Ankle power biofeedback attenuates the distal-to-proximal redistribution in older adults

BackgroundCompared to young adults, older adults walk slower, with shorter strides, and with a characteristic decrease in ankle power output. Seemingly in response, older adults rely more than young on hip power output, a phenomenon known as a distal-to-proximal redistribution. Nevertheless, older adults can increase ankle power to walk faster or uphill, revealing a translationally important gap in our understanding.Research questionOur purpose was to implement a novel ankle power biofeedback paradigm to encourage favorable biomechanical adaptations (i.e. reverse the distal-redistribution) during habitual speed walking in older adults.Methods10 healthy older adults walked at their preferred speeds while real-time visual biofeedback provided target increases and decreases of 10 and 20% different from preferred ankle power. We evaluated the effect of changes in ankle power on joint kinetics, kinematics, and propulsive ground reaction forces. Pre and post overground walking speed assessments evaluated the effect of increased ankle power recall on walking speed.ResultsBiofeedback systematically elicited changes in ankle power; increasing and decreasing ankle power by 14% and 17% when targeting ±20% different from preferred, respectively. We observed a significant negative correlation between ankle power and hip extensor work. Older adults relied more heavily on changes in ankle angular velocity than ankle moment to modulate ankle power. Lastly, older adults walked almost 11% faster when recalling increased ankle power overground.SignificanceOlder adults are capable of increasing ankle power through targeted ankle power biofeedback – effects that are accompanied by diminished hip power output and attenuation of the distal-to-proximal redistribution. The associated increase in preferred walking speed during recall suggests a functional benefit to increased ankle power output via transfer to overground walking. Further, our mechanistic insights allude to translational success using ankle angular velocity as a surrogate to modulate ankle power through biofeedback.     

Rate of torque development is the primary contributor to quadriceps avoidance gait following total knee arthroplasty

BackgroundFollowing rehabilitation for total knee arthroplasty, “quadriceps avoidance gait”, defined by limited knee flexion angle excursion during walking, persists and contributes to poor long-term outcomes. Given the presence of several post-surgical impairments, identifying the contribution of multiple factors to knee flexion angle excursion is important to developing targeted interventions to improve recovery after total knee arthroplasty.Research questionsWhich outcomes continue to improve following rehabilitation for total knee arthroplasty? What are the primary contributors to impaired knee flexion angle excursion during walking following total knee arthroplasty?MethodsPeak muscle strength and rate of torque development of the quadriceps, hip abductors, and hip external rotators, five-time sit-to-stand test, Knee Injury & Osteoarthritis Outcome Score, and gait mechanics were assessed in 24 participants at three and six months post-surgery. Paired sample t-tests or Wilcoxon Signed-Rank tests were used to compare outcomes between assessments. Stepwise multiple linear regression were used to assess the contribution of each measure to knee flexion angle excursion.ResultsSignificant improvements were noted in all outcomes except hip external rotation rate of torque development, gait speed, and knee flexion angle excursion. Quadriceps rate of torque development and knee pain significantly contributed to knee flexion angle excursion at three months (Adjusted R² = 0.342), while quadriceps rate of torque development and peak hip external rotation strength significantly contributed at six months (Adjusted R² = 0.436).SignificanceWhile higher pain levels at three months and greater peak hip external rotation muscle strength at six months contribute to impaired knee flexion angle excursion, quadriceps rate of torque development was the primary contributor to knee flexion angle excursion at both three and six months after surgery. Implementing strategies to maximize quadriceps rate of torque development during rehabilitation may help to reduce quadriceps avoidance gait after total knee arthroplasty.     

Congenital Heart Disease and Women’s Health Across the Life Span: Focus on Reproductive Issues

From adolescence to older age, women with congenital heart disease (CHD) face unique challenges. In this review we explore the ways in which CHD affects women’s sexual and reproductive health and, in turn, how their sexual and reproductive history affects the course of their CHD. In adolescence, special attention must be paid to menstrual irregularities and concerns of developing sexuality and self-image. Discussions about sexuality and reproduction are an important part of transition planning and must be done with an awareness of the adolescent’s developing understanding and maturity. Pregnancy imposes a hemodynamic load on the heart which may lead to cardiac, obstetric, and fetal/neonatal complications in women with CHD. Prepregnancy counselling must include an assessment of maternal and fetal risk according to several well developed models. Counselling should also include discussions about fertility and alternatives to pregnancy when appropriate. Recommendations for contraception must be made according to the patient’s cardiac lesion. In caring for women with CHD during pregnancy, a multidisciplinary cardio-obstetrics team is recommended to optimize care. More research is needed into the long-term impact of pregnancy on the prognosis of patients with CHD. As women with CHD increasingly survive into old age, more attention will need to be directed toward the treatment of menopause and acquired heart disease in this population.     

