The quality of reporting in case reports of permanent neonatal diabetes mellitus: a cross-sectional study.

BACKGROUND: Although randomized trials and systematic reviews provide the best evidence to guide medical practice, many permanent neonatal diabetes mellitus (PNDM) studies have been published as case reports. However, the quality of these studies has not been assessed. The purpose of this study was to assess the extent to which the current case reports for PNDM comply with the Case Report (CARE) guidelines and to explore variables associated with the reporting. METHOD: Six English and four Chinese databases were searched from their inception to December 2022 for PNDM case reports. The 23 items CARE checklist was used to measure reporting quality. Primary outcome was the adherence rate of each CARE item and second outcome was total reporting score for each included PNDM case report. Linear and logistic regression analyses were used to examine the connection between five pre-specified predictor variables and the reporting quality. The predictor variables were impact factor of the published journal (<3.4 vs. ≥3.4, categorized according to the median), funding (yes vs. no), language (English vs. other language), published journal type (general vs. special) and year of publication (>2013 vs. ≤ 2013). RESULT: In total, 105 PNDM case reports were included in this study. None of the 105 PNDM case reports fulfilled all 23 items of the CARE checklist. The response rate of 11 items were under 50%, including prognostic characteristics presentation (0%), patient perspective interpretation (0%), diagnostic challenges statement (2.9%), clinical course summary (21.0%), diagnostic reasoning statement (22.9%), title identification (24.8%), case presentation (33.3%), disease history description (34.3%), strengths and limitations explanation (41.0%), informed consent statement (45.7%), and lesson elucidation (47.6%). This study identified that the PNDM case reports published in higher impact factor journals were statistically associated with a higher reporting quality. CONCLUSION: The reporting of case reports for PNDM is generally poor. As a result, this information may be misleading to providers, and the clinical applications may be detrimental to patient care. To improve reporting quality, journals should encourage strict adherence to the CARE guidelines.

Effect of important modifiers on harmful effects in evidence synthesis practice of adverse events were insufficiently investigated: an empirical investigation.

BACKGROUND: Safety is important in the assessment of health interventions, while the results of adverse events are often susceptive to potential effect modifiers since the event risk tends to be rare. In this study, we investigated whether the potential impact of the important effect modifiers on harmful effects was analyzed in meta-analyses of adverse events. METHODS: Systematic reviews of healthcare interventions, had adverse events as the exclusive outcomes, had at least one meta-analysis, and published between 1st January 2015, and 1st January 2020 were collected. An adverse event was defined as any untoward medical occurrence in a patient or subject in healthcare practice. Six effect modifiers that are the most important for harmful effects were identified by a group discussion. The proportions of eligible systematic reviews that investigated the potential impact of the six effect modifiers on harmful effects were summarized. RESULTS: We identified 279 systematic reviews eligible for this study. Except for the modifier of interventions/controls (70.61%, 197/279), most of the systematic reviews failed to investigate the potential impact of treatment duration (21.15%, 59/279), dosage (24.73%, 69/279), age (11.47%, 32/279), risk of bias (6.45%, 18/279), and source of funding (1.08%, 3/279) on harmful effects. Systematic reviews with meta-analyses containing more studies were more likely to investigate the potential impacts of these modifiers on the effects, but the proportion was still low (2.3% to 33.3%). Systematic reviews that developed a protocol were significantly more likely to investigate the potential impact of all these effect modifiers (e.g. treatment duration: odds ratio = 5.08, 95% CI: 2.76 to 9.35) on the results. CONCLUSIONS: Current systematic reviews rarely investigated the potential impact of the important effect modifiers on harmful effects. Methodological guidelines for meta-analysis of adverse events should consider "effect modifier" as one of the domains to help systematic review authors better investigate harmful effects.

Diversity and distribution of CO2-fixing microbial community along elevation gradients in meadow soils on the Tibetan Plateau.

