'A more human approach I haven't found that really': experiences of hoarding difficulties and seeking help.

BACKGROUND AND AIMS: People with hoarding behaviours often struggle to engage in treatment. This study aimed to explore the experiences of a sample of people who identify as engaging in hoarding behaviours and who are seeking support. Exploring motivation to seek help, the barriers those who hoard face in accessing support and what facilitates accepting help, can aid understanding of how best to intervene. METHOD: Eight individuals who self-identified as seeking help in relation to hoarding behaviours were recruited via social media and support groups. Interviews were conducted by telephone or video call, before being transcribed and analysed using interpretative phenomenological analysis. RESULTS: Participants described complex help-seeking narratives and reported continued ambivalence about addressing their hoarding behaviours. The four group experiential themes identified were Wrestling with identity; Who can I trust?; Services don't fit; and Being overlooked: 'they're too busy looking at the thing, not the person'. Difficulties trusting others and services were identified; services were experienced as rejecting and many participants sought help for problems other than their hoarding. Problems accessing appropriate help for hoarding were predominant in the narratives, although participants who had accessed peer support described this as valuable. CONCLUSIONS: There are both internal (e.g. fear of judgement; feeling overwhelmed) and external (e.g. service gaps) barriers that make finding useful help for hoarding behaviours very difficult. Services may facilitate those seeking help by taking a compassionate and person-centred approach to hoarding problems.

'Would I risk it again?' The long-term impacts of a traumatic birth, as experienced by fathers.

BACKGROUND: Extensive research has explored the impact of traumatic births on mothers, capturing enduring adverse outcomes as well as post-traumatic growth. The literature on fathers' experiences of birth trauma is more limited and little is known of the ongoing impact. The present study aimed to investigate the long-term effects of attending a traumatic birth. METHOD: Semi-structured interviews were completed with fathers who identified as having a traumatic birth experience two or more years ago. Thematic analysis was conducted on eight interview transcripts. RESULTS: Despite the time since the birth trauma, fathers described ongoing impact, which is captured in five themes. Four of these focus on the negative impacts: their attempts to cope by boxing away emotions, which they thought they should not feel; anxieties over having further children; negative effects on parenting; and ongoing distress or negative impact on their wellbeing. The final theme highlighted some positives from the experience, primarily a strengthened relationship with their partner. CONCLUSIONS: Traumatic birth can result in fathers experiencing difficulties beyond the perinatal period, whilst thinking that they should not feel or discuss their distress. As a result of a traumatic birth fathers can experience ongoing guilt and poor mental health, which may lead them to delay subsequent pregnancies. Most participants had not accessed support regarding the traumatic birth, instead coping by trying to avoid their memories and emotional reaction. These findings highlight the need for increased acknowledgement of the impact of birth trauma and intervention for fathers, during and after the perinatal period.

How to use podcasts in neurology.

Virtual learning resources such as podcasts and social media are increasingly used in medical education. Podcasts are one example of virtual learning, where prerecorded audio files are available to stream or download from the internet, usually without a fee and at any time. This gives listeners flexibility in when and where they engage with the educational material, enabling learning to be better tailored to individual needs. Podcasts are often enjoyed for their relaxed and conversational style. However, listeners must be aware of the lack of external peer review and incomplete coverage of information. There are also risks inherent to distant learning, including depersonalisation of medical education. We describe the roles that podcasts now play in neurological education, exploring some of the ways that they can be used to enhance neurological training both as a learner and educator and giving our top tips, based on our own experiences, for anyone keen to add to the expanding field of available podcasts.

Military and Civilian Trauma System Integration: A Global Case Series.

