Tag: statistics

BMJ. 2021 Nov 2;375:e068060. doi: 10.1136/bmj-2021-068060.

ABSTRACT

OBJECTIVE: To determine if inhaled and intranasal ciclesonide are superior to placebo at decreasing respiratory symptoms in adult outpatients with covid-19.

DESIGN: Randomised, double blind, placebo controlled trial.

SETTING: Three Canadian provinces (Quebec, Ontario, and British Columbia).

PARTICIPANTS: 203 adults aged 18 years and older with polymerase chain reaction confirmed covid-19, presenting with fever, cough, or dyspnoea.

INTERVENTION: Participants were randomised to receive either inhaled ciclesonide (600 μg twice daily) and intranasal ciclesonide (200 μg daily) or metered dose inhaler and nasal saline placebos for 14 days.

MAIN OUTCOME MEASURES: The primary outcome was symptom resolution at day 7. Analyses were conducted on the modified intention-to-treat population (participants who took at least one dose of study drug and completed one follow-up survey) and adjusted for stratified randomisation by sex.

RESULTS: The modified intention-to-treat population included 203 participants: 105 were randomly assigned to ciclesonide (excluding two dropouts and one loss to follow-up) and 98 to placebo (excluding three dropouts and six losses to follow-up). The median age was 35 years (interquartile range 27-47 years) and 54% were women. The proportion of participants with resolution of symptoms by day 7 did not differ significantly between the intervention group (42/105, 40%) and control group (34/98, 35%); absolute adjusted risk difference 5.5% (95% confidence interval -7.8% to 18.8%). Results might be limited to the population studied, which mainly included younger adults without comorbidities. The trial was stopped early, therefore could have been underpowered.

CONCLUSION: Compared with placebo, the combination of inhaled and intranasal ciclesonide did not show a statistically significant increase in resolution of symptoms among healthier young adults with covid-19 presenting with prominent respiratory symptoms. As evidence is insufficient to determine the benefit of inhaled and intranasal corticosteroids in the treatment of covid-19, further research is needed.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04435795.

PMID:34728476 | DOI:10.1136/bmj-2021-068060

BMJ Glob Health. 2021 Nov;6(11):e006760. doi: 10.1136/bmjgh-2021-006760.

ABSTRACT

This paper describes the lessons from scaling up a verbal autopsy (VA) intervention to improve data about causes of death according to a nine-domain framework: governance, design, operations, human resources, financing, infrastructure, logistics, information technologies and data quality assurance. We use experiences from China, Myanmar, Papua New Guinea, Philippines and Solomon Islands to explore how VA has been successfully implemented in different contexts, to guide other countries in their VA implementation. The governance structure for VA implementation comprised a multidisciplinary team of technical experts, implementers and staff at different levels within ministries. A staged approach to VA implementation involved scoping and mapping of death registration processes, followed by pretest and pilot phases which allowed for redesign before a phased scale-up. Existing health workforce in countries were trained to conduct the VA interviews as part of their routine role. Costs included training and compensation for the VA interviewers, information technology (IT) infrastructure costs, advocacy and dissemination, which were borne by the funding agency in early stages of implementation. The complexity of the necessary infrastructure, logistics and IT support required for VA increased with scale-up. Quality assurance was built into the different phases of the implementation. VA as a source of cause of death data for community deaths will be needed for some time. With the right technical and political support, countries can scale up this intervention to ensure ongoing collection of quality and timely information on community deaths for use in health planning and better monitoring of national and global health goals.

PMID:34728477 | DOI:10.1136/bmjgh-2021-006760

BMJ Open Respir Res. 2021 Nov;8(1):e000974. doi: 10.1136/bmjresp-2021-000974.

ABSTRACT

BACKGROUND: Neural mechanisms may play an important role in non-eosinophilic asthma (NEA). This study compared airway sensory nerve reactivity, using capsaicin challenge, in eosinophilic asthma (EA) and NEA and non-asthmatics.