Soil CO2-fixing microbes play a significant role in CO2-fixation in the terrestrial ecosystems, particularly in the Tibetan Plateau. To understand carbon sequestration by soil CO2-fixing microbes and the carbon cycling in alpine meadow soils, microbial diversity and their driving environmental factors were explored along an elevation gradient from 3900 to 5100 m, on both east and west slopes of Mila Mountain region on the Tibetan Plateau. The CO2-fixing microbial communities were characterized by high-throughput sequencing targeting the cbbL gene, encoding the large subunit for the CO2-fixing protein ribulose 1, 5-bisphosphate carboxylase/oxygenase. The overall OTU (Operational Taxonomic Unit) abundance is concentrated at an altitude between 4300 and 4900 m. The diversity of CO2-fixing microbes is the highest in the middle altitude area, and on the east slope is higher than those on the west slope. In terms of microbial community composition, Proteobacteria is dominant, and the most abundant genera are Cupriavidus, Rhodobacter, Sulfurifustis and Thiobacillus. Altitude has the greatest influence on the structural characteristics of CO2-fixing microbes, and other environmental factors are significantly correlated with altitude. Therefore, altitude influences the structural characteristics of CO2-fixing microbes by driving environmental factors. Our results are helpful to understand the variation in soil microbial community and its role in soil carbon cycling along elevation gradients.

Rapid evidence synthesis approach for limits on the search date: How rapid could it be?

Rapid reviews have been widely employed to support timely decision-making, and limiting the search date is the most popular approach in published rapid reviews. We assessed the accuracy and workload of search date limits on the meta-analytical results to determine the best rapid strategy. The meta-analyses data were collected from the Cochrane Database of Systematic Reviews (CDSR). We emulated the rapid reviews by limiting the search date of the original CDSR to the recent 40, 35, 30, 25, 20, 15, 10, 7, 5, and 3 years, and their results were compared to the full meta-analyses. A random sample of 10% was drawn to repeat the literature search by the same timeframe limits to measure the relative workload reduction (RWR). The relationship between accuracy and RWR was established. We identified 21,363 meta-analyses of binary outcomes and 7683 meta-analyses of continuous outcomes from 2693 CDSRs. Our results suggested that under a maximum tolerance of 5% and 10% on the bias of magnitude, a limit on the recent 20 years can achieve good accuracy and at the same time save the most workload. Under the tolerance of 15% and 20% on the bias, a limit on the recent 10 years and 15 years could be considered. Limiting the search date is a valid rapid method to produce credible evidence for timely decisions. When conducting rapid reviews, researchers should consider both the accuracy and workload to make an appropriate decision.

Association between response rates and monetary incentives in sample study: a systematic review and meta-analysis.

OBJECTIVE: To investigate the effect of monetary incentive and the dose-response relationship of participants' response rates in surveys. METHODS: Three databases were searched for randomised controlled trials (RCTs) that investigated the effect of monetary incentives on participants' first and final response rates. First response is defined as the responses after the participant was initially contacted and final response is defined as the responses after several reminders were sent. The potential dose-response relationship of the amount of monetary incentive on the relative response rate (RRR) was established by fitting a restricted cubic spline function based on the robust-error meta-regression model. RESULTS: 105 RCTs were identified. The first RRR increased by 49% (RRR=1.49; 95% CI 1.29 to 1.72) when monetary incentives were provided. Dose-response analysis revealed that an amount between US$6.25 and US$8 had the maximum effect on increasing the first response rate. On average, the final RRR increased almost by 20% (RRR=1.18; 95% CI 1.11 to 1.25) with monetary incentive compared to no-monetary incentive. An amount between US$10 and US$15 had the maximum effect on the final response rate, with an increase in the final RRR of 34% (RRR=1.34; 95% CI 1.19 to 1.51). There was a significant increase in the response rate when two or more reminders were sent. CONCLUSION: Monetary incentives and reminders improve the response rates. Future studies need to consider providing monetary incentives and sending at least two reminders to increase the response rate and reduce the chances of non-response bias.

