabetes subtypes show different metabolic and complication profiles
Lancet Diabetes Endocrinol
Prospective German cohorts of 600 and 483 adults; mixed autoimmune and insulin-resistant phenotype appeared earlier along beta-cell decline. Observational classification, not a validated treatment-selection rule. Abstract reviewed. - Risk-reducing mastectomy is associated with lower mortality in BRCA1/2 carriers
JAMA Netw Open
Network meta-analysis of 5 observational studies, 7,937 women; all-cause mortality HR 0.37 versus MRI screening. Very low certainty; critical risk of bias in 4 studies; overall breast-cancer mortality difference versus MRI was not significant. Abstract reviewed. - Selected HER2-positive breast cancer responders retain favourable five-year outcomes without chemotherapy
Nat Med
PHERGain phase 2; 86 PET/pCR-selected chemotherapy-free responders had 92.4% five-year invasive disease-free survival. Post-randomization descriptive subgroup; not proof that chemotherapy can routinely be omitted. Abstract reviewed. - Remimazolam meets delirium noninferiority criteria against propofol in neurovascular surgery
Br J Anaesth
Single-centre trial; 686 analysed; delirium 12.8% versus 10.8%, risk-difference CI −2.85 to 6.80 percentage points. Wide 10-point noninferiority margin; less hypotension with remimazolam plus flumazenil reversal. Abstract reviewed. - EP262 fails to improve chronic spontaneous urticaria in a phase 2 trial
Allergy
CALM-CSU; 113 adults; neither dose significantly improved UAS7 versus placebo at six weeks. Planned second part was terminated. Publisher full text reviewed. - Maternal energy-protein supplements do not improve later infant growth in a Nepal trial
Am J Clin Nutr
MINT factorial trial; 1,568 infants; supplementation during pregnancy or lactation did not improve length-for-age at six months. This does not negate established birth-outcome indications in undernourished populations. Abstract reviewed. - Guided digital CBT-I improves insomnia in patients with coexisting sleep apnoea
Am J Respir Crit Care Med
88-person trial; insomnia-score change −9.5 versus −4.0 at three months; short-term apnoea-hypopnoea index also improved. Small study with limited follow-up. Abstract reviewed. - Stem-cell transplantation yields durable remission in some patients with severe systemic sclerosis
Lancet Rheumatol
NISSC1-LTE; 80-person cohort, 10-year progression-free survival 60%; 43% remained in remission without immunosuppression. No concurrent comparator; transplant-related deaths occurred in 6%. Abstract reviewed. - Updated Duke criteria improve sensitivity but leave many endocarditis cases uncertain
Clin Infect Dis
Retrospective cohort of 3,448 suspected episodes with guideline-concordant imaging; 29–33% remained possible endocarditis. Sensitivity improved with a specificity trade-off. Abstract reviewed. - One-hour troponin pathways do not consistently shorten emergency-department stays
Lancet
Individual-participant meta-analysis of 5 trials and 110,933 presentations; no clear length-of-stay or discharge advantage. Safety estimates were imprecise and heterogeneity substantial. Abstract reviewed. - Twice-yearly depemokimab maintains asthma control through two years
Lancet Respir Med
SWIFT/AGILE; 629 extension participants; exacerbation rate remained about 0.5 per year in continuing recipients. Second year was open-label without a concurrent placebo group. Abstract reviewed. - Adding oxymetazoline to budesonide improves steroid-refractory nasal obstruction
JAMA Otolaryngol Head Neck Surg
60-person trial; four-week response 83% versus 36%, with successful three-week weaning. Longer-term rebound congestion remains uncertain. Abstract reviewed. - Left bundle-branch area pacing reduces heart-failure events compared with right ventricular pacing
JAMA
LEAP-Block; 499 randomized, 482 primary-analysis patients with preserved ejection fraction and high pacing burden. Composite outcome 2.4% versus 12.5%; no significant mortality difference. Abstract reviewed. - Adding pembrolizumab to lung SBRT adds toxicity without improving event-free survival
J Clin Oncol
KEYNOTE-867; 448 patients with unresected stage I–II NSCLC; EFS HR 0.92 (95% CI 0.69–1.24). Severe treatment-related events 20.4% versus 3.7%; five treatment-related deaths with pembrolizumab. Trial stopped early. Abstract reviewed. - High-volume injections offer no lasting benefit for Achilles tendinopathy
BMJ
Inject; 192 adults; injections with or without corticosteroid did not improve pain/disability versus sham at 12 months. Transient steroid benefit did not persist. Abstract reviewed. - Perioperative esketamine reduces chronic pain after thoracoscopic lung surgery
Br J Anaesth
Multicentre trial; 873 analysed; three-month chronic pain 14.7% versus 21.2%. Primary pain threshold included mild pain; longer-term benefit remains uncertain. Abstract reviewed. - mRNA RSV vaccination is associated with fewer RSV infections and hospitalisations
JAMA Netw Open
Veterans target-trial emulation; estimated effectiveness 60.3% against documented infection and 81.8% against hospitalisation over 24 weeks. Observational, predominantly male cohort; not a head-to-head vaccine comparison. Abstract reviewed. - Exercise prehabilitation does not increase curative surgery completion in gastroesophageal cancer
JAMA Netw Open
PRESET-RCT; 202 analysed; failure to reach surgery 9.9% versus 7.9%. Secondary survival favoured control (HR 1.58); requires investigation and does not establish a general harmful effect of exercise. Abstract reviewed. - Acmopatide produces weight loss with modest glycaemic improvement in type 1 diabetes
Diabetes Care
Phase 2; 111 adults with overweight/obesity, 16 weeks; weight change −3.3% to −6.7% versus +0.3%. HbA1c benefit nominally significant at one dose; no severe hypoglycaemia or ketoacidosis observed, but small short trial. Abstract reviewed. - Specialist ILD clinic care is associated with fewer admissions and lower mortality
Chest
Single-health-system retrospective cohort; mortality HR 0.57 and hospitalisation HR 0.46. Referral and residual confounding prevent causal conclusions. Abstract reviewed. - Prespecified azithromycin exposure shows no clear association with new NTM isolation
Chest
Danish nested case-control studies in bronchiectasis and COPD; estimates were imprecise. Broader recent-exposure definitions showed associations, potentially reflecting indication-driven testing; this does not prove absence of risk. Abstract reviewed. - Darovasertib plus crizotinib shows tumour responses in untreated metastatic uveal melanoma
J Clin Oncol
OptimUM-01 single-arm phase 2; 44 patients; response rate 34.1%, median PFS 7 months. Gastrointestinal toxicity common; no randomized comparator. Abstract overall-survival estimate and confidence interval are internally inconsistent and are not reported here. Abstract reviewed. - Repinatrabit lowers phenylalanine in adults with phenylketonuria in a phase 2 trial
NEJM
JNT517-101 research correspondence; adults with baseline phenylalanine above 600 µmol/L. Publisher abstract reports a reduction in this biochemical surrogate; numerical effect, safety and clinical outcomes could not be assessed from the accessible abstract. - IVF yields more early live births than stimulated IUI in unexplained infertility
NEJM
FIIX; 737 couples randomized. Stage-one live births 55% with IVF versus 31% with IUI; after access to subsequent IVF, cumulative rates were 71% versus 70%. Primary analysis excluded couples affected by COVID lockdowns. Public NEJM abstract reviewed. - Antenatal STI screening does not reduce the primary adverse-birth composite
Clin Infect Dis
Philani Ndiphile RCT; repeated screening reduced preterm birth as a secondary outcome. Abstract reviewed. - Laparoscopic liver resection reduces morbidity with similar long-term cancer outcomes
Ann Intern Med
Individual-participant meta-analysis of four RCTs; 761 patients with colorectal liver metastases. Abstract reviewed. - Long, short and mini splints show no significant difference after flexor tendon repair
BMJ
FIRST; 430 randomized; no significant difference in hand-function scores. Abstract reviewed. - Videolaryngoscopy improves first-attempt nasotracheal intubation success in infants
Lancet Child Adolesc Health
NasoVISI; 83% versus 75% success in infants undergoing cardiac procedures; complications similar. Abstract reviewed. - Eculizumab shows preliminary kidney benefit in anti-GBM disease
Nephrol Dial Transplant
Phase 2; 16 treated patients versus 40 nonrandomized controls; confirmatory trials needed. Abstract reviewed. - Semaglutide is associated with lower mortality than pooled GLP-1 comparators in haemodialysis
Diabetes Care
Observational target-trial emulation; mortality sHR 0.82; benefit not significant versus liraglutide alone. Abstract reviewed. - SGLT2 inhibitors show no overall excess harm in adults aged 75 or older with diabetes
