Evidence updates

ConfirmsBMJ, November 2026Clinical pharmacology

Antihypertensive withholding before non-cardiac surgery: Effect of discontinuing antihypertensives on perioperative hypotension in older patients before non-cardiac surgery: multicentre, randomised, double blind, controlled trial

Multicentre, randomised, double blind, placebo controlled trial at five tertiary teaching hospitals in China (November 2020 to December 2023). 2036 patients aged 60 to 80 who had taken an ACE inhibitor or ARB for at least two weeks and were having non-cardiac surgery under general anaesthesia got either their usual ACE inhibitor or ARB or an identical placebo capsule on the morning of surgery.

In older patients taking an ACE inhibitor or ARB, leaving out the morning dose on the day of surgery reduced perioperative hypotension and vasopressor use, with no significant difference in 30-day complications or mortality.

Key numbers:

Analysed 2012 patients (mean age 68.8 years; 1008 placebo, 1004 usual drug). Perioperative hypotension: 314/1008 (31.2%) when the dose was withheld vs 457/1004 (45.5%) when it was given (adjusted OR 0.52, 95% CI 0.43 to 0.63; absolute difference -14.4%, 95% CI -18.5% to -10.1%). Vasopressor use: 28.5% vs 41.1% (adjusted OR 0.54, 95% CI 0.44 to 0.66). Duration of hypotension: adjusted mean difference -1.3 minutes (95% CI -1.8 to -0.8). There were no significant differences in intraoperative fluid volume, postoperative hypotension, 30-day complications or mortality.

Caveats:

The primary outcome is a surrogate: mean arterial pressure below 65 mm Hg, or a fall of 30% or more from baseline that needed treatment. The absolute gain in hypotension duration was small. The trial was in Chinese tertiary centres, in patients aged 60 to 80 having general anaesthesia, so it may not apply to younger or older patients or to other types of anaesthesia. The 30-day clinical outcomes were secondary end points, so a modest effect on complications cannot be ruled out.

Read the paperNote: Perioperative assessment and care of older patientsNote: Hypertension, including hypertensive emergenciesNote: Heart failure

RefineN Engl J Med, November 2026Haematology

PEPPER (aspirin vs warfarin vs rivaroxaban after hip or knee replacement): Prevention of Venous Thromboembolism after Total Hip or Knee Replacement

Randomised, comparative-effectiveness noninferiority trial in 18,883 patients having elective total hip or knee arthroplasty. Patients got 30 days of aspirin 81 mg twice daily, warfarin (target INR 2.0) or rivaroxaban 10 mg daily. The primary effectiveness outcome was death from any cause or symptomatic VTE through 6 months; the primary safety outcome was bleeding, reoperation for wound problems or MI through 6 months. Both were assessed blinded. The noninferiority margin for the risk difference was 0.69 percentage points.

Aspirin was not noninferior to rivaroxaban or warfarin for death or symptomatic VTE, and rivaroxaban and warfarin were not noninferior to aspirin for bleeding, wound reoperation or MI. No agent was shown to be better on both counts.

Key numbers:

Per-protocol n = 15,317 of 18,883 randomised (7214 hip, 8103 knee). Death or symptomatic VTE (crude): aspirin 77/6090 (1.26%), warfarin 52/4231 (1.23%), rivaroxaban 47/4996 (0.94%). Pairwise 6-month risks: aspirin vs rivaroxaban 1.24% vs 0.94%, difference 0.30 points (95% CI -0.20 to 0.81); aspirin vs warfarin 1.24% vs 1.01%, difference 0.23 points (95% CI -0.34 to 0.81). Safety composite (crude): aspirin 2.91%, warfarin 3.36%, rivaroxaban 3.48%. Pairwise: rivaroxaban vs aspirin 3.70% vs 3.02%, difference 0.68 points (95% CI -0.04 to 1.41); warfarin vs aspirin 3.65% vs 2.88%, difference 0.77 points (95% CI -0.04 to 1.58). Intention-to-treat results were similar.

Caveats:

Failing noninferiority is not the same as proving inferiority: the confidence intervals for both outcomes cross zero, and the upper limits for the safety outcome reach about 1.4 to 1.6 points. Aspirin was given as 81 mg twice daily for 30 days from the start with no initial LMWH, unlike the NICE hip regimen and the once-daily 75 mg or 150 mg dose NICE uses. Event rates were low, and about one in five randomised patients were not in the per-protocol analysis. LMWH and apixaban were not tested.

Read the paperNote: Venous thromboembolism: DVT, PE and complicationsNote: Heparins and direct oral anticoagulants: pharmacology and reversalNote: Warfarin pharmacology, monitoring and reversal

ConfirmsThe Lancet, November 2026Palliative medicine

Prepare for Kidney Care: Preparing for responsive management versus renal dialysis in older people living with kidney failure and frailty or multimorbidity in the UK (Prepare for Kidney Care): a two-arm, superiority, parallel-group, open-label, pragmatic, phase 3, individually randomised controlled trial

Open-label, pragmatic, phase 3 superiority RCT at 31 UK kidney centres (recruitment 2017 to 2024). 445 people with eGFR below 15 mL/min/1.73 m² confirmed on a second reading and not due to AKI, aged 80 or over, or aged 65 to 79 with WHO performance status 3 or more or Davies comorbidity score 2 or more (median age 82, 31% female), randomised 1:1 to prepare for responsive management (protocolised conservative kidney management) or to prepare for dialysis. Primary outcome: QALYs (survival combined with EQ-5D-5L) by intention to treat, mean follow-up 4.5 years.

In older people with kidney failure and frailty or multimorbidity, preparing for conservative kidney management did not produce significantly different quality-adjusted survival from preparing for dialysis, and was associated with fewer dialysis access complications.

Key numbers:

Mean QALYs 1.354 (responsive management, n=228) vs 1.472 (dialysis preparation, n=217); adjusted mean difference -0.147 (95% CI -0.350 to 0.056), p=0.16. Dialysis access complications: adjusted IRR 0.41 (95% CI 0.19 to 0.88), based on 74 events in 36 participants across both groups. Deaths, reported among serious adverse events: 157/228 (69%) vs 136/217 (63%). Hospital admissions 510 vs 442, with admission rates described as similar.

Caveats:

Superiority trial with a non-significant result: this does not show the two approaches are equivalent, and the point estimate favoured dialysis preparation (the confidence interval allows up to about 4 months more full-health life with dialysis preparation). Open label. Only 7% of 6120 screened patients were randomised. It compared preparation strategies by intention to treat, not treatment actually received. Harm outcomes were not prespecified and access complications rest on few events. UK setting.

Read the paperNote: CKD in palliative careNote: Initiating chronic dialysisNote: Frailty

RefineN Engl J Med, November 2026Cardiology

STREAM: Discontinuing Statins in Older Adults without Cardiovascular Disease

International, open-label, noninferiority RCT. 1,880 adults aged 70 or older with at least two chronic conditions, taking a statin for primary prevention, randomised 1:1 to stop or continue statins and other lipid-lowering therapy. Primary outcome: nonfatal MI, nonfatal ischaemic stroke or death from any cause, whichever came first, analysed as the difference in restricted mean event-free survival time at 2 years (noninferiority margin -5.2 weeks).

In multimorbid adults aged 70 or older on statins for primary prevention, stopping the statin met noninferiority for MI, ischaemic stroke or death at 2 years, but crude event rates were higher after stopping (12.7% vs 9.2%).

Read the paperNote: Polypharmacy and deprescribingNote: Absolute cardiovascular risk assessment and primary preventionNote: Lipoprotein disorders and dyslipidaemia

ConfirmsAm J Gastroenterol, October 2026Gastroenterology and hepatology

ACG Clinical Guideline: Preventive Care for Patients With Cirrhosis: ACG Clinical Guideline: Preventive Care for Patients With Cirrhosis

American College of Gastroenterology clinical practice guideline (Tapper et al.). A writing group of hepatology experts and two GRADE methodologists framed PICO questions, ran librarian-assisted searches of PubMed, Embase and the Cochrane Library, and prioritised systematic reviews, meta-analyses and randomised trials. Output is 18 GRADE-assessed recommendations and 6 key concept statements across four domains: prevention of cirrhosis-specific complications, infection prevention, lifestyle factors, and non-liver conditions.

Preventive care in cirrhosis should be delivered systematically, with strong recommendations for carvedilol or band ligation for high-risk oesophageal varices, 6-monthly HCC surveillance, hepatitis A testing and vaccination, influenza, COVID-19 and RSV immunisation, and smoking cessation counselling.

