The process of inflammation is orchestrated by macrophages, according to their state of differentiation: thus, classically activated (M1) macrophages initiate the process by elaborating proinflammatory cytokines and reactive oxygen species, whereas the latter phase is controlled by alternatively activated macrophages (M2) to resolve inflammation and promote tissue remodelling with the release of growth factors. In a simple human inflammatory response, such as acute crystal arthropathy, macrophages progress linearly through M1 and M2 phases; however, in chronic inflammatory responses, such as atherosclerosis and Diabetic Nephropathy (DN), both M1 and M2 macrophages may coexist, leading to persistent inflammation and fibrosis. A key macrophage receptor that regulates conversion from M1 to M2 is CD163, the hemoglobin scavenger receptor. Scavenging of hemoglobin:haptoglobin (Hb:Hp) complexes via CD163 leads to nuclear translocation of the transcription factor Nrf2 (NF-E2-related factor 2), upregulation of heme oxygenase (HO)-1 cytoprotective protein, and release of interleukin (IL)-10 anti-inflammatory cytokine; IL-10 is then linked in a positive feedback loop to further CD163 expression. The potency of this M1/M2 switching pathway is underscored by the fact that human Hp2 polymorphisms are associated with worsened clinical outcomes for diabetic complications, including DN. Parallel observations in animals show that HO-1 activation by hemin protects against DN in rodent models of diabetes. This review discusses the concept that Nrf2/HO-1 acts as a 'therapeutic funnel' through which a range of natural and synthetic anti-oxidants may drive M1 to M2 switching and improved kidney function in diabetes. We also discuss our observations on the evolution of M1/M2 phenotypes in a human model of wound healing which has presented intriguing potential drug targets for DN, such as eotaxin/CCR3.

Background Small island developing states (SIDS) have limited absolute resources for responding to national disasters, including health emergencies. Since the first confirmed case of COVID-19 in the Caribbean on 1st March 2020, non-pharmaceutical interventions (NPIs) have been widely used to control the resulting COVID-19 outbreak. We document the variety of government measures introduced across the Caribbean and explore their impact on aspects of outbreak control. Methods Drawing on publically available information, we present confirmed cases and confirmed deaths to describe the extent of the Caribbean outbreak. We document the range of outbreak containment measures implemented by national Governments, focussing on measures to control movement and gatherings. We explore the temporal association of containment measures with the start of the outbreak in each country, and with aggregated information on human movement, using smartphone positioning data. We include a set of comparator countries to provide an international context. Results As of 25th May, the Caribbean reported 18,755 confirmed cases and 631 deaths. There have been broad similarities but also variation in the number, the type, the intensity, and particularly the timing of the NPIs introduced across the Caribbean. On average, Caribbean governments began controlling movement into countries 27 days before their first confirmed case and 23 days before comparator countries. Controls on movement within country were introduced 9 days after the first case and 36 days before comparators. Controls on gatherings were implemented 1 day before the first confirmed case and 30 days before comparators. Confirmed case growth rates and numbers of deaths have remained low across much the Caribbean. Stringent Caribbean curfews and stay-at-home orders coincided with large reductions in community mobility, regularly above 60%, and higher than most international comparator countries. Conclusion Stringent controls to limit movement, and specifically the early timing of those controls has had an important impact on containing the spread of COVID-19 across much of the Caribbean. Very early controls to limit movement into countries may well be particularly effective for small island developing states. With much of the region economically reliant on international tourism, and with steps to open borders now being implemented, it is critical that the region draws on a solid evidence-base to balance the competing demands of economic wellbeing and public health.

This review identifies important positive effects of educational interventions on improving patient knowledge of sickle cell disease and depression. Effects on patients' knowledge were maintained for longer than for caregivers. The effect on knowledge was significant but small and whether it offers any clinical benefit is uncertain. Significant factors limiting these effects could be trials being under powered as well as attrition rates. Effects were not statistically significant in assessments of secondary outcomes, possibly due to the paucity of the number of trials and patients and caregivers. Trials showed moderate to high heterogeneity which might impact the results. To better study effects on outcomes, further controlled trials are needed with rigorous attention given to improve recruitment and retention and to decrease bias. Predetermined protocols using similar measurements should be used across multiple sites.

