Systematic Review of Women Leading and Participating in Nephrology Randomized Clinical Trials.

Introduction: Women are underrepresented in the leadership of and participation in randomized controlled trials (RCTs). We conducted a bibliometric review of nephrology RCTs to examine trial leadership by women and participation of women in nephrology RCTs. Methods: A bibliometric review of RCTs published in top medical, surgical, or nephrology journals was conducted using MEDLINE and EMBASE from January 2011 to December 2021. Leadership by women as corresponding authors, women trial participation, and trial characteristics were examined with duplicate independent data extraction. Logistic regression was used to examine associations between trial characteristics and women leadership and trial participation. Results: A total of 1770 studies were screened and 395 RCTs met eligibility criteria. The number (%) of women in corresponding, first, and last authorship positions were as follows: 89 (22%), 109 (28%), and 74 (19%), respectively, without change over time (P = 0.94). The median percentage (interquartile range [IQR]) of women trial participants was 39.0% (13.5%) with no difference between women or men lead authors (P = 0.15). Men lead authors were statistically less likely to enroll women in RCTs. Women lead authors were less likely to be funded by industry (odds ratio [OR]: 0.30; 95% confidence interval [CI]: 0.14-0.63; P = 0.002) or lead international trials (OR: 0.11; 95% CI: 0.01-0.83; P = 0.03). Trials with sex-specific eligibility criteria were more likely to have women leaders (OR: 2.56; 95% CI: 1.19-5.49; P = 0.02) than those without. Discussion: Gender inequalities in RCT leadership and RCT participation exist in nephrology and did not improve over time. Strategies to improve inequalities need to be implemented and evaluated.

Economic Evaluations of Chimeric Antigen Receptor T-Cell Therapies for Hematologic and Solid Malignancies: A Systematic Review.

OBJECTIVES: This study aimed to systematically review evidence on the cost-effectiveness of chimeric antigen receptor T-cell (CAR-T) therapies for patients with cancer. METHODS: Electronic databases were searched in October 2022 and updated in September 2023. Systematic reviews, health technology assessments, and economic evaluations that compared costs and effects of CAR-T therapy in patients with cancer were included. Two reviewers independently screened studies, extracted data, synthesized results, and critically appraised studies using the Philips checklist. Cost data were presented in 2022 US dollars. RESULTS: Our search yielded 1809 records, 47 of which were included. Most of included studies were cost-utility analysis, published between 2018 and 2023, and conducted in the United States. Tisagenlecleucel, axicabtagene ciloleucel, idecabtagene vicleucel, ciltacabtagene autoleucel, lisocabtagene maraleucel, brexucabtagene autoleucel, and relmacabtagene autoleucel were compared with various standard of care chemotherapies. The incremental cost-effectiveness ratio (ICER) for CAR-T therapies ranged from $9424 to $4 124 105 per quality-adjusted life-year (QALY) in adults and from $20 784 to $243 177 per QALY in pediatric patients. Incremental cost-effectiveness ratios were found to improve over longer time horizons or when an earlier cure point was assumed. Most studies failed to meet the Philips checklist due to a lack of head-to-head comparisons and uncertainty surrounding CAR-T costs and curative effects. CONCLUSIONS: CAR-T therapies were more expensive and generated more QALYs than comparators, but their cost-effectiveness was uncertain and dependent on patient population, cancer type, and model assumptions. This highlights the need for more nuanced economic evaluations and continued research to better understand the value of CAR-T therapies in diverse patient populations.

Evidence for clinician underprescription of and patient non-adherence to guideline-recommended cardiovascular medications among adults with peripheral artery disease: protocol for a systematic review and meta-analysis.