Many meta-analyses of rare events in the Cochrane Database of Systematic Reviews were underpowered.

BACKGROUND AND OBJECTIVE: Meta-analysis is a statistical method with the ability to increase the power for statistical inference, while it may still face the problem of being underpowered. In this study, we investigated the power to detect certain true effects for published meta-analyses of rare events. METHODS: We extracted data from the Cochrane Database of Systematic Reviews for meta-analyses of rare events from January 2003 to May 2018. We retrospectively estimated the power to detect a 10-50% relative risk reduction (RRR) of eligible meta-analyses. The proportion of meta-analyses achieved a sufficient power (≥0.8) were estimated. RESULTS: We identified 4,177 meta-analyses. The median power to detect 10%, 30%, and 50% RRR were 0.06 (interquartile range [IQR]: 0.05 to 0.06), 0.08 (IQR: 0.06 to 0.15), and 0.17 (IQR: 0.10 to 0.42), respectively); the corresponding proportion of meta-analyses that reached sufficient power were 0.32%, 3.68%, and 11.81%. Meta-analyses incorporating data from more studies had higher probability to achieve a sufficient power (rate ratio = 2.49, 95% CI: 1.76, 3.52, P < 0.001). CONCLUSION: Most of the meta-analyses of rare events in Cochrane systematic reviews were underpowered. Future meta-analysis of rare events should report the power of the results to support informative conclusions.

Mechanisms Underlying the Antidepressant Effect of Acupuncture via the CaMK Signaling Pathway.

The CaMK pathway has been proven to play an important role in regulating cognitive function and emotional response. Acupuncture through the CaMK pathway improves depression-like behavior and the molecular mechanism related to its antidepressant remains to be explored. In this study, we aimed to determine whether the ability of acupuncture at Baihui (GV20) and Shenting (GV24) points to treat depression is related to the regulation of key proteins in the CaMK pathway. A rat model of depression was induced by chronic unpredicted mild stress (CUMS). Model rats in the electroacupuncture group were subjected to acupuncture at the Baihui (GV20) and Shenting (GV24) acupoints once a day for 20 min. Model rats in the fluoxetine group were gavaged with fluoxetine (1.8 mg/kg). Immunohistochemistry and Western blotting assays were used to evaluate immunoreactivity for and the protein expression levels of CaMKII, CaMKIV, and CaM. The results showed that electroacupuncture had a significant effect in rats with depression. Electroacupuncture and fluoxetine regulated the expression of key proteins in the CaMK signaling pathway, which is related to depression, in the hippocampi of rats. This indicates that acupuncture at Baihui (GV20) and Shenting (GV24) may alleviate depressive symptoms and reduce work- and life-related burdens and stress by regulating the CaMK signaling pathway.

Acupuncture for knee osteoarthritis with sensitized acupoints: results from a pilot, feasibility randomized controlled trial.

BACKGROUND: Although previous clinical studies suggest possible benefits of acupuncture for knee osteoarthritis (KOA), the value of acupuncture at sensitized points is uncertain. We aimed to preliminarily assess the feasibility of performing a definitive randomized controlled trial to explore the effectiveness of acupuncture for KOA with highly sensitized acupoints. METHODS: In this randomized, single-blind, parallel, pilot trial, 36 participants with KOA were randomly assigned to receive acupuncture at highly sensitized acupoints (high-sensitization group) or at low/non-sensitized points (low/non-sensitization group) by a computer-generated random sequence. Both groups received three treatment sessions per week for four consecutive weeks (12 sessions in total). Assessments were performed at screening and at 4, 8, 12, and 16 weeks after randomization. Primary feasibility outcomes were patient recruitment, retention rate, and adherence to group treatment. Secondary outcomes included the change of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score from baseline to 16 weeks, the change of Short Form (SF)-12 health survey score, and safety outcomes. RESULTS: Patient recruitment of 36 patients took 2 months, achieving the recruitment target. Retention rates were similar between the treatment groups, 14 (77.8%) patients in the high-sensitization group completed the 16-week follow-up and compared to 14 (77.8%) patients in low/non-sensitization group, but the result was lower than expected. All patients received at least ten treatment sessions in total. The WOMAC total score and the pain, stiffness, and physical function score in the high-sensitization group were lower or very close to those in the control group at each assessment point. Similar results were observed on quality of life. No adverse events occurred. CONCLUSION: This trial has presented preliminary data on the feasibility of conducting a large trial to test the effectiveness of acupuncture at sensitized points in KOA patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03008668. Registered on 26 December 2016-retrospectively registered.

