Randomized Controlled Trials Research Articles

Application of norepinephrine in the treatment of septic shock: a meta-analysis.

To systematically evaluate the efficacy and safety of norepinephrine in the treatment of septic shock. Literature retrieval of eligible randomized controlled trials (RCTs) on norepinephrine in the treatment of septic shock was performed in three English databases including PubMed, Web of Science, and Medline from database establishment to October 1, 2023. The Cochrane risk bias tool was used to evaluate the quality of the included literature. RevMan 5.3 software was used for meta-analysis. A total of 14 RCTs were included in this study, and the risk of bias was low. Our meta-analysis showed that the norepinephrine group had significantly better outcomes in reducing the 28-day mortality rate (RR = 0.92; 95% CI, 0.86 ~ 0.99; P = 0.03), the incidence of arrhythmia (RR = 0.54; 95% CI, 0.45 ~ 0.64; P < 0.0001), and the length of stay in intensive care unit (ICU) (MD = - 1.03; 95% CI, - 1.85 to approximately - 0.21; P = 0.01) than those of the control group. However, there were no statistically significant differences in in-hospital mortality rate (RR = 0.97; 95% CI, 0.90 ~ 1.04; P = 0.4), the 90-day mortality rate (RR = 1.07; 95% CI, 0.97 ~ 1.18; P = 0.15), length of hospital stay (MD = 0.03; 95% CI, - 1.13 ~ 1.18; P = 0.96), and the rate of achieving target MAP (RR = 1.27; 95% CI, 0.72 ~ 2.26; P = 0.41) between the norepinephrine group and the control group. Norepinephrine has the advantages of improving 28-day mortality, shortening ICU hospitalization time, and reducing the incidence of arrhythmia. It is a more effective choice for the treatment of septic shock than other vasopressors, and the incidence of arrhythmia is low.

Acupuncture for uremic pruritus: A systematic review and meta-analysis protocol.

Uremic pruritus (UP) or chronic kidney disease-associated pruritus (CKD-aP) is one of the most intractable dermatologic symptom in patients with chronic kidney disease. Several randomized controlled trials (RCTs) have been conducted to investigate the antipruritic effects of acupuncture on UP/CKD-aP and suggested a significant therapeutic effect, while the evidence supporting the application of acupuncture is limited. This study will assess the efficacy and safety of acupuncture for patients with UP/CKD-aP. Data Sources: RCTs will be searched in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, Wanfang Database, VIP Database, the WHO International Clinical Trials Registry Platform portal and www.ClinicalTrials.gov from inception to 31st August 2024. Study eligibility criteria: RCTs in English and Chinese conducted on UP/CKD-aP patients will be included. Participants: Adult patients diagnosed with UP/CKD-aP will be included. Interventions: All acupuncture interventions in the management of UP/CKD-aP will be included, compared with no treatment, placebo or sham acupuncture, or other treatment agents. Outcome measures: The primary outcome will be the change in the severity of itching evaluated by validated scales. Study appraisal and svnthesis methods: If necessary, a meta-analysis will be performed for the pooled therapeutic effect by Review Manager 5.3, or a qualitative descriptive analysis will be presented. The data will be transformed into the risk ratio (RR) for binary data and the mean difference (MD) or standardized MD for continuous data for analysis. This review will update evidence of RCTs evaluating acupuncture for UP/CKD-aP. Anticipated challenges contain the methodological and clinical heterogeneity in terms of evaluation tools and acupuncture interventions within included studies. It will benefit patients and impact health-care decision-making regarding the models of care that are feasible for patients. PROSPERO CRD42021257001.

Stem cell therapy for non-ischemic dilated cardiomyopathy: a systematic review and meta-analysis