INTRODUCTION: International guidelines recommend that adults with peripheral artery disease (PAD) be prescribed antiplatelet, statin and antihypertensive medications. However, it is unclear how often people with PAD are underprescribed these drugs, which characteristics predict clinician underprescription of and patient non-adherence to guideline-recommended cardiovascular medications, and whether underprescription and non-adherence are associated with adverse health and health system outcomes. METHODS AND ANALYSIS: We will search MEDLINE, EMBASE and Evidence-Based Medicine Reviews from 2006 onwards. Two investigators will independently review abstracts and full-text studies. We will include studies that enrolled adults and reported the incidence and/or prevalence of clinician underprescription of or patient non-adherence to guideline-recommended cardiovascular medications among people with PAD; adjusted risk factors for underprescription of/non-adherence to these medications; and adjusted associations between underprescription/non-adherence to these medications and outcomes. Outcomes will include mortality, major adverse cardiac and limb events (including revascularisation procedures and amputations), other reported morbidities, healthcare resource use and costs. Two investigators will independently extract data and evaluate study risk of bias. We will calculate summary estimates of the incidence and prevalence of clinician underprescription/patient non-adherence across studies. We will also conduct subgroup meta-analyses and meta-regression to determine if estimates vary by country, characteristics of the patients and treating clinicians, population-based versus non-population-based design, and study risks of bias. Finally, we will calculate pooled adjusted risk factors for underprescription/non-adherence and adjusted associations between underprescription/non-adherence and outcomes. We will use Grading of Recommendations, Assessment, Development and Evaluation to determine estimate certainty. ETHICS AND DISSEMINATION: Ethics approval is not required as we are studying published data. This systematic review will synthesise existing evidence regarding clinician underprescription of and patient non-adherence to guideline-recommended cardiovascular medications in adults with PAD. Results will be used to identify evidence-care gaps and inform where interventions may be required to improve clinician prescribing and patient adherence to prescribed medications. PROSPERO REGISTRATION NUMBER: CRD42022362801.

A systematic review of the efficacy and safety of turmeric in the treatment of digestive disorders.

Turmeric has been gaining popularity as a treatment option for digestive disorders, although a rigorous synthesis of efficacy has not been conducted. This study aimed to summarize the evidence for the efficacy and safety of turmeric in the treatment of digestive disorders, including inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), dyspepsia, gastroesophageal reflux disease, and peptic ulcers. Literature searches were conducted in Medline, EMBASE, AMED, the Cochrane Central Register of Control Trials, and Dissertation Abstracts from inception to November 15, 2021. Dual independent screening of citations and full texts was conducted and studies meeting inclusion criteria were retained: randomized controlled trials (RCT) and comparative observational studies evaluating turmeric use in people of any age with one of the digestive disorders of interest. Extraction of relevant data and risk of bias assessments were performed by two reviewers independently. Meta-analysis was not conducted due to high heterogeneity. From 1136 citations screened, 26 eligible studies were retained. Most studies were assessed to have a high risk of bias, and many had methodological limitations. Descriptive summaries suggest that turmeric is safe, with possible efficacy in patients with IBD or IBS, but its effects were inconsistent for other conditions. The efficacy of turmeric in digestive disorders remains unclear due to the high risk of bias and methodological limitations of the included studies. Future studies should be designed to include larger sample sizes, use rigorous statistical methods, employ core outcome sets, and adhere to reporting guidance for RCTs of herbal interventions to facilitate more meaningful comparisons and robust conclusions.

The prevalence of non-contrast CT imaging abnormalities in reversible cerebral vasoconstriction syndrome: A systematic review and meta-analysis.

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is a syndrome of recurrent thunderclap headaches and reversible vasoconstriction of the cerebral arteries on neuroimaging within 3 months of onset. Initial non-contrast computed tomography (CT) can reveal abnormalities such as ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage (SAH) can be present in patients with RCVS and may delay diagnosis. AIMS: We conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines. We aimed to estimate the prevalence of imaging abnormalities on initial non-contrast CT head in adult patients with RCVS. DATA SOURCES & ELIGIBILITY CRITERIA: We searched electronic databases including MEDLINE, EMBASE, and the Cochrane Register of Clinical Trials from inception to August 2, 2022. Eligible studies included articles reporting the prevalence of non-contrast CT abnormalities on initial neuroimaging in patients with RCVS, aged 18 and older. Case series, observational studies and clinical trials were included. Data was extracted directly from included papers using a standardized data charting form. RESULTS: The search yielded 722 titles with duplicates removed. Twenty studies that included 379 patients with RCVS met inclusion criteria. We classified non-contrast CT abnormalities as either ischemic stroke, ICH, or SAH. We pooled prevalence data using a random effects model with the inverse-variance weighted method. The most common imaging finding was SAH with a pooled prevalence of 24% (95% CI:17%-33%), followed by ICH at 14% (95% CI:8%-22%), and ischemic stroke at 10% (95% CI:7%-14%). The pooled prevalence of any of these imaging abnormalities on initial non-contrast CT was 31% (95% CI:23%-40%). Risk of bias was moderate to very-high-risk for case-series and low-risk for observational studies. CONCLUSION: Our review demonstrates that one-third of patients with RCVS will have an abnormality on initial non-contrast CT head, including either an ischemic stroke, ICH, or SAH. These findings highlight the diagnostic challenges of RCVS imaging and contribute to our understanding of this disease.

Intraoperative pharmacologic opioid minimisation strategies and patient-centred outcomes after surgery: a scoping review.