Diabetes Care
Observational comparison with DPP-4 inhibitors; some safety estimates imprecise. Abstract reviewed. - Dual-ingredient bed nets reduce childhood malaria compared with pyrethroid-only nets
NEJM Evidence
Cluster RCT in Côte d’Ivoire; incidence ratios 0.57 with chlorfenapyr and 0.72 with PBO nets. Abstract reviewed. - Behavioural support improves smoking cessation with e-cigarettes
NEJM Evidence
RCT; validated six-month abstinence 21.1% with support versus 11.3% without; long-term safety not established. Abstract reviewed. - Pembrolizumab shows durable responses in drug-resistant gestational trophoblastic neoplasia
NEJM Evidence
Retrospective uncontrolled study; complete responses in 43 of 60 patients with measurable disease. Abstract reviewed. - Intraoperative iodine increases positive margins during cervical LEEP
Am J Obstet Gynecol
RCT; involved margins 17.5% versus 7.0%; 229 women. Abstract reviewed. - Less processed whole grains modestly improve HbA1c in type 2 diabetes
Am J Clin Nutr
12-week RCT; 160 adults; between-group HbA1c difference −2.2 mmol/mol. Abstract reviewed. - Efzofitimod does not improve steroid reduction in pulmonary sarcoidosis
Lancet Respir Med
EFZO-FIT phase 3; primary endpoint negative at 48 weeks. Abstract reviewed. - Preoperative oxytocin reduces screening-positive acute stress after fracture surgery
JAMA Intern Med
Single-centre RCT; probable disorder 15.9% versus 30.5% over three days; long-term benefit unknown. Abstract reviewed. - A self-guided online intervention reduces functional seizure frequency
JAMA Neurol
Re-PROGRAM RCT; 107 randomized; therapist-guided arm did not significantly reduce seizure frequency. Abstract reviewed. - Intranasal mebufotenin improves depressive symptoms in a phase 2b trial
JAMA
193 participants with treatment-resistant depression; low-dose active comparator and psychological support; eight-week follow-up. Abstract reviewed. - Izalontamab brengitecan prolongs progression-free survival after EGFR-TKI resistance
The Lancet
PANKU-Lung01; median 11.1 versus 5.7 months; grade 3 or worse treatment-related events 79% versus 62%. Abstract reviewed. - Sacituzumab tirumotecan improves survival in previously treated endometrial cancer
The Lancet
TroFuse-005; median survival 19.0 versus 12.1 months; more grade 3 or worse adverse events. Abstract reviewed. - Pembrolizumab alone prolongs progression-free survival versus chemotherapy in dMMR endometrial cancer
The Lancet
KEYNOTE-C93 interim analysis; no significant overall-survival benefit; comparator was chemotherapy alone, not current chemoimmunotherapy. Abstract reviewed. - Sacituzumab tirumotecan plus pembrolizumab improves progression-free survival in PD-L1-negative NSCLC
NEJM
OptiTROP-Lung06 interim analysis; 15.0 versus 5.7 months; overall-survival data immature. Abstract reviewed. - Osimertinib–savolitinib improves survival in MET-altered NSCLC after osimertinib
NEJM
SAFFRON phase 3; overall-survival HR 0.68 versus platinum-pemetrexed; restricted molecular population. Abstract reviewed. - Divarasib improves survival versus sotorasib or adagrasib in previously treated KRAS G12C NSCLC
NEJM
Krascendo 1; median survival 17.7 versus 12.0 months; control group predominantly received sotorasib. Abstract reviewed. - Self-assessment improves follow-up completion after early medical abortion
BJOG
Mate Whenua RCT; 94.5% versus 67.4% completed follow-up; more additional investigations. Abstract reviewed. - Dostarlimab produces sustained complete clinical responses in dMMR rectal cancer
Annals of Oncology
AZUR-1 single-arm interim study; 68% sustained clinical complete response for 12 months; not universal response or proven cure. Abstract reviewed. - Adding belzutifan or quavonlimab does not improve first-line renal cancer outcomes
Annals of Oncology
LITESPARK-012; neither addition to pembrolizumab–lenvatinib improved outcomes; more treatment discontinuation. Abstract reviewed. - Adding chemotherapy to pembrolizumab improves progression-free survival in PD-L1-high NSCLC
Annals of Oncology
PERSEE; 16.1 versus 6.9 months; grade 3 or worse treatment-related events 54% versus 19%; overall-survival CI crossed 1. Abstract reviewed. - Intensified adjuvant chemotherapy does not improve disease-free survival in high-risk colon cancer
Annals of Oncology
IROCAS; mFOLFIRINOX versus mFOLFOX6; more severe diarrhoea and fatigue. Abstract reviewed. - Camrelizumab-based neoadjuvant treatment improves event-free survival in rectal cancer
Lancet Oncol
UNION interim phase 3; three-year EFS 91.3% versus 77.4%; comparison with contemporary total neoadjuvant therapy still needed. Abstract reviewed. - Relatlimab–nivolumab retains a five-year survival advantage in advanced melanoma
Nat Med
RELATIVITY-047 follow-up; overall-survival HR 0.78 versus nivolumab; updated analysis. Abstract reviewed. - Pembrolizumab modestly improves progression-free but not overall survival in HR-positive breast cancer
Annals of Oncology
KEYNOTE-B49; PD-L1-positive HR+/HER2− disease; median PFS 6.7 versus 6.0 months. Abstract reviewed. - Atirmociclib–fulvestrant improves progression-free survival after prior CDK4/6 therapy
Annals of Oncology
FourLight-1 phase 2; median PFS 9.4 versus 6.6 months; overall-survival benefit unproven. Abstract reviewed. - Adjuvant cisplatin–gemcitabine does not establish superiority over capecitabine in biliary cancer
Annals of Oncology
ACTICCA-1; primary DFS comparison not significant; alternative restricted-mean analysis favoured combination; no significant OS benefit. Abstract reviewed. - Abemaciclib–fulvestrant does not significantly improve overall survival after prior CDK4/6 therapy
Annals of Oncology
postMONARCH final survival analysis; HR 0.80, 95% CI 0.60–1.06; PFS benefit persisted. Abstract reviewed. - Nivolumab–ipilimumab improves survival in MSI-H/dMMR metastatic colorectal cancer
Annals of Oncology
CheckMate 8HW final analysis; benefit versus nivolumab across all lines and versus first-line chemotherapy; greater toxicity than nivolumab. Abstract reviewed. - IVF yields more live births than surgery in a small endometriosis infertility trial
Am J Obstet Gynecol
55 randomized women plus 75 preference participants; trial stopped early; selected patients younger than 40. Abstract reviewed. - A shorter trifluridine–tipiracil schedule preserves survival with less neutropenia
The Lancet
PRABITAS; 14-day versus 28-day schedule with bevacizumab in refractory colorectal cancer; two treatment-related deaths versus none. Abstract reviewed. - Empagliflozin increases kidney-volume growth in a small ADPKD trial
J Am Soc Nephrol
50 participants; well tolerated but kidney-volume growth 10.5% versus 5.1% yearly; no significant chronic eGFR-slope difference. Abstract reviewed. - Enzalutamide does not improve metastasis-free survival with radiotherapy and ADT overall
J Clin Oncol
ENZARAD phase 3; eight-year MFS 74% versus 72%; subgroup findings do not establish overall benefit. Abstract reviewed. - Ravulizumab reduces proteinuria in IgA nephropathy
NEJM
I CAN: Phase 3 interim analysis; protein-to-creatinine ratio 43.4% lower than placebo at week 34; long-term kidney benefit not established here. - Povetacicept reduces proteinuria and haematuria in IgA nephropathy
NEJM
RAINIER (AIS-D08): RAINIER interim analysis; proteinuria fell 52% vs 4.3% at week 36; surrogate outcome. - Thrombectomy at 24–72 hours improves function but increases haemorrhage and death
NEJM
LATE-MT, 336 imaging-selected patients; symptomatic intracranial haemorrhage 4.8% vs 0%; mortality 6% vs 1.8%. - Remibrutinib reduces MS relapses compared with teriflunomide
The Lancet
Two phase 3 trials, 2007 patients; annualised relapse rates reduced by approximately 31–35%. - Sibeprenlimab preserves kidney function over two years in IgA nephropathy
NEJM
VISIONARY: VISIONARY final analysis, 510 patients; annual eGFR slope +0.3 vs −4.2 mL/min/1.73 m². - Atacicept slows kidney-function decline in IgA nephropathy
NEJM
ORIGIN 3: ORIGIN 3 final analysis; annual eGFR slope −0.6 vs −5.6 mL/min/1.73 m² through week 104. - Iptacopan shows sustained proteinuria reduction during longer-term IgA nephropathy follow-up
Kidney International
APPLAUSE-IgAN open-label rollover extension: Open-label extension to 48 months; no concurrent placebo comparator during extension; no new safety signal. - Rituximab is not superior to azathioprine for maintaining EGPA remission
JAMA
RCT, 98 patients; no significant remission-duration advantage; more severe infections, largely COVID-19. - Very low protein intake is associated with worse kidney and survival outcomes in CKD
JAMA Network Open
Korean cohort, 1861 patients; <0.6 g/kg/day associated with higher risk; does not prove that increasing protein is beneficial. - Music therapy does not shorten ventilator weaning in a small ICU trial
