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.

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.

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.

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.

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.

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.

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.

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.

The natural history of human immunodeficiency virus infection in screened HIV positive U.S. Air Force personnel: a preliminary report.

We prospectively studied 157 HIV antibody-positive U.S. Air Force personnel identified by universal ELISA screening and confirmed by Western blot. They were initially evaluated and then re-evaluated at least once at approximately 1 year intervals. In order to determine which if any demographic and serologic cofactors were significantly related to progression of immunodeficiency early in the course of disease, we compared these variables with the mean change in CD4 cells per month and with progression in Walter Reed stage. Upon entry into the study, the subjects were classified as follows: sex: 153 (97.5%) male, 4 (2.5%) female; race: 84 (53.5%) white, 63 (40.1%) black, 8 (5.1%) Hispanic, and 2 (1.3%) Oriental; age: mean of 28.6 years (63.0% between 20 and 32 years); and Walter Reed stage: 108 (68.8%) Walter Reed 1, 26 (16.6%) Walter Reed 2, 9 (5.7%) Walter Reed 3, 6 (3.8%) Walter Reed 4, 5 (3.2%) Walter Reed 5, and 3 (1.9%) Walter Reed 6. The mean follow-up period was 12.2 months (range of 2 to 35 months). The mean change in CD4 cells per month was -0.072 (range of -94.75 to +67.58). Factors at entry that are significantly related to loss of CD4 cells included serum IgA over 300 mg/dl (p = 0.0450) and anergy (p = 0.0093). Factors at entry significantly related to progression in Walter Reed stage included serum IgA over 300 mg/dl (p = 0.0001), low absolute CD4 count (p = 0.0001), and low CD4/CD8 ratio (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatric acquired immunodeficiency syndrome with negative human immunodeficiency virus antibody response by enzyme-linked immunosorbent assay and Western blot.

A 5-month-old white girl having persistent oral candidiasis was brought to medical attention because of acute respiratory distress, pneumonia, and hypoxia that worsened despite supportive care and antibiotics. Bronchial lavage fluid yielded Pneumocystis carinii. The diagnosis of acquired immunodeficiency syndrome (AIDS) was suspected, although enzyme-linked immunosorbent assay (ELISA) and Western blot tests were both negative for human immunodeficiency virus (HIV) antibody. Immunologic evaluation included the following results: a low normal CD4/CD8 ratio 0.88, CD4 lymphocytes 493/microL, and elevated IgA 539 mg/dL and IgM 175 mg/dL with normal IgG 492 mg/dL. Lymphocyte stimulation study results were depressed. Lymphocytes sent for culture were subsequently positive for HIV. The mother was HIV antibody positive by enzyme-linked immunosorbent assay and Western blot but belonged to no high-risk group and was asymptomatic except for chronic diarrhea. The father was HIV antibody negative. The patient was treated with pentamidine and IV gamma-globulin with good clinical response and a rapid decrease of IgM and IgA toward normal values. Subsequent candidal pneumonia and candidal esophagitis were treated successfully with amphotericin B. The patient has received prophylactic IV gamma-globulin infusions for 6 months and remains HIV negative by enzyme-linked immunosorbent assay and Western blot. This case of pediatric AIDS highlights the need to consider HIV infection in the differential diagnosis of any child with physical findings or illnesses suggestive of AIDS-related complex or AIDS, even when HIV serologic findings are negative and parents belong to no high-risk group. Parental testing for HIV antibody is suggested in such cases.

Cannabinoid-induced alterations in brain disposition of drugs of abuse.

Marijuana contains a complex mixture of compounds including tetrahydrocannabinol (THC), the major psychoactive constituent, and cannabidiol (CBD), a nonpsychoactive constituent. We have shown previously that CBD pretreatment of mice increases brain levels of THC and have now further characterized this effect and determined whether the brain pharmacokinetics of other drugs are also affected. CBD pretreatment of mice (30-60 min) increased brain levels of THC nearly 3-fold, whereas CBD co-administration did not. Because marijuana is often consumed with other drugs, the influence of cannabinoids on the brain levels of several other drugs of abuse was also determined. CBD pretreatment of mice increased brain levels (2- to 4-fold) of subsequently administered cocaine as well as phencyclidine (PCP). Although CBD pretreatment increased blood and brain levels of cocaine comparably, blood levels of PCP were only modestly elevated (up to 50%). Behavioral tests indicated that the CBD-mediated increases in the brain levels of THC, cocaine, and PCP correlated with increased pharmacological responses. Pretreatment with THC instead of CBD could similarly increase brain levels of cocaine, PCP, and CBD, although with a lower potency than CBD. On the other hand, pretreatment of mice with CBD had no effect on the brain levels of several other drugs of abuse including morphine, methadone, or methylenedioxyphenyl-methamphetamine. These findings demonstrate that cannabinoids can increase the brain concentrations and pharmacological actions of several other drugs of abuse, thereby providing a biochemical basis for the common practice of using marijuana concurrently with such drugs.