Read the paperNote: Chronic liver disease and cirrhosisNote: Management of chronic liver disease complicationsNote: Gastrointestinal bleeding

EmergingN Engl J Med, October 2026Endocrinology

CONNECT: Continuous Glucose Monitoring in Non-Insulin-Treated Type 2 Diabetes

Open-label randomised controlled trial in 22 US primary care practices. 283 adults (aged 21 to 84) with type 2 diabetes for at least 6 months, HbA1c 7.5% or higher, not using insulin and on a stable glucose-lowering regimen for 30 days, were assigned to real-time CGM (n=145) or routine care with intermittent blinded CGM (n=138) for 26 weeks. Primary outcome was HbA1c at 26 weeks; key CGM metrics were tested in a fixed hierarchy.

In adults with type 2 diabetes not on insulin and above HbA1c target, 26 weeks of real-time CGM lowered HbA1c by 0.9 percentage points more than routine care, with more time in range and no increase in hypoglycaemia.

Read the paperNote: Type 2 diabetes mellitus and its complicationsNote: Practical and psychological aspects of glucose monitoring and insulin therapyNote: Diabetes-related investigations

EmergingN Engl J Med, October 2026Medical oncology

DeLLphi-305: Tarlatamab-Durvalumab Maintenance for Extensive-Stage Small-Cell Lung Cancer

Phase 3, international, open-label RCT (NCT06211036) in 563 patients with extensive-stage SCLC without progression after first-line chemoimmunotherapy, randomised to tarlatamab (a DLL3-CD3 bispecific T-cell engager) plus durvalumab (282) or durvalumab alone (281) as maintenance. Primary endpoint overall survival, key secondary endpoint progression-free survival, both measured from randomisation at the start of maintenance. Prespecified interim analysis, median follow-up about 16 months.

Adding tarlatamab to durvalumab maintenance after first-line chemoimmunotherapy for extensive-stage SCLC improved median overall survival from 12.7 to 21.1 months.

Read the paperNote: Lung cancer and pleural malignancyNote: Organ toxicity of systemic cancer therapyNote: Immune toxicity of checkpoint inhibitors

ConfirmsJAMA, October 2026Palliative medicine

EQUAL ACP: Advance Care Planning for Black and White Older Adults With Serious Illness: The EQUAL ACP Randomized Trial

Multisite cluster randomised trial in 10 clinics in the southern United States (9 primary care, 1 geriatrics). 791 community-dwelling Black (427) and White (364) adults aged 65 or over with serious illness. Clinics were randomised to a facilitated approach (Respecting Choices First Steps; 409 participants) or a self-guided approach (Five Wishes; 382 participants), both delivered by lay ACP facilitators. Within each clinic and study group, participants were also randomised to a racially concordant or discordant facilitator. Primary outcome: new formal ACP (advance directive, clinician note or orders for life-sustaining treatment form in the medical record) and/or new informal ACP (participant-reported discussion with family about end-of-life care preferences) within 12 months, compared within each racial group. Registered as NCT03516994.

In older adults with serious illness, ACP completion at 12 months did not differ significantly between facilitated and self-guided approaches in either Black or White participants. About two thirds completed some form of ACP, mostly informal family discussions.

Read the paperNote: Ethics, advance care planning and respecting patient wishesNote: Ethics of caring for older patientsNote: Cultural and religious aspects of death and dying

RefineN Engl J Med, October 2026Nephrology

ICRAKI: Intermittent or Continuous Renal-Replacement Therapy in Acute Kidney Injury

Multicentre, open-label, randomised noninferiority trial in French ICUs. Critically ill adults on invasive ventilation and/or catecholamines with AKI and an indication for renal-replacement therapy were assigned to intermittent haemodialysis (IHD) or continuous renal-replacement therapy (CRRT) as the initial modality. Primary outcome: major adverse kidney event by day 90 (death, RRT dependence, or creatinine more than 25% above baseline). Stopped early after sequential interim analyses showed a sustained signal of higher mortality with IHD.

In ventilated or vasopressor-dependent ICU patients needing dialysis for AKI, starting with intermittent haemodialysis was not shown noninferior to CRRT and was associated with higher 90-day mortality.

Read the paperNote: Acute kidney injury and acute tubular necrosisNote: Modes of dialysis: haemodialysis and peritoneal dialysisNote: Principles of renal replacement therapy: what dialysis and transplantation replace

EmergingJournal of Clinical Oncology, October 2026Palliative medicine

MICRO (Methylphenidate for hematologic cancer-related fatigue): Methylphenidate for Hematologic Cancer-Related Fatigue: A Randomized Clinical Trial

Multicentre (Danish), double-blind, placebo-controlled, two-period crossover RCT in 152 adults with haematological cancer and fatigue (VAS fatigue 4 or more out of 10, haemoglobin 8.0 g/dL or more, no chemotherapy in the previous 8 weeks, no concurrent psychotropic drugs): 6 weeks of methylphenidate or placebo, a 1-week treatment-free washout, then crossover. Primary endpoint was the between-treatment difference in change in FACIT-Fatigue score from baseline to the end of each period.

In adults with haematological cancer and persistent fatigue who were off chemotherapy, 6 weeks of methylphenidate improved FACIT-Fatigue scores by 5 points more than placebo. Toxicity was mild, but adverse events were more common on methylphenidate.

Read the paperNote: Depression near the end of lifeNote: Chronic leukaemia: CLL and CMLNote: Non-Hodgkin lymphomaNote: Plasma cell dyscrasias and multiple myeloma

EmergingNew England Journal of Medicine, October 2026Neurology

MILD-MT: Trial of Endovascular Therapy for Mild Stroke with Large-Vessel Occlusion

Multicentre, open-label RCT in China with blinded outcome assessment. Adults aged 18 to 80 with no prior disability (premorbid mRS 0) and an NIHSS under 6 at randomisation (including patients whose NIHSS was 6 or more at onset but improved), from an anterior circulation LVO (intracranial ICA, M1 or M2, with or without an ipsilateral extracranial ICA occlusion). Imaging criteria: ASPECTS 6 or more, and on CT or MR perfusion a core of 50 mL or less and a mismatch of 50 mL or more, within 24 hours of onset or last known well. Randomised to EVT plus medical management or medical management alone, with rescue EVT allowed if the NIHSS rose by 4 or more within 24 hours of onset. Primary outcome: mRS 0 to 1 at 90 days. 304 randomised, 300 in the modified intention-to-treat analysis (144 EVT, 156 medical).

In mild anterior circulation LVO stroke (NIHSS under 6) with a small core and a large perfusion mismatch, EVT within 24 hours raised the rate of excellent 90-day outcome (mRS 0 to 1) from 50.0% to 69.4%, with no rise in symptomatic ICH but a 13.2% rate of serious procedure-related complications.

Read the paperNote: Ischaemic strokeNote: CT and MRI brain imagingNote: Transient ischaemic attack

RefineLancet, October 2026Medical oncology

PRABITAS: 14-day versus 28-day trifluridine-tipiracil plus bevacizumab for refractory metastatic colorectal cancer (PRABITAS): a pragmatic, multicentre, open-label, randomised, phase 3, non-inferiority trial in Japan.

Pragmatic, multicentre, open-label, randomised phase 3 non-inferiority trial at 178 hospitals in Japan. 972 patients with refractory metastatic colorectal cancer were randomised 1:1 (970 in the intention-to-treat population) to trifluridine-tipiracil 35 mg/m2 orally twice daily plus bevacizumab 5 mg/kg IV on either the conventional 28-day schedule (trifluridine-tipiracil days 1 to 5 and 8 to 12, bevacizumab days 1 and 15) or a 14-day schedule (trifluridine-tipiracil days 1 to 5, bevacizumab day 1). Eligibility was broader than in earlier trials and procedures followed routine practice. Primary endpoint was overall survival, with a non-inferiority hazard ratio margin of 1.25.

Giving trifluridine-tipiracil on days 1 to 5 of a 14-day cycle with bevacizumab was non-inferior to the standard 28-day schedule for overall survival and caused much less severe neutropenia and less anorexia.

