Hepatitis delta virus: Disease assessment and stratification.

Hepatitis D virus (HDV) causes one of the most severe forms of hepatitis in people with chronic hepatitis B (CHB) infection. Timely and accurate assessment of hepatitis delta virus (HDV) and disease stratification is mandatory for thorough pre-therapeutic evaluation for prioritizing treatment and outcome prediction. Viral biomarkers associated with HDV and hepatitis B virus (HBV) are crucial to aid in diagnosis, and monitoring of serum viral nucleic acids for both viruses is recommended. Liver biopsy remains the gold standard for staging of liver fibrosis and grading of histological activity and should remain central for diagnostic purposes, but is also of importance for research to enhance our understanding of HDV. The emergence of novel non-invasive tests for the assessment of liver fibrosis in HDV patients coupled with the well-recognized potential complications of liver biopsy has resulted in reduced utility of liver biopsy in clinical practice. Preliminary data suggest that these emerging non-invasive modalities appear to be reliable, and their use is supported, similar to other viral hepatitis. Nevertheless, further validation is required before their widespread adoption into clinical practice.

MOCCA-College: Preliminary Validity Evidence of a Cognitive Diagnostic Reading Comprehension Assessment.

As access to higher education increases, it is important to monitor students with special needs to facilitate the provision of appropriate resources and support. Although metrics such as the "reading readiness" ACT (formerly American College Testing) of provide insight into how many students may need such resources, they do not specify why a student may need support or how to provide that support. Increasingly, students are bringing reading comprehension struggles to college. Multiple-choice Online Causal Comprehension Assessment-College (MOCCA-College) is a new diagnostic reading comprehension assessment designed to identify who is a poor comprehender and also diagnose why they are a poor comprehender. Using reliability coefficients, receiver-operating characteristic curve analysis, and correlations, this study reports findings from the first year of a 3-year study to validate the assessment with 988 postsecondary students who took MOCCA-College, a subset of whom also provided data on other reading assessments (i.e., ACT, n = 377; Scholastic Aptitude Test [SAT], n = 192; and Nelson-Denny Reading Test [NDRT], n = 78). Despite some limitations (e.g., the sample is predominantly females from 4-year institutions), results indicate that MOCCA-College has good internal reliability, and scores are correlated with other reading assessments. Through a series of analyses of variance (ANOVAs), we also report how students identified by MOCCA-College as good and poor comprehenders differ in terms of demographics, cognitive processes used while reading, overall comprehension ability, and scores on admissions tests. Findings are discussed in terms of using MOCCA-College to help gauge which students may be at risk of reading comprehension difficulties, identify why they may be struggling, and inform directions in actionable instructional changes based on comprehension processing data.

Chronic Viral Hepatitis in Elite Athletes: Approaches to Risk Assessment, Prevention and Management.

Elite athletes who participate in contact sports are at risk of bleeding injuries, leading to transmission of blood-borne viruses including hepatitis type B, C and D (HBV, HCV and HDV) capable of causing chronic liver disease, liver failure and liver cancer. In view of the significant advances in the viral hepatitis field over the past decade, more structured approaches should be in place to screen for and manage viral hepatitis in elite athletes. HBV status should be assessed in all elite athletes, and those infected should receive nucleos(t)ide analogues for viral suppression, while uninfected individuals should receive HBV vaccination. The all-oral direct acting antivirals for HCV are highly effective and safe, thus the remaining challenge with hepatitis C is case identification and linkage to care. HDV is only found in HBV-infected individuals, which is characterized by rapid disease progression and higher rates of cirrhosis and liver cancer in infected subjects. Pegylated interferon was the mainstay of treatment for HDV infection until bulevirtide, a viral entry inhibitor, was recently approved by the European Union (EMA) and FDA in America, while multiple novel therapies are already in clinical trials as part of the HBV cure program. Overall, awareness of chronic viral hepatitis in athletes should be improved. Prevention remains the cornerstone of the management of viral hepatitis in sport coupled with rigorous disease assessment in infected individuals, and antiviral therapy where indicated.

Disparities of SARS-CoV-2 Nucleoprotein-Specific IgG in Healthcare Workers in East London, UK.

