Bullous Pemphigoid Severity and Levels of Antibodies to BP180 and BP230: A Systematic Review and Meta-Analysis.

Importance: The correlation between serum levels of autoantibodies against bullous pemphigoid (BP) antigens 180 (BP180) and 230 (BP230) with BP disease severity is unclear. Objective: To investigate the correlation of anti-BP180 and anti-BP230 immunoglobulin G (IgG) antibody levels with BP disease severity. Data Sources: A search was performed of the Cochrane Central Register of Controlled Trials, Embase, and PubMed databases from their respective inception to April 11, 2024. Study Selection: Studies evaluating the correlation between serum levels of anti-BP180 or anti-BP230 IgG measured using enzyme-linked immunosorbent assay (ELISA) and disease severity assessed per the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) or BP Disease Area Index (BPDAI) were included. No language or geographic restrictions were imposed. Nearly 0.4% of initially identified studies met the selection criteria. Data Extraction and Synthesis: One researcher extracted data and another researcher confirmed data. The risk of bias was independently assessed by these researchers using the Quality Assessment of Diagnostic Accuracy Studies 2 tool, with discrepancies resolved by discussion with a third researcher. A random-effects model meta-analysis and a subgroup analysis were conducted based on the ELISA kit manufacturers. Main Outcomes and Measures: Pooled correlation coefficients of antibody levels with ABSIS and BPDAI. Results: In all, 14 studies with 1226 participants were analyzed. The risk of bias of included studies was generally low. The meta-analysis found anti-BP180 autoantibody levels showed moderate correlation with objective BPDAI (r = 0.56; 95% CI, 0.46-0.64) at baseline, strong correlation (r = 0.63; 95% CI, 0.39-0.79) at 3-month follow-up, and moderate correlation (r = 0.53; 95% CI, 0.25-0.72) at 6-month follow-up. Anti-BP180 autoantibody levels also showed moderate correlation (r = 0.52; 95% CI, 0.39-0.62) with ABSIS at baseline, strong correlation (r = 0.62; 95% CI, 0.39-0.79) at 3-month follow-up, and moderate correlation (r = 0.53; 95% CI, 0.25-0.72) at 6-month follow-up. By contrast, anti-BP230 autoantibody levels showed no association with objective BPDAI and ABSIS at diagnosis and follow-up. The subgroup analysis found similar results when using different ELISA kits. Conclusions and Relevance: The findings of this systematic review and meta-analysis indicated that anti-BP180 autoantibody levels may serve as an adjunctive tool for monitoring BP disease severity and guiding clinical care for patients with BP.

Comparative efficacy and choice of lipid-lowering drugs for cardiovascular and kidney outcomes in patients with chronic kidney disease: A systematic review and network meta-analysis.

BACKGROUND: The effect of exact classes of lipid-lowering drugs (LLDs) on preventing major adverse cardiovascular events (MACEs) and poor renal outcomes is not well characterized in the chronic kidney disease (CKD) population. METHODS: We performed a frequentist random-effects network meta-analysis of randomized controlled trials (RCTs) to evaluate the protective effect of the LLDs in non-dialysis CKD patients. The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched for relevant trials published before March 31, 2024. The primary outcome was the incidence of MACEs. The secondary outcomes comprised all-cause mortality, end-stage kidney disease, changes in estimated glomerular filtration rate (eGFR) and proteinuria, and safety. RESULTS: Forty-nine eligible RCTs with 77,826 participants with non-dialysis CKD were included. With moderate confidence in the evidence, rosuvastatin and atorvastatin showed statistically significantly more efficacy in reducing the risk of MACE, with a pooled risk ratio of 0.55 (95% CI 0.33-0.91) for rosuvastatin and 0.67 (0.49-0.90) for atorvastatin, respectively, compared with the control group. For the change in the eGFR, atorvastatin (mean difference [MD], 1.40; 95% CI, 0.61 to 2.18), rosuvastatin (MD, 1.73; 95% CI, 0.63 to 2.83), and statin plus ezetimibe (MD, 2.35; 95% CI, 0.44 to 4.26) showed statistically significant increases in the mean eGFR. CONCLUSION: In patients with non-dialysis CKD, there is sufficient evidence to show that rosuvastatin and atorvastatin were statistically significantly more effective and preferable in reducing the risk of MACE and increasing the mean eGFR compared with the control group.