HBV患者血清YKL-40、CA19-9、GP73水平与其病情相关性

目的 分析HBV患者YKL-40、CA19-9、GP73水平差异及与患者病情轻重程度的相关性,探讨HBV患者病情的判定指标。方法 选取2015年5月—2018年5月收治的100例HBV患者,其中慢性HBV感染组40例、慢性乙型肝炎组36例、HBV相关肝硬化组24例,同期选择我院健康体检的健康者50例作为健康对照组;检测患者血中YKL-40、CA19-9、GP73水平;分析HBV感染患者血清YKL-40、CA19-9、GP73水平与病情轻重程度的相关性。结果 慢性HBV感染、慢性乙型肝炎及HBV相关肝硬化患者血中YKL-40水平分别为（36.38±4.19）ng/mL 、（49.02±4.32）ng/mL、（65.14±5.21）ng/mL ,CA19-9分别为（12.03±1.03）KU/L、（13.84±0.98）KU/L、（16.94±0.81）KU/L,GP73分别为（47.22±5.38）ng/mL 、（98.53±10.24）ng/mL 、（229.85±12.19）ng/mL,均明显高于对照组的（28.19±3.27）ng/mL 、（7.34±0.92）KU/L 、（30.93±3.89）ng/mL,均P=0.000 0。随着慢性HBV感染者、慢性乙型肝炎患者和不同HBV相关肝硬化患者肝脏炎症及纤维化程度加重,患者血中YKL-40、CA19-9和GP73也随之显著增加,均P=0.000 0;YKL-40、CA19-9和GP73均是影响HBV感染患者体内炎症坏死及肝脏纤维化的独立性影响因素,差异有统计学意义（P<0.05）。结论 HBV感染患者血清中YKL-40、CA19-9、GP73水平是HBV感染患者病情轻重程度的独立性影响因素。     

Hepatitis B surface antigen seroprevalence among pre- and post-vaccine cohorts in Cambodia, 2017

Background: Hepatitis B virus (HBV) infection is highly endemic in most low income countries including Cambodia. This nationwide serosurvey was conducted to assess the impact of hepatitis B vaccination and to determine whether Cambodia met the WHO regional 2017 target of hepatitis B surface antigen (HBsAg) seroprevalence less than 1% in five-year-old children.Methods: A cross-sectional multi-stage cluster survey was conducted among children born during 2010–2012 and their mothers in Cambodia. HBsAg prevalence was estimated by rapid point-of-care testing, and demographic data, including vaccination history, was collected. Vaccine coverage in children and the prevalence of HBsAg among children and mothers was calculated taking into account the complex survey design. Factors associated with children’s failure to receive timely (within 24 h) vaccination were analysed by multivariate logistic analysis.Findings: A total of 2,520 children 5–7 years old and 2,028 mothers were recruited. In total, 78.4% of children received hepatitis B vaccination birth-dose (HepB-BD); of these, 58.7% were administered ≤ 24 h. Birth at home or “other” location were independent risk factors for children’s failure to receive timely HepB-BD. Overall HBsAg seroprevalence was 4.39% (95%CI: 3.53%–5.45%) among mothers and 0.56% (95%CI: 0.32%–0.98%) among children. The prevalence among children without hepatitis B vaccination was 4.62% (95%CI: 1.31%–14.97%). Among children with a HBsAg-positive mother, prevalence was 10.11% (95%CI: 5.41%–18.11%).Interpretation: Having achieved the 2017 target of less than 1% HBsAg prevalence among 5 years old children, Cambodia can now focus on eliminating mother-to-child transmission of HBV. Moreover, the high HBsAg prevalence among mothers suggests that routine screening with proper linkage to care and treatment is needed. Strengthening measures to improve vaccination coverage further and eliminate mother-to-child transmission by coordinated programming with other services offering additional HBV interventions will help move towards the global goal of hepatitis B elimination by 2030.Funding: As per sources of funding.     

The cost-of-illness for invasive meningococcal disease caused by serogroup B Neisseria meningitidis (MenB) in Germany

Introduction

Invasive meningococcal disease (IMD) is a severe disease mainly affecting infants and young children. The most common serogroup causing IMD in Germany is the serogroup type B Neisseria meningitidis (MenB). The aim of the present study is to estimate the economic burden of MenB-related IMD in Germany.

