Population Incidence and Mortality of Sepsis in an Urban African Setting, 2013-2016.

BACKGROUND: Sepsis is an important cause of mortality globally, although population incidence estimates from low-income settings, including sub-Saharan Africa, are absent. We aimed to estimate sepsis incidence burden using routinely available data from a large urban hospital in Malawi. METHODS: We linked routine-care databases at Queen Elizabeth Central Hospital, Blantyre, Malawi, to provide admission and discharge data for 217 149 adults from 2013-2016. Using a definition of sepsis based on systemic inflammatory response syndrome criteria and Blantyre census population data, we calculated population incidence estimates of sepsis and severe sepsis and used negative binomial regression to assess for trends over time. Missing data were multiply imputed with chained equations. RESULTS: We estimate that the incidence rate of emergency department-attending sepsis and severe sepsis in adults was 1772 per 100 000 person-years (95% confidence interval [CI], 1754-1789) and 303 per 100 000 person-years (95% CI, 295-310), respectively, between 2013 and 2016, with a year-on-year decrease in incidence. In-hospital mortality for patients admitted to the hospital with sepsis and severe sepsis was 23.7% (95% CI, 22.7-24.7%) and 28.1% (95% CI, 26.1 - 30.0%), respectively, with no clear change over time. CONCLUSIONS: Sepsis incidence is higher in Blantyre, Malawi, than in high-income settings, from where the majority of sepsis incidence data are derived. Worldwide sepsis burden is likely to be underestimated, and data from low-income countries are needed to inform the public health response.

Drug resistance of Mycobacterium tuberculosis in Malawi: a cross-sectional survey.

OBJECTIVE: To document the prevalence of multidrug resistance among people newly diagnosed with - and those retreated for - tuberculosis in Malawi. METHODS: We conducted a nationally representative survey of people with sputum-smear-positive tuberculosis between 2010 and 2011. For all consenting participants, we collected demographic and clinical data, two sputum samples and tested for human immunodeficiency virus (HIV).The samples underwent resistance testing at the Central Reference Laboratory in Lilongwe, Malawi. All Mycobacterium tuberculosis isolates found to be multidrug-resistant were retested for resistance to first-line drugs - and tested for resistance to second-line drugs - at a Supranational Tuberculosis Reference Laboratory in South Africa. FINDINGS: Overall, M. tuberculosis was isolated from 1777 (83.8%) of the 2120 smear-positive tuberculosis patients. Multidrug resistance was identified in five (0.4%) of 1196 isolates from new cases and 28 (4.8%) of 581 isolates from people undergoing retreatment. Of the 31 isolates from retreatment cases who had previously failed treatment, nine (29.0%) showed multidrug resistance. Although resistance to second-line drugs was found, no cases of extensive drug-resistant tuberculosis were detected. HIV testing of people from whom M. tuberculosis isolates were obtained showed that 577 (48.2%) of people newly diagnosed and 386 (66.4%) of people undergoing retreatment were positive. CONCLUSION: The prevalence of multidrug resistance among people with smear-positive tuberculosis was low for sub-Saharan Africa - probably reflecting the strength of Malawi's tuberculosis control programme. The relatively high prevalence of such resistance observed among those with previous treatment failure may highlight a need for a change in the national policy for retreating this subgroup of people with tuberculosis.

Bleeding events and associated factors in a cohort of adult patients taking warfarin in Sarawak, Malaysia.

Evidence is emerging that rates of adverse events in patients taking warfarin may vary with ethnicity. This study investigated the rates of bleeds and thromboembolic events, the international normalised ratio (INR) status and the relationship between INR and bleeding events in Malaysia. Patients attending INR clinic at the Heart Centre, Sarawak General Hospital were enrolled on an ad hoc basis from May 2010 and followed up for 1 year. At each routine visit, INR was recorded and screening for bleeding or thromboembolism occurred. Variables relating to INR control were used as predictors of bleeds in logistic regression models. 125 patients contributed to 140 person-years of follow-up. The rates of major bleed, thromboembolic event and minor bleed per 100 person-years of follow-up were 1.4, 0.75 and 34.3. The median time at target range calculated using the Rosendaal method was 61.6% (IQR 44.6­74.1%). Of the out-of-range readings, 30.0% were below range and 15.4% were above. INR variability, (standard deviation of individuals' mean INR), was the best predictor of bleeding events, with an odds ratio of 3.21 (95% CI 1.10­9.38). Low rates of both major bleeds and thromboembolic events were recorded, in addition to a substantial number of INR readings under the recommended target range. This may suggest that the recommended INR ranges may not represent the optimal warfarin intensity for this population and that a lower intensity of therapy, as observed in this cohort, could be beneficial in preventing adverse events.

