Late presentation for hepatitis C treatment: prevalence and risk factors in the Swiss Hepatitis C Cohort

OBJECTIVE Patients with 'late presentation' (LP) of chronic hepatitis C infection (HCV) have already developed advanced liver disease before receiving direct-acting antiviral (DAA) treatment. Even after successful treatment, the risk of morbidity and premature death remains elevated, leading to an unnecessary disease burden. This study aimed to assess the prevalence of LP within the prospective observational Swiss Hepatitis C Cohort (SCCS) and evaluate risk factors as determinants of LP. METHODS Treatment-naïve participants of SCCS who received DAA treatment between 2014 and 2019 were included. Demographic, clinical and behavioural data were compared between the LP and non-LP strata. LP prevalence was calculated over time and by year. LASSO regression was used to identify potential risk factors for LP, and odds ratios were calculated by refitting logistic regression models. RESULTS In this explorative, retrospective case-control study using data of n = 5829 SCCS members, a total of 21.3% received their first HCV treatment. The cumulative LP prevalence decreased from mid-2015 and stabilised at 46.5% (n = 579) by the end of 2019. Male gender, higher age and a history of alcohol overuse were associated with a higher risk of LP. CONCLUSION Despite the study's limitations, LP prevalence was higher than anticipated, considering Switzerland's availability period and universal access to DAAs. Therefore, any HCV LP should be viewed as a healthcare system failure, primarily in high-income economies. As LP is directly linked to the disease burden, it must be included as a mandatory parameter in surveillance response systems of HCV elimination programs

A genetic validation study reveals a role of vitamin D metabolism in the response to interferon-alfa-based therapy of chronic hepatitis C

Background: To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C. Methodology/Principal Findings: Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D3<20 ng/mL) during all seasons, but 25(OH)D3 serum levels were not associated with treatment outcome. Conclusions/Significance: Our study suggests a role of bioactive vitamin D (1,25[OH]2D3, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D3 is not a suitable predictor of treatment outcome

Widely differing screening and treatment practice for osteoporosis in patients with inflammatory bowel diseases in the Swiss IBD cohort study.

Low bone mineral density (BMD) and osteoporosis remain frequent problems in patients with inflammatory bowel diseases (IBDs). Several guidelines with nonidentical recommendations exist and there is no general agreement regarding the optimal approach for osteoporosis screening in IBD patients. Clinical practice of osteoporosis screening and treatment remains insufficiently investigated.In the year 2014, a chart review of 877 patients included in the Swiss IBD Cohort study was performed to assess details of osteoporosis diagnostics and treatment. BMD measurements, osteoporosis treatment, and IBD medication were recorded.Our chart review revealed 253 dual-energy x-ray absorptiometry (DXA) scans in 877 IBD patients; osteoporosis was prevalent in 20% of tested patients. We identified widely differing osteoporosis screening rates among centers (11%-62%). A multivariate logistic regression analysis identified predictive factors for screening including steroid usage, long disease duration, and perianal disease; even after correction for all risk factors, the study center remained a strong independent predictor (odds ratio 2.3-21 compared to the center with the lowest screening rate). Treatment rates for patients with osteoporosis were suboptimal (55% for calcium, 65% for vitamin D) at the time of chart review. Similarly, a significant fraction of patients with current steroid medication were not treated with vitamin D or calcium (treatment rates 53% for calcium, 58% for vitamin D). For only 29% of patients with osteoporosis bisphosphonate treatment was started. Treatment rates also differed among centers, generally following screening rates. In patients with longitudinal DXA scans, calcium and vitamin D usage was significantly associated with improvement of BMD over time.Our analysis identified inconsistent usage of osteoporosis screening and underuse of osteoporosis treatment in IBD patients. Increasing awareness of osteoporosis as a significant clinical problem in IBD patients might improve patient care

Impact of SARS-CoV-2 on incidence, treatment and outcome of very preterm born infants in Switzerland: a retrospective, population-based cohort study.

AIMS OF THE STUDY To assess whether the COVID-19 pandemic caused by SARS-CoV-2 had an impact on incidence, treatment or major adverse short-term outcome of preterm-born infants in Switzerland. METHODS Retrospective cohort study of preterm infants born in 2020 based on two independent data sources from the Swiss Federal Statistics Office (FSO) and SwissNeoNet. Based on FSO data, we calculated the odds ratios for extremely preterm (22-27 weeks gestation), very preterm (28-31 weeks gestation), and late preterm (32-36 weeks gestation) births during the pandemic. Based on SwissNeoNet data of infants born between 22 and 31 weeks gestation, we compared infants born during the Swiss lockdown period in 2020 with infants born during the same period between 2015 and 2019, all infants of 2020 with all infants between 2015 and 2019 and infants born to mothers tested SARS-CoV-2 positive and negative. Possible associations with the pandemic were tested using logistic regression adjusted for case-mix. As a control, we compared births of 2019 with those of 2015-2018. RESULTS The FSO data revealed equivalent odds for extremely preterm births in 2020 (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.89-1.14), as well as somewhat lower odds ratios for very preterm (OR 0.9, 95% CI 0.82-1.00) and late preterm (OR 0.91, 95% CI 0.88-0.93) births in 2020. A comparison between 2019 and 2015-2018, however, revealed matching odds ratios rendering an association to the pandemic unlikely. In the SwissNeoNet data, 137 infants were born during lockdown in 2020 compared with 134 births per year during 2015-2019. When including all infants, 744 infants were compared to 845 births, respectively. The only difference observed in treatments and short term outcomes between 2020 and the reference years were a higher odds for respiratory distress syndrome (OR 1.6, 95% CI 1.08-2.37) and provision of continuous positive airway pressure (CPAP) (OR 1.39, 95% CI 1.05-1.84). CONCLUSIONS Our Swiss population-based analysis did not identify the elsewhere reported association between the COVID-19 pandemic and a reduced preterm birth rate. However, we can confirm a possible link between the COVID-19 pandemic and higher odds of respiratory distress syndrome, possibly coupled with CPAP requirements. Further observation of potential effects of the pandemic on health and health care provision to newborns may however be indicated based on the literature available so far and that our data only covers the first 9 months of the current pandemic

