A novel approach to estimate the impact of health workforce investments on health outcomes through increased coverage of HIV, TB and malaria services.

BACKGROUND: Globally, HIV, TB and malaria account for an estimated three million deaths annually. The Global Fund partnered with the World Health Organization to assist countries with health workforce planning in these areas through the development of an integrated health workforce investment impact tool. Our study illustrates the development of a user-friendly tool (with two MS Excel calculator subcomponents) that computes associations between human resources for health (HRH) investment inputs and reduced morbidity and mortality from HIV, TB, and malaria via increased coverage of effective treatment services. METHODS: We retrieved from the peer-reviewed literature quantitative estimates of the relation among HRH inputs and HRH employment and productivity. We converted these values to additional full-time-equivalent doctors, nurses and midwives (DNMs). We used log-linear regression to estimate the relation between DNMs and treatment service coverage outcomes for HIV, TB, and malaria. We then retrieved treatment effectiveness parameters from the literature to calculate lives saved due to expanded treatment coverage for HIV, TB, and malaria. After integrating these estimates into the tool, we piloted it in four countries. RESULTS: In most countries with a considerable burden of HIV, TB, and malaria, the health workforce investments include a mix of pre-service education, full remuneration of new hires, various forms of incentives and in-service training. These investments were associated with elevated HIV, TB and malaria treatment service coverage and additional lives saved. The country case studies we developed in addition, indicate the feasibility and utility of the tool for a variety of international and local actors interested in HRH planning. CONCLUSIONS: The modelled estimates developed for illustrative purposes and tested through country case studies suggest that HRH investments result in lives saved across HIV, TB, and malaria. Furthermore, findings show that attainment of high targets of specific treatment coverage indicators would require a substantially greater health workforce than what is currently available in most LMICs. The open access tool can assist with future HRH planning efforts, particularly in LMICs.

Designing for two: How enhancing human-centered design with behavioral nudges unlocked breakthroughs to promote young women's psychological safety and access to reproductive care in Tanzania.

Adolescent girls and young women (AGYW; ages 15-24) in sub-Saharan Africa face many barriers to accessing preventive sexual and reproductive health (SRH) services. We drew upon the strengths of two complementary approaches, human-centered design and behavioral economics, to craft a holistic, highly-tailored, and empathetic intervention to motivate AGYW to seek contraception and HIV self-test kits at community drug shops. To encourage engagement, we embedded "nudge" strategies at different opportunity points (uncovered during our design research) along the care-seeking and service delivery journey. Our Malkia Klabu intervention is a loyalty program designed to enhance drug shops' role as SRH providers through which AGYW earned punches for shop purchases redeemable for small prizes; free SRH products could be requested at any time. From our 4-month pilot in Shinyanga, Tanzania, we assess the extent to which different behavioral nudge strategies motivated behaviors as predicted by synthesizing findings from (1) in-depth interviews with AGYW and shopkeepers, (2) shop program records, (3) shop observations, and (4) customer exit surveys. Overall, we find that AGYW and shopkeepers were motivated by many intervention features as intended and consistent with hypothesized mechanisms. We found strong evidence of social norms for helping to spread awareness of Malkia Klabu among peers, prize incentives for drawing AGYW back to shops, and the opt-out default membership gift of an HIV self-test kit for encouraging testing uptake and exploration of contraceptives. Shopkeepers in both arms noted increased community status from distributing HIV self-testing kits (ego). Malkia Klabu shopkeepers experienced increased customer traffic and business revenues (incentives), which reduced shopkeepers' gatekeeping tendencies and earned them additional recognition as champions of AGYW well-being. Integrating human-centered design and behavioral economics was effective for developing an innovative and effective intervention that simultaneously met the different needs of economic actors in support of public health priorities.

Four Decades of Military Posttraumatic Stress: Protocol for a Meta-analysis and Systematic Review of Treatment Approaches and Efficacy.