Handheld point-of-care devices for snakebite coagulopathy: a scoping review.

Venom induced consumption coagulopathy (VICC) is a common complication of snakebite that is associated with hypofibrinogenaemia, bleeding, disability, and death. In remote tropical settings, where most snakebites occur, the 20-minute whole blood clotting test is used to diagnose VICC. Point-of-care (POC) coagulation devices could provide an accessible means of detecting VICC that is better standardised, quantifiable, and more accurate. In this scoping review, the mechanistic reasons that previously studied POC devices have failed in VICC are considered, and evidence-based recommendations are made to prioritise certain devices for clinical validation studies. Four small studies have evaluated a POC international normalised ratio (INR) device in patients with Australian Elapid, Daboia russelii and Echis carinatus envenoming. All of these studies used POC INR devices that rely on a thrombin substrate endpoint, which, unlike laboratory-based INR measurement, is known to underestimate INR in patients with hypofibrinogenaemia. Seventeen commercially available POC devices for measuring INR, activated clotting time (ACT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, and fibrin(ogen) degradation products (FDP) have been reviewed. POC INR devices that detect fibrin clot formation, as well as a novel POC device that quantifies fibrinogen were identified, that show promise for use in patients with VICC. These devices could support more accurate allocation of antivenom, reduce the time to antivenom administration, and provide improved clinical trial outcome measurement instruments. There is an urgent need for these promising POC coagulation devices to be validated in prospective clinical snakebite studies.

African polyvalent antivenom can maintain pharmacological stability and ability to neutralise murine venom lethality for decades post-expiry: evidence for increasing antivenom shelf life to aid in alleviating chronic shortages.

INTRODUCTION: Antivenom is a lifesaving medicine for treating snakebite envenoming, yet there has been a crisis in antivenom supply for many decades. Despite this, substantial quantities of antivenom stocks expire before use. This study has investigated whether expired antivenoms retain preclinical quality and efficacy, with the rationale that they could be used in emergency situations when in-date antivenom is unavailable. METHODS: Using WHO guidelines and industry test requirements, we examined the in vitro stability and murine in vivo efficacy of eight batches of the sub-Saharan African antivenom, South African Institute for Medical Research polyvalent, that had expired at various times over a period of 30 years. RESULTS: We demonstrate modest declines in immunochemical stability, with antivenoms older than 25 years having high levels of turbidity. In vitro preclinical analysis demonstrated all expired antivenoms retained immunological recognition of venom antigens and the ability to inhibit key toxin families. All expired antivenoms retained comparable in vivo preclinical efficacy in preventing the lethal effects of envenoming in mice versus three regionally and medically important venoms. CONCLUSIONS: This study provides strong rationale for stakeholders, including manufacturers, regulators and health authorities, to explore the use of expired antivenom more broadly, to aid in alleviating critical shortages in antivenom supply in the short term and the extension of antivenom shelf life in the longer term.

Neuromuscular Weakness and Paralysis Produced by Snakebite Envenoming: Mechanisms and Proposed Standards for Clinical Assessment.

