Association of healthy lifestyle behaviours with incident irritable bowel syndrome: a large population-based prospective cohort study.

OBJECTIVES: To evaluate the association between healthy lifestyle behaviours and the incidence of irritable bowel syndrome (IBS). DESIGN: Population-based prospective cohort study. SETTING: The UK Biobank. PARTICIPANTS: 64 268 adults aged 37 to 73 years who had no IBS diagnosis at baseline were enrolled between 2006 and 2010 and followed up to 2022. MAIN EXPOSURE: The five healthy lifestyle behaviours studied were never smoking, optimal sleep, high level of vigorous physical activity, high dietary quality and moderate alcohol intake. MAIN OUTCOME MEASURE: The incidence of IBS. RESULTS: During a mean follow-up of 12.6 years, 961 (1.5%) incident IBS cases were recorded. Among the 64 268 participants (mean age 55.9 years, 35 342 (55.0%) female, 7604 (11.8%) reported none of the five healthy lifestyle behaviours, 20 662 (32.1%) reported 1 behaviour, 21 901 (34.1%) reported 2 behaviours and 14 101 (21.9%) reported 3 to 5 behaviours at baseline. The multivariable adjusted hazard ratios associated with having 1, 2 and 3 to 5 behaviours for IBS incidence were 0.79 (95% confidence intervals 0.65 to 0.96), 0.64 (0.53 to 0.78) and 0.58 (0.46 to 0.72), respectively (P for trend <0.001). Never smoking (0.86, 0.76 to 0.98, P=0.02), high level of vigorous physical activity (0.83, 0.73 to 0.95, P=0.006) and optimal sleep (0.73, 0.60 to 0.88, P=0.001) demonstrated significant independent inverse associations with IBS incidence. No significant interactions were observed between these associations and age, sex, employment status, geographic location, gastrointestinal infection, endometriosis, family history of IBS or lifestyle behaviours. CONCLUSIONS: Adhering to a higher number of healthy lifestyle behaviours is significantly associated with a lower incidence of IBS in the general population. Our findings suggest the potential of lifestyle modifications as a primary prevention strategy for IBS.

Outcome prioritization and preferences among older adults with cancer starting chemotherapy in a randomized clinical trial.

INTRODUCTION: Older adults with cancer facing competing treatments must prioritize between various outcomes. This study assessed health outcome prioritization among older adults with cancer starting chemotherapy. METHODS: Secondary analysis of a randomized trial addressing vulnerabilities in older adults with cancer. Patients completed three validated outcome prioritization tools: 1) Health Outcomes Tool: prioritizes outcomes (survival, independence, symptoms) using a visual analog scale; 2) Now vs. Later Tool: rates the importance of quality of life at three times-today versus 1 or 5 years in the future; and 3) Attitude Scale: rates agreement with outcome-related statements. The authors measured the proportion of patients prioritizing various outcomes and evaluated their characteristics. RESULTS: A total of 219 patients (median [range] age 71 [65-88], 68% with metastatic disease) were included. On the Health Outcomes Tool, 60.7% prioritized survival over other outcomes. Having localized disease was associated with choosing survival as top priority. On the Now vs. Later Tool, 50% gave equal importance to current versus future quality of life. On the Attitude Scale, 53.4% disagreed with the statement "the most important thing to me is living as long as I can, no matter what my quality of life is"; and 82.2% agreed with the statement "it is more important to me to maintain my thinking ability than to live as long as possible". CONCLUSION: Although survival was the top priority for most participants, some older individuals with cancer prioritize other outcomes, such as cognition and function. Clinicians should elicit patient-defined priorities and include them in decision-making.

Relacorilant plus nab-paclitaxel for the treatment of metastatic pancreatic ductal adenocarcinoma: results from the open-label RELIANT study.

