Prevalence and determinants of anxiety and depression in end stage renal disease (ESRD). A comparison between ESRD patients with and without coexisting diabetes mellitus

Objective: To compare anxiety and/or depressive symptoms between patients with end-stage renal disease with and without comorbid diabetes and identify factors associated with symptoms of distress in this population. Methods: Data from two studies (conducted between 2010 and 2014) were pooled. A total of 526 patients on hemodialysis (68.8% with diabetes) completed the Hospital Anxiety and Depression Scale (HADS). Elevated symptoms were defined as HADS-Anxiety or HADS-Depression ≥ 8. Univariate and multivariate logistic regressions were used to estimate associations between diabetic status, and other socio-demographic and clinical factors with baseline clinical anxiety and depression. Results: A total of 233 (45.4%) reported elevated anxiety symptoms and 256 (49.9%) reported elevated depressive symptoms sufficient for caseness. Rates were not different between patients with and without diabetes. Risk for clinical depression was higher in patients who were single/unpartnered (OR = 1.828), Chinese vs. Malay (OR = 2.05), or had lower albumin levels (OR = 0.932). None of the parameters were associated with anxiety caseness. Conclusion: Sociocultural factors rather than comorbid burden may help identify patients at risk for depression. The high rates of anxiety and depression underlie the importance for monitoring and intervention in dialysis care

Apoptosis of αβ T lymphocytes in the nervous system in experimental autoimmune encephalomyelitis: Its possible implications for recovery and acquired tolerance

We have recently shown that apoptosis, an active process of cellular self-destruction, occurs in the central nervous system in Lewis rats with acute experimental autoimmune encephalomyelitis (EAE) induced by inoculation with myelin basic protein (MBP) and adjuvants. Conventional light and electron microscopic studies suggested that some of the apoptotic cells were oligodendrocytes and that others were hematogenous mononuclear cells. To determine whether any of the apoptotic cells were T lymphocytes, we used the technique of pre-embedding immunolabelling which allows sufficient preservation of the ultrastructure to permit recognition of apoptotic changes while at the same time preserving surface antigens so that the identity of the apoptotic cells can be determined by immunocytochemistry. Light microscopic immunocytochemistry using the mono-clonal antibodies OX-34 (CD2) and R73 (alpha beta T-cell receptor) revealed that 10% of the CD2+ cells and 5% of the alpha beta T lymphocytes in the parenchyma of the spinal cord were dying by apoptosis. The presence of apoptotic alpha beta T cells was confirmed by electron microscopy. About half of all the apoptotic cells within the spinal cord were labelled by these antibodies. It is possible that some of the unlabelled apoptotic cells were also T lymphocytes but that others were glial cells such as oligodendrocytes. One possible interpretation of this T-cell apoptosis is that it represents activation-induced cell death, which has recently been shown to provide a mechanism of clonal elimination of mature as well as immature autoreactive T cells. Another possible interpretation is that it is a result of corticosterone released during the course of EAE. The apoptotic elimination of target-antigen-specific lymphocytes within the target organ in this autoimmune disease may contribute to the subsidence of inflammation and, if ongoing, to the development of tolerance

Knowledge of pelvic floor problems: a study of third trimester, primiparous women

INTRODUCTION AND HYPOTHESIS: Pelvic floor problems in women (urinary incontinence, faecal incontinence, uterovaginal prolapse) are common, and have an adverse effect on quality of life. We hypothesized that there is low knowledge of these problems amongst primiparous women in their third trimester of pregnancy. METHODS: We conducted a cross-sectional study in antenatal clinics of three hospitals in London, UK, from 2011 to 2013. Primiparous women aged ≥18 years and in the third trimester of pregnancy answered questions on pelvic floor problems. Knowledge scores were calculated based on the proportion of questions answered correctly. RESULTS: A total of 249 women completed the question set. The average knowledge score across all domains was low at 45 %. Scores were lowest for the less common problems of faecal incontinence (35 %) and prolapse (36 %). The score for urinary incontinence was higher at 63 %, but low when questions explored more detailed levels of knowledge (41 %). Knowledge scores were positively associated with both education to tertiary level and the use of books as the information source on pregnancy and delivery. Only 35 % of women cited antenatal classes as a source. CONCLUSIONS: Knowledge of pelvic floor problems is low amongst third-trimester, primiparous women in this London-based population. Adequate knowledge of these problems is important for women to be able to make informed choices about their antenatal care and to seek help if problems arise. The data suggest scope for health-care professionals to raise these issues early during pregnancy, and to help women access accurate sources of information

Healthy Firms: Constraints to Growth among Private Health Sector Facilities in Ghana and Kenya

