The role of vitamin D in pre-eclampsia: a systematic review.

BACKGROUND: The etiology of pre-eclampsia (PE) is not yet fully understood, though current literature indicates an upregulation of inflammatory mediators produced by the placenta as a potential causal mechanism. Vitamin D is known to have anti-inflammatory properties and there is evidence of an inverse relationship between dietary calcium intake and the incidence of PE. Evidence of the role of vitamin D status and supplementation in the etiology and prevention of PE is reviewed in this article along with identification of research gaps to inform future studies. METHODS: We conducted a structured literature search using MEDLINE electronic databases to identify published studies until February 2015. These sources were retrieved, collected, indexed, and assessed for availability of pregnancy-related data on PE and vitamin D. RESULTS: Several case-control studies and cross-sectional studies have shown an association between vitamin D status and PE, although evidence has been inconsistent. Clinical trials to date have been unable to show an independent effect of vitamin D supplementation in preventing PE. CONCLUSIONS: The included clinical trials do not show an independent effect of vitamin D supplementation in preventing PE; however, issues with dose, timing, and duration of supplementation have not been completely addressed.

Perspectives and presentation of mental health among women from rural Maharashtra (India): A qualitative study.

Objectives: A significant gap is observed between the proportion of individuals suffering from mental health (MH)-related conditions and those receiving adequate MH care services, especially in rural areas. This study highlights and contextualizes MH concerns and its extant knowledge as well as gender roles in rural Maharashtra (India). Methods: Using in-depth interviews, MH themes were highlighted analytically among 72 female beneficiaries of Svatantra from the six administrative divisions (Konkan, Nashik, Pune, Aurangabad, Amravati and Nagpur) in the state of Maharashtra, India. Results: The notion that MH concerns exist among women from rural communities was well supported. Along with MH concerns, the participants reported somatic concerns in the context of adverse life experiences. Furthermore, systemic issues such as financial problems, familial concerns, presence of addictions and pressures of gender role-related responsibilities were significant triggers for MH problems. Conclusions: Overall, this study aimed at improving the understanding of the MH needs of women in rural Maharashtra, which can further catalyze an exploration of their general MH and devise suitable interventions for the same.

A mixed methods approach identifying facilitators and barriers to guide adaptations to InterCARE strategies: an integrated HIV and hypertension care model in Botswana.

BACKGROUND: Botswana serves as a model of success for HIV with 95% of people living with HIV (PLWH) virally suppressed. Yet, only 19% of PLWH and hypertension have controlled blood pressure. To address this gap, InterCARE, a care model that integrates HIV and hypertension care through a) provider training; b) adapted electronic health record; and c) treatment partners (peer support), was designed. This study presents results from our baseline assessment of the determinants and factors used to guide adaptations to InterCARE implementation strategies prior to a hybrid type 2 effectiveness-implementation study. METHODS: This study employed a convergent mixed methods design across two clinics (one rural, one urban) to collect quantitative and qualitative data through facility assessments, 100 stakeholder surveys (20 each PLWH and hypertension, existing HIV treatment partners, clinical healthcare providers (HCPs), and 40 community leaders) and ten stakeholder key informative interviews (KIIs). Data were analyzed using descriptive statistics and deductive qualitative analysis organized by the Consolidated Framework for Implementation Research (CFIR) and compared to identify areas of convergence and divergence. RESULTS: Although 90.3% of 290 PLWH and hypertension at the clinics were taking antihypertensive medications, 52.8% had uncontrolled blood pressure. Results from facility assessments, surveys, and KIIs identified key determinants in the CFIR innovation and inner setting domains. Most stakeholders (> 85%) agreed that InterCARE was adaptable, compatible and would be successful at improving blood pressure control in PLWH and hypertension. HCPs agreed that there were insufficient resources (40%), consistent with facility assessments and KIIs which identified limited staffing, inconsistent electricity, and a lack of supplies as key barriers. Adaptations to InterCARE included a task-sharing strategy and expanded treatment partner training and support. CONCLUSIONS: Integrating hypertension services into HIV clinics was perceived as more advantageous for PLWH than the current model of hypertension care delivered outside of HIV clinics. Identified barriers were used to adapt InterCARE implementation strategies for more effective intervention delivery. TRIAL REGISTRATION: ClinicalTrials.gov, ClinicalTrials.gov Identifier: NCT05414526 . Registered 18 May 2022 - Retrospectively registered.

