Strengthening Healthcare Capacity Through a Responsive, Country-Specific, Training Standard: The KITSO AIDS Training Program’s Sup-port of Botswana’s National Antiretroviral Therapy Rollout

In parallel with the rollout of Botswana’s national antiretroviral therapy (ART) program, the Botswana Ministry of Health established the KITSO AIDS Training Program by entering into long-term partnerships with the Botswana–Harvard AIDS Institute Partnership for HIV Research and Education and others to provide standardized, country-specific training in HIV/AIDS care. The KITSO training model has strengthened human capacity within Botswana’s health sector and been indispensable to successful ART rollout. Through core and advanced training courses and clinical mentoring, different cadres of health care workers have been trained to provide high-quality HIV/AIDS care at all ART sites in the country. Continuous and standardized clinical education will be crucial to sustain the present level of care and successfully address future treatment challenges

Early Mortality and AIDS Progression Despite High Initial Antiretroviral Therapy Adherence and Virologic Suppression in Botswana

Background Adverse outcomes occurring early after antiretroviral therapy (ART) initiation are common in sub-Saharan Africa, despite reports of high levels of ART adherence in this setting. We sought to determine the relationship between very early ART adherence and early adverse outcomes in HIV-infected adults in Botswana. Methods This prospective cohort study of 402 ART-naïve, HIV-infected adults initiating ART at a public HIV clinic in Gaborone, Botswana evaluated the relationship between suboptimal early ART adherence and HIV treatment outcomes in the initial months after ART initiation. Early adherence during the interval between initial ART dispensation and first ART refill was calculated using pill counts. In the primary analysis patients not returning to refill and those with adherence \u3c0.95 were considered to have suboptimal early adherence. The primary outcome was death or loss to follow-up during the first 6 months of ART; a secondary composite outcome included the primary outcome plus incident opportunistic illness (OIs) and virologic failure. We also calculated the percent of early adverse outcomes theoretically attributable to suboptimal early adherence using the population attributable risk percent (PAR%). Results Suboptimal early adherence was independently associated with loss to follow-up and death (adjusted OR 2.3, 95% CI 1.1–4.8) and with the secondary composite outcome including incident OIs and virologic failure (adjusted OR 2.6, 95% CI 1.4–4.7). However, of those with early adverse outcomes, less than one-third had suboptimal adherence and approximately two-thirds achieved virologic suppression. The PAR% relating suboptimal early adherence and primary and secondary outcomes were 14.7% and 17.7%, respectively. Conclusions Suboptimal early adherence was associated with poor outcomes, but most early adverse outcomes occurred in patients with optimal early adherence. Clinical care and research efforts should focus on understanding early adverse outcomes that occur despite optimal adherence

A longitudinal study of stavudine-associated toxicities in a large cohort of South African HIV infected subjects

<p>Abstract</p> <p>Background</p> <p>There has been major improvement in the survival of HIV-1 infected individuals since the South African Government introduced highly active anti-retroviral therapy (HAART) in the public sector in 2004. This has brought new challenges which include the effects of stavudine-related toxicities.</p> <p>Methods</p> <p>Prospective analysis of a cohort of 9040 HIV-infected adults who were initiated on HAART at the Themba Lethu Clinic (TLC) in Johannesburg between April 1, 2004 to December 31, 2007, and followed up until June 30, 2008.</p> <p>Results</p> <p>Amongst the 9040 study subjects, 8497(94%) were on stavudine based therapy and 5962 (66%) were women. The median baseline CD4 count was 81 cells/mm³(IQR 29-149). Median follow up on HAART was 19 months (IQR: 9.1-31.6). The proportion of HAART-related side effects for stavudine compared to non-stavudine containing regimens were, respectively: peripheral neuropathy,17.1% vs. 11.2% (p < 0.001); symptomatic hyperlactataemia, 5.7% vs. 2.2% (p < 0.0005); lactic acidosis, 2.5 vs. 1.3% (p = 0.072); lipoatrophy, 7.3% vs. 4.6% (p < 0.05). Among those on stavudine-based regimens, incidence rates for peripheral neuropathy were 12.1 cases/100 person-years (95%CI 7.0-19.5), symptomatic hyperlactataemia 3.6 cases/100 person-years (95%CI 1.2-7.5), lactic acidosis 1.6 cases/100 person-years (95%CI 0.4-5.2) and lipoatrophy 4.6 cases/100 person-years (95%CI 2.1-9.6). Females experienced more toxicity when compared to males in terms of symptomatic hyperlactataemia (p < 0.0001), lactic acidosis (p < 0.0001), lipoatrophy (p < 0.0001) and hypertension (p < 0.05).</p> <p>Conclusions</p> <p>We demonstrate significant morbidity associated with stavudine. These data support the latest WHO guidelines, and provide additional evidence for other resource limited HAART rollout programs considering the implementation of non-stavudine based regimens as first line therapy.</p

