Prevalence of Spontaneous Clearance of Hepatitis C Virus Infection Doubled From 1998 to 2017.

Strategic planning for hepatitis C virus (HCV) screening and treatment requires up-to-date information on the prevalence of HCV spontaneous clearance. Published estimates of HCV spontaneous clearance range from 15% to 60%.1-3 We conducted an observational study over 20 years to evaluate trends in the prevalence of HCV spontaneous clearance. Our goals were to estimate the proportion of HCV-antibody-positive patients who were viremic, and to identify factors associated with viremia, thus facilitating prediction of the number of patients needing treatment.

No Difference in Effectiveness of 8 vs 12 Weeks of Ledipasvir and Sofosbuvir for Treatment of Hepatitis C in Black Patients.

BACKGROUND & AIMS: Treatment with the combination of ledipasvir and sofosbuvir for 12 weeks has been approved by the Food and Drug Administration for patients with genotype 1 hepatitis C virus (HCV) infection; some patients can be treated with an 8-week course. Guidelines recommend a 12-week treatment course for black patients, but studies have not compared the effectiveness of 8 vs 12 weeks in black patients who are otherwise eligible for an 8-week treatment regimen. METHODS: We conducted an observational study of Kaiser Permanente Northern California members with HCV genotype 1 infection who were eligible for 8 weeks of treatment with ledipasvir and sofosbuvir (treatment-naïve, no cirrhosis, no HIV infection, level of HCV RNA <6 million IU/mL) and were treated for 8 or 12 weeks from October 2014 through December 2016. We used χ2 analyses to compare sustained virologic response 12 weeks after the end of treatment (SVR12) among patients treated for 8 vs 12 weeks, and adjusted Poisson models to identify factors associated with receipt of 12 weeks of therapy among patients eligible for 8 weeks. RESULTS: Of 2653 patients eligible for 8 weeks of treatment with ledipasvir and sofosbuvir, 1958 (73.8%) received 8 weeks of treatment and 695 (26.2%) received 12 weeks; the proportions of patients with SVR12 were 96.3% and 96.3%, respectively (P = .94). Among 435 black patients eligible for the 8-week treatment regimen, there was no difference in the proportions who achieved an SVR12 following 8 vs 12 weeks' treatment (95.6% vs 95.8%; P = .90). Male sex, higher transient elastography or FIB-4 scores, higher INR and level of bilirubin, lower level of albumin, obesity, diabetes, and ≥15 alcohol drinks consumed/week were independently associated with receiving 12 weeks of treatment among patients eligible for the 8-week treatment regimen, but were not associated with reduced SVR12 after 8 weeks of treatment. CONCLUSION: In an observational study of patients who received ledipasvir and sofosbuvir treatment for HCV genotype 1 infection, we found that contrary to guidelines, 8-week and 12-week treatment regimens do not result in statistically significant differences in SVR12 in black patients. Patient characteristics were associated with receipt of 12-week regimens among patients eligible for 8 weeks, but were not associated with reduced SVR12 after 8 weeks. Shorter treatment courses might therefore be more widely used without compromising treatment effectiveness.

IFNL4 genotype and other personal characteristics to predict response to 8-week sofosbuvir-based treatment for chronic hepatitis C.

BACKGROUND: Shorter duration therapy for hepatitis C virus (HCV) infection might reduce treatment costs and increase the number of patients treated and cured. We determined factors associated with treatment response after an 8-week sofosbuvir-based therapy and developed a simple model to predict an individual's likelihood of treatment success. METHODS: Among 2907 patients who received ledipasvir/sofosbuvir for 8 weeks, we determined failure rates by demographic and clinical characteristics, and IFNL4-∆G/TT genotype. We estimated the average IFNL4 genotype-related treatment failure rate in major ancestry groups by applying our IFNL4 genotype results to genotype distributions from reference populations. We created a treatment response model based on three personal characteristics. RESULTS: Overall, 4.4% of the patients failed treatment. We observed significantly lower failure rates for persons <50 years (1.6%), females (2.6%), those carrying the IFNL4-TT/TT genotype (1.8%), those with HCV RNA <5.8 log10 copies/mL (2.0%) or HCV genotype-1B infection (2.6%). In a model based on ancestry, age and sex, the predicted probability of treatment failure ranged from 0.5% among females of East Asian ancestry <50 years of age to 8.5% among males of African ancestry age ≥65 years. CONCLUSION: Applying this algorithm at the point-of-care might facilitate HCV elimination, especially in low- and middle-income countries.

