Systematic review and meta-analysis of the association between long working hours and hypertension risk.

BACKGROUND: Hypertension, a major public health problem worldwide, has been linked to lifestyle factors and work conditions, with conflicting evidence on the association between long work hours and risk of hypertension. METHODS: We conducted a systematic review and meta-analysis of observational studies to investigate the relationship between working hours and hypertension or blood pressure, assessed the risk of bias and performed subgroup analyses. The protocol was registered with the International Prospective Register of Systematic Reviews. RESULTS: The pooled OR for the association between long working hours and risk of hypertension was 1.09 (95% CI: 0.88 to 1.35) in the 15 studies that used hypertension as the outcome. In the three studies that used blood pressure as the outcome, diastolic blood pressure was higher among those with long working hours compared with those with non-long working hours (1.24 mm Hg, 95% CI: 0.19 to 2.29). In subgroup analysis, the pooled OR for the association between long working hours and risk of hypertension was 1.28 (95% CI: 1.14 to 1.44) and 1.00 (95% CI: 0.64 to 1.56) in women and men, respectively. CONCLUSIONS: Although this study could not clearly confirm the relationship between long working hours and hypertension, the subgroup analysis suggests that long working hours may be associated with hypertension, particularly among women. More reliable research is needed to establish causality. PROSPERO REGISTRATION NUMBER: CRD42023406961.

Report for the Eighth Asian National Control Laboratory Network meeting in 2023: Self-sufficiency strategy of plasma-derived medicinal products and regulatory harmonisation.

The Eighth Asian National Control Laboratory (NCL) Network meeting, entitled "Biological Products Quality Control and Self-Sufficiency Strategy focusing on plasma-derived medicinal products (PDMPs)" was held in Seoul on 31 August 2023. The participants were NCL experts from Indonesia, Japan, Malaysia, the Philippines, Vietnam, and the Republic of Korea. Special lectures included the PDMPs self-sufficiency strategies of the World Health Organization (WHO) and Indonesian Food and Drug Authority, and a case study on Global Benchmarking Tool (GBT) assessment for vaccines by the Korea Ministry of Food and Drug Safety. The NCL delegates shared their current experiences with national lot releases and biological standardisation. The meeting contributed to a mutual understanding of the progress of the PDMPs self-sufficiency among Asian countries, the WHO's support strategies, and the NCL's plan for the preparation of the WHO GBT assessment. In the panel discussion, all participants agreed that building capacity in blood safety in the Asian region and harmonisation of relevant international regulatory requirements will support appropriate emergency preparedness, particularly source materials in the region, and will build the foundation for resolving the PDMPs supply insecurity that has worsened after the COVID-19 pandemic in some countries.

Comparative Effectiveness of Cognitive Behavioral Therapy and Behavioral Therapy in Obesity: A Systematic Review and Network Meta-Analysis.

We aimed to evaluate the effects of obesity treatment with behavioral therapy (BT) and cognitive behavioral therapy (CBT) interventions compared with multiple comparators and find effective techniques or combinations of techniques in BT and CBT interventions for weight loss. We systematically searched electronic databases and selected randomized controlled trials using CBT or BT intervention for obesity treatment in overweight adults or adults with obesity without psychological symptoms. Both pairwise meta-analysis and network meta-analysis were performed to comprehensively evaluate the comparative effects between interventions. We classified the techniques used in BT and CBT interventions and compared the treatment effects between techniques. Compared with no treatment as a common comparator, CBT was most effective for weight loss, followed by BT, usual care (UC), and minimal care (MC). CBT was a more effective intervention than BT, but the effect of CBT compared to BT was not remarkable in network estimates. The most used BT techniques were feedback and monitoring, and the most used CBT technique was cognitive restructuring. Our results indicated that CBT and BT are effective interventions for weight loss, and that successful weight loss requires more aggressive interventions such as BT or CBT than MC and UC.

Report on the seventh meeting of national control laboratories for vaccines and biologicals of the WHO Western Pacific and South-East Asia member states.