Respiratory and airway-protective muscle weakness caused by the blockade of neuromuscular transmission is a major cause of early mortality from snakebite envenoming (SBE). Once weakness is manifest, antivenom appears to be of limited effectiveness in improving neuromuscular function. Herein, we review the topic of venom-induced neuromuscular blockade and consider the utility of adopting clinical management methods originally developed for the safe use of neuromuscular blocking agents by anesthesiologists in operating rooms and critical care units. Failure to quantify neuromuscular weakness in SBE is predicted to cause the same significant morbidity that is associated with failure to do so in the context of using a clinical neuromuscular block in surgery and critical care. The quantitative monitoring of a neuromuscular block, and an understanding of its neurophysiological characteristics, enables an objective measurement of weakness that may otherwise be overlooked by traditional clinical examination at the bedside. This is important for the initial assessment and the monitoring of recovery from neurotoxic envenoming. Adopting these methods will also be critical to the conduct of future clinical trials of toxin-inhibiting drugs and antivenoms being tested for the reversal of venom-induced neuromuscular block.

A long-term observational study of paediatric snakebite in Kilifi County, south-east Kenya.

INTRODUCTION: Estimates suggest that one-third of snakebite cases in sub-Saharan Africa affect children. Despite children being at a greater risk of disability and death, there are limited published data. This study has determined the: population-incidence and mortality rate of hospital-attended paediatric snakebite; clinical syndromes of snakebite envenoming; and predictors of severe local tissue damage. METHODS: All children presenting to Kilifi County Hospital, Kenya with snakebite were identified through the Kilifi Health and Demographic Surveillance System (KHDSS). Cases were prospectively registered, admitted for at least 24-hours, and managed on a paediatric high dependency unit (HDU). Households within the KHDSS study area have been included in 4-monthly surveillance and verbal autopsy, enabling calculation of population-incidence and mortality. Predictors of severe local tissue damage were identified using a multivariate logistic regression analysis. RESULTS: Between 2003 and 2021, there were 19,606 admissions to the paediatric HDU, of which 584 were due to snakebite. Amongst young children (≤5-years age) the population-incidence of hospital-attended snakebite was 11.3/100,000 person-years; for children aged 6-12 years this was 29.1/100,000 person-years. Incidence remained consistent over the study period despite the population size increasing (98,967 person-years in 2006; and 153,453 person-years in 2021). Most cases had local envenoming alone, but there were five snakebite associated deaths. Low haemoglobin; raised white blood cell count; low serum sodium; high systolic blood pressure; and an upper limb bite-site were independently associated with the development of severe local tissue damage. CONCLUSION: There is a substantial burden of disease due to paediatric snakebite, and the annual number of cases has increased in-line with population growth. The mortality rate was low, which may reflect the species causing snakebite in this region. The identification of independent predictors of severe local tissue damage can help to inform future research to better understand the pathophysiology of this important complication.

Correction: The 20-minute whole blood clotting test (20WBCT) for snakebite coagulopathy-A systematic review and meta-analysis of diagnostic test accuracy.

[This corrects the article DOI: 10.1371/journal.pntd.0009657.].

Where do those data go? Reuse of screening results from clinical trials to estimate population prevalence of HBV infection in adults in Kilifi, Kenya.

Chronic hepatitis B infection (CHB) is a significant problem worldwide with around 300 million people infected. Ambitious goals have been set towards its elimination as a public health threat by 2030. However, accurate seroprevalence estimates in many countries are lacking or fail to provide representative population estimates, particularly in the WHO African Region (AFRO). This means the full extent of HBV infection is not well described, leading to a lack of investment in diagnostics, treatment and disease prevention. Clinical trials in the WHO AFRO region have been increasing over time and many test for infectious diseases including hepatitis B virus (HBV) to determine baseline eligibility for participants, however these screening data are not reported. Here we review data from six clinical trials completed at the KEMRI-Wellcome Trust Research Programme between 2016 and 2023 that screened for HBV using hepatitis B surface antigen (HBsAg) as part of the trial exclusion criteria. 1727 people had HBsAg results available, of which 60 tested positive. We generated a crude period HBV prevalence estimate of 3.5% (95% CI 2.6-4.5%), and after standardisation for sex and age to account for the population structure of the Kilifi Health Demographics Surveillance System (KHDSS), the prevalence estimate increased to 5.0% (95% CI 3.4-6.6%). The underrepresentation of women in these trials was striking with 1263/1641 (77%) of participants being male. Alanine aminotransferase (ALT) was significantly higher in the HBsAg positive group but was not outside the normal range. We argue that routine collation and publishing of data from clinical trials could increase precision and geographical representation of global HBV prevalence estimates, enabling evidence-based provision of clinical care pathways and public health interventions to support progress towards global elimination targets. We do acknowledge when using clinical trials data for seroprevalence estimates, that local population structure data is necessary to allow standardisation of results, and the point of care tests used here are limited in sensitivity and specificity.

