Caring behaviors among nurses have positive and negative impacts on patient care quality and the essence of nursing leadership paradigms. Most studies on caring behavior among nurses in Ethiopia have reported inconsistent findings and are regionally dispersed. It is believed that combining regional evidence to obtain nationally representative information could help program implementers. Therefore, the objective of this review was to estimate the pooled prevalence of caring behaviors and associated factors among nurses working in Ethiopia.

PubMed, Scopus, Web of Science, EMBASE, Science Direct and African Journals Online were used to search for relevant studies. Additionally, studies were identified through manual reference searches. Data extraction was performed using Microsoft Excel, and analysis was conducted using STATA software V. 18. Funnel plots, Egger's test, and meta-regression were employed to assess publication bias. Heterogeneity (I²) and the overall estimate were calculated. Subgroup analysis was conducted based on study region and publication year. The pooled odds ratio was calculated for the main factors associated with caregiving behavior.

A total of 7 studies were included that involved 2,206 nursing professionals. According to the random effects model, the pooled prevalence of good care behavior was 63% (95% CI: 55%, 72%) among nurses. According to the subgroup analysis, the highest prevalence was observed in the Oromia region (80.3%), and studies with a sample size of 300 had a higher prevalence of 52% caring behavior. Higher professional satisfaction (AOR = 1.84; 95% CI 1.41, 2.27), higher job satisfaction (AOR = 3.04; 95% CI 1.13, 4.94), a low workload (OR = 3.14; 95% CI 2.04, 4.25) and good relationships with coworkers (AOR = 4.72; 95% CI 1.57, 7.87) were factors associated with caring behaviors among nurses working in Ethiopia.

Caring behavior among nurses is moderately good, with professional satisfaction, job satisfaction, low workload, and good relationships with workers that affect the caring behaviors among nurses working in Ethiopia. Strategies must be designed to improve satisfaction packages to improve caring behavior among nurses and ultimately improve the quality of nursing care.

The PROSPERO registration number is CRD42024570781.

Crash injury risk is reduced when a child correctly uses an appropriate restraint; however, incorrect restraint use remains widespread. The aim of this study was to determine whether product information developed using a user-driven approach increases correct child restraint use.

We conducted a two-arm double-blinded parallel randomised controlled trial in New South Wales, Australia 2019-2021. Participants were current drivers who were either an expectant parent or a parent of at least one child residing in the greater Sydney metropolitan area who were interested in purchasing a new child restraint. The intervention was user-driven product information consisting of instructions printed on an A3 sheet of paper, swing tags with key reminders and a video accessed via Quick Response codes printed on the materials. The control group received a postcard summarising legal child restraint requirements. The primary outcome was the correctness of child restraint use observed during home visit approximately 6 months after restraint purchase. Correct use was defined as no serious error or <2 minor errors. The secondary outcome was a count of observed errors.

427 participants were recruited. Home visits were conducted for 372 (190 intervention and 182 control). Correct use was more common in the intervention group (37.4%) compared with the control group (24.2%, p=0.006). Participants receiving the intervention were 1.87 times more likely to correctly use their restraint than those in the control group (95% CI 1.19 to 2.93).

The results provide evidence for the effectiveness of user-driven instructions as a countermeasure to restraint misuse.

ACTRN12617001252303.

Increasing legalization of recreational cannabis and availability of cannabinoid products has resulted in expanded use, which is associated with adverse effects including concerns over increased risk of motor vehicle collision (MVC). We aimed to explore the association between cannabis consumption and MVC.

We searched MEDLINE, EMBASE, CINAHL, Cochrane library, SCOPUS, PsycInfo, Web of Science, TRID from inception to November 2024. We included studies assessing the association between cannabis consumption on MVC fatalities, any injuries, and culpability/unsafe driving actions. Pairs of reviewers independently screened search results, extracted data, and assessed risk of bias. We used a DerSimonian and Laird random-effects model for all meta-analyses and the GRADE approach to assess the certainty of evidence.

We included 31 studies with 328,388 individuals. Low certainty evidence suggests that cannabis consumption may be associated with an increased risk of MVC fatality (8 studies, OR 1.55, 95% CI: 1.20 to 1.98) with an absolute risk increase (ARI) of 14 more deaths per 100,000 MVC's. Low certainty evidence from 9 case-control studies suggests cannabis consumption may be associated with an increased risk of injury due to MVC (OR 2.00, [95% CI: 1.31-3.07]; absolute risk increase of 6.8%). We are uncertain about the association of cannabis consumption with MVC culpability/unsafe driving action as the evidence was only very low certainty.

Low certainty evidence suggests that cannabis consumption may increase risk of MVC fatality and risk of injury from MVC. The association between cannabis use and risk of unsafe driving is uncertain.

CRD42022357478.

Modern clinical trials can capture tens of thousands of clinicogenomic measurements per individual. Discovering predictive biomarkers, as opposed to prognostic markers, remains challenging. To address this, we present a neural network framework based on contrastive learning-the Predictive Biomarker Modeling Framework (PBMF)-that explores potential predictive biomarkers in an automated, systematic, and unbiased manner. Applied retrospectively to real clinicogenomic datasets, particularly for immuno-oncology (IO) trials, our algorithm identifies biomarkers of IO-treated individuals who survive longer than those treated with other therapies. We demonstrate how our framework retrospectively contributes to a phase 3 clinical trial by uncovering a predictive, interpretable biomarker based solely on early study data. Patients identified with this predictive biomarker show a 15% improvement in survival risk compared to those in the original trial. The PBMF offers a general-purpose, rapid, and robust approach to inform biomarker strategy, providing actionable outcomes for clinical decision-making.

