Water filtration by endobenthic sandprawns enhances resilience against eutrophication under experimental global change conditions.

Identifying processes that confer resilience against global change is a scientific challenge but is central to managing ecosystem functionality in future. Detecting resilience-enhancing mechanisms is especially relevant in coastal ecosystems, where multi-stressor interactions can drive degradation over time. Here, we quantify the resilience-conferring potential of endobenthic sandprawns against eutrophication, including under high temperatures. We show using a global change mesocosm experiment that sandprawn presence was associated with declines in phytoplankton biomass, particularly under eutrophic conditions, where sandprawns reduced phytoplankton biomass by approximately 74% and prevented a shift to extreme eutrophy. Eutrophic waters were nanophytoplankton-dominated, but sandprawn presence countered this, resulting in even contributions of pico- and nanophytoplankton. Our findings highlight the potential for sandprawns to increase resilience against eutrophication by limiting phytoplankton blooms, preventing extreme eutrophy and counteracting nanophytoplankton dominance. Incorporating endobenthic crustaceans into resilience-based management practices can assist in arresting future water quality declines in coastal ecosystems.

Glycated haemoglobin (HbA1c) use and glycaemic control in patients living with diabetes mellitus attending public healthcare facilities in KwaZulu-Natal Province, South Africa.

BACKGROUND: Ideal control of diabetes mellitus (DM) remains a global goal, which has not yet been reached. As part of an integrated public healthcare strategy, data with subsequent analysis of diabetes control achieved in patients living with DM (PLWD) need to be available. Diabetes control data from KwaZulu-Natal (KZN) Province, South Africa, are scarce. Smaller studies conducted in public and private healthcare sectors of KZN have shown suboptimal DM control. OBJECTIVES: To identify the percentage of glycated haemoglobin (HbA1c) tests done in KZN public healthcare facilities, and to provide a glimpse into diabetes control being achieved in each KZN district municipality. METHODS: Data regarding the number of HbA1c tests performed, number of patients with an HbA1c ≤7% and number of diabetes visits were accessed from the KZN Department of Health Information Systems and analysed. RESULTS: The majority of HbA1c tests were performed in the metro municipality of eThekwini (p<0.001). Approximately two-thirds (64.5%) of PLWD in whom HbA1c tests had been performed, were suboptimally controlled. In 5 of the 11 KZN district municipalities more than two-thirds of PLWD had an HbA1c >7%. Most of the patients in 9 of the 11 district municipalities showed suboptimal control of their DM. The total number of HbA1c tests performed in KZN represents approximately one-tenth of the total number of diabetes treatment visits. This trend was prevalent in all 11 district municipalities, where the incidence of DM was on an upward trajectory. CONCLUSIONS: Our study demonstrated that the majority of PLWD visiting public healthcare facilities in KZN have suboptimal glycaemic control. They are at increased risk of developing diabetes-related complications, further burdening the healthcare fiscus of low- to middle-income countries. We also showed that the number of HbA1c tests being performed, in the presence of suboptimal control, was well below par. This finding serves to emphasise the need for strategies to be implemented to increase awareness of HbA1c testing for the monitoring of glycaemic control, and for making point-of-care HbA1c testing readily available in these healthcare facilities.

The burden of hypertension in KwaZulu-Natal Province, South Africa: A 6-year perspective.

