Development of a Library of Thiophene-Based Drug-Like Lego Molecules: Evaluation of Their Anion Binding, Transport Properties, and Cytotoxicity.

The anion-binding and transport properties of an extensive library of thiophene-based molecules are reported. Seventeen bis-urea positional isomers, with different binding conformations and lipophilicities, have been synthesized by appending α- or ß-thiophene or α-, ß-, or γ-benzo[b]thiophene moieties to an ortho-phenylenediamine central core, yielding six subsets of positional isomers. Through 1 H NMR, X-ray crystallography, molecular modelling, and anion efflux studies, it is demonstrated that the most active transporters adopt a pre-organized binding conformation capable of promoting the recognition of chloride, using urea and C-H binding groups in a cooperative fashion. Additional large unilamellar vesicle-based assays, carried out under electroneutral and electrogenic conditions, together with N-methyl-d-glucamine chloride assays, have indicated that anion efflux occurs mainly through an H+ /Cl- symport mechanism. On the other hand, the most efficient anion transporter displays cytotoxicity against tumor cell lines, while having no effects on a cystic fibrosis cell line.

Correction to: Human-centered design as a guide to intervention planning for non-communicable diseases: the BIGPIC study from Western Kenya.

An amendment to this paper has been published and can be accessed via the original article.

Human-centered design as a guide to intervention planning for non-communicable diseases: the BIGPIC study from Western Kenya.

BACKGROUND: Non-communicable disease (NCD) care in Sub-Saharan Africa is challenging due to barriers including poverty and insufficient health system resources. Local culture and context can impact the success of interventions and should be integrated early in intervention design. Human-centered design (HCD) is a methodology that can be used to engage stakeholders in intervention design and evaluation to tailor-make interventions to meet their specific needs. METHODS: We created a Design Team of health professionals, patients, microfinance officers, community health workers, and village leaders. Over 6 weeks, the Design Team utilized a four-step approach of synthesis, idea generation, prototyping, and creation to develop an integrated microfinance-group medical visit model for NCD. We tested the intervention with a 6-month pilot and conducted a feasibility evaluation using focus group discussions with pilot participants and community members. RESULTS: Using human-centered design methodology, we designed a model for NCD delivery that consisted of microfinance coupled with monthly group medical visits led by a community health educator and a rural clinician. Benefits of the intervention included medication availability, financial resources, peer support, and reduced caregiver burden. Critical concerns elicited through iterative feedback informed subsequent modifications that resulted in an intervention model tailored to the local context. CONCLUSIONS: Contextualized interventions are important in settings with multiple barriers to care. We demonstrate the use of HCD to guide the development and evaluation of an innovative care delivery model for NCDs in rural Kenya. HCD can be used as a framework to engage local stakeholders to optimize intervention design and implementation. This approach can facilitate the development of contextually relevant interventions in other low-resource settings. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02501746, registration date: July 17, 2015.

Preparedness of HIV care and treatment clinics for the management of concomitant non-communicable diseases: a cross-sectional survey.

BACKGROUND: In Sub-Saharan Africa, epidemiological studies have reported an increasing burden of non-communicable diseases (NCD) among people living with HIV. NCD management can be feasibly integrated into HIV care; however, clinic readiness to provide NCD services in these settings should first be assessed and gaps in care identified. METHODS: A cross-sectional survey conducted in July 2013 assessed the resources available for NCD care at 14 HIV clinics in Dar es Salaam, Tanzania. Survey items related to staff training, protocols, and resources for cardiovascular disease risk factor screening, management, and patient education. RESULTS: 43 % of clinics reported treating patients with hypertension; however, only 21 % had a protocol for NCD management. ECHO International Health standards for essential clinical equipment were used to measure clinic readiness; 36 % met the standard for blood pressure cuffs, 14 % for glucometers. Available laboratory tests for NCD included blood glucose (88 %), urine dipsticks (78 %), and lipid panel (57 %). 21 % had a healthcare worker with NCD training. All facilities provided some form of patient education, but only 14 % included diabetes, 57 % tobacco cessation, and 64 % weight management. CONCLUSIONS: A number of gaps were identified in this sample of HIV clinics that currently limit the ability of Tanzanian healthcare workers to diagnose and manage NCD in the context of HIV care. Integrated NCD and HIV care may be successfully achieved in these settings with basic measures incorporated into existing infrastructures at minimal added expense, i.e., improving access to basic functioning equipment, introducing standardized treatment guidelines, and improving healthcare worker education.

