Efficacy,immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.     

Sofosbuvir-velpatasvir en pacientes mexicanos con hepatitis C: una revisión retrospectiva

IntroductionThe sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking.MethodsA retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment.ResultsOverall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported.ConclusionTreatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.     

Accuracy of intentionally tilted implant placement in the maxilla using dynamic navigation: a retrospective clinical analysis

The aim of this retrospective study was to investigate the accuracy of dynamic navigation for the placement of intentionally tilted implants in the posterior maxilla. The study included 12 patients with edentulism or continuous multiple tooth loss, who had 48 implants inserted under dynamic navigation guidance in the posterior maxilla. Twenty-four implants near maxillary sinuses were intentionally tilted. The average platform deviation was 1.3 ± 0.4 mm (range 0.8–2.3 mm), apex deviation was 1.1 ± 0.5 mm (range 0.2–2.3 mm), and axis deviation was 3.1 ± 1.0° (range 1.8–6.7°). The other 24 implants were axially positioned. The average platform deviation was 1.5 ± 0.5 mm (range 0.7–3.1 mm), apex deviation was 1.3 ± 0.7 mm (range 0.5–3.1 mm), and axis deviation was 3.2 ± 1.5° (range 1.5–7.7°). There was no significant difference in platform deviation, apex deviation, or axis deviation between the tilted implants and implants in the axial position (P > 0.05). This analysis indicates that a dynamic navigation system can be used as a method of guidance to place intentionally tilted implants as accurately as axially positioned implants in the posterior maxilla, thereby preventing damage to the maxillary sinuses and the need to graft bone.     

‘It felt like there was always someone there for us’: Supporting children affected by domestic violence and abuse who are identified by general practice

One in five children in the UK are affected by domestic violence and abuse. However, primary care clinicians (GPs and nurses) struggle to effectively identify and support children and young people living in homes where it is present. The IRIS+ (Enhanced Identification and Referral to Improve Safety) training and advocacy support intervention aimed to improve how clinicians respond to children and young people affected by domestic violence and abuse. IRIS+ training was delivered as part of a feasibility study to four general practices in an urban area in England (UK). Our mixed method design included interviews and questionnaires about the IRIS+ intervention with general practice patients, including children and young people as well as with clinicians and advocacy service providers. We collected the number of identifications and referrals by clinicians of children experiencing domestic violence and abuse through a retrospective search of medical and agency records 10 months after the intervention. Forty-nine children exposed to domestic violence and abuse were recorded in medical records. Thirty-five children were referred to a specialist domestic violence and abuse support service over a period of 10 months. Of these, 22 received direct or indirect support. The qualitative findings indicated that children benefitted from being referred by clinicians to the service. However, several barriers at the patient and professional level prevented children and young people from being identified and supported. Some of these barriers can be addressed through modifications to professional training and guidance, but others require systematic and structural changes to the way health and social care services work with children affected by domestic violence and abuse.     

社区动脉粥样硬化风险研究的进展和展望

社区动脉粥样硬化风险（ARIC）研究是1987年由美国心、肺和血液研究所资助的关注非洲裔美国人心血管健康的最大研究。旨在调查心脏病的危险因素以及心血管疾病与认知之间的联系。ARIC研究的许多发现加深了对动脉粥样硬化性心血管病病因的了解,在心血管病预防领域做出了重大贡献,证明了以人群为基础的研究对改善健康和预防疾病的重要性。主要概述ARIC研究的起源、目的、研究设计、对心血管医学的贡献以及未来的发展方向。     

Long-term health-related quality of life of breast cancer survivors remains impaired compared to the age-matched general population especially in young women. Results from the prospective controlled BREX exercise study

ObjectiveTo investigate long-term health-related quality of life (HRQoL) changes over time in younger compared to older disease-free breast cancer survivors who participated in a prospective randomized exercise trial.MethodsSurvivors (aged 35–68 years) were randomized to a 12-month exercise trial after adjuvant treatment and followed up for ten years. HRQoL was assessed with the generic 15D instrument during follow-up and the younger (baseline age ≤ 50) and older (age >50) survivors’ HRQoL was compared to that of the age-matched general female population (n = 892). The analysis included 342 survivors.ResultsThe decline of HRQoL compared to the population was steeper and recovery slower in the younger survivors (p for interaction < 0.001). The impairment was also larger among the younger survivors (p = 0.027) whose mean HRQoL deteriorated for three years after treatment and started to slowly improve thereafter but still remained below the population level after ten years (difference −0.017, 95% CI: −0.031 to −0.004). The older survivors’ mean HRQoL gradually approached the population level during the first five years but also remained below it at ten years (difference −0.019, 95% CI: −0.031 to −0.007). The largest differences were on the dimensions of sleeping and sexual activity, on which both age groups remained below the population level throughout the follow-up.ConclusionsHRQoL developed differently in younger and older survivors both regarding the most affected dimensions of HRQoL and the timing of the changes during follow-up. HRQoL of both age groups remained below the population level even ten years after treatment.     

