Length of stay in Denmark before HIV diagnosis and linkage to care: a population-based study of migrants living with HIV, Denmark, 1995 to 2020.

BackgroundMigrants face an increased risk of HIV infection and late presentation for HIV care.AimTo examine delays in HIV diagnosis, linkage to care (LTC), and risk of late presentation for migrants living with HIV in Denmark.MethodsWe conducted a population-based, nationwide study of adult migrants (n = 2,166) presenting for HIV care between 1 January 1995 and 31 December 2020 in Denmark. Time from immigration to HIV diagnosis and from diagnosis to LTC, and late presentation were assessed, stratified by migrants' geographical regions of origin, using descriptive statistics.ResultsThe demographics of the migrant population changed over time. Overall, migrants diagnosed with HIV after immigration to Denmark resided a median of 3.7 (IQR: 0.8-10.2) years in Denmark before diagnosis. Median time from HIV diagnosis to LTC was 6 (IQR: 0-24) days. Migrants diagnosed with HIV infection before immigration had a median of 38 (IQR: 0-105) days from arrival in Denmark to LTC. The corresponding median times for 2015-20 alone were 4.1 (IQR: 0.9-13.1) years, 0 (IQR: 0-8) days, and 62 (IQR: 25-152) days, respectively. The overall proportion of late presentation among migrants diagnosed with HIV after immigration was 60%, and highest among migrants from sub-Saharan Africa and East and South Asia.ConclusionHIV diagnosis is still substantially delayed in Danish migrants, while LTC is timely. The proportions with late presentation are high. These results call for targeted interventions to reduce the number of migrants with undiagnosed HIV infections and of late presenters.

Improved Survival Among Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Treated With Remdesivir and Dexamethasone. A Nationwide Population-Based Cohort Study.

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.

National survey of current practice and opinions on rehabilitation for intermittent claudication in the Danish Public Healthcare System.

Objective. International guidelines recommend rehabilitation including supervised exercise therapy in patients with Intermittent Claudication (IC), but knowledge of the implementation in clinical practice is limited. This study aims to investigate current practice and opinions on rehabilitation for patients with IC among vascular surgeons and rehabilitation departments in the municipalities and hospitals. Design. Three electronic cross-sectional surveys were distributed nationally to the Danish vascular surgeons (n = 131) and to rehabilitation departments in the municipalities (n = 92) and hospitals (n = 33). Results. The response rates were 70% among the vascular surgeons, 98% among the municipalities and 94% among the hospitals. Vascular surgeons utilize oral advice to exercise by self-administered walking, pharmacological treatment, and revascularization to improve walking distance in patients with IC. Currently, only 12% of the vascular surgeons referred to rehabilitation to improve walking distance, while almost all vascular surgeons (96%) would refer their patients to IC rehabilitation, if it was available. Only 14% of municipalities and none of the hospitals, who treat patients with IC, have a rehabilitation program designed specifically for patients with IC. However, 59% of the rehabilitation departments in the municipalities and 26% in the hospitals included patients with IC in rehabilitation program designed for other patient groups - mostly cardiac patients. There was consensus among the groups of respondents that future IC specific rehabilitation should include an initial conversation, supervised exercise therapy, smoking cessation, and patient education according to guidelines. Conclusion. Vascular surgeons support referral and participation in IC rehabilitation to improve walking distance in patients with IC. Despite some hospitals and municipalities included patients with IC in rehabilitation nearly all services fail to meet current guideline as specific services tailored to patient with IC is almost non-existent in Denmark. Our findings call for action for services to comply with current recommendations of structured, systematic rehabilitation for patients with IC.

Prescription of antimicrobials in primary health care as a marker to identify people living with undiagnosed HIV infection, Denmark, 1998 to 2016.