BACKGROUND: Hypertension (HPT) and its complications continue to pose a global threat and contribute to premature mortality worldwide. The adverse interactions between HPT, obesity and COVID-19 are currently being witnessed globally and represent a collision of pandemics. Understanding the burden that this non-communicable disease (NCD) poses in KwaZulu-Natal (KZN) Province, South Africa (SA), would help in developing improved public healthcare strategies. OBJECTIVES: To describe the burden of HPT in all the districts of KZN over a 6-year period. METHODS: HPT data are routinely collected from all KZN public health facilities (both clinics and hospitals) as part of the District Health Information System (DHIS). In this retrospective study, we accessed HPT records from the DHIS over a period of 6 years (2014 - 2019, inclusive). Data collected included the number of patients screened, diagnosed and initiated on therapy for HPT, together with the number of obese patients. RESULTS: The slopes for HPT screening were positive at both clinics and hospitals in KZN (considerably more at clinics than hospitals, with a difference in elevations of slopes of p<0.001), with a significantly greater percentage of the population having been screened at rural clinics than at hospitals (difference in elevation of slopes p<0.001). A significantly greater number of patients aged <40 years (p<0.001) were being screened for HPT at clinics than at hospitals (2017/18, 2018/19, 2019/20), while hospitals screened considerably more patients aged ≥40 years in 2017 - 2018 (p<0.001). The numbers of new hypertensives diagnosed and having treatment initiated were on an upward slope at both clinics and hospitals, with clinics having a greater elevation of slope than hospitals (p<0.001), irrespective of patient age. A significantly greater number of patients aged ≥40 years (p<0.05) were diagnosed with HPT at both clinics and hospitals in KZN (2017/18, 2018/19, 2019/20). KZN clinics remained the first port of call for known hypertensives throughout the study period. Obesity was prevalent at both clinic and hospital level, although figures were significantly higher at clinics. Over 80% of the obesity burden was carried by the rural clinics and hospitals. CONCLUSIONS: Screening, diagnosis, treatment initiation and chronic management of HPT occur mainly at rural clinic level. The SA government needs to heed these findings and redirect resources (staffing and equipment) to this level. The prevalence of obesity was highest at rural healthcare facilities (clinics more than hospitals). More needs to be done to combat the obesity pandemic if we are to win the battle against NCDs (HPT and diabetes mellitus). A significant number of patients aged <40 years are being screened for HPT, which bodes well for the province, as early diagnosis and treatment of HPT are vital to prevent complications.

Clinical outcomes after first-line HIV treatment failure in South Africa: the next cascade of care.

INTRODUCTION: There is limited literature on the appropriateness of viral load (VL) monitoring and management of detectable VL in public health settings in rural South Africa. METHODS: We analysed data captured in the electronic patient register from HIV-positive patients ≥ 15 years old initiating antiretroviral therapy (ART) in 17 public sector clinics in rural KwaZulu-Natal, during 2010-2016. We estimated the completion rate for VL monitoring at 6, 12, and 24 months. We described the cascade of care for those with any VL measurement ≥ 1000 HIV-1 RNA copies/mL after ≥ 20 weeks on ART, including the following proportions: (1) repeat VL within 6 months; (2) re-suppressed; (3) switched to second-line regimen. RESULTS: There were 29 384 individuals who initiated ART during the period [69% female, median age 31 years (interquartile range 25-39)]. Of those in care at 6, 12, and 24 months, 40.7% (9861/24 199), 34% (7765/22 807), and 25.5% (4334/16 965) had a VL test at each recommended time-point, respectively. The VL results were documented at all recommended time-points for 12% (2730/22 807) and 6.2% (1054/16 965) of ART-treated patients for 12 and 24 months, respectively. Only 391 (18.3%) of 2135 individuals with VL ≥ 1000 copies/mL on first-line ART had a repeat VL documenting re-suppression or were appropriately changed to second-line with persistent failure. Completion of the treatment failure cascade occurred a median of 338 days after failure was detected. CONCLUSION: We found suboptimal VL monitoring and poor responses to virologic failure in public-sector ART clinics in rural South Arica. Implications include increased likelihood of morbidity and transmission of drug-resistant HIV.

Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I.