[A global core outcome measurement set for snakebite clinical trials]. / Définition d'un jeu universel de critères de décision de base pour les essais cliniques sur les morsures de serpent.

Background: Snakebite clinical trials have often used heterogeneous outcome measures and there is an urgent need for standardisation. Method: A globally representative group of key stakeholders came together to reach consensus on a globally relevant set of core outcome measurements. Outcome domains and outcome measurement instruments were identified through searching the literature and a systematic review of snakebite clinical trials. Outcome domains were shortlisted by use of a questionnaire and consensus was reached among stakeholders and the patient group through facilitated discussions and voting. Results: Five universal core outcome measures should be included in all future snakebite clinical trials: mortality, WHO disability assessment scale, patient-specific functional scale, acute allergic reaction by Brown criteria, and serum sickness by formal criteria. Additional syndrome-specific core outcome measures should be used depending on the biting species. Conclusion: This core outcome measurement set provides global standardisation, supports the priorities of patients and clinicians, enables meta-analysis, and is appropriate for use in low-income and middle-income settings.

A global core outcome measurement set for snakebite clinical trials.

Snakebite clinical trials have often used heterogeneous outcome measures and there is an urgent need for standardisation. A globally representative group of key stakeholders came together to reach consensus on a globally relevant set of core outcome measurements. Outcome domains and outcome measurement instruments were identified through searching the literature and a systematic review of snakebite clinical trials. Outcome domains were shortlisted by use of a questionnaire and consensus was reached among stakeholders and the patient group through facilitated discussions and voting. Five universal core outcome measures should be included in all future snakebite clinical trials-mortality, WHO disability assessment scale, patient-specific functional scale, acute allergic reaction by Brown criteria, and serum sickness by formal criteria. Additional syndrome-specific core outcome measures should be used depending on the biting species. This core outcome measurement set provides global standardisation, supports the priorities of patients and clinicians, enables meta-analysis, and is appropriate for use in low-income and middle-income settings.

TRUE-1: Trial of Repurposed Unithiol for snakebite Envenoming phase 1 (safety, tolerability, pharmacokinetics and pharmacodynamics in healthy Kenyan adults).

Background: Snakebites affect over 5 million people each year, and over 100,000 per year die as a result. The only available treatment is antivenom, which has many shortcomings including high cost, intravenous administration, and high risk of adverse events. One of the most abundant and harmful components of viper venoms are the zinc-dependent snake venom metalloproteinases (SVMPs). Unithiol is a chelating agent which is routinely used to treat heavy metal poisoning. In vivo experiments in small animal models have demonstrated that unithiol can prevent local tissue damage and death caused by a certain viper species. This phase I clinical trial will assess the safety of ascending doses of unithiol with a view for repurposing for snakebite indication. Methods: This open label, single agent, phase I clinical trial of a repurposed drug has a primary objective to evaluate the safety of escalating doses of unithiol, and a secondary objective to describe its pharmacokinetics. In total, 64 healthy Kenyan volunteers from Kilifi County will be dosed in consecutive groups of eight, with dose escalation decisions dependent on review of safety data by an independent data safety monitoring board. Four groups will receive ascending single oral doses, two will receive multiple oral doses, and two will receive single intravenous doses. Follow-up will be for 6-months and includes full adverse event reporting. Pharmacokinetic analysis will define the Cmax, Tmax, half-life and renal elimination. Conclusions: This clinical trial will assess the safety and tolerability of a promising oral therapeutic in a relevant setting where snakebites are prevalent. Unithiol is likely to be safer than antivenom, is easier to manufacture, has activity against diverse snake species, and can be administered orally, and thus shows promise for repurposing for tropical snakebite. Pan African Clinical Trials Registry: PACTR202103718625048 (3/3/2021).