BackgroundDevelopment of additional diagnostic strategies for earlier HIV diagnosis are needed as approximately 50% of newly diagnosed HIV-infected individuals continue to present late for HIV care.AimWe aimed to analyse antimicrobial consumption in the 3 years preceding HIV diagnosis, assess whether there was a higher consumption in those diagnosed with HIV compared with matched controls and whether the level of consumption was associated with the risk of HIV infection.MethodsWe conducted a nested case-control study, identifying all individuals (n = 2,784 cases) diagnosed with HIV in Denmark from 1998 to 2016 and 13 age-and sex-matched population controls per case (n = 36,192 controls) from national registers. Antimicrobial drug consumption was estimated as defined daily doses per person-year. We used conditional logistic regression to compute odds ratios and 95% confidence intervals.ResultsIn the 3 years preceding an HIV diagnosis, we observed more frequent and higher consumption of antimicrobial drugs in cases compared with controls, with 72.4% vs 46.3% having had at least one prescription (p < 0.001). For all antimicrobial classes, the association between consumption and risk of subsequent HIV diagnosis was statistically significant (p < 0.01). The association was stronger with higher consumption and with shorter time to HIV diagnosis.ConclusionHIV-infected individuals have a significantly higher use of antimicrobial drugs in the 3 years preceding HIV diagnosis than controls. Prescription of antimicrobial drugs in primary healthcare could be an opportunity to consider proactive HIV testing. Further studies need to identify optimal prescription cut-offs that could endorse its inclusion in public health policies.

Vertical transmission of hepatitis B virus during pregnancy and delivery in Denmark.

OBJECTIVE: In Denmark, pregnant women have been screened for hepatitis B virus (HBV) since 2005, and children born to HBV-infected mothers offered hepatitis B immunoglobulin at birth, vaccination against HBV at birth and after 1, 2 and 12 months. The purpose of this study was to determine the risk of vertical HBV transmission in children born to mothers with chronic HBV infection, to investigate the antibody response in the children and to investigate possible maternal predictive risk factors for HBV transmission. MATERIALS AND METHODS: Through the Danish Database for Hepatitis B and C, we identified 589 HBV-infected women who had given birth to 686 children, of whom 370 children were born to 322 women referred to hospital. 132 (36%) children, born to 109 mothers, were included in the study; 128 children had blood samples tested for HBsAg, anti-HBc (total), anti-HBs and HBV-DNA and four children had saliva samples tested for anti-HBc. RESULTS: We found vertical HBV transmission in Denmark to be 2.3% [95% CI: 0.5, 6.5], a high proportion of HBsAg-negative children with low levels of anti-HBs (18.4%) and a high proportion (15.2%) with resolved HBV infection. No maternal risk factor was statistically significantly associated with HBV vertical transmission. CONCLUSION: In a HBV low prevalence setting as Denmark, despite a national vaccination program, vertical HBV transmission occurred in 2.3% of children born to HBV-infected mothers. In addition, a high proportion of the children had insufficient anti-HBs levels and a high proportion had serological signs of resolved HBV infection.

The Danish contribution to the European DEMOCOPHES project: A description of cadmium, cotinine and mercury levels in Danish mother-child pairs and the perspectives of supplementary sampling and measurements.

Human biomonitoring (HBM) is an important tool, increasingly used for measuring true levels of the body burdens of environmental chemicals in the general population. In Europe, a harmonized HBM program was needed to open the possibility to compare levels across borders. To explore the prospect of a harmonized European HBM project, DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) was completed in 17 European countries. The basic measurements performed in all implemented countries of DEMOCOPHES included cadmium, cotinine and phthalate metabolites in urine and mercury in hair. In the Danish participants, significant correlations between mothers and children for mercury in hair and cotinine in urine were found. Mercury in hair was further significantly associated with intake of fish and area of residence. Cadmium was positively associated with BMI in mothers and an association between cadmium and cotinine was also found. As expected high cotinine levels were found in smoking mothers. For both mercury and cadmium significantly higher concentrations were found in the mothers compared to their children. In Denmark, the DEMOCOPHES project was co-financed by the Danish ministries of health, environment and food safety. The co-financing ministries agreed to finance a number of supplementary measurements of substances of current toxicological, public and regulatory interest. This also included blood sampling from the participants. The collected urine and blood samples were analyzed for a range of other persistent and non-persistent environmental chemicals as well as two biomarkers of effect. The variety of supplementary measurements gives the researchers further information on the exposure status of the participants and creates a basis for valuable knowledge on the pattern of exposure to various chemicals.

Exposure determinants of cadmium in European mothers and their children.

