Trial-level characteristics associate with treatment effect estimates: a systematic review of meta-epidemiological studies.

BACKGROUND: To summarize the up-to-date empirical evidence on trial-level characteristics of randomized controlled trials associated with treatment effect estimates. METHODS: A systematic review searched three databases up to August 2020. Meta-epidemiological (ME) studies of randomized controlled trials on intervention effect were eligible. We assessed the methodological quality of ME studies using a self-developed criterion. Associations between treatment effect estimates and trial-level characteristics were presented using forest plots. RESULTS: Eighty ME studies were included, with 25/80 (31%) being published after 2015. Less than one-third ME studies critically appraised the included studies (26/80, 33%), published a protocol (23/80, 29%), and provided a list of excluded studies with justifications (12/80, 15%). Trials with high or unclear (versus low) risk of bias on sequence generation (3/14 for binary outcome and 1/6 for continuous outcome), allocation concealment (11/18 and 1/6), double blinding (5/15 and 2/4) and smaller sample size (4/5 and 2/2) significantly associated with larger treatment effect estimates. Associations between high or unclear risk of bias on allocation concealment (5/6 for binary outcome and 1/3 for continuous outcome), double blinding (4/5 and 1/3) and larger treatment effect estimates were more frequently observed for subjective outcomes. The associations between treatment effect estimates and non-blinding of outcome assessors were removed in trials using multiple observers to reach consensus for both binary and continuous outcomes. Some trial characteristics in the Cochrane risk-of-bias (RoB2) tool have not been covered by the included ME studies, including using validated method for outcome measures and selection of the reported results from multiple outcome measures or multiple analysis based on results (e.g., significance of the results). CONCLUSIONS: Consistently significant associations between larger treatment effect estimates and high or unclear risk of bias on sequence generation, allocation concealment, double blinding and smaller sample size were found. The impact of allocation concealment and double blinding were more consistent for subjective outcomes. The methodological and reporting quality of included ME studies were dissatisfactory. Future ME studies should follow the corresponding reporting guideline. Specific guidelines for conducting and critically appraising ME studies are needed.

Association of physical activity and air pollution exposure with the risk of type 2 diabetes: a large population-based prospective cohort study.

BACKGROUND: The interplay between physical activity (PA) and air pollution in relation to type 2 diabetes (T2D) remains largely unknown. Based on a large population-based cohort study, this study aimed to examine whether the benefits of PA with respect to the risk of T2D are moderated by exposure to air pollution. METHODS: UK Biobank participants (n = 359,153) without diabetes at baseline were included. Information on PA was obtained using the International Physical Activity Questionnaire short form. Exposure to air pollution, including PM2.5, PMcoarse (PM2.5-10), PM10, and NO2, was estimated from land use regression models. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: During a median of 8.9 years of follow-up, 13,706 T2D events were recorded. Compared with a low PA level, the HRs for the risk of T2D among individuals with moderate and high PA were 0.82 (95% CI, 0.79-0.86) and 0.73 (95% CI, 0.70-0.77), respectively. Compared with low levels of air pollution, the HRs for risk of T2D for high levels of air pollution (PM2.5, PMcoarse, PM10, and NO2) were 1.19 (1.14-1.24), 1.06 (1.02-1.11), 1.13 (1.08-1.18), and 1.19 (1.14-1.24), respectively. There was no effect modification of the associations between PA and T2D by air pollution (all P-interactions > 0.05). The inverse associations between PA and T2D in each air pollution stratum were generally consistent (all P for trend < 0.05). CONCLUSION: A higher PA and lower air pollution level were independently associated with a lower risk of T2D. The beneficial effects of PA on T2D generally remained stable among participants exposed to different levels of air pollution. Further studies are needed to replicate our findings in moderately and severely polluted areas.

Complementary medicine use in US adults with a history of colorectal cancer: a nationally representative survey.

BACKGROUND: In the USA, colorectal cancer is among the top diagnosed cancers. The current study specifically targets the US adult population that have a history of colorectal cancer. METHODS: We used the 2017 National Health Interview Survey (NHIS) to investigate the prevalence and predictors of colorectal cancer survivors using complementary medicine in the past 12 months in a representative sample of the US population (N = 26,742). We descriptively analyzed the 12-month prevalence of any complementary medicine use separately for individuals with a prior diagnosis of colorectal cancer and those without. Using chi-squared tests and backward stepwise multiple logistic regression analyses, we identified predictors of complementary medicine use in the past 12 months. RESULTS: A weighted total of 1,501,481 US adults (0.6%) had a history of colorectal cancer. More individuals without (weighted n = 76,550,503; 31.2%) than those with a history of colorectal cancer (weighted n = 410,086; 27.3%) had used complementary medicine. The most commonly used complementary medicine among colorectal cancer patients was mind-body medicine, followed by chiropractic. A higher prevalence of complementary medicine use was associated with being female, higher educated and/or living in the US Midwest or South. CONCLUSIONS: In this study, over one fourth of the US colorectal cancer survivors had used complementary medicine. Mind-body medicine was found to be the most commonly used. With evidence supporting the effectiveness and safety of mind-body medicine use among colorectal cancer patients, promoting the use of evidence-based mind-body medicine for colorectal cancer management could be considered.

Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study.

OBJECTIVES: To evaluate the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort. METHODS: This population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. We evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. HRs and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables. RESULTS: At baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3-9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080). CONCLUSIONS: Regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.

Acupuncture and related interventions for carpal tunnel syndrome: systematic review.

OBJECTIVE: To synthesize evidence on the effectiveness of acupuncture and related therapies for primary carpal tunnel syndrome (CTS) by conducting a systematic review of randomized controlled trials (RCTs). DATA SOURCES: Nine databases were searched for potential RCTs from their inception till July 2019. REVIEW METHODS: RCTs which reported at least one of the three outcomes were included: symptom severity, functional status and pain. Included RCTs were appraised using the Cochrane Risk of Bias Tool. RESULTS: A total of 10 RCTs (728 participants) were included. Majority were at high risk of bias for blinding of participants, personnel and outcome assessors. When compared to conventional medications, manual acupuncture showed significant superior effect in reducing symptom than ibuprofen (mean difference (MD) on Symptom Severity Scale (SSS)) = -5.80, 95% confidence interval (CI): -7.95 to -3.65) and prednisolone (MD = -6.50, 95% CI: -10.1, -2.86). Electroacupuncture plus splinting was more effective in reducing symptom severity than splinting alone (SSS score: MD = -0.20, 95% CI: -0.36 to -0.03). Manual acupuncture showed significantly superior effect than ibuprofen in improving functional status (Functional Status Scale (FSS): MD = -1.84, 95% CI: -2.66 to -1.02). The combination of electroacupuncture and splinting showed more improvement in functional status compared to splinting alone (FSS: MD = -6.22, 95%CI: -10.7 to -1.71). Triple treatment of acupuncture, magnetic spectrum heat lamp and splinting showed stronger pain relief than splinting alone. CONCLUSION: For both symptom relief and function improvement, manual acupuncture is superior to ibuprofen while electroacupuncture plus splinting outperforms splinting alone. Limited evidence showed electroacupuncture's potential role in pain reduction.

Electroacupuncture plus on-demand gastrocaine for refractory functional dyspepsia: Pragmatic randomized trial.

BACKGROUND AND AIM: Treatment options for functional dyspepsia (FD) refractory to pharmacological treatments are limited but the effectiveness of electroacupuncture (EA) is uncertain. We assessed the effectiveness of EA combined with on-demand gastrocaine. METHODS: We conducted a single-center, assessor-blind, randomized parallel-group 2-arm trial on Helicobacter pylori negative FD patients of the postprandial distress syndrome subtype refractory to proton pump inhibitor, prokinetics, or H2 antagonists. Enrolled participants were block randomized in a 1:1 ratio, with concealed random sequence. The treatment and control groups both received on-demand gastrocaine for 12 weeks, but only those in treatment group were offered 20 sessions of EA over 10 weeks. The primary endpoint was the between-group difference in proportion of patients achieving adequate relief of symptoms at week 12. RESULTS: Of 132 participants randomly assigned to EA plus on-demand gastrocaine (n = 66) or on-demand gastrocaine alone (n = 66), 125 (94.7%) completed all follow-up at 12 weeks. The EA group had a compliance rate 97.7%. They had a significantly higher likelihood in achieving adequate symptom relief at 12 weeks, with a clinically relevant number needed to treat (NNT) value of 2.36 (95% CI: 1.74, 3.64). Among secondary outcomes, statistically and clinically significant improvements were observed among global symptom (NNT = 3.85 [95% CI: 2.63, 7.69]); postprandial fullness and early satiation (NNT = 5.00 [95% CI: 2.86, 25.00]); as well as epigastric pain, epigastric burning, and postprandial nausea (NNT = 4.17 [95% CI: 2.56, 11.11]). Adverse events were minimal and nonsignificant. CONCLUSION: For refractory FD, EA provides significant, clinically relevant symptom relief when added to on-demand gastrocaine (ChiCTR-IPC-15007109).

