Overall Risk Of Bias Research Articles

Viscoelastic haemostatic assays to guide therapy in elective surgery: an updated systematic review and meta-analysis.

Patients undergoing major surgery frequently experience major uncontrolled bleeding. The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy of using viscoelastic haemostatic assays to manage peri-operative bleeding in elective surgery. We searched PubMed/MEDLINE and Embase databases for randomised controlled trials according to pre-determined criteria. The primary outcomes were blood product requirements; duration of stay in the operating theatre or ICU; and surgical reintervention rate. We included 20 randomised controlled trials. The overall risk of bias was low to moderate. Twelve studies used thromboelastography-based transfusion algorithms, while eight used thromboelastometry. Viscoelastic haemostatic assay-guided therapy was associated with a statistically significant reduction in transfusion of red blood cells (standardised mean difference (95%CI) 0.16 (-0.29 to 0.02)), platelets (standardised mean difference (95%CI) -0.33 (-0.56 to -0.10)) and fresh frozen plasma (standardised mean difference (95%CI) -0.64 (-1.01 to -0.28)). There was no evidence of an effect of viscoelastic haemostatic assay-guided therapy on surgical reintervention (relative risk (95%CI) 1.09 (0.70-1.69)). Viscoelastic haemostatic assay-guided therapy was associated with lower blood loss and shorter ICU duration of stay. There was no evidence of any effect on total duration of stay and all-cause mortality. Viscoelastic haemostatic assay-guided therapy may reduce peri-operative blood product transfusion requirements and blood loss during major elective surgery, with no discernible effect on patient-centred outcomes. The overall quality of evidence was modest.

NCOG-13. ASSESSING CAREGIVER OUTCOMES OF PRIMARY BRAIN TUMOR PATIENTS: A SYSTEMATIC REVIEW OF THE LITERATURE

Abstract BACKGROUND Family caregivers in neuro-oncology are known to have high levels of unmet support needs. Intervention trials and effective support options are scarce. The Response Assessment in Neuro-Oncology (RANO-) Cares working group has been established to determine standards of caregiver outcomes (CO) research reporting in neuro-oncology. We present the current state of methodological quality of reporting on neuro-oncology caregiver outcomes in randomized controlled trials (RCTs). METHODS A systematic literature review (PubMed/Medline, Embase, Web of Science, Emcare, Cochrane Library, PsycINFO; July 2023) was performed to assess to what degree RCTs assessing outcomes of family caregivers of adult primary brain tumor patients adhere to established reporting standards. Using Covidence, screening and data extraction was independently performed by two researchers, with a third guiding consensus. A 33-item checklist (23 applicable to secondary analysis reports) based on the International Society for Quality of Life (ISOQOL) Research criteria for patient-reported outcome reporting was utilized to assess reporting standards. Risk of bias was assessed per RCT. RESULTS Fifteen publications (12 unique RCTs) included 684 neuro-oncology caregivers, with low overall risk of bias. Ten publications (66%) reported on COs as a primary aim and eight (80%) of these satisfied ≥2/3 of the key methodological criteria. Of the five secondary analysis reports (33%) two met ≥2/3 of applicable key criteria. Criteria often missed are related to sample size calculations, details on statistical approaches, discussion of limitations and clinical significance of studies. Only three of the 12 RCTs were definitive trials aimed at improving COs and five should be considered as pilot or feasibility studies. CONCLUSION RCTs investigating neuro-oncology COs have high reporting standards and risk of bias was low. Future studies should focus on specific caregiver interventions to reduce high caregiver burden and with that patients’ quality of life.

A Systematic Review of Dietary Lifestyle Interventions for Neuropathic Pain

Background/Objectives: Chronic severe neuropathic pain (NP) affects one in 10 individuals over the age of 30 in North America. Standard pharmacological interventions are associated with significant side effects and have limited effectiveness. Diets seeking to improve physiological health, support gut barrier integrity, and decrease systemic inflammation have recently emerged as powerful tools conferring neuroprotective and anti-inflammatory effects, potentially reducing the overall morbidity and mortality of multiple neurological and metabolic diseases. This systematic review aimed to synthesize the literature around NP outcomes following dietary interventions compared to routine standard of care. Methods: Following PRISMA guidelines, an initial search yielded 15,387 records after deduplication. Six interventional trials specifically assessing dietary interventions for neuropathic pain were included and analyzed. The dietary lifestyle interventions included low-fat plant-based, plant-based fasting-mimicking, low-calorie, potassium-reduced, gluten-free, and intermittent high-protein/Mediterranean diets. Results: The included studies described some statistically significant improvements in pain severity on objective quantitative sensory testing, electrophysiology, imaging, and subjective questionnaires. The overall risk of bias was moderate, with only one trial demonstrating a low risk of bias across all assessed domains. No serious adverse events were identified, and dietary interventions were generally well tolerated. Conclusions: The data collected and synthesized in this systematic review indicate that dietary lifestyle interventions may offer a low-risk, low-cost, low-tech option for chronic neuropathic pain management, potentially improving quality of life and reducing overall morbidity. However, given substantial variability across studies and a moderate risk of bias, further research is warranted to substantiate these findings.