Nurses' experiences of caring for people with COVID-19 in Hong Kong: a qualitative enquiry.

OBJECTIVES: Nurses are the largest group of healthcare workers on the front line of efforts to control the COVID-19 pandemic. An understanding of their nursing experiences, the challenges they encountered and the strategies they used to address them may inform efforts to better prepare and support nurses and public health measures when facing a resurgence of COVID-19 or new pandemics. This study aimed to explore the experiences of nurses caring for people with suspected or diagnosed COVID-19 in Hong Kong. DESIGN: A qualitative study was conducted using individual, semistructured interviews. All interviews were audio-recorded and transcribed verbatim for thematic analysis. SETTING: Participants were recruited from acute hospitals and a public health department in Hong Kong from June 2020 to August 2020. PARTICIPANTS: A purposive sample of registered nurses (N=39) caring for people with COVID-19 in Hong Kong were recruited. RESULTS: Two-thirds of the nurses had a master's degree and over a third had 6-10 years of nursing experience. Around 40% of the nurses cared for people with COVID-19 in isolation wards and a quarter performed COVID-19-related work for 31-40 hours/week. Most (90%) had training in COVID-19 and three-quarters had experience of working in infection control teams. Six key themes emerged: confronting resource shortages; changes in usual nursing responsibilities and care modes; maintaining physical and mental health; need for effective and timely responses from relevant local authorities; role of the community in public health protection and management; and advanced pandemic preparedness. CONCLUSIONS: Our study found that nurses possessed resilience, self-care and adaptability when confronting resource shortages, changing nursing protocols, and physical and mental health threats during the COVID-19 pandemic. However, coordinated support from the clinical environment, local authorities and community, and advanced preparedness would likely improve nursing responses to future pandemics.

Chronic disease stigma, skepticism of the health system, and socio-economic fragility: Qualitative assessment of factors impacting receptiveness to group medical visits and microfinance for non-communicable disease care in rural Kenya.

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of mortality in the world, and innovative approaches to NCD care delivery are being actively developed and evaluated. Combining the group-based experience of microfinance and group medical visits is a novel approach to NCD care delivery. However, the contextual factors, facilitators, and barriers impacting wide-scale implementation of these approaches within a low- and middle-income country setting are not well known. METHODS: Two types of qualitative group discussion were conducted: 1) mabaraza (singular, baraza), a traditional East African community gathering used to discuss and exchange information in large group settings; and 2) focus group discussions (FGDs) among rural clinicians, community health workers, microfinance group members, and patients with NCDs. Trained research staff members led the discussions using structured question guides. Content analysis was performed with NVivo using deductive and inductive codes that were then grouped into themes. RESULTS: We conducted 5 mabaraza and 16 FGDs. A total of 205 individuals (113 men and 92 women) participated in the mabaraza, while 162 individuals (57 men and 105 women) participated in the FGDs. In the context of poverty and previous experiences with the health system, participants described challenges to NCD care across three themes: 1) stigma of chronic disease, 2) earned skepticism of the health system, and 3) socio-economic fragility. However, they also outlined windows of opportunity and facilitators of group medical visits and microfinance to address those challenges. DISCUSSION: Our qualitative study revealed actionable factors that could impact the success of implementation of group medical visits and microfinance initiatives for NCD care. While several challenges were highlighted, participants also described opportunities to address and mitigate the impact of these factors. We anticipate that our approach and analysis provides new insights and methodological techniques that will be relevant to other low-resource settings worldwide.

Obesity and anthropometry in spina bifida: What is the best measure.