INTRODUCTION: Traumatic injury is a leading cause of morbidity globally, particularly in low-income and middle-income countries (LMICs). In high-income countries (HICs), it is well documented that military and civilian integration can positively impact trauma care in both healthcare systems, but it is unknown if this synergy could benefit LMICs. This case series examines the variety of integration between the civilian and military systems of various countries and international partnerships to elucidate if there are commonalities in facilitators and barriers. METHODS: A convenience sampling method was utilized to identify subject matter experts on civilian and military trauma system integration. Data were collected and coded through an iterative process, focusing on the historical impetuses and subsequent outcomes of civilian and military trauma care collaboration. RESULTS: Eight total case studies were completed, five addressing specific countries and three addressing international partnerships. Themes which emerged as drivers for integration included history of conflict, geography, and skill maintenance for military physicians. High-level government support was a central theme for successful integration, and financial issues were often seen as the greatest barrier. CONCLUSIONS: Various approaches in civilian-military integration exist throughout the world, and the studied nations and international partnerships demonstrated similar motivators and barriers to integration. This study highlights the need for further investigation, particularly in LMICs, where less is known about integration strategies.

Health equity for persons with disabilities: a global scoping review on barriers and interventions in healthcare services.

BACKGROUND: Persons with disabilities experience health inequities in terms of increased mortality, morbidity, and limitations in functioning when compared to the rest of the population. Many of the poor health outcomes experienced by persons with disabilities cannot be explained by the underlying health condition or impairment, but are health inequities driven by unfair societal and health system factors. A synthesis of the global evidence is needed to identify the factors that hinder equitable access to healthcare services for persons with disabilities, and the interventions to remove these barriers and promote disability inclusion. METHODS: We conducted a scoping review following the methodological framework proposed by Arksey and O'Malley, Int J Soc Res Methodol 8:19-32. We searched two scholarly databases, namely MEDLINE (Ovid) and Web of Science, the websites of Organizations of Persons with Disabilities and governments, and reviewed evidence shared during WHO-led consultations on the topic of health equity for persons with disabilities. We included articles published after 2011 with no restriction to geographical location, the type of underlying impairments or healthcare services. A charting form was developed and used to extract the relevant information for each included article. RESULTS: Of 11,884 articles identified in the search, we included 182 articles in this review. The majority of sources originated from high-income countries. Barriers were identified worldwide across different levels of the health system (such as healthcare costs, untrained healthcare workforces, issues of inclusive and coordinated services delivery), and through wider contributing factors of health inequities that expand beyond the health system (such as societal stigma or health literacy). However, the interventions to promote equitable access to healthcare services for persons with disabilities were not readily mapped onto those needs, their sources of funding and projected sustainability were often unclear, and few offered targeted approaches to address issues faced by marginalized groups of persons with disabilities with intersectional identities. CONCLUSION: Persons with disabilities continue to face considerable barriers when accessing healthcare services, which negatively affects their chances of achieving their highest attainable standard of health. It is encouraging to note the increasing evidence on interventions targeting equitable access to healthcare services, but they remain too few and sparce to meet the populations' needs. Profound systemic changes and action-oriented strategies are warranted to promote health equity for persons with disabilities, and advance global health priorities.

Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial.

