'Population laboratories' or 'laboratory populations'? Making sense of the Baltimore Longitudinal Study of Aging, 1965-1987

Interest among historians, philosophers and sociologists of science in population-based biomedical research has focused on the randomised controlled trial to the detriment of the longitudinal study, the temporally extended, serial observation of individuals residing in the same community. This is perhaps because the longitudinal study is regarded as having played a secondary role in the debates about the validity of populations-based approaches that helped to establish epidemiology as one of the constitutive disciplines of contemporary biomedicine. Drawing on archival data and publications relating to the Baltimore Longitudinal Study of Aging, we argue however that the historical development of the longitudinal study is richer and more significant than has been appreciated. We argue that this history is shaped by the tension between two sets of epistemic practices, devices and norms. On the one side there were those who emphasised randomisation and sampling to evidence claims about, and justify policies with respect to, the aetiology of disease. On the other side there were those who evoked the technical repertoire of physiological research, especially the notion of the ‘model organism’, to argue for a different integration of the individual in modern society.     

Relationship of Temperament and Character in Remitted Depressed Patients with Suicidal Ideation and Suicide Attempts—Results from the CRESCEND Study

The aim of this study was to evaluate the Temperament and Character Inventory (TCI) scores of a sample of Korean patients with remitted depression who had attempted suicide and reported suicidal ideation and to compare their scores with those of remitted depressed patients without suicidal ideation. Adult depression patients who had completed 12 weeks of follow-up (N = 138) were divided into three groups: patients with a history of suicide attempts (N = 23); patients with current suicidal ideation (N = 59); and patients without current suicidal ideation (N = 56). After controlling for covariates, no significant differences were found among the three groups on any measure of temperament or character except self-directedness and self-transcendence. The self-transcendence scores of the lifetime suicide-attempt group were significantly higher compared with those of the suicidal-ideation group; post hoc analysis revealed that self-directedness was significantly lower in the suicide-attempt group compared with the non-suicidal group. The results from the present study suggest that remitted depression patients with a history of suicide attempts do not differ from non-attempters in temperament, but do differ in certain character traits.     

Peripheral blood T-cell signatures from high-resolution immune phenotyping of γδ and αβ T-cells in younger and older subjects in the Berlin Aging Study II

Background

Aging and latent infection with Cytomegalovirus (CMV) are thought to be major factors driving the immune system towards immunosenescence, primarily characterized by reduced amounts of naïve T-cells and increased memory T-cells, potentially associated with higher morbidity and mortality. The composition of both major compartments, γδ as well as αβ T-cells, is altered by age and CMV, but detailed knowledge of changes to the γδ subset is currently limited.

Results

Here, we have surveyed a population of 73 younger (23–35 years) and 144 older (62–85 years) individuals drawn from the Berlin Aging Study II, investigating the distribution of detailed differentiation phenotypes of both γδ and αβ T-cells. Correlation of frequencies and absolute counts of the identified phenotypes with age and the presence of CMV revealed a lower abundance of Vδ2-positive and a higher amount of Vδ1-positive cells. We found higher frequencies of late-differentiated and lower frequencies of early-differentiated cells in the Vδ1+ and Vδ1-Vδ2-, but not in the Vδ2+ populations in elderly CMV-seropositive individuals confirming the association of these Vδ2-negative cells with CMV-immunosurveillance. We identified the highest Vδ1:Vδ2 ratios in the CMV-seropositive elderly. The observed increased CD4:CD8 ratios in the elderly were significantly lower in CMV-seropositive individuals, who also possessed a lower naïve and a larger late-differentiated compartment of CD8+ αβ T-cells, reflecting the consensus in the literature.

Conclusions

Our findings illustrate in detail the strong influence of CMV on the abundance and differentiation pattern of γδ T-cells as well as αβ T-cells in older and younger people. Mechanisms responsible for the phenotypic alterations in the γδ T-cell compartment, associated both with the presence of CMV and with age require further clarification.

