Driving delivery and uptake of catch-up vaccination among adolescent and adult migrants in UK general practice: a mixed methods pilot study.

BACKGROUND: Migrants in the UK and Europe face vulnerability to vaccine-preventable diseases (VPDs) due to missed childhood vaccines and doses and marginalisation from health systems. Ensuring migrants receive catch-up vaccinations, including MMR, Td/IPV, MenACWY, and HPV, is essential to align them with UK and European vaccination schedules and ultimately reduce morbidity and mortality. However, recent evidence highlights poor awareness and implementation of catch-up vaccination guidelines by UK primary care staff, requiring novel approaches to strengthen the primary care pathway. METHODS: The 'Vacc on Track' study (May 2021-September 2022) aimed to measure under-vaccination rates among migrants in UK primary care and establish new referral pathways for catch-up vaccination. Participants included migrants aged 16 or older, born outside of Western Europe, North America, Australia, or New Zealand, in two London boroughs. Quantitative data on vaccination history, referral, uptake, and sociodemographic factors were collected, with practice nurses prompted to deliver catch-up vaccinations following UK guidelines. Focus group discussions and in-depth interviews with staff and migrants explored views on delivering catch-up vaccination, including barriers, facilitators, and opportunities. Data were analysed using STATA12 and NVivo 12. RESULTS: Results from 57 migrants presenting to study sites from 18 countries (mean age 41 [SD 7.2] years; 62% female; mean 11.3 [SD 9.1] years in UK) over a minimum of 6 months of follow-up revealed significant catch-up vaccination needs, particularly for MMR (49 [86%] required catch-up vaccination) and Td/IPV (50 [88%]). Fifty-three (93%) participants were referred for any catch-up vaccination, but completion of courses was low (6 [12%] for Td/IPV and 33 [64%] for MMR), suggesting individual and systemic barriers. Qualitative in-depth interviews (n = 39) with adult migrants highlighted the lack of systems currently in place in the UK to offer catch-up vaccination to migrants on arrival and the need for health-care provider skills and knowledge of catch-up vaccination to be improved. Focus group discussions and interviews with practice staff (n = 32) identified limited appointment/follow-up time, staff knowledge gaps, inadequate engagement routes, and low incentivisation as challenges that will need to be addressed. However, they underscored the potential of staff champions, trust-building mechanisms, and community-based approaches to strengthen catch-up vaccination uptake among migrants. CONCLUSIONS: Given the significant catch-up vaccination needs of migrants in our sample, and the current barriers to driving uptake identified, our findings suggest it will be important to explore this public health issue further, potentially through a larger study or trial. Strengthening existing pathways, staff capacity and knowledge in primary care, alongside implementing new strategies centred on cultural competence and building trust with migrant communities will be important focus areas.

Effectiveness and safety of COVID-19 vaccines on maternal and perinatal outcomes: a systematic review and meta-analysis.

OBJECTIVE: To assess the effects of COVID-19 vaccines in women before or during pregnancy on SARS-CoV-2 infection-related, pregnancy, offspring and reactogenicity outcomes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Major databases between December 2019 and January 2023. STUDY SELECTION: Nine pairs of reviewers contributed to study selection. We included test-negative designs, comparative cohorts and randomised trials on effects of COVID-19 vaccines on infection-related and pregnancy outcomes. Non-comparative cohort studies reporting reactogenicity outcomes were also included. QUALITY ASSESSMENT, DATA EXTRACTION AND ANALYSIS: Two reviewers independently assessed study quality and extracted data. We undertook random-effects meta-analysis and reported findings as HRs, risk ratios (RRs), ORs or rates with 95% CIs. RESULTS: Sixty-seven studies (1 813 947 women) were included. Overall, in test-negative design studies, pregnant women fully vaccinated with any COVID-19 vaccine had 61% reduced odds of SARS-CoV-2 infection during pregnancy (OR 0.39, 95% CI 0.21 to 0.75; 4 studies, 23 927 women; I2=87.2%) and 94% reduced odds of hospital admission (OR 0.06, 95% CI 0.01 to 0.71; 2 studies, 868 women; I2=92%). In adjusted cohort studies, the risk of hypertensive disorders in pregnancy was reduced by 12% (RR 0.88, 95% CI 0.82 to 0.92; 2 studies; 115 085 women), while caesarean section was reduced by 9% (OR 0.91, 95% CI 0.85 to 0.98; 6 studies; 30 192 women). We observed an 8% reduction in the risk of neonatal intensive care unit admission (RR 0.92, 95% CI 0.87 to 0.97; 2 studies; 54 569 women) in babies born to vaccinated versus not vaccinated women. In general, vaccination during pregnancy was not associated with increased risk of adverse pregnancy or perinatal outcomes. Pain at the injection site was the most common side effect reported (77%, 95% CI 52% to 94%; 11 studies; 27 195 women). CONCLUSION: COVID-19 vaccines are effective in preventing SARS-CoV-2 infection and related complications in pregnant women. PROSPERO REGISTRATION NUMBER: CRD42020178076.