The metal cadmium (Cd) is a widespread environmental pollutant with documented adverse effects on the kidneys and bones from long-term environmental exposure, but with insufficiently elucidated public health consequences such as risk of cardiovascular disease, hormone-related cancer in adults and developmental effects in children. This study is the first pan-European human biomonitoring project that succeeded in performing harmonized measurements of Cd in urine in a comparable way in mother-child couples from 16 European countries. The aim of the study was to evaluate the overall Cd exposure and significant determinants of Cd exposure. A study population of 1632 women (24-52 years of age), and 1689 children (5-12 years of age), from 32 rural and urban areas, was examined within a core period of 6 months in 2011-2012. Women were stratified as smokers and non-smokers. As expected, smoking mothers had higher geometric mean (gm) urinary cadmium (UCd; 0.24 µg/g crea; n=360) than non-smoking mothers (gm 0.18 µg/g crea; n=1272; p<0.0001), and children had lower UCd (gm 0.065 µg/g crea; n=1689) than their mothers at the country level. Non-smoking women exposed to environmental tobacco smoke (ETS) at home had 14% (95% CI 1-28%) higher UCd than those who were not exposed to ETS at home (p=0.04). No influence of ETS at home or other places on UCd levels was detected in children. Smoking women with primary education as the highest educational level of the household had 48% (95% CI 18-86%) higher UCd than those with tertiary education (p=0.0008). The same observation was seen in non-smoking women and in children; however they were not statistically significant. In children, living in a rural area was associated with 7% (95% CI 1-13%) higher UCd (p=0.03) compared to living in an urban area. Children, 9-12 years had 7% (95% CI 1-13%) higher UCd (p=0.04) than children 5-8 years. About 1% of the mothers, and 0.06% of the children, exceeded the tolerable weekly intake (TWI) appointed by EFSA, corresponding to 1.0 µg Cd/g crea in urine. Poland had the highest UCd in comparison between the 16 countries, while Denmark had the lowest. Whether the differences between countries are related to differences in the degree of environmental Cd contamination or to differences in lifestyle, socioeconomic status or dietary patterns is not clear.

Lessons learnt on recruitment and fieldwork from a pilot European human biomonitoring survey.

Within the European Environment and Health Action Plan an initiative to establish a coherent human biomonitoring approach in Europe was started. The project COPHES (COnsortium to Perform Human biomonitoring on a European Scale ) developed recommendations for a harmonized conduct of a human biomonitoring (HBM) survey which came into action as the pilot study DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale). Seventeen European countries conducted a survey with harmonized instruments for, inter alia, recruitment, fieldwork and sampling, in autumn/winter 2011/2012. Based on the countries' experiences of conducting the pilot study, following lessons learnt were compiled: the harmonized fieldwork instruments (basic questionnaire, urine and hair sampling) turned out to be very valuable for future HBM surveys on the European scale. A school approach was favoured by most of the countries to recruit school-aged children according to the established guidelines and country specific experiences. To avoid a low participation rate, intensive communication with the involved institutions and possible participants proved to be necessary. The communication material should also include information on exclusion criteria and offered incentives. Telephone contact to the participants the day before fieldwork during the survey can prevent the forgetting of appointments and first morning urine samples. To achieve comparable results on the European scale, training of interviewers in all issues of recruitment, fieldwork and sampling through information material and training sessions is crucial. A survey involving many European countries needs time for preparation and conduct. Materials for quality control prepared for all steps of recruitment, fieldwork and sampling proved to be important to warrant reliable results.

Policy recommendations and cost implications for a more sustainable framework for European human biomonitoring surveys.