Hepatitis B virus-like particles expressing Plasmodium falciparum epitopes induce complement-fixing antibodies against the circumsporozoite protein

The repetitive structure of compact virus-like particles (VLPs) provides high density displays of antigenic sequences, which trigger key parts of the immune system. The hepatitis B virus (HBV) and human papilloma virus (HPV) vaccines exploit the assembly competence of structural proteins, which are the effective immunogenic components of the prophylactic HBV and HPV vaccines, respectively. To optimize vaccine designs and to promote immune responses against protective epitopes, the “Asp-Ala-Asp-Pro” (NANP)-repeat from the Plasmodium falciparum circumsporozoite protein (CSP) was expressed within the exposed, main antigenic site of the small HBV envelope protein (HBsAgS); this differs from the RTS,S vaccine, in which CSP epitopes are fused to the N-terminus of HBsAgS. The chimeric HBsAgS proteins are assembly competent, produce VLPs, and provide a high antigenic density of the NANP repeat sequence. Chimeric VLPs with four or nine NANP-repeats (NANP4 and NANP9, respectively) were expressed in mammalian cells, the HBsAgS- and CSP-specific antigenicity of the VLPs was determined, and the immunogenicity of the VLPs assessed in relation to the induction of anti-HBsAgS and anti-CSP antibody responses. The chimeric VLPs induced high anti-CSP titres in BALB/c mice independent of the number of the NANP repeats. However, the number of NANP repeats influenced the activity of vaccine-induced antibodies measured by complement fixation to CSP, one of the proposed effector mechanisms for Plasmodium neutralization in vivo. Sera from mice immunized with VLPs containing nine NANP repeats performed better in the complement fixation assay than the group with four NANP repeats. The effect of the epitope-specific density on the antibody quality may instruct VLP platform designs to optimize immunological outcomes and vaccine efficacy.     

Long-term effectiveness of zoster vaccine live for postherpetic neuralgia prevention

BackgroundPostherpetic neuralgia (PHN) occurs in 5–30% of individuals with herpes zoster (HZ) and is characterized by long-lasting pain. Zoster vaccine live (ZVL) is licensed for people 50 years and older to prevent HZ and PHN. This study evaluated vaccine effectiveness (VE) of ZVL against PHN.MethodsWe conducted an open cohort study within Kaiser Permanente Northern California with continuous accrual of people as they became age-eligible for ZVL. We defined PHN using a PHN diagnosis between 90 and 365 days after an incident episode of HZ. We estimated VE against PHN using Cox regression with a calendar timeline stratified by year of birth and adjusted for sex, race, influenza vaccination, outpatient visit frequency, comorbidities, and immune compromise status.ResultsFrom 2007 to 2016, 1·5 million people entered the study population and 33% received ZVL. During 7·6 million person-years of follow-up, there were 62,205 HZ cases, 4150 (6·7%) of which went on to develop PHN. Overall VE for PHN was 64·8% (95% CI 61·3, 68). VE was 82·8% (95% CI 77·6, 86·7) during the first year after vaccination, 58·3% (95% CI 50.1, 65.2) during the third year, and then waned more gradually to 48·7% (95% CI 30·2, 62·3) during the eighth year. VE in persons vaccinated when aged 80 years or older was similar to VE in younger vaccinees. VE in persons vaccinated when immune compromised was similar to VE in immune competent.ConclusionsOverall, ZVL was 65% effective against PHN. It was effective in all age groups and provided moderate protection through 8 years.     

The role of immune correlates of protection on the pathway to licensure,policy decision and use of group B Streptococcus vaccines for maternal immunization: considerations from World Health Organization consultations

The development of a group B Streptococcus (GBS) vaccine for maternal immunization constitutes a global public health priority, to prevent GBS-associated early life invasive disease, stillbirth, premature birth, maternal sepsis, adverse neurodevelopmental consequences, and to reduce perinatal antibiotic use. Sample size requirements for the conduct of a randomized placebo-controlled trial to assess vaccine efficacy against the most relevant clinical endpoints, under conditions of appropriate ethical standards of care, constitute a significant obstacle on the pathway to vaccine availability. Alternatively, indirect evidence of protection based on immunologic data from vaccine and sero-epidemiological studies, complemented by data from opsonophagocytic in vitro assays and animal models, could be considered as pivotal data for licensure, with subsequent confirmation of effectiveness against disease outcomes in post-licensure evaluations. Based on discussions initiated by the World Health Organization we present key considerations about the potential role of correlates of protection towards an accelerated pathway for GBS vaccine licensure and wide scale use. Priority activities to support progress to regulatory and policy decision are outlined.