Designing an implementation science clinical trial to integrate hypertension and cardiovascular diseases care into existing HIV services package in Botswana (InterCARE).

BACKGROUND: Despite success in HIV treatment, diagnosis and management of hypertension (HTN) and cardiovascular disease (CVD) remains suboptimal among people living with HIV (PLWH) in Botswana, with an overall HTN control of only 19% compared to 98% HIV viral suppressed. These gaps persist despite CVD primary care national guidelines and availability of free healthcare including antihypertensive medications. Our study aims to develop and test strategies to close the HTN care gap in PLWH, through integration into HIV care, leveraging the successful national HIV care and treatment program and strategies. METHODS: The InterCARE trial is a cluster randomized controlled hybrid type 2 effectiveness-implementation trial at 14 sites designed to enroll 4652 adults living with HIV and HTN plus up to 2326 treatment partners. Primary outcomes included effectiveness (HTN control) and implementation outcomes using the Reach Effectiveness Adoption Implementation and Maintenance framework, with explanatory mixed methods used to understand variability in outcomes. InterCARE trial's main strategies include healthcare worker HTN and CVD care training plus long-term practice facilitation, electronic health record (EHR) documentation of key indicators and use of reminders, and use of treatment partners to provide social support to people living with HIV and HTN. InterCARE started with formative research to identify contextual factors influencing care gaps using the Consolidated Framework for Implementation Research. Results were used to adapt initial and develop additional implementation strategies to address barriers and leverage facilitators. The package was pilot tested in two clinics, with findings used to further adapt or add strategies for the clinical trial. DISCUSSION: If successful, the InterCARE model can be scaled up to HIV clinics nationwide to improve diagnosis, management, and support in Botswana. The trial will provide insights for scale-up of HTN integration into HIV care in the region. TRIAL REGISTRATION: ClinicalTrials.gov reference NCT05414526. Registered 18 May 2022, https://clinicaltrials.gov/study/NCT05414526?term=NCT05414526.&rank=1 .

Quantitative outcomes of a type 2 single arm hybrid effectiveness implementation pilot study for hypertension-HIV integration in Botswana.

BACKGROUND: Successful HIV treatment programs have turned HIV into a chronic condition, but noncommunicable diseases such as hypertension jeopardize this progress. Hypertension control rates among people with HIV (PWH) are low owing to gaps in patient awareness, diagnosis, effective treatment, and management of both conditions at separate clinic visits. Integrated management, such as in our study, InterCARE, can enhance HIV-hypertension integration and blood pressure (BP) control. METHODS: Our pilot study was conducted in two Botswana HIV clinics between October 2021 and November 2022. Based on our formative work, we adopted three main strategies; Health worker training on HTN/cardiovascular disease (CVD) management, adaptation of HIV Electronic Health Record (EHR) for HTN/CVD care, and use of treatment partners to support PWH with hypertension for implementation. We employed the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework to assess implementation effectiveness and outcomes for BP control at baseline, 6 and 12 months. HIV viral load (VL) suppression was also measured to assess impact of integration on HIV care. RESULTS: We enrolled 290 participants; 35 (12.1%) were lost to follow-up, leaving 255 (87.9%) at 12-months. Median age was 54 years (IQR 46-62), and 77.2% were females. Our interventions significantly improved BP control to < 140/90 mmHg (or < 130/80 mmHg if diagnosis of diabetes or chronic kidney disease), from 137/290 participants, 47.2% at baseline to 206/290 participants, 71.0%, at 12 months (p < 0.001). Among targeted providers, 94.7% received training, with an associated significant increase in counseling on exercise, diet, and medication (all p < 0.001) but EHR use for BP medication prescribing and cardiovascular risk factor evaluation showed no adoption. In the intention-to-treat analysis, HIV VL suppression at 12 months decreased (85.5% vs 93.8%, p = 0.002) due to loss to follow-up but the per protocol analysis showed no difference in VL suppression between baseline and 12 months (97.3% vs 93.3%, p = 0.060). CONCLUSION: The InterCARE pilot study demonstrated that low-cost practical support measures involving the integration of HIV and hypertension/CVD management could lead to improvements in BP control. These results support the need for a large implementation and effectiveness trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05414526. Registered 18th May 2022.

