An empirical comparison of time-to-event models to analyse a composite outcome in the presence of death as a competing risk

CITATION:Haushona N, Esterhuizen TM, Thabane L, Machekano R. An empirical comparison of time-to-event models to analyse a composite outcome in the presence of death as a competing risk. Contemp Clin Trials Commun. 2020;19:100639. Published 2020 Aug 14. doi:10.1016/j.conctc.2020.100639Introduction: Competing risks arise when subjects are exposed to multiple mutually exclusive failure events, and the occurrence of one failure hinders the occurrence of other failure events. In the presence of competing risks, it is important to use methods accounting for competing events because failure to account for these events might result in misleading inferences. Methods and Objective: Using data from a multisite retrospective observational longitudinal study done in Ethiopia, we performed sensitivity analyses using Fine-Gray model, Cause-specific Cox (Cox-CSH) model, Cause-specific Accelerated Failure Time (CS-AFT) model, accounting for death as a competing risk to deter- mine baseline covariates that are associated with a composite of unfavourable retention in care outcomes in people living with Human Immune Virus who were on both Isoniazid preventive therapy (IPT) and antiretrovi- ral therapy (ART). Non-cause specific (non-CSH) model that does not account for competing risk was also per- formed. The composite outcome comprises of loss to follow-up, stopped treatment and death. Age, World Health Organisation (WHO) stage, gender, and CD4 count were the considered baseline covariates. Results: We included 3578 patients in our analysis. WHO stage III-or-IV was significantly associated with the composite of unfavourable outcomes, Sub-hazard ratio (SHR) = 1.31, 95% confidence interval (CI):1.04–1.65 for the sub-distribution hazard model, hazard ratio [HR] = 1.31, 95% CI:1.05–1.65, for the Cox-CSH model, and HR = 0.81, 95% CI:0.69–0.96, for the CS-AFT model. Gender and WHO stage were found to be signifi- cantly associated with the composite of unfavourable outcomes, HR = 1.56, 95% CI:1.27–1.90, HR = 1.28, 95% CI: 1.06–1.55 for males and WHO stage III-or-IV, respectively for the non-CSH model. Conclusions: Results show that WHO stage III-or-IV is significantly associated with unfavourable outcomes. The results from competing risk models were consistent. However, results obtained from the non-CSH model were inconsistent with those obtained from competing risk analysis models

The influence of second-hand cigarette smoke exposure during childhood and active cigarette smoking on crohn’s disease phenotype defined by the montreal classification scheme in a Western Cape population, South Africa

CITATION: Chivese, T., et al. 2015. The influence of second-hand cigarette smoke exposure during childhood and active cigarette smoking on crohn’s disease phenotype defined by the montreal classification scheme in a Western Cape population, South Africa. PLoS ONE, 10(9):1-12, doi:10.1371/journal.pone.0139597.The original publication is available at http://journals.plos.org/plosoneBackground: Smoking may worsen the disease outcomes in patients with Crohn’s disease (CD), however the effect of exposure to second-hand cigarette smoke during childhood is unclear. In South Africa, no such literature exists. The aim of this study was to investigate whether disease phenotype, at time of diagnosis of CD, was associated with exposure to second-hand cigarette during childhood and active cigarette smoking habits. Methods: A cross sectional examination of all consecutive CD patients seen during the period September 2011-January 2013 at 2 large inflammatory bowel disease centers in the Western Cape, South Africa was performed. Data were collected via review of patient case notes, interviewer-administered questionnaire and clinical examination by the attending gastroenterologist. Disease phenotype (behavior and location) was evaluated at time of diagnosis, according to the Montreal Classification scheme. In addition, disease behavior was stratified as ‘complicated’ or ‘uncomplicated’, using predefined definitions. Passive cigarette smoke exposure was evaluated during 3 age intervals: 0–5, 6–10, and 11–18 years. Results: One hundred and ninety four CD patients were identified. Cigarette smoking during the 6 months prior to, or at time of diagnosis was significantly associated with ileo-colonic (L3) disease (RRR = 3.63; 95%CI, 1.32–9.98, p = 0.012) and ileal (L1) disease (RRR = 3.54; 95%CI, 1.06–11.83, p = 0.040) compared with colonic disease. In smokers, childhood passive cigarette smoke exposure during the 0–5 years age interval was significantly associated with ileo-colonic CD location (RRR = 21.3; 95%CI, 1.16–391.55, p = 0.040). No significant association between smoking habits and disease behavior at diagnosis, whether defined by the Montreal scheme, or stratified as ‘complicated’ vs ‘uncomplicated’, was observed. Conclusion: Smoking habits were associated with ileo-colonic (L3) and ileal (L1) disease at time of diagnosis in a South African cohort.Publisher's versio

Patient satisfaction and treatment adherence of stable human immunodeficiency virus-positive patients in antiretroviral adherence clubs and clinics