Background: Health outcomes in developing countries continue to lag the developed world, and many countries are not on target to meet the Millennium Development Goals. The private health sector provides much of the care in many developing countries (e.g., approximately 50 percent in Sub-Saharan Africa), but private providers are often poorly integrated into the health system. Efforts to improve health systems performance will need to include the private sector and increase its contributions to national health goals. However, the literature on constraints private health care providers face is limited. Methodology/Principal Findings: We analyze data from a survey of private health facilities in Kenya and Ghana to evaluate growth constraints facing private providers. A significant portion of facilities (Ghana: 62 percent; Kenya: 40 percent) report limited access to finance as the most significant barrier they face; only a small minority of facilities report using formal credit institutions to finance day to day operations (Ghana: 6 percent; Kenya: 11 percent). Other important barriers include corruption, crime, limited demand for goods and services, and poor public infrastructure. Most facilities have paper-based rather than electronic systems for patient records (Ghana: 30 percent; Kenya: 22 percent), accounting (Ghana: 45 percent; Kenya: 27 percent), and inventory control (Ghana: 41 percent; Kenya: 24 percent). A majority of clinics in both countries report undertaking activities to improve provider skills and to monitor the level and quality of care they provide. However, only a minority of pharmacies report undertaking such activities

P171Elevated free fetal haemoglobin threatens vasculoprotection in the fetal circulation of preeclamptic pregnancy

Placental up-regulation of free fetal haemoglobin (fHbF) occurs in preeclamptic (PE) pregnancy. Heme oxygenase-1 (HO-1) is an important vasculoprotective enzyme in the catabolism of the associated heme porphyrin structure. We have previously shown that fHbF negatively influences the vasculoprotective capacity of the fetal circulation. Here we study fHbF levels in the fetal cord blood of pregnancies complicated by PE; a pathology associated with dysregulated fetoplacental vascular tone. We have previously shown that fHbF binds nitric oxide (NO) to elicit elevated vascular resistance in the fetoplacental circulation, using ex vivo human dual placental perfusion and in vitro placental endothelial cell shear stress studies. Furthermore, fHbF causes morphological changes to the fetoplacental endothelium. Here we hypothesise that elevated levels of fHbF in fetal plasma associated with placental pathology contribute to fetoplacental hypertension. Purpose: To evaluate and derive a robust cord blood collection and processing protocol for the accurate measurement of fetal plasma fHbF levels in normal and PE pregnancies. Methods: Fetal venous cord blood was collected by syringe and needle, or Vacutainer method into either EDTA or citrate tubes, within 10 minutes of partum. Plasma recovery occurred immediately, or after 30 minutes, prior to centrifugation at 2000g x 10 min at room temperature. Following evaluation to reduce mechanical haemolysis, newly collected normal & PE plasma (n=13 & 6, respectively) was subjected to ELISAs for HbF and HO-1. Results: Venipuncture collection of cord venous blood taken from the cord-placenta insertion point by Vacutainer system with a 21G needle, into citrate collection tubes with immediate centrifugation prevented mechanical haemolysis. There was no difference in plasma HO-1 between groups (medians = 5.9 & 5.3 ng/mL; normal & PE, respectively; Mann-Whitney). Whilst there was no difference in fHbF between groups (Mann-Whitney), variability was high in the PE group and there were some very high values for fHbF compared to the normal range, whilst fHbF values in the control group were within a tighter lower range (medians & ranges = 45.9 & 0-206 and 118.8 & 29-640 μg/mL). Conclusion: Fetal plasma HO-1 levels appear stable in preeclamptic fetal plasma, permitting fHbF to remain unchecked in some cases. High pathophysiological levels of fHbF in some cases of PE pregnancies are capable of evoking elevated vascular resistance within the fetoplacental circulation, caused by nitric oxide sequestration and disruption to the endothelium. Further evaluation is require

Cost-benefit analysis of introducing next-generation sequencing (metagenomic) pathogen testing in the setting of pyrexia of unknown origin

Pyrexia of unknown origin (PUO) is defined as a temperature of >38.3°C that lasts for >3 weeks, where no cause can be found despite appropriate investigation. Existing protocols for the work-up of PUO can be extensive and costly, motivating the application of recent advances in molecular diagnostics to pathogen testing. There have been many reports describing various analytical methods and performance of metagenomic pathogen testing in clinical samples but the economics of it has been less well studied. This study pragmatically evaluates the feasibility of introducing metagenomic testing in this setting by assessing the relative cost of clinically-relevant strategies employing this investigative tool under various cost and performance scenarios using Singapore as a demonstration case, and assessing the price and performance benchmarks, which would need to be achieved for metagenomic testing to be potentially considered financially viable relative to the current diagnostic standard. This study has some important limitations: we examined only impact of introducing the metagenomic test to the overall diagnostic cost and excluded costs associated with hospitalization and makes assumptions about the performance of the routine diagnostic tests, limiting the cost of metagenomic test, and the lack of further work-up after positive pathogen detection by the metagenomic test. However, these assumptions were necessary to keep the model within reasonable limits. In spite of these, the simplified presentation lends itself to the illustration of the key insights of our paper. In general, we find the use of metagenomic testing as second-line investigation is effectively dominated, and that use of metagenomic testing at first-line would typically require higher rates of detection or lower cost than currently available in order to be justifiable purely as a cost-saving measure. We conclude that current conditions do not warrant a widespread rush to deploy metagenomic testing to resolve any and all uncertainty, but rather as a front-line technology that should be used in specific contexts, as a supplement to rather than a replacement for careful clinical judgement

