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INTRODUCTION: Overweight and obesity are linked to increased hospitalization and mortality in COVID-19 patients. This study aimed to characterize induced immune responses and deep immune cell profiles stratified by BMI in hospitalized COVID-19 patients. METHODS AND RESULTS: This observational multicenter cohort pilot study included 122 adult patients with PCR-confirmed COVID-19 in Denmark, stratified by BMI (normal weight, overweight, obese). Inflammation was assessed using TruCulture® and immune cell profiles by flow cytometry with a customized antibody panel (DuraClone®). Patients with obesity had a more pro-inflammatory phenotype with increased TNF-α, IL-8, IL-17, and IL-10 levels post-T cell stimulation, and altered B cell profiles. Patients with obesity showed higher concentrations of naïve, transitional, and non-isotype switched memory B cells, and plasmablasts compared to normal weight patients and healthy controls. CONCLUSIONS: Obesity in hospitalized COVID-19 patients may correlate with elevated pro-inflammatory cytokines, anti-inflammatory IL-10, and increased B cell subset activation, highlighting the need for further studies.
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OBJECTIVES: We aimed to assess the extent of integration of non-communicable disease (NCD) assessment and management in HIV clinics across Europe. METHODS: A structured electronic questionnaire with 41 multiple-choice and rating-scale questions assessing NCD assessment and management was sent to 88 HIV clinics across the WHO European Region during March-May 2023. One response per clinic was collected. RESULTS: In all, 51 clinics from 34 countries with >100 000 people with HIV under regular follow-up responded. Thirty-seven clinics (72.6%) reported shared NCD care responsibility with the general practitioner. Systematic assessment for NCDs and integration of NCD management were common overall [median agreement 80%, interquartile range (IQR): 55-95%; and 70%, IQR: 50-88%, respectively] but were lowest in central eastern and eastern Europe. Chronic kidney disease (median agreement 96%, IQR: 85-100%) and metabolic disorders (90%, IQR: 75-100%) were regularly assessed, while mental health (72%, IQR: 63-85%) and pulmonary diseases (52%, IQR: 40-75%) were less systematically assessed. Some essential diagnostic tests such as glycated haemoglobin (HbA1c) for diabetes (n = 38/51, 74.5%), proteinuria for kidney disease (n = 30/51, 58.8%) and spirometry for lung disease (n = 11/51, 21.6%) were only employed by a proportion of clinics. The most frequent barriers for integrating NCD care were the lack of healthcare workers (n = 17/51, 33.3%) and lack of time during outpatient visits (n = 12/51, 23.5%). CONCLUSION: Most HIV clinics in Europe systematically assess and manage NCDs. People with HIV appear to be screened more frequently than the general population at the same age. There are, however, larger gaps among eastern European clinics in general and for clinics in all regions related to mental health, pulmonary diseases and the employment of some essential diagnostic tests.
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Infecciones por VIH , Enfermedades no Transmisibles , Humanos , Enfermedades no Transmisibles/terapia , Enfermedades no Transmisibles/epidemiología , Infecciones por VIH/diagnóstico , Infecciones por VIH/terapia , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Europa (Continente) , Encuestas y Cuestionarios , Organización Mundial de la Salud , Femenino , Masculino , Adulto , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiologíaRESUMEN
OBJECTIVES: In some eastern European countries, serious challenges exist to meet the HIV-, tuberculosis (TB)- and hepatitis-related target of the United Nations Sustainable Development Goals. Some of the highest incidence rates for HIV and the highest proportion of multi-drug-resistant (MDR) tuberculosis worldwide are found in the region. The purpose of this article is to review the challenges and important next steps to improve healthcare for people living with TB, HIV and hepatitis C (HCV) in eastern Europe. METHODS: References for this narrative review were identified through systematic searches of PubMed using pre-idientified key word for articles published in English from January 2000 to August 2020. After screening of titles and abstracts 37 articles were identified as relevant for this review. Thirty-eight further articles and sources were identified through searches in the authors' personal files and in Google Scholar. RESULTS: Up to 50% of HIV/MDR-TB-coinfected individuals in the region die within 2 years of treatment initiation. Antiretroviral therapy (ART) coverage for people living with HIV (PLHIV) and the proportion virological suppressed are far below the UNAIDS 90% targets. In theory, access to various diagnostic tests and treatment of drug-resistant TB exists, but real-life data point towards inadequate testing and treatment. New treatments could provide elimination of viral HCV in high-risk populations but few countries have national programmes. CONCLUSION: Some eastern European countries face serious challenges to achieve the sustainable development goal-related target of 3.3 by 2030, among others, to end the epidemics of AIDS and tuberculosis. Better integration of healthcare systems, standardization of health care, unrestricted substitution therapy for all people who inject drugs, widespread access to drug susceptibility testing, affordable medicines and a sufficiently sized, well-trained health workforce could address some of those challenges.
