Acute oral toxicity, cognitive-enhancing and anti-lipid peroxidation efficacy, and qualitative phytochemistry of the aqueous aerial part extract of Launaea cornuta (Hochst. ex. Oliv. &Hiern) C. Jeffrey.

At present, there is no cure for dementia or its related cognitive impairments. Available treatments only provide symptomatic relief and do not alter the disease's progression and they suffer serious drawbacks limiting their clinical use, hence the need for alternative therapies. Although Launaea cornuta has been used traditionally to treat cognitive deficits, its pharmacological efficacy and safety have not been empirically validated, prompting this study. Acute oral toxicity of the extract was examined in Swiss albino mice using the up-and-down procedure described by the Organisation for Economic Cooperation and Development guideline number 425. The Morris water maze technique was adopted in assessing cognitive-enhancing effects of the extract in ketamine-induced cognitive-impaired mice. The malondialdehyde concentrations in the whole brain of experimental mice involved in the MWM experiment were measured to determine the extract's anti-lipid peroxidation efficacy. Qualitative phytochemical screening of the extract was performed using standard procedures. Our results showed that the test extract was safe and did not cause any clinical signs of acute oral toxicity in mice at all doses (LD50 > 2000 mg/kg BW). Moreover, the extract significantly improved cognitive function in ketamine-induced cognitive-impaired mice in a dose-dependent manner, as indicated by reduced escape latency, navigation distance, and longer latency in the target quadrant during the probe trial. The extract also significantly reduced malondialdehyde concentrations in mice in a dose-dependent manner, demonstrating its antioxidative stress efficacy. The studied extract contained various phytochemicals associated with cognitive enhancement and antioxidant efficacy, among other pharmacologic effects. Further empirical studies are needed to determine and characterise the extract's specific cognitive-enhancing compounds, specific mechanisms of action, and complete toxicity profiles.

Impacts of the COVID-19 pandemic on access to HIV and reproductive health care among women living with HIV (WLHIV) in Western Kenya: A mixed methods analysis.

Introduction: The COVID-19 pandemic has impacted access to health services. Our objective was to understand the pandemic's impact on access to HIV, pregnancy, and family planning (FP) care among women living with HIV (WLHIV). Methods: Data were collected after June 2020, when questions about the pandemic were added to two ongoing mixed methods studies using telephone surveys and in-depth interviews among WLHIV in western Kenya. The Chaguo Langu (CL) study includes primarily non-pregnant WLHIV receiving HIV care at 55 facilities supported by AMPATH and the Opt4Mamas study includes pregnant WLHIV receiving antenatal care at five facilities supported by FACES. Our outcomes were self-reported increased difficulty refilling medication, accessing care, and managing FP during the pandemic. We summarized descriptive data and utilized multivariable logistic regression to evaluate predictors of difficulty refilling medication and accessing care. We qualitatively analyzed the interviews using inductive coding with thematic analysis. Results: We analyzed 1,402 surveys and 15 in-depth interviews. Many (32%) CL participants reported greater difficulty refilling medications and a minority (14%) reported greater difficulty accessing HIV care during the pandemic. Most (99%) Opt4Mamas participants reported no difficulty refilling medications or accessing HIV/pregnancy care. Among the CL participants, older women were less likely (aOR = 0.95, 95% CI: 0.92-0.98) and women with more children were more likely (aOR = 1.13, 95% CI: 1.00-1.28) to report difficulty refilling medications. Only 2% of CL participants reported greater difficulty managing FP and most (95%) reported no change in likelihood of using FP or desire to get pregnant. Qualitative analysis revealed three major themes: (1) adverse organizational/economic implications of the pandemic, (2) increased importance of pregnancy prevention during the pandemic, and (3) fear of contracting COVID-19. Discussion: The two unique participant groups included in our study encountered overlapping problems during the COVID-19 epidemic. Access to HIV services and antiretrovirals was interrupted for a large proportion of non-pregnant WLHIV in western Kenya, but access to pregnancy/family planning care was less affected in our cohort. Innovative solutions are needed to ensure HIV and reproductive health outcomes do not worsen during the ongoing pandemic.

