Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Ebola vaccination in the Democratic Republic of the Congo: Connections with Ebola exposure history, risk behaviors, and serology

Recent control efforts for Ebola Virus Disease (EVD) outbreaks in the Democratic Republic of Congo (DRC) employed a highly effective recombinant vesicular stomatitis virus-Zaire Ebola vaccine (rVSVΔG-ZEBOV-GP). Given the previously limited opportunities to study EVD vaccination in real-world outbreaks, little is known about this new vaccine in practice beyond its notable efficacy and safety. This dissertation aims to expand our knowledge of EVD vaccination to better understand the new landscape of EVD outbreaks which now includes effective vaccination and treatment. This dissertation focuses on studying the effects of EVD exposure history (being exposed to a family member with EVD, a close contact with EVD, a contact of a contact with EVD, or being potentially exposed to a patient with EVD in a healthcare setting) on post-vaccination transmission behaviors and vaccine immunogenicity. Additionally, this dissertation looks at how vaccination impacts occupational transmission risk among healthcare workers affected by EVD outbreaks in the DRC. Chapter 1 is a brief introduction to Ebola virus, EVD, and Ebola vaccination with a focus on the DRC. Chapter 2 uses longitudinal data from a vaccinated Congolese cohort to show that healthcare workers have unique post-vaccination risk behavior profiles. Chapter 3 uses another Congolese cohort to show that there are few longitudinal differences between vaccinated and unvaccinated healthcare workers, with the exception that vaccinated individuals are more likely to participate in funeral rites during a period containing a resurgent outbreak. Chapter 4 uses g-computation to assess the causal structure underlying EVD exposure history, baseline antibody titer, and vaccine immunogenicity. This chapter shows that while healthcare workers have lower titers at 21 days post vaccination, this does not seem to be mediated by baseline antibody titer. However, an increased baseline titer led to a more robust immune response to vaccination, regardless of EVD exposure history. Finally, Chapter 5 discusses in detail the overall strengths, limitations, and conclusions from this dissertation

Stronger Together: Results from a Randomized Controlled Efficacy Trial of a Dyadic Intervention to Improve Engagement in HIV Care Among Serodiscordant Male Couples in Three US Cities

Engagement in HIV care and a high level of antiretroviral therapy (ART) adherence for people living with HIV is crucial to treatment success and can minimize the population burden of the disease. Despite this, there is a critical gap in HIV prevention science around the development of interventions for serodiscordant male couples. This paper reports on the results of a randomized controlled trial to assess the efficacy of Stronger Together, a dyadic counseling intervention aimed at increasing engagement in and optimizing HIV care among serodiscordant male couples in Atlanta, GA, Boston, MA, and Chicago, IL. Between 2014 and 2017, 159 male serodiscordant couples (total N = 318) in Atlanta, GA, Boston, MA, and Chicago, IL were enrolled and equally randomized to either the Stronger Together intervention arm (a three-session dyadic intervention involving HIV testing and adherence counseling) or a standard of care (SOC) control arm. Couples completed individual study assessments via an audio computer assisted self-interviewing (ACASI) system at baseline, 6, 12 and 18 months. Primary outcomes included being prescribed and currently taking ART, and fewer missed doses of ART in the past 30 days; because the trial was not powered to examine viral suppression, we examined this as an exploratory outcome. Longitudinal data analysis was by an intention-to-treat approach. Participants ages ranged from 18 to 69 (mean = 35.9), and are predominantly white (77.5%), and college educated (68.4% earned a college degree or higher). Participants randomized to the Stronger Together arm had a significantly greater odds of being prescribed and currently taking ART over time than those in the SOC arm (at 12 months OR 2.75, 95%CI 1.35-4.67, p-value 0.020, and at 18 months OR 2.91, 95%CI 1.61-4.88, p-value 0.013). Similarly, those in the Stronger Together arm had a significantly lower odds of missing a dose of ART in the past 30 days over time compared to those in the SOC arm (at 12 months OR 0.28, 95%CI 0.09-0.81, p-value 0.019, and at 18 months OR 0.25, 95%CI 0.07-0.82, p-value 0.023). Among male couples in serodiscordant relationships, the Stronger Together intervention resulted in significantly improved HIV treatment outcomes at both 12 and 18 months of follow-up. This trial is the first to date to demonstrate evidence of efficacy for a dyadic counseling intervention and has the potential to fill a critical gap in secondary HIV prevention interventions for serodiscordant male couples

Changes in childhood vaccination coverage over time in the Democratic Republic of the Congo.

