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Traditional models to predict intensive care outcomes do not perform well in COVID-19. We undertook a comprehensive study of factors affecting mortality and functional outcome after severe COVID-19.In this prospective multicentre cohort study, we enrolled laboratory-confirmed, critically ill COVID-19 patients at six ICUs in the Skåne Region, Sweden, between May 11, 2020, and May 10, 2021. Demographics and clinical data were collected. ICU burden was defined as the total number of ICU-treated COVID-19 patients in the region on admission. Surviving patients had a follow-up at 90 days for assessment of functional outcome using the Glasgow Outcome Scale-Extended (GOSE), an ordinal scale (1-8) with GOSE ≥5 representing a favourable outcome. The primary outcome was 90-day mortality; the secondary outcome was functional outcome at 90 days.Among 498 included patients, 74% were male with a median age of 66 years and a median body mass index (BMI) of 30 kg/mIn critically ill COVID-19 patients, the 90-day mortality was 39% and increased considerably at age 60 or older. The ICU burden was associated with mortality, whereas a high BMI was not. A longer stay in the ICU was associated with unfavourable functional outcomes at 90 days.

Euroopa Liidu referendumid on oluline osa Euroopa integratsiooniprotsessist ning peamiselt puudutavad need kas vastava riigi astumist Euroopa Liitu või mõne liidu lepingu ratifitseerimist. Toimunud on ka kaks referendumit, kus teatud Euroopa Liidu liikmesriikide kodanikud on saanud otsustada liidu suhete üle kolmandate riikidega. Taolised referendumid võivad aga vetostada aastaid läbiräägitud ning ettevalmistatud assotsiatsiooni- või liitumisepingu ja nullida sellega kolmanda riigi pikaajalised jõupingutused. Töö eesmärgiks oli selgitada, 2016. aastal Hollandis Euroopa Liidu ja Ukraina vahelise assotsiatsioonileppe üle ja 1972. aastal Prantsusmaal Taani, Norra, Iirimaa ja Ühendkuningriigi Euroopa Liiduga liitumise küsimuses toimunud referendumi näitel, kuidas kasutati referendumit Euroopa Liidu välissuhteid ja laienemist puudutavate küsimuste otsustamisel ja millist mõju see vastava valdkonna arengule avaldas. Lisaks on töö eesmark selgitada välja miks viidi Prantsusmaa põhiseadusesse artikkel 88-5, mis puudutab nõuet korraldada edasiste laienemiste üle referendum ning mida see võib tähendada Euroopa Liidu edasisele laienemisele. Valitud juhtumite uurimiseks viidi läbi kvalitatiivne juhtumianalüüs ning selleks koondati mitmekesine hulk sekundaarseid allikaid, mida analüüsiti politiseerimise ja veto-õiguslike osalejate teooria olulisematele aspektidele tuginedes. Kui politiseerimise teooria andis konkreetse raamistiku, selgitamaks välja, kuidas referendumit kasutati ehk kas ja kuidas toimus politiseerimise protsess, siis veto-osalejate teooria aitas selgitada, kuidas on olenevalt riigi otsustusprotsessist võimalik referendumitega poliitilisi arenguid ja otsuseid vetostada. Analüüsi tulemusena selgus, et Hollandis ja Prantsusmaal toimus referendumi politiseerimine ning referendumi algatajad kasutasid referendumit ära kui enda poliitilise agenda läbisurumise ja oma poliitilise positsiooni tugevdamise instrumenti, tuues tegeliku referendumi küsimuse ainult ettekäändeks. Artikkel 88-5 viidi Prantsusmaa põhiseadusesse pidades eelkõige silmas Türgi liitumist Euroopa Liiduga ning see on potentsiaalselt kaugeleulatuvate tagajärgedega, eriti arvestades asjaolu, et Prantsusmaa sisepoliitikat iseloomustab tugev toetus parempopulistlikele ksenofoobsetele jõududele. Seega on referendumid väga vastuoluline ja kaheldava väärtusega poliitiliste ja ka välispoliitikat puudutavate otsuste tegemise instrument ning isegi kui referendumi tulemuse ei ole õiguslikult siduv, võivad Euroopa Liidu välissuhteid ja laienemist puudutavad referendumid panna küsimärgi alla edasise Euroopa integratsiooni ja ka kogu Euroopa Liidu tuleviku tervikuna., https://www.ester.ee/record=b5508235*est

