Genetic newborn screening and digital technologies: A project protocol based on a dual approach to shorten the rare diseases diagnostic path in Europe.

Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations. It focuses on genetic newborn screening and artificial intelligence-based tools which will be applied to a large European population of about 25.000 infants. The neonatal screening strategy will be based on targeted sequencing, while whole genome sequencing will be offered to all enrolled infants who may show early symptoms but have resulted negative at the targeted sequencing-based newborn screening. We will leverage artificial intelligence-based algorithms to identify patients using Electronic Health Records (EHR) and to build a repository "symptom checkers" for patients and healthcare providers. S4C will design an equitable, ethical, and sustainable framework for genetic newborn screening and new digital tools, corroborated by a large workout where legal, ethical, and social complexities will be addressed with the intent of making the framework highly and flexibly translatable into the diverse European health systems

HBsAg Seroclearance in Chinese Patients Receiving Lamivudine Therapy for Chronic Hepatitis B Virus Infection

We report two Chinese patients in whom lamivudine treatment resulted in HBsAg seroclearance. One patient received lamivudine, and another patient received 12-week famciclovir treatment followed by lamivudine. Lamivudine was maintained after HBeAg seroconversion. These two patients lost HBsAg at 24 and 27 months (ages, 23 and 19.3 years, respectively) and developed measurable titer of anti-HBs after 65 and 71 months of therapy, respectively. The liver biochemistry was normal after HBeAg seroconversion. The serum hepatitis B virus (HBV) DNA levels were undetectable (<200 copies/ml) both at the time of HBeAg seroconversion and at the last follow-up. Liver biopsy of one patient showed nearly normal histology, with undetectable intrahepatic total HBV DNA and covalently closed circular DNA. In conclusion, lamivudine therapy can result in HBsAg seroclearance at an early age even though the phenomenon is rare

Clinical Evaluation of the Digene Hybrid Capture II Test and the COBAS AMPLICOR Monitor Test for Determination of Hepatitis B Virus DNA Levels

The measurement of hepatitis B virus (HBV) DNA is important for the assessment of liver disease and treatment efficacy. Most commercially available assays for the determination of HBV DNA levels have limited linear ranges. This study was performed to evaluate the clinical performance of the Digene Hybrid Capture II (Digene HC II assay) and the COBAS AMPLICOR Monitor test (COBAS-AM assay), with special emphasis on anti-HBV e antigen (HBeAg)-positive patients with low HBV DNA levels. A total of 425 Chinese patients with chronic hepatitis B were recruited. A total of 107 patients were HBeAg positive, and 318 patients were HBeAg negative. The Digene HC II assay and the COBAS-AM assay had similar intra-assay and interassay variabilities. A total of 264 patients (62.1%) had HBV DNA levels undetectable by the Digene HC II assay, and 47 patients (11.1%) had HBV DNA levels undetectable by the COBAS-AM assay (P < 0.001). For the 161 patients with HBV DNA levels detectable by the Digene HC II assay, the HBV DNA levels obtained by the Digene HC II assay and by the COBAS-AM assay showed an excellent correlation (r = 0.95; P < 0.001). The linear ranges of the Digene HC II assay and the COBAS-AM assay marginally overlapped. Before HBV DNA levels could be determined by the COBAS-AM assay, predilution had to be performed for 158 of 161 patients (98.1%) with HBV DNA levels detectable by the Digene HC II assay and for 10 of 264 patients (3.8%) with HBV DNA levels undetectable by the Digene HC II assay. The cost for assaying each serum sample by using different strategies was calculated. The COBAS-AM assay was more sensitive than the Digene HC II assay and more suitable for monitoring low levels of HBV viremia

Determinants for the Occurrence of Acute Exacerbation of Hepatitis B Virus Infection in Chinese Patients after HBeAg Seroclearance