BACKGROUND: M184V/I cause high-level lamivudine (3TC) and emtricitabine (FTC) resistance and increased tenofovir disoproxil fumarate (TDF) susceptibility. Nonetheless, 3TC and FTC (collectively referred to as XTC) appear to retain modest activity against human immunodeficiency virus-1 with these mutations possibly as a result of reduced replication capacity. In this study, we determined how M184V/I impacts virus load (VL) in patients failing therapy on a TDF/XTC plus nonnucleoside reverse-transcriptase inhibitor (NNRTI)-containing regimen. METHODS: We compared VL in the absence and presence of M184V/I across studies using random effects meta-analysis. The effect of mutations on virus reverse-transcriptase activity and infectiousness was analyzed in vitro. RESULTS: M184I/V was present in 817 (56.5%) of 1445 individuals with virologic failure (VF). Virus load was similar in individuals with or without M184I/V (difference in log10 VL, 0.18; 95% confidence interval, .05-.31). CD4 count was lower both at initiation of antiretroviral therapy and at VF in participants who went on to develop M184V/I. L74I was present in 10.2% of persons with M184V/I but absent in persons without M184V/I (P < .0001). In vitro, L74I compensated for defective replication of M184V-mutated virus. CONCLUSIONS: Virus loads were similar in persons with and without M184V/I during VF on a TDF/XTC/NNRTI-containing regimen. Therefore, we did not find evidence for a benefit of XTC in the context of first-line failure on this combination.

Validation and effect on diabetes control of glycated haemoglobin (HbA1c) point-of-care testing.

BACKGROUND: Optimal control of diabetes mellitus (DM) remains daunting globally. Point-of-care testing (POCT) for glycated haemoglobin (HbA1c) enables the clinician to make immediate management decisions and thereby improve DM control and complications. Better control is increasingly being striven for in developing countries where availability of POCT devices is limited. METHODS: Every alternate patient who visited the diabetes clinic at Edendale Hospital, Durban, South Africa, between 1 June 2017 and 31 August 2017 was invited to participate in the study. These patients made up the POCT group, with the remainder making up the control laboratory group. The POCT group had Quo-Test HbA1c POCT done at the clinic visit and their treatment was adjusted based on the HbA1c reading, while the control group received standard treatment. The two groups of patients were reviewed at 3 months to identify differences in diabetes control between them. RESULTS: Data from 266 patients were analysed (135 in the POCT group v. 131 in the control group). There was no significant difference between the price of the POCT and laboratory HbA1c tests (p=0.823). The POCT and laboratory HbA1c values showed good correlation at baseline (r=0.995; p<0.001). The two groups of patients were evenly matched in respect of most demographic and clinical variables. Patients in the POCT group showed a significant improvement in mean (standard deviation) glycaemic control between baseline and 3 months (9.61 (2.46) v. 8.98 (2.15); p<0.043). No improvement was noted in the control group (9.58 (2.49) v. 9.43 (2.15); p=0.823). CONCLUSIONS: The Quo-Test HbA1c POCT had good correlation with standard laboratory methods in respect of both glycaemic control and price. Patients who had POCT at baseline showed a significant improvement in glycaemic control at 3 months. HbA1c POCT in the setting of a multifaceted approach to diabetes care has been shown to have definite benefits.

Deriving an optimal threshold of waist circumference for detecting cardiometabolic risk in sub-Saharan Africa.

BACKGROUND: Waist circumference (WC) thresholds derived from western populations continue to be used in sub-Saharan Africa (SSA) despite increasing evidence of ethnic variation in the association between adiposity and cardiometabolic disease and availability of data from African populations. We aimed to derive a SSA-specific optimal WC cut-point for identifying individuals at increased cardiometabolic risk. METHODS: We used individual level cross-sectional data on 24 181 participants aged ⩾15 years from 17 studies conducted between 1990 and 2014 in eight countries in SSA. Receiver operating characteristic curves were used to derive optimal WC cut-points for detecting the presence of at least two components of metabolic syndrome (MS), excluding WC. RESULTS: The optimal WC cut-point was 81.2 cm (95% CI 78.5-83.8 cm) and 81.0 cm (95% CI 79.2-82.8 cm) for men and women, respectively, with comparable accuracy in men and women. Sensitivity was higher in women (64%, 95% CI 63-65) than in men (53%, 95% CI 51-55), and increased with the prevalence of obesity. Having WC above the derived cut-point was associated with a twofold probability of having at least two components of MS (age-adjusted odds ratio 2.6, 95% CI 2.4-2.9, for men and 2.2, 95% CI 2.0-2.3, for women). CONCLUSION: The optimal WC cut-point for identifying men at increased cardiometabolic risk is lower (⩾81.2 cm) than current guidelines (⩾94.0 cm) recommend, and similar to that in women in SSA. Prospective studies are needed to confirm these cut-points based on cardiometabolic outcomes.International Journal of Obesity advance online publication, 31 October 2017; doi:10.1038/ijo.2017.240.

