Laxative use in adults with intellectual disabilities: development of prescribing guidelines.

BACKGROUND: Constipation is overrepresented in people with intellectual disabilities. Around 40% of people with intellectual disabilities who died prematurely were prescribed laxatives. A quarter of people with intellectual disabilities are said to be on laxatives. There are concerns that prescribing is not always effective and appropriate. There are currently no prescribing guidelines specific to this population. AIMS: To develop guidelines to support clinicians with their decision-making when prescribing laxatives to people with intellectual disabilities. METHOD: A modified Delphi methodology, the RAND/UCLA Appropriateness Method, was used. Step 1 comprised development of a bespoke six-item, open-ended questionnaire from background literature and its external validation. Relevant stakeholders, including a range of clinical experts and experts by experience covering the full range of intellectual disability and constipation, were invited to participate in an expert panel. Panel members completed the questionnaire. Responses were divided into 'negative consensus' and 'positive consensus'. Members were then invited to two panel meetings, 2 weeks apart, held virtually over Microsoft Teams, to build consensus. The expert-by-experience group were included in a separate face-to-face meeting. RESULTS: A total of 20 people (ten professional experts and ten experts by experience, of whom seven had intellectual disability) took part. There were five main areas of discussion to reach a consensus i.e. importance of diagnosis, the role of prescribing, practicalities of medication administration, importance of reviewing and monitoring, and communication. CONCLUSIONS: Laxative prescribing guidelines were developed by synthesising the knowledge of an expert panel including people with intellectual disabilities with the existing evidence base, to improve patient care.

Chronic constipation in people with intellectual disabilities in the community: cross-sectional study.

BACKGROUND: One-third to half of people with intellectual disabilities suffer from chronic constipation (defined as two or fewer bowel movements weekly or taking regular laxatives three or more times weekly), a cause of significant morbidity and premature mortality. Research on risk factors associated with constipation is limited. AIMS: To enumerate risk factors associated with constipation in this population. METHOD: A questionnaire was developed on possible risk factors for constipation. The questionnaire was sent to carers of people with intellectual disabilities on the case-loads of four specialist intellectual disability services in England. Data analysis focused on descriptively summarising responses and comparing those reported with and without constipation. RESULTS: Of the 181 people with intellectual disabilities whose carers returned the questionnaire, 42% reported chronic constipation. Constipation was significantly associated with more severe intellectual disability, dysphagia, cerebral palsy, poor mobility, polypharmacy including antipsychotics and antiseizure medication, and the need for greater toileting support. There were no associations with age or gender. CONCLUSIONS: People with intellectual disabilities may be more vulnerable to chronic constipation if they are more severely intellectually disabled. The associations of constipation with dysphagia, cerebral palsy, poor mobility and the need for greater toileting support suggests people with intellectual disabilities with significant physical disabilities are more at risk. People with the above disabilities need closer monitoring of their bowel health. Reducing medication to the minimum necessary may reduce the risk of constipation and is a modifiable risk factor that it is important to monitor. By screening patients using the constipation questionnaire, individualised bowel care plans could be implemented.

Characteristics of natural environment use by occupational therapists working in mental health: a scoping review protocol.

OBJECTIVE: The objective of this review is to identify and characterize the use of the natural environment/outdoor space by occupational therapists working in mental health care. INTRODUCTION: Research has shown that the natural environment is beneficial for our health and can be used to help people who are experiencing mental health problems. Occupational therapists are well placed to assess and utilize the environment when treating people with mental health problems; however, the use of the natural environment/outdoor space by occupational therapists working in mental health is unclear. INCLUSION CRITERIA: This scoping review will include both primary research and gray literature relating to the use of the natural environment/outdoor space in mental health occupational therapy practice. The review will be limited to studies published in English. There will be no geographical or age restrictions. METHODS: Embase (Ovid), MEDLINE (Ovid), CINAHL (EBSCO), PsycINFO (ProQuest), AMED (EBSCO), Trip Database, Emcare (Ovid), and OTSeeker will be searched for studies. Unpublished studies and gray literature will be searched using GreyNet and National Grey Literature Collection, alongside professional magazines and websites. Titles and abstracts will be screened by 2 independent reviewers for assessment against the inclusion criteria, followed by a full-text review and data extraction. Any disagreements will be discussed with a third reviewer. Data will be extracted using a data extraction tool developed by the reviewers, and presented in tabular format, accompanied by a narrative summary describing how the results relate to the review objective and question.

