Community perceptions of community health worker effectiveness: Contributions to health behaviour change in an urban health district in South Africa.

BACKGROUND: Community health worker (CHW) programmes contribute towards strengthening adherence support, improving maternal and child health outcomes and providing support for social services. They play a valuable role in health behaviour change in vulnerable communities. Large-scale, comprehensive CHW programmes at health district level are part of a South African (SA) strategy to re-engineer primary healthcare and take health directly into communities and households, contributing to universal health coverage. OBJECTIVE: These CHW programmes across health districts were introduced in SA in 2010 - 11. Their overall purpose is to improve access to healthcare and encourage healthy behaviour in vulnerable communities, through community and family engagements, leading to less disease and better population health. Communities therefore need to accept and support these initiatives. There is, however, inadequate local evidence on community perceptions of the effectiveness of such programmes. METHODS: A cross-sectional descriptive study to determine community perceptions of the role and contributions of the CHW programme was conducted in the Ekurhuleni health district, an urban metropolis in SA. Members from 417 households supported by CHWs were interviewed in May 2019 by retired nurses used as fieldworkers. Frequencies and descriptive analyses were used to report on the main study outcomes of community acceptance and satisfaction. RESULTS: Nearly all the study households were poor and had at least one vulnerable member, either a child under 5, an elderly person, a pregnant woman or someone with a chronic condition. CHWs had supported these households for 2 years or longer. More than 90% of households were extremely satisfied with their CHW; they found it easy to talk to them within the privacy of their homes and to follow the health education and advice given by the CHWs. The community members highly rated care for chronic conditions (82%), indicated that children were healthier (41%) and had safer pregnancies (6%). CONCLUSION: As important stakeholders in CHW programmes, exploring community acceptance, appreciation and support is critical in understanding the drivers of programme performance. Community acceptance of the CHWs in the Ekurhuleni health district was high. The perspective of the community was that the CHWs were quite effective. This was demonstrated when they reported changes in household behaviour with regard to improved access to care through early screening, referrals and improved management of chronic and other conditions.

Effectiveness of a large-scale, sustained and comprehensive community health worker program in improving population health: the experience of an urban health district in South Africa.

INTRODUCTION: South Africa is an upper middle-income country with wide wealth inequality. It faces a quadruple burden of disease and poor health outcomes, with access to appropriate and adequate health care a challenge for millions of South Africans. The introduction of large-scale, comprehensive community health worker (CHW) programs in the country, within the context of implementing universal health coverage, was anticipated to improve population health outcomes. However, there is inadequate local (or global) evidence on whether such programs are effective, especially in urban settings. METHODS: This study is part of a multi-method, quasi-experimental intervention study measuring effectiveness of a large-scale CHW program in a health district in an urban province of South Africa, where CHWs now support approximately one million people in 280,000 households. Using interviewer administered questionnaires, a 2019 cross-sectional survey of 417 vulnerable households with long-term CHW support (intervention households) are compared to 417 households with no CHW support (control households). Households were selected from similar vulnerable areas from all sub-levels of the Ekurhuleni health district. RESULTS: The 417 intervention and control households each had good health knowledge. Compared to controls, intervention households with long-term comprehensive CHW support were more likely to access early care, get diagnosed for a chronic condition, be put on treatment and be well controlled on chronic treatment. They were also more likely to receive a social grant, and have a birth certificate or identity document. The differences were statistically significant for social support, health seeking behavior, and health outcomes for maternal, child health and chronic care. CONCLUSION: A large-scale and sustained comprehensive CHW program in an urban setting improved access to social support, chronic and minor acute health services at household and population level through better health-seeking behavior and adherence to treatment. Direct evidence from households illustrated that such community health worker programs are therefore effective and should be part of health systems in low- and middle-income countries.

An analysis of the services provided by community health workers within an urban district in South Africa: a key contribution towards universal access to care.

