Hospital admission rates, length of stay, and in-hospital mortality for common acute care conditions in COVID-19 vs. pre-COVID-19 era.

OBJECTIVES: The impact of COVID-19 upon acute care admission rates and patterns are unknown. We sought to determine the change in rates and types of admissions to tertiary and specialty care hospitals in the COVID-19 era compared with pre-COVID-19 era. METHODS: Acute care admissions to the largest tertiary care referral hospital, designated national referral centers for cardiac, cancer and maternity hospital in the State of Qatar during March 2020 (COVID-19 era) and January 2020 and March 2019 (pre-COVID-19 era) were compared. We calculated total admissions, admissions for eight specific acute care conditions, in-hospital mortality rate, and length of stay at each hospital. RESULTS: A total of 18,889 hospital admissions were recorded. A sharp decline ranging from 9% to 75% was observed in overall admissions. A decline in both elective and non-elective surgeries was observed. A decline of 9%-58% was observed in admissions for acute appendicitis, acute coronary syndrome, stroke, bone fractures, cancer, and live births, whereas an increase in admissions due to respiratory tract infections was observed. Overall length of stay was shorter in the COVID-19 period possibly suggesting lesser overall disease severity, with no significant change in in-hospital mortality. Unadjusted mortality rate for Qatar showed marginal increase in the COVID-19 period. CONCLUSIONS: We observed a sharp decline in acute care hospital admissions, with a significant decline in admissions due to seven out of eight acute care conditions. This decline was associated with a shorter length of stay but not associated with a change in in-hospital mortality rate.

Depression and all-cause mortality risk in HIV-infected and HIV-uninfected US veterans: a cohort study.

OBJECTIVES: The contribution of depression to mortality in adults with and without HIV infection is unclear. We hypothesized that depression increases mortality risk and that this association is stronger among those with HIV infection. METHODS: Veterans Aging Cohort Study (VACS) data were analysed from the first clinic visit on or after 1 April 2003 (baseline) to 30 September 2015. Depression definitions were: (1) major depressive disorder defined using International Classification of Diseases, Ninth Revision (ICD-9) codes; (2) depressive symptoms defined as Patient Health Questionnaire (PHQ)-9 scores ≥ 10. The outcome was all-cause mortality. Covariates were demographics, comorbid conditions and health behaviours. RESULTS: Among 129 140 eligible participants, 30% had HIV infection, 16% had a major depressive disorder diagnosis, and 24% died over a median follow-up time of 11 years. The death rate was 25.3 [95% confidence interval (CI) 25.0-25.6] deaths per 1000 person-years. Major depressive disorder was associated with mortality [hazard ratio (HR) 1.04; 95% CI 1.01, 1.07]. This association was modified by HIV status (interaction P-value = 0.02). In HIV-stratified analyses, depression was significantly associated with mortality among HIV-uninfected veterans but not among those with HIV infection. Among those with PHQ-9 data (n = 7372), 50% had HIV infection, 22% had PHQ-9 scores ≥ 10, and 28% died over a median follow-up time of 12 years. The death rate was 27.3 (95% CI 26.1-28.5) per 1000 person-years. Depressive symptoms were associated with mortality (HR 1.16; 95% CI 1.04, 1.28). This association was modified by HIV status (interaction P-value = 0.05). In HIV-stratified analyses, depressive symptoms were significantly associated with mortality among veterans with HIV infection but not among those without HIV infection. CONCLUSIONS: Depression was associated with all-cause mortality. This association was modified by HIV status and method of depression ascertainment.

Tricyclic antidepressant use and the risk of fibrosis progression in hepatitis C-infected persons: Results from ERCHIVES.

