A mixed methods approach to evaluating community drug distributor performance in the control of neglected tropical diseases

BACKGROUND: Trusted literate, or semi-literate, community drug distributors (CDDs) are the primary implementers in integrated preventive chemotherapy (IPC) programmes for Neglected Tropical Disease (NTD) control. The CDDs are responsible for safely distributing drugs and for galvanising communities to repeatedly, often over many years, receive annual treatment, create and update treatment registers, monitor for side-effects and compile treatment coverage reports. These individuals are 'volunteers' for the programmes and do not receive remuneration for their annual work commitment. METHODS: A mixed methods approach, which included pictorial diaries to prospectively record CDD use of time, structured interviews and focus group discussions, was used to triangulate data on how 58 CDDs allocated their time towards their routine family activities and to NTD Programme activities in Uganda. The opportunity costs of CDD time were valued, performance assessed by determining the relationship between time and programme coverage, and CDD motivation for participating in the programme was explored. RESULTS: Key findings showed approximately 2.5 working weeks (range 0.6-11.4 working weeks) were spent on NTD Programme activities per year. The amount of time on NTD control activities significantly increased between the one and three deliveries that were required within an IPC campaign. CDD time spent on NTD Programme activities significantly reduced time available for subsistence and income generating engagements. As CDDs took more time to complete NTD Programme activities, their treatment performance, in terms of validated coverage, significantly decreased. Motivation for the programme was reported as low and CDDs felt undervalued. CONCLUSIONS: CDDs contribute a considerable amount of opportunity cost to the overall economic cost of the NTD Programme in Uganda due to the commitment of their time. Nevertheless, programme coverage of at least 75 %, as required by the World Health Organisation, is not being achieved and vulnerable individuals may not have access to treatment as a consequence of sub-optimal performance by the CDDs due to workload and programmatic factors

The frequency of osteogenic activities and the pattern of intermittence between periods of physical activity and sedentary behaviour affects bone mineral content: the cross-sectional NHANES study

BACKGROUND: Sedentary behaviours, defined as non exercising seated activities, have been shown to have deleterious effects on health. It has been hypothesised that too much sitting time can have a detrimental effect on bone health in youth. The aim of this study is to test this hypothesis by exploring the association between objectively measured volume and patterns of time spent in sedentary behaviours, time spent in specific screen-based sedentary pursuits and bone mineral content (BMC) accrual in youth. METHODS: NHANES 2005–2006 cycle data includes BMC of the femoral and spinal region via dual-energy X-ray absorptiometry (DEXA), assessment of physical activity and sedentary behaviour patterns through accelerometry, self reported time spent in screen based pursuits (watching TV and using a computer), and frequency of vigorous playtime and strengthening activities. Multiple regression analysis, stratified by gender was performed on N = 671 males and N = 677 females aged from 8 to 22 years. RESULTS: Time spent in screen-based sedentary behaviours is negatively associated with femoral BMC (males and females) and spinal BMC (females only) after correction for time spent in moderate and vigorous activity. Regression coefficients indicate that an additional hour per day of screen-based sitting corresponds to a difference of −0.77 g femoral BMC in females [95% CI: -1.31 to −0.22] and of −0.45 g femoral BMC in males [95% CI: -0.83 to −0.06]. This association is attenuated when self-reported engagement in regular (average 5 times per week) strengthening exercise (for males) and vigorous playing (for both males and females) is taken into account. Total sitting time and non screen-based sitting do not appear to have a negative association with BMC, whereas screen based sedentary time does. Patterns of intermittence between periods of sitting and moderate to vigorous activity appears to be positively associated with bone health when activity is clustered in time and inter-spaced with long continuous bouts of sitting. CONCLUSIONS: Some specific sedentary pursuits (screen-based) are negatively associated with bone health in youth. This association is specific to gender and anatomical area. This relationship between screen-based time and bone health is independent of the total amount of physical activity measured objectively, but not independent of self-reported frequency of strengthening and vigorous play activities. The data clearly suggests that the frequency, rather than the volume, of osteogenic activities is important in counteracting the effect of sedentary behaviour on bone health. The pattern of intermittence between sedentary periods and activity also plays a role in bone accrual, with clustered short bouts of activity interspaced with long periods of sedentary behaviours appearing to be more beneficial than activities more evenly spread in time

Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 × 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10(-3); combined P = 1.00 × 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions

Intracellular coexpression of CXC- and CC– chemokine receptors and their ligands in human melanoma cell lines and dynamic variations after xenotransplantation

