Age differences in the association of comorbid burden with adverse outcomes in SARS-CoV-2.

BACKGROUND: Older age and comorbid burden are both associated with adverse outcomes in SARS-CoV-2, but it is not known whether the association between comorbid burden and adverse outcomes differs in older and younger adults. OBJECTIVE: To compare the relationship between comorbid burden and adverse outcomes in adults with SARS-CoV-2 of different ages (18-64, 65-79 and ≥ 80 years). DESIGN, SETTING, AND PARTICIPANTS: Observational longitudinal cohort study of 170,528 patients who tested positive for SARS-CoV-2 in the US Department of Veterans Affairs (VA) Health Care System between 2/28/20 and 12/31/2020 who were followed through 01/31/2021. MEASUREMENTS: Charlson Comorbidity Index (CCI); Incidence of hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and death within 30 days of a positive SARS-CoV-2 test. RESULTS: The cumulative 30-day incidence of death was 0.8% in cohort members < 65 years, 7.1% in those aged 65-79 years and 20.6% in those aged ≥80 years. The respective 30-day incidences of hospitalization were 8.2, 21.7 and 29.5%, of ICU admission were 2.7, 8.6, and 11% and of mechanical ventilation were 1, 3.9 and 3.2%. Median CCI (interquartile range) ranged from 0.0 (0.0, 2.0) in the youngest, to 4 (2.0, 7.0) in the oldest age group. The adjusted association of CCI with all outcomes was attenuated at older ages such that the threshold level of CCI above which the risk for each outcome exceeded the reference group (1st quartile) was lower in younger than in older cohort members (p < 0.001 for all age group interactions). LIMITATIONS: The CCI is calculated based on diagnostic codes, which may not provide an accurate assessment of comorbid burden. CONCLUSIONS: Age differences in the distribution and prognostic significance of overall comorbid burden could inform clinical management, vaccination prioritization and population health during the pandemic and argue for more work to understand the role of age and comorbidity in shaping the care of hospitalized patients with SARS-CoV-2.

Lifestyle, anthropometric, socio-demographic and perinatal correlates of early adolescence hypertension: The Healthy Growth Study.

BACKGROUND AND AIMS: Various lifestyle, anthropometric, socio-demographic and perinatal characteristics have been separately associated with elevated blood pressure in children and adolescents. The aim of this study was to simultaneously evaluate all potential risk factors and to identify the most dominant correlates of early adolescence hypertension in a large group of school children 9-13 years old. METHODS AND RESULTS: A cross-sectional study with 1444 schoolchildren 9-13 years old, having full data on lifestyle, anthropometric, socio-demographic and perinatal indices, as well as blood pressure measurements. Early adolescents born large for their gestational age (LGA) (OR, 95% C.I. 0.49 (0.25-0.97)), those with higher levels of moderate to vigorous physical activity (MVPA) (OR, 95% C.I. 0.71 (0.53-0.96)) and those of a higher socioeconomic status (SES) (OR, 95% C.I. 0.51 (0.33-0.79)), had lower risk of hypertension, compared with their counterparts with appropriate birth weight, low levels of PA and with low SES respectively, independently of the variables used in the multivariate model. On the other hand, overweight and obese early adolescents (OR, 95% C.I. 2.61 (1.88-3.62)), those with central obesity (OR, 95% C.I. 1.75 (1.12-2.73)) and those having a hypertensive father (OR, 95% C.I. 1.93 (1.20-3.12)) had higher risk of hypertension compared with normal weight early adolescents and those without a family history of hypertension. CONCLUSIONS: Among the parameters examined, early adolescence abnormal body weight and central obesity, low PA, non LGA, low SES family and family history of hypertension were found to be independently associated with higher risk of hypertension. The identified correlates of early adolescence hypertension can be used by public health initiatives for early detection and management of this major public health problem, prioritizing early adolescents and families at the highest possible risk for hypertension.

Implications of HCV RNA level at week 4 of direct antiviral treatments for hepatitis C.

