Bridging the gap: improving correspondence between low-field and high-field magnetic resonance images in young people.

Background: Portable low-field-strength magnetic resonance imaging (MRI) systems represent a promising alternative to traditional high-field-strength systems with the potential to make MR technology available at scale in low-resource settings. However, lower image quality and resolution may limit the research and clinical potential of these devices. We tested two super-resolution methods to enhance image quality in a low-field MR system and compared their correspondence with images acquired from a high-field system in a sample of young people. Methods: T1- and T2-weighted structural MR images were obtained from a low-field (64mT) Hyperfine and high-field (3T) Siemens system in N = 70 individuals (mean age = 20.39 years, range 9-26 years). We tested two super-resolution approaches to improve image correspondence between images acquired at high- and low-field: (1) processing via a convolutional neural network ('SynthSR'), and (2) multi-orientation image averaging. We extracted brain region volumes, cortical thickness, and cortical surface area estimates. We used Pearson correlations to test the correspondence between these measures, and Steiger Z tests to compare the difference in correspondence between standard imaging and super-resolution approaches. Results: Single pairs of T1- and T2-weighted images acquired at low field showed high correspondence to high-field-strength images for estimates of total intracranial volume, surface area cortical volume, subcortical volume, and total brain volume (r range = 0.60-0.88). Correspondence was lower for cerebral white matter volume (r = 0.32, p = 0.007, q = 0.009) and non-significant for mean cortical thickness (r = -0.05, p = 0.664, q = 0.664). Processing images with SynthSR yielded significant improvements in correspondence for total brain volume, white matter volume, total surface area, subcortical volume, cortical volume, and total intracranial volume (r range = 0.85-0.97), with the exception of global mean cortical thickness (r = 0.14). An alternative multi-orientation image averaging approach improved correspondence for cerebral white matter and total brain volume. Processing with SynthSR also significantly improved correspondence across widespread regions for estimates of cortical volume, surface area and subcortical volume, as well as within isolated prefrontal and temporal regions for estimates of cortical thickness. Conclusion: Applying super-resolution approaches to low-field imaging improves regional brain volume and surface area accuracy in young people. Finer-scale brain measurements, such as cortical thickness, remain challenging with the limited resolution of low-field systems.

Age-associated alterations in thalamocortical structural connectivity in youths with a psychosis-spectrum disorder.

Psychotic symptoms typically emerge in adolescence. Age-associated thalamocortical connectivity differences in psychosis remain unclear. We analyzed diffusion-weighted imaging data from 1254 participants 8-23 years old (typically developing (TD):N = 626, psychosis-spectrum (PS): N = 329, other psychopathology (OP): N = 299) from the Philadelphia Neurodevelopmental Cohort. We modeled thalamocortical tracts using deterministic fiber tractography, extracted Q-Space Diffeomorphic Reconstruction (QSDR) and diffusion tensor imaging (DTI) measures, and then used generalized additive models to determine group and age-associated thalamocortical connectivity differences. Compared to other groups, PS exhibited thalamocortical reductions in QSDR global fractional anisotropy (GFA, p-values range = 3.0 × 10-6-0.05) and DTI fractional anisotropy (FA, p-values range = 4.2 × 10-4-0.03). Compared to TD, PS exhibited shallower thalamus-prefrontal age-associated increases in GFA and FA during mid-childhood, but steeper age-associated increases during adolescence. TD and OP exhibited decreases in thalamus-frontal mean and radial diffusivities during adolescence; PS did not. Altered developmental trajectories of thalamocortical connectivity may contribute to the disruptions observed in adults with psychosis.

Multimodal Neuroimaging Summary Scores as Neurobiological Markers of Psychosis.