Background The increasing prevalence of antiretroviral drug resistance in Sub-Saharan Africa threatens the success of HIV programs. We have characterized patterns of drug resistance mutations (DRMs) during the initial year of antiretroviral treatment (ART) in HIV-positive adults receiving care at Ethiopian health centers and investigated the impact of tuberculosis on DRM acquisition. Methods Participants were identified from a cohort of ART-naïve individuals aged ≥18 years, all of whom had been investigated for active tuberculosis at inclusion. Individuals with viral load (VL) data at 6 and/or 12 months after ART initiation were selected for this study. Genotypic testing was performed on samples with VLs ≥500 copies/mL obtained on these occasions and on pre-ART samples from those with detectable DRMs during ART. Logistic regression analysis was used to investigate the association between DRM acquisition and tuberculosis. Results Among 621 included individuals (110 [17.5%] with concomitant tuberculosis), 101/621 (16.3%) had a VL ≥500 copies/mL at 6 and/or 12 months. DRMs were detected in 64/98 cases with successful genotyping (65.3%). DRMs were detected in 7/56 (12.5%) pre-ART samples from these individuals. High pre-ART VL and low mid-upper arm circumference were associated with increased risk of DRM acquisition, whereas no such association was found for concomitant tuberculosis. Conclusions Among adults receiving health center–based ART in Ethiopia, most patients without virological suppression during the first year of ART had detectable DRM. Acquisition of DRM during this period was the dominant cause of antiretroviral drug resistance in this setting. Tuberculosis did not increase the risk of DRM acquisition.

Restricted capacity for viral load (VL) testing is a major obstacle for antiretroviral therapy (ART) programmes in high-burden regions. Algorithms for targeted VL testing could help allocate laboratory resources rationally. We validated the performance of the Viral Load Testing Criteria (VLTC), an algorithm with satisfactory performance in derivation (sensitivity 91%, specificity 43%).HIV-positive adults who had been receiving first-line ART for ≥12 months at three Ethiopian public ART clinics were included. Healthcare providers collected data on variables of the VLTC: current CD4 count, mid-upper arm circumference (MUAC) and self-reported treatment interruption. VL testing was performed in parallel. Performance of the algorithm for identification of patients with VL ≥ 1000 copies/ml was evaluated.Of 562 patients (female 62%, median ART duration 92 months), 33 (6%) had VL ≥ 1000 copies/ml. Sensitivity for the VLTC was 85% (95% CI, 68-95), specificity 60% (95% CI, 55-64), positive predictive value 12% (95% CI, 10-14) and negative predictive value 98% (95% CI, 97-99). Use of the algorithm would reduce the number of VL tests required by 57%. Misclassification occurred in 5/33 (15%) of subjects with VL ≥ 1000 copies/ml.In validation, the VLTC performed similarly well as derivation. Use of the VLTC may be considered for targeted VL testing for ART monitoring in high-burden regions.La capacité restreinte de mesure de la charge virale (CV) constitue un obstacle majeur pour les programmes de traitement antirétroviral (ART) dans les régions à prévalence élevée. Des algorithmes pour des tests ciblés de la CV pourraient aider à allouer les ressources de laboratoire de manière rationnelle. Nous avons validé la performance des critères de mesure de la charge virale (VLTC), un algorithme dont la performance de dérivation est satisfaisante (sensibilité de 91%, spécificité de 43%). MÉTHODES: Des adultes VIH positifs qui recevaient un ART de première ligne depuis au moins 12 mois dans trois cliniques ART publiques éthiopiennes ont été inclus. Les prestataires de soins de santé ont collecté des données sur les variables des VLTC: nombre actuel de CD4, périmètre brachial et interruption de traitement auto-déclarée. La mesure de la CV a été réalisée en parallèle. La performance de l'algorithme pour l'identification des patients avec une CV≥1000 copies/mL a été évaluée. RÉSULTATS: Sur 562 patients (femmes 62%, durée médiane de l’ART 92 mois), 33 (6%) avaient une CV ≥1000 copies/mL. La sensibilité des VLTC était de 85% (IC95%: 68-95), sa spécificité de 60% (IC95%: 55-64), sa valeur prédictive positive de 12% (IC95%: 10-14) et sa valeur prédictive négative de 98% (IC95%: 97-99). L'utilisation de l'algorithme réduirait le nombre de tests de CV requis de 57%. Une mauvaise classification est survenue chez 5/33 (15%) des sujets avec CV ≥1000 copies/ml.En validation, les VLTC ont obtenu une performance aussi bonne comme dérivation. L'utilisation des VLTC peut être envisagée pour des mesures ciblées de la CV dans le suivi des ART dans les régions à forte charge de morbidité.

