Task sharing with non-physician health-care workers for management of blood pressure in low-income and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Task sharing for the management of hypertension could be useful for understaffed and resource-poor health systems. We assessed the effectiveness of task-sharing interventions in improving blood pressure control among adults in low-income and middle-income countries. METHODS: We searched the Cochrane Library, PubMed, Embase, and CINAHL for studies published up to December 2018. We included intervention studies involving a task-sharing strategy for management of blood pressure and other cardiovascular risk factors. We extracted data on population, interventions, blood pressure, and task sharing groups. We did a meta-analysis of randomised controlled trials. FINDINGS: We found 3012 references, of which 54 met the inclusion criteria initially. Another nine studies were included following an updated search. There were 43 trials and 20 before-and-after studies. We included 31 studies in our meta-analysis. Systolic blood pressure was decreased through task sharing in different groups of health-care workers: the mean difference was -5·34 mm Hg (95% CI -9·00 to -1·67, I2=84%) for task sharing with nurses, -8·12 mm Hg (-10·23 to -6·01, I2=57%) for pharmacists, -4·67 mm Hg (-7·09 to -2·24, I2=0%) for dietitians, -3·67 mm Hg (-4·58 to -2·77, I2=24%) for community health workers, and -4·85 mm Hg (-6·12 to -3·57, I2=76%) overall. We found a similar reduction in diastolic blood pressure (overall mean difference -2·92 mm Hg, -3·75 to -2·09, I2=80%). The overall quality of evidence based on GRADE criteria was moderate for systolic blood pressure, but low for diastolic blood pressure. INTERPRETATION: Task-sharing interventions are effective in reducing blood pressure. Long-term studies are needed to understand their potential impact on cardiovascular outcomes and mortality. FUNDING: Wellcome Trust/DBT India Alliance

Task-sharing interventions for cardiovascular risk reduction and lipid outcomes in low- and middle-income countries: A systematic review and meta-analysis.

BACKGROUND: One of the potential strategies to improve health care delivery in understaffed low- and middle-income countries (LMICs) is task sharing, where specific tasks are transferred from more qualified health care cadre to a lesser trained cadre. Dyslipidemia is a major risk factor for cardiovascular disease but often it is not managed appropriately. OBJECTIVE: We conducted a systematic review with the objective to identify and evaluate the effect of task sharing interventions on dyslipidemia in LMICs. METHODS: Published studies (randomized controlled trials and observational studies) were identified via electronic databases such as PubMed, Embase, Cochrane Library, PsycINFO, and CINAHL. We searched the databases from inception to September 2016 and updated till 30 June 2017, using search terms related to task shifting, and cardiovascular disease prevention in LMICs. All eligible studies were summarized narratively, and potential studies were grouped for meta-analysis. RESULTS: Although our search yielded 2938 records initially and another 1628 in the updated search, only 15 studies met the eligibility criteria. Most of the studies targeted lifestyle modification and care coordination by involving nurses or allied health workers. Eight randomized controlled trials were included in the meta-analysis. Task sharing intervention were effective in lowering low-density lipoprotein cholesterol (-6.90 mg/dL; 95% CI -11.81 to -1.99) and total cholesterol (-9.44 mg/dL; 95% CI -17.94 to -0.93) levels with modest effect size. However, there were no major differences in high-density lipoprotein cholesterol (-0.29 mg/dL; 95% CI -0.88 to 1.47) and triglycerides (-14.31 mg/dL; 95% CI -33.32 to 4.69). The overall quality of evidence based on Grading of Recommendations Assessment, Development and Evaluation was either "low" or "very low". CONCLUSION: Available data are not adequate to make recommendations on the role of task sharing strategies for the management of dyslipidemia in LMICs. However, the studies conducted in LMICs demonstrate the potential use of this strategy especially in terms of reduction in low-density lipoprotein cholesterol and total cholesterol levels. Our review calls for the need of well-designed and large-scale studies to demonstrate the effect of task-sharing strategy on lipid management in LMICs

Stage progression and neurological symptoms in Trypanosoma brucei rhodesiense sleeping sickness: role of the CNS inflammatory response

