The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study

<p>Introduction: Children presenting for the first time with inflammatory bowel disease (IBD) offer a unique opportunity to study aetiological agents before the confounders of treatment. Microaerophilic bacteria can exploit the ecological niche of the intestinal epithelium; Helicobacter and Campylobacter are previously implicated in IBD pathogenesis. We set out to study these and other microaerophilic bacteria in de-novo paediatric IBD.</p> <p>Patients and Methods: 100 children undergoing colonoscopy were recruited including 44 treatment naïve de-novo IBD patients and 42 with normal colons. Colonic biopsies were subjected to microaerophilic culture with Gram-negative isolates then identified by sequencing. Biopsies were also PCR screened for the specific microaerophilic bacterial groups: Helicobacteraceae, Campylobacteraceae and Sutterella wadsworthensis.</p> <p>Results: 129 Gram-negative microaerophilic bacterial isolates were identified from 10 genera. The most frequently cultured was S. wadsworthensis (32 distinct isolates). Unusual Campylobacter were isolated from 8 subjects (including 3 C. concisus, 1 C. curvus, 1 C. lari, 1 C. rectus, 3 C. showae). No Helicobacter were cultured. When comparing IBD vs. normal colon control by PCR the prevalence figures were not significantly different (Helicobacter 11% vs. 12%, p = 1.00; Campylobacter 75% vs. 76%, p = 1.00; S. wadsworthensis 82% vs. 71%, p = 0.312).</p> <p>Conclusions: This study offers a comprehensive overview of the microaerophilic microbiota of the paediatric colon including at IBD onset. Campylobacter appear to be surprisingly common, are not more strongly associated with IBD and can be isolated from around 8% of paediatric colonic biopsies. S. wadsworthensis appears to be a common commensal. Helicobacter species are relatively rare in the paediatric colon.</p&gt

A randomised controlled trial and cost-effectiveness evaluation of "booster" interventions to sustain increases in physical activity in middle-aged adults in deprived urban neighbourhoods

Background: Systematic reviews have identified a range of brief interventions which increase physical activity in previously sedentary people. There is an absence of evidence about whether follow up beyond three months can maintain long term physical activity. This study assesses whether it is worth providing motivational interviews, three months after giving initial advice, to those who have become more active. Methods/Design: Study candidates (n = 1500) will initially be given an interactive DVD and receive two telephone follow ups at monthly intervals checking on receipt and use of the DVD. Only those that have increased their physical activity after three months (n = 600) will be randomised into the study. These participants will receive either a "mini booster" (n = 200), "full booster" (n = 200) or no booster (n = 200). The "mini booster" consists of two telephone calls one month apart to discuss physical activity and maintenance strategies. The "full booster" consists of a face-to-face meeting with the facilitator at the same intervals. The purpose of these booster sessions is to help the individual maintain their increase in physical activity. Differences in physical activity, quality of life and costs associated with the booster interventions, will be measured three and nine months from randomisation. The research will be conducted in 20 of the most deprived neighbourhoods in Sheffield, which have large, ethnically diverse populations, high levels of economic deprivation, low levels of physical activity, poorer health and shorter life expectancy. Participants will be recruited through general practices and community groups, as well as by postal invitation, to ensure the participation of minority ethnic groups and those with lower levels of literacy. Sheffield City Council and Primary Care Trust fund a range of facilities and activities to promote physical activity and variations in access to these between neighbourhoods will make it possible to examine whether the effectiveness of the intervention is modified by access to community facilities. A one-year integrated feasibility study will confirm that recruitment targets are achievable based on a 10% sample.Discussion: The choice of study population, study interventions, brief intervention preceding the study, and outcome measure are discussed

Context Dependent Neuroprotective Properties of Prion Protein (Prp)

Although it has been known for more than twenty years that an aberrant conformation of the prion protein (PrP) is the causative agent in prion diseases, the role of PrP in normal biology is undetermined. Numerous studies have suggested a protective function for PrP, including protection from ischemic and excitotoxic lesions and several apoptotic insults. On the other hand, many observations have suggested the contrary, linking changes in PrP localization or domain structure—independent of infectious prion conformation—to severe neuronal damage. Surprisingly, a recent report suggests that PrP is a receptor for toxic oligomeric species of a-β, a pathogenic fragment of the amyloid precursor protein, and likely contributes to disease pathogenesis of Alzheimer’s disease. We sought to access the role of PrP in diverse neurological disorders. First, we confirmed that PrP confers protection against ischemic damage using an acute stroke model, a well characterized association. After ischemic insult, PrP knockouts had dramatically increased infarct volumes and decreased behavioral performance compared to controls. To examine the potential of PrP’s neuroprotective or neurotoxic properties in the context of other pathologies, we deleted PrP from several transgenic models of neurodegenerative disease. Deletion of PrP did not substantially alter the disease phenotypes of mouse models of Parkinson’s disease or tauopathy. Deletion of PrP in one of two Huntington’s disease models tested, R6/2, modestly slowed motor deterioration as measured on an accelerating rotarod but otherwise did not alter other major features of the disease. Finally, transgenic overexpression of PrP did not exacerbate the Huntington’s motor phenotype. These results suggest that PrP has a context-dependent neuroprotective function and does not broadly contribute to the disease models tested herein.Ellison Medical FoundationWhitaker Health Sciences Fund Fellowshi