METHODS: Thirty-eight asthmatics and 19 non-asthmatics (aged 14-21 years) underwent combined hypertonic saline challenge/sputum induction, fractional exhaled nitric oxide, atopy and spirometry tests, followed by capsaicin challenge. EA and NEA were defined using a sputum eosinophil cut-point of 2.5%. Airway hyperreactivity was defined as a ≥15% drop in FEV₁ during saline challenge. Sensory nerve reactivity was defined as the lowest capsaicin concentration that evoked 5 (C5) coughs.

RESULTS: Non-eosinophilic asthmatics (n=20) had heightened capsaicin sensitivity (lower C5) compared with non-asthmatics (n=19) (geometric mean C5: 58.3 µM, 95% CI 24.1 to 141.5 vs 193.6 µM, 82.2 to 456.0; p<0.05). NEA tended to also have greater capsaicin sensitivity than EA, with the difference in capsaicin sensitivity between NEA and EA being of similar magnitude (58.3 µM, 24.1 to 141.5 vs 191.0 µM, 70.9 to 514.0) to that observed between NEA and non-asthmatics; however, this did not reach statistical significance (p=0.07). FEV₁ was significantly reduced from baseline following capsaicin inhalation in both asthmatics and non-asthmatics but no differences were found between subgroups. No associations with capsaicin sensitivity and atopy, sputum eosinophils, blood eosinophils, asthma control or treatment were observed.

CONCLUSION: NEA, but not EA, showed enhanced capsaicin sensitivity compared with non-asthmatics. Sensory nerve reactivity may therefore play an important role in the pathophysiology of NEA.

PMID:34728474 | DOI:10.1136/bmjresp-2021-000974

BMJ Open Respir Res. 2021 Nov;8(1):e001023. doi: 10.1136/bmjresp-2021-001023.

ABSTRACT

BACKGROUND: WHO defines hypoxaemia, a low peripheral arterial oxyhaemoglobin saturation (SpO₂), as <90%. Although hypoxaemia is an important risk factor for mortality of children with respiratory infections, the optimal SpO₂ threshold for defining hypoxaemia is uncertain in low-income and middle-income countries (LMICs). We derived a SpO₂ threshold for hypoxaemia from well children in Bangladesh residing at low altitude.

METHODS: We prospectively enrolled well, children aged 3-35 months participating in a pneumococcal vaccine evaluation in Sylhet district, Bangladesh between June and August 2017. Trained health workers conducting community surveillance measured the SpO₂ of children using a Masimo Rad-5 pulse oximeter with a wrap sensor. We used standard summary statistics to evaluate the SpO₂ distribution, including whether the distribution differed by age or sex. We considered the 2.5th, 5th and 10th percentiles of SpO₂ as possible lower thresholds for hypoxaemia.

RESULTS: Our primary analytical sample included 1470 children (mean age 18.6±9.5 months). Median SpO₂ was 98% (IQR 96%-99%), and the 2.5th, 5th and 10th percentile SpO₂ was 91%, 92% and 94%. No child had a SpO₂ <90%. Children 3-11 months had a lower median SpO₂ (97%) than 12-23 months (98%) and 24-35 months (98%) (p=0.039). The SpO₂ distribution did not differ by sex (p=0.959).

CONCLUSION: A SpO₂ threshold for hypoxaemia derived from the 2.5th, 5th or 10th percentile of well children is higher than <90%. If a higher threshold than <90% is adopted into LMIC care algorithms then decision-making using SpO₂ must also consider the child’s clinical status to minimise misclassification of well children as hypoxaemic. Younger children in lower altitude LMICs may require a different threshold for hypoxaemia than older children. Evaluating the mortality risk of sick children using higher SpO₂ thresholds for hypoxaemia is a key next step.

PMID:34728475 | DOI:10.1136/bmjresp-2021-001023

Cancer Epidemiol Biomarkers Prev. 2021 Nov 2:cebp.0503.2021. doi: 10.1158/1055-9965.EPI-21-0503. Online ahead of print.

ABSTRACT

BACKGROUND: Body mass index (BMI) change after a lung cancer diagnosis has been associated with non-small cell lung cancer (NSCLC) survival. This study aimed to quantify the association based on a large-scale observational study.