The immune status of migrant populations in Europe and implications for vaccine-preventable disease control: a systematic review and meta-analysis.

BACKGROUND: Ensuring vaccination coverage reaches established herd immunity thresholds (HIT) is the cornerstone of any vaccination programme. Diverse migrant populations in European countries have been associated with cases of vaccine-preventable diseases (VPD) and outbreaks, yet it is not clear to what extent they are an under-immunised group. METHODS: We did a systematic review and meta-analysis to synthesise peer-reviewed published primary research reporting data on the immune status of migrants in EU/EEA countries, the UK and Switzerland, calculating their pooled immunity coverage for measles, mumps, rubella, and diphtheria using random-effects models. We searched on Web of Science, Embase, Global Health and MEDLINE (January 1st 2000 to June 10th 2022), with no language restrictions. The protocol is registered with PROSPERO (CRD42018103666). FINDINGS: Of 1103 abstracts screened, 62 met eligibility criteria, of which 39 were included in the meta-analysis. The meta-analysis included 75 089 migrants, predominantly from outside Europe. Pooled immunity coverage among migrant populations was well below the recommended HIT for diphtheria (n = 7, 57.4% [95% CI: 43.1-71.7%] I2 = 99% vs HIT 83-86%), measles (n = 21, 83.7% [95% CI: 79.2-88.2] I2 = 99% vs HIT 93-95%), and mumps (n = 8, 67.1% [95% CI: 50.6-83.6] I2 = 99% vs HIT 88-93%), and midway for rubella (n = 29, 85.6% [95% CI: 83.1-88.1%] I2 = 99% vs HIT 83-94%), with high heterogeneity across studies. INTERPRETATION: Migrants in Europe are an under-immunised group for a range of important VPDs, with this study reinforcing the importance of engaging children, adolescents, and adults in 'catch-up' vaccination initiatives on arrival for vaccines, doses, and boosters they may have missed in their home countries. Co-designing strategies to strengthen catch-up vaccination across the life-course in under-immunised groups is an important next step if we are to meet European and global targets for VPD elimination and control and ensure vaccine equity.

Evolution of the clinical simulation approach to assess digital health technologies.

Coronavirus 2019 (COVID-19) has catalysed digital transformation in the health space. However, it remains a challenge to generate timely and cost-effective evidence for digital health technologies (DHTs) to ensure their safety and efficacy. Traditional methods, such as randomised controlled trials (RCTs), are ill-suited for assessing DHTs for reasons of speed, agility, cost and context. Clinical simulation using high-fidelity synthetic patient cases is emerging as a promising yet underexplored method to evaluate DHTs. It offers several advantages, including conducting remote multi-site testing at low cost, inclusion of high-risk patient profiles that are usually excluded from RCTs and adaptability to different local clinical settings. This article shares some of the insights from studies using clinical simulation conducted at the Institute of Global Health Innovation (IGHI) at Imperial College London and describes the evolution of this approach as well as future opportunities.