The effects of clinical decision support systems on insulin use: A systematic review.

BACKGROUND: A clinical decision support system (CDSS) is a computerized system using case-based reasoning to assist clinicians in assessing disease status, in selecting appropriate therapy or in making other clinical decisions. Previous randomized controlled trials (RCTs or trials) have shown that CDSSs have the potential to improve the insulin use, but the evidence was conflicting and uncertain. The purpose of our study was to determine whether a CDSS improves the use of insulin. METHOD: PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from their inception to October 2018. The quality assessment was based on the risk of bias criteria of the Cochrane Handbook. RESULTS: Twenty-four RCTs, involving 7653 participants, were included. Thirteen of those trials (54.2%) used a computerized algorithm or a computer-assisted insulin protocol for insulin dose and therapy adjustment, of which 30.8% (four of 13) found significant changes. Of 10 trials that measured mean blood glucose levels and the 11 trials reported HbA1c, the computerized insulin dose adjustment resulted in lower mean blood glucose levels in 70.0% (seven of 10) and 36.4% (four of 11) of RCTs, respectively. Additionally, a significant reduction of hyperglycaemia events was reported in three of six RCTs. The evidence in a majority of the 24 RCTs was of moderate quality. CONCLUSIONS: CDSSs have the potential to improve the insulin use and blood glucose control in a clinical setting. The methodologies in these studies were of mixed quality. Better designed and longer-term studies are required to ensure a larger and more reliable evidence base on the effects of CDSS intervention on insulin use.

Assessment of the abstract reporting of systematic reviews of dose-response meta-analysis: a literature survey.

BACKGROUND: There is an increasing number of published systematic reviews (SR) of dose-response meta-analyses (DRMAs) over the past decades. However, the quality of abstract reporting of these SR-DRMAs remains to be understood. We conducted a literature survey to investigate the abstract reporting of SR-DRMAs. METHODS: Medline, Embase, and Wiley online Library were searched for eligible SR-DRMAs. The reporting quality of SR-DRMAs was assessed by the modified PRISMA-for-Abstract checklist (14 items). We summarized the adherence rate of each item and categorized them as well complied (adhered by 80% or above), moderately complied (50 to 79%), and poorly complied (less than 50%). We used total score to reflect the abstract quality and regression analysis was employed to explore the potential influence factors for it. RESULTS: We included 529 SR-DRMAs. Eight of 14 items were moderately (3 items) or poorly complied (5 items) while only 6 were well complied by these SR-DRMAs. Most of the SR-DRMAs failed to describe the methods for risk of bias assessment (30.2, 95% CI: 26.4, 34.4%) and the results of bias assessment (48.8, 95% CI: 44.4, 53.1%). Few SR-DRMAs reported the funding (2.3, 95% CI: 1.2, 3.9%) and registration (0.6, 95% CI: 0.1, 1.6%) information in the abstract. Multivariable regression analysis suggested word number of abstracts [> 250 vs. ≤ 250 (estimated ß = 0.31; 95% CI: 0.02, 0.61; P = 0.039)] was positively associated with the abstract reporting quality. CONCLUSION: The abstract reporting of SR-DRMAs is suboptimal, substantial effort is needed to improve the reporting. More word number may benefit for the abstract reporting. Given that reporting of abstract largely depends on the reporting and conduct of the SR-DRMA, review authors should also focus on the completeness of SR-DRMA itself.