BACKGROUND AND HYPOTHESIS: Structural brain alterations are well-established features of schizophrenia but they do not effectively predict disease/disease risk. Similar to polygenic risk scores in genetics, we integrated multifactorial aspects of brain structure into a summary "Neuroscore" and examined its potential as a marker of disease. STUDY DESIGN: We extracted measures from T1-weighted scans and diffusion tensor imaging (DTI) models from three studies with schizophrenia and healthy individuals. We calculated individual-level summary scores (Neuroscores) for T1-weighted and DTI measures and a combined score (Multimodal Neuroscore-MM). We assessed each score's ability to differentiate schizophrenia cases from controls and its relationship to clinical symptomatology, intelligence quotient (IQ), and medication dosage. We assessed Neuroscore specificity by performing all analyses in a more inclusive psychosis sample and by using scores generated from MDD effect sizes. STUDY RESULTS: All Neuroscores significantly differentiated schizophrenia cases from controls (T1 d = 0.56, DTI d = 0.29, MM d = 0.64) to a greater degree than individual brain regions. Higher Neuroscores (ie, increased liability) were associated with lower IQ (T1 ß = -0.26, DTI ß = -0.15, MM ß = -0.30). Higher T1-weighted Neuroscores were associated with higher positive and negative symptom severity (Positive ß = 0.21, Negative ß = 0.16); Higher Multimodal Neuroscores were associated with higher positive symptom severity (ß = 0.30). SZ Neuroscores outperformed MDD Neuroscores in predicting IQ (T1: z = 3.5, q = 0.0007; MM: z = 1.8, q = 0.05). CONCLUSIONS: Neuroscores are a step toward leveraging widespread structural brain alterations in psychosis to identify robust neurobiological markers of disease. Future studies will assess ways to improve neuroscore calculation, including developing the optimal methods to calculate neuroscores and considering disorder overlap.

Corrigendum: Examining human-animal interactions and their effect on multidimensional frailty in later life: a scoping review.

[This corrects the article DOI: 10.3389/fpubh.2023.1214127.].

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium.

BACKGROUND: The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. METHODS: For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. FINDINGS: Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. INTERPRETATION: COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. FUNDING: Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization.

Examining human-animal interactions and their effect on multidimensional frailty in later life: a scoping review.

This scoping review sought to compile outcomes associated with any human-animal interaction study regarding adults aged 50 and older in any living context and concerning a multidimensional (i.e., physical, psychological, cognitive, and social) perspective of frailty. Despite our best attempts at incorporating the broadest inclusion criteria possible, only four articles were relevant to this review. Participants across the included studies were rural, community-dwelling Japanese or Chinese individuals aged 60 years and older. Thematic analysis of reported results includes dog ownership as a protective factor regarding frailty, the interconnected health effects of pet ownership, and increased meaning and purpose through pet ownership implications. More research is needed globally to determine how human-animal interactions may moderate frailty comprehensively, as well as the efficacy and appropriateness of these interactions or interventions in older adult populations and across cultural boundaries.

Invasive pneumococcal surveillance to assess the potential benefits of extended spectrum conjugate vaccines (PCV15/PCV20) in older adults.

The introduction of pneumococcal conjugate vaccines (PCV) into the childhood vaccination programme has reduced invasive pneumococcal disease (IPD). Although anticipated from data elsewhere, surveillance in Ireland has confirmed reductions in IPD amongst those ⩾65 years of age due to a decline of PCV serotypes in this age group. Currently, direct protection against IPD in the elderly is focused on immunisation with the 23-valent pneumococcal polysaccharide vaccine (PPV23). However, immunity may not be as effective as with PCV and, furthermore, PPV23 uptake is poor in Ireland. Hence, consideration should be given to providing a PCV to this age group.

Exploring Knowledge Translation Concepts in U.S. Occupational Therapy Research: A Content Analysis.