Glycemic index and insulin index after a standard carbohydrate meal consumed with live kombucha: A randomised, placebo-controlled, crossover trial.

Introduction: Kombucha is a complex probiotic beverage made from fermented tea, yet despite extensive historical, anecdotal, and in-vivo evidence for its health benefits, no controlled trials have been published on its effect on humans. Methods: We conducted a randomised placebo-controlled, cross-over study that examined the Glycemic Index (GI) and Insulin Index (II) responses after a standardised high-GI meal consumed with three different test beverages (soda water, diet lemonade soft drink and an unpasteurised kombucha) in 11 healthy adults. The study was prospectively registered with the Australian New Zealand Clinical Trials Registry (anzctr.org.au: 12620000460909). Soda water was used as the control beverage. GI or II values were calculated by expressing the 2-h blood glucose or insulin response as a percentage of the response produced by 50 g of glucose dissolved in water. Results: There was no statistically significant difference in GI or II between the standard meal consumed with soda water (GI: 86 and II: 85) or diet soft drink (GI: 84 and II: 81, (p = 0.929 for GI and p = 0.374 for II). In contrast, when kombucha was consumed there was a clinically significant reduction in GI and II (GI: 68, p = 0.041 and II: 70, p = 0.041) compared to the meal consumed with soda water. Discussion: These results suggest live kombucha can produce reductions in acute postprandial hyperglycemia. Further studies examining the mechanisms and potential therapeutic benefits of kombucha are warranted.

LGBTQI + Migrants: A Systematic Review and Conceptual Framework of Health, Safety and Wellbeing during Migration.

The health and safety of LGBTQI+ migrants or migrants who are of diverse sexual orientation, gender identity or expression (SOGIE) remains an under-studied area, particularly for the period during transit from their place of origin to destination. This systematic review aims to describe the literature on the health risks and consequences among SOGIE migrants during transit and examine their access and use of services. Six peer-reviewed databases and websites of nine large migration organisations were searched to identify the literature on forced migrants and sexual and gender minorities. Twenty English-language studies from 2000-2021 were included and analysed drawing on a conceptual framework. Studies emerged from six regions and the majority of research participants identified as gay men. In general, quality appraisal demonstrated studies as either medium or high quality. Findings suggested five common themes associated with SOGIE health and well-being, including: daily exposure to discrimination, harassment and violence; coping, social support and resilience; access to services; mental health; and physical and sexual health. Depression, anxiety and post-traumatic stress disorder (PTSD) were prevalent amongst SOGIE migrants, particularly when associated with detention or camp environments, and were exacerbated by social isolation. Barriers to accessing healthcare were identified and specific sexual health services were often found lacking, especially for trans persons. Unsurprisingly, during transit, SOGIE migrants are very likely to experience the double marginalisation of their migrant or minority status and their gender identity. Results indicate that services for SOGIE migrants need to tailor service access and support approaches to respond to the particular health and protection needs of SOGIE individuals in each setting.

Development of a Website for a Living Network Meta-analysis of Atopic Dermatitis Treatments Using a User-Centered Design: Multimethod Study.

BACKGROUND: A rapid expansion of systemic immunological treatment options for atopic dermatitis (AD) has created a need for clinically relevant and understandable comparative efficacy and safety information for patients and clinicians. Given the scarcity of head-to-head trials, network meta-analysis (NMA) is an alternative way to enable robust comparisons among treatment options; however, NMA results are often complex and difficult to directly implement in shared decision-making. OBJECTIVE: The aim of this study is to develop a website that effectively presents the results of a living systematic review and NMA on AD treatments to patient and clinician users. METHODS: We conducted a multimethod study using iterative feedback from adults with AD, adult caregivers of children with AD, dermatologists, and allergists within a user-centered design framework. We used questionnaires followed by workshops among patients and clinicians to develop and improve the website interface. Usability testing was done with a caregiver of a patient with eczema. RESULTS: Questionnaires were completed by 31 adults with AD or caregivers and 94 clinicians. Patients and caregivers felt it was very important to know about new treatments (20/31, 65%). Clinicians felt the lack of evidence-based comparisons between treatments was a barrier to care (55/93, 59%). "Avoiding dangerous side effects" was ranked as the most important priority for patients (weighted ranking 5.2/7, with higher ranking being more important), and "improving patients' overall symptoms" was the most important priority for clinicians (weighted ranking 5.0/6). A total of 4 patients and 7 clinicians participated in workshops; they appreciated visualizations of the NMA results and found the website valuable for comparing different treatments. The patients suggested changes to simplify the interface and clarify terminology related to comparative efficacy. The user in the usability testing found the website intuitive to navigate. CONCLUSIONS: We developed a website, "eczematherapies.com," with a user-centered design approach. Visualizations of NMA results enable users to compare treatments as part of their shared decision-making process.