The Efficacy of Active Warming in Prehospital Trauma Care: A Systematic Review and Meta-Analysis

Background/Objectives: Hypothermia can affect multiple organ systems and reduce patient comfort and is an independent predictor of mortality in trauma patients. Early prevention and management prehospitally is critical and can be approached by “warming” patients using active and/or passive measures. Therefore, this systematic review aimed to determine the efficacy of prehospital active warming (AW) in trauma patients. Methods: MEDLINE, Embase, Web of Science and CENTRAL were searched up to June 2024 for studies meeting our inclusion and exclusion criteria. Six studies were identified: four randomised controlled trials (RCTs), a non-randomised trial and an observational study. A risk-of-bias assessment was conducted using either the Cochrane Risk of Bias 2 tool or the ROBINS-I tool. Results: For the primary outcome of end core body temperature (CBT), our meta-analysis calculated a statistically significant mean difference of 0.62 °C ([95%CI: 0.17, 1.07], p = 0.007), favouring AW. For the secondary outcomes of end heart rate and end systolic blood pressure, the mean differences favoured the AW and control groups, respectively, but were not statistically significant (p = 0.45 and p = 0.64). Two of the four RCTs had an overall moderate to high risk of bias, whilst the two observational studies had a high risk of bias. Conclusions: Overall, our results suggest that AW may be effective at managing CBT, but our results are limited by a small sample size, a serious/high overall risk of bias and variable study characteristics. Larger, high-quality studies are needed to inform clinical practice and guidelines.

Comparison of first-line chemotherapy regimens in unresectable locally advanced or metastatic pancreatic cancer: a systematic review and Bayesian network meta-analysis

In advanced pancreatic ductal adenocarcinoma (PDAC), first-line chemotherapy is the standard of care. Due to the absence of head-to-head comparisons in clinical trials, we performed this systematic review and network meta-analysis to compare treatment options for PDAC in terms of their efficacy and toxicity. PubMed, the Cochrane Central Register of Controlled Trials, Embase, and oncological meetings websites were searched until Nov 15, 2023. We included phase 2-3 randomised controlled trials published after Jan 1, 2000, evaluating first-line treatments in patients with previously untreated, unresectable, locally advanced or metastatic PDAC. Primary endpoints assessed were progression-free survival and overall survival. Summary data were extracted from published reports. The deviance information criterion was used to choose between a random-effects or fixed-effects model. Hazard ratios (HRs) with 95% credible intervals were estimated using a Bayesian approach. The risk of bias was evaluated using the Cochrane Risk of Bias 2 (RoB 2) tool and studies were graded as low, some concerns, or high risk of bias. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. This systematic review and network meta-analysis is registered with PROSPERO, CRD42023450330. 6050 records were screened and 79 randomised controlled trials (22 168 patients) were included in the analysis. Gemcitabine was the most frequent comparator (in 50 [63%] of 79 trials) and was considered as the reference treatment. A fixed-effect model was used to analyse the primary outcomes. Regarding progression-free survival (71 trials, 19 479 patients), the most effective treatments were gemcitabine plus nab-paclitaxel alternating folinic acid, fluorouracil, and oxaliplatin ([FOLFOX] HR 0·32, 95% credible interval 0·22-0·47), cisplatin, nab-paclitaxel, capecitabine, and gemcitabine ([PAXG] 0·35, 0·22-0·55), and liposomal irinotecan in combination with fluorouracil, leucovorin, and oxaliplatin ([NALIRIFOX] 0·43, 0·34-0·54), followed by fluorouracil, leucovorin, irinotecan, and oxaliplatin ([FOLFIRINOX] 0·55, 0·47-0·65) and gemcitabine plus nab-paclitaxel (0·62, 0·54-0·72). Similar results were observed for overall survival (79 trials, 22 104 patients): PAXG (HR 0·40, 95% credible interval 0·25-0·65), gemcitabine plus nab-paclitaxel alternating FOLFOX (0·46, 0·32-0·66), and NALIRIFOX (0·56, 0·45-0·70) had the highest benefit, followed by FOLFIRINOX (0·66, 0·56-0·78) and gemcitabine plus nab-paclitaxel (0·67, 0·59-0·77). The overall risk of bias was low to some concerns. Certainty of evidence was low. Our findings suggest that NALIRIFOX and FOLFIRINOX should be the preferred options for patients who can tolerate these regimens, with gemcitabine plus nab-paclitaxel remaining a viable alternative, particularly in patients unfit for triplet therapy. Phase 3 randomised controlled trials investigating concomitant or sequential quadruplets are warranted. None.

Implants versus autologous tissue flaps for breast reconstruction following mastectomy.