Impact of the COVID-19 Public Health Crisis and a Structured COVID Unit on Physician Behaviors in Code Status Ordering.

Purpose: Code status orders are standard practice impacting end-of-life care for individuals. This study reviews the impact of a COVID unit on physician behaviors towards goal-concordant end-of-life care at an urban academic tertiary-care hospital. Methods: We conducted a retrospective cohort study of code status ordering on adult inpatients comparing the pre-pandemic period to patients who tested positive, negative and were not tested during the pandemic from January 1, 2019, to December 31, 2020. Results: We analyzed 59,471 unique patient encounters (n = 35,317 pre-pandemic and n = 24,154 during). 1,631 cases of COVID-19 were seen. The rate of code status orders among all inpatients increased from 22% pre-pandemic to 29% during the pandemic (P < .001). Code status orders increased for both patients who were COVID-negative (32% P < .001) and COVID-positive (65% P < .001). Being in a cohorted COVID unit increased code status ordering by an odds of 4.79 (P < .001). Compared to the pre-pandemic cohort, the COVID-positive cohort is less female (50% to 56% P < .001), more Black (66% to 61% P < .001), more Hispanic (6.5% to 5%) and less white (26% to 30% P < .001). Compared to Black patients, white patients had lower odds (.86) of code status ordering (P < .001). Other race/ethnicity categories were not significant. Conclusions: Code status ordering remains low. Compared to pre-pandemic rates, the frequency of orders placed significantly increased for all patients during the pandemic. The largest increase occurred in patients with COVID-19. This increase likely occurred due to protocols in the COVID unit and disease uncertainty.

Cross-sectional analysis of factors associated with medication adherence in western Kenya.

OBJECTIVES: Poor medication adherence in low-income and middle-income countries is a major cause of suboptimal hypertension and diabetes control. We aimed to identify key factors associated with medication adherence in western Kenya, with a focus on cost-related and economic wealth factors. SETTING: We conducted a cross-sectional analysis of baseline data of participants enrolled in the Bridging Income Generation with Group Integrated Care study in western Kenya. PARTICIPANTS: All participants were ≥35 years old with either diabetes or hypertension who had been prescribed medications in the past 3 months. PRIMARY AND SECONDARY OUTCOME MEASURES: Baseline data included sociodemographic characteristics, wealth and economic status and medication adherence information. Predictors of medication adherence were separated into the five WHO dimensions of medication adherence: condition-related factors (comorbidities), patient-related factors (psychological factors, alcohol use), therapy-related factors (number of prescription medications), economic-related factors (monthly income, cost of transportation, monthly cost of medications) and health system-related factors (health insurance, time to travel to the health facility). A multivariable analysis, controlling for age and sex, was conducted to determine drivers of suboptimal medication adherence in each overarching category. RESULTS: The analysis included 1496 participants (73.7% women) with a mean age of 60 years (range 35-97). The majority of participants had hypertension (69.2%), 8.8% had diabetes and 22.1% had both hypertension and diabetes. Suboptimal medication adherence was reported by 71.2% of participants. Economic factors were associated with medication adherence. In multivariable analysis that investigated specific subtypes of costs, transportation costs were found to be associated with worse medication adherence. In contrast, we found no evidence of association between monthly medication costs and medication adherence. CONCLUSION: Suboptimal medication adherence is highly prevalent in Kenya, and primary-associated factors include costs, particularly indirect costs of transportation. Addressing all economic factors associated with medication adherence will be important to improve outcomes for non-communicable diseases. TRIAL REGISTRATION NUMBER: NCT02501746.

Mental health resources, barriers, and intervention needs among women in rural Maharashtra, India: A qualitative study.

This research paper focuses on the mental health needs, the need for mental health interventions and barriers in mental healthcare of women living in rural Maharashtra, India. Using a mixed-methods approach, the study has collected data from a sample of women living in the rural areas of Maharashtra through in-depth interviews. The data collected has been analyzed to identify the barriers and obstacles in mental healthcare, how the existing community support serves as a resource as well as the desire for potential mental healthcare interventions among participants. The findings of the study are expected to contribute to the development of effective mental health interventions tailored to the specific needs of women living in the rural areas of Maharashtra. Overall, this research paper aims to improve the understanding of the mental health needs of women in rural Maharashtra and provide insights for policymakers and mental health practitioners to develop effective interventions to promote their mental well-being.