NCF1 (p47phox)-deficient chronic granulomatous disease: comprehensive genetic and flow cytometric analysis.

Mutations in NCF1 (p47phox) cause autosomal recessive chronic granulomatous disease (CGD) with abnormal dihydrorhodamine (DHR) assay and absent p47phox protein. Genetic identification of NCF1 mutations is complicated by adjacent highly conserved (>98%) pseudogenes (NCF1B and NCF1C). NCF1 has GTGT at the start of exon 2, whereas the pseudogenes each delete 1 GT (ΔGT). In p47phox CGD, the most common mutation is ΔGT in NCF1 (c.75_76delGT; p.Tyr26fsX26). Sequence homology between NCF1 and its pseudogenes precludes reliable use of standard Sanger sequencing for NCF1 mutations and for confirming carrier status. We first established by flow cytometry that neutrophils from p47phox CGD patients had negligible p47phox expression, whereas those from p47phox CGD carriers had ∼60% of normal p47phox expression, independent of the specific mutation in NCF1 We developed a droplet digital polymerase chain reaction (ddPCR) with 2 distinct probes, recognizing either the wild-type GTGT sequence or the ΔGT sequence. A second ddPCR established copy number by comparison with the single-copy telomerase reverse transcriptase gene, TERT We showed that 84% of p47phox CGD patients were homozygous for ΔGT NCF1 The ddPCR assay also enabled determination of carrier status of relatives. Furthermore, only 79.2% of normal volunteers had 2 copies of GTGT per 6 total (NCF1/NCF1B/NCF1C) copies, designated 2/6; 14.7% had 3/6, and 1.6% had 4/6 GTGT copies. In summary, flow cytometry for p47phox expression quickly identifies patients and carriers of p47phox CGD, and genomic ddPCR identifies patients and carriers of ΔGT NCF1, the most common mutation in p47phox CGD.

Valve-in-Valve Transcatheter Aortic Valve Replacement and Bioprosthetic Valve Fracture Comparing Different Transcatheter Heart Valve Designs: An Ex Vivo Bench Study.