Women who have a mastectomy for breast cancer treatment or risk reduction may be offered different options for breast reconstruction, including use of implants or the woman's own tissue (autologous tissue flaps). The choice of technique depends on factors such as the woman's preferences, breast characteristics, preoperative imaging, comorbidities, smoking habits, prior chest or breast irradiation, and planned adjuvant therapies. To assess the effects of implants versus autologous tissue flaps for postmastectomy breast reconstruction on women's quality of life, satisfaction, and short- and long-term surgical complications. We searched the Cochrane Breast Cancer Group's Specialised Register, CENTRAL, MEDLINE, Embase, and two trials registries in July 2022. We included studies that compared implant-based reconstruction with autologous tissue-based reconstruction following mastectomy for breast cancer treatment or risk reduction. The minimum eligible sample size was 100 participants. Two review authors independently assessed risk of bias and extracted data using standard Cochrane procedures. We used GRADE to assess the certainty of the evidence. Thirty-five non-randomised studies with 57,555 participants met our inclusion criteria. There were nine prospective cohort studies and 26 retrospective cohort studies. We judged 26 studies at serious overall risk of bias and the remaining studies at moderate overall risk of bias. Some studies measured quality of life and satisfaction using the BREAST-Q (scale of 0 to 100, higher is better). Implants may reduce postoperative psychosocial well-being compared with autologous tissue flaps (mean difference (MD) -4.26 points, 95% confidence interval (CI) -4.91 to -3.61; I² = 0%; 6 studies, 3335 participants; low-certainty evidence). Implants may reduce or have little to no effect on postoperative physical well-being compared with autologous tissue flaps, but the evidence is very uncertain (MD -1.92 points, 95% CI -4.44 to 0.60; I² = 87%; 6 studies, 3335 participants; very low-certainty evidence). Implants may reduce postoperative sexual well-being compared with autologous reconstruction (MD -6.63 points, 95% CI -7.55 to -5.72; I² = 0; 6 studies, 3335 participants; low-certainty evidence). Women who undergo breast reconstruction with implants versus autologous tissue flaps may be less satisfied with the breast, but the evidence is very uncertain (MD -8.17 points, 95% CI -11.41 to -4.92; I² = 90%; 6 studies, 3335 participants; very low-certainty evidence). This outcome refers to a woman's satisfaction with breast size, bra fit, appearance in the mirror (clothed or unclothed), and how the breast feels to touch. Women who undergo breast reconstruction with implants versus autologous tissue flaps may be less satisfied with the reconstruction (MD -5.96 points, 95% CI -10.24 to -1.68; I² = 62%; 4 studies, 1196 participants; low-certainty evidence). This outcome refers to whether the aesthetic outcome has met the woman's expectations, the impact surgery has had on her life, and whether she thinks she made the right decision to have the reconstruction. Implants may reduce or have little to no effect on the risk of short-term complications compared with autologous tissue flaps, but the evidence is very uncertain (risk ratio (RR) 0.80, 95% CI 0.63 to 1.03; I² = 91%; 22 studies, 34,244 participants; very low-certainty evidence). Implants may increase long-term complications compared with autologous tissue flaps, but the evidence is very uncertain (RR 1.56, 95% CI 1.09 to 2.22; I² = 94%; 17 studies, 26,930 participants; very low-certainty evidence). Implants may have little to no effect on the need for reintervention compared with autologous tissue flaps, but the evidence is very uncertain (RR 1.23, 95% CI 0.91 to 1.68; I² = 93%; 15 studies, 14,171 participants; very low-certainty evidence). Implants may reduce the duration of surgery compared with autologous tissue flaps, but the evidence is very uncertain (MD -125.04 minutes, 95% CI -131.41 to -118.67; I² = 0; 2 studies, 836 participants; very low-certainty evidence). The findings of this review show that autologous tissue-based reconstruction compared with implant-based reconstruction may improve participant-reported outcomes such as psychosocial well-being, sexual well-being, and satisfaction with the reconstruction. There is also very uncertain evidence to suggest that autologous tissue-based reconstruction increases satisfaction with the breast and reduces the risk of long-term complications compared with implants. Implant-based reconstruction may be a shorter procedure, but the evidence is very uncertain. Despite the growing demand for breast reconstruction, the best technique has not been adequately studied in randomised controlled trials (RCTs), and the evidence provided by non-randomised studies is often unsatisfactory. There is no superior breast reconstruction technique for all women. Future research should focus on the definition of decisional drivers to guide an evidence-based shared decision-making process in reconstructive breast surgery.

Social Disadvantage and Disparities in Chronic Liver Disease: A Systematic Review