Enhancing antibiotic stewardship by tackling "spurious" penicillin allergy.

Approximately 90-99% of patients with a label of penicillin allergy (PenA) are not allergic when comprehensively investigated. An inaccurate label of PenA has major public health implications-longer hospital stay, more frequent hospital admissions, greater use of fluoroquinolones, glycopeptides, cephalosporins and other expensive antibiotics resulting in significantly higher costs to the health service and predisposing to Clostridium difficile, methicillin-resistant Staphylococcus aureus infections and vancomycin-resistant enterococcus. We describe lessons learnt from recent studies regarding possible reasons contributing to an inaccurate label of PenA as well as propose a concerted multidisciplinary approach to address this important public health problem. Given the unmet need for allergy services in the UK and several other countries and knowledge gaps regarding PenA amongst healthcare professionals, we describe the potential role for a computerized clinical decision support system to enable non-specialists rapidly identify and de-label "low-risk" hospitalized patients with a label of PenA thereby obviating the need for allergy tests. This approach however needs rigorous evaluation for feasibility, safety, patient and physician acceptability, cost-effectiveness and its compatibility with information technology systems currently employed in the health service.

Caring for a patient with rabies: implications of the Milwaukee protocol for infection control and public health measures.

This article discusses the infection control and public health measures taken whilst managing a case of laboratory-confirmed rabies, and the challenges faced in implementing these measures. Case management requires intensive multi-disciplinary co-ordination. The Milwaukee protocol, which to date has five reported human rabies survivors associated with its use, has been suggested as a potential management pathway for human rabies. Consensus among hospital and public health clinicians would aid future deployment of this approach in selected cases.

Single-centre experience of allogeneic haemopoietic stem cell transplant in paediatric patients in Cape Town, South Africa.

BACKGROUND: Allogeneic haemopoietic stem cell transplant (Allo-HSCT) is a specialised and costly intervention, associated with significant morbidity and mortality. It is used to treat a broad range of paediatric conditions. South Africa (SA) is an upper middle-income country with limitations on healthcare spending. The role of paediatric Allo-HSCT in this setting is reviewed. OBJECTIVES: To review paediatric patients who underwent Allo-HSCT at the Groote Schuur Hospital/University of Cape Town Private Academic Hospital transplant unit in Cape Town, South Africa, and received post-transplant care at Red Cross War Memorial Children's Hospital, over the period January 2006 - December 2014 in respect of indications for the transplant, donor sources, conditioning regimens, treatment-related morbidity and overall survival (OS). METHODS: A retrospective analysis of patient records was performed and a database was created in Microsoft Access. Descriptive analyses of relevant demographic, clinical and laboratory data were performed. Summary statistics of demographic and clinical parameters were derived with Excel. OS was calculated from the date of transplant to the date of an event (death) or last follow-up using the Kaplan-Meier method in Statistica. RESULTS: A total of 48 children received Allo-HSCT: 24 for haematological malignancies, 20 for non-oncological haematological conditions, 3 for immune disorders and 1 for adrenoleukodystrophy. There were 28 boys (median age 7.5 years) and 20 girls (8.5 years). There were 31 sibling matched peripheral-blood stem cell (PBSC) transplants and 1 maternal haploidentical PBSC transplant. Stem cells were mobilised from bone marrow into peripheral blood by administering granulocyte-colony stimulating factor to donors. PBSCs were harvested by apheresis. Eight patients received 10/10 HLA-matched grafts from unrelated donors. Six were PBSC grafts and 2 were bone marrow grafts. Three of the unrelated PBSC grafts were from SA donors. Eight transplants used umbilical cord blood from international registries. OS for patients with non-oncological disorders was 91.3% (median follow-up 3.9 years), while that for oncology patients was 56.8% (1.9 years). Two of the survivors developed chronic graft-versus-host disease. CONCLUSIONS: OS for non-oncological conditions was excellent, while outcomes for oncological disorders were on par with those in high-income settings. Transplantation offers many patients the opportunity for long-term survival and has been shown to be both feasible and rewarding in a less well-resourced environment servicing an economically diverse population.