Experimental sleep restriction effect on adult body weight: a meta-analysis.

BACKGROUND: Sleep is increasingly recognized as a potential risk for overweight and obesity. Observational studies have shown links between short sleep duration with weight gain. However, the findings from longitudinal studies in adults are conflicting. This review aimed to examine the effectiveness of experimental sleep restriction on adult body weight. METHOD: A systematic search was undertaken in MEDLINE, EMBASE, PsycINFO, and CENTRAL (Cochrane center register of controlled trials) to identify experimental studies examining the effectiveness of sleep restriction on body weight, and search period was from January 2005 to June 2018. Meta-analysis was applied by using the random model. RESULTS: A total of 275 adults from six experimental studies were included. The pooled standard mean difference in body weight and body fat was 0.44 (95% CI - 0.13 to 1.02) (Z = 1.51, p > 0.05) and 0.35 kg (95% CI - 0.19 to 0.88) (Z = 1.27, p > 0.05), respectively. The experimental sleep restriction did not result in significant differences in adult body weight or body fat. Subgroup analysis showed that there were differences in weight gain between genders and races. CONCLUSION: The finding from this review cannot support the hypothesis from observational studies that short sleep leads to weight gain.

Protocol registration or development may benefit the design, conduct and reporting of dose-response meta-analysis: empirical evidence from a literature survey.

BACKGROUND: To investigate the prevalence of protocol registration (or development) among published dose-response meta-analyses (DRMAs), and whether DRMAs with a protocol are better than those not. METHODS: Three databases were searched for eligible DRMAs. The modified AMSTAR (14 items) and PRISMA checklists (26 items) were used to assess the methodological and reporting quality, with each item assigned 1 point if it met the requirement or 0 if not. We matched (1,2) DRMAs with registered or published protocol to those not, by region and publication years. The summarized quality score and compliance rate of each item were compared between the two groups. Multivariable regression was employed to see if protocol registration or development was associated with total quality score. RESULTS: We included 529 DRMAs, with 45 (8.51%) completed protocol registration or development. We observed a higher methodological score for DRMAs with protocol than the matched controls (9.47 versus 8.58, P <  0.01); this embodied in 4 out of 14 items of AMSTAR [e.g., Duplicate data extraction (rate difference, RD = 0.17, 95% CI: 0.04, 0.30; P = 0.01). A higher reporting score (cubic transformed) for DRMAs with protocol than the matched controls was also observed (11,875.00 versus 10,229.53, P <  0.01); which embodied in 6 out of 26 items of PRISMA [e.g. Describe methods for publication bias (RD = 0.08, 95% CI: 0.01, 0.14; P = 0.02)]. Regression analysis suggested positive association between protocol registration or development and total reporting score (P = 0.012) while not for methodological score (P = 0.87). CONCLUSIONS: Only a small proportion of DRMAs completed protocol registration or development, and those with protocol were better reported than those not. Protocol registration or development is highly desirable.

Design, Conduct, and Analysis of Surgical Randomized Controlled Trials: A Cross-sectional Survey.