INTRODUCTION: Community health worker teams are potential game-changers in ensuring access to care in vulnerable communities. Who are they? What do they actually do? Can they help South Africa realize universal health coverage? As the proactive arm of the health services, community health workers teams provide household and community education, early screening, tracing and referrals for a range of health and social services. There is little local or global evidence on the household services provided by such teams, beyond specific disease-oriented activities such as for HIV and TB. This paper seeks to address this gap. METHODS: Descriptive secondary data analysis of community health worker team activities in the Ekurhuleni health district, South Africa covering approximately 280,000 households with 1 million people. RESULTS: Study findings illustrated that community health workers in these teams provided early screening and referrals for pregnant women and children under five. They distributed condoms and chronic medication to homes. They screened and referred for hypertension, diabetes mellitus, HIV and TB. The teams also undertook defaulter and contact tracing, the majority of which was for HIV and TB clients. Psychosocial support provided was in the form of access to social grants, access to child and gender-based violence protection services, food parcels and other services. CONCLUSION: Community health workers form the core of these teams and perform several health and psychosocial services in households and poor communities in South Africa, in addition to general health education. The teams studied provided a range of activities across many health conditions (mother and child related, HIV and TB, non-communicable diseases), as well as social services. These teams provided comprehensive care in a large-scale urban setting and can improve access to care.

Tumor Biology as Predictor of Mortality in Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor, with the Milan criteria considered to be the gold standard for patient selection for liver transplantation (LT). MATERIALS AND METHODS: We performed a descriptive observational study, reviewing 20 years of experience of LT in patients with HCC in the Fundacion Valle del Lilí in Cali, Colombia. Subgroup analysis was undertaken for periods 1999 to 2007 and 2008 to 2015. RESULTS: Fifty-seven cases with a pretransplant HCC diagnosis were reviewed. In the first period patients within the Milan criteria had a recurrence-free survival at 5 years of 66.6%, and in those who exceeded the Milan criteria, recurrence-free survival was 75%. In the second period, patients within the Milan criteria, recurrence-free survival at 5 years was 93.5%, and in those who exceeded the Milan criteria, recurrence-free survival was 75.7%. No statistically significant difference was found in either period. For patients with mild and moderate tumor differentiation, the relapse survival rate at 5 years was 69.4% (95% confidence interval [CI] 35.8-87.8) and 74.7% (95% CI 44.5-90), respectively. All patients with poor tumor differentiation relapsed and died within 3 years. CONCLUSION: Global and recurrence-free survival among patients who met and patients who exceeded the Milan criteria was not significantly different, suggesting an expansion of the Milan criteria to include potential recipients who were previously excluded. Obtaining histologic differentiation and identifying vascular invasion will provide a more worthwhile contribution to LT decision making.

Nucleophilic addition of potassium alkynyltrifluoroborates to D-glucal mediated by BF3 x OEt2: highly stereoselective synthesis of alpha-C-glycosides.

A convenient, mild and highly stereoselective method for C-glycosidation (alkynylation) of D-glucal with various potassium alkynyltrifluoroborates, mediated by BF3x OEt2 and involving oxonium intermediates, preferentially provides the alpha-acetylene glycoside products with good yields.

Selective androgen receptor modulators based on a series of 7H-[1,4]oxazino[3,2-g]quinolin-7-ones with improved in vivo activity.

Modification on a lead series of [1,4]oxazino[3,2-g]quinolin-7-ones at the 2-position led to selective androgen receptor modulators with improved in vivo activity. The most potent analog (-)-33a exhibited full maintenance of levator ani muscle at 3mg/kg and reduced activity on ventral prostate weight in a 2-week orally-dosed and orchidectomized rat maintenance assay.

Substituted 6-(1-pyrrolidine)quinolin-2(1H)-ones as novel selective androgen receptor modulators.

The androgen receptor is a ligand inducible transcription factor that is involved in a broad range of physiological functions. Here we describe the discovery of a new class of orally available selective androgen receptor modulators. The lead compound, 6-[(2R,5R)-2-methyl-5-((R)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl]-4-trifluoromethylquinolin-2(1H)-one (6a), showed excellent anabolic activity in muscle with reduced effect on the prostate in a rat model of hypogonadism. The compound also improved bone strength in a rat model of post-menopausal osteoporosis.

Glutamate release inhibiting properties of the novel mGlu(5) receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP): complementary in vitro and in vivo evidence.

We have previously demonstrated that neuronal release of the excitatory amino acid glutamate is facilitated by the selective activation of presynaptic Group I metabotropic autoreceptors. Here we report the release inhibiting actions of the novel mGlu(5) receptor-selective antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), both in vitro and in vivo. These data provide compelling evidence for the presence of functional positive modulatory mGlu(5) subtype autoreceptors in the mammalian central nervous system.

