Comparing in-person, blended and virtual training interventions; a real-world evaluation of HIV capacity building programs in 16 countries in sub-Saharan Africa.

We sought to evaluate the impact of transitioning a multi-country HIV training program from in-person to online by comparing digital training approaches implemented during the pandemic with in-person approaches employed before COVID-19. We evaluated mean changes in pre-and post-course knowledge scores and self-reported confidence scores for learners who participated in (1) in-person workshops (between October 2019 and March 2020), (2) entirely asynchronous, Virtual Workshops [VW] (between May 2021 and January 2022), and (3) a blended Online Course [OC] (between May 2021 and January 2022) across 16 SSA countries. Learning objectives and evaluation tools were the same for all three groups. Across 16 SSA countries, 3023 participants enrolled in the in-person course, 2193 learners participated in the virtual workshop, and 527 in the online course. The proportions of women who participated in the VW and OC were greater than the proportion who participated in the in-person course (60.1% and 63.6%, p<0.001). Nursing and midwives constituted the largest learner group overall (1145 [37.9%] vs. 949 [43.3%] vs. 107 [20.5%]). Across all domains of HIV knowledge and self-perceived confidence, there was a mean increase between pre- and post-course assessments, regardless of how training was delivered. The greatest percent increase in knowledge scores was among those participating in the in-person course compared to VW or OC formats (13.6% increase vs. 6.0% and 7.6%, p<0.001). Gains in self-reported confidence were greater among learners who participated in the in-person course compared to VW or OC formats, regardless of training level (p<0.001) or professional cadre (p<0.001). In this multi-country capacity HIV training program, in-person, online synchronous, and blended synchronous/asynchronous strategies were effective means of training learners from diverse clinical settings. Online learning approaches facilitated participation from more women and more diverse cadres. However, gains in knowledge and clinical confidence were greater among those participating in in-person learning programs.

Cytomegalovirus-associated supraglottic mass in a patient on immunosuppressive therapy.

A 33-year-old woman on chronic immunosuppressive treatment for rheumatoid arthritis with a history of inhaled methamphetamine use presented with respiratory failure requiring mechanical ventilation for a prolonged period. After being given plasma exchange, pulses of methylprednisolone and a dose of cyclosporine for suspected ANCA (anti-neutrophilic cytoplasmic autoantibodies) vasculitis, she developed an obstructive supraglottic laryngeal mass that required a tracheostomy to bypass. Biopsy findings revealed the mass to be an inflammatory pseudomass secondary to cytomegalovirus (CMV). The mass resolved after several weeks of intravenous ganciclovir therapy. This is an extremely unusual presentation of localised CMV disease, with only two or three similar cases having been reported worldwide.

Assessing Testing Strategies and Duration of Quarantine in Contact Tracing for SARS-CoV-2: A Retrospective Study of San Francisco's COVID-19 Contact Tracing Program, June-August 2020.

We sought to assess the proportion of elicited close contacts diagnosed with coronavirus disease 2019 at the start of and before exiting quarantine in San Francisco. From June 8 to August 31, 6946 contacts were identified: 3008 (46.3%) were tested, 940 (13.5%) tested positive, and 90% tested positive in the first 9 days of quarantine.

Developing an interprofessional transition course to improve team-based HIV care for sub-Saharan Africa.