Introduction: Social determinants of health (SDOH) may impact chronic liver disease (CLD) outcomes but are not clearly understood. We conducted a systematic review to describe the associations of SDOH with mortality, hospitalizations, and readmissions among patients with CLD. Methods: This review was registered (PROSPERO ID: CRD42022346654) and identified articles through MEDLINE, Embase, Cochrane Library, and Scopus databases. The review included studies that reported SDOH characteristics within the domains of economic stability, health care access, education, social and community context, and the neighborhood built environment. Associated outcomes of interest were mortality, hospitalizations, or readmissions. The Cochrane Risk of Bias in Non-randomized Studies for Exposure (ROBINS-E) was used to assess study quality and risk of bias. Results: A total of 5,205 abstracts were screened, 60 articles underwent full-text review, and 27 articles were included in the final review. Poor economic stability, healthcare access, social support, and household/environmental conditions were associated with higher mortality and hospital readmissions among patients with CLD. Increasing distance (≥25 miles away) from a liver transplantation (LT) center was associated with higher mortality despite increasing access to the LT waitlist. When assessing the overall risk of bias among included studies, most had “Some Concern” (N=13, 48.1%) or “High Risk” (N=11, 40.7%) while a minority had “Very High Risk” (N=3, 11.1%). No studies were categorized as “Low Risk.” Conclusions: Unfavorable SDOH were associated with increased mortality and hospital readmissions among patients with CLD. Rigorous empirical research is needed to identify evidence-based strategies that aim to mitigate disparities among vulnerable populations.

Effectiveness of psychological interventions in endometriosis: a systematic review with meta-analysis.

Endometriosis is a chronic gynecological disease associated with chronic debilitating pain, poor mental health and quality of life. The objective of this paper is to evaluate the effectiveness of psychological interventions aimed at improving the pain, quality of life and mental health of women with endometriosis. A systematic review (SR) of the literature with meta-analysis (MA) was carried out. MEDLINE, Embase, PsycINFO and CENTRAL were searched to locate Randomized Controlled Trials (RCTs). The risk of bias assessment of each study was conducted using the Cochrane Collaboration's RoB 2.0 tool. Seven RCTs were included (N = 757). The data obtained suggest that psychological interventions reduce dyspareunia [standardized mean difference (SMD): -0.54, 95% CI: -0.86, -0.22] and dyschezia [mean difference (MD): -2.90, 95% CI: -4.55, -1.26] and increase mental health levels (SMD: 0.70, 95% CI: 0. 42, 0.99); they also point to a large reduction in levels of trait anxiety (MD: -6.63, 95% CI: -8.27, -4.99) and depression (MD: -2.49, 95% CI: -3.20, -1.79), and a likely reduction in state anxiety (MD: -9.72, 95% CI: -13.11, -6.33) experienced by women with endometriosis. It was also identified that psychological interventions probably slightly reduce pelvic pain and may increase physical health. However, most of the included studies have a high overall risk of bias or have certain concerns, which limit conclusions about the certainty of the evidence. The available evidence indicates that psychological interventions are effective in improving the pain, quality of life and mental health variables of women with endometriosis. https://www.crd.york.ac.uk/prospero/, CRD42024516100.

Effects of Yi Jin Jing on enhancing muscle strength and physical performance in older individuals: a systematic review and meta-analysis.

The aging population is rapidly increasing, leading to physical decline and higher risks of chronic diseases, including sarcopenia, which adversely affects muscle quality and strength. Yi Jin Jing (YJJ), a traditional Chinese exercise method, can enhance flexibility and strength, but evidence regarding its effectiveness in older adults is conflicting. This meta-analysis aims to systematically evaluate the effects of YJJ on muscle strength and physical performance in this demographic. We searched seven electronic databases: China National Knowledge Infrastructure, Wanfang Data, Sinomed, Web of Science, PubMed, Cochrane Library, and EMBASE to identify randomized controlled trials (RCTs). Following PRISMA guidelines, we quantified the effects of YJJ on muscle strength (grip strength, isokinetic strength) and physical performance (chair sit-to-stand, squatting-to-standing, shoulder flexibility, sit-and-reach tests). Treatment effects were calculated using Hedges'g. The Cochrane tool assessed risk of bias, the PEDro scale evaluated methodological quality, and the GRADE method assessed evidence quality. Data analysis was conducted using Stata 17.0 software, utilizing standardized mean differences (SMD) and 95% confidence intervals (CIs). This meta-analysis included 10 RCTs involving 590 participants. The overall risk of bias was assessed to be low. The methodological quality of these studies was generally moderate, and the quality of the main results varied from low to moderate. The findings revealed that YJJ had considerable effects on the chair sit-to-stand test (Hedges'g = 1.06), squatting-to-standing test (Hedges'g = 1.08), and small to moderate effects on handgrip strength (Hedges'g = 0.25), 60°/s extensor peak torque (Hedges'g = 0.47), 60°/s extensor average power (Hedges'g = 0.31), 60°/s extensor total work (Hedges'g = 0.29), 60°/s flexor peak torque (Hedges'g = 0.42), 60°/s flexor average power (Hedges'g = 0.37), and 180°/s extensor peak torque (Hedges'g = 0.29), and left shoulder flexibility (Hedges'g = 0.4). However, there were no significant improvement effects in 180°/s extensor average power (Hedges'g = 0.19), 180°/s extensor total work (Hedges'g = 0.11), 180°/s flexor peak torque (Hedges'g = 0.01), 180°/s flexor average power (Hedges'g = -0.08), right shoulder flexibility (Hedges'g = 0.09), and sit-and-reach test (Hedges'g = 0.15). YJJ significantly enhances specific aspects of physical performance, particularly chair sit-to-stand and squatting-to-standing tests, while showing small and moderate improvements in handgrip strength and knee muscle strength. However, it had no significant effects on other metrics, including shoulder flexibility and sit-and-reach tests. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024530487, Registration number: CRD42024530487.