Clinical outcomes and outcome measurement tools reported in randomised controlled trials of treatment for snakebite envenoming: A systematic review.

BACKGROUND: Snakebite is a priority neglected tropical disease and causes a range of complications that vary depending on the snake species. Randomised clinical trials have used varied outcome measures that do not allow results to be compared or combined. In accordance with the Core Outcomes Measurements in Effectiveness Trials (COMET) initiative, this systematic review aims to support the development of a globally relevant core outcome set for snakebite. METHODS: All randomised controlled trials, secondary analyses of randomised controlled trials and study protocols investigating the efficacy of therapeutics for human snakebite envenoming were eligible for inclusion. Study screening and data extraction were conducted in duplicate by two independent reviewers. All primary and secondary outcome measures were extracted and compiled, as were adverse event outcome measures. Similar outcome measures were grouped into domains. The study was prospectively registered with PROSPERO: CRD42020196160. RESULTS: This systematic review included 43 randomised controlled trials, two secondary analyses and 13 study protocols. A total of 382 outcome measures were extracted and, after duplicates were merged, there were 153 unique outcomes. The most frequently used outcome domain ('venom antigenaemia') was included in less than one third of the studies. The unique outcomes were classified into 60 outcome domains. Patient-centred outcomes were used in only three of the studies. DISCUSSION: Significant heterogeneity in outcome measures exists in snakebite clinical trials. Consensus is needed to select outcome measures that are valid, reliable, patient-centred and feasible. The results of this systematic review strongly support the development of a core outcome set for use in snakebite clinical trials.

The 20-minute whole blood clotting test (20WBCT) for snakebite coagulopathy-A systematic review and meta-analysis of diagnostic test accuracy.

BACKGROUND: The 20-minute whole blood clotting test (20WBCT) has been used to detect coagulopathy following snakebite for almost 50 years. A systematic review and meta-analysis of the 20WBCT was conducted to evaluate the accuracy of the 20WBCT to detect coagulopathy, indicative of systemic envenoming. METHODS AND FINDINGS: Databases were searched from inception up to 09/12/2020 to identify studies that compared the 20WBCT and INR/fibrinogen on five or more subjects. Data was extracted from full-text articles by two reviewers using a predetermined form. Authors of 29 studies that lacked sufficient details in the manuscript were contacted and included if data meeting the inclusion criteria were provided. Included studies were evaluated for bias using a tailored QUADAS-2 checklist. The study protocol was prospectively registered on PROSPERO database (CRD42020168953). The searches identified 3,599 studies, 15 met the inclusion criteria and 12 were included in the meta-analysis. Data was reported from 6 countries and included a total of 2,270 patients. The aggregate weighted sensitivity of the 20WBCT at detecting INR >1.4 was 0.84 (CI 0.61 to 0.94), the specificity was 0.91 (0.76 to 0.97) and the SROC AUC was 0.94 (CI 0.91 to 0.96). The aggregate weighted sensitivity of the 20WBCT at detecting fibrinogen <100 mg/dL was 0.72 (CI 0.58 to 0.83), the specificity was 0.94 (CI 0.88 to 0.98) and the SROC AUC was 0.93 (0.91 to 0.95). Both analyses that used INR and fibrinogen as the reference test displayed considerable heterogeneity. CONCLUSIONS: In the absence of laboratory clotting assays, the 20WBCT remains a highly specific and fairly sensitive bedside test at detecting coagulopathy following snakebite. However, clinicians should be aware of the importance of operator training, standardized equipment and the lower sensitivity of the 20WBCT at detecting mild coagulopathy and resolution of coagulopathy following antivenom.

Sensitivity of SARS-CoV-2 RNA polymerase chain reaction using a clinical and radiological reference standard.