Comparative Effects of Diabetes Self-Management Programs on Type 2 Diabetes Clinical Outcomes: A Systematic Review and Network Meta-Analysis.

AIMS: This systematic review and network meta-analysis compared the effects of various diabetes self-management programs: Diabetes Self-Management Education (DSME), Diabetes Self-Management Support (DSMS), and Diabetes Self-Management Education and Support (DSMES). METHODS: We searched four electronic databases for eligible articles up to March 1, 2023. Only randomized controlled trials investigating the effects of DSME, DSMS, or DSMES on glycated haemoglobin (HbA1c) level, fasting blood glucose (FBG), total cholesterol (TC), systolic blood pressure (SBP), and diastolic blood pressure (DBP) in adults with type 2 diabetes were included. Cochrane Risk of Bias 2.0 tool was used to assess each study quality, and Confidence in Network Meta-Analysis was applied to evaluate the certainty of the evidence. Data were pooled with a random-effects model under a frequentist framework. RESULTS: A total of 108 studies encompassing 17,735 participants (mean age 57.4 years) were analysed. DSMES, compared with usual care, significantly reduced HbA1c level (mean difference = -0.61%, 95% confidence interval [CI] = -0.74 to -0.49; certainty of evidence = moderate), FBG (-23.33 mg/dL; -31.33 to -15.34; high), TC (-5.62 mg/dL; -8.69 to -2.55; high), SBP (-3.05 mmHg; -5.20 to -0.91; high), and DBP (-2.15 mmHg; -3.36 to -0.95; high). Compared with DSME, DSMES showed significantly greater improvements in HbA1c levels (-0.23%; -0.40 to -0.07; high) and DBP (-1.82 mmHg; -3.47 to -0.17; high). DSMES was ranked as the top treatment for improving diabetes clinical outcomes (0.82-0.97) in people with type 2 diabetes. CONCLUSIONS: DSMES, in people with type 2 diabetes, yields the greatest improvement in the key clinical outcomes of HbA1c, fasting blood glucose, and blood pressure levels. Healthcare providers should incorporate the DSMES approach into their daily care routines. Approximately 30% of the studies reviewed raised some concerns about their quality, underscoring the need for high-quality studies in this area.

Visualizing the assumptions of network meta-analysis.

Network meta-analysis (NMA) incorporates all available evidence into a general statistical framework for comparing multiple treatments. Standard NMAs make three major assumptions, namely homogeneity, similarity, and consistency, and violating these assumptions threatens an NMA's validity. In this article, we suggest a graphical approach to assessing these assumptions and distinguishing between qualitative and quantitative versions of these assumptions. In our plot, the absolute effect of each treatment arm is plotted against the level of effect modifiers, and the three assumptions of NMA can then be visually evaluated. We use four hypothetical scenarios to show how violating these assumptions can lead to different consequences and difficulties in interpreting an NMA. We present an example of an NMA evaluating steroid use to treat septic shock patients to demonstrate how to use our graphical approach to assess an NMA's assumptions and how this approach can help with interpreting the results. We also show that all three assumptions of NMA can be summarized as an exchangeability assumption. Finally, we discuss how reporting of NMAs can be improved to increase transparency of the analysis and interpretability of the results.

The efficacy and acceptability of anti-inflammatory omega-3 polyunsaturated fatty acid supplements in sepsis management: a network meta-analysis of randomized controlled trials.

Sepsis is a critical medical condition associated with high mortality for patients. Current pharmacological strategies for sepsis management or prevention had not achieved satisfactory results. The omega-3 fatty acids, with anti-inflammatory benefits, are considered to be promising agents for sepsis management/prevention. The aim of this network meta-analysis (NMA) is to compare the efficacy of various dosages and formulations of fish oil supplements for sepsis management and sepsis prevention. The current NMA consisted of two parts: (1) sepsis management and (2) sepsis prevention. The PubMed, ClinicalKey, Embase, ProQuest, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov databases were systematically searched to date of February 22nd, 2024 for relevant randomized controlled trials (RCTs). RCTs were eligible for inclusion if they enrolled participants with a diagnosis of sepsis or who with high risk for sepsis. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed are (1) mortality rate in sepsis treatment or (2) incidence of sepsis in sepsis prevention. Our NMA, based on 28 RCTs and 1718 participants (mean age=51.6 years, mean female proportion=35.6 %), showed that (1) high dose parenteral fish oil supplement yield the lowest mortality rate in sepsis management in adult patients, and (2) high dose enteral fish oil supplement yield the lowest incidence of sepsis in pediatric patients. This study provides compelling evidence that high-dose fish oil supplements provide beneficial effects for both sepsis management and sepsis prevention. Our findings provide a preliminary rationale for future large-scale RCTs to investigate the role of fish oil supplementation in sepsis management or prevention.