BACKGROUND: Randomized controlled trial (RCT) testing surgical intervention faced challenges due to complexities of surgery and made it more difficult for surgeons and methodologists than pharmaceutical providers to build a well-design, conduct RCT. OBJECTIVE: We conducted a cross-sectional survey to address the methodological challenges of RCTs on surgical intervention and offer potential solutions. METHODS: We searched PubMed in order to summarize 2-arm parallel randomized trials for surgical interventions published in 2013. The information regarding general characteristics, general methodological and special surgical characteristics related to surgical trials comparing alternative procedures was gathered. RESULTS: Some 200 surgical trials were identified. The extent to which these trials in design, conduct and analysis differed substantially across items. The general information about sample size calculation (77.0%), lost to follow-up (71.5%), trial registration (55.5%), protocols of trials (56.0%), implementation of randomization (59.5%), concealment of randomization (56.0%); reporting of primary outcome as P value (67.0%). Surgery special information revealed that only 21.0% of trials considered surgeons' preference, approximately 12% to 50% of them controlled the quality of surgical interventions and none evaluated the effect of the learning curve. CONCLUSION: There is much room for improvement concerning the reported designs, conduct, and analysis of surgical RCTs. Considering the difficulty of surgical RCTs, some other approaches, such as surgeons' eligibility, performance of pilot studies, or implementation of pragmatic RCTs/expertise-based trials, should be feasibly implemented to overcome the presented challenges.

The methodological quality of dose-response meta-analyses needed substantial improvement: a cross-sectional survey and proposed recommendations.

OBJECTIVES: To investigate methodological quality of published dose-response meta-analysis (DRMA) and explore study characteristics associated with the quality. STUDY DESIGN AND SETTING: We searched three databases for published DRMAs and used a modified AMSTAR (15 items) checklist to assess the methodological quality. We summarized the compliance of those DRMAs to the AMSTAR items and used multivariable regression analysis to explore the association between prespecified study characteristics with the overall methodological quality. RESULTS: We identified 529 DRMAs. Of the methodological quality items, six were well complied (80% or more) and six poorly complied (30% or fewer) by these DRMAs. The median score was nine points [first and third quartile: 7, 10] and only 64/529 had score over 10 points. Regression analysis suggested that studies with more authors (ß = 0.19; 95% confidence interval [CI]: 0.05, 0.33), published more recently (ß = 0.29; 95% CI: 0.21, 0.36), with financial support (ß = 0.41; 95% CI: 0.13, 0.70), conducted by authors from European (other regions vs. European, ß = -0.68; 95% CI: -1.05, -0.31) were associated with better methodological quality. CONCLUSION: The methodological quality of published DRMAs was suboptimal. Substantial efforts are warranted to improve the quality, including developing methodology guideline, involving more methodological trained authors, and so forth.

Evaluation of clinical decision support systems for diabetes care: An overview of current evidence.

BACKGROUND: Systematic reviews (SRs) have shown that clinical decision support systems (CDSSs) have the potential to improve diabetes care. However, methods of measuring and presenting outcomes are varied, and conclusions have been inconsistent. In addition, the reporting and methodological quality in this field is unknown, which could affect the integrity and accuracy of research. Therefore, it is difficult to confirm whether CDSSs are effective in improving diabetes care. OBJECTIVE: To comprehensively evaluate the effects of CDSS on diabetes care and to examine the methodological and reporting qualities. METHODS: We searched PubMed, EMBASE, and Cochrane Library from their inception to February 2017. Systematic reviews investigating the effects of CDSS on diabetes care were included. Outcomes were determined in advance and assessed separately for process of care and patient outcomes. Methodological and reporting qualities were assessed by AMSTAR and PRISMA, respectively. RESULTS: Seventeen SRs, consisting of 222 unique randomized controlled trials and 102 nonrandomized controlled trials, were included. Evidence that CDDS significantly impacted patient outcomes was found in 32 of 102 unique studies of the 15 SRs that examined this effect (31%). A significant impact of CDSS on process of care was found in 117 out of 143 unique studies of the 11 SRs that examined this effect (82%). Ratings for overall scores of AMSTAR resulted in a mean score of 6.5 with a range of scores from 3.5 to 10.0. Reporting quality related to methodological domains was particularly incomplete. CONCLUSIONS: Clinical decision support systems improved the quality of diabetes care by inconsistently improving process of care or patient outcomes. There is evidence that CDSS for providing alerts, reminders, or feedback to participants were most likely to impact diabetes care. Poor reporting of methodological domains, together with qualitative or narrative methods to combine findings, may limit the confidence in research evidence.