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Infecciones por VIH , Hepatitis C , Mycobacterium tuberculosis , Tuberculosis , Atención a la Salud , Europa Oriental/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Humanos , Pruebas de Sensibilidad Microbiana , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiologíaRESUMEN
BACKGROUND: The European AIDS Clinical Society (EACS) Guidelines were revised in 2021 for the 17th time with updates on all aspects of HIV care. KEY POINTS OF THE GUIDELINES UPDATE: Version 11.0 of the Guidelines recommend six first-line treatment options for antiretroviral treatment (ART)-naïve adults: tenofovir-based backbone plus an unboosted integrase inhibitor or plus doravirine; abacavir/lamivudine plus dolutegravir; or dual therapy with lamivudine or emtricitabine plus dolutegravir. Recommendations on preferred and alternative first-line combinations from birth to adolescence were included in the new paediatric section made with Penta. Long-acting cabotegravir plus rilpivirine was included as a switch option and, along with fostemsavir, was added to all drug-drug interaction (DDI) tables. Four new DDI tables for anti-tuberculosis drugs, anxiolytics, hormone replacement therapy and COVID-19 therapies were introduced, as well as guidance on screening and management of anxiety disorders, transgender health, sexual health for women and menopause. The sections on frailty, obesity and cancer were expanded, and recommendations for the management of people with diabetes and cardiovascular disease risk were revised extensively. Treatment of recently acquired hepatitis C is recommended with ongoing risk behaviour to reduce transmission. Bulevirtide was included as a treatment option for the hepatitis Delta virus. Drug-resistant tuberculosis guidance was adjusted in accordance with the 2020 World Health Organization recommendations. Finally, there is new guidance on COVID-19 management with a focus on continuance of HIV care. CONCLUSIONS: In 2021, the EACS Guidelines were updated extensively and broadened to include new sections. The recommendations are available as a free app, in interactive web format and as an online pdf.
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Síndrome de Inmunodeficiencia Adquirida , Fármacos Anti-VIH , Tratamiento Farmacológico de COVID-19 , Infecciones por VIH , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adolescente , Adulto , Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/uso terapéutico , Niño , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Humanos , Lamivudine/uso terapéutico , LipopéptidosRESUMEN
BACKGROUND: There are limited data on outcomes of moderate to severe coronavirus disease 2019 (COVID-19) among patients treated with remdesivir and dexamethasone in a real-world setting. We sought to compare the effectiveness of standard of care (SOC) alone versus SOC plus remdesivir and dexamethasone. METHODS: Two population-based nationwide cohorts of individuals hospitalized with COVID-19 during February through December 2020 were studied. Death within 30 days and need of mechanical ventilation (MV) were compared by inverse probability of treatment weighted (ITPW) logistic regression analysis and shown as odds ratio (OR) with 95% confidence interval (CI). RESULTS: The 30-days mortality rate of 1694 individuals treated with remdesivir and dexamethasone in addition to SOC was 12.6% compared to 19.7% for 1053 individuals receiving SOC alone. This corresponded to a weighted OR of 30-day mortality of 0.47 (95% CI: .38-.57) for patients treated with remdesivir and dexamethasone compared to patients receiving SOC alone. Similarly, progression to MV was reduced (OR 0.36; 95% CI: .29-.46). CONCLUSIONS: Treatment of moderate to severe COVID-19 during June through December that included remdesivir and dexamethasone was associated with reduced 30-day mortality and need of MV compared to treatment in February through May.