     

How does social capital matter to the health status of older adults? Evidence from the China Health and Retirement Longitudinal Survey

This paper uses longitudinal data from China to examine the causal relationship between structural social capital and health among Chinese older adults. We employ various econometric strategies to control for the potential endogeneity of social capital and account for the possible contextual confounding effects by including community-level social capital. We use three indicators to measure individuals’ general, physical, and mental health. Results indicate that social capital has a significant and positive effect on general and physical health. Based on our primary IV findings, a one standard-deviation increase in social capital leads to a 4.9 standard-deviation decrease in the probability of having bad health and a 2.2 standard-deviation decrease in physical activity limitations. Our results are robust to a series of sensitivity checks. Further analysis suggests heterogeneous effects by age but not by gender or area of residence.     

Intake of Vitamin and Mineral Supplements and Longitudinal Association with HbA1c Levels in the General Non-Diabetic Population—Results from the MONICA/KORA S3/F3 Study

Background

Lower levels of hemoglobin A_1c (HbA_1c) are associated with a decreased risk of cardiovascular complications in diabetic and non-diabetic individuals. The aim of the study was to longitudinally investigate the association between the use of 11 vitamins and minerals (vitamins E, C, D, B₁, folic acid, carotenoids, calcium, magnesium, zinc, iron, and selenium) and change in HbA_1c levels over 10 years in non-diabetic individuals drawn from the general population.

Methods

Baseline data were available from 4447 subjects included in the population-based “Monitoring of Trends and Determinants in Cardiovascular Diseases” (MONICA) Augsburg S3 survey (1994/95). Follow-up data were derived from 2774 participants in the follow-up survey named “Cooperative Health Research in the Region of Augsburg” (KORA) F3 (2004/05). Vitamin/mineral intake from supplements and medications was assessed in a personal interview, where participants were asked to bring product packages of preparations that had been ingested during the last 7 days prior to the examination. Associations between regular vitamin/mineral intake amounts and HbA_1c levels measured at baseline and follow-up were investigated using generalized estimating equation models. For carotenoids, analyses were stratified by smoking status.

Results

None of the investigated nutrients except for carotenoids was significantly associated with changes in HbA_1c levels after 10 years. Regular intake of carotenoids from supplements and medications in amounts > 6.8mg/d (upper tertile) was associated with an absolute –0.26% (95% CI: –0.43 to –0.08) lower increase in HbA_1c levels compared with no intake of carotenoids. An inverse association was observed in those who never smoked but not in (former) smokers.

Conclusion

Larger prospective and intervention studies in non-diabetic/non-smoking individuals are needed to confirm the results and to assess whether the observed associations between carotenoid intake and change in HbA_1c levels are causal. If our results are confirmed, high carotenoid intake could be one strategy for the prevention of cardiovascular complications in non-diabetic people.     

Molecular Characterization of the Fecal Microbiota in Patients with Nonalcoholic Steatohepatitis – A Longitudinal Study

Background

The human gut microbiota has profound influence on host metabolism and immunity. This study characterized the fecal microbiota in patients with nonalcoholic steatohepatitis (NASH). The relationship between microbiota changes and changes in hepatic steatosis was also studied.

Methods

Fecal microbiota of histology-proven NASH patients and healthy controls was analyzed by 16S ribosomal RNA pyrosequencing. NASH patients were from a previously reported randomized trial on probiotic treatment. Proton-magnetic resonance spectroscopy was performed to monitor changes in intrahepatic triglyceride content (IHTG).

Results

A total of 420,344 16S sequences with acceptable quality were obtained from 16 NASH patients and 22 controls. NASH patients had lower fecal abundance of Faecalibacterium and Anaerosporobacter but higher abundance of Parabacteroides and Allisonella. Partial least-square discriminant analysis yielded a model of 10 genera that discriminated NASH patients from controls. At month 6, 6 of 7 patients in the probiotic group and 4 of 9 patients in the usual care group had improvement in IHTG (P = 0.15). Improvement in IHTG was associated with a reduction in the abundance of Firmicutes (R² = 0.4820, P = 0.0028) and increase in Bacteroidetes (R² = 0.4366, P = 0.0053). This was accompanied by corresponding changes at the class, order and genus levels. In contrast, bacterial biodiversity did not differ between NASH patients and controls, and did not change with probiotic treatment.

