Simple Clinical and Laboratory Predictors of Chikungunya versus Dengue Infections in Adults

10.1371/journal.pntd.0001786PLoS Neglected Tropical Diseases69

Comparative effectiveness of dual-action versus single-action antidepressants for the treatment of depression in people living with HIV/AIDS

Background Depression is the most common psychiatric comorbidity among people living with HIV/AIDS (PLWHA). Little is known about the comparative effectiveness between different types of antidepressants used to treat depression in this population. We compared the effectiveness of dual-action and single-action antidepressants in PLWHA for achieving remission from depression. Methods We used data from the Centers for AIDS Research Network of Integrated Clinic Systems to identify 1175 new user dual-action or single-action antidepressant treatment episodes occurring from 2005 to 2014 for PLWHA diagnosed with depression. The primary outcome was remission from depression defined as a Patient Health Questionnaire-9 (PHQ-9) score <5. Mean difference in PHQ-9 depressive symptom severity was a secondary outcome. The main approach was an intent-to-treat (ITT) evaluation complemented with a per protocol (PP) sensitivity analysis. Generalized linear models were fitted to estimate treatment effects. Results In ITT analysis, 32% of the episodes ended in remission for both dual-action and single-action antidepressants. The odds ratio (OR) of remission was 1.02 (95%CI=0.63,1.67). In PP analysis, 40% of dual-action episodes ended in remission compared to 32% in single-action episodes. Dual-action episodes had 1.33 times the odds of remission (95%CI=0.55,3.21), however the result was not statistically significant. Non-significant differences were also observed for depressive symptom severity. Limitations Missing data was common but was addressed with inverse probability weights. Conclusions Results suggest that single-action and dual-action antidepressants are equally effective in PLWHA. Remission was uncommon highlighting the need to identify health service delivery strategies that aid HIV providers in achieving full remission of their patients’ depression

Spiritually significant hallucinations: a patient-centred approach to tackle epistemic injustice

Summary This article uses three fictitious case vignettes to raise questions and educate on how clinicians can appropriately approach patients experiencing spiritually significant hallucinations. Religious hallucinations are common but are not pathognomonic of mental illness. They are often intimate experiences for the patient that raise complex questions about psychopathology for clinicians. When assessing a patient with religious hallucinations it is important that clinicians hold at the centre that person's personal experience and create a safe space in which they are listened to and epistemic injustices are avoided. Involvement of chaplaincy services is important not just to support the patient but also to ensure that as clinicians we seek support in understanding the religious nature of these experiences

A central role for hepatic conventional dendritic cells in supporting Th2 responses during helminth infection

Dendritic cells (DCs) are the key initiators of T-helper (Th) 2 immune responses against the parasitic helminth Schistosoma mansoni. Although the liver is one of the main sites of antigen deposition during infection with this parasite, it is not yet clear how distinct DC subtypes in this tissue respond to S. mansoni antigens in vivo, or how the liver microenvironment might influence DC function during establishment of the Th2 response. In this study, we show that hepatic DC subsets undergo distinct activation processes in vivo following murine infection with S. mansoni. Conventional DCs (cDCs) from schistosome-infected mice upregulated expression of the costimulatory molecule CD40 and were capable of priming naive CD4+ T cells, whereas plasmacytoid DCs (pDCs) upregulated expression of MHC class II, CD86 and CD40 but were unable to support the expansion of either naive or effector/memory CD4+ T cells. Importantly, in vivo depletion of pDCs revealed that this subset was dispensable for either maintenance or regulation of the hepatic Th2 effector response during acute S. mansoni infection. Our data provides strong evidence that S. mansoni infection favors the establishment of an immunogenic, rather than tolerogenic, liver microenvironment that conditions cDCs to initiate and maintain Th2 immunity in the context of ongoing antigen exposure

An Open System for Social Computation

Part of the power of social computation comes from using the collective intelligence of humans to tame the aggregate uncertainty of (otherwise) low veracity data obtained from human and automated sources. We have witnessed a surge in development of social computing systems but, ironically, there have been few attempts to generalise across this activity so that creation of the underlying mechanisms themselves can be made more social. We describe a method for achieving this by standardising patterns of social computation via lightweight formal specifications (we call these social artifacts) that can be connected to existing internet architectures via a single model of computation. Upon this framework we build a mechanism for extracting provenance meta-data across social computations

Body-mass index adjustments to increase the validity of body fatness assessment in UK black African and South Asian children: a cross-sectional calibration study