User perspectives on Implanon NXT in South Africa: A survey of 12 public-sector facilities

Abstract: Background. Implanon NXT, a long-acting reversible contraceptive, was introduced in South Africa (SA) in early 2014, aiming to expand the method mix and increase its effectiveness. Initial uptake was high, but has since declined considerably. In these early years after the implant's introduction, it is important to identify reasons for the decline, and remedy gaps in services. Objectives. To determine periods of use, reasons for the use and early removal of the implant Implanon NXT. Methods. In 2016, we recruited 152 women from six clinics in the City of Johannesburg, and six in North West Province, SA. A semistructured interview was administered to 91 women currently using the implant and 61 previous users. We examined user perspectives, factors influencing women's experiences with the implant and reasons for discontinuation. Results. The participants' mean age was 30 years, with only 15% aged <25. Implant uptake was motivated by convenience (less frequent visits required than for short-acting methods) and by favourable views of the method among friends, family and healthcare providers. Only about a quarter of women recalled being counselled pre-insertion about implant effectiveness, and half about side-effects pre-insertion. Among discontinuers, the median time to device removal was 8 months (interquartile range 6 - 12), and this was primarily as a result of side-effects (90%), especially bleeding-pattern changes and headaches. Removals were most common among married and cohabiting women, often ascribed to the effects of bleeding on their sexual relationships. Rumours and misinformation contributed to some removals. Overall, women's experiences with the implant were rated 'good' or 'very good' by 74% of those continuing use, many of whom reported not having experienced any side-effects or that these had diminished over time. Conclusion. Levels of acceptability among continuing users were high, mainly linked to the method's convenience. While early favourable views drove uptake, negative perceptions, if unaddressed, may now undermine services. Deficiencies in counselling around effectiveness and side-effects may extend to contraceptive services more generally. Women require more intensive support when experiencing sideeffects, including effective systematic approaches to ameliorating bleeding and headaches. Implant services could specifically target young women and first-time contraceptive users. These actions together could reverse the persistent decline in implant use in SA.

Uptake and early removals of Implanon NXT in South Africa: Perceptions and attitudes of healthcare workers

Background. The South African (SA) government introduced Implanon NXT, a long-acting subdermal contraceptive implant, in 2014 to expand contraceptive choice. Following an initial high uptake, its use declined considerably amid reports of early removals and frequent side-effects. We examine providers' perceptions of training and attitudes towards Implanon NXT, as well as their views on the causes of early removals and the impact on the implant service. Objective. To assess healthcare providers' perceptions and attitudes towards implant services in SA. Methods. In-depth interviews were conducted with eight nurses providing implant services in public facilities in Gauteng and North West Province. Emerging themes were identified, manually coded and thematically analysed following an interpretivism approach. Results. Nurses lacked confidence in providing implant services effectively, particularly removals, which they ascribed to the brief, cascade-type training received. Nurses generally held negative views towards the method. They also reported that side-effects are the most common reason for early removals ­ particularly irregular bleeding ­ and that men often do not support their partners who use the method. Lastly, it was found that providers require guidance on counselling regarding the method and standardised guidelines on the management of side-effects. Conclusion. Retraining and support of providers are needed to address competency gaps and negative attitudes towards the method. Assessment of providers' readiness to perform removal procedures is also important. Finally, effective plans are necessary to improve implant continuation rates, especially among women whose partners are unsupportive.