The risks and benefits of yoga for patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

OBJECTIVES: To determine the effectiveness and safety of yoga interventions on disease symptoms, quality of life and function in patients diagnosed with chronic obstructive pulmonary disease (COPD). DATA SOURCES: Medline/PubMed, Scopus, and CENTRAL (Cochrane Central Register of Controlled Trials) were searched through 6 June 2019. REVIEW METHODS: Randomized controlled trials assessing the effects of yoga on quality of life, dyspnea, exercise capacity, and pulmonary function (FEV1) in patients with COPD were included. Safety was defined as secondary outcome. Mean differences (MD) and standardized mean differences (SMD) with 95% confidence intervals (CIs) were computed. Risk of bias was assessed using the Cochrane tool. RESULTS: Eleven randomized controlled trials with a total of 586 patients were included. Meta-analysis revealed evidence for effects of yoga compared to no treatment on quality of life on the COPD Assessment Test (MD = 3.81; 95% CI = 0.97 to 6.65; P = 0.009, I2 = 70%), exercise capacity assessed by the 6-minute walk test (MD = 25.53 m; 95% CI = 12.16 m to 38.90 m; P = 0.001, I2 = 0%), and pulmonary function assessed by FEV1 predicted (MD = 3.95%; 95% CI = 2.74% to 5.17%; P < 0.001, I2 = 0%). Only the effects on exercise capacity and pulmonary function were robust against methodological bias. Effects were only present in breathing-focused yoga interventions but not in interventions including yoga postures. Adverse events were reported infrequently. CONCLUSION: This meta-analysis found robust effects of yoga on exercise capacity and pulmonary function in patients with COPD. Yoga, specifically yoga breathing techniques, can be an effective adjunct intervention for patients with COPD. Yoga's safety needs to be assessed in more depth in future studies.

Health Behavior Change and Complementary Medicine Use: National Health Interview Survey 2012.

Background and objectives: Complementary and alternative medicine (CAM) use has been associated with preventive health behaviors. However, the role of CAM use in patients' health behaviors remains unclear. This study aimed to determine the extent to which patients report that CAM use motivates them to make changes to their health behaviors. Materials and Methods: This secondary analysis of 2012 National Health Interview Survey data involved 10,201 CAM users living in the United States who identified up to three CAM therapies most important to their health. Analyses assessed the extent to which participants reported that their CAM use motivated positive health behavior changes, specifically: eating healthier, eating more organic foods, cutting back/stopping drinking alcohol, cutting back/quitting smoking cigarettes, and/or exercising more regularly. Results: Overall, 45.4% of CAM users reported being motivated by CAM to make positive health behavior changes, including exercising more regularly (34.9%), eating healthier (31.4%), eating more organic foods (17.2%), reducing/stopping smoking (16.6% of smokers), or reducing/stopping drinking alcohol (8.7% of drinkers). Individual CAM therapies motivated positive health behavior changes in 22% (massage) to 81% (special diets) of users. People were more likely to report being motivated to change health behaviors if they were: aged 18-64 compared to those aged over 65 years; of female gender; not in a relationship; of Hispanic or Black ethnicity, compared to White; reporting at least college education, compared to people with less than high school education; without health insurance. Conclusions: A sizeable proportion of respondents were motivated by their CAM use to undertake health behavior changes. CAM practices and practitioners could help improve patients' health behavior and have potentially significant implications for public health and preventive medicine initiatives; this warrants further research attention.

Barriers and Facilitators to Implementing Interventions for Reducing Avoidable Hospital Readmission: Systematic Review of Qualitative Studies.

BACKGROUND: Avoidable hospital readmission is a major problem among health systems. Although there are effective peri-discharge interventions for reducing avoidable hospital readmission, successful implementation is challenging. This systematic review of qualitative studies aimed to identify barriers and facilitators to implementing peri-discharge interventions from providers' and service users' perspectives. METHODS: We searched four databases for potentially eligible qualitative studies from databases' inception to March 2020, and updated literature search for studies published between January 2020 to October 2021. Barriers and facilitators to implementing peri-discharge interventions were identified and mapped onto the Consolidated Framework for Implementation Research (CFIR) constructs. Inductive analysis of the CFIR constructs was performed to yield thematic areas that illustrated the relationship between various facilitators and barriers, generating practical insights to key implementation issues. RESULTS: Thirteen qualitative studies were included in this systematic review. Key issues were clustered in the CFIR constructs of Design Quality and Complexity of the intervention, strength of Network and Communication, being responsive to Patient Needs with sufficient Resource support, and External Incentives. The three thematic areas were rationality of the interventions, readiness and effort of multidisciplinary implementation teams, and influence of external stakeholders. Common barriers included (i) limited resources, (ii) poor communication among team members, (iii) incompatibility between the new intervention and existing work routine, (iv) complicated implementation process, (v) low practicality of supporting instruments, and (vi) lack of understanding about the content and effectiveness of the new interventions. Common facilitators were (i) information sharing via regular meetings on implementation issues, (ii) organizational culture that values quality and accountability, (iii) financial penalties for hospitals with high avoidable readmissions rates, (iv) external support offered via quality improvement programs and community resources, and (v) senior leadership support. CONCLUSION: This study synthesized commonly-presenting barriers and facilitators to implementing peri-discharge interventions among different healthcare organizations. Findings may inform development of implementation strategies in different health systems after appropriate tailoring, based on a consensus-based formative research process.