METHODS: Included in the study were 7,547 NSCLC patients with prospectively collected BMI data from Massachusetts General Hospital and Brigham and Women’s Hospital/Dana Faber Cancer Institute. Cox proportional hazards regression with time-dependent covariates was used to estimate effect of time varying post-diagnosis BMI change rate (% per month) on overall survival (OS), stratified by clinical subgroups. Spline analysis was conducted to quantify the non-linear association. A Mendelian Randomization (MR) analysis with a total of 3,495 patients further validated the association.

RESULTS: There was a J-shape association between post-diagnosis BMI change and OS among NSCLC patients. Specifically, a moderate BMI decrease (0.5-2.0; HR = 2.45, 95% CI = 2.25-2.67) and large BMI decrease ({>= 2.0; HR = 4.65, 95% CI = 4.15-5.20) were strongly associated with worse OS, whereas moderate weight gain (0.5-2.0) reduced the risk for mortality (HR = 0.78, 95% CI = 0.68-0.89) and large weight gain (>= 2.0) slightly increased the risk of mortality without reaching statistical significance (HR = 1.10, 95% CI = 0.86-1.42). MR analyses supported the potential causal roles of post-diagnosis BMI change in survival.

CONCLUSIONS: This study indicates that BMI change after diagnosis was associated with mortality risk.

IMPACT: Our findings, which reinforce the importance of post-diagnosis BMI surveillance, suggesting that weight loss or large weight gain maybe unwarranted.

PMID:34728470 | DOI:10.1158/1055-9965.EPI-21-0503

BMJ Open. 2021 Nov 2;11(11):e053309. doi: 10.1136/bmjopen-2021-053309.

ABSTRACT

INTRODUCTION: Abdominal surgery is associated with common complications, including decreased or poor appetite, abdominal distension, abdominal pain caused by decreased or absent gastrointestinal motility, anal arrest with flatus and defecation, and nausea and vomiting resulting from the use of anaesthetics and opioid analgesics. These complications seriously affect postoperative recovery, prolong hospital stay and aggravate patient burden. This study aims to investigate for the first time the efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with electroacupuncture (EA) therapy for rapid recovery after laparotomy for gastrointestinal surgery. There have been no clinical studies of this combination therapy.

METHODS AND ANALYSIS: This will be a prospective, single-centre, three-arm, randomised controlled trial. A total of 480 patients undergoing abdominal surgery will be stratified according to surgery type (ie, gastric or colorectal procedure) and randomised into three groups; namely, the EA, TEAS +EA and control groups. The control group will receive enhanced recovery after surgery (ERAS)-standardised perioperative management, including preoperative education, optimising the anaesthesia scheme, avoiding intraoperative hypothermia, restrictive fluid infusion and reducing surgical trauma. The EA group will receive EA stimulation at LI4, PC6, ST36, ST37 and ST39 based on the ERAS-standardised perioperative management. Moreover, the TEAS +EA group will receive ERAS-standardised perioperative management; EA stimulation at the LI4, PC6, ST36, ST37 and ST39; and TEAS stimulation at ST21 and SP15. The primary outcome will be the GI-2 (composite outcome of time to first defaecation and time to tolerance of a solid diet). Secondary outcomes will include the time of first passage of flatus, time to first defaecation, time to tolerance of a solid diet, time to first ambulation, hospital duration from operation to discharge, pain and nausea vomiting scores on the Visual Analogue Scale, medication use, incidence of postoperative complications and evaluation of treatment modality acceptability. All statistical analyses will be performed based on the intention-to-treat principle.

ETHICS AND DISSEMINATION: Ethics approval has been granted by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University (approval number: 2021; number 52). The results are expected to be published in peer-reviewed journals.

TRIAL REGISTRATION NUMBER: ChiCTR2100045646.

PMID:34728456 | DOI:10.1136/bmjopen-2021-053309

BMJ Open. 2021 Nov 2;11(11):e053412. doi: 10.1136/bmjopen-2021-053412.