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Tratamiento Farmacológico de COVID-19 , Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/uso terapéutico , Estudios de Cohortes , Dexametasona/uso terapéutico , Humanos , Estudios Retrospectivos , SARS-CoV-2RESUMEN
BACKGROUND: Early diagnosis of tuberculosis (TB) is important to reduce transmission, morbidity and mortality in people living with HIV (PLWH). METHODS: PLWH with a diagnosis of TB were enrolled from HIV and TB clinics in Eastern Europe and followed until 24 months. Delayed diagnosis was defined as duration of TB symptoms (cough, weight-loss or fever) for ≥ 1 month before TB diagnosis. Risk factors for delayed TB diagnosis were assessed using multivariable logistic regression. The effect of delayed diagnosis on mortality was assessed using Kaplan-Meier estimates and Cox models. FINDINGS: 480/740 patients (64.9%; 95% CI 61.3-68.3%) experienced a delayed diagnosis. Age ≥ 50 years (vs. < 50 years, aOR = 2.51; 1.18-5.32; p = 0.016), injecting drug use (IDU) (vs. non-IDU aOR = 1.66; 1.21-2.29; p = 0.002), being ART naïve (aOR = 1.77; 1.24-2.54; p = 0.002), disseminated TB (vs. pulmonary TB, aOR = 1.56, 1.10-2.19, p = 0.012), and presenting with weight loss (vs. no weight loss, aOR = 1.63; 1.18-2.24; p = 0.003) were associated with delayed diagnosis. PLWH with a delayed diagnosis were at 36% increased risk of death (hazard ratio = 1.36; 1.04-1.77; p = 0.023, adjusted hazard ratio 1.27; 0.95-1.70; p = 0.103). CONCLUSION: Nearly two thirds of PLWH with TB in Eastern Europe had a delayed TB diagnosis, in particular those of older age, people who inject drugs, ART naïve, with disseminated disease, and presenting with weight loss. Patients with delayed TB diagnosis were subsequently at higher risk of death in unadjusted analysis. There is a need for optimisation of the current TB diagnostic cascade and HIV care in PLWH in Eastern Europe.
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Infecciones por VIH , Tuberculosis , Anciano , Diagnóstico Tardío , Europa Oriental/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Tuberculosis/diagnóstico , Tuberculosis/epidemiologíaRESUMEN
BACKGROUND: Necrotizing fasciitis is a deep infection of the fascia and subcutaneous tissue with a high mortality rate. Meningitis is an infection of the membranes surrounding the brain with a likewise high mortality rate. Streptococcus pneumoniae is the most frequent cause of bacterial meningitis and it is an extremely rare cause of necrotizing fasciitis. Different subcapsular serotypes of S. pneumoniae are known to have diverse virulence. The serotype 9 N is associated with a high risk of death. CASE PRESENTATION: We report a case of a previously healthy 68-year-old female who presented at our clinic with complaints of pain in her left calf since having experienced a very painful leg cramp 3 weeks prior. Within a few hours after admission, she developed fever, neck stiffness and an altered mental state. Concurrently, the pain in her leg worsened. Upon further examination it was found that she suffered from both meningitis and necrotizing fasciitis due to S. pneumoniae, serotype 9 N. The patient survived and avoided leg amputation. CONCLUSIONS: The patient suffered from two very lethal infections simultaneously. Both of them were caused by S. pneumoniae. We believe that her favorable outcome was, a result of prompt surgical intervention and appropriate antibiotic treatment. Our case underlines the importance of continuous reevaluation of the symptoms and clinical findings in patients with unclear causes of severe illness, especially if the patient's condition changes.