Implementation science in traditional, complementary and integrative medicine: An overview of experiences from China and the United States.

BACKGROUND: The introduction of traditional, complementary and integrative medicine (TCIM) services into health systems has been advocated by the World Health Organization, but there is a paucity of reviews synthesising the experiences of (i) implementing TCIM services in conventional healthcare settings and (ii) introducing evidence-based practice in TCIM. Knowledge of the first issue will assist policymakers to innovate implementation interventions in their own health system contexts. Addressing the second issue will facilitate the closure of the evidence-practice gap in TCIM and improve the translation of research evidence into health outcome benefits. PURPOSE: The aim of this study was to identify, describe and analyse publications on these two key TCIM policy issues via an overview from an implementation science perspective. METHODS: Publications describing international experiences of implementing TCIM services or evidence for TCIM practices were identified by searching MEDLINE, EMBASE and Global Health databases in November 2021. The findings were summarised using a narrative synthesis approach. RESULTS: Sixty-three relevant publications were included in the analysis. Current experiences in China and the United Sates (US) reflect varying policy priorities at different stages of implementing TCIM services. In the US, where TCIM have yet to be introduced into mainstream healthcare settings, implementation interventions were designed to facilitate the provision of specific, evidence-based TCIM modalities via referrals from conventional clinicians. The application of these strategies at the health system, regulatory, financial, community, provider and patient levels provided a comprehensive picture of how TCIM implementation may be facilitated via multi-level interventions. In China, the major form of TCIM is traditional Chinese medicine (TCM), for which service provision has already been adopted at all levels of healthcare. With the high volume of clinical research that has been generated in the past several decades, a key policy question at this stage is how to translate TCM-related clinical evidence into practice. The development of clinical practice guidelines (CPGs) is the main implementation intervention, but adherence by TCM clinicians has been poor, due to the conflict between classical individualised practice and CPG standardisation. While tailoring interventions to facilitate CPG uptake is indicated, concurrent innovations in TCM clinical research methods would improve the compatibility between classical and CPG-based practice. CONCLUSION: Policymakers managing different stages of TCIM implementation will benefit from the experiences of practitioners in the US and China. Multi-level implementation interventions launched in the US provide ideas for the initial introduction of TCIM into a conventional medicine-dominated health system. As TCIM service provision and related clinical research become more common, China's experience will inform how clinical evidence related to TCIM may be disseminated and implemented to improve service quality.

Barriers and Facilitators to Receiving the COVID-19 Vaccination and Development of Theoretically-Informed Implementation Strategies for the Public: Qualitative Study in Hong Kong.

OBJECTIVES: enhancing uptake of COVID-19 vaccines is an important tool for managing the pandemic. However, in Hong Kong, the COVID-19 vaccination rate in the general population was unsatisfactory during the early phase of the vaccination program. This two-part study aimed to (i) identify barriers and facilitators to receiving vaccinations, and (ii) develop theoretically-informed implementation strategies for promoting uptake. METHODS: in part 1, 45 Hong Kong residents who differed in their willingness to vaccinate (willing (n = 15), were unwilling (n = 15), and were hesitant (n = 15)), were interviewed individually in February 2021. They were invited to express their perceptions of receiving the COVID-19 vaccination. The theoretical domains framework (TDF) was applied to guide the interviews and analyses. Behavioral diagnoses from these findings were then used to develop theoretically-informed implementation strategies in part 2, composed of behavior change techniques (BCTs) informed by the established BCT taxonomy. RESULTS: in part 1, the five main barriers were (i) concerns on severe and long-term side effects; (ii) low confidence in the safety and effectiveness due to concerns of their accelerated development; (iii) unclear information on logistical arrangements of the vaccination program; (iv) insufficient data on safety and effectiveness; and (v) perceived low protection ability conferred by the vaccines. The five main facilitators included (i) healthcare professionals' recommendations; (ii) news from TV, radio, and newspapers as main sources of trustworthy information; (iii) vaccine-related health education delivered by healthcare professionals; (iv) expectations of resuming to a normal social life; and (v) perceived benefits outweighing risks of mild and short-term side effects. CONCLUSIONS: seven implementation strategies were developed in part 2 based on the results above, namely (i) providing trustworthy vaccine-related information and scaling up the promotion; (ii) encouraging healthcare professionals to recommend vaccinations; (iii) giving incentives; (iv) using social influence approaches; (v) allowing a selection of COVID-19 vaccine brands; (vi) increasing accessibility for vaccinations; and (vii) emphasizing social responsibility.