OBJECTIVES: The authors assessed the effect of valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) followed by bioprosthetic valve fracture (BVF), testing different transcatheter heart valve (THV) designs in an ex vivo bench study. BACKGROUND: Bioprosthetic valve fracture can be performed to improve residual transvalvular gradients following VIV TAVR. METHODS: The authors evaluated VIV TAVR and BVF with the SAPIEN 3 (S3) (Edwards Lifesciences, Irvine, California) and ACURATE neo (Boston Scientific Corporation, Natick, Massachusetts) THVs. A 20-mm and 23-mm S3 were deployed in a 19-mm and 21-mm Mitroflow (Sorin Group USA, Arvada, Colorado), respectively. A small ACURATE neo was deployed in both sizes of Mitroflow tested. VIV TAVR samples underwent multimodality imaging, and hydrodynamic evaluation before and after BVF. RESULTS: A high implantation was required to enable full expansion of the upper crown of the ACURATE neo and allow optimal leaflet function. Marked underexpansion of the lower crown of the THV within the surgical valve was also observed. Before BVF, VIV TAVR in the 19-mm Mitroflow had high transvalvular gradients using either THV design (22.0 mm Hg S3, and 19.1 mm Hg ACURATE neo). After BVF, gradients improved and were similar for both THVs (14.2 mm Hg S3, and 13.8 mm Hg ACURATE neo). The effective orifice area increased with BVF from 1.2 to 1.6 cm2 with the S3 and from 1.4 to 1.6 cm2 with the ACURATE neo. Before BVF, VIV TAVR with the ACURATE neo in the 21-mm Mitroflow had lower gradients compared with S3 (11.3 mm Hg vs. 16 mm Hg). However, after BVF valve gradients were similar for both THVs (8.4 mm Hg ACURATE neo vs. 7.8 mm Hg S3). The effective orifice area increased from 1.5 to 2.1 cm2 with the S3 and from 1.8 to 2.2 cm2 with the ACURATE neo. CONCLUSIONS: BVF performed after VIV TAVR results in improved residual gradients. Following BVF, residual gradients were similar irrespective of THV design. Use of a small ACURATE neo for VIV TAVR in small (≤21 mm) surgical valves may be associated with challenges in achieving optimum THV position and expansion. BVF could be considered in selected clinical cases.

Hypertrophic Cardiomyopathy (HCM): New insights into Coronary artery remodelling and ischemia from FFRCT.

INTRODUCTION: Angina, myocardial ischemia, and coronary artery physiology in hypertrophic cardiomyopathy (HCM) are poorly understood. However, coronary computed tomography angiography (CCTA) with fractional flow reserve from CT (FFRCT) analysis offers a non-invasive method for evaluation of coronary artery volume to myocardial mass ratio (V/M) that may provide insight into such mechanisms. Thus, we sought to investigate changes in V/M in HCM. METHODS: A retrospective analysis was performed on 37 HCM patients and 37 controls matched for age, sex, and cardiovascular risk factors; CCTA-derived coronary artery lumen volume (V) and myocardial mass (M) were used to determine V/M. FFRCT values were calculated for the left anterior descending (LAD), left circumflex (LCx) and right coronary (RCA) arteries as well as the 3-vessel cumulative FFRCT values. RESULTS: HCM patients had significantly increased myocardial mass (176 ±â€¯84 vs. 119 ±â€¯27 g, p < 0.0001) and total coronary artery luminal volume (4112 ±â€¯1139 vs. 3290 ±â€¯924 mm3, p < 0.0001) that resulted from increases in segmented luminal volumes of both the left and right coronary artery systems. However, HCM patients had significantly decreased V/M (23.8 ±â€¯5.9 vs. 26.5 ±â€¯5.3 mm3/g; p = 0.026) which was further decreased when restricting V/M analysis to those HCM patients with septal hypertrophy (22.4 mm3/g, p = 0.01) that was mild-moderately predictive of HCM (AUC = 0.68). HCM patients also showed significantly lower nadir FFRCT values in the LCx (0.87 ±â€¯0.06 vs. 0.91 ±â€¯0.06, p = 0.02), and cumulative 3-vessel FFRCT values (2.58 ±â€¯0.18 vs. 2.63 ±â€¯0.14, p = 0.006). CONCLUSIONS: HCM patients demonstrate significantly greater coronary volume. Despite this, HCM patients suffer from decreased V/M. Further prospective studies evaluating the relationship between V/M, angina, and heart failure in HCM are needed.

X-linked carriers of chronic granulomatous disease: Illness, lyonization, and stability.