BACKGROUND: Over 85% of active members of the Canadian Armed Forces have been exposed to potentially traumatic events linked to the development of posttraumatic stress disorder (PTSD). At the time of transition to civilian life, as high as 1 in 8 veterans may be diagnosed with PTSD. Given the high prevalence of PTSD in military and veteran populations, the provision of effective treatment considering their unique challenges and experiences is critical for mental health support and the well-being of these populations. OBJECTIVE: This paper presents the protocol for a meta-analysis and systematic review that will examine the effectiveness of treatment approaches for military-related PTSD. METHODS: This PROSPERO-preregistered meta-analysis is being conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane guidelines. A comprehensive search of the literature was conducted using the databases PsycInfo, Medline, Embase, CINAHL, and ProQuest Dissertation & Theses. Effect sizes will be computed based on changes in PTSD symptom scores over time across studies using validated PTSD scales. A multilevel meta-analysis will examine the overall effects, between-study effects, and within-study effects of available evidence for PTSD treatments in military populations. Effect sizes will be compared between pharmacotherapeutic, psychotherapeutic, and alternative/emerging treatment interventions. Finally, meta-regression and subgroup analyses will explore the moderating roles of clinical characteristics (eg, PTSD symptom clusters), treatment approaches (eg, therapeutic orientations in psychotherapy and alternative therapies and classifications of drugs in pharmacotherapy), as well as treatment characteristics (eg, length of intervention) on treatment outcomes. RESULTS: The literature search was completed on April 14, 2021. After the removal of duplicates, a total of 12,002 studies were screened for inclusion. As of July 2021, title and abstract screening has been completed, with 1469 out of 12,002 (12.23%) studies included for full-text review. Full review is expected to be completed in the summer of 2021, with initial results expected for publication by early winter of 2021. CONCLUSIONS: This meta-analysis will provide information on the current state of evidence on the efficacy and effectiveness of various treatment approaches for military-related PTSD and identify factors that may influence treatment outcomes. The results will inform clinical decision-making for service providers and service users. Finally, the findings will provide insights into future treatment development and practice recommendations to better support the well-being of military and veteran populations. TRIAL REGISTRATION: PROSPERO CRD42021245754; https://tinyurl.com/y9u57c59. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/33151.

Implementation of an Internet-Based Acceptance and Commitment Therapy for Promoting Mental Health Among Migrant Live-in Caregivers in Canada: Protocol.

BACKGROUND: Psychological distress, isolation, feelings of powerlessness, and limited social support are realities faced by temporary migrant live-in caregivers in Canada. Furthermore, they experience multiple barriers in accessing mental health services due to their long work hours, limited knowledge of health resources, precarious employment, and immigration status. OBJECTIVE: The Women Empowerment - Caregiver Acceptance & Resilience E-Learning (WE2CARE) project is a pilot intervention research project that aims to promote the mental well-being and resiliency of migrant live-in caregivers. The objectives include exploring the effectiveness of this program in achieving the following: (1) reducing psychological distress (depression, anxiety, and stress); (2) promoting committed actions of self-care; and (3) building mutual support social networks. Further, participants' satisfaction with the intervention and their perceived barriers to and facilitators of practicing the self-care strategies embedded in WE2CARE will be examined. METHODS: A total of 36 live-in caregivers residing in the Greater Toronto Area will be recruited and randomly assigned to either the intervention or waitlist control group. The intervention group will receive a 6-week web-based psychosocial intervention that will be based on Acceptance and Commitment Therapy (ACT). Standardized self-reported surveys will be administered online preintervention, postintervention, and at 6 weeks postintervention to assess mental distress (Depression, Anxiety and Stress Scale), psychological flexibility (Acceptance and Action Questionnaire), mindfulness (Cognitive and Affective Mindfulness Scale - Revised), and resilience (Multi-System Model of Resilience Inventory). In addition, two focus groups will be held with a subset of participants to explore their feedback on the utility of the WE2CARE program. RESULTS: WE2CARE was funded in January 2019 for a year. The protocol was approved by the research ethics boards of Ryerson University (REB 2019-036) and the University of Toronto (RIS37623) in February and May 2019, respectively. Data collection started upon ethics approval and was completed by May 2020. A total of 29 caregivers completed the study and 20 participated in the focus groups. Data analyses are in progress and results will be published in 2021. CONCLUSIONS: WE2CARE could be a promising approach to reducing stress, promoting resilience, and providing a virtual space for peer emotional support and collaborative learning among socially isolated and marginalized women. The results of this pilot study will inform the adaptation of an ACT-based psychological intervention for online delivery and determine its utility in promoting mental health among disadvantaged and vulnerable populations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31211.

Presentation of breast cancer, help seeking behaviour and experience of patients in their cancer journey in Singapore: a qualitative study.