The results of subgroup analyses of clinical trials are important reference information when considering the generalizability of a study treatment, i.e., providing the best treatment for each individual patient. The results of subgroup analyses are often presented in publications, etc. as forest plots focusing on patient backgrounds. However, it is important to fully understand and grasp some of the issues involved in subgroup analyses and to interpret the results carefully to apply them in clinical practice. Although the literature includes some reports on how subgroup analyses should be evaluated and handled for the purpose of establishing medical practice guidelines, most of the papers have mainly evaluated the reliability of subgroup analyses from a statistical perspective; few of them have incorporated clinical importance in their evaluations. Therefore, in December 2019, we established a Subgroup Analysis Review Committee consisting of oncologists specializing in lung cancer treatment and statistical experts among the members of the Guidelines Review Committee of the Japanese Lung Cancer Association, with the aim of appropriately reflecting subgroup analysis in Japanese lung cancer practice guidelines. We developed a new evaluation strategy to incorporate clinical aspects as well as reliability assessment. Specifically, on the basis of a clinical and statistical review of the problems with subgroup analyses presented as clinical trial results, we developed criteria and procedures to ensure consistency and fairness in the citation of clinical guidelines.

Aim: Under the newly instituted health technology assessment (HTA) regulation (HTAR), health technology developers must build evidence packages that meet the needs for both the upcoming EU joint clinical assessment (JCA) and national decision-making. In-depth knowledge of local methodological requirements as well as preparedness for effective strategic development is crucial. This study aimed to review methodological guidance documents to map similarities/misalignments between the EU HTAR and select HTA agencies. Materials & methods: An environmental scan was performed in March 2024 and updated in December 2024 of the websites for European Network for HTA, the European Commission and HTA agencies in France, Germany, The Netherlands and Spain. The search aimed to systematically identify and summarize methodological guidance documents from the respective organizations on scoping considerations, evidence identification and synthesis. Results: Overall, published EU HTAR methods guidelines are detailed, prescriptive and make reference to a preference (or lack thereof) for specific analytical methods. There was consensus among EU JCA and local HTA guidelines that clinical comparative assessments should be based on a systematically identified, unbiased selected evidence base derived from various sources. However, agencies differed on guidance related to evidence derived from indirect treatment comparisons. Conclusion: An environmental scan of methods documents revealed that it will likely be challenging for health technology developers to build strong evidence packages that can support both EU JCA and local reimbursement decision-making. A greater understanding of the similarities and differences between EU and local HTA requirements will be needed, including a greater capacity to demonstrate value through advanced analytics.

There has been a renewed interest in identifying heterogenous treatment effects (HTEs) to guide personalized medicine. The objective was to illustrate the use of a step-by-step transparent parametric data-adaptive approach (the generalized HTE approach) based on the G-computation algorithm to detect heterogenous subgroups and estimate meaningful conditional average treatment effects (CATE). The following seven steps implement the generalized HTE approach: Step 1: Select variables that satisfy the backdoor criterion and potential effect modifiers; Step 2: Specify a flexible saturated model including potential confounders and effect modifiers; Step 3: Apply a selection method to reduce overfitting; Step 4: Predict potential outcomes under treatment and no treatment; Step 5: Contrast the potential outcomes for each individual; Step 6: Fit cluster modeling to identify potential effect modifiers; Step 7: Estimate subgroup CATEs. We illustrated the use of this approach using simulated and real data. Our generalized HTE approach successfully identified HTEs and subgroups defined by all effect modifiers using simulated and real data. Our study illustrates that it is feasible to use a step-by-step parametric and transparent data-adaptive approach to detect effect modifiers and identify meaningful HTEs in an observational setting. This approach should be more appealing to epidemiologists interested in explanation.

Hypertension is a major global health issue. Aldosterone synthase inhibitors (ASIs) have emerged as a promising therapeutic strategy for blood pressure control.

A thorough search of the MEDLINE and Embase databases up to March 30, 2024, identified randomized trials comparing ASIs with a placebo for hypertension treatment. Data extraction was done independently by 2 authors. Both random-effects (Restricted maximum likelihood) and fixed-effects meta-analyses were conducted to account for diversity and study size, respectively. Risk ratios for binary outcomes and mean differences for continuous outcomes were calculated.

Seven randomized controlled trials involving 1440 patients (mean age, 60 years; 39% women) were included. The analysis showed that ASIs reduced office systolic blood pressure by 6.3 mm Hg ([95% CI, -8.8 to -3.8]; P<0.0001) and diastolic blood pressure by 2.2 mm Hg ([95% CI, -4.2 to -0.2]; P=0.03). The risk ratio for adverse events was 1.1 ([95% CI, 0.9-1.2]; P=0.3), with a similar trend for serious adverse events (risk ratio, 1.0 [95% CI, 0.5-2.3]; P=0.95). No treatment-related deaths occurred. However, the risk of hyperkalemia was higher with ASIs (risk ratio, 2.5 [95% CI, [1.2-5.4]; P<0.02).

ASIs effectively reduce systolic and diastolic blood pressure in hypertensive patients and have a tolerable safety profile. The increased risk of hyperkalemia requires careful monitoring. These findings suggest ASIs are a potential treatment option for hypertension, pending further research in larger studies.

Type 2 diabetes mellitus (T2DM) is two to three times more common in people with severe mental illness (SMI) than in the general population. Supporting self-management in diabetes is fundamental to improving clinical outcomes. The DIAMONDS trial aims to evaluate the clinical and cost effectiveness of a novel, codesigned, supported diabetes self-management programme for people with T2DM and SMI.