Background: South Africa has experienced a substantial increase in access to antiretroviral treatment (ART) in recent years. Effective strategies to manage access to treatment need to be incorporated into and implemented in ART programmes. Antiretroviral treatment adherence clubs are a new strategy that is being implemented in various parts of South Africa. Aim: The aim of the study was to investigate treatment adherence and patient satisfaction of stable human immunodeficiency virus (HIV) patients on ART in ART adherence clubs and clinics. Setting: The study was conducted in the Eden district of the Western Cape, South Africa. Methods: A cross-sectional analytical study was conducted to examine the relationships between patient satisfaction and treatment adherence in ART adherence clubs and clinics in the Eden district, Western Cape province, South Africa. Validated questionnaires were used to measure patient satisfaction and self-reported treatment adherence. Results: The study included 320 participants (98 club and 222 clinic) from 13 primary health care clinics. The analyses showed that higher levels of satisfaction could be predicted with club participants compared to clinic participants (p = 0.05). There was no significant difference between clinic and club participants with regards to treatment adherence. However, being adherent was more likely in participants who were satisfied (odds ratio = 3.18, 95% confidence interval [1.14–7.11], p < 0.01). Conclusion: Antiretroviral treatment adherence clubs provide a service that patients are more satisfied with although they are not more adherent to treatment. This strategy may be effective for the delivery of long-term care for patients on ART

Nurse led home-based care for people with HIV/AIDS

Background Home-based care is used in many countries to increase quality of life and limit hospital stay, particularly where public health services are overburdened. Home-based care objectives for HIV/AIDS can include medical care, delivery of antiretroviral treatment and psychosocial support. This review assesses the effects of home-based nursing on morbidity in people infected with HIV/AIDS. Methods The trials studied are in HIV positive adults and children, regardless of sex or setting and all randomised controlled. Home-based care provided by qualified nurses was compared with hospital or health-facility based treatment. The following electronic databases were searched from January 1980 to March 2015: AIDSearch, CINAHL, Cochrane Register of Controlled Trials, EMBASE, MEDLINE and PsycINFO/LIT, with an updated search in November 2016. Two authors independently screened titles and abstracts from the electronic search based on the study design, interventions and types of participant. For all selected abstracts, full text articles were obtained. The final study selection was determined with use of an eligibility form. Data extraction was performed independently from assessment of risk of bias. The results were analysed by narrative synthesis, in order to be able to obtain relevant effect measures plus 95% confidence intervals. Results Seven studies met the inclusion criteria. The trial size varied from 37 to 238 participants. Only one trial was conducted in children. Five studies were conducted in the USA and two in China. Four studies looked at home-based adherence support and the rest at providing home-based psychosocial support. Reported adherence to antiretroviral drugs improved with nurse-led home-based care but did not affect viral load. Psychiatric nurse support in those with existing mental health conditions improved mental health and depressive symptoms. Home-based psychological support impacted on HIV stigma, worry and physical functioning and in certain cases depressive symptoms. Conclusions Nurse-led home-based interventions could help adherence to antiretroviral therapy and improve mental health. Further larger scale studies are needed, looking in more detail at improving medical care for HIV, especially related to screening and management of opportunistic infections and co-morbidities

Investigating the association between diabetes mellitus, depression and psychological distress in a cohort of South African teachers

Background. Diabetes mellitus (DM) may increase the risk of depression as a result of a sense of threat of debilitating complications or because of associated lifestyle changes. Depression may increase the risk of type 2 diabetes as a result of poor health behaviours.Objective. To determine the association between diabetes mellitus, depression and psychological distress in a cohort of South African (SA) teachers.Methods. Teachers from 111 public schools in the Metro South District of the Cape Metropolitan area, SA, were invited to participate in this study. The Center for Epidemiologic Studies Depression Scale (CES-D) and the Kessler Psychological Distress Scale (K10) were used to assess depression and psychological distress, respectively. A professional nurse completed a physical examination and collected blood for measurement of glucose, cholesterol and serum creatinine.Results. Of the 388 teachers who completed the questionnaires, 67.5% were female and the average age was 46.2 years (standard deviation 8.7). Psychological distress was identified in 28.1% of the cohort and depression in 15.5%, and 7.7% were found to fulfil criteria for DM. A diagnosis of DM was associated with an increased risk of depression (adjusted odds ratio (AOR) 3.90; 95% confidence interval (CI) 1.33 - 11.37) and psychological distress (AOR 3.62; 95% CI 1.31 - 10.00).Conclusion. The high prevalence of obesity and DM in this cohort of SA teachers is of concern. A diagnosis of DM was strongly associated with an increased risk of depression and psychological distress

High prevalence of cardiovascular risk factors in Durban South African Indians: The Phoenix Lifestyle Project

