Bulevirtide Combined with Pegylated Interferon for Chronic Hepatitis D.

BACKGROUND: In a phase 3 trial, bulevirtide monotherapy led to a virologic response in patients with chronic hepatitis D. Pegylated interferon (peginterferon) alfa-2a is recommended by guidelines as an off-label treatment for this disease. The role of combination therapy with bulevirtide and peginterferon alfa-2a, particularly with regard to finite treatment, is unclear. METHODS: In this phase 2b, open-label trial, we randomly assigned patients to receive peginterferon alfa-2a alone (180 µg per week) for 48 weeks; bulevirtide at a daily dose of 2 mg or 10 mg plus peginterferon alfa-2a (180 µg per week) for 48 weeks, followed by the same daily dose of bulevirtide for 48 weeks; or bulevirtide at a daily dose of 10 mg alone for 96 weeks. All the patients were followed for 48 weeks after the end of treatment. The primary end point was an undetectable level of hepatitis D virus (HDV) RNA at 24 weeks after the end of treatment. The primary comparison was between the 10-mg bulevirtide plus peginterferon alfa-2a group and the 10-mg bulevirtide monotherapy group. RESULTS: A total of 24 patients received peginterferon alfa-2a alone, 50 received 2 mg and 50 received 10 mg of bulevirtide plus peginterferon alfa-2a, and 50 received 10 mg of bulevirtide monotherapy. At 24 weeks after the end of treatment, HDV RNA was undetectable in 17% of the patients in the peginterferon alfa-2a group, in 32% of those in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of those in the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of those in the 10-mg bulevirtide group. For the primary comparison, the between-group difference was 34 percentage points (95% confidence interval, 15 to 50; P<0.001). At 48 weeks after the end of treatment, HDV RNA was undetectable in 25% of the patients in the peginterferon alfa-2a group, in 26% of those in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of those in the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of those in the 10-mg bulevirtide group. The most frequent adverse events were leukopenia, neutropenia, and thrombocytopenia. The majority of adverse events were of grade 1 or 2 in severity. CONCLUSIONS: The combination of 10-mg bulevirtide plus peginterferon alfa-2a was superior to bulevirtide monotherapy with regard to an undetectable HDV RNA level at 24 weeks after the end of treatment. (Funded by Gilead Sciences; MYR 204 ClinicalTrials.gov number, NCT03852433.).

Bulevirtide monotherapy in patients with chronic HDV: Efficacy and safety results through week 96 from a phase III randomized trial.

BACKGROUND & AIMS: Bulevirtide (BLV), a first-in-class entry inhibitor, is approved in Europe for the treatment of chronic hepatitis delta (CHD). BLV monotherapy was superior to delayed treatment at week (W) 48, the primary efficacy endpoint, in the MYR301 study (NCT03852719). Here, we assessed if continued BLV therapy until W96 would improve virologic and biochemical response rates, particularly among patients who did not achieve virologic response at W24. METHODS: In this ongoing, open-label, randomized phase III study, patients with CHD (N = 150) were randomized (1:1:1) to treatment with BLV 2 mg/day (n = 49) or 10 mg/day (n = 50), each for 144 weeks, or to delayed treatment for 48 weeks followed by BLV 10 mg/day for 96 weeks (n = 51). Combined response was defined as undetectable hepatitis delta virus (HDV) RNA or a decrease in HDV RNA by ≥2 log10 IU/ml from baseline and alanine aminotransferase (ALT) normalization. Other endpoints included virologic response, ALT normalization, and change in HDV RNA. RESULTS: Of 150 patients, 143 (95%) completed 96 weeks of the study. Efficacy responses were maintained and/or improved between W48 and W96, with similar combined, virologic, and biochemical response rates between BLV 2 and 10 mg. Of the patients with a suboptimal early virologic response at W24, 43% of non-responders and 82% of partial responders achieved virologic response at W96. Biochemical improvement often occurred independently of virologic response. Adverse events were mostly mild, with no serious adverse events related to BLV. CONCLUSIONS: Virologic and biochemical responses were maintained and/or increased with longer term BLV therapy, including in those with suboptimal early virologic response. BLV monotherapy for CHD was safe and well tolerated through W96. IMPACT AND IMPLICATIONS: In July 2023, bulevirtide was fully approved for the treatment of chronic hepatitis delta (CHD) in Europe based on clinical study results from up to 48 weeks of treatment. Understanding the efficacy and safety of bulevirtide over the longer term is important for healthcare providers. In this analysis, we demonstrate that bulevirtide monotherapy for 96 weeks in patients with CHD was associated with continued improvements in combined, virologic, and biochemical responses as well as liver stiffness from week 48 at both the 2 mg and 10 mg doses. Patients with suboptimal virologic responses to bulevirtide at week 24 also benefited from continued therapy, with the majority achieving virologic response or biochemical improvement by week 96. GOV IDENTIFIER: NCT03852719.