Reduced risk of pertussis among persons ever vaccinated with whole cell pertussis vaccine compared to recipients of acellular pertussis vaccines in a large US cohort.

BACKGROUND: Unexpected waning of immunity after pertussis vaccination is now well described. In this study we examined whether prior vaccination with whole-cell pertussis vaccine (wP) at any point provided superior protection contrasted with a solely acellular pertussis vaccine (aP) series. We utilized the coincidence of a large outbreak of pertussis with the termination of wP availability, providing populations of children who had been vaccinated with combinations of wP and aP. METHODS: Kaiser Permanente (KP) is an integrated healthcare system with complete electronic records and a centralized laboratory. Cases of laboratory-confirmed pertussis and vaccination data for members aged 8-20 years were retrieved. RESULTS: Among 263 496 persons aged 8-20 years, 904 cases of pertussis were identified. In patients with a full history of vaccinations administered by KP, those with 5 total doses of only aP had an 8.57 relative risk (RR) of pertussis (P < .0001) contrasted to those with ≥1 wP dose. With 6 doses of aP, the RR of disease was 3.55 (P < .0001). When external vaccine records were included, the results were similar. CONCLUSIONS: We found a markedly increased risk of disease associated with an entirely aP series. This risk was mitigated, but not eliminated, by the presence of a sixth dose of pertussis vaccine (Tdap). Receipt of 1 or more wP doses markedly augmented the durability of immunity from subsequent aP doses. It appears that a wholly acellular pertussis vaccine series is significantly less effective and durable than one that contains the traditional whole cell vaccine.

Lessons From the Field: Rapid Antigen Testing Is Efficient and Practical for Mitigation of Coronavirus Disease 2019 Outbreaks in Long-Term Care Facilities.

Background: Mitigation of coronavirus disease 2019 (COVID-19) outbreaks in long-term care facilities (LTCFs) is facilitated by rapid identification and isolation of infectious individuals to interrupt viral transmission. Immunochromatographic (IC) tests, or rapid antigen tests, have high sensitivity and specificity during the contagious period for COVID-19. Mathematical modeling predicts frequent IC surveillance will be more efficient than polymerase chain reaction (PCR)-based strategies, especially during community surges when reporting of PCR results can be delayed. However, there are few published field studies evaluating IC testing strategies in this long-term care setting. Methods: In fall and winter of 2020, the Marin Health and Human Services Department implemented thrice-weekly IC mass testing by nonlaboratory workers in outbreaks that occurred in 2 LTCFs, in addition to then-standard semiweekly PCR testing. The IC test performance was characterized using same-day PCR specimens as reference standard. Cumulative incidence and duration of transmission for the 2 IC intervention facility outbreaks were compared with 6 reference LTCFs that used weekly to semiweekly PCR alone during an outbreak response. Results: Of 123 same-day test pairs, IC test sensitivity and specificity were 75% (95% confidence interval [CI], 48%-93%) and 100% (95% CI, 97%-100%), respectively. The median duration of outbreak transmission was 19.5 days in the 2 intervention sites and 28 days in the reference facilities (P = .40). Cumulative incidence for the outbreaks among LTCF residents was 41% in the intervention facilities versus 52% in the reference facilities (P = .04, Fisher 2-sided exact). Conclusions: Thrice-weekly mass IC testing as used by nonlaboratory personnel can be highly practical and effective for COVID-19 outbreak mitigation in the LTCF setting.

Unexpectedly limited durability of immunity following acellular pertussis vaccination in preadolescents in a North American outbreak.

BACKGROUND: Despite widespread childhood vaccination against Bordetella pertussis, disease remains prevalent. It has been suggested that acellular vaccine may be less effective than previously believed. During a large outbreak, we examined the incidence of pertussis and effectiveness of vaccination in a well-vaccinated, well-defined community. METHODS: Our center provides care to 135 000 patients, 40% of the population of Marin County, California. A total of 171 patients tested positive for B. pertussis from 1 March to 31 October 2010 by polymerase chain reaction (PCR). Electronic medical records were reviewed for demographic characteristics and vaccination status. RESULTS: We identified 171 cases of clinical pertussis, 132 of which were in pediatric patients. There was a notable increase in cases among patients aged 8-12 years. The rate of testing peaked among infants but remained relatively constant across ages until 12 years. The rate of positive tests was low for ages 0-6 years and increased among preadolescents, peaking among those aged 12 years. The vaccination rate among PCR-positive preadolescents were approximately equal to that of controls. The vaccine effectiveness was 41%, 24%, and 79% for children aged 2-7 years, 8-12 years, 13-18 years, respectively. CONCLUSIONS: Our data suggests that the current schedule of acellular pertussis vaccine doses is insufficient to prevent outbreaks of pertussis. We noted a markedly increased rate of disease from ages 8-12 years, proportionate to the interval since the last scheduled vaccine. Stable rates of testing ruled out selection bias. The possibility of earlier or more numerous booster doses of acellular pertussis vaccine either as part of routine immunization or for outbreak control should be entertained.