Critical Care Medicine
RCT, 100 patients; primary outcome negative; some agitation and sedation outcomes improved. - Retatrutide reduces obstructive sleep apnoea severity in adults with overweight or obesity
NEJM
Two phase 3 OSA cohorts, 691 participants. At 80 weeks, 9–12 mg reduced AHI by roughly 14–24 events/hour more than placebo. Includes the previously reported TRIUMPH-1 OSA cohort; gastrointestinal adverse events were most common. First-online metadata: 20 October; the article Notes section gives 21 October. - EIT-guided PEEP reduces pulmonary complications after laparoscopic colorectal surgery
British Journal of Anaesthesia
Single-centre RCT, 117 patients. Thirty-day pulmonary complications: 49.2% versus 72.4% with fixed PEEP of 5 cm H2O; larger confirmation needed. - Starting statins after an atherosclerotic event is associated with better survival in dialysis patients
Kidney International
Observational REIN registry study, 5,534 patients. Four-year absolute mortality difference −6.2 percentage points; residual confounding remains possible. - Semaglutide shows no unexpected safety signal across kidney-function subgroups in FLOW
Kidney International
Prespecified descriptive safety analysis, 3,533 participants. Fewer serious adverse events across eGFR groups; gastrointestinal discontinuations were more frequent than with placebo. - Dupilumab and swallowed topical steroids rank among the most effective eosinophilic oesophagitis treatments
Journal of Allergy and Clinical Immunology
Network meta-analysis of 48 RCTs, 3,963 participants. Benefits extend to symptoms and quality of life; indirect comparisons do not establish universal superiority. - Higher tidal volume relative to predicted body weight is associated with NIV failure
Critical Care Medicine
Meta-analysis of 11 observational studies, 1,136 patients. Evidence concerns prognosis, mainly hypoxaemic respiratory failure; it does not prove that reducing tidal volume improves outcomes. - Lower carbohydrate intake in gestational diabetes is associated with better glucose profiles but poorer nutrient intake
Diabetes Care
Observational baseline analysis within DiGest, 215 women. Lower intake was associated with better glycaemia but less fibre and micronutrients; carbohydrate intake itself was not randomised. - Shorter diabetes duration and no insulin use predict remission after metabolic surgery
Diabetes Care
ARMMS-T2D follow-up, 262 patients. Ever achieving remission over median 11 years: 58% after surgery versus 3% with medical/lifestyle care; this is not sustained remission in everyone. - Androgen receptor inhibitors are associated with longer survival than abiraterone in metastatic hormone-sensitive prostate cancer
JAMA Network Open
Retrospective cohort, 3,404 patients; adjusted HR 0.74. Conflicting observational evidence and treatment-selection bias prevent a causal superiority claim. - Skin toxicity during enfortumab–pembrolizumab treatment is associated with longer survival
JAMA Network Open
Cohort of 185 patients with advanced urothelial cancer. Potential response marker requiring validation; the finding does not justify tolerating dangerous toxicity. - Weakening universal hepatitis B birth-dose vaccination is projected to increase childhood infections
Annals of Internal Medicine
US modelling study: chronic infections projected to increase 19% with deferred vaccination and 83% with shared decision-making. Predictions depend on coverage and transmission assumptions. - Unused opioids commonly remain at home months after emergency-department discharge
JAMA Network Open
Canadian prospective cohort. Among relevant respondents, 84% had unused opioids at two weeks and 61.9% at three months; safe storage was uncommon. - Point-of-care high-sensitivity troponin shortens emergency-department stays
Circulation
ICare-FASTER cluster RCT, 59,980 presentations. Adjusted stay fell by 47 minutes; 30-day MI or cardiac death was 0.39% in both groups. - Individualised cardiac-index-guided therapy does not reduce major postoperative complications
JAMA
PELICAN RCT, 1,095 analysed patients. Seven-day composite complications: 44.3% versus 46.9%; RR 0.94, 95% CI 0.83–1.08. - Supplemental operating-room air purification does not reduce infection-related complications
Anesthesiology
ORACLE cluster RCT, 110,538 enrolled operations. Inpatient primary composite: 8.1% versus 8.2%; stopped for futility. Applies to the tested supplemental system. - Sixteen-fraction postmastectomy radiotherapy is noninferior when internal mammary nodes require treatment
Journal of Clinical Oncology
HypoMast-IMNI phase 3 RCT, 1,494 randomised. Five-year locoregional recurrence 1.7% versus 2.2%; grade 3 acute skin toxicity 1.7% versus 12.2%. - Four-day intensive exposure therapy outperforms unguided online CBT for OCD
JAMA Network Open
Single-centre RCT, 119 adults. Greater symptom improvement persisted at three months; comparator was unguided internet CBT, not equivalent therapist-led treatment. - Home brain stimulation plus cognitive training fails to improve depression beyond sham
JAMA Network Open
Randomised trial, 109 analysed participants. Feasible home treatment, but no significant six-week antidepressant benefit; efficacy was a secondary outcome. - Remote aerobic exercise accelerates recovery after youth concussion
JAMA Pediatrics
MSTEP RCT, 210 participants. Better symptoms and quality of life at three months, without significant group differences at six months. - Seven-day continuous ECG detects more clinically important arrhythmias in children
JAMA Pediatrics
Single-centre study, 435 children. Major arrhythmia detection 6.2% versus 2.3% with 24-hour Holter or event recording; not a randomised outcomes trial. - Adding midostaurin fails to improve overall remission in older adults receiving venetoclax–cytarabine for AML
Blood
INTERVENE phase 2 RCT, 120 randomised patients. Composite remission 72% versus 68%; an encouraging FLT3-ITD subgroup signal remains exploratory. - Oropouche infection in pregnancy is associated with fetal loss and infant CNS abnormalities
The Lancet Infectious Diseases
Prospective Brazilian cohort, 544 enrolled. Confirmed infection associated with approximately threefold fetal-loss risk; observational estimates have wide uncertainty. - Prenatal phosphatidylcholine improves some childhood outcomes in a small trial
American Journal of Obstetrics and Gynecology
RCT, 206 women; 142 children had behavioural follow-up. Less social withdrawal and higher cognitive scores, but no significant attention benefit and substantial attrition; not enough for routine high-dose supplementation. - Initial opioid or gabapentinoid treatment for acute low back pain is associated with greater subsequent opioid harm
JAMA Network Open
Cohort of 399,500 opioid-naive Medicaid patients. Higher subsequent opioid-use-disorder/overdose risk; observational associations do not establish causality. - Slow-wave sleep signals may help localise epileptogenic tissue
Sleep
Exploratory intracranial EEG study in 22 patients. Improved surgical outcomes remain unproven. - Minocycline–EDTA–ethanol lock improves catheter salvage in bloodstream infection
Clinical Infectious Diseases
Multicentre randomised trial, 241 patients. Catheter retention was 57% versus 38%; both groups received systemic antibiotics. - Camrelizumab improves pathological complete response with anthracycline-free chemotherapy in triple-negative breast cancer
Annals of Oncology
Phase 3 trial: pathological complete response 57.5% versus 45.4%. Comparator was chemotherapy alone, not current standard chemoimmunotherapy. - Persistent high-titre factor VIII inhibitors develop after investigational haemophilia gene therapy
Blood
Both ASC618 recipients developed persistent inhibitors; the trial was halted. Product-specific safety signal, not an established class effect. - Linezolid restrictions reduce resistance but are associated with higher mortality in VRE-positive patients
Clinical Infectious Diseases
Quasiexperimental study of 521,493 admissions. Overall mortality did not increase; findings highlight safeguards for high-risk patients. - A long-form troponin T assay improves myocardial infarction discrimination in kidney dysfunction
Nephrology Dialysis Transplantation
Prospective diagnostic study of 1,811 patients with elevated conventional high-sensitivity troponin T. Greatest advantage at low eGFR; further validation needed. - Abnormal six-week postpartum blood pressure predicts later cardiovascular disease
BJOG
Cohort with hypertensive disorders of pregnancy: adjusted hazard ratio 1.96. Substantial missing blood-pressure data limit interpretation. - Higher antihistamine doses offer diminishing benefit and greater sedation in chronic urticaria
Journal of Allergy and Clinical Immunology