BACKGROUND: The use of surrogate markers for targeting viral load (VL) testing could be an alternative to universal VL testing during antiretroviral treatment (ART) and would allow for more effective resource allocation. We investigated the correlation between levels of HIV RNA and interferon-γ-inducible protein 10 (IP-10) in Ethiopian adults at 12 months after ART initiation. In addition, we specifically investigated differences in IP-10 levels between patients with and without virological suppression.SETTING: Cohort of HIV-positive adults receiving ART at Ethiopian health centers.METHODS: Using a nested case-control design, individuals without virological suppression (HIV RNA ≥ 150 copies/mL) at 12 months after ART initiation were gender-matched with virologically suppressed controls (1:2 ratio). IP-10 levels were correlated with HIV RNA, and the distribution of IP-10 was compared for 3 VL strata

In 2017,for the first time, more than half of all people living with HIV (PLHIV) had access to antiretroviral treatment (ART). This expansion of ART has in part been achieved through decentralization of HIV care in resource-limited settings. There, many PLHIV now receive care at ART clinics integrated within the primary health care system. At these clinics, non-physician clinicians are responsible for all aspects of care. Concomitant tuberculosis (TB) is common among PLHIV in many high-burden countries. Therefore, clinicians at these clinics must be able to diagnose and treat concomitant TB in parallell with ART in order to achieve satisfactory outcome of care. Failing ART results in high mortality and risk of drug resistance development that can be detrimental both for the individual and for the community at large. The first three papers in this thesis explores aspects of ART outcome among patients receiving care at Ethiopian public health centers. In particular, the impact of concomitant TB on ART outcome is investigated. For this purpose, 812 ART-naïve adults eligible to start ART (CD4 count

Background In order to increase treatment coverage, antiretroviral treatment (ART) is provided through primary health care in low-income high-burden countries, where tuberculosis (TB) co-infection is common. We investigated the long-term outcome of health center–based ART, with regard to concomitant TB. Methods ART-naïve adults were included in a prospective cohort at Ethiopian health centers and followed for up to 4 years after starting ART. All participants were investigated for active TB at inclusion. The primary study outcomes were the impact of concomitant TB on all-cause mortality, loss to follow-up (LTFU), and lack of virological suppression (VS). Kaplan-Meier survival estimates and Cox proportional hazards models with multivariate adjustments were used. Results In total, 141/729 (19%) subjects had concomitant TB, 85% with bacteriological confirmation (median CD4 count TB, 169 cells/mm3; IQR, 99–265; non-TB, 194 cells/mm3; IQR, 122–275). During follow-up (median, 2.5 years), 60 (8%) died and 58 (8%) were LTFU. After ≥6 months of ART, 131/630 (21%) had lack of VS. Concomitant TB did not influence the rates of death, LTFU, or VS. Male gender and malnutrition were associated with higher risk of adverse outcomes. Regardless of TB co-infection status, even after 3 years of ART, two-thirds of participants had CD4 counts below 500 cells/mm3. Conclusions Concomitant TB did not impact treatment outcomes in adults investigated for active TB before starting ART at Ethiopian health centers. However, one-third of patients had unsatisfactory long-term treatment outcomes and immunologic recovery was slow, illustrating the need for new interventions to optimize ART programs.