BACKGROUND: With funding from the United States Health Resources Service Administration (HRSA), a consortium of health professional training institutions from Africa developed HIV-specific, interprofessional, team-based educational resources to better support trainees during the transition period between pre-service training and professional practice. METHODS: Ten faculty members representing nine medical and nursing schools in sub-Saharan Africa (SSA) developed a training package of modules focused on core clinical, public health, interprofessional education (IPE), and quality improvement (QI) domains related to HIV service delivery. Curriculum development was informed by a rapid needs assessment of existing tools and future needs for HIV education across 27 SSA health professions training institutions. A total of 17 modules were developed, targeted at newly qualified health care professionals to be taught in a series of two-day workshops meant to complement existing institution specific HIV-curricula. RESULTS: Between April and July 2019, a comprehensive case-based HIV training package was developed to support trainees in transition from pre-service training to independent professional practice. Each module, addressing different elements of interprofessional practice, was intended to be delivered in an interprofessional format. Thus far, 70 health professions training institutions in 14 countries have implemented the program; 547 educators facilitated STRIPE workshops, with a total of 5027 learners trained between September 2019 and September 2020. CONCLUSIONS: To our knowledge this is the first IPE HIV-specific curriculum explicitly focused on enhancing the quality of training provided to graduating health care professionals working in SSA. The collaborative, cross-institutional, interprofessional approach to curriculum development provides a benchmark for how best-practice approaches to education can be disseminated in SSA.

Cytomegalovirus-associated esophageal stricture as a manifestation of the immune reconstitution inflammatory syndrome.

Cytomegalovirus (CMV) esophagitis is well described in immunocompromised individuals, however, esophageal stricture due to CMV is rare. CMV disease in the setting of the immune reconstitution inflammatory syndrome (IRIS) usually takes the form of an immune-recovery uveitis or retinitis. We describe a young female patient with HIV who developed an esophageal stricture due to CMV within 6 months of starting antiretroviral therapy (ART). The patient responded well to treatment which involved 14 days of intravenous ganciclovir and esophageal dilatation. This is the first description of a patient developing gastrointestinal cytomegalovirus disease as a manifestation of IRIS.

Monitoring psychoactive substance use at six European festivals through wastewater and pooled urine analysis.

The consumption of psychoactive substances is considered a growing problem in many communities. Moreover, new psychoactive substances (NPS) designed as (legal) substitutes to traditional illicit drugs are relatively easily available to the public through e-commerce and retail shops, but there is little knowledge regarding the extent and actual use of these substances. This study aims to gain new and complementary information on NPS and traditional illicit drug use at six music festivals across Europe by investigating wastewater and pooled urine. Samples were collected, between 2015 and 2018, at six music festivals across Europe with approximately 465.000 attendees. Wastewater samples were also collected during a period not coinciding with festivals. A wide-scope screening for 197 NPS, six illicit drugs and known metabolites was applied using different chromatography-mass spectrometric strategies. Several illicit drugs and in total 21 different NPS, mainly synthetic cathinones, phenethylamines and tryptamines, were identified in the samples. Ketamine and the traditional illicit drugs, such as amphetamine-type stimulants, cannabis and cocaine were most abundant and/or frequently detected in the samples collected, suggesting a higher use compared to NPS. The analyses of urine and wastewater is quick and a high number of attendees may be monitored anonymously by analysing only a few samples which allows identifying the local profiles of use of different drugs within a wide panel of psychoactive substances. This approach contributes to the development of an efficient surveillance system which can provide timely insight in the trends of NPS and illicit drugs use.

Component alignment and clinical outcome following total knee arthroplasty: a randomised controlled trial comparing an intramedullary alignment system with patient-specific instrumentation.

AIMS: We conducted a randomised controlled trial to assess the accuracy of positioning and alignment of the components in total knee arthroplasty (TKA), comparing those undertaken using standard intramedullary cutting jigs and those with patient-specific instruments (PSI). PATIENTS AND METHODS: There were 64 TKAs in the standard group and 69 in the PSI group. The post-operative hip-knee-ankle (HKA) angle and positioning was investigated using CT scans. Deviation of > 3° from the planned position was regarded as an outlier. The operating time, Oxford Knee Scores (OKS) and Short Form-12 (SF-12) scores were recorded. RESULTS: There were 14 HKA-angle outliers (22%) in the standard group and nine (13%) in the PSI group (p = 0.251). The mean HKA-angle was 0.5° varus in the standard group and 0.2° varus in the PSI group (p = 0.492). The accuracy of alignment in the coronal and axial planes and the proportion of outliers was not different in the two groups. The femoral component was more flexed (p = 0.035) and there were significantly more tibial slope outliers (29% versus 13%) in the PSI group (p = 0.032). Operating time and the median three-month OKS were similar (p = 0.218 and p = 0.472, respectively). Physical and mental SF-12 scores were not significantly different at three months (p = 0.418 and p = 0.267, respectively) or at one year post-operatively (p = 0.114 and p = 0.569). The median one-year Oxford knee score was two points higher in the PSI group (p = 0.049). CONCLUSION: Compared with standard intramedullary jigs, the use of PSI did not significantly reduce the number of outliers or the mean operating time, nor did it clinically improve the accuracy of alignment or the median Oxford Knee Scores. Our data do not support the routine use of PSI when undertaking TKA. Cite this article: Bone Joint J 2016;98-B:1043-9.