This multicentre, two-armed, parallel, individually randomised controlled trial will be conducted in National Health Service mental health trusts across England. We will recruit 380 participants (≥18 years old) with a diagnosis of SMI (schizophrenia, bipolar disorder, schizoaffective disorder, psychosis and severe depression) and T2DM. Eligible and consenting participants will be randomised to the DIAMONDS intervention or treatment as usual. The intervention group will receive one-to-one sessions with a trained DIAMONDS Coach for six months. These sessions will focus on goal setting, action planning and diabetes self-management education, supported by a paper-based workbook and an optional digital application. Individuals allocated to the control group will continue to receive usual care and may be offered National Institute for Health and Care Excellence-recommended generic diabetes self-management education programmes in line with usual practice. The primary outcome is the difference in glycated haemoglobin (HbA1c) between both groups at 12 months postrandomisation. The secondary outcomes include measures of physical and mental health, diabetes complications and physical activity. Economic and process evaluations will also be performed. Outcomes will be collected at baseline and at six and 12 month post-randomisation.

This study received ethics approval by the West of Scotland Research Ethics Committee 3 (22/WS/0117). Findings will be published in peer-reviewed, academic and professional journals. We will also be producing plain language summaries, infographics and audio summaries on the website, as well as attending conferences and dissemination events. A summary of the results will be distributed to all participants and other relevant stakeholders, and we will use social media channels, websites and knowledge exchange events to communicate our findings beyond academic audiences.

ISRCTN22275538.

The majority of randomised controlled trials in acute stroke and many for prevention are neutral, i.e. they failed to reach statistical significance. However, many of these will find apparent benefit in a component of a subgroup, findings which may be 'chased' in a follow-up trial. The evidence to date is that these follow-on trials are very likely to be neutral.

We discuss the issue of chasing subgroups in neutral trials and illustrate the challenges in five pairs of exemplar acute stroke trials. Problems in the exemplar trials include failing to define the subgroup in advance or even changing its definition, failing to show that both the interaction test and the primary outcome in the component were statistically significant, failing to publish additional information on the positive subgroup component, having too many subgroups, failing to make the follow-on trial large enough and failing to report the findings of the follow-on trial.

When chasing a positive component in a subgroup, it is vital that the subgroup: should be plausible biologically, defined a priori and have a significant interaction test. Further the number of subgroups should be limited and the component of interest should be statistically significant. Explanations should be given as to why the component is positive and other components of the subgroup are negative. Other outcomes should also show potential benefit. Unless this guidance is followed, it is highly likely that follow-on trials will be neutral as has occurred previously.

Background: Although digital cognitive behavioral therapy (dCBT) is considered effective for anxiety disorders, there is considerable heterogeneity in its efficacy across studies, and its varied treatment content and clinical components may explain such heterogeneity. Objective: This review aimed to identify the efficacy of digital cognitive behavioral therapy for panic disorder and agoraphobia, and examine whether applying relevant clinical components of interoceptive exposure, inhibitory-learning-based exposure, and personalization of treatment enhances its efficacy. Methods: Randomized controlled trials of dCBT for panic disorder and agoraphobia with passive or active controls were identified from OVID Medline, Embase, Cochrane Library, and PsycINFO. The overall effect sizes for dCBT groups (interventions through digital platforms based on the internet, mobile, computers, VR, etc.) were aggregated against passive control (placebo/sham) and active control (traditional CBT) groups. For subgroup analysis, key intervention components such as interoceptive exposure, inhibitory learning, and personalization were assessed dichotomously (0 or 1) along with other study characteristics. The stepwise meta-regression models were applied with traditional and Bayesian statistical testing. The risk of bias and publication bias of included studies were assessed. Results: Among the 31 selected studies, dCBT had an overall effect size of g = 0.70 against passive control and g = -0.05 against active control. In subgroup analysis, interoceptive exposure improved the clinical effects for both controls, and inhibitory learning and personalization increased the clinical effects for passive control along with therapist guide/support and the length of sessions. Many studies were vulnerable to therapist bias and attrition bias. No publication bias was detected. Conclusions: The heterogeneity in clinical effects of dCBT for panic and agoraphobia can be explained by the different intervention factors they include. For effective dCBT, therapists should consider the clinical components relevant to the treatment.

OBJECTIVE: To investigate whether magnetic resonance imaging (MRI) findings modified the outcomes of early surgery compared to exercise and education in young patients with meniscal tears. DESIGN: A secondary effect modifier analysis of a randomized controlled trial. METHODS: The primary outcome was change from baseline to 12 months in the mean score of 4 Knee injury and Osteoarthritis Outcome Score subscales (KOOS4). Three potential MRI-defined effect modifiers were predefined: (1) the type of meniscal tear (simple vs bucket handle or complex), (2) the meniscus affected (medial vs lateral), and (3) the presence of knee effusion/synovitis (yes/no). We used a linear mixed model to investigate the difference in mean change between the treatment groups, stratified by each of the 3 potential effect modifiers, and estimated the interactions. An adjusted effect difference ≥ 10 points (0-100 scale) was considered clinically relevant. RESULTS: Data from all participants (60 in the surgery group and 61 in the exercise group) were analyzed. The mean (SD) age was 29.7 (6.6) years, and 28% were female. A potential effect modification was observed for knee effusion/synovitis, with its presence implying an increase of the effect of early surgery by 11 points on the KOOS4 (P = .07). CONCLUSION: Knee effusion/synovitis on MRI potentially modified the treatment effect with a clinically relevant difference in change of the KOOS4 in patients with effusion/synovitis, favoring early surgery. We found no indication that patients with bucket handle or complex versus simple tears or medial versus lateral tears benefited more from early surgery. J Orthop Sports Phys Ther 2025;55(3):1-11. Epub 30 January 2025. doi:10.2519/jospt.2025.12994.

