Justification and reporting of subgroup analyses were lacking or inadequate in randomized controlled trials

Objectives: The aim of the article was to assess the appropriateness and rationales of subgroup analyses planned in protocols of randomized controlled trials and reported in subsequent corresponding trial publications. Study Design and Setting: We searched PubMed to identify trial protocols published in journals during 2006–2017. From a total of 3,774 initially identified records, we included a random sample of 479 protocols and identified 280 trial publications corresponding to the included protocols. Results: Subgroup analyses were specified in 19% of the protocols and reported in 21% of the trial publications. Of the 94 protocols with planned subgroup analyses, 32% mentioned testing for interaction, and only three considered statistical power. Subgroup analyses were not prespecified in 56% of the 59 trial publications with subgroup analyses. Subgroup analyses were stated as prespecified in nine trial publications, without support evidence from the corresponding protocols. Subgroup analyses were often reported insufficiently for assessing the consistency of subgroup effects across studies. Justifications for subgroup analyses were provided in only four trial protocols and seven trial publications. Conclusion: Inappropriate specification and reporting of subgroup analyses remain problematic in protocols and reports of randomized controlled trials. Justifications or rationales for subgroup analyses were only rarely provided in trial protocols and reports

Vaccination against COVID-19 and societys return to normality in England: a modelling study of impacts of different types of naturally acquired and vaccine-induced immunity

Objectives:  To project impacts of mass vaccination against COVID-19, and investigate possible impacts of different types of naturally acquired and vaccine-induced immunity on future dynamics of SARS-CoV-2 transmission from 2021 to 2024 in England. Design:  Deterministic, compartmental, discrete-time Susceptible-Exposed-Infectious-Recovered (SEIR) modelling. Participants:  Population in England. Interventions:  Mass vaccination programmes. Outcome measures:  Daily and cumulative number of deaths from COVID-19. Results:  If vaccine efficacy remains high (85%), the vaccine-induced sterilising immunity lasts ≥182 days, and the reinfectivity is greatly reduced (by ≥60%), annual mass vaccination programmes can prevent further COVID-19 outbreaks in England. Under optimistic scenarios, with annual revaccination programmes, the cumulative number of COVID-19 deaths is estimated to be from 130 000 to 150 000 by the end of 2024. However, the total number of COVID-19 deaths may be up to 431 000 by the end of 2024, under scenarios with compromised vaccine efficacy (62.5%), short duration of natural and vaccine immunity (365/182 days) and small reduction in reinfectivity (30%). Under the assumed scenarios, more frequent revaccinations are associated with smaller total numbers and lower peaks of daily deaths from COVID-19. Conclusions:  Under optimistic scenarios, mass immunisation using efficacious vaccines may enable society safely to return to normality. However, under plausible scenarios with low vaccine efficacy and short durability of immunity, COVID-19 could continue to cause recurrent waves of severe morbidity and mortality despite frequent vaccinations. It is crucial to monitor the vaccination effects in the real world, and to better understand characteristics of naturally acquired and vaccine-induced immunity against SARS-CoV-2

Effect of age on the prognostic value of left ventricular function in patients with acute coronary syndrome:a prospective registry study

Objective: This study aims to study the prognostic impact of LV function on mortality and examine the effect of age on the prognostic value of left ventricular function.  Methods: We examined the Myocardial Ischaemia National Audit Project (MINAP) registry (2006-2010) data with a mean follow up of 2.1 years. LV function was categorized into good (ejection fraction (EF) ≥50%), moderate (EF 30-49%) and poor (EF <30%) categories. Cox-proportional hazards models were constructed to examine the prognostic significance of LV function in different age groups (<65, 65-74, 75-84 and ≥85 years) on all-cause mortality adjusting for baseline variables.  Results: Of 424,848 patients, LV function data available for 123,609. Multiple imputations were used to impute missing values of LV function and the final sample for analyses were drawn from 414,305. After controlling for confounders, 339,887 participants were included in the regression models. For any age group, mortality was higher with worsening degree of LV impairment. Increased age reduced the adverse prognosis associated with reduced LV function (hazard ratios (HRs) of death comparing poor LV function to good LV function were 2.11 95%CI 1.88-2.37 for age <65 years and 1.28 95%CI 1.20-1.36 for age ≥85 years. Older patients had a high mortality risk even in those with good LV function. HRs of mortality for ≥85 compared to <65 years (HR=1.00) within good, moderate and poor ejection fractions groups were 5.89, 4.86 and 3.43, respectively.  Conclusions: In patients with ACS, clinicians should interpret the prognostic value of LV function taking into account patient’s age