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Fascitis Necrotizante/diagnóstico , Meningitis/diagnóstico , Streptococcus pneumoniae/genética , Anciano , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , ADN Bacteriano/metabolismo , Fascitis Necrotizante/microbiología , Fascitis Necrotizante/terapia , Femenino , Humanos , Meningitis/tratamiento farmacológico , Meningitis/microbiología , Serogrupo , Trasplante de Piel , Streptococcus pneumoniae/aislamiento & purificaciónRESUMEN
BACKGROUND: Efavirenz-based antiretroviral therapy (ART) regimens are preferred for treatment of adult HIV-positive patients co-infected with tuberculosis (HIV/TB). Few studies have compared outcomes among HIV/TB patients treated with efavirenz or non-efavirenz containing regimens. METHODS: HIV-positive patients aged ≥16 years with a diagnosis of tuberculosis recruited to the TB:HIV study between Jan 1, 2011, and Dec 31, 2013 in 19 countries in Eastern Europe (EE), Western Europe (WE), and Latin America (LA) who received ART concomitantly with TB treatment were included. Patients either received efavirenz-containing ART starting between 15 days prior to, during, or within 90 days after starting tuberculosis treatment, (efavirenz group), or other ART regimens (non-efavirenz group). Patients who started ART more than 90 days after initiation of TB treatment, or who experienced ART interruption of more than 15 days during TB treatment were excluded. We describe rates and factors associated with death, virological suppression, and loss to follow up at 12 months using univariate, multivariate Cox, and marginal structural models to compare the two groups of patients. RESULTS: Of 965 patients (647 receiving efavirenz-containing ART, and 318 a non-efavirenz regimen) 50% were from EE, 28% from WE, and 22% from LA. Among those not receiving efavirenz-containing ART, regimens mainly contained a ritonavir-boosted protease inhibitor (57%), or raltegravir (22%). At 12 months 1.4% of patients in WE had died, compared to 20% in EE: rates of virological suppression ranged from 21% in EE to 61% in WE. After adjusting for potential confounders, rates of death (adjusted Hazard Ratio; aHR, 95%CI: 1.13, 0.72-1.78), virological suppression (aHR, 95%CI: 0.97, 0.76-1.22), and loss to follow up (aHR, 95%CI: 1.17, 0.81-1.67), were similar in patients treated with efavirenz and non-efavirenz containing ART regimens. CONCLUSION: In this large, prospective cohort, the response to ART varied significantly across geographical regions, whereas the ART regimen (efavirenz or non-efavirenz containing) did not impact on the proportion of patients who were virologically-suppressed, lost to follow up or dead at 12 months.
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Antirretrovirales/uso terapéutico , Antituberculosos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Tuberculosis/tratamiento farmacológico , Adulto , Alquinos , Benzoxazinas/uso terapéutico , Ciclopropanos , Europa (Continente) , Europa Oriental , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/mortalidad , Humanos , América Latina , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento , Tuberculosis/complicacionesRESUMEN
Mortality of HIV/tuberculosis (TB) patients in Eastern Europe is high. Little is known about their causes of death. This study aimed to assess and compare mortality rates and cause of death in HIV/TB patients across Eastern Europe and Western Europe and Argentina (WEA) in an international cohort study. Mortality rates and causes of death were analysed by time from TB diagnosis (<3 months, 3-12 months or >12 months) in 1078 consecutive HIV/TB patients. Factors associated with TB-related death were examined in multivariate Poisson regression analysis. 347 patients died during 2625 person-years of follow-up. Mortality in Eastern Europe was three- to ninefold higher than in WEA. TB was the main cause of death in Eastern Europe in 80%, 66% and 61% of patients who died <3 months, 3-12 months or >12 months after TB diagnosis, compared to 50%, 0% and 15% in the same time periods in WEA (p<0.0001). In multivariate analysis, follow-up in WEA (incidence rate ratio (IRR) 0.12, 95% CI 0.04-0.35), standard TB-treatment (IRR 0.45, 95% CI 0.20-0.99) and antiretroviral therapy (IRR 0.32, 95% CI 0.14-0.77) were associated with reduced risk of TB-related death. Persistently higher mortality rates were observed in HIV/TB patients in Eastern Europe, and TB was the dominant cause of death at any time during follow-up. This has important implications for HIV/TB programmes aiming to optimise the management of HIV/TB patients and limit TB-associated mortality in this region.