OBJECTIVES: Diagnostic tests for SARS-CoV-2 are important for epidemiology, clinical management, and infection control. Limitations of oro-nasopharyngeal real-time PCR sensitivity have been described based on comparisons of single tests with repeated sampling. We assessed SARS-CoV-2 PCR clinical sensitivity using a clinical and radiological reference standard. METHODS: Between March-May 2020, 2060 patients underwent thoracic imaging and SARS-CoV-2 PCR testing. Imaging was independently double- or triple-reported (if discordance) by blinded radiologists according to radiological criteria for COVID-19. We excluded asymptomatic patients and those with alternative diagnoses that could explain imaging findings. Associations with PCR-positivity were assessed with binomial logistic regression. RESULTS: 901 patients had possible/probable imaging features and clinical symptoms of COVID-19 and 429 patients met the clinical and radiological reference case definition. SARS-CoV-2 PCR sensitivity was 68% (95% confidence interval 64-73), was highest 7-8 days after symptom onset (78% (68-88)) and was lower among current smokers (adjusted odds ratio 0.23 (0.12-0.42) p < 0.001). CONCLUSIONS: In patients with clinical and imaging features of COVID-19, PCR test sensitivity was 68%, and was lower among smokers; a finding that could explain observations of lower disease incidence and that warrants further validation. PCR tests should be interpreted considering imaging, symptom duration and smoking status.

Is continuous positive airway pressure (CPAP) a new standard of care for type 1 respiratory failure in COVID-19 patients? A retrospective observational study of a dedicated COVID-19 CPAP service.

The aim of this case series is to describe and evaluate our experience of continuous positive airway pressure (CPAP) to treat type 1 respiratory failure in patients with COVID-19. CPAP was delivered in negative pressure rooms in the newly repurposed infectious disease unit. We report a cohort of 24 patients with type 1 respiratory failure and COVID-19 admitted to the Royal Liverpool Hospital between 1 April and 30 April 2020. Overall, our results were positive; we were able to safely administer CPAP outside the walls of a critical care or high dependency unit environment and over half of patients (58%) avoided mechanical ventilation and a total of 19 out of 24 (79%) have survived and been discharged from our care.

Attitudes of serodiscordant couples towards antiretroviral-based HIV prevention strategies in Kenya: a qualitative study.

This qualitative study aims to gain in-depth information about the attitudes of HIV-serodiscordant couples towards two new methods of HIV prevention; Pre-Exposure Prophylaxis and Treatment as Prevention, both of which have been recently recommended by the World Health Organisation. Semi-structured interviews were conducted with 38 individuals in a serodiscordant relationship in Western Kenya. Topic guides were used to elicit information on perceived benefits, concerns, and preferences towards Treatment as Prevention and Pre-Exposure Prophylaxis. Data evaluation and thematic generation were developed using framework analysis. Results suggest that the majority of participants, irrespective of gender and HIV status, found Treatment as Prevention the more acceptable strategy. Key factors influencing this decision were HIV-negative participants' limited motivation to take prophylactic antiretrovirals and the likely health improvements Treatment as Prevention offers HIV-positive partners. However, issues were raised concerning the likelihood of low concurrent condom use and poor medication adherence when using these preventative approaches. It was concluded that the adoption of Treatment as Prevention as a method of HIV control in Kenya is likely to be more readily accepted by serodiscordant couples than Pre-exposure Prophylaxis. However, future implementation of either strategy would require measures to address the possibility of risk compensation and poor adherence.

Attitudes of serodiscordant couples towards antiretroviral-based HIV prevention strategies in Kenya: a qualitative study.