BackgroundStem cell therapy is the transplantation of human cells to aid the healing of damaged or wounded tissues and cells. Only a few small-scale trials have been conducted to investigate stem cell therapy for non-ischemic dilated cardiomyopathy (DCM). We aimed to perform a systematic review and meta-analysis to assess the efficacy and safety of stem cell therapy for DCM.MethodsA comprehensive search of the databases of PubMed, Embase, Web of Science Core Collection, Cochrane Library, and ProQuest was conducted from their inception to June 30, 2024, to access randomized controlled trials (RCTs) that were centered on stem cell therapy for DCM. The primary outcome was left ventricular ejection fraction (LVEF), and the secondary outcomes included left ventricular end-diastolic dimension (LVEDD), left ventricular end-diastolic volume (LVEDV), 6-min walk test (6MWT), NYHA functional classification, quality of life (QoL) such as Minnesota Living with Heart Failure Questionnaire (MLHFQ) and Kansas City Cardiomyopathy Questionnaire (KCCQ), N-terminal pro-brain natriuretic peptide (NT-proBNP), and VO2 peak. Moreover, major adverse cardiovascular events (MACEs) were also recorded. The Cochrane risk-of-bias assessment tool was used to evaluate the quality of the included RCTs, and the certainty of the evidence was assessed using the GRADE method. Sensitivity analysis was taken into consideration to determine the stability of the results. This review was registered with PROSPERO (CRD42024568912).ResultsEleven RCTs involving 637 participants were included in the quantitative analysis. The results indicated that there was a significant increase in mean LVEF (MD = 4.84, 95% CI 3.25–6.42, P < 0.00001) and considerable decrease in LVEDV (MD = − 29.51, 95% CI − 58.07 to − 0.95, P = 0.04) and NT-proBNP (MD = − 737.55, 95% CI − 904.28 to − 570.82, P < 0.00001) in DCM patients treated with stem cell therapy compared with controls. Stem cell therapy was also related to the improvement in functional capacity, as evaluated by 6MWT (MD = 44.32, 95% CI 34.70 − 53.94, P < 0.00001) and NYHA functional classification (MD = − 0.63, 95% CI − 0.96 to − 0.30, P = 0.0002). It also had positive effects on improving QoL, including significantly decreasing MLHFQ score (MD = − 16.60, 95% CI − 26.57 to − 6.63, P = 0.001) and increasing the KCCQ score (MD = 14.76, 95% CI 7.76 − 21.76, P < 0.0001). No significant differences were observed in LVEDD, VO2 peak, and MACEs between the two groups. The GRADE analysis revealed that the evidence was graded from low to moderate. Sensitivity analysis of the results suggested that the results were stable.ConclusionThe systematic review and meta-analysis indicates that stem cell therapy may be an effective and safe approach to improve cardiac function and quality of life in DCM patients. Nevertheless, given the limitations of existing studies, larger well-designed RCTs are required to confirm and support our findings.

Influence of study characteristics on harm estimates from randomised controlled trials in patients with inflammatory arthritis receiving biological or synthetic antirheumatic drugs: a meta-epidemiological study

ObjectiveTo examine the association between study characteristics and the harms reported in randomised controlled trials (RCTs) on biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in patients with inflammatory arthritis...

Recurrence of Retinopathy of Prematurity Following Anti-vascular Endothelial Growth Factor (Anti-VEGF) Therapy: A Systematic Review and Meta-Analysis.

Retinopathy of prematurity (ROP) is a neovascular disorder which affects premature infantsand can lead to childhood blindness. Treatment includes laser photocoagulation and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, both effective options. However, laser photocoagulation can lead to refractive errors, while anti-VEGF therapy can result in disease recurrence. Our systematic review aimed to evaluate the recurrence rates of ROP following treatment with anti-VEGF agents compared to other anti-VEGF agents and laser photocoagulation. We also aimed to measure the retreatment intervals and assess successful retreatment rates to identify the most effectivetreatment modality. Our review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included both randomized controlled trials (RCTs) and non-randomized comparative studies (NCS). A thorough search of MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed. Studies were assessed using the Cochrane Risk of Bias (RoB2) tool and the Newcastle-Ottawa Scale (NOS). Random-effects and fixed-effects models were used to measure pooled estimates. The outcomes were reported as risk ratios (RR) and standardized mean differences (SMD). A total of 21 studies (six RCTs and 15NCS) with 6,152 eyes were included. Overall, anti-VEGF agents showed a higher risk of recurrence compared to laser photocoagulation (RR=2.14, 95% CI: 1.06-4.33, p=0.03). Conbercept demonstrated a significantly lower risk of recurrence than laser photocoagulation and ranibizumab (RR=0.47, 95% CI: 0.39-0.58, p<0.00001), while aflibercept showed a higher recurrence risk compared to bevacizumab (RR=12.61, 95% CI: 6.43-24.73, p<0.00001). Bevacizumab was associated with a longer retreatment interval than laser photocoagulation (SMD=0.89, 95% CI: 0.61-1.17, p<0.00001). No significant differences in retreatment success rates between bevacizumab and laser photocoagulation were observed. Anti-VEGF therapy is effective in the treatment of ROP; however, it is associated with a higher risk of recurrence compared to laser photocoagulation. Conbercept shows greater efficacy in reducing recurrence risk and prolonging the retreatment interval compared to ranibizumab. Aflibercept demonstrated inconsistent outcomes. No significant difference in recurrence rates was observed between bevacizumab and ranibizumab. Recurrences occurred significantly later when anti-VEGF therapy was used compared to laser photocoagulation. Successful retreatment rates between bevacizumab and laser photocoagulation were similar.

The Great Controversy of Obstructive Sleep Apnea Treatment for Cardiovascular Risk Benefit: Advancing the Science Through Expert Consensus. An Official American Thoracic Society Workshop Report.

