Revisiting the association between vitamin D deficiency and active tuberculosis: A prospective case-control study in Taiwan.

BACKGROUND: To revisit the association between vitamin D deficiency (VDD, defined as serum 25(OH)D < 20 ng/ml) and incident active tuberculosis (TB), after two potentially underpowered randomized trials showed statistically non-significant 13%-22% decrease in TB incidence in vitamin D supplementation groups. METHODS: We prospectively conducted an age/sex-matched case-control study that accounting for body-mass index (BMI), smoking, and other confounding factors to examine the association between VDD and active TB among non-HIV people in Taiwan (latitude 24°N), a high-income society which continues to have moderate TB burden. RESULTS: We enrolled 62 people with incident active TB and 248 people in control group. The TB case patients had a significantly higher proportion of VDD compared to the control group (51.6% vs 29.8%, p = 0.001). The 25(OH)D level was also significantly lower in TB patients compared to control group (21.25 ± 8.93 ng/ml vs 24.45 ± 8.36 ng/ml, p = 0.008). In multivariable analysis, VDD (adjusted odds ratio [aOR]: 3.03, p = 0.002), lower BMI (aOR: 0.81, p < 0.001), liver cirrhosis (aOR: 8.99, p = 0.042), and smoking (aOR: 4.52, p = 0.001) were independent risk factors for incident active TB. CONCLUSIONS: VDD is an independent risk factor for incident active TB. Future randomized trials examining the effect of vitamin D supplementation on TB incidence should focus on people with a low BMI or other risk factors to maximize the statistical power.

Positive benefit-risk ratio of Psoraleae Fructus: Comprehensive safety assessment and osteogenic effects in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (PF), the dried fruit of Psoralea corylifolia L., is a commonly used traditional medicine that has contributed to the treatment of orthopedic diseases for thousands of years in China. However, recent PF-related liver injury reports have drawn widespread attention regarding its potential hepatotoxicity risks. AIM OF THE STUDY: This study was aimed to evaluate the long-term efficacy and chronic toxicity of PF using a 26-week administration experiment on rats in order to simulate the clinical usage situation. MATERIALS AND METHODS: The PF aqueous extract was consecutively administrated to rats daily at dosages of 0.7, 2.0, and 5.6 g/kg (equivalent to 1-8 times the clinical doses for humans) for as long as 26 weeks. Samples were collected after 13, 26, and 32 weeks (withdrawal for 6 weeks) since the first administration. The chronic toxicity of PF was evaluated by conventional toxicological methods, and the efficacy of PF was evaluated by osteogenic effects in the natural growth process. RESULTS: In our experiments, only the H group (5.6 g/kg) for 26-week PF treatment demonstrated liver or kidney injury, which the injuries were reversible after 6 weeks of withdrawal. Notably, the PF treatment beyond 13 weeks showed significant benefits for bone growth and development in rats, with a higher benefit-risk ratio in female rats. CONCLUSIONS: PF displayed a promising benefit-risk ratio in the treatment and prevention of osteoporosis, a disease that lacks effective medicine so far. This is the first study to elucidate the benefit-risk balance associated with clinical dosage and long-term use of PF, thereby providing valuable insights for rational clinical use and risk control of PF.

Risk of Corneal Graft Rejection and Vaccination: A Matched Case-Control Study From a United States Integrated Health Care System.

PURPOSE: Data on vaccine-associated corneal transplant rejections are limited. We examined the association between graft rejection and vaccination. DESIGN: Matched case-control METHODS: We used electronic health records to identify corneal transplant recipients between January 2008 and August 2022 at Kaiser Permanente Southern California. Cases were transplant recipients who experienced a graft rejection (outcome) during the study period. Randomly selected controls who did not experience a corneal graft rejection at their matched cases' index date (rejection date) were matched in a 3:1 ratio to cases. For controls, index date was determined by adding the number of days between transplant and graft rejection of their matched case to the control's transplant date. RESULTS: The study included 601 cases and 1803 matched controls (mean age 66 years [s.d. 17.0], 52% female, 47% non-Hispanic white). Twenty-three% of cases and 22% of controls received ≥1 vaccinations within 12 weeks prior to the index date. The adjusted odds ratio (aOR) for vaccination in the 12 weeks prior to index date, comparing cases to controls was 1.17 (95% CI: 0.91, 1.50]). The aOR was 1.09 (0.84, 1.43) for 1 vaccination, 1.53 (0.90, 2.61) for 2 vaccinations, and 1.79 (0.55, 5.57) for ≥3 vaccinations. The aOR was 1.60 (0.81, 3.14) for mRNA vaccines, and 1.19 (0.80, 1.78) for adjuvanted/high dose vaccines. CONCLUSIONS: We found no evidence to suggest an association between vaccination and graft rejection. Our findings provide support for the completion of recommended vaccinations for corneal transplant recipients, without significantly increasing the risk of graft rejection.