Dose-response network meta-analysis of 211 trials. Efficacy and sedation differ between second-generation agents; evidence certainty varies. - An EGFR-targeted antibody–toxin establishes a dose for further testing in recurrent glioma
Nature Medicine
Single-arm phase 1 study, 81 patients. Dose-limiting toxicity at the highest dose; no controlled survival benefit established. - Plant sterols fail to lower LDL cholesterol in a small obesity trial
The American Journal of Clinical Nutrition
Randomised crossover trial, 23 participants. Two grams daily for eight weeks produced no significant LDL reduction versus placebo. - Primary-care decision support modestly reduces falls and fall-related injuries
JAMA Network Open
Cluster-randomised trial involving 11,945 older adults. Coded falls and fall-related injuries decreased by 9% and 6% relatively. - Three high-flow nasal oxygen weaning strategies show no clear difference in success
Critical Care Medicine
Randomised trial, 87 patients, comparing flow-first, oxygen-first and simultaneous reduction. Small sample does not establish equivalence. - Preoperative sphincter botulinum toxin fails to prevent pancreatic fistula
Annals of Surgery
PREBOT pilot randomised trial stopped for futility. Findings do not support routine use before distal pancreatectomy. - Inhaled SPL84 shows early lung-function signals in mutation-specific cystic fibrosis
European Respiratory Journal
Phase 2a study, 17 participants with the 3849+10kb C→T mutation. Exploratory results do not establish efficacy. - Vaginal laser provides no additional benefit for breast cancer survivors taking aromatase inhibitors
JAMA Network Open
Twelve-month secondary analysis of a sham-controlled trial. Both groups received first-line nonhormonal care; no added sexual or vaginal benefit. - Prehospital GFAP testing shows promise for detecting intracranial haemorrhage in nontraumatic coma
JAMA Network Open
Diagnostic study in 65 selected patients; sensitivity 97%. External validation is needed before routine triage use. - Organ preservation is associated with better long-term quality of life after rectal cancer treatment
JAMA Network Open
Post hoc cohort analysis of two trials. Watch-and-wait was associated with better bowel outcomes, but treatment choice was not randomised. - Flexible ICU visiting may reduce delirium
Critical Care Medicine
Meta-analysis of 13 randomised trials, 3,861 patients. Relative risk 0.48; low-certainty evidence with substantial heterogeneity. - Expert pathology plus molecular testing resolves most ambiguous melanocytic tumours
Journal of Clinical Oncology
Prospective referral study, 994 cases. Definitive diagnosis in 97.2%, supported by long-term follow-up. - Astatine-211–CD45 radioimmunotherapy shows activity before transplantation, with liver toxicity limiting dosing
Journal of Clinical Oncology
First-in-human study, 45 patients. Sinusoidal obstruction syndrome was an important toxicity. - Microangiopathic lesions predict poorer immunosuppressive response in IgA nephropathy
Nephrology Dialysis Transplantation
Prospective cohort, 620 patients. Nonresponse 61% versus 26.2%; observational findings do not establish an alternative treatment strategy. - Recent antibiotic exposure predicts same-class resistance and inactive empirical therapy
Clinical Infectious Diseases
Observational analysis of 1.17 million culture episodes across three health systems. Adjusted associations do not establish causation. - Real-world Lu-177 PSMA outcomes do not establish an optimal taxane sequence
JAMA Network Open
Observational study, 850 patients. Confounding limits treatment-sequence comparisons; prospective evidence is needed. - Once-weekly mosnodenvir prevents detectable dengue infection in most participants in a small human-challenge study
NEJM
Research correspondence: phase 2a challenge study, 24 participants. Five of six participants in each weekly-dose group had no signs of DENV-3 infection versus none of six receiving placebo. Breakthrough variants occurred; field efficacy and protection against other serotypes remain unproven. - Continuous glucose monitoring improves glycaemic control in non-insulin-treated type 2 diabetes
NEJM
CONNECT randomised trial. Outcome currently verified from the sponsor report; publication identity and date corroborated by publisher-deposited metadata. Original full text was inaccessible during review. - Intermittent renal replacement fails noninferiority to continuous therapy in critically ill patients with AKI
NEJM
ICRAKI randomised trial, stopped early. Mortality was 63.1% with intermittent versus 53.5% with continuous therapy. Interpret alongside early termination. - Isoflurane sedation does not improve survival in acute hypoxaemic respiratory failure
JAMA
SAVE-ICU randomised trial. Hospital mortality was 42.5% versus 43.8%; more hypoxaemia rescue interventions with isoflurane. - Earlier vasopressin initiation does not reduce mortality in septic shock
JAMA
VASSPR cluster-randomised trial, 3,959 patients. Compared initiation strategies at different norepinephrine thresholds; 28-day mortality was similar. - Adding dobutamine reduces AKI during surgical source control for septic shock
JAMA
Randomised trial, 584 patients. New or worsening AKI: 22.8% versus 34.7%. More tachycardia; findings apply to this specific perioperative setting. - Talazoparib adds toxicity without establishing additional benefit in hormone-naive metastatic prostate cancer
Nature Medicine
Phase 2 trial, 54 patients. The combination met its prespecified activity threshold, but the exploratory comparison with enzalutamide alone was not significant; severe toxicity was greater. - Personalised ovarian cancer vaccines induce immune responses in an early-phase trial
Nature Medicine
Ten vaccinated patients received NeoVax with delayed anti-PD-1 therapy. Feasibility and biological activity demonstrated; comparative clinical benefit remains unproven. - Selpercatinib produces durable responses in children and young adults with RET-altered solid tumours
Journal of Clinical Oncology
Single-arm phase 1/2 study, 36 patients. Objective response rate 53%; predominantly thyroid cancers. - Virologic failure is uncommon with injectable cabotegravir–rilpivirine but can compromise future treatment
Clinical Infectious Diseases
Dat’AIDS observational cohort, 2,196 patients. Failure in 1.9%; resistance emerged in half of genotyped failure cases. - Bariatric surgery is associated with lower overall obesity-related cancer risk
JAMA Surgery
Large Nordic cohort. Associations differed by cancer site, including a higher pancreatic cancer signal; causation cannot be established. - Auricular acupressure improves rosacea outcomes when added to standard treatment
JAMA Dermatology
Single-centre sham-controlled trial, 204 patients. Clear or almost-clear skin at eight weeks: 56.9% versus 35.3%. Replication needed. - Cardiac radioablation is associated with reduced ventricular tachycardia burden in refractory cases
European Heart Journal
STOPSTORM prospective registry. Substantial reduction among evaluable patients, but no randomised comparator; treatment-related serious adverse events occurred. - Ponatinib–blinatumomab improves event-free survival over imatinib–chemotherapy in Ph-positive ALL
NEJM
Phase 3 randomised trial, 236 patients. Two-year event-free survival was 86% versus 67%. - Oral icotrokinra improves clinical response in ulcerative colitis
NEJM
Phase 2b trial, 252 patients. Week-12 clinical response was 55–63% versus 27%; formal remission comparison favoured the highest dose. - Injectable HIV therapy maintains suppression in African adults with adherence challenges
NEJM
IMPALA noninferiority trial in initially suppressed patients. Confirmed virologic failure occurred in five injectable-therapy recipients versus none receiving oral therapy. - AAV vector integration is identified in a paraspinal tumour after gene therapy
NEJM
Research correspondence describing a child with Krabbe disease. Molecular safety signal from a single case; does not quantify incidence or establish a class-wide risk. - Rusfertide reduces phlebotomy requirements and improves haematocrit control in polycythaemia vera
Journal of Clinical Oncology
VERIFY phase 3 trial, 293 patients. Primary response: 77% versus 33% with placebo, alongside standard care. - First-trimester benzodiazepine exposure is not associated with increased overall congenital malformations
Annals of Internal Medicine
Large observational study; adjusted relative risk 0.99. Restricted to live births and does not establish safety for other pregnancy outcomes. - Asundexian increases lower gastrointestinal bleeding despite similar overall major bleeding rates
Circulation
Secondary OCEANIC-STROKE safety analysis. Lower-GI bleeding: 1.7% versus 1.0%; the overall major bleeding difference was not significant. - DDX41-associated myelodysplastic syndrome has lower relapse after transplantation
Blood