Recent preclinical studies have suggested an antifibrotic role for tricyclic antidepressants (TCA). Using the Electronically Retrieved Cohort of hepatitis C virus (HCV) Infected Veterans, we aimed to evaluate the impact of TCA use on fibrosis progression and development of hepatocellular carcinoma (HCC) among HCV-infected persons. Subjects were categorized according to use of TCAs, selective serotonin reuptake inhibitors (SSRI) or no antidepressants. TCAs or selective serotonin uptake inhibitors use was defined according to cumulative defined daily dose (cDDD), and categories were mutually exclusive. Subjects with HIV coinfection, hepatitis B surface antigen (HbsAg) positivity, cirrhosis or HCC at baseline were excluded. Outcomes were liver fibrosis progression measured by APRI scores and incident HCC. We utilized Cox proportional hazards regression to determine predictors of cirrhosis, defined as APRI > 2, and incident hepatocellular carcinoma (iHCC). Among 128 201 eligible HCV+ persons, 4% received TCAs, 43% received selective serotonin uptake inhibitors, and 53% received no antidepressants. Fewer TCAs users had drug abuse (34% and 43%) and alcohol abuse (32% vs 42%) compared to selective serotonin uptake inhibitor users. After adjusting for age, baseline APRI score, diabetes, hypertension, alcohol use, drug abuse and HCV RNA levels, TCAs use was associated with decreased risk of cirrhosis (hazard ratio [HR] = 0.77, 95% CI = 0.60, 0.99) and delayed time to development of cirrhosis, but not with decreased iHCC. In conclusion among a large cohort of HCV-positive Veterans, TCAs use was associated with decreased fibrosis progression and lower risk of developing cirrhosis. These data provide supportive evidence for the beneficial effects of TCAs on progression of liver fibrosis in patients with chronic HCV infection.

Risk of End-Stage Renal Disease in HIV-Positive Potential Live Kidney Donors.

New federal regulations allow HIV-positive individuals to be live kidney donors; however, potential candidacy for donation is poorly understood given the increased risk of end-stage renal disease (ESRD) associated with HIV infection. To better understand this risk, we compared the incidence of ESRD among 41 968 HIV-positive participants of North America AIDS Cohort Collaboration on Research and Design followed for a median of 5 years with the incidence of ESRD among comparable HIV-negative participants of National Health and Nutrition Examination III followed for a median of 14 years. We used risk associations from multivariable Cox proportional hazards regression to derive cumulative incidence estimates for selected HIV-positive scenarios (no history of diabetes, hypertension, AIDS, or hepatitis C virus coinfection) and compared these estimates with those from similarly selected HIV-negative scenarios. For 40-year-old HIV-positive individuals with health characteristics that were similar to those of age-matched kidney donors, viral load <400 copies/mL, and CD4+ count ≥500 cells/µL, the 9-year cumulative incidence of ESRD was higher than that of their HIV-negative peers, yet still low: 2.5 versus 1.1 per 10 000 among white women, 3.0 versus 1.3 per 10 000 among white men, 13.2 versus 3.6 per 10 000 among black women, and 15.8 versus 4.4 per 10 000 among black men. HIV-positive individuals with no comorbidities and well-controlled disease may be considered low-risk kidney donor candidates.

Performance of the Pooled Cohort atherosclerotic cardiovascular disease risk score in hepatitis C virus-infected persons.

Chronic hepatitis C virus (HCV) infection has been associated with an increased risk for cardiovascular disease (CVD). The recommended Pooled Cohort atherosclerotic cardiovascular disease (ASCVD) risk equation for estimation of 10-year CVD risk has not been validated in HCV-infected populations. We examined the performance of the ASCVD risk score in HCV-infected persons, using the national Electronically Retrieved Cohort of HCV Infected Veterans to derive a cohort of HCV-infected and uninfected subjects without baseline ASCVD, hepatitis B, or HIV infection, and with low-density lipoprotein cholesterol level<190 mg/dL. Performance of the ASCVD risk equation was assessed by Cox proportional hazard regression, C-statistics and Hosmer-Lemeshow statistic. The cohort included 70 490 HCV-infected and 97 766 HCV-uninfected men with mean age of 55 years, 56% White and 29% Black. Incident CVD event rates were similar between the two groups (13.2 and 13.4 events/1000 person-years), with a higher incidence of coronary heart disease events in the HCV-uninfected group and of stroke events in the HCV-infected group. Adjusting for ASCVD risk score, HCV infection was associated with higher risk for an ASCVD event in the subgroup with baseline ASCVD risk ≥7.5% (HR: 1.19, P<.0001). C-statistics were poor in both the HCV-infected and uninfected groups (0.60 and 0.61, respectively). By Hosmer-Lemeshow test, the ASCVD risk equation overestimated risk amongst lower risk patients and underestimated risk amongst higher risk patients in both the HCV-infected and uninfected groups. Further investigation is needed to determine whether a modified equation to accurately predict ASCVD risk in HCV-infected persons is warranted.

