A pilot study of a Community Health Agent-led type 2 diabetes self-management program using Motivational Interviewing-based approaches in a public primary care center in São Paulo, Brazil

Abstract Background Rates of noncommunicable diseases (NCDs) such as type 2 diabetes are escalating in low and middle-income countries such as Brazil. Scalable primary care-based interventions are needed to improve self-management and clinical outcomes of adults with diabetes. This pilot study examines the feasibility, acceptability, and outcomes of training community health agents (CHAs) in Motivational Interviewing (MI)-based counseling for patients with poorly controlled diabetes in a primary care center in São Paulo, Brazil. Methods Nineteen salaried CHAs participated in 32 h of training in MI and behavioral action planning. With support from booster training sessions, they used these skills in their regular monthly home visits over a 6 month period with 57 diabetes patients with baseline HbA1cs > 7.0%. The primary outcome was patients’ reports of the quality of diabetes care as measured by the Portuguese version of the Patient Assessment of Chronic Illness Care (PACIC) scale. Secondary outcomes included changes in patients’ reported diabetes self-management behaviors and in A1c, blood pressure, cholesterol and triglycerides. We also examined CHAs’ fidelity to and experiences with the intervention. Results Patients reported improvements over the 6 month period in quality of diabetes care received (PACIC score improved 33 (+/−19) to 68 (+/−21) (p < .001)). They reported increases in physical activity (p = .001), consumption of fruits and vegetables (p < .001) and medication adherence (p = .002), but no decreases in consumption of high-fat foods (p = .402) or sweets (p = .436). Participants had mean 6-month A1c levels 0.34% points lower than at baseline (p = .08) and improved mean LDL (−16.1 mg/dL, p = .005) and triglyceride levels (−38.725 mg/dL, p = .002). Of the 16 CHAs observed in fidelity assessments, 13 were categorized as medium- or high-performing on MI skills, while 3 were low-performing. CHAs expressed enthusiasm about learning new skills, and many described a shift from advice-giving to encouraging patients to define their own goals. Conclusion In resource-scarce settings, it is essential to fully utilize existing primary care resources to stem the epidemic of diabetes and other NCDs. Our pilot results support the potential of training CHAs to incorporate effective diabetes self-management support into their routine patient encounters. Trial registration NCT02994095 12/14/2016 Registered retrospectively.http://deepblue.lib.umich.edu/bitstream/2027.42/135718/1/12913_2016_Article_1968.pd

Multiple micronutrients and docosahexaenoic acid supplementation during pregnancy : A randomized controlled study

Maternal dietary intake during pregnancy needs to meet increased nutritional demands to maintain metabolism and to support fetal development. Docosahexaenoic acid (DHA) is essential for fetal neuro-/visual development and in immunomodulation, accumulating rapidly within the developing brain and central nervous system. Levels available to the fetus are governed by the maternal diet. In this multicenter, parallel, randomized controlled trial, we evaluated once-daily supplementation with multiple micronutrients and DHA (i.e., multiple micronutrient supplementation, MMS) on maternal biomarkers and infant anthropometric parameters during the second and third trimesters of pregnancy compared with no supplementation. Primary efficacy endpoint: change in maternal red blood cell (RBC) DHA (wt% total fatty acids) during the study. Secondary variables: other biomarkers of fatty acid and oxidative status, vitamin D, and infant anthropometric parameters at delivery. Supplementation significantly increased RBC DHA levels, the omega-3 index, and vitamin D levels. Subscapular skinfold thickness was significantly greater with MMS in infants. Safety outcomes were comparable between groups. This first randomized controlled trial of supplementation with multiple micronutrients and DHA in pregnant women indicated that MMS significantly improved maternal DHA and vitamin D status in an industrialized setting\u2014an important finding considering the essential roles of DHA and vitamin D

Validation of ultrasound bioimaging to predict worm burden and treatment efficacy in preclinical filariasis drug screening models

Filariasis is a global health problem targeted for elimination. Curative drugs (macroflaricides) are required to accelerate elimination. Candidate macroflaricides require testing in preclinical models of flariasis. The incidence of infection failures and high intra-group variation means that large group sizes are required for drug testing. Further, a lack of accurate, quantitative adult biomarkers results in protracted timeframes or multiple groups for endpoint analyses. Here we evaluate intra-vital ultrasonography (USG) to identify B. malayi in the peritonea of gerbils and CB.17 SCID mice and assess prognostic value in determining drug efcacy. USG operators, blinded to infection status, could detect intra-peritoneal flarial dance sign (ipFDS) with 100% specifcity and sensitivity, when >5 B. malayi worms were present in SCID mice. USG ipFDS was predictive of macroflaricidal activity in randomized, blinded studies comparing fubendazole, albendazole and vehicle-treated SCID mice. Semi-quantifcation of ipFDS could predict worm burden >10 with 87–100% accuracy in SCID mice or gerbils. We estimate that pre-assessment of worm burden by USG could reduce intra-group variation, obviate the need for surgical implantations in gerbils, and reduce total SCID mouse use by 40%. Thus, implementation of USG may reduce animal use, refne endpoints and negate invasive techniques for assessing anti-flarial drug efcacy

Discontinuous gas exchange cycles and active ventilation in pupae of the bumblebee Bombus terrestris

Discontinuous release of CO2 (bursts) or discontinuous gas exchange cycles (DGC), metabolic rate (MR) and ventilation movements were simultaneously recorded from the pupae of the bumblebee Bombus terrestris by means of an electrolytic respirometer and an infrared gas analyser (IRGA) combined with an infrared actograph (IRA). After recovering from stress, the early stage pupae showed irregular continuous respiration, mid-stage pupae displayed regular DGC. The bursts of CO2 release tended to coincide with abdominal contractions. In late stage pupae all bursts of CO2 were associated with active ventilation. During interburst periods, spikes appeared on the respirograms interpreted as micro-cycles of passive suction ventilation (PSV). After removal from their cocoons, the pupae exhibited frequent periods of muscular activity due to stress. Water loss of pupae inside cocoons was significantly less than that from pupae without cocoons