Contraception use and HIV outcomes among women initiating dolutegravir-containing antiretroviral therapy in Kenya: a retrospective cohort study.

INTRODUCTION: The rollout of dolutegravir (DTG) in low- and middle-income countries was disrupted by a potential association reported with periconceptional DTG exposure among women living with HIV (WLHIV) and infant neural tube defects. This prompted countries to issue interim guidance limiting DTG use among women of reproductive potential to those on effective contraception. Data to understand the potential impact of such guidance on WLHIV are limited. METHODS: We conducted a retrospective cohort analysis of WLHIV 15-49 years initiating DTG-containing antiretroviral treatment (ART) in Kenya from 2017 to 2020. We determined baseline effective (oral, injectable or lactational amenorrhea) and very effective (implant, intrauterine device or female sterilization) contraception use among women who initiated DTG before (Group 1) or during (Group 2) the interim guideline period. We defined incident contraception use in each group as the number of contraceptive methods initiated ≤180 days post-guideline (Group 1) or post-DTG initiation (Group 2). We determined the proportions of all women who switched from DTG- to non-nucleoside reverse transcriptase inhibitor (NNRTI)- (efavirenz or nevirapine) containing ART ≤12 months post-DTG initiation, compared their viral suppression (<1000 copies/ml) and conducted multivariable logistic regression to determine factors associated with switching from DTG to NNRTI-containing ART. RESULTS: Among 5155 WLHIV in the analysis (median age 43 years), 89% initiated DTG after transitioning from an NNRTI. Baseline effective and very effective contraception use, respectively, by the group were: Group 1 (12% and 13%) and Group 2 (41% and 35%). Incident contraception use in each group was <5%. Overall, 498 (10%) women switched from DTG to an NNRTI. Viral suppression among those remaining on DTG versus switched to NNRTI was 95% and 96%, respectively (p = 0.63). In multivariable analysis, incident effective and very effective contraception use was not associated with switching. CONCLUSIONS: Baseline, but not incident, effective contraception use was higher during the interim guideline period compared to before it, suggesting women already using effective contraception were preferentially selected to initiate DTG after the guideline was released. These findings reveal challenges in the implementation of policy which ties antiretroviral access to contraceptive use. Future guidance should capture nuances of contraception decision-making and support women's agency to make informed decisions.

Disparities in Dolutegravir Uptake Affecting Females of Reproductive Age With HIV in Low- and Middle-Income Countries After Initial Concerns About Teratogenicity : An Observational Study.

BACKGROUND: The transition to dolutegravir-containing antiretroviral therapy (ART) in low- and middle-income countries (LMICs) was complicated by an initial safety signal in May 2018 suggesting that exposure to dolutegravir at conception was possibly associated with infant neural tube defects. On the basis of additional evidence, in July 2019, the World Health Organization recommended dolutegravir for all adults and adolescents living with HIV. OBJECTIVE: To describe dolutegravir uptake and disparities by sex and age group in LMICs. DESIGN: Observational cohort study. SETTING: 87 sites that began using dolutegravir in 11 LMICs in the Asia-Pacific; Caribbean, Central and South America network for HIV epidemiology (CCASAnet); and sub-Saharan African regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. PATIENTS: 134 672 patients aged 16 years or older who received HIV care from January 2017 through March 2020. MEASUREMENTS: Sex, age group, and dolutegravir uptake (that is, newly initiating ART with dolutegravir or switching to dolutegravir from another regimen). RESULTS: Differences in dolutegravir uptake among females of reproductive age (16 to 49 years) emerged after the safety signal. By the end of follow-up, the cumulative incidence of dolutegravir uptake among females 16 to 49 years old was 29.4% (95% CI, 29.0% to 29.7%) compared with 57.7% (CI, 57.2% to 58.3%) among males 16 to 49 years old. This disparity was greater in countries that began implementing dolutegravir before the safety signal and initially had highly restrictive policies versus countries with a later rollout. Dolutegravir uptake was similar among females and males aged 50 years or older. LIMITATION: Follow-up was limited to 6 to 8 months after international guidelines recommended expanding access to dolutegravir. CONCLUSION: Substantial disparities in dolutegravir uptake affecting females of reproductive age through early 2020 are documented. Although this disparity was anticipated because of country-level restrictions on access, the results highlight its extent and initial persistence. PRIMARY FUNDING SOURCE: National Institutes of Health.