Comparing clinical outcomes in HIV-infected and uninfected older men hospitalized with community-acquired pneumonia.

OBJECTIVES: Outcomes of community-acquired pneumonia (CAP) among HIV-infected older adults are unclear. METHODS: Associations between HIV infection and three CAP outcomes (30-day mortality, readmission within 30 days post-discharge, and hospital length of stay [LOS]) were examined in the Veterans Aging Cohort Study (VACS) of male Veterans, age ≥ 50 years, hospitalized for CAP from 10/1/2002 through 08/31/2010. Associations between the VACS Index and CAP outcomes were assessed in multivariable models. RESULTS: Among 117 557 Veterans (36 922 HIV-infected and 80 635 uninfected), 1203 met our eligibility criteria. The 30-day mortality rate was 5.3%, the mean LOS was 7.3 days, and 13.2% were readmitted within 30 days of discharge. In unadjusted analyses, there were no significant differences between HIV-infected and uninfected participants regarding the three CAP outcomes (P > 0.2). A higher VACS Index was associated with increased 30-day mortality, readmission, and LOS in both HIV-infected and uninfected groups. Generic organ system components of the VACS Index were associated with adverse CAP outcomes; HIV-specific components were not. Among HIV-infected participants, those not on antiretroviral therapy (ART) had a higher 30-day mortality (HR 2.94 [95% CI 1.51, 5.72]; P = 0.002) and a longer LOS (slope 2.69 days [95% CI 0.65, 4.73]; P = 0.008), after accounting for VACS Index. Readmission was not associated with ART use (OR 1.12 [95% CI 0.62, 2.00] P = 0.714). CONCLUSION: Among HIV-infected and uninfected older adults hospitalized for CAP, organ system components of the VACS Index were associated with adverse CAP outcomes. Among HIV-infected individuals, ART was associated with decreased 30-day mortality and LOS.

Virologic response and haematologic toxicity of boceprevir- and telaprevir-containing regimens in actual clinical settings.

Effectiveness, safety and tolerability of boceprevir (BOC) and telaprevir (TPV) in actual clinical settings remain unknown. We determined rates of sustained virologic response (SVR) and haematologic adverse effects among persons treated with BOC- or TPV-containing regimens, compared with pegylated interferon/ribavirin (PEG/RBV). Using an established cohort of hepatitis C virus (HCV)-infected persons, Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), we identified those treated with a BOC- or TPV-containing regimen and HCV genotype 1-infected controls treated with PEG/RBV. We excluded those with HIV coinfection and missing HCV RNA values to determine SVR. Primary endpoints were SVR (undetectable HCV RNA ≥12 weeks after treatment completion) and haematologic toxicity (grade 3/4 anaemia, neutropenia and thrombocytopenia). We evaluated 2288 persons on BOC-, 409 on TPV-containing regimen and 6308 on PEG/RBV. Among these groups, respectively, 31%, 43% and 9% were treatment-experienced; 17%, 37% and 14% had baseline cirrhosis; 63%, 54% and 48% were genotype 1a. SVR rates among noncirrhotics were as follows: treatment naïve: 65% (BOC), 67% (TPV) and 31% (PEG/RBV); treatment experienced: 57% (BOC), 54% (TPV) and 13% (PEG/RBV); (P-value not significant for BOC vs TPV; P < 0.0001 for BOC or TPV vs PEG/RBV). Haematologic toxicities among BOC-, TPV- and PEG/RBV-treated groups were as follows: grade 3/4 anaemia 7%, 11% and 3%; grade 4 thrombocytopenia 2.2%, 5.4% and 1.7%; grade 4 neutropenia 8.2%, 5.6% and 3.4%. SVR rates are higher and closer to those reported in pivotal clinical trials among BOC- and TPV-treated persons compared with PEG/RBV-treated persons. Haematologic adverse events are frequent, but severe toxicity is uncommon.