The prevalence of obstructive sleep apnea (OSA) is on the rise, driven by various factors including more sensitive diagnostic criteria, increased awareness, enhanced technology through at-home testing enabling easy and cost-effective diagnosis, and a growing incidence of comorbid conditions such as obesity. Treating symptomatic patients with OSA syndrome to enhance quality of life remains a cornerstone approach. However, there is a lack of consensus regarding treatment to improve cardiovascular disease (CVD) outcomes, particularly in light of overall negative results from several randomized controlled trials (RCT) indicating no benefit of positive airway pressure (PAP) therapy on primary and secondary CVD events. These RCTs were limited by suboptimal PAP adherence, use of composite CVD outcomes, and limited diversity and generalizability to Sleep Clinic patients. As such, this workshop assembled clinical experts, as well as researchers in basic and translational science, epidemiology, clinical trials, and population health to discuss the current state, and future research directions to guide personalized therapeutic strategies and future research directions in OSA. There was overall consensus among workshop participants that OSA represents a heterogeneous disease with variable endotypes and phenotypes, and heterogeneous responses to treatment. Future research should prioritize employing multi-modal therapeutic approaches within innovative and adaptive trial designs, focusing on specific subgroups of OSA patients hypothesized to benefit from a CVD perspective. Future work should also be inclusive of diverse populations and consider the life-course of OSA to better comprehend treatment strategies that can address the disproportionate impact of OSA on racially minoritized groups. Further, a more holistic approach to sleep must be adopted to include broader assessments of symptoms, sleep duration, and comorbid sleep and circadian disorders. Finally, it is imperative to establish a sleep research consortium dedicated to collecting raw data and biospecimens categorized by OSA subtypes. This will facilitate mechanistic determinations, foster collaborative research, and help bolster the pipeline of early-career researchers.

Impact of DPP-4 inhibitors on interleukin levels in type 2 diabetes mellitus.

Accumulating evidence had implicated pathological involvement of interleukins (ILs) in progression and complications in patients with type 2 diabetes mellitus (T2DM). Dipeptidyl peptidase-4 inhibitors (DPP-4i) produced favorable effects on glucose homeostasis in T2DM. This study aimed to evaluate the impact of DPP-4i on interleukins (ILs) concentrations in T2DM. PubMed, Embase and the Cochrane library were systematically searched for relevant articles from inception to May 31, 2024. Related searching items were used including DPP-4i, T2DM and randomized controlled trials (RCTs). Placebo- or active agents-controlled human studies were screened. All the RCTs were identified if they provided detailed information on changes of ILs during DPP-4i treatment. A total of 14 RCTs involving 850 participants were identified. Pooled estimates revealed that DPP-4i significantly lower IL-6 concentrations (-0.54 pg/mL, 95% CI, -0.82 to -0.25, I2 = 10%, P = 0.0003) compared to placebo. Similar effects were demonstrated for IL-1β (-16.33 pg/mL, 95% CI, -19.56 to -13.11, I2 = 0%, P<0.00001), whereas the effect on IL-18 was not statistically significant (-13.55 pg/mL, 95% CI, -76.95 to 49.85, I2 = 0%, P = 0.68). Subgroup analysis on IL-6 demonstrated that marked effects were found in groups of basal IL-6 concentrations (< 5 pg/mL), BMI (≥ 28 kg/m2) and type of DPP-4i (linagliptin). DPP-4i favorably decreased concentrations of IL-6 in patients with T2DM. The impact of DPP-4i on IL-1β and IL-18 needed to be explored with more studies. Further trials should be performed to elucidate this anti-inflammatory effect of DPP-4i during treatment of T2DM.

Direct Oral Anticoagulants Versus Aspirin for Stroke Prevention After Embolic Stroke of Undetermined Source: An Updated Meta-Analysis of Randomized Controlled Trials

Background: Four randomized controlled trials (RCTs) did not show a benefit of direct oral anticoagulant (DOAC) treatment compared with antiplatelet therapy for the prevention of recurrent strokes in patients with embolic stroke of undetermined source (ESUS). However, the balance between efficacy and safety in subgroups needs to be better defined. We aimed to assess the relative benefits of DOACs in key subgroups of adult patients with ESUS. Methods: We searched major databases (PubMed, Embase, CENTRAL, and Web of Science) for RCTs published from inception to 16 June 2024. The primary outcome was recurrent stroke, and the main safety outcomes were major bleeding and clinically relevant non-major bleeding (CRNB). We assessed the risk of bias using the Cochrane Risk of Bias tool 2. Results: We identified four RCTs, involving a total of 13,970 patients with ESUS. Compared to antiplatelet therapy, treatment with DOAC did not reduce the risk of recurrent stroke (RR 0.95, 95% CI 0.83–1.08, p = 0.45) or ischemic stroke (RR 0.92, 95% CI 0.80–1.05, p = 0.22) or increase major bleeding (RR 1.57, 95% CI 0.87–2.83; p = 0.14). DOAC treatment was associated with a significantly higher risk of CRNMB compared to aspirin (RR 1.52, 95% CI: 1.22–1.90; p = 0.0002). The subgroup analysis demonstrated that use of DOACs was associated with a significant protective effect in patients aged 75 or older (RR 0.76, 95% CI 0.60–0.97, p = 0.03) and when the time from index stroke to randomization was ≥8 days (RR 0.80, 95% CI 0.66–0.97, p = 0.02) in preventing recurrency of any type of stroke. Conclusions: Our meta-analysis showed lack of overall benefit of anticoagulation with DOAC compared to antiplatelet therapy for recurrent stroke prevention in adult patients with ESUS. However, the subgroup analyses suggest the possibility of interactions between age and timing of randomization since stroke and treatment with an DOAC in terms of recurrent stroke prevention. Further research toward tailoring the antithrombotic strategy according to patient characteristics is needed.