Despite increased vaccination rates, the burden, morbidity and mortality associated with vaccine preventable diseases remains high. In the Democratic Republic of the Congo (DRC), potentially unreliable data and geographically varied program provision call for a better understanding of vaccination coverage and its changes over time at the country and province level. To assess changes in the proportion of children who were fully vaccinated over time in the DRC, vaccination histories for children 12-59 months of age were obtained from both the 2007 and 2013-2014 Demographic and Health Surveys (DHS). Changes were assessed, both at the country- and province-levels, to identify potential geographic variations. Vaccination coverage improved 70% between the DHS waves: 26% compared to 44% of 12-59 month-old children met full vaccination criteria in 2007 and 2013-2014, respectively (n2007 = 3032 and n2013-14 = 6619). Similarly, there was an overall trend across both DHS waves where as year of birth increased, so did vaccination coverage. There was geographic variation in immunization changes with most central and eastern provinces increasing in coverage and most northern, western and southern provinces having decreased vaccination coverage at the second time point. Using nationally representative data, we identified significant changes over time in vaccination coverage which may help to inform future policy, interventions and research to improve vaccination rates among children in the DRC. This study is the first of its kind for the population of DRC and provides an important initial step towards better understanding trends in vaccination coverage over time

Changes in childhood vaccination coverage over time in the Democratic Republic of the Congo

Despite increased vaccination rates, the burden, morbidity and mortality associated with vaccine preventable diseases remains high. In the Democratic Republic of the Congo (DRC), potentially unreliable data and geographically varied program provision call for a better understanding of vaccination coverage and its changes over time at the country and province level. To assess changes in the proportion of children who were fully vaccinated over time in the DRC, vaccination histories for children 12-59 months of age were obtained from both the 2007 and 2013-2014 Demographic and Health Surveys (DHS). Changes were assessed, both at the country- and province-levels, to identify potential geographic variations. Vaccination coverage improved 70% between the DHS waves: 26% compared to 44% of 12-59 month-old children met full vaccination criteria in 2007 and 2013-2014, respectively (n2007 = 3032 and n2013-14 = 6619). Similarly, there was an overall trend across both DHS waves where as year of birth increased, so did vaccination coverage. There was geographic variation in immunization changes with most central and eastern provinces increasing in coverage and most northern, western and southern provinces having decreased vaccination coverage at the second time point. Using nationally representative data, we identified significant changes over time in vaccination coverage which may help to inform future policy, interventions and research to improve vaccination rates among children in the DRC. This study is the first of its kind for the population of DRC and provides an important initial step towards better understanding trends in vaccination coverage over time

COVID-19 Vaccine Acceptability and Financial Incentives among Unhoused People in Los Angeles County: a Three-Stage Field Survey.

Unhoused people have higher COVID-19 mortality and lower vaccine uptake than housed community members. Understanding vaccine hesitancy among unhoused people is key for developing programs that address their unique needs. A three-round, rapid, field-based survey was conducted to describe attitudes toward COVID-19 vaccination. Round 1 assessed vaccine brand preference, round 2 assessed intention to accept a financial incentive for vaccination, and round 3 measured vaccine uptake and assessed reasons for vaccine readiness during implementation of a financial incentive program. A total of 5177 individuals were approached at COVID-19 vaccination events for unhoused people in Los Angeles County from May through November 2021. Analyses included 4949 individuals: 3636 (73.5%) unsheltered and 1313 (26.5%) sheltered. Per self-report, 2008 (40.6%) were already vaccinated, 1732 (35%) wanted to get vaccinated, 359 (7.3%) were not yet ready, and 850 (17.2%) did not want to get vaccinated. Brand preference was evenly split among participants (Moderna 31.0%, J&J 35.5%, either 33.5%, p = 0.74). Interest in a financial incentive differed between those who were not yet ready and those who did not want to get vaccinated (43.2% vs. 16.2%, p < 0.01). After implementing a financial incentive program, 97.4% of participants who indicated interest in vaccination were vaccinated that day; the financial incentive was the most cited reason for vaccine readiness (n = 731, 56%). This study demonstrated the utility of an iterative, field-based assessment for program implementation during the rapidly evolving pandemic. Personal engagement, a variety of brand choices, and financial incentives could be important for improving vaccine uptake among unhoused people