Predicting Biochemical Recurrence of Prostate Cancer Post-Prostatectomy Using Artificial Intelligence: A Systematic Review.

Background/Objectives: Biochemical recurrence (BCR) after radical prostatectomy (RP) is a significant predictor of distal metastases and mortality in prostate cancer (PCa) patients. This systematic review aims to evaluate the accuracy of artificial intelligence (AI) in predicting BCR post-RP. Methods: Adhering to PRISMA guidelines, a comprehensive literature search was conducted across Medline, Embase, Web of Science, and IEEE Xplore. Studies were included if they utilised AI to predict BCR in patients post-RP. Studies involving patients who underwent radiotherapy or salvage RP were excluded. This systematic review was registered on PROSPERO (International prospective register of systematic reviews) under the ID CRD42023482392. Results: After screening 9764 articles, 24 met the inclusion criteria. The included studies involved 27,216 patients, of whom 7267 developed BCR. AI algorithms developed using radiological parameters demonstrated higher predictive accuracy (median AUROC of 0.90) compared to algorithms based solely on pathological variables (median AUROC of 0.74) or clinicopathological variables (median AUROC of 0.81). According to the Prediction Model Risk of Bias Assessment Tool (PROBAST), the overall risk of bias was unclear in three studies due to ambiguous inclusion criteria and the exclusion of many patients because of missing follow-up data. In seven studies, the developed AI outperformed or was at least equivocal to traditional methods of BCR prediction. Conclusions: AI shows promise in predicting BCR post-RP, particularly when radiological data were used in its development. However, the significant variability in AI performance and study methodologies highlights the need for larger, standardised prospective studies with external validation prior to clinical application.

Efficacy of an erector spinae plane block for renal colic: a systematic review and meta-analysis

Background and aimThe passage of kidney stones through the ureter creates renal colic, a severe visceral abdominal pain. Renal colic is typically managed with non-steroidal anti-inflammatory drugs and opioids. Yet,...

Effectiveness of Acupuncture in Improving Quality of Life for Patients with Advanced Cancer: A Systematic Review and Meta-Analysis.

To investigate the effect of acupuncture on advanced cancer patients by meta-analysis. Nine databases (the Cochrane Central Register of Controlled Trials, MEDLINE, Web of Science, Embase, China National Knowledge Infrastructure, the Cumulative Index to Nursing and Allied Health Literature, Chinese Biomedical Literature Database, China Science and Technology Journal Database, and WanFang Data) were searched for randomized controlled trials (RCTs) on acupuncture in advanced cancer patients published from inception to February 13, 2023 and updated to June 1, 2023. Primary outcomes were quality of life (QOL), while secondary outcomes were pain, fatigue, and adverse events (side effects). Data synthesis was performed using RevMan V.5.3 to calculate pooled effect sizes. RoB-2 was used for the risk of bias, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. Totally 17 RCTs involving 1,178 participants were included, 15 of which were pooled for meta-analysis. Most studies demonstrated some concern for the overall risk of bias. The pooled data indicated that acupuncture was associated with improved QOL [mean difference (MD)=6.67, 95% confidence interval (CI): 5.09 to 8.26], pain (MD=-1.18, 95% CI -2.28 to -0.08), and adverse events (risk ratio=0.30, 95% CI: 0.26 to 0.57) compared with control groups. Fatigue outcome was not included. Heterogeneity was substantial, and GRADE evidence was very low for both QOL and pain. Acupuncture could benefit patients with advanced cancer and is considered safe compared with usual care. However, the evidence regarding QOL and pain outcomes requires further validation. It is crucial to encourage the development of high-quality studies to strengthen this evidence. (Registry No. CRD42023423539).

Vitamin D serum levels and temporomandibular disorders: A systematic review and meta-analysis

ObjectiveThis systematic review evaluates the connection between vitamin D serum levels, deficiency, and temporomandibular disorders (TMD), offering a meta-analysis of the existing evidence in this domain. DesignThe Scopus, ISI Web of Science, and Pubmed databases were searched for human studies concerning the connection between vitamin D and TMD comprising a control group. A random-effect model with forest plots was used for vitamin D serum levels mean difference (MD), vitamin D deficiency odds ratio (OR), and risk difference (RD) between subjects with and without TMD. Subgroup analysis was conducted based on ethnicity, overall risk of bias, TMD diagnosis method, and study designs. A p-value lower than 0.05 was considered significant. The certainty of the meta-evidence was evaluated according to the GRADE approach. ResultsOf the 2621 identified unique records, 15 studies were included in the study, eight of which were considered for the meta-analysis. The meta-analysis revealed a significant vitamin D deficiency OR (3.85; 95 % CI: 2.35 – 5.43; Certainty: Low) and RD (22 %; 95 % CI: 11 % - 32 %; Certainty: Very low), and vitamin D serum levels MD (-5.03 ng/mL; 95 % CI: −9.92 – −0.13; Certainty: Very low) between subjects with and without TMD. Among subgroup analyses, only the difference in vitamin D MD between Middle Eastern and European patients was significant (P < 0.01). ConclusionConsidering the low to very low certainty of the evidence, vitamin D serum levels are significantly lower, and vitamin D deficiency is significantly more prevalent in TMD patients.

