Survival of South-African HIV infected patients

In sub-Saharan Africa, resource-limitation results in scarce availability of HIV prognostic tools such as CD4+ T-Lymphocyte (CD4) count and HIV viral load. To facilitate counselling and clinical decisions in this setting, widely available and inexpensive markers of prognosis are required. Chapter one gives an overview of the epidemiology and pathophysiology of HIV infection (with particular reference to sub-Saharan Africa), and its clinical manifestations. Staging systems for HIV infection and aspects of management in resource-poor environments are briefly discussed. Chapter two describes the epidemiological, pathophysiological and clinical aspects of tuberculosis (TB) in HIV infected patients, the commonest opportunistic infection in sub-Saharan Africa. It further provides HIV and TB prevalence data from the Western Cape, South Africa. In chapter three a study is presented demonstrating the usefulness of the total lymphocyte count (TLC) in combination with the World Health Organisation (WHO) clinical staging system to predict outcome in 831 HIV positive patients. A TLC of 1250/μL was found to be the equivalent of a CD4 count of 200/μL. Patients with early HIV disease (WHO stage 1&2) had low annual rates of progression to AIDS : 3-4% if the TLC was above 1250/μL, 12-14% if the TLC was below 1250/μL. Annual progression to AIDS increased to 25% and 46% in patients with clinical stage 3 and a TLC above or below 1250/μL respectively. Patients with AIDS had 30-55% one-year mortality rates depending on the TLC. Chapter four illustrates that pulmonary tuberculosis (PTB) in HIV infected patients presents with a radiographic spectrum reflecting the degree of HIV induced immune suppression. Chest radiographs and pre-treatment total lymphocyte counts provide prognostic information. Upper zone cavitatory infiltrates typical of reactivation PTB were associated with a preserved CD4 count (mean 389/μL) and predicted a 100% two-year survival. Pleural effusions were associated with a mean CD4 count of 184/μL and predicted 65% two-year survival. Patients with atypical radiographic presentation, including lower and mid-zone infiltrates, hilar and mediastinal adenopathy or interstitial patterns, had low CD4 counts (mean 105/μL) and a 36% survival at two years. Rather than classifying every patient with pleura-pulmonary tuberculosis as WHO stage 3, incorporation of the prognostic value of the chest radiograph into the clinical staging system, such that typical reactivation PTB becomes stage 2, tuberculous pleural effusion stage 3 and atypical PTB stage 4, would enhance the prognostic accuracy of HIV related tuberculosis. Chapter five demonstrates that patients with AIDS could be categorized accord ing to one of three survival patterns, relating to the type of opportunistic illness. One-year survival rates were highest for extra-pulmonary tuberculosis and herpes simplex virus infection (70% ); intermediate for oesophageal candidiasis, cryptococcal meningitis, kaposi sarcoma and pneumocystis carinii pneumonia (45%) ; and poorest for the HIV wasting syndrome, AIDS-dementia complex and performance status 4 (20%). Despite the overall poor prognosis associated with the acquired immunodeficiency syndrome, a substantial proportion of patients survive, even in the absence of anti-retroviral therapy, for a number of years. Chapter six concludes by proposing how the data presented in this thesis could be used in the clinical management of patients with HIV infection in a resource limited environment

