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Treating HCV infection reduces overall mortality and reduces the risk of multiple extrahepatic complications. Whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications is unknown.We identified HCV-positive individuals treated for HCV, and propensity score-matched them to HCV-positive/untreated and HCV-uninfected individuals in ERCHIVES between 2002-2016. We extracted cause of death data from the National Center for Health Statistics' National Death Index. Viral hepatitis-associated liver-related mortality rates among treated and untreated HCV-infected persons were calculated by treatment and attainment of sustained virologic response (SVR).Among 50,674 HCV-positive/treated (Group A), 31,749 HCV-positive/untreated (Group B) and 73,526 HCV-uninfected persons (Group C), 8.6% in Group A, 35.0% in Group B, and 14.3% in Group C died. Among those who died, viral hepatitis-associated liver-related mortality rates per 100 patient-years (95% CI) were: 0.28 (0.27-0.30) for Group A; 1.44 (1.38-1.49) for Group B; and 0.06 (0.05-0.06) for Group C; (p0.0001 for both comparisons). Among HCV-positive/treated persons, rates were 0.06 (0.05-0.06) for those with SVR vs. 0.78 (0.74-0.83) for those without SVR. In competing risks Cox proportional hazards analysis, treatment with all-oral DAA regimens (adjusted hazard ratio 0.11; 95% CI 0.09-0.14) and SVR (adjusted hazard ratio 0.10; 95% CI 0.08-0.11) were associated with reduced hazards of liver-related mortality.Treatment for HCV is associated with a significant reduction in viral hepatitis-associated liver-related mortality, which is particularly pronounced in those treated with DAA regimens and those who attain SVR. This may account for a significant proportion of the reduction in all-cause mortality reported in previous studies.Treating hepatitis C virus (HCV) infection is known to reduce overall mortality. However, whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications was previously unknown. Herein, we show that while treating HCV with direct-acting antiviral regimens has numerous extrahepatic benefits, a significant benefit can be attributed specifically to the reduction in liver-related mortality.

Summary Background Type 2 diabetes is affecting people at an increasingly younger age, particularly in the Middle East and in north Africa. We aimed to assess whether an intensive lifestyle intervention would lead to significant weight loss and improved glycaemia in young individuals with early diabetes. Methods This open-label, parallel-group, randomised controlled trial (DIADEM-I), done in primary care and community settings in Qatar, compared the effects of an intensive lifestyle intervention with usual medical care on weight loss and glycaemic outcomes in individuals with type 2 diabetes, aged 18–50 years, with a short diabetes duration (≤3 years), had a BMI of 27·0 kg/m2 or more, and who were from the Middle East and north Africa region. Participants were randomly allocated (1:1) either to the intensive lifestyle intervention group or the usual medical care control group by a computer-generated sequence and an online randomisation service. The intensive lifestyle intervention comprised a total diet replacement phase, in which participants were given formula low-energy diet meal replacement products followed by gradual food reintroduction combined with physical activity support, and a weight-loss maintenance phase, involving structured lifestyle support. Participants in the control group received usual diabetes care, which was based on clinical guidelines. The primary outcome was weight loss at 12 months after receiving the assigned intervention. Our analysis was based on the intention-to-treat principle. Key secondary outcomes included diabetes control and remission. The trial was registered with the ISRCTN registry, ISRCTN20754766, and ClinicalTrials.gov , NCT03225339 . Findings Between July 16, 2017, and Sept 30, 2018, we enrolled and randomly assigned 158 participants (n=79 in each group) to the study. 147 participants (70 in the intervention group and 77 in the control group) were included in the final intention-to-treat analysis population. Between baseline and 12 months, the mean bodyweight of participants in the intervention group reduced by 11·98 kg (95% CI 9·72 to 14·23) compared with 3·98 kg (2·78 to 5·18) in the control group (adjusted mean difference −6·08 kg [95% CI −8·37 to −3·79], p Interpretation Our findings show that the intensive lifestyle intervention led to significant weight loss at 12 months, and was associated with diabetes remission in over 60% of participants and normoglycaemia in over 30% of participants. The provision of this lifestyle intervention could allow a large proportion of young individuals with early diabetes to achieve improvements in key cardiometabolic outcomes, with potential long-term benefits for health and wellbeing. Funding Qatar National Research Fund.

