Birth Cohort Testing for Hepatitis C Virus: Implications for Clinical Social Workers in Health Care Settings

The Centers for Disease Control and Prevention recommends one-time hepatitis C virus (HCV) testing for baby boomers born between 1945–1965 in the United States. This public health initiative is known as birth cohort (baby boomer) testing for HCV. The intent of birth cohort testing is to identify and mobilize undiagnosed HCV-infected persons into care and treatment. Subsequently, clinical social workers in health care settings can anticipate a substantial increase in the number of HCV-infected persons presenting for care and treatment. The purpose of this article is to inform clinical social workers in health care settings of HCV, the standard of care and treatment for HCV, and clinical dilemmas associated with HCV patient care. Epidemiology and natural history of HCV, the standard of care and treatment for HCV, and etiology and management of neuropsychiatric adverse effects associated with patient care are discussed.     

An Economic Evaluation of the Cost-Effectiveness of Opt-Out Hepatitis B and Hepatitis C Testing in an Emergency Department Setting in the United Kingdom

ObjectivesThe prevalence of hepatitis is high in emergency department (ED) attendees in the United Kingdom, with a prevalence of up to 2% for hepatitis B (HBV) HBsAg, and 2.9% for hepatitis C (HCV) RNA. The aim of this paper is to perform an economic evaluation of opt-out ED-based HCV and HBV testing.MethodsA Markov model was developed to analyze the cost-effectiveness of opt-out HCV and HBV testing in EDs in the UK. The model used data from UK studies of ED testing to parameterize the HCV and HBV prevalence (1.4% HCV RNA, 0.84% HBsAg), test costs, and intervention effects (contact rates and linkage to care). For HCV, we used an antibody test cost of £3.64 and RNA test cost of £68.38, and assumed direct-acting antiviral treatment costs of £10 000. For HBV, we used a combined HBsAg and confirmatory test cost of £5.79. We also modeled the minimum prevalence of HCV (RNA-positive) and HBV (HBsAg) required to make ED testing cost-effective at a £20 000 willingness to pay per quality-adjusted life-year threshold.ResultsIn the base case, ED testing was highly cost-effective, with HCV and HBV testing costing £8019 and £9858 per quality-adjusted life-year gained, respectively. HCV and HBV ED testing remained cost-effective at 0.25% HCV RNA or HBsAg prevalence or higher.ConclusionsEmergency department testing for HCV and HBV is highly likely to be cost-effective in many areas across the UK depending on their prevalence. Ongoing studies will help evaluate ED testing across different regions to inform testing guidelines.     

Effect of Interpregnancy Interval on Infant Low Birth Weight: A Retrospective Cohort Study Using the Michigan Maternally Linked Birth Database

Objective: To examine the relationship between interpregnancy interval and low birth weight (LBW), using the retrospective cohort design. Methods: We used the maternally linked Michigan livebirth data documented between 1989 and 2000 to evaluate LBW in relation to interpregnancy (i.e., delivery-to-conception) interval, overall and at levels of other reproductive risk factors. We fit separate logistic regression models for pairs of first-second, second-third, third-fourth, and fourth-fifth births to control for confounding. Results: Of the 565,911 infants identified, 5.5% had LBW. Univariate and stratified analyses showed that the risk for LBW was lowest when the interpregnancy interval was 18–23 months, and increased with shorter or longer intervals. This J-shaped relationship persisted after controlling for all risk factors simultaneously. For example, among the first-second birth pairs, the adjusted odds ratios (AORs) for LBW associated with interpregnancy intervals <6, 24–59, 60–95, and 96–136 months were 1.4 (95% confidence interval [CI] = 1.3–1.5), 1.5 (95% CI = 1.3–1.6), 1.1 (95% CI = 1.0–1.1) and 1.5 (95% CI = 1.3–1.8), respectively, compared with an interval of 18–23 months. Among the second-third birth pairs, the AORs were 1.5 (95% CI = 1.3–1.6), 1.3 (95% CI = 1.2–1.4), 1.1 (95% CI = 1.0–1.1), and 1.6 (95% CI = 1.3–2.0), respectively. Among the third-fourth birth pairs, the AORs were 1.2 (95% CI = 1.1–1.4), 1.3 (95% CI = 1.1–1.5), 1.0 (95% CI = 0.9–1.1), and 1.4 (95% CI = 1.0–2.0), respectively. Among the fourth-fifth birth pairs, the AORs were 1.3 (95% CI = 1.1–1.6), 1.2 (95% CI = 0.9–1.5), 1.1 (95% CI = 1.0–1.4), and 1.3 (95% CI = 0.8–2.3), respectively. The population attributable risk associated with interpregnancy intervals shorter than 18 months or longer than 23 months was 9.4%. Conclusion: These data suggest that spacing pregnancies appropriately could be used as a strategy for preventing LBW.     

