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Oral melatonin is a potential alternative treatment for hypertension and nocturnal hypertension. However, high‐quality and relevant meta‐analyses are lacking. This meta‐analysis aimed to investigate whether oral melatonin supplementation reduces daytime/asleep blood pressure and cardiovascular risk, improves sleep quality, and is well‐tolerated compared with placebo. Relevant articles were searched in multiple databases, including MEDLINE, EMBASE, CINAHL Complete, and the Cochrane Library, from their inception to June 2021. The included studies were randomized controlled trials recruiting patients with hypertension, using oral melatonin as the sole intervention, and investigating its effect on blood pressure. The mean out‐of‐office (including 24‐h, daytime, and asleep) systolic and diastolic blood pressures, sleep quality, and side effects were compared between the melatonin and placebo arms using pairwise random‐effect meta‐analyses. A risk of bias assessment was performed using the Cochrane risk‐of‐bias tool. Four studies were included in the analysis and only one study was considered to have a low risk of bias. No study reported on cardiovascular risk or outcomes. Only controlled‐release melatonin (not an immediate‐release preparation) reduced asleep systolic blood pressure by 3.57 mm Hg (95% confidence interval: –7.88 to .73; I2 = 0%). It also reduced asleep and awake diastolic blood pressure, but these differences were not statistically significant. Melatonin improves sleep efficacy and total sleep time and is safe and well‐tolerated. Due to the limited number of high‐quality trials, the quality of evidence was low to very low. Therefore, adequately powered randomized controlled trials on melatonin are warranted.

During COVID-19, the public actively sought non-pharmacological and self-management approaches to prevent infection. Little is known on the use of traditional, complementary and integrative medicine (TCIM) by the public as preventive measures. This study investigated the prevalence and patterns of TCIM use during the pandemic, and identified factors associated with its use among the general population in Hong Kong. An online cross-sectional survey was conducted from November to December 2020. The survey solicited information on the respondents' sociodemographic characteristics, risk perception of the pandemic, and use of TCIM before and during the pandemic. Logistic regression analysis was conducted to determine predictors of TCIM use. In total, 632 responses (completion rate = 88.1%) were analyzed. TCIM was used by 44.0% of respondents during the pandemic. The most popular forms of TCIM were vitamins or other dietary supplements (n = 160, 25.3%) and Chinese herbal medicine (n = 122, 19.3%) during the pandemic. The most frequently reported indication was strengthening the immune system, especially for vitamins or other dietary supplements (n = 142/160, 88.8%). Respondents who reported using TCIM were more likely to be female (adjusted odds ratio [aOR] = 1.82, 95% confidence interval [CI] = 1.29-2.59), had higher education attainment (aOR = 2.21, 95% CI = 1.39-3.59), and older-aged (age >55 years: aOR = 1.77, 95% CI = 1.04-3.02). Respondents who resided in districts with moderate to high number of confirmed COVID-19 cases (aOR = 1.60, 95% CI = 1.07-2.42) and had a higher level of risk perception (aOR = 1.04, 95% CI = 1.01-1.07) were also more likely to use TCIM. TCIM was used commonly in Hong Kong during the COVID-19 pandemic. While vaccination and social distancing remain the mainstay of controlling the pandemic, professional bodies should proactively consider public preferences and provide information regarding the effectiveness and safety of TCIM for COVID-19 prevention and treatment.

Background A proliferation of theories, models, and frameworks (TMFs) have been developed in the implementation science field to facilitate the implementation process. The basic features of these TMFs have been identified by several reviews. However, systematic appraisals on the quality of these TMFs are inadequate. To fill this gap, this study aimed to assess the usability, applicability, and testability of the current TMFs in a structured way. Methods A scoping review method was employed. Electronic databases were searched to locate English and Chinese articles published between January 2000 and April 2022. Search terms were specific to implementation science. Additionally, hand searches were administered to identify articles from related reviews. Purpose and characteristics such as the type of TMF, analytical level, and observation unit were extracted. Structured appraisal criteria were adapted from Birken et al.’s Theory Comparison and Selection Tool (T-CaST) to conduct an in-depth analysis of the TMFs’ usability, applicability, and testability. Results A total of 143 TMFs were included in this analysis. Among them, the most common purpose was to identify barriers and facilitators. Most TMFs applied the descriptive method to summarize the included constructs or the prescriptive method to propose courses of implementation actions. TMFs were mainly mid-range theories built on existing conceptual frameworks or demonstrated grand theories. The usability of the TMFs needs to be improved in terms of the provision of conceptually matched strategies to barriers and facilitators and instructions on the TMFs usage. Regarding the applicability, little attention was paid to the constructs of macro-level context, stages of scale-up and sustainability, and implementation outcomes like feasibility, cost, and penetration. Also, fewer TMFs could propose recommended research and measurement methods to apply the TMFs. Lastly, explicit hypotheses or propositions were lacking in most of the TMFs, and empirical evidence was lacking to support the claimed mechanisms between framework elements in testability. Conclusions Common limitations were found in the usability, application, and testability of the current TMFs. The findings of this review could provide insights for developers of TMFs for future theoretical advancements.