BACKGROUND: Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19 (AZD1222), in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older. METHODS: In this report of the phase 2 component of a single-blind, randomised, controlled, phase 2/3 trial (COV002), healthy adults aged 18 years and older were enrolled at two UK clinical research facilities, in an age-escalation manner, into 18-55 years, 56-69 years, and 70 years and older immunogenicity subgroups. Participants were eligible if they did not have severe or uncontrolled medical comorbidities or a high frailty score (if aged ≥65 years). First, participants were recruited to a low-dose cohort, and within each age group, participants were randomly assigned to receive either intramuscular ChAdOx1 nCoV-19 (2·2 × 1010 virus particles) or a control vaccine, MenACWY, using block randomisation and stratified by age and dose group and study site, using the following ratios: in the 18-55 years group, 1:1 to either two doses of ChAdOx1 nCoV-19 or two doses of MenACWY; in the 56-69 years group, 3:1:3:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY; and in the 70 years and older, 5:1:5:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY. Prime-booster regimens were given 28 days apart. Participants were then recruited to the standard-dose cohort (3·5-6·5 × 1010 virus particles of ChAdOx1 nCoV-19) and the same randomisation procedures were followed, except the 18-55 years group was assigned in a 5:1 ratio to two doses of ChAdOx1 nCoV-19 or two doses of MenACWY. Participants and investigators, but not staff administering the vaccine, were masked to vaccine allocation. The specific objectives of this report were to assess the safety and humoral and cellular immunogenicity of a single-dose and two-dose schedule in adults older than 55 years. Humoral responses at baseline and after each vaccination until 1 year after the booster were assessed using an in-house standardised ELISA, a multiplex immunoassay, and a live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) microneutralisation assay (MNA80). Cellular responses were assessed using an ex-vivo IFN-γ enzyme-linked immunospot assay. The coprimary outcomes of the trial were efficacy, as measured by the number of cases of symptomatic, virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were by group allocation in participants who received the vaccine. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. This study is ongoing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137. FINDINGS: Between May 30 and Aug 8, 2020, 560 participants were enrolled: 160 aged 18-55 years (100 assigned to ChAdOx1 nCoV-19, 60 assigned to MenACWY), 160 aged 56-69 years (120 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY), and 240 aged 70 years and older (200 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY). Seven participants did not receive the boost dose of their assigned two-dose regimen, one participant received the incorrect vaccine, and three were excluded from immunogenicity analyses due to incorrectly labelled samples. 280 (50%) of 552 analysable participants were female. Local and systemic reactions were more common in participants given ChAdOx1 nCoV-19 than in those given the control vaccine, and similar in nature to those previously reported (injection-site pain, feeling feverish, muscle ache, headache), but were less common in older adults (aged ≥56 years) than younger adults. In those receiving two standard doses of ChAdOx1 nCoV-19, after the prime vaccination local reactions were reported in 43 (88%) of 49 participants in the 18-55 years group, 22 (73%) of 30 in the 56-69 years group, and 30 (61%) of 49 in the 70 years and older group, and systemic reactions in 42 (86%) participants in the 18-55 years group, 23 (77%) in the 56-69 years group, and 32 (65%) in the 70 years and older group. As of Oct 26, 2020, 13 serious adverse events occurred during the study period, none of which were considered to be related to either study vaccine. In participants who received two doses of vaccine, median anti-spike SARS-CoV-2 IgG responses 28 days after the boost dose were similar across the three age cohorts (standard-dose groups: 18-55 years, 20 713 arbitrary units [AU]/mL [IQR 13 898-33 550], n=39; 56-69 years, 16 170 AU/mL [10 233-40 353], n=26; and ≥70 years 17 561 AU/mL [9705-37 796], n=47; p=0·68). Neutralising antibody titres after a boost dose were similar across all age groups (median MNA80 at day 42 in the standard-dose groups: 18-55 years, 193 [IQR 113-238], n=39; 56-69 years, 144 [119-347], n=20; and ≥70 years, 161 [73-323], n=47; p=0·40). By 14 days after the boost dose, 208 (>99%) of 209 boosted participants had neutralising antibody responses. T-cell responses peaked at day 14 after a single standard dose of ChAdOx1 nCoV-19 (18-55 years: median 1187 spot-forming cells [SFCs] per million peripheral blood mononuclear cells [IQR 841-2428], n=24; 56-69 years: 797 SFCs [383-1817], n=29; and ≥70 years: 977 SFCs [458-1914], n=48). INTERPRETATION: ChAdOx1 nCoV-19 appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. Further assessment of the efficacy of this vaccine is warranted in all age groups and individuals with comorbidities. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.

The impact of prehabilitation interventions on affective and functional outcomes for young to midlife adult cancer patients: A systematic review.