The Biregional Network of National Control Laboratories (NCLs) of the WHO Western Pacific and South-East Asia Regions has been meeting annually since 2018 to enhance NCLs' voluntary participation capacity. Its seventh meeting was hosted by the Korea National Institute of Food and Drug Safety Evaluation (NIFDS) of the Ministry of Food and Drug Safety (MFDS), in conjunction with the Global Bio Conference, in Seoul on September 6, 2022. Over 60 participants from seven countries, (India, Indonesia, Japan, Korea, Malaysia, the Philippines, and Vietnam) attended the meeting on-site and online. The theme of this meeting was 'Quality Control Issues and International Trends for Biologicals including Vaccines and Plasma-Derived Medicinal Products.' Three special speeches were presented on sharing the quality control system for biologicals, including NCLs' considerations in preparing the WHO Listed Authorities and sharing MFDS experiences. Furthermore, the participating NCLs shared country-specific issues related to national lot releases during the COVID-19 pandemic and acknowledged the meeting's crucial role in response preparedness for pandemic emergencies and enhancing regulatory capacity through coalitions and information exchange among NCLs. The NIFDS will cooperate closely with other Asian NCLs to enhance biological product quality control, aiming to establish regional standards and standardize test methods through collaboration.

A collaborative study to establish the second national standard for hepatitis B immunoglobulin in Korea.

This study aimed to establish a second national standard for hepatitis B immunoglobulin (HBIG) that can be used for potency assays of hepatitis B and normal immunoglobulin. The candidate material was manufactured using a process approved as Good Manufacturing Practice. The freeze-dried candidate preparation was tested for physicochemical and biological properties, including pH, residual moisture, molecular size distribution, and potency. A collaborative study was performed involving four laboratories, including the National Institute of Food and Drug Safety Evaluation, as an official national control laboratory in Korea and manufacturers. The potency was calibrated against the second international standard for HBIG using two enzyme immunoassays: enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay. Results from 240 assays were obtained from four laboratories, and combined potency estimates were obtained by calculating the geometric means. Intra- and inter-laboratory variability showed acceptable geometric coefficients of variation of 1.3-6.0 and 3.2-3.6%, respectively. The candidate preparation showed satisfactory stability in accelerated thermal degradation and real-time stability tests. Based on these results, the potency value of 105 IU/vial was assigned (95% confidence intervals: 100.0-109.2 IU/vial), and it was deemed suitable to serve as the Korean national standard for HBIG.

Comparison of the clinical effectiveness of treatments for aromatase inhibitor-induced arthralgia in breast cancer patients: A systematic review with network meta-analysis.

Aromatase inhibitor-induced arthralgia (AIA) contributes to poor adherence of aromatase inhibitor therapies in patients with breast cancer. A systematic review using network meta-analysis (NMA) was conducted to examine the clinical effectiveness of multiple therapies and rank probabilities for the management of AIA. Randomized controlled trials (RCTs) assessing treatments for AIA in postmenopausal women with stage 0-III hormone receptor-positive breast cancer were searched from inception to October 2021. The main NMA involved 1516 participants from 17 RCTs. Acupuncture was the highest ranked intervention to improve pain intensity followed by sham acupuncture, multicomponent herbal medicine, exercise, duloxetine, vitamin D, omega-3 fatty acids, physical therapy, testosterone, and inactive controls. Single natural products were inferior to controls. The current review provides new insights into the management of AIA in breast cancer survivors for increased survival and can be utilized to make evidence-based decisions regarding treatment.

Radiotherapy for bone metastases of hepatocellular carcinoma: a hybrid systematic review with meta-analyses.