Risk Prediction Models for Adverse Drug Reactions and Adverse Drug Events in Older Adults – A Systematic Review and Meta-analysis

Abstract Background Adverse drug reactions (ADRs) and adverse drug events (ADEs) are common and result in significant morbidity, mortality and healthcare costs. As the world’s population ages, the consumption of medications and healthcare will increase. Models predicting ADR risks in older adults have previously been found to lack reliability and validity. The aim of this systematic review and meta-analysis is to provide an updated, comprehensive quality assessment and analysis of ADR-risk prediction tools in older adults. Methods Standard computerised-databases and citations were searched (2012 to 2023) to identify relevant peer-reviewed studies. Studies which developed and/or validated an ADR/ADE prediction model for use in older adults were included. Four studies from a previous systematic review were also included. The TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) guidelines were used to evaluate each of the included studies. Random effects models were used to derive a pooled discrimination estimate (area under the receiver operation curve; AUROC) for model development studies and model validation studies. The prediction model risk of bias assessment tool (PROBAST) was applied to evaluate bias. Results Five out of 11,481 titles, plus four previous studies, met all inclusion criteria and underwent TRIPOD evaluation. Meta-analysis resulted in a favourable pooled AUROC 0.75 (95% CI 0.57, 0.87; I-squared= 96.65%) for model development studies and 0.70 (95% CI 0.57, 0.80; I-squared= 90.53%) for model validation studies but there was substantial heterogeneity. Studies had poor adherence (range 32-50%; median 44%; IQR 11.5%) to TRIPOD guidelines. The overall risk of bias was high for all included studies. Conclusion Seven risk prediction models were identified, all exhibiting poor adherence to TRIPOD guidelines which may question the investigational rigor of the studies and their usability. This underscores the need for the development of a validated, robust and reliable tool worthy of implementation and testing in a real-world setting.

Integrating randomized controlled trials and non-randomized studies of interventions to assess the effect of rare events: a Bayesian re-analysis of two meta-analyses

BackgroundThere is a growing trend to include non-randomised studies of interventions (NRSIs) in rare events meta-analyses of randomised controlled trials (RCTs) to complement the evidence from the latter. An important consideration when combining RCTs and NRSIs is how to address potential bias and down-weighting of NRSIs in the pooled estimates. The aim of this study is to explore the use of a power prior approach in a Bayesian framework for integrating RCTs and NRSIs to assess the effect of rare events.MethodsWe proposed a method of specifying the down-weighting factor based on judgments of the relative magnitude (no information, and low, moderate, serious and critical risk of bias) of the overall risk of bias for each NRSI using the ROBINS-I tool. The methods were illustrated using two meta-analyses, with particular interest in the risk of diabetic ketoacidosis (DKA) in patients using sodium/glucose cotransporter-2 (SGLT-2) inhibitors compared with active comparators, and the association between low-dose methotrexate exposure and melanoma.ResultsNo significant results were observed for these two analyses when the data from RCTs only were pooled (risk of DKA: OR = 0.82, 95% confidence interval (CI): 0.25–2.69; risk of melanoma: OR = 1.94, 95%CI: 0.72–5.27). When RCTs and NRSIs were directly combined without distinction in the same meta-analysis, both meta-analyses showed significant results (risk of DKA: OR = 1.50, 95%CI: 1.11–2.03; risk of melanoma: OR = 1.16, 95%CI: 1.08–1.24). Using Bayesian analysis to account for NRSI bias, there was a 90% probability of an increased risk of DKA in users receiving SGLT-2 inhibitors and an 91% probability of an increased risk of melanoma in patients using low-dose methotrexate.ConclusionsOur study showed that including NRSIs in a meta-analysis of RCTs for rare events could increase the certainty and comprehensiveness of the evidence. The estimates obtained from NRSIs are generally considered to be biased, and the possible influence of NRSIs on the certainty of the combined evidence needs to be carefully investigated.