Treating the Hardest to Treat: Reframing the Hospital Admission as an Opportunity to Initiate Hepatitis C Treatment.

BACKGROUND: Chronic hepatitis C (CHC) is traditionally treated in the outpatient setting. Despite the excellent tolerability, shortened treatment duration, and high cure rates of newer direct-acting antivirals (DAAs), many vulnerable patients remain untreated due to issues with linkage to care. AIMS: This study sought to reframe and establish the hospital admission as a unique opportunity to initiate antiviral treatment for patients with CHC, particularly those with psychosocial or linkage to care issues. METHODS: Patients with untreated CHC were identified either on the Psychiatry or Med/Surg wards at the Veterans Affairs Palo Alto Health Care System (VAPAHCS). If found to be appropriate for treatment initiation, patients were started on antivirals during their hospitalization and followed closely while inpatient and after discharge to assess for sustained virologic response (SVR), treatment tolerability, and treatment completion. RESULTS: Overall, 36% (23) of potential treatment candidates were initiated on DAA treatment during their hospitalization. Of these patients, 91.3% had documented treatment completion with an intention-to-treat and modified intention-to-treat SVR rate of 91.3% and 100%, respectively. CONCLUSIONS: We establish the hospital admission as a valuable opportunity for HCV treatment initiation, yielding excellent treatment outcomes in those who would not otherwise be treated and achieved a modified intention-to-treat response rate of 100%.

Why differentiating between health system support and health system strengthening is needed.

There is increasing recognition that efforts to improve global health cannot be achieved without stronger health systems. Interpretation of health system strengthening (HSS) has varied widely however, with much of the focus to-date on alleviating input constraints, whereas less attention has been given to other performance drivers. It is important to distinguish activities that support the health system, from ones that strengthen the health system. Supporting the health system can include any activity that improves services, from distributing mosquito nets to procuring medicines. These activities improve outcomes primarily by increasing inputs. Strengthening the health system is accomplished by more comprehensive changes to performance drivers such as policies and regulations, organizational structures, and relationships across the health system to motivate changes in behavior and/or allow more effective use of resources to improve multiple health services. Even organizations that have made significant investments in health systems have not provided guidance on what HSS entails. While both supporting and strengthening are important and necessary, it is nonetheless important to make a distinction. If activities fail to produce improvements in system performance because they were incorrectly labeled as system strengthening, the value of HSS investments could quickly be discredited. Not distinguishing supportive activities from strengthening ones will lead to unmet expectations of stronger health systems, as well as neglect of critical system strengthening activities. Distinguishing between these two types of activities will improve programming impact.

Uncovering the Drivers of Childhood Immunization Inequality with Caregivers, Community Members and Health System Stakeholders: Results from a Human-Centered Design Study in DRC, Mozambique and Nigeria.

BACKGROUND: The importance of immunization for child survival underscores the need to eliminate immunization inequalities. Few existing studies of inequalities use approaches that view the challenges and potential solutions from the perspective of caregivers. This study aimed to identify barriers and context-appropriate solutions by engaging deeply with caregivers, community members, health workers, and other health system actors through participatory action research, intersectionality, and human-centered design lenses. METHODS: This study was conducted in the Demographic Republic of Congo, Mozambique and Nigeria. Rapid qualitative research was followed by co-creation workshops with study participants to identify solutions. We analyzed the data using the UNICEF Journey to Health and Immunization Framework. RESULTS: Caregivers of zero-dose and under-immunized children faced multiple intersecting and interacting barriers related to gender, poverty, geographic access, and service experience. Immunization programs were not aligned with needs of the most vulnerable due to the sub-optimal implementation of pro-equity strategies, such as outreach vaccination. Caregivers and communities identified feasible solutions through co-creation workshops and this approach should be used whenever possible to inform local planning. CONCLUSIONS: Policymakers and managers can integrate HCD and intersectionality mindsets into existing planning and assessment processes, and focus on overcoming root causes of sub-optimal implementation.