Hepatitis C virus treatment and survival in patients with hepatitis C and human immunodeficiency virus co-infection and baseline anaemia.

The impact of pretreatment anaemia on survival in individuals with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection is not known. Moreover, HCV treatment is offered less frequently to individuals with anaemia, due to haematological side effects of the treatment regimen. This study aimed to determine the effect of HCV treatment on survival among HCV/HIV co-infected individuals with pretreatment anaemia using the Electronically Retrieved Cohort of HCV-Infected Veterans (ERCHIVES). Individuals with HCV/HIV co-infection were included in current analyses. Participants were considered treated if they were prescribed ≥ 4 weeks of HCV treatment. All-cause mortality data were obtained using record linkage. Survival analyses were performed using Cox proportional hazard models. Among 5000 HCV/HIV co-infected individuals, 1671 (33.4%) had pretreatment anaemia. In a follow-up period of up to 7 years (19,500 person-years), individuals with anaemia had significantly higher mortality rate compared with those without anaemia [144.2 (95% CI: 134.5-154.7) vs 47.5 (44.0-51.2) per 1000 person-years, respectively]. Among individuals with anaemia, HCV treatment was associated with significantly lower mortality rate [66.6 (44.3-100.2) vs 149.6 (139.2-160.5) per 1000 person-years, for treated vs untreated, respectively]. Treatment remained associated with substantial survival benefit after taking into account the effect of multiple comorbidities (hazards ratio: 0.34, 95% CI: 0.21-0.62). These data suggest that HCV/HIV co-infected individuals with pretreatment anaemia have significantly higher mortality compared with those without anaemia. HCV treatment is associated with substantial survival benefit in this group. Additional studies are needed to determine strategies to improve HCV treatment rates among this group.

Health-related quality of life in subjects with HCV/HIV coinfection: results from ACTG 5178 study.

Although health-related quality of life (HRQOL) is diminished in HCV/HIV, the relationship between virologic response and maintenance therapy with HRQOL in this population is unknown. ACTG 5178 was a phase 2, randomized trial, with three steps - Step 1: all subjects received pegylated interferon (PEG-IFN)/ribavirin (P/R) for 12 weeks. Step 2: subjects who failed to achieve early viral response (EVR) were randomized to PEG-IFN or observational control for an additional 72 weeks. Step 3: subjects with EVR from step 1 continued on P/R for a total of 72 weeks with 24 weeks follow-up off-therapy. HRQOL, symptom distress and depression levels were measured at multiple time points. In step 1 (n = 329), there was a significant decline in HRQOL in all dimensions. In step 3 (n = 169), the overall HRQOL and three of its eight dimensions (general health, role function and pain score) were increased, and achievement of sustained virologic response was associated with increased general health and cognitive function. In step 2 (n = 85), there was no significant change in HRQOL and no significant difference between groups (PEG-IFN vs observational control). There was a significant decline in HRQOL during the initial 12 weeks of therapy. Thereafter, the HRQOL profile differed for subjects with EVR vs without EVR. Maintenance therapy with PEG-IFN had no impact on the HRQOL.

Hepatitis B reactivation and outcomes in persons treated with directly acting antiviral agents against hepatitis C virus: results from ERCHIVES.