Electronic Alert Systems for Patients With Acute Kidney Injury: A Systematic Review and Meta-Analysis.

Importance: The acute kidney injury (AKI) electronic alert (e-alert) system was hypothesized to improve the outcomes of AKI. However, its association with different patient outcomes and clinical practice patterns remains systematically unexplored. Objective: To assess the association of AKI e-alerts with patient outcomes (mortality, AKI progression, dialysis, and kidney recovery) and clinical practice patterns. Data Sources: A search of Embase and PubMed on March 18, 2024, and a search of the Cochrane Library on March 20, 2024, to identify all relevant studies. There were no limitations on language or article types. Study Selection: Studies evaluating the specified outcomes in adult patients with AKI comparing AKI e-alerts with standard care or no e-alerts were included. Studies were excluded if they were duplicate cohorts, had insufficient outcome data, or had no control group. Data Extraction and Synthesis: Two investigators independently extracted data and assessed bias. The systematic review and meta-analysis followed the PRISMA guidelines. Random-effects model meta-analysis, with predefined subgroup analysis and trial sequential analyses, were conducted. Main Outcomes and Measures: Primary outcomes included mortality, AKI progression, dialysis, and kidney recovery. Secondary outcomes were nephrologist consultations, post-AKI exposure to nonsteroidal anti-inflammatory drugs (NSAID), post-AKI angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker (ACEI/ARB) prescription, hospital length of stay, costs, and AKI documentation. Results: Thirteen unique studies with 41 837 unique patients were included (mean age range, 60.5-79.0 years]; 29.3%-48.5% female). The risk ratios (RRs) for the AKI e-alerts group compared with standard care were 0.96 for mortality (95% CI, 0.89-1.03), 0.91 for AKI stage progression (95% CI, 0.84-0.99), 1.16 for dialysis (95% CI, 1.05-1.28), and 1.13 for kidney recovery (95% CI, 0.86-1.49). The AKI e-alerts group had RRs of 1.45 (95% CI, 1.04-2.02) for nephrologist consultation, 0.75 (95% CI, 0.59-0.95) for post-AKI NSAID exposure. The pooled RR for post-AKI ACEI/ARB exposure in the AKI e-alerts group compared with the control group was 0.91 (95% CI, 0.78-1.06) and 1.28 (95% CI, 1.04-1.58) for AKI documentation. Use of AKI e-alerts was not associated with lower hospital length of stay (mean difference, -0.09 [95% CI, -0.47 to 0.30] days) or lower cost (mean difference, US $655.26 [95% CI, -$656.98 to $1967.5]) but was associated with greater AKI documentation (RR, 1.28 [95% CI, 1.04-1.58]). Trial sequential analysis confirmed true-positive results of AKI e-alerts on increased nephrologist consultations and reduced post-AKI NSAID exposure and its lack of association with mortality. Conclusions and Relevance: In this systematic review and meta-analysis, AKI e-alerts were not associated with a lower risk for mortality but were associated with changes in clinical practices. They were associated with lower risk for AKI progression. Further research is needed to confirm these results and integrate early AKI markers or prediction models to improve outcomes.

Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network meta-analysis.