Introduction: SARS-CoV-2 antibody detection serves as an important diagnostic marker for past SARS-CoV-2 infection and is essential to determine the spread of COVID-19, monitor potential COVID-19 long-term effects, and to evaluate possible protection from reinfection. A study was conducted across three hospital sites in a large central London NHS Trust in the UK, to evaluate the prevalence and duration of SARS-CoV-2 IgG antibody positivity in healthcare workers. Methods: A matrix equivalence study consisting of 228 participants was undertaken to evaluate the Abbott Panbio™ COVID-19 IgG/IgM rapid test device. Subsequently, 2001 evaluable healthcare workers (HCW), representing a diverse population, were enrolled in a HCW study between June and August 2020. A plasma sample from each HCW was evaluated using the Abbott Panbio™ COVID-19 IgG/IgM rapid test device, with confirmation of IgG-positive results by the Abbott ArchitectTM SARS-CoV-2 IgG assay. 545 participants, of whom 399 were antibody positive at enrolment, were followed up at 3 months. Results: The Panbio™ COVID-19 IgG/IgM rapid test device demonstrated a high concordance with laboratory tests. SARS-CoV-2 antibodies were detected in 506 participants (25.3%) at enrolment, with a higher prevalence in COVID-19 frontline (28.3%) than non-frontline (19.9%) staff. At follow-up, 274/399 antibody positive participants (68.7%) retained antibodies; 4/146 participants negative at enrolment (2.7%) had seroconverted. Non-white ethnicity, older age, hypertension and COVID-19 symptoms were independent predictors of higher antibody levels (OR 1.881, 2.422-3.034, 2.128, and 1.869 respectively), based on Architect™ index quartiles; participants in the first three categories also showed a greater antibody persistence at 3 months. Conclusion: The SARS-CoV-2 anti-nucleocapsid IgG positivity rate among healthcare staff was high, declining by 31.3% during the 3-month follow-up interval. Interestingly, the IgG-positive participants with certain risk factors for severe COVID-19 illness (older age, Black or Asian Ethnicity hypertension) demonstrated greater persistence over time when compared to the IgG-positive participants without these risk factors.

Musculoskeletal pain in Primary Care Physiotherapy: Associations with demographic and general health characteristics.

BACKGROUND: Many patients reporting musculoskeletal pain present to Primary Care Physiotherapy with costly comorbid overlapping complaints that remain medically unexplained. These subjective health complaints (SHC) incorporate coexisting multi-site musculoskeletal pain and varied non-musculoskeletal complaints (e.g. anxiety, tiredness). The role of these non-musculoskeletal complaints is acknowledged in spinal musculoskeletal disorders, but less so for peripheral musculoskeletal disorders. OBJECTIVE: This cross-sectional study explored the relationships between self-reported musculoskeletal pain sites, non-musculoskeletal complaints and disability among people reporting spinal or peripheral musculoskeletal pain. METHODS: Fifty individuals with spinal musculoskeletal pain and fifty with peripheral musculoskeletal pain provided data on disability, number of musculoskeletal pain sites and non-musculoskeletal complaints. Relationships between these variables were examined for each group using Pearson's correlation coefficient and linear regression analysis. RESULTS: Participants with spinal musculoskeletal pain recorded significantly more pain sites and non-musculoskeletal complaints than participants with peripheral musculoskeletal pain. However, there was no significant difference in disability between the groups. Non-musculoskeletal complaints were significantly associated with disability (correlation = 0.41, p < 0.01) and number of pain sites (correlation = 0.42, p < 0.01). Number of pain sites and disability were not significantly associated in either group. Participants with spinal musculoskeletal pain reported more tiredness, dizziness, anxiety and sleep problems. Participants reporting dizziness, anxiety, sadness/depression and sleep problems had higher disability. CONCLUSION: Further studies must confirm the robustness of these associations, to permit comparisons between clinical and general populations and aid identification of causal factors. Considering SHC within individualised management programmes may improve outcomes.

Community Vision and Interagency Alignment: A Community Planning Process to Promote Active Transportation.

In 2010, the Brooklyn Active Transportation Community Planning Initiative launched in 2 New York City neighborhoods. Over a 2-year planning period, residents participated in surveys, school and community forums, neighborhood street assessments, and activation events-activities that highlighted the need for safer streets locally. Consensus among residents and key multisectoral stakeholders, including city agencies and community-based organizations, was garnered in support of a planned expansion of bicycling infrastructure. The process of building on community assets and applying a collective impact approach yielded changes in the built environment, attracted new partners and resources, and helped to restore a sense of power among residents.

Cost-Effectiveness Analysis of Alternative Antiviral Strategies for the Treatment of HBeAg-Positive and HBeAg-Negative Chronic Hepatitis B in the United Kingdom.