Knowledge, attitudes and practice survey about antimicrobial resistance and prescribing among physicians in a hospital setting in Lima, Peru

BACKGROUND: Misuse of antimicrobials (AMs) and antimicrobial resistance (AMR) are global concerns. The present study evaluated knowledge, attitudes and practices about AMR and AM prescribing among medical doctors in two large public hospitals in Lima, Peru, a middle-income country. METHODS: Cross-sectional study using a self-administered questionnaire RESULTS: A total of 256 participants completed the questionnaire (response rate 82%). Theoretical knowledge was good (mean score of 6 +/- 1.3 on 7 questions) in contrast to poor awareness (< 33%) of local AMR rates of key-pathogens. Participants strongly agreed that AMR is a problem worldwide (70%) and in Peru (65%), but less in their own practice (22%). AM overuse was perceived both for the community (96%) and the hospital settings (90%). Patients' pressure to prescribing AMs was considered as contributing to AM overuse in the community (72%) more than in the hospital setting (50%). Confidence among AM prescribing was higher among attending physicians (82%) compared to residents (30%, p < 0.001%). Sources of information considered as very useful/useful included pocket-based AM prescribing guidelines (69%) and internet sources (62%). Fifty seven percent of participants regarded AMs in their hospitals to be of poor quality. Participants requested more AM prescribing educational programs (96%) and local AM guidelines (92%). CONCLUSIONS: This survey revealed topics to address during future AM prescribing interventions such as dissemination of information about local AMR rates, promoting confidence in the quality of locally available AMs, redaction and dissemination of local AM guidelines and addressing the general public, and exploring the possibilities of internet-based training

Arachnoid cyst in a patient with psychosis: Case report

<p>Abstract</p> <p>Background</p> <p>The aetiology of a psychotic disturbance can be due to a functional or organic condition. Organic aetiologies are diverse and encompass organ failures, infections, nutritional deficiencies and space-occupying lesions. Arachnoid cysts are rare, benign space-occupying lesions formed by an arachnoid membrane containing cerebrospinal fluid (CSF). In most cases they are diagnosed by accident. Until recently, the coexistence of arachnoid cysts with psychiatric disturbances had not been closely covered in the literature. However, the appearance of some references that focus on a possible link between arachnoid cysts and psychotic symptoms has increased the interest in this subject and raised questions about the etiopathogeny and the therapeutic approach involved.</p> <p>Clinical presentation</p> <p>We present the clinical report of a 21-year-old man, characterised by the insidious development of psychotic symptoms of varying intensity, delusional ideas with hypochondriac content, complex auditory/verbal hallucinations in the second and third persons, and aggressive behaviour. The neuroimaging studies revealed a voluminous arachnoid cyst at the level of the left sylvian fissure, with a marked mass effect on the left temporal and frontal lobes and the left lateral ventricle, as well as evidence of hypoplasia of the left temporal lobe. Despite the symptoms and the size of the cyst, the neurosurgical department opted against surgical intervention. The patient began antipsychotic therapy and was discharged having shown improvement (behavioural component), but without a complete remission of the psychotic symptoms.</p> <p>Conclusion</p> <p>It is difficult to be absolutely certain whether the lesion had influence on the patient's psychiatric symptoms or not.</p> <p>However, given the anatomical and neuropsychological changes, one cannot exclude the possibility that the lesion played a significant role in this psychiatric presentation. This raises substantial problems when it comes to choosing a therapeutic strategy.</p

Search for astronomical neutrinos from blazar TXS 0506+056 in super-kamiokande

We report a search for astronomical neutrinos in the energy region from several GeV to TeV in the direction of the blazar TXS 0506+056 using the Super-Kamiokande detector following the detection of a 100 TeV neutrinos from the same location by the IceCube collaboration. Using Super-Kamiokande neutrino data across several data samples observed from 1996 April to 2018 February we have searched for both a total excess above known backgrounds across the entire period as well as localized excesses on smaller timescales in that interval. No significant excess nor significant variation in the observed event rate are found in the blazar direction. Upper limits are placed on the electron- and muon-neutrino fluxes at the 90% confidence level as 6.0 × 10−7 and 4.5 × 10−7–9.3 × 10−10 [erg cm−2 s−1], respectively

A needs assessment study for optimising prescribing practice in secondary care junior doctors: the Antibiotic Prescribing Education among Doctors (APED).