Read the paperNote: Colorectal cancerNote: Organ toxicity of systemic cancer therapyNote: Oncology trials: dose escalation, response criteria and survival endpoints

EmergingLancet, October 2026Immunology and allergy

RAPIDe-3: Oral deucrictibant for on-demand treatment of hereditary angioedema attacks: a phase 3, multicentre, randomised, double-blind, placebo-controlled crossover trial

Phase 3, double-blind, placebo-controlled 2 x 2 crossover RCT at 59 sites in 24 countries. Adolescents (12 to 17 years) and adults (18 to 75 years) with HAE (including normal C1-INH HAE with a documented genetic variant), at least two attacks in the 3 months before screening and experience using conventional on-demand therapy effectively. Participants were randomised 1:1 (stratified by age and long-term prophylaxis use) to treat two attacks, one with oral deucrictibant 20 mg immediate-release capsule and one with placebo, in either order. Primary endpoint: time to onset of symptom relief (Patient Global Impression of Change at least "a little better").

A single 20 mg oral dose of deucrictibant, a bradykinin B2 receptor antagonist, gave symptom relief of HAE attacks much faster than placebo and was generally well tolerated.

Read the paperNote: AngioedemaNote: Complement deficienciesNote: Interpreting complement profiles

EmergingLancet, September 2026Endocrinology

ACHIEVE-4: Cardiovascular safety of orforglipron versus insulin glargine in adults with type 2 diabetes at increased cardiovascular risk (ACHIEVE-4): a phase 3, event-driven, randomised, open-label, non-inferiority, active comparator trial

Phase 3, event-driven, randomised (1:1), open-label, non-inferiority trial of once-daily oral orforglipron (a non-peptide GLP-1 receptor agonist, maximum tolerated dose up to 36 mg) against once-daily titrated insulin glargine. It enrolled 2749 adults at 317 sites in 16 countries and territories. All had type 2 diabetes (HbA1c 7.0 to 10.5%) on up to three glucose-lowering drugs (metformin, a sulfonylurea and/or an SGLT2 inhibitor), BMI 25 kg/m2 or more, and established cardiovascular disease (85.9%) or chronic kidney disease (37.6%). Mean age 63 years, mean HbA1c 8.2%, mean BMI 33 kg/m2. Median follow-up was 2 years.

Oral orforglipron was non-inferior to insulin glargine for major adverse cardiovascular events in high-risk type 2 diabetes, with no significant difference between groups, less hypoglycaemia and far more gastrointestinal adverse events.

Read the paperNote: Type 2 diabetes mellitus and its complicationsNote: Obesity and metabolic syndromeNote: Hypoglycaemia

EmergingJ Hepatol, September 2026Gastroenterology and hepatology

EASL-EASD-EASO MASH pharmacotherapy guidance: EASL-EASD-EASO guidance on the use of resmetirom and semaglutide as MASH-targeted therapy

Joint European society guidance (EASL, EASD, EASO), issued after regulatory approval of both drugs, covering patient selection, starting, monitoring and stopping resmetirom and semaglutide in adults with MASH.

Pharmacotherapy is recommended for adults with non-cirrhotic MASH and fibrosis stage F2-F3 (on non-invasive tests or biopsy), alongside structured lifestyle intervention and optimised management of comorbidities. Choice should be individualised to preferences, risks and cardio-renal-metabolic profile. Semaglutide may be preferred with obesity, type 2 diabetes, established cardiovascular disease or high cardiovascular risk. Resmetirom may be prioritised without obesity, or when a GLP-1 receptor agonist is already in use or not tolerated.

Read the paperNote: MASLD and MASH (formerly NAFLD and NASH)Note: Liver biopsy and non-invasive assessment of fibrosisNote: Chronic liver disease and cirrhosis

EmergingN Engl J Med, September 2026Respiratory and sleep medicine

OBERON and TITANIA: Tozorakimab to Prevent COPD Exacerbations

Two replicate phase 3, multicentre, double-blind, placebo-controlled RCTs. OBERON compared tozorakimab (446) with placebo (431); TITANIA compared tozorakimab (438) with placebo (435). Adults aged 40 or over with spirometry-confirmed COPD (post-bronchodilator FEV1/FVC below 0.70), at least 10 pack-years, symptoms with cough and sputum (CAT 10 or more, cough and phlegm items each 2 or more), and at least 2 moderate or 1 severe exacerbation in the prior year despite optimised dual or triple inhaled therapy at a stable dose for at least 3 months. Asthma and asthma-COPD overlap were excluded; there was no blood eosinophil criterion. Add-on tozorakimab (anti-IL-33 monoclonal antibody) 300 mg SC or placebo every 4 weeks for 52 weeks. Primary end point: annualised rate of moderate or severe exacerbations in former smokers; first key secondary end point: the same rate in the overall population of current and former smokers.

In two replicate trials, add-on tozorakimab reduced moderate or severe COPD exacerbations by about 30% compared with placebo, both in former smokers and in the overall population of current and former smokers, in patients enrolled without any eosinophil threshold.

Read the paperNote: Chronic obstructive pulmonary diseaseNote: Asthma

RefineLancet Gastroenterol Hepatol, September 2026Gastroenterology and hepatology

PROFILE 5-year follow-up: Long-term outcomes of top-down therapy versus a conventional step-up strategy in adults newly diagnosed with Crohn's disease: 5-year follow-up of the PROFILE trial

Long-term follow-up of a multicentre open-label RCT at 40 UK hospitals. Patients aged 16 to 80 with newly diagnosed Crohn's disease were randomised to top-down infliximab plus an immunomodulator or protocolised step-up treatment for 48 weeks, then returned to local standard care. Objective outcomes were extracted from records for up to 5 years after the week 48 visit and analysed by original randomisation (intention to treat), with Kaplan-Meier and Cox models. Primary outcome: Crohn's-related abdominal surgery.

Starting infliximab plus an immunomodulator at diagnosis, rather than stepping up, was associated with fewer Crohn's-related operations, hospital admissions and progressions to stricturing or penetrating disease over about 5 years, with no difference in serious infection or cancer.

Read the paperNote: Inflammatory bowel diseaseNote: Immunosuppressants and biologics in IBD: indications and pre-treatment screening

EmergingN Engl J Med, August 2026Infectious diseases

POET II: Response-Tailored or Standard-Duration Antibiotic Treatment for Infective Endocarditis

International, open-label, randomised trial in 508 adults in stable condition with left-sided infective endocarditis due to Staphylococcus aureus, Enterococcus faecalis or streptococci (255 response-tailored, 253 standard). Before randomisation, all patients had received at least a prespecified 2 to 4 weeks of therapy (depending on organism and complications) and met criteria for clinical stabilisation. The response-tailored group then stopped antibiotics, while the standard group continued to a usual total of 4 to 6 weeks. Primary outcomes at 6 months after randomisation were days alive without antibiotics (tested for superiority) and a composite of death from any cause, unplanned cardiac surgery or symptomatic embolism (tested for noninferiority, margin 7.5 percentage points). Relapse of bacteraemia or endocarditis was a key secondary outcome.

In stabilised left-sided endocarditis, stopping antibiotics early gave more antibiotic-free days and was noninferior for death, unplanned surgery or embolism, but relapse was about three times more common.

Read the paperNote: Infective endocarditisNote: BacteraemiaNote: Prosthetic joint, heart valve and cardiac device infections

RefineNew England Journal of Medicine, August 2026Geriatric medicine

STAREE: Atorvastatin, Cardiovascular Events, and Disability-free Survival in Older Adults

Double-blind, placebo-controlled RCT in general practices across Australia. 9971 community-dwelling adults aged 70 or older (mean 74.7 years, 51.9% women) without cardiovascular disease, diabetes or dementia, randomised 1:1 to atorvastatin 40 mg daily (4984) or placebo (4987). Exclusions included total cholesterol above 7.5 mmol/L, eGFR below 45 or persistent proteinuria, and serious illness likely to cause death within 5 years. Two primary end points tested hierarchically: major cardiovascular events (CV death, nonfatal MI or stroke, coronary revascularisation) and disability-free survival (death from any cause, dementia or persistent physical disability). Median follow-up 5.9 years.

In community-dwelling adults aged 70 or older without cardiovascular disease, diabetes or dementia, atorvastatin 40 mg reduced major cardiovascular events by about 30% but did not extend survival free of dementia or persistent physical disability.

Read the paperNote: Polypharmacy and deprescribingNote: Lipoprotein disorders and dyslipidaemiaNote: Frailty

RefineAnn Rheum Dis, July 2026Rheumatology

2025 EULAR recommendations for PMR and large vessel vasculitis: 2025 EULAR recommendations for the management of polymyalgia rheumatica and primary large vessel vasculitis

EULAR task force recommendation update (28 members from 13 European countries, Canada, India and the USA), informed by three systematic literature reviews to 31 December 2024 and structured voting; 4 overarching principles, 12 recommendations and 2 quality indicators covering PMR, GCA and Takayasu arteritis in one set.