BACKGROUND: Little is known about the presentation, help seeking behaviour for breast cancer in Singapore. Nor was there a study exploring the experience of patients in their breast cancer journey. METHODS: A qualitative interview study with thematic analysis, conducted with 36 patients. RESULTS: There is no clear pattern of presentation for breast cancer by cancer stage at diagnosis, age and ethnicity in the cancer journey of this group of patients. Patients were diagnosed with early to advanced stages cancer regardless of when they presented or took up treatment in their cancer journey. The reasons patients sought medical attention also did not appear to differ between the stages of cancer diagnosed, ethnic and age. Without setting a measure to define early and late presentation, we found that women shared similar experience in their breast cancer journey, regardless of age, ethnicity and stage of cancer at diagnosis. Poor knowledge of breast cancer (symptoms and causes); few practised regular BSE; denial of symptom; fear of hospitalisation, diagnosis and treatment; worries and stress over financial burden of treatment; misinformation in magazine and online sources; diet; stress; caring responsibility; support network; and use of alternative medicine before and after diagnosis were identified in patients' narratives. Strong social support; fear of being an emotional and financial burden for the family; and financial worries during treatment were also the recurring themes after diagnosis. CONCLUSION: A measure of breast cancer presentation - that accounts for the patient's experience in the cancer journey, the time interval and tumour biology - that is meaningful to patients, clinicians and researchers is needed. For research on late and delayed presentation, details on BSE practice - how often, when and was it done correctly - will improve the accuracy of time delay interval. For the public, concerted efforts to improve knowledge of breast cancer, survival and prognosis for early-diagnosed cancer, and the importance of regular and correct technique to perform BSE, are critical and urgent to address the rising breast cancer incidence in the country.

Potato Peels and Their Bioactive Glycoalkaloids and Phenolic Compounds Inhibit the Growth of Pathogenic Trichomonads.

Potato peel, a waste product of the potato processing industry, is high in bioactive compounds. We investigated the in vitro antitrichomonad activity of potato peel powders prepared from commercial Russet, red, purple, and fingerling varieties as well as several known potato components, alkaloids and phenolic compounds, against three pathogenic strains of trichomonads. Trichomonas vaginalis is a sexually transmitted protozoan parasite that causes the human disease trichomoniasis. Two distinct strains of the related Tritrichomonas fetus infect cattle and cats. The glycoalkaloids α-chaconine and α-solanine were highly active against all parasite lines, while their common aglycone solanidine was only mildly inhibitory. α-Solanine was several times more active than α-chaconine. The phenolic compounds caffeic and chlorogenic acids and quercetin were mildly active against the parasites. Most of the potato peel samples were at least somewhat active against all three trichomonad species, but their activities were wide-ranging and did not correspond to their glycoalkaloid and phenolic content determined by HPLC. The two Russet samples were the most active against all three parasites. The purple potato peel sample was highly active against bovine and mostly inactive against feline trichomonads. None of the test substances were inhibitory toward several normal microflora species, suggesting the potential use of the peels for targeted therapeutic treatments against trichomonads.

Phytochemical-rich foods inhibit the growth of pathogenic trichomonads.

BACKGROUND: Plants produce secondary metabolites that often possess widespread bioactivity, and are then known as phytochemicals. We previously determined that several phytochemical-rich food-derived preparations were active against pathogenic foodborne bacteria. Trichomonads produce disease (trichomoniasis) in humans and in certain animals. Trichomonads are increasingly becoming resistant to conventional modes of treatment. It is of interest to test bioactive, natural compounds for efficacy against these pathogens. METHODS: Using a cell assay, black tea, green tea, grape, pomegranate, and jujube extracts, as well as whole dried jujube were tested against three trichomonads: Trichomonas vaginalis strain G3 (found in humans), Tritrichomonas foetus strain D1 (found in cattle), and Tritrichomonas foetus-like organism strain C1 (found in cats). The most effective of the test substances was subsequently tested against two metronidazole-resistant Trichomonas vaginalis strains, and on normal mucosal flora. RESULTS: Black tea extract inhibited all the tested trichomonads, but was most effective against the T. vaginalis organisms. Inhibition by black tea was correlated with the total and individual theaflavin content of the two tea extracts determined by HPLC. Metronidazole-resistant Trichomonas vaginalis strains were also inhibited by the black tea extract. The response of the organisms to the remaining preparations was variable and unique. We observed no effect of the black tea extract on common normal flora bacteria. CONCLUSIONS: The results suggest that the black tea, and to a lesser degree green tea, grape seed, and pomegranate extracts might present possible natural alternative therapeutic agents to treat Trichomonas vaginalis infections in humans and the related trichomonad infections in animals, without negatively affecting the normal flora.