The potential of Human Biomonitoring (HBM) in exposure characterisation and risk assessment is well established in the scientific HBM community and regulatory arena by many publications. The European Environment and Health Strategy as well as the Environment and Health Action Plan 2004-2010 of the European Commission recognised the value of HBM and the relevance and importance of coordination of HBM programmes in Europe. Based on existing and planned HBM projects and programmes of work and capabilities in Europe the Seventh Framework Programme (FP 7) funded COPHES (COnsortium to Perform Human Biomonitoring on a European Scale) to advance and improve comparability of HBM data across Europe. The pilot study protocol was tested in 17 European countries in the DEMOCOPHES feasibility study (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) cofunded (50%) under the LIFE+ programme of the European Commission. The potential of HBM in supporting and evaluating policy making (including e.g. REACH) and in awareness raising on environmental health, should significantly advance the process towards a fully operational, continuous, sustainable and scientifically based EU HBM programme. From a number of stakeholder activities during the past 10 years and the national engagement, a framework for sustainable HBM structure in Europe is recommended involving national institutions within environment, health and food as well as European institutions such as ECHA, EEA, and EFSA. An economic frame with shared cost implications for national and European institutions is suggested benefitting from the capacity building set up by COPHES/DEMOCOPHES.

Fish consumption patterns and hair mercury levels in children and their mothers in 17 EU countries.

The toxicity of methylmercury (MeHg) in humans is well established and the main source of exposure is via the consumption of large marine fish and mammals. Of particular concern are the potential neurodevelopmental effects of early life exposure to low-levels of MeHg. Therefore, it is important that pregnant women, children and women of childbearing age are, as far as possible, protected from MeHg exposure. Within the European project DEMOCOPHES, we have analyzed mercury (Hg) in hair in 1799 mother-child pairs from 17 European countries using a strictly harmonized protocol for mercury analysis. Parallel, harmonized questionnaires on dietary habits provided information on consumption patterns of fish and marine products. After hierarchical cluster analysis of consumption habits of the mother-child pairs, the DEMOCOPHES cohort can be classified into two branches of approximately similar size: one with high fish consumption (H) and another with low consumption (L). All countries have representatives in both branches, but Belgium, Denmark, Spain, Portugal and Sweden have twice as many or more mother-child pairs in H than in L. For Switzerland, Czech Republic, Hungary, Poland, Romania, Slovenia and Slovakia the situation is the opposite, with more representatives in L than H. There is a strong correlation (r=0.72) in hair mercury concentration between the mother and child in the same family, which indicates that they have a similar exposure situation. The clustering of mother-child pairs on basis of their fish consumption revealed some interesting patterns. One is that for the same sea fish consumption, other food items of marine origin, like seafood products or shellfish, contribute significantly to the mercury levels in hair. We conclude that additional studies are needed to assess and quantify exposure to mercury from seafood products, in particular. The cluster analysis also showed that 95% of mothers who consume once per week fish only, and no other marine products, have mercury levels 0.55 µg/g. Thus, the 95th percentile of the distribution in this group is only around half the US-EPA recommended threshold of 1 µg/g mercury in hair. Consumption of freshwater fish played a minor role in contributing to mercury exposure in the studied cohort. The DEMOCOPHES data shows that there are significant differences in MeHg exposure across the EU and that exposure is highly correlated with consumption of fish and marine products. Fish and marine products are key components of a healthy human diet and are important both traditionally and culturally in many parts of Europe. Therefore, the communication of the potential risks of mercury exposure needs to be carefully balanced to take into account traditional and cultural values as well as the potential health benefits from fish consumption. European harmonized human biomonitoring programs provide an additional dimension to national HMB programs and can assist national authorities to tailor mitigation and adaptation strategies (dietary advice, risk communication, etc.) to their country's specific requirements.

Changes in exercise capacity in people with Cystic Fibrosis after one year of Elexacaftor/Tezacaftor/Ivacaftor treatment - A Danish prospective cohort.