INTRODUCTION: External beam radiation therapy (EBRT) is commonly used as a palliative treatment for bone metastases of hepatocellular carcinoma (HCC). We planned a hybrid systematic review that meta-analyzed the efficacy and feasibility of EBRT and reviewed the literature to answer specific clinical questions. METHODS: The PubMed, Medline, Embase, and Cochrane Library databases were searched through 1 December 2021. Primary endpoints were overall survival (OS) and response rate (RR). Secondary endpoints were comparative data, including treatment response and survival related to dose escalation, number of metastases, and fractionation scheme. Formal pooled analyses were performed on the primary endpoints, and the secondary endpoints were systematically reviewed. Complications were also reviewed. RESULTS: Nineteen studies involving 1613 patients with HCC and bone metastases were included. The median OS was 6 months (range: 3-13 months). The pooled one-year OS was 23.1% (95% confidence interval [CI]: 18.4-28.6); pooled pain RR was 81.5% (95% CI: 76.4-85.7) and of pain complete remission was 26.5% (95% CI: 21.7-32.0). Pain response might be related to dose escalation, considering the moderate consistency of results and plausibility, with a low-quality grade of evidence†. Considering the indeterminate results, we cannot suggest that dose escalation is correlated with OS. The oligometastasis status might be related to better OS, considering the high consistency of results and plausibility with low to moderate quality of evidence. Hypofractionated EBRT might yield comparable efficacy to conventional EBRT, with a low-quality grade of evidence. There were few complications of grade ≥3, except for hematologic complications, which ranged from 11.5to 34%. CONCLUSION: EBRT is an efficient and feasible palliative option. Clinical consideration of hematologic complications is necessary. Future studies are needed to increase the quality of evidence for actual clinical questions. †Reference to a system of the American Society for Radiation Oncology primary liver cancer clinical guidelines.

Evaluation of the Reporting Standard Guidelines of Network Meta-Analyses in Physical Therapy: A Systematic Review.

The concept of network meta-analyses (NMA) has been introduced to the field of physical therapy. However, the reporting standard guidelines of these studies have not been evaluated. In this systematic review, we included all published NMA physical therapy studies that compared the clinical efficacy of three or more interventions to evaluate whether NMAs in physical therapy exhibit adequate reporting recommendations. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched up to 30 June 2022. Among the 252 identified articles, 19 NMAs including 805 randomized controlled trials were included. We applied both preferred reporting items for systematic reviews and meta-analysis (PRISMA) and PRISMA-NMA checklists, which are 27- and 32-item reporting standard guidelines assessment tools, respectively. Protocol registrations (68.4%), risk of bias across studies (63.2%), additional analysis (57.9%), and funding (31.6%) were problematic items considering the PRISMA guidelines. Four studies reported all five new NMA-reporting items, and 15 (78.9%) did not address items S1-5 from the PRISMA-NMA guidelines. The median score (interquartile range) of the reporting standard guidelines was 27.0 (25.8-28.0). The identified shortcomings of published NMAs should be addressed while training researchers, and they should be encouraged to apply PRISMA-NMA, as a recognized tool for assessing NMA reporting guidelines is required.

Comparative effectiveness of a low-calorie diet combined with acupuncture, cognitive behavioral therapy, meal replacements, or exercise for obesity over different intervention periods: A systematic review and network meta-analysis.

Objective: The aim of this study was to evaluate the comparative effectiveness of a low-calorie diet (LCD) combined with acupuncture, cognitive behavioral therapy (CBT), meal replacements (MR), and exercise on weight loss. Methods: The electronic databases MEDLINE, EMBASE, CENTRAL, CNKI, RISS, and KISS were searched systematically. Randomized controlled trials (RCTs) that directly compared the effect of a low-calorie diet (LCD)-combined acupuncture, CBT, and exercise and an MR-based diet on weight loss with LCD-alone for adults with simple obesity (body mass index [BMI] > 25) published before August 2021 were included in the study. Two investigators extracted and coded the data using a template. Any disagreements between investigators were resolved through discussion. Changes in BMI or weight were transformed to Hedges' g values with a 95% CI, and network meta-analyses using a Bayesian random-effects model were conducted. Results: A total of thirty-two trials involving 3,364 patients were finally included in the study. The effect sizes of four interventions were medium, in the order of acupuncture (Hedges' g = 0.48, 95% CI = 0.25 - 0.71), CBT (Hedges' g = 0.42, 95% CI = 0.20 - 0.63), MR (Hedges' g = 0.32, 95% CI = 0.19 - 0.45), and exercise (Hedges' g = 0.27, 95% CI = 0.06 - 0.46).In terms of intervention period, acupuncture was effective in the short period (≤ 12 weeks, Hedges' g = 0.39, 95% CI = 0.12 - 0.67) and the long period (>12 weeks, Hedges' g = 0.89, 95% CI = 0.37 - 1.40), whereas CBT (Hedges' g = 0.51, 95% CI = 0.26 - 0.76) and exercise (Hedges' g = 0.37, 95% CI = 0.12 - 0.59) were effective only in the long period. MR was effective only in the short period (Hedges' g = 0.35, 95% CI = 0.18 - 0.53). Conclusions: This study suggests that acupuncture, CBT, MR, and exercise for simple obesity show a medium effect size, and their effectiveness differs according to the intervention period.