BACKGROUND: Chronic granulomatous disease (CGD) is characterized by recurrent life-threatening bacterial and fungal infections and aberrant inflammation. Mutations in CYBB cause X-linked CGD and account for 65% to 70% of cases in Western countries. OBJECTIVE: We sought to understand the clinical manifestations associated with the X-linked CGD carrier state. METHODS: We undertook a comprehensive retrospective study of 162 affected female subjects. We examined dihydrorhodamine 123 (DHR) oxidation data for percentage of X-chromosome inactivation. We correlated lyonization (%DHR+) with clinical features. Where possible, we followed %DHR+ values over time. RESULTS: Clinical data were available for 93 female subjects: %DHR+ values were 46% (mean) and 47% (median; SD, 24). Using the %DHR+ value as the criterion for X inactivation, 78% of patients had levels of inactivation of 20% to 80%, suggesting random inactivation that was independent of age. In contrast, carriers with CGD-type infections had median %DHR+ values of 8% (n = 14; range, 0.06% to 48%), and those with only autoimmune or inflammatory manifestations had median %DHR+ values of 39% (n = 31; range, 7.4% to 74%). Those with both infections and autoimmunity had low %DHR+ values (n = 6; range, 3% to 14%). A %DHR+ value of less than 10% was strongly associated with infections (odds ratio, 99). Strong association persisted when %DHR+ values were less than 20% (odds ratio, 12). Autoimmunity was not associated with %DHR+ values. In 2 sets of identical twins, the %DHR+ populations tracked closely over time. Although the %DHR+ populations were very similar between sisters, those between mothers and daughters were unrelated. CONCLUSIONS: A low %DHR+ value strongly predicts infection risk in X-linked CGD carriers, and the carrier state itself is associated with autoimmunity.

Demographic correlates of medication knowledge in Hong Kong early psychosis patients.

AIM: Patient knowledge of prescribed medications is important for accurate medication consumption. Not many studies have identified the demographic correlates of medication knowledge in psychiatric patients, and fewer have performed so for non-Western societies, which may present different results owing to distinct cultural factors. Our objective was to identify the demographic correlates of medication knowledge in early psychosis patients from Hong Kong. METHODS: A short questionnaire comprising questions on six components of medication knowledge was administered to 105 consecutive early psychosis patients from an outpatient clinic in Hong Kong. A suite of patient demographics was assembled from clinicians' records. RESULTS: Poor medication knowledge was characterized by patients of older age (>30 years), low education level (≤Form 3), overall negative family relationships (as compared with overall positive ones) and shorter treatment duration (≤4 years). Shorter treatment duration most consistently predicted poor medication knowledge, displaying significant (P < 0.05) associations with four out of six knowledge components. Patients (54.3%) did not know the English names of their medication. CONCLUSIONS: Specific groups of early psychosis patients are at risk of having poor medication knowledge; these individuals should be identified to receive regular health education. Contrary to findings from non-psychosis groups, short treatment duration was unequivocally associated with poorer medication knowledge in patients with early psychosis. Local replacements for English medication names should be considered in non-English speaking societies, especially in areas of mental health treatment.

Social Isolation in Chinese Older Adults: Scoping Review for Age-Friendly Community Planning.

Chinese older adults may be at increased risk of social isolation and loneliness, and a fragmented understanding exists about the challenges they face for social participation in their neighbourhoods and communities. A scoping review was undertaken to describe the current knowledge on social isolation and loneliness in urban-dwelling Chinese older adults living in Western societies to inform future research, practice, and policy in Canada. Nineteen articles met the inclusion criteria. The World Health Organization's age-friendly community framework contextualized the study findings. Studies identified issues related to (1) social participation; (2) community support and health services; (3) housing; (4) community and information; (5) respect and social inclusion; (6) outdoor spaces and public buildings; (7) civic participation and employment; and (8) transportation. Social isolation and loneliness is a growing concern in this population in Canada, and additional research is needed to identify its scope and effective interventions.

Early Functional Limitations in Cognitively Normal Older Adults Predict Diagnostic Conversion to Mild Cognitive Impairment.