BACKGROUND: Cystic Fibrosis (CF) is an inherited multiorgan disease that causes lung damage and early death. People with CF (pwCF) experience diminished exercise capacity compared to the general population. This is due to an accelerated decline in lung function resulting from recurrent lung infections, declining lung function and nutritional challenges. Since 2020 the CFTR-modulator Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been approved for pwCF aged 12 and above in Denmark. Initial experiences with the medication have shown promising results, including improved lung function and disease stability. To date a limited number of studies have evaluated the impact of CFTR-modulators on exercise capacity in pwCF. OBJECTIVE: The study aims to assess the impact of one year of ETI treatment, without any further intervention, on exercise capacity measured through cardiopulmonary exercise test (CPET) in pwCF aged 12 years and above. METHODS: A Danish prospective registry cohort study including pwCF from CF-Center Copenhagen, Copenhagen University Hospital and CF-Center Aarhus, Aarhus University Hospital. Participants underwent CPET before initiating ETI and at follow up one year later. Primary outcomes were VO2 peak (ml/kg/min), secondary outcomes were VO2 peak (ml/min), VO2 peak (% pred), watt-max, HR-max and saturation at max. The difference between baseline and follow-up was assessed using a paired-sample t-test and regression analyses were applied to relevant outcomes. RESULTS: We included 229 pwCF in the analyses. An increase in oxygen uptake, VO2 peak (ml/kg/min) from baseline to follow-up was observed; 0.6, 95% CI [0.06; 1.09] p = 0.03. Moreover, significant increase was noted for all other CPET outcomes. Regression analysis showed that changes in FEV1% pred and BMI could explain some of the differences, 0.05 ml/kg/min, 95% CI [0.01, 0.1] p = 0.02 and -0.5 ml/kg/min, 95% CI [-0.8, -0.2] p = 0.002 respectively. CONCLUSION: Among Danish pwCF we found a significant, but not clinically relevant, increase in oxygen uptake, after one year of ETI treatment.

Human liver cell spheroids in extended perfusion bioreactor culture for repeated-dose drug testing.

UNLABELLED: Primary cultures of human hepatocyte spheroids are a promising in vitro model for long-term studies of hepatic metabolism and cytotoxicity. The lack of robust methodologies to culture cell spheroids, as well as a poor characterization of human hepatocyte spheroid architecture and liver-specific functionality, have hampered a widespread adoption of this three-dimensional culture format. In this work, an automated perfusion bioreactor was used to obtain and maintain human hepatocyte spheroids. These spheroids were cultured for 3-4 weeks in serum-free conditions, sustaining their phase I enzyme expression and permitting repeated induction during long culture times; rate of albumin and urea synthesis, as well as phase I and II drug-metabolizing enzyme gene expression and activity of spheroid hepatocyte cultures, presented reproducible profiles, despite basal interdonor variability (n = 3 donors). Immunofluorescence microscopy of human hepatocyte spheroids after 3-4 weeks of long-term culture confirmed the presence of the liver-specific markers, hepatocyte nuclear factor 4α, albumin, cytokeratin 18, and cytochrome P450 3A. Moreover, immunostaining of the atypical protein kinase C apical marker, as well as the excretion of a fluorescent dye, evidenced that these spheroids spontaneously assemble a functional bile canaliculi network, extending from the surface to the interior of the spheroids, after 3-4 weeks of culture. CONCLUSION: Perfusion bioreactor cultures of primary human hepatocyte spheroids maintain a liver-specific activity and architecture and are thus suitable for drug testing in a long-term, repeated-dose format.

Anal carcinoma in HIV-infected patients in the period 1995-2009: a Danish nationwide cohort study.

BACKGROUND: Several studies have demonstrated an increased risk of non-AIDS cancers in HIV patients and, for some cancers, also in relatives of HIV patients. We aimed to estimate (1) the risk of anal carcinoma among HIV patients and their parents, and (2) the mortality after a diagnosis of anal carcinoma. METHODS: We used Poisson regression to estimate the incidence rate ratios (IRR) of anal carcinoma in (1) a population of HIV patients identified from the Danish HIV Cohort Study (n = 4993) compared with a population control cohort matched on age and gender (n = 59,916) for the period 1995-2009, and (2) parents of HIV patients compared with parents of controls for the period 1978-2009. Cancer diagnoses were identified from The Danish Cancer Registry. We further estimated the mortality rate ratios (MRR) of HIV patients compared with controls after the diagnosis of anal carcinoma. RESULTS: Thirty-six HIV patients versus 8 population controls were diagnosed with anal carcinoma. HIV patients had an increased risk of anal carcinoma (IRR 77.9, 95% CI 36.2-167.7), especially among men who have sex with men (MSM) (IRR 101.4, 95% CI 39.3-261.5). Fathers of HIV patients had an increased risk of anal carcinoma (IRR 7.4, 95% CI 1.4-38.3) compared to fathers of population controls. Mortality after diagnosis of anal carcinoma was increased in male HIV patients compared with the male control cohort (MRR 3.2, 95% CI 1.1-9.2). CONCLUSIONS: Danish HIV patients, especially MSM, have a considerably increased risk of anal carcinoma. We cannot exclude that fathers of HIV patients have an increased risk of anal carcinoma.