Siblings, Stories and the Self: the sociological significance of young people’s sibling relationships

This article explores the significance of intra-generational ties with siblings to sociological understandings of the formation of social identity and sense of self in young people’s lives. Drawing on data from a qualitative study exploring young people’s sense of who they are and who they have the potential to become in the future, it is demonstrated that young people’s identities are often constructed in relation to how they are similar to or different from their sibling(s). Literature expounding the role of stories in the construction of the self is used to suggest that the comparing that is at the heart of the relational construction of sibling identities can occur through the telling and re-telling of family stories within the politics and power dynamics of existing relationships. The article concludes by suggesting that sibling relationships be conceptualized as part of a web of relationships in which young people are embedded

Macrofilaricidal Activity after Doxycycline Only Treatment of Onchocerca volvulus in an Area of Loa loa Co-Endemicity: A Randomized Controlled Trial

The control of onchocerciasis in Africa relies on the sustained delivery of ivermectin. In certain areas, annual treatments delivered with high population coverage for at least 15–17 years can break transmission. In other endemic settings this strategy alone is thought to be insufficient to eradicate the disease. One of the major limitations occurs in areas that are co-endemic with another filarial infection caused by Loa loa, due to the risk of a rare severe adverse event associated with the rapid killing of L. loa microfilariae in heavily parasitized individuals. There are also concerns over recent evidence of reduced efficacy of ivermectin and the possible development of resistance. An alternative approach is to target the Wolbachia bacterial endosymbionts of Onchocerca volvulus with the antibiotic, doxycycline. In an area of Cameroon co-endemic for onchocerciasis and loiasis we conducted a trial comparing doxycycline with or without ivermectin treatment to ivermectin treatment alone. A six-week course of doxycycline delivers macrofilaricidal and sterilizing activities, which is not dependent upon co-administration of ivermectin. Doxycycline is well tolerated in patients co-infected with moderate intensities of L. loa microfilariae. The trial indicates that anti-wolbachial therapy is a feasible alternative to ivermectin in communities co-endemic for onchocerciasis and loiasis

Designing antifilarial drug trials using clinical trial simulators

Lymphatic filariasis and onchocerciasis are neglected tropical diseases (NTDs) targeted for elimination by mass (antifilarial) drug administration. These drugs are predominantly active against the microfilarial progeny of adult worms. New drugs or combinations are needed to improve patient therapy and to enhance the effectiveness of interventions in persistent hotspots of transmission. Several therapies and regimens are currently in (pre-)clinical testing. Clinical trial simulators (CTSs) project patient outcomes to inform the design of clinical trials but have not been widely applied to NTDs, where their resource-saving payoffs could be highly beneficial. We demonstrate the utility of CTSs using our individual-based onchocerciasis transmission model (EPIONCHO-IBM) that projects trial outcomes of a hypothetical macrofilaricidal drug. We identify key design decisions that influence the power of clinical trials, including participant eligibility criteria and post-treatment follow-up times for measuring infection indicators. We discuss how CTSs help to inform target product profiles

Targeting the Wolbachia Cell Division Protein FtsZ as a New Approach for Antifilarial Therapy

Filarial nematode parasites are responsible for a number of devastating diseases in humans and animals. These include lymphatic filariasis and onchocerciasis that afflict 150 million people in the tropics and threaten the health of over one billion. The parasites possess intracellular bacteria, Wolbachia, which are needed for worm survival. Clearance of these bacteria with certain antibiotics leads to parasite death. These findings have pioneered the approach of using antibiotics to treat and control filarial infections. In the present study, we have investigated the cell division process in Wolbachia for new drug target discovery. We have identified the essential cell division protein FtsZ, which has a GTPase activity, as an attractive Wolbachia drug target. We describe the molecular characterization and catalytic properties of the enzyme and demonstrate that the GTPase activity is inhibited by the natural product, berberine, and small molecule inhibitors identified from a high-throughput screen. We also found that berberine was effective in reducing motility and reproduction in B. malayi parasites in vitro. Our results should facilitate the discovery of selective inhibitors of FtsZ as a novel antibiotic approach for controlling filarial infection

The Wolbachia endosymbiont as an anti-filarial nematode target

Human disease caused by parasitic filarial nematodes is a major cause of global morbidity. The parasites are transmitted by arthropod intermediate hosts and are responsible for lymphatic filariasis (elephantiasis) or onchocerciasis (river blindness). Within these filarial parasites are intracellular alpha-proteobacteria, Wolbachia, that were first observed almost 30 years ago. The obligate endosymbiont has been recognized as a target for anti-filarial nematode chemotherapy as evidenced by the loss of worm fertility and viability upon antibiotic treatment in an extensive series of human trials. While current treatments with doxycycline and rifampicin are not practical for widespread use due to the length of required treatments and contraindications, anti-Wolbachia targeting nevertheless appears a promising alternative for filariasis control in situations where current programmatic strategies fail or are unable to be delivered and it provides a superior efficacy for individual therapy. The mechanisms that underlie the symbiotic relationship between Wolbachia and its nematode hosts remain elusive. Comparative genomics, bioinfomatic and experimental analyses have identified a number of potential interactions, which may be drug targets. One candidate is de novo heme biosynthesis, due to its absence in the genome sequence of the host nematode, Brugia malayi, but presence in Wolbachia and its potential roles in worm biology. We describe this and several additional candidate targets, as well as our approaches for understanding the nature of the host-symbiont relationship