Gaps in monitoring systems for Implanon NXT services in South Africa: An assessment of 12 facilities in two districts

Background. Implanon NXT, a long-acting subdermal contraceptive implant, was introduced in South Africa (SA) in early 2014 as part of an expanded contraceptive method mix. After initial high levels of uptake, reports emerged of frequent early removals and declines in use. Monitoring of progress and challenges in implant service delivery could identify aspects of the programme that require strengthening. Objectives. To assess data management and record keeping within implant services at primary care facilities. Methods. We developed a checklist to assess the tools used for monitoring implant services and data reporting to district offices. The checklist was piloted in seven facilities. An additional six high-volume and six low-volume implant insertion clinics in the City of Johannesburg (CoJ), Gauteng Province, and the Dr Kenneth Kaunda District, North West Province, were selected for assessment. Results. All 12 facilities completed a Daily Head Count Register, which tallied the number of clients attending the clinic, but not information about implant use. A more detailed Tick Register recorded services that clinic attendees received, with nine documenting number of implant insertions and six implant removals. A more specific tool, an Insertion Checklist, collected data on insertion procedures and client characteristics, but was only used in CoJ (five of six facilities). Other registers, which were developed de novo by staff at individual facilities, captured more detailed information about insertions and removals, including reasons. Five of six low-volume insertion facilities used these registers, but only three of six high-volume facilities. No facilities used the form specifically developed by the National Department of Health for implant pharmacovigilance. Nine of 12 clinics reported data on numbers of insertions to the district office, six reported removals and none provided data on reasons for removals. Conclusion. For data to inform effective decision-making and quality improvement in implant services in SA, standardised reporting guidelines and data collection tools are needed, reinforced by staff training and quality assessment of data collection. Staff often took the initiative to fill gaps in reporting systems. Current systems are unable to accurately monitor uptake or discontinuation, or identify aspects of services requiring strengthening. Lack of pharmacovigilance data is especially concerning. Deficiencies noted in these monitoring systems may be common to family planning services more broadly, which warrants investigation.

Lessons learnt from the introduction of the contraceptive implant in South Africa

In 2014, South Africa (SA) introduced the subdermal contraceptive implant with the aim of expanding the contraceptive method mix and availability of long-acting reversible methods in the public sector. Three years on, concerns have been raised about the decline in uptake, early implant removals and challenges in service delivery. This article explores the lessons learnt from the introduction of contraceptive technologies elsewhere and applies these to the SA context. Drawing on the World Health Organization's conceptual framework for the introduction of new contraceptive methods, and subsequent literature on the topic, lessons are classified into six cross-cutting themes. Recommendations highlight the need for SA to review and explore strategies to strengthen current implant services, including the provision of improved provider training aimed at sensitive, client-centred approaches; increased community engagement; and improved systems for programmatic monitoring and evaluation. With implementation of these recommendations, worrying trends in the provision of implants could be reversed.

Strengthening implant provision and acceptance in South Africa with the 'Any woman, any place, any time' approach: An essential step towards reducing unintended pregnancies

Progress in reducing unintended pregnancies in South Africa is slow. The implant, introduced in 2014, expanded the range of available longacting reversible contraceptives (LARCs) and held much promise. Uptake, however, has declined precipitously, in spite of its 'unmatched effectiveness' and high levels of satisfaction for most users. We propose policy and provider interventions to raise implant use, underscored by a 'LARC-first' approach. Contraceptive counselling should focus on the particular benefits of LARCs and methods be presented in order of effectiveness. Moreover, implants hold particular advantages for certain groups, especially adolescents and young women, in whom it is considered first-line contraception. Provision of immediate postpartum and post-abortion implants is safe and highly acceptable, yet remains under-utilised. Implant services at HIV and tuberculosis clinics are a key priority, as is inclusion of LARC provision within school health services. Implants could also be delivered by existing mobile outreach services, for example in sex worker programmes. Services could be built around nurses dedicated solely to providing implants, with other health workers receiving brief refresher training. Women who experience side-effects, especially abnormal bleeding, require timely interventions, following a standardised protocol, including use of medications. Encouraging return for side-effects, follow-up phone calls and home visits would raise continuation rates. Removal services require doctor support or designated nurses at specific centres. Limited access to removal services, health workers' resistance or botched procedures will further undermine implant provision. Rapid implant demonstration projects in postpartum wards, schools, outreach services and by dedicated providers may rapidly advance the field. Together, the actions outlined here will ensure that the implant fulfils its potential and reinvigorates family planning services.