OBJECTIVE: Cancer remains one of the most enduring health crises of the modern world. Prehabilitation is a relatively new intervention aimed at preparing individuals for the stresses associated with treatment from diagnosis. Prehabilitation can include exercise, psychological and nutrition-based interventions. The present systematic review aimed to assess the efficacy of prehabilitation on affective and functional outcomes for young to midlife adult cancer patients (18-55 years). Outcomes of interest included prehabilitation programme composition, duration, mode of delivery and measures used to determine impact on affective and functional outcomes. METHODS: The following databases were searched with controlled and free text vocabulary; Psychological Information database (PsychINFO), Culmunated Index to Nursing and Allied Health Literature (CINAHL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE) and Public MEDLINE (PubMed). Abstract and full-text screening was conducted with a secondary reviewer and final texts were subject to risk of bias analysis. RESULTS: Thirteen texts were included at full-text. These included data of 797 prehabilitation participants (mean age 53 years) and a large representation of female participants (71% average). Evidence was found for the efficacy of psychological prehabilitation for anxiety reduction. Prehabilitation did not significantly affect health related quality of life. Findings moderately supported the therapeutic validity of exercise prehabilitation for functional outcomes, both in terms of clinical and experimental improvement with respect to the quality of evidence. Variation between all prehabilitation types was observed. There was insufficient evidence to support the efficacy of psychological prehabilitation on stress, distress or depression. CONCLUSION: Implications for future research are highlighted and then discussed with respect to this young to midlife age group.

Arterial Line Placement Pitfalls Can Be Demonstrated and Visualized With an Inexpensive, Wearable Trainer.

BACKGROUND: Radial arterial line placement is commonly performed in various clinical settings, including the emergency department. However, learners are successful on the first attempt only half of the time. Simulation can provide learners with procedure practice opportunities outside of clinical practice to increase confidence and chances of success. OBJECTIVES: We set out to build an arterial line trainer that would be inexpensive and reusable, wearable, anatomically realistic, and echogenic to allow for ultrasound use. We also hoped to devise a clear option that would allow for demonstration of procedure pitfalls. DISCUSSION: The arterial line trainer requires 4 hours of assembly time and costs $160. This includes enough material to make 48 tissue pads. The ballistics gel pad is echogenic; it can be customized with clear gel for direct anatomic visualization or dyed gel for more realism. The trainer also has a pulsatile artery for practice using anatomic landmarks. Visualization of the following important arterial line placement pitfalls is possible: suboptimal angle of approach, inadequate advancement of the catheter, and through-and-through vessel puncture. CONCLUSIONS: Our inexpensive trainer can help physicians and physicians in training conceptualize, practice, and troubleshoot the pitfalls of arterial line placement. Training programs looking to help learners understand the mechanics of arterial line placement may find it a useful tool.

Drivers of Scope of Practice in Family Medicine: A Conceptual Model.

PURPOSE: The purpose of this study was to explore family medicine graduates' attitudes and perspectives on modifiable and unmodifiable factors that influenced their scope of practice and career choices. By understanding how these factors intersect to influence desired and actual scope of practice decisions, we hope to inform strategies to address training and health care workforce needs. METHODS: During 5 focus group discussions, comprised of a total of 32 family physicians who either resided in or attended a residency program in western North Carolina, we explored family physicians' attitudes and perspectives on their desired and actual scope of practice. We used thematic analysis to identify patterns in the qualitative data. RESULTS: We created a conceptual framework to understand the complex factors which influence family physicians' scope of practice. Personal factors were found to impact desired scope, while workplace, environmental, and population factors influenced actual scope of practice. Stressors in each of these 4 categories often caused family physicians to narrow their scope of practice. Our study highlights specific supports that, if in place, enable physicians to maintain their desired broad scope of practice. CONCLUSIONS: Our study indicates that the national trend toward family physicians narrowing their scope of practice can be addressed by providing specific supports during training, residency, and mid-career. Understanding personal, workplace, environmental, and population factors that influence scope of practice can inform specific interventions that create desirable jobs for family physicians and improve their ability to meet changing population needs.

Low Bottleneck Detection in Long-Lived Species Despite Lost Genetic Diversity: A Case Study of Tuatara and Eastern Massasauga Rattlesnakes.