Sandwiches, 6 Feet Apart: Reflections on Community (and Medical School) During COVID-19.

During the COVID-19 pandemic, medical students were removed from clinical clerkships. During this time of uncertainty, 4 clinical medical students at the University of Michigan returned to the community to support their neighbors experiencing homelessness. They did so by making brown bag lunches for people sleeping on the streets and acting as community volunteers in temporary shelters. Though formal education was stalled, they reconnected with the initial desire that led them to pursue medical education in the first place and developed key skills in communication, relating to others, and compassion that they believe will enable them to become better physicians in the future.

Staying on the Right Side of the Regulatory Authorities.

This article provides reviews of the following: principal regulatory frameworks governing the supply of feed products for horses, focusing on the United States and Europe with guidance on compliance; key federal, state, or country requirements to ensure safe and accurately labeled products; rules concerning antidoping with a review of naturally occurring prohibited substances commonly found in feedstuffs; essential information for brand holders of equine nutrition products, practicing veterinarians, independent nutritionists, research scientists, competition riders and racehorse trainers, and those responsible for the direct feeding of horses.

How I Do It: Pilot Study of Video-Based Feedback as an Educational Tool for Medical Students' Presentations on Morning Rounds.

OBJECTIVE: Morning rounds are a bedrock learning opportunity during clinical rotations in medical school. Specific feedback is critical for students to improve presentation skills and build confidence, however, current feedback mechanisms are fragmented and nonstandard. We aimed to assess whether video-based coaching of morning rounds could improve student feedback and self-awareness without increasing anxiety during patient presentations. DESIGN: Medical students during core clinical clerkships were filmed presenting on morning rounds during their surgery clerkship. A designated faculty coach reviewed the video prior to an in-person coaching session. Students reviewed the video with faculty and were coached on content, presentation style, and presence. A short survey assessed students' pre- and postcoaching confidence, skill, and the utility of the coaching session. SETTING: University of Michigan Health System, Department of Surgery, Division of General Surgery, Ann Arbor, Michigan PARTICIPANTS: Eight medical student volunteers during their core clinical clerkships at University of Michigan Medical School during the surgery clerkship. RESULTS: Comparison of pre- and post self-assessments showed that students underestimated their knowledge of basic and clinical science and overestimated their clinical assessment skills and ability to appropriately address the core components of a presentation. Most students (75%) did not think that the filming process altered their performance and only 25% of students felt increased anxiety due to filming. All students agreed that the feedback session was useful and helped them understand how to improve their oral presentations. CONCLUSION: This pilot demonstrates the feasibility and value of video-based coaching as an educational tool for medical students on clerkships. A larger sample size is needed to further evaluate the effectiveness of video-based coaching in establishing baseline clinical abilities and identifying potential areas for improvement.

The Impact of Rotavirus Vaccines on Genotype Diversity: A Comprehensive Analysis of 2 Decades of Australian Surveillance Data.

Background: Introduction of rotavirus vaccines into national immunization programs (NIPs) could result in strain selection due to vaccine-induced selective pressure. This study describes the distribution and diversity of rotavirus genotypes before and after rotavirus vaccine introduction into the Australian NIP. State-based vaccine selection facilitated a unique comparison of diversity in RotaTeq and Rotarix vaccine states. Methods: From 1995 to 2015, the Australian Rotavirus Surveillance Program conducted genotypic analysis on 13051 rotavirus-positive samples from children <5 years of age, hospitalized with acute gastroenteritis. Rotavirus G and P genotypes were determined using serological and heminested multiplex reverse-transcription polymerase chain reaction assays. Results: G1P[8] was the dominant genotype nationally in the prevaccine era (1995-2006). Following vaccine introduction (2007-2015), greater genotype diversity was observed with fluctuating genotype dominance. Genotype distribution varied based on the vaccine implemented, with G12P[8] dominant in states using RotaTeq, and equine-like G3P[8] and G2P[4] dominant in states and territories using Rotarix. Conclusions: The increased diversity and differences in genotype dominance observed in states using RotaTeq (G12P[8]), and in states and territories using Rotarix (equine-like G3P[8] and G2P[4]), suggest that these vaccines exert different immunological pressures that influence the diversity of rotavirus strains circulating in Australia.

Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth.

BACKGROUND: A strategy of administering a neonatal rotavirus vaccine at birth to target early prevention of rotavirus gastroenteritis may address some of the barriers to global implementation of a rotavirus vaccine. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) in preventing rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB, administered according to a neonatal schedule (0 to 5 days, 8 weeks, and 14 weeks of age) or an infant schedule (8 weeks, 14 weeks, and 18 weeks of age), or placebo. The primary analysis was conducted in the per-protocol population, which included only participants who received all four doses of vaccine or placebo within the visit windows, with secondary analyses performed in the intention-to-treat population, which included all participants who underwent randomization. RESULTS: Among the 1513 participants in the per-protocol population, severe rotavirus gastroenteritis occurred up to the age of 18 months in 5.6% of the participants in the placebo group (28 of 504 babies), in 1.4% in the neonatal-schedule vaccine group (7 of 498), and in 2.7% in the infant-schedule vaccine group (14 of 511). This resulted in a vaccine efficacy of 75% (95% confidence interval [CI], 44 to 91) in the neonatal-schedule group (P<0.001), 51% (95% CI, 7 to 76) in the infant-schedule group (P=0.03), and 63% (95% CI, 34 to 80) in the neonatal-schedule and infant-schedule groups combined (combined vaccine group) (P<0.001). Similar results were observed in the intention-to-treat analysis (1649 participants); the vaccine efficacy was 68% (95% CI, 35 to 86) in the neonatal-schedule group (P=0.001), 52% (95% CI, 11 to 76) in the infant-schedule group (P=0.02), and 60% (95% CI, 31 to 76) in the combined vaccine group (P<0.001). Vaccine response, as evidenced by serum immune response or shedding of RV3-BB in the stool, occurred in 78 of 83 participants (94%) in the neonatal-schedule group and in 83 of 84 participants (99%) in the infant-schedule group. The incidence of adverse events was similar across the groups. No episodes of intussusception occurred within the 21-day risk period after administration of any dose of vaccine or placebo, and one episode of intussusception occurred 114 days after the third dose of vaccine in the infant-schedule group. CONCLUSIONS: RV3-BB was efficacious in preventing severe rotavirus gastroenteritis when administered according to a neonatal or an infant schedule in Indonesia. (Funded by the Bill and Melinda Gates Foundation and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612001282875 .).

Metabolomic and Gene Expression Profiles Exhibit Modular Genetic and Dietary Structure Linking Metabolic Syndrome Phenotypes in Drosophila.

Genetic and environmental factors influence complex disease in humans, such as metabolic syndrome, and Drosophila melanogaster serves as an excellent model in which to test these factors experimentally. Here we explore the modularity of endophenotypes with an in-depth reanalysis of a previous study by Reed et al. (2014), where we raised 20 wild-type genetic lines of Drosophila larvae on four diets and measured gross phenotypes of body weight, total sugar, and total triglycerides, as well as the endophenotypes of metabolomic and whole-genome expression profiles. We then perform new gene expression experiments to test for conservation of phenotype-expression correlations across different diets and populations. We find that transcript levels correlated with gross phenotypes were enriched for puparial adhesion, metamorphosis, and central energy metabolism functions. The specific metabolites L-DOPA and N-arachidonoyl dopamine make physiological links between the gross phenotypes across diets, whereas leucine and isoleucine thus exhibit genotype-by-diet interactions. Between diets, we find low conservation of the endophenotypes that correlate with the gross phenotypes. Through the follow-up expression study, we found that transcript-trait correlations are well conserved across populations raised on a familiar diet, but on a novel diet, the transcript-trait correlations are no longer conserved. Thus, physiological canalization of metabolic phenotypes breaks down in a novel environment exposing cryptic variation. We cannot predict the physiological basis of disease in a perturbing environment from profiles observed in the ancestral environment. This study demonstrates that variation for disease traits within a population is acquired through a multitude of physiological mechanisms, some of which transcend genetic and environmental influences, and others that are specific to an individual's genetic and environmental context.

Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered at birth or in infancy: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Despite the success of rotavirus vaccines, suboptimal vaccine efficacy in regions with a high burden of disease continues to present a challenge to worldwide implementation. A birth dose strategy with a vaccine developed from an asymptomatic neonatal rotavirus strain has the potential to address this challenge and provide protection from severe rotavirus disease from birth. METHODS: This phase 2a randomised, double-blind, three-arm, placebo-controlled safety and immunogenicity trial was undertaken at a single centre in New Zealand between Jan 13, 2012, and April 17, 2014. Healthy, full-term (≥36 weeks gestation) babies, who weighed at least 2500 g, and were 0-5 days old at the time of randomisation were randomly assigned (1:1:1; computer-generated; telephone central allocation) according to a concealed block randomisation schedule to oral RV3-BB vaccine with the first dose given at 0-5 days after birth (neonatal schedule), to vaccine with the first dose given at about 8 weeks after birth (infant schedule), or to placebo. The primary endpoint was cumulative vaccine take (serum immune response or stool shedding of vaccine virus after any dose) after three doses. The immunogenicity analysis included all randomised participants with available outcome data. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611001212943. FINDINGS: 95 eligible participants were randomised, of whom 89 were included in the primary analysis. A cumulative vaccine take was detected in 27 (90%) of 30 participants in the neonatal schedule group after three doses of RV3-BB vaccine compared with four (13%) of 32 participants in the placebo group (difference in proportions 0·78, 95% CI 0·55-0·88; p<0·0001). 25 (93%) of 27 participants in the infant schedule group had a cumulative vaccine take after three doses compared with eight (25%) of 32 participants in the placebo group (difference in proportions 0·68, 0·44-0·81; p<0·0001). A serum IgA response was detected in 19 (63%) of 30 participants and 20 (74%) of 27 participants, and stool shedding of RV3-BB was detected in 21 (70%) of 30 participants and 21 (78%) of 27 participants in the neonatal and infant schedule groups, respectively. The frequency of solicited and unsolicited adverse events was similar across the treatment groups. RV3-BB vaccine was not associated with an increased frequency of fever or gastrointestinal symptoms compared with placebo. INTERPRETATION: RV3-BB vaccine was immunogenic and well tolerated when given as a three-dose neonatal or infant schedule. A birth dose strategy of RV3-BB vaccine has the potential to improve the effectiveness and implementation of rotavirus vaccines. FUNDING: Australian National Health and Medical Research Council, the New Zealand Health Research Council, and the Murdoch Childrens Research Institute.

Australian Rotavirus Surveillance Program annual report, 2012.

This report from the Australian Rotavirus Surveillance Program, together with collaborating laboratories Australia-wide, describes the rotavirus genotypes responsible for the hospitalisation of children with acute gastroenteritis during the period 1 January to 31 December 2012. During the survey period, 1,300 faecal samples were referred to the centre for rotavirus G and P genotype analysis, and of these 748 were confirmed as rotavirus positive. A total of 491 specimens were collected from children under 5 years of age, while 257 were from older children and adults. Genotype analysis revealed that G1P[8] was the dominant type in this reporting period, identified in 35% of strains nationally. Genotype G2P[4] was the second most common strain nationally, representing 28% of samples, followed by genotype G12P[8] (23%). This represents the first report where G12P[8] strains are a major cause of disease in this community. Fluctuations in genotype distribution were also observed based on the vaccine type in use. Genotype G2P[4] was more common in states and territories using Rotarix while G1P[8] was more common in states using RotaTeq. This survey of rotavirus strains circulating in 2012 highlights the continued fluctuations in rotavirus genotypes, with an annual change in dominant genotypes as well as emergence of a previously rare genotype, suggesting a dynamic wild-type population.