We aimed to determine whether the HCV viral load after four weeks of treatment (W4VL) with direct-acting antiviral agents (DAAs) predicts sustained virologic response (SVR) in a real-world clinical setting. We identified 21 095 patients who initiated DAA-based antiviral treatment in the national Veterans Affairs (VA) healthcare system from 01/01/2014 to 06/30/2015. Week 4 viral load was categorized as undetectable, detectable below quantification (DBQ), detectable above quantification (DAQ) with viral load ≤42 IU/mL and DAQ with viral load >42 IU/mL. Week 4 viral load was undetectable in 36.1%, detectable below quantification in 45.6%, DAQ ≤42 in 9.3%, DAQ >42 in 9.1%. Detectable above quantification was much more common and undetectable week 4 viral load much less common when tested with the Abbott RealTime HCV assay vs the Roche COBAS AmpliPrep/COBAS TaqMan Version 2 assay. Compared to patients with undetectable week 4 viral load (SVR=93.5%), those with detectable below quantification (SVR=91.8%, adjusted odds ratio [AOR] 0.79, P-value=.001), DAQ ≤42 (SVR=90.0%, AOR 0.63, P-value<.001) and DAQ >42 (SVR=86.2%, AOR 0.52, P-value<.001) had progressively lower likelihood of achieving SVR after adjusting for baseline characteristics and treatment duration. Among genotype 1-infected patients who were potentially eligible for 8-week sofosbuvir/ledipasvir monotherapy, we did not find evidence that treatment for 12 weeks instead of 8 weeks was associated with higher SVR, even among those with detectable above quantification. In summary, DBQ and DAQ W4VL are very common in real-world practice, contrary to what was reported in clinical trials, and strongly predict reduced SVR across genotypes and clinically relevant patient subgroups. Whether and how week 4 viral load results should influence treatment decisions requires further study.

Transformation of hepatitis C antiviral treatment in a national healthcare system following the introduction of direct antiviral agents.

BACKGROUND: Highly effective direct antiviral agents (DAAs) for hepatitis C virus (HCV) were introduced recently. Their utilisation has been limited by high cost and low access to care. AIM: To describe the effect of DAAs on HCV treatment and cure rates in the United States Veterans Affairs (VA) national healthcare system. METHODS: We identified all HCV antiviral treatment regimens initiated from 1 January 1999 to 31 December 2015 (n = 105 369) in the VA national healthcare system, and determined if they resulted in sustained virological response (SVR). RESULTS: HCV antiviral treatment rates were low (1981-6679 treatments/year) in the interferon era (1999-2010). The introduction of simeprevir and sofosbuvir in 2013 and ledipasvir/sofosbuvir and paritaprevir/ombitasvir/ritonavir/dasabuvir in 2014 were followed by increases in annual treatment rates to 9180 in 2014 and 31 028 in 2015. The number of patients achieving SVR was 1313 in 2010, the last year of the interferon era, and increased 5.6-fold to 7377 in 2014 and 21-fold to 28 084 in 2015. The proportion of treated patients who achieved SVR increased from 19.2% in 1999 and 36.0% in 2010 to 90.5% in 2015. Within 2015, monthly treatment rates ranged from 727 in July to 6868 in September correlating with the availability of funds for DAAs. CONCLUSIONS: DAAs resulted in a 21-fold increase in the number of patients achieving HCV cure. Treatment rates in 2015 were limited primarily by the availability of funds. Further increases in funding and cost reductions of DAAs in 2016 suggest that the VA could cure the majority of HCV-infected Veterans in VA care within the next few years.

Rates and predictors of response to anti-viral treatment for hepatitis C virus in HIV/HCV co-infection in a nationwide study of 619 patients.