Herbal medicine for the treatment of non-erosive reflux disease: A systematic review and meta-analysis.

Non-erosive reflux disease (NERD) is the most prevalent gastroesophageal reflux disease. Currently, proton pump inhibitors are the most commonly used treatment for NERD. Recently, the demand for herbal medicines with relatively few side effects is increasing and trials confirming the effectiveness and safety of herbal medicines for the treatment of NERD have been conducted. This study aimed to investigate the effectiveness and safety of herbal medicine in the treatment of NERD through published randomized-controlled trials. Ten electronic databases were searched from inception until May 2023. Disease, intervention-related terms, and publication type keywords were combined as search terms. Studies designed as randomized controlled trials, including participants diagnosed with NERD with any type of herbal medicine as a treatment intervention were included. Data extraction and analysis were conducted by 2 independent reviewers. The total clinical efficacy rate was assessed as a primary outcome, while the secondary outcomes were recurrence rate, reflux diagnostic questionnaire score, short-form 36 health survey score, and serum motilin level. The risk of bias in each study and quality of evidence were assessed. Thirty-four randomized controlled trials involving 3759 patients were analyzed. Herbal medicine was significantly more effective in improving total clinical efficacy, recurrence rate, reflux diagnostic questionnaire score, some domains of short-form 36 health survey, and serum motilin levels in patients with NERD than conventional medical therapy. No severe intervention-related adverse effects were observed. Regarding the quality of evidence, most outcomes were revealed to have moderate to low levels of evidence. This systematic review and meta-analysis suggests that herbal medicine can be an effective and safe therapy for NERD; however, there are several limitations regarding the methodological quality of the included studies. Further research with high methodological quality is necessary to improve the quality of evidence.

Application of CAR-T cell therapy in B-cell lymphoma: a meta-analysis of randomized controlled trials.

This study aims to compare the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) immunotherapy with standard treatment for B-cell lymphoma, providing evidence-based support for the more efficient use of CAR-T cell immunotherapy. We conducted a comprehensive literature search of high-quality randomized controlled trials (RCTs) on CAR-T therapy for B-cell lymphoma in the following databases: Wanfang, Web of Science, CNKI, VIP database, and PubMed, up to February 2024. The outcome measures included objective remission rate (ORR), complete remission rate (CRR), and incidence of adverse reactions. Subgroup analysis was performed based on the differences in co-stimulatory domains. Meta-analysis was conducted using Review Manager 5.4 and Stata software. A total of five RCTs involving 1670 patients were included in this meta-analysis. The results showed that the CAR-T treatment group had significantly higher ORR (RR: 1.47, 95% CI 1.23-1.76, I2 = 80%, p < 0.0001), CRR (RR: 2.19, 95% CI 2.16-3.79, I2 = 93%, p = 0.005), cytokine release syndrome (CRS) incidence (RR: 34.51, 95% CI 2.27-523.78, I2 = 98%, p = 0.01), neurotoxicity (NT) incidence (RR: 6.00, 95% CI 1.82-19.75, I2 = 80%, p = 0.003), neutropenia incidence (RR: 1.39, 95% CI 1.02-1.88, I2 = 93%, p = 0.03), leukopenia incidence (RR: 1.39, 95% CI 1.04-1.87, I2 = 61%, p = 0.03), and headache incidence (RR: 1.56, 95% CI 1.25-1.95, I2 = 34%, p < 0.0001) compared to the standard treatment group. Subgroup analysis based on co-stimulatory domains revealed that the 4-1BB subgroup had higher incidences of CRR, CRS, NT and leukopenia than the CD28 subgroup; however, the CD28 subgroup exhibited higher ORR and neutropenia than the 4-1BB subgroup. CAR-T cell immunotherapy demonstrates superior efficacy compared to standard therapy in treating B-cell lymphoma. However, CAR-T treatment can lead to adverse reactions such as CRS and NT. Infusion of an appropriate dose of CAR-T cells (e.g., 100 × 106) may be a strategy to mitigate the risk of CRS and NT.

The effects of mindfulness therapy on infertile female patients: A meta-analysis.