Herbal medicine for functional dyspepsia: Network meta-analysis of placebo-controlled randomised trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Conventional treatments for functional dyspepsia (FD) are limited. Herbal medicine (HM) use is prevalent despite unclear comparative effectiveness among different formulae. AIM OF THE STUDY: This network meta-analysis (NMA) aimed to evaluate the comparative effectiveness of HM formulae for FD against placebo. MATERIALS AND METHODS: Seven international and Chinese databases were searched for randomised controlled trials (RCTs) on HM versus placebo. Risk of bias among RCTs was assessed using Cochrane Risk-of-Bias Tool 2. Data from RCTs were extracted for random-effect pairwise meta-analyses. NMAs were performed to evaluate the comparative effectiveness of HM formulae. GRADE partially contextualised framework was adopted to facilitate NMA result interpretation. RESULTS: Twelve different HM formulae were identified from fifteen RCTs of mediocre quality. At 8-week follow-up, pairwise meta-analyses indicated that HM was superior to placebo in alleviating global symptoms (pooled risk difference (RD): 0.20; 95% confidence interval (CI): 0.11-0.29), with effect size larger than the minimally clinically important difference of 0.20 RD. Sensitivity analysis showed no significant impact on results attributable to risk of bias. NMAs demonstrated that Xiao Yao Pill and Modified Ban Xia Xie Xin Decoction probably have a large beneficial effect on alleviating global symptoms (RD: 0.37; 95% CI: 0.03-0.99) and postprandial fullness (standardised mean difference: -0.93; 95% credible interval: -1.61 to -0.06), respectively. No serious adverse events were reported. CONCLUSIONS: Xiao Yao Pill and Modified Ban Xia Xie Xin Decoction may be considered as an alternative among patients unresponsive to conventional treatments. The comparative effectiveness of these two formulae should be evaluated in future trials.

Latent tree analysis for the identification and differentiation of evidence-based Traditional Chinese Medicine diagnostic patterns: A primer for clinicians.

BACKGROUND: A supplementary chapter on the diagnostic patterns of Traditional Medicine, including Traditional Chinese Medicine (TCM), was introduced into the latest edition of the International Classification of Diseases (ICD-11). However, evidence-based rules are yet to be developed for pattern differentiation in patients with specific conventional medicine diagnoses. Without such standardised rules, the level of diagnostic agreement amongst practitioners is unsatisfactory. This may reduce the reliability of practice and the generalisability of clinical research. PURPOSE: Using cross-sectional study data from patients with functional dyspepsia, we reviewed and illustrated a quantitative approach that combines TCM expertise and computer algorithmic capacity, namely latent tree analysis (LTA), to establish score-based pattern differentiation rules. REVIEW OF METHODS: LTA consists of six major steps: (i) the development of a TCM clinical feature questionnaire; (ii) statistical pattern discovery; (iii) statistical pattern interpretation; (iv) TCM diagnostic pattern identification; (v) TCM diagnostic pattern quantification; and (vi) TCM diagnostic pattern differentiation. Step (i) involves the development of a comprehensive questionnaire covering all essential TCM clinical features of the disease of interest via a systematic review. Step (ii) to (iv) required input from TCM experts, with the algorithmic capacity provided by Lantern, a dedicated software for TCM LTA. MOTIVATIONAL EXAMPLE TO ILLUSTRATE THE METHODS: LTA is used to quantify the diagnostic importance of various clinical features in each TCM diagnostic pattern in terms of mutual information and cumulative information coverage. LTA is also capable of deriving score-based differentiation rules for each TCM diagnostic pattern, with each clinical feature being provided with a numerical score for its presence. Subsequently, a summative threshold is generated to allow pattern differentiation. If the total score of a patient exceeded the threshold, the patient was diagnosed with that particular TCM diagnostic pattern. CONCLUSIONS: LTA is a quantitative approach to improving the inter-rater reliability of TCM diagnosis and addressing the current lack of objectivity in the ICD-11. Future research should focus on how diagnostic information should be coupled with effectiveness evidence derived from network meta-analysis. This will enable the development of an implementable diagnostics-to-treatment scheme for further evaluation. If successful, this scheme will transform TCM practice in an evidence-based manner, while preserving the validity of the model.