EULAR now manages PMR, GCA and Takayasu arteritis in one set of recommendations. All suspected cases go to a specialist, suspected GCA within 24 hours, with immediate glucocorticoids only when GCA is strongly suspected. The goal is to stop glucocorticoids within 1 year in PMR and within 12 to 18 months in GCA and Takayasu. Upadacitinib joins tocilizumab as adjunctive therapy for GCA, and IL-6 receptor inhibitors are added for selected PMR.

Read the paperNote: Polymyalgia rheumatica and giant cell arteritisNote: Takayasu arteritis

Stop doingBMJ, July 2026Dermatology

Antihistamines for atopic dermatitis network meta-analysis: Antihistamines for atopic dermatitis (eczema): systematic review and network meta-analysis of randomised trials

Systematic review and Bayesian random effects network meta-analysis of 47 randomised trials (6230 children and adults, mainly moderate to severe atopic dermatitis; searches to 5 May 2025) of add-on oral H1 antihistamines, H2 blockers, mast cell stabilisers (nedocromil, sodium cromoglycate) or combinations. Outcomes were severity (objective SCORAD 0 to 83, minimal important difference 8.2), itch (0 to 10 numerical rating scale, minimal important difference 3), sleep disturbance, flares, eczema-related quality of life and harms, rated with GRADE.

Adding an oral H1 antihistamine to usual eczema treatment probably reduces severity and itch by amounts well below what patients would notice, may not improve sleep or reduce flares, and first-generation agents probably increase cognitive impairment.

Read the paperNote: Atopic dermatitis (eczema)Note: Anticholinergic toxidromeNote: Polypharmacy and deprescribing

RefineN Engl J Med, July 2026Haematology

ENDURANCE (ECOG-ACRIN E1A11): Continuous or Fixed-Duration Maintenance Therapy in Multiple Myeloma

Phase 3 open-label RCT (NCT01863550) with two randomisations. Adults with standard-risk newly diagnosed myeloma who were transplant-ineligible or not planning upfront autologous transplant (1087 enrolled) first received VRd or KRd induction. Of these, 516 who completed induction without progression were randomised to lenalidomide 15 mg daily on days 1 to 21 of 28, either for 2 years (n=256) or until progression (n=260). The primary end point was overall survival from the maintenance randomisation, with the trial designed to show that continuous therapy was superior (80% power for a 50% improvement in median overall survival). Median follow-up was 86 months.

In standard-risk myeloma without upfront transplant, lenalidomide maintenance until progression showed no overall survival gain over stopping at 2 years, and it caused more toxicity.

Read the paperNote: Plasma cell dyscrasias and multiple myelomaNote: Serum and urine electrophoresis, immunofixation and free light chainsNote: Principles of cytotoxic chemotherapy: cell kinetics, dosing, combination and resistance

RefineN Engl J Med, July 2026General medicine

EPCAT III: Rivaroxaban Then Aspirin vs. Aspirin Alone after Total Hip or Knee Arthroplasty

Multicentre, double-blind, randomised non-inferiority trial of 5429 adults having elective total hip or knee arthroplasty. For the first 5 days after surgery, patients got either aspirin 81 mg daily or rivaroxaban 10 mg daily. All patients then took aspirin 81 mg daily for a further 9 days after knee arthroplasty (14 days in total) or 30 days after hip arthroplasty (35 days in total). The primary effectiveness outcome was symptomatic VTE (proximal DVT or PE) at 90 days, with a non-inferiority margin of 0.7 percentage points. The primary safety outcome was major or clinically relevant non-major bleeding.

After elective hip or knee arthroplasty, aspirin alone was non-inferior to 5 days of rivaroxaban then aspirin for preventing symptomatic VTE, with no clinically relevant difference in bleeding.

Read the paperNote: Venous thromboembolism: DVT, PE and complicationsNote: Perioperative assessment and care of older patientsNote: Heparins and direct oral anticoagulants: pharmacology and reversal

ConfirmsN Engl J Med, July 2026Infectious diseases

GoGoVax: Meningococcal B Vaccine to Prevent Neisseria gonorrhoeae Infection

Multicentre, double-blind, placebo-controlled RCT at 7 Australian sites (NCT04415424). 654 men who have sex with men with a recent diagnosis of gonorrhoea or infectious syphilis, either HIV-negative on PrEP or living with HIV, were randomised 1:1 to two doses of 4CMenB (Bexsero) or placebo. Quarterly STI screening, including gonorrhoea NAAT from urogenital, anorectal and oropharyngeal sites, for 2 years. Primary outcome: first gonorrhoea infection after vaccination in the per-protocol population (587 participants who received both doses and attended at least two follow-up visits after the second dose).

In high-risk men who have sex with men, two doses of 4CMenB did not reduce gonorrhoea compared with placebo (vaccine efficacy -0.5%).

Read the paperNote: Immunisation to prevent infection, including HPV, hepatitis B and other STIsNote: Chlamydia, gonorrhoea and Mycoplasma genitaliumNote: HIV infection

EmergingJAMA Dermatol, July 2026Dermatology

Ixekizumab with or without tirzepatide (phase 3b): Ixekizumab With or Without Tirzepatide in Adults With Psoriasis and Overweight or Obesity: A Phase 3b Randomized Clinical Trial

Open-label, randomised (1:1), 52-week phase 3b trial at 72 US sites, with masked assessors for psoriasis outcomes. 281 adults were randomised and 274 formed the modified intention-to-treat population (138 combination, 136 ixekizumab alone). Eligible adults had moderate to severe plaque psoriasis (sPGA 3 or more, PASI 12 or more, BSA 10% or more) and either obesity (BMI 30 or more) or BMI 27 to under 30 with a weight-related comorbidity; mean BMI 39.2. Prior failure of or intolerance to an IL-17 inhibitor or GLP-1 receptor agonist was an exclusion. All received ixekizumab plus diet and exercise advice; half also received weekly tirzepatide, started at 2.5 mg and increased every 4 weeks to the maximum tolerated dose of 5, 10 or 15 mg (83.9% reached 15 mg). Primary end point: PASI 100 and 10% or more weight loss together at week 36.

In adults with psoriasis and overweight or obesity, adding tirzepatide to ixekizumab made complete skin clearance with 10% or more weight loss far more likely at 36 weeks (27.1% v 5.8%), mostly through weight loss, with a smaller gain in complete clearance alone (PASI 100 40.6% v 29.0%).

Read the paperNote: PsoriasisNote: Systemic immunosuppressants and biologics in dermatologyNote: Obesity and metabolic syndrome

RefineGenet Med, June 2026Genetic and metabolic medicine

ACMG points to consider on VUS reporting: Points to consider for the reporting of variants of uncertain significance in germline genetic and genomic testing: A statement of the American College of Medical Genetics and Genomics (ACMG)

Professional society practice statement from the ACMG Laboratory Quality Assurance Committee, covering the classification, reporting, communication and clinical use of germline VUS. It is a consensus document for laboratories and clinicians, not a trial.

The ACMG recommends that laboratories report VUS in a way that openly separates those more likely to be reclassified as benign (VUS-low) from those where a clinician may want to put more effort into follow-up (VUS-high).

Read the paperNote: Counselling about variants of uncertain significance and incidental findingsNote: Single gene testing and interpreting common genetic test resultsNote: Legal and ethical principles of genetic testing

RefineAnn Intern Med, June 2026Endocrinology

ACP living guideline on pharmacologic treatment of overweight and obesity: Pharmacologic Treatments With Lifestyle Modifications in Nonpregnant Adults With Overweight or Obesity in Outpatient Settings: A Living Clinical Guideline From the American College of Physicians (April 2026)

Living clinical practice guideline from the American College of Physicians, based on systematic reviews of pharmacologic treatments and graded with GRADE. It covers nonpregnant adults with obesity, or overweight with a comorbidity, treated in outpatient settings, and will be updated as new evidence emerges.

For adults with BMI 30 or more, ACP conditionally suggests semaglutide or tirzepatide first-line (moderate certainty), phentermine-topiramate second, liraglutide third and naltrexone-bupropion fourth (low certainty), always with lifestyle modification.