OBJECTIVE: To evaluate the comparative effectiveness and acceptability of oral monotherapy using psychedelics and escitalopram in patients with depressive symptoms, considering the potential for overestimated effectiveness due to unsuccessful blinding. DESIGN: Systematic review and Bayesian network meta-analysis. DATA SOURCES: Medline, Cochrane Central Register of Controlled Trials, Embase, PsycINFO, ClinicalTrial.gov, and World Health Organization's International Clinical Trials Registry Platform from database inception to 12 October 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials on psychedelics or escitalopram in adults with depressive symptoms. Eligible randomised controlled trials of psychedelics (3,4-methylenedioxymethamphetamine (known as MDMA), lysergic acid diethylamide (known as LSD), psilocybin, or ayahuasca) required oral monotherapy with no concomitant use of antidepressants. DATA EXTRACTION AND SYNTHESIS: The primary outcome was change in depression, measured by the 17-item Hamilton depression rating scale. The secondary outcomes were all cause discontinuation and severe adverse events. Severe adverse events were those resulting in any of a list of negative health outcomes including, death, admission to hospital, significant or persistent incapacity, congenital birth defect or abnormality, and suicide attempt. Data were pooled using a random effects model within a Bayesian framework. To avoid estimation bias, placebo responses were distinguished between psychedelic and antidepressant trials. RESULTS: Placebo response in psychedelic trials was lower than that in antidepression trials of escitalopram (mean difference -3.90 (95% credible interval -7.10 to -0.96)). Although most psychedelics were better than placebo in psychedelic trials, only high dose psilocybin was better than placebo in antidepression trials of escitalopram (mean difference 6.45 (3.19 to 9.41)). However, the effect size (standardised mean difference) of high dose psilocybin decreased from large (0.88) to small (0.31) when the reference arm changed from placebo response in the psychedelic trials to antidepressant trials. The relative effect of high dose psilocybin was larger than escitalopram at 10 mg (4.66 (95% credible interval 1.36 to 7.74)) and 20 mg (4.69 (1.64 to 7.54)). None of the interventions was associated with higher all cause discontinuation or severe adverse events than the placebo. CONCLUSIONS: Of the available psychedelic treatments for depressive symptoms, patients treated with high dose psilocybin showed better responses than those treated with placebo in the antidepressant trials, but the effect size was small. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023469014.

Quality and correctness of AI-generated versus human-written abstracts in psychiatric research papers.

This study aimed to assess the ability of an artificial intelligence (AI)-based chatbot to generate abstracts from academic psychiatric articles. We provided 30 full-text psychiatric papers to ChatPDF (based on ChatGPT) and prompted generating a similar style structured or unstructured abstract. We further used 10 papers from Psychiatry Research as active comparators (unstructured format). We compared the quality of the ChatPDF-generated abstracts with the original human-written abstracts and examined the similarity, plagiarism, detected AI-content, and correctness of the AI-generated abstracts. Five experts evaluated the quality of the abstracts using a blinded approach. They also identified the abstracts written by the original authors and validated the conclusions produced by ChatPDF. We found that the similarity and plagiarism were relatively low (only 14.07% and 8.34%, respectively). The detected AI-content was 31.48% for generated structure-abstracts, 75.58% for unstructured-abstracts, and 66.48% for active comparators abstracts. For quality, generated structured-abstracts were rated similarly to originals, but unstructured ones received significantly lower scores. Experts rated 40% accuracy with structured abstracts, 73% with unstructured ones, and 77% for active comparators. However, 30% of AI-generated abstract conclusions were incorrect. In conclusion, the data organization capabilities of AI language models hold significant potential for applications to summarize information in clinical psychiatry. However, the use of ChatPDF to summarize psychiatric papers requires caution concerning accuracy.

Effect of inhaled aromatherapy on sleep quality in critically ill patients: A systematic review and network meta-analysis.

AIM: This study aimed to compare the effect of inhaled aromatherapy using various essential oils on the sleep quality of critically ill patients. BACKGROUND: Inhalation of essential oils significantly promotes the physiological and psychological health of patients in intensive care units (ICUs). However, research identifying and ranking the effects of different essential oils on the sleep quality of critically ill patients is lacking. DESIGN: This study followed the PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-Analyses of Health Care Interventions (PRISMA-NMA) guidelines. METHODS: A comprehensive search of five databases (Embase, MEDLINE, the Cochrane Library, CINAHL and PsycINFO) was conducted from their inception to March 15, 2023 (with an additional eligible study included dated August 14, 2023). Google Scholar was used as a supplementary method. Frequentist NMA was used to determine the effects of various essential oils. Certainty of evidence (CoE) was assessed using Confidence in Network Meta-Analysis (CINeMA). RESULTS: A total of 11 trials involving 690 critically ill patients were included in the analysis. The NMA of inhaled aromatherapy revealed that the combination of lavender, Matricaria recutita, and neroli essential oils (ratio 6:2:0.5) resulted in the most significant improvement in sleep quality compared to usual care, followed by Rosa damascene, peppermint, Citrus aurantium, pure sunflower oil and lavender oil alone. The overall CoE for the results was rated as low. CONCLUSIONS: The results of this study indicate that a combination of lavender, Matricaria recutita and neroli essential oils significantly positively affected sleep quality among critically ill patients. Despite the low quality of evidence, inhaled aromatherapy is non-invasive and easy to use. RELEVANCE TO CLINICAL PRACTICE: Inhaled aromatherapy can effectively improve sleep quality among critically ill patients. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution applies to this work. STUDY REGISTRATION: The study protocol was registered to the PROSPERO International Prospective Register of Systematic Reviews (protocol number CRD42023433194).

