Palliative Sedation in COVID-19 End-of-Life Care. Retrospective Cohort Study.

Background and Objectives: Descriptions of end-of-life in COVID-19 are limited to small cross-sectional studies. We aimed to assess end-of-life care in inpatients with COVID-19 at Alicante General University Hospital (ALC) and compare differences according to palliative and non-palliative sedation. Material and Methods: This was a retrospective cohort study in inpatients included in the ALC COVID-19 Registry (PCR-RT or antigen-confirmed cases) who died during conventional admission from 1 March to 15 December 2020. We evaluated differences among deceased cases according to administration of palliative sedation. Results: Of 747 patients evaluated, 101 died (13.5%). Sixty-eight (67.3%) died in acute medical wards, and 30 (44.1%) received palliative sedation. The median age of patients with palliative sedation was 85 years; 44% were women, and 30% of cases were nosocomial. Patients with nosocomial acquisition received more palliative sedation than those infected in the community (81.8% [9/11] vs 36.8% [21/57], p = 0.006), and patients admitted with an altered mental state received it less (20% [6/23] vs. 53.3% [24/45], p = 0.032). The median time from admission to starting palliative sedation was 8.5 days (interquartile range [IQR] 3.0-14.5). The main symptoms leading to palliative sedation were dyspnea at rest (90%), pain (60%), and delirium/agitation (36.7%). The median time from palliative sedation to death was 21.8 h (IQR 10.4-41.1). Morphine was used in all palliative sedation perfusions: the main regimen was morphine + hyoscine butyl bromide + midazolam (43.3%). Conclusions: End-of-life palliative sedation in patients with COVID-19 was initiated quite late. Clinicians should anticipate the need for palliative sedation in these patients and recognize the breathlessness, pain, and agitation/delirium that foreshadow death.

Efficacy and Safety of Switching to Dolutegravir/Lamivudine Fixed-Dose 2-Drug Regimen vs Continuing a Tenofovir Alafenamide-Based 3- or 4-Drug Regimen for Maintenance of Virologic Suppression in Adults Living With Human Immunodeficiency Virus Type 1: Phase 3, Randomized, Noninferiority TANGO Study.

BACKGROUND: The 2-drug regimen dolutegravir (DTG) + lamivudine (3TC) is indicated for treatment-naive adults with human immunodeficiency virus type 1 (HIV-1). We present efficacy and safety of switching to DTG/3TC in virologically suppressed individuals. METHODS: TANGO is an open-label, multicenter, phase 3 study that randomized adults (1:1, stratified by baseline third agent class) with HIV-1 RNA <50 copies/mL to switch to once-daily fixed-dose DTG/3TC or remain on a tenofovir alafenamide (TAF)-based regimen. The primary end point was proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48 (US Food and Drug Administration Snapshot algorithm) in the intention-to-treat-exposed population (4% noninferiority margin). RESULTS: 743 adults were enrolled; 741 received ≥1 dose of study drug (DTG/3TC, N = 369; TAF-based regimen, N = 372). At week 48, proportion of participants with HIV-1 RNA ≥50 copies/mL receiving DTG/3TC was 0.3% (1/369) vs 0.5% (2/372) with a TAF-based regimen (adjusted treatment difference [95% confidence interval], -0.3 [-1.2 to .7]), meeting noninferiority criteria. No participants receiving DTG/3TC and 1 receiving a TAF-based regimen met confirmed virologic withdrawal criteria, with no emergent resistance at failure. Drug-related grade ≥2 adverse events and withdrawals due to adverse events occurred in 17 (4.6%) and 13 (3.5%) participants with DTG/3TC and 3 (0.8%) and 2 (0.5%) with a TAF-based regimen, respectively. CONCLUSIONS: DTG/3TC was noninferior in maintaining virologic suppression vs a TAF-based regimen at week 48, with no virologic failure or emergent resistance reported with DTG/3TC, supporting it as a simplification strategy for virologically suppressed people with HIV-1. CLINICAL TRIALS REGISTRATION: NCT03446573.

Infective endocarditis in elderly and very elderly patients.