Genetically predicted gut microbiome and risk of oral cancer.

PURPOSE: Mounting evidence suggests a possible link between gut microbiome and oral cancer, pointing to some potential modifiable targets for disease prevention. In the present study, Mendelian randomization (MR) was used to explore whether there was a causal link between gut microbiome and oral cancer. METHODS: The single nucleotide polymorphisms (SNPs) significantly associated with gut microbiome were served as instrumental variables. MR analyses were performed using genetic approaches such as inverse variance weighting (IVW), MR Egger and weighted median, with IVW as the primary approach, supplemented by MR Egger and weighted median. Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were used to detect the presence of horizontal pleiotropy and identify outlier SNPs. RESULTS: Causal effect estimates indicated that genetically predicted abundance of Prevotellaceae was associated with higher risk of oral cancer (odds ratio (OR) 1.80, 95% confidence interval (CI) 1.16-2.81, p = 0.009). There was no evidence of notable heterogeneity and horizontal pleiotropy. CONCLUSION: Genetically derived estimates suggest that Prevotellaceae may be associated with the risk of oral cancer. Such robust evidence should be given priority in future studies and explore the underlying mechanisms.

Bias analyses to investigate the impact of differential participation: Application to a birth defects case-control study.

BACKGROUND: Certain associations observed in the National Birth Defects Prevention Study (NBDPS) contrasted with other research or were from areas with mixed findings, including no decrease in odds of spina bifida with periconceptional folic acid supplementation, moderately increased cleft palate odds with ondansetron use and reduced hypospadias odds with maternal smoking. OBJECTIVES: To investigate the plausibility and extent of differential participation to produce effect estimates observed in NBDPS. METHODS: We searched the literature for factors related to these exposures and participation and conducted deterministic quantitative bias analyses. We estimated case-control participation and expected exposure prevalence based on internal and external reports, respectively. For the folic acid-spina bifida and ondansetron-cleft palate analyses, we hypothesized the true odds ratio (OR) based on prior studies and quantified the degree of exposure over- (or under-) representation to produce the crude OR (cOR) in NBDPS. For the smoking-hypospadias analysis, we estimated the extent of selection bias needed to nullify the association as well as the maximum potential harmful OR. RESULTS: Under our assumptions (participation, exposure prevalence, true OR), there was overrepresentation of folic acid use and underrepresentation of ondansetron use and smoking among participants. Folic acid-exposed spina bifida cases would need to have been ≥1.2× more likely to participate than exposed controls to yield the observed null cOR. Ondansetron-exposed cleft palate cases would need to have been 1.6× more likely to participate than exposed controls if the true OR is null. Smoking-exposed hypospadias cases would need to have been ≥1.2 times less likely to participate than exposed controls for the association to falsely appear protective (upper bound of selection bias adjusted smoking-hypospadias OR = 2.02). CONCLUSIONS: Differential participation could partly explain certain associations observed in NBDPS, but questions remain about why. Potential impacts of other systematic errors (e.g. exposure misclassification) could be informed by additional research.

Non-vaccination of dogs is linked to uncompleted COVID-19 vaccination protocols of owners.