Detection of uniparental isodisomy in autosomal recessive mitochondrial DNA depletion syndrome by high-density SNP array analysis.

Mitochondrial DNA (mtDNA) depletion syndrome encompasses a heterogeneous group of disorders characterized by a reduction in the mtDNA copy number. We identified two patients with clinical presentations consistent with mtDNA depletion syndrome (MDS), who were subsequently found to have apparently homozygous point mutations in TYMP and DGUOK, two of the nine nuclear genes commonly associated with these disorders. Further sequence analyses of parents indicated that in each case only one parent; the mother of the first and the father of the second, was a heterozygous carrier of the mutation identified in the affected child. The presence of underlying deletions was ruled out by use of a custom target array comparative genomic hybridization (CGH) platform. A high-density single-nucleotide polymorphism (SNP) array analysis revealed that the first patient had a region of copy-neutral absence of heterozygosity (AOH) consistent with segmental isodisomy for an 11.3 Mb region at the long-arm terminus of chromosome 22 (including the TYMP gene), and the second patient had results consistent with complete isodisomy of chromosome 2 (where the DGUOK gene is located). The combined sequencing, array CGH and SNP array approaches have demonstrated the first cases of MDS due to uniparental isodisomy. This diagnostic scenario also demonstrates the necessity of comprehensive examination of the underlying molecular defects of an apparently homozygous mutation in order to provide patients and their families with the most accurate molecular diagnosis and genetic counseling.

Pulmonary Vein Thrombosis in a Patient With Multiple Myeloma on Treatment With Lenalidomide.

Multiple myeloma (MM) poses inherent risk of thrombosis that can be amplified by the use of immunomodulator therapy. We present a patient with MM who was being treated with lenalidomide and dexamethasone when he developed progressive dyspnea on exertion consistent with a left lower pulmonary vein thrombosis (PVT) despite use of prophylactic aspirin. The PVT was not initially seen on standard computed tomography angiogram pulmonary embolism protocol but was seen on 192-slice multidetector computed tomography angiogram for assessment of coronary calcifications 8 months later. Subsequent treatment with full dose rivaroxaban resulted in full clot resolution and symptom improvement. PVT has not been previously reported with lenalidomide therapy and may not be a forefront differential diagnosis. In such cases, a multi-modality diagnostic approach may be beneficial. Consideration should be given to escalating venous thromboembolism prophylaxis to full dose anticoagulation during increased prothrombotic windows, such as the time of treatment initiation or dose adjustments, in low bleeding risk patients.

A successful program preventing nonventilator hospital-acquired pneumonia in a large hospital system.

OBJECTIVE: To develop and evaluate a program to presvent hospital-acquired pneumonia (HAP). DESIGN: Prospective, observational, surveillance program to identify HAP before and after 7 interventions. An order set automatically triggered in programmatically identified high-risk patients. SETTING: All 21 hospitals of an integrated healthcare system with 4.4 million members. PATIENTS: All hospitalized patients. INTERVENTIONS: Interventions for high-risk patients included mobilization, upright feeding, swallowing evaluation, sedation restrictions, elevated head of bed, oral care and tube care. RESULTS: HAP rates decreased between 2012 and 2018: from 5.92 to 1.79 per 1,000 admissions (P = .0031) and from 24.57 to 6.49 per 100,000 members (P = .0014). HAP mortality decreased from 1.05 to 0.34 per 1,000 admissions and from 4.37 to 1.24 per 100,000 members. Concomitant antibiotic utilization demonstrated reductions of broad-spectrum antibiotics. Antibiotic therapy per 100,000 members was measured as follows: carbapenem days (694 to 463; P = .0020), aminoglycoside days (154 to 61; P = .0165), vancomycin days (2,087 to 1,783; P = .002), and quinolone days (2,162 to 1,287; P < .0001). Only cephalosporin use increased, driven by ceftriaxone days (264 to 460; P = .0009). Benzodiazepine use decreased between 2014 to 2016: 10.4% to 8.8% of inpatient days. Mortality for patients with HAP was 18% in 2012% and 19% in 2016 (P = .439). CONCLUSION: HAP rates, mortality, and broad-spectrum antibiotic use were all reduced significantly following these interventions, despite the absence of strong supportive literature for guidance. Most interventions augmented basic nursing care. None had risks of adverse consequences. These results support the need to examine practices to improve care despite limited literature and the need to further study these difficult areas of care.