AIMS: To compare the clinical and epidemiological characteristics and the evolution of infective endocarditis in adults aged under 65 years, 65-79 years, and 80 years or older. METHODS: An observational retrospective cohort study in patients with infective endocarditis was performed in a public hospital in Spain from January 2013 to December 2017. RESULTS: Seventy-two patients were treated: 26 (36.1%) were under 65 years old, 28 (38.9%) were 65-79 years old, and 18 (25%) were aged 80 or older. Prosthetic valve endocarditis was less common in patients aged 65-79 years (3.6%) than in younger (23.1%; p = 0.047) or older (38.9%; p = 0.004) patients. In contrast, degenerative heart disease was more prevalent in the 65-79 year age group [64.3% compared to 15.4% (p < 0.001) in the youngest group, and 33.3% (p = 0.04) in the oldest]. Surgical interventions were similar in patients aged 65-79 (50%) and under 65 years (42.3%), but less common in people over 80 years (16.7%; p = 0.022). CONCLUSIONS: The characteristics of infective endocarditis are different in patients aged 65-79 years and in those over 80 years.

[Consensus statement on the clinical management of human immunodeficiency virus-associated neurocognitive disorders]. / Documento de consenso sobre el manejo clínico de los trastornos neurocognitivos asociados a la infección por el virus de la inmunodeficiencia humana (enero 2013).

OBJECTIVE: To develop a consensus document containing clinical recommendations for the management of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND). METHODS: We assembled a panel of experts appointed by GeSIDA and the Secretariat of the National AIDS Plan (PNS), including internal medicine physicians with expertise in the field of HIV, neuropsychologists, neurologists and neuroradiologists. Scientific information was reviewed to October 2012 in publications and conference papers. In support of the recommendations using two levels of evidence: the strength of the recommendation in the opinion of the experts (A, B, C) and the level of empirical evidence (I, II, III), two levels based on the criteria of the Infectious Disease Society of America, already used in previous documents GeSIDA/SPNS. RESULTS: Multiple recommendations for the clinical management of these disorders are provided, including two graphics algorithms, considering both the diagnostic and possible therapeutic strategies. CONCLUSIONS: Neurocognitive disorders associated with HIV infection is currently highly prevalent, are associated with a decreased quality of life and daily activities, and given the possibility of occurrence of an increase in the coming years, there is a need to adequately manage these disorders, from a diagnostic as well as therapeutic point of view, and always from a multidisciplinary perspective.

Isolation of Candida auris in large hospitals in the Autonomous Community of Valencia; population-based study (2013-2017).

BACKGROUND: Candida auris is an emerging multidrug-resistant and highly virulent yeast that spreads easily among patients. AIMS: To describe the characteristics of candidemia caused by C. auris in the southeast of Spain (Autonomous Community of Valencia - ACV) through a 5-year population-based study. METHODS: An analysis of all the episodes of candidemia diagnosed in the ACV, with approximately 4,500,000 inhabitants, during 2013-2017, was done. Data were obtained from the Epidemiological Surveillance Valencian Network, a network that collects all the microbiological data from the hospitals in the study region. RESULTS: Based on the records, 1.9% of the isolates recovered from the positive blood cultures (corresponding to 1789 patients) were yeasts. This implies an annual rate of 7.09 cases/100,000 inhabitants. Of the 23 yeast species isolated, Candida albicans was the most frequent (37.3%), showing a higher frequency than Candida parapsilosis (28.4%) and Candida glabrata (15.6%) (p<0.0001). It is remarkable the emergence of C. auris during 2016 and 2017, as this species became the fourth more prevalent in 2016 (9.2%), and the third in 2017 (15.7%). Fungemia was more common in hospitals with >500 beds (63.3% versus 36.7% in small hospitals) (p<0.0001), and C. auris was mostly isolated in large hospitals (8.5% versus 0.3%); its incidence was higher in autumn and among the age group of 65-84 years. CONCLUSIONS: The information about the local epidemiology of candidemia is essential in order to decide the best empirical treatment approach. This study reports the novel presence of C. auris in large hospitals. This pathogen has usually resistance to several antifungals and causes severe fungemia, so the results of this work reveal the need to monitor the presence of this species systematically.

Association of Human Papillomavirus Genotype 16 Viral Variant and Viral Load with Cervical High-grade Intraepithelial Lesions.