BACKGROUND: Higher risk of hepatitis B reactivation (HBV-r) has been reported in patients with hepatitis C treated with newer directly acting antiviral agents (DAAs). AIM: To determine the proportion of persons who develop HBV-r and its clinical consequences among DAA treated vs pegylated interferon/ribavirin (PEG/RBV) treated persons. METHODS: We calculated the proportion of persons who developed HBV viral reactivation (HBV-r; new detectable HBV DNA or increase of >1 log10 ); serum alanine aminotransferase flare (>5 times baseline); all-cause mortality and hepatic decompensation in persons treated with a newer DAA regimen or PEG/RBV. Kaplan-Meier curves were used to demonstrate survival and hepatic decompensation by treatment group and HBV-r. RESULTS: In 34 632 persons treated with DAA and 23 475 treated with PEG/RBV, HBV-r rate per 1000 person-years was 30.04 (10.41, 49.67) and 25.42 (95% CI 17.23, 33.62) respectively (P = .8). When stratified by SVR or by baseline HBsAg status, HBV-r was not different between groups. Kaplan-Meier survival curves comparing each regimen stratified by presence or absence of HBV-r did not demonstrate a significant difference in incidence of hepatic decompensation over time. For overall survival, there was no difference between PEG/RBV treated persons with or without HBV-r. For DAA treated persons, those with HBV-r had a shortened survival, though the numbers at risk were small. CONCLUSIONS: HBV-r is relatively uncommon after DAA therapy and not higher than among those treated with a PEG/RBV regimen. The small numbers of persons treated with a DAA regimen who do develop HBV-r have a shortened survival compared to those without HBV-r.

Proton pump inhibitors are associated with accelerated development of cirrhosis, hepatic decompensation and hepatocellular carcinoma in noncirrhotic patients with chronic hepatitis C infection: results from ERCHIVES.

BACKGROUND: Proton pump inhibitors are among the most commonly prescribed medications in the United States. Their safety in cirrhosis has recently been questioned, but their overall effect on disease progression in noncirrhotic patients with chronic liver disease remains unclear. AIM: To determine the impact of proton pump inhibitors on the progression of liver disease in noncirrhotic patients with hepatitis C virus (HCV) infection. METHODS: Using the electronically retrieved cohort of HCV-infected veterans (ERCHIVES) database, we identified all subjects who received HCV treatment and all incident cases of cirrhosis, hepatic decompensation and hepatocellular carcinoma. Proton pump inhibitor use was measured using cumulative defined daily dose. Multivariate Cox regression analysis was performed after adjusting univariate predictors of cirrhosis and various indications for proton pump inhibitor use. RESULTS: Among 11 526 eligible individuals, we found that exposure to proton pump inhibitors was independently associated with an increased risk of developing cirrhosis (hazard ratio [HR]: 1.32; 95% confidence interval: [1.17, 1.49]). This association remained robust to sensitivity analysis in which only patients who achieved sustained virologic response were analysed as well as analysis excluding those with alcohol abuse/dependence. Proton pump inhibitor exposure was also independently associated with an increased risk of hepatic decompensation (HR: 3.79 [2.58, 5.57]) and hepatocellular carcinoma (HR: 2.01 [1.50, 2.70]). CONCLUSIONS: In patients with chronic HCV infection, increasing proton pump inhibitor use is associated with a dose-dependent risk of progression of chronic liver disease to cirrhosis, as well as an increased risk of hepatic decompensation and hepatocellular carcinoma.

Effectiveness, treatment completion and safety of sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir + dasabuvir in patients with chronic kidney disease: an ERCHIVES study.

BACKGROUND: Chronic kidney disease (CKD) was a relative contraindication to hepatitis C virus (HCV) treatment in the interferon/ribavirin era. AIM: To determine the efficacy, tolerability and safety of sofosbuvir/ledipasvir (SOF/LDV) and paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens in persons with CKD. METHODS: We identified persons initiated on a SOF/LDV or PrOD regimen from October 30, 2014 to April 30, 2016. We excluded those with missing HCV genotype or eGFR values. We determined treatment completion and sustained virologic response (SVR) rates, and proportion developing worsening renal function or grade 3/4 haematologic toxicity. RESULTS: Among 13 663 persons on SOF/LDV±ribavirin, 14% and 1% persons had CKD Stage 3 and 4-5 respectively, 67.8% completed treatment, 98.2% achieved SVR. Treatment completion or SVR rates did not decline with advanced CKD or ribavirin administration. Among 3961 persons on PrOD±ribavirin, 9% and 3% persons had CKD Stage 3 and 4-5, respectively, 74.0% completed treatment and 98.2% achieved SVR. A decrease in treatment completion rates was seen in CKD stage 4-5 and those on ribavirin, but this did not impact SVR rates. A >10 mL/min/1.73 m2 drop in eGFR from baseline was observed in 30%-38% of persons with baseline eGFR ≥60 mL/min/1.73 m2 , but in only 0%-6% with CKD4-5. Grade 3/4 anaemia was more frequent in persons with CKD4-5, but ribavirin co-administration did not appear to affect this. CONCLUSIONS: SOF/LDV and PrOD achieved high SVR rates in CKD population. Treatment completion rates were lower than expected. A decline in eGFR and development of anaemia were observed in a substantial proportion of persons, but the clinical implications remain unclear.