Transplant cohort: two-year relapse 17% versus 34%. Observational prognostic finding, with only 49 germline DDX41 cases. - High-risk genotypes identify persistent arrhythmia risk despite recovered ejection fraction
European Heart Journal
Dilated cardiomyopathy cohort, 2,660 patients. Supports genotype-informed risk assessment; does not itself establish an ICD treatment strategy. - About one in six women undergo repeat surgery after ovarian endometriosis surgery
American Journal of Obstetrics and Gynecology
Finnish registry cohort, 13,912 women, with long-term follow-up. Younger age and family history were associated with greater reoperation risk. - Real-time AI feedback shows feasibility for improving personalised seizure detection
Nature Medicine
Feasibility study involving 13 patients. Detection performance findings do not establish improved clinical outcomes. - Perfusion mismatch does not identify a thrombectomy-responsive subgroup in medium-vessel stroke
JAMA Network Open
Exploratory ESCAPE-MeVO analysis, 309 patients. Tested perfusion measures did not modify the treatment effect. - Digital education increases hereditary cancer genetic testing uptake, although overall uptake remains low
JAMA Network Open
MiGHT randomised trial, 793 participants. Digital intervention improved six-month uptake; coaching showed benefit at 12 months. - Systemic allergic reaction rates are similar after mRNA COVID vaccination and placebo in an underpowered trial
Journal of Allergy and Clinical Immunology
Placebo-controlled trial including people with severe allergy histories. Recruitment fell well below target; rare-event safety conclusions remain limited. - A nine-valent E. coli vaccine fails to demonstrate protection against invasive disease in older adults
The Lancet Infectious Diseases
E.mbrace phase 3 trial, 17,701 vaccinated participants. Stopped for futility; development discontinued. - Three-week postmastectomy radiotherapy is noninferior for reconstruction complications
Journal of Clinical Oncology
RT CHARM randomised trial. Sixteen versus 25 fractions; two-year reconstruction complication rates 12.3% versus 10.2%. - Early-pregnancy anti-CGRP exposure is associated with increased miscarriage risk
JAMA Neurology
Claims-based cohort: adjusted hazard ratio 1.42. No corresponding association with propranolol; residual confounding remains possible. - Phenobarbital and diazepam show similar hospital outcomes for alcohol withdrawal
JAMA Internal Medicine
Comparative-effectiveness study, 24,643 patients. No clear difference in length of stay or invasive ventilation; not a randomised equivalence trial. - A blood-test-informed model improves lung cancer risk prediction in Danish cohorts
Journal of Clinical Oncology
CPH-Lung external validation: discrimination exceeded PLCOm2012. Screening mortality benefit and broader generalisability remain untested. - Fibrinogen concentrate reduces transfusion requirements in adults with acquired hypofibrinogenaemia
British Journal of Anaesthesia
Meta-analysis of 58 studies. Findings driven largely by cardiac surgery; no demonstrated mortality benefit. - Increased left ventricular mass predicts adverse outcomes in children with cirrhosis
Journal of Hepatology
Prognostic study in paediatric transplant candidates. Potential adjunct to established risk scores; prospective validation needed. - First unplanned admission in pancreatic cancer identifies substantial unmet palliative care needs
Journal of Pain and Symptom Management
Three-centre retrospective cohort. Median survival after admission 3.8 months; most patients had not received prior specialist palliative assessment. - Explaining uncertainty reduces willingness to take new cancer drugs in hypothetical decisions
JAMA Internal Medicine
Two randomised communication studies, 6,272 adults. Outcomes were hypothetical choices, not actual treatment decisions. - Availability of home-based cardiac rehabilitation is associated with higher participation
JAMA Network Open
Cohort of 405,907 veterans. Association supports improving access; does not prove that programme availability caused the increase. - Routine diagnostic coding misses most hospital delirium in older adults
Age and Ageing
Population-based cohort of 9,956 older adults. Only 11.9% of admissions with chart-identified delirium carried a delirium discharge code. - A low-glycaemic-load breakfast improves glucose profiles in gestational diabetes
American Journal of Clinical Nutrition
Small crossover trial: 20 women completed both dietary periods with usable glucose data. One-hour post-breakfast glucose was 5.0 versus 7.5 mmol/L. Short-term glucose outcomes; pregnancy outcomes were not established. - Automatic endotracheal cuff-pressure control reduces ventilator-associated pneumonia in children
CHEST
RCT, 241 children. VAP occurred in 13.3% versus 24.0% with intermittent manual monitoring. The primary outcome favoured automatic control; unadjusted time-to-event analysis was not significant. - Day-two CRP identifies patients at low risk of anastomotic leakage after colon cancer surgery
Annals of Surgery
Two cohorts, 614 patients. CRP below 100 mg/L on postoperative day 2 had negative predictive values of 98.8–99.0%. Residual leakage risk remained about 1%; this supports rather than replaces clinical assessment. - Greater antibiotic exposure is associated with emerging multidrug resistance in cirrhosis
Clinical Infectious Diseases
Prospective cohort, 256 adults. Newly acquired resistant organisms were associated with higher 180-day mortality (HR 2.15). Observational exposure thresholds are not universal prescribing cutoffs. - Tomosynthesis does not significantly reduce two-year interval breast cancers compared with digital mammography
The Lancet Oncology
TOSYMA: approximately 99,000 screen-negative women. Invasive interval cancers: 14.2 versus 18.6 per 10,000; adjusted OR 0.76 (95% CI 0.55–1.06). The primary endpoint was not statistically significant. - Dupilumab improves symptoms in a small trial of chronic rhinosinusitis without nasal polyps
Journal of Allergy and Clinical Immunology
Phase II placebo-controlled trial, 33 adults. Patient-reported symptoms and quality of life improved; CT changes and rescue-medication reductions were not significant. Larger trials are needed. - Roxadustat does not reduce infarct size after primary PCI for STEMI
JAMA Network Open
Phase II RCT, 158 patients. Infarct size at 30 days was 23.3% versus 22.0% (P=.51). Secondary ventricular-remodelling signals were exploratory. - Switching to benralizumab may help selected EGPA patients after mepolizumab failure
CHEST
Retrospective cohort, 68 patients. Complete response occurred in 32% and 38% discontinued glucocorticoids. Responses were not always sustained; there was no randomized comparator. - Tongue-swab PCR misses most asymptomatic tuberculosis in household screening
Clinical Infectious Diseases
High-volume PCR sensitivity was approximately 35% for asymptomatic TB versus 64% in symptomatic clinic patients, limiting its use for community screening. - A community programme produces a modest improvement in children’s BMI
JAMA Network Open
Cluster RCT, 437 children. Adjusted between-group BMI z-score difference was −0.19 at 12 months. Reported sugary-drink and water intake did not differ significantly. - Bavdegalutamide shows early activity in androgen-receptor-mutated prostate cancer
Journal of Clinical Oncology
Phase I/II study. Among 20 patients with AR T878/H875 mutations, 60% achieved a PSA reduction of at least 50%. Activity was lower in other molecular groups; comparative benefit remains unproven. - Oral deucrictibant rapidly relieves hereditary angioedema attacks
The Lancet
RAPIDe-3 phase III crossover trial. Median onset of symptom relief: 1.28 hours versus more than 12 hours with placebo. The paired primary analysis included 88 participants. - Nicotinamide riboside fails to benefit early Parkinson disease and produces worse clinical scores
JAMA
NOPARK phase III RCT, 410 randomized. At 52 weeks, the primary clinical score favoured placebo by 2.72 points. Findings do not support use as a disease-modifying treatment. - Pre-emptive kidney transplantation is associated with better graft outcomes but no survival advantage
JAMA Network Open
Target-trial emulation, 32,770 recipients. Mortality HR 1.02, with less delayed graft function and death-censored graft failure. Observational evidence among transplant recipients; not proof that transplantation should be delayed. - TENS does not reduce pain during IUD insertion
American Journal of Obstetrics and Gynecology
Sham-controlled RCT, 98 analyzed participants. Insertion pain was 50.8 versus 50.6 mm on a 100-mm scale (P=.97). - Sofetabart mipitecan shows early activity in heavily pretreated ovarian cancer
Annals of Oncology