Bacteriophages in gut samples from pediatric Crohn's disease patients: metagenomic analysis using 454 pyrosequencing.

BACKGROUND: The role of bacteriophage in Crohn's disease (CD) is unknown. This study investigated the abundance of phages in ileal and colonic samples from pediatric CD patients and controls. METHODS: Ileal and colonic biopsies from 6 CD patients, gut wash samples from 3 CD patients, and ileal biopsies from 6 noninflammatory bowel disease patients (controls) were analyzed for the presence of bacteriophage using 454 high-throughput pyrosequencing. A sequence-independent single-primer amplification method was used to amplify viral sequences. RESULTS: A total of 186,143 high quality reads were obtained from the 4 sample populations. Contigs and sequence clusters (generated from unassembled singletons) were aligned with sequences from the National Center for Biotechnology Information viral reference database and analyzed by MEGAN. The largest number of viral hits was obtained from the CD gut wash samples (n = 691), followed by CD ileal samples (n = 52), control ileum samples (n = 20), and CD colonic samples (n = 1). The most abundant virus sequences identified belonged to the Caudovirales phage. CONCLUSIONS: Our study characterized a diverse phage community in the gut of CD patients. In this study, we have identified differences in phage composition between CD patients and control individuals. The large abundance of phages in CD ileum tissue and CD gut wash sample suggests a role of phage in CD development. The role of phage dysbiosis in CD is currently unknown but opens up a new area of research.

Identification of strains of RotaTeq rotavirus vaccine in infants with gastroenteritis following routine vaccination.

BACKGROUND: RotaTeq vaccine was introduced into the Australian National Immunisation Program in 2007. This study identified and characterised rotavirus strains excreted by infants who presented with symptoms of gastroenteritis following recent RotaTeq vaccination. METHODS: Fecal samples (N = 61) from children who developed gastroenteritis following recent RotaTeq vaccination were forwarded to the Australian Rotavirus Surveillance Program (ARSP). RotaTeq-positive samples were genotyped and regions of the VP3, VP4, VP6, and VP7 genes were sequenced. Also, 460 rotavirus-positive ARSP routine surveillance samples were analyzed by dot-blot Northern hybridization to detect RotaTeq vaccine-derived strains circulating in the community. RESULTS: Thirteen of the 61 samples collected from infants developing gastroenteritis after RotaTeq vaccination contained vaccine-derived (vd) rotavirus strains. Of these, 4 contained a vdG1P[8] strain derived by reassortment between the G1P[5] and G6P[8] parental vaccine strains. Northern hybridization analysis of 460 surveillance samples identified 3 samples that contained RotaTeq vaccine-derived strains, including 2 vdG1P[8] reassortant vaccine strains. CONCLUSIONS: During replication and excretion of RotaTeq vaccine, reassortment of parental strains can occur. Shedding of RotaTeq vaccine strains in 7 of 13 infants was associated with underlying medical conditions that may have altered their immune function. The benefits of vaccination outweigh any small risk of vaccine-associated gastroenteritis.

Disrupted stimulus control but not reward sensitivity in individuals with autism spectrum disorders: a matching law analysis.

The matching law suggests that behavior is emitted in proportion to the level of reinforcement available. The current study investigated this effect in individuals with autism spectrum disorders (ASD), and focused on the effects of magnitude of reinforcement (Study 1), and rate of reinforcement (Studies 2 and 3), on matching performance. Studies 1 and 2 employed lower functioning children with ASD, and demonstrated matching in both groups, but that the group with ASD displayed greater levels of stimulus bias. Study 3 employed higher functioning children with ASD, and found little evidence of matching, but higher stimulus bias in the group with ASD. These effects suggest a disruption of stimulus control, but not reward sensitivity, in individuals with ASD.

Expression profile of genes involved in pathogenesis of pediatric Crohn's disease.