Late aspergilloma of a renal allograft without need for operative management: a case report and review of the literature.

Aspergillus infection localized to the renal allograft is a rare and potentially life-threatening infection and typically requires a combination of operative and medical management. We report the case of a renal allograft aspergilloma in a renal transplant patient presenting 2 years post transplant, successfully managed non-surgically. To our knowledge, this is the first report of a patient presenting with an allograft aspergilloma so long after transplantation and being successfully managed with antifungal therapy alone.

Cohort study of diabetes in HIV-infected adult patients: evaluating the effect of diabetes mellitus on immune reconstitution.

We conducted a retrospective cohort study assessing the association between diabetes mellitus (DM) and immune recovery in HIV-infected adults. Immune reconstitution after initiating antiretroviral therapy was more rapid in DM patients (120.4 cells/year) compared to non-DM patients (94.2 cells/year, p<0.023). Metformin use was associated with improved CD4 recovery (p=0.034).

Clinical challenges in the co-management of diabetes mellitus and tuberculosis in Southern Africa

Over the past 20 years; tuberculosis incidence in southern Africa has increased at an alarming rate; fuelled primarily by the human immunodeficiency virus epidemic. The emerging prevalence of diabetes mellitus in the region represents a new threat to tuberculosis control. The intersecting double burden is a cause for concern since diabetes mellitus increases the risk of tuberculosis and results in poor treatment outcomes. This review article discusses the evidence of a causal association between these two conditions; and examines the numerous clinical challenges that relate to tuberculosis and diabetes mellitus co-management. Diabetes is associated with a more advanced age and body weight in patients with tuberculosis; although not with a specific clinical presentation of tuberculosis. Rifampicin adversely alters glycaemic control by lowering the concentrations of most oral antidiabetic drugs. Poor glycaemic control; possibly exacerbated by tuberculosis and anti-tuberculous therapy; is an important contributing factor to tuberculosis case fatality and relapse. Clinicians need to be aware of these clinical and pharmacological challenges when co-managing these complex diseases

Diabetes mellitus in HIV-infected patients receiving antiretroviral therapy.

BACKGROUND: There is little in the literature on HIV and diabetes mellitus (DM) in sub-Saharan Africa. OBJECTIVE: To assess the characteristics of HIV and DM in patients receiving antiretroviral therapy (ART) in Botswana. METHODS: A retrospective case-control study was conducted at 4 sites. Each HIV-infected patient with DM (n=48) was matched with 2 HIV-infected controls (n=108) by age (±2 years) and sex. Primary analysis was conditional logistic regression to estimate univariate odds and 95% confidence intervals (CIs) for each characteristic. RESULTS: There was no significant association between co-morbid diseases, tuberculosis, hypertension or cancer and risk of diabetes. DM patients were more likely to have higher pre-ART weight (odds ratio (OR) 1.09; 95% CI 1.04 - 1.14). HIV-infected adults >70 kg were significantly more likely to have DM (OR 12.30; 95% CI 1.40 - 107.98). Participants receiving efavirenz (OR 4.58; 95% CI 1.44 - 14.57) or protease inhibitor therapy (OR 20.7; 95% CI 1.79 - 240.02) were more likely to have DM. Neither mean pre-ART CD4 cell count (OR 1.0; 95% CI 0.99 - 1.01) nor pre-ART viral load >100 000 copies/ml (OR 0.71; 95% CI 0.21 - 2.43) were associated with a significant risk of diabetes. CONCLUSIONS: These findings suggest a complex interrelation among traditional host factors and treatment-related metabolic changes in the pathogenesis of DM inpatients receiving ART. Notably, pre-ART weight, particularly if >70 kg, is associated with the diagnosis of diabetes in HIV-infected patients in Botswana.