Endogenous sulphur-containing amino acids: potent agonists at presynaptic metabotropic glutamate autoreceptors in the rat central nervous system.

We have recently demonstrated that presynaptically located metabotropic glutamate (mGlu) autoreceptors regulate synaptic glutamate release both in vitro and in vivo. We now report a positive modulatory action of the sulphur-containing amino acids (SCAAs), L-cysteic acid (CA) and L-cysteine sulphinic acid (CSA), at presynaptic group I mGlu receptors, specifically of the mGlu5 subtype, acting to enhance synaptic glutamate release from the rat forebrain in vitro. Neuronal glutamate release was monitored using electrically-evoked efflux of preloaded [(3)H]-D-aspartate from rat forebrain hemisections. Both CA (3 - 100 muM) and CSA (1 - 100 microM), in addition to the selective group I mGlu receptor agonist, (S)-3,5-dihydroxyphenylglycine ((S)-DHPG), concentration-dependently enhanced electrically-stimulated efflux of [(3)H]-D-aspartate from the rat forebrain slices. Basal efflux of label remained unchanged. The inhibitory activity of the broad spectrum mGlu receptor antagonist, (+/-)-alpha-methyl-4-carboxyphenylglycine ((+/-)-MCPG; 200 microM), coupled with the inactivity of the selective mGlu1 receptor antagonists, (R,S)-1-aminoindan-1,5-dicarboxylic acid ((R,S)-AIDA; 100 - 500 microM) and the more potent (+)-2-methyl-4-carboxyphenylglycine (LY367385; 10 microM) against these responses, indicates an action of the SCAAs at the mGlu5 receptor subtype. This proposal is supported by the potent inhibition of these responses by the selective, non-competitive mGlu5 receptor antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 10 microM). The observed enhancement of the responses to high concentrations of CA by the selective mGlu5 receptor desensitization inhibitor, cyclothiazide (CYZ; 10 microM), is also consistent with this concept. Administration of the agonists in the presence of bovine serum albumin (BSA; 5 - 15 mg ml(-1)) markedly attenuated the positive modulatory responses observed, strongly supporting a role for arachidonic acid in the expression of these mGlu5 receptor-mediated responses. The regulatory actions of SCAAs on synaptic glutamate release demonstrated in the present study may provide a physiological function for these putative neurotransmitter amino acids in the mammalian brain. These central actions of the SCAAs may have wide-ranging implications for a range of neurological and neuropsychiatric disease states and their treatment.

Decreased expression of Toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide.

The lumenal surface of the colonic epithelium is continually exposed to Gram-negative commensal bacteria and LPS. Recognition of LPS by Toll-like receptor (TLR)-4 results in proinflammatory gene expression in diverse cell types. Normally, however, commensal bacteria and their components do not elicit an inflammatory response from intestinal epithelial cells (IEC). The aim of this study is to understand the molecular mechanisms by which IEC limit chronic activation in the presence of LPS. Three IEC lines (Caco-2, T84, HT-29) were tested for their ability to activate an NF-kappaB reporter gene in response to purified, protein-free LPS. No IEC line responded to LPS, whereas human dermal microvessel endothelial cells (HMEC) did respond to LPS. IEC responded vigorously to IL-1beta in this assay, demonstrating that the IL-1 receptor signaling pathway shared by TLRs was intact. To determine the reason for LPS hyporesponsiveness in IEC, we examined the expression of TLR4 and MD-2, a critical coreceptor for TLR4 signaling. IEC expressed low levels of TLR4 compared with HMEC and none expressed MD-2. To determine whether the low level of TLR4 expression or absent MD-2 was responsible for the LPS signaling defect in IEC, the TLR4 or MD-2 gene was transiently expressed in IEC lines. Transient transfection of either gene individually was not sufficient to restore LPS signaling, but cotransfection of TLR4 and MD-2 in IEC led to synergistic activation of NF-kappaB and IL-8 reporter genes in response to LPS. We conclude that IEC limit dysregulated LPS signaling by down-regulating expression of MD-2 and TLR4. The remainder of the intracellular LPS signaling pathway is functionally intact.

Metabotropic glutamate autoreceptors of the mGlu(5) subtype positively modulate neuronal glutamate release in the rat forebrain in vitro.