IMPORTANCE: As a new Accreditation Council for Occupational Therapy Education® standard, knowledge translation (KT) is an important concept to occupational therapy. A better understanding of KT in occupational therapy research could inform its relevance to occupational therapy education, research, and practice. OBJECTIVE: To answer the question "To what extent does published U.S.-based occupational therapy research that is explicitly underpinned by a KT theory, model, or framework reflect processes and concepts outlined in the knowledge-to-action (KTA) framework?" DESIGN: A systematic search was conducted to purposively sample U.S.-based occupational therapy research. A content analysis of 11 articles explored concepts of the KTA framework. OUTCOMES AND MEASURES: KTA was used as a conceptual foundation. RESULTS: Multiple sources of data mapped onto concepts in the knowledge creation cycle and each of the first five concepts of the knowledge action cycle. We found that three concepts from the knowledge action cycle-monitor knowledge use, evaluate outcomes, and sustain knowledge use-were not well represented in the sample. CONCLUSIONS AND RELEVANCE: Future research on the monitoring, evaluation, and sustained use of occupational therapy interventions is needed. The adoption of new interventions is important, and the knowledge of how they are sustained in practice will facilitate the clinical integration of future interventions. What This Article Adds: Occupational therapy research that uses KT lacks an emphasis on monitoring and sustaining evidence-informed interventions. Future research on the integration of such interventions into clinical practice is needed so that best practices in occupational therapy can be promoted.

Effectiveness of 10 and 13-valent pneumococcal conjugate vaccines against invasive pneumococcal disease in European children: SpIDnet observational multicentre study.

BACKGROUND: Pneumococcal conjugate vaccines covering 10 (PCV10) and 13 (PCV13) serotypes have been introduced in the infant immunization schedule of most European countries in 2010-11. To provide additional real-life data, we measured the effectiveness of PCV10 and PCV13 against invasive pneumococcal disease (IPD) in children of 12 European sites (SpIDnet). METHODS: We compared the vaccination status of PCV10 and PCV13 serotype IPD (cases) to that of nonPCV13 serotype IPD (controls) reported in 2012-2018. We calculated pooled effectiveness as (1-vaccination odds ratio)*100, and measured effectiveness over time since booster dose. RESULTS: The PCV13 and PCV10 studies included 2522 IPD cases from ten sites and 486 cases from four sites, respectively. The effectiveness of ≥ 1 PCV13 dose was 84.2% (95 %CI: 79.0-88.1) against PCV13 serotypes (n = 2353) and decreased from 93.1% (87.8-96.1) < 12 months to 85.1% (72.0-92.1) ≥ 24 months after booster dose. PCV13 effectiveness of ≥ 1 dose was 84.7% (55.7-94.7) against fatal PCV13 IPD, 64.5% (43.7-77.6), 83.2% (73.7-89.3) and 85.1% (67.6-93.1) against top serotypes 3, 19A and 1, respectively, and 85.4% (62.3-94.4) against 6C. Serotype 3 and 19A effectiveness declined more rapidly. PCV10 effectiveness of ≥ 1 dose was 84.8% (69.4-92.5) against PCV10 serotypes (n = 370), 27.2% (-187.6 to 81.6) and 85.3% (35.2-96.7) against top serotypes 1 and 7F, 32.5% (-28.3 to 64.5) and -14.4% (-526.5 to 79.1) against vaccine-related serotypes 19A and 6C, respectively. CONCLUSIONS: PCV10 and PCV13 provide similar protection against IPD due to the respective vaccine serotype groups but serotype-specific effectiveness varies by serotype and vaccine. PCV13 provided individual protection against serotype 3 and vaccine-related serotype 6C IPD. PCV10 effectiveness was not significant against vaccine-related serotypes 19A and 6C. PCV13 effectiveness declined with time after booster vaccination. This multinational study enabled measuring serotype-specific vaccine effectiveness with a precision rarely possible at the national level. Such large networks are crucial for the post-licensure evaluation of vaccines.

Serotype Replacement after Introduction of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccines in 10 Countries, Europe.

We evaluated invasive pneumococcal disease (IPD) during 8 years of infant pneumococcal conjugate vaccine (PCV) programs using 10-valent (PCV10) and 13-valent (PCV13) vaccines in 10 countries in Europe. IPD incidence declined during 2011-2014 but increased during 2015-2018 in all age groups. From the 7-valent PCV period to 2018, IPD incidence declined by 42% in children <5 years of age, 32% in persons 5-64 years of age, and 7% in persons >65 years of age; non-PCV13 serotype incidence increased by 111%, 63%, and 84%, respectively, for these groups. Trends were similar in countries using PCV13 or PCV10, despite different serotype distribution. In 2018, serotypes in the 15-valent and 20-valent PCVs represented one third of cases in children <5 years of age and two thirds of cases in persons >65 years of age. Non-PCV13 serotype increases reduced the overall effect of childhood PCV10/PCV13 programs on IPD. New vaccines providing broader serotype protection are needed.

Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data.

BACKGROUND: Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. METHODS: In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. FINDINGS: 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 837 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0·32 [95% CI 0·27-0·37]) and 82% at 8 weeks (0·18 [0·14-0·23]) following the week in which significant changes in population movements were recorded. INTERPRETATION: The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide. FUNDING: Wellcome Trust (UK), Robert Koch Institute (Germany), Federal Ministry of Health (Germany), Pfizer, Merck, Health Protection Surveillance Centre (Ireland), SpID-Net project (Ireland), European Centre for Disease Prevention and Control (European Union), Horizon 2020 (European Commission), Ministry of Health (Poland), National Programme of Antibiotic Protection (Poland), Ministry of Science and Higher Education (Poland), Agencia de Salut Pública de Catalunya (Spain), Sant Joan de Deu Foundation (Spain), Knut and Alice Wallenberg Foundation (Sweden), Swedish Research Council (Sweden), Region Stockholm (Sweden), Federal Office of Public Health of Switzerland (Switzerland), and French Public Health Agency (France).

Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Project.

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.

Serotype Distribution of Remaining Pneumococcal Meningitis in the Mature PCV10/13 Period: Findings from the PSERENADE Project.

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5-7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites (N = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed.

Learning health systems from an academic perspective: establishing a collaboratory within a school of medicine and health sciences.

Learning Health Systems (LHSs) seek continuous improvement through the translation and integration of internally and externally generated knowledge across stakeholders within and external to the organization, yet current approaches are primarily described from the healthcare delivery perspective, leaving teaching and research responsibilities underexposed. Academic medical centers offer a unique perspective on LHSs because their mission includes teaching, research, and healthcare. This introduces an opportunity to enact, educate, and study processes and outcomes of LHSs within a single system. Little information is available to describe these processes and outcomes, resulting in a knowledge gap regarding the role of education and research in the quality improvement cycles and learning of LHSs. To close this knowledge gap, The George Washington University School of Medicine and Health Sciences initiated the Health Research and Education Collaboratory (GW Collaboratory) in 2017. The GW Collaboratory was established to study mechanisms supporting continuous quality improvement and learning in health systems within an academic medical center. We envision the GW Collaboratory as interconnected knowledge nodes facilitating collaboration among clinicians, patients, researchers, and educators to study the knowledge generation, dissemination, application, and evaluation required for continuous quality improvement and learning. We employ a project-based approach to foster communities of learning focused on exploring specific health problems of interest. We propose the GW Collaboratory as one model by which academic medical centers can contribute to the science of LHS.

Youth Soccer Parents' Perceptions of Long-Term Effects of Concussion .

Increased focus on sports-related concussion (SRC) in football in the media, and mandatory concussion education for parents of youth sport athletes, may result in parental concern that youth athletes will experience long-term effects from concussion. We sought to identify beliefs about long-term effects of concussion in parents of youth soccer athletes. Four hundred and eleven parents from soccer leagues in three states completed a survey assessing parents' perceptions and knowledge of long-term effects of SRC. Nearly all youth soccer parents surveyed (96.5%) believe there are long-term effects from SRCs, 76% reported concern their child would sustain a concussion, and 71% had talked with their child about concussion symptoms/reporting. Parents ranked tackle football as having the highest risk for concussion, followed by soccer, ice hockey, cheerleading, and lacrosse. Parents of children that had previously sustained a concussion were 8.3x more likely to be concerned their child would sustain a concussion, and parents with a personal history of concussion were 2x more likely to consider not allowing their child to participate in youth sports. There are wide-spread beliefs among youth soccer parents regarding long-term effects of SRCs, and concerns their children will sustain concussions while participating in youth sports.

Group Gardening in a Native American Community: A Collaborative Approach.

