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Assessing the Risk of Bias in Randomized Clinical Trials With Large Language Models
Importance Large language models (LLMs) may facilitate the labor-intensive process of systematic reviews. However, the exact methods and reliability remain uncertain. Objective To explore the feasibility and reliability of using LLMs to assess risk of bias (ROB) in randomized clinical trials (RCTs). Design, Setting, and Participants A survey study was conducted between August 10, 2023, and October 30, 2023. Thirty RCTs were selected from published systematic reviews. Main Outcomes and Measures A structured prompt was developed to guide ChatGPT (LLM 1) and Claude (LLM 2) in assessing the ROB in these RCTs using a modified version of the Cochrane ROB tool developed by the CLARITY group at McMaster University. Each RCT was assessed twice by both models, and the results were documented. The results were compared with an assessment by 3 experts, which was considered a criterion standard. Correct assessment rates, sensitivity, specificity, and F1 scores were calculated to reflect accuracy, both overall and for each domain of the Cochrane ROB tool; consistent assessment rates and Cohen kappa were calculated to gauge consistency; and assessment time was calculated to measure efficiency. Performance between the 2 models was compared using risk differences. Results Both models demonstrated high correct assessment rates. LLM 1 reached a mean correct assessment rate of 84.5% (95% CI, 81.5%-87.3%), and LLM 2 reached a significantly higher rate of 89.5% (95% CI, 87.0%-91.8%). The risk difference between the 2 models was 0.05 (95% CI, 0.01-0.09). In most domains, domain-specific correct rates were around 80% to 90%; however, sensitivity below 0.80 was observed in domains 1 (random sequence generation), 2 (allocation concealment), and 6 (other concerns). Domains 4 (missing outcome data), 5 (selective outcome reporting), and 6 had F1 scores below 0.50. The consistent rates between the 2 assessments were 84.0% for LLM 1 and 87.3% for LLM 2. LLM 1's kappa exceeded 0.80 in 7 and LLM 2's in 8 domains. The mean (SD) time needed for assessment was 77 (16) seconds for LLM 1 and 53 (12) seconds for LLM 2. Conclusions In this survey study of applying LLMs for ROB assessment, LLM 1 and LLM 2 demonstrated substantial accuracy and consistency in evaluating RCTs, suggesting their potential as supportive tools in systematic review processes.
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Efficacy and safety of repetitive transcranial magnetic stimulation combined with antidepressants in children and adolescents with depression: A systematic review and meta-analysis
Objective: Non-invasive brain stimulation (NIBS) is beneficial to adult patients with depression, but its safety and efficacy in combination with antidepressants in children and adolescents with depression are not clear. We conducted a preliminary meta-analysis to objectively evaluate its clinical effect and provide information for future research and clinical practice. Methods: PubMed, Cochrane Library, Embase, and Web of Science were searched systematically to find clinical trials published in English before April 11, 2023. Stata software was used for meta-analysis, and random or fixed effect models were used to combine effect sizes. Results: Nine studies were eligible and included (n = 393). No articles about children were included in the analysis. The results showed that the remission rate was 40% (95% confidence interval [CI]: 13% to 71%). The scores of Children's Depression Rating Scale (CRDS) and Hamilton's depression scale (HAMD) significantly decreased compared to baseline value (MD = -27.04, 95% CI: -30.95, -23.12 and MD = -12.78, 95% CI: -19.55 to -6.01). In addition, the incidence of all adverse events was 13% (95% CI: 5%, 23%), and all were minor pain-related events. Conclusion: The combination of NIBS and antidepressants has been shown to notably alleviate depressive symptoms in adolescents, offering a considerable level of safety. This therapeutic synergy is particularly effective in patients with major depressive disorder, where repetitive transcranial magnetic stimulation augmented with antidepressants can enhance the amelioration of depressive symptoms. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023442215, PROSPERO CRD42023442215.