INTRODUCTION: Transmission in serodiscordant couples (SDCs) accounts for approximately half of all new HIV infections, both in Kenya and the wider sub-Saharan region (1). With evidence to suggest inconsistent condom use within this population (2), the World Health Organization has recommended two new methods of HIV prevention for SDCs: Treatment as Prevention (TasP) and Pre-Exposure Prophylaxis (PrEP). However, there has been little research about the attitudes of SDCs towards these strategies (3, 4); knowledge that is paramount for successfully predicting the acceptability and efficacy of each method, as well as for informing decisions regarding HIV policy changes in Kenya. METHODS: An exploratory, qualitative study was conducted in the Muhoroni constituency of Nyando district, Kenya from January to March 2013. Purposive sampling was predominately used to recruit 21 HIV-positive and 17 HIV-negative individuals in a serodiscordant relationship from four hospitals and health centres. During face-to-face semi-structured interviews, topic guides were used to elicit information about participants' attitudes and preferences towards TasP and PrEP. Collected data underwent framework analysis, allowing the development of overarching categories, sub-themes and inductive interpretation. RESULTS: The majority of participants, irrespective of gender and HIV status, found TasP more acceptable than PrEP. A key factor influencing this decision was HIV-negative participants' limited motivation to take and adhere to antiretrovirals (ARVs), primarily due to a predominantly external health locus of control, a lack of cultural acceptance of prophylactic medication and concerns about side effects. In addition to this, the likely health improvements TasP offers HIV-positive partners, as well as the attitude that the sick individual should be the first to receive HIV medication, also contributed to this conclusion. Issues of risk compensation were raised, with some HIV-negative partners indicating a desire to stop using condoms if ARV-based prevention methods were available. CONCLUSIONS: Findings from the study indicate that TasP may represent a more viable approach to HIV prevention in Kenya than PrEP. Couples' preferences, however, may differ depending on local attitudes towards prophylaxis and health locus of control.

Essential therapeutics skills required of junior doctors.

Junior doctors are responsible for the majority of in-hospital prescription errors. Little research has explored their confidence to prescribe, or practical therapeutics related tasks which they are required to perform in day-to-day practice. This survey aimed to explore these areas, gather feedback regarding therapeutics teaching at undergraduate level, and to apply findings to undergraduate training at University of Birmingham. Questionnaire-based survey of all first-year postgraduate doctors (PG1) attending teaching hospitals in the Birmingham and Worcester regions towards the end of the PG1 year. Doctors were asked about difficulties in prescribing, satisfaction with undergraduate training, and how frequently they undertook particular tasks pertaining to therapeutics. Qualitative data on suggestions for improving the curriculum were also collected. Difficulties were commonly encountered with prescribing warfarin, controlled drugs and syringe-driven drugs. Most (87.4 %) had been required to administer intravenous medications. Nearly all had prescribed to 'special groups' such as the elderly (100 %) and patients with renal disease (98.3 %). Thirty-seven percent were not satisfied with their undergraduate therapeutics teaching, and many (56.2 %) recommended making teaching more relevant to clinical practice. Many PG1s expressed difficulties in prescribing potentially dangerous medications. Although better than other UK surveys, significant numbers were not satisfied with undergraduate teaching. The strong opinion was for teaching to become more practical and more relevant. Prescriptions which PG1s are commonly asked to write have been described. Findings have guided improvements to undergraduate teaching and assessment in therapeutics at the University of Birmingham, and may offer guidance to other medical schools.

Development and validation of systems for rational use of viral load testing in adults receiving first-line ART in sub-Saharan Africa.

BACKGROUND: World Health Organization (WHO) immunological and clinical criteria for monitoring first-line antiretroviral treatment (ART) offer low accuracy for predicting viral failure. Targeting viral load assays to those at high risk has been recommended and a system to do this has been developed in Cambodia. Systems for use in sub-Saharan African populations were evaluated. METHODS: A new Ugandan-based scoring system for targeting viral load assays was developed from data from the first 4 years of a Ugandan cohort (N = 559) receiving first-line ART. The accuracy of this, the Cambodian system and the WHO criteria to predict viral failure, through targeting viral load assays, were compared in a separate population of 496 Ugandans. RESULTS: The new Ugandan scoring system included CD4 cell count, mean cell volume, adherence, and HIV-associated clinical events as predictors of viral failure. In the validation population, the Ugandan system undertook viral load assays in 61 (12.3%) cases offering 20.5% sensitivity and 100% positive predictive value (PPV) to predict viral failure. The Cambodian system undertook viral load assays in 33 (6.7%) cases producing 23.1% sensitivity and 90.0% PPV. WHO criteria recommended viral load assays in 72 (14.5%) cases offering 30.8% sensitivity and 100% PPV. CONCLUSION: Locally developed algorithms based on clinical and immunological criteria may offer little additional accuracy over WHO criteria for targeting viral load assays. When possible, confirming viral load before switching therapy is recommended. Scoring systems are more flexible than WHO criteria in allowing ART providers to choose the proportion of the population that undergo targeted viral load testing.