BACKGROUND: Seven drugs are licensed for the treatment of chronic hepatitis B (CHB) in the United Kingdom. Which initial treatment, secondary therapy, and whether antivirals should be given alone or in combination are questions of considerable uncertainty. OBJECTIVE: The aim of this model was to undertake a comprehensive economic evaluation of all antiviral treatments for CHB to recommend the most cost-effective therapeutic sequence. METHODS: We developed a probabilistic Markov model to compare the cost-effectiveness of all clinically relevant antiviral treatment sequences for nucleos(t)ide-naive adults with hepatitis B e-antigen (HBeAg)-positive or HBeAg-negative CHB. Relative rates of HBeAg seroconversion and viral suppression were obtained from a network meta-analysis. Data on mortality, antiviral drug resistance, durability of response, adverse events, and costs were obtained from published literature. Results are reported in terms of lifetime costs, quality-adjusted life-years (QALYs), and expected net benefit. RESULTS: In the base-case analysis, pegylated interferon alpha-2a (peg-IFN α-2a) followed by tenofovir disoproxil fumarate was most effective and cost-effective in HBeAg-positive patients, with a cost of £7488 per QALY gained compared with no treatment. In HBeAg-negative patients, peg-IFN α-2a followed by entecavir was most effective and cost-effective, with a cost of £6981 per QALY gained. The model was robust to a wide range of sensitivity analyses. CONCLUSIONS: Peg-IFN α-2a followed by tenofovir disoproxil fumarate or entecavir is the most effective antiviral treatment strategy for people with both variants of CHB. At a cost of less than £10,000 per QALY gained, these sequences are considered cost-effective in England and Wales. The results of this analysis were used to inform 2013 National Institute for Health and Care Excellence guideline recommendations.

Hepatitis delta virus testing, epidemiology and management: a multicentre cross-sectional study of patients in London.

BACKGROUND: Hepatitis delta virus (HDV) testing is recommended for all patients with hepatitis B virus (HBV) infection. HDV infection is associated with severe liver disease and interferon is the only available treatment. OBJECTIVES: To determine the rate of anti-HDV antibody testing in HBV patients; and to describe the epidemiology, clinical characteristics and management of HDV-infected patients at four hospitals in London. STUDY DESIGN: The anti-HDV testing rate was estimated by reviewing clinical and laboratory data. Cross-sectional data collection identified HDV-infected patients who had attended the study centres between 2005 and 2012. RESULTS: At a centre with clinic-led anti-HDV testing, 40% (67/168) of HBV patients were tested. Recently diagnosed HBV patients were more likely to be screened than those under long-term follow-up (62% vs 36%, P=0.01). At a centre with reflex laboratory testing, 99.4% (3543/3563) of first hepatitis B surface antigen positive samples were tested for anti-HDV. Across the four study centres there were 55 HDV-infected patients, of whom 50 (91%) had immigrated to the UK and 27 (49%) had evidence of cirrhosis. 31 patients received interferon therapy for HDV with an end of treatment virological response observed in 10 (32%). CONCLUSIONS: The anti-HDV testing rate was low in a centre with clinic-led testing, but could not be evaluated in all centres. The HDV-infected patients were of diverse ethnicity, with extensive histological evidence of liver disease and poor therapeutic responses. Future recommendations include reflex laboratory testing algorithms and a prospective cohort study to optimise the investigation and management of these patients.

Assessment of bone mineral density in tenofovir-treated patients with chronic hepatitis B: can the fracture risk assessment tool identify those at greatest risk?

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is an established nucleotide analogue in the treatment of chronic hepatitis B. Bone mineral density loss has been described in TDF-treated patients with human immunodeficiency virus infection, but limited data exist for patients with chronic hepatitis B. Dual X-ray absorptiometry (DEXA) was used to determine bone mineral density changes in TDF-exposed patients. We evaluated the accuracy of the Fracture Risk Assessment Tool (FRAX) as an alternative to DEXA in clinical practice. METHODS: A total of 170 patients were studied: 122 were exposed to TDF, and 48 were controls. All patients underwent DEXA, and demographic details were recorded. FRAX scores (before and after DEXA) were calculated. RESULTS: TDF was associated with a lower hip T score (P = .02). On univariate and multivariate analysis, advancing age, smoking, lower body mass index, and TDF exposure were independent predictors of low bone mineral density. In addition, the pre-DEXA FRAX score was an accurate predictor of the post-DEXA FRAX treatment recommendation (100% sensitivity and 83% specificity), area under the curve 0.93 (95% CI, .87-.97, P < .001). CONCLUSIONS: TDF-treated patients with chronic hepatitis B have reduced bone mineral density, but the reduction is limited to 1 anatomical site. Age and advanced liver disease are additional contributing factors, underlining the importance of multifactorial fracture risk assessment. FRAX can accurately identify those at greatest risk of osteoporotic fracture.

Health economic analysis of Breast Cancer Index in patients with ER+, LN- breast cancer.