Recent trends and patterns in HIV-1 transmitted drug resistance in the United Kingdom.

OBJECTIVES: Transmission of drug-resistant HIV-1 has decreased in the UK since the early 2000s. This analysis reports recent trends and characteristics of transmitted drug resistance (TDR) in the UK from 2010 to 2013. METHODS: Resistance tests conducted in antiretroviral treatment (ART)-naïve individuals between 2010 and 2013 were analysed for the presence of transmitted drug resistance mutations (TDRMs), defined as any mutations from a modified 2009 World Health Organization surveillance list, or a modified 2013 International Antiviral Society-USA list for integrase tests. Logistic regression was used to examine associations between demographics and the prevalence of TDRMs. RESULTS: TDRMs were observed in 1223 (7.5%) of 16 425 individuals; prevalence declined from 8.1% in 2010 to 6.6% in 2013 (P = 0.02). The prevalence of TDRMs was higher among men who have sex with men (MSM) compared with heterosexual men and women (8.7% versus 6.4%, respectively) with a trend for decreasing TDRMs among MSM (P = 0.008) driven by a reduction in nucleoside reverse transcriptase inhibitor (NRTI)-related mutations. The most frequently detected TDRMs were K103N (2.2%), T215 revertants (1.6%), M41L (0.9%) and L90M (0.7%). Predicted phenotypic resistance to first-line ART was highest to the nonnucleoside reverse transcriptase inhibitors (NNRTIs) rilpivirine and efavirenz (6.2% and 3.4%, respectively) but minimal to NRTIs, including tenofovir, and protease inhibitors (PIs). No major integrase TDRMs were detected among 101 individuals tested while ART-naïve. CONCLUSIONS: We observed a decrease in TDRMs in recent years. However, this was confined to the MSM population and rates remained stable in those with heterosexually acquired HIV infection. Resistance to currently recommended first-line ART, including integrase inhibitors, remained reassuringly low.

Gram-negative bacteraemia; a multi-centre prospective evaluation of empiric antibiotic therapy and outcome in English acute hospitals.

Increasing antibiotic resistance makes choosing antibiotics for suspected Gram-negative infection challenging. This study set out to identify key determinants of mortality among patients with Gram-negative bacteraemia, focusing particularly on the importance of appropriate empiric antibiotic treatment. We conducted a prospective observational study of 679 unselected adults with Gram-negative bacteraemia at ten acute english hospitals between October 2013 and March 2014. Appropriate empiric antibiotic treatment was defined as intravenous treatment on the day of blood culture collection with an antibiotic to which the cultured organism was sensitive in vitro. Mortality analyses were adjusted for patient demographics, co-morbidities and illness severity. The majority of bacteraemias were community-onset (70%); most were caused by Escherichia coli (65%), Klebsiella spp. (15%) or Pseudomonas spp. (7%). Main foci of infection were urinary tract (51%), abdomen/biliary tract (20%) and lower respiratory tract (14%). The main antibiotics used were co-amoxiclav (32%) and piperacillin-tazobactam (30%) with 34% receiving combination therapy (predominantly aminoglycosides). Empiric treatment was inappropriate in 34%. All-cause mortality was 8% at 7 days and 15% at 30 days. Independent predictors of mortality (p <0.05) included older age, greater burden of co-morbid disease, severity of illness at presentation and inflammatory response. Inappropriate empiric antibiotic therapy was not associated with mortality at either time-point (adjusted OR 0.82; 95% CI 0.35-1.94 and adjusted OR 0.92; 95% CI 0.50-1.66, respectively). Although our study does not exclude an impact of empiric antibiotic choice on survival in Gram-negative bacteraemia, outcome is determined primarily by patient and disease factors.

The EPIICAL project: an emerging global collaboration to investigate immunotherapeutic strategies in HIV-infected children.

