Diabetes status and post-load plasma glucose concentration in relation to site-specific cancer mortality: findings from the original Whitehall study

ObjectiveWhile several studies have reported on the relation of diabetes status with pancreatic cancer risk, the predictive value of this disorder for other malignancies is unclear. Methods: The Whitehall study, a 25year follow-up for mortality experience of 18,006 men with data on post-challenge blood glucose and self-reported diabetes, allowed us to address these issues. Results: There were 2158 cancer deaths at follow-up. Of the 15 cancer outcomes, diabetes status was positively associated with mortality from carcinoma of the pancreas and liver, while the relationship with lung cancer was inverse, after controlling for a range of potential covariates and mediators which included obesity and socioeconomic position. After excluding deaths occurring in the first 10years of follow-up to examine the effect of reverse causality, the magnitude of the relationships for carcinoma of the pancreas and lung was little altered, while for liver cancer it was markedly attenuated. Conclusions: In the present study, diabetes status was related to pancreatic, liver, and lung cancer risk. Cohorts with serially collected data on blood glucose and covariates are required to further examine this area

Development of a scale to measure stigma related to podoconiosis in Southern Ethiopia

Background: Health-related stigma adds to the physical and economic burdens experienced by people suffering from neglected tropical diseases (NTDs). Previous research into the NTD podoconiosis showed significant stigma towards those with the disease, yet no formal instrument exists by which to assess stigma or interventions to reduce stigma. We aimed to develop, pilot and validate scales to measure the extent of stigma towards podoconiosis among patients and in podoconiosis-endemic communities. Methods: Indicators of stigma were drawn from existing qualitative podoconiosis research and a literature review on measuring leprosy stigma. These were then formulated into items for questioning and evaluated through a Delphi process in which irrelevant items were discounted. The final items formed four scales measuring two distinct forms of stigma (felt stigma and enacted stigma) for those with podoconiosis and those without the disease. The scales were formatted as two questionnaires, one for podoconiosis patients and one for unaffected community members. 150 podoconiosis patients and 500 unaffected community members from Wolaita zone, Southern Ethiopia were selected through multistage random sampling to complete the questionnaires which were interview-administered. The scales were evaluated through reliability assessment, content and construct validity analysis of the items, factor analysis and internal consistency analysis. Results: All scales had Cronbach’s alpha over 0.7, indicating good consistency. The content and construct validity of the scales were satisfactory with modest correlation between items. There was significant correlation between the felt and enacted stigma scales among patients (Spearman’s r = 0.892; p < 0.001) and within the community (Spearman’s r = 0.794; p < 0.001). Conclusion: We report the development and testing of the first standardised measures of podoconiosis stigma. Although further research is needed to validate the scales in other contexts, we anticipate they will be useful in situational analysis and in designing, monitoring and evaluating interventions. The scales will enable an evidencebased approach to mitigating stigma which will enable implementation of more effective disease control and help break the cycle of poverty and NTDs

Patients' perceptions of podoconiosis causes, prevention and consequences in East and West Gojam, Northern Ethiopia

BACKGROUND Podoconiosis is a form of non-filarial elephantiasis that affects barefoot individuals in highland tropical areas. The disease presents with bilateral, asymmetric swelling of the legs, usually confined to below the knee. This study aimed to assess podoconiosis patients' perceptions of prevention, control, causes and familial clustering of the disease, and to document physical, social and economic impairments associated with the disease, with the ultimate aim of enabling development of tailored interventions in this region. METHODS This descriptive study is part of the largest cross-sectional community-based household survey yet conducted on podoconiosis. It was completed in November and December, 2011, in Debre Eliyas and Dembecha Woredas of East and West Gojam Zones, northern Ethiopia, and consisted of a house-to-house census by community health workers followed by interviews of identified patients using a structured questionnaire. RESULTS In the 17,553 households surveyed, 1,319 patients were identified. More male as compared to female patients were married (84.6% vs. 53.6%, χ(2) = 157.1, p < 0.0001) while more female as compared to male patients were divorced (22.5% vs. 3.6%, χ(2) = 102.3, p < 0.0001). Less than half of the study subjects believed podoconiosis could be prevented (37.5%) or controlled (40.4%) and many (41.3%) did not know the cause of podoconiosis. Two-fifths of the study subjects had a relative affected with podoconiosis. Approximately 13% of the respondents had experienced one or more forms of social stigmatization. The coping strategies adopted by patients to mitigate the physical impairments caused by podoconiosis were: working only occasionally (44.9%), avoiding physically demanding tasks (32.4%), working fewer hours (21.9%) or completely stopping work (8%). Most study subjects (96.4%) had noticed a decline in their income following the development of podoconiosis, and 78% said they were poorer than their healthy neighbours. CONCLUSION This study shows that podoconiosis has strong psychosocial, physical and economic impacts on patients in East and West Gojam Zones of northern Ethiopia. Concerns related to familial clustering, poor understanding of the causes and prevention of podoconiosis all add to the physical burden imposed by the disease. Strategies that may ease the impact of podoconiosis include delivery of tailored health education on the causes and prevention of disease, involving patients in intervention activities, and development of alternative income-generating activities for treated patients

