Genetic polymorphisms in monoamine neurotransmitter systems show only weak association with acute post-surgical pain in humans

BACKGROUND: Candidate gene studies on the basis of biological hypotheses have been a practical approach to identify relevant genetic variation in complex traits. Based on previous reports and the roles in pain pathways, we have examined the effects of variations of loci in the genes of monoamine neurotransmitter systems including metabolizing enzymes, receptors and transporters on acute clinical pain responses in humans. RESULTS: Variations in the catecholamine metabolizing enzyme genes (MAOA and COMT) showed significant associations with the maximum post-operative pain rating while the serotonin transporter gene (SLC6A4) showed association with the onset time of post-operative pain. Analgesic onset time after medication was significantly associated with the norepinephrine transporter gene (SLC6A2). However, the association between COMT genetic variation and pain sensitivity in our study differ from previous studies with small sample sizes, population stratification and pain phenotype derived from combining different types of pain stimuli. Correcting for multiple comparisons did not sustain these genetic associations between monoamine neurotransmitter systems and pain sensitivity even in this large and homogeneous sample. CONCLUSION: These results suggest that the previously reported associations between genetic polymorphisms in the monoamine neurotransmitter systems and the interindividual variability in pain responses cannot be replicated in a clinically relevant pain phenotype

Prevalence of constipation in people with intellectual disabilities:a systematic review

Background. Constipation can lead to serious health issues and death. This systematic review summarises international research pertaining to the prevalence of constipation in people with intellectual disability. Method. Studies published from 1990 to January 2016 were identified using Medline, Cinahl, PsycINFO, Web of Science, email requests, and cross-citations. Studies were reviewed narratively. Results. 31 studies were identified. Constipation rates of 50% or more were reported in 14 studies; 21 studies reported rates over 33%. Based on the most representative study, over 25% of people with intellectual disability received a repeat prescription for laxatives in one year, compared to 0.1% of people without intellectual disability. Constipation was more common in those with cerebral palsy and profound intellectual disability, and associated with immobility but not age. Conclusion. Constipation is a significant issue for people with intellectual disability across the life course and should be actively considered as a diagnosis in this population

Obesity in British children with and without intellectual disability:cohort study

Background Reducing the prevalence of and inequities in the distribution of child obesity will require developing interventions that are sensitive to the situation of ‘high risk’ groups of children. Children with intellectual disability appear to be one such group. We aimed to estimate the prevalence of obesity in children with and without intellectual disability in a longitudinal representative sample of British children and identify risk factors associated with obesity at age 11. Methods Information was collected on a nationally representative sample of over 18,000 at ages 9 months, 3, 5, 7 and 11 years. We used UK 1990 gender-specific growth reference charts and the LMS Growth programme to identify age and gender-specific overweight and obesity BMI thresholds for each child at ages five, seven and eleven years. Results Children with intellectual disabilities were significantly more likely than other children to be obese at ages five (OR=1.32[1.03-1.68]), seven (OR=1.39[1.05-1.83]) and eleven (OR=1.68[1.39-2.03]). At ages five and seven increased risk of obesity among children with intellectual disabilities was only apparent among boys. Among children with intellectual disability risk of obesity at age eleven was associated with persistent maternal obesity, maternal education, child ethnicity and being bullied at age five. Conclusions Children with intellectual disability are a high-risk group for the development of obesity, accounting for 5-6% of all obese children. Interventions to reduce the prevalence and inequities in the distribution of child obesity will need to take account of the specific situation of this group of children

Increased risk of cardiovascular and renal disease, and diabetes for all women diagnosed with gestational diabetes mellitus in New Zealand:A national retrospective cohort study

Background: Gestational diabetes mellitus increases the risk of developing type 2 diabetes. The aim of this study is to compare cardiometabolic and renal outcomes for all women in New Zealand with gestational diabetes (2001–2010) with women without diabetes, 10–20 years following delivery. Methods: A retrospective cohort study, utilizing a national dataset providing information for all women who gave birth between 1 January 2001 and 31 December 2010 (n = 604 398). Adolescent girls <15 years, women ≥50 years and women with prepregnancy diabetes were excluded. In total 11 459 women were diagnosed with gestational diabetes and 11 447 were matched (for age and year of delivery) with 57 235 unexposed (control) women. A national hospital dataset was used to compare primary outcomes until 31 May 2021.Results: After controlling for ethnicity, women with gestational diabetes were significantly more likely than control women to develop diabetes—adjusted hazard ratio (HR) 20.06 and 95% confidence interval (CI) 18.46–21.79; a first cardiovascular event 2.19 (1.86–2.58); renal disease 6.34 (5.35–7.51) and all-cause mortality 1.55 (1.31–1.83), all p values <.0001. The HR and 95% CI remained similar after controlling for significant covariates: diabetes 18.89 (17.36–20.56), cardiovascular events 1.79 (1.52–2.12), renal disease 5.42 (4.55–6.45), and all-cause mortality 1.44 (1.21–1.70). When time-dependent diabetes was added to the model, significance remained for cardiovascular events 1.33 (1.10–1.61), p = .003 and renal disease 2.33 (1.88–2.88), p < .0001 but not all-cause mortality.Conclusions: Women diagnosed with gestational diabetes have an increased risk of adverse cardiometabolic and renal outcomes. Findings highlight the importance of follow-up screening for diabetes, cardiovascular risk factors, and renal disease