An Ethics-based approach to Global Health Research Part 3: Emphasis on Partnership Funding.

Acquiring funding for global health research within pharmacy can be challenging, particularly for new investigators who may have a strong interest in resolving global dilemmas related to health. Moreover, there can be inherent imbalances and ethical issues when navigating the funding process for global partnerships. There exists a lack of literature providing ethical guidance for mitigating dilemmas that may arise. This commentary discusses current funding streams for investigators interested in global pharmacy research, as well as specific recommendations for the funding process. These recommendations include managing award funds, ethical considerations for funding research partnerships, and balancing power between low to middle income countries and high-income countries. Lastly, case examples of funding partnerships involving pharmacy are highlighted, emphasizing important lessons learned. This commentary addresses the critical need for providing global health researchers with both important considerations and experience-based recommendations for navigating global funding partnerships using an ethical approach.

Leveraging peer-based support to facilitate HIV care in Kenya.

Rakhi Karwa and colleagues discuss a program in which peer navigators support care for people with HIV at a Kenyan hospital.

Targeted Spontaneous Reporting: Assessing Opportunities to Conduct Routine Pharmacovigilance for Antiretroviral Treatment on an International Scale.

INTRODUCTION: Targeted spontaneous reporting (TSR) is a pharmacovigilance method that can enhance reporting of adverse drug reactions related to antiretroviral therapy (ART). Minimal data exist on the needs or capacity of facilities to conduct TSR. OBJECTIVES: Using data from the International epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium, the present study had two objectives: (1) to develop a list of facility characteristics that could constitute key assets in the conduct of TSR; (2) to use this list as a starting point to describe the existing capacity of IeDEA-participating facilities to conduct pharmacovigilance through TSR. METHODS: We generated our facility characteristics list using an iterative approach, through a review of relevant World Health Organization (WHO) and Uppsala Monitoring Centre documents focused on pharmacovigilance activities related to HIV and ART and consultation with expert stakeholders. IeDEA facility data were drawn from a 2009/2010 IeDEA site assessment that included reported characteristics of adult and pediatric HIV care programs, including outreach, staffing, laboratory capacity, adverse event monitoring, and non-HIV care. RESULTS: A total of 137 facilities were included: East Africa (43); Asia-Pacific (28); West Africa (21); Southern Africa (19); Central Africa (12); Caribbean, Central, and South America (7); and North America (7). Key facility characteristics were grouped as follows: outcome ascertainment and follow-up; laboratory monitoring; documentation-sources and management of data; and human resources. Facility characteristics ranged by facility and region. The majority of facilities reported that patients were assigned a unique identification number (n = 114; 83.2 %) and most sites recorded adverse drug reactions (n = 101; 73.7 %), while 82 facilities (59.9 %) reported having an electronic database on site. CONCLUSION: We found minimal information is available about facility characteristics that may contribute to pharmacovigilance activities. Our findings, therefore, are a first step that can potentially assist implementers and facility staff to identify opportunities and leverage their existing capacities to incorporate TSR into their routine clinical programs.

Meeting the Needs of Underserved Patients in Western Kenya by Creating the Next Generation of Global Health Pharmacists.