BACKGROUND: Postoperative patient-centred outcome measures are essential to capture the patient's experience after surgery. Although a large number of pharmacologic opioid minimisation strategies (i.e. opioid alternatives) are used for patients undergoing surgery, it remains unclear which strategies are most promising in terms of patient-centred outcome improvements. This scoping review had two main objectives: (1) to map and describe evidence from clinical trials assessing the patient-centred effectiveness of pharmacologic intraoperative opioid minimisation strategies in adult surgical patients, and (2) to identify promising pharmacologic opioid minimisation strategies. METHODS: We searched MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases from inception to February 2023. We included trials investigating the use of opioid minimisation strategies in adult surgical patients and reporting at least one patient-centred outcome. Study screening and data extraction were conducted independently by at least two reviewers. RESULTS: Of 24,842 citations screened for eligibility, 2803 trials assessed the effectiveness of intraoperative opioid minimisation strategies. Of these, 457 trials (67,060 participants) met eligibility criteria, reporting at least one patient-centred outcome. In the 107 trials that included a patient-centred primary outcome, patient wellbeing was the most frequently used domain (55 trials). Based on aggregate findings, dexmedetomidine, systemic lidocaine, and COX-2 inhibitors were promising strategies, while paracetamol, ketamine, and gabapentinoids were less promising. Almost half of the trials (253 trials) did not report a protocol or registration number. CONCLUSIONS: Researchers should prioritise and include patient-centred outcomes in the assessment of opioid minimisation strategy effectiveness. We identified three potentially promising pharmacologic intraoperative opioid minimisation strategies that should be further assessed through systematic reviews and multicentre trials. Findings from our scoping review may be influenced by selective outcome reporting bias. STUDY REGISTRATION: OSF - https://osf.io/7kea3.

Emergent radiotherapy for pelvic malignancies: a narrative review.

BACKGROUND AND OBJECTIVE: Patients with primary genitourinary (GU), gynecologic (GYN) and gastrointestinal (GI) cancers can develop life-threatening or critical function-threatening symptoms that necessitate emergent intervention with palliative radiotherapy (RT). Unfortunately, research describing the use of RT in this critical setting is lacking. We aimed to review literature describing emergent palliative RT for primary pelvic malignancies and provide a narrative synthesis of relevant studies. METHODS: A medical librarian searched Ovid MEDLINE, Embase Classic, and Embase databases for relevant English language references from 1946-2022. No restrictions were placed on study type, publication type or date. References for GU, GYN and GI cancers were grouped and synthesized separately. KEY CONTENT AND FINDINGS: The treatment of bleeding from primary pelvic tumors was the only indication for emergent RT identified, however, no references reported dedicated cohorts of patients treated for bleeding in the emergent setting. Most references were retrospective single institution studies describing various dose fractionation schemes for non-emergent palliative RT. Outcome measures and response assessment times varied. The latency to hemostasis after RT commencement was not well described; most studies reported outcomes captured weeks or months following treatment. In general, high rates of hemostasis for GU, GYN and GI tumors have been reported following RT schedules ranging from a single fraction to many weeks of fractionated treatments. Bleeding seems to respond more favorably than other symptoms including pain and obstruction. CONCLUSIONS: Managing bleeding was the only indication for emergent RT identified in our search. Scant data exist that describe the latency to a hemostatic response following RT. This is an important knowledge gap in the literature given how commonly patients are affected by this complication of primary pelvic malignancies.

Physical activity, suicidal ideation, suicide attempt and death among individuals with mental or other medical disorders: A systematic review of observational studies.

A growing body of research has demonstrated the potential role for physical activity as an intervention across mental and other medical disorders. However, the association between physical activity and suicidal ideation, attempts, and deaths has not been systematically appraised in clinical samples. We conducted a PRISMA 2020-compliant systematic review searching MEDLINE, EMBASE, and PsycINFO for observational studies investigating the influence of physical activity on suicidal behavior up to December 6, 2023. Of 116 eligible full-text studies, seven (n = 141691) were included. Depression was the most frequently studied mental condition (43%, k = 3), followed by chronic pain as the most common other medical condition (29%, k = 2). Two case-control studies examined suicide attempts and found an association between physical activity and a reduced frequency of such attempts. However, in studies examining suicidal ideation (k = 3) or suicide deaths (k = 2), no consistent associations with physical activity were observed. Overall, our systematic review found that physical activity may be linked to a lower frequency of suicide attempts in non-prospective studies involving individuals with mental disorders.

Rethinking cervical spine clearance in obtunded trauma patients: An updated systematic review and meta-analysis.