Read the paperNote: Obesity and metabolic syndromeNote: Incretin-based therapies: GLP-1 receptor agonists, dual agonists and DPP-4 inhibitorsNote: Bariatric surgery: indications and complications

RefineN Engl J Med, June 2026General medicine

ARISE FLUIDS: Vasopressors or Fluids in Early Septic Shock

Open-label multicentre randomised trial in emergency departments, run by the ANZICS Clinical Trials Group and the ACEM Clinical Trials Network. Adults with suspected infection, lactate above 2 mmol/L, at least one dose of IV antimicrobial and SBP below 90 or MAP below 65 mmHg despite at least 1 L of IV fluid (and no more than 2 L in total), enrolled within 6 hours of ED presentation, were assigned to restricted fluids with early vasopressors or larger fluid volumes with later vasopressors. The protocol ran for at least 6 hours and up to 24 hours. 1000 randomised, 963 in the intention-to-treat analysis (481 vs 482).

After the first 1 to 2 L of fluid in septic shock, stopping routine further fluid and starting vasopressors early gave no difference in days alive and out of hospital at day 90 compared with a larger-volume fluid strategy, and caused less pulmonary oedema.

Read the paperNote: Fever, sepsis and septic shockNote: Hypotension and shock

EmergingN Engl J Med, June 2026Nephrology

FIND-CKD: Finerenone in Persons with Chronic Kidney Disease without Diabetes

Phase 3, multicentre, double-blind, placebo-controlled RCT (NCT05047263, funded by Bayer). 1,584 adults without diabetes (793 finerenone, 791 placebo) with CKD (eGFR 25 to <90 mL/min/1.73 m2) and albuminuria (UACR 200 to 3500 mg/g, about 23 to 395 mg/mmol). All were on a stable, maximum tolerated dose of an ACE inhibitor or ARB and had potassium of 4.8 mmol/L or less at screening. People with polycystic kidney disease, lupus nephritis, ANCA vasculitis or other kidney disease needing immunosuppression, and people with symptomatic HFrEF who had an indication for an MRA, were excluded. Participants were randomised to finerenone 10 or 20 mg daily or placebo. Primary outcome: total eGFR slope (mean annual change from baseline to month 32).

In adults with albuminuric CKD without diabetes already on a RAS inhibitor, finerenone slowed eGFR decline over 32 months compared with placebo, at the cost of more hyperkalaemia.

Read the paperNote: Delaying progression of chronic kidney diseaseNote: HyperkalaemiaNote: Chronic kidney disease

EmergingN Engl J Med, June 2026Immunology and allergy

HAELO: Lonvoguran Ziclumeran - In Vivo CRISPR Gene Editing in Hereditary Angioedema

Phase 3, double-blind, placebo-controlled RCT (NCT06634420). 80 patients aged 16 or older with HAE due to C1 inhibitor deficiency were randomised 2:1 to a single 50 mg IV infusion of lonvoguran ziclumeran (lonvo-z), an in vivo CRISPR gene-editing therapy, or placebo. Primary outcome: investigator-confirmed monthly attack rate from weeks 5 to 28. Median follow-up 7.5 months (range 4.9 to 12.8). Industry funded.

In a phase 3 trial, a single infusion of lonvo-z cut the HAE attack rate by 87% compared with placebo over weeks 5 to 28.

Read the paperNote: AngioedemaNote: Complement deficienciesNote: Interpreting complement profiles

EmergingN Engl J Med, June 2026Rheumatology

INDIGO: Obexelimab for the Treatment of IgG4-Related Disease

Phase 3, multicentre, double-blind, placebo-controlled RCT of 194 adults with active IgG4-related disease (97 per group), recruited January 2023 to November 2024. All met the 2019 ACR/EULAR classification criteria and had a flare needing glucocorticoids to be started or increased. Patients with disease in only one organ system that was mainly fibrotic, or B-cell-directed therapy in the previous 6 months, were excluded. Participants had weekly subcutaneous obexelimab 250 mg or placebo for 52 weeks, and both groups followed a standardised glucocorticoid taper to zero by week 8. The primary end point was time to first flare needing rescue therapy, as judged by both the investigator and an independent adjudication committee.

Obexelimab binds CD19 and FcγRIIb at the same time, which inhibits B-cell activity without depleting B cells. After steroids were stopped, it roughly halved flares needing rescue therapy, nearly doubled complete remission at one year and cut rescue glucocorticoid exposure compared with placebo.

Read the paperNote: IgG4-related diseaseNote: HypophysitisNote: Chronic pancreatitis and exocrine insufficiencyNote: Interpreting immunoglobulins and protein electrophoresis

RefineLancet, June 2026Infectious diseases

SNAP (benzylpenicillin domain): Benzylpenicillin versus flucloxacillin or cloxacillin for the treatment of penicillin-susceptible Staphylococcus aureus bacteraemia (SNAP): an international, multicentre, open-label, non-inferiority randomised controlled trial

Open-label, Bayesian, non-inferiority randomised trial within the penicillin-susceptible S. aureus (PSSA) silo of the SNAP adaptive platform. It ran at 67 hospitals in eight countries, including Australia and New Zealand, from February 2022 to June 2024. Patients of all ages were enrolled, and this report covers adults. PSSA had to be confirmed by phenotypic penicillin disc testing to EUCAST or CLSI criteria. Participants were randomised 1:1 to IV benzylpenicillin (1.8 g 4-hourly or 2.4 g 6-hourly) or an anti-staphylococcal penicillin (flucloxacillin 2 g 6-hourly, or cloxacillin 2 g 4-hourly where flucloxacillin was unavailable). The primary outcome was all-cause mortality at 90 days, and non-inferiority was defined as an adjusted odds ratio below 1.20.

In adults with penicillin-susceptible S. aureus bacteraemia, benzylpenicillin halved the odds of acute kidney injury compared with flucloxacillin or cloxacillin, and it was very probably no worse for 90-day mortality, although the prespecified non-inferiority criterion was not formally met. The authors conclude benzylpenicillin should be preferred.

Read the paperNote: BacteraemiaNote: Infective endocarditisNote: Osteomyelitis

RefineN Engl J Med, June 2026Infectious diseases

SNAP (cefazolin domain): Cefazolin for Methicillin-Susceptible Staphylococcus aureus Bacteremia

Open-label randomised domain of an international Bayesian adaptive platform trial (SNAP, NCT05137119), February 2022 to August 2024; 1287 adults with penicillin-resistant MSSA bacteraemia evaluable for 90-day mortality.

In adults with penicillin-resistant MSSA bacteraemia, cefazolin was noninferior to flucloxacillin or cloxacillin for 90-day mortality and was associated with less acute kidney injury.

Read the paperNote: BacteraemiaNote: Central line and intravascular catheter infectionsNote: Fever, sepsis and septic shock

ConfirmsBMJ, May 2026Geriatric medicine

Calcium and vitamin D meta-analysis: Calcium, vitamin D, or combined supplementation to prevent fractures and falls: systematic review and meta-analysis

Systematic review and meta-analysis of 69 randomised trials (153,902 adults; median of trial mean ages 71 years; 87% of trials community dwelling) comparing calcium, vitamin D or both with placebo or no treatment in adults not taking osteoporosis drugs, long-term corticosteroids or active vitamin D analogues. Primary outcome was any fracture. GRADE certainty was judged against prespecified thresholds for a clinically important absolute effect (for example 2% for any fracture, 0.7% for hip fracture, 3% for risk of falling).

In adults not on osteoporosis drugs, calcium, vitamin D or both together give little to no absolute reduction in fractures, and none of them meaningfully prevents falls.

Read the paperNote: Non-surgical management of osteoporotic fracturesNote: Falls in older peopleNote: Polypharmacy and deprescribingNote: Osteoporosis and osteopenia

ConfirmsN Engl J Med, May 2026Dermatology

GALECRUSTED: higher-dose v standard-dose ivermectin with permethrin in severe scabies: Combined Oral Ivermectin and 5% Permethrin Cream to Treat Severe Scabies

Phase 3 blinded randomised superiority trial in France (NCT02841215). Adults with severe scabies, either crusted (hyperkeratosis at two or more sites) or profuse (spreading scaly eruption of the neck, face or trunk without hyperkeratosis), confirmed by parasitological or dermoscopic assessment. Pregnant and breastfeeding women were excluded. Patients were randomised 1:1 to oral ivermectin 400 or 200 micrograms/kg, taken with food, on days 0, 7 and 14. Both groups also applied 5% permethrin cream head to toe on days 0 and 7 and a daily emollient. The primary outcome was cure, defined as no mites, eggs or mite faeces on parasitological or dermoscopic assessment on days 18 and 21, plus no active clinical lesions on day 28.