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Coinfección/mortalidad , Infecciones por VIH/mortalidad , Tuberculosis/mortalidad , Adulto , Fármacos Anti-VIH/uso terapéutico , Antituberculosos/uso terapéutico , Argentina , Causas de Muerte , Estudios de Cohortes , Europa (Continente) , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Análisis Multivariante , Tuberculosis/complicaciones , Tuberculosis/tratamiento farmacológicoRESUMEN
Background: All-cause and AIDS-mortality in Europe has been decreasing between 1996 and 2020. However, regional differences as well as their drivers remain unclear. This study investigates mortality differences and their drivers, including usage of and response to antiretroviral therapy (ART) and active tuberculosis (TB), among people with HIV across Europe. Methods: People with HIV enrolled in EuroSIDA were followed from 2001 through 2020. Immunologic-virologic status (IVS) was categorized as poor (CD4-cell count ≤350 cells/mm3 and viral load (VL) > 200 copies/ml), good (CD4 ≥ 500 and VL < 200), or intermediate (remaining combinations). Participants missing either CD4-cell count or VL were categorized as unknown. Regional differences in mortality were analyzed using multivariable Poisson regression with interaction analyses between regions of Europe and IVS, ART, or TB status. Findings: 20,364 people with HIV were included: 13,715/20,346 (67.3%) from Western, 3020/20,364 (14.8%) from Central Eastern, and 3629/20,364 (17.8%) from Eastern Europe. At enrolment, median age was 40 years (inter-quartile range (IQR): 33-48), median CD4-cell count 449 cells/mm3 (IQR: 291-638), and most were male 14,993/20,346 (73.3%). A total of 2639 died during 192,591 person-years of follow-up (crude mortality rate 13.7/1000 person-years, 95% CI: 13.2-14.2), 519/2639 (19.7%) from AIDS (2.7/1000 person-years, 2.5-2.9). All-cause and AIDS-mortality rates decreased over time but remained higher in Eastern Europe after adjusting for confounders. Being off ART (aIRR 2.42; 95% CI 2.14-2.74), poor IVS (aIRR 4.2; 95% CI 3.39-5.20) and prior TB (aIRR 3.33; 95% CI 2.75-4.03) were associated with higher all-cause mortality. For all-cause mortality the effect of ART (test for interaction: p < 0.001) and IVS (p = 0.02), but not TB (p = 0.5) varied across regions. Interpretation: Overall mortality and AIDS-mortality rates decreased over time, but remained higher in Eastern Europe. A poor IVS, being off ART and prior active TB were related to higher mortality. Eastern Europe had the highest proportion of people with poor or unknown IVS, emphasizing the continued need to improve HIV care with a focus on early diagnosis, ART initiation, and adherence. Funding: EuroSIDA has received funding from ViiV Healthcare LLC, Janssen Scientific Affairs, Janssen R&D, Bristol-Myers Squibb Company, Merck Sharp & Dohme Corp, Gilead Sciences and the European Union's Seventh Framework Programme for research, technological development and demonstration under EuroCoord grant agreement nË 260694. The study is also supported by a grant from the Danish National Research Foundation and by the International Cohort Consortium of Infectious Disease (RESPOND).
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OBJECTIVES: Tuberculosis (TB) risk after initiation of antiretroviral treatment (ART) is not well described in a European setting, with an average TB incidence of 25/105 in the background population. METHODS: We included all adult persons with HIV starting ART in the RESPOND cohort between 2012 and 2020. TB incidence rates (IR) were assessed for consecutive time intervals post-ART initiation. Risk factors for TB within 6 months from ART initiation were evaluated using Poisson regression models. RESULTS: Among 8441 persons with HIV, who started ART, 66 developed TB during 34,239 person-years of follow-up [PYFU], corresponding to 1.87/1000 PYFU (95% confidence interval [CI]: 1.47-2.37). TB IR was highest in the first 3 months after ART initiation (14.41/1000 PY (95%CI 10.08-20.61]) and declined at 3-6, 6-12, and >12 months post-ART initiation (5.89 [95%CI 3.35-10.37], 2.54 [95%CI 1.36-4.73] and 0.51 [95%CI 0.30-0.86]), respectively. Independent risk factors for TB within the first 6 months after ART initiation included follow-up in Northern or Eastern Europe region, African origin, baseline CD4 count <200 cells/mm3, HIV RNA >100,000 copies/mL, injecting drug use and heterosexual transmission. CONCLUSIONS: TB IR was highest in the first 3 months post-ART initiation and was associated with baseline risk factors, highlighting the importance of thorough TB risk assessment at ART initiation.
