External validation of the Dat'AIDS score: A risk score for predicting 5-year overall mortality in people living with HIV aged 60 years or older.

OBJECTIVE: To perform an external validation of the Dat'AIDS score for predicting 5-year overall mortality among people with HIV (PWH) aged 60 years or older. METHODS: This was a multi-centre prospective cohort study at all sites participating in the Swiss HIV Cohort Study (SHCS). We calculated the Dat'AIDS score in PWH aged 60 years or older at their first visit between 1 January 2015 and 1 January 2020. People living with HIV-2 and those whose Dat'AIDS score could not be calculated were excluded. Patients were followed until 1 January 2020. The primary endpoint was all-cause mortality. Vital status was collected throughout the study period. We obtained population and score descriptive statistics and assessed the score's discrimination and calibration. RESULTS: We included 2205 participants (82% male) of median [interquartile range (IQR)] age 62.0 (60.3-67.0) years, mostly with viraemia <50 copies/mL (92.7%). Median follow-up time was 15.9 years and median (IQR) CD4 cell count at enrolment was 586 (420-782) cells/µL. In all, 152 deaths were recorded during a total follow-up period of 7147 patient-years. The median (IQR) observed Dat'AIDS score was 3 (0-8). Discriminative capacities were good as the C-statistic was 0.73 (95% CI: 0.69-0.77) and consistent across all subgroups. Comparison of observed and expected survival probabilities showed good calibration. CONCLUSIONS: External validation of the Dat'AIDS score in patients aged 60 years or older showed that it could be a useful tool not only for research purposes, but also to identify older patients at a higher mortality risk and to tailor the most appropriate interventions.

Can we forecast poor outcome in herpes simplex and varicella zoster encephalitis? A narrative review.

Herpes simplex virus (HSV) and varicella zoster virus (VZV) are among the most commonly diagnosed infectious causes of sporadic encephalitis worldwide. Despite treatment, mortality and morbidity rates remain high, especially for HSV encephalitis. This review is intended to provide an overview of the existing scientific literature on this topic from the perspective of a clinician who is confronted with serious decisions about continuation or withdrawal of therapeutic interventions. We performed a literature review searching two databases and included 55 studies in the review. These studies documented or investigated specifically outcome and predictive parameters of outcome of HSV and/or VZV encephalitis. Two reviewers independently screened and reviewed full-text articles meeting the inclusion criteria. Key data were extracted and presented as a narrative summary. Both, HSV and VZV encephalitis have mortality rates between 5 and 20% and complete recovery rates range from 14 to 43% for HSV and 33 to 49% for VZV encephalitis. Prognostic factors for both VZV and HSV encephalitis are older age and comorbidity, as well as severity of disease and extent of magnetic resonance imaging (MRI) lesions on admission, and delay in treatment initiation for HSV encephalitis. Although numerous studies are available, the main limiting factors are the inconsistent patient selection and case definitions as well as the non-standardised outcome measures, which hampers the comparability of the studies. Therefore, larger and standardised observational studies applying validated case definitions and outcome measures including quality of life assessment are required to provide solid evidence to answer the research question.

Hepatitis B Virus (HBV) Replication During Tenofovir Therapy Is Frequent in Human Immunodeficiency Virus/HBV Coinfection.

In the Swiss HIV Cohort Study, 61 of 222 (27%) HIV-suppressed persons with chronic hepatitis B virus (HBV) infection had HBV replication after 2 years on tenofovir, of whom 77% were suppressed thereafter. Self-reported adherence to therapy and HBV viral load at tenofovir initiation were predictors of persistent replication.

Travel related histoplasmosis - a diagnostic challenge in a patient with tumor necrosis factor alpha (TNF-α) inhibitor therapy.

INTRODUCTION: In a non-endemic setting, disseminated histoplasmosis is a rare travel-related health problem of immunosuppressed returnees from endemic regions. METHODS: We describe the case of a 68-year-old man with rheumatoid arthritis and tumor necrosis factor alpha (TNF-α) inhibitor treatment-related immunodeficiency, who suffered from disseminated histoplasmosis after traveling to Brazil. Based on this case, we discuss challenges and pitfalls associated with the diagnosis of disseminated histoplasmosis in a non-endemic setting. RESULTS: The disease mimicked a hemophagocytic lymphohistiocytosis (HLH) like syndrome. Histoplasma capsulatum was microscopically detected in bronchoalveolar fluid and bone marrow aspirate smears, but was initially misclassified as Leishmania spp., another class of pathogens, which may cause HLH like syndromes in immunocompromised individuals. DISCUSSION: Since the clinical symptoms of histoplasmosis are nonspecific and physicians in non-endemic regions might not be familiar with this disease pattern, there is a risk of delayed diagnosis of travel related cases. Taking a thorough travel history is key in unclear cases of illness in immunocompromised patients.

Emergence of letermovir resistance in solid organ transplant recipients with ganciclovir resistant cytomegalovirus infection: A case series and review of the literature.

Ganciclovir (GCV)-resistant cytomegalovirus (CMV) infection is a common problem among solid organ transplant (SOT) recipients without prior CMV immunity (CMV D+/R-). GCV-resistant CMV represents a particular challenge for CMV management. Letermovir is a recently licensed antiviral agent for primary CMV prophylaxis in allogenic hematopoietic stem cell transplant (HSCT) recipients. Given the favorable safety profile and its oral bioavailability letermovir may be considered a valuable off-label option for secondary prophylaxis of GCV-resistant CMV in SOT recipients. Here, we describe our experience with letermovir as secondary prophylaxis for GCV-resistant CMV in two renal transplant recipients and review the literature in regard of previously published cases. Letermovir resistance emerged after a few months of secondary prophylaxis in the two renal transplant recipients. In both cases, the previously described UL56 C325Y letermovir resistance mutation was detected. In vitro studies of letermovir suggest a relatively low genetic barrier to resistance. Therefore, caution is warranted when using letermovir as secondary prophylaxis for GCV-resistant CMV infection.