Examining treatment effects in subgroups of patients defined by demographic, genetic, or clinical characteristics is increasingly of interest given the pursuit of personalized medicine and the importance of representation and equity in treatment decisions. The magnitude or even the direction of the treatment effect may vary across subgroups, and these differential treatment effects could have clinical implications. Subgroup analyses require caution in their interpretation, however, because of the high probability of a false-positive or false-negative conclusion. We outline study design and analysis considerations for responsibly investigating and reporting differential treatment effects across subgroups in oncology trials, with examples from the National Cancer Institute's National Clinical Trials Network and Community Oncology Research Program. Recommendations include ensuring appropriate representation of patients from subgroups of interest, recognizing power and multiplicity limitations, and treating exploratory subgroup analyses as hypothesis generating rather than practice changing.

Breast cancer patients encounter challenges managing acute and chronic symptoms during and after treatment, leading to emotional fluctuations and diminished quality of life. Health education aims to improve knowledge and life skills; however, its specific impact on breast cancer patients' self-efficacy is unclear.

To assess the effects of health education on self-efficacy, depressive symptoms, anxiety, distress, and life quality in breast cancer patients.

Randomized controlled studies were systematically screened in 7 databases from inception of the database to May 1, 2024. Literature quality was assessed using the Cochrane Risk of Bias Assessment tool. Results were pooled using random-effects meta-analyses and reported as standardized mean difference. Heterogeneity was reported using I2 statistic.

Sixteen articles were included. Participants in the intervention group exhibited enhanced self-efficacy in posttest (standardized mean difference [SMD], 0.12; 95% confidence interval [CI], 0.01-0.23; P = .04, I2 = 8%) and during the follow-up period (SMD, 0.30; 95% CI, 0.09-0.52; P = .006, I2 = 63%), decreased depressive symptoms (SMD, -0.30; 95% CI, -0.52 to -0.08; P = .0007, I2 = 17%), and increased life quality (SMD, 0.25; 95% CI, 0.01-0.49; P = .04, I2 = 48%) during the follow-up period.

Health education can enhance self-efficacy, reduce depressive symptoms, and improve the life quality of breast cancer patients. However, more rigorous research is needed to evaluate their effectiveness due to suboptimal blinding.

The study underscores the critical role of health education in breast cancer management, emphasizing the necessity of integrating comprehensive health education programs into standard care protocols.

The PATH Statement (2020) proposed predictive modeling for examining heterogeneity in treatment effects (HTE) in randomized clinical trials (RCTs). It distinguished risk modeling, which develops a multivariable model predicting individual baseline risk of study outcomes and examines treatment effects across risk strata, from effect modeling, which directly estimates individual treatment effects from models that include treatment, multiple patient characteristics and interactions of treatment with selected characteristics.

To identify, describe and evaluate findings from reports that cite the Statement and present predictive modeling of HTE in RCTs.

We identified reports using PubMed, Google Scholar, Web of Science, SCOPUS through July 5, 2024. Using double review with adjudication, we assessed consistency with Statement recommendations, credibility of HTE findings (applying criteria adapted from the Instrument to assess Credibility of Effect Modification Analyses (ICEMAN)), and clinical importance of credible findings.

We identified 65 reports (presenting 31 risk models, 41 effect models). Contrary to Statement recommendations, only 25 of 48 studies with positive overall findings included a risk model; most effect models included multiple predictors with little prior evidence for HTE. Claims of HTE were noted in 23 risk modeling and 31 effect modeling reports, but risk modeling met credibility criteria more frequently (87 vs 32 percent). For effect models, external validation of HTE findings was critical in establishing credibility. Credible HTE from either approach was usually judged clinically important (24 of 30). In 19 reports from trials suggesting overall treatment benefits, modeling identified subgroups of 5-67% of patients predicted to experience no benefit or net treatment harm. In five that found no overall benefit, subgroups of 25-60% of patients were nevertheless predicted to benefit.

Multivariable predictive modeling identified credible, clinically important HTE in one third of 65 reports. Risk modeling found credible HTE more frequently; effect modeling analyses were usually exploratory, but external validation served to increase credibility.

The INCREASE trial introduced a novel therapeutic option for Pulmonary Hypertension caused by Interstitial Lung Disease. Subsequently to this trial, several subgroup analyses were conducted, aiming to explore specific effects within subgroups.

This study aimed to evaluate the subgroup analyses performed in the INCREASE trial and to identify potentially reliable subgroup effects.

A methodological assessment of the subgroup analyses was performed. Claims of subgroup effect were evaluated using three different tools: Sun, X et al. 2012, Gil-Sierra, M.D et al. 2020, and Schandelmaier, S et al. 2020. Additionally, all statistically significant subgroup effects that were not claimed by the authors were evaluated.

Five claims of subgroup effect were identified; none of them achieved statistical significance when assessed using an interaction test. The evaluation conducted with the three tools consistently yielded very low credibility for all the claims. During the assessment, a statistically significant subgroup effect of moderate credibility was identified, which the authors did not claim: iTre appeared to improve exercise capacity exclusively in patients with Pulmonary Vascular Resistance ⋝ 4 WUs.