Child and family predictors of insomnia from early childhood to adolescence

BackgroundInsomnia is prevalent among children and adolescents and is associated with a wide range of negative outcomes. Knowledge about its determinants is therefore important, but due to the lack of longitudinal studies, such knowledge is limited. The aim of the present inquiry is to identify child and family predictors of future pediatric insomnia within a psycho-bio-behavioral framework.MethodsA representative community sample (n = 1,037) was followed biennially from 4 to 14 years of age (2007–2017). Insomnia was defined based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria and was diagnosed by a semistructured clinical interview of children (from age eight years of age) and parents (all ages). Predictors included parent ratings of child emotional reactivity, family functioning, and marital conflict; self-reports of personality; and teacher-rated emotion regulation skills.ResultsRandom intercept cross-lagged analyses revealed that within-person increases (ie, relative to the child's typical levels across childhood) in emotional reactivity and decreases in emotion regulation skills predicted insomnia diagnosis two years later from ages 4 to 14 after adjusting for previous insomnia and all unmeasured time-invariant factors. Previous insomnia was the strongest predictor of later insomnia, whereas family functioning and marital conflict did not predict insomnia.ConclusionsIncreases in emotional reactivity and decreases in emotion regulation skills predicted insomnia above and beyond all unmeasured time-invariant factors and could be targets for interventions. Previous insomnia predicted later insomnia, thereby underscoring the importance of detecting, preventing, and treating insomnia at an early age.     

Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle

Deep brain stimulation (DBS) in psychiatric illnesses has been clinically tested over the past 20 years. The clinical application of DBS to the superolateral branch of the medial forebrain bundle in treatment‐resistant depressed patients—one of several targets under investigation—has shown to be promising in a number of uncontrolled open label trials. However, there are remain numerous questions that need to be investigated to understand and optimize the clinical use of DBS in depression, including, for example, the relationship between the symptoms, the biological substrates/projections and the stimulation itself. In the context of precision and customized medicine, the current paper focuses on clinical and experimental research of medial forebrain bundle DBS in depression or in animal models of depression, demonstrating how clinical and scientific progress can work in tandem to test the therapeutic value and investigate the mechanisms of this experimental treatment. As one of the hypotheses is that depression engenders changes in the reward and motivational networks, the review looks at how stimulation of the medial forebrain bundle impacts the dopaminergic system.     

Effect of Race and Ethnicity on Risk of Radiotherapy Toxicity and Implications for Radiogenomics

AimsPatient factors affect the risk of radiotherapy toxicity, but many are poorly defined. Studies have shown that race affects cancer incidence, survival, drug response, molecular pathways and epigenetics. Effects on radiosensitivity and radiotherapy toxicity are not well studied. The aim of the present study was to identify the effects of race and ethnicity on the risk of radiotherapy toxicity.Materials and methodsA systematic review was carried out of PubMed, Ovid Medline and Ovid Embase with no year limit. PRISMA 2020 guidelines were followed. Two independent assessors reviewed papers.ResultsOf 607 papers screened, 46 fulfilled the inclusion criteria. Papers were published between 1996 and 2021 and involved 30–28,354 individuals (median 433). Most involved patients with prostate (33%), breast (26%) and lung (9%) cancer. Both early and late toxicities were studied. Some studies reported a higher risk of toxicity in White men with prostate cancer compared with other races and ethnicities. For breast cancer patients, some reported an increased risk of toxicity in White women compared with other race and ethnic groups. In general, it was difficult to draw conclusions due to insufficient reporting and analysis of race and ethnicity in published literature.ConclusionsReporting of race and ethnicity in radiotherapy studies must be harmonised and improved and frameworks are needed to improve the quality of reporting. Further research is needed to understand how ancestral heritage might affect radiosensitivity and risk of radiotherapy toxicity.