About 186 million people in the world suffer from infertility, and there is one infertile couple in every 4-6 couples. It is thus essential to find effective psychological treatment. To conduct a systematic review of previous meta-analyses on mindfulness-based therapy outcomes in infertile female patients and a meta-analysis of studies nested within these meta-analyses. Randomized controlled trials (RCTS) on the efficacy of mindset-based interventions in infertile female patients were retrieved from PubMed, The Cochrane Library, Embase, Web of Science, CNI, VIP Database, and Wanfang Database until March 1, 2023. Two researchers screened the literature, extracted data according to inclusion and exclusion criteria, and conducted quality control according to Cochrane Handbook 5.1.0. When there was ambiguity, a third party determined it. The meta-analysis was performed using RevMan 5.3 software. 14 randomized controlled trials involving 1784 patients were included. Meta-analysis showed that compared with conventional care, mindfulness-based intervention can effectively relieve anxiety in female infertility patients [SMD =-2.25, 95% CI (-2.90, -1.60), P< 0.00001], depression [SMD =-2.25, 95% CI (-2.99, -1.52), P< 0.00001], perceived stress [SMD =-0.99, 95% CI (-1.27, -0.71), P< 0.00001], improved quality of life, physiological function [MD = 14.03, 95% CI (11.98, 16.07), P< 0.00001], Role limitations due to physical problems [MD = 11.30, 95% CI (5.71, 16.90), P< 0.0001], vitality [MD = 11.55, 95% CI (9.46, 13.65), P< 0.00001], mental health [MD = 17.32, 95% CI (15.29, 19.35), P< 0.00001]. Existing evidence shows that mindfulness therapy can effectively relieve the anxiety and depression of infertile women, reduce the level of stress, and improve the quality of life and sleep quality. However, due to the limited quantity and quality of the literature, multi-center, large-sample, and high-quality randomized controlled studies should be conducted in the future.

Subcutaneous furosemide in heart failure: a systematic review.

Intravenous loop diuretics are the primary treatment for congestion in patients with decompensated heart failure (HF). Furosemide is the most commonly used loop diuretic and is licensed for administration either orally, intramuscularly or intravenously but not subcutaneously. Recently developed, pH-neutral, concentrated, 'skin-friendly' preparations of furosemide have been developed which allow subcutaneous administration. In this systematic review, we summarize and critically appraise the current evidence for subcutaneous furosemide in patients with HF. The electronic databases MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov registry were searched up to 31 December 2023. Of the 17 studies identified, 5 were randomised controlled trials (RCTs), 2 were non-randomised controlled studies, 3 were prospective observational cohort studies, and 7 were retrospective observational studies.All RCTs utilised novel pH-neutral, subcutaneous preparations of furosemide. Bioavailability of novel subcutaneous preparations were similar to intravenous furosemide 10mg/ml: 99.7% for an 8mg/ml preparation and 112% for a 30mg/ml preparation. Natriuresis and diuresis were also similar with novel subcutaneous and conventional intravenous furosemide. Adverse events of novel preparations included infusion site pain or discomfort, localised skin erythema and minimal swelling. All studies of conventional subcutaneous furosemide were non-randomised with very limited data re bioavailability or diuretic and natriuretic effect. Conventional subcutaneous furosemide was associated with substantial skin irritation (affecting 3-23% of patients), and skin infections requiring treatment with antibiotics (3-17%). Novel, pH-neutral preparations of subcutaneous furosemide achieved similar diuresis, natriuresis, and bioavailability to intravenous furosemide, and were well tolerated. Novel preparations may be a treatment option for patients with HF.

Efficacy of lasmiditan, rimegepant and ubrogepant for acute treatment of migraine in triptan insufficient responders: systematic review and network meta-analysis

BackgroundNovel abortive treatments for migraine, ditans and gepants, have promising implications in triptan-insufficient responders with minimal existing comparative data. Our study aims to synthesize evidence through a systematic review and network meta-analysis to assess the comparative efficacy of lasmiditan, rimegepant and ubrogepant in triptan-insufficient responders.MethodWe searched PubMed, Embase, CENTRAL, and EBSCO Open Dissertations up to May 2024. We included randomized controlled trials (RCTs) that compared novel abortive treatments, including lasmiditan, rimegepant, and ubrogepant, in migraine patients who self-reported insufficient response to triptans. Outcomes are represented using relative risks with corresponding 95% confidence intervals (CI). The surface under the cumulative ranking curve (SUCRA) was used to rank each medication.ResultsA total of five phase 3 RCTs involving 3,004 patients were included in the analysis. All three agents were significantly superior to placebo for two-hour pain freedom (RR = 1.93, 95% CI [1.52, 2.46]), freedom from the most bothersome symptoms at two hours (RR = 1.55, 95% CI [1.37, 1.75]), and pain relief at two hours (RR = 1.46, 95% CI [1.35, 1.58]). No statistically significant differences in efficacy outcomes were observed among the three agents. However, lasmiditan 200 mg had the highest cumulative probability for two-hour pain freedom and relief (SUCRA 0.9, 0.8, respective), while rimegepant led in relieving the most bothersome symptoms (SUCRA 0.7).ConclusionLasmiditan, rimegepant, and ubrogepant are effective for acute treatment of migraine in triptan-insufficient responders, with high-dose lasmiditan showing the highest efficacy for pain control.