ABSTRACT

BACKGROUND: HIV, diabetes and hypertension have a high disease burden in sub-Saharan Africa. Healthcare is organised in separate clinics, which may be inefficient. In a cohort study, we evaluated integrated management of these conditions from a single chronic care clinic.

OBJECTIVES: To determined the feasibility and acceptability of integrated management of chronic conditions in terms of retention in care and clinical indicators.

DESIGN AND SETTING: Prospective cohort study comprising patients attending 10 health facilities offering primary care in Dar es Salaam and Kampala.

INTERVENTION: Clinics within health facilities were set up to provide integrated care. Patients with either HIV, diabetes or hypertension had the same waiting areas, the same pharmacy, were seen by the same clinical staff, had similar provision of adherence counselling and tracking if they failed to attend appointments.

PRIMARY OUTCOME MEASURES: Retention in care, plasma viral load.

FINDINGS: Between 5 August 2018 and 21 May 2019, 2640 patients were screened of whom 2273 (86%) were enrolled into integrated care (832 with HIV infection, 313 with diabetes, 546 with hypertension and 582 with multiple conditions). They were followed up to 30 January 2020. Overall, 1615 (71.1%)/2273 were female and 1689 (74.5%)/2266 had been in care for 6 months or more. The proportions of people retained in care were 686/832 (82.5%, 95% CI: 79.9% to 85.1%) among those with HIV infection, 266/313 (85.0%, 95% CI: 81.1% to 89.0%) among those with diabetes, 430/546 (78.8%, 95% CI: 75.4% to 82.3%) among those with hypertension and 529/582 (90.9%, 95% CI: 88.6 to 93.3) among those with multimorbidity. Among those with HIV infection, the proportion with plasma viral load <100 copies/mL was 423(88.5%)/478.

CONCLUSION: Integrated management of chronic diseases is a feasible strategy for the control of HIV, diabetes and hypertension in Africa and needs evaluation in a comparative study.

PMID:34728457 | DOI:10.1136/bmjopen-2021-053412

BMJ Open. 2021 Nov 2;11(11):e052887. doi: 10.1136/bmjopen-2021-052887.

ABSTRACT

INTRODUCTION: Atrial fibrillation (AF) is a major cardiovascular health problem: it is common, chronic and incurs substantial healthcare expenditure because of stroke. Oral anticoagulation reduces the risk of thromboembolic stroke in those at higher risk; but for a number of patients, stroke is the first manifestation of undetected AF. There is a rationale for the early diagnosis of AF, before the first complication occurs, but population-based screening is not recommended. Previous prediction models have been limited by their data sources and methodologies. An accurate model that uses existing routinely collected data is needed to inform clinicians of patient-level risk of AF, inform national screening policy and highlight predictors that may be amenable to primary prevention.

METHODS AND ANALYSIS: We will investigate the application of a range of deep learning techniques, including an adapted convolutional neural network, recurrent neural network and Transformer, on routinely collected primary care data to create a personalised model predicting the risk of new-onset AF over a range of time periods. The Clinical Practice Research Datalink (CPRD)-GOLD dataset will be used for derivation, and the CPRD-AURUM dataset will be used for external geographical validation. Both comprise a sizeable representative population and are linked at patient-level to secondary care databases. The performance of the deep learning models will be compared against classic machine learning and traditional statistical predictive modelling methods. We will only use risk factors accessible in primary care and endow the model with the ability to update risk prediction as it is presented with new data, to make the model more useful in clinical practice.

ETHICS AND DISSEMINATION: Permissions for CPRD-GOLD and CPRD-AURUM datasets were obtained from CPRD (ref no: 19_076). The CPRD ethical approval committee approved the study. The results will be submitted as a research paper for publication to a peer-reviewed journal and presented at peer-reviewed conferences.

TRIAL REGISTRATION DETAILS: A systematic review to incorporate within the overall project was registered on PROSPERO (registration number CRD42021245093). The study was registered on ClinicalTrials.gov (NCT04657900).

PMID:34728455 | DOI:10.1136/bmjopen-2021-052887

BMJ Open. 2021 Nov 2;11(11):e052663. doi: 10.1136/bmjopen-2021-052663.