BACKGROUND: The effectiveness of anti-viral treatment for hepatitis C virus (HCV) in HIV/HCV co-infected patients in 'real world', clinical practice is unclear. AIMS: To determine the rates and predictors of sustained virological response (SVR) to anti-viral treatment for HCV with pegylated interferon (PEG-IFN) and ribavirin in HIV/HCV co-infected patients. METHODS: We identified all HIV/HCV co-infected patients who received anti-viral treatment with PEG-IFN and ribavirin in the Veterans Affairs healthcare system nationally between 2002 and 2009 (n = 665). RESULTS: Sustained virological response was achieved in 21.6% overall, 16.7% among patients with genotype 1 HCV (n = 491) and 44% among patients with genotype 2 or 3 HCV (n = 116). Among genotype 1-infected patients, characteristics that were negatively associated with SVR independently included baseline HCV viral load >2 million IU/mL [adjusted odds ratio (AOR) 0.41, 95% CI 0.2-0.7], Black race [AOR 0.56 (0.3-0.96)], diabetes [AOR 0.42 (0.2-0.9)], baseline anaemia [AOR 0.42 (0.2-0.97)], serum aspartate aminotransferase/alanine aminotransferase ratio ≥1.2 [AOR 0.48 (0.2-0.97)] and use of zidovudine [AOR 0.41 (0.2-0.9)]; characteristics positively associated with SVR included a starting dose of ribavirin ≥1000-1200 mg/day [AOR 2.0 (1.1-3.7)] and erythropoietin use during treatment [AOR 2.9 (1.6-5.0)]. Among genotype 2 or 3 infected patients, only erythropoietin use was an independent predictor of SVR [AOR 3.1 (1.2-7.8)], while a starting dose of ribavirin >800 mg/day was not associated with SVR. CONCLUSIONS: Sustained virological response rates achieved with PEG-IFN and ribavirin in HIV/HCV co-infected patients are low in clinical practice. The use of erythropoietin was the most important, modifiable factor associated with SVR.

Are patients with Child's A cirrhosis and hepatocellular carcinoma appropriate candidates for liver transplantation?

We aimed to estimate the survival benefit derived from transplantation in patients with stage II hepatocellular carcinoma (HCC) and Child's A cirrhosis, defined as the mean lifetime with transplantation minus the mean lifetime with treatments other than transplantation. We calculated the posttransplantation survival of all adult, first-time, deceased-donor, liver transplant recipients in the United States since the introduction of the Model for End-Stage Liver Disease based priority system in February 2002 (n = 36,791). We estimated the posttreatment survival of patients with Child's A cirrhosis and stage II HCC treated by radiofrequency ablation (RFA) ± transarterial chemoembolization (TACE) or surgical resection by conducting a systematic review of the medical literature. In patients with Child's A cirrhosis and stage II HCC, the estimated median survival benefit of liver transplantation compared to RFA ± TACE was 1.5 months at 3 years (range -3.5 to 5.6) and 5.7 months at 5 years (range 0.7-11.4), whereas compared to surgical resection it was 0.7 months at 3 years (range -2.9 to 3) and 2.8 months at 5 years (range -4.4 to 5.7). Liver transplantation in patients with stage II HCC and Child's A cirrhosis results in a very low survival benefit and may not constitute optimal use of scarce liver donor organs.

[Acquired Gitelman syndrome associated with Sjögren's syndrome and scleroderma]. / Syndrome de Gitelman acquis au cours d'un syndrome de Gougerot-Sjögren associé à une sclérodermie.

Tubulopathy can complicate autoimmune diseases. It is usually a distal tubular acidosis, but Fanconi syndrome or Bartter syndrome has been exceptionally reported. We report a case of acquired Gitelman syndrome in a 32-year-old male who also presented diffuse scleroderma autoimmune thyroiditis, and Sjögren's syndrome. Only three cases of Sjögren syndrome associated with Gitelman syndrome have been previously reported in literature. The absence of other cases in the family and absence of mutation SLC12A3 emphasise the relation between autoimmune disease and this tubulopathy.

Effect of moderate intake of sweeteners on metabolic health in the rat.