Despite the known importance of vaccines as one of the greatest achievements in medical science, vaccine hesitancy has been increasing in the last decade and has become a major threat to global health. The growth of vaccine hesitancy worldwide became more evident with the onset of COVID-19 and raised the fear that this hesitancy would also impact companion animal vaccination. This study aimed to characterize vaccine-hesitant groups regarding companion animals and human vaccinations, as well as to explore the possible association between vaccine hesitancy in pets and their owners. An anonymous online survey containing 27 closed questions was conducted, including questions about dog health, such as vaccination, neutering, and homeopathy use, as well as questions about the COVID-19 vaccination status of the owner and motivations for vaccinating or not vaccinating their pets. Most participants (81.5 %) reported receiving three or more doses of the COVID-19 vaccine. Not vaccinating against COVID-19 or having an incomplete vaccination protocol was associated with an increase in the age range of participants (odds ratio [OR] = 1.43), not having higher education (OR = 7.70), and being in extreme income ranges (less than two minimum wages [OR = 7.57] and more than 10 [OR = 5.20]). The use of homeopathy in humans (OR = 3.24) and dogs (OR = 3.74) was associated with non-vaccination against COVID-19. Owners who were not fully vaccinated against COVID-19 were almost six times more likely to not vaccinate their dogs (OR = 5.94). Non-vaccination of dogs was also associated with non-neutering (OR = 3.56), keeping the dog in contact with other dogs (OR = 2.09), and an increase in the number of dogs in the house increased the chance of not vaccinating the animals (OR = 1.30). The present study revealed a strong association between non-vaccination against COVID-19 and non-vaccination in companion dogs, raising the hypothesis that vaccination hesitancy is a growing challenge in veterinary medicine. In addition, the characteristics of Brazilians who are reluctant to be vaccinated against COVID-19 or immunize their companion animals are described here for the first time.

Adoption of Electronic Health Record Among Substance Use Disorder Treatment Programs: Nationwide Cross-Sectional Survey Study.

BACKGROUND: Electronic health record (EHR) systems have been shown to be associated with improvements in care processes, quality of care, and patient outcomes. EHR also has a crucial role in the delivery of substance use disorder (SUD) treatment and is considered important for addressing SUD crises, including the opioid epidemic. However, little is known about the adoption of EHR in SUD treatment programs or the organizational-level factors associated with the adoption of EHR in SUD treatment. OBJECTIVE: We examined the adoption of EHR in SUD programs, with a focus on changes in adoption from 2014 to 2017, and identified organizational-level factors associated with EHR adoption. METHODS: We used data from the 2014 and 2017 National Drug Abuse Treatment System Surveys. Our analysis included 1027 SUD programs (531 in 2014 and 496 in 2017). We used chi-square and Mann-Whitney U tests for categorical and continuous variables, respectively, to assess changes in EHR adoption, technology use, program, and client characteristics. We also investigated differences in characteristics and barriers to adoption by EHR adoption status (adopted EHR vs had not adopted or were planning to adopt EHR). We then conducted multivariate logistic regressions to examine internal and external factors associated with EHR adoption. RESULTS: The adoption of EHR increased significantly from 57.6% (306/531) in 2014 to 69.2% (343/496) in 2017 (P<.001), showing that nearly one-third (153/496, 30.8%) of SUD programs had not yet adopted an EHR system by 2017. We identified a significant increase in technology use and ownership by a parent company (P=.01 and P<.001) and a decrease in the percentage of uninsured patients in 2017 (P<.001), compared to 2014. Our analysis further showed significant differences by adoption status for three major barriers to adoption: (1) start-up costs, (2) ongoing financial costs, and (3) privacy or security concerns (P<.001). Programs that used computerized scheduling (adjusted odds ratio [AOR] 3.02, 95% CI 2.23-4.09) and billing systems (AOR 2.29, 95% CI 1.62-3.25) were more likely to adopt EHR. Similarly, ownership type, such as private nonprofit (AOR 1.86, 95% CI 1.31-2.65) and public (AOR 2.14, 95% CI 1.27-3.67), or interest in participating in a patient-centered medical home (AOR 1.93, 95% CI 1.29-2.92), were associated with an increased likelihood to adopt EHR. Overall, SUD programs were more likely to adopt an EHR system in 2017 compared to 2014 (AOR 1.44, 95% CI 1.07-1.94). CONCLUSIONS: Our findings highlighted that SUD programs may be on track to achieve widespread EHR adoption. However, there is a need for focused strategies, resources, and policies explicitly designed to systematically address barriers and tackle obstacles to expanding the adoption of EHR systems. These efforts must be holistic and address factors at multiple organizational levels.

Associations between maternal stressful life events experiences and risk of neural tube defects in offspring: a systematic review and meta-analysis.