Perceptions of the Doctor-Patient Relationship Among Patients in a Private, Secondary-Level Hospital in Southern India.

Introduction: An epidemic of non-communicable diseases (NCDs) in India is fueling a growing demand for primary care and hospitalization services. Difficulties in coordinating inpatient and outpatient care create significant barriers to providing high-quality medical care. In this paper, we describe patient experiences, perceptions, and expectations of doctor-patient relationships in a secondary-level private hospital in Karnataka, India. Methods: We conducted a cross-sectional, mixed-method needs assessment with surveys and in-depth interviews at Dr. TMA Pai Hospital (TMAPH), a secondary-level, private sector hospital in Karnataka, India. Inclusion criteria included all adults over 18 years old hospitalized at TMAPH in the past year. Patients were consecutively recruited from August 2019-October 2019 and asked to rate aspects of their relationship with their primary care provider (PCP). Descriptive statistics and multivariable logistic regression were used to analyze predictors of the doctor-patient relationship. Patients were interviewed regarding their perceptions of care coordination and doctor-patient relationships. General Thematic Analysis was utilized to analyze qualitative data and develop themes. Quantitative and qualitative findings were then merged to interpret the various dimensions of doctor-patient relationships. Results: A total of 150 patients (47.3% male) enrolled. Ten patients underwent qualitative interviews. The median patient age was 67 years (IQR 56-76). 112 (74.7%) of patients identified a PCP either at or outside of TMAPH. 89% had diabetes and/or hypertension. Compared to patients without a PCP, having a PCP led to a significantly higher adjusted odds of always spending optimal time with their doctors (aOR 2.7, 95% CI 1.1-6.8, p = 0.04), and always receiving clear instructions on managing their medical conditions (aOR 2.5, 95% CI 1.0-6.1, p = 0.04). The following themes were developed from patient interviews: (1) patients trusted and respected their PCP believing they were receiving high quality care; and (2) despite perceived fragmentation in care, patients spoke favorably of their relationships with their doctors. Conclusions: Among a sample of recently hospitalized patients, those with a PCP reported more positive doctor-patient relationships, though rates of dissatisfaction with doctors were still high. Further research and strategies are required to optimize continuity of care and doctor-patient relationships across the entire continuum of outpatient and inpatient care.

Maintaining care delivery for non-communicable diseases in the face of the COVID-19 pandemic in western Kenya.

The coronavirus disease 2019 (COVID-19) pandemic has disrupted health systems worldwide, gravely threatening continuity of care for non-communicable diseases (NCDs), particularly in low-resource settings. We describe our efforts to maintain the continuity of care for patients with NCDs in rural western Kenya during the COVID-19 pandemic, using a five-component approach: 1) Protect: protect staff and patients; 2) Preserve: ensure medication availability and clinical services; 3) Promote: conduct health education and screenings for NCDs and COVID-19; 4) Process: collect process indicators and implement iterative quality improvement; and 5) Plan: plan for the future and ensure financial risk protection in the face of a potentially overwhelming health and economic catastrophe. As the pandemic continues to evolve, we must continue to pursue new avenues for improvement and expansion. We anticipate continuing to learn from the evolving local context and our global partners as we proceed with our efforts.

Inhibition of calpain but not caspase activity by spectrin fragments.

Calpains and caspases are ubiquitous cysteine proteases that are associated with a variety of cellular pathways. Calpains are involved in processes such as long term potentiation, cell motility and apoptosis, and have been shown to cleave non-erythroid (brain) alpha- and beta-spectrin and erythroid beta-spectrin. The cleavage of erythroid alpha-spectrin by calpain has not been reported. Caspases play an important role in the initiation and execution of apoptosis, and have been shown to cleave non-erythroid but not erythroid spectrin. We have studied the effect of spectrin fragments on calpain and caspase activities. The erythroid and non-erythroid spectrin fragments used were from the N-terminal region of alpha-spectrin, and C-terminal region of beta-spectrin, both consisting of regions involved in spectrin tetramer formation. We observed that the all spectrin fragments exhibited a concentration-dependent inhibitory effect on calpain, but not caspase activity. It is clear that additional studies are warranted to determine the physiological significance of calpain inhibition by spectrin fragments. Our findings suggest that calpain activity is modulated by the presence of spectrin partial domains at the tetramerization site. It is not clear whether the inhibitory effect is substrate specific or is a general effect. Further studies of this inhibitory effect may lead to the identification and development of new therapeutic agents specifically for calpains, but not for caspases. Proteins/peptides with a coiled coil helical conformation should be studied for potential inhibitory effects on calpain activity.