Highlights • Among 16,912 HCW tested, 10.6% tested positive for COVID-19 • 5% acquired infection at a COVID-19 facility and 95% at a non-COVID-19 facility • Exposure to a colleague (45%) or a patient (29%) were reported at non-COVID sites • Full PPE adherence was 82% at COVID-19 but only 68% at non-COVID-19 facilities, Background Our aim was to determine the prevalence of COVID-19 infection in healthcare workers (HCW) in a national healthcare system and to understand the risk factors for infection. Methods The study was conducted at Hamad Medical Corporation in Qatar, a national healthcare system with 14 hospitals and >28,000 employees, between March 10-June 24, 2020. Data on COVID-19+ HCW were retrieved from the electronic health records and employment records, followed by an email survey and a focused telephone interview. Results Among 16,912 HCW tested, 10.6% tested positive. Hospitalization rate was 11.6%, 1.3% required supplemental oxygen, 0.6% needed intensive care unit admission and 0.3% required mechanical ventilation. There were no deaths. In a follow-up survey of 393 HCW, 5% reported acquiring infection at a COVID-19-designated facility and 95% at a non-COVID-19 facility having acquired the infection through accidental exposure to a colleague (45%) or a patient (29%). Full PPE adherence was 82% at COVID-19-designated but only 68% at non-COVID-19 facilities. Conclusions COVID-19 infection among HCW often occurs among those not directly working with COVID-19 patients. PPE use is less stringent in such settings. Risk of exposure and need for strict PPE must be stressed upon all HCW in all settings.

The renal PTH/PTHrP receptor is down-regulated in rats with chronic renal failure. Hypocalcemia, hyperphosphatemia, and resistance to the action of PTH are well characterized features in the setting of advanced chronic renal failure (CRF). Although the underlying mechanisms are ill-understood, clinical and experimental evidence points to both PTH receptor down-regulation and post-receptor abnormalities in their pathogenesis. In the present study we have examined the effect of advanced CRF in rats on the renal expression of PTH/PTHrP receptor (PTH-R). CRF was created by a standard two-step operation (5/6 nephrectomy). Four weeks thereafter, 19 uremic rats were compared with 23 sham-operated rats. Uremic rats had higher mean (± SD) plasma creatinine levels than control rats, 164 ± 107 µM versus 43 ± 5 µM, respectively. They also had higher plasma phosphorus and iPTH levels, 4.70 ± 1.71mM versus 2.59 ± 0.37mM and 561 ± 336 versus 27 ± 18 pg/ml, respectively. Mean plasma total calcium and blood ionized calcium were significantly lower in uremic than in control rats, 2.13 ± 0.06mM versus 2.61 ± 0.10mM and 1.07 ± 0.11 versus 1.31 ±0.06mM, respectively. Mean plasma calcitriol concentration was also significantly lower in uremic than in control rats, 39.8 ± 14.6 and 80.4 ± 15.2 pg/ml, respectively. Nine out of the 19 rats were examined for renal PTH-R gene expression. We show for the first time that the level of PTH-R mRNA in the kidney of uremic rats was markedly decreased compared with that of normal rats, the ratio PTH-R mRNA/β-actin mRNA being 0.47 ± 0.12 versus 0.99 ± 0.23, respectively, and the ratio PTH-R mRNA/28S being 8.9 ± 4.7 versus 19.6 ± 11.1, respectively. This decrease was associated with a marked reduction in PTH-sensitive adenylyl cyclase activity in crude renal membranes from uremic rats. The values of basal adenylyl cyclase activity and subsequently after stimulation by forskolin and NaF were also significantly reduced in comparison to that of normal rats. These data indicate that rats with severe CRF have reduced renal PTH-R expression, associated with diminished basal and PTH-sensitive adenylyl cyclase activity. These abnormalities could be important in the pathogenesis of the secondary hyperparathyroidism of CRF.