OBJECTIVES: Multiple factors associated with neural tube defects (NTDs) risk have been identified, yet there is little evidence on the possible effects of maternal stressful life events. In this study, we aimed to investigate the association between stressful life events during the periconceptional period and risk of NTDs in offspring. METHODS: Relevant literature was searched in PubMed, Springer Link, ScienceDirect, and Cochrane Library up to July 2023. The pooled odds ratio (OR) and 95% confidence interval (CI) of NTDs risk with maternal stressful life events were estimated using a random effects model. Publication bias was assessed using Egger's regression asymmetry test and Begg's rank correlation test with Begg's funnel plot. RESULTS: Analysis results showed that mothers who experienced stressful life events during the periconceptional period were at greater risk of having NTDs offspring (OR: 1.37, 95% CI: 1.08-1.73) than those who did not. In subgroup analysis, the pooled OR was 1.37 (1.13-1.67) and 1.73 (0.36-8.32) for with and without adjusting for folic acid supplementation in each included study, while was 1.37 (1.13-1.67) and 1.64 (0.39-6.88) for exposure time of three months preconception until three months post conception and one year preconception until three months post conception, respectively. CONCLUSIONS: This study suggests that maternal stressful life events during the periconceptional period are significantly associated with higher NTDs risk in offspring. Tailored approaches for evaluating the risk and policy of NTDs among women of childbearing age should emphasize individual stressful experiences before and during early pregnancy.

Examining the Association between Coffee Intake and the Risk of Developing Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.

Irritable bowel syndrome (IBS) is a highly prevalent disorder of brain-gut interaction with a significant impact on quality of life. Coffee is a widely consumed beverage with numerous bioactive compounds that have potential effects on human health and disease states. Current studies on the effect of regular coffee consumption on the risk of developing IBS symptoms have yielded conflicting results. This systematic review and meta-analysis aimed to determine whether coffee intake is associated with developing IBS. A systematic literature search was performed in three electronic databases, namely PubMed, EMBASE, and The Cochrane Library, from inception until 31 March 2023. All original studies reporting associations between coffee intake and IBS were considered for inclusion. Odds ratios (ORs) were calculated for each study, and estimates were pooled, and where appropriate, 95% confidence intervals (95% CI) and p-values were calculated. Eight studies comprising 432,022 patients were included in the final meta-analysis. Using a fixed-effects model, coffee drinkers (any intake) had a reduced likelihood of developing IBS compared to controls, with a pooled OR of 0.84 (95% CI: 0.80 to 0.84). Sensitivity analysis confirmed the stability of the estimates. Future research should prioritise prospective cohort studies that are robust and closely track the development of incident IBS in previously healthy individuals.

Dietary risk factors in gastrointestinal cancers: A case-control study in North India.

Background: One-third of all cancer deaths are preventable by alterations in diet. Methods: A case control study was conducted in a Regional Cancer Center in North India to evaluate the relationship of diet with selected gastrointestinal cancers. A total of 171 cases, 151 hospital controls, and 167 healthy controls were interviewed using food frequency questionnaire. Data was analyzed using odds ratio with 95% confidence interval and Chi-square test. Results: Two to three times increased risk of GI cancers was observed with hot and salted tea. Alcohol [OR 2.30 (1.32-4)] and smoking [OR (2.77 (1.77-4.33)] emerged as risk factors in healthy controls among whom freshly prepared food had significant protective effect [OR 0.57 (0.37-0.88)]. Sweet tea showed protective effect in hospital and healthy controls (OR 0.33 and 0.26, respectively). NSAIDS was associated with significantly higher risk of GI cancers. Consumption of dietary fibers decreased risk, which was significant for wheat and pulses but insignificant for rice. Vegetables and fruits showed significant protective effect ranging from 20 to 80% while intake of non-vegetarian foods showed significantly higher odds among controls (OR 2.37-13.4). Odds of GI cancer cases having consumed chutneys and pickles were significantly higher in comparison to healthy controls while consumption of dairy products showed protection. Low and medium intake of mixed spices inclusive of curcumin showed protection (OR 0.13 and 0.39, respectively) while intake of red chillies was associated with 2-30 times significantly higher odds. Conclusions: We have been able to generate baseline evidence of association between diet and selected GI cancers to encourage prevention and further research.

Effects of Vitamin D on Migraine: A Meta-Analysis.