Development of a long-term care service integration self-assessment tool.

The World Health Organization emphasizes the importance of providing integrated care for older people. Taiwan is the fastest aging country in the world. In 2016, Taiwan implemented the Long-Term Care Plan 2.0 (TLTCP 2.0), aimed at providing integrated long-term care (LTC) services in communities. However, LTC service agencies have not been able to evaluate the level of integrated care they provide due to the lack of an effective assessment tool. To address this need, this study sets out to develop an integration assessment tool, namely the Self-Assessment for Service Integration in Long-Term Care (SASI-LTC), which will allow LTC agencies to self-evaluate their current level of integration from multiple perspectives. The SASI-LTC was developed based on Evashwick's framework, underwent two rounds of Delphi panels with twenty-six experts, and a pilot test with 243 valid questionnaires from administrators of Tier A agencies who are responsible for integrating LTC. The Delphi experts assessed the content with high levels of agreement using medians, the scale content validity index (SCVI) and item content validity index (ICVI). The SASI-LTC included four domains (inter-entity organization and management, integrated care coordination, integrated resources, and integrated information systems) with thirty items. The SASI-LTC showed good reliability (Cronbach's α = 0.94) and good validity, and a confirmatory factor analysis showed a good model fit index [χ2/df = 1.38; RMSEA = 0.040; CFI = 0.963; SRMR = 0.049] in pilot testing. While the SASI-LTC is a useful and feasible tool for Taiwan's LTC service agencies to evaluate their level of integration in providing LTC services, it could also be used in other countries with minor adjustments to localization of items related to financial integration.

A network meta-analysis of non-invasive brain stimulation interventions for autism spectrum disorder: Evidence from randomized controlled trials.

The efficacy and acceptability of various non-invasive brain stimulation (NIBS) interventions for autism spectrum disorder remain unclear. We carried out a systematic review for randomized controlled trials (RCTs) regarding NIBS for reducing autistic symptoms (INPLASY202370003). Sixteen articles (N = 709) met the inclusion criteria for network meta-analysis. Effect sizes were reported as standardized mean differences (SMDs) or odds ratios with 95 % confidence intervals (CIs). Fourteen active NIBS interventions, including transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation, and transcranial pulse stimulation were analyzed. Only anodal tDCS over the left dorsolateral prefrontal cortex paired with cathodal tDCS over an extracephalic location (atDCS_F3 + ctDCS_E) significantly improved autistic symptoms compared to sham controls (SMD = - 1.40, 95 %CIs = - 2.67 to - 0.14). None of the NIBS interventions markedly improved social-communication symptoms or restricted/repetitive behaviors in autistic participants. Moreover, no active NIBS interventions exhibited significant dropout rate differences compared to sham controls, and no serious adverse events were reported for any intervention.

Response trajectory to left dorsolateral prefrontal rTMS in major depressive disorder: A systematic review and meta-analysis: Trajectory of rTMS.

The depression response trajectory after a course of repetitive transcranial magnetic stimulation(rTMS) remains understudied. We searched for blinded randomized controlled trials(RCTs) that examined conventional rTMS over left dorsolateral prefrontal cortex(DLPFC) for major depressive episodes(MDE). The effect size was calculated as the difference in depression improvement, between active and sham rTMS. We conducted a random-effects dose-response meta-analysis to model the response trajectory from the beginning of rTMS to the post-treatment follow-up phase. The area under curve (AUC) of the first 8-week response trajectory was calculated to compare antidepressant efficacy between different rTMS protocols. We included 40 RCTs(n = 2012). The best-fitting trajectory model exhibited a logarithmic curve(X2=17.7, P < 0.001), showing a gradual ascent with tapering off around the 3-4th week mark and maintaining until week 16. The maximum effect size was 6.1(95 %CI: 1.25-10.96) at week 16. The subgroup analyses showed distinct trajectories across different rTMS protocols. Besides, the comparisons of AUC showed that conventional rTMS protocols with more pulse/session group or more total pulses were associated with greater efficacy than those with fewer pulse/session or fewer total pulses, respectively. A course of conventional left DLPFC rTMS could lead to both acute antidepressant effects and sustained after-effects, which were modeled by different rTMS protocols in MDE.