Due to methodological limitations, the credibility of subgroup claims from the authors of the INCREASE was lacking and, therefore, should not be relied upon to inform decisions on an individual basis.

The EUnetHTA Core Model® is well-established in the HTA community. Some recommendations of corresponding guidance documents leave room for alternative methodological choices. Considering the new HTA regulation (HTAR), we aimed to identify needs for concretization (NCs) in EUnetHTA guidance and provide indicative methodological options.

We carried out a qualitative document analysis and structured group discussion. Twenty-two EUnetHTA documents were screened using transparent criteria. Identified NCs were classified into topics according to the PRISMA statement and presented to Austrian HTA practitioners (n = 11) during a structured group discussion. Participants rated NC's importance. To identify potential solutions, selected key handbooks for generic (Cochrane) and HTA-specific (IQWIG/NICE) evidence synthesis were systematically reviewed and matching content was charted against the NCs.

Thirty-two topics with varying numbers of NCs were identified, twenty-six during the screening process, and six from the group discussion. Most of the topics related to evidence synthesis methods (nine topics), evidence eligibility criteria (nine topics), risk of bias (three topics), and certainty assessment (three topics). Other topics related to information sources, search strategy, data collection process, data items, effect measures, and reporting bias. One or more methodological approaches and recommendations could be identified for each identified topic from the included methodological handbooks.

Our analysis identified a need for concretization in some EUnetHTA guidelines. The structured overview of methodological options may support HTA doers in adapting and applying the guidelines to the national and local practical context.

Limited language proficiency is an established barrier to research participation among racialized populations. While prior studies have highlighted the underrepresentation of racialized populations in venous thromboembolism (VTE) research, the impact of limited language proficiency as a reason for nonconsent among eligible patients is unknown.

To determine the impact of language barrier as the primary reason for VTE research non-participation.

We reviewed all prospective VTE studies conducted at a research-intensive academic thrombosis research program in Canada between 2014 and 2024. Studies with screening logs that systematically and consecutively captured eligibility assessment and reasons for nonconsent were included. Primary outcome was nonconsent of a screen-eligible patient due to limited language proficiency as the reported reason. We derived pooled estimates of nonconsent due to limited language proficiency as a proportion of consented participants and determined subgroup rates by phase of VTE management, associated medical conditions, and recruitment settings.

Screening logs of 28 studies with 22 057 screening events, 8317 screen-eligible patients, and 3320 consented participants were included. For every 100 consented participants, 3.2 (95% CI, 2.0-5.3) screen-eligible individuals were unable to provide consent due to limited language proficiency. Rates of nonconsent were highest in studies involving cancer (5.6 per 100 participants; 95% CI, 2.9-10.4) and in studies recruiting patients from ambulatory settings outside of the thrombosis clinic (10.8 per 100 participants; 95% CI, 4.8-22.6).

Language proficiency is a key barrier to VTE research participation. Urgent implementation of targeted interventions aimed at mitigating linguistic barriers is essential to ensure equitable opportunities for VTE research participation for racialized patients disproportionately affected by language proficiency.

Optimal medical therapy (OMT) is a modifiable factor that decreases mortality and cardiovascular events in patients with severe peripheral arterial disease. We hypothesized that preintervention OMT would be associated with improved 1-year reintervention and major adverse limb event (MALE) rates after elective endovascular revascularization for intermittent claudication (IC).

Using the Vascular Quality Initiative (2010-2020), we identified patients with IC undergoing elective endovascular, hybrid, and open surgical interventions. Preoperative antiplatelet, statin, and nonsmoking status defined OMT components and created three groups: complete (all components), partial (1-2 components), and no OMT. The primary outcome was 1-year reintervention. Secondary outcomes included MALE and factors associated with OMT usage. Multivariable logistic regression generated adjusted odds ratios (aOR).

There were 39,088 patients (14,907 [38.1%] complete, 22,054 [56.4%)] partial, 2127 [5.4%] no OMT) who met our criteria. Patients with any OMT were more frequently older with more cardiovascular diseases and diabetes (P < .0001). Patients without OMT were more likely to be Black or with Medicare or Medicaid (P < .05). Observed 1-year reintervention (5.3% complete OMT, 6.1% partial OMT, 8.3% no OMT; P < .001) and MALE (5.6% complete OMT, 6.3% partial OMT, 8.8% no OMT; P < .001) were decreased by partial or complete OMT compared with no OMT. Complete OMT significantly decreased the adjusted odds of reintervention and MALE by 28% (aOR, 0.72, 95% confidence interval [95% CI], 0.59-0.88) and 30% (aOR, 0.70; 95% CI, 0.58-0.85), respectively, compared with no OMT. Partial OMT decrease the adjusted odds of reintervention and MALE by 24% (aOR, 0.76; 95% CI, 0.63-0.92) and 26% (aOR, 0.74; 95% CI, 0.62-0.89), respectively.

Preintervention OMT is an underused, modifiable risk factor associated with improved 1-year reintervention and MALE. Vascular surgeons are uniquely positioned to initiate and maintain OMT in patients with IC before revascularization to optimize patient outcomes.

High-dose haemodiafiltration has been shown, in a randomised clinical trial, to result in a 23% lower risk of mortality for patients with kidney failure when compared with conventional high-flux haemodialysis. Nevertheless, whether treatment effects differ across subgroups, whether a dose-response relationship with convection volume exists, and the effects on cause-specific mortality remain unclear. The aim of this individual patient data meta-analysis was to compare the effects of haemodiafiltration and standard haemodialysis on all-cause and cause-specific mortality.