Implementation of tuberculosis infection control measures at HIV care and treatment sites in sub-Saharan Africa.

SETTING: A total of 663 human immunodeficiency virus (HIV) care and treatment sites in nine tuberculosis (TB) affected African countries, serving over 900,000 persons living with HIV. OBJECTIVE: To determine the implementation of infection control (IC) measures and whether program and facility characteristics were associated with implementation of these measures. DESIGN: A survey was conducted to assess the presence of a TB IC plan, triage practices for TB suspects, location of sputum collection and availability of particulate respirators. The association of facility characteristics with IC measures was examined using bivariate and multivariate methods. RESULTS: Forty-seven per cent (range across countries [RAC] 2-77%) of sites had written TB IC plans; 60% (RAC 5-93%) practiced triage; of those with access to microscopy, 83% (RAC 59-91%) performed sputum collection outdoors and 13% (RAC 0-36%) in ventilated indoor rooms; 16% (RAC 1-87%) had particulate respirators available. Sites providing anti-tuberculosis treatment were more likely to have written IC plans (54% vs. 12%, P < 0.0001) and particulate respirators (18% vs. 8%, P = 0.0126), and to perform TB triage (65% vs. 40%, P = 0.0001) than those without anti-tuberculosis treatment services. CONCLUSIONS: To protect HIV-infected patients and health care workers, there is an urgent need to scale up IC practices at HIV care and treatment sites, particularly at sites without anti-tuberculosis treatment services.

Assessing capacity for diagnosing tuberculosis in children in sub-Saharan African HIV care settings.

Research on the prevalence of pediatric-specific tuberculosis (TB) diagnostics in sub-Saharan Africa is scarce. We assessed the availability of pediatric TB diagnostic tests at 651 pediatric human immunodeficiency virus care and treatment sites across nine African countries: 54% of the sites had access to sputum culture capacity and 51% to chest X-ray services. While 87% of sites had access to smear microscopy, only 6% had the capacity to perform sputum induction and 5% to perform gastric aspirate. These findings confirm that diagnostic resources for the accurate diagnosis of pediatric TB are limited. Capacity-building initiatives to improve sputum collection in children are urgently required.

Addressing the challenge of the emerging NCD epidemic: lessons learned from Botswana's response to the HIV epidemic.

Botswana has the second highest prevalence of human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS) in the world, and yet it has built one of Africa's most progressive and comprehensive HIV programs. While public health infrastructure has responded remarkably to the HIV epidemic, the prevalence of non-communicable diseases (NCDs), particularly diabetes mellitus and cardiovascular disease, in both HIV-infected and non-infected individuals, is increasing rapidly. Applying lessons learned from the scale-up of HIV/AIDS services may help with the implementation of an effective response to the challenges of the emerging NCD epidemic. We suggest that a successful response should include integrated service delivery, capacity building to provide disease-specific care, and strong partnerships to mobilize communities.