Efficacy and feasibility of surgery and external radiotherapy for hepatocellular carcinoma with portal invasion: A meta-analysis.

BACKGROUND: External beam radiation therapy (EBRT) and surgery are local treatment modalities for patients with hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT). This meta-analysis aims to evaluate the effectiveness and feasibility of these treatment modalities. METHODS: PubMed, Medline, Embase, and Cochrane Library databases were systematically searched until April 2021. The primary endpoint was overall survival (OS) of the patients; the adverse effects of the treatment were also investigated. RESULTS: A total of 59 studies involving 9525 patients with HCC and PVT were included in this meta-analysis. All studies were non-randomized series, including seven comparative studies, and the remainder were single-arm studies or studies with comparative groups other than surgery or EBRT. The pooled rates of Child-Pugh class A were 74.6% and 95.3% in the EBRT and surgery arms, respectively, and the pooled main PVT rates were 40.7% and 15.5% in the EBRT and surgery arms, respectively (p < 0.001). Pooled 1- and 2-year OS rates of the EBRT arm were 44.1% (95% CI:40.3-48.0) and 21.7% (95% CI:18.9-24.8), respectively. In the subgroup of EBRT studies without main PVT, pooled 1- and 2-year OS rates were 59.9% (95% CI:48.9-70.1) and 30.5% (95% CI:15.2-51.8), respectively. In the surgery arm, the correlation rates were 62.8% (95% CI:55.0-70.0) and 42.5% (95% CI:34.4-51.0), respectively. The pooled 1-, and 2-year OS rates of surgery arm were significantly higher than those of EBRT arm (ps < 0.001), and not significantly different with the EBRT subgroup without main PVT (p = 0.762, 0.353, respectively). In studies of surgery accompanied by EBRT, the 1- and 2-year OS rates were 77.1% (95% CI:69.6-83.2) and 45.4% (95% CI:19.8-73.7), respectively. The pooled rates of grade≥3 toxicities ranged from 1.8 to 4.3%, depending on the type. CONCLUSION: Surgery can yield a favorable survival outcome, whereas EBRT can be widely considered for patients, including those with inferior clinical profiles. Further studies are warranted to determine the possibility of improving the clinical outcomes of surgery accompanied by EBRT.

Benefit of adjuvant radiotherapy for gallbladder cancer: a comparability-based meta-analysis.

BACKGROUND AND PURPOSE: The benefits of adjuvant radiotherapy (ART) in gallbladder cancer (GBC) treatment remain inconclusive owing to the rarity of GBC and lack of randomized studies. METHODS: PubMed, Medline, Embase, and Cochrane Library were systematically searched until March 2021. The primary endpoint was overall survival (OS). Comparative clinical studies that reported survival outcomes in GBC patients treated with or without ART were included. The comparability of each study was assessed by considering all possible clinical indicators (group 2: ART arm with poor clinical profile; group 1: ART arm with statistically similar profile or no evidence of having inferior clinical factors compared to non-ART arm). RESULTS: Twenty-one studies involving 6876 GBC patients were reviewed. In pooled analyses of OS, the odds ratio (OR) was 1.26 (p = 0.111) neither favoring ART or non-ART arms. In subgroup analyses considering comparability, the OR significantly favored the ART arm (1.92, p = 0.008) among comparability group 1 studies, whereas it was 1.03 (p = 0.865) in comparability group 2 studies. The pooled rate of 5-year OS in the ART vs. non-ART arms was 44.9% vs. 20.9% in group 1 and 34.1% vs. 40.0% in group 2. With ART, significant reduction in locoregional recurrence (OR 0.21, p = 0.001) but not in distant metastasis (OR 1.32, p = 0.332) was noted. CONCLUSION: ART not only showed benefits in patients with a similar clinical profile to those treated without ART but also yielded comparable survival in patients with an inferior clinical profile. Our results suggest the more active application of ART in GBC treatment. PROTOCOL REGISTRATION: This study is registered in PROSPERO (CRD42021240624, available at: https://www.crd.york.ac.uk/ ).