Met de benen op de (keuken)tafel? Formeel en informeel in het sociale domein

Rondom de transities in het sociale domein is een schat aan nieuwe woorden gaan klinken. Woorden die vaak evenmin als de praktische verschuivingen die ze vergezellen eenduidig zijn. Die meerduidigheid, gecombineerd met een razendsnelle inburgering van de nieuwe woorden als een jargon van voor zonneklaar gehouden vaktermen is begrijpelijk. Je wilt niet kletsen maar werken. Maar die twee zijn in het sociaal werk niet zo makkelijk uit elkaar te houden, zeker niet in een periode van transitie waarin zowel de praktijken als de woorden veranderen. Richard de Brabander en ik (2015) schreven daar eerder over in het artikel “Leren van ambivalenties”. Enig geklets of, zoals filosofen dat vaak noemen, enige interpretatiearbeid is deel van het werk. Dat geklets is natuurlijk niet oeverloos: praktijk en interpretatie vormen elkaars oever. Alleen bezig zijn met interpretatie wordt gezwets in de ruimte, alleen bezig zijn met “de” praktijk wordt blinde dadendrang.De noodzaak interpretatiearbeid te beschouwen als deel van praktisch werken wordt ook bij regelmaat onderstreept door uitspraken van auteurs die publiceren over allerlei praktische kwesties die zich ten aanzien van transities en transitietaal voordoen. Zo schrijven Hilhorst en Van der Lans (2014) over de verschuiving in de betekenis van het concept “Eigen kracht”. Dat had aanvankelijk, zeggen zij, betrekking op het uitnodigen van intimi van de hulpvrager bij besluiten over de juiste vorm van hulp en kreeg later de betekenis van uitnodigen van die intimi om die hulp zelf uit te voeren. Een verschuiving met onder andere als concreet gevolg een toename van hulpeloze posen bij betrokkenen. In hetzelfde jaar schrijft socioloog Trommel in de hem kenmerkende robuuste stijl over de spraakverwarring rondom “de participatiesamenleving”: “Dan is er die tenenkrommende newspeak, met als dieptepunt de sociologische absurditeit van de ‘participatiesamenleving’. Een samenleving bestaat omdat mensen eraan deelnemen, zo eenvoudig is dat…” (Trommel, 2014, p. 75). Dat is niet alleen leuk gevonden, maar ook behartigenswaardig voor de praktijk van sociaal werk, waar het een belangrijk doel van beleid is om sociale uitsluiting te voorkomen en maatschappelijke betrokkenheid te vergroten. Er zijn veel andere voorbeelden te noemen van de praktisch betekenisvolle meerduidigheid van taal die rondom de transities een rol speelt. Taal-praktijk combinaties die tot uitdrukking komen in woorden als “zelfredzaamheid” (niet alleen ADL, maar wat dan wel?), “eigen verantwoordelijkheid van de burger” (om goed binnen de lijntjes te kleuren of is dat te kinderlijk?), “(verplicht) vrijwillig” (?!) en, last but not least, in het begrippenpaar “formeel & informeel”. Ik zal me hier verder op dat begrippenpaar concentreren

AIDS in Africa- survival according to AIDS-defining illness

Objective. Evaluation of prognostic significance of the type of AIDS-defining illness (ADI) and performance status in a cohort of AIDS patients.Design, setting, subjects, outcome measures. A retrospective analysis of 280 patients with AIDS, as defined by the proposed World Health Organisation (WHO) clinical staging system, who attended two Cape Town-based HIV clinics between 1984 and 1997. Patients were stratified according to the type of initial ADI. Survival associated with each opportunistic event was determined by Kaplan-Meier analysis. Cox proportional hazard analysis was used to determine relative risk for death associated with three strata of ADI.Results. Median survival associated with various initial ADls varied from less than 3 months (encephalopathy and wasting), to over 2 years (extrapulmonary tuberculosis and herpes simplex virus infection). This effect of ADI on outcome was most striking in patients with relatively preserved CD4 counts (CD4 > 50/μl). A performance status score 4 predicted 50% mortality at 1 month, irrespective of co-morbidity.Conclusion. The type of ADl is an important determinant of survival, particularly in patients with preserved CD4 counts. The stratification of patients by type of ADI and performance status may be useful in the management of patients with advanced HIV infection in resource-limited environments

Anatomic Fat Depots and Coronary Plaque Among Human Immunodeficiency Virus-Infected and Uninfected Men in the Multicenter AIDS Cohort Study.

Methods.  In a cross-sectional substudy of the Multicenter AIDS Cohort Study, noncontrast cardiac computed tomography (CT) scanning for coronary artery calcium (CAC) scoring was performed on all men, and, for men with normal renal function, coronary CT angiography (CTA) was performed. Associations between fat depots (visceral adipose tissue [VAT], abdominal subcutaneous adipose tissue [aSAT], and thigh subcutaneous adipose tissue [tSAT]) with coronary plaque presence and extent were assessed with logistic and linear regression adjusted for age, race, cardiovascular disease (CVD) risk factors, body mass index (BMI), and human immunodeficiency virus (HIV) parameters. Results.  Among HIV-infected men (n = 597) but not HIV-uninfected men (n = 343), having greater VAT was positively associated with noncalcified plaque presence (odds ratio [OR] = 1.04, P < .05), with a significant interaction (P < .05) by HIV serostatus. Human immunodeficiency virus-infected men had lower median aSAT and tSAT and greater median VAT among men with BMI <25 and 25-29.9 kg/m(2). Among HIV-infected men, VAT was positively associated with presence of coronary plaque on CTA after adjustment for CVD risk factors (OR = 1.04, P < .05), but not after additional adjustment for BMI. There was an inverse association between aSAT and extent of total plaque among HIV-infected men, but not among HIV-uninfected men. Lower tSAT was associated with greater CAC and total plaque score extent regardless of HIV serostatus. Conclusions.  The presence of greater amounts of VAT and lower SAT may contribute to increased risk for coronary artery disease among HIV-infected persons

Inflammatory Markers Associated With Subclinical Coronary Artery Disease: The Multicenter AIDS Cohort Study.