OBJECTIVES: To examine whether specific types of early functional limitations in cognitively normal older adults are associated with subsequent development of mild cognitive impairment (MCI), as well as the relative predictive value of self versus informant report in predicting diagnostic conversion to MCI. DESIGN: As a part of a longitudinal study design, participants underwent baseline and annual multidisciplinary clinical evaluations, including a physical and neurological examination, imaging, laboratory work, and neuropsychological testing. SETTING: Data used in this study were collected as part of longitudinal research at the University of California, Davis Alzheimer's Disease Center. PARTICIPANTS: Individuals diagnosed as having normal cognition at study baseline who had an informant who could complete informant-based ratings and at least one follow-up visit (N = 324). MEASUREMENTS: Participants and informants each completed the Everyday Cognition Scale (ECog), an instrument designed to measure everyday function in six cognitively relevant domains. RESULTS: Self- and informant-reported functional limitations on the ECog were associated with significantly greater risk of diagnostic conversion to MCI (informant: hazard ratio (HR) = 2.0, 95% confidence interval (CI) = 1.3-3.2, P = .002), with self-report having a slightly higher hazard (HR = 2.3, 95% CI = 1.4-3.6, P < .001). When controlling for baseline cognitive abilities, the effect remained significant for self- and informant-reported functional limitations. CONCLUSION: Deficits in everyday memory and executive function domains were the strongest predictors of diagnostic conversion to MCI. Detection of early functional limitations may be clinically useful in assessing the future risk of developing cognitive impairment in cognitively normal older adults.

Splenectomy as a Destination: Improving Quality of Care Among Asplenic Veterans Through a Travel Clinic.

BACKGROUND: Asplenic patients are at risk for severe infections, but adherence to recommended preventive education and vaccination is poor. The goal of this study was to demonstrate that a targeted intervention can improve vaccination rates in a population of asplenic veterans. METHODS: Surgically asplenic patients actively receiving care in our health care system were identified via a database search. Patients were contacted via mailed letters and encouraged to attend an existing travel clinic with a new process designed for asplenic patients. In the clinic, patients were educated on the risks of asplenia and proper preventive precautions, a vaccination history was taken, and patients were administered any additional indicated vaccines. RESULTS: The database search yielded 113 patients; an additional 14 asplenic patients were identified and referred to the clinic by providers, and 2 were referred prior to planned splenectomy. Among all asplenic patients, the first-year referral rate to clinic was 38/129 (29%). During the first year of the intervention, there were increases in the rates of 3 of 4 recommended vaccinations: pneumococcal conjugate, 19% to 55% (P <.001); Haemophilus influenzae type B, 19% to 35% (P = .007); and meningococcal vaccine, 24% to 43% (P = .002). The pneumococcal polysaccharide vaccination rate increased from 91% to 93% (P = .62). CONCLUSIONS: Targeted interventions can improve guideline-based care for asplenic patients. The creation of a clinic designed for asplenic patients led to increases in 3 of 4 recommended vaccinations. This strategy may be applicable to other health care systems with similar numbers of asplenic patients.

Cytoskeletal abnormalities and neutrophil dysfunction in WDR1 deficiency.

Cell motility, division, and structural integrity depend on dynamic remodeling of the cellular cytoskeleton, which is regulated in part by actin polymerization and depolymerization. In 3 families, we identified 4 children with recurrent infections and varying clinical manifestations including mild neutropenia, impaired wound healing, severe stomatitis with oral stenosis, and death. All patients studied had similar distinctive neutrophil herniation of the nuclear lobes and agranular regions within the cytosol. Chemotaxis and chemokinesis were markedly impaired, but staphylococcal killing was normal, and neutrophil oxidative burst was increased both basally and on stimulation. Neutrophil spreading on glass and cell polarization were also impaired. Neutrophil F-actin was elevated fourfold, suggesting an abnormality in F-actin regulation. Two-dimensional differential in-gel electrophoresis identified abnormal actin-interacting protein 1 (Aip1), encoded by WDR1, in patient samples. Biallelic mutations in WDR1 affecting distinct antiparallel ß-strands of Aip1 were identified in all patients. It has been previously reported that Aip1 regulates cofilin-mediated actin depolymerization, which is required for normal neutrophil function. Heterozygous mutations in clinically normal relatives confirmed that WDR1 deficiency is autosomal recessive. Allogeneic stem cell transplantation corrected the immunologic defect in 1 patient. Mutations in WDR1 affect neutrophil morphology, motility, and function, causing a novel primary immunodeficiency.