In adults with severe (crusted or profuse) scabies, doubling oral ivermectin to 400 micrograms/kg alongside permethrin cream was not superior to the standard 200 micrograms/kg dose for cure.

Read the paperNote: Scabies and head liceNote: High-risk groups for infection and the global burden of infectious disease

EmergingN Engl J Med, May 2026Haematology

MajesTEC-9: Teclistamab in Multiple Myeloma with One to Three Previous Lines of Therapy

Open-label phase 3 randomised trial of 593 adults with relapsed or refractory myeloma after 1 to 3 prior lines, all previously treated with an anti-CD38 antibody and lenalidomide. Teclistamab monotherapy (BCMA x CD3 bispecific antibody) vs investigator's choice of pomalidomide, bortezomib and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd). Antimicrobial prophylaxis and immunoglobulin replacement were recommended. Primary outcome: progression-free survival by independent review.

In myeloma previously treated with an anti-CD38 antibody and lenalidomide, after 1 to 3 prior lines, teclistamab monotherapy improved progression-free and overall survival compared with PVd or Kd, at the cost of more severe infections.

Read the paperNote: Plasma cell dyscrasias and multiple myelomaNote: Complications of immunosuppressionNote: Febrile neutropenia

EmergingN Engl J Med, May 2026Medical oncology

RASolute 302: Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer

Phase 3, international, open-label RCT (NCT06625320). 500 adults with previously treated metastatic pancreatic ductal adenocarcinoma, ECOG 0 to 1, measurable disease (RECIST 1.1), documented RAS status (mutant or wild-type), no prior direct RAS-targeted therapy and no known CNS metastases. Randomised to oral daraxonrasib (248) or investigator's choice chemotherapy (252): gemcitabine plus nab-paclitaxel, mFOLFIRINOX, liposomal irinotecan plus 5-FU/leucovorin, or FOLFOX. Dual primary end points: overall survival and progression-free survival in the RAS G12 population (91.8% of patients). Key secondary end points included OS and PFS in the overall population (RAS G12, G13 or Q61 mutations, or no RAS mutation identified).

In previously treated metastatic pancreatic cancer, the oral RAS(ON) inhibitor daraxonrasib roughly doubled median overall survival and progression-free survival compared with investigator's choice chemotherapy, with fewer discontinuations for treatment-related toxicity.

Read the paperNote: Pancreatic cancerNote: Organ toxicity of systemic cancer therapyNote: Genetic testing in cancer including BRCA

RefineJAMA, April 2026Geriatric medicine

Levothyroxine discontinuation study (Dutch single-arm): Discontinuation of Levothyroxine in Adults Aged 60 Years or Older

Single-group, open-label prospective study at 58 general practices in the Netherlands, enrolling January 2020 to July 2022. Participants were community-dwelling adults aged 60 or older who had taken a stable levothyroxine dose of 150 mcg/day or less for at least 1 year, with TSH under 10 mIU/L; 370 started the discontinuation phase. Doses were reduced stepwise to a protocol, with thyroid function checked at least 6 weeks after each reduction. Primary outcome: off levothyroxine at 1 year with TSH under 10 mIU/L and free T4 within the reference range. There was no control group.

About a quarter of older adults on levothyroxine 150 mcg/day or less stopped it and kept adequate thyroid function at 1 year, rising to nearly two thirds of those on 50 mcg/day or less, with no clinically relevant change in thyroid-related quality of life.

Read the paperNote: Polypharmacy and deprescribingNote: HypothyroidismNote: Interpreting thyroid function tests and thyroid antibodies

RefineCirculation (published simultaneously in JACC), March 2026Cardiology

2026 ACC/AHA dyslipidemia guideline: 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Multi-society clinical practice guideline from the ACC/AHA Joint Committee on Clinical Practice Guidelines, built on a systematic literature search (MEDLINE, EMBASE, Cochrane Library, AHRQ and others; October to December 2024). It covers high LDL-C, hypertriglyceridaemia and elevated Lp(a), and replaces the 2018 AHA/ACC blood cholesterol guideline.

The 2026 ACC/AHA guideline brings back numeric LDL-C and non-HDL-C goals, with LDL-C below 55 mg/dL (about 1.4 mmol/L) and non-HDL-C below 85 mg/dL (about 2.2 mmol/L) for very high-risk ASCVD. It also recommends measuring Lp(a) at least once in adulthood and replaces the Pooled Cohort Equations with PREVENT-ASCVD for primary prevention risk estimation.

Read the paperNote: Lipoprotein disorders and dyslipidaemiaNote: Stable ischaemic heart diseaseNote: CT coronary angiography and coronary calcium score

EmergingN Engl J Med, March 2026Rheumatology

ALLEGORY: Efficacy and Safety of Obinutuzumab in Active Systemic Lupus Erythematosus

Phase 3, multicentre, double-blind, placebo-controlled RCT (NCT04963296). 303 adults with active SLE on standard therapy, excluding proliferative or membranous lupus nephritis, randomised 1:1 to obinutuzumab 1000 mg IV (n=151) or placebo (n=152) on day 1 and weeks 2, 24 and 26. Primary end point: SRI-4 response at week 52, with rescue medication, major concomitant-therapy violations or early discontinuation for death, lack of efficacy or adverse events counted as non-response. Funded by F. Hoffmann-La Roche.

Adding the type II anti-CD20 antibody obinutuzumab to standard therapy in active SLE without proliferative or membranous nephritis raised the week-52 SRI-4 response from 53.5% to 76.7% and improved every key secondary end point, including sustained glucocorticoid dose reduction and time to first flare.

Read the paperNote: Systemic lupus erythematosusNote: Non-TNF biologics: IL-6, IL-17, IL-12/23, B-cell and T-cell costimulation blockadeNote: Acute and chronic glomerulonephritis

EmergingN Engl J Med, March 2026Cardiology

CHAMPION-AF: Left Atrial Appendage Closure or Anticoagulation for Atrial Fibrillation

Ongoing international RCT of 3,000 patients with non-valvular AF who were suitable for anticoagulation (CHA2DS2-VASc 2 or more in men, 3 or more in women; mean age 72, 32% women, mean score 3.5), randomised 1:1 to Watchman FLX left atrial appendage closure or a NOAC. Open label, with blinded outcome assessment. Primary efficacy endpoint (CV death, stroke or systemic embolism at 3 years) tested for noninferiority with a 4.8 percentage point margin; primary safety endpoint (non-procedure-related bleeding) tested for superiority. Funded by the device manufacturer.

In AF patients who could take anticoagulation, appendage closure was noninferior to a NOAC for CV death, stroke or systemic embolism at 3 years and had a 45% lower hazard of non-procedure-related bleeding.

Read the paperNote: Atrial fibrillationNote: Atrial flutter

RefineN Engl J Med, March 2026Haematology

COBRRA: Bleeding Risk with Apixaban vs. Rivaroxaban in Acute Venous Thromboembolism

International open-label RCT with blinded outcome assessment, 2760 adults with acute symptomatic PE or proximal DVT, apixaban vs rivaroxaban for 3 months

In acute VTE, apixaban caused less than half as much clinically relevant bleeding as rivaroxaban over 3 months of treatment.

Read the paperNote: Venous thromboembolism: DVT, PE and complicationsNote: Tests for patients on DOACs

RefineJAMA, March 2026Clinical pharmacology

EHR deprescribing nudges (NUDGE-EHR-2): Electronic Health Record Intervention and Deprescribing for Older Adults: A Randomized Clinical Trial

Three-arm pragmatic cluster RCT in primary care at one US academic health system (Mass General Brigham, Epic EHR). 201 primary care physicians were randomised 1:1:1 (67 per arm). The trial covered 1,146 patients aged 65 or older (mean age 73.6) who had been prescribed at least 90 pills of a benzodiazepine or Z-drug, or at least 90 pills each of two strongly anticholinergic medicines, in the previous 180 days. In the precommitment arm, an EHR message at the first visit asked the physician to start a deprescribing discussion with the patient, and a second EHR reminder at the next visit encouraged deprescribing. In the boostering arm, an alert at the first visit encouraged deprescribing, with an in-basket reminder 4 weeks later. The third arm was usual care. Mean follow-up was about 290 days.