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Patients with long-term health sequelae of COVID-19 (post-COVID-19 condition) experience both physical and cognitive manifestations. However, there is still uncertainty about the prevalence of physical impairment in these patients and whether there is a link between physical and cognitive function. The aim was to assess the prevalence of physical impairment and investigate the association with cognition in patients assessed in a post-COVID-19 clinic. In this cross-sectional study, patients referred to an outpatient clinic ≥ 3 months after acute infection underwent screening of their physical and cognitive function as part of a comprehensive multidisciplinary assessment. Physical function was assessed with the 6-Minute Walk Test, the 30 s Sit-to-Stand Test and by measuring handgrip strength. Cognitive function was assessed with the Screen for Cognitive Impairment in Psychiatry and the Trail Making Test-Part B. Physical impairment was tested by comparing the patients' performance to normative and expected values. Association with cognition was investigated using correlation analyses and the possible explanatory variables regarding physical function were assessed using regression analyses. In total, we included 292 patients, the mean age was 52 (±15) years, 56% were women and 50% had been hospitalised during an acute COVID-19 infection. The prevalence of physical impairment ranged from 23% in functional exercise capacity to 59% in lower extremity muscle strength and function. There was no greater risk of physical impairment in previously hospitalised compared with the non-hospitalised patients. There was a weak to moderate association between physical and cognitive function. The cognitive test scores had statistically significant prediction value for all three outcomes of physical function. In conclusion, physical impairments were prevalent amongst patients assessed for post-COVID-19 condition regardless of their hospitalisation status and these were associated with more cognitive dysfunction.
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COVID-19 , Disfunción Cognitiva , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Transversales , Fuerza de la Mano/fisiología , COVID-19/epidemiología , Cognición/fisiología , Disfunción Cognitiva/psicologíaRESUMEN
BACKGROUND: Eastern Europe has a high burden of tuberculosis (TB)/HIV coinfection with high mortality shortly after TB diagnosis. This study assesses TB recurrence, mortality rates and causes of death among TB/HIV patients from Eastern Europe up to 11âyears after TB diagnosis. METHODS: A longitudinal cohort study of TB/HIV patients enrolled between 2011 and 2013 (at TB diagnosis) and followed-up until end of 2021. A competing risk regression was employed to assess rates of TB recurrence, with death as competing event. Kaplan-Meier estimates and a multivariable Cox-regression were used to assess long-term mortality and corresponding risk factors. The Coding Causes of Death in HIV (CoDe) methodology was used for adjudication of causes of death. RESULTS: Three hundred and seventy-five TB/HIV patients were included. Fifty-three (14.1%) were later diagnosed with recurrent TB [incidence rate 3.1/100 person-years of follow-up (PYFU), 95% confidence interval (CI) 2.4-4.0] during a total follow-up time of 1713 PYFU. Twenty-three of 33 patients with data on drug-resistance (69.7%) had multidrug-resistant (MDR)-TB. More than half with recurrent TB ( n â=â30/53, 56.6%) died. Overall, 215 (57.3%) died during the follow-up period, corresponding to a mortality rate of 11.4/100 PYFU (95% CI 10.0-13.1). Almost half of those (48.8%) died of TB. The proportion of all TB-related deaths was highest in the first 6 ( n â=â49/71; 69%; P â<â0.0001) and 6-24 ( n â=â33/58; 56.9%; P â<â0.0001) months of follow-up, compared deaths beyond 24âmonths ( n â=â23/85; 26.7%). CONCLUSION: TB recurrence and TB-related mortality rates in PWH in Eastern Europe are still concerningly high and continue to be a clinical and public health challenge.