Population bottlenecks can reduce genetic diversity and may lead to inbreeding depression. However, some studies have provided evidence that long lifespans buffer negative genetic effects of bottlenecks. Others have cautioned that longevity might merely mask the effects of genetic drift, which will still affect long-term population viability. We used microsatellite data from actual populations of tuatara (Sphenodon punctatus) and eastern massasaugas (Sistrurus catenatus) as a starting point for simulated population declines to evaluate the performance of bottleneck tests under a range of scenarios. We quantified losses in genetic diversity for each scenario and assessed the power of commonly used tests (i.e., M-ratio, heterozygosity excess, and mode-shift) to detect known bottlenecks in these moderate- to long-lived species. Declines in genetic diversity were greater in bottlenecks simulated for eastern massasaugas, the shorter-lived species, and mode-shift and heterozygosity excess tests were more sensitive to population declines in this species. Conversely, M-ratio tests were more sensitive to bottlenecks simulated in tuatara. Despite dramatic simulated population declines, heterozygosity excess and mode-shift tests often failed to detect bottlenecks in both species, even when large losses in genetic diversity had occurred (both allelic diversity and heterozygosity). While not eliminating type II error, M-ratio tests generally performed best and were most reliable when a critical value (Mc) of 0.68 was used. However, in tuatara simulations, M-ratio tests had high rates of type I error when Mc was calculated assuming θ = 10. Our results suggest that reliance on these tests could lead to misguided species management decisions.

Characterisation of clinical and immune reactivity to barley and rye ingestion in children with coeliac disease.

OBJECTIVE: Barley and rye are major components of the Western diet, and historic feeding studies indicate that they cause clinical effects in patients with coeliac disease (CD). This toxicity has been attributed to sequence homology with immunogenic wheat sequences, but in adults with CD, these cereals stimulate unique T cells, indicating a critical contribution to gluten immunity independent of wheat. Clinical and immune feeding studies with these grains in children with CD are sparse. We undertook a barley and rye feeding study to characterise the clinical and T-cell responses in children with CD. DESIGN: 42 children with human leucocyte antigen (HLA)-DQ2.5+ (aged 3-17 years) consumed barley or rye for 3 days. Blood-derived gluten-specific T cells were tested for reactivity against a panel of barley (hordein) and rye (secalin) peptides. Hordein and secalin-specific T-cell clones were generated and tested for grain cross-reactivity. T-cell receptor sequencing was performed on sorted single cells. T-cell responses were compared with those observed in adults with CD. RESULTS: 90% of the children experienced adverse symptoms, mostly GI, and 61% had detectable gluten-specific T-cell responses targeting peptides homologous to those immunogenic in adults. Deamidation was important for peptide reactivity. Homozygosity for HLA-DQ2.5 predicted a stronger T-cell response. Gluten-specific T cells showed striking similarities in their cross-reactivity between children and adults. CONCLUSIONS: Barley and rye induce a consistent range of clinical and T-cell responses in children with CD. The findings highlight the importance of a series of dominant hordein and secalin peptides pathogenic in children with CD, some independent of wheat, which closely correspond to those seen in adults.

Blocking matrix metalloproteinase-mediated syndecan-4 shedding restores the endothelial glycocalyx and glomerular filtration barrier function in early diabetic kidney disease.

