Integration of antenatal care services with health programmes in low- and middle-income countries: systematic review.

BACKGROUND: Antenatal care (ANC) presents a potentially valuable platform for integrated delivery of additional health services for pregnant women-services that are vital to reduce the persistently high rates of maternal and neonatal mortality in low- and middle-income countries (LMICs). However, there is limited evidence on the impact of integrating health services with ANC to guide policy. This review assesses the impact of integration of postnatal and other health services with ANC on health services uptake and utilisation, health outcomes and user experience of care in LMICs. METHODS: Cochrane Library, MEDLINE, Embase, CINAHL Plus, POPLINE and Global Health were searched for studies that compared integrated models for delivery of postnatal and other health services with ANC to non-integrated models. Risk of bias of included studies was assessed using the Cochrane Effective Practice and Organisation of Care (EPOC) criteria and the Newcastle-Ottawa Scale, depending on the study design. Due to high heterogeneity no meta-analysis could be conducted. Results are presented narratively. FINDINGS: 12 studies were included in the review. Limited evidence, with moderate- to high-risk of bias, suggests that integrated service delivery results in improved uptake of essential health services for women, earlier initiation of treatment, and better health outcomes. Women also reported improved satisfaction with integrated services. CONCLUSIONS: The reported evidence is largely based on non-randomised studies with poor generalizability, and therefore offers very limited policy guidance. More rigorously conducted and geographically diverse studies are needed to better ascertain and quantify the health and economic benefits of integrating health services with ANC.

Health impact of external funding for HIV, tuberculosis and malaria: systematic review.

BACKGROUND: Since 2002, development assistance for health has substantially increased, especially investments for HIV, tuberculosis (TB) and malaria control. We undertook a systematic review to assess and synthesize the existing evidence in the scientific literature on the health impacts of these investments. METHODS AND FINDINGS: We systematically searched databases for peer-reviewed and grey literature, using tailored search strategies. We screened studies for study design and relevance, using predefined inclusion criteria, and selected those that enabled us to link health outcomes or impact to increased external funding. For all included studies, we recorded dataset and study characteristics, health outcomes and impacts. We analysed the data using a causal-chain framework to develop a narrative summary of the published evidence. Thirteen articles, representing 11 individual studies set in Africa and Asia reporting impacts on HIV, tuberculosis and malaria, met the inclusion criteria. Only two of these studies documented the entire causal-chain spanning from funding to programme scale-up, to outputs, outcomes and impacts. Nonetheless, overall we find a positive correlation between consecutive steps in the causal chain, suggesting that external funds for HIV, tuberculosis and malaria programmes contributed to improved health outcomes and impact. CONCLUSIONS: Despite the large number of supported programmes worldwide and despite an abundance of published studies on HIV, TB and malaria control, we identified very few eligible studies that adequately demonstrated the full process by which external funding has been translated to health impact. Most of these studies did not move beyond demonstrating statistical association, as opposed to contribution or causation. We thus recommend that funding organizations and researchers increase the emphasis on ensuring data capture along the causal pathway to demonstrate effect and contribution of external financing. The findings of these comprehensive and rigorously conducted impact evaluations should also be made publicly accessible.

Integration of priority population, health and nutrition interventions into health systems: systematic review.

BACKGROUND: Objective of the study was to assess the effects of strategies to integrate targeted priority population, health and nutrition interventions into health systems on patient health outcomes and health system effectiveness and thus to compare integrated and non-integrated health programmes. METHODS: Systematic review using Cochrane methodology of analysing randomised trials, controlled before-and-after and interrupted time series studies. We defined specific strategies to search PubMed, CENTRAL and the Cochrane Effective Practice and Organisation of Care Group register, considered studies published from January 1998 until September 2008, and tracked references and citations. Two reviewers independently agreed on eligibility, with an additional arbiter as needed, and extracted information on outcomes: primary (improved health, financial protection, and user satisfaction) and secondary (improved population coverage, access to health services, efficiency, and quality) using standardised, pre-piloted forms. Two reviewers in the final stage of selection jointly assessed quality of all selected studies using the GRADE criteria. RESULTS: Of 8,274 citations identified 12 studies met inclusion criteria. Four studies compared the benefits of Integrated Management of Childhood Illnesses in Tanzania and Bangladesh, showing improved care management and higher utilisation of health facilities at no additional cost. Eight studies focused on integrated delivery of mental health and substance abuse services in the United Kingdom and United States of America. Integrated service delivery resulted in better clinical outcomes and greater reduction of substance abuse in specific sub-groups of patients, with no significant difference found overall. Quality of care, patient satisfaction, and treatment engagement were higher in integrated delivery models. CONCLUSIONS: Targeted priority population health interventions we identified led to improved health outcomes, quality of care, patient satisfaction and access to care. Limited evidence with inconsistent findings across varied interventions in different settings means no general conclusions can be drawn on the benefits or disadvantages of integrated service delivery.