Phase I study, 105 patients. Overall response 50.5%; median progression-free survival 8.1 months. No comparator; clinically important toxicity occurred. - Varegacestat shrinks desmoid tumours in an early dose-finding trial
Journal of Clinical Oncology
Randomized phase II dose-finding study, 42 patients. The 1.2-mg daily group had about 52% median tumour-volume reduction at week 16. No placebo or standard-treatment comparator. - Physician-supervised conversational AI proves feasible before primary-care appointments
The Lancet
Single-arm feasibility study: 98 patients completed AI interaction and consultation. No predefined safety stops occurred; supervisors recorded one hallucination and supplemented five interactions. Does not establish safety for autonomous use. - Sibling comparisons weaken the association between maternal influenza and offspring neuropsychiatric disorders
JAMA Network Open
Korean and Japanese cohorts: approximately 2.75 million mother–child pairs. Modest population associations became nonsignificant in sibling analyses, suggesting familial confounding. - A urine Aspergillus assay shows promise for diagnosing invasive aspergillosis
Clinical Infectious Diseases
Diagnostic studies found approximately 92% sensitivity and 88% specificity in the principal dataset. Cross-reactivity and performance in broader populations require consideration. - Digital CBT for insomnia produces sustained improvements compared with online education
Sleep
Meta-analysis covering 25 studies; 10 randomized comparisons supported benefits lasting up to 12 months. Specifically evaluates the SHUTi programme. - Continuous glucose monitoring is associated with sustained glycaemic improvement and lower albuminuria
JAMA Network Open
Observational target-trial emulation in 25,648 adults with type 2 diabetes. HbA1c was approximately 0.8 percentage points lower at three years; no eGFR benefit was demonstrated. - Facilitated advance-care planning does not clearly outperform a self-guided approach
JAMA
EQUAL ACP cluster-randomized trial, 791 older adults with serious illness. No significant difference in completion within either prespecified racial group; this does not establish equivalence. - Robotic radical hysterectomy reduces mainly minor intraoperative complications without improving postoperative recovery
JAMA Surgery
Exploratory secondary analysis of the 900-patient RACC trial. Postoperative morbidity was similar. This report does not establish oncological safety. - Patient characteristics may modify the kidney-safety balance between cefepime and piperacillin–tazobactam
American Journal of Respiratory and Critical Care Medicine
Secondary modelling analysis of ACORN. A predicted-benefit subgroup favoured cefepime for survival without acute kidney injury; prospective clinical validation remains needed. - Changing donors for a second transplant is associated with less MDS relapse
Blood
Observational study of 313 adults. Donor change was associated with lower relapse risk, HR 0.56, but no significant overall-survival advantage. - Adding sitagliptin reduces acute graft-versus-host disease after alternative-donor transplantation
Journal of Clinical Oncology
Phase 3 randomized trial, 190 patients. Grade II–IV acute GVHD occurred in 14.7% versus 31.6% with ATG-based prophylaxis alone. No significant long-term survival benefit was demonstrated. - Lanthanum is associated with fewer cardiovascular events than sevelamer in dialysis patients
Journal of the American Society of Nephrology
Observational target-trial emulation, 10,518 matched patients. Major cardiovascular events: HR 0.79. Residual confounding prevents a definitive treatment-superiority conclusion. - Lipid-rich plaques may identify patients deriving greater benefit from preventive PCI
Circulation
Post hoc PREVENT analysis, 598 patients. Benefit was concentrated in lipid-rich plaques. Hypothesis-generating subgroup evidence, not a new standalone indication for PCI. - Fluvoxamine shows a modest benefit for long-COVID fatigue
Annals of Internal Medicine
Adaptive randomized trial, 399 adults. Fatigue scores improved versus placebo at 60 and 90 days. Longer-term benefit is unknown; metformin findings were inconclusive. - Conduction-system pacing is noninferior to biventricular pacing for ventricular recovery after AV-node ablation
European Heart Journal
CONDUCT-AF randomized trial, 82 patients with refractory AF, heart failure and narrow QRS. Similar six-month LVEF improvement; shorter procedural and fluoroscopy times. - Cryotherapy does not significantly reduce the primary measure of taxane neuropathy
Annals of Oncology
CryoPac randomized trial, 268 randomized patients. Neuropathy occurred in 74% versus 84% of analysed patients, P=.071. Some sensory symptoms improved; attrition limits interpretation. - Long-acting cabotegravir–rilpivirine maintains HIV suppression through 96 weeks in adolescents
The Lancet Child & Adolescent Health
MOCHA single-arm phase 1/2 study, 144 previously suppressed adolescents. No confirmed virological failures through week 96; no randomized comparator. - A new evidence review clarifies drug benefits for menopausal vasomotor symptoms
Annals of Internal Medicine
Systematic review of 90 trials. Estrogens improved symptom frequency and severity; several nonhormonal treatments improved frequency. Comparative and long-term harms evidence was limited. - Durvalumab–tremelimumab shows activity in previously underrepresented patients with poor-prognosis liver cancer
Journal of Hepatology
SIERRA single-arm phase 3b study, 111 patients with impaired liver function, performance status 2 or major portal-vein involvement. Response rate 14.4%; no comparative survival evidence. - Glofitamab plus polatuzumab–R-CHP produces high response rates in newly diagnosed DLBCL
Blood
Single-arm phase 2 study, 41 patients. Best complete-response rate 95%; promising but requires randomized confirmation. - Longer follow-up reveals limited durability of early in-vivo CAR-T responses in myeloma
Nature Medicine
Four-patient follow-up: median progression-free survival was four months; three patients progressed and subsequently died. Important qualification of an initially encouraging early report. - Pausing selected arthritis treatments for COVID vaccination increases flares without improving antibody responses
JAMA Internal Medicine
COVER randomized trial, 840 patients. A two-week interruption increased flares. Applies to the studied biologics and JAK inhibitors. - Financial incentives improve smoking cessation among people referred for lung cancer screening
JAMA
Randomized trial. Six-month sustained abstinence was 8.8% with free pharmacotherapy plus incentives versus 4.3% with usual care. - Navigation, reminders and automatic referral improve colonoscopy completion after a positive stool test
JAMA Internal Medicine
Systematic review/meta-analysis, 21 studies. Several practical interventions improved follow-up; effects varied across studies. - Earlier disclosure of Alzheimer blood biomarkers improves diagnostic confidence and changes management
JAMA Neurology
Randomized trial, 220 participants. High-confidence diagnoses at three months: 50.0% versus 4.6%. Improved long-term patient outcomes remain unproven. - Starting ocrelizumab earlier preserves a disability benefit over ten years
JAMA Neurology
OPERA trial extension. Confirmed disability progression was lower with immediate versus two-year-delayed initiation: HR 0.76. Long-term follow-up was open-label with attrition. - Early surgery is associated with better survival in asymptomatic severe primary mitral regurgitation
JAMA Network Open
Observational target-trial emulation, 802 patients. Surgery within six months was associated with lower mortality, HR 0.69; residual confounding remains possible. - Apixaban shows the most favourable anticoagulation balance in disabled nursing-home residents with atrial fibrillation
JAMA Network Open
Observational study, 26,940 residents. Anticoagulants were associated with fewer strokes but more major bleeding; apixaban had the most favourable profile among those studied. - Safiglipron meets glycaemic noninferiority versus dapagliflozin, with the highest dose showing superiority
Nature Medicine
OUTSTAND-2 phase 3 trial, 810 adults. All three doses met glycaemic noninferiority; 90 mg met the prespecified superiority criterion. Gastrointestinal adverse events were more frequent. - A widely used pediatric sepsis alert misses most children meeting sepsis criteria
JAMA Pediatrics
Multicentre evaluation of 166,943 emergency encounters. Sensitivity was 36% overall and 30% before sepsis onset; positive predictive value was 3%. The study evaluated the Epic Pediatric Sepsis Early Detection Model. - Side-to-side gastrojejunostomy does not reduce delayed gastric emptying after pancreatoduodenectomy
Annals of Surgery
IPAD randomized trial, 158 patients. Delayed emptying: 38.0% versus 30.4% with end-to-side reconstruction; difference not significant. - Sotatercept is associated with improved disease measures in pediatric pulmonary hypertension
