Intramuscular Immunisation with Chlamydial Proteins Induces Chlamydia trachomatis Specific Ocular Antibodies.

BACKGROUND: Ocular infection with Chlamydia trachomatis can cause trachoma, which is the leading cause of blindness due to infection worldwide. Despite the large-scale implementation of trachoma control programmes in the majority of countries where trachoma is endemic, there remains a need for a vaccine. Since C. trachomatis infects the conjunctival epithelium and stimulates an immune response in the associated lymphoid tissue, vaccine regimens that enhance local antibody responses could be advantageous. In experimental infections of non-human primates (NHPs), antibody specificity to C. trachomatis antigens was found to change over the course of ocular infection. The appearance of major outer membrane protein (MOMP) specific antibodies correlated with a reduction in ocular chlamydial burden, while subsequent generation of antibodies specific for PmpD and Pgp3 correlated with C. trachomatis eradication. METHODS: We used a range of heterologous prime-boost vaccinations with DNA, Adenovirus, modified vaccinia Ankara (MVA) and protein vaccines based on the major outer membrane protein (MOMP) as an antigen, and investigated the effect of vaccine route, antigen and regimen on the induction of anti-chlamydial antibodies detectable in the ocular lavage fluid of mice. RESULTS: Three intramuscular vaccinations with recombinant protein adjuvanted with MF59 induced significantly greater levels of anti-MOMP ocular antibodies than the other regimens tested. Intranasal delivery of vaccines induced less IgG antibody in the eye than intramuscular delivery. The inclusion of the antigens PmpD and Pgp3, singly or in combination, induced ocular antigen-specific IgG antibodies, although the anti-PmpD antibody response was consistently lower and attenuated by combination with other antigens. CONCLUSIONS: If translatable to NHPs and/or humans, this investigation of the murine C. trachomatis specific ocular antibody response following vaccination provides a potential mouse model for the rapid and high throughput evaluation of future trachoma vaccines

Evidence for strategies that improve recruitment and retention of adults aged 65 years and over in randomised trials and observational studies: a systematic review

Background: adults aged ≥65 years are often excluded from health research studies. Lack of representation reduces generalisability of treatments for this age group. Objective: to evaluate the effectiveness of strategies that improve recruitment and retention of adults aged ≥65 in observational studies and randomised controlled trials (RCTs). Methods: searches conducted in 10 databases for RCTs of recruitment and retention strategies in RCTs or observational studies. Two reviewers screened abstracts and full-text articles for eligibility and extracted data. Studies without separate data for adults aged ≥65 were discarded. Risk of bias assessed using the Cochrane Risk of Bias tool. Results were synthesised narratively. Results: thirty-two studies were included in the review (n = 75,444). Twelve studies had low risk of bias, of which 10 had successful strategies including: Opt-out versus opt-in increased recruitment (13.6% (n = 261)-18.7% (n = 36) difference; two studies); Advance notification increased retention (1.6% difference, OR 1.45; 95% CI 1.01, 2.10, one study (n = 2,686); 9.1% difference at 4 months, 1.44; 1.08, 1.92, one study (n = 753)); Hand-delivered versus postal surveys increased response (25.1% difference; X2 = 11.40, P < 0.01; one study (n = 139)); Open randomised design versus blinded RCT increased recruitment (1.56; 1.05, 2.33) and retention (13.9% difference; 3.1%, 24.6%) in one study (n = 538). Risk of bias was high/unclear for studies in which incentives or shorter length questionnaires increased response. Discussion: in low risk of bias studies, few of the strategies that improved participation in older adults had been tested in ≥1 study. Opt-out and advance notification strategies improved recruitment and retention, respectively, although an opt-out approach may have ethical limitations. Evidence from single studies limits the generalisability of other strategies

Validity of two simple measures for estimating life-course socio-economic position in cross-sectional postal survey data in an older population: results from the North Staffordshire Osteoarthritis Project (NorStOP)