Human papillomavirus genotype 16 (HPV16) is by far the genotype most strongly associated with cervical cancer; viral variant and/or viral load of HPV16 could modulate this association. The objective was to determine the association between the viral variant and viral load of HPV16 and the presence of cervical high-grade lesions. This cross-sectional study included all women in whom HPV infection was found by cervical smear during routine gynecologic health checks. Women with single or multiple HPV16 infections (n = 176) were selected for viral variant and viral load analysis. Smear results were classified using the Bethesda system. HPV types were classified according to the International Agency for Research on Cancer. Odds ratios (OR) with their 95% confidence intervals (CI) were estimated by logistic regression, adjusted for age, immigrant status, and coinfection with other high-risk genotypes. No statistically significant associations were found regarding the detected viral variants. A viral load above the median (>1,367.79 copies/cell) was associated with a significant risk of high-grade epithelial lesion or carcinoma, after adjusting for age, immigrant status, coinfections, and viral variant: (adjusted OR 7.89; 95% CI: 2.75-22.68). This relationship showed a statistically significant dose-response pattern after categorizing by viral load tertiles: adjusted OR for a viral load greater than the third tertile was 17.23 (95% CI: 4.20-70.65), with adjusted linear P trend = 0.001. In patients infected with HPV16, viral load is associated with high-grade intraepithelial lesions or cervical carcinoma. This could be useful as prognostic biomarker of neoplastic progression and as screening for cervical cancer.

[Expert recommendations for the diagnosis and treatment of chronic hepatitis C infection in the prison setting]. / Recomendaciones de expertos sobre el diagnóstico y tratamiento de la hepatitis C crónica en el medio penitenciario.

The prevalence of HCV infection in Spanish prisons is very high (38.5%). The characteristics of the infected patients, particularly the high rate of HIV coinfection, makes it very likely that the morbidity and mortality produced by serious liver disease secondary to this infection will increase considerably in the coming years. A group of Spanish experts with experience in patients who are inmates has been invited to establish a series of recommendations for the diagnosis and treatment of chronic hepatitis C infection in Spanish prisons.

[Association between inflammatory markers and microbial translocation in patients with human immunodeficiency virus infection taking antiretroviral treatment]. / Asociación entre marcadores inflamatorios y traslocación bacteriana en pacientes con infección por el virus de la inmunodeficiencia humana en tratamiento antirretroviral.

BACKGROUND AND OBJECTIVE: Inflammatory biomarkers are increased in patients with human immunodeficiency virus (HIV) infection. Antiretroviral treatment (ART) improves some parameters but do not normalize them. The aim of this study is to determine those factors (including microbial translocation) associated with higher inflammation in HIV treated patients. PATIENTS AND METHODS: Transversal observational study. INCLUSION CRITERIA: HIV patients receiving ART with an HIV viral load (VL)<400 copies/mL. Selection of patients: consecutively between November 2011 and January 2012. Main variable: plasma levels of interleukin 6 (IL-6) and tumour necrosis factor α (TNF-α). Main explanatory variable: microbial translocation markers (16S ribosomal DNA and sCD14). Patients with IL-6 or TNF-α levels above percentile 75 (group 1) were compared with the rest of patients (group 2). Odds ratio (OR) were determined. RESULTS: Eighty-one patients were included (73% male, median age 45 years, 48% stage C). Twenty-six percent had chronic hepatitis C. Median CD4 cell was 493/mm(3) and 30% had detectable HIV VL. 16S ribosomal DNA was detected in 21% of patients. Factors associated with the higher levels of inflammatory markers were 16S ribosomal DNA (OR 77, P<.0001), sCD14 levels (P<.0001) and history of cardiovascular disease (OR 15, P<.01). In multivariate analysis, associations remained for 16S ribosomal DNA (OR 62, P<.0001) and previous cardiovascular disease (OR 25, P<.01). CONCLUSIONS: In patients with HIV infection receiving treatment, the higher levels of inflammatory markers are associated with microbial translocation and past cardiovascular events.

[Expert recommendations for the diagnosis and treatment of chronic hepatitis C infection in the prison setting]. / Recomendaciones de expertos sobre el diagnóstico y tratamiento de la hepatitis C crónica en el medio penitenciario.

The prevalence of HCV infection in Spanish prisons is very high (38.5%). The characteristics of the infected patients, particularly the high rate of HIV coinfection, makes it very likely that the morbidity and mortality produced by serious liver disease secondary to this infection will increase considerably in the coming years. A group of Spanish experts with experience in patients who are inmates has been invited to establish a series of recommendations for the diagnosis and treatment of chronic hepatitis C infection in Spanish prisons.