BACKGROUND: Modulation of glucocorticoid receptor (GR) activity in tumor cells enhances chemotherapy efficacy. We evaluated the selective GR modulator relacorilant plus nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who had received at least 2 prior therapy lines. PATIENTS AND METHODS: In this open-label, single-arm, phase III study, patients received once-daily oral relacorilant (100 mg, titrated to 150 mg in 25 mg increments/cycle) and nab-paclitaxel (80 mg/m2) on days 1, 8, and 15 of 28-day cycles. The primary efficacy endpoint was objective response rate (ORR) by blinded independent central review. Progression-free survival (PFS), overall survival (OS), target gene modulation, and safety were also assessed. RESULTS: Of 43 patients enrolled, 31 were evaluable for ORR (12 did not reach first postbaseline radiographic assessment). An interim analysis to assess whether ORR was ≥10% showed no confirmed responses and the study was discontinued. Two (6.5%) patients attained unconfirmed partial responses and 15 (48.4%) had stable disease. Fourteen of 31 (45.2%) patients had reductions in target lesion size, despite prior nab-paclitaxel exposure in 12 of the 14. Median PFS and OS were 2.4 months (95% CI, 1.4-4.2) and 3.9 months (95% CI, 2.8-4.9), respectively. The most common adverse events were fatigue and nausea. RNA analysis confirmed that relacorilant plus nab-paclitaxel suppressed 8 cortisol target genes of interest. CONCLUSION: Relacorilant plus nab-paclitaxel showed modest antitumor activity in heavily pretreated patients with mPDAC, with no new safety signals. Studies of this combination in other indications with a high unmet medical need are ongoing.

Safety of pressurized intraperitoneal aerosolized chemotherapy in biliary cancer patients with peritoneal metastases.

Biliary tract cancers are a rare diagnosis with a rising incidence. Up to 20% of patients have peritoneal metastases, resulting in symptoms of ascites, abdominal pain and potential bowel obstruction. A standard of care systemic treatment comprises gemcitabine, cisplatin and durvalumab (gem/cis/durva). However, the clinical benefit among patients with peritoneal metastases remains unknown. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) delivers chemotherapy directly to the peritoneal space, which could potentially improve efficacy with minimal systemic toxicity. We describe the design of a Phase I study investigating PIPAC with nab-paclitaxel plus systemic gem/cis/durva among biliary tract cancer patients with peritoneal metastases who have not received prior systemic treatment. The primary end point is safety of PIPAC with nab-paclitaxel in combination with systemic gem/cis/durva.Clinical Trial Registration: NCT05285358 (ClinicalTrials.gov).

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Association between fish oil and glucosamine use and mortality in patients diagnosed with cancer: the role of the Life Essential 8 score and cancer prognosis.

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.

Methodological quality of systematic reviews on sepsis treatments: A cross-sectional study.

OBJECTIVE: Systematic reviews (SRs) offer updated evidence to support decision-making on sepsis treatments. However, the rigour of SRs may vary, and methodological flaws may limit their validity in guiding clinical practice. This cross-sectional study appraised the methodological quality of SRs on sepsis treatments. METHODS: We searched MEDLINE, EMBASE, and Cochrane Database for eligible SRs on randomised controlled trials on sepsis treatments with at least one meta-analysis published between 2018 and 2023. We extracted SRs' bibliographical characteristics with a pre-designed form and appraised their methodological quality using AMSTAR (A MeaSurement Tool to Assess systematic Reviews) 2. We applied logistic regressions to explore associations between bibliographical characteristics and methodological quality ratings. RESULTS: Among the 102 SRs, two (2.0%) had high overall quality, while respectively four (3.9%), seven (6.9%) and 89 (87.3%) were of moderate, low, and critically low quality. Performance in several critical methodological domains was poor, with only 32 (31.4%) considering the risk of bias in primary studies in result interpretation, 22 (21.6%) explaining excluded primary studies, and 16 (15.7%) applying comprehensive searching strategies. SRs published in higher impact factor journals (adjusted odds ratio: 1.19; 95% confidence interval: 1.05 to 1.36) was associated with higher methodological quality. CONCLUSIONS: The methodological quality of recent SRs on sepsis treatments is unsatisfactory. Future reviewers should address the above critical methodological aspects. More resources should also be allocated to support continuous training in critical appraisal among healthcare professionals and other evidence users.

Immersive and Nonimmersive Virtual Reality-Assisted Active Training in Chronic Musculoskeletal Pain: Systematic Review and Meta-Analysis.