BACKGROUND: Since few cohorts encompass the whole life-course, many studies that measure socio-economic position (SEP) across the life-course rely on participant recall of SEP measures from cross-sectional postal or interview surveys. It is also particularly important that SEP measures should be appropriate for the age of the population studied, as the level of missing data has been shown to increase in older people. The aim of this study was to investigate the accuracy of recall of two SEP measures in older adults, age left school and longest job, by examining their validity in a general population postal survey in North Staffordshire, UK. METHODS: Sets of questions on education and longest job were included in a questionnaire at different stages of the study. All patients aged 50+ registered with three general practices were sent a baseline Health Questionnaire. 6 years later, 3410 responders were mailed a follow-up Health Questionnaire; a sub-sample of these participants took part in independent qualitative interviews. Validity was assessed by: percentage completion; internal percentage agreement within each set of questions; percentage agreement of qualitative and quantitative data for age left school and longest job; comparing recall of age left school with historical change in legal school leaving age; comparing frequency of pottery job titles with those in 1981 Census data for Stoke-on-Trent. RESULTS: The adjusted response to different stages of the study was 71-85%. Completion of questions was 83-98%. Internal agreement was 84-97% (education) and 95-100% (longest job). Comparison of survey and interview data showed 86% agreement (± 1 year) for age left school and 91% agreement for longest job. The change in age left school data concurred with the historical shift in legal school leaving age. 11% of job titles were pottery in NorStOP data and 15% in Stoke-on-Trent Census data. CONCLUSIONS: The results from this study provide evidence for the accuracy of recall of two simple measures of SEP (age left school and longest job) in a postal survey of older adults. Consistency with evidence from external datasets indicated the potential validity of these measures for studying life-course SEP in population surveys

Commentary on a paper by Holden et al.

No abstrac

Does attrition during follow-up of a population cohort study inevitably lead to biased estimates of health status?

Attrition is a potential source of bias in cohort studies. Although attrition may be inevitable in cohort studies of older people, there is little empirical evidence as to whether bias due to such attrition is also inevitable. Anonymised primary care data, routinely collected in clinical practice and independent of any cohort research study, represents an ideal unselected comparison dataset with which to compare primary care data from consenting responders to a cohort study. Our objective was to use this method as a novel means to assess if (i) responders at follow-up stages in a cohort study remain representative of responders at baseline and (ii) attrition biases estimates of longitudinal associations. We compared primary care consultation morbidities and prescription prevalences among circa 32,000 patients aged 50+ who contribute to an anonymised general practice database (Consultations in Primary Care Archive (CiPCA)) with those from patients aged 50+ in the North Staffordshire Osteoarthritis Project (NorStOP) cohort, United Kingdom (2002-2008; n=16,159). 8,197 (51%) persons responded to the NorStOP baseline survey and consented to medical record review. 5,121 and 3,311 responded at 3- and 6-year follow-ups. Differences in consulting prevalence of non-musculoskeletal morbidities between NorStOP responders and CiPCA comparison population did not increase over the two follow-up points except for ischaemic heart disease. Differences observed at baseline for osteoarthritis-related consultations were generally unchanged at the two follow-ups (standardised prevalence ratios for osteoarthritis (1.09-1.13) and joint pain (1.12-1.23)). Age and gender adjusted associations between baseline consultation for chronic morbidity and future new osteoarthritis and related consultations were similar in CiPCA (adjusted Hazard Ratio: 1.40; 95% Confidence Interval: 1.34,1.47) and NorStOP 6-year responders (1.32; 1.15,1.51). There was little evidence that responders at follow-ups represented any further selection bias to that present at baseline. Attrition in cohort studies of older people does not inevitably indicate bias

Widespread pain and depression are key modifiable risk factors associated with reduced social participation in older adults: A prospective cohort study in primary care.

In older adults, reduced social participation increases the risk of poor health-related quality of life, increased levels of inflammatory markers and cardiovascular disease, and increased mortality. Older adults frequently present to primary care, which offers the potential to deliver interventions at the point of care to increase social participation. The aim of this prospective study was to identify the key modifiable exposures that were associated with reduced social participation in a primary care population of older adults.The study was a population-based prospective cohort study. Participants (n = 1991) were those aged ≥65 years who had completed questionnaires at baseline, and 3 and 6-year follow-ups. Generalized linear mixed modeling framework was used to test for associations between exposures and decreasing social participation over 6 years.At baseline, 44% of participants reported reduced social participation, increasing to 49% and 55% at 3 and 6-year follow-up. Widespread pain and depression had the strongest independent association with reduced social participation over the 6-year follow-up period. The prevalence of reduced social participation for those with widespread pain was 106% (adjusted incidence rate ratio 2.06, 95% confidence interval 1.72, 2.46), higher than for those with no pain. Those with depression had an increased prevalence of 82% (adjusted incidence rate ratio 1.82, 95% confidence interval 1.62, 2.06). These associations persisted in multivariate analysis.Population ageing will be accompanied by increasing numbers of older adults with pain and depression. Future trials should assess whether screening for widespread pain and depression, and targeting appropriate treatment in primary care, increase social participation in older people