Improving the quality of reporting of systematic reviews of dose-response meta-analyses: a cross-sectional survey.

BACKGROUND: Dose-response meta-analysis (DRMA) is a useful tool to investigate potential dose-response relationship between certain exposure or intervention and the outcome of interest. A large number of DRMAs have been published in the past several years. However, the standard of reporting for such studies is not known. METHODS: Medline, Embase, and Wiley Library were searched for systematic reviews with DRMAs (SR-DRMAs) published from January 2011 to July 2017. We used the combination of PRISMA and MOOSE statements, containing 33 items, to assess the reporting of included SR-DRMAs. The adherence of reporting was defined as the proportion of SR-DRMAs meeting the reporting requirement of an item. We explored the association between five pre-specified variables with the total score of reporting on both fully as well as each domain of the checklist. RESULTS: In total, 529 SR-DRMAs were eligible. Ten out of 33 items were under reported, and this mainly refers to the methods domain: only a small proportion of SR-DRMAs stated whether a review protocol existed (45, 8.5%); clarified the qualifications of searchers (1.7%); presented full electronic search strategy (25.9%); described any effort to include all available studies (22.9%), described methods for languages other than English (27.4%), and stated the process for selecting studies (20.2%). Multiple regression analysis suggested that studies with more authors (regression coefficient = 0.78; 95% CI: 0.35, 1.20; P <  0.001), published more recently (regression coefficient = 0.38; 95% CI: 0.28 to 0.47; trend P <  0.001), used reporting guideline (regression coefficient = 0.98; 95% CI: 0.68 to 1.32; P <  0.001), and involvement of methodologist (regression coefficient = 0.86; 95% CI: 0.42 to 1.32; P <  0.001) were associated with higher score of reporting. Further regression suggested that the improvement on the quality mainly concentrated on the methods and results domains. CONCLUSIONS: The reporting of SR-DRMAs needs to be further improved, particularly in the issues refer to the methods. The quality of reporting may improve when involving more authors and methodologists and employing any reporting guidelines.

Acupuncture treatment for knee osteoarthritis with sensitive points: protocol for a multicentre randomised controlled trial.

INTRODUCTION: There is a lack of curative medical treatment for patients with knee osteoarthritis (KOA). Acupuncture represents an important alternative therapy. According to the theory of traditional Chinese medicine and preliminary clinical evidence, the patients' acupoints and tender points may become sensitised when the body suffers from a disease state; stimulation of such sensitive points could lead to a disease improvement. It is thus hypothesised that acupuncture at highly sensitised points on patients with KOA would achieve better treatment outcomes than acupuncture at low/non-sensitised points. Previously, we conducted a pilot trial to prove the feasibility of further investigation. METHODS AND ANALYSIS: A three-arm, parallel, multicentre randomised controlled trial of 666 patients will be conducted at four hospitals of China. Eligible patients with KOA who consent to participate will be randomly assigned to a high-sensitisation group (patients receive acupuncture treatment at high-sensitive points), a low/non-sensitisation group (patients receive acupuncture treatment at low/non-sensitive points) or a waiting-list group (patients receive standard acupuncture treatment after the study is concluded) via a central randomisation system using 1:1:1 ratio. The primary outcome is the change of Western Ontario and McMaster Universities Osteoarthritis Index total score from baseline to 16 weeks. Outcome assessors and data analysts will be blinded and participants will be asked not to reveal their allocation to assessors. The outcome analyses will be performed both on the intention-to-treat and per-protocol population. The primary analyses will test if acupuncture at highly sensitised points would achieve statistically better treatment outcomes than acupuncture at low/non-sensitised points and no acupuncture (ie, waiting list), respectively. A small number of prespecified subgroup analyses will be conducted. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Bioethics Subcommittee of West China Hospital, Sichuan University: 2017 (Number 228). Results will be expected to be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03299439.