This review aimed to systematically review and meta-analyze the effects of interventions in improving bracing compliance among adolescent idiopathic scoliosis (AIS) patients. Eight databases were searched from their inception to April 2022. The eligibility criteria included controlled studies that used any type of intervention to enhance bracing compliance in braced AIS patients. Two researchers independently screened articles and extracted data based on the PICO (participant, intervention, comparator, and outcome) framework. Quality appraisal of included studies was performed using GRADE (overall assessment), and the risk of bias was assessed with Cochrane RoB Tool 2 for randomized controlled trials (RCT) and ROBINS-I for non-RCT studies. The primary outcome was bracing compliance and secondary outcomes included Cobb Angle and measurements for quality of life. Six eligible studies involving 523 participants were included. All studies were evaluated as low or very low quality with a high risk of bias. Four types of interventions were identified, including sensor monitoring (n = 2, RCTs), auto-adjusted brace (n = 1, RCT), more intensive or collaborated medical care (n = 2), and psychosocial intervention (n = 1). A meta-analysis of 215 patients from the three RCTs suggested that the compliance-enhancing intervention group had 2.92 more bracing hours per day than the usual care control (95%CI [1.12, 4.72], P = 0.001). In subgroup analysis, sensor monitoring significantly improved bracing wearing quantity compared to usual care (3.47 hours/day, 95%CI [1.48, 5.47], P = 0.001), while other aforementioned interventions did not show a significant superiority. Compliance-enhancing interventions may be favorable in preventing curve progression and promoting quality of life, but the improvements cannot be clarified according to limited evidence. In conclusion, although the results of this study suggested that sensor monitoring may be the most promising approach, limited high-quality evidence precludes reliable conclusions. Future well-designed RCTs are required to confirm the actual benefit of compliance-improving interventions in clinical practice.

ObjectiveSocial distancing is one of the main non-pharmaceutical interventions used in the control of the COVID-19 pandemic. This scoping review aims to synthesise research findings on the effectiveness of different types and levels of social distancing measures in the earlier stage of COVID-19 pandemic without the confounding effect of mass vaccination.DesignScoping review.Data sourcesMEDLINE, Embase, Global Health and four other databases were searched for eligible studies on social distancing for COVID-19 published from inception of the databases to 30 September 2020.Study selection and data extractionEffectiveness studies on social distancing between individuals, school closures, workplace/business closures, public transport restrictions and partial/full lockdown were included. Non-English articles, studies in healthcare settings or not based on empirical data were excluded.ResultsAfter screening 1638 abstracts and 8 additional articles from other sources, 41 studies were included for synthesis of findings. The review found that the outcomes of social distancing measures were mainly indicated by changes in Rt, incidence and mortality, along with indirect indicators such as daily contact frequency and travel distance. There was adequate empirical evidence for the effect of social distancing at the individual level, and for partial or full lockdown at the community level. However, at the level of social settings, the evidence was moderate for school closure, and was limited for workplace/business closures as single targeted interventions. There was no evidence for a separate effect of public transport restriction.ConclusionsIn the community setting, there was stronger evidence for the combined effect of different social distancing interventions than for a single intervention. As fatigue of preventive behaviours is an issue in public health agenda, future studies should analyse the risks in specific settings such as eateries and entertainment to implement and evaluate measures which are proportionate to the risk.