The rise in prevalence of obesity, diabetes, metabolic syndrome, and fatty liver disease has been linked to increased consumption of fructose-containing foods or beverages. Our aim was to compare the effects of moderate consumption of fructose-containing and non-caloric sweetened beverages on feeding behavior, metabolic and serum lipid profiles, and hepatic histology and serum liver enzymes, in rats. Behavioral tests determined preferred (12.5-15%) concentrations of solutions of agave, fructose, high fructose corn syrup (HFCS), a combination of HFCS and Hoodia (a putative appetite suppressant), or the non-caloric sweetener Stevia (n=5/gp). HFCS intake was highest, in preference and self-administration tests. Groups (n=10/gp) were then assigned to one of the sweetened beverages or water as the sole source of liquid at night (3 nights/wk, 10wks). Although within the normal range, serum cholesterol was higher in the fructose and HFCS groups, and serum triglycerides were higher in the Agave, HFCS, and HFCS/Hoodia groups (vs. water-controls, p<0.05). Liver histology was normal in all groups with no evidence of steatosis, inflammation, or fibrosis; however serum alanine aminotransferase was higher in the fructose and HFCS groups (vs. water-controls, p<0.05). Serum inflammatory marker levels were comparable among Stevia, agave, fructose, HFCS, and water-consuming groups, however levels of IL-6 were significantly lower in association with the ingestion of Hoodia. There were no differences in terminal body weights, or glucose tolerance assessed by 120-min IVGTTs performed at the end of the 10-week regimen. We conclude that even moderate consumption of fructose-containing liquids may lead to the onset of unfavorable changes in the plasma lipid profile and one marker of liver health, independent of significant effects of sweetener consumption on body weight.

Serum bilirubin and colorectal cancer risk: a population-based cohort study.

BACKGROUND: Bilirubin has antioxidant properties and has been postulated to protect against the development of malignancies. AIM: To investigate whether baseline serum bilirubin concentration predicts the incidence of colorectal cancer in a nationally representative sample of the US population. METHODS: Participants of the first National Health and Nutrition Examination Survey were divided into four groups based on quartiles of baseline serum bilirubin concentration in mg/dL: <0.38 (n = 1410), 0.38 to <0.5 (n = 1287), 0.5 to <0.6 (n = 1048) and > or = 0.6 (n = 1742). The incidence of colorectal cancer during the following 20 years was determined from hospitalization records and death certificates. RESULTS: 110 cases of colorectal cancer-related death or hospitalization were identified among 5487 participants during 88,339 person-years of follow-up (12 per 10,000 person-years). There was no association between baseline serum bilirubin concentration and the incidence of colorectal cancer either in unadjusted analyses or after adjusting for age, gender, ethnicity, smoking, body mass index, alcohol consumption and educational attainment. CONCLUSIONS: Baseline serum bilirubin concentration did not predict the subsequent incidence of colorectal cancer in this population-based cohort study.

Is Helicobacter pylori seropositivity related to body mass index in the United States?

BACKGROUND: Helicobacter pylori infection may decrease serum ghrelin and increase gastric leptin levels, which may, in turn, decrease body mass index. AIM: To determine whether H. pylori seropositivity is associated with body mass index. METHODS: Serum H. pylori and cytotoxin-associated gene product A (CagA) antibody levels were measured on 6724 adult participants of the third National Health and Nutrition Examination Survey (1988-91). We evaluated the association between H. pylori/CagA antibody status [both negative (-/-), H. pylori-positive/CagA-negative (+/-), or both positive (+/+)] and body mass index, adjusting for sociodemographic factors. We also investigated whether H. pylori/cytotoxin-associated gene product A antibody status was associated with fasting serum leptin levels. RESULTS: H. pylori/CagA antibody status was not associated with obesity (body mass index > or = 30 kg/m(2)) [adjusted odds ratio (OR) 1.2, 95% CI: 0.9-1.6 comparing (+/+) to (-/-) and adjusted OR 1.1, 95% CI: 0.8-1.5 comparing (+/-) to (-/-)], overweight (body mass index 25 to <30 kg/m(2)) [adjusted OR 1.0, 95% CI: 0.7-1.2 comparing (+/+) to (-/-) and adjusted OR 1.0, 95% CI: 0.8-1.3 comparing (+/-) to (-/-)], or fasting serum leptin level in the USA population. CONCLUSIONS: H. pylori seropositivity and CagA antibody status are not associated with body mass index or fasting serum leptin level.

Terlipressin for acute esophageal variceal hemorrhage.