Interferon free hepatitis C treatment regimens: the beginning of another era.

Hepatitis C is a virus affecting millions worldwide and is a major health risk. With the potentially severe adverse event profile of the current backbone of therapy, interferon, there is an impetus to discover interferon free treatment regimens. With the development of new oral direct acting antivirals, interferon free regimens may be available in the next few years. This article discusses some of the preliminary data from interferon free studies.

Conflicts and communication between high-achieving Chinese American adolescents and their parents.

Drawing on in-depth interview data collected on 18 high-achieving Chinese American students, the authors examine domains of acculturation-based conflicts, parent and child internal conflicts, and conflict resolution in their families. Their analyses show that well-established negative communication patterns in educational expectations, divergent attitudes toward other races and country of origin, and cultural and language barriers contributed to parent-child conflicts. Their findings also illustrate important internal conflicts both adolescents and parents had along the cultural tightrope of autonomy and relatedness. Finally, the vertical in-group conflict resolution style that was evidenced in youths' accounts raises questions about cultural differences in constructive versus destructive conflict resolution styles.

Comorbidities associated with the increasing burden of hepatitis C infection.

BACKGROUND: Hepatitis C virus (HCV) infection is implicated in an increasing number of liver transplantations, hospitalizations and healthcare costs. AIMS: We present an updated assessment of comorbidities associated with HCV in comparison to the general US population. METHODS: Cross-sectional retrospective review of data from 800 patients with HCV evaluated between January 1998 and November 2007. Patient data were prospectively collected using a standardized questionnaire completed at the first encounter and was compared with general US epidemiological data. Odds ratios and 95% confidence intervals (CI) are reported. RESULTS: HCV conferred a 44% (CI 1.16-1.78) and 25% (CI 1.01-1.54) increased risk of diabetes (12.5 vs. 7.3-8.4%; P=0.001) and obesity (23.9 vs. 19.8-33.1%; P=0.041), respectively, compared with the US population. Human immunodeficiency virus (HIV) (5.3 vs. 0.3%; P<0.001) and end-stage renal disease (ESRD) (4.5 vs. 0.2%; P<0.001) were 16- and 13-fold more prevalent in HCV. Interestingly, HCV bestowed 90% decreased odds (CI 0.09-0.15) for hyperlipidaemia (12.3 vs. 53.2-56.1%; P<0.001). The HCV population had a higher prevalence of significant alcohol consumption (41.5 vs. 4.7%; P<0.001), current smoking (57.7 vs. 18.8-20.8%; P<0.001), drug use (46.8 vs. 14.6-15.6%; P<0.001), incarceration (6.6 vs. 2.7%; P<0.001) and tattoos (20.3 vs. 14%; P=0.011), as well as chronic fatigue (44.6 vs. 11.3-19%; P<0.001) and depression (29.3 vs. 5.0-10.3%; P<0.001). CONCLUSION: HCV poses an increasing healthcare burden associated with increased prevalence of diabetes, obesity, HIV, ESRD, maladaptive lifestyle habits and poor quality of life. Practitioners should be cognizant of these trends in order to appropriately manage these comorbidities.

Viral resistance in hepatitis B: prevalence and management.

Hepatitis B is a DNA virus affecting hundreds of millions of individuals worldwide. As the clinical sequelae of cirrhosis and hepatocellular cancer are increasingly recognized to be related to viral levels, the impetus increases to offer treatment to those previously not treated. With the development of more robust antivirals with reasonable safety profiles, long-term treatment is becoming more common. The oral nucleos(t)ide analogs have become the preferred first-line therapies for most genotypes of hepatitis B. Five are now available, all with different potencies and resistance profiles. Long-term data spanning several years are now available for most compounds in this arena. This article focuses on the common natural variants and those secondary to nucleos(t)ide therapy, as well as diagnostic methods to detect resistance.