Characterization of a cyanobacterial-like uptake [NiFe] hydrogenase: EPR and FTIR spectroscopic studies of the enzyme from Acidithiobacillus ferrooxidans.

Electron paramagnetic resonance (EPR) and Fourier transform IR studies on the soluble hydrogenase from Acidithiobacillus ferrooxidans are presented. In addition, detailed sequence analyses of the two subunits of the enzyme have been performed. They show that the enzyme belongs to a group of uptake [NiFe] hydrogenases typical for Cyanobacteria. The sequences have also a close relationship to those of the H(2)-sensor proteins, but clearly differ from those of standard [NiFe] hydrogenases. It is concluded that the structure of the catalytic centre is similar, but not identical, to that of known [NiFe] hydrogenases. The active site in the majority of oxidized enzyme molecules, 97% in cells and more than 50% in the purified enzyme, is EPR-silent. Upon contact with H(2) these sites remain EPR-silent and show only a limited IR response. Oxidized enzyme molecules with an EPR-detectable active site show a Ni(r)*-like EPR signal which is light-sensitive at cryogenic temperatures. This is a novelty in the field of [NiFe] hydrogenases. Reaction with H(2) converts these active sites to the well-known Ni(a)-C* state. Illumination below 160 K transforms this state into the Ni(a)-L* state. The reversal, in the dark at 200 K, proceeds via an intermediate Ni EPR signal only observed with the H(2)-sensor protein from Ralstonia eutropha. The EPR-silent active sites in as-isolated and H(2)-treated enzyme are also light-sensitive as observed by IR spectra at cryogenic temperatures. The possible origin of the light sensitivity is discussed. This study represents the first spectral characterization of an enzyme of the group of cyanobacterial uptake hydrogenases.

Direct observation of multiple protonation states in recombinant human purple acid phosphatase.

To date, most spectroscopic studies on mammalian purple acid phosphatases (PAPs) have been performed at a single pH, typically pH 5. The catalytic activity of these enzymes is, however, pH dependent, with optimal pH values of 5.5-6.2 (depending on the form). For example, the pH optimum of PAPs isolated as single polypeptides is around pH 5.5, which is substantially lower that of proteolytically cleaved PAPs (ca. pH 6.2). In addition, the catalytic activity of single polypeptide PAPs at their optimal pH values is four to fivefold lower than that of the proteolytically cleaved enzymes. In order to elucidate the chemical basis for the pH dependence of these enzymes, the spectroscopic properties of both the single polypeptide and proteolytically cleaved forms of recombinant human PAP (recHPAP) and their complexes with inhibitory anions have been examined over the pH range 4 to 8. The EPR spectra of both forms of recHPAP are pH dependent and show the presence of three species: an inactive low pH form (pHpK( a,2)). The pK( a,1) values observed by EPR for the single polypeptide and proteolytically cleaved forms are similar to those previously observed in kinetics studies. The spectroscopic properties of the enzyme-phosphate complex (which should mimic the enzyme-substrate complex), the enzyme-fluoride complex, and the enzyme-fluoride-phosphate complex (which should mimic the ternary enzyme-substrate-hydroxide complex) were also examined. EPR spectra show that phosphate binds to the diiron center of the proteolytically cleaved form of the enzyme, but not to that of the single polypeptide form. EPR spectra also show that fluoride binds only to the low pH form of the enzymes, in which it presumably replaces a coordinated water molecule. The binding of fluoride and phosphate to form a ternary complex appears to be cooperative.