C'est au Botswana que se trouve la deuxième prévalence la plus élevée du virus de l'immunodéficience humaine/syndrome d'immunodéficience acquise (VIH/SIDA) au monde, et pourtant il a élaboré les programmes les plus progressifs et complets du VIH de toute l'Afrique. Alors que l'infrastructure de santé publique a répondu remarquablement à l'épidémie de VIH, la prévalence des maladies non transmissibles (NCD), particulièrement du diabète sucré et des maladies cardiovasculaires, augmente rapidement à la fois chez les sujets infectés et non infectés par le VIH. L'application des leçons retenues de l'extension des services VIH/SIDA peut aider à la mise en œuvre d'une réponse efficiente au défi de l'émergence de l'épidémie des NCD. Nous suggérons qu'une réponse couronnée de succès comporte la fourniture de services intégrés, la formation des compétences à fournir des soins spécifiques à la maladie ainsi que de puissants partenariats pour mobiliser les collectivités.

Botsuana presenta la segunda prevalencia más alta de infección por el virus de la inmunodeficiencia humana (VIH) y síndrome de inmunodeficiencia adquirida (SIDA) en el mundo y sin embargo, ha establecido uno de los programas más progresistas e integrales contra el VIH en África. Si bien la infraestructura de salud pública ha respondido de manera sobresaliente a la epidemia de infección por el VIH, la prevalencia de enfermedades no transmisibles (NCD), en especial la diabetes y las enfermedades cardiovasculares, progresa rápidamente en todas las personas, ya sea que padezcan o no la infección por el virus. Las enseñanzas extraídas de la ampliación de escala de los servicios contra el VIH y el SIDA podrían contribuir a poner en práctica una respuesta eficaz frente a los retos que plantea la epidemia incipiente de NCD. En el presente artículo se propone que la eficacia de esta respuesta exige los siguientes elementos: la prestación de servicios integrados, el fortalecimiento de la capacidad de suministrar una atención orientada a enfermedades específicas y el establecimiento de colaboraciones dinámicas que movilicen las comunidades.

TNF receptors differentially signal and are differentially expressed and regulated in the human heart.

Tumor necrosis factor (TNF) utilizes two receptors, TNFR1 and 2, to initiate target cell responses. We assessed expression of TNF, TNFRs and downstream kinases in cardiac allografts, and compared TNF responses in heart organ cultures from wild-type ((WT)C57BL/6), TNFR1-knockout ((KO)), TNFR2(KO), TNFR1/2(KO) mice. In nonrejecting human heart TNFR1 was strongly expressed coincidentally with inactive apoptosis signal-regulating kinase-1 (ASK1) in cardiomyocytes (CM) and vascular endothelial cells (VEC). TNFR2 was expressed only in VEC. Low levels of TNF localized to microvessels. Rejecting cardiac allografts showed increased TNF in microvessels, diminished TNFR1, activation of ASK1, upregulated TNFR2 co-expressed with activated endothelial/epithelial tyrosine kinase (Etk), increased apoptosis and cell cycle entry in CM. Neither TNFR was expressed significantly by cardiac fibroblasts. In (WT)C57BL/6 myocardium, TNF activated both ASK1 and Etk, and increased both apoptosis and cell cycle entry. TNF-treated TNFR1(KO) myocardium showed little ASK1 activation and apoptosis but increased Etk activation and cell cycle entry, while TNFR2(KO) myocardium showed little Etk activation and cell cycle entry but increased ASK1 activation and apoptosis. These observations demonstrate independent regulation and differential functions of TNFRs in myocardium, consistent with TNFR1-mediated cell death and TNFR2-mediated repair.

A one-stop carpal tunnel clinic.

INTRODUCTION: By December 2008, 90% of referrals requiring hospital admission will need to be seen and treated within the 18-week patient pathway. Previously, patients within our trust with suspected carpal tunnel syndrome had to wait 3 months to see a specialist in clinic and, once assessed, would have to wait up to a further 6 months for an open carpal tunnel decompression under local anaesthetic (OCTD/LA). We set up a one-stop clinic, where patients would have their out-patient consultation and surgery on the same day. We evaluated the clinic in order to assess whether it led to reduced waiting times whilst maintaining good clinical outcome and patient satisfaction. PATIENTS AND METHODS: Patients were selected on the basis of the standard referral letter alone. Those selected were then assessed by a single surgeon in the clinic. The patients deemed appropriate underwent an OCTD/LA and were discharged the same day. Patients were followed up with a patient satisfaction and Boston questionnaire. RESULTS: Forty-six patients underwent 63 OCTD/LA, waiting an average of 2.2 months (9 weeks) from referral. There was high patient satisfaction and improvement in symptoms following treatment in the clinic. CONCLUSIONS: We believe a one-stop carpal tunnel clinic can be an efficient and cost-effective way of treating this common condition.