Antiprotozoal Effects of the Tomato Tetrasaccharide Glycoalkaloid Tomatine and the Aglycone Tomatidine on Mucosal Trichomonads.

The present study investigated the inhibitory effects of the commercial tetrasaccharide tomato glycoalkaloid tomatine and the aglycone tomatidine on three mucosal pathogenic protozoa that are reported to infect humans, cattle, and cats, respectively: Trichomonas vaginalis strain G3, Tritrichomonas foetus strain D1, and Tritrichomonas foetus strain C1. A preliminary screen showed that tomatine at 100 µM concentration completely inhibited the growth of all three trichomonads. In contrast, the inhibition of all three pathogens by tomatidine was much lower, suggesting the involvement of the lycotetraose carbohydrate side chain in the mechanism of inhibition. Midpoints of concentration-response sigmoid plots of tomatine on the three strains correspond to IC50 values, the concentration that inhibits 50% of growth of the pathogenic protozoa. The concentration data were used to calculate the IC50 values for G3, D1, and C1 of 7.9, 1.9, and 2.2 µM, respectively. The results show an approximately 4-fold variation from the lowest to the highest value (lowest activity). Although the inhibition by tomatine was not as effective as that of the medicinal drug metronidazole, the relatively low IC50 values for both T. vaginalis and T. foetus indicated tomatine as a possible natural alternative therapeutic for trichomoniasis in humans and food-producing (cattle and pigs) and domestic (cats) animals. Because tomatine has the potential to serve as a new antiprotozoan functional (medical) food, the distribution of this glycoalkaloid in tomatoes and suggestions for further research are discussed.

A systematic review of the role of proprietary and patent medicine vendors in healthcare provision in Nigeria.

BACKGROUND: Interventions to reduce the burden of disease and mortality in sub-Saharan Africa increasingly recognize the important role that drug retailers play in delivering basic healthcare services. In Nigeria, owner-operated drug retail outlets, known as patent and proprietary medicine vendors (PPMVs), are a main source of medicines for acute conditions, but their practices are not well understood. Greater understanding of the role of PPMVs and the quality of care they provide is needed in order to inform ongoing national health initiatives that aim to incorporate PPMVs as a delivery mechanism. OBJECTIVE AND METHODS: This paper reviews and synthesizes the existing published and grey literature on the characteristics, knowledge and practices of PPMVs in Nigeria. We searched published and grey literature using a number of electronic databases, supplemented with website searches of relevant international agencies. We included all studies providing outcome data on PPMVs in Nigeria, including non-experimental studies, and assessed the rigor of each study using the WHO-Johns Hopkins Rigor scale. We used narrative synthesis to evaluate the findings. RESULTS: We identified 50 articles for inclusion. These studies provided data on a wide range of PPMV outcomes: training; health knowledge; health practices, including drug stocking and dispensing, client interaction, and referral; compliance with regulatory guidelines; and the effects of interventions targeting PPMVs. In general, PPMVs have low health knowledge and poor health treatment practices. However, the literature focuses largely on services for adult malaria, and little is known about other health areas or services for children. CONCLUSIONS: This review highlights several concerns with the quality of the private drug retail sector in Nigeria, as well as gaps in the existing evidence base. Future research should adopt a more holistic view of the services provided by PPMV shops, and evaluate intervention strategies that may improve the services provided in this sector.

Kibdelomycin is a potent and selective agent against toxigenic Clostridium difficile.

Clostridium difficile is the causative agent of C. difficile-associated diarrhea (CDAD), with increased risk in elderly populations. Kibdelomycin, a novel natural-product inhibitor of type II topoisomerase enzymes, was evaluated for activity against C. difficile and gastrointestinal anaerobic organisms. Toxigenic C. difficile isolates (n=168) from U.S. hospitals and anaerobic Gram-positive and Gram-negative organisms (n=598) from Chicago-area hospitals were tested. Kibdelomycin showed potent activity against toxigenic C. difficile (MIC90=0.25 µg/ml) and most Gram-positive aerobic organisms but had little activity against Bacteroides species (MIC50>32 µg/ml; n=270). Potent anti-C. difficile activity was also observed in the hamster model of C. difficile colitis. Dosing at 1.6 mg/kg (twice-daily oral dose) resulted in protection from a lethal infection and a 2-log reduction in C. difficile cecal counts. A 6.25-mg/kg twice-daily oral dose completely eliminated detectable C. difficile counts in cecal contents. A single 6.25-mg/kg oral dose showed that cecal contents were exposed to the drug at >2 µM (eightfold higher than the MIC), with no significant plasma exposure. These findings support further exploration of kibdelomycin for development of an anti-C. difficile agent.