BACKGROUND: Virtual reality (VR) in different immersive conditions has been increasingly used as a nonpharmacological method for managing chronic musculoskeletal pain. OBJECTIVE: We aimed to assess the effectiveness of VR-assisted active training versus conventional exercise or physiotherapy in chronic musculoskeletal pain and to analyze the effects of immersive versus nonimmersive VR on pain outcomes. METHODS: This systematic review of randomized control trials (RCTs) searched PubMed, Scopus, and Web of Science databases from inception to June 9, 2024. RCTs comparing adults with chronic musculoskeletal pain receiving VR-assisted training were included. The primary outcome was pain intensity; secondary outcomes included functional disability and kinesiophobia. Available data were pooled in a meta-analysis. Studies were graded using the Cochrane Risk-of-Bias Tool version 2. RESULTS: In total, 28 RCTs including 1114 participants with some concerns for a high risk of bias were identified, and 25 RCTs were included in the meta-analysis. In low back pain, short-term outcomes measured post intervention showed that nonimmersive VR is effective in reducing pain (standardized mean difference [SMD] -1.79, 95% CI -2.72 to -0.87; P<.001), improving disability (SMD -0.44, 95% CI -0.72 to -0.16; P=.002), and kinesiophobia (SMD -2.94, 95% CI -5.20 to -0.68; P=.01). Intermediate-term outcomes measured at 6 months also showed that nonimmersive VR is effective in reducing pain (SMD -8.15, 95% CI -15.29 to -1.01; P=.03), and kinesiophobia (SMD -4.28, 95% CI -8.12 to -0.44; P=.03) compared to conventional active training. For neck pain, immersive VR reduced pain intensity (SMD -0.55, 95% CI -1.02 to -0.08; P=.02) but not disability and kinesiophobia in the short term. No statistical significances were detected for knee pain or other pain regions at all time points. In addition, 2 (8%) studies had a high risk of bias. CONCLUSIONS: Both nonimmersive and immersive VR-assisted active training is effective in reducing back and neck pain symptoms. Our study findings suggest that VR is effective in alleviating chronic musculoskeletal pain. TRIAL REGISTRATION: PROSPERO CRD42022302912; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=302912.

The Provision and Perceptions of Telemedicine Services Among Traditional Chinese Medicine Practitioners During COVID-19: A Cross-Sectional Study in Hong Kong, China.

Objectives: Telemedicine has been widely used during the COVID-19 pandemic. Among other health care professionals, Chinese medicine practitioners (CMPs) face practical challenges in providing telemedicine consultations. This study aims to explore CMPs' experience and perceptions of telemedicine service provision before and during the pandemic. Methods: A territory-wide cross-sectional online survey was conducted in Hong Kong between April and May 2022. A structured questionnaire with open-ended questions was used to investigate the provision of and perception on telemedicine service, as well as usability of telemedicine among CMPs. Results: A total of 195 CMPs participated the survey. Before COVID-19, 42% (81/195) had been providing telemedicine services, and the proportion doubled during COVID-19. CMPs in the private sector are the main providers. Mobile apps including WhatsApp, WeChat, and Zoom were commonly used for consultations (75%, 120/161). Barriers in providing telemedicine included inability of conducting physical examination on patients (69%, 134/195), legal and ethical concerns over medical negligence (61%, 118/195), and patients' incompetence on e-literacy (50%, 98/195). Respondents urged professional and regulatory bodies to provide an explicit clinical guideline that demonstrate best practice in traditional Chinese medicine telemedicine, and to clarify legal and ethical implications of such practice. Conclusions: CMPs demonstrated their competency in telemedicine, and most of them provided telemedicine during COVID-19. Development of appropriate guidelines on the provision of telemedicine would support CMPs to continue provision after the pandemic, whereas a user-friendly and comprehensive telemedicine e-platform would enhance quality of such service. Facilitating patients with lower e-literacy to access telemedicine is key to reduce disparities.

Ampullary Adenocarcinoma, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology.

