The Role of early-life psychological factors in the development of chronic disease: a longitudinal analysis applied to the onset of cancer, diabetes, and asthma in mid-life.

Background: There is increasing evidence that psychological factors such as stress and depression might have an influence in the onset of many physical illnesses, but less is known about their effect from early life. This study is an epidemiological life-course analysis to test: (1) the hypotheses that early-life psychological factors are linked to later development of chronic disease (cancer, diabetes, and asthma) in mid-life, (2) whether such associations can be explained by pre-existing confounding factors, and (3) whether such links are mediated by other biological, behavioural, social, and cognitive factors. Methods: The data were from two ongoing prospective longitudinal studies following the lives of about 17,000 people born in Great Britain in one particular week in 1958 and 1970. Outcomes included diagnosis of cancer, asthma, and diabetes up to the year 2000. Psychological measures taken from ages 5 to 16 years were the main predictors. Associations were examined using discrete-time survival analysis and structural equation models, adjusting for potential confounders and mediators. Results: In the 1958 cohort, a standard deviation increase in the scores of conduct problems at ages 11 and 16 years, indicating severe behavioural problems, was associated with 2 to 34% increase in the odds of being diagnosed with cervical or all cancers after adjusting for childhood confounders. These effects were completely mediated by adulthood psychological distress and health behaviours. Only the teacher-reported behavioural problems significantly predicted the risk of diabetes after adjusting for family history of diabetes and sex (odds ratios of 1.05 to 1.08, p<O.Ol). These associations were partly mediated by mid-life psychological distress and adiposity. Significant associations were observed between most of the childhood psychological factors and adult-onset asthma even after adjusting for possible confounders and mediators. Conclusions: Childhood problem behaviours may predict chronic disease risk over the life-course either directly or mediated through adulthood factors. A consistent pathway among the disease groups was through adulthood psychological distress. Such continuities from childhood to adulthood psychological distress to the disease may be explained by the substantial biological plausibility of the association between psychological factors and physical health, primarily via alteration of the endocrine and the immune systems. The importance of promoting positive emotional and behavioural development in early life is stressed

The role of early-life psychological factors in the development of chronic disease : a longitudinal analysis applied to the onset of cancer, diabetes, and asthma in mid-life

Background: There is increasing evidence that psychological factors such as stress and depression might have an influence in the onset of many physical illnesses, but less is known about their effect from early life. This study is an epidemiological life-course analysis to test: (1) the hypotheses that early-life psychological factors are linked to later development of chronic disease (cancer, diabetes, and asthma) in mid-life, (2) whether such associations can be explained by pre-existing confounding factors, and (3) whether such links are mediated by other biological, behavioural, social, and cognitive factors. Methods: The data were from two ongoing prospective longitudinal studies following the lives of about 17,000 people born in Great Britain in one particular week in 1958 and 1970. Outcomes included diagnosis of cancer, asthma, and diabetes up to the year 2000. Psychological measures taken from ages 5 to 16 years were the main predictors. Associations were examined using discrete-time survival analysis and structural equation models, adjusting for potential confounders and mediators. Results: In the 1958 cohort, a standard deviation increase in the scores of conduct problems at ages 11 and 16 years, indicating severe behavioural problems, was associated with 2 to 34% increase in the odds of being diagnosed with cervical or all cancers after adjusting for childhood confounders. These effects were completely mediated by adulthood psychological distress and health behaviours. Only the teacher-reported behavioural problems significantly predicted the risk of diabetes after adjusting for family history of diabetes and sex (odds ratios of 1.05 to 1.08, p<O.Ol). These associations were partly mediated by mid-life psychological distress and adiposity. Significant associations were observed between most of the childhood psychological factors and adult-onset asthma even after adjusting for possible confounders and mediators. Conclusions: Childhood problem behaviours may predict chronic disease risk over the life-course either directly or mediated through adulthood factors. A consistent pathway among the disease groups was through adulthood psychological distress. Such continuities from childhood to adulthood psychological distress to the disease may be explained by the substantial biological plausibility of the association between psychological factors and physical health, primarily via alteration of the endocrine and the immune systems. The importance of promoting positive emotional and behavioural development in early life is stressed.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Significant pain variability in persons with, or at high risk of, knee osteoarthritis: preliminary investigation based on secondary analysis of cohort data