Conclusions

NASH patients have fecal dysbiosis, and changes in microbiota correlate with improvement in hepatic steatosis. Further studies are required to investigate the mechanism underlying the interaction between gut microbes and the liver.     

Effectiveness of Front-Of-Pack Nutrition Labels in French Adults: Results from the NutriNet-Santé Cohort Study

Background

To date, no consensus has emerged on the most appropriate front-of-pack (FOP) nutrition label to help consumers in making informed choices. We aimed to compare the effectiveness of the label formats currently in use: nutrient-specific, graded and simple summary systems, in a large sample of adults.

Methods

The FOP label effectiveness was assessed by measuring the label acceptability and understanding among 13,578 participants of the NutriNet-Santé cohort study, representative of the French adult population. Participants were exposed to five conditions, including four FOP labels: Guideline Daily Amounts (GDA), Multiple Traffic Lights (MTL), 5-Color Nutrition Label (5-CNL), Green Tick (Tick), and a “no label” condition. Acceptability was evaluated by several indicators: attractiveness, liking and perceived cognitive workload. Objective understanding was assessed by the percentage of correct answers when ranking three products according to their nutritional quality. Five different product categories were tested: prepared fish dishes, pizzas, dairy products, breakfast cereals, and appetizers. Differences among the label effectiveness were compared with chi-square tests.

Results

The 5-CNL was viewed as the easiest label to identify and as the one requiring the lowest amount of effort and time to understand. GDA was considered as the least easy to identify and to understand, despite being the most attractive and liked label. All FOP labels were found to be effective in ranking products according to their nutritional quality compared with the “no label” situation, although they showed differing levels of effectiveness (p<0.0001). Globally, the 5-CNL performed best, followed by MTL, GDA and Tick labels.

Conclusions

The graded 5-CNL label was considered as easy to identify, simple and rapid to understand; it performed well when comparing the products’ nutritional quality. Therefore, it is likely to present advantages in real shopping situations where choices are usually made quickly.     

Results of Observational Studies: Analysis of Findings from the Nurses’ Health Study

Background

The role of observational studies in informing clinical practice is debated, and high profile examples of discrepancies between the results of observational studies and randomised controlled trials (RCTs) have intensified that debate. We systematically reviewed findings from the Nurses’ Health Study (NHS), one of the longest and largest observational studies, to assess the number and strength of the associations reported and to determine if they have been confirmed in RCTs.

Methods

We reviewed NHS publication abstracts from 1978–2012, extracted information on associations tested, and graded the strength of the reported effect sizes. We searched PubMed for RCTs or systematic reviews for 3 health outcomes commonly reported in NHS publications: breast cancer, ischaemic heart disease (IHD) and osteoporosis. NHS results were compared with RCT results and deemed concordant when the difference in effect sizes between studies was ≤0.15.

Findings

2007 associations between health outcomes and independent variables were reported in 1053 abstracts. 58.0% (1165/2007) were statistically significant, and 22.2% (445/2007) were neutral (no association). Among the statistically significant results that reported a numeric odds ratio (OR) or relative risk (RR), 70.5% (706/1002) reported a weak association (OR/RR 0.5–2.0), 24.5% (246/1002) a moderate association (OR/RR 0.25–0.5 or 2.0–4.0) and 5.0% (50/1002) a strong association (OR/RR ≤0.25 or ≥4.0). 19 associations reported in NHS publications for breast cancer, IHD and osteoporosis have been tested in RCTs, and the concordance between NHS and RCT results was low (≤25%).

Conclusions

NHS publications contain a large number of analyses, the majority of which reported statistically significant but weak associations. Few of these associations have been tested in RCTs, and where they have, the agreement between NHS results and RCTs is poor.     