Background. There is increasing awareness of the potential health benefits derived from gardening activities. Gardening practices are gaining momentum in Native American (NA) communities, yet no efforts have applied a community-based participatory research approach within a social-ecological model to understand opportunities and barriers for group gardening on an American Indian reservation. Objectives. The primary objective of this study was to identify influences across social-ecological levels that promote or hinder the implementation of community gardens and use of locally grown foods on the reservation; a secondary objective was to assess the feasibility of implementing a group gardening program for NA adults and potential of collecting health outcome measures. Method. Community members and academicians collaborated to develop and implement this study. The study (1) conducted interviews with key stakeholders to identify influences across social-ecological levels that promote or hinder the implementation of community gardens and using locally produced food and (2) assessed the physical and psychological well-being of NA adults participating in a group gardening feasibility study. Results. Major factors influencing using locally grown food and community gardens that emerged from nine interviews included knowledge/experience, self-efficacy, Elders, traditional ways, community values, generational gaps, and local tribal policies. Twenty NA adults with prediabetes or diabetes participated in the feasibility study. The Profile of Mood States Inventory showed consistently positive change in score for participants in the group gardening program versus the comparison group. Conclusions. This study identified key influences for growing locally grown food, and approaches for implementing group gardening programs for NA adults.

Invasive Streptococcus pneumoniae Infections and Vaccine Failures in Children in Ireland From the Postvaccine Era From 2007 to 2018.

BACKGROUND: Invasive pneumococcal disease (IPD) causes life-threatening illnesses including meningitis and bloodstream infection. Here, we report the impact of 7- and 13-valent pneumococcal conjugate vaccines (PCV7/PCV13) after introduction into the Irish pediatric immunization schedule in 2008 and 2010, respectively, and the clinical details surrounding suspected PCV vaccine failures. METHODS: Serotyping and antimicrobial susceptibility testing of all culture-confirmed cases referred from children <16 years of age from July 2007 to June 2018 were assessed. Surveillance data were assessed to identify any potential vaccine failures. RESULTS: The number of IPD cases has decreased by >50% since the introduction of PCVs. The most significant decline PCV serotypes in children <2 years of age, with a 97% decline in PCV7 serotypes, incidence rate ratio (IRR) 0.03, 95% confidence interval (CI): 0.00-0.21; and a 78% decline PCV13-only (PCV13-7) serotypes, IRR 0.22, 95% CI: 0.05-1.04, respectively. However, there has been an increase in non-PCV13 serotypes in children <2 years during the same period (IRR: 2.82, 95% CI: 1.02-7.84; P = 0.0463), with similar serotype trends observed for those 2-4 and 5-15 years of age. There were no clear vaccine replacement serotypes, instead a number of different serotypes emerged. Sixteen vaccine failures were identified, 10 of which were postbooster vaccine failures. Most failures were serotype 19A and resistant to antimicrobials. CONCLUSIONS: Further reducing the incidence of IPD is more challenging as the number of non-PCV13 serotypes has expanded and is now less susceptible to antimicrobials. Consequently, higher valency or broader target vaccines are now required to further prevent IPD in children.

A phase 1, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics of single and multiple doses of lisdexamfetamine dimesylate in Japanese and Caucasian healthy adult subjects.