The dose-effect relationship of six stimulation parameters with rTMS over left DLPFC on treatment-resistant depression: A systematic review and meta-analysis.

This study aimed to evaluate the association of the six parameters, namely stimulation intensity, stimulation frequency, pulses per session, treatment duration, number of sessions, and total number of pulses with the efficacy of conventional transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex for patients with treatment-resistant depression (TRD). A random-effects dose-response meta-analysis of blinded randomized controlled trials (RCTs) involving 2391 participants were conducted to examine the dose-effect relationship of six stimulation parameters. Any of the six parameters significantly individually predicted proportion of variance in efficacy: pulses per session (R²=52.7%), treatment duration (R²=51.2%), total sessions (R²=50.9%), frequency (R²=49.6%), total pulses (R²=49.5%), and intensity (R²= 40.4%). Besides, we identified frequency as a potential parameter interacting with the other five parameters, resulting in a significant increase in variance(ΔR2) ranging from 5.0% to 16.7%. Finally, we found that RCTs using frequency > 10 Hz compared to those of 10 Hz showed better dose-effect relationships. We conclude that the six stimulation parameters significantly predict the dose-effect relationship of conventional rTMS on TRD. Besides, higher stimulation frequency, higher stimulation intensity, and adequate number of pulses were associated with treatment efficacy.

Efficacy and acceptability of different probiotic products plus laxatives for pediatric functional constipation: a network meta-analysis of randomized controlled trials.

The prevalence of pediatric constipation ranges from 0.7 to 29.6% across different countries. Functional constipation accounts for 95% of pediatric constipation, and the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. We aimed to compare the efficacy and acceptability of different probiotic supplements for pediatric functional constipation. The current frequentist model-based network meta-analysis (NMA) included RCTs of probiotic supplements for functional constipation in children. The primary outcome was changes in bowel movement or stool frequency; acceptability outcome was all-cause discontinuation. Nine RCTs were included (N = 710; mean age = 5.5 years; 49.4% girls). Most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives (standardized mean difference (SMD) = 1.87, 95% confidence interval (95% CI) = 0.85 to 2.90) were associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments (SMD = 1.37, 95% CI: 0.32 to 2.43). All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments.  Conclusion: The results of our NMA support the application of an advanced combination of probiotics and laxatives for pediatric functional constipation if there is no concurrent contraindication.  Registration: PROSPERO (CRD42022298724). What is Known: • Despite of the high prevalence of pediatric constipation, which ranges from 0.7% to 29.6%, the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. The widely heterogeneous strains of probiotics let the traditional meta-analysis, which pooled all different strains into one group, be nonsense and insignificant. What is New: • By conducting a comprehensive network meta-analysis, we aimed to compare the efficacy and acceptability of different strains of probiotic supplements for pediatric functional constipation. Network meta-analysis of nine randomized controlled trials revealed that the most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives was associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments. All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments.

Microbiome of periodontitis and peri-implantitis before and after therapy: Long-read 16S rRNA gene amplicon sequencing.