Do directly acting antiviral agents for HCV increase the risk of hepatic decompensation and decline in renal function? Results from ERCHIVES.

BACKGROUND: Directly acting antiviral agents (DAA) have been associated with hepatic decompensation, especially in patients with pre-treatment cirrhosis, but this risk is not well defined. AIM: To determine the incidence of hepatic decompensation, liver transplantation, death and worsening renal function in patients treated with a Paritaprevir/ritonavir, Ombitasvir, Dasabuvir (PrOD), sofosbuvir/simeprevir or sofosbuvir/ledipasvir regimen. METHODS: We followed ERCHIVES participants treated with the above regimens for up to 12 weeks post-treatment. We excluded those with HIV, HBsAg+ and pre-existing diagnosis of hepatic decompensation and hepatocellular carcinoma. RESULTS: Of 3728 persons on PrOD, 1578 on sofosbuvir/simeprevir and 10 440 on sofosbuvir/ledipasvir, incidence rates (95% CI) of hepatic decompensation/1000 patient-years were 10.6 (5.89-17.36) for the PrOD, 32.4 (20.74-48.16) for the sofosbuvir/simeprevir and 13.0 (9.74-17.10) for the sofosbuvir/ledipasvir. Among those with baseline cirrhosis, these rates were 36.9 (19.1-64.5), 61.8 (38.2-94.5) and 41.1 (29.9-55.2) respectively, while among those without cirrhosis at baseline, these rates were 2.7 (0.6-8.0), 7.5 (1.5-21.8) and 2.7 (1.2-5.4). Advanced fibrosis was associated with increased risk of hepatic decompensation in all groups [HR (95% CI) per 0.5 unit increase in FIB-4 score: PrOD 1.11 (1.07-1.16); sofosbuvir/simeprevir 1.03 (1.01-1.05); sofosbuvir/ledipasvir 1.02 (1.01-1.03)]. There were no deaths. Proportion of persons with eGFR decrease >30 ml/min/1.73 m2 was higher among the PrOD group, but presence of cirrhosis did not appear to affect this. CONCLUSIONS: The incidence of hepatic decompensation in persons treated with PrOD, up to 12 weeks after completion of treatment, was comparable to those treated with sofosbuvir/ledipasvir regimen, and was lower than among those treated with a sofosbuvir/simeprevir regimen. Such risk was predominantly observed in those with pre-treatment cirrhosis.

Rates and predictors of hepatitis C virus treatment in HCV-HIV-coinfected subjects.

BACKGROUND: True treatment rates and the impact of comorbidities on treatment rates for hepatitis C virus in the HCV-HIV-coinfected subjects are unknown. AIM: To quantify the rates of treatment prescription and the effect of comorbidities on hepatitis C virus treatment rates in HCV-HIV-coinfected veterans. METHODS: The Veterans Affairs National Patient Care Database was used to identify all hepatitis C virus-infected subjects between 1999 and 2003 using ICD-9 codes. Demographics, comorbidities and pharmacy data were retrieved. We used logistic regression to compare the predictors of hepatitis C virus treatment in hepatitis C virus-monoinfected and HCV-HIV-coinfected subjects. FINDINGS: We identified 120 507 hepatitis C virus-infected subjects, of which 6502 were HIV coinfected. 12% of the hepatitis C virus-monoinfected and 7% of the -coinfected subjects were prescribed hepatitis C virus treatment (P < 0.0001). Those not prescribed treatment were older (48.6 years vs. 47.7 years, P = 0.007) and more likely to be black (52% vs. 32%, P < 0.0001). HIV coinfected was less likely to be prescribed hepatitis C virus treatment (OR 0.74, 95% CI: 0.67-0.82). Among the coinfected subjects, the following were associated with non-treatment (OR, 95% CI): black race (0.45, 0.35-0.57); Hispanic race (0.56, 0.38-0.82); drug use (0.68, 0.53-0.88); anaemia (0.17, 0.11-0.26); bipolar disorder (0.63, 0.40-0.99); major depression (0.72, 0.53-0.99); mild depression (0.47, 0.35-0.62). CONCLUSIONS: A small number of HCV-HIV-coinfected veterans are prescribed treatment for hepatitis C virus. Non-treatment is associated with increasing age, minority race, drug use and psychiatric illness. Further studies are needed to determine the eligibility for treatment and reasons for non-treatment for hepatitis C virus.