Impact of SARS-CoV-2 on incidence, treatment and outcome of very preterm born infants in Switzerland: a retrospective, population-based cohort study

AIMS OF THE STUDY: To assess whether the COVID-19 pandemic caused by SARS-CoV-2 had an impact on incidence, treatment or major adverse short-term outcome of preterm-born infants in Switzerland. METHODS: Retrospective cohort study of preterm infants born in 2020 based on two independent data sources from the Swiss Federal Statistics Office (FSO) and SwissNeoNet. Based on FSO data, we calculated the odds ratios for extremely preterm (22-27 weeks gestation), very preterm (28-31 weeks gestation), and late preterm (32-36 weeks gestation) births during the pandemic. Based on SwissNeoNet data of infants born between 22 and 31 weeks gestation, we compared infants born during the Swiss lockdown period in 2020 with infants born during the same period between 2015 and 2019, all infants of 2020 with all infants between 2015 and 2019 and infants born to mothers tested SARS-CoV-2 positive and negative. Possible associations with the pandemic were tested using logistic regression adjusted for case-mix. As a control, we compared births of 2019 with those of 2015-2018. RESULTS: The FSO data revealed equivalent odds for extremely preterm births in 2020 (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.89-1.14), as well as somewhat lower odds ratios for very preterm (OR 0.9, 95% CI 0.82-1.00) and late preterm (OR 0.91, 95% CI 0.88-0.93) births in 2020. A comparison between 2019 and 2015-2018, however, revealed matching odds ratios rendering an association to the pandemic unlikely. In the SwissNeoNet data, 137 infants were born during lockdown in 2020 compared with 134 births per year during 2015-2019. When including all infants, 744 infants were compared to 845 births, respectively. The only difference observed in treatments and short term outcomes between 2020 and the reference years were a higher odds for respiratory distress syndrome (OR 1.6, 95% CI 1.08-2.37) and provision of continuous positive airway pressure (CPAP) (OR 1.39, 95% CI 1.05-1.84). CONCLUSIONS: Our Swiss population-based analysis did not identify the elsewhere reported association between the COVID-19 pandemic and a reduced preterm birth rate. However, we can confirm a possible link between the COVID-19 pandemic and higher odds of respiratory distress syndrome, possibly coupled with CPAP requirements. Further observation of potential effects of the pandemic on health and health care provision to newborns may however be indicated based on the literature available so far and that our data only covers the first 9 months of the current pandemic

Revealing viral and cellular dynamics of HIV-1 at the single-cell level during early treatment periods

While combination therapy completely suppresses HIV-1 replication in blood, functional virus persists in CD4$^{+}$ T cell subsets in non-peripheral compartments that are not easily accessible. To fill this gap, we investigated tissue-homing properties of cells that transiently appear in the circulating blood. Through cell separation and in vitro stimulation, the HIV-1 "Gag and Envelope reactivation co-detection assay" (GERDA) enables sensitive detection of Gag+/Env+ protein-expressing cells down to about one cell per million using flow cytometry. By associating GERDA with proviral DNA and polyA-RNA transcripts, we corroborate the presence and functionality of HIV-1 in critical body compartments utilizing t-distributed stochastic neighbor embedding (tSNE) and density-based spatial clustering of applications with noise (DBSCAN) clustering with low viral activity in circulating cells early after diagnosis. We demonstrate transcriptional HIV-1 reactivation at any time, potentially giving rise to intact, infectious particles. With single-cell level resolution, GERDA attributes virus production to lymph-node-homing cells with central memory T cells (T$_{CM}$s) as main players, critical for HIV-1 reservoir eradication

Impact of different urinary tract infection phenotypes within the first year post-transplant on renal allograft outcomes.

In this study we investigated the clinical impact of different urinary tract infection (UTI) phenotypes occurring within the first year after renal transplantation. The population included 2368 transplantations having 2363 UTI events. Patients were categorized into four groups based on their compiled UTI events observed within the first year after transplantation: (i) no colonization or UTI [n=1404; 59%], (ii) colonization only [n=353; 15%], (iii) occasional UTI with 1-2 episodes [n=456; 19%], and (iv) recurrent UTI with ≥3 episodes [n=155; 7%]. One-year mortality and graft loss rate were not different among the four groups, but patients with recurrent UTI had a 7-10ml/min lower eGFR at one year (44ml/min vs 54, 53 and 51ml/min; p<0.001). UTI phenotypes had no impact on long-term patient survival (p=0.33). However, patients with recurrent UTI demonstrated a 10% lower long-term death-censored allograft survival (p<0.001). Furthermore, recurrent UTI was a strong and independent risk factor for reduced death-censored allograft survival in a multivariable analysis (HR 4.41, 95% CI 2.53-7.68, p<0.001). We conclude that colonization and occasional UTI have no impact on pertinent outcomes, but recurrent UTI are associated with lower one-year eGFR and lower long-term death-censored allograft survival. Better strategies to prevent and treat recurrent UTI are needed