A process evaluation of the scale up of a youth-friendly health services initiative in northern Tanzania

BACKGROUND: While there are a number of examples of successful small-scale, youth-friendly services interventions aimed at improving reproductive health service provision for young people, these projects are often short term and have low coverage. In order to have a significant, long-term impact, these initiatives must be implemented over a sustained period and on a large scale. We conducted a process evaluation of the 10-fold scale up of an evaluated youth-friendly services intervention in Mwanza Region, Tanzania, in order to identify key facilitating and inhibitory factors from both user and provider perspectives. METHODS: The intervention was scaled up in two training rounds lasting six and 10 months. This process was evaluated through the triangulation of multiple methods: (i) a simulated patient study; (ii) focus group discussions and semi-structured interviews with health workers and trainers; (iii) training observations; and (iv) pre- and post-training questionnaires. These methods were used to compare pre- and post-intervention groups and assess differences between the two training rounds. RESULTS: Between 2004 and 2007, local government officials trained 429 health workers. The training was well implemented and over time, trainers' confidence and ability to lead sessions improved. The district-led training significantly improved knowledge relating to HIV/AIDS and puberty (RR ranged from 1.06 to 2.0), attitudes towards condoms, confidentiality and young people's right to treatment (RR range: 1.23-1.36). Intervention health units scored higher in the family planning and condom request simulated patient scenarios, but lower in the sexually transmitted infection scenario than the control health units. The scale up faced challenges in the selection and retention of trained health workers and was limited by various contextual factors and structural constraints. CONCLUSIONS: Youth-friendly services interventions can remain well delivered, even after expansion through existing systems. The scaling-up process did affect some aspects of intervention quality, and our research supports others in emphasizing the need to train more staff (both clinical and non-clinical) per facility in order to ensure youth-friendly services delivery. Further research is needed to identify effective strategies to address structural constraints and broader social norms that hampered the scale up

Generating demand and community support for sexual and reproductive health services for young people: A review of the Literature and Programs

BACKGROUND: This review investigates the effectiveness of interventions aimed at generating demand for and use of sexual and reproductive health (SRH) services by young people; and interventions aimed at generating wider community support for their use. METHODS: Reports and publications were found in the peer-reviewed and grey literature through academic search engines; web searches; the bibliographies of known conference proceedings and papers; and consultation with experts. The studies were reviewed against a set of inclusion criteria and those that met these were explored in more depth. RESULTS: The evidence-base for interventions aimed at both generating demand and community support for SRH services for young people was found under-developed and many available studies do not provide strong evidence. However, the potential of several methods to increase youth uptake has been demonstrated, this includes the linking of school education programs with youth friendly services, life skills approaches and social marketing and franchising. There is also evidence that the involvement of key community gatekeepers such as parents and religious leaders is vital to generating wider community support. In general a combined multi-component approach seems most promising with several success stories to build on. CONCLUSIONS: Many areas for further research have been highlighted and there is a great need for more rigorous evaluation of programmes in this area. In particular, further evaluation of individual components within a multi-component approach is needed to elucidate the most effective interventions

Provider imposed restrictions to clients’ access to family planning in urban Uttar Pradesh, India: a mixed methods study

BACKGROUND: Medical barriers refer to unnecessary policies or procedures imposed by health care providers that are not necessarily medically advised; these restrictions impede clients’ access to family planning (FP). This mixed methods study investigates provider imposed barriers to provision of FP using recent quantitative and qualitative data from urban Uttar Pradesh, India. METHODS: Baseline quantitative data were collected in six cities in Uttar Pradesh, India from service delivery points (SDP), using facility audits, exit interviews, and provider surveys; for this study, the focus is on the provider surveys. More than 250 providers were surveyed in each city. Providers were asked about the FP methods they provide, and if they restrict clients’ access to each method based on age, parity, partner consent, or marital status. For the qualitative research, we conducted one-on-one interviews with 21 service providers in four of the six cities in Uttar Pradesh. Each interview lasted approximately 45 minutes. RESULTS: The quantitative findings show that providers restrict clients’ access to spacing and long-acting and permanent methods of FP based on age, parity, partner consent and marital status. Qualitative findings reinforce that providers, at times, make judgments about their clients’ education, FP needs and ability to understand FP options thereby imposing unnecessary barriers to FP methods. CONCLUSIONS: Provider restrictions on FP methods are common in these urban Uttar Pradesh sites. This means that women who are young, unmarried, have few or no children, do not have the support of their partner, or are less educated may not be able to access or use FP or their preferred method. These findings highlight the need for in-service training for staff, with a focus on reviewing current guidelines and eligibility criteria for provision of methods

Inhibitors of Helicobacter pylori Protease HtrA Found by ‘Virtual Ligand’ Screening Combat Bacterial Invasion of Epithelia

Background: The human pathogen Helicobacter pylori (H. pylori) is a main cause for gastric inflammation and cancer. Increasing bacterial resistance against antibiotics demands for innovative strategies for therapeutic intervention. Methodology/Principal Findings: We present a method for structure-based virtual screening that is based on the comprehensive prediction of ligand binding sites on a protein model and automated construction of a ligand-receptor interaction map. Pharmacophoric features of the map are clustered and transformed in a correlation vector (‘virtual ligand’) for rapid virtual screening of compound databases. This computer-based technique was validated for 18 different targets of pharmaceutical interest in a retrospective screening experiment. Prospective screening for inhibitory agents was performed for the protease HtrA from the human pathogen H. pylori using a homology model of the target protein. Among 22 tested compounds six block E-cadherin cleavage by HtrA in vitro and result in reduced scattering and wound healing of gastric epithelial cells, thereby preventing bacterial infiltration of the epithelium. Conclusions/Significance: This study demonstrates that receptor-based virtual screening with a permissive (‘fuzzy’) pharmacophore model can help identify small bioactive agents for combating bacterial infection

Modeling of Human Prokineticin Receptors: Interactions with Novel Small-Molecule Binders and Potential Off-Target Drugs

The Prokineticin receptor (PKR) 1 and 2 subtypes are novel members of family A GPCRs, which exhibit an unusually high degree of sequence similarity. Prokineticins (PKs), their cognate ligands, are small secreted proteins of ∼80 amino acids; however, non-peptidic low-molecular weight antagonists have also been identified. PKs and their receptors play important roles under various physiological conditions such as maintaining circadian rhythm and pain perception, as well as regulating angiogenesis and modulating immunity. Identifying binding sites for known antagonists and for additional potential binders will facilitate studying and regulating these novel receptors. Blocking PKRs may serve as a therapeutic tool for various diseases, including acute pain, inflammation and cancer.Ligand-based pharmacophore models were derived from known antagonists, and virtual screening performed on the DrugBank dataset identified potential human PKR (hPKR) ligands with novel scaffolds. Interestingly, these included several HIV protease inhibitors for which endothelial cell dysfunction is a documented side effect. Our results suggest that the side effects might be due to inhibition of the PKR signaling pathway. Docking of known binders to a 3D homology model of hPKR1 is in agreement with the well-established canonical TM-bundle binding site of family A GPCRs. Furthermore, the docking results highlight residues that may form specific contacts with the ligands. These contacts provide structural explanation for the importance of several chemical features that were obtained from the structure-activity analysis of known binders. With the exception of a single loop residue that might be perused in the future for obtaining subtype-specific regulation, the results suggest an identical TM-bundle binding site for hPKR1 and hPKR2. In addition, analysis of the intracellular regions highlights variable regions that may provide subtype specificity