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Coinfección , Infecciones por VIH , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por VIH/tratamiento farmacológico , Estudios Longitudinales , Tuberculosis/complicaciones , Tuberculosis/epidemiología , Tuberculosis/tratamiento farmacológico , Europa Oriental/epidemiología , Factores de Riesgo , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Coinfección/tratamiento farmacológico , Antituberculosos/uso terapéutico , Europa (Continente)/epidemiologíaRESUMEN
BACKGROUND: The combined effectiveness of remdesivir and dexamethasone in subgroups of hospitalised patients with COVID-19 is poorly investigated. METHODS: In this nationwide retrospective cohort study, we included 3826 patients with COVID-19 hospitalised between February 2020 and April 2021. The primary outcomes were use of invasive mechanical ventilation and 30-day mortality, comparing a cohort treated with remdesivir and dexamethasone with a previous cohort treated without remdesivir and dexamethasone. We used inverse probability of treatment weighting logistic regression to assess associations with progression to invasive mechanical ventilation and 30-day mortality between the two cohorts. The analyses were conducted overall and by subgroups based on patient characteristics. RESULTS: Odds ratio for progression to invasive mechanical ventilation and 30-day mortality in individuals treated with remdesivir and dexamethasone compared to treatment with standard of care alone was 0.46 (95% confidence interval, 0.37-0.57) and 0.47 (95% confidence interval, 0.39-0.56), respectively. The reduced risk of mortality was observed in elderly patients, overweight patients and in patients requiring supplemental oxygen at admission, regardless of sex, comorbidities and symptom duration. CONCLUSIONS: Patients treated with remdesivir and dexamethasone had significantly improved outcomes compared to patients treated with standard of care alone. These effects were observed in most patient subgroups.
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COVID-19 , Humanos , Anciano , SARS-CoV-2 , Estudios Retrospectivos , Tratamiento Farmacológico de COVID-19 , Antivirales/uso terapéutico , Dexametasona/uso terapéuticoRESUMEN
[This corrects the article DOI: 10.1038/s43856-022-00178-5.].
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BACKGROUND: State-of-the-art care involving the utilisation of multiple health care interventions is the basis for an optimal long-term clinical prognosis for HIV-patients. We evaluated health care for HIV patients based on four key indicators. METHODS: Four indicators of health care were assessed: Compliance with current guidelines on initiation of: 1) combination antiretroviral therapy (cART); 2) chemoprophylaxis; 3) frequency of laboratory monitoring; and 4) virological response to cART (proportion of patients with HIV-RNA < 500copies/ml for >90% of time on cART). RESULTS: 7097 EuroSIDA patients were included from Northern (n = 923), Southern (n = 1059), West Central (n = 1290) East Central (n = 1366), Eastern (n = 1964) Europe, and Argentina (n = 495). Patients in Eastern Europe with a CD4 < 200cells/mm(3) were less likely to initiate cART and Pneumocystis jiroveci-chemoprophylaxis compared to patients from all other regions, and less frequently had a laboratory assessment of their disease status. The proportion of patients with virological response was highest in Northern, 89% vs. 84%, 78%, 78%, 61%, 55% in West Central, Southern, East Central Europe, Argentina and Eastern Europe, respectively (p < 0.0001). Compared to Northern, patients from other regions had significantly lower odds of virological response; the difference was most pronounced for Eastern Europe and Argentina (adjusted OR 0.16 [95%CI 0.11-0.23, p < 0.0001]; 0.20[0.14-0.28, p < 0.0001] respectively). CONCLUSIONS: This assessment of HIV health care utilization revealed pronounced regional differences in adherence to guidelines and can help to identify gaps and direct target interventions. It may serve as a tool for the assessment and benchmarking of the clinical management of HIV patients in any setting worldwide.