Pharmacist interventions in the control of hypertension and adherence to anti-hypertensive treatment: A systematic review and meta-analysis of randomised controlled trials

Abstract Introduction Non-adherence to antihypertensive therapy is one of the major barriers for the achievement of blood pressure (BP) control and has a significant cost burden1. Non-adherence is also thought to be one of the leading factors leading to ethnic disparities in hypertension control in the UK2. Pharmacists have an important role in the management of hypertension and non-adherence due to their ideal position to promote optimal use of medication3. Many have advocated for pharmacist involvement in team-based hypertension management, however which pharmaceutical care interventions are most effective remains unclear. There have been many new studies in recent years exploring the effect of pharmacist interventions in hypertension and this meta-analysis provides an update of the current literature and quantification of the results. Aim This study aimed to systematically evaluate the efficacy of pharmacist-delivered interventions for adults with hypertension and examine the intervention characteristics associated with greater BP-lowering efficacy. The primary outcome was the change in BP and secondary outcomes were % achieving BP control. Methods Systematic review and meta-analysis of randomized controlled trials (RCTs). This review was registered on PROSPERO. Embase, CENTRAL, MedLine, Psychinfo and CINAHL were searched until February 2024. Eligible studies included adult patients with a diagnosis of essential hypertension where a pharmacist intervention (alone or collaborative care) targeting BP control was compared with control (usual care). Exclusion criteria included secondary hypertension, pregnancy, children and review articles/case studies. The risk of bias was assessed by the Cochrane risk-of-bias tool for RCTs. The primary outcome was change in BP. We extracted data on sample and intervention characteristics. Meta-analysis was performed using Comprehensive Meta-Analysis Software v4. Moderator analyses examined the association between intervention effects and intervention features. This study was a systematic review and meta-analysis of already completed trials and so ethical approval was not required. Results 2402 articles were retrieved. After removal of duplicates, 1538 were screened by title and abstract against the inclusion criteria. 88 studies with 25,516 participants were included. Mean intervention duration was 7.2 months (range 1-14 months). The overall pooled mean differences in systolic BP (SBP) and diastolic BP (DBP) between pharmacist intervention and control were -7.39 (-8.56, -6.23) mmHg and -3.99 (-4.61, -3.37) mmHg respectively, both P&amp;lt;0.001. With BP control, pharmacist interventions caused a significant increase in those achieving BP control compared to usual care (+21 (16.88, 25.27) %, P&amp;lt;0.001). Duration of intervention had no influence on change in SBP or DBP (both P&amp;gt;0.05). Discussion Pharmacists can make a significant impact in the management of hypertension in respect to increasing treatment adherence and improving BP control and this study highlights the importance of including them as part of the multidisciplinary team responsible for patient care. Limitations of the present study include the inability to extract individual patient data and stratification by ethnicity, socioeconomic status and gender. However, pharmacist interventions in hypertension significantly reduced SBP and DBP and improved BP control. Identifying the characteristics of the most effective interventions can lead to better treatment adherence and BP-lowering in patients with hypertension.

Does intraoperative wound irrigation with diluted povidone-iodine prevent surgical site infection in spine surgery?

This study employed meta-analysis to evaluate whether the application of intraoperative wound irrigation (IOWI) with povidone-iodine (PI) in spine surgery effectively reduces the incidence of postoperative surgical site infection (SSI). The present study was conducted strictly following the methodological guidance provided by the Cochrane Handbook. The protocol of this work was registered with PROSPERO. Two researchers independently conducted electronic searches in Medline via PubMed, Embase, Cochrane Library, and Web of Science. The bias risk of each included study was evaluated by two assessors. We performed statistical analysis on the dataset using STATA software. Fourteen studies involving a total of 6777 patients were included in the present work. The risk of bias of six included randomized controlled trials (RCTs) was considered as low-to-moderate risk, and the quality scores of the eight included retrospective cohort studies were rated as high quality. The results of this meta-analysis indicated a significant difference in the incidence of postoperative SSI between the two groups (RR = 0.29, 95% CI: (0.18, 0.47)). Moreover, patients who underwent IOWI with PI had lower rates of deep and superficial infections after spine surgery compared with the controlled group (superficial infection: RR = 0.28, 95%CI: (0.14, 0.54); Deep infection: RR = 0.24, 95%CI: (0.10, 0.60)). The sensitivity analysis results indicated good robustness and high evidence strength after data consolidation in the overall rate of postoperative SSI and the incidence of deep/superficial infection. IOWI with PI solution during spinal surgery can effectively reduce the incidence of postoperative SSI.

The Optimized Use of a Contact-Free Continuous Monitoring System on Clinical Outcomes During COVID-19.

The purpose of this study was to examine the impact of a contact-free continuous monitoring system on clinical outcomes including unplanned intensive care unit (ICU) transfer (primary), length of stay (LOS), code blue, and mortality. A secondary aim was to evaluate the return on investment associated with implementing the contact-free continuous monitoring program during the COVID public health emergency. An interrupted time series evaluation was conducted to examine the association between the use of contact-free continuous monitoring and clinical outcomes. A cost-benefit analysis was planned to evaluate the return on investment. Use of contact-free continuous monitoring was not significantly associated with unplanned ICU transfers, deaths, ICU LOS, and or rapid response team calls. However, there were significant increases in code blue events (P = 0.02) and mean hospital LOS (P = 0.01) in the postimplementation period when compared with the preimplementation period. Due to the lack of improvement, costs were calculated but a cost-benefit analysis was not conducted. Contact-free continuous monitoring bed use during the COVID-19 public health emergency was not associated with improvements in clinical outcomes, although there was substantial confounding. Future studies should include large randomized controlled trials to control for factors not under direct experimental control including unit staffing, staff turnover, and differences in the patient population related to surges in the COVID-19 pandemic.