Geographical access to GPs and modes of cancer diagnosis in England: a cross-sectional study

Background: Poor geographical access to health services and routes to a cancer diagnosis such as emergency presentations have previously been associated with worse cancer outcomes. However, the extent to which access to GPs determines the route that patients take to obtain a cancer diagnosis is unknown. Methods: We used a linked dataset of cancer registry and hospital records of patients with a cancer diagnosis between 2006 and 2010 across eight different cancer sites. Primary outcomes were defined as 'desirable routes to diagnosis' [screen-detected and 2-week wait (TWW) referrals] and 'less desirable routes' [emergency presentations and death certificate only (DCO)]. All other routes (GP referral, inpatient elective and other outpatient) were specified as the reference category. Geographical access was measured as travel time in minutes from patients to their GP, and multinomial logistic regression was used to estimate relative risk ratios (RRR). Results: Longer travel was associated with increased risk of diagnosis via emergency and DCO, but decreased risk of diagnosis via screening and TWW. Patients travelling over 30 minutes had the highest risk of a DCO diagnosis, which was statistically significant for breast, colorectal, lung, prostate, stomach and ovarian cancers (compared with patients with travel times ≤10 minutes: RRR 5.89, 7.02, 2.30, 4.75, 10.41; P < 0.01 and 3.51, P < 0.05). Discussion: Poor access to GPs may discourage early engagement with health services, decreasing the likelihood of screening uptake and increasing the likelihood of emergency presentations. Extra effort is needed to promote early diagnosis in more distant patients

Factors associated with the consultation of general practitioners among adults aged 16 and over: analysis of data from 2019 Health Survey for England

Background - Understanding of factors associated with demands for general practice (GP) care is crucial for policy decision makers to appropriately allocate health care resources. Aim -To investigate factors associated with the frequency of GP consultations. Design and setting -Data on 8086 adults aged ≥16 years was obtained from cross-sectional Health Survey for England 2019. Methods -The primary outcome was the frequency of consultations of a GP in the last 12 months. Multivariable ordered logistic regression analysis was used to evaluate associations between GP consultations and a range of sociodemographic and health-related factors. Results –Frequency of GP consultations for all reasons was higher among females (odds ratio: 1.81, 95% confidence interval: 1.64-2.01), those aged 75 and over (1.48, 1.15-1.92), ethnic minority (Black 1.42, 1.09-1.84; Asian 1.53, 1.25-1.87), lowest household income (1.53, 1.29-1.83), adults with long-lasting illness (3.78, 3.38-4.22), former smokers (1.17, 1.04-1.22), overweight (1.14, 1.01-1.29) and obesity (1.32, 1.16-1.50). Predictors of consultations for physical health problems were similar to predictors of consultations for any health problems. However, younger age was associated with more consultations for mental health problems, or a combination of mental and physical health problems. Conclusions - The higher frequency of consultation of general practitioners is associated with female sex, older age, ethnic minority, socioeconomically disadvantaged, existence of lasting illnesses, smoking, overweight and obesity. Older age is associated with increased consultations for physical health problems, but associated with reduced consultations for mental health or a combination of mental and physical health problems. Key words: General practice, consultation frequency, sociodemographic factor

Socioeconomic position and depression in South African adults with long term health conditions: a longitudinal study of causal pathways