BACKGROUND: Cervical spine injuries (CSI) are often challenging to diagnose in obtunded adult patients with blunt trauma and the optimal imaging modality remains uncertain. This study systematically synthesized the last decade of evidence to determine the type of imaging required to clear the c-spine in obtunded patients with blunt trauma. METHODS: A systematic review with meta-analysis was conducted and reported using PRISMA 2020 guidelines. The protocol was registered on June 22, 2022 (PROSPERO CRD42022341386). MEDLINE (Ovid), EMBASE, and Cochrane Library were searched for studies published between January 1, 2012, and October 17, 2023. Studies comparing CT alone to CT combined with MRI for c-spine clearance were included. Two independent reviewers screened articles for eligibility in duplicate. Meta-analysis was conducted using a random-effect model. Risk of bias and quality assessment were performed using the ROBINS-I and QUADAS-2. The certainty of evidence was assessed using the GRADE methodology. RESULTS: 744 obtunded trauma patients from six included studies were included. Among the 584 that had a negative CT scan, the pooled missed rate of clinically significant CSI using CT scans alone was 6 % (95 % CI: 0.02 to 0.17), and the pooled missed rate of CSI requiring treatment was 7 % (95 % CI: 0.02 to 0.18). High heterogeneity was observed among included studies (I² > 84 %). The overall risk of bias was moderate, and the quality of evidence was low due to the retrospective nature of the included studies and high heterogeneity. CONCLUSIONS: Limited evidence published in the last decade found that CT scans alone may not be sufficient for detecting clinically significant CSI and injuries requiring treatment in obtunded adult patients with blunt trauma. IMPLICATIONS OF KEY FINDINGS: Clinicians should be aware of the limitations of CT scans and consider using MRI when appropriate. Future research should focus on prospective studies with standardized outcome measures and uniform reporting.

Test Characteristics of Emergency Medicine-Performed Point-of-Care Ultrasound for the Diagnosis of Acute Cholecystitis: A Systematic Review and Meta-analysis.

Acute cholecystitis accounts for up to 9% of hospital admissions for acute abdominal pain, and best practice entails early surgical management. Ultrasound is the standard modality used to confirm diagnosis. Our objective was to perform a systematic review and meta-analysis to determine the diagnostic accuracy of emergency physician-performed point-of-care ultrasound for the diagnosis of acute cholecystitis when compared with a reference standard of final diagnosis (informed by available surgical pathology, discharge diagnosis, and radiology-performed ultrasound). We completed a systematic review and meta-analysis, registered in PROSPERO, in adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched 7 databases as well as gray literature in the form of select conference abstracts from inception to February 8, 2023. Two independent reviewers completed study selection, data extraction, and risk of bias (QUADAS-2) assessment. Disagreements were resolved by consensus with a third reviewer. Data were extracted from eligible studies to create 2 × 2 tables for diagnostic accuracy meta-analysis. Hierarchical Summary Receiver Operating Characteristic models were constructed. Of 1855 titles/abstracts, 40 were selected for full-text review. Ten studies (n=2356) were included. Emergency physician-performed point-of-care ultrasound with final diagnosis as the reference standard (7 studies, n=1,772) had a pooled sensitivity of 70.9% (95% confidence interval [CI] 62.3 to 78.2), specificity of 94.4% (95% CI 88.2 to 97.5), positive likelihood ratio of 12.7 (5.8 to 27.5), and negative likelihood ratio of 0.31 (0.23 to 0.41) for the diagnosis of acute cholecystitis. Emergency physician-performed point-of-care ultrasound has high specificity and moderate sensitivity for the diagnosis of acute cholecystitis in patients with clinical suspicion. This review supports the use of emergency physician-performed point-of-care ultrasound to rule in a diagnosis of acute cholecystitis in the emergency department, which may help expedite definitive management.

Risk Factors for Surgical Site Infection after Lower Limb Revascularisation Surgery: a Systematic Review and Meta-Analysis of Prognostic Studies.

