Assessing the rate of non-linkage to care and identifying barriers in individuals living with hepatitis B. Results of the LINK-B study.

BACKGROUND & AIMS: Hepatitis B infection is the most frequent cause of chronic hepatitis and liver cancer worldwide. Active searching for individuals with chronic hepatitis B has been proposed as a strategy to achieve the elimination of this virus. The primary aim of this study was to link to specialists HBsAg-positive individuals detected in a laboratory database and to characterize individuals who were not linked to care. METHODS: We performed a retrospective-prospective evaluation of all HBsAg-positive serum samples identified in the central laboratory of the Northern Barcelona area between January 2018 and June 2022. After reviewing the patients' clinical charts, all those not linked to care were given an appointment with a specialist. RESULTS: Medical records of 2765 different HBsAg-positive serum samples were reviewed and 2590 individuals were identified: 844 (32.6%) were not linked to a specialist, 653 were candidates for linkage, and 344 attended the specialist visit. The two main reasons why they were not under specialist care were administrative issues, such as living in another region (12.1%) and lacking contact details (4.1%), and low life expectancy (2.8%). Individuals who did not attend their scheduled visit were mainly young [38.1 ± 12.9 vs. 44.0 ± 14.0 (p < .001)], non-White European [75.3% vs. 58.1% (p < .001)] and men [70.7% vs. 56.4% (p < .001)]. CONCLUSIONS: One in every three HBsAg-positive individuals in our setting was not currently under specialist care. Of particular note, half of them had never attended a specialist consultation, an essential step for evaluating the disease and starting therapy in some countries.

In-Host HEV Quasispecies Evolution Shows the Limits of Mutagenic Antiviral Treatments.

Here, we report the in-host hepatitis E virus (HEV) quasispecies evolution in a chronically infected patient who was treated with three different regimens of ribavirin (RBV) for nearly 6 years. Sequential plasma samples were collected at different time points and subjected to RNA extraction and deep sequencing using the MiSeq Illumina platforms. Specifically, we RT-PCR amplified a single amplicon from the core region located in the open-reading frame 2 (ORF2). At the nucleotide level (genotype), our analysis showed an increase in the number of rare haplotypes and a drastic reduction in the frequency of the master (most represented) sequence during the period when the virus was found to be insensitive to RBV treatment. Contrarily, at the amino acid level (phenotype), our study revealed conservation of the amino acids, which is represented by a high prevalence of the master sequence. Our findings suggest that using mutagenic antivirals concomitant with high viral loads can lead to the selection and proliferation of a rich set of synonymous haplotypes that express the same phenotype. This can also lead to the selection and proliferation of conservative substitutions that express fitness-enhanced phenotypes. These results have important clinical implications, as they suggest that using mutagenic agents as a monotherapy treatment regimen in the absence of sufficiently effective viral inhibitors can result in diversification and proliferation of a highly diverse quasispecies resistant to further treatment. Therefore, such approaches should be avoided whenever possible.

LINK-B: study protocol of a retrospective and prospective project for identification and linkage to care of people living with hepatitis B in a large health area of Barcelona.

INTRODUCTION: An estimated 290 million people are living with hepatitis B virus (HBV) worldwide; in Spain, the prevalence of hepatitis B virus surface antigen (HBsAg) is 0.4%. In our setting, many HBsAg-positive individuals are not linked to care, which implies a barrier to receiving treatment and controlling the infection. The main objective of this project is to evaluate the performance of a programme designed to achieve appropriate linkage to specialist care of HBsAg-positive individuals, newly tested or previously tested and lost to follow-up. METHODS AND ANALYSIS: This is a retrospective and prospective study in which all HBsAg-positive cases recorded in the microbiology database will be identified. The retrospective phase will include cases detected between 2018 and 2020, and the prospective phase will run from January 2021 to June 2022. The project will be carried out in a tertiary university hospital covering the northern health area of Barcelona with a catchment population of 450 000 inhabitants and 16 affiliated primary care centres. The central laboratory detects approximately 1200 HBsAg-positive individuals every year; therefore, we expect to identify around 4000 patients over the duration of the project. The medical records of HBsAg-positive individuals will be consulted to identify and retrieve those who have not been appropriately linked to care. Candidates will be contacted to offer specialist disease assessment and follow-up. A website will be created to provide HBV-related information to primary care physicians, and a mobile phone application will be available to patients to improve the linkage circuits and ensure follow-up continuity. ETHICS AND DISSEMINATION: The Vall d'Hebrón Hospital Ethics Committee (PR(AG)201/2021) and the Spanish Agency of Medicines and Medical Devices approved this study. The findings will be disseminated through peer-reviewed publications and conference presentations. This programme could increase the number of HBsAg-positive individuals properly linked to care and achieve better HBV monitoring, which will have a positive impact on WHO's viral hepatitis elimination goals.