Ampullary cancers refer to tumors originating from the ampulla of Vater (the ampulla, the intraduodenal portion of the bile duct, and the intraduodenal portion of the pancreatic duct), while periampullary cancers may arise from locations encompassing the head of the pancreas, distal bile duct, duodenum, or ampulla of Vater. Ampullary cancers are rare gastrointestinal malignancies, and prognosis varies greatly based on factors such as patient age, TNM classification, differentiation grade, and treatment modality received. Systemic therapy is used in all stages of ampullary cancer, including neoadjuvant therapy, adjuvant therapy, and first-line or subsequent-line therapy for locally advanced, metastatic, and recurrent disease. Radiation therapy may be used in localized ampullary cancer, sometimes in combination with chemotherapy, but there is no high-level evidence to support its utility. Select tumors may be treated surgically. This article describes NCCN recommendations regarding management of ampullary adenocarcinoma.

Associations of dietary supplement use with all-cause and cause-specific mortality in patients diagnosed with cancer: a large prospective cohort study in the UK Biobank.

PURPOSE: Despite the increasing popularity of supplement use among the cancer community, the current evidence on its effect on mortality in large studies is inconclusive. This study examined the association of dietary supplement use with mortality risk in a large population-based cohort. METHODS: This prospective cohort study analyzed data from the UK Biobank on participants who were diagnosed with cancer before July 31, 2019 and self-reported whether they had regular intake of dietary supplements (vitamins, minerals, or non-vitamin non-mineral [NVNM] supplements) after cancer diagnosis. The associations between the use of supplements with mortality were analyzed using Cox proportional hazards models, adjusting for confounders (sociodemographic factors, lifestyle and comorbidities). RESULTS: This analysis included 30,239 participants (mean age: 60.0 years; 61.9% female). Over half (57.8%) were supplement users. At a median follow-up of 11.9 years, 5577 all-cause deaths were registered. A marginal protective effect of supplement use on the risk of all-cause (adjusted hazard ratio [aHR] = 0.95, 95% CI = 0.90-0.99) and cancer (aHR = 0.89, 95% CI = 0.83-0.95) mortality were found, but not the risk of mortality due to other causes. In subgroup analyses, only NVNM dietary supplements were significantly associated with a lower risk of all-cause mortality (aHR = 0.88, 95% CI = 0.83-0.93). Both vitamins (aHR = 0.93, 95% CI = 0.87-0.99) and NVNM dietary supplements (aHR = 0.88, 95% CI = 0.82-0.94) were associated with a modest decrease in cancer mortality which were marginally significant. CONCLUSIONS: This is one of the largest cohort studies that identified the associations of dietary supplements with survival in the cancer population. However, the associations are small and should be interpreted cautiously due to the variations among different supplements and the small effect size. Future studies should investigate the effect of individual supplements, particularly NVNM supplements, on improving other cancer-related outcomes.

Effectiveness of Hypertonic Dextrose Injection (Prolotherapy) in Plantar Fasciopathy: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To systematically review the effectiveness of hypertonic dextrose prolotherapy (DPT) in plantar fasciopathy (PF) compared with other non-surgical treatments. DATA SOURCES: PubMed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, Allied and Complementary Medicine Database, Global Health, Ovid Nursing Database, Dimensions, and WHO ICTRP were searched from inception to April 30th, 2022. STUDY SELECTION: Two independent reviewers selected randomized controlled trials (RCTs) that evaluated the effectiveness of DPT in PF compared with non-surgical treatments. Outcomes included pain intensity, foot and ankle function, and plantar fascia thickness. DATA EXTRACTION: Two independent reviewers conducted data extraction. Risk of bias (RoB) assessment was conducted using the Cochrane Risk of Bias 2 (RoB 2) tool, and certainty of evidence was assessed with Grading of Recommendation Assessment, Development, and Evaluation (GRADE). DATA SYNTHESIS: Eight RCTs (n=469) met the inclusion criteria. Pooled results favored the use of DPT versus normal saline (NS) injections in reducing pain (weighted mean difference [WMD] -41.72; 95% confidence interval [CI] -62.36 to -21.08; P<.01; low certainty evidence) and improving function [WMD -39.04; 95% CI -55.24 to -22.85; P<.01; low certainty evidence] in the medium term. Pooled results also showed corticosteroid (CS) injections was superior to DPT in reducing pain in the short term [standardized mean difference 0.77; 95% CI 0.40 to 1.14; P<.01; moderate certainty evidence]. Overall RoB varied from "some concerns" to "high". The overall certainty of evidence presented ranges from very low to moderate based on the assessment with the GRADE approach. CONCLUSION: Low certainty evidence demonstrated that DPT was superior to NS injections in reducing pain and improving function in the medium term, but moderate certainty evidence showed that it was inferior to CS in reducing pain in the short term. Further high-quality RCTs with standard protocol, longer-term follow-up, and adequate sample size are needed to confirm its role in clinical practice.

