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Objective To update, synthesise and provide meta-analytical evidence of the associations between domain-specific physical activity (PA) and mental health and mental ill-health outcomes. Design Systematic review and multilevel meta-analysis. Data sources In March 2024, we systematically searched five databases. Eligibility criteria Methods employed replicated those of a previous review in 2017. All studies examining associations between domain-specific PA and specified mental health outcomes were included. Results 372 studies met inclusion criteria and 361 were included in the meta-analysis. Across the 372 studies (combined sample size of 3 323 711), 338 examined leisure-time PA, 54 work-related PA, 72 transport-related PA, 44 household PA, 5 school sport and 8 physical education. Multilevel meta-analyses showed that leisure-time PA (r=0.205, 95% CI 0.157 to 0.253), transport-related PA (r=0.138, 95% CI 0.042 to 0.231) and household PA (r=0.096, 95% CI 0.025 to 0.165) were positively associated with mental health . Leisure-time PA (r=−0.149, 95% CI −0.189 to –0.11) and school sport (r=−0.096, 95% CI −0.115 to –0.077) were inversely associated with mental ill health . However, work-related PA (r=0.134 95% CI 0.069 to 0.199) was positively associated with mental ill health . Conclusion The direction of the association between PA and mental health/mental ill health is dependent on the domain in which PA occurs. Promoting PA for leisure purposes is likely to yield the greatest benefits for both promoting mental health and preventing mental ill health. As such, leisure-time PA should be prioritised in messaging, guidelines and interventions/programmes designed to support mental health through PA. PROSPERO registration number CRD42024510303.

Abstract Aims Type 2 myocardial infarction due to myocardial oxygen supply–demand imbalance is associated with poor outcomes. There are no guidelines to inform care for these patients. The consensus on the assessment and management of type 2 myocardial infarction is gained. Methods and results An international e-Delphi study including experts in type 2 myocardial infarction identified through systematic review was conducted. Participants were asked to describe their approach to (i) definition and diagnosis, (ii) risk stratification, (iii) assessment of coronary artery disease and cardiac function, (iv) specialty management, (v) treatment and secondary prevention, and (vi) communication and rehabilitation. Statements generated in round one were circulated, with consensus defined a priori as ≥70% agreement on a 5-point Likert scale. Where no consensus was reached, statements were amended and recirculated for a final round. The response rate was 56% (38/68), 54% (37/68), and 72% (49/68) in the first, second, and third rounds, respectively. Following the first round, 67 unique statements were generated across six domains. Overall, consensus was achieved on 64% (43/67) of statements. Consensus was achieved for 42% (5/12) of statements on the diagnosis of type 2 myocardial infarction, 75% (3/4) on risk stratification, 50% (9/18) on the assessment of coronary artery disease and cardiac function, 60% (6/10), on specialty management, 100% (9/9) on treatment and secondary prevention, and 79% (11/15) on communication and rehabilitation. Conclusion Consensus was obtained across a number of domains for the assessment and management of patients with type 2 myocardial infarction. However, there was limited agreement amongst experts on the diagnostic criteria, which may benefit from refinement.

ObjectiveIn the phase 3 head‐to‐head MANDARA study (NCT04157348), benralizumab demonstrated noninferiority to mepolizumab in inducing remission (defined as Birmingham Vasculitis Activity Score [BVAS] of 0 and oral glucocorticoid [OGC] dosage ≤4 mg/day at weeks 36 and 48) in patients with eosinophilic granulomatosis with polyangiitis (EGPA). This analysis investigated a more stringent definition of remission that included discontinuation of OGCs and being relapse‐free.MethodsPatients aged ≥18 years with documented relapsing or refractory EGPA receiving OGCs at ≥7.5 mg/day with or without immunosuppressive therapy for ≥4 weeks before enrollment were randomized (1:1) to benralizumab at 30 mg or mepolizumab at 300 mg subcutaneously every 4 weeks for 52 weeks. The proportion of patients achieving remission off OGCs, defined as BVAS of 0, OGC dose of 0 mg/day (at weeks 36 and 48) and no relapses during the double‐masked period, was assessed.ResultsPatients (n = 140) were randomized to benralizumab (n = 70) or mepolizumab (n = 70). The adjusted percentage of patients with remission off OGCs was 23.5% (n = 16) with benralizumab versus 11.1% (n = 8) with mepolizumab (difference 12.47 [95% confidence interval 0.46–24.48], P = 0.042). Of those who achieved remission off OGCs, 100% of benralizumab‐treated patients and 98.6% of mepolizumab‐treated patients achieved remission within the first 36 weeks of treatment.ConclusionThe administration of anti–interleukin‐5/receptor (IL‐5/R) therapies, benralizumab and mepolizumab, enable discontinuation of OGCs in some patients with EGPA, while avoiding relapses. These findings suggest that adding anti‐IL‐5/R therapy to standard primary treatment for patients with EGPA may improve response.