Objective: The aim of this study was to evaluate the difference in mean serum 25-hydroxy vitamin D level between migraineurs and nonmigraineurs, the association between hypovitaminosis D and migraine, and the effects of oral vitamin D supplementation on migraine-related symptoms as compared to placebo. Methods: Relevant databases were searched for observational studies and randomized-controlled trials (RCTs) which evaluated the difference in mean serum 25-hydroxy vitamin D level between migraineurs and nonmigraineurs; the association between hypovitaminosis D and migraine; and the effects of vitamin D supplementation on migraine-frequency, duration, and severity. Pooled mean difference and odds ratio were calculated (random-effects model, RevMan version 5.3). Results: Ten observational studies and two RCTs were included. The serum 25-hydroxy vitamin D level in the migraineurs was significantly lower than that in the nonmigraineurs [mean difference - 4.44 ng/mL (95% CI: -6.11, -2.77)] (low-GRADE evidence). Hypovitaminosis D was found to be significantly associated with migraine [OR: 1.95 (95% CI: 1.07, 3.58)] (low-GRADE evidence). As compared to placebo, oral vitamin D supplementation significantly reduced the monthly migraine-frequency [mean difference: -2.20 (95% CI: -3.04, -1.36)]. ,: although it did not reduce the migraine-duration [mean difference: -16.00 hours per month (95% CI: -42.77, 10.76)] and migraine-severity score [standardized mean difference: -0.23 (95% CI: -0.79, 0.32)] (moderate-GRADE evidence). Conclusion: Serum 25-hydroxy vitamin D level was significantly lower in the migraineurs than that in the nonmigraineurs, and hypovitaminosis D was significantly associated with migraine. Oral vitamin D supplementation significantly reduced migraine-frequency, but not its duration and severity.

MiRNAs as biomarkers for diagnosis of neonatal sepsis: a systematic review and meta-analysis.

BACKGROUND: The relationship between circulating miRNAs and neonatal sepsis and the mechanism of action are still unclear at this time. Therefore, the potential diagnostic role of miRNAs in neonatal sepsis (NS) was studied through meta-analysis. METHOD: Web of Science, Cochrane Library, PubMed, and Embase are retrieved, supplemented by manual search, and the search was conducted to find related studies without time limit until May 2022.The quality of the literature was assessed via QUADAS criteria and meta-analyzed via Stata 11.0 software, including the assessment of specificity, sensitivity, likelihood ratio and diagnostic odds ratio. Then, sensitivity analysis and heterogeneity testing were conducted, and finally, the summary receiver operating characteristics (SROC) curve was drawn. RESULT: This study included 14 articles, including 20 miRNAs and 1597 newborns(control group: 727 and case group: 870). Among them, one article was of low quality, three articles were of high quality, and the rest were of medium quality. According to the results of random effects model analysis, the pooled specificity and sensitivity of miRNA for the diagnosis of NS were 0.83 (95%CI: 0.79-0.87) and 0.76 (95%CI: 0.72-0.80), respectively. And negative likelihood ratio, positive likelihood ratio, and diagnostic odds ratio were 0.29 (95%CI: 0.24-0.34), 4.51 (95%CI: 3.52-5.78), and 15.81 (95%CI: 10.71-23.35), respectively. The area under the SROC curve was 0.86, and there was no evidence publication bias detected in the funnel plot. CONCLUSION: Circulating miRNAs may be very useful in the development of early diagnostic strategies for neonatal sepsis.

Herbal Supplement Use for Evidence-Based Indications in US Adults: An Analysis of National Survey Data.

Objective: Understanding the changes in consumer use of herbal products and what has influenced these changes is key in the promotion of evidence informed use. The last analysis of evidence informed herbal supplement use involved the 2002 National Health Interview Survey (NHIS) analysis. This study reproduces and expands upon that earlier analysis, with the most recent NHIS dataset to report herb use patterns. It also explores the guiding resources consulted by consumers in their decision to use. Methods: Secondary analysis of cross-sectional data from the NHIS identified the 10 herbal supplements with the most reported use in 2012. The reasons reported by the NHIS for taking herbal supplements were compared with the 2019 Natural Medicines Comprehensive Database (NMCD) to determine whether reasons cited in consumption were supported by evidence. Logistic regression models were fit according to NHIS sampling weights to examine the relationship between evidence-based use and user characteristics, guiding resources, and health care professional engagement surrounding use. Results: Of the 181 reported uses of herb supplements for a specific health condition, 62.5% were for reasons supported by evidence-based indications (EBIs). The odds of herb use consistent with evidence significantly increased for those reporting higher education status (odds ratio [OR] = 3.01, 95% confidence interval [CI] [1.70-5.34]). Herbal supplement use consistent with EBIs was more likely among those who disclosed their herb use to a health care professional (OR = 1.77, 95% CI [1.26-2.49]). Evidence-based herb use was also less frequently informed by Media sources (OR = 0.43, 95% CI [0.28-0.66]) compared with non-EBI use. Conclusion: Approximately 62% of the reasons cited for taking the most consumed herbs in 2012 were in alignment with 2019 EBIs. This increase may be due to improved awareness of health care professionals and/or an increase of evidence for traditional uses of herbal products. Future research should explore the role of each of these stakeholders in improving evidence-based herb use in the general population.