The Use of Traditional, Complementary, and Integrative Medicine in Cancer: Data-Mining Study of 1 Million Web-Based Posts From Health Forums and Social Media Platforms.

BACKGROUND: 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. OBJECTIVE: This study leveraged multiple forums and social media platforms to explore patients' use, interest, and perception of TCIM for cancer care. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Contextualizing evidence-based nurse-led interventions for reducing 30-day hospital readmissions using GRADE evidence to decision framework: A Delphi study.

BACKGROUND: High 30-day readmission rates increase hospital costs and negatively impact patient outcomes in many healthcare systems, including Hong Kong. Evidence-based and local adaptable nurse-led interventions have not been established for reducing 30-day hospital readmissions among general medical patients in Hong Kong's public healthcare system. AIMS: The aim of this study was to select and refine evidence-based nurse-led interventions for reducing 30-day hospital readmissions among general medical patients in Hong Kong's public healthcare system using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) framework. METHODS: Eighteen local healthcare stakeholders were recruited to carry out a two-step process. In step 1, stakeholders were invited to prioritize nurse-led interventions which were supported by existing evidence and suggest important combinations of different interventions. For all interventions prioritized in step 1, step 2 involved stakeholders performing a two-round Delphi questionnaire aiming to generate consensus-based interventions appropriate to the local context. GRADE EtD framework was applied to guide the decision-making process, taking into account certainty of evidence, benefits and harms, resource use, equity, acceptability, and feasibility. RESULTS: Four out of eight nurse-led interventions reached a positive consensus with percentage agreement ranging from 70.6% to 82.4%. GRADE EtD criteria ratings showed that over 70% of stakeholders agreed these four interventions were probably acceptable and feasible, though the certainty of evidence was low or moderate. Half of stakeholders believed their desirable effects compared to undesirable effects were large. However, the resources required and how these nurse-led interventions might affect health inequities when implemented were uncertain. Preliminary implementation issues included high complexity of delivering multiple nurse-led intervention components, and challenges of coordinating different involved parties in delivering the interventions. Appropriate resource allocation and training should be provided to address these potential problems, as suggested by stakeholders. LINKING EVIDENCE TO ACTION: Using the GRADE EtD framework, four nurse-led interventions were recommended by healthcare stakeholders as possible strategies for reducing 30-day hospital readmissions among general medical patients in Hong Kong. To address preliminary implementation issues, nurses' role as care coordinators should also be strengthened to ensure smooth delivery of nurse-led intervention components, and to facilitate multidisciplinary collaboration during service delivery.

Patient-Defined Goals and Preferences Among Adults With Advanced Neuroendocrine Tumors.

BACKGROUND: Patient preferences (quantity vs quality of life; present vs future health) have not been investigated in patients with neuroendocrine tumors (NETs). The goal of this cross-sectional study was to evaluate patient values toward treatment goals and competing health outcomes among adults with NETs. PATIENTS AND METHODS: Patients with well-differentiated, grade 1 or 2, advanced NETs starting a new systemic therapy completed 4 tools: (1) Health Outcomes Tool, which ranks the importance of 4 outcomes (survival, function/independence, freedom from pain, freedom from symptoms); (2) Attitude Scale, which identifies the extent to which patients agree with statements related to health outcomes; (3) Now versus Later Tool, which ranks the relative importance of quality of life (QoL) now versus 1 and 5 years from now; and (4) Prognosis and Treatment Perceptions Questionnaire, which identifies the amount of information the patient prefers to receive about their disease and treatment, the patient's treatment goal, the patient's perception of the physician's treatment goal, and self-reported health status. RESULTS: We recruited 60 patients with NETs (50.0% aged ≥65 years; 96.7% with stage IV disease). Primary tumor locations included the gastrointestinal tract (41.7%), pancreas (30.0%), and lung (21.7%). A plurality of patients reported maintaining independence as their most important health outcome (46.7%), followed by survival (30.0%), freedom from pain (11.7%), and freedom from symptoms (11.7%). A total of 67% of patients agreed with the statement, "I would rather live a shorter life than lose my ability to take care of myself"; 85.0% agreed with the statement, "It is more important to me to maintain my thinking ability than to live as long as possible." When asked to choose between current QoL versus QoL 1 year or 5 years in the future as more important, 48.3% and 40.0% of patients valued their QoL 1 year and 5 years in the future, respectively, more than their current QoL. Only 51.7% of patients believed their physician's treatment goals aligned with their own. CONCLUSIONS: Adult patients with NETs strongly value independence over survival. More communication between patients with NETs and their physicians is needed to ensure that patient preferences are incorporated into treatment plans.

