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BackgroundChronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice.Methods and findingsA total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0-4, 103 events) and high risk groups (risk score ≥ 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria.ConclusionsBoth traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.

BackgroundChronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice.Methods and findingsA total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0-4, 103 events) and high risk groups (risk score ≥ 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria.ConclusionsBoth traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.

Objective: To understand challenges in care after stillbirth and provide tailored solutions.Design: Multi-centre case study.Setting: Three maternity hospitals.Population: Parents with a stillborn baby, maternity staff.Methods: Thematic analysis of parent interviews and staff focus groups and service provision investigation.Outcomes: 1 Themes; 2 Triangulation matrix; 3 Recommendations.Results: Twenty-one women, 14 partners, and 22 staff participated. Service Provision: Care for parents after stillbirth varies excessively; there are misconceptions; post-mortem does not delay follow-up.Presentation: Women 'do not feel right' before stillbirth; their management is haphazard and should be standardised.Diagnosis: Stillbirth is an emergency for parents but not always for staff; communication can seem cold; well-designed bereavement space is critical. Birth: Staff shift priorities to mother and future, but for parents their baby is still a baby; parents are not comfortable with staff recommending vaginal birth as the norm; there are several reasons why parents ask for a caesarean; better care involves clear communication, normal behaviour, and discussion of coping strategies. Post-mortem: Parents are influenced by discussions with staff. Staff should 'sow seeds', clarify its respectful nature, delineate its purpose, and explain the timescale.Follow-up: It is not standardised; parents wish to see their multi-professional team.Conclusions: There is unacceptable variation in care after stillbirth, and insensitive interactions between staff and bereaved parents. Understanding parents' needs, including why they ask for caesarean birth, will facilitate joint decision-making. Every bereaved parent is entitled to good, respectful care.Tweetable Abstract: Care too varied & interactions often insensitive after stillbirth; national pathway & training urgently needed PLAIN LANGUAGE SUMMARY: Why and how was the study carried out? Previous studies have shown that improving care after stillbirth is important for families. We investigated the opinions of bereaved parents and maternity staff to find ways to improve care. At three hospitals in 2013, all women who experienced a stillbirth were invited to an interview along with their partners. Thirty-five parents of 21 babies agreed to participate. Twenty-two obstetricians and midwives took part in focus group discussions. What were the main findings? Care was often not as good as it should and could be. Communication with parents was not always as sensitive as they would have liked because staff did not have appropriate training. Some women reported they did not 'feel right' before going to hospital. Once they arrived, there was no standard approach to how care was given. Sometimes there were long delays before the death of the baby was confirmed and action was taken. After it had been confirmed that the baby had died, staff focussed on the mothers' needs, but the parents' priorities were still with their baby. There were several reasons why parents asked for a caesarean birth that staff had not considered. Staff influenced parents' decisions about post-mortem examinations. Parents found it helpful when staff explained the respectful nature and purpose of the examination. After discharge from hospital, there was no consistent plan for how follow-up care would be given. Parents would have liked more information about their next hospital appointment. What are the limitations of the work? The parents interviewed depended on their memories of the details of the care, which happened some time ago. In staff group discussions, junior doctors may not have spoken openly because there were senior doctors present. Further research is necessary to understand and improve care globally. What is the implication for parents? Every bereaved parent is entitled to the best possible care after stillbirth, but some do not get good care. Parents and staff made suggestions that can help to develop processes for how care is given after stillbirth. These suggestions can also inform staff training, so that every single parent is treated respectfully and participates in decision making. [ABSTRACT FROM AUTHOR]

