Nevin Manimala

Heart. 2024 Apr 17:heartjnl-2023-323577. doi: 10.1136/heartjnl-2023-323577. Online ahead of print.

ABSTRACT

BACKGROUND: Loop diuretics are commonly prescribed in the community, not always to patients with a recorded diagnosis of heart failure (HF). The rate of HF events in patients prescribed loop diuretics without a diagnosis of HF is unknown.

METHODS: This was a propensity-matched cohort study using data from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office of National Statistics in the UK. Patients prescribed a loop diuretic without a diagnosis of HF (loop diuretic group) between 1 January 2010 and 31 December 2015 were compared with patients with HF (HF group)-analysis A, and patients with risk factors for HF (either ischaemic heart disease, or diabetes and hypertension-at-risk group)-analysis B. The primary endpoint was an HF event (a composite of presentation with HF symptoms, HF hospitalisation, HF diagnosis (analysis B only) and all-cause mortality).

RESULTS: From a total population of 180 384 patients (78 968 in the loop diuretic group, 28 177 in the HF group and 73 239 in the at-risk group), there were 59 694 patients, 22 352 patients and 57 219 patients in the loop diuretic, HF and at-risk groups, respectively, after exclusion criteria were applied. After propensity matching for age, sex and comorbidities, patients in the loop diuretic group had a similar rate of HF events as those in the HF group (71.9% vs 72.1%; HR=0.92 (95% CI 0.90 to 0.94); p<0.001), and twice as those in the at-risk group (59.2% vs 35.7%; HR=2.04 (95% CI 2.00 to 2.08); p<0.001).

CONCLUSIONS: Patients prescribed a loop diuretic without a recorded diagnosis of HF experience HF events at a rate comparable with that of patients with a recorded diagnosis of HF; many of these patients may have undiagnosed HF.

PMID:38631899 | DOI:10.1136/heartjnl-2023-323577

Alcohol Clin Exp Res (Hoboken). 2024 Apr 17. doi: 10.1111/acer.15331. Online ahead of print.

ABSTRACT

BACKGROUND: Adolescence is a sensitive stage of oral microbial development that often coincides with the initiation and escalation of alcohol use. Thus, adolescents may be particularly susceptible to alcohol-induced alterations in the oral microbiome, though minimal research has been done in this area. Understanding the connection between the oral microbiome and alcohol use during adolescence is important to understand fully the biological consequences of alcohol use to mitigate potential adverse outcomes.

METHODS: Saliva samples were collected from adolescents aged 17-19 who used alcohol heavily (n = 21, 52.4% female) and those who did not use alcohol or any other substances (n = 18, 44.4% female). We utilized 16S rRNA sequencing to examine differences in microbial diversity and composition between the groups.

RESULTS: For alpha diversity, evenness was significantly lower in the drinking group than the control group as indicated by Pielou’s evenness, Shannon, and Simpson indices. There were no statistically significant findings for beta diversity. Differential abundance analyses revealed higher abundances of Rothia and Corynebacterium in the alcohol-using group using both centered-log-ratio and relative abundance normalization. These genera are known for their high capacity to convert alcohol into acetaldehyde, a toxic metabolite reported to play a role in the neurobiological effects of alcohol. An unclassified Clostridia UCG-014, Streptobacillus, Comamonas, unclassified Lachnospiraceae, and Parvimonas were also identified as significantly different between groups when using only one of the normalization techniques.

CONCLUSIONS: This is the first study designed specifically to compare the oral microbiome of adolescents who use alcohol with that of control participants. Our findings reveal distinct alcohol-related differences in microbial composition and taxon abundance, emphasizing the importance of understanding the impact on the oral microbiome of alcohol use during adolescence. Because the oral microbiome is malleable, this study provides foundational work for future prevention and intervention studies.

PMID:38631877 | DOI:10.1111/acer.15331

Nihon Hoshasen Gijutsu Gakkai Zasshi. 2024 Apr 17. doi: 10.6009/jjrt.2024-1425. Online ahead of print.

ABSTRACT

In this study, we investigated the effects of various disinfectants used to prevent infectious diseases on medical images and medical equipment. First, we investigated the effect of residual disinfectant on medical images in CT, mammography (MMG), and general imaging systems. Acrylic discs with various disinfectants attached were photographed using each imaging device, and visual evaluation and changes in image signal values were evaluated. We also conducted a questionnaire survey of each manufacturer regarding cleaning methods for medical devices. With CT/MMG, residual disinfectant could be visually confirmed on the image. Although this could not be confirmed with the general imaging system, a significant difference was confirmed in the image signal values of the general imaging system through statistical analysis. This is thought to be largely due to the influence of nonlinearity in the short-time imaging range of general imaging equipment. In addition, from the responses to a questionnaire survey of each medical device manufacturer, we were able to understand detailed cleaning methods that are not covered in medical device instruction manuals.

PMID:38631870 | DOI:10.6009/jjrt.2024-1425

BMJ Open. 2024 Apr 17;14(4):e071266. doi: 10.1136/bmjopen-2022-071266.

