Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic 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 Findings A 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 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 = 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. Conclusions Both 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.Peer reviewe

Disseminated Nocardia otitidiscaviarum in a patient with AIDS

A case of disseminated infection due to Nocardia otitidiscaviarum is described in a Caucasian man infected with the human immunodeficiency virus. The patient presented with no previous AIDS-defining conditions, a CD4 lymphocyte count of 206 cells/mm3 and enlarging intra-abdominal and chest wall abscesses with bilateral pulmonary infiltrates. Aggressive surgical debridement and antimicrobial therapy with trimethoprim/sulfamethoxazole and amikacin resulted in clinical cure. Long term suppressive therapy was needed to prevent relapse

Disseminated Nocardia Otitidiscaviarum in a Patient with AIDS

A case of disseminated infection due to Nocardia otitidiscaviarum is described in a Caucasian man infected with the human immunodeficiency virus. The patient presented with no previous AIDS-defining conditions, a CD4 lymphocyte count of 206 cells/mm3 and enlarging intra-abdominal and chest wall abscesses with bilateral pulmonary infiltrates. Aggressive surgical debridement and antimicrobial therapy with trimethoprim/sulfamethoxazole and amikacin resulted in clinical cure. Long term suppressive therapy was needed to prevent relapse.Peer Reviewe

Cohort profile: the Ontario HIV treatment network cohort study (OCS)

The Ontario HIV Treatment Network Cohort Study (OCS) is an observational, open dynamic cohort of people who are receiving medical care for human immunodeficiency virus (HIV) infection in Ontario, Canada. Established in the mid-1990s, the OCS has its roots in AIDS activists' demands for research that would improve the quality of life of people living with HIV while respecting their privacy. It is a collaborative and community-driven study, including a Governance Committee made up of people with HIV and other stakeholders that evaluates analysis project proposals for community relevance and ethics. From 1995 to 2010, a total of 5644 participants were enrolled and 27 720 person-years of observation were accumulated; follow-up will continue until at least 2015. In the initial years of study, the focus was on clinical data from medical chart reviews. It has since evolved into a comprehensive study that collects extensive de-identified information on clinical, laboratory and psychosocial and behavioural measures based on medical chart abstractions, interviews using a standardized questionnaire and linkage with external administrative health databases in Ontario. Interested collaborators are encouraged to submit analysis project proposals as instructed on the study website (www.ohtncohortstudy. ca)

Adequacy of mental health services for HIV-positive patients with depression: Ontario HIV Treatment Network Cohort Study

Background: Major depression can profoundly impact clinical and quality-of-life outcomes of people living with HIV, and this disease is underdiagnosed and undertreated in many HIV-positive individuals. Here, we describe the prevalence of publicly funded primary and secondary mental health service use and antidepressant use, as well as mental health care for depression in accordance with existing Canadian guidelines for HIV-positive patients with depression in Ontario, Canada. Methods: We conducted a prospective cohort study linking data from the Ontario HIV Treatment Network Cohort Study with administrative health databases in the province of Ontario, Canada. Current depression was assessed using the Center for Epidemiologic Depression Scale or the Kessler Psychological Distress Scale. Multivariable regressions were used to characterize prevalence outcomes. Results: Of 990 HIV-positive patients with depression, 493 (50%) patients used mental health services; 182 (18%) used primary services (general practitioners); 176 (18%) used secondary services (psychiatrists); and 135 (14%) used both. Antidepressants were used by 407 (39%) patients. Patients who identified as gay, lesbian, or bisexual, as having low income or educational attainment, or as non-native English speakers or immigrants to Canada were less likely to obtain care. Of 493 patients using mental health services, 250 (51%) received mental health care for depression in accordance with existing Canadian guidelines. Conclusions: Our results showed gaps in delivering publicly funded mental health services to depressed HIV-positive patients and identified unequal access to these services, particularly among vulnerable groups. More effective mental health policies and better access to mental health services are required to address HIV-positive patient needs and reduce depression's impact on their lives

Quem chegar por último é mulher do padre: as Cartas de Perdão de concubinas de padres na baixa Idade Média portuguesa Last one there's the priest's wife: the Letters of Pardon to priests concubines in lower portuguese Middle Ages

Na sociedade medieval portuguesa, a prática do concubinato clerical representou uma ameaça ao celibato e ao casamento religioso, instituições fundamentais para o projeto de ordenamento social defendido pela Igreja e pela monarquia. Nos séculos XIV e XV, as leis civis definiram o concubinato clerical como um crime. No entanto, havia a possibilidade de absolvição ou diminuição da pena por meio das Cartas de Perdão, importante instrumento jurídico para compreender as representações de gênero que mediaram o olhar da justiça, forjando a imagem das concubinas como pecadoras e criminosas.<br>In the medieval Portuguese society, the practice of clerical concubinage represented a threat to celibacy and religious marriages. These were fundamental institutions to the social ordination project defended by the Church and the monarchy. In the fourteenth and fifteenth centuries the civil laws defined clerical concubinage as crime. However, there was the possibility of acquittal or sentence reduction by means of Letters of Pardon, an important legal tool to understand the gender representations that have mediated the eye of justice, forging the image of concubines as sinners and criminals

Activating the synthesis of progerin, the mutant prelamin A in Hutchinson–Gilford progeria syndrome, with antisense oligonucleotides

Hutchinson–Gilford progeria syndrome (HGPS) is caused by point mutations that increase utilization of an alternate splice donor site in exon 11 of LMNA (the gene encoding lamin C and prelamin A). The alternate splicing reduces transcripts for wild-type prelamin A and increases transcripts for a truncated prelamin A (progerin). Here, we show that antisense oligonucleotides (ASOs) against exon 11 sequences downstream from the exon 11 splice donor site promote alternate splicing in both wild-type and HGPS fibroblasts, increasing the synthesis of progerin. Indeed, wild-type fibroblasts transfected with these ASOs exhibit progerin levels similar to (or greater than) those in fibroblasts from HGPS patients. This progerin was farnesylated, as judged by metabolic labeling studies. The synthesis of progerin in wild-type fibroblasts was accompanied by the same nuclear shape and gene-expression perturbations observed in HGPS fibroblasts. An ASO corresponding to the 5′ portion of intron 11 also promoted alternate splicing. In contrast, an ASO against exon 11 sequences 5′ to the alternate splice site reduced alternate splicing in HGPS cells and modestly lowered progerin levels. Thus, different ASOs can be used to increase or decrease ‘HGPS splicing’. ASOs represent a new and powerful tool for recreating HGPS pathophysiology in wild-type cells