Impact of active placebo controls on estimated drug effects in randomised trials: a systematic review of trials with both active placebo and standard placebo.

BACKGROUND: An estimated 60% of pharmacological randomised trials use placebo control interventions to blind (i.e. mask) participants. However, standard placebos do not control for perceptible non-therapeutic effects (i.e. side effects) of the experimental drug, which may unblind participants. Trials rarely use active placebo controls, which contain pharmacological compounds designed to mimic the non-therapeutic experimental drug effects in order to reduce the risk of unblinding. A relevant improvement in the estimated effects of active placebo compared with standard placebo would imply that trials with standard placebo may overestimate experimental drug effects. OBJECTIVES: We aimed to estimate the difference in drug effects when an experimental drug is compared with an active placebo versus a standard placebo control intervention, and to explore causes for heterogeneity. In the context of a randomised trial, this difference in drug effects can be estimated by directly comparing the effect difference between the active placebo and standard placebo intervention. SEARCH METHODS: We searched PubMed, CENTRAL, Embase, two other databases, and two trial registries up to October 2020. We also searched reference lists and citations and contacted trial authors. SELECTION CRITERIA: We included randomised trials that compared an active placebo versus a standard placebo intervention. We considered trials both with and without a matching experimental drug arm. DATA COLLECTION AND ANALYSIS: We extracted data, assessed risk of bias, scored active placebos for adequacy and risk of unintended therapeutic effect, and categorised active placebos as unpleasant, neutral, or pleasant. We requested individual participant data from the authors of four cross-over trials published after 1990 and one unpublished trial registered after 1990. Our primary inverse-variance, random-effects meta-analysis used standardised mean differences (SMDs) of active versus standard placebo for participant-reported outcomes at earliest post-treatment assessment. A negative SMD favoured the active placebo. We stratified analyses by trial type (clinical or preclinical) and supplemented with sensitivity and subgroup analyses and meta-regression. In secondary analyses, we investigated observer-reported outcomes, harms, attrition, and co-intervention outcomes. MAIN RESULTS: We included 21 trials (1462 participants). We obtained individual participant data from four trials. Our primary analysis of participant-reported outcomes at earliest post-treatment assessment resulted in a pooled SMD of -0.08 (95% confidence interval (CI) -0.20 to 0.04; I2 = 31%; 14 trials), with no clear difference between clinical and preclinical trials. Individual participant data contributed 43% of the weight of this analysis. Two of seven sensitivity analyses found more pronounced and statistically significant differences; for example, in the five trials with low overall risk of bias, the pooled SMD was -0.24 (95% CI -0.34 to -0.13). The pooled SMD of observer-reported outcomes was similar to the primary analysis. The pooled odds ratio (OR) for harms was 3.08 (95% CI 1.56 to 6.07), and for attrition, 1.22 (95% CI 0.74 to 2.03). Co-intervention data were limited. Meta-regression found no statistically significant association with adequacy of the active placebo or risk of unintended therapeutic effect. AUTHORS' CONCLUSIONS: We did not find a statistically significant difference between active and standard placebo control interventions in our primary analysis, but the result was imprecise and the CI compatible with a difference ranging from important to irrelevant. Furthermore, the result was not robust, because two sensitivity analyses produced a more pronounced and statistically significant difference. We suggest that trialists and users of information from trials carefully consider the type of placebo control intervention in trials with high risk of unblinding, such as those with pronounced non-therapeutic effects and participant-reported outcomes.

Homeopathy can offer empirical insights on treatment effects in a null field.

OBJECTIVES: A "null field" is a scientific field where there is nothing to discover and where observed associations are thus expected to simply reflect the magnitude of bias. We aimed to characterize a null field using a known example, homeopathy (a pseudoscientific medical approach based on using highly diluted substances), as a prototype. STUDY DESIGN AND SETTING: We identified 50 randomized placebo-controlled trials of homeopathy interventions from highly cited meta-analyses. The primary outcome variable was the observed effect size in the studies. Variables related to study quality or impact were also extracted. RESULTS: The mean effect size for homeopathy was 0.36 standard deviations (Hedges' g; 95% confidence interval: 0.21, 0.51) better than placebo, which corresponds to an odds ratio of 1.94 (95% CI: 1.69, 2.23) in favor of homeopathy. 80% of studies had positive effect sizes (favoring homeopathy). Effect size was significantly correlated with citation counts from journals in the directory of open-access journals and CiteWatch. We identified common statistical errors in 25 studies. CONCLUSION: A null field like homeopathy can exhibit large effect sizes, high rates of favorable results, and high citation impact in the published scientific literature. Null fields may represent a useful negative control for the scientific process.