This study was performed to determine the factors for predicting the occurrence of acute exacerbation of hepatitis B virus infection in HBeAg-negative patients. Two hundred and sixteen patients with known times of HBeAg seroclearance were recruited. Liver biochemistry and virologic markers were monitored. Precore and core promoter mutations were determined by a line probe assay. The median age at HBeAg seroclearance was 34.5 years. The median follow-up duration was 26.4 months. Fifty-six (27.9%) patients had acute exacerbations. By Cox regression analysis, male gender, older age, and core promoter mutations at the time of HBeAg seroclearance were independently associated with the occurrence of acute exacerbation after HBeAg seroclearance (P = 0.025, 0.018, and 0.001, respectively). Fourteen (7.0%) patients had HBeAg seroreversion within a median follow-up period of 11.6 months after HBeAg seroclearance. By Cox regression analysis, older age at HBeAg seroclearance was independently associated with the chance of HBeAg seroreversion (P = 0.01). We concluded that male patients with core promoter mutations and delayed HBeAg seroclearance had a higher cumulative chance of acute exacerbation in the HBeAg-negative phase. Patients with delayed HBeAg seroclearance had a higher frequency of HBeAg seroreversion

Detection of Intrahepatic Hepatitis B Virus DNA and Correlation with Hepatic Necroinflammation and Fibrosis

Assessment of intrahepatic hepatitis B virus (HBV) DNA levels in patients with chronic hepatitis B is important in understanding the natural history of the disease and designing antiviral therapy regimens. However, there is no standardized method for the measurement of intrahepatic HBV DNA levels. We describe a convenient novel method for the measurement of intrahepatic HBV DNA levels based on a modified COBAS Amplicor HBV Monitor test for HBV DNA measurement and real-time PCR β-actin gene detection for human genomic DNA (hgDNA) quantitation. Fifteen hepatitis B e antigen (HBeAg)-positive patients, 26 patients positive for antibody to HBeAg (anti-HBe), and 8 control patients were recruited. The mean between-run coefficient of variation for the β-actin real-time PCR assay was 15.4%. All eight control patients had undetectable intrahepatic and serum HBV DNA levels. All chronic hepatitis B patients had detectable intrahepatic HBV DNA levels, and all but one anti-HBe-positive patient had detectable serum HBV DNA levels. HBeAg-positive patients had higher median intrahepatic and serum HBV DNA levels than anti-HBe-positive patients (6,950 versus 676 HBV DNA copies/ng of hgDNA, respectively [P < 0.001] and 184 × 10(6) versus 6.65 × 10(6) copies/ml, respectively [P < 0.001]). The intrahepatic HBV DNA levels correlated strongly with the serum HBV DNA levels (r = 0.842; P < 0.001) and with the degree of fibrosis (P = 0.014). We conclude that the method that we describe is reliable and convenient for the measurement of intrahepatic HBV DNA levels and has potential clinical significance

Interactive association between negative emotion regulation and savoring is linked to anxiety symptoms among college students

Objective: This study tested the interactive relationships between college students’ perceived capability of regulating negative emotions and savoring positive emotions on mental health outcomes, including anxiety and depressive symptoms. Participants: Participants were healthy undergraduates (n = 167) recruited from two universities in Hong Kong. Methods: Students completed four scales assessing their perceived capability of using strategies to regulate negative and positive emotions and their anxiety and depressive symptoms. Results: Findings revealed that both anxiety and depressive symptoms were negatively linked to perceived capabilities of regulating negative emotions and savoring positive emotions. Furthermore, regulating negative emotions interacted with savoring positive emotions to predict anxiety symptoms. Conclusions: The need to simultaneously perform negative and positive emotion regulation is highlighted. The results suggest the priority of regulating negative emotions over savoring positive emotions in alleviating anxiety symptoms. Nevertheless, enhancing positive emotion shows greater benefits for those who are less adept at regulating negative emotions

Real-Time PCR Assay Using Molecular Beacon for Quantitation of Hepatitis B Virus DNA