On July 17, 2024, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials, published from database inception, comparing online haemodiafiltration versus haemodialysis designed to measure mortality outcomes. The primary outcome was all-cause mortality. Hazard ratios were generated using Cox proportional hazards regression models reporting hazard ratios and 95% CIs. Subgroup analyses based on predefined patient characteristics and dose-response analyses using natural splines for convection volume were performed. This analysis is registered with PROSPERO (CRD42024511514).

Five trials (n=4153 patients; 2070 receiving haemodialysis and 2083 receiving haemodiafiltration) were eligible for inclusion in this analysis. After a median follow-up of 30 months (IQR 24-36), all-cause mortality occurred in 477 patients (23·3%) treated with haemodiafiltration compared with in 559 patients (27·0%) treated with haemodialysis (hazard ratio 0·84 [95% CI 0·74-0·95]). No evidence of a differential effect across subgroups was noted. A graded relationship between convection volume and mortality risk was apparent: as the volume increased, the mortality risk decreased.

Compared with haemodialysis, online haemodiafiltration reduces all-cause mortality in people with kidney failure. Results do not differ across patient and treatment characteristics and the risk reduction appears to be dose-dependent. In conclusion, the present analysis strengthens the notion that haemodiafiltration can be considered as a superior alternative to the present standard (ie, haemodialysis).

European Commission Research and Innovation, Horizon 2020.

Do five baseline moderators identify patients with chronic low back pain who respond best to cognitive functional therapy (CFT) when compared with usual care?

Secondary analysis of the RESTORE randomised controlled trial.

A total of 492 adults with low back pain for > 3 months with at least moderate pain-related activity limitation.

Participants were allocated to CFT alone or CFT plus biofeedback; these two groups were combined for this secondary analysis. The control group was usual care.

The outcome was activity limitation measured using the Roland Morris Disability Questionnaire (RMDQ) at 3, 6, 13, 26, 40 and 52 weeks. Investigated effect modifiers were baseline measures of activity limitation, cognitive flexibility, pain intensity, self-efficacy and catastrophising.

Baseline levels of activity limitation and, potentially, cognitive flexibility were associated with different effects of CFT treatment, while pain intensity, self-efficacy and catastrophising were not. Patients who had higher baseline activity limitation had greater treatment effects at 13 and 52 weeks. A person with a baseline RMDQ score of 18 (90th percentile) would on average be 6.1 (95% CI 4.8 to 7.4) points better at 13 weeks if they received CFT compared with usual care. However, a person with a baseline score of 7 (10th percentile) would on average be 3.6 (95% CI 2.6 to 4.6) points better at 13 weeks.

The finding that CFT is most effective among patients who are most disabled and incur the greatest burden strongly suggests that CFT should be considered as a treatment for this group of patients.

ACTRN12618001396213.

Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. Glycaemic control decreases the risk of adverse pregnancy outcomes for the affected pregnant individual and the infant exposed in utero. One in four individuals with GDM will require pharmacotherapy to achieve glycaemic control. Injectable insulin has been the mainstay of pharmacotherapy. Oral metformin is an alternative option increasingly used in clinical practice. Both insulin and metformin reduce the risk of adverse pregnancy outcomes, but comparative effectiveness data from a well-characterised, adequately powered study of a diverse US population remain lacking. Because metformin crosses the placenta, long-term safety data, in particular, the risk of childhood obesity, from exposed children are also needed. In addition, the patient-reported experiences of individuals with GDM requiring pharmacotherapy remain to be characterised, including barriers to and facilitators of metformin versus insulin use.

In a two-arm open-label, pragmatic comparative effectiveness randomised controlled trial, we will determine if metformin is not inferior to insulin in reducing adverse pregnancy outcomes, is comparably safe for exposed individuals and children, and if patient-reported factors, including facilitators of and barriers to use, differ between metformin and insulin. We plan to recruit 1572 pregnant individuals with GDM who need pharmacotherapy at 20 US sites using consistent diagnostic and treatment criteria for oral metformin versus injectable insulin and follow them and their children through delivery to 2 years post partum. More information is available at www.decidestudy.org.

The Institutional Review Board at The Ohio State University approved this study (IRB: 2024H0193; date: 7 December 2024). We plan to submit manuscripts describing the results of each study aim, including the pregnancy outcomes, the 2-year follow-up outcomes, and mixed-methods assessment of patient experiences for publication in peer-reviewed journals and presentations at international scientific meetings.

NCT06445946.

Traumatic brain injury (TBI) is a significant public health issue characterized by high mortality rates and long-term complications. This commentary examines the controversial role of the use of albumin in the fluid management of patients with severe TBI. Despite its physiological benefits, the clinical use of albumin remains controversial due to the fact that various studies have yielded mixed results. Serum albumin is important for maintaining normovolemia, primarily through its contribution to colloid osmotic pressure, which helps to retain fluid in the circulatory system. This review highlights the existing evidence, examines inconsistencies in guideline recommendations, and suggests future research directions to clarify the efficacy and safety of the use of albumin in maintaining normovolemia in patients with TBI. The review also discusses the potential benefits of small-volume resuscitation strategies for the management of acute kidney injury in TBI patients, drawing parallels with the management of septic acute kidney injury. The need for further well-designed randomized controlled trials and ethical considerations in studies regarding the use of hyperoncotic albumin in TBI management is emphasized.