Removal of steroid estrogens in carbonaceous and nitrifying activated sludge processes

This is the post-print version of the final paper published in Chemosphere. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2010 Elsevier B.V.A carbonaceous (heterotrophic) activated sludge process (ASP), nitrifying ASP and a nitrifying/denitrifying ASP have been studied to examine the role of process type in steroid estrogen removal. Biodegradation efficiencies for total steroid estrogens (ΣEST) of 80 and 91% were recorded for the nitrifying/denitrifying ASP and nitrifying ASP respectively. Total estrogen biodegradation (ΣEST) was only 51% at the carbonaceous ASP, however, the extent of biodegradation in the absence of nitrification clearly indicates the important role of heterotrophs in steroid estrogen removal. The low removal efficiency did not correlate with biomass activity for which the ASPcarbonaceous recorded 80 μg kg−1 biomass d−1 compared to 61 and 15 μg kg−1 biomass d−1 at the ASPnitrifying and ASPnitrifying/denitrifying respectively. This finding was explained by a moderate correlation (r2 = 0.55) between total estrogen loading (ΣEST mg m−3 d−1) and biomass activity (μg ΣEST degraded kg−1 d−1) and has established the impact of loading on steroid estrogen removal at full-scale. At higher solids retention time (SRT), steroid estrogen biodegradation of >80% was observed, as has previously been reported. It is postulated that hydraulic retention time (HRT) is as important as SRT as this governs both reaction time and loading. This observation is based on the high specific estrogen activity determined at the ASPcarbonaceous plant, the significance of estrogen loading and the positive linear correlation between SRT and HRT.Public Utilities Board of Singapore, Anglian Water Ltd., Severn Trent Water Ltd., Thames Water Utilities Ltd., United Utilities Plc., and Yorkshire Water Services Ltd

The combined diabetes and renal control trial (C-DIRECT) - a feasibility randomised controlled trial to evaluate outcomes in multi-morbid patients with diabetes and on dialysis using a mixed methods approach

Background: This cluster randomised controlled trial set out to investigate the feasibility and acceptability of the “Combined Diabetes and Renal Control Trial” (C-DIRECT) intervention, a nurse-led intervention based on motivational interviewing and self-management in patients with coexisting end stage renal diseases and diabetes mellitus (DM ESRD). Its efficacy to improve glycaemic control, as well as psychosocial and self-care outcomes were also evaluated as secondary outcomes. Methods: An assessor-blinded, clustered randomised-controlled trial was conducted with 44 haemodialysis patients with DM ESRD and ≥ 8% glycated haemoglobin (HbA1c), in dialysis centres across Singapore. Patients were randomised according to dialysis shifts. 20 patients were assigned to intervention and 24 were in usual care. The C-DIRECT intervention consisted of three weekly chair-side sessions delivered by diabetes specialist nurses. Data on recruitment, randomisation, and retention, and secondary outcomes such as clinical endpoints, emotional distress, adherence, and self-management skills measures were obtained at baseline and at 12 weeks follow-up. A qualitative evaluation using interviews was conducted at the end of the trial. Results: Of the 44 recruited at baseline, 42 patients were evaluated at follow-up. One patient died, and one discontinued the study due to deteriorating health. Recruitment, retention, and acceptability rates of C-DIRECT were generally satisfactory HbA1c levels decreased in both groups, but C-DIRECT had more participants with HbA1c < 8% at follow up compared to usual care. Significant improvements in role limitations due to physical health were noted for C-DIRECT whereas levels remained stable in usual care. No statistically significant differences between groups were observed for other clinical markers and other patient-reported outcomes. There were no adverse effects. Conclusions: The trial demonstrated satisfactory feasibility. A brief intervention delivered on bedside as part of routine dialysis care showed some benefits in glycaemic control and on QOL domain compared with usual care, although no effect was observed in other secondary outcomes. Further research is needed to design and assess interventions to promote diabetes self-management in socially vulnerable patients