Background and objectives Arteriovenous malformations (AVMs) with perinidal aneurysms and single draining vein are associated with an elevated risk of rupture and increased procedural complexity. The role of preoperative embolization in this high-risk anatomical subset remains unclear. This study aimed to evaluate the safety and efficacy of microsurgery with preoperative embolization, compared with microsurgery alone in patients with such AVMs. Methods We conducted a multicenter retrospective analysis of an AVM registry from the MISTA (Multicenter International Study for Treatment of Brain AVMs) consortium and included AVMs with perinidal aneurysms and a single draining vein. Baseline characteristics, angiographic outcomes, functional outcomes, and complication rates were compared. Propensity score weighting (PSW) using the covariate balancing method was applied to adjust for baseline differences. Results Out of a total of 1919 patients, 65 met the inclusion criteria; 45 patients underwent preoperative embolization followed by microsurgery, and 20 underwent microsurgery alone. After adjustment, complete obliteration rates were similar between groups (OR 0.87, 95% CI 0.04 to 16.33, P=0.92), as were rates of functional independence at discharge and follow-up. Overall complication, symptomatic complication, and mortality rates did not differ significantly between groups. However, permanent complications were significantly lower in patients with preoperative embolization (OR 0.06, 95% CI 0.004 to 0.84, P=0.03). Discussion In patients with AVMs featuring perinidal aneurysms and single draining vein, preoperative embolization followed by microsurgery was associated with fewer permanent complications and no increase in adverse outcomes compared with microsurgery alone. However, given the small number of events, this finding should be interpreted cautiously.

ABSTRACTBackgroundErenumab‐induced medication overuse headache (MOH) remission in participants with chronic migraine (CM) in a prospective, Phase 4, randomized, placebo‐controlled trial with an open‐label treatment period (OLTP). We present 1‐year results from the combined double‐blind treatment period (DBTP) and OLTP for the stratified nonopioid cohort.MethodsParticipants with CM‐MOH were randomized 1:1:1 to subcutaneous 70 or 140 mg erenumab every 4 weeks (QM) or placebo for the initial 24 weeks (DBTP). Those successfully completing DBTP could continue the 28‐week OLTP, maintaining the same erenumab dose received during DBTP or, if receiving placebo, randomly assigned 1:1 to erenumab 70 or 140 mg QM. OLTP endpoints were exploratory.ResultsOverall, 552 participants received erenumab (70 mg, n = 274; 140 mg, n = 278); 95.3% completed OLTP. One‐year MOH relapse in participants who achieved MOH remission at DBTP Month 6 was 2.7% (3/111) and 2.4% (3/124) with erenumab 70 and 140 mg, respectively; absence of MOH at study end was observed in 69.0% (189/274) and 75.5% (210/278) of participants. Sustained MOH absence over 1 year was reported in 60.5% (107/177) and 68.8% (119/173) of participants, respectively. Sustained improvements in measures of headache days, medication days, and function were observed in both groups. No new safety concerns were identified (grade ≥ 3, 35 [6.3%]; serious, 17 [3.1%]; adverse events leading to treatment discontinuation, 5 [0.9%]).ConclusionsErenumab was effective in inducing and sustaining MOH remission and improving function over 1 year. Treatment compliance remained high, with safety events consistent with erenumab's known safety profile.Trial RegistrationNCT03971071

BACKGROUND: This individual participant data meta-analysis aimed to determine whether time to treatment influences the effect of intraarterial thrombolysis (IAT), intravenous thrombolysis, and conservative standard therapy on visual outcomes in nonarteritic central retinal artery occlusion. METHODS: We searched MEDLINE, CENTRAL, and Embase up to June 2023 for studies reporting treatment modality and peri-treatment best-corrected visual acuity (BCVA) for ≥5 participants, excluding patients with nonsevere vision loss (BCVA <1.0 logarithm of the minimum angle of resolution [logMAR]) or treated after 24 hours of symptom onset. The primary outcome was recovery from severe vision loss (final BCVA <1.0 logMAR). We used mixed-effect models and local polynomial regression to investigate nonlinear relationships between time to treatment and recovery from severe vision loss. RESULTS: Of 4074 screened studies, individual participant data were sought from 52, with 35 contributing individual participant data for 1038 participants. In total, 783 patients met inclusion criteria (age, 64.8±13.3 years; 35.5% female; baseline BCVA, 2.3±0.5 logMAR). For every hour decrease in time to treatment, thrombolysis was associated with greater improvement in BCVA (intraarterial, 0.02 logMAR [95% CI, 0–0.04]; intravenous, 0.04 logMAR [95% CI, 0.00–0.07]) than conservative standard therapy (0.01 logMAR [95% CI, 0–0.02]). A nonlinear relationship was detected for intraarterial thrombolysis with a changepoint at 8 hours (95% CI, 6.7–9.4). Thrombolysis was associated with increased recovery from severe vision loss compared with conservative standard therapy (intraarterial within 6 hours: odds ratio, 2.72 [95% CI, 1.02–7.28], 27.2% versus 12.0%; intravenous within 4.5 hours: odds ratio, 3.32 [95% CI, 1.24–8.92], 28.8% versus 11.1%). Findings were consistent in subgroup analysis restricted to patients receiving recombinant tissue-type plasminogen activator. Monte-Carlo simulations showed that a randomized controlled trial would require 95 participants per group to achieve 80% power to detect an odds ratio of 3.0 for recovery from severe vision loss. CONCLUSIONS: Early intervention in nonarteritic central retinal artery occlusion is associated with improvement in visual recovery, with intraarterial thrombolysis and intravenous thrombolysis outperforming nonthrombolytic treatments. These findings warrant confirmation in sufficiently powered randomized controlled trials.