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Comparison of effectiveness and safety of lasmiditan and CGRP-antagonists for the acute treatment of migraine in adults: systematic review and network meta-analysis of randomised trials
ObjectiveTo compare the outcomes associated with the use of lasmiditan, rimegepant, ubrogepant, and zavegepant for the acute management of migraine headaches.MethodsWe searched four electronic databases from database inception to August 31, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the acute treatment of migraine. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of evidence using the CINeMA approach. We conducted frequentist network meta-analyses (NMA) to summarise the evidence. Data were analyzed using R-4.3.1.ResultsA total of 18 eligible studies including 10 different types of interventions with 22,429 migraine patients were included. NMA results showed that compared to ubrogepant (25 mg and 50 mg) and zavegepant, lasmiditan (100 mg and 200 mg) exhibits an elevated probability of achieving pain relief within a 2-hour interval. Similarly, relative to zavegepant, rimegepant (75 mg) and ubrogepant (50 mg and 100 mg) demonstrate an enhanced likelihood of sustaining pain relief over a 24-hour period. Furthermore, in contrast to ubrogepant (25 mg) and lasmiditan (50 mg), rimegepant (75 mg) presents a heightened probability of achieving freedom from photophobia within 2 h. Regarding safety, lasmiditan carries the highest risk of adverse events, which are associated with an increased incidence of adverse effects, including dizziness, somnolence, asthenia, paresthesia, and fatigue.ConclusionsIn this NMA, a spectrum of evidence ranging from very low to high levels underscores the favorable efficacy and tolerability of rimegepant 75 mg and ubrogepant 100 mg, positioning them as potential candidates for the acute management of migraine. Concurrently, lasmiditan (100 mg and 200 mg) exhibits notable efficacy, albeit accompanied by an increased susceptibility to adverse events. These findings should still be approached with caution, primarily due to the intrinsic limitations associated with indirect comparisons.
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CAR-T-cell therapies
Authors' objectives: The chimeric antigen receptor (CAR) T-cell therapies tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel) are provisionally listed in Appendix 1 of the Health Insurance Benefits Ordinance in Switzerland until 31 December 2024 for the third-line treatment of B-cell acute lymphoblastic leukaemia (B-ALL), diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL). This health technology assessment (HTA) evaluates the available evidence regarding the efficacy, effectiveness, safety, costs, cost-effectiveness and budget impact of tisa-cel and axi-cel compared to standard care in these populations. Ethical, legal, social and organisational issues associated with these therapies are also explored.
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The efficacy and acceptability of group trauma-focused cognitive behavior therapy for the treatment of post-traumatic stress disorder in children and adolescents: A systematic review and meta-analysis
BACKGROUND: Group trauma-focused cognitive behavior therapy (TF-CBT) is widely used to treat post-traumatic stress disorder (PTSD) in children and adolescents. However, the available evidence remains unclear. METHOD: PubMed, EMBASE, Cochrane, Web of Science, PsycINFO, CINAHL, ProQuest Dissertations, LILACS, and international trial registers were searched from database inception to April 30, 2022. We included randomized controlled trials (RCTs) that compared TF-CBT with any control condition for treating children and adolescents with PTSD. Analyses were performed using Review Manager version 5.3 and Stata 16.0. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. This study was registered with PROSPERO (CRD42020206096). RESULTS: Eleven RCTs involving 1942 patients were included. Group TF-CBT was significantly more effective than other treatments at post-treatment (standardized mean difference [SMD]: -0.43, 95% confidence interval [CI]: -0.65 to -0.22), follow-up (SMD: -0.33, 95% CI: -0.52 to -0.13), and in relieving depressive symptoms (SMD: -0.29, 95% CI: -0.49 to -0.09), but not in terms of acceptability. Subgroup analyses showed that group TF-CBT was superior to other treatments in studies including children with post-traumatic stress symptoms (PTSS) (SMD: -0.54, 95% CI: -0.79 to -0.28) and psychiatric comorbidities (SMD: -0.48, 95% CI: -0.72 to -0.23). LIMITATIONS: The small sample sizes of identified studies limited some findings. CONCLUSION: When considering effectiveness at post-treatment and follow-up or the reduction of depressive symptoms, group TF-CBT could be a good choice for children and adolescents with PTSD. Among these patients, those with PTSS or psychiatric comorbidities may benefit the most.
