Nevin Manimala

Lancet. 2026 Feb 28;407(10531):876-891. doi: 10.1016/S0140-6736(25)02365-7.

ABSTRACT

BACKGROUND: Antipsychotic drugs are the established treatment for acute schizophrenia but differ in receptor-binding profiles. In 2024, a new-in-class muscarinic receptor agonist (xanomeline-trospium) was licenced, acting upstream of antidopaminergic agents, and providing hope to decrease the adverse effects burden of antipsychotics. We aimed to compare the efficacy and tolerability of antipsychotics by performing network meta-analysis of randomised controlled trials (RCTs).

METHODS: This systematic review (PROSPERO, CRD42022380708) included blinded and open RCTs investigating antipsychotic drugs in participants of any age with acute psychotic symptoms of schizophrenia over 3 weeks to 3 months. Included antipsychotics comprised 23 primarily dopamine-receptor blocking medications and the muscarinic receptor agonist xanomeline-trospium in different applications. We searched Cochrane Schizophrenia group’s register, previous reviews, and five Chinese databases for trials published from database inception until July 26, 2024 and contacted authors to assess trials’ methodological quality; only trials with appropriate randomisation indicated were included. The primary outcome was rating scale-measured overall symptoms of schizophrenia (efficacy) analysed with random-effects frequentist network meta-analysis. Secondary outcomes comprised 32 further efficacy and tolerability outcomes. The confidence in the estimates was assessed using the Confidence in Network Meta-Analysis approach.

FINDINGS: After screening 18 859 references and contacting authors of 5428 trials, we included 438 RCTs. Of those, 388 RCTs with 78 193 participants (28 448 women and 49 745 men) provided usable data for at least one outcome. 5117 Chinese trials were identified but most were excluded because authors did not reply or reported serious methodological concerns. 256 double-blind studies with 58 948 participants provided usable data for the primary outcome. All antipsychotics reduced symptoms more than placebo with standardised mean differences ranging from -0·90 (95% CI -1·03 to -0·77) to -0·23 (-0·39 to -0·06). Particularly clozapine, as well as amisulpride, olanzapine, and risperidone were more efficacious than at least three other antipsychotics (confidence in estimates were low-to-moderate). Adverse effects varied across medications.

INTERPRETATION: This network meta-analysis provides evidence for small-to-medium clinically relevant differences between antipsychotics in efficacy; this finding warrants stronger and more specific emphasis in clinical guidelines. Nonetheless, important differences in tolerability need to be considered for individualised drug choice, with partial dopamine agonists having overall better tolerability and xanomeline-trospium lacking adverse effects of dopamine-blocking agents but resulting in cholinergic and anticholinergic adverse events. Future research should directly compare xanomeline-trospium with other antipsychotics to confirm its efficacy; modern trials using clozapine early in schizophrenia are needed to establish whether it improves outcomes and prevents chronification.

FUNDING: German Research Foundation, German Ministry of Research, Technology and Space, and National Natural Science Foundation of China.

PMID:41763745 | DOI:10.1016/S0140-6736(25)02365-7

Lancet. 2026 Feb 28;407(10531):855-866. doi: 10.1016/S0140-6736(25)02305-0.

ABSTRACT

BACKGROUND: Total hip replacement is a successful operation that aims to restore function and quality of life to millions of people globally. Knowing how long a total hip replacement might last is important for patients, surgeons, and health-care institutions for planning and resource allocation. Over the past 20 years, the use of contemporary bearing surfaces for total hip replacement has substantially altered implant wear and, possibly, longevity. To date, there has been no large-scale study that examines survivorship of these modern implants. We aimed to determine the survivorship of contemporary total hip replacements and bearing materials.

METHODS: We focused solely on the assessment of modern bearing surfaces: highly cross-linked polyethylene versus metal or third-generation and fourth-generation ceramic heads and ceramic-on-ceramic primary total hip replacement in adult patients. We conducted a search of MEDLINE and Embase from database inception to June 13, 2024, including articles that reported a minimum of 10 years of survivorship, irrespective of fixation method or surgical approach. We then conducted a meta-analysis combining data from eight national joint registries assessing all-cause revision within the various bearing combinations. We extrapolated the extracted data to estimate survivorship to 30 years, using the multivariable random-effects model from the registry data. The primary outcome was survivorship of the hip replacement, defined as time from primary total hip replacement to first all-cause revision, expressed as a percentage of unrevised implants at specific timepoints. This study is registered with PROSPERO (CRD42024572518).