Risk Stratification for Postoperative Pulmonary Complications following Major Cardiothoracic and Abdominal Surgery - development of the PPC Risk Prediction Score for Physiotherapists Clinical Decision-making.

INTRODUCTION: Major cardiothoracic or abdominal surgery can lead to the development of postoperative pulmonary complications (PPC), associated with increased morbidity and prolonged length of hospital stay. Preventive chest physiotherapy is routinely provided, but optimization of treatment strategies is needed to improve patient outcome and resource utilization. OBJECTIVE: To develop a preoperative risk prediction scorelr to assist clinical decision-making regarding physiotherapy interventions. METHODS: A prospective observational single-center study included 339 of 577 eligible patients admitted for major elective cardiothoracic or abdominal surgery. Primary outcome measure was PPC amendable to chest physiotherapy. RESULTS: A total of 113 patients (33.3%) developed a PPC. Logistic regression modeling identified four independent predictors of PPC presented with odds ratio (OR) and 95% confidence interval. Reduced lung function (FEV1 > 50% to <75% OR 2.4 (1.4; 4.3) and FEV1 ≤ 50% OR 4.7 (1.4;16.0)), Recent unintended weight loss OR 4.5 (1.1; 18.7), Sternotomy OR 3.5 (2.0; 6.0) and Thoraco-abdominal incision OR 4.5 (2.1; 10.1). Based on assigned point values, a score dividing patients into three risk groups was developed. The score had moderate discrimination (c-statistic 0.70). CONCLUSION: By following recommended guidelines (TRIPOD) a preoperative risk prediction score including four predictors of PPC was developed. External validation of the score is currently being investigated.

Risk stratification for post-operative pulmonary complications following major cardiothoracic or abdominal surgery: Validation of the PPC Risk Prediction Score for physiotherapist's clinical decision-making.

INTRODUCTION: Patients undergoing major cardiothoracic or abdominal surgery are at increased risk of developing post-operative pulmonary complications (PPC), but respiratory physiotherapy can prevent PPC. We have previously developed the PPC Risk Prediction Score to allocate physiotherapists' resources and stratify patients into three risk groups. In this study, we performed a temporal external validation of the PPC Risk Prediction Score. Such validation is rare and adds to the originality of this study. METHODS: A cohort of 360 patients, admitted to undergo elective cardiothoracic or abdominal surgery, were included. Performance and clinical usefulness of the PPC Risk Prediction Score were estimated through discrimination, calibration and clinical usefulness, and the score was updated. RESULTS: The score showed c-statistics of 0.62. Related to clinical usefulness, a cut point at 8 gave a sensitivity of 0.49 and a specificity of 0.70, whereas a cut point at 12 gave a sensitivity of 0.13 and a specificity of 0.95. Two predictors included in the development sample score, thoraco-abdominal incision odds ratio (OR) 2.74 (1.12;6.71) and sternotomy OR 2.09 (1.18;3.72), were statistically significantly associated to PPC in the validation sample. CONCLUSIONS: The score was not able to discriminate between patients with and without PPC; neither was the updated score, but the study identified clinically relevant risk factors for developing PPC.

Treatment effect modifiers in hospitalised patients with COVID-19 receiving remdesivir and dexamethasone.

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.

Late presenters, repeated testing, and missed opportunities in a Danish nationwide HIV cohort.