Assessing the Risk Factors of Cyber and Mobile Phone Bullying Victimization in a Nationally Representative Sample of Singapore Youth.

This study utilized routine activity theory to examine the relationships between online behaviors, target suitability, and cyber and mobile phone-based bullying victimization in a nationally representative sample of youth from nine schools across Singapore. Key measures in all three categories-access to technology, online routine behaviors, and target suitability-were significant predictors of both forms of bullying victimization. In particular, females and victims of physical bullying were more likely to experience both forms of victimization. Access to technology and online routine behaviors predicted cyber and mobile phone-based bullying victimization differently. These findings demonstrate that routine activity theory is a viable framework to understand online bullying in non-Western nations, consistent with the existing literature on Western nations.

Individual and contextual determinants of resident-on-resident abuse in nursing homes: a random sample telephone survey of adults with an older family member in a nursing home.

Few empirical investigations of elder abuse in nursing homes address the frequency and determinants of resident-on-resident abuse (RRA). A random sample of 452 adults with an older adult relative, ≥65 years of age, in a nursing home completed a telephone survey regarding elder abuse experienced by that elder family member. Using a Linear Structural Relations (LISREL) modeling design, the study examined the association of nursing home resident demographic characteristics (e.g., age, gender), health and behavioral characteristics (e.g., diagnosis of Alzheimer's Disease, Activities of Daily Living (ADLs), Instrumental Activities of Daily Living (IADLs), types of staff abuse (e.g., physical, emotional), and factors beyond the immediate nursing home setting (e.g., emotional closeness of resident with family members) with RRA. Mplus statistical software was used for structural equation modeling. Main findings indicated that resident-on-resident mistreatment of elderly nursing home residents is associated with the age of the nursing home resident, all forms of staff abuse, all ADLs and IADLs, and emotional closeness of the older adult to the family.

Electrochemical impedance spectroscopy as an alternative to determine dielectric constant of potatoes at various moisture contents.

The dielectric (DE) properties, specifically the DE constant (ε') and loss factor (ε''), were measured for vacuum-dried and freeze-dried potato samples at a microwave frequency of 2.45 GHz over a range of different moisture contents (MCs) using a DE probe and also a 2-probe electrochemical impedance spectroscopy (EIS). Third-order polynomial models (ε' = f1(MC); and ε'' = f2(MC)) at room temperature were developed for regression analysis. Additionally, at various temperatures (T), biphasic 3rd-order polynomial models (ε' = f1(MC, T); and ε'' = f2(MC, T)) were obtained to determine ε' and ε'' as a function of MC and T using measured data. The vacuum-dried potato sample showed a good fitness of ε' and ε'' (R² = 0.95 and 0.96, respectively) to the regression model with the range of MCs from 18% to 80% (w/w), while the freeze-dried potato sample showed a good fitness of ε' and ε'' to the 1st-phase regression model with MC < 50% w/w (R² = 0.95 and 0.96, respectively) and the 2nd-phase regression model with MC > 50% w/w (R² = 0.94 to 0.96). EIS measurements were also used to obtain correlation impedances for ε' and ε'' determined by the DE probe method. The resulted regression analysis meets the demands for simple, rapid, and accurate assessment for transient values of ε' and ε'' of food products during dehydration/drying processes. The EIS method was verified to be a successful alternative to direct measurements of ε' and ε''.

Electrochemical impedance spectroscopic technique with a functionalized microwire sensor for rapid detection of foodborne pathogens.