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Intravenous immunoglobulin for treatment of hospitalized COVID-19 patients: an evidence mapping and meta-analysis
Background: The clinical efficacy and safety of intravenous immunoglobulin (IVIg) treatment for COVID-19 remain controversial. This study aimed to map the current status and gaps of available evidence, and conduct a meta-analysis to further investigate the benefit of IVIg in COVID-19 patients. Methods: Electronic databases were searched for systematic reviews/meta-analyses (SR/MAs), primary studies with control groups, reporting on the use of IVIg in patients with COVID-19. A random-effects meta-analysis with subgroup analyses regarding study design and patient disease severity was performed. Our outcomes of interest determined by the evidence mapping, were mortality, length of hospitalization (days), length of intensive care unit (ICU) stay (days), number of patients requiring mechanical ventilation, and adverse events. Results: We included 34 studies (12 SR/MAs, 8 prospective and 14 retrospective studies). A total of 5571 hospitalized patients were involved in 22 primary studies. Random-effects meta-analyses of very low to moderate evidence showed that there was little or no difference between IVIg and standard care or placebo in reducing mortality (relative risk [RR] 0.91; 95% CI 0.78-1.06; risk difference [RD] 3.3% fewer), length of hospital (mean difference [MD] 0.37; 95% CI - 2.56, 3.31) and ICU (MD 0.36; 95% CI - 0.81, 1.53) stays, mechanical ventilation use (RR 0.92; 95% CI 0.68-1.24; RD 2.8% fewer), and adverse events (RR 0.98; 95% CI 0.84-1.14; RD 0.5% fewer) of patients with COVID-19. Sensitivity analysis using a fixed-effects model indicated that IVIg may reduce mortality (RR 0.76; 95% CI 0.60-0.97), and increase length of hospital stay (MD 0.68; 95% CI 0.09-1.28). Conclusion: Very low to moderate certainty of evidence indicated IVIg may not improve the clinical outcomes of hospitalized patients with COVID-19. Given the discrepancy between the random- and fixed-effects model results, further large-scale and well-designed RCTs are warranted
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The Efficacy, Safety, and Economic Outcomes of Using Ferric Derisomaltose for the Management of Iron Deficiency in China: A Rapid Health Technology Assessment.
Intravenous (IV) iron supplementation is the preferred treatment option for managing severe iron deficiency (ID) and ID anemia (IDA). Three of the available IV iron preparations are ferric derisomaltose (FDI), ferric carboxymaltose (FCM), and iron sucrose (IS). The objective of the present work was to review the published literature about the efficacy, safety, quality of life (QoL), and economic outcomes of using FDI, FCM, and IS for the treatment of ID. A systematic literature search was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies were assessed for quality using appropriate tools, and data were extracted and analyzed for key outcomes. The evidence synthesis was based on published systematic literature reviews (SLRs), meta-analyses (MAs), indirect treatment comparisons (ITCs), and health technology assessments (HTAs); we also included economic evaluations performed from a Chinese perspective. Out of 337 initial hits, the review included 12 studies. The findings indicated that FDI, FCM, and IS had comparable efficacy in terms of hemoglobin (Hb) improvement. FDI showed a better safety profile with a lower risk of hypophosphatemia, hypersensitivity reactions, and cardiovascular adverse events (AEs) compared to IS and FCM. FDI also demonstrated better cost-effectiveness compared to IS, with potential cost savings attributed to fewer infusions and improved compliance. None of the included studies evaluated QoL after IV iron administration for ID. FDI offers a safe, efficacious, and cost-effective treatment option for ID. It exhibits comparable efficacy to FCM and IS but presents a better safety profile and economic advantage. FDI fulfills the criteria of efficacy, safety, economy, innovation, suitability, and accessibility, making it a promising choice for ID management in China.
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Self-management support needs of patients with inflammatory arthritis and the content of self-management interventions: A scoping review
BACKGROUND: Self-management skills can empower a person to manage the physical, psychological, and social impact of a health condition. However, the components of self-management interventions differ widely between studies and interventions. By performing a scoping review, we aimed to describe patients' self-management needs and how health professionals (HPs) can provide effective self-management support to patients with inflammatory arthritis (IA). OBJECTIVES: 1) to identify the evidence for self-management support needs of patients with IA, and 2) to identify the content (theory/theoretical approach, mode of delivery, duration and frequency) of self-management interventions that target patients with IA. METHODS: In May 2021, we performed a systematic literature search (from 2000 onward) in five databases (CINAHL (Ebsco), Cochrane Library, Embase (Ovid), Medline (Ovid) and PsycINFO (Ovid)) regarding self-management in patients with IA. RESULTS: Out of 11,748 records identified, we included 31 articles describing patients' support needs and 33 articles describing the content of self-management interventions. Patients' support needs were sorted into six topics: 1) disease impact and the pharmacological treatment, 2) care continuity and relations with HPs, 3) the importance of non-pharmacological treatment, 4) the need for support from family and friends, 5) support needs related to work issues, and 6) contextual preferences for self-management support. The theory/theoretical approach, mode of delivery, duration and frequency varied widely and were often unclearly or insufficiently described. In addition, the self-management concept was scarcely - or not - defined in the included articles. The identified topics for support needs were compared with the described content in the included articles. Only a few self-management interventions focused on patients' need for support in relation to work, and to family and friends. CONCLUSION: HPs provided self-management support to patients with IA in various ways, but there were gaps between the patients' support needs and the identified interventions. In developing self-management interventions, the self-management concept needs to be defined and a clear theory is required to support the development of the intervention. Future studies should seek to investigate various modes of delivery, frequency and duration, to develop effective interventions that meet patients' support needs.