OBJECTIVE: Diagnosis of obesity using traditional body mass index (BMI) using length may not be a reliable indicator of body composition in spina bifida (SB). We examine traditional and surrogate measures of adiposity in adults with SB, correlated with activity, metabolic disease, attitudes towards exercise and quality of life. DESIGN: Adult subjects with SB underwent obesity classification using BMI by length and arm span, abdominal girth and percent trunk fat (TF) on dual energy X-ray absorptiometry (DXA). Quality of life measures, activity level and metabolic laboratory values were also reviewed. RESULTS: Among eighteen subjects (6 male, 12 female), median age was 26.5 (range 19-37) years, with level of lesion 16.7% ≤L2, 61.1% L3-4, and 22.2% ≥L5, respectively. Median weight was 71.8 (IQR 62.4, 85.8) kg, similar between sexes (P = 0.66). With median length of 152.0 (IQR 141.8, 163.3) cm, median conventional BMI was 29.4 m/kg2, with 7 (43.8%) subjects with BMI >30. Median BMI by arm span was 30.2 m/kg2, abdominal girth of 105.5 cm, and TF 45.7%. More subjects were classified as obese using alternate measures, with 9 (56.3%) by arm span, 14 (82.4%) by abdominal girth and 15 (83.3%) by TF (P = 0.008). Reclassification of obesity from conventional BMI was significant when using TF (P = 0.03). No difference in quality of life measures, activity level and metabolic abnormalities was demonstrated between obese and non-obese subjects. CONCLUSIONS: Conventional determination of obesity using BMI by length is an insensitive marker in adults with SB. Adults with SB are more often classified as obese using TF by DXA.

Cardiac Disease Associated with Human Immunodeficiency Virus Infection.

Over the last 2 decades human immunodeficiency virus (HIV) infection has become a chronic disease requiring long-term management. Aging, antiretroviral therapy, chronic inflammation, and several other factors contribute to the increased risk of cardiovascular disease in patients infected with HIV. In low-income and middle-income countries where antiretroviral therapy access is limited, cardiac disease is most commonly related to opportunistic infections and end-stage manifestations of HIV/acquired immunodeficiency syndrome, including HIV-associated cardiomyopathy, pericarditis, and pulmonary arterial hypertension. Cardiovascular screening, prevention, and risk factor management are important factors in the management of patients infected with HIV worldwide.

Development and evaluation of a service-learning model for preclinical student education in cardiovascular disease prevention.

BACKGROUND: Cardiovascular diseases are the leading cause of preventable morbidity and mortality in the USA. Medical schools must prepare trainees to address prevention, including improving ability in counseling patients to modify lifestyle risk factors. Most medical students do not receive significant training or clinical experience in preventive medicine until the clinical years of medical school. To enhance student education in disease prevention and lifestyle counseling, and simultaneously target cardiovascular disease prevention in high-risk Chicago neighborhoods, the Northwestern University Feinberg School of Medicine and Chicago Department of Public Health with support from the GE Foundation, developed the Keep Your Heart Healthy program. METHODS: Medical students participated in intensive faculty-led training. They subsequently screened local residents to identify and counsel for cardiovascular disease risk factors. Fifty-one predominantly preclinical medical students screened residents of the Humboldt Park and North Lawndale neighborhoods in Chicago, IL, at 31 screening events from August to December 2013. Fifty students (98% response rate) completed a survey assessing the educational value of various program components following the pilot. RESULTS: Of all respondents, 92% of students reported improved knowledge of cardiovascular disease prevention and 94% reported improved knowledge of vulnerable populations and health equity. The majority (88%) reported that their participation supplemented material they learned in the classroom. Eighty-six percent of students reported that their encounters with community participants were of educational value. Integration of this program into the medical school curriculum was supported by 68% of students. CONCLUSION: Keep Your Heart Healthy educates primarily preclinical medical students in cardiovascular disease prevention and prepares them to apply this knowledge for patient counseling. Results from student surveys demonstrate that this service-learning initiative enhances medical student knowledge in cardiovascular disease prevention, supplements classroom material, and provides students a valuable opportunity to apply interviewing and counseling skills in a real patient encounter.