Publications

We report the case of a 51-year-old woman presenting with a targetoid rash and pancytopenia after a tick bite. Initial evaluation was notable for severe neutropenia on the complete blood cell count differential, a positive Lyme IgM antibody, and a peripheral blood smear demonstrating atypical lymphocytes. While her pancytopenia was initially attributed to tick-borne illness, peripheral flow cytometry showed 7% myeloblasts, and a bone marrow biopsy confirmed 60% blasts. The patient was ultimately diagnosed with acute myelogenous leukemia, in addition to early, localized Lyme disease. This case highlights the differential diagnosis for pancytopenia, cytopenia patterns for different tick-borne illnesses, the risk of premature closure in internal medicine, and management of Lyme disease in hosts with altered immunity.

Background

We examine changes in soluble inflammatory cytokines and T-cell activation after antiretroviral therapy (ART) initiation in an ACTG nested case-control study.

Methods

Cases were 143 HIV-infected adults who developed a non-AIDS event; 315 controls remained event-free. Specimens were tested pre-ART, year 1 post-ART and at the visit preceding the event. Conditional logistic regression evaluated the associations of biomarker changes with non-AIDS events.

Results

Inflammatory and most activation biomarkers declined from pre-ART to year 1 for cases and controls. Subsequently, inflammatory biomarkers remained mostly stable in controls but not cases. Cellular activation markers generally declined for both cases and controls between year 1 and the pre-event sampling. Controls with greater pre-ART RNA levels or lower CD4+ levels had higher biomarker levels while also experiencing greater biomarker declines in the first year of ART. Changes in biomarkers to year 1 showed no significant associations with non-AIDS events. Cases, however, had significantly greater increases in all plasma biomarkers (but not cellular activation) from year 1 to the visit preceding the event.

Conclusions

Inflammation increases prior to non-AIDS events in treated HIV-infected adults. These biomarker changes may reflect subclinical disease processes or other alterations in the inflammatory environment that causally contribute to disease.

Clinical Trials registration

NCT00001137 https://clinicaltrials.gov/ct2/show/NCT00001137.

We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.

BACKGROUND

The improvement of existing medical training programmes in resource-constrained settings is seen as key to addressing the challenge of retaining medical graduates trained at considerable cost both in-country and abroad. In Botswana, the establishment of the national Medical Internship Training Programme (MIT) in 2014 was a first step in efforts to promote retention through the expansion and standardization of internship training, but MIT faces a major challenge related to variability between incoming trainees due to factors such as their completion of undergraduate medical training in different settings. To address this challenge, in August 2016 we piloted a bridging programme for foreign and locally trained medical graduates that aimed to facilitate their transition into internship training. This study aimed to describe the programme and evaluate its impact on the participants' self-rated perceptions of their knowledge, experience, clinical skills, and familiarity with Botswana's healthcare system.

METHODS

We conducted a national, intensive, two-week programme designed to facilitate the transition from medical student to intern and to prepare all incoming interns for their work in Botswana's health system. Participants included all interns entering in August 2016. Formats included lectures, workshops, simulations, discussions, and reflection-oriented activities. The Kellogg Foundation Outcomes Logic Model was used to evaluate the programme, and participants self-rated their knowledge, skills, and attitudes across each of the programme objectives on paired questionnaires before and after participation.

RESULTS

48/54 participants (89%) provided paired data. Participants reported a high degree of satisfaction with the programme (mean 4.2/5). Self-rated preparedness improved after participation (mean 3.2 versus 3.7, p < 0.001), as did confidence across 18/19 knowledge/skill domains, suggesting that participants felt that the programme prepared them for their internship training. Exploratory analysis revealed that 20/25 participants (80%) reporting either no effect or a negative effect following participation had rated themselves "extremely" or "quite" prepared beforehand, suggesting the programme grounded expectations for interns who initially were overconfident. In contrast, no interns who had initially rated themselves "moderately" or "somewhat" prepared reported a decline in their self-rated sense of preparedness. Interns commented on the benefits of learning about roles/responsibilities, interacting with clinicians from Botswana's healthcare sectors, and the sense of community the programme engendered.

CONCLUSIONS

This programme was feasible to implement and was well-received by participants. Overall, participants perceived an enhancement of their knowledge, skills, and expectations about their role in Botswana's health system after completion of the programme. Our results are likely to be of interest to educators dedicated to training, professional transitions, and career pathways in similar settings in the region and beyond.