BackgroundDespite evidence for higher risk of coronary artery disease among HIV+ individuals, the underlying mechanisms are not well understood. We investigated associations of inflammatory markers with subclinical coronary artery disease in 923 participants of the Multicenter AIDS Cohort Study (575 HIV+ and 348 HIV- men) who underwent noncontrast computed tomography scans for coronary artery calcification, the majority (n=692) also undergoing coronary computed tomography angiography.Methods and resultsOutcomes included presence and extent of coronary artery calcification, plus computed tomography angiography analysis of presence, composition, and extent of coronary plaques and severity of coronary stenosis. HIV+ men had significantly higher levels of interleukin-6 (IL-6), intercellular adhesion molecule-1, C-reactive protein, and soluble-tumor necrosis factor-α receptor (sTNFαR) I and II (all P<0.01) and a higher prevalence of noncalcified plaque (63% versus 54%, P=0.02) on computed tomography angiography. Among HIV+ men, for every SD increase in log-interleukin-6 and log intercellular adhesion molecule-1, there was a 30% and 60% increase, respectively, in the prevalence of coronary stenosis ≥50% (all P<0.05). Similarly, sTNFαR I and II in HIV+ participants were associated with an increase in prevalence of coronary stenosis ≥70% (P<0.05). Higher levels of interleukin-6, sTNFαR I, and sTNFαR II were also associated with greater coronary artery calcification score in HIV+ men (P<0.01).ConclusionsHigher inflammatory marker levels are associated with greater prevalence of coronary stenosis in HIV+ men. Our findings underscore the need for further study to elucidate the relationships of inflammatory pathways with coronary artery disease in HIV+ individuals

Sex Hormone-Binding Globulin Levels Are Inversely Associated With Nonalcoholic Fatty Liver Disease in HIV-Infected and -Uninfected Men.

BackgroundNonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. Elevated sex hormone-binding globulin (SHBG) levels have been observed in the setting of HIV and may protect against some metabolic disorders. We aimed to investigate whether higher SHBG levels may protect against NAFLD in men with/without HIV.MethodsNAFLD was assessed using noncontrast computed tomography in 530 men in the Multicenter AIDS Cohort Study (MACS) who drank <3 alcoholic drinks/d and were uninfected with chronic hepatitis C or B (340HIV+, 190HIV-). Morning serum samples were tested for SHBG, total testosterone (TT), and adiponectin. Multivariable logistic regression was used to assess associations between HIV, SHBG, TT, adiponectin, and NAFLD.ResultsMedian SHBG was highest among HIV+/NAFLD- men and lowest among HIV-/NAFLD+ men. Adjusted for demographics, HIV, visceral adiposity, HOMA-IR, TT, and PNPLA3 genotype, higher SHBG was associated with lower odds of NAFLD (odds ratio [OR], 0.52 per doubling; 95% confidence interval [CI], 0.34-0.80). In separate multivariable models without SHBG, HIV (OR, 0.46; 95% CI, 0.26-0.79) and higher adiponectin (OR, 0.66 per doubling; 95% CI, 0.49-0.89) were associated with lower NAFLD odds, whereas TT was not significantly associated (OR, 0.74 per doubling; 95% CI, 0.53-1.04). Adjusting for SHBG attenuated the associations of HIV (OR, 0.61; 95% CI, 0.34-1.08) and adiponectin (OR, 0.74; 95% CI, 0.54-1.02) with NAFLD.ConclusionsSHBG levels were higher among HIV+ men, were independently associated with lower NAFLD, and could partially explain the associations of HIV and higher adiponectin with lower NAFLD in our cohort. These findings suggest that SHBG may protect against NAFLD, supporting further prospective and mechanistic studies

The “TIDE”-Algorithm for the Weaning of Patients With Cardiogenic Shock and Temporarily Mechanical Left Ventricular Support With Impella Devices. A Cardiovascular Physiology-Based Approach