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Varenicline and related interventions on smoking cessation: A systematic review and network meta-analysis
Background: Based on randomized controlled trials, a network meta-analysis was conducted to compare treatment effects across varenicline and related smoking interventions. Methods: English databases were screened for randomized controlled trials reporting the effect of varenicline as treatment for smoking. The risk of bias in included trials was assessed using the Cochrane Handbook tool. Stata 15.1 software was used to perform network meta-analysis, and the GRADE approach was used to assess the evidence credibility on the tobacco treatment effects of different interventions. Results: Thirty-four studies involving 26,130 smokers were included in the network meta-analysis. Varenicline and 11 other interventions were reported, yielding 66 pairs of comparisons. Network meta-analysis showed that varenicline monotherapy or its combination with other interventions were superior in achieving smoking cessation compared to bupropion, nicotine replacement therapy, counselling, and placebo. Furthermore, compared to the varenicline, evident abstinence superiority was found in varenicline + bupropion (odds ratio = 1.49, 95% confidence interval [1.02, 2.18]). Finally, the surface under the cumulative ranking curve value indicated that varenicline + bupropion has the highest probability to become the best intervention. Conclusions: Varenicline monotherapy increased the odds of smoking cessation further than bupropion monotherapy, nicotine replacement therapy, counselling, and placebo, while varenicline combined with other interventions may even achieve a better abstinence effect. More credible evidence has been reported indicating that the combination of varenicline and bupropion is a superior treatment for smoking.
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Cognitive behavior therapy for insomnia in cancer patients: a systematic review and network meta-analysis
Objective: The aim of this study was to examine the most effective delivery format of cognitive behavioral therapy for insomnia (CBT-I) on insomnia in cancer patients. Methods: We searched five databases up to February 2021 for randomized clinical trials that compared CBT-I with inactive or active controls for insomnia in cancer patients. Outcomes were insomnia severity, sleep efficiency, sleep onset latency (SOL), wake after sleep onset (WASO), and total sleep time (TST). Pairwise meta-analyses and frequentist network meta-analyses with the random-effects model were applied for data analyses. Results: Sixteen unique trials including 1523 participants met inclusion criteria. Compared with inactive control, CBT-I could significantly reduce insomnia severity (mean differences [MD] = -4.98 points, 95% confidence interval [CI]: -5.82 to -4.14), SOL (MD = -12.29 min, 95%CI: -16.48 to -8.09), and WASO (MD = -16.58 min, 95%CI: -22.00 to -11.15), while increasing sleep efficiency (MD = 7.62%, 95%CI: 5.82% to 9.41%) at postintervention. Compared with active control, CBT-I could significantly reduce insomnia severity (MD = -2.75 points, 95%CI: -4.28 to -1.21), SOL (MD = -13.56 min, 95%CI: -18.93 to -8.18), and WASO (MD = -6.99 min, 95%CI: -11.65 to -2.32) at postintervention. These effects diminished in short-term follow-up and almost disappeared in long-term follow-up. Most of the results were rated as "moderate" to "low" certainty of evidence. Network meta-analysis showed that group CBT-I had an increase in sleep efficiency of 10.61%, an increase in TST of 21.98 min, a reduction in SOL of 14.65 min, and a reduction in WASO of 24.30 min, compared with inactive control at postintervention, with effects sustained at short-term follow-up. Conclusions: CBT-I is effective for the management of insomnia in cancer patients postintervention, with diminished effects in short-term follow-up. Group CBT-I is the preferred choice based on postintervention and short-term effects. The low quality of evidence and limited sample size demonstrate the need for robust evidence from high-quality, large-scale trials providing long-term follow-up data.