Maternal stress during pregnancy and gestational duration: A cohort study from the Danish National Birth Cohort

Background

Preterm birth is one of the most important contributors to neonatal mortality and morbidity. Experiencing stress during pregnancy may increase the risk of adverse birth outcomes, including preterm birth. This association has been observed in previous studies, but differences in measures used limit comparability.

Objective

The objective of the study was to investigate the association between two measures of maternal stress during pregnancy, life stress and emotional distress, and gestation duration.

Methods

Women recruited in the Danish National Birth Cohort from 1996 to 2002, who provided information on their stress level during pregnancy and expecting a singleton baby, were included in the study. We assessed the associations between the level of life stress and emotional distress in quartiles, both collected at 31 weeks of pregnancy on average, and the rate of giving birth using Cox regression within intervals of the gestational period.

Results

A total of 80,991 pregnancies were included. Women reporting moderate or high levels of life stress vs no stress had a higher rate of giving birth earlier within all intervals of gestational age (e.g. high level: 27–33 weeks: hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.04, 1.84; 34–36 weeks: 1.10, 95% CI 0.97, 1.25; 37–38 weeks: 1.21, 95% CI 1.15, 1.28). These associations between life stress and preterm birth were mainly driven by pregnancy worries. For emotional distress, a high level of distress was associated with shorter length of gestation in the preterm (27–33 weeks: 1.38, 95% CI 1.02, 1.86; 34–36 weeks: 1.05, 95% CI 0.91, 1.19) and early term (1.11, 95% CI 1.04, 1.17) intervals.

Conclusions

Emotional distress and life stress were shown to be associated with gestational age at birth, with pregnancy-related stress being the single stressor driving the association. This suggests that reverse causality may, at least in parts, explain the earlier findings of stress as a risk factor for preterm birth.     

Phthalate metabolites and bisphenol A in urines from German school-aged children: Results of the Duisburg Birth Cohort and Bochum Cohort Studies

Some phthalates and also bisphenol A (BPA) interfere with the human endocrine system and are labelled as reproductive toxicants. Children's exposure to these contaminants is suspected to be associated with developmental disorders and other health impairments.We provide biomonitoring data on 21 urinary phthalate metabolite and BPA levels in first morning urine of 8–10 year old children. Participants were children born between 1999 and 2002 of the Duisburg birth cohort (8–9 years, N = 113) and of the Bochum cohort study (8–10 years, N = 352). Additionally, for the Duisburg birth cohort we compare current data of children from Duisburg (8–9 years) with data from 2 years earlier when the children were 6–7 years old. We analyzed influences of important covariates on exposure levels by multiple regression analysis and those from two sampling time points by generalized equation estimation models adjusted for important covariates. Compared to recently published studies the phthalate metabolite and BPA concentrations were within the range of background levels. There were no significant differences between children from Bochum and Duisburg. Comparison between the two Duisburg birth cohort data sets (2007–2008 and 2009–2010) showed significant correlations for most of the phthalate metabolites (r_Spearman between 0.25 and 0.51; p ≤ 0.05) but not for BPA (r_Spearman= 0.162; p = 0.143). Most of the phthalate metabolites in the groups of the 6–7 and 8–9 years old Duisburg children were negatively associated with higher age, except for BPA concentrations with nearly constant levels. Exposure levels may be influenced by changes in child specific exposure patterns with age but also by the rapidly changing phthalate market.     