Complicating features of asthma.

The recognition of factors other than asthma that make asthma worse, are confused with asthma, or occur concurrently with asthma and may or may not interact with asthma is as important as dealing with the asthma itself. In this article I have tried to give an overview of some of these factors: what they are, how they affect patients with asthma, and what to do about them. The recognition of a covert chronic sinusitis, for example, is often key to controlling a person's disease when it appears that everything is being done appropriately. Close attention to these factors will increase the success of treatment of asthma and improve the quality of life of patients.

Monocrotaline metabolism and distribution in Fisher 344 and Sprague-Dawley rats.

The metabolism and distribution of 14C-monocrotaline in Fisher 344 (F344) rats was compared with that in Sprague-Dawley (SD) rats. In vitro microsomal preparations, in situ isolated perfused livers and in vivo excretion and distribution studies were used to discern any differences between these two strains. These strains have previously been shown to differ in their susceptibility to monocrotaline-induced pulmonary hypertension. Hepatic phase I metabolism appears to be similar in both strains with N-oxidation and dehydrogenation to the reactive pyrroles as the major pathways. During the liver perfusions, SD rats generated more monocrotalic acid than F344 rats, but the microsome and excretion studies demonstrated no significant differences in the amount of monocrotalic acid. Monocrotalic acid is a stable byproducer of dehydromonocrotaline reacting with cellular nucleophiles and indicates the amount of monocrotaline dehydrogenation when carboxylesterase activity is negligible. These data suggest that the differences in strain susceptibility to pulmonary vascular toxicity is most likely due to differences in their response to the toxic metabolites.

Effects of maternal distraction and reprimands on toddlers' transgressions and negative affect.

Misbehaviors occur at a high rate during the toddler years, and parents use a variety of methods to control these behaviors. The present investigation compared the effectiveness of two commonly used strategies, distraction and reprimands. Twenty mothers and their 17- to 39-month-old children were observed in a laboratory setting in which mothers used either distraction then reprimands or reprimands followed by distraction in response to their children's transgressions. When reprimands were used as the initial strategy, they were significantly more effective than distraction in controlling children's transgressions. Distraction was effective in maintaining low rates of transgression when preceded by a period of reprimands. However, when reprimands were instituted following a period of distraction, children's rates of negative affect increased significantly. Implications for the etiology and management of child behavior problems are discussed.

Treatment of young children's bedtime refusal and nighttime wakings: a comparison of "standard" and graduated ignoring procedures.

Young children with sleep problems received either "standard" or graduated ignoring treatment. Both brief treatments were superior to a wait-list control condition and resulted in comparable improvements in bedtime and nighttime sleep problems. At bedtime, the treatments did not differ with respect to maternal compliance and stress. For nighttime wakings, mothers in the graduated ignoring group reported higher rates of compliance and less treatment-related stress. Maternal characteristics predicted treatment outcome in the standard ignoring condition. Following treatment, only positive side effects were observed. When compared to the wait-list group, mothers in the standard ignoring group reported less verbose discipline and decreased stress in parenting, while mothers in the graduated ignoring group reported improved parent-child relationships. Treatment gains were maintained over a 2-month follow-up period.

A longitudinal study of mothers' overreactive discipline and toddlers' externalizing behavior.

The association between children's externalizing behavior problems and mothers' overreactive discipline was examined in a longitudinally assessed sample of toddlers and their mothers. Path analyses indicated that mothers' overreactive discipline and children's externalizing behaviors were significantly and similarly stable over a 2 1/2-year period. No evidence of a cross-time influence of either variable on the other was observed. Mothers' overreactive discipline at Time 2 had a significant effect on Time 2 externalizing behavior. No significant effects of children's behavior on mothers' discipline were found. Mothers' depressive symptomatology and marital discord predicted initial overreactivity and were related to externalizing problems through their relations to overreactivity. The results support the appropriateness of implementing parenting interventions for externalizing problems before age 2 years.

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).

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.

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.