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Comparative efficacy and acceptability of cognitive behavioral therapy delivery formats for insomnia in adults: A systematic review and network meta-analysis
This review compared the efficacy and acceptability of different delivery formats for cognitive behavioral therapy for insomnia (CBT-I) in insomnia. We searched five databases for randomized clinical trials that compared one CBT-I delivery format against another format or control conditions for insomnia in adults. We used pairwise meta-analyses and frequentist network meta-analyses with the random-effects model to synthesize data. A total of 61 unique trials including 11,571 participants compared six CBT-I delivery formats with four control conditions. At post-intervention, with low to high certainty evidence, individual, group, guided self-help, digital assisted, and unguided self-help CBT-I could significantly increase sleep efficiency and total sleep time (TST) and reduce sleep onset latency (SOL), wake after sleep onset (WASO), and insomnia severity compared with treatment as usual (MD range for sleep efficiency: 7.81%-12.45%; MD range for TST: 16.14-33.96 min; MD range for SOL:-22.42 to-13.81 min; MD range for WASO:-40.84 to-19.48 min; MD range for insomnia severity:-6.40 to-3.93) and waitlist (MD range for sleep efficiency: 7.68%-12.32%; MD range for TST: 12.67-30.49 min; MD range for SOL:-19.07 to-10.46 min; MD range for WASO:-47.10 to-19.15 min; MD range for insomnia severity:-7.59 to-5.07). The effects of different CBT-I formats per-sisted at short-term follow-up (4 wk-6 mo). Individual, group, and digital assisted CBT-I delivery formats would be the more appropriate choices for insomnia in adults, based on post-intervention and short-term effects. Further trials are needed to investigate the long-term effects of different CBT-I formats. (c) 2022 Elsevier Ltd. All rights reserved.
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The effect of Varenicline and Bupropion on smoking cessation: A network meta-analysis of 20 randomized controlled trials
Objective: A network meta-analysis (NMA) was conducted to investigate the effect of varenicline (VAR), bupropion (BUP), and nicotine replacement therapy (NRT) on smoking cessation. Methods: Eight databases were searched in May 2021, and only randomized controlled trials (RCTs) using varenicline, bupropion, or NRT (single or combined) for smoking cessation were included. The risk of bias in the included RCTs was assessed using the Cochrane Handbook tool. Stata 15.1 software was used to perform NMA, and the quality of the evidence was evaluated using Confidence in Network Meta-analysis (CINeMA). Findings: Twenty RCTs involving 16,702 smokers were included. The risk of bias results showed that 10 RCTs were rated as high, three were low, and seven were unclear. A total of 21 pairs were compared based on seven interventions. The NMA showed that, compared to the placebo (PLA), the other six interventions had significant efficacy in smoking cessation, where VAR + BUP showed the best effect of all treatments (odds ratio (OR) = 6.08, 95% confidence interval (CI) [3.47, 10.66]). Moreover, VAR + BUP was superior to VAR + NRT (OR = 1.66, 95% CI [1.07, 2.59]) and the three monotherapies (VAR, BUP, and NRT). In the monotherapies, the results of pairwise comparisons of VAR, BUP, and NRT did not show significant differences. Finally, the surface under the cumulative ranking curve (SUCRA) value indicated that VAR + BUP had the greatest probability of becoming the best intervention. Conclusions: The efficacy of VAR, BUP, and NRT alone increased the odds of smoking abstinence better than the placebo, combined interventions were superior to monotherapy, and VAR combined with other interventions had a better smoking cessation effect.
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Chinese Medicine as an Adjunctive Treatment for Gastric Cancer: Methodological Investigation of meta-Analyses and Evidence Map
Background: Many meta-analyses (MAs) on Chinese medicine (CM) as an adjunctive treatment for gastric cancer have been published in recent years. However, the pooled evidence reported in MAs and their methodological quality remain unknown. Therefore, we designed a study to comprehensively evaluate and summarize the current evidence of CMs for gastric cancer in published MAs. Methods: A systematic search on MAs published in English from inception to 1st September 2021 was conducted in PubMed and Embase. The AMSTAR-2 tool was used to evaluate the methodological quality of the included MAs, and the results of the quality assessment were visualized using the evidence mapping method. Stata 17/SE was used for statistical analysis (Registration number: INPLASY202190005). Results: A total of 20 MAs (16 pairwise and 4 network MAs) were included from 118 records. These MAs were published in 14 journals from 2013 to 2021, with the number of patients and trials ranging from 688 to 6,857, and from 10 to 85, respectively. A large number of CMs (e.g., AiDi, FuFangKuShen, and HuaChanSu) in combination with chemotherapy for gastric cancer were identified among the included MAs. According to the pooled results reported in MAs, when compared to chemotherapy alone, CMs in combination with chemotherapy not only improve various outcomes on efficacy (e.g., objective response rate, quality of life) but also reduce various adverse reactions (e.g., leucopenia, nausea and vomiting). Only 2 MAs were low in terms of the overall methodological quality, while the other 18 MAs were all critically low. The methodology was required to be advanced significantly, mainly involving: study protocol and registration, explanation for the inclusion of study design, list of excluded studies with justifications, adequate details of included studies, reporting on funding sources of primary studies, and evaluation of the potential impact of risk of bias. In addition, MAs that received funds support (β = 2.68; 95%CI: 0.40 to 4.96; p = 0.024) or were published in journals with higher impact factor (β = 2.81; 95%CI: 0.69 to 4.92; p = 0.012) had a higher score on the overall methodological quality in the univariate analysis, but the results were not statistically significant according to the multivariate analysis. Conclusion: Combining CMs with chemotherapy can potentially improve clinical outcomes and reduce the relevant adverse effects in patients with gastric cancer. However, the methodological quality of relevant MAs requires significant improvement, and the current evidence needs to be validated through multinational trials that are well-designed and have a large sample size.