A Methodological Quality Evaluation of Meta-Analyses on Nursing Home Research: Overview and Suggestions for Future Directions.

(1) Background: The nursing home (NH) research field lacks quality reporting about meta-analyses (MAs), and most gradings of MA evidence are biased on analyzing the effectiveness of independent variables in randomized control trials. (2) Objectives: This study aimed to perform a critical methodological review of MAs in the NH research field. (3) Methods: We searched the articles from four databases (PubMed, MEDLINE, CINAHL, and PsycINFO) until 15th January 2021. We reviewed a total of 41 published review articles in the NH research field. (4) Results: The studies primarily fell into the following categories: medicine (17/41), nursing (7/41), and psychiatry or psychology (6/41); 36.6% of the reviewed studies did not use any validated MA guidelines. The lowest correctly reported PRISMA 2000 guideline item was protocol and registration (14.6%), and more than 50% of articles did not report risk of bias. Moreover, 78.0% of studies did not describe missing reports of effect size formula. (5) Discussion: NH researchers must follow appropriate and updated guidelines for their MAs in order to provide validated reviews, as well as consider statistical issues such as the complexity of interventions, proper grouping, and scientific effect-size calculations to improve the quality of their study. Future quality review studies should investigate more diverse studies.

Adjuvant Radiotherapy for Extrahepatic Cholangiocarcinoma: A Quality Assessment-Based Meta-Analysis.

INTRODUCTION: The benefits of adjuvant radiotherapy (ART) for extrahepatic cholangiocarcinoma are uncertain largely because existing publications lack clear comparisons between ART and non-ART arms. METHODS: PubMed, Medline, Embase, and the Cochrane library were systematically searched until December 2020. The primary endpoint was overall survival (OS). Sensitivity analysis was performed for studies with reliable comparability (i.e., no favorable prognosticators in the ART arm that could skew the data). RESULTS: Twenty-three studies involving 1,731 patients with extrahepatic cholangiocarcinoma were reviewed. The overall median of all median prescribed doses was 50.4 Gy; brachytherapy or an intraoperative boost of 10-21 Gy was applied in 5 studies. The pooled 1-, 3-, and 5-year OS rates in the non-ART and ART arms were 69.2% versus 81.0%, p = 0.035; 34.3% versus 44.7%, p = 0.025; 25.6% versus 31.7%, p = 0.115, respectively. The corresponding pooled locoregional recurrence rates were 52.1% versus 34.9% (p = 0.014). The pooled rate of grade ≥3 gastrointestinal complications was 9.8%. Sensitivity analysis performed on 14 eligible studies showed that the ART arms had a lower pooled R0 rate (36.8% vs. 63.2%, p = 0.02) and a higher rate of positive lymph nodes (47.4% vs. 34.9%, p = 0.08). The pooled 1-, 3-, and 5-year OS rates in the non-ART versus ART arms of the selected studies were 78.2% versus 84.9%, p = 0.143; 38.5% versus 49.2%, p = 0.026; and 27.8% versus 34.5%, p = 0.11, respectively. CONCLUSIONS: ART was shown to improve OS in all studies and in those selected for their reliable comparability.

A Reporting Quality Assessment of Systematic Reviews and Meta-Analyses in Sports Physical Therapy: A Review of Reviews.

This review of reviews aimed to evaluate the reporting quality of published systematic reviews and meta-analyses in the field of sports physical therapy using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review of reviews included a literature search; in total, 2047 studies published between January 2015 and December 2020 in the top three journals related to sports physical therapy were screened. Among the 125 identified articles, 47 studies on sports physical therapy were included in the analysis (2 systematic reviews and 45 meta-analyses). There were several problems areas, including a lack of reporting for key components of the structured summary (10/47, 21.3%), protocol and registration (18/47, 38.3%), risk of bias in individual studies (28/47, 59.6%), risk of bias across studies (24/47, 51.1%), effect size and variance calculations (5/47, 10.6%), additional analyses (25/47, 53.2%), and funding (10/47, 21.3%). The quality of the reporting of systematic reviews and meta-analyses of studies on sports physical therapy was low to moderate. For better evidence-based practice in sports physical therapy, both authors and readers should examine assumptions in more detail, and report valid and adequate results. The PRISMA guideline should be used more extensively to improve reporting practices in sports physical therapy.