BACKGROUND AND AIM: Expression profiling of genes specific to pediatric Crohn's Disease (CD) patients was performed to elucidate the molecular mechanisms underlying disease cause and pathogenesis at disease onset. METHODS: We used suppressive subtractive hybridization (SSH) and differential screening analysis to profile the mRNA expression patterns of children with CD and age- and sex-matched controls without inflammatory bowel disease (IBD). RESULTS: Sequence analysis of 1000 clones enriched by SSH identified 75 functionally annotated human genes, represented by 430 clones. The 75 genes have potential involvement in gene networks, such as antigen presentation, inflammation, infection mechanism, connective tissue development, cell cycle and cancer. Twenty-eight genes were previously described in association with CD, while 47 were new genes not previously reported in the context of IBD. Additionally, 29 of the 75 genes have been previously implicated in bacterial and viral infections. Quantitative real-time reverse transcription polymerase chain reaction performed on ileal-derived RNA from 13 CD and nine non-IBD patients confirmed the upregulation of extracellular matrix gene MMP2 (P = 0.001), and cell proliferation gene REG1A (P = 0.063) in our pediatric CD cohort. CONCLUSION: The retrieval of 28 genes previously reported in association with adult CD emphasizes the importance of these genes in the pediatric setting. The observed upregulation of REG1A and MMP2, and their known impact on cell proliferation and extracellular matrix remodeling, agrees with the clinical behavior of the disease. Moreover, the expressions of bacterial- and virus-related genes in our CD-patient tissues support the concept that microbial agents are important in the etiopathogenesis of CD.

Identification of an antibody-binding epitope on the rotavirus A non-structural protein NSP2 using phage display analysis.

The non-structural protein 2 (NSP2) of rotavirus has important roles in rotavirus replication associated with RNA binding, hydrolysis of NTPs and RNA, and helix destabilizing properties. A cell-culture assay using an NSP2-specific mAb and polyclonal antiserum to block virus replication showed a 73 and 96 % reduction in the amount of virus produced during replication, respectively. Phage display technology was used to identify the antibody-binding region on the NSP2 protein with the motif (244)T-(Y/F)-Ø-Ø-Ø-X-K-Ø-G(252), where Ø is a hydrophilic residue and X is any amino acid. This region was mapped to the three-dimensional NSP2 crystal structure to visualize the epitope. Analysis revealed identity to a region on NSP2 that mapped to a site exposed on the surface of the protein, which could possibly interfere with a functionally important region of the protein. Antibody binding to this region could disrupt the essential roles of NSP2, such as the formation of viroplasms with NSP5 or the interaction with viral RNA, thereby indicating a possible mechanism for the observed inhibition of virus replication. Genetic analysis of the putative binding region of NSP2 revealed a high level of conservation, suggesting that the region is under strict control.

Distribution of rotavirus genotypes after introduction of rotavirus vaccines, Rotarix® and RotaTeq®, into the National Immunization Program of Australia.

BACKGROUND: Rotavirus vaccines, RotaTeq and Rotarix, were introduced into the Australian National Immunization Program on July 1, 2007. The simultaneous introduction in different Australian states and territories provides a unique opportunity to compare the affect of each vaccine on the types of circulating rotavirus strains. This report describes the rotavirus genotypes responsible for the hospitalization of children during the first 2-year period after vaccine introduction. METHODS: A total of 764 rotavirus-associated diarrheal cases were collected from children presenting to hospital in 10 Australian centers. Rotavirus genotype was determined using reverse transcription polymerase chain reaction assays. RESULTS: G1P[8] was the dominant genotype nationally (52%), followed by G2P[4] (19.8%), G9P[8] (12.2%), and G3P[8] (11%). Differences in the prevalence rates of G2P[4] and G3P[8] were seen in the various states. G2P[4] strains were more prevalent in states using Rotarix, whereas G3P[8] strains were more prevalent in states using RotaTeq. CONCLUSIONS: Differences in rotavirus genotypes were observed across Australia, which suggest that different immune pressures are exerted by the different vaccines, but do not necessarily imply lack of protection by either vaccine. These differences may simply be related to the variation that can occur because of natural annual fluctuation in rotavirus strain prevalence.