FINDINGS: We identified 1 904 237 total hip arthroplasties across 29 clinical studies (n=5203) and eight national joint registries (n=1 899 034). Pooled analysis of the included studies showed an all-cause implant survivorship of 0·97 (0·96-0·98) under the random-effects model. Survivorship estimate based on joint registry data was at 93·6% (95% CI 92·3-94·7) at 20 years. Extrapolating these data indicates a predicted survivorship of 92·8% (91·2-94·2) at 25 years and 92·1% (90·1- 93·7) at 30 years.

INTERPRETATION: The estimated 92% 30-year survivorship of contemporary total hip replacement suggests that advances in bearing surface technology have greatly improved the long-term durability of total hip replacements and might influence patient counselling, health-care planning, and device regulation.

FUNDING: None.

PMID:41763743 | DOI:10.1016/S0140-6736(25)02305-0

Lancet. 2026 Feb 28;407(10531):826-827. doi: 10.1016/S0140-6736(25)02517-6.

NO ABSTRACT

PMID:41763728 | DOI:10.1016/S0140-6736(25)02517-6

Ann Otol Rhinol Laryngol. 2026 Feb 28:34894261423285. doi: 10.1177/00034894261423285. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the effects of using Exparel^® bupivacaine liposome suspension 1.3% (13.3 mg/mL) as an adjunct to standard of care medication in adult tonsillectomy patients.

STUDY DESIGN: Randomized controlled trial.

SETTING: Community Hospital.

METHODS: The study arm (n = 22) received Exparel^® bupivacaine liposome suspension 1.3% (13.3 mg/mL) as an adjunct to the standard of care (SOC) medication bupivacaine HCl 0.25% (2.5 mg/mL) with epinephrine (5 μg/mL). The control group (n = 20) received SOC bupivacaine HCl 0.25% with epinephrine (5 μg/mL). All injections were administered after the excision of the tonsil, prior to conclusion of the operative procedure. Pre- and post-operative clinicopathologic variables of interest were collated from electronic medical records and daily pain diaries. Results were analyzed via standard univariate statistics, linear mixed models, and Poisson regression.

RESULTS: The Exparel^® + SOC group experienced significantly less pain at post operative day (POD) 3 compared to the control group (P < .05). Mean pain score decreased on average by 1.23 points in the Exparel^® + SOC group and increased on average by 0.39 points in the control group (adj. P-value < .001). Similarly, analysis showed that maximum pain score decreased on average by 0.64 points in the Exparel^® + SOC and increased on average by 0.61 points the control group (adj. P-value < .001). There was a statistically significant decrease in dose of oxycodone use between POD 3 and POD 5 within the Exparel^® + SOC group (16.39 vs 7.22 mg, P-value = .035). The relative proportion of patients who took oxycodone was less in the Exparel^® + SOC group compared to the control group across all PODs.

CONCLUSION: Use of Exparel^® in adult tonsillectomy may decrease post-operative opioid use compared to standard of care treatment. These findings may serve as guidance for best practices in adult tonsillectomy.

PMID:41763725 | DOI:10.1177/00034894261423285

PDA J Pharm Sci Technol. 2026 Feb 28;80(1):137-138. doi: 10.5731/pdajpst.2026.26109.

ABSTRACT

For more than 40 years, the Limulus Amebocyte Lysate (LAL) test has served as the standard method for bacterial endotoxin Testing (BET). The critical proteins required for endotoxin detection in LAL assays are sourced from amoebocytes-blood cells extracted from horseshoe crabs.Animal-free reagents have been developed to support conservation efforts and the 3Rs (Replacement, Reduction, and Refinement). One such alternative is the recombinant cascade reagent (rCR), which contains three recombinant proteins that replicate the natural enzymatic cascade found in horseshoe crab amoebocytes to detect bacterial endotoxins.This study assessed the equivalency of rCR to FDA-licensed LAL reagents using 563 pharmaceutically relevant samples. Of these, 134 samples were contaminated with natural environmental endotoxin (NEE), allowing for a direct statistical comparison.Results showed that the rCR assays were equivalent in performance to FDA-licensed LAL assays, detecting endotoxin at similar levels under real-world conditions. Equivalency was demonstrated using methods consistent with those outlined in compendial guidance for bacterial endotoxin testing.

PMID:41763684 | DOI:10.5731/pdajpst.2026.26109

Women Birth. 2026 Feb 26;39(2):102184. doi: 10.1016/j.wombi.2026.102184. Online ahead of print.