BACKGROUND: While knee osteoarthritis (OA) is characterised as a slowly progressive disease, acute flares, episodes of severe pain, and substantial fluctuations in pain intensity appear to be part of the natural history for some patients. We sought to estimate what proportion of symptomatic community-dwelling adults might be affected, and to identify patient and problem characteristics associated with higher risk of such variability in pain. METHODS: We analysed data collected at baseline, 18, 36, 54, and 72 month follow-up of a prospective cohort of symptomatic adults aged over 50 years with current/recent knee pain. At each time point we estimated the proportion of participants reporting 'significant pain variability' (defined as worst pain intensity in the past 6 months ≥5/10 and ≥2 points higher than average pain intensity during the same 6-month period). The associations between significant pain variability and demographic, socioeconomic, lifestyle, clinical, radiographic, and healthcare utilisation factors measured at baseline were estimated by adjusted odds ratios and 95% confidence intervals (aOR; 95%CI) from multivariable discrete-time survival analysis. RESULTS: Seven hundred and nineteen participants were included in the final analysis. At each time point, 23-32% of participants were classed as reporting significant pain variability. Associated factors included: younger age (aOR (per year): 0.96; 95% CI 0.94, 0.97), higher BMI (per kg/m(2):1.03; 1.01, 1.06), higher WOMAC Pain score (per unit: 1.06; 1.03, 1.10), longer time since onset (e.g. 1-5 years vs < 1 year: 1.79; 1.16, 2.75) and morning stiffness (≤30 min vs none: 1.43; 1.10, 1.85). The models accounting for multiple periods of significant symptom variability found similar associations. CONCLUSIONS: Our findings are consistent with studies showing that, for some patients OA symptoms are significantly variable over time. Future prospective studies on the nature and frequency of flare ups are needed to help determine triggers and their underlying pathophysiology in order to suggest new avenues for effective episode management of OA to complement long-term behaviour change

Human resource inequalities at the base of India\u27s public health care system

This paper examines the extent of inequalities in human resource provision at India\u27s Heath Sub-Centres (HSC)—first level of service provision in the public health system. ‘Within state’ inequality explained about 71% and ‘between state’ inequality explained the remaining 29% of the overall inter-HSC inequality. The Northern states had a lower health worker share relative to the extent of their HSC provision. Contextual factors that contributed to ‘between’ and ‘within’ district inequalities were the percentages of villages connected with all-weather roads and having primary schools. Analysis demonstrates a policy and programming need to address ‘within State’ inequalities as a priority

Clinical diagnostic model for sciatica developed in primary care patients with low back-related leg pain

Background Identification of sciatica may assist timely management but can be challenging in clinical practice. Diagnostic models to identify sciatica have mainly been developed in secondary care settings with conflicting reference standard selection. This study explores the challenges of reference standard selection and aims to ascertain which combination of clinical assessment items best identify sciatica in people seeking primary healthcare. Methods Data on 394 low back-related leg pain consulters were analysed. Potential sciatica indicators were seven clinical assessment items. Two reference standards were used: (i) high confidence sciatica clinical diagnosis; (ii) high confidence sciatica clinical diagnosis with confirmatory magnetic resonance imaging findings. Multivariable logistic regression models were produced for both reference standards. A tool predicting sciatica diagnosis in low back-related leg pain was derived. Latent class modelling explored the validity of the reference standard. Results Model (i) retained five items; model (ii) retained six items. Four items remained in both models: below knee pain, leg pain worse than back pain, positive neural tension tests and neurological deficit. Model (i) was well calibrated (p = 0.18), discrimination was area under the receiver operating characteristic curve (AUC) 0.95 (95% CI 0.93, 0.98). Model (ii) showed good discrimination (AUC 0.82; 0.78, 0.86) but poor calibration (p = 0.004). Bootstrapping revealed minimal overfitting in both models. Agreement between the two latent classes and clinical diagnosis groups defined by model (i) was substantial, and fair for model (ii). Conclusion Four clinical assessment items were common in both reference standard definitions of sciatica. A simple scoring tool for identifying sciatica was developed. These criteria could be used clinically and in research to improve accuracy of identification of this subgroup of back pain patients

Novel approach to characterising individuals with low back-related leg pain: cluster identification with latent class analysis and 12-month follow-up

Traditionally, low back-related leg pain (LBLP) is diagnosed clinically as referred leg pain or sciatica (nerve root involvement). However, within the spectrum of LBLP, we hypothesised that there may be other unrecognised patient subgroups. This study aimed to identify clusters of patients with LBLP using latent class analysis and describe their clinical course. The study population was 609 LBLP primary care consulters. Variables from clinical assessment were included in the latent class analysis. Characteristics of the statistically identified clusters were compared, and their clinical course over 1 year was described. A 5 cluster solution was optimal. Cluster 1 (n = 104) had mild leg pain severity and was considered to represent a referred leg pain group with no clinical signs, suggesting nerve root involvement (sciatica). Cluster 2 (n = 122), cluster 3 (n = 188), and cluster 4 (n = 69) had mild, moderate, and severe pain and disability, respectively, and response to clinical assessment items suggested categories of mild, moderate, and severe sciatica. Cluster 5 (n = 126) had high pain and disability, longer pain duration, and more comorbidities and was difficult to map to a clinical diagnosis. Most improvement for pain and disability was seen in the first 4 months for all clusters. At 12 months, the proportion of patients reporting recovery ranged from 27% for cluster 5 to 45% for cluster 2 (mild sciatica). This is the first study that empirically shows the variability in profile and clinical course of patients with LBLP including sciatica. More homogenous groups were identified, which could be considered in future clinical and research settings