Pharmacological Interventions for the Management of Cancer-Related Fatigue Among Cancer Survivors: Systematic Review and Meta-Analysis.

OBJECTIVE: Current guidelines have different recommendations on applying pharmacological interventions for managing cancer-related fatigue (CRF) among cancer survivors. This systematic review aims to synthesize clinical evidence on pharmacological interventions for managing CRF. METHODS: Five databases were searched for potential randomized controlled trials (RCTs) from their inception until October 2020. RCTs assessing the effect of pharmacological treatments for CRF among cancer survivors were considered eligible. Clinical significance was determined by comparing the estimated effect with that of minimal important difference (MID). The risk of bias of each included RCT was appraised using the Cochrane risk of bias tool for randomized trials 2. Data were synthesized using random-effect pairwise meta-analyses. RESULTS: A total of 15 RCTs (1238 participants) were included. The majority presented some concerns of bias arising from the randomization process and selection of the reported results. Meta-analysis showed that psychostimulant and wakefulness agents had statistically significant while clinically insignificant effects on the treatment of CRF (pooled weighted mean difference [WMD]: 2.8, 95% confidence interval [CI]: 0.2-5.4, I2: 0%, 3 RCTs, MID: 3.0-6.0). Three natural products, including Renshen Yangrong Tang (mean difference [MD]: -16.1, 95% CI: -8.9 to -23.3, MID: -17.3 to -11.4), Tualang honey (MD: 11.2, 95% CI: 7.1-15.3, MID: 3.0-6.0), and Shenmai injection plus Peptisorb (MD: -1.6, 95% CI: -2.1 to -1.1, MID: -1.1 to -0.8) demonstrated statistically and clinically significant effect in reducing CRF. CONCLUSIONS: Existing evidence showed promising effects of 3 natural products in reducing CRF among cancer survivors. The results from this study need to be further confirmed with well-designed and adequately powered RCTs that use validated instruments for the measurement of CRF.

Non-specific effects of acupuncture and sham acupuncture in clinical trials from the patient's perspective: a systematic review of qualitative evidence.

BACKGROUND: Previous clinical trials have demonstrated that both acupuncture and sham acupuncture exert significant, non-specific effects on treatment outcomes when compared to no-treatment controls. A recently developed framework (mechanisms in orthodox and complementary and alternative medicine-MOCAM) suggests that the non-specific effects of acupuncture originate from multiple domains (e.g. patient characteristics, acupuncturist skill/technique, the patient-acupuncturist relationship, and the acupuncture environment). However, it remains to be determined precisely how these domains influence the non-specific effects of treatment among patients receiving acupuncture and sham acupuncture in clinical trials. Therefore, we conducted a systematic review to synthesize existing qualitative evidence on how trial participants randomized to acupuncture and sham acupuncture groups experience non-specific effects, regardless of the types of medical condition investigated. METHODS: This systematic review included primary qualitative studies embedded in randomized controlled trials designed to investigate acupuncture or sham acupuncture interventions. Eligible studies published in English were derived from a search of five international databases. The methodological quality of included studies was evaluated using the Critical Appraisal Skills Programme (CASP) tool. Using a framework synthesis approach, the identified MOCAM framework was adapted based on the synthesis of the available qualitative evidence. RESULTS: A total of 20 studies of high methodological quality were included. Our proposed model indicated that the effects of acupuncture may be increased by maintaining a professional status, applying a holistic treatment approach, practicing empathy, and providing patients with an appropriate explanation of the theory behind acupuncture and sham acupuncture. From the patient's perspective, the efficacy of treatment can be increased by following the lifestyle modification advice provided by acupuncturists, maintaining a positive attitude toward treatment efficacy, actively engaging with acupuncturists during consultation, and making behavioral changes based on experience gained during the trial. CONCLUSION: The results of this study may provide a basis for improving and standardizing key components of non-specific effects in acupuncture treatment, and for improving the isolation of specific effects in future clinical trials involving acupuncture and sham acupuncture.

Evaluating traditional Chinese medicine diagnostic instruments for functional dyspepsia: systematic review on measurement properties.