Discovery of wall teichoic acid inhibitors as potential anti-MRSA ß-lactam combination agents.

Innovative strategies are needed to combat drug resistance associated with methicillin-resistant Staphylococcus aureus (MRSA). Here, we investigate the potential of wall teichoic acid (WTA) biosynthesis inhibitors as combination agents to restore ß-lactam efficacy against MRSA. Performing a whole-cell pathway-based screen, we identified a series of WTA inhibitors (WTAIs) targeting the WTA transporter protein, TarG. Whole-genome sequencing of WTAI-resistant isolates across two methicillin-resistant Staphylococci spp. revealed TarG as their common target, as well as a broad assortment of drug-resistant bypass mutants mapping to earlier steps of WTA biosynthesis. Extensive in vitro microbiological analysis and animal infection studies provide strong genetic and pharmacological evidence of the potential effectiveness of WTAIs as anti-MRSA ß-lactam combination agents. This work also highlights the emerging role of whole-genome sequencing in antibiotic mode-of-action and resistance studies.

Prostatic soy isoflavone concentrations exceed serum levels after dietary supplementation.

BACKGROUND: The effects of soy isoflavones on prostate cancer may be concentration-dependent. The impact of soy supplementation on isoflavone concentrations in prostate tissues and serum remain unclear. OBJECTIVE: To assess and compare concentrations of soy isoflavones in prostate tissue and serum among 19 men with prostate cancer who had elected to undergo radical prostatectomy. METHODS: Participants were randomized to receive either daily soy supplements (82 mg/day aglycone equivalents) or placebos for 2 weeks (14 days) prior to surgery. Serum samples were obtained at the time of the surgery. Isoflavone concentrations were measured by HPLC/ESI-MS-MS. RESULTS: The median (25th, 75th percentile) total isoflavone concentration in the isoflavone-supplemented group was 2.3 micromol/L (1.2, 6.9) in the prostate tissue and 0.7 micromol/L (0.2, 1.2) in the serum. Total isoflavone concentrations in this group were an average of approximately 6-fold higher in prostate tissue compared to serum; the tissue versus serum ratio was significantly lower for genistein than daidzein, 4-fold versus 10-fold, P = 0.003. Tissue and serum levels of isoflavones among the placebo group were negligible with a few exceptions. CONCLUSIONS: The findings from the present study suggest that prostate tissue may have the ability to concentrate dietary soy isoflavones to potentially anti-carcinogenic levels.

Antihypertensive effects of tannins isolated from traditional Chinese herbs as non-specific inhibitors of angiontensin converting enzyme.

The tannins are natural polyphenols, able to precipitate water-soluble alkaloids and possess an inhibitory action on the angiotensin converting enzyme (ACE). We identified 18 polyphenolic compounds (tannins) from Chinese herbs and examined the in vitro effects of these tannins on ACE activity, including determination of the 50% inhibitory concentrations (IC50), specificity and mode of inhibition. We also assessed the in vivo inhibitory effect of the tannins on angiotensin I-induced blood pressure elevation in spontaneously hypertensive rats (SHR). Nine tannins with an IC50 <200 microM for ACE inhibitors were identified belonging to three tannin classes: caffeoylquinates, flavan-3-ols and gallotannins. In vitro, we found caffeoylquinates chelate the ACE zinc cofactor. Two of the flavan-3-ols: epigallocatechin-3-O-gallate and epigallocatechin-3-O-methylgallate, and one of gallotannin: 1, 2, 3, 4, 6-penta-O-galloyl-beta-D-glucose were non-specific inhibitors because also reduced the activity of trypsin and chymotrypsin. The ACE inhibition of 1, 2, 3, 4, 6-penta-O-galloyl-beta-D-glucose was also reduced after addition of bovine serum albumin, suggesting a non-specific mode of action. In vivo, 1,2,3,6-tetra-O-galloyl-beta-D-glucose and epigallocatechin-3-O-methylgallate had a strong dose-dependent hypotensive effect reducing the blood pressure significantly in the SHR with infusion of the angiotensin I. These findings indicate that some of the tannins isolated from herbs inhibit ACE activity non-specifically. The ACE inhibitory effect of these tannins may explain the hypotensive effects of some traditional Chinese herbs.