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Infliximab reference product versus biosimilar for the treatment of rheumatoid arthritis
Authors' objectives: Background: In Switzerland, relatively low biosimilar prescription rates have prompted the interest of the authorities. A health technology assessment (HTA) was requested to compare the available evidence of the infliximab reference product and its biosimilar for treating rheumatoid arthritis (RA). Objective: This HTA examines the efficacy, effectiveness and safety of the infliximab biosimilar compared to its reference product in RA and presents the health economic impact of a potentially increased biosimilar utilization in Switzerland. Furthermore, ethical, legal, social and organisational aspects of treatment initiation with biosimilars or switching to biosimilars are analysed. Research questions: Is it safe, efficacious and effective 1) to initiate treatment with infliximab biosimilar instead of the infliximab reference product, 2) to switch treatment from the infliximab reference product to infliximab biosimilar and 3) to switch treatment from infliximab biosimilar to the infliximab reference product in patients with RA?
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Clinical Efficacy and Safety of Proton and Carbon Ion Radiotherapy for Prostate Cancer: A Systematic Review and Meta-Analysis
Background & Carbon ion radiotherapy (CIRT) and proton beam therapy (PBT) are promising methods for prostate cancer, however, the consensus of an increasing number of studies has not been reached. We aimed to provide systematic evidence for evaluating the efficacy and safety of CIRT and PBT for prostate cancer by comparing photon radiotherapy. Materials and Methods: We searched for studies focusing on CIRT and PBT for prostate cancer in four online databases until July 2021. Two independent reviewers assessed the quality of included studies and used the GRADE approach to rate the quality of evidence. R 4.0.2 software was used to conduct the meta-analysis. A meta-regression test was performed based on the study design and tumor stage of each study. Results: A total of 33 studies including 13 CIRT- and 20 PBT-related publications, involving 54,101, participants were included. The quality of the included studies was found to be either low or moderate quality. Random model single-arm meta-analysis showed that both the CIRT and PBT have favorable efficacy and safety, with similar 5-year overall survival (OS) (94 vs 92%), the incidence of grade 2 or greater acute genitourinary (AGU) toxicity (5 vs 13%), late genitourinary (LGU) toxicity (4 vs 5%), acute gastrointestinal (AGI) toxicity (1 vs 1%), and late gastrointestinal (LGI) toxicity (2 vs 4%). However, compared with CIRT and PBT, photon radiotherapy was associated with lower 5-year OS (72-73%) and a higher incidence of grade 2 or greater AGU (28-29%), LGU (13-14%), AGI (14-19%), and LGI toxicity (8-10%). The meta-analysis showed the 3-, 4-, and 5-year local control rate (LCR) of CIRT for prostate cancer was 98, 97, and 99%; the 3-, 4-, 5-, and 8-year biochemical relapse-free rate (BRF) was 92, 91, 89, and 79%. GRADE assessment results indicated that the certainty of the evidence was very low. Meta-regression results did not show a significant relationship based on the variables studied (P < 0.05). Conclusions: Currently available evidence demonstrated that the efficacy and safety of CIRT and PBT for prostate cancer were similar, and they may significantly improve the OS, LCR, and reduce the incidence of GU and GI toxicity compared with photon radiotherapy. However, the quantity and quality of the available evidence are insufficient. More high-quality controlled studies are needed in the future.