BACKGROUND: Pattern diagnosis-guided treatments in Traditional Chinese Medicine (TCM) has been recognised by the eleventh revision of the International Classification of Diseases (ICD-11). Accurate pattern diagnosis requires reliable and valid diagnostic instruments that guide the collection of TCM clinical data without bias. This study synthesised the existing TCM diagnostic instruments for functional dyspepsia (FD) and appraised their quality regarding their development process and measurement properties. METHODS: Seven electronic databases were searched for validation studies on TCM diagnostic instruments for FD. Synthesis and appraisal of the included studies were performed following the COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) Initiative guidelines adapted for TCM diagnostic instruments. Risk of bias assessment was conducted using the COSMIN Risk of Bias Checklist. RESULTS: Five studies were included, with five unique TCM diagnostic instruments for FD identified. All five diagnostic instruments were of inadequate quality in terms of their development process, implying a shortcoming in their relevance, comprehensibility, and comprehensiveness. Only the criterion validity of Stomach Qi Deficiency Pattern Assessment Scale was of sufficient quality and had no risk of bias in its validation. CONCLUSION: The quality of TCM diagnostic instruments for FD warrants urgent improvements. None of them was considered reliable or valid for guiding TCM pattern diagnosis. To support the evidence base of the standardization of TCM patterns in ICD-11, TCM diagnostic instruments should be developed and validated rigorously under the COSMIN guidelines. Amendments should be made on the guidelines to accommodate the features and uniqueness of TCM diagnostic process.

Effectiveness of nurse-led peri-discharge interventions for reducing 30-day hospital readmissions: Network meta-analysis.

BACKGROUND: Existing systematic reviews have compared the effectiveness of nurse-led peri-discharge interventions comprising different components with usual care on reducing all-cause 30-day hospital readmissions. However, conflicting results were reported. OBJECTIVE: We conducted a network meta-analysis to evaluate the comparative effectiveness of different nurse-led peri-discharge interventions, compared with usual care, for reducing all-cause 30-day hospital readmissions. DESIGN: Network meta-analysis. METHODS: A total of five international databases were searched for systematic reviews of randomized controlled trials. Additional searches for most updated randomized controlled trials published between 2014 to 2019 were conducted. Data from included randomized controlled trials were extracted for random-effect pairwise meta-analyses. Pooled risk ratios with 95% confidence interval were used to quantify impact of nurse-led peri-discharge interventions on all-cause 30-day hospital readmissions. Network meta-analysis was used to evaluate the comparative effectiveness of different interventions. RESULTS: From two systematic reviews and additional randomized controlled trial searches, 12 eligible randomized controlled trials (n=150,840) assessing 15 different nurse-led peri-discharge interventions were included. For reducing all-cause 30-day hospital readmissions, pairwise meta-analysis showed that there was no significant difference between nurse-led peri-discharge interventions and usual care (pooled risk ratios = 0.86, 95% confidence interval: 0.71-1.04, moderate quality of evidence). Network meta-analysis indicated no significant difference across different interventions despite variation in complexity. CONCLUSIONS: Our results indicated that nurse-led peri-discharge interventions were not significantly different from usual care for reducing all-cause 30-day hospital readmissions. Simpler nurse-led peri-discharge interventions are on par with more complex interventions in terms of effectiveness. Benefits of nurse-led peri-discharge interventions may vary across health system context. Therefore, careful consideration is required prior to implementation. REGISTRATION DETAILS: The protocol for this study has been registered in PROSPERO (Registration No. CRD42020186938). Tweetable abstract: This study suggested that nurse-led peri-discharge interventions do not differ from usual care for reducing all-cause 30-day hospital readmissions.

Methodological quality of systematic reviews on interventions for osteoarthritis: a cross-sectional study.