Screening for Hepatitis C in injecting drug users: a cost utility analysis

BACKGROUND: Hepatitis C is a major public health problem of increasing importance among injecting drug users, among whom screening has been proposed. We therefore estimated the cost utility of screening for hepatitis C infection among people with a history of injecting drug use in contact with drug misuse services. METHODS: A spreadsheet-based model of screening using ELISA followed by polymerase chain reaction tests and treatment using combination therapy with interferon alpha and ribavirin was developed. Parameters were informed by literature review, expert opinion and a survey of current screening practice in England. A range of one-way sensitivity analyses were carried out to explore uncertainty in the results for cost effectiveness. RESULTS: Screening for HCV is likely to yield benefits in the population concerned at around 28,000 pounds per quality adjusted life year. This estimate is reasonably stable when explored in extensive one-way sensitivity analysis but appeared sensitive to the proportion of HCV positive people who accept biopsy or treatment and the utility gains associated with successful drug treatment. Important other areas of uncertainty include the effects of mortality from other causes on the cost effectiveness of screening in this population and the time at which symptoms would have led to presentation in the absence of a screening programme. CONCLUSION: Screening for HCV in this population is moderately cost effective, although some caution must remain in accepting this estimate given the current uncertainties in this field, and further research is required.     

Maternal Vitamin C and Iron Intake during Pregnancy and the Risk of Islet Autoimmunity and Type 1 Diabetes in Children: A Birth Cohort Study

Our aim was to study the associations between maternal vitamin C and iron intake during pregnancy and the offspring’s risk of developing islet autoimmunity and type 1 diabetes. The study was a part of the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) prospective birth cohort including children genetically at risk of type 1 diabetes born between 1997–2004. The diets of 4879 mothers in late pregnancy were assessed with a validated food frequency questionnaire. The outcomes were islet autoimmunity and type 1 diabetes. Cox proportional hazards regression analysis adjusted for energy, family history of diabetes, human leukocyte antigen (HLA) genotype and sex was used for statistical analyses. Total intake of vitamin C or iron from food and supplements was not associated with the risk of islet autoimmunity (vitamin C: HR 0.91: 95% CI (0.80, 1.03), iron: 0.98 (0.87, 1.10)) or type 1 diabetes (vitamin C: 1.01 (0.87, 1.17), iron: 0.92 (0.78, 1.08)), neither was the use of vitamin C or iron supplements associated with the outcomes. In conclusion, no association was found between maternal vitamin C or iron intake during pregnancy and the risk of islet autoimmunity or type 1 diabetes in the offspring.     

Preconception Hemoglobin Concentration and Risk of Low Birth Weight and Small-for-Gestational-Age: A Large Prospective Cohort Study in China

Less is known about the impact of maternal preconception anemia on birth outcomes. We aimed to examine associations between preconception hemoglobin (Hb) concentrations with risk of low birth weight (LBW) and small-for-gestational-age (SGA). This study was from a large population-based prospective cohort in China and included 124,725 women with singleton live births delivered at gestational ages of 28–45 weeks who were registered before pregnancy. Maternal Hb concentrations were measured during registration, and other health-related information was recorded prospectively. Logistic regression was used to evaluate the associations between preconception Hb concentrations with risk of LBW and SGA, adjusting for potential confounders. The results showed women with preconception anemia accounted for 22.28%. The incidences of LBW/SGA were 2.37%/6.30% among anemic women, and 2.01%/5.48% among non-anemic women, respectively. Preconception mild anemia increased by 17% (95% confidence interval (CI): 1.06, 1.28) and 14% (95% CI: 1.07, 1.21) the risk for LBW and SGA, while moderate-to-severe anemia had no significant association with LBW and SGA. Compared with the 120–129 g/L group, a U-shaped association was observed between preconception Hb concentrations with LBW and SGA. In conclusion, not only maternal anemia but also elevated Hb concentrations before pregnancy contribute to an increased risk of LBW and SGA.     