A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia

<p>Abstract</p> <p>Background</p> <p>Antipsychotic medications often have a variety of side effects, however, it is not well understood how the presence of specific side effects correlate with adherence in a real-world setting. The aim of the current study was to examine the relationship between these variables among community-dwelling patients with schizophrenia.</p> <p>Methods</p> <p>Data were analyzed from a 2007-2008 nationwide survey of adults who self-reported a diagnosis of schizophrenia and were currently using an antipsychotic medication (N = 876). The presence of side effects was defined as those in which the patient reported they were at least "somewhat bothered". Adherence was defined as a score of zero on the Morisky Medication Adherence Scale. To assess the relationship between side effects and adherence, individual logistic regression models were fitted for each side effect controlling for patient characteristics. A single logistic regression model assessed the relationship between side effect clusters and adherence. The relationships between adherence and health resource use were also examined.</p> <p>Results</p> <p>A majority of patients reported experiencing at least one side effect due to their medication (86.19%). Only 42.5% reported complete adherence. Most side effects were associated with a significantly reduced likelihood of adherence. When grouped as side effect clusters in a single model, extra pyramidal symptoms (EPS)/agitation (odds ratio (OR) = 0.57, p = 0.0007), sedation/cognition (OR = 0.70, p = 0.033), prolactin/endocrine (OR = 0.69, p = 0.0342), and metabolic side effects (OR = 0.64, p = 0.0079) were all significantly related with lower rates of adherence. Those who reported complete adherence to their medication were significantly less likely to report a hospitalization for a mental health reason (OR = 0.51, p = 0.0006), a hospitalization for a non-mental health reason (OR = 0.43, p = 0.0002), and an emergency room (ER) visit for a mental health reason (OR = 0.60, p = 0.008).</p> <p>Conclusions</p> <p>Among patients with schizophrenia, medication side effects are highly prevalent and significantly associated with medication nonadherence. Nonadherence is significantly associated with increased healthcare resource use. Prevention, identification, and effective management of medication-induced side effects are important to maximize adherence and reduce health resource use in schizophrenia.</p

A new microdeletion syndrome involving TBC1D24, ATP6V0C, and PDPK1 causes epilepsy, microcephaly, and developmental delay

PURPOSE: Contiguous gene deletions are known to cause several neurodevelopmental syndromes, many of which are caused by recurrent events on chromosome 16. However, chromosomal microarray studies (CMA) still yield copy-number variants (CNVs) of unknown clinical significance. We sought to characterize eight individuals with overlapping 205-kb to 504-kb 16p13.3 microdeletions that are distinct from previously published deletion syndromes. METHODS: Clinical information on the patients and bioinformatic scores for the deleted genes were analyzed. RESULTS: All individuals in our cohort displayed developmental delay, intellectual disability, and various forms of seizures. Six individuals were microcephalic and two had strabismus. The deletion was absent in all 13 parents who were available for testing. The area of overlap encompasses seven genes including TBC1D24, ATP6V0C, and PDPK1 (also known as PDK1). Bi-allelic TBC1D24 pathogenic variants are known to cause nonsyndromic deafness, epileptic disorders, or DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, seizures). Sanger sequencing of the nondeleted TBC1D24 allele did not yield any additional pathogenic variants. CONCLUSIONS: We propose that 16p13.3 microdeletions resulting in simultaneous haploinsufficiencies of TBC1D24, ATP6V0C, and PDPK1 cause a novel rare contiguous gene deletion syndrome of microcephaly, developmental delay, intellectual disability, and epilepsy

The assessment of depression in people with multiple sclerosis : a systematic review of psychometric validation studies

Background: The prevalence of depression in people with multiple sclerosis (PwMS) is high; however, symptoms common to both conditions makes measurement difficult. There is no high quality overview of validation studies to guide the choice of depression inventory for this population. Methods: A systematic review of studies validating the use of generic depression inventories in people with MS was conducted using MEDLINE and PsycINFO. Studies validating the use of depression inventories in PwMS and published in English were included; validation studies of tests for cognitive function and general mental health were excluded. Eligible studies were then quality assessed using the COSMIN checklist and findings synthesised narratively by instrument and validity domain. Results: Twenty-one studies (N=5,991 PwMS) evaluating 12 instruments were included in the review. Risk of bias varied greatly between instrument and validity domain. Conclusions: The review of validation studies was constrained by poor quality reporting and outcome reporting bias. Well-conducted evaluations of some instruments are unavailable for some validity domains. This systematic review provides an evidence base for trade-offs in the selection of an instrument for assessing self-reported symptoms of depression in research or clinical practice involving people with MS. We make detailed and specific recommendations for where further research is needed. Registration: PROSPERO CRD42014010597 Keywords Depression; Multiple Sclerosis; Reproducibility of Results; Psychometrics; Chronic Diseas