BackgroundChemokines have been implicated in tumor progression and metastasis. In melanoma, chemokine receptors have been implicated in organ selective metastasis by regulating processes such as chemoattraction, adhesion and survival.MethodsIn this study we have analyzed, using flow cytometry, the systems formed by the chemokine receptors CXCR3, CXCR4, CXCR7, CCR7 and CCR10 and their ligands in thirteen human melanoma cell lines (five established from primary tumors and eight established from metastasis from different tissues). WM-115 and WM-266.4 melanoma cell lines (obtained from a primary and a metastatic melanoma respectively) were xenografted in nude mice and the tumors and cell lines derived from them were also analyzed.ResultsOur results show that the melanoma cell lines do not express or express in a low degree the chemokine receptors on their cell surface. However, melanoma cell lines show intracellular expression of all the aforementioned receptors and most of their respective ligands. When analyzing the xenografts and the cell lines obtained from them we found variations in the intracellular expression of chemokines and chemokine receptors that differed between the primary and metastatic cell lines. However, as well as in the original cell lines, minute or no expression of the chemokine receptors was observed at the cell surface.ConclusionsCoexpression of chemokine receptors and their ligands was found in human melanoma cell lines. However, this expression is intracellular and receptors are not found at the cell membrane nor chemokines are secreted to the cell medium. The levels of expressed chemokine receptors and their ligands show dynamic variations after xenotransplantation that differ depending on the origin of the cell line (from primary tumor or from metastasis)

A qualitative study of professional and client perspectives on information flows and decision aid use

<p>Abstract</p> <p>Background</p> <p>This paper explores the meanings given by a diverse range of stakeholders to a decision aid aimed at helping carers of people in early to moderate stages of dementia (PWD) to select community based respite services. Decision aids aim to empower clients to share decision making with health professionals. However, the match between health professionals' perspectives on decision support needs and their clients' perspective is an important and often unstudied aspect of decision aid use.</p> <p>Methods</p> <p>A secondary analysis was undertaken of qualitative data collected as part of a larger study. The data included twelve interviews with carers of people with dementia, three interviews with expert advisors, and three focus groups with health professionals. A theoretical analysis was conducted, drawing on theories of 'positioning' and professional identity.</p> <p>Results</p> <p>Health professionals are seen to hold varying attitudes and beliefs about carers' decision support needs, and these appeared to be grounded in the professional identity of each group. These attitudes and beliefs shaped their attitudes towards decision aids, the information they believed should be offered to dementia carers, and the timing of its offering. Some groups understood carers as needing to be protected from realistic information and consequently saw a need to filter information to carer clients.</p> <p>Conclusion</p> <p>Health professionals' beliefs may cause them to restrict information flows, which can limit carers' ability to make decisions, and limit health services' ability to improve partnering and shared decision making. In an era where information is freely available to those with the resources to access it, we question whether health professionals should filter information.</p

Comparison of endothelial progenitor cell function in type 2 diabetes with good and poor glycemic control

<p>Abstract</p> <p>Background</p> <p>Endothelial progenitor cells (EPCs) play an important role in vascular repair and a decrease in the number of EPCs is observed in type 2 diabetes. However, there is no report on the change of EPCs after glycemic control. This study therefore aimed to investigate the EPC number and function in patients with good and poor glycemic control.</p> <p>Methods</p> <p>The number of EPCs was studied using flow cytometry by co-expression of CD34 and VEGFR2. The EPCs were cultured and characterized by the expression of UEA-I, CD34, VEGFR2, vWF and Dil-Ac-LDL engulfment, as well as the ability to form capillary-like structures. An <it>in vitro </it>study on the effect of hyperglycemia on the proliferation and viability of the cultured EPCs was also performed.</p> <p>Results</p> <p>The number of EPCs in type 2 diabetes was significantly decreased compared with healthy controls and there was an inverse correlation between the EPC numbers and plasma glucose, as well as HbA1_C. The number and function of EPCs in patients with good glycemic control were recovered compared with those with poor glycemic control. When glucose was supplemented in the culture <it>in vitro</it>, there was a negative effect on the proliferation and viability of EPCs, in a dose-dependent manner, whereas the enhancement of apoptosis was observed.</p> <p>Conclusion</p> <p>There was EPC dysfunction in type 2 diabetes which might be improved by strict glycemic control. However, the circulating EPC number and proliferative function in patients with good glycemic control did not reach the level in healthy controls.</p

The relation between amyotrophic lateral sclerosis and inorganic selenium in drinking water: a population-based case-control study