CHEST
Retrospective series of 66 children and young adults. Functional and haemodynamic measures improved; bleeding occurred in 23%. Uncontrolled evidence cannot establish pediatric efficacy or safety. - A chemotherapy-sparing combination shows activity after EGFR-inhibitor resistance in lung cancer
The Lancet Respiratory Medicine
AMAZE-lung single-arm phase 2 trial, 61 patients. Amivantamab–lazertinib–bevacizumab achieved a 33% response rate at 12 weeks; grade 3–4 treatment-related toxicity occurred in 43%. - Mosunetuzumab–polatuzumab shows durable activity in older, unfit or frail patients with large B-cell lymphoma
Blood
Phase 1/2 study, 101 full-dose participants, median age 81. End-of-treatment complete response 56.4%; no randomized comparator and infection-related deaths occurred. - Contrast-enhanced ultrasound improves the yield and safety of subpleural lung biopsy
CHEST
Multicentre randomized trial, 2,485 participants. Diagnostic yield: 88.8% versus 78.9% with CT and 76.0% with conventional ultrasound; complications were also lower. - Combining nutritional supplements with routine immunization increases measles vaccine uptake
Nature Medicine
NutriVax cluster-randomized trial, northern Nigeria. Card-verified first-dose coverage improved by approximately 20 percentage points relative to control over time. - Urine cell-free RNA shows promise for bladder cancer detection and treatment-response prediction
Nature Medicine
Diagnostic biomarker study, 683 urine samples. Localized cancer detection achieved 95% sensitivity at 90% specificity. Prospective clinical-utility validation is needed. - Longer opioid-use-disorder treatment around childbirth is associated with fewer postpartum overdoses or deaths
JAMA Network Open
Cohort study, 9,360 pregnancies. Longer medication coverage was associated with lower risk through one year postpartum; this was not randomized evidence. - Chronic immune-related toxicity affects nearly half of patients receiving adjuvant anti–PD-1 for melanoma
JAMA Network Open
Multicentre cohort, 303 patients. Chronic adverse events occurred in 48%, supporting continued monitoring after treatment ends. - Iatrogenic menopause before age 45 is associated with increased cardiovascular and overall mortality
JAMA Network Open
Meta-analysis, 36 studies and approximately 2.6 million women. Cardiovascular morbidity was elevated; mortality excess was concentrated in earlier menopause. - Survodutide reduces weight and HbA1c in adults with obesity and type 2 diabetes
NEJM
SYNCHRONIZE-2 phase 3 trial, 752 participants. Weight change at 76 weeks reached −9.8% versus −3.9% with placebo; gastrointestinal adverse events were common. - Major pathological response after neoadjuvant melanoma immunotherapy predicts excellent five-year survival
Nature Medicine
Pooled analysis, 1,038 patients. Five-year survival approached 98–99% among major responders to checkpoint inhibitors. Comparisons between treatment regimens were not randomized. - Intranasal BPZE1 induces mucosal pertussis immunity in children without compromising Tdap responses
The Lancet Infectious Diseases
Phase 2b randomized trial, 368 enrolled children aged 6–17. Immunogenicity and tolerability findings support further development; clinical protection was not established. - Low-dose interleukin-2 fails to preserve beta-cell function in newly diagnosed type 1 diabetes
The Lancet Diabetes & Endocrinology
DIABIL-2 randomized trial, 141 participants. Regulatory T cells increased, but the primary C-peptide outcome did not improve. - Tirabrutinib produces responses in relapsed or refractory primary CNS lymphoma
Blood
PROSPECT single-arm phase 2 trial, 48 patients. Overall response 67%; complete response 44%. No control group; one treatment-related fatal infection occurred. - Pulse corticosteroids show no clear survival advantage in acute exacerbations of idiopathic pulmonary fibrosis
American Journal of Respiratory and Critical Care Medicine
SAFER randomized trial, 100 patients. No significant 28- or 90-day mortality benefit; estimates were imprecise. Compared two steroid regimens, not steroids against no steroids. - Adding inhaled liposomal amikacin improves culture conversion in newly diagnosed MAC lung disease
American Journal of Respiratory and Critical Care Medicine
ENCORE phase 3b trial, 425 patients. Month-13 conversion: 82.4% versus 55.6%. Both groups received azithromycin and ethambutol; the comparator was not a rifampicin-containing triple regimen. - Eight weeks of sofosbuvir–velpatasvir is noninferior to twelve weeks in selected patients with hepatitis C
The Lancet
RESOLVE randomized trial, 880 treatment-naive, noncirrhotic patients. Per-protocol sustained virological response: 98.8% versus 99.0%. - Orforglipron meets cardiovascular noninferiority versus insulin glargine in high-risk type 2 diabetes
The Lancet
ACHIEVE-4 phase 3 trial, 2,749 patients. Cardiovascular events: 4.2% versus 5.0%, HR 0.84. This establishes noninferiority, not cardiovascular superiority. - Robotic hip replacement shows no overall implant-survival advantage over conventional surgery
The BMJ
Registry target-trial emulation, 666,283 procedures. Matched five-year implant survival was 98.8% in both groups; malposition-related revisions were lower with robotics. - Robotic esophagectomy increases lymph-node yield without an established survival advantage
JAMA Surgery
Randomized trial, 218 patients. Median node yield: 36 versus 32. Complications were similar; one-year survival did not differ. - Retatrutide produces substantial weight loss in adults with obesity without diabetes
NEJM
TRIUMPH-1 phase 3 trial, 2,339 participants. Treatment-regimen estimate at 80 weeks: up to 25.0% weight loss versus 3.9% with placebo. - Retatrutide produces substantial weight loss in adults with obesity and type 2 diabetes
The Lancet
Phase 3, 1,152 participants. At 80 weeks, weight fell 18.8% with 12 mg versus 5.1% with placebo, using the primary treatment-regimen estimand. Gastrointestinal adverse effects were more frequent. - Oral safiglipron improves HbA1c and weight in early type 2 diabetes
Nature Medicine
Phase 3, 284 adults. Placebo-adjusted HbA1c reduction up to 1.45 percentage points at 32 weeks; no cardiovascular-outcome evidence. - Petrelintide reduces weight in a phase 2 obesity trial
The Lancet Diabetes & Endocrinology
Phase 2. Weight loss up to 9.8% versus 1.7% at the 28-week primary endpoint. No direct comparison with GLP-1 drugs. - Gepotidacin improves uncomplicated UTI symptoms within 24 hours in many patients
JAMA Network Open
Single-arm phase 3b study. 54.4% had symptom improvement at 24 hours; no comparator to establish superiority. - Supervised exercise improves persistent knee symptoms after ACL reconstruction
Annals of Internal Medicine
Randomized trial, 184 young adults. Modest additional improvement at four months; differences narrowed at twelve months, with no demonstrated cartilage benefit. - Facilitated cascade testing increases BRCA testing among at-risk relatives
Journal of Clinical Oncology
Cluster-randomized trial. Six-month testing uptake: 73.2% with navigation versus 50.7% with standard care. - Hypotension prediction software shows no superiority over proactive blood-pressure management
Anesthesiology
Randomized trial, 100 surgical patients. No significant reduction in hypotension versus intervention at MAP ≤73 mmHg. The trial does not establish equivalence. - Implanted radiation tiles improve local control after brain-metastasis surgery
Journal of Clinical Oncology
Phase 3 RCT. Better surgical-bed recurrence outcomes than postoperative stereotactic radiation; no established overall-survival benefit. - Garetosmab reduces new heterotopic bone lesions in fibrodysplasia ossificans progressiva
The Lancet
Phase 3, 63 adults. One and two new lesions in the active-dose groups versus 19 with placebo at 56 weeks. Small trial in an ultrarare disease. - Lower blood-pressure targets reduce vasopressor exposure in critically ill children
JAMA
RCT, 1,900 children. Vasopressor exposure fell, but the primary outcome combining mortality and ventilation duration did not significantly improve. - Fasting beyond 12 hours adds little to routine laboratory testing
JAMA Internal Medicine
Large cross-sectional analysis. Supports test-specific fasting requirements; it does not mean fasting is unnecessary for every test. - Tacrolimus and mycophenolate show no significant difference in sustained lupus-nephritis response
Kidney International
RCT, 130 patients, both with glucocorticoids. Response at 96 weeks 58.5% versus 69.2%; differing adverse effects. Absence of significance does not establish equivalence. - Influenza vaccination reduced the risk of hospitalisation and severe outcomes during the 2024–2025 season.