Engagement and outcomes of cancer patients referred to a tobacco cessation program at a National Cancer Institute-designated cancer center.

INTRODUCTION: Tobacco cessation is a critical but challenging intervention for cancer patients. Our National Cancer Institute-designated Comprehensive Cancer Center instituted a tobacco cessation program in 2019. This manuscript reports on the first 2 years of our experience. METHODS: Patients were referred to the program by their care team, and a certified tobacco treatment specialist contacted patients remotely and provided behavioral therapy and coordinated pharmacotherapy. We retrospectively captured data from patients with a cancer diagnosis referred to the tobacco cessation program. Univariate and multivariable logistic regression analyses with the backward elimination approach were performed to determine factors associated with patient acceptance of referral to the tobacco cessation program. Tobacco cessation rates after referral to the program were also captured. RESULTS: Between July 2019 and August 2021, 194 patients were referred to the tobacco cessation program. Of the 194 patients referred, 93 agreed to enroll in the tobacco cessation program (47.9%), of which 84 requested pharmacotherapy (90.3%). Twenty-four were able to cease tobacco use (25.8%). Only 7 patients out of the 101 patients (6.9%) who declined cessation services were successful (p < 0.001). On univariate logistic regression, race (p = 0.027) and marital status (p = 0.020) were associated with referral acceptance. On multivariable analysis, single patients (odds ratio [OR] = 0.33) and Caucasian patients (OR = 0.43) were less likely to accept a referral. CONCLUSIONS: Access to tobacco cessation services is a critical component of comprehensive cancer care. Our experience highlights the need to understand patient-specific factors associated with engagement with a tobacco cessation program during cancer treatment. The use of pharmacotherapy is also a critical component of successful tobacco cessation.

The uptake of key Essential Nutrition Action (ENA) messages and its predictors among mothers of children aged 6-24 months in Southern Ethiopia, 2021: A community-based crossectional study.

BACKGROUND: Essential nutrition action(ENA) is a framework for managing advocacy, establishing a foundation, and implementing a comprehensive package of preventive nutritional activities. Essential Nutrition Actions study studies provide current information on each nutrition action, allowing health systems to focus more on nutrition, which is critical in tackling the "double burden" of malnutrition: underweight and overweight. Hence, this study aimed at assessing the level of ENA practice and its predictors among mothers of children aged 6 to 24 months in southern Ethiopia. METHODS: A community-based cross-sectional study was conducted from May 1 to 30, 2021 among randomly selected 633 mothers of children aged 6-24 months. A multi-stage sampling technique was used to access study participants. Data were collected by using a pretested, structured interviewer-administered questionnaire. To identify predictors of ENA practice, bivariable and multivariable logistic regression were used. The strength of the association was measured using an adjusted odds ratio with 95 percent confidence intervals. The statistical significance was declared at a p-value less than 0.05. RESULTS: A total of 624 participants took part in the study, with a response rate of 98.6%. The uptake of key ENA messages among mothers was measured using 27 items, and it was found to be 47.4% (95% CI: 43.8, 51.4). Complementary feeding was the commonest ENA message practiced by 66.7% of respondents, while prevention of iodine deficiency disorder was practiced by only 33.7% of respondents. Variables namely, mother's education level of college and above [AOR: 3.90, 95% CI: 1.79, 8.51], institutional delivery [AOR: 2.75, 95% CI: 1.17,6.49], having PNC service [AOR: 2.95, 95% CI: 1.91, 4.57], being knowledgeable on ENA message [AOR: 2.37, 95% CI: 1.81, 3.26] and being a model household [AOR: 3.83,95% CI: 2.58, 5.69] were positively associated with a good uptake of key ENA messages. On the other hand, primiparity [AOR: 0.32, 95% CI: 0.21,0.56] was identified as a negative predictor. CONCLUSION: The overall practice of key Essential nutrition action messages in the study area was low as compared to studies. Stakeholders must step up their efforts to improve and hasten the utilization of maternal and child health services, especially institutional delivery and Postnatal care by focusing on uneducated women to promote compliance to key ENA messages. Furthermore, health workers need to focus on awareness-raising and model household creation.