The endothelial glycocalyx is a key component of the glomerular filtration barrier. We have shown that matrix metalloproteinase (MMP)-mediated syndecan 4 shedding is a mechanism of glomerular endothelial glycocalyx damage in vitro, resulting in increased albumin permeability. Here we sought to determine whether this mechanism is important in early diabetic kidney disease, by studying streptozotocin-induced type 1 diabetes in DBA2/J mice. Diabetic mice were albuminuric, had increased glomerular albumin permeability and endothelial glycocalyx damage. Syndecan 4 mRNA expression was found to be upregulated in isolated glomeruli and in flow cytometry-sorted glomerular endothelial cells. In contrast, glomerular endothelial luminal surface syndecan 4 and Marasmium oreades agglutinin lectin labelling measurements were reduced in the diabetic mice. Similarly, syndecan 4 protein expression was significantly decreased in isolated glomeruli but increased in plasma and urine, suggesting syndecan 4 shedding. Mmp-2, 9 and 14 mRNA expression were upregulated in isolated glomeruli, suggesting a possible mechanism of glycocalyx damage and albuminuria. We therefore characterised in detail the activity of MMP-2 and 9 and found significant increases in kidney cortex, plasma and urine. Treatment with MMP-2/9 inhibitor I for 21 days, started six weeks after diabetes induction, restored endothelial glycocalyx depth and coverage and attenuated diabetes-induced albuminuria and reduced glomerular albumin permeability. MMP inhibitor treatment significantly attenuated glomerular endothelial and plasma syndecan 4 shedding and inhibited plasma MMP activity. Thus, our studies confirm the importance of MMPs in endothelial glycocalyx damage and albuminuria in early diabetes and demonstrate that this pathway is amenable to therapeutic intervention. Hence, treatments targeted at glycocalyx protection by MMP inhibition may be of benefit in diabetic kidney disease.

A coalescent-based estimator of genetic drift, and acoustic divergence in the Pteronotus parnellii species complex.

Determining the processes responsible for phenotypic variation is one of the central tasks of evolutionary biology. While the importance of acoustic traits for foraging and communication in echolocating mammals suggests adaptation, the seldom-tested null hypothesis to explain trait divergence is genetic drift. Here we derive FST values from multi-locus coalescent isolation-with-migration models, and couple them with estimates of quantitative trait divergence, or PST, to test drift as the evolutionary process responsible for phenotypic divergence in island populations of the Pteronotus parnellii species complex. Compared to traditional comparisons of PST to FST, the migration-based estimates of FST are unidirectional instead of bidirectional, simultaneously integrate variation among loci and individuals, and posterior densities of PST and FST can be compared directly. We found the evolution of higher call frequencies is inconsistent with genetic drift for the Hispaniolan population, despite many generations of isolation from its Puerto Rican counterpart. While the Hispaniolan population displays dimorphism in call frequencies, the higher frequency of the females is incompatible with sexual selection. Instead, cultural drift toward higher frequencies among Hispaniolan females might explain the divergence. By integrating Bayesian coalescent and trait analyses, this study demonstrates a powerful approach to testing genetic drift as the default evolutionary mechanism of trait differentiation between populations.

Safety and Immunogenicity of Zoster Vaccine Live in Human Immunodeficiency Virus-Infected Adults With CD4+ Cell Counts >200 Cells/mL Virologically Suppressed on Antiretroviral Therapy.

Background: Herpes zoster (HZ) risk is increased in human immunodeficiency virus (HIV)-infected persons. Live attenuated zoster vaccine (ZV) reduces HZ incidence and severity in adults; safety and immunogenicity data in HIV-infected adults are limited. Methods: We conducted a randomized, double-blind, placebo-controlled trial in HIV-infected adults virally suppressed on antiretroviral therapy (ART). Participants, stratified by CD4+ count (200-349 or ≥350 cells/µL), were randomized 3:1 to receive ZV or placebo on day 0 and week 6. The primary endpoint was serious adverse event or grade 3/4 signs/symptoms within 6 weeks after each dose. Immunogenicity (varicella zoster virus [VZV]-specific glycoprotein enzyme-linked immunosorbent assay and interferon-γ enzyme-linked immunospot assay responses) was assessed at 6 and 12 weeks postvaccination. Results: Of 395 participants (296 ZV vs 99 placebo), 84% were male, 47% white, 29% black, and 22% Hispanic; median age was 49 years. Safety endpoints occurred in 15 ZV and 2 placebo recipients (5.1% [95% confidence interval {CI}, 2.9%-8.2%] vs 2.1% [95% CI, .3%-7.3%]; P = .26). Injection site reactions occurred in 42% of ZV (95% CI, 36.3%-47.9%) vs 12.4% of placebo recipients (95% CI, 6.6%-20.6%) (P < .001). Week 12 median natural log VZV antibody titer was higher for ZV (6.30 [Q1, Q3, 5.64, 6.96]) vs placebo (5.48 [Q1, Q3, 4.63, 6.44]; P < .001) overall and in the high CD4+ stratum (P = .003). VZV antibody titers were similar after 1 or 2 ZV doses. Polymerase chain reaction-confirmed HZ occurred in 2 participants (1 ZV; 1 placebo); none was vaccine strain related. Conclusions: Two doses of ZV in HIV-infected adults suppressed on ART with CD4+ counts ≥200 cells/µL were safe and immunogenic. Clinical Trials Registration: NCT00851786.