Objectives: Mechanical circulatory support (MCS) is often required to stabilize therapy-refractory cardiogenic shock patients. Left ventricular (LV) unloading by mechanical ventricular support (MVS) via percutaneous devices, such as with Impella® axial pumps, alone or in combination with extracorporeal life support (ECLS, ECMELLA approach), has emerged as a potential clinical breakthrough in the field. While the weaning from MCS is essentially based on the evaluation of circulatory stability of patients, weaning from MVS holds a higher complexity, being dependent on bi-ventricular function and its adaption to load. As a result of this, weaning from MVS is mostly performed in the absence of established algorithms. MVS via Impella is applied in several cardiogenic shock etiologies, such as acute myocardial infarction (support over days) or acute fulminant myocarditis (prolonged support over weeks, PROPELLA). The time point of weaning from Impella in these cohorts of patients remains unclear. We here propose a novel cardiovascular physiology-based weaning algorithm for MVS. Methods: The proposed algorithm is based on the experience gathered at our center undergoing an Impella weaning between 2017 and 2020. Before undertaking a weaning process, patients must had been ECMO-free, afebrile, and euvolemic, with hemodynamic stability guaranteed in the absence of any inotropic support. The algorithm consists of 4 steps according to the acronym TIDE: (i) Transthoracic echocardiography under full Impella-unloading; (ii) Impella rate reduction in single 8-24 h-steps according to patients hemodynamics (blood pressure, heart rate, and ScVO2), including a daily echocardiographic assessment at minimal flow (P2); (iii) Dobutamine stress-echocardiography; (iv) Right heart catheterization at rest and during Exercise-testing via handgrip. We here present clinical and hemodynamic data (including LV conductance data) from paradigmatic weaning protocols of awake patients admitted to our intensive care unit with cardiogenic shock. We discuss the clinical consequences of the TIDE algorithm, leading to either a bridge-to-recovery, or to a bridge-to-permanent LV assist device (LVAD) and/or transplantation. With this protocol we were able to wean 74.2% of the investigated patients successfully. 25.8% showed a permanent weaning failure and became LVAD candidates. Conclusions: The proposed novel cardiovascular physiology-based weaning algorithm is based on the characterization of the extent and sustainment of LV unloading reached during hospitalization in patients with cardiogenic shock undergoing MVS with Impella in our center. Prospective studies are needed to validate the algorithm

Diagnostic Accuracy and Acceptability of the Primary Care Posttraumatic Stress Disorder Screen for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) among US Veterans

Importance: Posttraumatic stress disorder (PTSD) is a serious mental health disorder that can be effectively treated with empirically based practices. PTSD screening is essential for identifying undetected cases and providing patients with appropriate care. Objective: To determine whether the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PC-PTSD-5) is a diagnostically accurate and acceptable measure for use in Veterans Affairs (VA) primary care clinics. Design, Setting, and Participants: This cross-sectional, diagnostic accuracy study enrolled participants from May 19, 2017, to September 26, 2018. Participants were recruited from primary care clinics across 2 VA Medical Centers. Session 1 was conducted in person, and session 2 was completed within 30 days via telephone. A consecutive sample of 1594 veterans, aged 18 years or older, who were scheduled for a primary care visit was recruited. Data analysis was performed from March 2019 to August 2020. Exposures: In session 1, participants completed a battery of questionnaires. In session 2, a research assistant administered the PC-PTSD-5 to participants, and then a clinician assessor blind to PC-PTSD-5 results conducted a structured diagnostic interview for PTSD. Main Outcomes and Measures: The range of PC-PTSD-5 cut points overall and across gender was assessed, and diagnostic performance was evaluated by calculating weighted κ values. Results: In total, 495 of 1594 veterans (31%) participated, and 396 completed all measures and were included in the analyses. Participants were demographically similar to the VA primary care population (mean [SD] age, 61.4 [15.5] years; age range, 21-93 years) and were predominantly male (333 participants [84.1%]) and White (296 of 394 participants [75.1%]). The PC-PTSD-5 had high levels of diagnostic accuracy for the overall sample (area under the receiver operating characteristic curve [AUC], 0.927; 95% CI, 0.896-0.959), men (AUC, 0.932; 95% CI, 0.894-0.969), and women (AUC, 0.899, 95% CI, 0.824-0.974). A cut point of 4 ideally balanced false negatives and false positives for the overall sample and for men. However, for women, this cut point resulted in high numbers of false negatives (6 veterans [33.3%]). A cut point of 3 fit better for women, despite increasing the number of false positives. Participants rated the PC-PTSD-5 as highly acceptable. Conclusions and Relevance: The PC-PTSD-5 is an accurate and acceptable screening tool for use in VA primary care settings. Because performance parameters will change according to sample, clinicians should consider sample characteristics and screening purposes when selecting a cut point