Aims. There is convincing evidence that lower socioeconomic position is associated with increased risk of mental disorders. However, the mechanisms involved are not well understood. This study aims to elucidate the causal pathways between socioeconomic position and depression symptoms in South African adults. Two possible causal theories are examined: social causation, which suggests that poor socioeconomic conditions cause mental ill health; and social drift, which suggests that those with poor mental health are more likely to drift into poor socioeconomic circumstances.Methods. The study used longitudinal and cross-sectional observational data on 3904 adults, from a randomised trial carried out in 38 primary health care clinics between 2011 and 2012. Structural equation models and counterfactual mediation analyses were used to examine causal pathways in two directions. First, we examined social causation pathways, with language (a proxy for racial or ethnic category) being treated as an exposure, while education, unemployment, income and depression were treated as sequential mediators and outcomes. Second, social drift was explored with depression treated as a potential influence on health-related quality of life, job loss and, finally, income.Results. The results suggest that the effects of language on depression at baseline, and on changes in depression during follow-up, were mediated through education and income but not through unemployment. Adverse effects of unemployment and job loss on depression appeared to be mostly mediated through income. The effect of depression on decreasing income appeared to be mediated by job loss.Conclusions. These results suggest that both social causation and social selection processes operate concurrently. This raises the possibility that people could get trapped in a vicious cycle in which poor socioeconomic conditions lead to depression, which, in turn, can cause further damage to their economic prospects. This study also suggests that modifiable factors such as income, employment and treatable depression are suitable targets for intervention in the short to medium term, while in the longer term reducing inequalities in education will be necessary to address the deeply entrenched inequalities in South Africa

Asbestos exposure and mesothelioma in South Africa

Objectives. To describe the exposure experiences of South African mesothelioma  cases, with emphasis on the contribution made to the caseload by different fibre  types, the proportion of subjects with no recall of asbestos exposure and only environmental contact, and the importance of putative causes other than asbestos.Design. A multicentred case-control study.Subjects and setting. 123 patients with mesothelioma interviewed by trained  interviewers in study centres established in  Johannesburg, Kimberley, Pretoria, Bloemfontein, Cape Town and Port Elizabeth.Results. A convincing history of asbestos exposure was obtained in the overwhelming majority of cases (only 5 cases had unlikely asbestos exposure). Twenty-three subjects had worked on Cape crocidolite mines, 3 at Penge (an amosite mine), 3 on mines  producing amosite and Transvaal crocidolite and 1 on a Transvaal crocidolite mine. Exclusively environmental exposure  accounted for at least 18% of cases; 91% of these cases (20/'22 subjects) had had contact with Cape crocidolite. There was a relative paucity of cases linked to amosite and no convincing chrysotile case. Non-asbestos causes occur rarely, if at all; in South  Africa.Conclusion. The preponderance of crocidolite cases, followed by amosite and then chrysotile cases, is consistent with the view that there is a fibre gradient of mesotheliomagenic potential for South African asbestos (crocidolite &gt; amosite &gt;chrysotile)

Self-reported quality of care for older adults from 2004 to 2011: a cohort study

Background: little is known about changes in the quality of medical care for older adults over time. Objective: to assess changes in technical quality of care over 6 years, and associations with participants' characteristics. Design: a national cohort survey covering RAND Corporation-derived quality indicators (QIs) in face-to-face structured interviews in participants' households. Participants: a total of 5,114 people aged 50 or more in four waves of the English Longitudinal Study of Ageing. Methods: the percentage achievement of 24 QIs in 10 general medical and geriatric clinical conditions was calculated for each time point, and associations with participants' characteristics were estimated using logistic regression. Results: participants were eligible for 21,220 QIs. QI achievement for geriatric conditions (cataract, falls, osteoarthritis and osteoporosis) was 41% [95% confidence interval (CI): 38–44] in 2004–05 and 38% (36–39) in 2010–11. Achievement for general medical conditions (depression, diabetes mellitus, hypertension, ischaemic heart disease, pain and cerebrovascular disease) improved from 75% (73–77) in 2004–05 to 80% (79–82) in 2010–11. Achievement ranged from 89% for cerebrovascular disease to 34% for osteoarthritis. Overall achievement was lower for participants who were men, wealthier, infrequent alcohol drinkers, not obese and living alone. Conclusion: substantial system-level shortfalls in quality of care for geriatric conditions persisted over 6 years, with relatively small and inconsistent variations in quality by participants' characteristics. The relative lack of variation by participants' characteristics suggests that quality improvement interventions may be more effective when directed at healthcare delivery systems rather than individuals