Life Expectancy of Insured People With and Without Hepatitis C Virus Infection, 2007-2017.

Among 25 291 and 4 921 830 people with and without hepatitis C, life expectancy at age 20 increased 1.8 years and 0.3 years from the interferon to interferon-free era, respectively. Increases were highest for racial and/or ethnic minority groups with hepatitis C.

Reasons for rejection of abstracts submitted to the Annual Conference of the Association for Professionals in Infection Control and Epidemiology: Ensuring transparency and encouraging quality.

The Abstracts Committee of the Association for Professionals in Infection Control and Epidemiology noted high rejection rates for submitted abstracts, often for minor infractions of guidelines. This study examines the reasons for abstract rejection and identified that a substantial portion of abstracts were rejected for readily correctable errors (nonadherence to submission guidelines [71.6%]), prior to consideration of scientific value. This finding will hopefully guide future submissions.

Hepatitis C treatment uptake and response among human immunodeficiency virus/hepatitis C virus-coinfected patients in a large integrated healthcare system.

U.S. guidelines recommend that patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) be prioritized for HCV treatment with direct-acting antiviral agents (DAAs), but the high cost of DAAs may contribute to disparities in treatment uptake and outcomes. We evaluated DAA initiation and effectiveness in HIV/HCV-coinfected patients in a U.S.-based healthcare system during October 2014-December 2017. Of 462 HIV/HCV-coinfected patients, 276 initiated DAAs (70% cumulative proportion treated over three years). Lower likelihood of DAA initiation was observed among patients with Medicare (government-sponsored insurance) versus commercial insurance (adjusted rate ratio [aRR] = 0.62, 95% CI = 0.46-0.84), patients with drug abuse diagnoses (aRR = 0.72, 95% CI = 0.54-0.97), patients with CD4 cell count <200 cells/µl versus ≥500 (aRR = 0.45, 95% CI = 0.23-0.91), and patients without prior HCV treatment (aRR = 0.68, 95% CI = 0.48-0.97). There were no significant differences in DAA initiation by age, gender, race/ethnicity, socioeconomic status, HIV transmission risk, alcohol use, smoking, fibrosis level, HIV RNA levels, antiretroviral therapy use, hepatitis B infection, or number of outpatient visits. Ninety-five percent of patients achieved sustained virologic response (SVR). We found little evidence of sociodemographic disparities in DAA initiation among HIV/HCV-coinfected patients, and SVR rates were high. Efforts are needed to increase DAA uptake among coinfected Medicare enrollees, patients with drug abuse diagnoses, patients with low CD4 cell count, and patients receiving first-time HCV treatment.

Identification of copy number variants associated with BPES-like phenotypes.

Blepharophimosis-Ptosis-Epicanthus inversus syndrome (BPES) is a well-characterized rare syndrome that includes an eyelid malformation associated with (type I) or without premature ovarian failure (type II). Patients with typical BPES have four major characteristics: blepharophimosis, ptosis, epicanthus inversus and telecanthus. Mutations in the FOXL2 gene, encoding a forkhead transcription factor, are responsible for the majority of both types of BPES. However, many patients with BPES-like features, i.e., having at least two major characteristics of BPES, have an unidentified cause. Here, we report on a group of 27 patients with BPES-like features, but without an identified genetic defect in the FOXL2 gene or flanking region. These patients were analyzed with whole-genome high-density arrays in order to identify copy number variants (CNVs) that might explain the BPES-like phenotype. In nine out of 27 patients (33%) CNVs not previously described as polymorphisms were detected. Four of these patients displayed psychomotor retardation as an additional clinical characteristic. In conclusion, we demonstrate that BPES-like phenotypes are frequently caused by CNVs, and we emphasize the importance of whole-genome copy number screening to identify the underlying genetic causes of these phenotypes.

Disparities in Initiation of Direct-Acting Antiviral Agents for Hepatitis C Virus Infection in an Insured Population.