OBJECTIVE: To systematically review and meta-analyse adjusted risk factors for surgical site infection (SSI) after lower limb revascularisation surgery. DATA SOURCES: MEDLINE, Embase, Evidence Based Medicine Reviews, and the Cochrane Central Register of Controlled Trials (inception to 28 April 2022). REVIEW METHODS: Systematic review and meta-analysis conducted according to PRISMA guidelines. After protocol registration, databases were searched. Studies reporting adjusted risk factors for SSI in adults who underwent lower limb revascularisation surgery for peripheral artery disease were included. Adjusted odds ratios (ORs) were pooled using random effects models. GRADE was used to assess certainty. RESULTS: Among 6 377 citations identified, 50 studies (n = 271 125 patients) were included. The cumulative incidence of SSI was 12 (95% confidence interval [CI] 10 - 13) per 100 patients. Studies reported 139 potential SSI risk factors adjusted for a median of 12 (range 1 - 69) potential confounding factors. Risk factors that increased the pooled adjusted odds of SSI included: female sex (pooled OR 1.41, 95% CI 1.20 - 1.64; high certainty); dependent functional status (pooled OR 1.18, 95% CI 1.03 - 1.35; low certainty); being overweight (pooled OR 1.82, 95% CI 1.29 - 2.56; moderate certainty), obese (pooled OR 2.20, 95% CI 1.44 - 3.36; high certainty), or morbidly obese (pooled OR 1.65, 95% CI 1.08 - 2.52; moderate certainty); chronic obstructive pulmonary disease (pooled OR 1.42, 95% CI 1.17 - 1.71; high certainty); chronic limb threatening ischaemia (pooled OR 1.67, 95% CI 1.22 - 2.29; moderate certainty); chronic kidney disease (pooled OR 2.13, 95% CI 1.18 - 3.83; moderate certainty); intra-operative (pooled OR 1.23, 95% CI 1.02 - 1.49), peri-operative (pooled OR 1.92, 95% CI 1.27 - 2.90), or post-operative (pooled OR 2.21, 95% CI 1.44 - 3.39) blood transfusion (moderate certainty for all); urgent or emergency surgery (pooled OR 2.12, 95% CI 1.22 - 3.70; moderate certainty); vein bypass and or patch instead of endarterectomy alone (pooled OR 1.86, 95% CI 1.33 - 2.59; moderate certainty); an operation lasting ≥ 3 hours (pooled OR 1.86, 95% CI 1.33 - 2.59; moderate certainty) or ≥ 5 hours (pooled OR 1.60, 95% CI 1.18 - 2.17; moderate certainty); and early or unplanned re-operation (pooled OR 4.50, 95% CI 2.18 - 9.32; low certainty). CONCLUSION: This systematic review identified evidence informed SSI risk factors following lower limb revascularisation surgery. These may be used to develop improved SSI risk prediction tools and to identify patients who may benefit from evidence informed SSI prevention strategies.

Examining Workplace Practices Used to Facilitate Successful Integration of Internationally Educated Nurses Into Acute Care Settings: A Scoping Review.

BACKGROUND: Although the recruitment of internationally educated nurses (IENs) seems to be an effective strategy to sustain a diversified nursing workforce, challenges with transition to practice continue to be documented in the literature. Prelicensure bridging programs purport to facilitate practice readiness; however, IENs who complete these programs also experience difficulties. Little is known about tailored workplace-based bridging programs. This scoping review maps out our current understanding of IEN integration and education strategies implemented within acute care settings and identifies areas for further research. METHOD: Arksey and O'Malley's (2005) five-step scoping review was used to explore current literature and highlight gaps based on the needs of IENs during transition into acute care. RESULTS: Two themes were identified: the need for tailored clinical practice bridging programs within acute care settings and the impact of corporate involvement and social structures on IEN integration. CONCLUSION: Inconsistencies in IEN integration practices point to the significance of implementing tailored, workplace-based bridging programs to ensure safe and full scope of practice. [J Contin Educ Nurs. 2024;55(4):195-201.].

Barriers and enablers to and strategies for promoting domestic plasma donation throughout the world: Overarching protocol for three systematic reviews.

INTRODUCTION: The growing demand for plasma protein products has caused concern in many countries who largely rely on importing plasma products produced from plasma collected in the United States and Europe. Optimizing recruitment and retention of a diversity of plasma donors is therefore important for supporting national donation systems that can reliably meet the most critical needs of health services. This series of three systematic reviews aims to synthesize the known barriers and enablers to source plasma donation from the qualitative and survey-based literature and identify which strategies that have shown to be effective in promoting increased intention to, and actual donation of, source plasma. METHODS AND ANALYSIS: Primary studies involving source or convalescent plasma donation via plasmapheresis will be included. The search strategy will capture all potentially relevant studies to each of the three reviews, creating a database of plasma donation literature. Study designs will be subsequently identified in the screening process to facilitate analysis according to the unique inclusion criteria of each review (i.e., qualitative, survey, and experimental designs). The search will be conducted in the electronic databases SCOPUS, MEDLINE, EMBASE, PsycINFO, and CINAHL without date or language restrictions. Studies will be screened, and data will be extracted, in duplicate by two independent reviewers with disagreements resolved through consensus. Reviews 1 and 2 will draw on the Theoretical Domains Framework and Intersectionality, while Review 3 will be informed by Behaviour Change Intervention Ontologies. Directed content analysis and framework analysis (Review 1), and descriptive and inferential syntheses (Reviews 2 and 3), will be used, including meta-analyses if appropriate. DISCUSSION: This series of related reviews will serve to provide a foundation of what is known from the published literature about barriers and enablers to, and strategies for promoting, plasma donation worldwide.