BACKGROUND: Appropriate antimicrobial prescribing is essential for patient care, yet up to half of antimicrobial prescriptions written in the UK are sub-optimal. Improving prescriber education has recently been promoted as a mechanism to optimise antimicrobial use, but identification of key learning objectives to facilitate this is so far lacking. Using qualitative methods we investigated junior doctor knowledge, attitudes, and behaviours around antimicrobial prescribing to identify key areas to address in future educational programmes. METHODS: A cross-sectional survey of qualified doctors in training in West London was undertaken exploring antimicrobial prescribing practices and educational needs. RESULTS: Among 140 junior doctors from 5 London hospitals, a third (34 %) reported prescribing primarily unsupervised, and two thirds (67 %) reported difficulties obtaining prescribing support outside of hours. 20 % stated not feeling confident in writing an antimicrobial prescription, but confidence was increased through having confirmatory diagnostic results (24) and obtaining advice from a senior doctor (26 %); whether this senior was from their own specialty, or an infection-specialist, varied significantly (p < 0.01) by experience. Only a small percentage (5-13 %; depending on number of years post-qualification) of participants stated their previous antimicrobial education was effective. 60 % of those in their first year post qualification reported wanting further education in antimicrobial prescribing, rising to 74 % among more experienced junior doctors. Specific areas of educational need identified were (i) principles of antimicrobial prescribing, (ii) diagnosis of infections, (iii) clinical review of patients with infections, (iv) prescribing in the context of antimicrobial resistance, and (v) laboratory testing and test results. CONCLUSIONS: A significant proportion of junior doctors report lone prescribing of antimicrobials in the context of low self-perceived confidence and knowledge in this field, and frequent difficulty in accessing help when necessary. Innovative training, targeting five specific areas identified through this needs assessment, is urgently needed by junior doctors practising in secondary care

Identification of Streptococcus pneumoniae by a real-time PCR assay targeting SP2020.

Real-time PCR targeting lytA (the major autolysin gene) and piaB (permease gene of the pia ABC transporter) are currently used as the gold-standard culture-independent assays for Streptococcus pneumoniae identification. We evaluated the performance of a new real-time PCR assay - targeting SP2020 (putative transcriptional regulator gene) - and compared its performance with the assays previously described. A collection of 150 pneumococci, 433 non-pneumococci and 240 polymicrobial samples (obtained from nasopharynx, oropharynx, and saliva; 80 from each site) was tested. SP2020 and lytA-CDC assays had the best performance (sensitivity of 100% for each compared to 95.3% for piaB). The specificity for lytA and piaB was 99.5% and for SP2020 was 99.8%. Misidentifications occurred for the three genes: lytA, piaB and SP2020 were found in non-pneumococcal strains; piaB was absent in some pneumococci including a serotype 6B strain. Combining lytA and SP2020 assays resulted in no misidentifications. Most polymicrobial samples (88.8%) yielded concordant results for the three molecular targets. The remaining samples seemed to contain non-typeable pneumococci (0.8%), and non-pneumococci positive for lytA (1.7%) or SP2020 (8.7%). We propose that combined detection of both lytA-CDC and SP2020 is a powerful strategy for the identification of pneumococcus either in pure cultures or in polymicrobial samples

Predictors of mortality in HIV-infected patients starting antiretroviral therapy in a rural hospital in Tanzania

\ud \ud Studies of antiretroviral therapy (ART) programs in Africa have shown high initial mortality. Factors contributing to this high mortality are poorly described. The aim of the present study was to assess mortality and to identify predictors of mortality in HIV-infected patients starting ART in a rural hospital in Tanzania. This was a cohort study of 320 treatment-naïve adults who started ART between October 2003 and November 2006. Reliable CD4 cell counts were not available, thus ART initiation was based on clinical criteria in accordance with WHO and Tanzanian guidelines. Kaplan-Meier models were used to estimate mortality and Cox proportional hazards models to identify predictors of mortality. Patients were followed for a median of 10.9 months (IQR 2.9-19.5). Overall, 95 patients died, among whom 59 died within 3 months of starting ART. Estimated mortality was 19.2, 29.0 and 40.7% at 3, 12 and 36 months, respectively. Independent predictors of mortality were severe anemia (hemoglobin <8 g/dL; adjusted hazard ratio [AHR] 9.20; 95% CI 2.05-41.3), moderate anemia (hemoglobin 8-9.9 g/dL; AHR 7.50; 95% CI 1.77-31.9), thrombocytopenia (platelet count <150 x 109/L; AHR 2.30; 95% CI 1.33-3.99) and severe malnutrition (body mass index <16 kg/m2; AHR 2.12; 95% CI 1.06-4.24). Estimated one year mortality was 55.2% in patients with severe anemia, compared to 3.7% in patients without anemia (P < 0.001). Mortality was found to be high, with the majority of deaths occurring within 3 months of starting ART. Anemia, thrombocytopenia and severe malnutrition were strong independent predictors of mortality. A prognostic model based on hemoglobin level appears to be a useful tool for initial risk assessment in resource-limited settings.\u