ABSTRACT

OBJECTIVES: This systematic review aimed to assess the performance and clinical feasibility of machine learning (ML) algorithms in prediction of in-hospital mortality for medical patients using vital signs at emergency departments (EDs).

DESIGN: A systematic review was performed.

SETTING: The databases including Medline (PubMed), Scopus and Embase (Ovid) were searched between 2010 and 2021, to extract published articles in English, describing ML-based models utilising vital sign variables to predict in-hospital mortality for patients admitted at EDs. Critical appraisal and data extraction for systematic reviews of prediction modelling studies checklist was used for study planning and data extraction. The risk of bias for included papers was assessed using the prediction risk of bias assessment tool.

PARTICIPANTS: Admitted patients to the ED.

MAIN OUTCOME MEASURE: In-hospital mortality.

RESULTS: Fifteen articles were included in the final review. We found that eight models including logistic regression, decision tree, K-nearest neighbours, support vector machine, gradient boosting, random forest, artificial neural networks and deep neural networks have been applied in this domain. Most studies failed to report essential main analysis steps such as data preprocessing and handling missing values. Fourteen included studies had a high risk of bias in the statistical analysis part, which could lead to poor performance in practice. Although the main aim of all studies was developing a predictive model for mortality, nine articles did not provide a time horizon for the prediction.

CONCLUSION: This review provided an updated overview of the state-of-the-art and revealed research gaps; based on these, we provide eight recommendations for future studies to make the use of ML more feasible in practice. By following these recommendations, we expect to see more robust ML models applied in the future to help clinicians identify patient deterioration earlier.

PMID:34728454 | DOI:10.1136/bmjopen-2021-052663

BMJ Open. 2021 Nov 2;11(11):e048241. doi: 10.1136/bmjopen-2020-048241.

ABSTRACT

OBJECTIVE: Amid the COVID-19 pandemic, social stigma towards COVID-19 infection has become a major component of public discourse and social phenomena. As such, we aimed to develop and validate the COVID-19 Public Stigma Scale (COVID-PSS).

DESIGN AND SETTING: National-based survey cross-sectional study during the lockdown in Thailand.

PARTICIPANTS: We invited the 4004 adult public to complete a set of measurement tools, including the COVID-PSS, global fear of COVID-19, perceived risk of COVID-19 infection, Bogardus Social Distance Scale, Pain Intensity Scale and Insomnia Severity Index.

METHODS: Factor structure dimensionality was constructed and reaffirmed with model fit by exploratory and confirmatory factor analyses and non-parametric item response theory (IRT) analysis. Psychometric properties for validity and reliability were tested. An anchor-based approach was performed for classifying the proper cut-off scores.

RESULTS: After factor analysis, IRT analysis and test for model fit, we created the final 10-item COVID-PSS with a three-factor structure: stereotype, prejudice and fear. Face and content validity were established through the public and experts’ perspectives. The COVID-PSS was significantly correlated (Spearman rank, 95% CI) with the global fear of COVID-19 (0.68, 95% CI 0.66 to 0.70), perceived risk of COVID-19 infection (0.79, 95% CI 0.77 to 0.80) and the Bogardus Social Distance Scale (0.50, 95% CI 0.48 to 0.53), indicating good convergent validity. The correlation statistics between the COVID-PSS and the Pain Intensity Scale and Insomnia Severity Index were <0.2, supporting the discriminant validity. The reliability of the COVID-PSS was satisfactory, with good internal consistency (Cronbach’s α of 0.85, 95% CI 0.84 to 0.86) and test-retest reproducibility (intraclass correlation of 0.94, 95% CI 0.86 to 0.96). The proposed cut-off scores were as follows: no/minimal (≤18), moderate (19-25) and high (≥26) public stigma towards COVID-19 infection.

CONCLUSIONS: The COVID-PSS is practical and suitable for measuring stigma towards COVID-19 in a public health survey. However, cross-cultural adaptation may be needed.

PMID:34728443 | DOI:10.1136/bmjopen-2020-048241