Educational Level, Anticoagulation Quality, and Clinical Outcomes in Elderly Patients with Acute Venous Thromboembolism: A Prospective Cohort Study.

Whether the level of education is associated with anticoagulation quality and clinical outcomes in patients with acute venous thromboembolism (VTE) is uncertain. We thus aimed to investigate the association between educational level and anticoagulation quality and clinical outcomes in elderly patients with acute VTE. We studied 817 patients aged ≥65 years with acute VTE from a Swiss prospective multicenter cohort study (09/2009-12/2013). We defined three educational levels: 1) less than high school, 2) high school, and 3) post-secondary degree. The primary outcome was the anticoagulation quality, expressed as the percentage of time spent in the therapeutic INR range (TTR). Secondary outcomes were the time to a first recurrent VTE and major bleeding. We adjusted for potential confounders and periods of anticoagulation. Overall, 56% of patients had less than high school, 25% a high school degree, and 18% a post-secondary degree. The mean percentage of TTR was similar across educational levels (less than high school, 61%; high school, 64%; and post-secondary, 63%; P = 0.36). Within three years of follow-up, patients with less than high school, high school, and a post-secondary degree had a cumulative incidence of recurrent VTE of 14.2%, 12.9%, and 16.4%, and a cumulative incidence of major bleeding of 13.3%, 15.1%, and 15.4%, respectively. After adjustment, educational level was neither associated with anticoagulation quality nor with recurrent VTE or major bleeding. In elderly patients with VTE, we did not find an association between educational level and anticoagulation quality or clinical outcomes.

Echocardiography does not predict mortality in hemodynamically stable elderly patients with acute pulmonary embolism.

BACKGROUND: The evidence on the prognostic value of transthoracic echocardiography (TTE) in elderly, hemodynamically stable patients with Pulmonary Embolism (PE) is limited. OBJECTIVES: To evaluate the prevalence of common echocardiographic signs of right ventricular (RV) dysfunction and their prognostic impact in hemodynamically stable patients aged ≥65years with acute PE in a prospective multicenter cohort. METHODS: TTE was performed by cardiologists. We defined RV dysfunction as a RV/left ventricular ratio >0.9 or RV hypokinesis (primary definition) or the presence of ≥1 or ≥2 of 6 predefined echocardiographic signs (secondary definitions). Outcomes were overall mortality and mortality/non-fatal recurrent venous thromboembolism (VTE) at 30days, adjusting for the Pulmonary Embolism Severity Index risk score and highly sensitive troponin T values. RESULTS: Of 400 patients, 36% had RV dysfunction based on our primary definition, and 81% (≥1 sign) and 53% (≥2 signs) based on our secondary definitions, respectively. Using our primary definition, there was no association between RV dysfunction and mortality (adjusted HR 0.90, 95% CI 0.31-2.58) and mortality/non-fatal VTE (adjusted HR 1.09, 95% CI 0.40-2.98). Similarly, there was no statistically significant association between the presence of ≥1 or ≥2 echocardiographic signs (secondary definitions) and clinical outcomes. CONCLUSION: The prevalence of echocardiographic RV dysfunction varied widely depending upon the definition used. There was no association between RV dysfunction and clinical outcomes. Thus, TTE may not be suitable as a stand-alone risk assessment tool in elderly patients with acute PE. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov. Identifier: NCT00973596.

Corticosteroid treatment for community-acquired pneumonia--the STEP trial: study protocol for a randomized controlled trial.

BACKGROUND: Community-acquired pneumonia (CAP) is the third-leading infectious cause of death worldwide. The standard treatment of CAP has not changed for the past fifty years and its mortality and morbidity remain high despite adequate antimicrobial treatment. Systemic corticosteroids have anti-inflammatory effects and are therefore discussed as adjunct treatment for CAP. Available studies show controversial results, and the question about benefits and harms of adjunct corticosteroid therapy has not been conclusively resolved, particularly in the non-critical care setting. METHODS/DESIGN: This randomized multicenter study compares a treatment with 7 days of prednisone 50 mg with placebo in adult patients hospitalized with CAP independent of severity. Patients are screened and enrolled within the first 36 hours of presentation after written informed consent is obtained. The primary endpoint will be time to clinical stability, which is assessed every 12 hours during hospitalization. Secondary endpoints will be, among others, all-cause mortality within 30 and 180 days, ICU stay, duration of antibiotic treatment, disease activity scores, side effects and complications, value of adrenal function testing and prognostic hormonal and inflammatory biomarkers to predict outcome and treatment response to corticosteroids. Eight hundred included patients will provide an 85% power for the intention-to-treat analysis of the primary endpoint. DISCUSSION: This largest to date double-blind placebo-controlled multicenter trial investigates the effect of adjunct glucocorticoids in 800 patients with CAP requiring hospitalization. It aims to give conclusive answers about benefits and risks of corticosteroid treatment in CAP. The inclusion of less severe CAP patients will be expected to lead to a relatively low mortality rate and survival benefit might not be shown. However, our study has adequate power for the clinically relevant endpoint of clinical stability. Due to discontinuing glucocorticoids without tapering after seven days, we limit duration of glucocorticoid exposition, which may reduce possible side effects. TRIAL REGISTRATION: 7 September 2009 on ClinicalTrials.gov: NCT00973154.