ABSTRACT

PROBLEM: Despite evidence supporting benefits of upright and flexible sacral positions during labour, most women continue to birth in supine positions.

BACKGROUND: Historically, women have laboured and birthed in positions that optimise gravity, encouraging physiological birth. However, many women birth in supine positions, even though upright positions are associated with shorter duration of second stage and favourable outcomes.

AIM: To observe the proportion of time nulliparous women spent in upright and supine positions during the active second stage of labour, and to explore associations with birth outcomes.

METHODS: This prospective observational study included term nulliparous women who were planning a vaginal birth. Midwives recorded commencement of, and all position changes during second stage. Data were analysed using descriptive statistics and regression modelling.

FINDINGS: Of 330 participants, 216 (65%) birthed physiologically, 114 (35%) had an instrumental birth. Women who birthed physiological more frequently adopted all-fours position or used a birth stool, whereas those who had an instrumental birth were more often in semi-recumbent or lithotomy positions. For every 10% increase in time spent in upright positions during the active second stage, the likelihood of physiological birth increased by 26%. Conversely, each 10% increase in time spent in a supine position there was a 30% increased likelihood of instrumental birth.

DISCUSSION: Findings indicate a clear association between upright positioning during the active second stage of labour and increased rates of physiological birth.

CONCLUSION: Nulliparous women may benefit from being actively supported to adopt upright positions during the second stage of labour.

PMID:41762541 | DOI:10.1016/j.wombi.2026.102184

Cancer Epidemiol. 2026 Feb 26;102:103030. doi: 10.1016/j.canep.2026.103030. Online ahead of print.

ABSTRACT

BACKGROUND: Timely treatment is a vital component of high-quality cancer care. We compared a national purpose-specific dataset of cancer waiting times (CWT) with routinely collected hospital datasets (‘comparator datasets’) as sources of data on the timeliness of kidney cancer treatment in England.

METHODS: 11,937 patients diagnosed with kidney cancer between 1st July 2022 and 31st December 2023 were included, using national linked cancer registry and CWT records. The primary analysis compared CWT records and those in comparator datasets (Hospital Episode Statistics, Systemic Anti-Cancer Therapy, and Radiotherapy datasets) in terms of the number, percentage, and timing of patients receiving treatment. Using CWT records, a secondary analysis assessed the effects of the ‘waiting time adjustment policy’ to account for patient treatment deferral on distributions of waiting times at patient and provider levels.

RESULTS: 6971 patients were identified as having received treatment (within 100 days of decision-to-treat) according to either CWT or comparator datasets. Of these patients, 6434 (92.3%) had treatment according to both CWT and comparator datasets, with 5836 patients (90.7% of 6434) identified as receiving treatment on the same day across both dataset groups, demonstrating strong agreement. Using the waiting time adjustment policy, the mean number of days to treatment decreased from 29.2 to 27.3 days at the patient-level and from 24.3 to 22.6 days at the provider-level.

CONCLUSION: This study demonstrates strong agreement in treatment records from a national, purpose-specific, and comparator datasets. Strengths of both data sources can be harnessed in linked data to evaluate treatment timeliness, enabling more detailed assessments of specific treatments and better definition of the start of treatment pathways.

PMID:41762537 | DOI:10.1016/j.canep.2026.103030

Cancer Epidemiol. 2026 Feb 26;102:103016. doi: 10.1016/j.canep.2026.103016. Online ahead of print.

ABSTRACT

BACKGROUND: The target trial emulation (TTE) framework, proposed by Hernán and Robins, uses observational data to emulate a randomized controlled trial (RCT). TTEs are increasingly being applied in oncology research. This scoping review aims to describe the characteristics of oncology TTEs, evaluate their adherence to the TTE framework, and assess the concordance of results between TTEs and corresponding RCTs.

METHODS: A comprehensive search was conducted in MEDLINE and Embase from inception to December 25th 2025. Only oncology TTEs evaluating treatment interventions were eligible. Data was extracted on study characteristics, adherence to the TTE framework, reported cohort characteristics, the concordance of TTEs emulating specific RCTs using Cohen’s Kappa coefficient, and the correlation of Ln hazard ratio (HR) using Pearson’s correlation coefficient.