Cost-Utility Analysis of Direct-Acting Antivirals for Treatment of Chronic Hepatitis C Genotype 1 and 6 in Vietnam

ObjectiveVery few cost-utility analyses have either evaluated direct-acting antivirals (DAAs) on hepatitis C virus (HCV) genotype 6 patients or undertaken societal perspective. Recently, DAAs have been introduced into the Vietnamese health insurance drug list for chronic hepatitis C (CHC) treatment without empirical cost-effectiveness evidence. This study was conducted to generate these data on DAAs among CHC patients with genotypes 1 and 6 in Vietnam.MethodsA hybrid decision-tree and Markov model was employed to compare costs and quality-adjusted life-years (QALYs) of available DAAs, including (1) sofosbuvir/ledipasvir, (2) sofosbuvir/velpatasvir, and (3) sofosbuvir plus daclatasvir, with pegylated-interferon plus ribavirin (PR). Primary data collection was conducted in Vietnam to identify costs and utility values. Incremental cost-effectiveness ratios were estimated from societal and payer perspectives. Uncertainty and scenario analyses and value of information analyses were performed.ResultsAll DAAs were cost-saving as compared with PR in CHC patients with genotypes 1 and 6 in Vietnam, and sofosbuvir/velpatasvir was the most cost-saving regimen, from both societal and payer perspectives. From the societal perspective, DAAs were associated with the increment of quality-adjusted life-years by 1.33 to 1.35 and decrement of costs by $6519 to $7246. Uncertainty and scenario analyses confirmed the robustness of base-case results, whereas the value of information analyses suggested the need for further research on relative treatment efficacies among DAA regimens.ConclusionsAllocating resources for DAA treatment for HCV genotype 1 and 6 is surely a rewarding public health investment in Vietnam. It is recommended that the government rapidly scale up treatment and enable financial accessibility for HCV patients.     

Screening for hepatitis C virus in the Dartmoor prison population: an observational study

BACKGROUND: Prisons are a potential setting for hepatitis C screening. This study describes prisoner flows through such screening for all prisoners entering Dartmoor prison between 1 January 1998 and 30 June 2001. METHODS: We identified numbers at each step of the screening pathway, from screening to result, referral, biopsy and outcome. We describe the proportions of those screened who were seropositive; seropositives who were confirmed virus-positive; virus-positive cases attending for biopsy; and virus-positive cases eligible for treatment. RESULTS: Of 3034 entries into Dartmoor, 12 per cent were screened, with 16 per cent of these seropositive. Seventynine per cent of seropositive prisoners with a polymerase chain reaction result were confirmed virus-positive, and 27 per cent of these prisoners had a biopsy. Two prisoners were eligible for treatment. CONCLUSIONS: Screening uptake is low. Attrition rates are high, especially at the referral interface between the prison and specialist care. Finally, the yield of individuals eligible for treatment is low, at 7/1000 tested.     

Management Strategies for Ribavirin-Induced Hemolytic Anemia in the Treatment of Hepatitis C: Clinical and Economic Implications

Objectives: Recently published studies have demonstrated increased efficacy and cost-effectiveness of combination therapy with interferon and α-2b/ribavirin compared with interferon-alpha monotherapy in the treatment of chronic hepatitis C (CHC). Combination therapy is associated with a clinically important adverse effect: ribavirin-induced hemolytic anemia (RIHA). The objective of this study was to evaluate the direct health-care costs and management of RIHA during treatment of CHC in a clinical trial setting.
Methods: A systematic literature review was conducted to synthesize information on the incidence and management of RIHA. Decision-analytic techniques were used to estimate the cost of treating RIHA. Uncertainty was evaluated using sensitivity analyses.
Results: RIHA, defined as a reduction in hemoglobin to less than 100 g/L, occurs in approximately 7% to 9% of patients treated with combination therapy. The standard of care for management of RIHA is reduction or discontinuation of the ribavirin dosage. We estimated the direct cost of treating clinically significant RIHA to be $170 per patient receiving combination therapy per 48-week treatment course (range $68–$692). The results of the one-way sensitivity analyses ranged from $57 to $317. In comparison, the cost of 48 weeks of combination therapy is $16,459.
Conclusions: The direct cost of treating clinically significant RIHA is 1% ($170/$16,459) of drug treatment costs. Questions remain about the optimal dose of ribavirin and the incidence of RIHA in a real-world population. Despite these uncertainties, this initial evaluation of the direct cost of treating RIHA provides an estimate of the cost and management implications of this clinically important adverse effect.     