Investigating how individual characteristics modify treatment effects can improve understanding, interpretation, and translation of trial findings. The purpose of this secondary analysis was to identify treatment effect modifiers of the MI-NAV trial, a 3 arm, parallel randomized controlled trial which compared motivational interviewing and stratified vocational advice intervention in addition to usual case management (UC), to UC alone. This study included (n = 514) participants with musculoskeletal disorders on sick leave for at least 50% of their contracted work hours for at least 7 consecutive weeks with the Norwegian Labour and Welfare Administration. Sickness absence days was the primary outcome, measured from baseline assessment date until the 6-month follow-up. Potential treatment effect modifiers, identified a priori and informed by expert consultation and literature, were evaluated using linear regression models and statistical interaction tests. For motivational interviewing versus UC, age (mean difference [MD] -.7, 95% confidence interval [CI] -1.5 to .2; P = .13) and self-perceived health status (MD -.3, 95% CI -.7 to .1; P = .19) were identified as potential effect modifiers (P ≤ .2). For stratified vocational advice intervention versus UC, analgesic medication use (MD -26.2, 95% CI -45.7 to -6.7; P = .009) was identified as a treatment effect modifier (P ≤ .05). These findings may assist in more targeted treatment adaptation and translation as well as the planning of future clinical trials. PERSPECTIVE: This secondary analysis of the MI-NAV trial found that analgesic medication use, age, and self-perceived health may modify the effect of 2 vocational interventions on reducing sickness absence in people with musculoskeletal disorders.

This article continues from a prior commentary on evaluating the risk of bias in randomised controlled trials addressing nutritional interventions. Having provided a synopsis of the risk of bias issues, we now address how to understand trial results, including the interpretation of best estimates of effect and the corresponding precision (eg, 95% CIs), as well as the applicability of the evidence to patients based on their unique circumstances (eg, patients' values and preferences when trading off potential desirable and undesirable health outcomes and indicators (eg, cholesterol), and the potential burden and cost of an intervention). Authors can express the estimates of effect for health outcomes and indicators in relative terms (relative risks, relative risk reductions, OR or HRs)-measures that are generally consistent across populations-and absolute terms (risk differences)-measures that are more intuitive to clinicians and patients. CIs, the range in which the true effect plausibly lies, capture the precision of estimates. To apply results to patients, clinicians should consider the extent to which the study participants were similar to their patients, the extent to which the interventions evaluated in the study are applicable to their patients and if all patient-important outcomes of potential benefit and harm were reported. Subsequently, clinicians should consider the values and preferences of their patients with respect to the balance of the benefits, harms and burdens (and possibly the costs) when making decisions about dietary interventions.

Periodontal disease may be an important modifiable risk factor for stroke.

To determine the contribution of markers of periodontal disease to stroke risk globally, within subpopulations, and by stroke subtypes.

INTERSTROKE is the largest international case-control study of risk factors for first acute stroke. All participants were asked a standardised set of questions about the presence or absence of painful teeth, painful gums or lost teeth, as markers of periodontal disease, within the previous year. The total number of reported variables was calculated per participant. Multivariable conditional logistic regression examined the association of these variables with acute stroke.

In 26901 participants, across 32 countries, there was a significant multivariable association between lost teeth and stroke (OR 1.11, 95 % CI 1.01 - 1.22), but not painful teeth (OR 1.00, 95 % CI 0.91-1.10) or painful gums (OR 1.01, 95 % CI 0.89 - 1.14). When these symptoms were considered together there was a graded increased odds of stroke, with the largest magnitude of association seen if a patient reported all three of painful teeth, painful gums and lost teeth (OR 1.34, 95 % CI 1.00 - 1.79).

Our findings suggest that features of severe periodontal disease are a risk factor for acute stroke. Periodontal disease should be considered as a potentially modifiable risk factor for stroke.

This overview of reviews aims to identify evidence on the benefits (i.e. tobacco use abstinence and reduction in smoking frequency) and harms (i.e. possible adverse events/outcomes) of smoking cessation interventions among adults aged 18 years and older.

We searched Medline, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, the CADTH Health Technology Assessment Database and several other websites for grey literature. Searches were conducted on November 12, 2018, updated on September 24, 2020, with publication years 2008 to 2020. Two reviewers independently performed title-abstract and full-text screening considering pre-determined inclusion criteria. Data extraction and quality assessments were initially completed by two reviewers independently (i.e. 73% of included studies (n = 22)) using A Measurement Tool to Assess Systematic Reviews-2 (AMSTAR 2), and the remainder done by one reviewer and verified by another due to resources and feasibility. The application of Grading of Recommendations Assessment, Development and Evaluation (GRADE) was performed by one independent reviewer and verified by another.

A total of 22 Cochrane systematic reviews evaluating the impact of smoking cessation interventions on outcomes such as tobacco use abstinence, reduction in smoking frequency, quality of life and possible adverse events were included. Pharmaceutical (i.e. varenicline, cytisine, nicotine replacement therapy (NRT), bupropion) and behavioural interventions (i.e. physician advice, non-tailored print-based self-help materials, stage-based individual counselling, etc.) showed to have increased smoking cessation; whereas, data for mobile phone-based interventions including text messaging, hypnotherapy, acupuncture, continuous auricular stimulation, laser therapy, electrostimulation, acupressure, St John's wort, S-adenosyl-L-methionine (SAMe), interactive voice response systems and other combination treatments were unclear. Considering harms related to smoking cessation interventions, small/mild harms (i.e. increased palpitations, chest pain, nausea, insomnia, headache) were observed following NRT, varenicline and cytisine use. There were no data on harms related to behavioural therapies (i.e. individual or group counselling self-help materials, internet interventions), combination therapies or other therapies (i.e. laser therapy, electrostimulation, acupressure, St John's wort, SAMe).