Cognitive behavioural therapy for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis

BackgroundTreatment of fatigue is important for many patients with multiple sclerosis (MS). While pharmacological options have not shown consistent benefit, psychological interventions offer another avenue of treatment. Cognitive behavioural therapy (CBT) involves strategies to change maladaptive cognition and illness behaviours that modulate how patients with MS respond to fatigue. The aim of this study was to perform a systematic review and meta-analysis to determine the effectiveness of CBT for the treatment of fatigue in patients with MS. MethodsFive databases (Cochrane Central Register of Controlled Trials, MEDLINE/PubMed, Embase, Emcare and PsycINFO) were searched up until 31 July 2023. Randomised controlled trials involving adult patients with MS and fatigue, comparing CBT with another intervention or usual treatment were included. Studies were required to measure fatigue severity and/or the impact of fatigue as the primary outcome(s). Each study was assessed for bias using the Cochrane Risk of Bias tool version 2. Studies with sufficient data were used for meta-analysis to quantify the short- and long-term effects of CBT on MS-related fatigue. The level of certainty provided by the body of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. ResultsEight studies were included in the review and six studies contributed to the meta-analysis. Most studies had a low overall risk of bias. CBT interventions differed in the number, duration and frequency of sessions, mode of delivery and therapist. There were significant short- (standardised mean difference (SMD) -0.58, 95% confidence interval (95%CI) -0.85 to -0.31, P-value < 0.0001) and long-term (SMD -0.36, 95%CI -0.52 to -0.19, P-value < 0.0001) effects supporting CBT. The evidence provided a low level of certainty for the short-term effect because of heterogeneity of results and possible publication bias, while there was high certainty for the long-term result. ConclusionThe study provides secondary evidence that CBT has moderate short-term and small long-term effects in reducing fatigue in patients with MS. CBT should be regarded as a viable evidence-based intervention, particularly in the absence of established alternatives. Future research should identify the ideal characteristics of a fatigue-specific CBT intervention, patient factors that predict treatment response and strategies to maintain initial improvements over time.

Assistive technologies, including orthotic devices, for the management of contractures in adults after a stroke.

Contractures (reduced range of motion and increased stiffness of a joint) are a frequent complication of stroke. Contractures can interfere with function and cause cosmetic and hygiene problems. Preventing and managing contractures might improve rehabilitation and recovery after stroke. To assess the effects of assistive technologies for the management of contractures in adults after a stroke. We searched CENTRAL, MEDLINE, Embase, five other databases, and three trials registers in May 2022. We also searched for reference lists of relevant studies, contacted experts in the field, and ran forward citation searches. Randomised controlled studies (RCTs) that used electrical, mechanical, or electromechanical devices to manage contractures in adults with stroke were eligible for inclusion in this review. We planned to include studies that compared assistive technologies against no treatment, routine therapy, or another assistive technology. Three review authors (working in pairs) selected all studies, extracted data, and assessed risk of bias. The primary outcomes were passive joint range of motion (PROM) with and without standardised force, and indirect measures of PROM. The secondary outcomes included hygiene. We also wanted to evaluate the adverse effects of assistive technology. Effects were expressed as mean differences (MDs) or standardised mean differences (SMDs) with 95% confidence intervals (CIs). Seven studies fulfilled the inclusion criteria. Five of these were meta-analysed; they included 252 adults treated in acute and subacute rehabilitation settings. All studies compared assistive technology with routine therapy; one study also compared assistive technology with no treatment, but we were unable to obtain separate data for stroke participants. The assistive technologies used in the studies were electrical stimulation, splinting, positioning using a hinged board, and active repetitive motor training using a non-robotic device with electrical stimulation. Only one study applied stretching to end range. Treatment duration ranged from four to 12 weeks. The overall risk of bias was high for all studies. We are uncertain whether: • electrical stimulation to wrist extensors improves passive range of wrist extension (MD -7.30°, 95% CI -18.26° to 3.66°; 1 study, 81 participants; very low-certainty evidence); • a non-robotic device with electrical stimulation to shoulder flexors improves passive range of shoulder flexion (MD -9.00°, 95% CI -25.71° to 7.71°; 1 study; 50 participants; very low-certainty evidence); • assistive technology improves passive range of wrist extension with standardised force (SMD -0.05, 95% CI -0.39 to 0.29; four studies, 145 participants; very low-certainty evidence): • a non-robotic device with electrical stimulation to elbow extensors improves passive range of elbow extension (MD 0.41°, 95% CI -0.15° to 0.97°; 1 study, 50 participants; very low-certainty evidence). One study reported the adverse outcome of pain when using a hinged board to apply stretch to wrist and finger flexors, and another study reported skin breakdown when using a thumb splint. No studies reported hygiene or indirect measures of PROM. Only seven small RCTs met the eligibility criteria of this review, and all provided very low-certainty evidence. Consequently, we cannot draw firm conclusions on the effects of assistive technology compared with routine therapy or no therapy. It was also difficult to confirm whether there is a risk of harm associated with treatment using assistive technology. Future studies should apply adequate treatment intensity (i.e. magnitude and the duration of stretch) and use valid and reliable outcome measures. Such studies might better identify the role of assistive technology in the management of contractures in adults after a stroke.