Factors associated with remaining teeth of older adults in the state of São Paulo,Brazil, 2002

Objectives: The objective of this study was to verify the association between the number of teeth present with socio-demographic and economic variables and with the access to dental services and self-perception of oral health among the elderly. Materials and Methods: The sample was composed of individuals from 65 to 74 years of age, which was representative of the state of São Paulo (n = 781). In this study, the analysis of data considered dentate elderly only, who were divided into two groups: those with one to 19 teeth and those with 20 teeth or more. The chi-squared test was used in the bivariate analysis and the logistic regression was also performed (p < 0.05). Results: Among the 313 dentate elderly, 235 (75.1%) presented one to 19 teeth. The average number of teeth was 9.5 for the elderly with fewer teeth and 25 for those with more teeth. In the bivariate analysis, all variables related to the access to dental services were associated and the chances of having less teeth was among elderly who did not visit the dentist for a long time and among those who sought public dental services and did not receive information on how to avoid oral problems. In addition, the elderly who classified their speech as not good were those who presented with fewer teeth. Conclusion: Most subjects presented one to 19 teeth and this fact was directly associated, among others factors, to the unsatisfactory perception that they reported in relation to their speech and to the too long period without visiting the dentist.     

Does Clinical Management Improve Outcomes following Self-Harm? Results from the Multicentre Study of Self-Harm in England

Background

Evidence to guide clinical management of self-harm is sparse, trials have recruited selected samples, and psychological treatments that are suggested in guidelines may not be available in routine practice.

Aims

To examine how the management that patients receive in hospital relates to subsequent outcome.

Methods

We identified episodes of self-harm presenting to three UK centres (Derby, Manchester, Oxford) over a 10 year period (2000 to 2009). We used established data collection systems to investigate the relationship between four aspects of management (psychosocial assessment, medical admission, psychiatric admission, referral for specialist mental health follow up) and repetition of self-harm within 12 months, adjusted for differences in baseline demographic and clinical characteristics.

Results

35,938 individuals presented with self-harm during the study period. In two of the three centres, receiving a psychosocial assessment was associated with a 40% lower risk of repetition, Hazard Ratios (95% CIs): Centre A 0.99 (0.90–1.09); Centre B 0.59 (0.48–0.74); Centre C 0.59 (0.52–0.68). There was little indication that the apparent protective effects were mediated through referral and follow up arrangements. The association between psychosocial assessment and a reduced risk of repetition appeared to be least evident in those from the most deprived areas.

Conclusion

These findings add to the growing body of evidence that thorough assessment is central to the management of self-harm, but further work is needed to elucidate the possible mechanisms and explore the effects in different clinical subgroups.     

Profiles of Organic Food Consumers in a Large Sample of French Adults: Results from the Nutrinet-Santé Cohort Study

Background

Lifestyle, dietary patterns and nutritional status of organic food consumers have rarely been described, while interest for a sustainable diet is markedly increasing.

Methods

Consumer attitude and frequency of use of 18 organic products were assessed in 54,311 adult participants in the Nutrinet-Santé cohort. Cluster analysis was performed to identify behaviors associated with organic product consumption. Socio-demographic characteristics, food consumption and nutrient intake across clusters are provided. Cross-sectional association with overweight/obesity was estimated using polytomous logistic regression.

Results

Five clusters were identified: 3 clusters of non-consumers whose reasons differed, occasional (OCOP, 51%) and regular (RCOP, 14%) organic product consumers. RCOP were more highly educated and physically active than other clusters. They also exhibited dietary patterns that included more plant foods and less sweet and alcoholic beverages, processed meat or milk. Their nutrient intake profiles (fatty acids, most minerals and vitamins, fibers) were healthier and they more closely adhered to dietary guidelines. In multivariate models (after accounting for confounders, including level of adherence to nutritional guidelines), compared to those not interested in organic products, RCOP participants showed a markedly lower probability of overweight (excluding obesity) (25≤body mass index<30) and obesity (body mass index ≥30): −36% and −62% in men and −42% and −48% in women, respectively (P<0.0001). OCOP participants (%) generally showed intermediate figures.

Conclusions

Regular consumers of organic products, a sizeable group in our sample, exhibit specific socio-demographic characteristics, and an overall healthy profile which should be accounted for in further studies analyzing organic food intake and health markers.     

Predicting Neuropathy and Reactions in Leprosy at Diagnosis and Before Incident Events—Results from the INFIR Cohort Study

Background

Leprosy is a disease of skin and peripheral nerves. The process of nerve injury occurs gradually through the course of the disease as well as acutely in association with reactions. The INFIR (ILEP Nerve Function Impairment and Reactions) Cohort was established to identify clinically relevant neurological and immunological predictors for nerve injury and reactions.