BackgroundThe aim of this study was to establish the prevalence and risk factors for intergenerational (IG)-sex in females aged 15–19 residing in Barbados.MethodsThis cross sectional cluster survey was conducted in a 2.6% national sample in the age range (n = 261) recruited from multiple polling districts chosen with a probability proportional to size. Consent was obtained from participants aged ≥18 years or from parents/guardians of participants <18 years, with participant assent. The prevalence of age at first sex was analyzed using a life table approach and risk factors for IG sex (defined as sexual relations with a male 10 or more years older) were analyzed by logistic regression, adjusting for age.Results51.0% of adolescent females in the survey reported ever having had sex, among whom prevalence of IG-sex was 13.2% (95% CI: 6.7-19.8) at first sex, 29.0% (22.3-35.7) within the preceding twelve months, and 34.8% (24.3-45.4) ever. Condom use at first sex was positively related to willingness to have sex (F statistic = 9.8, p = 0.001). The strongest determinant for IG-sex was age of sexual debut (age adjusted Odds Ratio [95% CI]: 0.58[0.41-0.83]), followed by money or gifts received from the partner (2.91[1.17-7.23] and self-esteem (0.33[0.11-0.95]).ConclusionsThe survey establishes a high rate of IG-sex in Barbados, a ‘high income’ country. Most insightful is that risk of IG-sex nearly halved for every year at which first sex was delayed. A high proportion of coerced sex was reported at first sexual experience and this was linked to poor condom use. Affirmative prevention approaches are recommended to boost self-acclamation of adolescent women within less coercive relationships, especially during their first sexual encounter.

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BackgroundComprehensive care in homozygous sickle cell disease (HbSS) entails universal neonatal screening and subsequent monitoring of identified patients, a process which has been streamlined in the neighbouring island of Jamaica. In preparation for a similar undertaking in Barbados, we have developed a database of persons with known HbSS, and have piloted processes for documenting clinical manifestations. We now present a brief clinical profile of these findings with comparisons to the Jamaican cohort.MethodsHbSS participants were recruited from clinics and support groups. A history of select clinical symptoms was taken and blood and urine samples and echocardiograms were analysed. A re-analysis of data from a previous birth cohort was completed.ResultsForty-eight persons participated (32 F/16 M); age range 10–62 yrs. 94% had a history of ever having a painful crisis. In the past year, 44% of participants had at least one crisis. There were >69 crises in 21 individuals; 61% were self-managed at home and the majority of the others were treated and discharged from hospital; few were admitted. The prevalence of chronic leg ulceration was 27%. Forty-two persons had urinalysis, 44% were diagnosed with albuminuria (urinary protein/creatinine ratio ≥30 mg/g). Thirty-two participants had echocardiography, 28% had a TRJV ≥ 2.5 m/s. Re-analysis of the incidence study revealed a sickle gene frequency (95% CI) of 2.01% (0.24 to 7.21).ConclusionAlthough we share a common ancestry, it is thought that HbSS is less common and less severe in Barbados compared to Jamaica. The Jamaican studies reported a sickle gene frequency of 3.15 (2.81 to 3.52); the prevalence of chronic leg ulcers and albuminuria was 29.5% and 42.5% respectively. These comparisons suggest that our initial thoughts may be speculative and that HbSS may be an underestimated clinical problem in Barbados. A prospective neonatal screening programme combined with centralized, routine monitoring of HbSS morbidity and outcomes will definitively answer this question and will improve the evidence-based care and management of HbSS in Barbados.

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Objectives The aims of this feasibility study were to (1) examine the implementation of a community-based health advocate (CHA) training programme to develop the clinical skills needed to support a diabetes remission protocol based on a low-calorie diet (LCD) and (2) investigate if participant weight loss can be achieved and diabetes remission induced under these conditions. Methods This tripartite study followed a type 2 implementation-effectiveness design. Three faith-based organisations (FBOs) were purposively selected as study sites. Implementation outcomes were guided by the Consolidated Framework for Implementation Research. During the pre-implementation phase, site ‘readiness’ to facilitate the intervention was determined from a site visit and an interview with the FBOs’ leadership. During the implementation phase, congregants could volunteer for the 10-week CHA training which included practical exercises in weight, glucose and blood pressure (BP) measurement, and a summative practical assessment. Acceptability and implementation effectiveness were assessed via survey. During the intervention phase, other congregants and community members with T2DM or pre-diabetes and overweight were invited to participate in the 12-week LCD. Anti-diabetic medication was discontinued on day 1 of the intervention. Clinical effectiveness was determined from the change in weight, fasting blood glucose (FBG) and BP which were monitored weekly at the FBO by the CHA. HbA1C was performed at weeks 1 and 12. Results The FBOs were found to be ready as determined by their adequate resources and engagement in health-related matters. Twenty-nine CHAs completed the training; all attained a passing grade at ≥1 clinical station, indicating implementation effectiveness. CHA feedback indicated that the programme structure was acceptable and provided sufficient access to intervention-related material. Thirty-one persons participated in the LCD (11 T2DM:20 pre-diabetes). Mean (95%CI) weight loss was 6.0 kg (3.7 to 8.2), 7.9 kg in males vs 5.7 kg in females; A1C (%) decreased from 6.6 to 6.1, with a greater reduction in those with T2DM when compared to pre-diabetes. FBG decreased from 6.4 to 6.0mmol/L. T2DM remission rates were 60% and 90% by A1C<6.5% and FBG<7mmol/L respectively. Pre-diabetes remission was 18% and 40% by A1C<5.7% and FBG<5.6 respectively. Conclusion Implementation of a community-based diabetes remission protocol is both feasible and clinically effective. Its sustainability is to be determined. Adaptability to other disorders or other settings should be investigated. Trial registration NCT03536377 registered on 24 May 2018.