Sex Differences in Moderate-to-Severe Traumatic Brain Injury Randomized Controlled Trials.

Understanding sex differences among persons with moderate-to-severe traumatic brain injury (TBI) is critical to addressing the unique needs of both males and females from acute care through to rehabilitation. Epidemiological studies suggest that 7 of every 10 persons with moderate-to-severe TBI are male, with females representing about 30%-33%. To examine the proportion of female and male individuals included in randomized controlled trials (RCTs) of interventions for moderate-to-severe TBI. A systematic review was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines up to and including December 2022 using MEDLINE, PubMed, Scopus, CINAHL, EMBASE and PsycINFO databases. Studies were included if they met the following criteria: (1) human participants with a mean age ≥18 years, (2) ≥50% of the sample had moderate-to-severe TBI and (3) the study design was a RCT. Data extracted included author, year, country, sample size, number of female/male participants and time post-injury. 595 RCTs met the criteria for inclusion, published between 1978 and 2022, totaling 86,662 participants. The average proportion of female participants was 23.14%, and the percentage increased a small but significant amount over time. There was a significantly lower percentage of female participants in RCTs initiated in the acute phase (≤ 1 month) when compared with RCTs conducted in the chronic phase (≥ 6 months) post-injury (p < 0.001). Female participants are underrepresented in RCTs of moderate-to-severe TBI. Addressing this underrepresentation is critical to establish effective treatments for all persons with TBI.

Generalizability of pharmaceutical randomized controlled trial eligibility criteria for progressive pulmonary fibrosis.

Progressive pulmonary fibrosis (PFF) is of substantial interest for novel pharmacotherapy discovery, but little is known about clinical trial eligibility criteria. We evaluated eligibility criteria of PPF randomized controlled trials (RCTs), their representativeness in registry patients, and forced vital capacity (FVC) changes and mortality according to trial eligibility. A systematic search was used to identify completed and in-progress phase II and III PPF RCTs. Common clinical trial eligibility criteria used in ≥60% of previous PPF RCTs were identified. The most common criteria for PPF used in RCTs ("trial-PPF criteria") and the clinical practice guideline definition of PPF ("guideline-PPF criteria") were both applied to patients enrolled in a prospective multicenter Canadian registry. Common trial eligibility criteria were tested for their frequency and association with health outcomes in registry patients who met trial-PPF and guideline-PPF criteria. Ten different definitions of PPF were used in 16 RCTs. At the time of meeting PPF definitions, 50% of 864 patients with trial-PPF and 44% of 408 patients with guideline-PPF met the common trial eligibility criteria. For both definitions, trial-eligible patients had more rapid 1-year FVC decline but better transplant-free survival than trial-ineligible patients. Patients with unclassifiable interstitial lung disease (ILD) had higher proportion of trial exclusion compared to those with connective tissue disease-associated ILD and fibrotic hypersensitivity pneumonitis. Annual FVC decline (trial-PPF: -67 to -21 mL; guideline-PPF: -116 to -41 mL) and 1-year transplant-free survival (trial-PPF: 90.5 to 97.5%; guideline-PPF: 87 to 96.2%) varied in trial-eligible patients across ILD subtypes. Existing RCTs use a variety of definitions for PPF with eligibility criteria that have limited representativeness. FVC decline and transplant-free survival vary according to trial eligibility and ILD subtypes.