In the present study we have examined the role of presynaptic group I metabotropic glutamate (mGlu) receptors in the control of neuronal glutamate release using rat forebrain slices pre-loaded with [(3)H]D-aspartate. We have also addressed the question of which group I mGlu receptor subtype, mGlu(1) or mGlu(5), mediates the facilitatory response observed by the use of a range of established and some more novel agonists and antagonists showing selectivity for these receptors. The electrically-stimulated release of pre-loaded [(3)H]D-aspartate from rat forebrain slices was markedly potentiated by the potent group I mGlu receptor agonist, L-quisqualic acid (L-QUIS), in a concentration-dependent manner (EC(50) 17.31 microM). This response was inhibited by the mGlu receptor antagonists (S)-MCPG (100 microM) and (RS)-MTPG (100 microM) but not by the AMPA-type ionotropic glutamate receptor antagonist, NBQX (100 microM). The selective group I mGlu receptor agonist (S)-3, 5-dihydroxyphenylglycine ((S)-DHPG) also enhanced electrically-stimulated efflux of label, although responses diminished with high (10-100 microM) concentrations of the agonist. Maximum responses were fully restored when (S)-DHPG (10 microM) was applied in the presence of the proposed mGlu(5) receptor desensitization inhibitor, cyclothiazide (10 microM). The positive modulatory response to (S)-DHPG (1 microM) was powerfully inhibited by (S)-MCPG (IC(50) 0.08 microM) but was resistant to the mGlu(1) receptor antagonists, (RS)-AIDA (1-500 microM), CPCCOEt (0.1-100 microM) and (+)-2-methyl-4-carboxyphenylglycine (LY367385) (0.1-10 microM). The recently developed, selective mGlu(5) receptor agonist (RS)-2-chloro-5-hydroxyphenylglycine ((RS)-CHPG) enhanced electrically-stimulated [(3)H]D-aspartate efflux from rat forebrain slices with a similar concentration-response profile to that of (S)-DHPG. Responses to this receptor subtype-selective agonist were also blocked by (S)-MCPG (IC(50) 1.13 microM) but were unaffected by (RS)-AIDA (500 microM), CPCCOEt (100 microM) or LY367385 (10 microM). These results indicate that the positive modulation of neuronal glutamate release seen in the rat forebrain in the presence of group I mGlu receptor agonists is mediated by presynaptically located mGlu(5) glutamate autoreceptors. The pharmacological profile of these receptors appears to be distinct from that of postsynaptic mGlu receptors. Novel antagonists acting at these presynaptic receptors may provide new drugs for the experimental therapy of a range of acute or chronic neurodegenerative disorders.

Immunoprecipitation of interleukin-1 receptors from a mouse thymoma cell line, EL-4.

Receptors for the monokine, interleukin-1 (IL-1), have been successfully immunoprecipitated with a xenogeneic antiserum raised in our laboratories. Receptors solubilized from mouse cell membranes as well as nascent chains of molecules that could bind IL-1 were immunoprecipitated. Receptor complexes were identified on mouse cell lines which express IL-1 receptors by affinity cross-linkage of the radiolabeled ligands, IL-1-alpha or IL-1-beta. Soluble IL-1 or IL-1 nonspecifically associated with membranes of cells which do not express IL-1 receptors was not immunoprecipitated. It is apparent, thus, that antibodies present in the xenogeneic antiserum could specifically bind to the IL-1 receptor moiety within the complex. The major proportion of IL-1 receptor complexes that were reproducibly immunoprecipitated had a molecular weight of 97,000. Cell membrane associated receptors for the monokine, tumor necrosis factor, were not immunoprecipitated. These antibodies have contributed to the understanding of the role of IL-1 receptors in cytolytic effector T cell generation and should contribute further in the purification and characterization of the IL-1 receptor moiety, as well as in determining IL-1-mediated mechanisms of cellular activation.

Rapid in vitro replication of group B streptococcus in term human amniotic fluid.

4-hour in vitro growth curves of a type III group B streptococcus (GBS) and Escherichia coli were examined in sterile term human amniotic fluid specimens. Both bacterial strains proliferated despite ratios of phosphate to elemental zinc in the range reportedly inhibitory for E. coli. After 4 h of incubation, despite comparable inocula, GBS numbers exceeded those of E. coli by 10-fold. The strikingly rapid growth of some GBS strains in amniotic fluid may represent yet another factor responsible for perinatal GBS infection of the human neonate.