<p>Abstract</p> <p>Background</p> <p>A community in northern Italy was previously reported to have an excess incidence of amyotrophic lateral sclerosis among residents exposed to high levels of inorganic selenium in their drinking water.</p> <p>Methods</p> <p>To assess the extent to which such association persisted in the decade following its initial observation, we conducted a population-based case-control study encompassing forty-one newly-diagnosed cases of amyotrophic lateral sclerosis and eighty-two age- and sex-matched controls. We measured long-term intake of inorganic selenium along with other potentially neurotoxic trace elements.</p> <p>Results</p> <p>We found that consumption of drinking water containing ≥ 1 μg/l of inorganic selenium was associated with a relative risk for amyotrophic lateral sclerosis of 5.4 (95% confidence interval 1.1-26) after adjustment for confounding factors. Greater amounts of cumulative inorganic selenium intake were associated with progressively increasing effects, with a relative risk of 2.1 (95% confidence interval 0.5-9.1) for intermediate levels of cumulative intake and 6.4 (95% confidence interval 1.3-31) for high intake.</p> <p>Conclusion</p> <p>Based on these results, coupled with other epidemiologic data and with findings from animal studies that show specific toxicity of the trace element on motor neurons, we hypothesize that dietary intake of inorganic selenium through drinking water increases the risk for amyotrophic lateral sclerosis.</p

Temporal changes in key maternal and fetal factors affecting birth outcomes: A 32-year population-based study in an industrial city

<p>Abstract</p> <p>Background</p> <p>The link between maternal factors and birth outcomes is well established. Substantial changes in society and medical care over time have influenced women's reproductive choices and health, subsequently affecting birth outcomes. The objective of this study was to describe temporal changes in key maternal and fetal factors affecting birth outcomes in Newcastle upon Tyne over three decades, 1961–1992.</p> <p>Methods</p> <p>For these descriptive analyses we used data from a population-based birth record database constructed for the historical cohort <b>Pa</b>rticulate <b>M</b>atter and <b>P</b>erinatal <b>E</b>vents <b>R</b>esearch (PAMPER) study. The PAMPER database was created using details from paper-based hospital delivery and neonatal records for all births during 1961–1992 to mothers resident in Newcastle (out of a total of 109,086 singleton births, 97,809 hospital births with relevant information). In addition to hospital records, we used other sources for data collection on births not included in the delivery and neonatal records, for death and stillbirth registrations and for validation.</p> <p>Results</p> <p>The average family size decreased mainly due to a decline in the proportion of families with 3 or more children. The distribution of mean maternal ages in all and in primiparous women was lowest in the mid 1970s, corresponding to a peak in the proportion of teenage mothers. The proportion of older mothers declined until the late 1970s (from 16.5% to 3.4%) followed by a steady increase. Mean birthweight in all and term babies gradually increased from the mid 1970s. The increase in the percentage of preterm birth paralleled a two-fold increase in the percentage of caesarean section among preterm births during the last two decades. The gap between the most affluent and the most deprived groups of the population widened over the three decades.</p> <p>Conclusion</p> <p>Key maternal and fetal factors affecting birth outcomes, such as maternal age, parity, socioeconomic status, birthweight and gestational age, changed substantially during the 32-year period, from 1961 to 1992. The availability of accurate gestational age is extremely important for correct interpretation of trends in birthweight.</p

Chronic Methamphetamine Administration Causes Differential Regulation of Transcription Factors in the Rat Midbrain

Methamphetamine (METH) is an addictive and neurotoxic psychostimulant widely abused in the USA and throughout the world. When administered in large doses, METH can cause depletion of striatal dopamine terminals, with preservation of midbrain dopaminergic neurons. Because alterations in the expression of transcription factors that regulate the development of dopaminergic neurons might be involved in protecting these neurons after toxic insults, we tested the possibility that their expression might be affected by toxic doses of METH in the adult brain. Male Sprague-Dawley rats pretreated with saline or increasing doses of METH were challenged with toxic doses of the drug and euthanized two weeks later. Animals that received toxic METH challenges showed decreases in dopamine levels and reductions in tyrosine hydroxylase protein concentration in the striatum. METH pretreatment protected against loss of striatal dopamine and tyrosine hydroxylase. In contrast, METH challenges caused decreases in dopamine transporters in both saline- and METH-pretreated animals. Interestingly, METH challenges elicited increases in dopamine transporter mRNA levels in the midbrain in the presence but not in the absence of METH pretreatment. Moreover, toxic METH doses caused decreases in the expression of the dopamine developmental factors, Shh, Lmx1b, and Nurr1, but not in the levels of Otx2 and Pitx3, in saline-pretreated rats. METH pretreatment followed by METH challenges also decreased Nurr1 but increased Otx2 and Pitx3 expression in the midbrain. These findings suggest that, in adult animals, toxic doses of METH can differentially influence the expression of transcription factors involved in the developmental regulation of dopamine neurons. The combined increases in Otx2 and Pitx3 expression after METH preconditioning might represent, in part, some of the mechanisms that served to protect against METH-induced striatal dopamine depletion observed after METH preconditioning