BACKGROUND: Healthcare providers need reliable evidence for supporting the adoption of new interventions, of which the source of evidence often originates from systematic reviews (SRs). However, little assessment on the rigor of SRs related to osteoarthritis interventions has been conducted. This cross-sectional study aimed to evaluate the methodological quality and predictors among SRs on osteoarthritis interventions. METHODS: Four electronic databases (Cochrane Database of Systematic Reviews, MEDLINE, Embase, and PsycINFO) were searched, from 1 January 2008 to 10 October 2019. An SR was eligible if it focused on osteoarthritis interventions, and we performed at least one meta-analysis. Methodological quality was assessed using the validated AMSTAR 2 instrument. Multivariate regression analyses were conducted to assess predictors of methodological quality. RESULTS: In total, 167 SRs were included. The most SRs were non-Cochrane reviews (88.6%), and 54.5% investigated non-pharmacological interventions. Only seven (4.2%) had high methodological quality. Respectively, eight (4.8%), 25 (15.0%), and 127 (76.0%) SRs had moderate, low, and critically low quality. Main methodological weaknesses were as follows: only 16.8% registered protocol a priori, 4.2% searched literature comprehensively, 25.7% included lists of excluded studies with justifications, and 30.5% assessed risk of bias appropriately by considering allocation concealment, blinding of patients and assessors, random sequence generation and selective reported outcomes. Cochrane reviews [adjusted odds ratio (AOR) 251.5, 95% confidence interval (CI) 35.5-1782.6], being updates of previous SRs (AOR 3.9, 95% CI 1.1-13.7), and SRs published after 2017 (AOR 7.7, 95% CI 2.8-21.5) were positively related to higher methodological quality. CONCLUSION: Despite signs of improvement in recent years, most of the SRs on osteoarthritis interventions have critically low methodological quality, especially among non-Cochrane reviews. Future SRs should be improved by conducting comprehensive literature search, justifying excluded studies, publishing a protocol, and assessing the risk of bias of included studies appropriately.

Age, chronic non-communicable disease and choice of traditional Chinese and western medicine outpatient services in a Chinese population.

BACKGROUND: In 1997 Hong Kong reunified with China and the development of traditional Chinese medicine (TCM) started with this change in national identity. However, the two latest discussion papers on Hong Kong's healthcare reform have failed to mention the role of TCM in primary healthcare, despite TCM's public popularity and its potential in tackling the chronic non-communicable disease (NCD) challenge in the ageing population. This study aims to describe the interrelationship between age, non-communicable disease (NCD) status, and the choice of TCM and western medicine (WM) services in the Hong Kong population. METHODS: This study is a secondary analysis of the Thematic Household Survey (THS) 2005 dataset. The THS is a Hong Kong population representative face to face survey was conducted by the Hong Kong Administrative Region Government of China. A random sample of respondents aged >15 years were invited to report their use of TCM and WM in the past year, together with other health and demographic information. A total of 33,263 persons were interviewed (response rate 79.2%). RESULTS: Amongst those who received outpatient services in the past year (n = 18,087), 80.23% only visited WM doctors, 3.17% consulted TCM practitioners solely, and 16.60% used both type of services (double consulters). Compared to those who only consulted WM doctor, multinomial logistic regression showed that double consulters were more likely to be older, female, NCD patients, and have higher socioeconomic backgrounds. Further analysis showed that the association between age and double consulting was curvilinear (inverted U shaped) regardless of NCD status. Middle aged (45-60 years) NCD patients, and the NCD free "young old" group (60-75 years) were most likely to double consult. On the other hand, the relationship between age and use of TCM as an alternative to WM was linear regardless of NCD status. The NCD free segment of the population was more inclined to use TCM alone as they become older. CONCLUSION: In Hong Kong, most patients have chosen WM provided in the public sector as their sole outpatient service provider for NCD. Amongst TCM service users, middle aged NCD patients are more likely to choose both TCM and WM outpatient services. Meanwhile, older people without NCD are more likely to use TCM as their main form of care, but the size of this population group is small. These utilization patterns show that patients choose both modalities to manage their NCD and TCM should be considered within policies for supporting patients with NCD under the wider primary health and social care system that supports patient choice.

Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis.

Hypertonic dextrose injections (prolotherapy) is an emerging treatment for symptomatic knee osteoarthritis (OA) but its efficacy is uncertain. We conducted a systematic review with meta-analysis to synthesize clinical evidence on the effect of prolotherapy for knee OA. Fifteen electronic databases were searched from their inception to September 2015. The primary outcome of interest was score change on the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Three randomized controlled trials (RCTs) of moderate risk of bias and one quasi-randomized trial were included, with data from a total of 258 patients. In the meta-analysis of two eligible studies, prolotherapy is superior to exercise alone by a standardized mean difference (SMD) of 0.81 (95% CI: 0.18 to 1.45, p = 0.012), 0.78 (95% CI: 0.25 to 1.30, p = 0.001) and 0.62 (95% CI: 0.04 to 1.20, p = 0.035) on the WOMAC composite scale; and WOMAC function and pain subscale scores respectively. Moderate heterogeneity exists in all cases. Overall, prolotherapy conferred a positive and significant beneficial effect in the treatment of knee OA. Adequately powered, longer-term trials with uniform end points are needed to better elucidate the efficacy of prolotherapy.