In this study, a label-free biosensor based on electrochemical impedance measurement followed by dielectrophoretic force and antibody-antigen interaction was developed for detection and quantification of foodborne pathogenic bacteria. In our previous work, gold-tungsten wires (25 µm in diameter) were functionalized by coating with polyethyleneimine-streptavidin-anti-Escherichia coli antibodies to improve sensing specificity, and fluorescence intensity measurement was employed to quantify bacteria captured by the sensor. The focus of this research is to evaluate the performance of the developed biosensor by monitoring the changes of electron-transfer resistance (ΔR(et)) of the microwire after the bioaffinity reaction between bacterial cells and antibodies on its surface as an alternative quantification technique to fluorescence microscopy. Electrochemical impedance spectroscopy (EIS) has been used to detect and validate the resistance changes in a conventional three-electrode system in which [Fe(CN)6³â»]/[Fe(CN)64⁻] served as the redox probe. The impedance data demonstrated a linear relationship between the increments of ΔR(et) and the logarithmic concentrations of E. coli suspension in the range of 10³-108 CFU/mL. In addition, there were little changes of ΔR(et) when the sensor worked with Salmonella, which clearly evidenced the sensing specificity to E. coli. EIS was proven to be an ideal alternative to fluorescence microscopy for enumeration of captured cells.

Social-relational risk factors for predicting elder physical abuse: an ecological bi-focal model.

Annually in the United States, 1 to 5 million older adults, 65 and above, are physically or sexually injured or mistreated by their caregivers in family settings. This study examined the prevalence and risk factors involved in elder physical abuse by adult child caregivers, moving from the immediate elderly parent/adult child relationship context to more distal social support contexts, utilizing a subsample of 203 elderly participants from the Midlife Development in the United States study (MIDUS II, 2004-2006). LISREL modeling examined causal pathways between elderly demographic characteristics, physical/emotional health, and behavioral and contextual characteristics from an ecological perspective. Data modeling was accomplished using Mplus, PAXW, and SYSTAT statistical software packages. Results indicate that latent factors including older adult health, social isolation of the older adult, and adult child characteristics were significantly associated with elder physical abuse, as mediated by the quality of the elderly parent/adult child relationship.

Characterization of edible coatings consisting of pea starch, whey protein isolate, and Carnauba wax and their effects on oil rancidity and sensory properties of walnuts and pine nuts.

UNLABELLED: Edible coatings made of whey protein isolate (WPI), pea starch (PS), and their combinations with carnauba wax (CW) were prepared and characterized. WPI combined with CW formed stable emulsion while PS with CW formed unstable emulsion and both formulations produced non-homogeneous films. Addition of PS to WPI: CW combination at the ratio of 1:1:1, respectively, resulted in stable emulsion and homogenous films. The emulsion PS: WPI: CW (1:1:2) was stable and formed a continuous film but had less homogenous droplets size distribution when compared to 1:1:1 film. Combined films had a reduced tensile strength and elongation compared to single component films. WPI : CW (1:1) films had higher elastic modulus than the WPI films, but the modulus reduced by the addition of PS. All the coating formulations were effective in preventing oxidative and hydrolytic rancidity of walnuts and pine nuts stored at 25 °C throughout the storage (12 d) but were less effective at 50 °C. Increasing the concentration of CW from 1:1:1 to 1:1:2 in PS: WPI: CW formulation did not contribute in further prevention of oil rancidity at 25 °C. Using of PS: WPI: CW (1:1:1) coating on both nuts significantly (P < 0.05) improved their smoothness and taste but the PS: WPI: CW (1:1:2) coatings imparted unacceptable yellowish color on walnuts. PRACTICAL APPLICATION: Edible coating of walnuts and pine nuts by whey protein isolate, pea starch, and carnauba wax reduced the oxidative and hydrolytic rancidity of the nuts and improved sensory characteristics.

Using financing to motivate a for-profit health care provider to deliver family planning services: is it a cost-effective intervention? A study of AAR health services in Kenya.

Despite much discussion of the role of private health care providers, there are no tried and tested models for supporting for-profit providers in ways that produce cost-effective public health outcomes. This paper examines the cost effectiveness of using a loan mechanism to motivate a for-profit provider to deliver family planning services. The intervention examined directly resulted in a private provider delivering family planning services, however, it did not create a long-term financial incentive for the private provider to promote the use of family planning. The cost effectiveness of this intervention is analysed using a methodology that captures long term sustainability of the intervention within a traditional family planning outcome measure, such as couple years protection (CYP), by discounting future expected CYPs. Depending on the method for analysing costs and assumptions regarding future CYPs, this intervention produced family planning outcomes at no or very low cost (0 dollars-4.11 dollars per CYP). The analysis demonstrates that innovative family planning interventions with private providers should be considered as they can be more cost effective than traditional programmes.