Medication Errors and Blood Pressure Control Among Patients Managed for Hypertension in Public Ambulatory Care Clinics in Botswana.

Background The prevalence of hypertension in low- and middle-income countries is rapidly increasing, with most cases undiagnosed and many poorly controlled among those diagnosed. Medication reconciliation studies from high-income countries have demonstrated a high occurrence of antihypertensive medication errors and a strong association between medication errors and inadequate blood pressure control, but data from low- and middle-income countries are lacking. Methods and Results We conducted a cross-sectional study from April to October 2018 of adult patients on pharmacologic management for known hypertension at 7 public health facilities in Kweneng East District, Botswana. Our aims included to evaluate the frequency of uncontrolled hypertension, the frequency and type of medication errors causing discrepancies between patient-reported and prescribed antihypertensive medications, and the association between medication errors and uncontrolled hypertension. Descriptive analyses and multivariable logistic regression were used. The prevalence of uncontrolled hypertension was 55% among 280 enrolled adult patients, and 95 (34%) had ≥1 medication error. The most common errors included patients taking medications incorrectly (11.1%; 31/280), patients omitting medications (7.9%; 22/280), and unfilled prescriptions caused by pharmacy stock outs (7.5%%; 21/280). Uncontrolled hypertension was significantly associated with having ≥1 medication error compared with no errors (adjusted odds ratio, 3.26; 95% CI, 1.75-6.06; P<0.001). Conclusions Medication errors are strongly associated with poor blood pressure control in this setting. Further research is warranted to assess whether medication reconciliation and other low-cost interventions addressing root causes of medication errors can improve the control of hypertension and other chronic conditions in low- and middle-income countries.

HIV/AIDS and lipodystrophy: implications for clinical management in resource-limited settings.

INTRODUCTION: Lipodystrophy is a term used to describe a metabolic complication of fat loss, fat gain, or a combination of fat loss and gain, which is associated with some antiretroviral (ARV) therapies given to HIV-infected individuals. There is limited research on lipodystrophy in low- and middle-income countries, despite accounting for more than 95% of the burden of HIV/AIDS. The objective of this review was to evaluate the prevalence, pathogenesis and prognosis of HIV-related lipoatrophy, lipohypertrophy and mixed syndrome, to inform clinical management in resource-limited settings. METHODS: We conducted a structured literature search using MEDLINE electronic databases. Relevant MeSH terms were used to identify published human studies on HIV and lipoatrophy, lipohypertrophy, or mixed syndrome in low-, low-middle- and upper-middle-income countries through 31 March 2014. The search resulted in 5296 articles; after 1599 studies were excluded (958 reviews, 641 non-human), 3697 studies were extracted for further review. After excluding studies conducted in high-income settings (n=2808), and studies that did not meet inclusion criteria (n = 799), 90 studies were included in this review. RESULTS AND DISCUSSION: Of the 90 studies included in this review, only six were from low-income countries and eight were from lower middle-income economies. These studies focused on lipodystrophy prevalence, risk factors and side effects of antiretroviral therapy (ART). In most studies, lipodystrophy developed after the first six months of therapy, particularly with the use of stavudine. Lipodystrophy is associated with increased risk of cardiometabolic complications. This is disconcerting and anticipated to increase, given the rapid scale-up of ART worldwide, the increasing number and lifespan of HIV-infected patients on long-term therapy, and the emergence of obesity and non-communicable diseases in settings with extensive HIV burden. CONCLUSIONS: Lipodystrophy is common in resource-limited settings, and has considerable implications for risk of metabolic diseases, quality of life and adherence. Comprehensive evidence-based interventions are urgently needed to reduce the burden of HIV and lipodystrophy, and inform clinical management in resource-limited settings.