Hypoxia causes transgenerational impairments in reproduction of fish.

Hypoxia is amongst the most widespread and pressing problems in aquatic environments. Here we demonstrate that fish (Oryzias melastigma) exposed to hypoxia show reproductive impairments (retarded gonad development, decrease in sperm count and sperm motility) in F1 and F2 generations despite these progenies (and their germ cells) having never been exposed to hypoxia. We further show that the observed transgenerational reproductive impairments are associated with a differential methylation pattern of specific genes in sperm of both F0 and F2 coupled with relevant transcriptomic and proteomic alterations, which may impair spermatogenesis. The discovered transgenerational and epigenetic effects suggest that hypoxia might pose a dramatic and long-lasting threat to the sustainability of fish populations. Because the genes regulating spermatogenesis and epigenetic modifications are highly conserved among vertebrates, these results may also shed light on the potential transgenerational effects of hypoxia on other vertebrates, including humans.

Assessing for mild TBI among Iraq and Afghanistan veterans: Outcomes of injury severity and neurological factors.

OBJECTIVE: To investigate injury severity markers and neurological symptoms associated with clinician-confirmed mild traumatic brain injury (TBI) among Iraq and Afghanistan veterans. SETTING: Department of Veterans Affairs (VA) medical centre and five affiliated community-based outpatient clinics. PARTICIPANTS: Three hundred and fifty Iraq and Afghanistan veterans with positive initial VA TBI screens between 1 April 2007 and 1 June 2010 and clinician-confirmed TBI status by 1 December 2010. METHODS: Retrospective-cohort study of medical record data. Main measures included clinician-confirmed TBI status, injury severity markers (e.g. loss of consciousness (LOC), post-traumatic amnesia (PTA) or confusion/disorientation) and neurological symptoms. RESULTS: Among veterans who screened positive on the initial VA TBI and then received a clinician evaluation, 60% were confirmed to have a TBI diagnosis. Veterans reporting at least one LOC, confusion or PTA were almost 18-times more likely to receive a confirmed TBI diagnosis. Odds of clinician-confirmed TBI were 2.5-3-times greater among those who endorsed dizziness, poor coordination, headaches, nausea, vision problems and/or irritability, compared to those not endorsing these symptoms. Nausea had greatest utility for confirming a TBI. CONCLUSIONS: Identification of neurologic symptoms that most contribute to a clinician-confirmed diagnosis of TBI has potential for streamlining detection of TBI and symptoms needed for treatment.

Early Cognitively Based Functional Limitations Predict Loss of Independence in Instrumental Activities of Daily Living in Older Adults.

Older adults with early forms of neurodegenerative disease are at risk for functional disability, which is often defined by the loss of independence in instrumental activities of daily living (IADLs). The current study investigated the influence of mild changes in everyday functional abilities (referred to as functional limitations) on risk for development of incident functional disability. A total of 407 participants, who were considered cognitively normal or diagnosed with mild cognitive impairment (MCI) at baseline, were followed longitudinally over an average 4.1 years (range=0.8-9.2 years). Informant-based ratings from the Everyday Cognition (ECog; Farias et al., 2008) and the Instrumental Activities of Daily Living (Lawton & Brody, 1969) scales assessed the degree of functional limitations and incident IADL disability, respectively. Cox proportional hazards models revealed that more severe functional limitations (as measured by the Total ECog score) at baseline were associated with approximately a four-fold increased risk of developing IADL disability a few years later. Among the ECog domains, functional limitations in Everyday Planning, Everyday Memory, and Everyday Visuospatial domains were associated with the greatest risk of incident functional disability. These results remained robust even after controlling for participants' neuropsychological functioning on tests of executive functions and episodic memory. Current findings indicate that early functional limitations have prognostic value in identifying older adults at risk for developing functional disability. Findings highlight the importance of developing interventions to support everyday abilities related to memory, executive function, and visuospatial skills in an effort to delay loss of independence in IADLs.