Hypertonic dextrose prolotherapy (DPT) has been reported to be effective for temporomandibular disorders (TMDs) in clinical trials but its overall efficacy is uncertain. To conduct a systematic review with meta-analysis of randomized controlled trials (RCTs) to synthesize evidence on the effectiveness of DPT for TMDs. Eleven electronic databases were searched from their inception to October, 2020. The primary outcome of interest was pain intensity. Secondary outcomes included maximum inter-incisal mouth opening (MIO) and disability score. Studies were graded by “Cochrane risk of bias 2” tool; if data could be pooled, a meta-analysis was performed. Ten RCTs (n = 336) with some to high risk of bias were included. In a meta-analysis of 5 RCTs, DPT was significantly superior to placebo injections in reducing TMJ pain at 12 weeks, with moderate effect size and low heterogeneity (Standardized Mean Difference: − 0.76; 95% CI − 1.19 to − 0.32, I 2  = 0%). No statistically significant differences were detected for changes in MIO and functional scores. In this systematic review and meta-analysis, evidence from low to moderate quality studies show that DPT conferred a large positive effect which met criteria for clinical relevance in the treatment of TMJ pain, compared with placebo injections. Protocol registration at PROSPERO: CRD42020214305.

Patients with cancer are increasingly using forums and social media platforms to access health information and share their experiences, particularly in the use of traditional, complementary, and integrative medicine (TCIM). Despite the popularity of TCIM among patients with cancer, few related studies have used data from these web-based sources to explore the use of TCIM among patients with cancer. This study leveraged multiple forums and social media platforms to explore patients' use, interest, and perception of TCIM for cancer care. Posts (in English) related to TCIM were collected from Facebook, Twitter, Reddit, and 16 health forums from inception until February 2022. Both manual assessments and natural language processing were performed. Descriptive analyses were performed to explore the most commonly discussed TCIM modalities for each symptom and cancer type. Sentiment analyses were performed to measure the polarity of each post or comment, and themes were identified from posts with positive and negative sentiments. TCIM modalities that are emerging or recommended in the guidelines were identified a priori. Exploratory topic-modeling analyses with latent Dirichlet allocation were conducted to investigate the patients' perceptions of these modalities. Among the 1,620,755 posts available, cancer-related symptoms, such as pain (10/10, 100% cancer types), anxiety and depression (9/10, 90%), and poor sleep (9/10, 90%), were commonly discussed. Cannabis was among the most frequently discussed TCIM modalities for pain in 7 (70%) out of 10 cancer types, as well as nausea and vomiting, loss of appetite, anxiety and depression, and poor sleep. A total of 7 positive and 7 negative themes were also identified. The positive themes included TCIM, making symptoms manageable, and reducing the need for medication and their side effects. The belief that TCIM and conventional treatments were not mutually exclusive and intolerance to conventional treatment may facilitate TCIM use. Conversely, TCIM was viewed as leading to patients' refusal of conventional treatment or delays in diagnosis and treatment. Doctors' ignorance regarding TCIM and the lack of information provided about TCIM may be barriers to its use. Exploratory analyses showed that TCIM recommendations were well discussed among patients; however, these modalities were also used for many other indications. Other notable topics included concerns about the legalization of cannabis, acupressure techniques, and positive experiences of meditation. Using machine learning techniques, social media and health forums provide a valuable resource for patient-generated data regarding the pattern of use and patients' perceptions of TCIM. Such information will help clarify patients' needs and concerns and provide directions for research on integrating TCIM into cancer care. Our results also suggest that effective communication about TCIM should be achieved and that doctors should be more open-minded to actively discuss TCIM use with their patients.

Background The effect of supplements on mortality risk in patients with cancer remains uncertain and has scarcely been investigated in subgroups of patients with varying characteristics. This study aimed to investigate the association between two popular supplements, fish oil and glucosamine, and mortality risk in a large population-based cohort and determine whether cardiovascular health and clinical prognosis influence these associations. Methods This prospective cohort study analyzed the data of UK Biobank participants who were diagnosed with cancer. The associations of fish oil and glucosamine consumption with mortality were analyzed using Cox proportional hazards models. Subgroup analyses were performed to assess the effects of Life Essential 8 [LE8] scores (a measure of cardiovascular health) and cancer prognosis (grouped according to the survival rates of specific cancer types) on the associations between supplement use and mortality. Results This analysis included 14,920 participants (mean age = 59.9 years; 60.2% female). One third (34.1%) of the participants reported using fish oil, and one fifth (20.5%) reported using glucosamine. Over a median follow-up of 12.0 years, 2,708 all-cause deaths were registered. The use of fish oil was associated with reduced risks of all-cause mortality (adjusted hazard ratio [aHR] = 0.89, 95% Confidence Interval [CI] = 0.81–0.97) and cancer mortality (aHR = 0.89, 95% CI = 0.81–0.98). Similarly, glucosamine use was associated with reduced risks of all-cause mortality (aHR = 0.83, 95% CI = 0.74–0.92) and cancer mortality (aHR = 0.83, 95% CI = 0.74–0.93) in the fully adjusted model. Subgroup analyses revealed that the protective effects of fish oil and glucosamine against mortality risk were only observed in patients with LE8 scores lower than the mean score or a poor cancer prognosis. Additionally, the association between glucosamine use and a reduced risk of CVD-related mortality was only observed in patients with lower LE8 scores. Conclusions This large cohort study identified the potential differential impact of LE8 scores and cancer prognosis on the associations of fish oil and glucosamine supplementation with survival in patients with cancer. This suggests the importance of considering these factors in future research on supplements and in the provision of personalized integrative cancer care.