Quantification and viability analyses of Pseudokirchneriella subcapitata algal cells using image-based cytometry

This work aims to evaluate the feasibility of using image-based cytometry (IBC) in the analysis of algal cell quantification and viability, using Pseudokirchneriella subcapitata as a cell model. Cell concentration was determined by IBC to be in a linear range between 1×105 and 8×106 cells mL1. Algal viability was defined on the basis that the intact membrane of viable cells excludes the SYTOX Green (SG) probe. The disruption of membrane integrity represents irreversible damage and consequently results in cell death. Using IBC, we were able to successfully discriminate between live (SG-negative cells) and dead algal cells (heat-treated at 65 °C for 60 min; SG-positive cells). The observed viability of algal populations containing different proportions of killed cells was well correlated (R 2=0.994) with the theoretical viability. The validation of the use of this technology was carried out by exposing algal cells of P. subcapitata to a copper stress test for 96 h. IBC allowed us to follow the evolution of cell concentration and the viability of copper-exposed algal populations. This technology overcomes several main drawbacks usually associated with microscopy counting, such as labour-intensive experiments, tedious work and lack of the representativeness of the cell counting. In conclusion, IBC allowed a fast and automated determination of the total number of algal cells and allowed us to analyse viability. This technology can provide a useful tool for a wide variety of fields that utilise microalgae, such as the aquatic toxicology and biotechnology fields.FCT Strategic Project PEst- OE/EQB/LA0023/2013. The post-doctoral grant from FCT (SFRH/BPD/72816/2010)

Contribution of main causes of death to social inequalities in mortality in the whole population of Scania, Sweden

BACKGROUND: To more efficiently reduce social inequalities in mortality, it is important to establish which causes of death contribute the most to socioeconomic mortality differentials. Few studies have investigated which diseases contribute to existing socioeconomic mortality differences in specific age groups and none were in samples of the whole population, where selection bias is minimized. The aim of the present study was to determine which causes of death contribute the most to social inequalities in mortality in each age group in the whole population of Scania, Sweden. METHODS: Data from LOMAS (Longitudinal Multilevel Analysis in Skåne) were used to estimate 12-year follow-up mortality rates across levels of socioeconomic position (SEP) and workforce participation in 975,938 men and women aged 0 to 80 years, during 1991–2002. RESULTS: The results generally showed increasing absolute mortality differences between those holding manual and non-manual occupations with increasing age, while there were inverted u-shaped associations when using relative inequality measures. Cardiovascular diseases (CVD) contributed to 52% of the male socioeconomic difference in overall mortality, cancer to 18%, external causes to 4% and psychiatric disorders to 3%. The corresponding contributions in women were 55%, 21%, 2% and 3%. Additionally, those outside the workforce (i.e., students, housewives, disability pensioners, and the unemployed) showed a strongly increased risk of future mortality in all age groups compared to those inside the workforce. Even though coronary heart disease (CHD) played a major contributing role to the mortality differences seen, stroke and other types of cardiovascular diseases also made substantial contributions. Furthermore, while the most common types of cancers made substantial contributions to the socioeconomic mortality differences, in some age groups more than half of the differences in cancer mortality could be attributed to rarer cancers. CONCLUSION: CHD made a major contribution to the socioeconomic differences in overall mortality. However, there were also important contributions from diseases with less well understood mechanistic links with SEP such as stroke and less-common cancers. Thus, an increased understanding of the mechanisms connecting SEP with more rare causes of disease might be important to be able to more successfully intervene on socioeconomic differences in health

Coffee consumption and prostate cancer risk: further evidence for inverse relationship

<p>Abstract</p> <p>Background</p> <p>Higher consumption of coffee intake has recently been linked with reduced risk of aggressive prostate cancer (PC) incidence, although meta-analysis of other studies that examine the association between coffee consumption and overall PC risk remains inconclusive. Only one recent study investigated the association between coffee intake and grade-specific incidence of PC, further evidence is required to understand the aetiology of aggressive PCs. Therefore, we conducted a prospective study to examine the relationship between coffee intake and overall as well as grade-specific PC risk.</p> <p>Methods</p> <p>We conducted a prospective cohort study of 6017 men who were enrolled in the Collaborative cohort study in the UK between 1970 and 1973 and followed up to 31st December 2007. Cox Proportional Hazards Models were used to evaluate the association between coffee consumption and overall, as well as Gleason grade-specific, PC incidence.</p> <p>Results</p> <p>Higher coffee consumption was inversely associated with risk of high grade but not with overall risk of PC. Men consuming 3 or more cups of coffee per day experienced 55% lower risk of high Gleason grade disease compared with non-coffee drinkers in analysis adjusted for age and social class (HR 0.45, 95% CI 0.23-0.90, p value for trend 0.01). This association changed a little after additional adjustment for Body Mass Index, smoking, cholesterol level, systolic blood pressure, tea intake and alcohol consumption.</p> <p>Conclusion</p> <p>Coffee consumption reduces the risk of aggressive PC but not the overall risk.</p