Reversible cerebellar oedema secondary to profound hypomagnesaemia.

Magnesium is the second most abundant intracellular cation. Deficiency can cause several neurological complications, including cerebellar syndromes, with various MRI findings. These include cerebellar oedema, presumably through a similar mechanism to that in posterior reversible encephalopathy syndrome (PRES). People particularly vulnerable to deficiency include those with high alcohol consumption, excessive loss due to gastrointestinal pathology and those taking certain medications, including proton pump inhibitors. We report three patients with cerebellar syndromes associated with hypomagnesaemia. These cases support the previously reported association between hypomagnesaemia and reversible cerebellar dysfunction and illustrate the range of potential presentations. They highlight an uncommon but treatable cause of cerebellar ataxia that may present to acute neurological liaison services.

Lyme disease: diagnosis and management.

Lyme disease (borreliosis) is a tick-borne bacterial infection caused by the spirochaete Borrelia burgdoferi, transmitted by hard-backed Ixodes ticks. Actual numbers of cases are increasing and it appears that the distribution across the UK is widening; however, it occurs most frequently in area of woodland, with temperate climate. It typically presents in mid to late summer. Lyme disease is a multisystem disease. The nervous system is the second most commonly affected system after the skin. Other systemic manifestations, such as carditis, keratitis, uveitis and inflammatory arthritis, rarely occur in European Lyme disease. In 2018, the National Institute for Health and Care Excellence has updated its guidelines on the diagnosis and management of Lyme disease. Here, we highlight important aspects of this guidance and provide a more detailed review of the clinical spectrum of neuroborreliosis, illustrated by cases we have seen.

Duodenal Bacteria From Patients With Celiac Disease and Healthy Subjects Distinctly Affect Gluten Breakdown and Immunogenicity.

BACKGROUND & AIMS: Partially degraded gluten peptides from cereals trigger celiac disease (CD), an autoimmune enteropathy occurring in genetically susceptible persons. Susceptibility genes are necessary but not sufficient to induce CD, and additional environmental factors related to unfavorable alterations in the microbiota have been proposed. We investigated gluten metabolism by opportunistic pathogens and commensal duodenal bacteria and characterized the capacity of the produced peptides to activate gluten-specific T-cells from CD patients. METHODS: We colonized germ-free C57BL/6 mice with bacteria isolated from the small intestine of CD patients or healthy controls, selected for their in vitro gluten-degrading capacity. After gluten gavage, gliadin amount and proteolytic activities were measured in intestinal contents. Peptides produced by bacteria used in mouse colonizations from the immunogenic 33-mer gluten peptide were characterized by liquid chromatography tandem mass spectrometry and their immunogenic potential was evaluated using peripheral blood mononuclear cells from celiac patients after receiving a 3-day gluten challenge. RESULTS: Bacterial colonizations produced distinct gluten-degradation patterns in the mouse small intestine. Pseudomonas aeruginosa, an opportunistic pathogen from CD patients, exhibited elastase activity and produced peptides that better translocated the mouse intestinal barrier. P aeruginosa-modified gluten peptides activated gluten-specific T-cells from CD patients. In contrast, Lactobacillus spp. from the duodenum of non-CD controls degraded gluten peptides produced by human and P aeruginosa proteases, reducing their immunogenicity. CONCLUSIONS: Small intestinal bacteria exhibit distinct gluten metabolic patterns in vivo, increasing or reducing gluten peptide immunogenicity. This microbe-gluten-host interaction may modulate autoimmune risk in genetically susceptible persons and may underlie the reported association of dysbiosis and CD.