Objective. To describe a novel training model used to create a sustainable public health-focused pharmacy residency based in Kenya and to describe the outcomes of this training program on underserved populations. Design. The postgraduate year 2 residency was designed to expose trainees to the unique public health facets of inpatient, outpatient, and community-based care delivery in low and middle-income countries. Public health areas of focus included supply chain management, reproductive health, pediatrics, HIV, chronic disease management, and teaching. Assessment. The outcomes of the residency were assessed based on the number of new clinical programs developed by residents, articles and abstracts written by residents, and resident participation in grant writing. To date, six residents from the United States and eight Kenyan residents have completed the residency. Eleven sustainable patient care services have been implemented as a result of the residency program. Conclusion. This pharmacy residency training model developed accomplished pharmacists in public health pharmacy, with each residency class expanding funding and clinical programming, contributing to curriculum development, and creating jobs.

Are single mothers' higher smoking rates mediated by dysfunctional coping styles?

BACKGROUND: Smoking prevalence has been shown to be considerably higher among single mothers as compared to their married or cohabiting counterparts. This study examines whether this could be attributed to single mothers' different capability in dealing with stress. METHODS: Based on cross-sectional data of 3129 German mothers, the study explores the associations between single motherhood, coping styles and moderate and heavy smoking pattern using a regression-based 'parallel multiple mediator model'. RESULTS: Single mothers showed higher rates of negative coping styles than partnered mothers, holding for 'self-blame/rumination' (p < 0.001), 'blaming others' (p = 0.048) and in particular for 'substance consumption' (p < 0.001). With respect to positive coping styles the findings were heterogeneous: while partnered mothers scored higher on 'active influence' (p < 0.001), single mothers showed higher values of 'positive self-verbalisation' (p < 0.001). Evidence for a mediating effect of coping styles on the relationship between single motherhood and moderate as well as heavy smoking was only found for 'substance consumption'. Moreover, single motherhood may moderate the effect of 'self-blame/rumination' on heavy smoking (p = 0.025). Against expectations, higher levels of 'active influence' were not associated with lower but with significant higher odds of moderate smoking (OR = 1.19). CONCLUSION: Single mothers compared to partnered mothers showed a different ability to cope with stress. However, only the coping strategy 'substance consumption' mediates the relationship between single motherhood and smoking. Exclusively in single mothers, 'self-blame/rumination' was associated with heavy smoking, indicating that they might utilize smoking as a way to come to terms with negative ruminative thoughts.

The effect of psychosocial stress on single mothers' smoking.

BACKGROUND: Evidence suggests an increased risk of smoking among single mothers as compared to their cohabitating counterparts. This article examines the role of psychosocial stress in mediating the relationship between single motherhood and smoking. METHODS: Data were derived from a cross-sectional population based sample of German women (n = 3129) with underage children (0-18 years of age). Perceived stress was measured with 13 items covering socioeconomic as well as family- and parenting-related stressors. According to Baron and Kenny (1986) a series of logistic regression models was applied to investigate the role of psychosocial stress as a mediator on the relationship between single motherhood and smoking. RESULTS: About 44.0% of single mothers smoked daily, whereas only 26.2% of cohabitating mothers did. Single mothers reported more stress related to their economic situation, occupation and family than partnered mothers. Out of the original 13 stressors only 'conflicts with the partner or ex-partner' and 'financial worries' remained significant in explaining single mothers' higher risk of smoking. Against expectation, stress due to household requirements and family demands was associated with lower odds of single mothers' smoking. After controlling for psychosocial stress, the odds ratio of single mothers' moderate smoking (< 20 cig./day) decreased slightly from 1.75 to 1.66 (explained fraction XF = 12.0%) and with respect to heavy smoking (≥ 20 cig./day) more pronounced from 2.56 to 2.01 (XF = 35.3%). CONCLUSIONS: It can be stated that single mothers' heavy more than moderate smoking appeared to be mediated by perceived psychosocial stress. Out of all stressors considered, financial worries were of paramount significance in explaining single mothers' heavy smoking while some family-related stressors rather appeared to keep single mothers from smoking. Overall, a higher stress exposure explains partly but not sufficiently single mothers' increased smoking rates.