The quality of reporting in randomized controlled trials of acupuncture for knee osteoarthritis: A cross-sectional survey.

OBJECTIVE: To assess the reporting quality of acupuncture trials for knee osteoarthritis (KOA), and explore the factors associated with the reporting. METHOD: Three English and four Chinese databases were searched from inception to December 2016 for randomized control trials testing effects of acupuncture for knee osteoarthritis. We used the standard CONSORT (2010 version), CONSORT Extension for Non-Pharmacological Treatments, and STRICTA for measuring the quality of reporting. Using pre-specified study characteristics, we undertook regression analyses to examine factors associated with the reporting quality. RESULTS: A total of 318 RCT reports were included. For the standard CONSORT, ten items were substantially under-reported (reported in less than 5% of RCTs), including specification of important changes to methods after trial commencement (0.6%), description of any changes to trial outcomes (0.0%), implementation of interim analyses and stopping guidelines (0.6%), statement about why the trial ended or was stopped (1.6%), statement about the registration status (4.4%), accessibility of full trial protocol (4.7%), implementation of randomization (4.7%), description of the similarity of interventions (3.5%), conduct of ancillary analyses (3.8%) and presentation of methods for additional analyses (4.4%). Four of the STRICTA items were under-reported (reported in less than 10% of RCTs), including description of acupuncture style (8.5%), presentation of extent to which treatment varied (1.3%), statement of practitioner background (7.2%) and rationale for the control (9.1%). For CONSORT Extension, the reporting was poor across all items (reported in less than 10% of trials). Trials including authors with expertise in epidemiology or statistics, published in English, or enrolling patients from multiple centers were more likely to have better reporting. CONCLUSIONS: The reporting in RCTs of acupuncture for KOA was generally poor. To improve the reporting quality, journals should encourage strict adherence to the reporting guidelines.

Risk of bias and methodological issues in randomised controlled trials of acupuncture for knee osteoarthritis: a cross-sectional study.

OBJECTIVE: To assess risk of bias and to investigate methodological issues concerning the design, conduct and analysis of randomised controlled trials (RCTs) testing acupuncture for knee osteoarthritis (KOA). METHODS: PubMed, EMBASE, Cochrane Central Register of Controlled Trials and four major Chinese databases were searched for RCTs that investigated the effect of acupuncture for KOA. The Cochrane tool was used to examine the risk of bias of eligible RCTs. Their methodological details were examined using a standardised and pilot-tested questionnaire of 48 items, together with the association between four predefined factors and important methodological quality indicators. RESULTS: A total of 248 RCTs were eligible, of which 39 (15.7%) used computer-generated randomisation sequence. Of the 31 (12.5%) trials that stated the allocation concealment, only one used central randomisation. Twenty-five (10.1%) trials mentioned that their acupuncture procedures were standardised, but only 18 (7.3%) specified how the standardisation was achieved. The great majority of trials (n=233, 94%) stated that blinding was in place, but 204 (87.6%) did not clarify who was blinded. Only 27 (10.9%) trials specified the primary outcome, for which 7 used intention-to-treat analysis. Only 17 (6.9%) trials included details on sample size calculation; none preplanned an interim analysis and associated stopping rule. In total, 46 (18.5%) trials explicitly stated that loss to follow-up occurred, but only 6 (2.4%) provided some information to deal with the issue. No trials prespecified, conducted or reported any subgroup or adjusted analysis for the primary outcome. CONCLUSION: The overall risk of bias was high among published RCTs testing acupuncture for KOA. Methodological limitations were present in many important aspects of design, conduct and analyses. These findings inform the development of evidence-based methodological guidance for future trials assessing the effect of acupuncture for KOA.