Results suggest that pharmacological and behavioural interventions may help the general smoking population quit smoking with observed small/mild harms following NRT or varenicline. Consequently, evidence regarding ideal intervention strategies and the long-term impact of these interventions for preventing smoking was unclear.

PROSPERO CRD42018099691.

Ischemic stroke is a serious and sudden cerebrovascular condition that significantly affects individual's health and imposes a substantial economic burden on medical management. Despite its widespread use in China, there is still a lack of reliable evidence regarding the efficacy of Shenmai injection (SMI) in acute ischemic stroke (AIS). We aimed to comprehensively assess the effectiveness and safety of SMI in treating AIS through a systematic review and meta-analysis.

Randomized controlled studies (RCTs) investigating the efficacy of SMI in treating AIS were searched for in eight databases from the inception of each database till January 2024. We utilized the ROB 2.0 to assess the risk of bias. A meta-analysis was conducted using Review Manager 5.4, while sensitivity analyses and publication bias assessments were conducted using Stata 16.1.

A total of 17 studies involving 1,603 AIS patients were included in our meta-analysis. Our results showed that SMI plus conventional treatments (CTs) was more effective than CTs alone in improving the total effective rate (RR 1.22, 95% CI: 1.14 to 1.30, p < 0.00001), the Barthel index (BI) (MD 12.18, 95% CI: 10.30 to 14.06, p < 0.00001), and reducing the National Institute of Health Stroke Scale Score (NIHSS) score (MD -3.05, 95% CI: 3.85 to -2.24, p < 0.00001) and Modified Rankin Scale (mRS) (MD -0.68, 95% CI: 0.86 to-0.49, p < 0.00001). In addition, SMI combination therapy was better than CTs alone in decreasing the levels of IL-6, IL-18, and hs-CRP. SMI therapy also enhanced the cerebral hemorheology of patients by reducing levels of fibrinogen and plasma viscosity. However, there was no significant difference in the incidence of adverse events, including elevated transaminase, rash, nausea, bleeding, urticaria, headache, vomiting, chest tightness, and facial flushes. Moreover, no serious adverse effects or life-threatening events were reported.

Our study shows that combining SMI with CTs effectively enhances the neurological function of patients with acute cerebral infarction. However, our findings should be interpreted considering the significant heterogeneity and suboptimal quality of the analyzed trials.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024504675, Identifier PROSPERO, CRD42024504675.

Subgroup analysis aims to identify subgroups (usually defined by baseline/demographic characteristics), who would (or not) benefit from an intervention under specific conditions. Often performed post hoc (not pre-specified in the protocol), subgroup analyses are prone to elevated type I error due to multiple testing, inadequate power, and inappropriate statistical interpretation. Aside from the well-known Bonferroni correction, subgroup treatment interaction tests can provide useful information to support the hypothesis. Using data from a previously published randomized trial where a p value of 0.015 was found for the comparison between standard and Hemopatch® groups in (the subgroup of) 135 patients who had hand-sewn pancreatic stump closure we first sought to determine whether there was interaction between the number and proportion of the dependent event of interest (POPF) among the subgroup population (patients with hand-sewn stump closure and use of Hemopatch®), Next, we calculated the relative excess risk due to interaction (RERI) and the "attributable proportion" (AP). The p value of the interaction was p = 0.034, the RERI was - 0.77 (p = 0.0204) (the probability of POPF was 0.77 because of the interaction), the RERI was 13% (patients are 13% less likely to sustain POPF because of the interaction), and the AP was - 0.616 (61.6% of patients who did not develop POPF did so because of the interaction). Although no causality can be implied, Hemopatch® may potentially decrease the POPF after distal pancreatectomy when the stump is closed hand-sewn. The hypothesis generated by our subgroup analysis requires confirmation by a specific, randomized trial, including only patients undergoing hand-sewn closure of the pancreatic stump after distal pancreatectomy.Trial registration: INS-621000-0760.

Uncertainty remains regarding antithrombotic treatment in cervical artery dissection. This analysis aimed to explore whether certain patient profiles influence the effects of different types of antithrombotic treatment.

This was a post hoc exploratory analysis based on the per-protocol dataset from TREAT-CAD (NCT02046460), a randomized controlled trial comparing aspirin to anticoagulation in patients with cervical artery dissection. We explored the potential effects of distinct patient profiles on outcomes in participants treated with either aspirin or anticoagulation. Profiles included (1) presenting with ischemia (no/yes), (2) occlusion of the dissected artery (no/yes), (3) early versus delayed treatment start (median), and (4) intracranial extension of the dissection (no/yes). Outcomes included clinical (stroke, major hemorrhage, death) and magnetic resonance imaging outcomes (new ischemic or hemorrhagic brain lesions) and were assessed for each subgroup in separate logistic models without adjustment for multiple testing.

All 173 (100%) per-protocol participants were eligible for the analyses. Participants without occlusion had decreased odds of events when treated with anticoagulation (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.07-0.86). This effect was more pronounced in participants presenting with cerebral ischemia (n = 118; OR = 0.16, 95% CI = 0.04-0.55). In the latter, those with early treatment (OR = 0.26, 95% CI = 0.07-0.85) or without intracranial extension of the dissection (OR = 0.34, 95% CI = 0.11-0.97) had decreased odds of events when treated with anticoagulation.

Anticoagulation might be preferable in patients with cervical artery dissection presenting with ischemia and no occlusion or no intracranial extension of the dissection. These findings need confirmation. ANN NEUROL 2024;95:886-897.