Follow-up evaluation of patients with liver test abnormalities detected during SARS-CoV2 infection.

Abnormal liver function tests (A-LFTs) during admission for coronavirus disease-19 (COVID-19) are frequent, but its evolution after COVID-19 resolution remains unexplored. We evaluated factors related to A-LFTs during COVID-19 and assessed the liver outcome after patients' discharge. This is a observational study including: (1) retrospective analysis of variables related to A-LFTs during COVID-19; and (2) follow-up evaluation with blood test, transient elastography and liver biopsy in those with persistent A-LFTs. A-LFTs were defined according to CTCAEv4.0. Among 595 patients, 366 (61.5%) showed A-LFTs. The ratio of partial pressure of oxygen and inspired oxygen fraction (P/F) below 200, ferritin ≥1000 ng/mL, male gender and antibiotic and immunomodulatory treatments were related to A-LFTs. Follow-up evaluation was performed in 153 individuals. Persistent A-LFTs at follow-up was similar in patients with/without A-LFTs during admission (14.1% vs. 4.9%, p = 0.104). Fifteen (93%) and 58 (39%) patients with/without A-LFTs at follow-up showed metabolic fatty liver disease criteria (p < 0.001), which were histologically confirmed. In conclusion, A-LFTs during COVID-19 were related to infection severity. Abnormalities remitted at follow-up in >80% of patients, and no correlation between A-LFTs at admission and at follow-up was found. Most patients with A-LFTs at follow-up had non-invasive and histologically proven fatty liver disease.

Motor control using cranio-cervical flexion exercises versus other treatments for non-specific chronic neck pain: A systematic review and meta-analysis.

BACKGROUND: Chronic neck pain affects a significant percentage of the adult population. Commonly, the pain is of unknown origin. In those cases, some alterations in motor control (MC) can appear in the deep cervical muscles. The specific training of these muscles could improve muscular function and reduce pain and disability. OBJECTIVE: To determine whether MC, using cranio-cervical flexion (CCF), is more effective than other treatments for non-specific chronic neck pain (NSCNP). DESIGN: Systematic review with meta-analysis. METHODS: A search was done in journals and in a variety of databases, between December 2017 and March 2018. Randomized clinical trials (RCTs) and systematic reviews of RCTs comparing MC with other treatments in adults with NSCNP, regarding pain and disability, were included. Risk of bias was analysed using the Cochrane risk of bias tool. Data was analysed using a random effects model. Heterogeneity was evaluated using the I2statistic. The quality of the evidence was measured using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Ten articles were included for qualitative review; nine were used for a quantitative analysis about the effect of MC on pain and eight for the analysis regarding disability. The meta-analysis comparing MC versus other treatments showed significant differences regarding pain and disability. CONCLUSIONS: MC interventions for NSCNP patients reduces pain and disability. MC seems to be more effective to reduce pain and disability than other treatments.

Influence of catch up growth on spatial learning and memory in a mouse model of intrauterine growth restriction.

BACKGROUND: Intrauterine growth restriction (IUGR) and rapid postnatal weight gain or catch up growth (CUG) increase the susceptibility to metabolic syndrome during adult life. Longitudinal studies have also revealed a high incidence of learning difficulties in children with IUGR. The aim of the present study was to investigate the effect of nutrition and CUG on learning memory in an IUGR animal model. We hypothesized that synaptic protein expression and transcription, an essential mechanism for memory consolidation, might be affected by intrauterine undernutrition. METHODS: IUGR was induced by 50% maternal caloric undernutrition throughout late gestation. During the suckling period, dams were either fed ad libitum or food restricted. The pups were divided into: Normal prenatal diet-Normal postnatal diet (NN), Restricted prenatal diet- Normal postnatal diet + catch up growth (RN+), Normal prenatal diet-Restricted postnatal diet (NR) and Restricted prenatal diet-Restricted postnatal diet (RR). At 4 weeks of age, memory was assessed via a water maze test. To evaluate synaptic function, 2 specific synaptic proteins (postsynaptic density-95 [PSD95], synaptophysin) as well as insulin receptors (IR) were tested by Western Blot and quantitative polymerase chain reaction (qPCR). Brain-derived neurotrophic factor and serum insulin levels were also studied. RESULTS AND CONCLUSIONS: The RN+ group presented a learning curve similar to the NN animals. The RR animals without CUG showed learning disabilities. PSD95 was lower in the RR group than in the NN and RN+ mice. In contrast, synaptophysin was similar in all groups. IR showed an inverse expression pattern to that of the PSD95. In conclusion, perinatal nutrition plays an important role in learning. CUG after a period of prenatal malnutrition seems to improve learning skills. The functional alterations observed might be related to lower PSD95 activity and a possible dysfunction in the hormone regulation of synaptic plasticity.