Levels of hepatitis B virus (HBV) DNA in the blood serve as an important marker in monitoring the disease progression and treatment efficacy of chronic HBV infection. Several commercial assays are available for accurate measurement of HBV genomic DNA, but many of them are hampered by relatively low sensitivity and limited dynamic range. The aim of this study was to develop a sensitive and accurate assay for measuring HBV genomic DNA using real-time PCR with a molecular beacon (HBV beacon assay). The performance of this assay was validated by testing serial dilutions of the two EUROHEP HBV DNA standards (ad and ay subtypes) of known concentrations. The assay showed low intra-assay (<7%) and interassay (<5%) variations for both subtypes. Its dynamic range was found to be 10(1) to 10(7) copies per reaction (1.0 × 10(2) to 1.0 × 10(9) copies ml(−1)). The assay was further evaluated clinically using serum samples from 175 individuals with chronic hepatitis B. The HBV DNA level measured by this assay showed good correlation with that measured by the commercially available COBAS AMPLICOR HBV Monitor test (r = 0.901; P < 0.001). The higher sensitivity and broader dynamic range of this assay compared to the existing commercial assays will provide an ideal tool for monitoring disease progression and treatment efficacy in HBV-infected patients, in particular for those with low levels of HBV viremia

A randomized controlled study to evaluate the effects of lifestyle intervention program for patients with severe mental illness taking Second Generation Antipsychotics (SGAs) in body weight management and monitoring their Body Mass Index (BMI)

Background: Second generation antipsychotics (SGAs) are strongly associated with accelerated body weightgain resulting in overweight and obesity in patients with severe mental illness (SMI). Evidence found that lifestyleinterventions used behavioral techniques to improve dietary habits and increase physical activity can reduce the increasein patients’ body weight and BMI. Methods: Randomized Controlled Trial (RCT) on 54 patients with severe mental illnesswere randomized with 27 patients joined in the Lifestyle Intervention group (LIP) and 27 patients in treatment as usual group(TAU) from September/2018 to October/2019. The intervention group attended the educational talks on medication, dietcontrol and physical exercise and use of a daily record. Result: After twelve months, the LIP presented a decrease of 1.25kg(CI 95% -0.73 to 3.24) and treatment as usual TAU presented with a significant increase of 1.65kg CI 95% -2.84 to -0.45)(p=0.009). The BMI of the LIP showed a decrease of 0.51kg/m2 (CI 95% -0.29 to 1.33) and the TAU presented an increaseof 0.66kg/m2. Conclusion: The TAU shows a significant increase of body weight while the LIP group had a decrease inbody weight under the Life Intervention program. This study was not intended for patients to reduce body weight, rather toprevent their body weight to increase and enhance their quality of life through understanding physical health, exercise anddietary habit

A randomized controlled study to evaluate the effects of lifestyle intervention program for patients with severe mental illness taking Second Generation Antipsychotics (SGAs) in body weight management and monitoring their Body Mass Index (BMI)

Background: Second generation antipsychotics (SGAs) are strongly associated with accelerated body weightgain resulting in overweight and obesity in patients with severe mental illness (SMI). Evidence found that lifestyleinterventions used behavioral techniques to improve dietary habits and increase physical activity can reduce the increasein patients’ body weight and BMI. Methods: Randomized Controlled Trial (RCT) on 54 patients with severe mental illnesswere randomized with 27 patients joined in the Lifestyle Intervention group (LIP) and 27 patients in treatment as usual group(TAU) from September/2018 to October/2019. The intervention group attended the educational talks on medication, dietcontrol and physical exercise and use of a daily record. Result: After twelve months, the LIP presented a decrease of 1.25kg(CI 95% -0.73 to 3.24) and treatment as usual TAU presented with a significant increase of 1.65kg CI 95% -2.84 to -0.45)(p=0.009). The BMI of the LIP showed a decrease of 0.51kg/m2 (CI 95% -0.29 to 1.33) and the TAU presented an increaseof 0.66kg/m2. Conclusion: The TAU shows a significant increase of body weight while the LIP group had a decrease inbody weight under the Life Intervention program. This study was not intended for patients to reduce body weight, rather toprevent their body weight to increase and enhance their quality of life through understanding physical health, exercise anddietary habit