Background. Previous studies show a high prevalence of cardiovascular (CV) risk factors in South African (SA) Asian Indians, with the emergence of premature coronary artery disease in young Indian subjects.Objective. To determine the prevalence of CV risk factors in this population.Methods. This was a cross-sectional study of randomly selected adults aged 15 - 64 years from the suburb of Phoenix in Durban, KwaZulu-Natal Province, SA. All participants had demographic, anthropometric and biochemical measurements using the modified World Health Organization (WHO) STEPwise survey methods. Hypertension, obesity, lipid abnormalities and diabetes mellitus (DM) were diagnosed using WHO criteria. Age-standardised frequencies for glycaemic indices were calculated according to the WHO standard world population distribution. Results. Of the 1 428 subjects who responded (response rate 72.1%), complete data for analysis were available on 1 378 (1 001 women). The mean age was 45.5 (standard deviation 13) years. There were high prevalences of hypertension (47.5%), DM (20.1%), total body obesity (raised body mass index) (32.4%) and increased waist circumference (73.1%). The ‘thin-fat’ Asian phenotype (isolated abdominal obesity) was found in only 4.8% of participants. High prevalences of total body obesity (32.1%), increased waist circumference (31.3%) and insulin resistance (28.2%) were documented in the youngest age group. Over half of the males and 14.6% of females were current smokers. Diabetic dyslipidaemia was found in 61 subjects (4.4%). In multivariate analysis, age, triglycerides and waist circumference measurement were significant independent risk factors associated with DM and, together with fasting glucose, also predicted hypertension. Conclusion. Compared with Asian Indian subjects with similar environmental exposure in previous studies, the magnitude of change in risk factor prevalence over the past two decades has been of epidemic proportions.

Age at diagnosis as a prognostic factor in South African children with neuroblastoma

PURPOSE : Low- and middle-income countries (LMICs) reported a higher median age at diagnosis of neuroblastoma (NB) compared to high-income countries. The aim was to determine if the optimal age at diagnosis, which maximizes the difference in overall survival between younger versus older patients in the South African population was similar to the internationally validated 18 months age cut-point. METHODS : Four hundred sixty NB patients diagnosed between 2000 and 2016 were included. Receiver operating characteristic (ROC) curves were used to predict potential age cut-point values for overall survival in all risk group classifications. Risk ratios, sensitivity, specificity, and positive and negative predictive values at the specific cut-points were estimated with 95% confidence intervals, and time to mortality by age at the specific cut-points was shown with Kaplan-Meier curves and compared using log-rank tests. RESULTS : The median age at diagnosis for the total cohort was 31.9 months (range 0.2-204.7). For high-risk (HR), intermediate-risk, low-risk, and very low-risk patients, the median age at diagnosis was, respectively, 36 months (range 0.4-204.7), 16.8 months (range 0.7-145.1), 14.2 months (range 2.0-143.5), and 8.7 months (range 0.2-75.6). The ROC curves for the total NB cohort (area under the curve [AUC] 0.696; P < .001) and HR (AUC 0.682; P < .001) were analyzed further. The optimal cut-point value for the total cohort was at 19.1 months (sensitivity 59%; specificity 78%). The HR cohort had potential cut-point values identified at 18.4 months age at diagnosis (sensitivity 45%; specificity 87%) and 31.1 months (sensitivity 67%; specificity 62%). The 19.1 months cut-point value in the total cohort and the 18.4 months cut-point value in HR were as useful in predicting overall survival as 18 months age at diagnosis. CONCLUSION : The 18 months cut-point value appears to be the appropriate age for prognostic determination, despite the higher median age at diagnosis in South Africa.https://wileyonlinelibrary.com/journal/pbchj2022Paediatrics and Child Healt

Improving early childhood care and development, HIV testing, treatment and support, and nutrition in Mokhotlong, Lesotho: study protocol for a cluster randomized controlled trial

Background Since 1990, the lives of 48 million children under the age of 5 have been saved because of increased investments in reducing child mortality. However, despite these unprecedented gains, more than 200 million children in low and middle income countries (LMIC) cannot meet their developmental potential due to poverty, poor health and nutrition, and lack of necessary stimulation and care. Lesotho has high levels of poverty, HIV and malnutrition, all of which affect child development outcomes. There is a unique opportunity to address these complex issues through the widespread network of informal preschools in rural villages in the country, which provide a setting for inclusive, integrated Early Childhood Care and Development (ECCD), HIV and nutrition interventions. Methods We are conducting a cluster randomised controlled trial in Mokhotlong district, Lesotho, to evaluate a newly developed community-based intervention programme to integrate HIV testing and treatment services, ECCD, and nutrition education for caregivers with children aged 1-5 years living in rural villages. Caregivers and their children are randomly assigned by village to intervention or control condition. We select, train, and supervise community health workers recruited to implement the intervention, which consists of nine group-based sessions with caregivers and children over 12 weeks (eight weekly sessions, and a ninth top up session one month later), followed by a locally hosted community health outreach day event. Group-based sessions focus on using early dialogic booksharing to promote cognitive development and caregiver-child interaction, health-related messages, including motivation for HIV-testing and treatment uptake for young children, and locally appropriate nutrition education. All children aged 1-5 years and their primary caregivers living in study villages are eligible for participation. Caregivers and their children will be interviewed and assessed at baseline, immediately after completion of the intervention, and 12 months post intervention. Discussion This study provides a unique opportunity to assess the potential of an integrated early childhood development intervention to prevent or mitigate developmental delays in children living in a context of extreme poverty and high HIV rates in rural Lesotho. This paper presents the intervention content and research protocol for the study