Adding ribavirin to newer DAA regimens does not affect SVR rates in HCV genotype 1 infected persons: results from ERCHIVES.

BACKGROUND: Ribavirin is a key component of several hepatitis C virus (HCV) treatment regimens. However, its utility in combination with newer directly acting anti-viral agents regimens is unclear. AIM: To determine the SVR rates with paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimen ± ribavirin and compare this with sofosbuvir/simeprevir and sofosbuvir/ledipasvir regimens. METHODS: We used Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a well-established national cohort of HCV-infected Veterans to identify HCV genotype 1 infected persons initiated on the above regimens. We excluded those with HIV coinfection, positive HBsAg and missing HCV RNA. RESULTS: We identified 1235 persons on PrOD (75.5% ribavirin), 1254 on sofosbuvir/simeprevir (16.9% ribavirin) and 4247 on sofosbuvir/ledipasvir (23.3% ribavirin). Among HCV genotype 1a infected persons, ribavirin was prescribed to 99.2% on PrOD, 18.2% on sofosbuvir/simeprevir and 23.3% on sofosbuvir/ledipasvir. The SVR rates ranged from 92.6% to 100% regardless of the treatment regimen, presence of cirrhosis or HCV subtype, except in PrOD group without ribavirin, HCV genotype 1a without cirrhosis (SVR 80%, N = 5). There were minor, clinically insignificant differences in SVR rates in those treated with or without ribavirin in each of the treatment groups, regardless of presence of cirrhosis at baseline. In multivariable logistic regression analysis, ribavirin use was not associated with achieving SVR in any group. CONCLUSIONS: In HCV genotype 1 infected persons, PrOD, sofosbuvir/simeprevir and sofosbuvir/ledipasvir regimens, are associated with high rates of SVR in actual clinical settings, which are comparable to clinical trials results (except PrOD genotype 1a with cirrhosis where the number was too small). The benefit of adding ribavirin to these regimens in the ERCHIVES treated cohort is not established.

Personal digital assistant infectious diseases applications for health care professionals.

Personal digital assistants (PDAs; also known as "handheld computers," "pocket personal computers," and Palm Pilots) provide immediate access to vital and clinically relevant infectious diseases information at the point of care. Several infectious diseases applications are available that provide information on pathogens, diagnosis, medication, and treatment. In this article, 4 infectious diseases PDA applications are reviewed: ePocrates ID (part of ePocrates Rx Pro), the Johns Hopkins Division of Infectious Diseases Antibiotic Guide, the 2002 Sanford Guide to Antimicrobial Therapy, and Infectious Diseases and Antimicrobials Notes. Drug information, including clinical pharmacology, dosing in patients with renal insufficiency, adverse reactions, and drug interactions, is evaluated for completeness and accuracy by comparison of each application with the package insert. Treatment recommendations for 6 diseases are compared with current practice guidelines. Each PDA infectious diseases application reviewed has unique advantages and disadvantages. This critical review will help health care professionals select the infectious diseases PDA application best tailored to meet their individual information needs.

Nasal tuberculosis in the 20th century.