Thrombin generation, bleeding and hemostasis in humans: Protocol for a scoping review of the literature.

INTRODUCTION: Hemostasis and bleeding are difficult to measure. Thrombin generation assays (TGAs) can measure both procoagulant and anticoagulant contributions to coagulation. TGAs might prove useful for the study of bleeding disorders. There has been much progress in TGA methodology over the past two decades, but its clinical significance is uncertain. We will undertake a scoping review of the literature to synthesize available information on the application of TGAs towards the study of bleeding and hemostasis, TGA methodologies being used and to summarize available literature on associations between TGA parameters, bleeding and hemostatic outcomes. METHODS AND ANALYSIS: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched in collaboration with an information specialist. Title/abstract and full-text screening will be carried out independently and in duplicate; eligible study types will include randomized controlled trials, non-randomized studies, systematic reviews, and case series reporting TGA results and bleeding/hemostatic outcomes among humans. Mapping the information identified will be carried out with results presented using qualitative data analytical techniques. ETHICS AND DISSEMINATION: This scoping review will use published, publicly available information. Research ethics approval will not be required. We will disseminate our findings using conference presentations, peer-reviewed publications, social media, and engagement with knowledge users. This review will outline knowledge gaps concerning TGAs, better delineate its applicability as a clinically relevant assay for bleeding. and seek to identify ongoing barriers to its widespread adoption in clinical research, and eventually, in the clinical setting. TRAIL REGULATIONS: Registration ID with Open Science Framework: osf.io/zp4ge.

Influence of pulmonary rehabilitation on symptoms of anxiety and depression in interstitial lung disease: A systematic review of randomized controlled trials.

BACKGROUND: Interstitial lung diseases (ILDs) cause fibrosis of lung parenchyma, leading to impaired quality of life, dyspnea, and functional decline. Individuals with ILD experience a high prevalence of anxiety and depression. Recent research has demonstrated pulmonary rehabilitation (PR) alleviates symptoms of anxiety and depression in those with COPD. RESEARCH QUESTION: What is the influence of PR on symptoms of anxiety and depression in individuals with ILD? STUDY DESIGN: We conducted a PRISMA-2020-compliant systematic review of randomized controlled trials (RCTs) investigating PR's effect on anxiety and depression in patients with ILD. We searched MEDLINE, EMBASE, Cochrane, and PsycINFO from inception until April 3, 2023. A narrative synthesis was conducted where a quantitative approach was not feasible. RESULTS: Five RCTs (n = 281) were included. Idiopathic pulmonary fibrosis (IPF) was the most common type of ILD (k = 3). One study reported clinically-significant improvements in symptoms of anxiety among patients with IPF, and two studies for symptoms of depression among patients with sarcoidosis. Dropout rates were similar between intervention and control groups. All studies were at a high risk of bias. INTERPRETATION: Pulmonary rehabilitation is not detrimental to anxiety or depression for patients with ILD, and may improve symptoms of anxiety in IPF and depression in sarcoidosis. However, no conclusion can be drawn from available evidence, which is limited by heterogeneous populations/interventions, sample sizes and unexpectedly low prevalences of clinically-significant anxiety or depression. Further adequately powered RCTs that focus on anxiety and depressive symptoms as primary outcomes are needed.

Pharmacological interventions for antipsychotic-related sialorrhea: a systematic review and network meta-analysis of randomized trials.