AIM: To assess safety, tolerability, and pharmacokinetics of lisdexamfetamine dimesylate in Japanese and Caucasian healthy adults. METHODS: A phase 1, double-blind, randomized, placebo-controlled, single- and multiple-dose study in Japanese and Caucasian subjects. Subjects received lisdexamfetamine 20 mg or placebo on Day 1, then lisdexamfetamine 20 mg/d (Days 4-8), 50 mg/d (Days 9-13), 70 mg/d (Days 14-18), or matching placebo. Pharmacokinetic parameters for lisdexamfetamine and d-amphetamine were estimated by noncompartmental analysis. RESULTS: Fifteen Japanese and 19 Caucasian subjects were enrolled and randomized. The lisdexamfetamine and d-amphetamine plasma concentration-time curves were similar for both ethnic groups following single and multiple doses. Mean area under the concentration-time curves for d-amphetamine were higher (by 11%-15%) in Japanese than Caucasian subjects following multiple dosing of lisdexamfetamine. Mean bodyweight was 17% lower in Japanese than Caucasian subjects. Weight-corrected means for oral clearance were similar in both ethnic groups, with no unexpected accumulation of d-amphetamine. Lisdexamfetamine was generally well tolerated by both ethnic groups, with no serious adverse events reported. The 10/12 Japanese and 11/16 Caucasian subjects who received lisdexamfetamine completed the study; two Japanese and three Caucasian subjects discontinued due to adverse events. Most adverse events were of mild severity. CONCLUSION: Pharmacokinetics were generally similar for Japanese and Caucasian subjects; the minor differences observed were likely due to bodyweight differences in the two ethnic groups. Lisdexamfetamine was generally well tolerated. Adverse events were consistent with the established safety profile of lisdexamfetamine and were similar in both ethnic groups.

Effect of childhood pneumococcal conjugate vaccination on invasive disease in older adults of 10 European countries: implications for adult vaccination.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) have the potential to prevent pneumococcal disease through direct and indirect protection. This multicentre European study estimated the indirect effects of 5-year childhood PCV10 and/or PCV13 programmes on invasive pneumococcal disease (IPD) in older adults across 13 sites in 10 European countries, to support decision-making on pneumococcal vaccination policies. METHODS: For each site we calculated IPD incidence rate ratios (IRR) in people aged ≥65 years by serotype for each PCV10/13 year (2011-2015) compared with 2009 (pre-PCV10/13). We calculated pooled IRR and 95% CI using random-effects meta-analysis and PCV10/13 effect as (1 - IRR)*100. RESULTS: After five PCV10/13 years, the incidence of IPD caused by all types, PCV7 and additional PCV13 serotypes declined 9% (95% CI -4% to 19%), 77% (95% CI 67% to 84%) and 38% (95% CI 19% to 53%), respectively, while the incidence of non-PCV13 serotypes increased 63% (95% CI 39% to 91%). The incidence of serotypes included in PCV13 and not in PCV10 decreased 37% (95% CI 22% to 50%) in six PCV13 sites and increased by 50% (95% CI -8% to 146%) in the four sites using PCV10 (alone or with PCV13). In 2015, PCV13 serotypes represented 20-29% and 32-53% of IPD cases in PCV13 and PCV10 sites, respectively. CONCLUSION: Overall IPD incidence in older adults decreased moderately after five childhood PCV10/13 years in 13 European sites. Large declines in PCV10/13 serotype IPD, due to the indirect effect of childhood vaccination, were countered by increases in non-PCV13 IPD, but these declines varied according to the childhood vaccine used. Decision-making on pneumococcal vaccination for older adults must consider the indirect effects of childhood PCV programmes. Sustained monitoring of IPD epidemiology is imperative.

Encountering offenders in community palliative care settings: challenges for care provision.

BACKGROUND: There is very little research into the way that offender management strategies impinge on the practices and decision-making of palliative care personnel in community settings. AIMS: To improve understanding of the challenges that community palliative care service providers encounter when caring for people who have been sentenced to custody and are under the supervision of the prison or probation services. METHODS: This paper discusses one part of a larger multidisciplinary study on bereavement, loss and grief in the criminal justice system. It reports the findings from a focus group with 10 health professionals working within specialist community palliative care services. Thematic analysis was undertaken to identify and explicate the most significant themes arising from the transcript data. RESULTS: There were situations where the participants were able to identify that patients were under the jurisdiction of the criminal justice system or had relatives in custody. Three themes emerged that highlighted distinctive aspects of providing care to this patient group. These themes were: patients under prison, probation or police supervision altered the dynamics of care provision; prisoners were restricted from supporting or contacting their dying relatives in the community; and participants (professionals) were obstructed from supporting patients at home because of criminal or antisocial behaviour by relatives of the dying. CONCLUSIONS: Health professionals face multiple challenges that curtail them from fully realising the aims of palliative care for patients and relatives under criminal justice supervision, in ways that merit further consideration and research.