Reporting standards in randomized controlled trials involving neuro-oncology caregivers: A systematic review report from the RANO-Cares working group

Abstract BACKGROUND Family caregivers in neuro-oncology (e.g., spouse, family member, friend to a patient) have high unmet support needs, yet intervention trials and effective support options are scarce. The Response Assessment in Neuro-Oncology (RANO-) Cares working group investigated the methodological quality of neuro-oncology caregiver outcomes reporting in randomized controlled trials (RCTs). METHODS A systematic review was performed to evaluate to what extent RCTs assessing outcomes of caregivers of adult primary brain tumor patients adhere to minimum reporting standards. A 33-item checklist (23 applicable to secondary analysis reports) based on the International Society for Quality of Life Research (ISOQOL) criteria for patient-reported outcome (PRO) reporting was used. Risk of bias was assessed per RCT. RESULTS Fifteen publications from 11 unique RCTs included 676 neuro-oncology caregivers, with low overall risk of bias. Ten publications (66%) reported on caregiver outcomes as a primary aim, of which eight (80%) satisfied ≥2/3 of the key methodological criteria. Of the five secondary analysis reports (33%) two (40%) met ≥2/3 of applicable key criteria. Criteria often not reported adequately included sample size calculations (reported adequately in n=8, 53%), participant flow (n=9, 60%) window for data collection (n=1, 6%), and extent of (n=10, 66%), reasons for (n=9, 60%), and statistical approaches in dealing with (n=4, 26%) missing data. CONCLUSION Whilst there are opportunities to enhance reporting standards, RCTs that include neuro-oncology caregiver outcomes generally adhere to high quality reporting standards, and have low risk of bias, indicating good potential to impact clinical practice.

Comparing the effectiveness and safety of videolaryngoscopy and direct laryngoscopy for endotracheal intubation in the paediatric emergency department: a systematic review and meta-analysis.

Endotracheal intubation is an uncommon procedure for children in the emergency department but can be technically difficult and cause significant adverse effects. Videolaryngoscopy (VL) offers improved first-pass success rates over direct laryngoscopy (DL) for both adults and children undergoing elective surgery. This systematic review was designed to evaluate current evidence regarding how the effectiveness and safety of VL compares to DL for intubation of children in emergency departments. Four databases (MEDLINE, Embase, CENTRAL and Web of Science) were searched on 11th May 2023 for studies comparing first-pass success of VL and DL for children undergoing intubation in the emergency department. Studies including adult patients or where intubation occurred outside of the emergency department were excluded. Quality assessment of included studies was carried out using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. Meta-analysis was undertaken for first-pass success and adverse event rate. Ten studies met the inclusion criteria representing 5,586 intubations. All included studies were observational. Significantly greater first-pass success rate was demonstrated with VL compared to DL (OR 1.64, 95% CI [1.21-2.21], p = 0.001). There was no significant difference in risk of adverse events between VL and DL (OR 0.79, 95% CI [0.52-1.20], p = 0.27). The overall risk of bias was moderate to serious for all included studies. VL can offer improved first-pass success rates over DL for children intubated in the emergency department. However, the quality of current evidence is low and further randomised studies are required to clarify which patient groups may benefit most from use of VL. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=415039, Identifier CRD42023415039.

Sarcopenia interventions in long-term care facilities targeting sedentary behaviour and physical inactivity: A systematic review.

Sedentary behaviour and physical inactivity are independent risk factors for sarcopenia for long-term care facility residents. Understanding the components, mechanisms and context of interventions that target change in these risk factors can help optimize sarcopenia management approaches. This study aimed to identify, appraise and synthesize the interventions targeting sedentary behaviour and physical inactivity, construct a Theory of Change logic model, inform complex sarcopenia intervention development and identify areas for improvement. Eight electronic databases, including Embase and Web of Science, were searched for eligible interventional studies from inception until February 2024. Narrative synthesis was used. The Theory of Change was applied to develop a logic model presenting the synthesized results. A Cochrane risk of bias assessment tool was used for quality appraisal. The study included 21 articles involving 1014 participants, with mean ages ranging from 72.5 to 90.4years. The proportion of female participants ranged from 8.0% to 100.0%. The applied sarcopenia diagnosis criteria varied, including those of the Asian Working Group for Sarcopenia and the European Working Group on Sarcopenia in Older People. The overall risk of bias in the included studies was moderate. Interventions primarily targeted physical inactivity, with resistance training being the most common intervention type. The reporting of intervention adherence was insufficient (only 11 out of 21 included studies provided adherence reports), and adherence overall and by intervention type was not possible to discern due to inconsistent criteria for high adherence across these studies. Four categories of intervention input were identified: educational resources; exercise equipment and accessories; monitoring and tailoring tools; and motivational strategies. Intervention activities fell into five categories: determining the intervention plan; educating; tailoring; organizing, supervising, assisting and motivating; and monitoring. While sarcopenia-related indicators were commonly used as desired outcomes, intermediate outcomes (i.e., sedentary time and physical activity level) and other long-term outcomes (i.e., economic outcomes) were less considered. Contextual factors affecting intervention use included participant characteristics (i.e., medical condition and education level) and intervention provider characteristics (i.e., trustworthiness). The findings led to the development of a novel logic model detailing essential components for interventions aimed at managing sarcopenia in long-term care facilities, with a focus on addressing sedentary behaviour and physical inactivity. Future sarcopenia interventions in long-term care facilities should fully attend to sedentary behaviour, enhance adherence to interventions through improved education, monitoring, tailoring and motivation and establish an agreed standard set of outcome measures.