Salvage External Beam Radiotherapy after Incomplete Transarterial Chemoembolization for Hepatocellular Carcinoma: A Meta-Analysis and Systematic Review.

Background and objective: Although transarterial chemoembolization (TACE) has been the commonest local modality for hepatocellular carcinoma (HCC), incomplete repsonse occurs especially for tumors with a large size or difficult tumor accessment. The present meta-analysis assessed the efficacy and feasibility of external beam radiotherapy (EBRT) as a salvage modality after incomplete TACE. Materials and Methods: We systematically searched the PubMed, Embase, Medline, and Cochrane databases. The primary endpoint was overall survival (OS), and the secondary endpoints included the response ratem toxicity of grade 3, and local control. Results: Twelve studies involving 757 patients were included; the median of portal vein thrombosis rate was 25%, and the pooled median of tumor size was 5.8 cm. The median prescribed dose ranged from 37.3 to 150 Gy (pooled median: 54 Gy in *EQD2). The pooled one- and two-year OS rates were 72.3% (95% confidence interval (CI): 60.2-81.9%) and 50.5% (95% CI: 35.6-65.4%), respectively; the pooled response and local control rates were 72.2% (95% CI: 65.4-78.1%) and 86.6 (95% CI: 80.1-91.2%) respectively. The pooled rates of grade ≥3 gastrointestinal toxicity, radiation-induced liver disease, hepatotoxicity, and hematotoxicity were 4.1%, 3.5%, 5.7%, and 4.9%, respectively. Local control was not correlated with intrahepatic (p = 0.6341) or extrahepatic recurrences (p = 0.8529) on meta-regression analyses. Conclusion: EBRT was feasible and efficient in regard to tumor response and control; after incomplete TACE. Out-field recurrence, despite favorable local control, necessitates the combination of EBRT with systemic treatments. *Equivalent dose in 2 Gy per fraction scheme.

The Beneficial Effects of Eccentric Exercise in the Management of Lateral Elbow Tendinopathy: A Systematic Review and Meta-Analysis.

As a first-line treatment for lateral elbow tendinopathy (LET), eccentric exercise has been suggested as a conservative treatment method. This study aimed to investigate the impact of eccentric exercise on LET with regard to pain reduction, and strength and functional improvement. The PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched, and studies up to May 2021 were included if (1) randomization was used for patient allocation, (2) the study comprised patients with LET, (3) the intervention was eccentric exercise, and (4) the primary outcomes included improvement in pain intensity, muscle strength, or function. The meta-analysis comprised of six studies, totaling 429 participants. Additional eccentric exercise with underlying adjuvant therapy significantly improved the visual analog scale (VAS) scores (standardized mean difference [SMD], -0.63; 95% confidence interval [CI], -0.90--0.36) and muscle strength (SMD, 1.05; 95% CI, 0.78-1.33) compared with adjuvant therapy alone. Compared with the concentric or isotonic exercise group, the eccentric exercise group showed significantly improved VAS scores (SMD, -0.30; 95% CI, -0.58--0.02). However, no differences in muscle strength and function were observed between the two groups. Eccentric exercise can improve pain and muscle strength in patients with LET. The limited number of included studies and heterogeneous exercise parameters are important when interpreting these findings.

Addendum to the Acknowledgments: Stepwise-Hierarchical Pooled Analysis for Synergistic Interpretation of Meta-analyses Involving Randomized and Observational Studies: Methodology Development.

[This corrects the article DOI: 10.2196/29642.].

Critical evaluation of reporting quality of network meta-analyses assessing the effectiveness of acupuncture.