AIMS: The microbial profiles of peri-implantitis and periodontitis (PT) are inconclusive. The controversies mainly arise from the differences in sampling sites, targeted gene fragment, and microbiome analysis techniques. The objective of this study was to explore the microbiomes of peri-implantitis (PI), control implants (CI), PT and control teeth (CT), and the microbial change of PI after nonsurgical treatment (PIAT). METHODS: Twenty-two patients diagnosed with both PT and peri-implantitis were recruited. Clinical periodontal parameters and radiographic bone levels were recorded. In each patient, the subgingival and submucosal plaque samples were collected from sites with PI, CI, PT, CT, and PIAT. Microbiome diversity was analyzed by high-throughput amplicon sequencing using full-length of 16S rRNA gene by next generation sequencing. RESULTS: The 16S rRNA gene sequencing analysis revealed 512 OTUs in oral microbiome and 377 OTUs reached strain levels. The PI and PT groups possessed their own unique core microbiome. Treponema denticola was predominant in PI with probing depth of 8-10 mm. Interestingly, Thermovirga lienii DSM 17291 and Dialister invisus DSM 15470 were found to associate with PI. Nonsurgical treatment for peri-implantitis did not significantly alter the microbiome, except Rothia aeria. CONCLUSION: Our study suggests Treponemas species may play a pivotal role in peri-implantitis. Nonsurgical treatment did not exert a major influence on the peri-implantitis microbiome in short-term follow-up. PT and peri-implantitis possess the unique microbiome profiles, and different therapeutic strategies may be suggested in the future.

Efficacy and acceptability of noninvasive brain stimulation for treating posttraumatic stress disorder symptoms: A network meta-analysis of randomized controlled trials.

INTRODUCTION: Despite its high lifetime prevalence rate and the elevated disability caused by posttraumatic stress disorder (PTSD), treatments exhibit modest efficacy. In consideration of the abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC) and amygdala in PTSD, several randomized controlled trials (RCTs) addressing the efficacy of different noninvasive brain stimulation (NIBS) modalities for PTSD management have been undertaken. However, previous RCTs have reported inconsistent results. The current network meta-analysis (NMA) aimed to compare the efficacy and acceptability of various NIBS protocols in PTSD management. METHODS: We systematically searched ClinicalKey, Cochrane Central Register of Controlled Trials, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov to identify relevant RCTs. The targeted RCTs was those comparing the efficacy of NIBS interventions, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and transcutaneous cervical vagal nerve stimulation, in patients with PTSD. The NMA was conducted using a frequentist model. The primary outcomes were changes in the overall severity of PTSD and acceptability (to be specific, rates of dropouts for any reason). RESULTS: We identified 14 RCTs that enrolled 686 participants. The NMA demonstrated that among the investigated NIBS types, high-frequency rTMS over bilateral DLPFCs was associated with the greatest reduction in overall PTSD severity. Further, in comparison with the sham controls, excitatory stimulation over the right DLPFC with/without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms, including depression and anxiety symptoms, and overall PTSD severity. CONCLUSIONS: This NMA demonstrated that excitatory stimulation over the right DLPFC with or without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms. TRIAL REGISTRATION: PROSPERO CRD42023391562.

Comparison of different medical treatments for primary hyperaldosteronism: a systematic review and network meta-analysis.

Background: The effectiveness and side effects between different medical treatments in patients with primary hyperaldosteronism have not been systematically studied. Objective: To analyze the efficacy between different mineralocorticoid receptor antagonists (MRAs) and epithelial sodium channel (ENaC) inhibitors in a network meta-analysis (NMA) framework, while also evaluating adverse events. Design: Systematic review and NMA. Data sources and methods: The systematic review and NMA was reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, MEDLINE, the Cochrane library, and Excerpta Medica database (EMBASE) were searched for randomized controlled trials (RCTs) involving adult patients with primary hyperaldosteronism until 23 June 2023. Studies that compared the efficacy and side effects of different medical treatments of primary hyperaldosteronism were included. The primary outcomes included the effect on blood pressure, serum potassium, and major adverse cardiovascular events. The secondary outcomes were adverse events related to MRAs (hyperkalemia and gynecomastia). Frequentist NMA and pairwise meta-analysis were conducted. Results: A total of 5 RCTs comprising 392 participants were included. Eplerenone, esaxerenone, and amiloride were compared to spironolactone and demonstrated comparable effect on the reduction of systolic blood pressure. In comparison to spironolactone, eplerenone exhibited a less pronounced effect on reducing diastolic blood pressure [-4.63 mmHg; 95% confidence interval (CI): -8.87 to -0.40 mmHg] and correcting serum potassium (-0.2 mg/dL; 95% CI: -0.37 to -0.03 mg/dL). Spironolactone presented a higher risk of gynecomastia compared with eplerenone (relative risk: 4.69; 95% CI: 3.58-6.14). Conclusion: The present NMA indicated that the blood pressure reduction and potassium-correcting effects of the three MRAs may demonstrate marginal differences, with confidence levels in the evidence being very low. Therefore, further research is needed to explore the efficacy of these MRAs, especially regarding their impact on mortality and cardiovascular outcomes. Trial registration: PROSPERO (CRD: 42023446811).