BACKGROUND: Terlipressin (triglycyl lysine vasopressin) is a synthetic analogue of vasopressin, which has been used in the treatment of acute variceal hemorrhage. In contrast to vasopressin, terlipressin can be administered as intermittent injections instead of continuous intravenous infusion and it has a safer adverse reactions profile. However, its effectiveness remains uncertain. OBJECTIVES: To determine if treatment with terlipressin improves outcome in acute esophageal variceal hemorrhage and is safe. SEARCH STRATEGY: Randomized clinical trials were identified by searching the following databases (November 1999): The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Controlled Trials Register on The Cochrane Library (Issue 3, 1999), MEDLINE, EMBASE, Biosis, and Current Contents. The bibliographies of identified publications were checked. Experts in the field and the manufacturers of terlipressin were contacted. For the update of this review, no new randomized clinical trials were identified on any of the databases (October 2002). SELECTION CRITERIA: All randomized clinical trials, which compared terlipressin with: (a) placebo or no treatment, (b) balloon tamponade, (c) endoscopic treatment, (d) octreotide, (e) somatostatin and (f) vasopressin, in the setting of acute variceal hemorrhage. DATA COLLECTION AND ANALYSIS: Eligibility, trial quality assessment and data extraction were done independently by two reviewers. The primary outcome measure was mortality. Secondary outcomes were failure of initial hemostasis, rebleeding, procedures required for uncontrolled bleeding or rebleeding, transfusion requirements and length of hospitalization. MAIN RESULTS: Twenty studies were identified for all the comparison groups, involving 1609 patients. There were seven studies (with 443 patients) comparing terlipressin to placebo, five of which were considered to be high quality studies based on the Jadad scale. The meta-analysis indicates that terlipressin was associated with a statistically significant reduction in all cause mortality compared to placebo (relative risk 0.66, 95% confidence interval 0.49 to 0.88). Three studies (with 302 patients) were identified comparing terlipressin to somatostatin, two of which were high quality studies; only one high quality study (219 patients) comparing terlipressin to endoscopic treatment was identified. Within the limited power provided by these small numbers of patients, no statistically significant difference was demonstrated between terlipressin and either somatostatin or endoscopic treatment in any of the outcomes. For the remaining comparison groups (terlipressin versus balloon tamponade, terlipressin versus octreotide, and terlipressin versus vasopressin) only small, low quality studies were identified and no difference was demonstrated in any of the major outcomes. There was no significant difference between the terlipressin group and any of the comparison groups in the number of adverse events that caused death or withdrawal of medication. REVIEWER'S CONCLUSIONS: On the basis of a 34% relative risk reduction in mortality, terlipressin should be considered to be effective in the treatment of acute variceal hemorrhage. Further, since no other vasoactive agent has been shown to reduce mortality in single studies or meta-analyses, terlipressin might be the vasoactive agent of choice in acute variceal bleeding.

Systematic review: terlipressin in acute oesophageal variceal haemorrhage.

BACKGROUND: Controversy exists surrounding pharmacological therapy in acute variceal bleeding. AIM: To determine the efficacy and safety of terlipressin. METHODS: Randomized trials were identified and duplicate, independent, review identified 20 randomized trials involving 1609 patients that compared terlipressin with placebo, balloon tamponade, endoscopic treatment, octreotide, somatostatin or vasopressin for treatment of acute oesophageal variceal haemorrhage. RESULTS: Meta-analysis showed that compared to placebo, terlipressin reduced mortality (relative risk 0.66, 95% CI 0.49-0.88), failure of haemostasis (relative risk 0.63, 95% CI 0.45-0.89) and the number of emergency procedures per patient required for uncontrolled bleeding or rebleeding (relative risk 0.72, 95% CI 0.55-0.93). When used as an adjuvant to endoscopic sclerotherapy, terlipressin reduced failure of haemostasis (relative risk 0.75, 95% CI 0.58-0.96), and had an effect on reducing mortality that approached statistical significance (relative risk 0.74, 95% CI 0.53-1.04). No significant difference was demonstrated between terlipressin and endoscopic sclerotherapy, balloon tamponade, somatostatin or vasopressin. Haemostasis was achieved more frequently with octreotide compared to terlipressin (relative risk 1.62, 95% CI 1.05-2.50), but this result was based on unblinded studies. Adverse events were similar between terlipressin and the other comparison groups except for vasopressin, which caused more withdrawals due to adverse events. CONCLUSIONS: Terlipressin is a safe and effective treatment for acute oesophageal variceal bleeding, with or without adjuvant endoscopic sclerotherapy. Terlipressin appears to reduce mortality in acute oesophageal variceal bleeding compared to placebo, and is the only pharmacological agent shown to do so. Future studies will be required to detect potential mortality differences between terlipressin and other therapeutic approaches.