RESULTS: A total of 94 studies were identified, representing 106 unique TTEs. All TTEs reported on the treatment strategies, outcomes measured, and data analysis plan, while only 75.5 % presented a clearly defined time zero. In addition, only 20.8 % of TTEs reported on patient performance status, for the purpose of adjusting confounders. Additionally, among the 20 TTEs that explicitly emulated a published RCT, there was poor to fair concordance (Cohen’s Kappa = 0.20) between the reported results of the statistical hypothesis testing of survival outcomes between the respective TTE and corresponding RCT. The Pearson’s correlation coefficient between Ln HRs of TTE and RCT was 0.44.

CONCLUSION: The TTE framework adoption and adherence in oncology has been substantial. However, the poor to fair agreement between corresponding TTEs and RCTs demonstrates the potential caveats of using TTEs as a replacement for RCTs in the evaluation of treatment efficacy, notwithstanding atypical scenarios where RCTS may not be feasible. One potential source of residual bias may be the lack of adjustments based on patient performance status. Significant gaps in reporting of critical oncology endpoints pose further challenges. Future research should continue to standardize reporting guidelines, specifically aligning with the recently published TARGET framework, to improve the utilization of TTEs in oncology.

PMID:41762536 | DOI:10.1016/j.canep.2026.103016

J Environ Manage. 2026 Feb 26;402:129141. doi: 10.1016/j.jenvman.2026.129141. Online ahead of print.

ABSTRACT

Phosphorus (P) limitation constrains ecological restoration in arid limestone mine regions, where inorganic P is predominantly present in recalcitrant forms. We examined whether soil amendments and drought-tolerant shrub species are associated with shifts in inorganic phosphorus (IP) fractions through modifications of soil properties and microbial community structure during early-stage restoration. A field experiment combining four substrate amendment strategies and seven drought-tolerant shrub species was conducted under microsite-based planting conditions in degraded calcareous soils. Our results demonstrate that organic amendments increased available P by 10.73% relative to the control and were associated with higher soil water content (SWC) and microbial biomass. Partial least squares structural equation modeling (PLS-SEM) revealed that SWC was positively associated with labile P (LP), whereas microbial biomass indicators showed statistical associations with recalcitrant P (RP) pools. Microbial community analyses revealed that Actinobacteriota and Bacteroidota were significantly correlated with LP and RP fractions, while Proteobacteria were linked to moderate-cycling P (MP), suggesting potential functional differentiation among microbial groups. We therefore propose a conceptual framework of “functional specialization-dynamic equilibrium”, in which soil physicochemical conditions and microbial community composition jointly influence IP distribution patterns at the microsite scale. These findings highlight how localized amendment strategies and shrub selection may contribute to improving P availability during early restoration stages, while longer-term and multi-season validation is required to assess temporal stability and field-scale generalizability.

PMID:41762507 | DOI:10.1016/j.jenvman.2026.129141

Radiography (Lond). 2026 Feb 26;32(3):103363. doi: 10.1016/j.radi.2026.103363. Online ahead of print.

ABSTRACT

INTRODUCTION: Selecting a college major is a critical decision with long-term implications. While personality assessments like the Myers-Briggs Type Indicator (MBTI) explore person-career fit, radiographers’ personality profiles and their relationship with professional quality of life remain uninvestigated. This study aims to identify predominant MBTI types among radiographers and examine their correlation with career satisfaction facets, including compassion satisfaction, burnout, and secondary traumatic stress.

METHODS: Cross-sectional, quantitative study was conducted among radiographers in public healthcare setups in Bahrain. Participants (n = 98) completed an online MBTI assessment and a survey comprising demographic questions and the Professional Quality of Life Scale (ProQOL). Data were analyzed for descriptive statistics and one-way ANOVA.

RESULTS: The most prevalent personality types were ESTJ (21.1 %) and ESFJ (18.4 %), with the Sentinel (SJ) temperament group comprising 50 % of the sample. The sample was characterized by preferences for Extraversion (60.5 %), Sensing (63 %), Feeling (63.2 %), and Judging (76.3 %). No statistically significant relationships were found between the 16 MBTI types and the ProQOL subscales of Compassion Satisfaction, Burnout or Secondary Traumatic Stress.

CONCLUSION: A distinct MBTI profile is prevalent among radiographers, yet no significant association with ProQOL-measured career satisfaction was found. This suggests satisfaction is influenced by factors beyond personality. The findings provide a foundational typology and call for longitudinal studies on the personality-profession interplay.

IMPLICATIONS FOR PRACTICE: The common profile (ESTJ/ESFJ) does not predict job satisfaction, refining recruitment into a guide rather than a filter. This informs tailored education and career mentoring, enhancing support for all profession members beyond typological constraints.

PMID:41762474 | DOI:10.1016/j.radi.2026.103363