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Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Investigación sobre Servicios de Salud , Atención al Paciente/métodos , Adulto , Argentina/epidemiología , Benchmarking , Quimioprevención/métodos , Monitoreo de Drogas/métodos , Europa (Continente)/epidemiología , Femenino , Adhesión a Directriz/estadística & datos numéricos , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Carga ViralRESUMEN
BACKGROUND: Common long-term sequelae after COVID-19 include fatigue and cognitive impairment. Although symptoms interfere with daily living, the underlying pathology is largely unknown. Previous studies report relative hypometabolism in frontal, limbic and cerebellar regions suggesting focal brain involvement. We aimed to determine whether absolute hypometabolism was present and correlated to same day standardized neurocognitive testing. METHODS: Fourteen patients included from a long COVID clinic had cognitive testing and quantitative dynamic [18F]FDG PET of the brain on the same day to correlate cognitive function to metabolic glucose rate. RESULTS: We found no hypometabolism in frontal, limbic and cerebellar regions in cognitively impaired relative to cognitive intact patients. In contrast, the cognitive impaired patients showed higher cerebellar metabolism (p = 0.03), which correlated with more severe deficits in working memory and executive function (p = 0.03). CONCLUSIONS: Hypermetabolism in the cerebellum may reflect inefficient brain processing and play a role in cognitive impairments after COVID-19.
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The development of vaccine candidates for COVID-19 has been rapid, and those that are currently approved display high efficacy against the original circulating strains. However, recently, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged with increased transmission rates and less susceptibility to vaccine induced immunity. A greater understanding of protection mechanisms, including antibody longevity and cross-reactivity towards the variants of concern (VoCs), is needed. In this study, samples collected in Denmark early in the pandemic from paucisymptomatic subjects (n = 165) and symptomatic subjects (n = 57) infected with SARS-CoV-2 were used to assess IgG binding and inhibition in the form of angiotensin-converting enzyme 2 receptor (ACE2) competition against the wild-type and four SARS-CoV-2 VoCs (Alpha, Beta, Gamma, and Omicron). Antibodies induced early in the pandemic via natural infection were cross-reactive and inhibited ACE2 binding of the VoC, with reduced inhibition observed for the Omicron variant. When examined longitudinally, sustained cross-reactive inhibitory responses were found to exist in naturally infected paucisymptomatic subjects. After vaccination, receptor binding domain (RBD)-specific IgG binding increased by at least 3.5-fold and inhibition of ACE2 increased by at least 2-fold. When vaccination regimens were compared (two doses of Pfizer-BioNTech BNT162b2 (n = 50), or one dose of Oxford-AstraZeneca ChAdOx1 nCoV-19 followed by Pfizer-BioNTech BNT162b2 (ChAd/BNT) (n = 15)), higher levels of IgG binding and inhibition were associated with mix and match (ChAd/BNT) prime-boosting and time since vaccination. These results are particularly relevant for countries where vaccination levels are low.
Asunto(s)
COVID-19 , Pandemias , Enzima Convertidora de Angiotensina 2 , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/epidemiología , COVID-19/prevención & control , ChAdOx1 nCoV-19 , Humanos , Inmunoglobulina G , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , VacunaciónRESUMEN
A large proportion of patients exhibit persistently reduced pulmonary diffusion capacity after COVID-19. It is unknown whether this is due to a post-COVID restrictive lung disease and/or pulmonary vascular disease. The aim of the current study was to investigate the association between initial COVID-19 severity and haemoglobin-corrected diffusion capacity to carbon monoxide (DLco) reduction at follow-up. Furthermore, to analyse if DLco reduction could be linked to pulmonary fibrosis (PF) and/or thromboembolic disease within the first months after the illness, a total of 67 patients diagnosed with COVID-19 from March to December 2020 were included across three severity groups: 12 not admitted to hospital (Group I), 40 admitted to hospital without intensive care unit (ICU) admission (Group II), and 15 admitted to hospital with ICU admission (Group III). At first follow-up, 5 months post SARS-CoV-2 positive testing/4 months after discharge, lung function testing, including DLco, high-resolution CT chest scan (HRCT) and ventilation-perfusion (VQ) single photon emission computed tomography (SPECT)/CT were conducted. DLco was reduced in 42% of the patients; the prevalence and extent depended on the clinical severity group and was typically observed as part of a restrictive pattern with reduced total lung capacity. Reduced DLco was associated with the extent of ground-glass opacification and signs of PF on HRCT, but not with mismatched perfusion defects on VQ SPECT/CT. The severity-dependent decline in DLco observed early after COVID-19 appears to be caused by restrictive and not pulmonary vascular disease.