Background: There is a lack of study comprehensively comparing the effects of all existing types of interventions on global cognition among patients with mild cognitive impairment (MCI). Aims: To conduct a network meta-analysis to evaluate the effectiveness of different types of interventions in improving global cognition among MCI patients. Methods: Randomized controlled trials (RCTs) assessing the effects of pharmacological or non-pharmacological interventions on the Mini-Mental State Examination (MMSE) in MCI patients were included. Two authors independently screened the studies and extracted the data. Random-effects network meta-analysis was used to synthesize the data. Results were summarized as mean difference (MD) and corresponding 95% CIs of MMSE in forest plots. Results: Fifty RCTs with 5,944 MCI patients met the inclusion criteria and 49 were included in the network meta-analysis. Compared with the control group, cognition-based intervention (MD = 0.80, 95% CI 0.04–1.57), physical exercise (MD = 1.92, 95% CI 1.19–2.64), combined physical exercise and cognition-based intervention (MD = 1.86, 95% CI 0.60–3.12), and antioxidants (MD = 0.94, 95% CI 0.04–1.83) had positive effects on MMSE in participants with MCI. There was no significant difference between all other interventions included and the control group. Conclusions: This study suggested that cognition-based intervention, physical exercise, combined physical exercise and cognition-based intervention, and antioxidants could be among the most effective interventions on global cognition in older adults with MCI. The availability, acceptability, and cost-effectiveness of interventions should also be taken into consideration when selecting interventions. Registration: PROSPERO CRD42020171985.

ObjectivesTo assess the therapeutic effects and safety of Tongxie Yaofang (TXYF) granules vs placebo as an alternative treatment for diarrhoea-predominant irritable bowel syndrome (IBS-D). We hypothesised that TXYF would improve clinical responses among patients with IBS-D.DesignA randomised, double-blind, placebo-controlled, phase II, superiority trial.SettingOutpatients attending the Fangshan Hospital, Beijing University of Chinese Medicine, Beijing, China.Participants96 eligible participants included men and women ranging from late adolescence to middle adulthood (18–65 years), diagnosed with IBS-D according to the Rome IV criteria. In addition, they were required to have an irritable bowel syndrome symptom severity score (IBS-SSS) of at least 75.InterventionsTXYF granules (3.7 g) twice daily (taken orally before meals) or placebo for 8 weeks.Primary and secondary outcomesThe primary outcome was the response rate measured by the change in IBS-SSS compared with baseline at week 8. Secondary outcomes included stool frequency; stool consistency at weeks 4, 8 and 20; and quality of life, anxiety and depression at week 8; and safety was monitored throughout the trial.ResultsThe TXYF and placebo groups each comprised 48 participants. The response rate was not significantly different at week 8 between the two groups (the unadjusted treatment effect estimate (intention-to-treat analysis) was 1.12 (95% CI (0.89, 1.41)), p=0.348). Both groups had a high and similar rate of symptom reduction (79.2% (38/48) vs 70.8% (34/48)). There were no statistically significant differences between the two groups on secondary outcomes, although both groups showed substantial improvements. Adverse events in the TXYF and placebo groups were one (sinus arrhythmia) and two (elevated transaminases, weakly positive faecal occult blood), respectively. No serious adverse events occurred.ConclusionsDespite showing clinically meaningful improvements in IBS-D symptoms and a reasonable safety profile after 8 weeks, no significant differences were observed between the TXYF and placebo groups. This suggests that the severity of IBS-D symptoms in both treatment arms might have decreased over time, regardless of the treatment, and highlights the need to investigate the relationship between IBS-D and patient psychology. Future large-scale, rigorously designed trials with longer treatment and follow-up periods are essential to evaluate the therapeutic effects and safety of TXYF, and to explore the psychological factors.Trial registration numberISRCTN12453166.