Green Tea Consumption and Risk of Depression Symptoms: A Systematic Review and Meta-Analysis of Observational Studies.

This systematic review and meta-analysis aimed to investigate the association between green tea consumption and depression symptom risk, using subgroup analyses concerning study design, geographical region of study, adjustment factors, age, cut-off for the highest consumption category, and depression assessment methods applied. We used PubMed to search for relevant literature. The inclusion criteria were studies that (a) investigated this association as a primary or secondary outcome; (b) published in English; (c) assessed and reported hazard ratios or odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for depression symptoms, or included sufficient information to allow their calculation; (d) included at least two groups differentiated based on green tea consumption (e.g., high and low); (e) reported the prevalence of depression symptoms in each group; and (f) reported the sample size for each group. Eight articles were found to meet all criteria. The results indicated that high green tea consumption is inversely associated with depression symptoms. The pooled OR was 0.66 (95% CI 0.58-0.74), and significant heterogeneity was not observed. Subgroup analysis showed that study design impacted results (cohort study [one study]: OR=0.29, 95% CI=0.04-2.14; cross-sectional study [seven studies]: OR=0.66, 95% CI=0.59-0.75). These findings suggest that green tea consumption reduces the risk of depression symptoms. This association was also observed in the cohort study included, but the results in which did not reach the significant level. Therefore, further cohort studies are needed to confirm the potential causal relationship in this regard.

Adherence to lipid monitoring and its impact on treat intensification of LDL-C lowering therapies at an urban academic medical center.

BACKGROUND: Lipid monitoring is recommended by treatment guidelines to assess efficacy and adherence to lipid lowering therapy, but the available data is mostly limited to integrated health delivery systems with less diverse populations. OBJECTIVE: To determine the proportion of patients that completed appropriate lipid monitoring at an urban academic medical center and whether lipid monitoring is associated with treatment intensification. METHODS: Adults prescribed ≥1 LDL-C lowering therapy and with ≥1 outpatient encounter during 2018 and 2019 were included. Appropriate lipid monitoring was defined as ≥1 lipid panel obtained during the 12 month follow up period. Treatment intensification was defined as a dose increase, change to a higher intensity statin, or addition of a new LDL-C lowering therapy. The association between lipid monitoring and treatment intensification were assessed using regression models. RESULTS: Of the 12,332 patients on LDL-C lowering therapy, 88% had ≥1 lipid panel. The average patient was 60 years of age, 50% were female, and 50% identified as black or African American. On regression analysis (odds ratio [OR], 95% confidence interval [CI]), lipid monitoring occurred less frequently in adults >75 years of age (0.63, 0.44 to 0.90), black or African American individuals (0.78, 0.69 to 0.89), and those insured by Medicaid (0.72, 0.61 to 0.86). The odds of treatment intensification steadily increased with the number of lipid panels compared to those without lipid monitoring. CONCLUSION: Lipid monitoring is associated with treatment intensification but occurs less frequently in adults >75 years of age, black or African American individuals, and those insured by Medicaid.

Tea consumption and gastric cancer: a pooled analysis from the Stomach cancer Pooling (StoP) Project consortium.

BACKGROUND: Evidence from epidemiological studies on the role of tea drinking in gastric cancer risk remains inconsistent. We aimed to investigate and quantify the relationship between tea consumption and gastric cancer in the Stomach cancer Pooling (StoP) Project consortium. METHODS: A total of 9438 cases and 20,451 controls from 22 studies worldwide were included. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of gastric cancer for regular versus non-regular tea drinkers were estimated by one and two-stage modelling analyses, including terms for sex, age and the main recognised risk factors for gastric cancer. RESULTS: Compared to non-regular drinkers, the estimated adjusted pooled OR for regular tea drinkers was 0.91 (95% CI: 0.85-0.97). When the amount of tea consumed was considered, the OR for consumption of 1-2 cups/day was 1.01 (95% CI: 0.94-1.09) and for >3 cups/day was 0.91 (95% CI: 0.80-1.03). Stronger inverse associations emerged among regular drinkers in China and Japan (OR: 0.67, 95% CI: 0.49-0.91) where green tea is consumed, in subjects with H. pylori infection (OR: 0.68, 95% CI: 0.58-0.80), and for gastric cardia cancer (OR: 0.64, 95% CI: 0.49-0.84). CONCLUSION: Our results indicate a weak inverse association between tea consumption and gastric cancer.