EHR prompts to primary care physicians, designed using behavioural science, increased deprescribing of sedative-hypnotics and strongly anticholinergic medicines in older adults. At least one target medicine was deprescribed in 26.8% of patients with usual care, 36.8% with precommitment and 34.3% with boostering.

Read the paperNote: Polypharmacy and deprescribingNote: Benzodiazepine and Z-drug harms and dependenceNote: Prescribing in special populations

ConfirmsN Engl J Med, March 2026Cardiology

Ez-PAVE: Intensive LDL Cholesterol Targeting in Atherosclerotic Cardiovascular Disease

Open-label superiority RCT, South Korea, n=3048 adults with established atherosclerotic cardiovascular disease, LDL target below 1.4 versus below 1.8 mmol/L, median follow-up 3.0 years (registered as a factorial trial that also randomised ezetimibe-rosuvastatin combination versus statin monotherapy)

In established ASCVD, treating to an LDL target below 1.4 mmol/L cut 3-year major cardiovascular events by about a third compared with a target below 1.8 mmol/L, with similar rates of prespecified safety events.

Read the paperNote: Lipoprotein disorders and dyslipidaemiaNote: Stable ischaemic heart diseaseNote: Acute coronary syndromes

ConfirmsLancet Rheumatology, March 2026Rheumatology

GO TEST Overture: A treat-to-target strategy versus symptom-driven management of gout in the Netherlands (GO TEST Overture): a multicentre, open-label, pragmatic, superiority, randomised controlled trial

Multicentre, open-label, pragmatic superiority RCT at 8 Dutch secondary care rheumatology centres; n=308 adults with gout and hyperuricaemia not on urate-lowering therapy (87% male, mean age 66).

Titrating oral urate-lowering therapy to a serum urate below 0.36 mmol/L gave more patients remission at 18 to 24 months than symptom-driven care, with no excess of adverse events.

Read the paperNote: Gout and calcium pyrophosphate diseaseNote: Acute monoarthritis

RefineN Engl J Med, March 2026Respiratory and sleep medicine

HI-PEITHO: Ultrasound-Facilitated, Catheter-Directed Fibrinolysis for Acute Pulmonary Embolism

Multinational, adaptive-design randomised trial with blinded outcome adjudication (treatment open-label). 544 adults aged 18 to 80 (mean age 58, 43% women) with normotensive acute PE, RV:LV ratio 1.0 or more on CTPA, raised troponin and at least two new signs of cardiorespiratory distress: heart rate 100 or more, systolic BP 110 mmHg or less, or respiratory rate over 20 (or SpO2 under 90% on room air). Patients were randomised 1:1 to ultrasound-facilitated catheter-directed alteplase (2 mg bolus then 1 mg/h per catheter for 7 hours, total 9 or 18 mg) plus heparin, or heparin alone. Funded by Boston Scientific.

In intermediate-risk PE with RV strain, raised troponin and early cardiorespiratory distress, catheter-directed low-dose alteplase plus heparin cut the 7-day composite of PE-related death, cardiorespiratory decompensation or collapse, or symptomatic recurrence from 10.3% to 4.0%, mainly by preventing decompensation or collapse.

Read the paperNote: Venous thromboembolism: DVT, PE and complications

ConfirmsN Engl J Med, March 2026Respiratory and sleep medicine

SOHO: High-Flow or Standard Oxygen in Acute Hypoxemic Respiratory Failure

Open-label, multicentre randomised trial in France (1116 randomised, 1110 analysed) of adults with acute hypoxaemic respiratory failure (PaO2:FiO2 200 or less, respiratory rate over 25, pulmonary infiltrate on chest imaging). Heated humidified high-flow nasal oxygen at 50 L/min or more versus standard oxygen by face mask or non-rebreather mask at 10 L/min or more, both titrated to SpO2 92 to 96%. Exclusions included hypercapnia (PaCO2 over 45 mmHg), need for emergent intubation, haemodynamic instability, GCS 12 or less, exacerbation of severe chronic lung disease, cardiogenic pulmonary oedema, COVID-19, post-extubation failure, recent abdominal or cardiothoracic surgery and do-not-intubate orders. Primary outcome: death by day 28.

High-flow nasal oxygen did not reduce 28-day mortality compared with standard oxygen in acute hypoxaemic respiratory failure. Intubation by day 28 was modestly lower with high-flow.

Read the paperNote: Acute and chronic respiratory failureNote: Non-invasive ventilationNote: Pulse oximetry and oxygen therapy

ConfirmsNEJM Evidence, February 2026General medicine

HIT (targeted hyponatraemia correction): A Randomized Trial of Targeted Hyponatremia Correction in Hospitalized Patients

Randomised, controlled, parallel-group trial at nine European centres. It enrolled 2173 adult inpatients with hypotonic hyponatraemia (plasma sodium below 130 mmol/L) who were expected to stay in hospital at least another 24 hours. It excluded severe symptomatic cases needing ICU care, non-hypotonic hyponatraemia (plasma osmolality above 280 mOsm/kg) and patients receiving end-of-life care. In the intervention arm, diagnosis and treatment followed the 2014 European guideline, with daily review and changes to treatment until sodium targets were reached. The control arm got routine care decided by treating teams. Primary outcome: death or rehospitalisation within 30 days.

In hospitalised patients with chronic hyponatraemia, targeted correction normalised sodium more often than routine care (60.4% vs 46.2%) but did not reduce 30-day death or rehospitalisation (20.5% vs 21.8%).

Read the paperNote: Hyponatraemia and hypernatraemiaNote: Fluid and electrolyte balance investigations

ConfirmsJAMA, February 2026Neurology

OPTION: Tenecteplase for Acute Non-Large Vessel Occlusion 4.5 to 24 Hours After Ischemic Stroke: The OPTION Randomized Clinical Trial

Randomised, open-label trial with blinded outcome assessment at 48 centres in China (enrolment June 2023 to August 2025). 570 adults were randomised and 566 analysed (282 tenecteplase, 284 control). Inclusion: prestroke mRS 0 to 1, NIHSS 6 to 25 (or 4 to 5 with a disabling deficit), 4.5 to 24 hours from last seen well. ICA, M1 and vertebrobasilar occlusions were excluded, and all patients had salvageable tissue on CT perfusion (core under 50 mL, mismatch ratio at least 1.2, mismatch volume at least 10 mL). Patients received an IV bolus of tenecteplase 0.25 mg/kg (maximum 25 mg) plus standard care, or standard medical treatment (antiplatelet therapy) alone. Primary outcome: mRS 0 to 1 at 90 days.

In patients with non-LVO ischaemic stroke and perfusion mismatch 4.5 to 24 hours after onset, tenecteplase made an excellent 90-day outcome (mRS 0 to 1) more likely than antiplatelet-based standard care, at the cost of a small rise in symptomatic ICH.

Read the paperNote: Ischaemic strokeNote: CT and MRI brain imaging

ConfirmsStroke, January 2026Neurology

2026 AHA/ASA Acute Ischemic Stroke Guideline: 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association

Clinical practice guideline from the AHA/ASA. It is based on a literature search run from September to December 2024, with high-impact studies added up to March 2025, and replaces the 2018 guideline and its 2019 update.

The 2026 AHA/ASA guideline accepts tenecteplase as an alternative to alteplase within 4.5 hours, supports imaging-selected thrombolysis beyond 4.5 hours, extends thrombectomy to selected large core and basilar occlusion strokes, and prefers dual antiplatelet therapy over thrombolysis for non-disabling deficits. This brings US guidance largely into line with the Australian and NZ living guidelines.

Read the paperNote: Ischaemic strokeNote: Transient ischaemic attackNote: CT and MRI brain imaging

EmergingJAMA, January 2026Genetic and metabolic medicine

CORALreef HeFH: Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial

Phase 3, double-blind, placebo-controlled RCT at 59 sites in 17 countries. 303 adults with heterozygous FH on a moderate- or high-intensity statin (about 82% high intensity; 64% also on ezetimibe), with LDL-C at least 1.4 mmol/L (prior ASCVD) or 1.8 mmol/L (no ASCVD). Randomised 2:1 to oral enlicitide 20 mg daily (n=202) or placebo (n=101) for 52 weeks. Homozygous FH and active or recent PCSK9 inhibitor treatment were excluded. Primary outcome: percentage change in LDL-C at week 24.

In adults with heterozygous FH already on statins, a once-daily oral PCSK9 inhibitor (enlicitide) lowered LDL-C by about 59% more than placebo at 24 weeks, the effect lasted to 52 weeks, and adverse events were similar to placebo.