The distance to the Perseus spiral arm in the Milky Way.

We have measured the distance to the massive star-forming region W3OH in the Perseus spiral arm of the Milky Way to be 1.95 +/- 0.04 kiloparsecs (5.86 x10(16) km). This distance was determined by triangulation, with Earth's orbit as one segment of a triangle, using the Very Long Baseline Array. This resolves the long-standing problem that there is a discrepancy of a factor of 2 between different techniques used to determine distances. The reason for the discrepancy is that this portion of the Perseus arm has anomalous motions. The orientation of the anomalous motion agrees with spiral density-wave theory, but the magnitude of the motion is somewhat larger than most models predict.

A star in a 15.2-year orbit around the supermassive black hole at the centre of the Milky Way.

Many galaxies are thought to have supermassive black holes at their centres-more than a million times the mass of the Sun. Measurements of stellar velocities and the discovery of variable X-ray emission have provided strong evidence in favour of such a black hole at the centre of the Milky Way, but have hitherto been unable to rule out conclusively the presence of alternative concentrations of mass. Here we report ten years of high-resolution astrometric imaging that allows us to trace two-thirds of the orbit of the star currently closest to the compact radio source (and massive black-hole candidate) Sagittarius A*. The observations, which include both pericentre and apocentre passages, show that the star is on a bound, highly elliptical keplerian orbit around Sgr A*, with an orbital period of 15.2 years and a pericentre distance of only 17 light hours. The orbit with the best fit to the observations requires a central point mass of (3.7 +/- 1.5) x 10(6) solar masses (M(*)). The data no longer allow for a central mass composed of a dense cluster of dark stellar objects or a ball of massive, degenerate fermions.

Immunostimulatory sequence DNA linked to the Amb a 1 allergen promotes T(H)1 cytokine expression while downregulating T(H)2 cytokine expression in PBMCs from human patients with ragweed allergy.

BACKGROUND: Recent studies have demonstrated that bacterially derived immunostimulatory sequences (ISSs) of DNA can activate the mammalian innate immune system and promote the development of T(H)1 cells. Promotion of T(H)1 immunity by means of immunotherapy in allergic patients has led to the alleviation of symptoms that result from allergen-specific T(H)2 responses. OBJECTIVE: Our purpose was to investigate whether the T(H)1-enhancing properties of ISSs could be used to alter the T(H)2-dominated immune response of allergic PBMCs in vitro. METHODS: Ragweed protein-linked ISS (PLI) was generated from a specific, highly active 22-base ISS and Amb a 1, the immunodominant allergen in ragweed pollen, to combine the T(H)1-enhancing properties of ISSs with allergen selectivity, and its activity was investigated in PBMC cultures from subjects with ragweed allergy. RESULTS: PLI was markedly successful at reversing the dominant allergen-induced T(H)2 profile while greatly enhancing IFN-gamma production. Delivering ISSs in a linked form proved to be much more effective at modulating the resulting cytokine profile than delivering free ISSs in a mixture with unlinked Amb a 1. PLI also demonstrated cytokine-modulating properties, even when used to stimulate cells that had already been primed for 6 days with Amb a 1. The antigen specificity of the action of PLI was confirmed by the observations that PLI enhances Amb a 1--specific T-cell proliferation. CONCLUSION: These data indicate that delivery of ISSs within an antigen-specific context exhibits potent cytokine-modulating activity and, combined with its reduced allergenicity, makes this molecule a strong candidate for use in improved immunotherapy applications.