BACKGROUND: We aimed to estimate the incidence and predictors of late presentation among human immunodeficiency virus (HIV)-infected individuals in Denmark. METHODS: Incidence rates (IR) of presentation with advanced HIV (CD4 < 200 cells/µl and/or acquired immune deficiency syndrome (AIDS)) and late presentation (CD4 < 350 cells/µl and/or AIDS) were calculated per 100,000 population aged 16-60 y. Mortality rate ratios (MRR) were estimated using Poisson regression analysis. RESULTS: Three thousand and twenty-seven individuals were diagnosed with HIV in 1995-2009; 34.7% presented with advanced HIV and 51.2% were late presenters. The IR of HIV was stable (6.2/100,000 population), but IR of presentation with advanced HIV declined during the study period from 2.2 (95% confidence interval (CI) 1.8-2.8) to 1.1 (95% CI 0.8-1.5). Age >50 y, heterosexuals of non-Danish origin, 'other' route of transmission, and diagnosis before 2002 were associated with an increased risk of presenting with advanced HIV, whereas a negative HIV test prior to diagnosis was associated with a significantly reduced risk. A total of 414 individuals (40.0%) had attended a hospital 1-3 y before presenting with advanced HIV. After 2002 the proportion of men who have sex with men with a negative HIV test prior to diagnosis increased (incidence rate ratio (IRR) 1.3, 95% CI 1.1-1.6), coinciding with a reduction in IR of presentation with advanced HIV. Mortality rates were increased the first 2 y following presentation with advanced HIV (MRR 5.9, 95% CI 3.6-9.4 and MRR 2.5, 95% CI 1.4-4.1, respectively). CONCLUSION: In a setting with a low HIV prevalence, the rate of presentation with advanced HIV can potentially be reduced by repeated HIV testing of individuals with a continuous high risk of transmission and by adhering to guidelines for targeted HIV testing.

Change in exercise capacity measured by Cardio-pulmonary Exercise Testing (CPET) in Danish people with cystic fibrosis after initiation of treatment with Lumacaftor/Ivacaftor and Tezacaftor/Ivacaftor.

BACKGROUND: Since 2015, when the first cystic fibrosis transmembrane conductance regulator (CFTR) modulators were approved for people with cystic fibrosis (CF) homozygous for F508del-CFTR, studies have shown improved lung function after initiation of the treatment and patients experience improved physical capacity. The aim of this study was to investigate change in exercise capacity after initiation of Lumacaftor/Ivacaftor and Tezacaftor/Ivacaftor treatment (LUM/IVA, TEZ/IVA). METHODS: We performed a single group prospective observational cohort study with follow-up at six and 12 months. The study examined change in exercise capacity in people with CF initiating treatment with LUM/IVA and TEZ/IVA, measured by cardio-pulmonary exercise testing (CPET). Inclusion criteria were people with CF homozygous for F508del-CFTR aged 12 years or older eligible for LUM/IVA and TEZ/IVA treatment from June 2017 until June 2019. Primary outcomes were change in VO2peak and maximal workload. Secondary outcomes were change in muscle strength, muscle power and body composition in a subgroup of the study population. RESULTS: A total of 91 patients were included in the analysis. The mean change in VO2peak and VO2peak divided by body weight from baseline to 12-months follow-up was 145.7 (91.2;200.2) ml/min and 1.07 (95% CI 0.19;1.95) ml/min/kg, respectively. The mean change in maximal workload between baseline and 12 months was 14.2 Watt (95% CI 9.1;19.2). All improvements in exercise capacity were statistically significant. CONCLUSIONS: Patients in this study improved their exercise capacity by a statistically significant increase in VO2peak and maximal workload 12 months after initiation of treatment with LUM/IVA and TEZ/IVA.

Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic ß-cells.

Fatty acid-induced damage in pancreatic ß-cells is assumed to play an important role in the development of type 2 diabetes. Lactogens (prolactin, placental lactogen and growth hormone) improve ß-cell survival via STAT5 activation but the molecular targets are incompletely characterized. The aim of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic ß-cells, and to examine this in relation to ß-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP2, FATP1 and FATP4 were unchanged. RNAi against FAT/CD36 decreased fatty acid-induced apoptosis. Over-expression of constitutively active STAT5 was able to mimic hGH's suppression of FAT/CD36 expression, whereas dominant negative STAT5 was unable to block the effect of hGH indicating that STAT5 did not bind directly to the FAT/CD36 promoter. The hGH-mediated suppression of FAT/CD36 mRNA was associated with a decrease in palmitate uptake and fatty acid-induced basal hyper-secretion of insulin resulting in improved glucose-stimulated insulin secretion. This study suggests that hGH can protect ß-cells against fatty acid-induced damages.