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.

Comparing diagnostic performance of Cantonese-Chinese version of Rome IV criteria and a short Reference Standard for functional dyspepsia in China.

INTRODUCTION: Functional dyspepsia (FD) is diagnosed based on self-reported symptoms and negative upper gastrointestinal endoscopic findings. The Rome criteria were not adopted as a diagnostic instrument in clinical guidelines due to their complexity. Different guidelines used relatively simple symptom assessment schemes with contents that vary significantly. A previously evaluated short Reference Standard may serve as a more standardised tool for guidelines. We evaluated its diagnostic accuracy against the Rome IV criteria in a cross-sectional study in Hong Kong. METHODS: A total of 220 dyspeptic patients sampled consecutively from a tertiary hospital and the community completed the Rome IV diagnostic questionnaire, which was translated into Cantonese-Chinese, and the Reference Standard. Sensitivity, specificity, positive and negative likelihood ratios (LRs), and area under the receiver operating characteristics curve (AUC), with 95% confidence intervals (CIs), were calculated. RESULTS: Among the participants, 160 (72.7%) fulfilled the Reference Standard with negative upper gastrointestinal endoscopic results. The Reference Standard identified patients with Rome IV-defined FD with 91.1% (95% CI 82.6%-96.4%) sensitivity and 37.6% (95% CI 29.6%-46.1%) specificity. The positive and negative LRs were 1.46 (95% CI 1.26-1.69) and 0.24 (95% CI 0.11-0.49), respectively. The AUC value was 0.64 (95% CI 0.59-0.69). CONCLUSIONS: The Reference Standard can rule out patients without Rome IV-defined FD. It may be used as an initial screening tool for FD in settings where the use of the Rome IV criteria is impractical. It may also provide a uniform definition and diagnostic rule for future updates of clinical guidelines.

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.

Impact of information framing and vaccination characteristics on parental COVID-19 vaccine acceptance for children: a discrete choice experiment.

This study aimed to test the influence of vaccination characteristics and gain/loss-framing of information, on parental acceptance of the coronavirus disease 2019 (COVID-19) vaccination for their minor children. A discrete choice experiment was conducted among parents of children aged 0-17 years from September to October 2021 in Hong Kong. Respondents were randomly assigned to four groups with different framing of information and asked to choose hypothetical vaccination alternatives, described by seven attributes that were derived from prior qualitative interviews. A mixed logit model was adopted to analyze the effect of attributes and information framing on parental vaccination acceptance. The vaccine acceptance rates under different scenarios were also estimated. A total of 298 valid responses were obtained. It was found that the BioNTech brand, higher efficacy, less serious adverse events and more vaccination coverage in children significantly improved parental acceptance. Additionally, loss-framing increased parental acceptance compared with gain-framing, while the presentation of mortality information did not make a difference. Acceptance was also associated with parental uptake of the COVID-19 vaccine and the children's age. CONCLUSION: The findings imply that factors including gain/loss information framing, importance of vaccine characteristics, and peer influence have a significant effect on parents' decisions to get their children vaccinated. Parents with younger children had greater vaccine hesitancy, and information framing techniques should be considered in vaccination promotion for combating such vaccine hesitancy. Future studies could be conducted to identify the moderators and mediators of information framing to facilitate its implementation. WHAT IS KNOWN: • Parental acceptance of COVID-19 vaccine was found to be associated with various socio-economic and psychosocial factors, while the evidence on impact of vaccination characteristics was limited. • Behavioral interventions, including information framing, have been used to promote various health behaviors. WHAT IS NEW: • Loss-framing of information on vaccine effectiveness improves vaccine acceptance, while additional information on how the vaccine reduces death does not make a difference, which can be used to inform communication with the public in vaccination promotion. • The social norm (i.e., the vaccine uptake amongst other people) is important for increasing the parental vaccine acceptance rate.