To assess the diagnostic performance of urine lipoarabinomannan (LAM) detection for TB screening in HIV-positive adults in Ethiopia.Testing for LAM was performed using the Determine TB-LAM lateral flow assay on urine samples from participants in a prospective cohort with baseline bacteriological categorisation for active TB in sputum. Characteristics of TB patients with regard to LAM status were determined. Participants were followed for 6 months to evaluate survival, retention in care and incident TB.Positive LAM results were found in 78/757 participants. Among 128 subjects with definite (confirmed by culture and/or Xpert MTB/RIF) TB, 33 were LAM-positive (25.8%); the respective figure for clinically diagnosed cases was 2/20 (10%). Five of the remaining 43 LAM-positive individuals had died during the 6-month follow-up period, whereas 38 remained in care without clinical signs of TB. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 25.8%, 92.9%, 42.3% and 86.0%, respectively. Among TB patients, LAM positivity was associated with higher WHO clinical stage, lower body mass index (BMI), CD4 cell and haemoglobin levels, and with increased mortality. A combination algorithm of urine LAM testing and sputum smear microscopy detected 49 (38.2%) of definite TB cases; among those with CD4 count ≤100 cells/mmThe performance of urine LAM testing for TB detection was poor in this population. However, this was improved among subjects with CD4 count ≤100 cells/mm

Introduction: Antiretroviral therapy (ART) initiation during treatment for tuberculosis (TB) improves survival in HIV/TB co-infected patients. Data on ART outcome for HIV/TB co-infected patients managed in primary health care in low-income regions is limited. We compared virological suppression rates, mortality and retention in care in HIV-positive adults receiving care in five Ethiopian health centres with regard to TB co-infection. Material and Methods: HIV-positive ART-naive adults eligible for ART initiation were prospectively recruited from October 2011 until March 2013. At inclusion, all patients submitted sputum for microbiological TB testing (smear microscopy, liquid culture and PCR). Virological suppression rates after six months of ART (VS; viral load

Among HIV-infected, antiretroviral therapy (ART)–naive adults with positive World Health Organization tuberculosis (TB) symptom screening, clinical scoring could categorize patients for the risk of TB. This strategy would reduce the proportion of patients requiring TB testing before starting ART., Background The World Health Organization (WHO) tuberculosis (TB) symptom screening instrument (WHO-TB) can identify human immunodeficiency virus (HIV)-infected individuals at low risk of tuberculosis (TB); however, many patients report WHO-TB symptoms and require further TB investigations. We hypothesized that further clinical scoring could classify subjects with a positive WHO-TB screening result (WHO-TB+) for the likelihood of TB. Methods HIV-infected adults eligible to initiate antiretroviral therapy (ART) were recruited and prospectively followed at 5 Ethiopian health centers. Irrespective of symptoms, all participants underwent sputum bacteriological testing for TB. Symptoms, physical findings, hemoglobin, and CD4 cell count results were compared between subjects with and those without bacteriologically confirmed TB. Variables associated with TB in WHO-TB+ individuals were used to construct a scoring algorithm with multiple logistic regression analysis. Results Among 812 participants, 137 (16.9%) had TB. One hundred fifty-nine persons (20%) had a negative WHO-TB screen, 10 of whom had TB (negative predictive value [NPV], 94% [95% confidence interval {CI}, 90%–97.5%]). For WHO-TB+ subjects, the following variables were independently associated with TB, and were assigned 1 point each in the clinical scoring algorithm: cough, Karnofsky score ≤80, mid-upper arm circumference

Rates of virological suppression after 6 months of ART were high in a cohort of 678 HIV-positive adults managed in Ethiopian health centers, with no significant difference with regard to concomitant tuberculosis at baseline (TB 135; non-TB 543)., Background. Antiretroviral therapy (ART) initiation during treatment for tuberculosis (TB) improves survival in human immunodeficiency virus (HIV)/TB-coinfected patients. We compared virological suppression (VS) rates, mortality, and retention in care in HIV-positive adults receiving care in 5 Ethiopian health centers with regard to TB coinfection. Methods. Human immunodeficiency virus-positive ART-naive adults eligible for ART initiation were prospectively recruited. At inclusion, all patients underwent microbiological investigations for TB (sputum smear, liquid culture, and polymerase chain reaction). Virological suppression rates after 6 months of ART (VS; viral load