BACKGROUND: and purpose: Network meta-analyses (NMAs) comparing the effectiveness of multiple acupuncture have been published but the key concepts underlying NMAs have not been properly reported. This critical evaluation aims to assess the completeness of reporting for NMAs of acupuncture to enhance the validity of findings. MATERIALS AND METHODS: Five databases were searched. The characteristics and reporting quality based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension Statement for reporting of NMA (PRISMA-NMA) were evaluated. NMAs were categorized into two groups according to the publication date, reporting guideline, and intervention. The group differences and correlation coefficients were calculated. RESULTS: Forty-two NMAs of acupuncture were evaluated. The reporting quality for new items in the key concepts of NMAs was low (median 70.0 % (interquartile range 60.0-80.0)). While the issue of consistency was well reported, the assumption of transitivity and network geometry showed poor reporting. Seventeen studies that followed the PRISMA-NMA guideline showed a higher reporting rate for essential concepts of NMA. The recency of publication did not guarantee clear reporting. CONCLUSION: The reporting quality of NMAs of acupuncture was low. The researchers should follow the guidelines on the reporting of NMAs.

Stepwise-Hierarchical Pooled Analysis for Synergistic Interpretation of Meta-analyses Involving Randomized and Observational Studies: Methodology Development.

BACKGROUND: The necessity of including observational studies in meta-analyses has been discussed in the literature, but a synergistic analysis method for combining randomized and observational studies has not been reported. Observational studies differ in validity depending on the degree of the confounders' influence. Combining interpretations may be challenging, especially if the statistical directions are similar but the magnitude of the pooled results are different between randomized and observational studies (the "gray zone"). OBJECTIVE: To overcome these hindrances, in this study, we aim to introduce a logical method for clinical interpretation of randomized and observational studies. METHODS: We designed a stepwise-hierarchical pooled analysis method to analyze both distribution trends and individual pooled results by dividing the included studies into at least three stages (eg, all studies, balanced studies, and randomized studies). RESULTS: According to the model, the validity of a hypothesis is mostly based on the pooled results of randomized studies (the highest stage). Ascending patterns in which effect size and statistical significance increase gradually with stage strengthen the validity of the hypothesis; in this case, the effect size of the observational studies is lower than that of the true effect (eg, because of the uncontrolled effect of negative confounders). Descending patterns in which decreasing effect size and statistical significance gradually weaken the validity of the hypothesis suggest that the effect size and statistical significance of the observational studies is larger than the true effect (eg, because of researchers' bias). CONCLUSIONS: We recommend using the stepwise-hierarchical pooled analysis approach for meta-analyses involving randomized and observational studies.

Is the Concurrent Use of Sorafenib and External Radiotherapy Feasible for Advanced Hepatocellular Carcinoma? A Meta-Analysis.

We evaluate the feasibility of a concurrent application of sorafenib and external beam radiation therapy (EBRT) for advanced hepatocellular carcinoma (HCC). PubMed, Embase, Medline, and Cochrane Library were searched up to 9 April 2021. The primary endpoint was grade ≥3 complications, and the secondary endpoint was overall survival (OS). Subgroup analyses were performed for studies with the EBRT targets, intrahepatic vs. non-intrahepatic lesions (e.g., extrahepatic metastases or malignant vessel involvement only). Eleven studies involving 512 patients were included in this meta-analysis. Pooled rates of gastrointestinal, hepatologic, hematologic, and dermatologic grade ≥3 toxicities were 8.1% (95% confidence interval (CI): 4.8-13.5, I2 = ~0%), 12.9% (95% CI: 7.1-22.1, I2 = 22.4%), 9.1% (95% CI: 3.8-20.3, I2 = 51.3%), and 6.8% (95% CI: 3.8-11.7, I2 = ~0%), respectively. Pooled grade ≥3 hepatologic and hematologic toxicity rates were lower in studies targeting non-intrahepatic lesions than those targeting intrahepatic lesions (hepatologic: 3.3% vs. 17.1%, p = 0.041; hematologic: 3.3% vs. 16.0%, p = 0.078). Gastrointestinal and dermatologic grade ≥3 complications were not significantly different between the subgroups. Regarding OS, concurrent treatment was more beneficial than non-concurrent treatment (odds ratio: 3.3, 95% CI: 1.3-8.59, p = 0.015). One study reported a case of lethal toxicity due to tumor rupture and gastrointestinal bleeding. Concurrent treatment can be considered and applied to target metastatic lesions or local vessel involvement. Intrahepatic lesions should be treated cautiously by considering the target size and hepatic reserve.