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Comparative efficacies of different immunotherapy regimens in recurrent implantation failure: A systematic review and network meta-analysis
For patients with recurrent implantation failure (RIF), immune system imbalances have become the focus of research. The effects of different classes of immunotherapies on improving pregnancy outcomes have not been fully established. This network meta-analysis was performed to assess the impact of popular immunotherapies in women with RIF. We systematically searched the Cochrane Central Register of Controlled Trials, PubMed, Embase, and Web of Science databases as well as clinical trial registration websites. Randomized controlled trials comparing immunotherapeutic outcomes were included. We performed the random-effects network metaanalysis to compare efficacy measures. A total of 21 trials involving 2277 participants and 8 immunotherapies were eligible for this study. Patients that had been administered with PBMCs, G-CSF, PRP, and sirolimus exhibited higher CPR than those administered with the placebo (2.63, 1.71-4.06; 2.03, 1.35-3.05; 1.98, 1.02-3.84; 2.55, 1.36-4.79; and 3.95, 1.33-11.72, respectively). For IR, only PBMCs and G-CSF were significantly more effective than the placebo (2.92, 1.39-6.12; 2.66, 1.16-6.06, respectively). In terms of LBR, PBMCs (2.96, 1.67-5.27) and sirolimus (3.55, 1.18-10.64) were effective. However, r-hLIF (0.25, 0.10-0.62) had a reduced risk of LBR. No therapeutic regimen was found to have significantly decreased MR, but PBMCs exhibited the lowest rank among all interventions (0.28, 0.06-1.44). To improve clinical pregnancy while reducing miscarriage outcomes, PBMCs might be a beneficent therapeutic option for RIF in the future.
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Characteristics of systematic reviews evaluating treatments for COVID-19 registered in PROSPERO
Characteristics and research collaboration of registered systematic reviews (SRs) on treatment modalities for coronavirus disease-2019 (COVID-19) remain unclear. This study analysed research collaboration, interventions and outcome measures in registered SRs on COVID-19 treatments and pointed out the relevant problems. PROSPERO (international prospective register of systematic reviews) was searched for SRs on COVID-19 treatments as of 2 June 2020. Excel 2016 was used for descriptive analyses of the extracted data. VOSviewer 1.6.14 software was used to generate network maps for collaborations between countries and institutions. A total of 189 SRs were included, which were registered by 301 institutions from 39 countries. China (69, 36.50%) exhibited the highest output. Cooperation between countries was not close enough. As an institution, the Chengdu University of Traditional Chinese Medicine (7, 3.70%) had the highest output. There was close cooperation between institutions. Interventions included antiviral therapy (81, 42.86%), respiratory support (16, 8.47%), circulatory support (11, 5.82%), plasma therapy for convalescent patients (11, 5.82%), immunotherapy (9, 4.76%), TCM (traditional Chinese medicine) treatment (9, 4.76%), rehabilitation treatment (5, 2.65%), anti-inflammatory treatment (16, 8.47%) and other treatments (31, 16.40%). Concerning antiviral therapy (81, 42.86%), the most commonly used antiviral agents were chloroquine/hydroxychloroquine (26, 13.76%), followed by remdesivir (12, 6.35%), lobinavir/ritonavir (11, 5.82%), favipiravir (5, 2.65%), ribavirin (5, 2.65%), interferon (5, 2.65%), abiron (4, 2.12%) and abidor (4, 2.12%). The most frequently used primary and secondary outcomes were the mortality rate (92, 48.68%) and hospital stay length (48, 25.40%), respectively. The expression of the outcomes was not standardised. Many COVID-19 SRs on treatment modalities have been registered, with a low completion rate. Although there was some collaboration between countries and institutions in the currently registered SRs on treatment modalities for COVID-19 on PROSPERO, cooperation between countries should be further enhanced. More attention should be directed towards identifying deficiencies of outcome measures, and the standardisation of results should be maximised.
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Effectiveness of smartphone-based self-management interventions on self-efficacy, self-care activities, health-related quality of life and clinical outcomes in patients with type 2 diabetes: A systematic review and meta-analysis
OBJECTIVES: To review the evidence and determine the effectiveness of smartphone-based self-management interventions on self-efficacy, self-care activities, health-related quality of life, glycated hemoglobin, body mass index (BMI), and blood pressure (BP) levels of adults with type 2 diabetes mellitus . METHODS: A systematic search of five databases (PubMed, Embase, Cochrane, CINAHL and Scopus) was conducted. Studies published in English from January 2007 to January 2018 were considered. Only randomized controlled trials (RCTs) of smartphone-based self-management interventions for patients with type 2 diabetes mellitus that reported any of the study outcomes were included. Two reviewers independently screened the studies, extracted data and assessed the quality of the studies. Meta-analyses were conducted for the different study outcomes. RESULTS: A total of 26 articles, consisting of 22 studies with 2645 participants, were included in the review. The results from meta-analysis on the studies revealed that as compared to control group, participants received smartphone-based self-management intervention had better self-efficacy with large effect size of 0.98 (P < 0.001), self-care activities with effect size of 0.90 (P < 0.001), health related quality of life with effect size of 0.26 (p=0.01), and lower glycated hemoglobin (pooled MD=-0.55; p<0.001). Subgroup analyses were also conducted for self-efficacy as significant heterogeneity was present among the studies. The effects on BMI and BP were not statistically significant. CONCLUSIONS: Smartphone-based self-management interventions appear to have beneficial effects on self-efficacy, self-care activities and health-relevant outcomes for patients with type 2 diabetes mellitus. However, more research with good study design is needed to evaluate the effectiveness of smartphone-based self-care interventions for T2DM.