OBJECTIVES: Breast Cancer Index (BCI) is a novel gene expression-based test for patients with estrogen receptor positive (ER+), lymph node negative (LN-) breast cancer that predicts risk of recurrence over 10 years, and also specifically predicts risk of late (≥5 y) recurrences and likelihood of benefit from extended (≥5 y) endocrine therapy. The objective of this study was to evaluate cost utility of BCI from a US third-party payer perspective. STUDY DESIGN: Two fact-based economic models were developed to project the cost and effectiveness of BCI in a hypothetical population of patients with ER+, LN- breast cancer compared with standard clinicopathologic diagnostic modalities. METHODS: Costs associated with adjuvant chemotherapy, toxicity, followup, endocrine therapy, and recurrence were modeled over 10 years. The models examined cost utility compared with standard practice when used at diagnosis and in patients disease-free at 5 years post diagnosis. RESULTS: Use of BCI was projected to be cost saving in both models. In the newly diagnosed population, net cost savings were $3803 per patient tested. In the 5 years post diagnosis population, BCI was projected to yield a net cost savings of $1803 per patient tested. Sensitivity analyses demonstrated that BCI was cost saving across a wide range of clinically relevant input assumptions. CONCLUSIONS: BCI was projected to be cost saving when used either at diagnosis or at 5 years post diagnosis. Cost savings are achieved through projected impact on adjuvant chemotherapy use, extended endocrine therapy use, and endocrine therapy compliance. These findings require validation in additional cohorts, including studies of real-world clinical practice.

The role of liver fibrosis assessment in the management of patients with chronic hepatitis B infection: lessons learned from a single centre experience.

Background & Aims. Assess the clinical utility of the Prati criteria and normal ALT (<40 IU/L) in a cohort of patients with chronic hepatitis B infection (CHB). Methods. Serology, radiology, and histology were obtained in 140 patients with CHB. Results. HBeAg(+) group: 7 patients (7/56-12% HBeAg(+) group) misclassified as "immunotolerant", with HBV DNA > 6 log copies/ml and normal ALT, who in fact had moderate/severe fibrosis on liver biopsy. HBeAg(-) group: 10 patients with normal ALT and moderate/severe fibrosis on liver biopsy; 4 of these patients had >3 log copies/ml HBV DNA levels and 6 patients misclassified as "inactive carriers" with negative HBV DNA levels normal ALT and moderate/severe fibrosis (6/84-7% HBeAg(-) group). Two male HBeAg(+) and three male HBeAg(-) patients with ALT between 20 and 30 IU/L and moderate/severe fibrosis on liver biopsy would have been further mischaracterised using the Prati criteria for normal ALT. Age and ethnic group were more important predictors of moderate/severe fibrosis in multivariate analysis. Conclusion. HBeAg status, age, ethnic origin with longitudinal assessment of LFTs and viral load should be studied in patients with "normal ALT" at the upper end of normal range (ALT 20-40 IU/L) to appropriately classify patients and identify patients for liver fibrosis assessment to inform treatment decisions.

Shepherding change: how the market, healthcare providers, and public policy can deliver quality care for the 21st century.

BACKGROUND: Data are scarce that inform the ways consumers of health care and caregivers help improve the care that is delivered. The healthcare system is quite broad. To improve it, we first must understand it, understand its various subsystems, and understand how they shape individual behavior. DISCUSSION: Both consumers and providers can effectively improve health care. An example of an influential consumer is provided, focusing a successful effort to improve care in the intensive care unit. The overall model for improving outcomes assumes providers can be classified into high-quality and low-quality providers. The model then aims to increase the number of people exposed to high-quality caregivers. There are three primary levers for driving this change: using market forces, provider improvements, and policy change. This article touches briefly on the first and focuses on the second and third. CONCLUSION: A number of grassroots programs highlight ways providers can improve care by approaching patient safety and quality as a science. In addition, the Josie King Act and its legislative progeny provide some hope that a new policy environment can reward and reinforce providers' efforts to drive up safety and quality.

Adolescent drug trafficking trends in the United Kingdom--a 10-year retrospective analysis.

This paper reports data from HM Customs and Excise (HMCE) of recorded cases of adolescent drug trafficking through all sea and air points of entry into the UK over a 10-year period (May 1992-May 2002). We report the characteristics of 38 cases of mixed gender and nationality ranging in age between 13 and 18 years who have been apprehended by HMCE due to the illegal importation of drugs. Highlighted is an increasing trend in UK national male and female adolescents being apprehended for drug trafficking. Of particular note is the observation that more young adolescent females were apprehended importing large consignments of Class A substances than their male counterparts.

Why we must end insurance discrimination against mental health care.

In this Policy Essay, Representative Patrick Kennedy argues that insurance discrimination against those suffering from mental illness constitutes a serious and often overlooked deficiency of the modern American health care system. While the Mental Health Parity Act of 1996 was an important step toward resolutions of this issue, many loopholes remain that allow insurance companies to deny much-needed coverage to those suffering from such illnesses. This Essay details how improving access to health insurance for the mentally ill is not only socially beneficial, but also economically sound; the cost of instituting mental health parity is far outweighed by the costs that employers bear because of the reduced productivity of untreated mental illness sufferers. Representative Kennedy recommends that these problems may be addressed by additional mental health policy legislation--specifically, the proposed Paul Wellstone Act.