Accounting for Intergenerational Cascade Testing in Economic Evaluations of Clinical Genomics: A Scoping Review

ObjectivesClinical genomics is emerging as a diagnostic tool in the identification of blood relatives at risk of developing heritable diseases. Our objective was to identify how genetic cascade screening has been incorporated into health economic evaluations.MethodsA scoping review was conducted to identify how multiple generations of a family were included in economic evaluations of clinical genomic sequencing, how many and which relatives were included, and uptake rates. Databases were searched for full economic evaluations of genetic interventions that screened multiple generations of families and were in English language, and no restrictions were made for disease or publication type. Data were synthesized using a narrative approach.ResultsTwenty-five studies were included covering a range of diseases in various countries. Markov cohort models were mostly used with hypothetical populations and unsupported by clinical evidence. Cascade testing was either the primary intervention or secondary to the index cases. The number and type of relatives were based on assumptions or identified through population or family records, clinical registry data, or clinical literature. Studies included only immediate family members and the uptake of testing ranged between 20% and 100%. All interventions were reported as cost-effective, and a higher number of relatives was a key driver.ConclusionsSeveral economic evaluations have considered the impacts of cascade testing interventions within clinical genomics. Ideally, models supported with high-quality clinical data are needed and, in their absence, transparent and justifiable assumptions of uptake rates and choices about including relatives. Consideration of more appropriate modeling types is required.     

全国医院感染监测网对持续血液透析患者丙型肝炎病毒感染现况调查

目的了解持续性血液透析患者丙型肝炎病毒（HCV）感染的情况,为预防与控制提出对策。方法利用全国医院感染管理办公平台开发调查统计程序,面对全国自愿参加调查的医院,采用横断面调查的方法对2010年3月10日-4月10日所有持续进行血液透析治疗患者的HCV感染情况及相关因素开展调查。结果全国共有423所医院参与此次调查,审核合格有395所（93.38%）医院进入统计。共调查透析患者21 918人,未做HCV检查者448人,HCV阳性患者1 506人,阳性率7.01%（1 506/21 470）。首次透析开始后发现HCV阳性1 060人,阳性率5.04%（1 060/21 024）。按透析患者数、每月每台透析机透析人次数及每名护士每月操作透析机透析人次数进行分层,各组组间HCV阳性率差异有统计学意义（均P＜0.01）;不同透析持续时间以及在不同医院数进行血液透析的患者HCV感染率差异亦有统计学意义（P＜0.01）。结论工作量大的医院、透析持续时间长的患者、在多个医院透析过的患者HCV感染率较高。     

Cost-Effectiveness of Telaprevir in Patients with Genotype 1 Hepatitis C in Australia

BackgroundProtease inhibitors such as telaprevir (Incivo) are reimbursed in Australia for the treatment of patients with genotype 1 hepatitis C virus (HCV) infection in combination with pegylated interferon and ribavirin (PR).ObjectivesTo assess the cost-effectiveness of telaprevir plus PR compared with PR alone in 1) previously untreated patients and 2) patients who had received treatment with PR earlier.MethodsSustained virological response rates and average treatment durations of telaprevir and PR (given with or without telaprevir) were taken from the telaprevir ADVANCE and REALIZE clinical trials but were modified to take account of differences in prescribing rules between the trials and Australian clinical practice. The probability of transitioning between Markov disease states was based on data from the Australian Kirby Institute where possible and supplemented using data from the published literature. Utility values obtained from the EuroQol five-dimensional questionnaire data collected in the ADVANCE and REALIZE trials were used to represent the utility during HCV treatment. Utility values for Markov health states were taken from the published literature. Unit costs (2014 AU $) were taken from Australian sources.ResultsIn treatment-naive patients, the discounted cost per life-years gained was AU $37,706 and the discounted cost per quality-adjusted life-year was AU $19,283. In treatment-experienced patients, the discounted cost per life-year gained was AU $23,855 and the discounted cost per quality-adjusted life-year was AU $14,948.ConclusionTelaprevir plus PR in the Australian setting is cost-effective when compared with PR alone in patients infected with genotype 1 HCV.     