Due to extensive pathophysiological changes in critically ill patients, standard dosing of antibiotics may lead to inadequate drug exposure. This is concerning, as insufficient plasma drug concentrations may lead to treatment failure, whereas excessive drug exposure may increase the risk of toxic adverse events. The role of inflammation as a factor influencing the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics remains largely unknown. PK/PD target attainment of antibiotics can be improved through therapeutic drug monitoring, i.e., measurement of drug concentrations in the blood with subsequent dosage adjustment to reach a certain target. Besides, population PK models may be used to predict drug exposure and tailor dosing in an individual patient (model‐informed precision dosing). Inflammatory biomarkers have been proposed to measure inflammation levels and guide antibiotic treatment. However, their potential to guide antibiotic dosing is unclear. This narrative review describes associations between inflammation and PK/PD of antibiotics in critically ill patients, and the role of biomarkers, therapeutic drug monitoring and model‐informed precision dosing in improving antibiotic dosing. A focus of future research should be on the interplay between inflammation and PK/PD of antibiotics by including inflammatory biomarkers in PK/PD models and using big data to predict antibiotic exposure in critically ill patients.

Abstract The aim of this international meta-analysis was to quantify the predictive value of BMI for incident fracture and relationship of this risk with age, sex, follow-up time, and BMD. A total of 1 667 922 men and women from 32 countries (63 cohorts), followed for a total of 16.0 million person-years were studied. 293 325 had FN BMD measured (2.2 million person-years follow-up). An extended Poisson model in each cohort was used to investigate relationships between WHO-defined BMI categories (Underweight: &lt;18.5 kg/m2; Normal: 18.5-24.9 kg/m2; Overweight: 25.0-29.9 kg/m2; Obese I: 30.0-34.9 kg/m2; Obese II: ≥35.0 kg/m2) and risk of incident osteoporotic, major osteoporotic and hip fracture (HF). Inverse-variance weighted β-coefficients were used to merge the cohort-specific results. For the subset with BMD available, in models adjusted for age and follow-up time, the hazard ratio (95% CI) for HF comparing underweight with normal weight was 2.35 (2.10-2.60) in women and for men was 2.45 (1.90-3.17). Hip fracture risk was lower in overweight and obese categories compared to normal weight [obese II vs normal: women 0.66 (0.55-0.80); men 0.91 (0.66-1.26)]. Further adjustment for FN BMD T-score attenuated the increased risk associated with underweight [underweight vs normal: women 1.69 (1.47-1.96); men 1.46 (1.00-2.13)]. In these models, the protective effects of overweight and obesity were attenuated, and in both sexes, the direction of association reversed to higher fracture risk in Obese II category [Obese II vs Normal: women 1.24 (0.97-1.58); men 1.70 (1.06-2.75)]. Results were similar for other fracture outcomes. Underweight is a risk factor for fracture in both men and women regardless of adjustment for BMD. However, while overweight/obesity appeared protective in base models, they became risk factors after additional adjustment for FN BMD, particularly in the Obese II category. This effect in the highest BMI categories was of greater magnitude in men than women. These results will inform the second iteration of FRAX®.

Background/Objectives: High-risk percutaneous coronary interventions (HR-PCIs) often require mechanical circulatory support (MCS) to maintain hemodynamic stability. Intra-aortic balloon pump (IABP) and percutaneous left ventricular assist device (PLVAD) are two commonly used MCS devices that differ in their mechanisms. We aimed to evaluate and compare the clinical outcomes associated with IABP and PLVAD use in HR-PCIs without cardiogenic shock. Methods: We conducted a search of PubMed, Scopus, Cochrane, Mendeley, Web of Science, and Embase to identify relevant randomized controlled trials and cohort studies, and we included 13 studies for the systematic review and meta-analysis. The primary goal was to define the difference in early mortality (in-hospital and 30-day mortality), major bleeding, and major adverse cardiovascular event (MACE) components (cardiogenic shock, acute kidney injury (AKI), and stroke/TIA) in IABP and PLVAD. We used a random-effects model with the Mantel–Haenszel statistical method to estimate odds ratios (ORs) and 95% confidence intervals. Results: Among 1 trial and 12 cohort studies (35,554 patients; 30,351 IABP and 5203 PLVAD), HR-PCI with IABP was associated with a higher risk of early mortality (OR = 1.53, 95% CI [1.21, 1.94]) and cardiogenic shock (OR = 2.56, 95% CI [1.98, 3.33]) when compared to PLVAD. No significant differences were found in the rates of arrhythmia, major bleeding, AKI, stroke/TIA, or hospital length of stay. Conclusions: In high-risk PCIs, PLVAD use is associated with lower early mortality and cardiogenic shock risk compared to IABP, with no significant differences in other major outcomes.