During the last decade, tuberculosis has reemerged as a major health problem in the United States. Much of the blame for this resurgence has been attributed to human immunodeficiency virus infection, although homelessness and deterioration of the social infrastructure have also been implicated. Extrapulmonary tuberculosis is uncommon, and nasal tuberculosis is rare. The latter usually manifests as nasal obstruction or discharge. Only 35 cases of nasal tuberculosis were identified in a search of the English-language medical literature from the last 95 years. They are reviewed here. In addition, we describe a new manifestation of nasal tuberculosis, exemplifying the variety of ways in which this may occur.

Cervical adenitis due to Mycobacterium fortuitum in patients with acquired immunodeficiency syndrome.

Rapidly growing mycobacteria, an infrequent cause of human disease, are increasingly being recognized as human pathogens rather than mere colonizers. Rapidly growing mycobacteria infrequently cause disease in patients with acquired immunodeficiency syndrome (AIDS). It is unclear whether patients with AIDS are more predisposed than others to infection by these organisms. The optimal regimen and duration of treatment is similarly uncertain. Mycobacterium fortuitum is a rare cause of lymphadenitis or neck abscess. We report two cases of M fortuitum neck abscesses in patients with AIDS which were successfully treated with antibiotics after initial drainage. In one of these patients, M fortuitum neck abscess was the AIDS-defining illness. We also present a review of the cases reported in literature. It appears that such infections may be treated with a combination of ciprofloxacin and clarithromycin after incision and drainage of the abscess.

Non Candida albicans fungal peritonitis in continuous ambulatory peritoneal dialysis patients.

We report four episodes of non Candida albicans peritonitis (NCAP) in 3 patients on continuous ambulatory peritoneal dialysis (CAPD). Risk factors for NCAP included diabetes mellitus and prior antibiotic use in half of the cases. The antibiotic treatment was prescribed for exit-site infection (ESI) or peritonitis in the patient. Treatment for NCAP included antifungal therapy with oral fluconazole or intravenous amphotericin B. The NCAP resulted in catheter loss in 100% of the patients over time. Initial catheter salvage in one patient was followed 6 months later by catheter loss following treatment of a bacterial peritonitis that was complicated by the development of Candida (Torulopsis) glabrata peritonitis unresponsive to treatment with intravenous amphotericin B. Although the literature suggests that Candida peritonitis responds to oral fluconazole with and without catheter removal, this series suggests that the treatment of NCAP includes removal of the peritoneal dialysis catheter with appropriate antifungal agents.

The incidence, predictors and management of anaemia and its association with virological response in HCV / HIV coinfected persons treated with long-term pegylated interferon alfa 2a and ribavirin.

BACKGROUND: The association of anaemia with outcomes in the HCV/HIV coinfected persons undergoing HCV treatment remains unclear. AIMS: To study the incidence, predictors and management of anaemia, and its association with outcomes among persons treated with pegylated interferon and weight-based ribavirin. METHODS: Retrospective analysis of a prospective controlled treatment trial of HCV/HIV coinfection. RESULTS: Among 329 subjects enrolled, 40% developed anaemia during the first 12-18 weeks of treatment (median haemoglobin decrease at week 4: 2.2 g/dL). Among 169 subjects who achieved early virological response and received therapy for 72 weeks, 55% eventually developed anaemia. However, median haemoglobin levels stayed stable after 12-18 weeks of initial therapy. Among these 169 subjects, 45% were prescribed an erythropoiesis stimulating agent (ESA), with 17% receiving it prior to a drop in haemoglobin meeting protocol definition of anaemia. Only 27% completed the study without any ribavirin dose modification. Age >40 years, lower BMI, zidovudine use and lower entry haemoglobin were significant predictors of anaemia in the multi-covariate model. Among all 329, sustained virological response (SVR) rate was similar in those with or without anaemia (23% vs. 30%; P=0.17) with no evidence of association between anaemia or ESA use and treatment response. CONCLUSIONS: Anaemia is common in HCV/HIV coinfected persons undergoing HCV treatment, and only a minority of them are able to maintain ribavirin dose. Persons with age >40 years, lower baseline haemoglobin and lower baseline BMI should be monitored carefully. Prescription of erythropoiesis stimulating agent is common, but anaemia or erythropoiesis stimulating agent use is not associated with SVR.