Increasing Ebola transmission behaviors 6 months post-vaccination: Comparing vaccinated and unvaccinated populations near 2018 Mbandaka Ebola outbreak in the Democratic Republic of Congo.

BackgroundIn 2018, the Democratic Republic of the Congo (DRC) declared its 9th and 10th Zaire ebolavirus (EBOV) outbreaks, in the Equateur province (end: July 2018), and in the eastern provinces including North Kivu (end: June 2020). The DRC Ministry of Health deployed the rVSV-vectored glycoprotein (VSV-EBOV) vaccine in response during both outbreaks.MethodsA cohort of vaccinated and unvaccinated individuals from the Equateur province were enrolled and followed prospectively for 6 months. Among participants included in this analysis, 505 were vaccinated and 1,418 were unvaccinated. Differences in transmission behaviors pre- and post- outbreak were identified, along with associations between behaviors and vaccination.ResultsThere was an overall increase in the proportion of both unvaccinated and vaccinated individuals in Mbandaka who participated in risky activities post-outbreak. Travel outside of the province pre-outbreak was associated with vaccination. Post-outbreak, vaccinated individuals were less likely to participate in funeral traditions than unvaccinated individuals.ConclusionA net increase in activities considered high risk was observed in both groups despite significant efforts to inform the population of risky behaviors. The absence of a reduction in transmission behavior post-outbreak should be considered for improving future behavior change campaigns in order to prevent recurrent outbreaks

Hesitancy to receive the novel coronavirus vaccine and potential influences on vaccination among a cohort of healthcare workers in the Democratic Republic of the Congo.

Hesitancy to receive the COVID-19 vaccine among healthcare workers (HCWs) in low-resource settings, such as the Democratic Republic of the Congo (DRC), is a major global health challenge. This study identifies changes in willingness to receive vaccination among 588 HCWs in the DRC and reported influences on COVID-19 vaccination intentions. Up to 25 repeated measures were collected from participants between August 2020 to August 2021. Among the overall cohort, between August 2020 and mid-March 2021, the proportion of HCWs in each period of data collection reporting COVID-19 vaccine hesitancy ranged from 8.6% (95% CI: 5.97, 11.24) to 24.3% (95% CI: 20.12, 28.55). By early April 2021, the proportion reporting hesitancy more than doubled (52.0%; 95% CI: 46.22, 57.83). While hesitancy in the cohort began to decline by late-June 2021, 22.6% (95% CI: 18.05, 27.18) respondents indicated hesitancy in late-August 2021 which remains greater than the proportion of hesitancy at any time prior to early-March 2021. Patterns in reported influences on COVID-19 vaccination were varied with the proportion reporting some influences (e.g., no serious side effects, country of vaccine production) remaining stable throughout the year and other factors (e.g., recommendation of Ministry of Health, ease of vaccination) falling in popularity among respondents. Agreement that the national vaccination schedule should be followed apart from the COVID-19 vaccine remained high among respondents throughout the study period. This study shows that, among a cohort of HCWs in the DRC who have likely been influenced by regional, national, and global factors, COVID-19 vaccine hesitancy has fluctuated during the pandemic and should not be treated as a static factor. Additional research to determine which factors most influence HCWs' willingness to receive the COVID-19 vaccine offers opportunities to reduce vaccine hesitancy among this important population through tailored public health messaging