Methodology/Principal Findings

The study, in two centres in India, recruited 188 new, previously untreated patients with multi-bacillary leprosy who had no recent nerve damage. These patients underwent a series of novel blood tests and nerve function testing including motor and sensory nerve conduction, warm and cold detection thresholds, vibrometry, dynamometry, monofilament sensory testing and voluntary muscle testing at diagnosis and at monthly follow up for the first year and every second month for the second year. During the 2 year follow up a total of 74 incident events were detected. Sub-clinical changes to nerve function at diagnosis and during follow-up predicted these new nerve events. Serological assays at baseline and immediately before an event were not predictive; however, change in TNF alpha before an event was a statistically significant predictor of that event.

Conclusions/Significance

These findings increase our understanding of the processes of nerve damage in leprosy showing that nerve function impairment is more widespread than previously appreciated. Any nerve involvement, including sub-clinical changes, is predictive of further nerve function impairment. These new factors could be used to identify patients at high risk of developing impairment and disability.     

Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with CAP – Results from the German competence network CAPNETZ

Background

Aim of this study was to evaluate the correlation of inflammatory markers procalcitonin (PCT), C-reactive protein (CRP) and leukocyte count (WBC) with microbiological etiology of CAP.

Methods

We enrolled 1337 patients (62 ± 18 y, 45% f) with proven CAP. Extensive microbiological workup was performed. In all patients PCT, CRP, WBC and CRB-65 score were determined. Patients were classified according to microbial diagnosis and CRB-65 score.

Results

In patients with typical bacterial CAP, levels of PCT, CRP and WBC were significantly higher compared to CAP of atypical or viral etiology. There were no significant differences in PCT, CRP and WBC in patients with atypical or viral etiology of CAP. In contrast to CRP and WBC, PCT markedly increased with severity of CAP as measured by CRB-65 score (p < 0.0001). In ROC analysis for discrimination of patients with CRB-65 scores > 1, AUC for PCT was 0.69 (95% CI 0.66 to 0.71), which was higher compared to CRP and WBC (p < 0.0001). CRB-65, PCT, CRP and WBC were higher (p < 0.0001) in hospitalised patients in comparison to outpatients.

Conclusion

PCT, CRP and WBC are highest in typical bacterial etiology in CAP but do not allow individual prediction of etiology. In contrast to CRP and WBC, PCT is useful in severity assessment of CAP.     

Diversity of developmental patterns in achelate lobsters—today and in the Mesozoic

Modern achelate lobsters, slipper and spiny lobsters, have a specific post-embryonic developmental pattern with the following phases: phyllosoma, nisto (slipper lobsters) or puerulus (spiny lobsters), juvenile and adult. The phyllosoma is a peculiar larva, which transforms through a metamorphic moult into another larval form, the nisto or puerulus which largely resembles the juvenile. Unlike the nisto and puerulus, the phyllosoma is characterised by numerous morphological differences to the adult, e.g. a thin head shield, elongate appendages, exopods on these appendages and a special claw. Our reinvestigation of the 85 million years old fossil “Eryoneicus sahelalmae” demonstrates that it represents an unusual type of achelatan lobster larva, characterised by a mixture of phyllosoma and post-phyllosoma characters. We ascribe it to its own genus: Polzicaris nov. gen. We study its significance by comparisons with other cases of Mesozoic fossil larvae also characterised by a mixture of characters. Accordingly, all these larvae are interpreted as ontogenetic intermediates between phyllosoma and post-phyllosoma morphology. Remarkably, most of the larvae show a unique mixture of retained larval and already developed post-larval features. Considering the different—and incompatible—mixture of characters of each of these larvae and their wide geographical and temporal distribution, we interpret all these larvae as belonging to distinct species. The particular character combinations in the different larvae make it currently difficult to reconstruct an evolutionary scenario with a stepwise character acquisition. Yet, it can be concluded that a larger diversity of larval forms and developmental patterns occurred in Mesozoic than in modern faunas.     

Predictors of chemoradiation related febrile neutropenia prophylaxis in older adults – Experience from a limited resource setting

Aim

To identify risk factors that lower efficacy of antibiotic prophylaxis of febrile neutropenia among older patients on chemoradiation.