Purpose: Diabetes is the leading cause of new cases of blindness among adults aged 20–74 years within the United States. The Innovative Network for Sight Research group (INSIGHT) designed the Diabetic Eye Screening Study (DESS) to examine the feasibility and short-term effectiveness of non-mydriatic diabetic retinopathy (DR) screening for adults with diabetes in community-based settings. Methods: Study enrollment began in December 2011 at four sites: an internal medicine clinic at a county hospital in Birmingham, Alabama; a Federally-qualified community healthcare center in Miami-Dade County, Florida; a university-affiliated outpatient pharmacy in Philadelphia, Pennsylvania; and a medical home in Winston-Salem, North Carolina. People 18 years or older with previously diagnosed diabetes were offered free DR screening using non-mydriatic retinal photography that was preceded by a brief questionnaire addressing demographic information and previous eye care use. Visual acuity was also measured for each eye. Images were evaluated at a telemedicine reading center by trained evaluators using the National Health System DR grading classification. Participants and their physicians were sent screening report results and telephoned for a follow-up survey 3 months post-screening to determine whether participants had sought follow-up comprehensive eye care and their experiences with the screening process. Results: Target enrollment at each site was a minimum of 500 persons. Three of the four sites met this enrollment goal. Conclusion: The INSIGHT/DESS is intended to establish the feasibility and short-term effectiveness of DR screening using non-mydriatic retinal photography in persons with diabetes who seek services in community-based clinic and pharmacy settings. [ABSTRACT FROM PUBLISHER]

Background: Hepatitis C virus (HCV) and/or hepatitis B virus (HBV) coinfection with human immunodeficiency virus (HIV) has a greater risk of mortality than either HCV or HBV infection alone and is frequently associated with hepatitis flares after antiretroviral therapy (ART) initiation.Methods: We performed a retrospective cohort study of 287 HIV-positive persons coinfected with HBV and/or HCV (70 had HBV coinfection only, 207 had HCV coninfection only, and 10 had HBV and HCV coinfections) who had pre-ART plasma samples evaluated for biomarkers associated with death (within 4 years) and/or hepatitis flare (within 4 months) after ART initiation. A predictive biomarker risk score was calculated.Results: Forty-eight deaths and 50 hepatitis flares occurred. Nonsurvivors were older, had more prior AIDS-defining events, and had higher pre-ART triglycerides and aspartate transaminase levels. Detectable hyaluronic acid and higher d-dimer, interleukin 6, interleukin 8, and soluble CD14 levels were associated with death in univariate models and with a composite biomarker risk score. The risk of hepatitis flares was higher with HBV coinfection only (24.3%) and with HBV and HCV coinfection (50%) than with HCV coinfection only (13.5%). Higher levels of alanine transaminase and interleukin 10 were also associated with hepatitis flares.Conclusions: Among HIV-positive patients coinfected with HBV and/or HCV who are initiating ART, biomarkers of inflammation and coagulation are associated with an increased risk of death, whereas HBV coinfection and higher pre-ART interleukin 10 levels are associated with hepatitis flares. [ABSTRACT FROM AUTHOR]

Purpose: Serious non-AIDS (SNA) diseases are important causes of morbidity and mortality in the HAART era. We describe development of standard criteria for 12 SNA events for Endpoint Review Committee (ERC) use in START, a multicenter international HIV clinical trial. Methods: SNA definitions were developed based upon the following: (1) criteria from a previous trial (SMART), (2) review of published literature, (3) an iterative consultation and review process with the ERC and other content experts, and (4) evaluation of draft SNA criteria using retrospectively collected reports in another trial (ESPRIT). Results: Final criteria are presented for acute myocardial infarction, congestive heart failure, coronary artery disease requiring drug treatment, coronary revascularization, decompensated liver disease, deep vein thrombosis, diabetes mellitus, end-stage renal disease, non-AIDS cancer, peripheral arterial disease, pulmonary embolism, and stroke. Of 563 potential SNA events reported in ESPRIT and reviewed by an ERC, 72% met 'confirmed' and 13% 'probable' criteria. Twenty-eight percent of cases initially reviewed by the ERC required follow-up discussion (adjudication) before a final decision was reached. Conclusion: HIV clinical trials that include SNA diseases as clinical outcomes should have standardized SNA definitions to optimize event reporting and validation and should have review by an experienced ERC with opportunities for adjudication. [ABSTRACT FROM AUTHOR]