Antipsychotic-induced sialorrhea carries a significant burden, but evidence-based treatment guidance is incomplete, warranting network meta-analysis (NMA) of pharmacological interventions for antipsychotic-related sialorrhea. PubMed Central/PsycInfo/Cochrane Central database/Clinicaltrials.gov/WHO-ICTRP and the Chinese Electronic Journal Database (Qikan.cqvip.com) were searched for published/unpublished RCTs of antipsychotic-induced sialorrhea (any definition) in adults, up to 06/12/2023. We assessed global/local inconsistencies, publication bias, risk of bias (RoB2), and confidence in the evidence, conducting subgroup/sensitivity analyses. Co-primary efficacy outcomes were changes in saliva production (standardized mean difference/SMD) and study-defined response (risk ratios/RRs). The acceptability outcome was all-cause discontinuation (RR). Primary nodes were molecules; the mechanism of action (MoA) was secondary. Thirty-four RCTs entered a systematic review, 33 NMA (n = 1958). All interventions were for clozapine-induced sialorrhea in subjects with mental disorders. Regarding individual agents and response, metoclopramide (RR = 3.11, 95% C.I. = 1.39-6.98), cyproheptadine, (RR = 2.76, 95% C.I. = 2.00-3.82), sulpiride (RR = 2.49, 95% C.I. = 1.65-3.77), propantheline (RR = 2.39, 95% C.I. = 1.97-2.90), diphenhydramine (RR = 2.32, 95% C.I. = 1.88-2.86), benzhexol (RR = 2.32, 95% C.I. = 1.59-3.38), doxepin (RR = 2.30, 95% C.I. = 1.85-2.88), amisulpride (RR = 2.23, 95% C.I. = 1.30-3.81), chlorpheniramine (RR = 2.20, 95% C.I. = 1.67-2.89), amitriptyline (RR = 2.09, 95% C.I. = 1.34-3.26), atropine, (RR = 2.03, 95% C.I. = 1.22-3.38), and astemizole, (RR = 1.70, 95% C.I. = 1.28-2.26) outperformed placebo, but not glycopyrrolate or ipratropium. Across secondary nodes (k = 28, n = 1821), antimuscarinics (RR = 2.26, 95% C.I. = 1.91-2.68), benzamides (RR = 2.23, 95% C.I. = 1.75-3.10), TCAs (RR = 2.23, 95% C.I. = 1.83-2.72), and antihistamines (RR = 2.18, 95% C.I. = 1.83-2.59) outperformed placebo. In head-to-head comparisons, astemizole and ipratropium were outperformed by several interventions. All secondary nodes, except benzamides, outperformed the placebo on the continuous efficacy outcome. For nocturnal sialorrhea, neither benzamides nor atropine outperformed the placebo. Active interventions did not differ significantly from placebo regarding constipation or sleepiness/drowsiness. Low-confidence findings prompt caution in the interpretation of the results. Considering primary nodes' co-primary efficacy outcomes and head-to-head comparisons, efficacy for sialorrhea is most consistent for the following agents, decreasing from metoclopramide through cyproheptadine, sulpiride, propantheline, diphenhydramine, benzhexol, doxepin, amisulpride, chlorpheniramine, to amitriptyline, and atropine (the latter not for nocturnal sialorrhea). Shared decision-making with the patient should guide treatment decisions regarding clozapine-related sialorrhea.

Prevalence of spontaneous recanalisation of complete internal carotid occlusion: protocol for a systematic scoping review.

INTRODUCTION: Although previously thought to be a rare occurrence, spontaneous recanalisation is not uncommon, with a growing number of reports describing this phenomenon. However, the frequency, time course and mechanism of spontaneous recanalisation remain unknown. A better characterisation of these events is essential to ensuring adequate identification and proper future trial design for treatment. OBJECTIVE: To describe the current body of literature around spontaneous recanalisation following internal carotid occlusion. METHODS AND ANALYSIS: With the assistance of an information specialist, we will search MEDLINE, Embase, Cochrane Central Register for Controlled Trials and Web of Science for studies of adults with spontaneous recanalisation or transient occlusion of the internal carotid artery. Two reviewers will independently collect data on included studies pertaining to publication data, study population information, timepoints of initial presentation, recanalisation and subsequent follow-up. ETHICS AND DISSEMINATION: Primary data will not be collected; therefore, formal ethics is not required. The findings of this study will be disseminated through peer-reviewed publications and presentations at academic conferences.

Intraoperative pharmacologic opioid minimisation strategies and patient-centred outcomes after surgery: a scoping review protocol.