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Assessing the efficacy of mobile health apps using the basic principles of cognitive behavioral therapy: Systematic review
BACKGROUND: Cognitive behavioral therapy (CBT) in its basic principle has developed itself as a stand-alone, substantial method of therapy. With effective application in therapy for a range of mental health issues, the spread of CBT methods to Web-based therapy sources is evident. The development of mobile phone apps using CBT principles is increasing within the research area. Despite the move to Web-based methods of therapy, it is argued that these methods lack the same efficacy of face-to-face therapy sessions. OBJECTIVE: The aim of this review was to assess extent research findings with regard to the effectiveness of CBT-related mobile health (mHealth) apps. By assessing only studies employing a randomized controlled trial design, the review aimed to determine app efficacy within the highly regarded method of investigation. METHODS: A comprehensive literature search was conducted across several databases. Search results were filtered, and results were subject to strict inclusion and exclusion criteria because of the nature of the review. Where possible, analysis of effect size was calculated and results reported. RESULTS: A total of 8 studies investigating the effectiveness of mHealth CBT-related apps across a range of mental health issues were reviewed. Three studies used the app against a control group, and 5 studies used the app intervention against another form of treatment or intervention. A range of effect sizes were seen across all included studies (d=-0.13 to 1.83; 0.03-1.44), with the largest effects often being seen when comparing the data from pre- to posttest for the app engaged group. CONCLUSIONS: The studies reviewed support the use of mHealth apps containing CBT principles for a range of mental health issues. However, the effectiveness over longer time periods should be assessed. Researchers and professionals should seek to collaborate effectively when creating new apps to enhance their effectiveness as a treatment for the general public.
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Effects of self-management on chronic kidney disease: A meta-analysis
BACKGROUND: Self-management programs may facilitate the improvement of outcomes in medical, role, and emotional management and health-related quality of life in patients with chronic kidney disease. Studies on the effect of three self-management tasks have reported conflicting findings. In addition, systematic reviews are unavailable. OBJECTIVE: This study evaluated the effects of self-management programs on medical, role, and emotional management and health-related quality of life in chronic kidney disease. DESIGN: Meta-analysis of randomized controlled studies. DATA SOURCES: The meta-analysis involved an online search of the English literature from PubMed, Cochrane, Web of Science, and CINAHL and the Chinese literature from the Airiti Library that were published from the inception of the websites until January 1, 2017. REVIEW METHODS: The meta-analysis was conducted to evaluate the effects of self-management on chronic kidney disease outcomes. Electronic databases were searched by using keywords: chronic kidney disease, end-stage renal disease, renal failure, dialysis, self-management, self-efficacy, empowerment, cognitive behavioral, and educational. The methodological quality of randomized controlled trials was assessed using the Cochrane Handbook. Data were analyzed using Comprehensive Meta-Analysis software 2.0. RESULTS: Eighteen randomized controlled trials met our inclusion criteria. The results revealed that the self-management program significantly enhanced the effects of self-management on outcomes of medical, role, and emotional management and health-related quality of life in patients with chronic kidney disease. The following Hedges' g (effect size) values were obtained: (1) interdialytic weight gain, -0.36 (95% confidence interval, -0.60 to -0.12, p<0.01); (2) self-efficacy, 0.57 (95% confidence interval, 0.18-0.96, p<0.01); (3) anxiety, -0.95 (95% confidence interval, -1.65 to -0.25, p=0.01); (4) depression, -0.63 (95% confidence interval, -0.85 to -0.41, p<0.01) (5) health-related quality of life for the mental component of the SF-36, 0.71 (95% confidence interval, 0.45-0.97, p<0.01); (6) the physical component of the SF-36, 0.61 (95% confidence interval, 0.35-0.86, p<0.01); and (7) the Kidney Disease Quality of Life, 0.41 (95% confidence interval, 0.17-0.65, p<0.01). DISCUSSION: This study revealed a small effect of self-management on interdialytic weight gain; medium effects on self-efficacy, depression, and health-related quality of life; and a large effect on anxiety. However, high-quality randomized controlled trial designs are required to confirm these results, although the existing evidence can guide clinical practitioners and health policy makers.
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