ABSTRACT

INTRODUCTION: Fetal alcohol spectrum disorder (FASD) is a neurodevelopmental disorder caused by alcohol exposure during pregnancy. FASD is associated with neurodevelopmental deviations, and 50%-94% of children with FASD meet the Diagnostic and Statistical Manual of Mental Disorders-fifth edition diagnostic criteria for attention deficit hyperactivity disorder (ADHD). There is a paucity of evidence around medication efficacy for ADHD symptoms in children with FASD. This series of N-of-1 trials aims to provide pilot data on the feasibility of conducting N-of-1 trials in children with FASD and ADHD.

METHODS AND ANALYSIS: A pilot N-of-1 randomised trial design with 20 cycles of stimulant and placebo (four cycles of 2-week duration) for each child will be conducted (n=20) in Melbourne, Australia.Feasibility and tolerability will be assessed using recruitment and retention rates, protocol adherence, adverse events and parent ratings of side effects. Each child’s treatment effect will be determined by analysing teacher ADHD ratings across stimulant and placebo conditions (Wilcoxon rank). N-of-1 data will be aggregated to provide an estimate of the cohort treatment effect as well as individual-level treatment effects. We will assess the sample size and number of cycles required for a future trial. Potential mediating factors will be explored to identify variables that might be associated with treatment response variability.

ETHICS AND DISSEMINATION: The study was approved by the Hospital and Health Service Human Research Ethics Committee (HREC/74678/MonH-2021-269029), Monash (protocol V6, 25 June 2023).Individual outcome data will be summarised and provided to participating carers and practitioners to enhance care. Group-level findings will be presented at a local workshop to engage stakeholders. Findings will be presented at national and international conferences and published in peer-reviewed journals. All results will be reported so that they can be used to inform prior information for future trials.

TRIAL REGISTRATION NUMBER: NCT04968522.

PMID:38631835 | DOI:10.1136/bmjopen-2022-071266

Ann Clin Biochem. 2024 Apr 17:45632241252006. doi: 10.1177/00045632241252006. Online ahead of print.

ABSTRACT

BACKGROUND: Parametric regression analysis is widely used in methods comparisons and more recently in checking the concordance of test results following receipt of new reagent lots. The greater frequency of reagent-lot evaluations increases pressure to detect bias with smallest possible sample sizes (i.e. smallest consumption of time and resources). This study revisits bias detection using the joint slope, intercept confidence region as an alternative to slope and intercept confidence intervals.

METHODS: Four cases were considered representing constant errors, proportional errors (constant CV) and two more complicated error patterns typical of immunoassays. Maximum:minimum range ratios varied from 2:1 to 2000:1. After setting a maximum tolerable difference a series of slope, intercept combinations, each of which predicted the critical difference, were systematically evaluated in simulations which determined the minimum sample size required to detect the difference, firstly using slope, intercept confidence intervals and secondly using the joint slope, intercept confidence region.

RESULTS: At small to moderate range ratios, bias detection by joint confidence region required greatly reduced sample sizes to the extent that it should encourage reagent-lot evaluations or, alternatively, transform those already routinely performed into considerably less costly exercises.

CONCLUSIONS: While some software is available to calculate joint confidence regions in real-life analyses, shifting this testing method into the mainstream will require a greater number of software developers incorporating the necessary code into their regression programs. The computer program used to conduct this study is freely available and can be used to model any laboratory test.

PMID:38631810 | DOI:10.1177/00045632241252006

BMJ Open Gastroenterol. 2024 Apr 17;11(1):e001337. doi: 10.1136/bmjgast-2023-001337.

ABSTRACT

OBJECTIVE: Our objective was to perform a systemic evaluation of the risk of bias in randomised controlled trial (RCT) reports published on inflammatory bowel disease (IBD).

DESIGN: We assessed the risk of bias using the Cochrane tool, as indicators of poor methodology or subsequently poor reporting. We systematically selected, with dual independent judgements, all studies published on IBD with no time limits and assessed the methodological quality of included studies again using independent dual ratings.

RESULTS: 563 full texts were included after selection and review. No abstract publications were free of any source of bias. Full-text publications still fared badly, as only 103 full-text papers exhibited a low risk of bias in all reporting domains when excluding blinding. RCTs published in journals with higher impact factor (IF) were associated with an overall reduced rate of being at high risk. However, only 6% of full RCT publications in journals with an IF greater than 10, published in the past 5 years, were free of bias.The trend over time is towards improved reporting in all areas. Trials published by larger author teams, in full-text form and by industry and public sponsorship were positively correlated with a lower risk of bias. Only allocation concealment showed a statistically significant improvement with time (p=0.037).

CONCLUSION: These findings are consistent with those of other specialties in the literature. While this unclear risk of bias may represent poor reporting of methods instead of poor methodological quality, it leaves readers and future secondary researchers with significant questions regarding such key issues.

PMID:38631808 | DOI:10.1136/bmjgast-2023-001337

BMJ Glob Health. 2024 Apr 17;9(4):e013940. doi: 10.1136/bmjgh-2023-013940.