Read the paperNote: Lipoprotein disorders and dyslipidaemiaNote: Non-statin lipid-lowering agents: ezetimibe, PCSK9 inhibitors, fibrates and omega-3Note: Autosomal dominant and recessive inheritance, penetrance and carrier risk

RefineKidney Int, January 2026Nephrology

KDIGO 2026 anaemia in CKD guideline: KDIGO 2026 Clinical Practice Guideline for the Management of Anemia in Chronic Kidney Disease (CKD)

International clinical practice guideline updating KDIGO 2012. Recommendations are based on systematic reviews by an Evidence Review Team and graded with GRADE; practice points are ungraded consensus statements reflecting the work group's expert judgement.

KDIGO now sets iron start thresholds by dialysis modality (proactive IV iron in haemodialysis, separate ferritin and TSAT thresholds outside haemodialysis), recommends that ESA-treated adults be kept below Hb 115 g/L, and prefers ESAs over HIF-PHIs as first-line therapy.

Read the paperNote: Anaemia in chronic kidney diseaseNote: Chronic kidney diseaseNote: Complications of dialysis

RefineMed J Aust, January 2026Clinical pharmacology

NACSTOP 2: Early Cessation of Acetylcysteine Treatment After Paracetamol Overdose (NACSTOP 2): A Non-Inferiority Randomised Controlled Trial

Open-label, non-inferiority randomised controlled trial in the emergency departments of six Australian metropolitan hospitals (four in Melbourne, two in Sydney), December 2019 to July 2024. Participants needed acetylcysteine after a single or staggered paracetamol ingestion, had ALT below 40 IU/L at presentation, and had ALT below 40 IU/L and paracetamol below 20 mg/L after 12 hours of acetylcysteine. The intervention arm stopped acetylcysteine at least 12 hours after starting and completed the 20-hour infusion period with IV compound sodium lactate; controls received the full two-bag regimen (200 mg/kg over 4 hours, then 100 mg/kg over 16 hours). Primary outcome: change in ALT from presentation to 20 hours after starting acetylcysteine; non-inferiority required the upper 95% CI of the difference in median ALT change to be below 3 IU/L.

In low-risk patients with normal ALT at presentation and normal ALT plus paracetamol below 20 mg/L after 12 hours of treatment, stopping acetylcysteine at about 13 hours was non-inferior to the full 20-hour two-bag regimen for change in ALT, and no patient in either arm developed hepatic injury or hepatotoxicity.

Read the paperNote: Paracetamol poisoningNote: Acute liver disease and acute liver failureNote: Drug-induced hepatitis

EmergingGenet Med, January 2026Genetic and metabolic medicine

Systematic review of adult outcomes of genomic disorders: Adult outcomes of clinically relevant genomic disorders: A systematic review and meta-analysis

Systematic review and random-effects meta-analysis. The search targeted 14 molecularly confirmed deletion syndromes, taking only studies with at least 5 adults. Of 1352 studies screened, 53 with nonoverlapping samples covered 13 syndromes. Results were pooled across syndromes and by syndrome.

In mostly young adult samples (under 30 to 40 years for most), obesity, diabetes, hypertension and dyslipidaemia were common across recurrent deletion syndromes, and a few studies pointed to premature death. Heterogeneity was high and partly explained by syndrome, so the authors warn against treating rare deletion syndromes as one group.

Read the paperNote: Karyotype and chromosome microarrayNote: Indications for referral to clinical genetics servicesNote: Tetralogy of Fallot

RefineJAMA, December 2025Obstetric medicine

CIRCUIT: Closed-Loop Insulin Delivery in Type 1 Diabetes in Pregnancy: The CIRCUIT Randomized Clinical Trial

Open-label RCT at 14 diabetes-in-pregnancy clinics in Canada and Australia (enrolment 2021 to 2024). 91 pregnant women with type 1 diabetes enrolled before 14 weeks were randomised 1:1 to a closed-loop system (Tandem t:slim X2 with Control-IQ and Dexcom G6, advised to use the lowest sleep target of about 6.2 to 6.7 mmol/L 24 hours a day) or standard care (injections or open-loop pump) with the same CGM. Primary outcome: percentage time in the pregnancy range of 3.5 to 7.8 mmol/L from 16 to 34 weeks.

A commercial closed-loop system without pregnancy-specific targets, run on its lowest target around the clock, increased time in the pregnancy glucose range by 12.5 percentage points over standard care with CGM, with less time below range.

Read the paperNote: Pre-existing diabetes in pregnancyNote: Type 1 diabetes mellitus and its complicationsNote: Diabetes care: cultural context, Indigenous health and multidisciplinary teams

RefineAm J Obstet Gynecol, December 2025Obstetric medicine

Postpartum HDP management systematic review: Postpartum management of the hypertensive disorders of pregnancy: a systematic review and meta-analysis

Systematic review and random-effects meta-analysis of randomised controlled trials of any intervention (drug, surgical or model of care) to lower blood pressure in women with postpartum hypertension; 44 trials included, 40 with usable data, searches updated to September 2025.

Adding a loop diuretic (mainly furosemide) to an antihypertensive improved postpartum blood pressure control. In nonsevere hypertension the authors concluded that enalapril or amlodipine were effective compared with nifedipine, and in severe hypertension diltiazem lowered blood pressure more than nifedipine. Postnatal blood pressure self-monitoring or self-management, or lifestyle programs, lowered blood pressure at 8 months postpartum. All evidence was of low or very low certainty.

Read the paperNote: Chronic and gestational hypertension in pregnancyNote: Pre-eclampsia and eclampsia

EmergingLancet, December 2025Obstetric medicine

PREVENT-PE: Scheduled birth at term for the prevention of pre-eclampsia (PREVENT-PE): an open-label randomised controlled trial

Open-label, adaptive randomised controlled trial at two UK maternity hospitals. Women aged 16 or over with a singleton pregnancy and no pre-eclampsia, attending a routine scan at 35+0 to 36+6 weeks, were randomised 1:1 (8,136 randomised, 8,094 analysed). The intervention group had a pre-eclampsia risk assessment combining maternal factors, mean arterial pressure, PlGF and sFlt-1; those at a risk of 1 in 50 or higher were offered planned early-term birth, with earlier timing (from 37 weeks) for higher risk. The control group had usual care at term. Primary outcome was birth with pre-eclampsia by ISSHP criteria.

Screening at 36 weeks and offering planned early-term birth, timed by risk, to women at a pre-eclampsia risk of 1 in 50 or higher reduced pre-eclampsia by about 30%, without increasing emergency caesarean section or neonatal unit admission.

Read the paperNote: Pre-eclampsia and eclampsiaNote: Chronic and gestational hypertension in pregnancy

RefineArthritis Rheumatol, November 2025Rheumatology

2025 ACR Guideline for SLE: 2025 American College of Rheumatology (ACR) Guideline for the Treatment of Systemic Lupus Erythematosus

GRADE-based clinical practice guideline covering non-renal SLE in adults and children. It used PICO questions with systematic literature reviews, a 13-member patient panel and a voting panel (mostly adult and paediatric rheumatologists, plus dermatologists and people with SLE) that needed at least 70% agreement on both direction and strength. It makes 35 recommendations: 3 strong and 32 conditional. Lupus nephritis is covered in the separate 2024 ACR guideline. The previous ACR SLE guideline was the 1999 adult guideline.

The ACR now recommends hydroxychloroquine for everyone with SLE, continued indefinitely. Prednisone should be tapered to 5 mg/day or less (ideally zero) within 6 months, and conventional or biologic immunosuppression introduced early to control disease and limit glucocorticoid exposure.

Read the paperNote: Systemic lupus erythematosusNote: Antiproliferative immunosuppressants: azathioprine, mycophenolate and cyclophosphamideNote: Non-TNF biologics: IL-6, IL-17, IL-12/23, B-cell and T-cell costimulation blockade

RefineN Engl J Med, November 2025Neurology

CREST-2: Medical Management and Revascularization for Asymptomatic Carotid Stenosis

Two parallel observer-blinded RCTs at 155 centres in 5 countries; 2485 patients with asymptomatic carotid stenosis of 70% or more, each comparing intensive medical management alone with medical management plus stenting (n=1245) or plus endarterectomy (n=1240).

Adding carotid stenting to intensive medical management lowered 4-year stroke or death in asymptomatic 70% or greater stenosis, but adding endarterectomy did not give a significant benefit.

Read the paperNote: Ischaemic strokeNote: Transient ischaemic attack