Determining one-year trajectories of low back related leg pain in primary care patients: growth mixture modelling of a prospective cohort study

Objective The clinical presentation and outcome of patients with back and leg pain in primary care are heterogeneous and may be better understood by identification of homogeneous and clinically meaningful subgroups. Subgroups of patients with different back pain trajectories have been identified, but little is known about the trajectories for patients with back‐related leg pain. This study sought to identify distinct leg pain trajectories, and baseline characteristics associated with membership of each group, in primary care patients. Methods Monthly data on leg pain intensity were collected over 12 months for 609 patients participating in a prospective cohort study of adult patients seeking healthcare for low back and leg pain including sciatica, of any duration and severity, from their general practitioner. Growth mixture modelling was used to identify clusters of patients with distinct leg pain trajectories. Trajectories were characterised using baseline demographic and clinical examination data. Multinomial logistic regression was used to predict latent class‐membership with a range of covariates. Results Four clusters were identified: (1) improving mild pain (58%), (2) persistent moderate pain (26%), (3) persistent severe pain (13%), and (4) improving severe pain (3%). Clusters showed statistically significant differences with a number of baseline characteristics. Conclusion Four trajectories of leg pain were identified. Clusters 1, 2 and 3 were generally comparable to back pain trajectories, while cluster 4, with major improvement in pain, is infrequently identified. Awareness of such distinct patient groups improves understanding of the course of leg pain and may provide a basis of classification for intervention

A systematic review of randomisation method use in RCTs and association of trial design characteristics with method selection

Background: When conducting a randomised controlled trial, there exist many different methods to allocate participants, and a vast array of evidence-based opinions on which methods are the most effective at doing this, leading to differing use of these methods. There is also evidence that study characteristics affect the performance of these methods, but it is unknown whether the study design affects researchers’ decision when choosing a method. Methods: We conducted a review of papers published in five journals in 2019 to assess which randomisation methods are most commonly being used, as well as identifying which aspects of study design, if any, are associated with the choice of randomisation method. Randomisation methodology use was compared with a similar review conducted in 2014. Results: The most used randomisation method in this review is block stratification used in 162/330 trials. A combination of simple, randomisation, block randomisation, stratification and minimisation make up 318/330 trials, with only a small number of more novel methods being used, although this number has increased marginally since 2014. More complex methods such as stratification and minimisation seem to be used in larger multicentre studies. Conclusions: Within this review, most methods used can be classified using a combination of simple, block stratification and minimisation, suggesting that there is not much if any increase in the uptake of newer more novel methods. There seems to be a noticeable polarisation of method use, with an increase in the use of simple methods, but an increase in the complexity of more complex methods, with greater numbers of variables included in the analysis, and a greater number of strata

Promoting Independence in Dementia (PRIDE): A Feasibility Randomized Controlled Trial

Background: There is a need for interventions to foster and maintain independence for people with dementia to support community living, improve morale, and reduce stigma. We investigated a social intervention to promote living well and enhance independence for people with mild dementia.Methods: In this two arm parallel group, feasibility RCT at six sites in England, participants were randomized (1:1) to the PRIDE intervention (encompassing social, physical, and cognitive domains supported by a facilitator over three sessions) compared to usual care only. The main objective was to determine the feasibility of a main trial with respect to measures of recruitment, retention, and adherence to the intervention.Results: During a 7-month period, 402 people were invited to the trial, 148 were screened (37%, 95% confidence interval (CI)=32– 42%), 137 were eligible at pre-consent, 94 consented to the trial (69% of those eligible, 95% CI=60– 76%), and 92 were randomized (46 to each group). Of those allocated to the intervention, 42 (91%) received at least one of three intervention sessions. Outcome assessment follow-up visits were completed for 73 participants at 6 months (79%, 95% CI=70– 87%), and this was similar for both groups.Conclusion: A large multi-center trial of the PRIDE intervention in community-dwelling people with mild dementia is feasible using systematic recruitment strategies. The intervention was successfully delivered and well received by participants. Findings from this study will be used to refine the design and processes for a definitive RCT.Trial Registration: ISRCTN, ISRCTN11288961, registered on 23 October 2018