BackgroundExcess childhood body fatness, overweightness, and obesity are a major public health challenge in the UK. Accurate assessments, usually based on body-mass index (BMI), are crucial. However, recent studies have demonstrated that BMI underestimates body fatness in South Asian children and overestimates it in black African children. These errors are a concern in these ethnic minority populations, particularly UK South Asians, who are at high risk of obesity, type 2 diabetes, and cardiovascular disease. We aimed to develop BMI adjustments for these children to ensure that BMI relates to body fatness in the same way as for white European children.MethodsFour recent UK population-based studies, which used deuterium dilution assessments of fat mass as a reference method, were pooled to include 1725 children (52% girls) aged 4–12 years (mean 9·3, SD 1·6) of white European, South Asian, and black African origins. A height-standardised fat-mass index (FMI) was derived to represent body fatness. Linear regression models were fitted, separately by sex, to quantify ethnic differences in BMI–FMI associations and to provide ethnic-specific BMI adjustments.FindingsThe FMI derived for this study population and used in analyses was fat mass/height5, which was independent of height for the 4–12-year age-group. BMI consistently underestimated body fatness in South Asians, requiring a BMI adjustment of +1·12 kg/m2 (95% CI 0·83–1·41) for boys and +1·07 (0·74–1·39) for girls, irrespective of age and FMI. BMI overestimated body fatness in black Africans. However, adjustments for black African children were more complex, with statistically significant interactions between black African ethnicity and FMI (p=0·004 boys, p=0·003 girls) and between FMI and age-group (p\u3c0·0001 boys and girls). BMI adjustments therefore varied by age-group and FMI level, between −0·24 and −2·84 kg/m2 for boys and between −0·22 and −2·86 kg/m2 for girls for unadjusted BMI values of 13 kg/m2 in 10–12 year-olds and 25 kg/m2 in 4–6 year-olds, respectively.InterpretationBMI underestimated body fatness in South Asians and overestimated it in black Africans. Ethnic-specific adjustments—increasing BMI in South Asians and reducing BMI in black Africans—can improve the accuracy of body fatness assessment in these children.FundingThis work was supported by the British Heart Foundation (grant ref PG/15/19/31336) and National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care (South London) (grant ref CLAHRC-2013-10022). Primary data collection was funded by the British Heart Foundation (PG/11/42/28895), BUPA Foundation (TBF-S09-019), Child Growth Foundation (GR 10/03), and Wellcome Trust (WT094129MA). MF is supported by Great Ormond Street Hospital Childrens\u27 Charity

Are Ethnic and Gender Specific Equations Needed to Derive Fat Free Mass from Bioelectrical Impedance in Children of South Asian, Black African-Caribbean and White European Origin? Results of the Assessment of Body Composition in Children Study

Background Bioelectrical impedance analysis (BIA) is a potentially valuable method for assessing lean mass and body fat levels in children from different ethnic groups. We examined the need for ethnic- and gender-specific equations for estimating fat free mass (FFM) from BIA in children from different ethnic groups and examined their effects on the assessment of ethnic differences in body fat. Methods Cross-sectional study of children aged 8–10 years in London Primary schools including 325 South Asians, 250 black African-Caribbeans and 289 white Europeans with measurements of height, weight and arm-leg impedance (Z; Bodystat 1500). Total body water was estimated from deuterium dilution and converted to FFM. Multilevel models were used to derive three types of equation {A: FFM = linear combination(height+weight+Z); B: FFM = linear combination(height2/Z); C: FFM = linear combination(height2/Z+weight)}. Results Ethnicity and gender were important predictors of FFM and improved model fit in all equations. The models of best fit were ethnicity and gender specific versions of equation A, followed by equation C; these provided accurate assessments of ethnic differences in FFM and FM. In contrast, the use of generic equations led to underestimation of both the negative South Asian-white European FFM difference and the positive black African-Caribbean-white European FFM difference (by 0.53 kg and by 0.73 kg respectively for equation A). The use of generic equations underestimated the positive South Asian-white European difference in fat mass (FM) and overestimated the positive black African-Caribbean-white European difference in FM (by 4.7% and 10.1% respectively for equation A). Consistent results were observed when the equations were applied to a large external data set. Conclusions Ethnic- and gender-specific equations for predicting FFM from BIA provide better estimates of ethnic differences in FFM and FM in children, while generic equations can misrepresent these ethnic differences

Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE).

AIMS/HYPOTHESIS: Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children. METHODS: In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school. RESULTS: Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers. CONCLUSIONS/INTERPRETATION: Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes

Regular breakfast consumption and type 2 diabetes risk markers in 9- to 10-year-old children in the child heart and health study in England (CHASE): a cross-sectional analysis.

BACKGROUND: Regular breakfast consumption may protect against type 2 diabetes risk in adults but little is known about its influence on type 2 diabetes risk markers in children. We investigated the associations between breakfast consumption (frequency and content) and risk markers for type 2 diabetes (particularly insulin resistance and glycaemia) and cardiovascular disease in children. METHODS AND FINDINGS: We conducted a cross-sectional study of 4,116 UK primary school children aged 9-10 years. Participants provided information on breakfast frequency, had measurements of body composition, and gave fasting blood samples for measurements of blood lipids, insulin, glucose, and glycated haemoglobin (HbA1c). A subgroup of 2,004 children also completed a 24-hour dietary recall. Among 4,116 children studied, 3,056 (74%) ate breakfast daily, 450 (11%) most days, 372 (9%) some days, and 238 (6%) not usually. Graded associations between breakfast frequency and risk markers were observed; children who reported not usually having breakfast had higher fasting insulin (percent difference 26.4%, 95% CI 16.6%-37.0%), insulin resistance (percent difference 26.7%, 95% CI 17.0%-37.2%), HbA1c (percent difference 1.2%, 95% CI 0.4%-2.0%), glucose (percent difference 1.0%, 95% CI 0.0%-2.0%), and urate (percent difference 6%, 95% CI 3%-10%) than those who reported having breakfast daily; these differences were little affected by adjustment for adiposity, socioeconomic status, and physical activity levels. When the higher levels of triglyceride, systolic blood pressure, and C-reactive protein for those who usually did not eat breakfast relative to those who ate breakfast daily were adjusted for adiposity, the differences were no longer significant. Children eating a high fibre cereal breakfast had lower insulin resistance than those eating other breakfast types (p for heterogeneity <0.01). Differences in nutrient intakes between breakfast frequency groups did not account for the differences in type 2 diabetes markers. CONCLUSIONS: Children who ate breakfast daily, particularly a high fibre cereal breakfast, had a more favourable type 2 diabetes risk profile. Trials are needed to quantify the protective effect of breakfast on emerging type 2 diabetes risk. Please see later in the article for the Editors' Summary