产前诊断预防唐氏综合征策略的经济学评价

目的:评估我国产前诊断预防唐氏综合征的成本—效果和成本—效益,为决策者和医疗服务供方提供循证信息。方法:在查阅文献和对4个城市的现场调查基础上,从社会角度,对产前诊断预防唐氏综合征策略进行经济学评估。结果:在目前临床水平下,在10000名孕妇队列中对35岁以上高风险人群直接行羊膜腔穿刺产前诊断的策略(年龄筛查策略)能筛出0.67个唐氏综合征病例;而采用外周血两联筛查(AFP HCG),对阳性者再行羊膜腔穿刺的产前诊断策略(孕母血筛查策略)能筛出1.39个病例。孕妇年龄筛查策略和孕母血筛查策略预防1例唐氏综合征的成本分别为107582.09元和469328.46元,效益成本比分别为4.22和1.00。敏感性分析显示降低孕母血筛查成本、提高筛查覆盖率和羊膜腔穿刺产前诊断接受率能使孕母血筛查策略更有成本效果。结论:从国际经验看,孕母血筛查策略比年龄筛查策略更具成本效果。但在我国,由于孕母血筛查策略的低覆盖率、羊膜腔穿刺产前诊断接受率低和孕母血筛查的较高价格导致孕母血筛查策略并不更经济。有关技术应用的卫生系统因素是技术实施效率的重要影响因素。     

Hepatitis B Elimination in Children of Slovenian Origin Born in Slovenia After the Introduction of Preventive Strategies: the Results of a National Study

IntroductionIn Slovenia national strategies to prevent hepatitis B virus (HBV) infection in children were introduced in the mid-nineties. The aim of the present study was to analyze the epidemiological characteristics of chronic hepatitis B infection in children in Slovenia after the introduction of mandatory HBV vaccination of children and mandatory screening of pregnant women for HBV surface antigen (HBsAg) with consecutive active and passive immunization of newborns of HBsAg-positive mothers.MethodsChildren from all regions of Slovenia whose blood samples tested positive for HBsAg at the national reference laboratory for viral hepatitis between January 1997 and December 2010 were included. Demographic, epidemiological and virological data were reviewed retrospectively. Statistical evaluation of the patients’ characteristics was performed and possible trends during the observation period determined.ResultsAmong 52 HBsAg-positive children, there were 22 (42.3%) girls and 30 (57.7%) boys. Among 40 children tested for HBeAg, 17 were positive (42.5%). The most frequent risk factor for acquiring HBV infection was “presence of HBV infection within the family” (24/35; 68.8%). A significant association between the presence of HBeAg and a viral load of >20,000 IU/ml was found (p=0.001). The difference in the proportion of children of Slovenian origin born before 1994 and after was statistically significant (p=0.039). A statistically significant negative linear trend of the number of diagnosed children in the observed period was found (p=0.006).ConclusionsPrevention strategies adopted in the mid-nineties have resulted in the elimination of chronic hepatitis B in children of Slovenian origin born in Slovenia.     

Homosexuality, Birth Order, and Evolution: Toward an Equilibrium Reproductive Economics of Homosexuality

The survival of a human predisposition for homosexuality can be explained by sexual orientation being a polygenetic trait that is influenced by a number of genes. During development these shift male brain development in the female direction. Inheritance of several such alleles produces homosexuality. Single alleles make for greater sensitivity, empathy, tendermindedness, and kindness. These traits make heterosexual carriers of the genes better fathers and more attractive mates. There is a balanced polymorphism in which the feminizing effect of these alleles in heterosexuals offsets the adverse effects. (on reproductive success) of these alleles' contribution to homosexuality. A similar effect probably occurs for genes that can produce lesbianism in females. The whole system survives because it serves to provide a high degree of variability among the personalities of offspring, providing the genotype with diversification and reducing competition among offspring for the same niches. An allele with a large effect can survive in these circumstances in males, but it is less likely to survive in females. The birth order effect on homosexuality is probably a by-product of a biological mechanism that shifts personalities more in the feminine direction in the later born sons, reducing the probability of these sons engaging in unproductive competition with each other.