INTRODUCTION: For close to a century opioid administration has been a standard of care to complement anaesthesia during surgery. Considering the worldwide opioid epidemic, this practice is now being challenged and there is a growing use of systemic pharmacological opioid minimising strategies. Our aim is to conduct a scoping review that will examine clinical trials that have evaluated the impact of intraoperative opioid minimisation strategies on patient-centred outcomes and identify promising strategies. METHODS AND ANALYSIS: Our scoping review will follow the framework developed by Arksey and O'Malley. We will search MEDLINE, Embase, CENTRAL, Web of Science and CINAHL from their inception approximately in March 2023. We will include randomised controlled trials, assessing the impact of systemic intraoperative pharmacologic opioid minimisation strategies on patient-centred outcomes. We define an opioid minimisation strategy as any non-opioid drug with antinociceptive properties administered during the intraoperative period. Patient-centred outcomes will be defined and classified based on the consensus definitions established by the Standardised Endpoints in Perioperative Medicine initiative (StEP-COMPAC group) and informed by knowledge users and patient partners. We will use a coproduction approach involving interested parties. Our multidisciplinary team includes knowledge users, patient partners, methodologists and knowledge user organisations. Knowledge users will provide input on methods, outcomes, clinical significance of findings, implementation and feasibility. Patient partners will participate in assessing the relevance of our design, methods and outcomes and help to facilitate evidence translation. We will provide a thorough description of available clinical trials, compare their reported patient-centred outcome measures with established recommendations and identify promising strategies. ETHICS AND DISSEMINATION: Ethics approval is not required for the review. Our scoping review will inform future research including clinical trials and systematic reviews through identification of important intraoperative interventions. Results will be disseminated through a peer-reviewed publication, presentation at conferences and through our network of knowledge user collaborators. REGISTRATION: Open Science Foundation (currently embargoed).

The impact of time to hemostatic intervention and delayed care for patients with traumatic hemorrhage: A systematic review.

BACKGROUND: Uncontrolled bleeding is a common cause of preventable mortality in trauma. While it is intuitive that delays to hemostasis may lead to worse outcomes, the impacts of these delays remain incompletely explored. This systematic review aimed to characterize the extant definitions of delayed hemostatic intervention and to quantify the impacts of delays on clinical outcomes. METHODS: We searched EMBASE, MEDLINE, and Web of Science from inception to August 2022. Studies defining "delayed intervention" and those comparing times to intervention among adults presenting to hospital with blunt or penetrating injuries who required major hemostatic intervention were eligible. The coprimary outcomes were mortality and the definition of delay to hemostasis used. Secondary outcomes included units of packed red blood cells received, length of stay in hospital, and length of stay in intensive care. RESULTS: We identified 2,050 studies, with 24 studies including 10,168 patients meeting the inclusion criteria. The majority of studies were retrospective observational cohort studies, and most were at high risk of bias. A variety of injury patterns and hemostatic interventions were considered, with 69.6% of studies reporting a statistically significant impact of increased time to intervention on mortality. Definitions of delayed intervention ranged from 10 minutes to 4 hours. Conflicting data were reported for impact of time on receipt of blood products, while one study found a significant impact on intensive care length of stay. No studies assessed length of stay in hospital. CONCLUSION: The extant literature is heterogeneous with respect to injuries included, methods of hemostasis employed, and durations of delay examined. While the majority of the included studies demonstrated a statistically significant relationship between time to intervention and mortality, an evidence-informed definition of delayed intervention for bleeding trauma patients at large has not been solidified. In addition, standardized research is needed to establish targets, which could reduce morbidity and mortality. LEVEL OF EVIDENCE: Systematic Review; Level IV.

Sex-based analysis of treatment responses in animal models of sepsis: a preclinical systematic review protocol.

BACKGROUND: The importance of investigating sex- and gender-dependent differences has been recently emphasized by major funding agencies. Notably, the influence of biological sex on clinical outcomes in sepsis is unclear, and observational studies suffer from the effect of confounding factors. The controlled experimental environment afforded by preclinical studies allows for clarification and mechanistic evaluation of sex-dependent differences. We propose a systematic review to assess the impact of biological sex on baseline responses to disease induction as well as treatment responses in animal models of sepsis. Given the lack of guidance surrounding sex-based analyses in preclinical systematic reviews, careful consideration of various factors is needed to understand how best to conduct analyses and communicate findings. METHODS: MEDLINE and Embase will be searched (2011-present) to identify preclinical studies of sepsis in which any intervention was administered and sex-stratified data reported. The primary outcome will be mortality. Secondary outcomes will include organ dysfunction, bacterial load, and IL-6 levels. Study selection will be conducted independently and in duplicate by two reviewers. Data extraction will be conducted by one reviewer and audited by a second independent reviewer. Data extracted from included studies will be pooled, and meta-analysis will be conducted using random effects modeling. Primary analyses will be stratified by animal age and will assess the impact of sex at the following time points: pre-intervention, in response to treatment, and post-intervention. Risk of bias will be assessed using the SYRCLE's risk-of-bias tool. Illustrative examples of potential methods to analyze sex-based differences are provided in this protocol. DISCUSSION: Our systematic review will summarize the current state of knowledge on sex-dependent differences in sepsis. This will identify current knowledge gaps that future studies can address. Finally, this review will provide a framework for sex-based analysis in future preclinical systematic reviews. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022367726.