OBJECTIVES: The cost of direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection may contribute to treatment disparities. However, few data exist on factors associated with DAA initiation. METHODS: We conducted a retrospective cohort study of HCV-infected Kaiser Permanente Northern California members aged ≥18 during October 2014 to December 2016, using Poisson regression models to evaluate demographic, behavioral, and clinical factors associated with DAA initiation. RESULTS: Of 14 790 HCV-infected patients aged ≥18 (median age, 60; interquartile range, 53-64), 6148 (42%) initiated DAAs. DAA initiation was less likely among patients who were non-Hispanic black (adjusted rate ratio [aRR] = 0.7; 95% confidence interval [CI], 0.7-0.8), Hispanic (aRR = 0.8; 95% CI, 0.7-0.9), and of other minority races/ethnicities (aRR = 0.9; 95% CI, 0.8-1.0) than among non-Hispanic white people and among those with lowest compared with highest neighborhood deprivation index (ie, a marker of socioeconomic status) (aRR = 0.8; 95% CI, 0.7-0.8). Having maximum annual out-of-pocket health care costs >$3000 compared with ≤$3000 (aRR = 0.9; 95% CI, 0.8-0.9) and having Medicare (aRR = 0.8; 95% CI, 0.8-0.9) or Medicaid (aRR = 0.7; 95% CI, 0.6-0.8) compared with private health insurance were associated with a lower likelihood of DAA initiation. Behavioral factors (eg, drug abuse diagnoses, alcohol use, and smoking) were also significantly associated with a lower likelihood of DAA initiation (all P < .001). Clinical factors associated with a higher likelihood of DAA initiation were advanced liver fibrosis, HCV genotype 1, previous HCV treatment (all P < .001), and HIV infection ( P = .007). CONCLUSIONS: Racial/ethnic and socioeconomic disparities exist in DAA initiation. Substance use may also influence patient or provider decision making about DAA initiation. Strategies are needed to ensure equitable access to DAAs, even in insured populations.

Good Nursing Is Good Antibiotic Stewardship.

: Resistance to antibiotics has increased dramatically in the United States, with serious associated medical, social, and economic consequences. The most promising approach to this national crisis is a new understanding of the need for the careful and responsible use of antibiotics, both for the benefit of society and for the optimal care of each patient. This multidisciplinary approach, called antimicrobial stewardship, has typically involved specialists but not necessarily nurses, who perform numerous antibiotic-related activities daily and should be an integral part of antimicrobial stewardship programs. In this article, we use patient examples to review several stewardship activities and illustrate how nurses are essential to the appropriate use of antibiotics.

Eight- or 12-Week Treatment of Hepatitis C with Ledipasvir/Sofosbuvir: Real-World Experience in a Large Integrated Health System.

BACKGROUND: Second-generation direct-acting antiviral agents are integral to treatment of hepatitis C (HCV) infection. Eight-week courses of ledipasvir/sofosbuvir (LDV/SOF) have been supported in some studies, but data are limited on efficacy in real-world use. Controversy exists regarding applicability of clinical trials to real-world effectiveness. We report virologic responses of patients with HCV genotype 1 infection receiving LDV/SOF for 8 or 12 weeks in a large integrated healthcare system. METHODS: All patients receiving LDV/SOF, without ribavirin, were identified from pharmacy records, and outcomes are reported. Only treatment-naïve patients without evidence of cirrhosis and hepatitis C viral load less than 6 million IU/ml were candidates for 8-week therapy. Treatment was at clinician discretion, but delivered by a multidisciplinary team and reviewed for appropriateness and adherence to these criteria by one of the authors, all experienced in hepatitis C treatment. Sustained viral response at 12 weeks (SVR 12) was contrasted between those receiving 8 and those receiving 12 weeks of treatment. RESULTS: Completed prescriptions for LDV/SOF, without ribavirin, as of 30 September 2015 were identified in 1021 patients. Five patients discontinued therapy due to medical reasons and 35 had incomplete follow-up viral load data, thus there were 981 evaluable patients: 377 treated for 8 weeks and 604 treated for 12 weeks. SVR 12 was virtually identical at 93.6 and 93.5%, respectively. Baseline characteristics differed between the two groups, as only treatment-naïve, non-cirrhotic, non-HIV-infected patients were eligible for an 8-week course of therapy. CONCLUSIONS: Eight-week courses of LDV/SOF are comparable to 12-week courses in real-world use among selected patients supported by a multidisciplinary team.