Background: Detection of active tuberculosis (TB) before antiretroviral therapy (ART) initiation is important, but optimal diagnostic methods for use in resource-limited settings are lacking. We assessed the prevalence of TB, evaluated the diagnostic yield of Xpert MTB/RIF in comparison with smear microscopy and culture, and the impact of Xpert results on clinical management in HIV-positive adults eligible for ART at health centers in a region of Ethiopia. Methods: Participants were prospectively recruited and followed up at 5 health centers. Trained nurses collected data on socio-demographic characteristics, medical history and symptoms, and performed physical examination. Two paired morning sputum samples were obtained, and lymph node aspirates in case of lymphadenopathy. Diagnostic yield of Xpert MTB/RIF in sputum was compared with smear microscopy and liquid culture. Results: TB was diagnosed in 145/812 participants (17.9%), with bacteriological confirmation in 137 (16.9%). Among bacteriologically confirmed cases, 31 were smear-positive (22.6%), 96 were Xpert-positive (70.1%), and 123 were culture-positive (89.8%). Xpert MTB/RIF increased the TB detection rate by 64 cases (47.4%) compared with smear microscopy. The overall sensitivity of Xpert MTB/RIF was 66.4%, and was not significantly lower when testing one compared with two samples. While Xpert MTB/RIF was 46.7% sensitive among patients with CD4 cell counts greater than200 cells/mm(3), this increased to 82.9% in those with CD4 cell counts less than= 100 cells/mm(3). Compared with Xpert-positive TB patients, Xpert-negative cases had less advanced HIV and TB disease characteristics. Conclusions: Previously undiagnosed TB is common among HIV-positive individuals managed in Ethiopian health centers. Xpert MTB/RIF increased TB case detection, especially in patients with advanced immunosuppression. An algorithm based on the use of a single morning sputum sample for individuals with negative sputum smear microscopy could be considered for intensified case finding in patients eligible for ART. However, technical and cost-effectiveness issues relevant for low-income countries warrant further study.

Background. Injecting drug use (IDU) may lead to exposure to a range of carcinogenic agents. We investigated the risk and distribution of cancers among individuals with a history of IDU in Sweden. Material and Methods. The cancer incidence in a cohort of longitudinally followed participants in a needle exchange program (NEP), recruited between 1987 and 2007, was compared to that in the Swedish general population, matching for age group and gender. Baseline demographic and drug use data were collected and longitudinal testing of serological markers for HIV, hepatitis B and C virus was performed during NEP participation. Standardized incidence ratios (SIR) for types of cancer found in the study cohort were calculated, using data from the Swedish National Cancer Registry for reference. Results. The mean follow-up time for the 3255 participants was 11.8 years, constituting 38 419 person years at risk. The mean age at end of follow-up was 42.7 years, and 75% of participants were men. Seventy-eight cases of cancer were observed (SIR 1.1 [95% CI = 0.9-1.4]). The SIR was significantly increased for five cancer types among men; primary liver, laryngeal, lung, oropharyngeal and non-melanoma skin cancer (respective SIR 12.8 [95% CI = 4.2-30.0], 9.2 [95% CI = 1.9-26.8], 3.2 [95% CI = 1.5-6.1], 7.3 [95% CI = 1.5-21.2], and 3.5 [95% CI = 1.1-8.2]), and for cancers of endocrine organs among women (5.3 [95% CI = 1.7-12.4]). Conclusion. Although the standardized overall cancer incidence in this relatively young IDU cohort was similar to that in the general population, the risk of specific types of cancer was significantly increased, suggesting that IDU confers elevated risks for certain malignancies. These findings prompt further studies to investigate causative factors and suggest the need for surveillance among persons with a history of IDU.