Addressing the quality and scope of paediatric primary care in South Africa: Evaluating contextual impacts of the introduction of the Practical Approach to Care Kit for children (PACK Child)

Background: Despite significant reductions in mortality, preventable and treatable conditions remain leading causes of death and illness in children in South Africa. The PACK Child intervention, comprising clinical decision support tool (guide), training strategy and health systems strengthening components, was developed to expand on WHO’s Integrated Management of Childhood Illness programme, extending care of children under 5 years to those aged 0-13 years, those with chronic conditions needing regular follow-up, integration of curative and preventive measures and routine care of the well child. In 2017-2018, PACK Child was piloted in 10 primary healthcare facilities in the Western Cape Province. Here we report findings from an investigation into the contextual features of South African primary care that shaped how clinicians delivered the PACK Child intervention within clinical consultations. Methods: Process evaluation using linguistic ethnographic methodology which provides analytical tools for investigating human behaviour, and the shifting meaning of talk and text within context. Methods included semi-structured interviews, focus groups, ethnographic observation, audio-recorded consultations and documentary analysis. Analysis focused on how mapped contextual features structured clinician-caregiver interactions. Results: Primary healthcare facilities demonstrated an institutionalised orientation to minimising risk upheld by provincial documentation, providing curative episodic care to children presenting with acute symptoms, and preventive care including immunisations, feeding and growth monitoring, all in children 5 years or younger. Children with chronic illnesses such as asthma rarely receive routine care. These contextual features constrained the ability of clinicians to use the PACK Child guide to facilitate diagnosis of long-term conditions, elicit and manage psychosocial issues, and navigate use of the guide alongside provincial documentation. Conclusion: Our findings provide evidence that PACK Child is catalysing a transition to an approach that strikes a balance between assessing and minimising risk on the day of acute presentation and a larger remit of care for children over time. However, optimising success of the intervention requires reviewing priorities for paediatric care which will facilitate enhanced skills, knowledge and deployment of clinical staff to better address acute illnesses and long-term health conditions of children of all ages, as well as complex psychosocial issues surrounding the child

Comorbidities between tuberculosis and common mental disorders: A scoping review of epidemiological patterns and person-centred care interventions from low-to-middle income and BRICS countries

Background : There is increasing evidence that the substantial global burden of disease for tuberculosis unfolds in concert with dimensions of common mental disorders. Person-centred care holds much promise to ameliorate these comorbidities in low-tomiddle income countries and emerging economies. Towards this end, this paper aimed to review 1) the nature and extent of tuberculosis and common mental disorder comorbidity and 2) person-centred tuberculosis care in low-to-middle income countries and emerging economies. Main text : A scoping review was conducted of English-language studies published from 2000-2019 in peer-reviewed and grey literature, using established guidelines, for each of the study objectives. Four broad tuberculosis/mental disorder comorbidities were described in the literature, namely alcohol use and tuberculosis, depression and tuberculosis, anxiety and tuberculosis, and general mental health and tuberculosis. Rates of comorbidity varied widely across countries for depression, anxiety, alcohol use and general mental health. Alcohol use and tuberculosis were significantly related, especially in the context of poverty. The initial tuberculosis diagnostic episode had substantial socio-psychological effects on service users. While men tended to report higher rates of alcohol use and treatment default, women in general had worse mental health outcomes. Older age and a history of mental illness were also associated with pronounced tuberculosis and mental disorder comorbidity. Person-centred tuberculosis care interventions were almost absent, with only one study from Nepal identified. Conclusions : There is an emerging body of evidence describing the nature and extent of tuberculosis and mental disorders comorbidity in low-to-middle income countries. Despite the potential of person-centred interventions, evidence is limited. This review highlights a pronounced need to address psychosocial comorbidities with TB in LMICs, where models of person-centred TB care in routine care platforms may yield promising outcomes