Bone marrow versus peripheral blood allogeneic haematopoietic stem cell transplantation for haematological malignancies in adults.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is an established treatment option for many malignant and non-malignant haematological disorders. Peripheral blood stem cells represent the main stem cell source in malignant diseases due to faster engraftment and practicability issues compared with bone marrow stem cells. Since the early 2000s, there have been many developments in the clinical field. Allo-HSCT using haploidentical family donors (haplo-HSCT) has emerged as an alternative for people who do not have human leukocyte antigen (HLA)-matched siblings or unrelated donors. In addition, the introduction of new methods and strategies in allo-HSCT, such as the use of post-transplant cyclophosphamide (PT-Cy), better donor selection, the more frequent administration of anti-thymocyte globulins (ATGs), but also improved management of side effects such as graft-versus-host disease (GvHD) and infection, have impacted outcomes after allo-HSCT. In addition, as transplant indications and strategies continue to adapt in line with novel research findings, the effect of the stem cell source on post-transplant outcomes is unclear. For our analysis, we considered peripheral blood stem cells as the standard graft source for adults with haematological malignancies. This is an update of a review first published in 2014. To assess the effect of bone marrow transplantation versus peripheral blood stem cell transplantation in adults with haematological malignancies with regard to overall survival, disease-free survival, incidence of non-relapse or transplant-related mortality, incidence of extensive chronic graft-versus-host disease (GvHD), incidence of acute GvHD grades III to IV, incidence of overall chronic GvHD, and quality of life. For this update we searched CENTRAL, MEDLINE, Embase, and two trials registries on 2 November 2022 with no language restrictions. We included randomised controlled trials (RCTs) comparing bone marrow transplantation (BMT) with peripheral blood stem cell transplantation (PBSCT) in adults (aged ≥ 18 years) with haematological malignancies. Two review authors independently selected studies and extracted data. We evaluated risk of bias using the original Cochrane risk of bias tool (RoB 1), and we evaluated the certainty of the evidence using the GRADE approach. The updated search identified no new studies for inclusion. We found two additional reports relating to a previously included study; they provided new data on quality of life and infection rates after transplantation. As these are clinically relevant outcomes, quality of life was added to the summary of findings table (replacing acute GvHD II to IV), and rate of infection was added to our list of secondary outcomes. We included nine RCTs with a total of 1521 participants. Overall, the risk of bias in the included studies was low. Median participant age across studies ranged from 21 to 45 years, and studies took place in Canada, the USA, New Zealand, Brazil, Australia, Egypt, and across Europe. Bone marrow transplantation (BMT) compared with peripheral blood stem cell transplantation (PBSCT) likely results in little to no difference in overall survival (hazard ratio (HR) for all-cause death 1.07, 95% CI 0.91 to 1.25; 6 studies, 1330 participants; moderate-certainty evidence). There may be little to no difference between BMT and PBSCT in terms of disease-free survival (HR for disease recurrence or all-cause death 1.04, 95% CI 0.89 to 1.21; 6 studies, 1225 participants; low-certainty evidence) and non-relapse or transplant-related mortality (HR 0.98, 95% CI 0.76 to 1.28; 3 studies, 758 participants; low-certainty evidence). BMT compared with PBSCT likely results in lower rates of extensive chronic GvHD (HR 0.69, 95% CI 0.54 to 0.90; 4 studies, 765 participants; moderate-certainty evidence) and overall chronic GvHD (HR 0.72, 95% CI 0.61 to 0.85; 4 studies, 1121 participants; moderate-certainty evidence). BMT compared with PBSCT may reduce the incidence of acute GvHD grades III to IV, although the 95% CI of the HR is also compatible with no effect (HR 0.75, 95% CI 0.55 to 1.02; 3 studies, 925 participants; moderate-certainty evidence). Evidence from two trials that used different quality of life assessment instruments suggests that BMT compared with PBSCT may be associated with higher quality of life five years after transplantation. Moderate-certainty evidence suggests little to no difference in overall survival following allo-HSCT using bone marrow versus peripheral blood stem cells (the current clinical standard stem cell source). Low-certainty evidence suggests little to no difference between the stem cell sources in terms of disease-free survival and non-relapse or transplant-related survival. BMT likely reduces the risk of extensive chronic GvHD and overall chronic GvHD compared with PBSCT. Evidence from two RCTs suggests that BMT compared with PBSCT may result in higher long-term quality of life, possibly due to the lower chronic GvHD incidence. With this update, we aimed to supply the most recent data on the choice of stem cell source for allo-HSCT in adults by including new evidence published up to November 2022. We identified no new ongoing studies and no new RCTs with published results. Further research in this field is warranted.

Prenatal exercise and its effects on postpartum mental health: systematic review and meta-analysis.

The perinatal period, spanning from pregnancy through the first year after childbirth, is characterized by significant physiological, psychological, and socio-contextual changes. Women face complex stressors including psychosocial pressures, financial constraints, interpersonal dynamics, anticipatory stress related to parenthood, hormonal fluctuations, and societal expectations. These factors collectively influence the perinatal experience, increasing vulnerabilities and stress levels. A systematic review was conducted in October 2023 using PubMed, SPORTDiscus, PsycInfo, and Scopus databases. Only English-language publications were included. For the meta-analysis, only randomized controlled trials (RCTs) using the Edinburgh Postnatal Depression Scale (EPDS) were considered. Data extraction was performed independently by two reviewers using Covidence, focusing on study characteristics, population demographics, interventions, and outcomes. The initial search identified 2,373 articles, with 1,196 duplicates removed, leaving 1,177 articles. After screening titles and abstracts, 1,247 were excluded for not meeting the inclusion criteria, resulting in 30 full-text articles reviewed for eligibility by two researchers. Nineteen studies were included in the systematic review, with four in the meta-analysis. Results indicated that higher levels of physical activity during pregnancy were consistently associated with improved postpartum mental health outcomes, including reduced depressive symptoms, lower anxiety, and enhanced overall well-being. Low-intensity exercises, such as yoga, were particularly effective in reducing postpartum depressive symptoms. The impact of moderate-intensity exercise varied, with some studies showing no significant effects. The meta-analysis of four RCTs using the EPDS demonstrated a significant reduction in depression and anxiety symptoms among postpartum women who participated in physical activity interventions, with a substantial overall effect size. Developing physical activity and exercise regimens encompassing a range of intensities can address the unique physiological and psychological demands of the perinatal period, maximizing the therapeutic benefits of physical activity interventions.