Exploring the equity of GP practice prescribing rates for selected coronary heart disease drugs: a multiple regression analysis with proxies of healthcare need

Background There is a small, but growing body of literature highlighting inequities in GP practice prescribing rates for many drug therapies. The aim of this paper is to further explore the equity of prescribing for five major CHD drug groups and to explain the amount of variation in GP practice prescribing rates that can be explained by a range of healthcare needs indicators (HCNIs). Methods The study involved a cross-sectional secondary analysis in four primary care trusts (PCTs 1–4) in the North West of England, including 132 GP practices. Prescribing rates (average daily quantities per registered patient aged over 35 years) and HCNIs were developed for all GP practices. Analysis was undertaken using multiple linear regression. Results Between 22–25% of the variation in prescribing rates for statins, beta-blockers and bendrofluazide was explained in the multiple regression models. Slightly more variation was explained for ACE inhibitors (31.6%) and considerably more for aspirin (51.2%). Prescribing rates were positively associated with CHD hospital diagnoses and procedures for all drug groups other than ACE inhibitors. The proportion of patients aged 55–74 years was positively related to all prescribing rates other than aspirin, where they were positively related to the proportion of patients aged >75 years. However, prescribing rates for statins and ACE inhibitors were negatively associated with the proportion of patients aged >75 years in addition to the proportion of patients from minority ethnic groups. Prescribing rates for aspirin, bendrofluazide and all CHD drugs combined were negatively associated with deprivation. Conclusion Although around 25–50% of the variation in prescribing rates was explained by HCNIs, this varied markedly between PCTs and drug groups. Prescribing rates were generally characterised by both positive and negative associations with HCNIs, suggesting possible inequities in prescribing rates on the basis of ethnicity, deprivation and the proportion of patients aged over 75 years (for statins and ACE inhibitors, but not for aspirin)

Therapeutic effects of methylphenidate for attention-deficit/hyperactivity disorder in children with borderline intellectual functioning or intellectual disability: A systematic review and meta-analysis

Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with intellectual disability in children, and may further compromise learning. Methylphenidate is a first-line treatment for ADHD, however no previous meta-analysis has evaluated its overall efficacy for ADHD in children with comorbid intellectual disability (ID) or borderline intellectual functioning. The PubMed/MEDLINE, Cochrane CENTRAL and ScienceDirect databases were systematically searched from inception through 2018/7/15 for clinical studies that investigated the effects of methylphenidate in children with ADHD and ID. A random-effects model meta-analysis was used for data synthesis. Eight studies (average Jadad score = 2.5) enrolling 242 participants receiving methylphenidate and 181 participants receiving placebo were included. The meta-analysis showed that methylphenidate led to a significant improvement in ADHD symptoms relative to placebo (Hedges’ g = 0.878, p < 0.001). Meta-regression analysis pointed to an association between the dose of methylphenidate and overall improvement in ADHD severity (slope = 1.334, p < 0.001). Finally, there was no significant difference in drop-out rate [odds ratio (OR) = 1.679, p = 0.260] or rate of treatment discontinuation due to adverse events (OR = 4.815, p = 0.053) between subjects receiving methylphenidate and those taking placebos. Our study suggests that methylphenidate retains its efficacy in children with ADHD and borderline intellectual functioning or ID

TALPID3/KIAA0586 Regulates Multiple Aspects of Neuromuscular Patterning During Gastrointestinal Development in Animal Models and Human

TALPID3/KIAA0586 is an evolutionary conserved protein, which plays an essential role in protein trafficking. Its role during gastrointestinal (GI) and enteric nervous system (ENS) development has not been studied previously. Here, we analyzed chicken, mouse and human embryonic GI tissues with TALPID3 mutations. The GI tract of TALPID3 chicken embryos was shortened and malformed. Histologically, the gut smooth muscle was mispatterned and enteric neural crest cells were scattered throughout the gut wall. Analysis of the Hedgehog pathway and gut extracellular matrix provided causative reasons for these defects. Interestingly, chicken intra-species grafting experiments and a conditional knockout mouse model showed that ENS formation did not require TALPID3, but was dependent on correct environmental cues. Surprisingly, the lack of TALPID3 in enteric neural crest cells (ENCC) affected smooth muscle and epithelial development in a non-cell-autonomous manner. Analysis of human gut fetal tissues with a KIAA0586 mutation showed strikingly similar findings compared to the animal models demonstrating conservation of TALPID3 and its necessary role in human GI tract development and patterning