A Rare Case of Bilateral Optic Neuritis and Guillain-Barré Syndrome Post Mycoplasma pneumoniae Infection.

Neurological complications are the most commonly encountered extra-pulmonary manifestation of infection with Mycoplasma pneumoniae (M. pneumoniae). Here the authors report the case of a 39-year-old woman who was admitted with acute-onset bilateral visual loss coinciding with ascending numbness. Clinical examination, neurological imaging, and nerve conduction studies revealed a syndrome of bilateral optic neuritis and Guillain-Barré syndrome (GBS). Serological testing confirmed recent exposure to M. pneumoniae. The patient did not experience any clinical benefit with pulsed intravenous methylprednisolone but demonstrated marked clinical and radiological improvement following 5 days of plasma exchange. This report will explore the diagnostic and therapeutic approach to patients with neuro-ophthalmological and neurological complications of M. pneumoniae infection in addition to discussing previously encountered cases.

Measurement of adherence in a randomised controlled trial of a complex intervention: supported self-management for adults with learning disability and type 2 diabetes.

BACKGROUND: Reporting adherence to intervention delivery and uptake is a detailed way of describing what was actually delivered and received, in comparison to what was intended. Measuring and reporting adherence is not routinely done well in complex interventions. The OK Diabetes trial (ISRCTN41897033) aimed to develop and subsequently test the feasibility of implementing a supported self-management intervention in adults with a learning disability and type 2 diabetes. A key study objective was to develop a measure of adherence to the intervention. METHODS: We conducted a systematic review of published literature, extracting data from included papers using a standardised proforma. We undertook a narrative synthesis of papers to determine the form and content of methods for adherence measurement for self-management interventions in this population that had already been developed. We used the framework and data extraction form developed for the review as the basis for an adherence measurement tool that we applied in the OK Diabetes trial. RESULTS: The literature review found variability in the quality and content of adherence measurement and reporting, with no standardised approach. We were able to develop an adherence measure based upon the review, and populate it with data collected during the OK Diabetes trial. The adherence tool proved satisfactory for recording and measuring adherence in the trial. CONCLUSION: There remains a need for a standardised approach to adherence measurement in the field of complex interventions. We have shown that it is possible to produce a simple, feasible measure for assessing adherence in the OK Diabetes trial.

Vascular Endothelial Growth Factor-A165b Is Protective and Restores Endothelial Glycocalyx in Diabetic Nephropathy.

Diabetic nephropathy is the leading cause of ESRD in high-income countries and a growing problem across the world. Vascular endothelial growth factor-A (VEGF-A) is thought to be a critical mediator of vascular dysfunction in diabetic nephropathy, yet VEGF-A knockout and overexpression of angiogenic VEGF-A isoforms each worsen diabetic nephropathy. We examined the vasculoprotective effects of the VEGF-A isoform VEGF-A165b in diabetic nephropathy. Renal expression of VEGF-A165b mRNA was upregulated in diabetic individuals with well preserved kidney function, but not in those with progressive disease. Reproducing this VEGF-A165b upregulation in mouse podocytes in vivo prevented functional and histologic abnormalities in diabetic nephropathy. Biweekly systemic injections of recombinant human VEGF-A165b reduced features of diabetic nephropathy when initiated during early or advanced nephropathy in a model of type 1 diabetes and when initiated during early nephropathy in a model of type 2 diabetes. VEGF-A165b normalized glomerular permeability through phosphorylation of VEGF receptor 2 in glomerular endothelial cells, and reversed diabetes-induced damage to the glomerular endothelial glycocalyx. VEGF-A165b also improved the permeability function of isolated diabetic human glomeruli. These results show that VEGF-A165b acts via the endothelium to protect blood vessels and ameliorate diabetic nephropathy.