Relationship Between Subjective Questionnaires and Videofluoroscopy of Dysphagia Evaluation: A Systematic Review and Meta-Analysis.

BACKGROUND: Early detection of dysphagia is important for preventing aspiration pneumonia. Although videofluoroscopy is currently the primary diagnostic tool for dysphagia, access to this tool may be limited because of radiation exposure risk, high cost, and other factors. PURPOSE: In this study, a meta-analysis was used to determine the strength of the correlation between dysphagia detection outcomes obtained using subjective questionnaires and videofluoroscopy. METHODS: The PubMed and Embase databases were searched for original articles up to December 2022. Studies published in English that used cross-sectional designs to assess the correlation between subjective questionnaires and videofluoroscopy were considered eligible for inclusion. The search terms used included "dysphagia," "questionnaire," and "videofluoroscopy." Two reviewers critically appraised and extracted the correlation coefficient r values. In addition, a random-effects meta-analysis was conducted. The Q statistic was used to assess the heterogeneity among the included studies. Publication bias was checked using the funnel plot and Egger's tests. Multilevel analysis was used to determine sensitivity to consider within-study correlations. In addition, subgroup analyses were conducted based on type of questionnaire, head and neck cancer, and English-speaking regions. RESULTS: The meta-analysis included five studies and 856 patients using the Eating Assessment Tool-10 and one study and 27 patients using the Sydney Swallow Questionnaire. The results of the random-effects meta-analysis showed a moderate relationship between the subjective questionnaires and videofluoroscopy ( r = .35, 95% CI [0.20, 0.48]). Similar results were also obtained using multilevel analysis ( r = .34, 95% CI [0.25, 0.42]). No publication bias was found for any of the studies ( p = .88). In the subgroup analyses, a moderate relationship between Eating Assessment Tool-10 and videofluoroscopy ( r = .31, 95% CI [0.19, 0.42]) and an ultrahigh relationship between Sydney Swallow Questionnaire and video-fluoroscopy ( r = .74, 95% CI [0.50, 0.87]) were found. Furthermore, moderate associations were observed within each head and neck cancer and English-speaking regions subgroup. However, no significant differences were found between these two subgroups. CONCLUSIONS: These results indicate the subjective questionnaires considered in this study share a moderate relationship with videofluoroscopy. Subjective questionnaires may be used as an auxiliary tool by nurses and homecare givers for the early assessment of dysphagia risk in patients.

Insights into optimal surgical fixation for posterior malleolar fractures.

Aims: The optimal management of posterior malleolar ankle fractures, a prevalent type of ankle trauma, is essential for improved prognosis. However, there remains a debate over the most effective surgical approach, particularly between screw and plate fixation methods. This study aims to investigate the differences in outcomes associated with these fixation techniques. Methods: We conducted a comprehensive review of clinical trials comparing anteroposterior (A-P) screws, posteroanterior (P-A) screws, and plate fixation. Two investigators validated the data sourced from multiple databases (MEDLINE, EMBASE, and Web of Science). Following PRISMA guidelines, we carried out a network meta-analysis (NMA) using visual analogue scale and American Orthopaedic Foot and Ankle Score (AOFAS) as primary outcomes. Secondary outcomes included range of motion limitations, radiological outcomes, and complication rates. Results: The NMA encompassed 13 studies, consisting of four randomized trials and eight retrospective ones. According to the surface under the cumulative ranking curve-based ranking, the A-P screw was ranked highest for improvements in AOFAS and exhibited lowest in infection and peroneal nerve injury incidence. The P-A screws, on the other hand, excelled in terms of VAS score improvements. Conversely, posterior buttress plate fixation showed the least incidence of osteoarthritis grade progression, postoperative articular step-off ≥ 2 mm, nonunions, and loss of ankle dorsiflexion ≥ 5°, though it underperformed in most other clinical outcomes. Conclusion: The NMA suggests that open plating is more likely to provide better radiological outcomes, while screw fixation may have a greater potential for superior functional and pain results. Nevertheless, clinicians should still consider the fragment size and fracture pattern, weighing the advantages of rigid biomechanical fixation against the possibility of soft-tissue damage, to optimize treatment results.