The EPIICAL (Early-treated Perinatally HIV-infected Individuals: Improving Children's Actual Life with Novel Immunotherapeutic Strategies) project arises from the firm belief that perinatally infected children treated with suppressive antiretroviral therapy (ART) from early infancy represent the optimal population model in which to study novel immunotherapeutic strategies aimed at achieving ART-free remission. This is because HIV-infected infants treated within 2-3 months of life have a much reduced viral reservoir size, and rarely show HIV-specific immunity but preserve normal immune development. The goal of EPIICAL is the establishment of an international collaboration to develop a predictive platform using this model to select promising HIV therapeutic vaccine candidates, leading to prioritisation or deprioritisation of novel immunotherapeutic strategies. To establish this platform, the EPIICAL Consortium aims to: develop predictive models of virological and immunological dynamics associated with response to early ART and to treatment interruption using available data from existing cohorts/studies of early-treated perinatally HIV-infected children; optimise methodologies to better characterise immunological, virological and genomic correlates/profiles associated with viral control; test novel immunotherapeutic strategies using in vivo proof-of-concept (PoC) studies with the aim of inducing virological, immunological and transcriptomic correlates/profiles equivalent to those defined by the predictive model. This approach will strengthen the capacity for discovery, development and initial testing of new therapeutic vaccine strategies through the integrated efforts of leading international scientific groups, with the aim of improving the health of HIV-infected individuals.

Mental health professionals and information sharing: carer perspectives.

BACKGROUND: The important role played by carers of those with mental health problems is frequently undervalued among healthcare professionals. AIMS: To identify the difficulties encountered by carers in relation to obtaining information from mental health teams. METHODS: Participants in the study included carers or family members of persons with mental illness who were affiliated with a support group in Ireland. Information was gathered using an 18-item self-report questionnaire. This is an amended version of the Carer Well-Being and Support Questionnaire for carers of people with a mental health problem or dementia. RESULTS: One-hundred and fifty-nine carers complete the questionnaire. On average respondents stated that they have been in the role of a carer for someone with a mental health problem for 14.4 years, spending a median of 20-h caring each week. Despite most carers maintaining that they are generally satisfied with the support offered to them from medical and/or care staff, the majority (56.3%) of respondents stated that they have specifically encountered difficulties accessing information from the treating mental health team. The main reasons given to them by the mental health team for withholding information include: lack of patient consent (46.2%) and unavailability of a team member (46.2%). From a carer perspective, respondents stated that the main reason they feel there is difficulty in accessing information is a lack of concern for their role as a carer in the patient's management (60.5%). More than 75% of all respondents are afraid of negative consequences for them or for the person in their care as a result of information being withheld by the treating team. CONCLUSIONS: Carer involvement is essential for the complete and effective management of individuals with mental illness. Confidentiality should not be used as a reason for completely excluding carers.

A real-time prospective evaluation of clinical pharmaco-economic impact of diagnostic label of 'penicillin allergy' in a UK teaching hospital.

AIMS: To perform a pharmaco-economic analysis of prescribing alternative antibiotics in patients with a diagnostic label of 'penicillin allergy' and assess whether collation of information from a structured history and liaison with the family physician could reduce costs. METHODS: A prospective pro-forma-based interview of randomly selected in-patients and their family physician was used to assess the validity of the diagnostic label of 'penicillin allergy'. Cost analysis of prescription of alternative antibiotics was performed and compared with first-line agents. RESULTS: 102 patients were assessed and only 40% (n=41) were found to have a history consistent with penicillin hypersensitivity, 40% (n=41) were likely 'not allergic' and 20% (n=20) had 'indeterminate' reactions. Total cost of antibiotics prescribed for patients with penicillin allergy was 1.82-2.58-fold higher than for first-line antibiotics. CONCLUSIONS: Obtaining a structured history from the patient and family physician alone can enable an accurate identification of penicillin allergy status. Total acquisition cost of second-line antibiotics is higher than if these patients were prescribed first-line antibiotics.