Effects of Hypertonic Dextrose Injection (Prolotherapy) in Lateral Elbow Tendinosis: A Systematic Review and Meta-analysis.

OBJECTIVE: To systematically review the effectiveness of hypertonic dextrose prolotherapy (DPT) on pain intensity and physical functioning in patients with lateral elbow tendinosis (LET) compared with other active non-surgical treatments. DATA SOURCES: Systematic search of Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Web of Science, PubMed, Dimensions, Global Health, NHS Health Technology Assessment, Allied and Complementary Medicine, and OVID nursing database from inception to June 15, 2021, without language restrictions. STUDY SELECTION: Two reviewers independently identified parallel or crossover randomized controlled trials that evaluated the effectiveness of DPT in LET. The search identified 245 records; data from 8 studies (354 patients) were included. DATA EXTRACTION: Two reviewers independently extracted data and assessed included studies. The Cochrane Risk of Bias 2 tool was used to evaluate risk of bias. The Grading of Recommendation Assessment, Development, and Evaluation approach was used to assess quality of the evidence. DATA SYNTHESIS: Pooled results favored the use of DPT in reducing tennis elbow pain intensity compared with active controls at 12 weeks postenrollment, with a standardized mean difference of -0.44 (95% confidence interval, -0.88 to -0.01, P=.04) and of moderate heterogeneity (I2=49%). Pooled results also favored the use of DPT on physical functioning compared with active controls at 12 weeks, with Disabilities of the Arm, Shoulder and Hand scores achieving a mean difference of -15.04 (95% confidence interval, -20.25 to -9.82, P<.001) and of low heterogeneity (I2=0.0%). No major related adverse events have been reported. CONCLUSIONS: DPT is superior to active controls at 12 weeks for decreasing pain intensity and functioning by margins that meet criteria for clinical relevance in the treatment of LET. Although existing studies are too small to assess rare adverse events, for patients with LET, especially those refractory to first-line treatments, DPT can be considered a nonsurgical treatment option in carefully selected patients. Further high-quality trials with comparison with other injection therapies are needed.

Comparative effectiveness of non-pharmacological interventions for depressive symptoms in mild cognitive impairment: systematic review with network meta-analysis.

OBJECTIVES: Depressive symptoms are common among mild cognitive impairment (MCI) patients. It is unknown how different the effects on depressive symptoms are among various pharmacological MCI interventions. This systematic review aimed to evaluate the comparative effectiveness of non-pharmacological MCI interventions on depressive symptoms among MCI patients. METHODS: A systematic review and network meta-analysis was conducted on randomized controlled trials (RCT) comparing the effect of different non-pharmacological MCI interventions on changes in depressive symptoms among MCI patients. RCTs were identified from MEDLINE, EMBASE, Cochrane Library, CINAHL, PsycINFO, and PsycARTICLES. Results were summarized as standardized mean differences (SMD) and 95% confidence intervals (CI). The surface under the cumulative ranking (SUCRA) was used to rank the effect of different interventions. RESULTS: Twenty-two RCTs were included in the network meta-analysis. Compared with non-active control, cognition-based intervention (SMD=-0.25, 95% CI: -0.46, -0.04) and physical exercise (SMD=-0.33, 95% CI: -0.56, -0.10) had significant positive effects to reduce depressive symptoms. Health education, psychosocial intervention, and the combination of physical exercise and cognition-based intervention had non-significant overall effects. The SUCRA demonstrated that physical exercise had the highest SUCRA for the reduction in depression symptoms (0.815). In subgroup analysis, health education, cognition-based intervention, physical exercise, and the combination of physical exercise and cognition-based intervention showed significant longer-term effects (6-12 months). CONCLUSION: Physical exercise and cognition-based intervention were effective interventions for depressive symptoms in MCI patients. This study can provide additional evidence for healthcare providers to make decisions for selecting available and appropriate interventions for MCI patients.