Background: Human African trypanosomiasis progresses from an early (hemolymphatic) stage, through CNS invasion to the late (meningoencephalitic) stage. In experimental infections disease progression is associated with neuroinflammatory responses and neurological symptoms, but this concept requires evaluation in African trypanosomiasis patients, where correct diagnosis of the disease stage is of critical therapeutic importance. Methodology/Principal Findings: This was a retrospective study on a cohort of 115 T.b.rhodesiense HAT patients recruited in Eastern Uganda. Paired plasma and CSF samples allowed the measurement of peripheral and CNS immunoglobulin and of CSF cytokine synthesis. Cytokine and immunoglobulin expression were evaluated in relation to disease duration, stage progression and neurological symptoms. Neurological symptoms were not related to stage progression (with the exception of moderate coma). Increases in CNS immunoglobulin, IL-10 and TNF-α synthesis were associated with stage progression and were mirrored by a reduction in TGF-β levels in the CSF. There were no significant associations between CNS immunoglobulin and cytokine production and neurological signs of disease with the exception of moderate coma cases. Within the study group we identified diagnostically early stage cases with no CSF pleocytosis but intrathecal immunoglobulin synthesis and diagnostically late stage cases with marginal CSF pleocytosis and no detectable trypanosomes in the CSF. Conclusions: Our results demonstrate that there is not a direct linkage between stage progression, neurological signs of infection and neuroinflammatory responses in rhodesiense HAT. Neurological signs are observed in both early and late stages, and while intrathecal immunoglobulin synthesis is associated with neurological signs, these are also observed in cases lacking a CNS inflammatory response. While there is an increase in inflammatory cytokine production with stage progression, this is paralleled by increases in CSF IL-10. As stage diagnostics, the CSF immunoglobulins and cytokines studied do not have sufficient sensitivity to be of clinical value

CD98hc facilitates B cell proliferation and adaptive humoral immunity.

The proliferation of antigen-specific lymphocytes and resulting clonal expansion are essential for adaptive immunity. We report here that B cell-specific deletion of the heavy chain of CD98 (CD98hc) resulted in lower antibody responses due to total suppression of B cell proliferation and subsequent plasma cell formation. Deletion of CD98hc did not impair early B cell activation but did inhibit later activation of the mitogen-activated protein kinase Erk1/2 and downregulation of the cell cycle inhibitor p27. Reconstitution of CD98hc-deficient B cells with CD98hc mutants showed that the integrin-binding domain of CD98hc was required for B cell proliferation but that the amino acid-transport function of CD98hc was dispensable for this. Thus, CD98hc supports integrin-dependent rapid proliferation of B cells. We propose that the advantage of adaptive immunity favored the appearance of CD98hc in vertebrates

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

Guidelines for the labelling of leucocytes with 111In-oxine

We describe here a protocol for labelling autologous white blood cells with 111In-oxine based on previously published consensus papers and guidelines. This protocol includes quality control and safety procedures and is in accordance with current European Union regulations and International Atomic Energy Agency recommendations

The Seroprevalence and Seroincidence of Enterovirus71 Infection in Infants and Children in Ho Chi Minh City, Viet Nam

Enterovirus 71 (EV71)-associated hand, foot and mouth disease has emerged as a serious public health problem in South East Asia over the last decade. To better understand the prevalence of EV71 infection, we determined EV71 seroprevalence and seroincidence amongst healthy infants and children in Ho Chi Minh City, Viet Nam. In a cohort of 200 newborns, 55% of cord blood samples contained EV71 neutralizing antibodies and these decayed to undetectable levels by 6 months of age in 98% of infants. The EV71 neutralizing antibody seroconversion rate was 5.6% in the first year and 14% in the second year of life. In children 5–15 yrs of age, seroprevalence of EV71 neutralizing antibodies was 84% and in cord blood it was 55%. Taken together, these data suggest EV71 force of infection is high and highlights the need for more research into its epidemiology and pathogenesis in high disease burden countries

The role of potential vorticity anomalies in the Somali Jet on Indian summer monsoon intraseasonal variability

The climate of the Indian subcontinent is dominated by rainfall arising from the Indian summer monsoon (ISM) during the summer season (June to September). Intraseasonal variability during the monsoon is characterized by periods of heavy rainfall interspersed by drier periods, known as active and break events respectively. Understanding and predicting such events is of vital importance for forecasting human impacts such as water resources. The Somali Jet is a key regional feature of this circulation. In the present study, we find that the spatial structure of Somali Jet potential vorticity (PV) anomalies varies considerably during active and break periods. Analysis of these anomalies shows a mechanism whereby sea surface temperature (SST) anomalies propagate north/northwestwards through the Arabian Sea, caused by a positive feedback loop joining anomalies in SST, convection, modification of PV by diabatic heating and mixing in the atmospheric boundary layer, wind stress curl, and upwelling processes. The feedback mechanism is consistent with observed coupled ocean-atmosphere system variability timescales of approximately 20 days. This research suggests that better understanding and prediction of monsoon subseasonal variability in the South Asian monsoon may be gained by analysis of the day-to-day dynamical evolution of PV in the Somali Jet