Terlipressin for acute esophageal variceal hemorrhage.

BACKGROUND: Terlipressin (triglycyl lysine vasopressin) is a synthetic analogue of vasopressin, which has been used in the treatment of acute variceal hemorrhage. In contrast to vasopressin, terlipressin can be administered as intermittent injections instead of continuous intravenous infusion and it has a safer adverse reactions profile. However, its effectiveness remains uncertain. OBJECTIVES: To determine if treatment with terlipressin improves outcome in acute esophageal variceal hemorrhage and is safe. SEARCH STRATEGY: Randomized clinical trials were identified by searching the following databases: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, the Cochrane Hepato-Biliary Group Controlled Trials Register, Biosis, and Current Contents. The bibliographies of identified publications were checked. Experts in the field and the manufacturers of terlipressin were contacted. SELECTION CRITERIA: All randomized clinical trials which compared terlipressin with: (a) placebo or no treatment, (b) balloon tamponade, (c) endoscopic treatment, (d) octreotide, (e) somatostatin and (f) vasopressin, in the setting of acute variceal hemorrhage. DATA COLLECTION AND ANALYSIS: Eligibility, trial quality assessment and data extraction were done independently by two reviewers. The primary outcome measure was mortality. Secondary outcomes were failure of initial hemostasis, rebleeding, procedures required for uncontrolled bleeding or rebleeding, transfusion requirements and length of hospitalization. MAIN RESULTS: Twenty studies were identified for all the comparison groups, involving 1609 patients. There were seven studies (with 443 patients) comparing terlipressin to placebo, five of which were considered to be high quality studies based on the Jadad scale. The meta-analysis indicates that terlipressin was associated with a statistically significant reduction in all cause mortality compared to placebo (relative risk 0.66, 95% confidence interval 0.49 to 0.88). Three studies (with 302 patients) were identified comparing terlipressin to somatostatin, two of which were high quality studies; only one high quality study (219 patients) comparing terlipressin to endoscopic treatment was identified. Within the limited power provided by these small numbers of patients, no statistically significant difference was demonstrated between terlipressin and either somatostatin or endoscopic treatment in any of the outcomes. For the remaining comparison groups (terlipressin versus balloon tamponade, terlipressin versus octreotide and terlipressin versus vasopressin) only small, low quality studies were identified and no difference was demonstrated in any of the major outcomes. There was no difference between the terlipressin group and any of the comparison groups in the number of adverse events that caused death or withdrawal of medication. REVIEWER'S CONCLUSIONS: On the basis of a 34% relative risk reduction in mortality, terlipressin should be considered to be effective in the treatment of acute variceal hemorrhage. Further, since no other vasoactive agent has been shown to reduce mortality in single studies or meta-analyses, terlipressin might be the vasoactive agent of choice in acute variceal bleeding.

Duplex sonography in detection of renal artery stenosis: a simplified approach using new parameters.

A case report illustrating a new investigation for detecting renal artery stenosis (RAS) is reported. Colour Doppler ultrasound evaluation of the readily accessible intrarenal arteries is a fast and accurate technique. Acceleration time and acceleration are the Doppler parameters used for measuring systolic upstroke on the waveforms obtained. Prolonged acceleration time (> or = 0.07s) and diminished acceleration (< or = 3 m/s2) indicate haemodynamically significant stenosis. Intrarenal Doppler ultrasound should provide a safe noninvasive screening examination for the detection of RAS.