The effects of implementing a point-of-care electronic template to prompt routine anxiety and depression screening in patients consulting for osteoarthritis (the Primary Care Osteoarthritis Trial): A cluster randomised trial in primary care

Background This study aimed to evaluate whether prompting general practitioners (GPs) to routinely assess and manage anxiety and depression in patients consulting with osteoarthritis (OA) improves pain outcomes. Methods and findings We conducted a cluster randomised controlled trial involving 45 English general practices. In intervention practices, patients aged ≥45 y consulting with OA received point-of-care anxiety and depression screening by the GP, prompted by an automated electronic template comprising five questions (a two-item Patient Health Questionnaire–2 for depression, a two-item Generalized Anxiety Disorder–2 questionnaire for anxiety, and a question about current pain intensity [0–10 numerical rating scale]). The template signposted GPs to follow National Institute for Health and Care Excellence clinical guidelines for anxiety, depression, and OA and was supported by a brief training package. The template in control practices prompted GPs to ask the pain intensity question only. The primary outcome was patient-reported current pain intensity post-consultation and at 3-, 6-, and 12-mo follow-up. Secondary outcomes included pain-related disability, anxiety, depression, and general health. During the trial period, 7,279 patients aged ≥45 y consulted with a relevant OA-related code, and 4,240 patients were deemed potentially eligible by participating GPs. Templates were completed for 2,042 patients (1,339 [31.6%] in the control arm and 703 [23.1%] in the intervention arm). Of these 2,042 patients, 1,412 returned questionnaires (501 [71.3%] from 20 intervention practices, 911 [68.0%] from 24 control practices). Follow-up rates were similar in both arms, totalling 1,093 (77.4%) at 3 mo, 1,064 (75.4%) at 6 mo, and 1,017 (72.0%) at 12 mo. For the primary endpoint, multilevel modelling yielded significantly higher average pain intensity across follow-up to 12 mo in the intervention group than the control group (adjusted mean difference 0.31; 95% CI 0.04, 0.59). Secondary outcomes were consistent with the primary outcome measure in reflecting better outcomes as a whole for the control group than the intervention group. Anxiety and depression scores did not reduce following the intervention. The main limitations of this study are two potential sources of bias: an imbalance in cluster size (mean practice size 7,397 [intervention] versus 5,850 [control]) and a difference in the proportion of patients for whom the GP deactivated the template (33.6% [intervention] versus 27.8% [control]). Conclusions In this study, we observed no beneficial effect on pain outcomes of prompting GPs to routinely screen for and manage comorbid anxiety and depression in patients presenting with symptoms due to OA, with those in the intervention group reporting statistically significantly higher average pain scores over the four follow-up time points than those in the control group. Trial registration ISRCTN registry ISRCTN4072198

Transitional events in the spectrophotometric regime between stripped envelope and superluminous supernovae

The division between stripped-envelope supernovae (SE-SNe) and superluminous supernovae (SLSNe) is not well-defined in either photometric or spectroscopic space. While a sharp luminosity threshold has been suggested, there remains an increasing number of transitional objects that reach this threshold without the spectroscopic signatures common to SLSNe. In this work, we present data and analysis on four SNe transitional between SE-SNe and SLSNe; the He-poor SNe 2019dwa and 2019cri, and the He-rich SNe 2019hge and 2019unb. Each object displays long-lived and variable photometric evolution with luminosities around the SLSN threshold of M-r < -19.8 mag. Spectroscopically however, these objects are similar to SE-SNe, with line velocities lower than either SE-SNe and SLSNe, and thus represent an interesting case of rare transitional events

Inequalities in health: a comparative study between ethnic Norwegians and Pakistanis in Oslo, Norway

BACKGROUND: The objective of the study was to observe the inequality in health from the perspective of socio-economic factors in relation to ethnic Pakistanis and ethnic Norwegians in Oslo, Norway. METHOD: Data was collected by using an open and structured questionnaire, as a part of the Oslo Health Study 2000–2001. Accordingly 13581 ethnic Norwegians (45% of the eligible) participated as against 339 ethnic Pakistanis (38% of the eligible). RESULTS: The ethnic Pakistanis reported a higher prevalence of poor self-rated health 54.7% as opposed to 22.1% (p < 0.001) in ethnic Norwegians, 14% vs. 2.6% (p < 0.001) in diabetes, and 22.0% vs. 9.9% (p < 0.001) in psychological distress. The socio-economic conditions were inversely related to self- rated health, diabetes and distress for the ethnic Norwegians. However, this was surprisingly not the case for the ethnic Pakistanis. Odd ratios did not interfere with the occurrence of diabetes, even after adjusting all the markers of socio-economic status in the multivariate model, while self-reported health and distress showed moderate reduction in the risk estimation. CONCLUSION: There is a large diversity of self-rated health, prevalence of diabetes and distress among the ethnic Pakistanis and Norwegians. Socio-economic status may partly explain the observed inequalities in health. Uncontrolled variables like genetics, lifestyle factors and psychosocial factors related to migration such as social support, community participation, discrimination, and integration may have contributed to the observed phenomenon. This may underline the importance of a multidisciplinary approach in future studies