The impact of inadequate health literacy in a musculoskeletal pain population

Musculoskeletal conditions are a major cause of ill-health and disability. Inadequate health literacy may partly explain why musculoskeletal self-management programmes are not effective for some patients. This study prospectively evaluates the impact of patients’ health literacy level on their musculoskeletal pain and physical function (PF) following usual primary care. 4720 primary care patients who had consulted for musculoskeletal pain were mailed a baseline questionnaire; responders were sent a 6-month follow-up. Outcome measures: PF and pain intensity at 6-months. Health literacy: Single-item Literacy Screener at baseline. Analysis was by linear regression. 1890 patients responded (40%). 17.3% (95%CI 15.6%-19.0%) of patients had inadequate health literacy. Inadequate health literacy was associated with older age (p<0.05), lower education, mental health and co-morbidities (all p<0.001), but not gender (p=0.642). At 6-month follow-up, patients with inadequate health literacy had lower PF (mean difference -12.2; -16.7,-7.6) and higher pain intensity (1.0; 0.6,1.4), adjusted for age, gender, education, mental health and co-morbidities, than patients with adequate health literacy. Differences in PF and particularly pain scores between patients with inadequate and adequate health literacy increase over 6 months. Future studies should develop interventions that better support musculoskeletal pain patients with inadequate health literacy to successfully manage their pain

The impact of workplace risk factors on the occurrence of neck and upper limb pain: a general population study

BACKGROUND: Work-related neck and upper limb pain has mainly been studied in specific occupational groups, and little is known about its impact in the general population. The objectives of this study were to estimate the prevalence and population impact of work-related neck and upper limb pain. METHODS: A cross-sectional survey was conducted of 10 000 adults in North Staffordshire, UK, in which there is a common local manual industry. The primary outcome measure was presence or absence of neck and upper limb pain. Participants were asked to give details of up to five recent jobs, and to report exposure to six work activities involving the neck or upper limbs. Psychosocial measures included job control, demand and support. Odds ratios (ORs) and population attributable fractions were calculated for these risk factors. RESULTS: The age-standardized one-month period prevalence of neck and upper limb pain was 44%. There were significant independent associations between neck and upper limb pain and: repeated lifting of heavy objects (OR = 1.4); prolonged bending of neck (OR = 2.0); working with arms at/above shoulder height (OR = 1.3); little job control (OR = 1.6); and little supervisor support (OR = 1.3). The population attributable fractions were 0.24 (24%) for exposure to work activities and 0.12 (12%) for exposure to psychosocial factors. CONCLUSION: Neck and upper limb pain is associated with both physical and psychosocial factors in the work environment. Inferences of cause-and-effect from cross-sectional studies must be made with caution; nonetheless, our findings suggest that modification of the work environment might prevent up to one in three of cases of neck and upper limb pain in the general population, depending on current exposures to occupational risk

Musculoskeletal consultations from childhood to adulthood: a longitudinal study

BACKGROUND: The Global Burden of Disease reports indicate that musculoskeletal conditions are important causes of disability worldwide. Such conditions may originate in childhood, but studies investigating changes longitudinally and from childhood to adulthood are infrequent. METHODS: Nine birth cohorts of children (starting at ages 7-15 years) were followed. Participants were identified from Consultations in Primary Care Archive, an electronic health record database of 11 English general practices. Musculoskeletal consultation prevalence figures were calculated, and reasons for consultation evaluated. RESULTS: Annual musculoskeletal consultation prevalence was similar across cohorts for each age. Prevalence increased from 6 to 16% between ages 7 and 22 and was higher in males until age 15, after which prevalence was higher in females. Pain was the most common reason for consultation. Back pain consultations increased from 1 consultation/1000 7 year olds to 84 consultations/1000 22 year olds. Lower limb pain consultations increased from 21 consultations/1000 7 year olds to 56 consultations/1000 22 year olds. CONCLUSIONS: This study shows that from childhood, individuals are more likely to seek healthcare for musculoskeletal consultations as they age, but rates are not increasing over time. Changes in consultation rates by age, gender and pain region may inform studies on the development of chronic musculoskeletal pain over the life-course