Clinical Infectious Diseases
Test-negative study across 26 US centres: estimated effectiveness 40% against hospitalisation, 58% against ICU admission, and 52% against death. - Vedolizumab-first treatment was associated with more steroid-free disease stability in ulcerative colitis.
JAMA Network Open
Swedish cohort of 3,263 patients. Hospitalisation rates did not differ significantly from infliximab or adalimumab. Observational comparison. - Timely hepatitis B birth-dose vaccination was associated with less mother-to-child transmission.
Clinical Infectious Diseases
Ethiopian observational study, 387 infants. Transmission occurred in 0/39 receiving birth-dose vaccination alone versus 20/131 without birth immunoprophylaxis. Small, nonrandomised groups. - Young stroke survivors receiving antithrombotic therapy faced substantial long-term bleeding risk.
JAMA Network Open
ODYSSEY cohort, 1,226 patients: five-year bleeding risk 10.7%. Bleeding and recurrent vascular events differ in severity; this does not establish that stopping treatment is beneficial. - Pregnancy hypertension marked later dementia risk, but the association weakened after accounting for subsequent vascular disease.
JAMA Network Open
Korean cohort of 1.37 million women. Adjusted HR fell from 1.96 to 1.15, becoming nonsignificant after additional adjustment. Few dementia events warrant caution. - Escitalopram and amitriptyline prolonged QTc, but trials detected no increase in early major cardiovascular events with antidepressants.
BMJ
- A multistrain probiotic was associated with fewer deaths or NEC in very preterm infants.
JAMA Network Open
Swedish cohort, 4,695 infants: adjusted RR 0.28 for death/NEC. Applies to the studied formulation and infants born at 28–31 weeks, not automatically to extremely preterm infants. - Therapeutic anticoagulation did not significantly reduce death or thrombosis in HERO-19.
JAMA Network Open
Small RCT, 139 hospitalised COVID-19 patients. HR 0.74, 95% CI 0.38–1.48; uncertainty remains substantial. - Intravenous iron improved haemoglobin and reduced transfusion compared with oral iron in pregnancy.
JAMA Network Open
Meta-analysis of 29 RCTs, 11,771 participants. Transfusion RR 0.63; haemoglobin at delivery approximately 0.59 g/dL higher. - Short oral corticosteroid courses were associated with serious adverse events in adults with type 2 diabetes.
JAMA Network Open
Self-controlled study of 36,048 patients. Increased gastrointestinal bleeding, pneumonia and heart failure during days 6–30 after initiation. - Atenolol was associated with fewer cardiovascular events than bisoprolol after MI without recorded heart failure.
NEJM Evidence
- Multicancer blood testing detected cancer in about 1 in 185 screened adults in PATHFINDER 2.
Nature Medicine
- Higher blood pressure, older age and tenecteplase dose were linked to intracranial bleeding after STEMI thrombolysis.
European Heart Journal
- The SAFE score showed the greatest clinical utility for predicting cirrhosis in steatotic liver disease.
JAMA Internal Medicine
- Protection from tuberculosis preventive treatment wanes sooner in high-burden settings.
The Lancet Respiratory Medicine
- RSV vaccination was associated with substantially fewer hospitalizations in older adults.
JAMA Network Open
- Higher maternal egg and peanut intake did not prevent infant egg or peanut allergy.
NEJM
- Carotid revascularization did not improve cognition beyond intensive medical treatment.
JAMA
- Whole grains modestly improved LDL cholesterol and other cardiometabolic risk factors.
European Heart Journal
- Lower intraoperative fluid use was not associated with more postoperative acute kidney injury.
JAMA Network Open
- Adding IVIG to prednisone improved early recovery in newly diagnosed inflammatory myopathy.
JAMA Neurology
- Nirsevimab was associated with substantially fewer infant RSV hospitalizations.
JAMA Network Open
- Adoption of azithromycin prophylaxis for unscheduled cesarean delivery was associated with fewer postpartum infections.
JAMA
- Febrile seizures were generally associated with minimal differences in later school performance.
JAMA Network Open
- Loberamisal improved stroke recovery in a Chinese phase 3 trial.
JAMA
- Oveporexton improved wakefulness and reduced cataplexy in narcolepsy type 1.
NEJM
- Starting with 30% oxygen rather than air did not reduce respiratory support in moderately preterm infants.
JAMA
- Tozorakimab reduced COPD exacerbations in two phase 3 trials.
NEJM
- Atezolizumab did not significantly improve event-free survival in early triple-negative breast cancer.
Nature Medicine
- Catheter-directed thrombolysis reduced early deterioration in intermediate-high-risk pulmonary embolism.
NEJM
- Omitting aspirin from initial low-dose prasugrel treatment in STEMI failed to demonstrate noninferior ischaemic protection.
NEJM
- Clopidogrel alone after 12 months of coronary stenting reduced bleeding but increased ischaemic events in high-risk patients.
NEJM
- A default prasugrel policy did not reduce ischaemic events versus ticagrelor after PCI for acute coronary syndrome.
NEJM
- Potent P2Y12 inhibitors with a DOAC raised bleeding concerns in AF with acute coronary syndrome.
Nature Medicine
- Atorvastatin reduced cardiovascular events in healthy adults aged ≥70, without improving disability-free survival.
NEJM
- DOAC therapy reduced net adverse clinical events in AF with one non-sex stroke-risk factor.
NEJM
- Eplontersen did not significantly reduce cardiovascular death or recurrent events in transthyretin amyloid cardiomyopathy.
NEJM
- Shorter, response-guided antibiotics increased treatment-free days in stable endocarditis but increased relapse.
NEJM
- Head elevation after thrombectomy did not significantly improve functional recovery compared with lying flat.
BMJ
- Preoperative intravenous iron reduced transfusions and modestly improved recovery after cardiac surgery in patients with anaemia.
BMJ
- Intravenous arginine did not shorten sickle-cell pain crises in children and young adults.
JAMA
- Daily zinc reduced infections in a small trial of young children with sickle-cell anaemia.
JAMA
- Platelets refrigerated for up to 21 days were noninferior to standard platelets for bleeding during cardiac surgery.
JAMA
- Five-fraction prostate radiotherapy improved bowel-related quality of life but was not superior for cancer control.
JAMA
- Intravenous anaesthesia did not improve days alive at home versus volatile anaesthesia after major noncardiac surgery.
JAMA
- A four-dose perioperative dapagliflozin regimen reduced acute kidney injury after elective cardiac surgery.
JAMA
- Weekly oral islatravir–lenacapavir was noninferior to daily bictegravir-based therapy for maintaining HIV suppression.
NEJM
- Oral amoxicillin step-down after clinical improvement was noninferior to continued IV treatment for severe childhood pneumonia without complicating factors.
The Lancet
- Perioperative enfortumab vedotin–pembrolizumab improved survival over cisplatin–gemcitabine in cisplatin-eligible muscle-invasive bladder cancer.
NEJM
- Thrombectomy did not improve recovery in medium or distal vessel stroke and caused more symptomatic haemorrhage.
JAMA
- Aspirin alone was noninferior to rivaroxaban followed by aspirin after hip or knee replacement.
NEJM
- Setmelanotide reduced BMI and hunger in acquired hypothalamic obesity, with more serious adverse events.
NEJM
- Rituximab was noninferior to ocrelizumab for MRI disease control in newly diagnosed relapsing multiple sclerosis.
NEJM
- Adding belzutifan to adjuvant pembrolizumab improved disease-free survival after kidney cancer surgery but increased severe toxicity.
NEJM