Prevalencia de trastornos del sueño y factores asociados en pacientes hospitalizados / Prevalence of sleep disorders and associated factors in inpatient

Objetivo Conocer la prevalencia de insomnio durante el ingreso en los pacientes hospitalizados en un servicio de medicina interna e identificar los factores asociados a la alteración del descanso nocturno. Método Estudio observacional y transversal de una muestra de pacientes hospitalizados por afecciones médicas, mayores de 18 años. El insomnio se valoró con la escala Atenas. Una enfermera administró un cuestionario de factores de riesgo que incluía factores sociodemográficos, motivo de ingreso, comorbilidades, medicamentos actuales, estado funcional, síntomas nocturnos y factores ambientales. Resultados Se reclutaron 299 pacientes, con una edad media de 73,7 años (DT 14,2). Se observó una prevalencia de insomnio global del 42,1%, algo superior en las mujeres (48,2%) que en los hombres (37,0%) (p = 0,052). En los menores de 65 años la prevalencia fue del 33,8% y en los pacientes de 65 años o más fue del 44,9% (p = 0,093). Los principales factores asociados al insomnio fueron los antecedentes de ansiedad, depresión y AVC, la pirosis, el dolor, el miedo y la pobre capacidad funcional durante el ingreso. Factores del entorno como el ruido, la sensación de frío o calor y los cambios de hábitos que comporta la hospitalización no alcanzaron la significación estadística. En los pacientes de 65 años o más el consumo de bloqueadores beta se asoció al insomnio. El análisis multivariado mostró como factores de riesgo independientes el AVC, la pirosis y el dolor (AU)

Objective: To determine the prevalence of insomnia in inpatient in an Internal Medicine Department and to identify risk factors of sleep disorders. Method: A cross-sectional observational study was designed. Inpatients over eighteen years old hospitalized for acute medical conditions were recruited. Insomnia was assessed by the Athens insomnia scale. A nurse administered a questionnaire on risk factors including sociodemographic factors, reason for admission, comorbidities, current medications, functional status, nocturnal symptoms, and environmental factors. Results: A total of 299 patients were recruited with a mean age of 73.7 years (SD 14.2). Overall prevalence of insomnia was 42.1%, slightly higher in women (48.2%) than in men (37.0%)(P = .052). In those less than 65 years the prevalence was 33.8%, and in patients aged 65 or over it was 44.9% (P = .093). The main factors associated with insomnia were a history of anxiety, depression and stroke, heartburn, pain, fear, and poor functional capacity at admission. Environmental factors such as noise, the sensation of cold or heat, and changing habits involved in hospitalization did not reach statistical significance. In patients 65 years or older, the use of beta-blockers was associated with insomnia. The multivariate analysis showed stroke, heartburn, and pain as independent risk factors for insomnia. Conclusions: Insomnia is highly prevalent among inpatient, and is associated with some treatable or modifiable factors (AU)

[Prevalence of sleep disorders and associated factors in inpatient]. / Prevalencia de trastornos del sueño y factores asociados en pacientes hospitalizados.

OBJECTIVE: To determine the prevalence of insomnia in inpatient in an Internal Medicine Department and to identify risk factors of sleep disorders. METHOD: A cross-sectional observational study was designed. Inpatients over eighteen years old hospitalized for acute medical conditions were recruited. Insomnia was assessed by the Athens insomnia scale. A nurse administered a questionnaire on risk factors including socio-demographic factors, reason for admission, comorbidities, current medications, functional status, nocturnal symptoms, and environmental factors. RESULTS: A total of 299 patients were recruited with a mean age of 73.7 years (SD 14.2). Overall prevalence of insomnia was 42.1%, slightly higher in women (48.2%) than in men (37.0%) (P=.052). In those less than 65 years the prevalence was 33.8%, and in patients aged 65 or over it was 44.9% (P=.093). The main factors associated with insomnia were a history of anxiety, depression and stroke, heartburn, pain, fear, and poor functional capacity at admission. Environmental factors such as noise, the sensation of cold or heat, and changing habits involved in hospitalization did not reach statistical significance. In patients 65 years or older, the use of beta-blockers was associated with insomnia. The multivariate analysis showed stroke, heartburn, and pain as independent risk factors for insomnia. CONCLUSIONS: Insomnia is highly prevalent among inpatient, and is associated with some treatable or modifiable factors.