ABSTRACT

INTRODUCTION: Neonatal mortality is a global public health challenge. Guatemala has the fifth highest neonatal mortality rate in Latin America, and Indigenous communities are particularly impacted. This study aims to understand factors driving neonatal mortality rates among Maya Kaqchikel communities.

METHODS: We used sequential explanatory mixed methods. The quantitative phase was a secondary analysis of 2014-2016 data from the Global Maternal and Newborn Health Registry from Chimaltenango, Guatemala. Multivariate logistic regression models identified factors associated with perinatal and late neonatal mortality. A number of 33 in-depth interviews were conducted with mothers, traditional Maya midwives and local healthcare professionals to explain quantitative findings.

RESULTS: Of 33 759 observations, 351 were lost to follow-up. There were 32 559 live births, 670 stillbirths (20/1000 births), 1265 (38/1000 births) perinatal deaths and 409 (12/1000 live births) late neonatal deaths. Factors identified to have statistically significant associations with a higher risk of perinatal or late neonatal mortality include lack of maternal education, maternal height <140 cm, maternal age under 20 or above 35, attending less than four antenatal visits, delivering without a skilled attendant, delivering at a health facility, preterm birth, congenital anomalies and presence of other obstetrical complications. Qualitative participants linked severe mental and emotional distress and inadequate maternal nutrition to heightened neonatal vulnerability. They also highlighted that mistrust in the healthcare system-fueled by language barriers and healthcare workers’ use of coercive authority-delayed hospital presentations. They provided examples of cooperative relationships between traditional midwives and healthcare staff that resulted in positive outcomes.

CONCLUSION: Structural social forces influence neonatal vulnerability in rural Guatemala. When coupled with healthcare system shortcomings, these forces increase mistrust and mortality. Collaborative relationships among healthcare staff, traditional midwives and families may disrupt this cycle.

PMID:38631704 | DOI:10.1136/bmjgh-2023-013940

Pharm Stat. 2024 Apr 17. doi: 10.1002/pst.2373. Online ahead of print.

ABSTRACT

Accurate frequentist performance of a method is desirable in confirmatory clinical trials, but is not sufficient on its own to justify the use of a missing data method. Reference-based conditional mean imputation, with variance estimation justified solely by its frequentist performance, has the surprising and undesirable property that the estimated variance becomes smaller the greater the number of missing observations; as explained under jump-to-reference it effectively forces the true treatment effect to be exactly zero for patients with missing data.

PMID:38631678 | DOI:10.1002/pst.2373

Pharm Stat. 2024 Apr 17. doi: 10.1002/pst.2374. Online ahead of print.

NO ABSTRACT

PMID:38631676 | DOI:10.1002/pst.2374

Acta Psychiatr Scand. 2024 Apr 17. doi: 10.1111/acps.13690. Online ahead of print.

ABSTRACT

INTRODUCTION: Overweight and obesity constitute a major concern among patients treated at forensic psychiatric departments. The present clinical feasibility study aimed at investigating the extent to which glucagon-like peptide 1 receptor agonist (GLP-1RA) treatment with once-daily liraglutide 3.0 mg could be a feasible pharmacological treatment of these conditions in patients with schizophrenia spectrum disorders hospitalised in forensic psychiatry.

METHODS: The 26-week, open-label feasibility study included participants aged 18-65 years diagnosed with a severe mental illness and hospitalised at a forensic psychiatric department. At the time of inclusion, all participants fulfilled the indication for using liraglutide as a treatment for overweight and obesity. Participants’ baseline examinations were followed by a 26-week treatment period with liraglutide injection once daily according to a fixed uptitration schedule of liraglutide, with a target dose of 3.0 mg. Each participant attended seven visits to evaluate the efficacy and adverse events. The primary endpoint was the number of “completers”, with adherence defined as >80% injections obtained in the period, weeks 12-26. Determining whether liraglutide is a feasible treatment was pre-defined to a minimum of 75% completers.

RESULTS: Twenty-four participants were included in the study. Sex, male = 19 (79.2%). Mean age: 42.3 [25th and 75th percentiles: 39.1; 48.4] years; body mass index (BMI): 35.7 [31.7; 37.5] kg/m²; glycated haemoglobin (HbA1c): 37 [35; 39] mmol/mol. Eleven out of 24 participants (46%) completed the study. For the completers, the median net body weight loss after 26 weeks of participation was -11.4 kg [-15.4; -5.9]. The net difference in HbA1C and BMI was -2.0 mmol/mol [-4; -1] and -3.6 kg/m² [-4.7; -1.8], respectively. The weight change and reduction in HbA1c and BMI were all statistically significant from baseline.

CONCLUSION: The study did not confirm our hypothesis that liraglutide is a feasible treatment for a minimum of 75% of the patients initiating treatment with liraglutide while hospitalised in a forensic psychiatric department. The high dropout rate may be due to the non-naturalistic setting of the clinical trial. For the proportion of patients compliant with the medication, liraglutide 3.0 mg was an efficient treatment for overweight.

PMID:38631670 | DOI:10.1111/acps.13690