Predictors of preeclampsia in women in the metformin in gestational diabetes (MiG) study

Background: Gestational Diabetes Mellitus (GDM), maternal obesity and pregnancy weight gain are associated with an increased risk of developing Preeclampsia (PE). The aim of this study was to examine the predictors of PE in women commencing pharmacotherapy for GDM in the Metformin in Gestational diabetes trial.Methods: Descriptive and logistic regression analyses examined the relationship between maternal enrolment characteristics and later development of PE.Results: 46 (6.3%) of 703 women developed PE. At enrolment ((30 (SD3.2) weeks gestation), women who later developed PE had higher HbA1c (6.14% (95% CI 5.84, 6.45) vs. 5.73% (95% CI 5.67, 5.78), P = 0.003), fasting triglycerides (2.93 mmol/L (95% CI 2.57, 3.29) vs. 2.55mmol/L (95% CI 2.47, 2.62), P = 0.03) and blood pressure. Their infants were born 9 days earlier (P < 0.001) but were otherwise not different. In univariate analysis, the strongest positive predictors for PE were Polynesian ethnicity (OR 2.75 (95% CI 1.48, 5.09), P= 0.001), personal or family history of PE (OR 2.65 (95% CI 1.36, 5.16), P=0.004), maternal HbA1c (OR 1.96 (95% CI 1.35, 2.89), P< 0.001), triglycerides (OR 1.45 (95% CI 1.07,1.97), P=0.002), and weight gain from early pregnancy (OR 1.09 (95% CI 1.03,1.17), P=0.01). HDL-C was a negative predictor of PE (OR 0.29 (95% CI 0.09, 0.94), P= 0.04).Following adjustment for Polynesian ethnicity and personal or family history of PE, and when further adjusted for HbA1c or early pregnancy BMI, these variables remained significant.Conclusion: Treatment allocation and BMI were not associated with risk of PE. Personal or family history of PE, Polynesian ethnicity, degree of hyperglycemia, maternal triglycerides and weight gain prior to treatment signal increased risk of subsequent PE in women needing pharmacotherapy for GDM

Kinin B1 receptors contributes to acute pain following minor surgery in humans

<p>Abstract</p> <p>Background</p> <p>Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B₁and B₂receptors. It is generally accepted that the B₂receptor is constitutively expressed, whereas the B₁receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels.</p> <p>Results</p> <p>Tissue injury resulted in a significant up-regulation in the gene expression of B₁and B₂receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B₁and B₂receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B₁and B₂receptors were correlated. Following tissue injury, B₁ligands des-Arg⁹-BK and des-Arg¹⁰-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B₁receptor but not B₂receptor.</p> <p>Conclusions</p> <p>These results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the early phase of inflammation and inflammatory pain. The up-regulation of B₁receptors may contribute to acute inflammatory pain through TRPV1 activation.</p

Estimating the Need for Social Care Services for Adults with Disabilities in England 2012-2030

Executive summary The aim of the project was to estimate changes in the need for social care services for adults with disabilities in England between 2012 and 2030. The project built upon and extended our previous work on estimating future need for social care services among adults with learning disabilities. The latest update of our previous work suggested that there will be sustained growth in the need for social care services for adults with learning disabilities over the time period 2011-2030, with estimated average annual increases varying from 1.2% to 5.1% (average 3.2%). Our previous approach was, however, based on a number of assumptions, some of which we believe to be highly robust, some less so. The most critical source of uncertainty in the model was in the validity of our estimates of the likely eligibility for social care services for new entrants at different levels of ‘need’, especially for potential new entrants with less severe disabilities. In our previous work we used estimates developed through a process of consultation with relevant stakeholders (primarily disabled people’s organisations and field agencies). One of the key aims of the present project was to test out and refine these assumptions through field-based research. Other aims of the present project were to: • update the estimates based on revised information; • extend the model to other adults with disabilities. Our proposed primary research involved attempting to collect information on the assessed level of eligibility for samples of 50 children aged 14-16 identified as having SEN in 10 CASSRs. In order to compensate for potential drop out we initially recruited 18 CASSRs who all indicated a strong commitment to participating in the project. Unfortunately, the fieldwork took place during 2010/11, a period of unprecedented turmoil within CASSRs in England. Despite extending the period of data collection by several months, only six CASSRs were able to provide any data and only two CASSRs were able to provide data on the target sample of 50 children. As a result, we were only able to collect information on 223 young people (45% of the target sample). Given the difficulties we encountered in our field work, we agreed with NIHR SSCR that we would also undertake some exploratory analyses of the association between SEN and the experimental disability statistics collected by DfE in Spring 2011. The aim of these analyses was to explore the relationship between SEN and disability (as defined under the Equality Act 2010) and to determine whether this information could be used to strengthen the estimates of assessed level of need for adult social care services. Unfortunately, the results of these analyses suggested that the disability data collected by the DfE were subject to a number of serious biases associated with social exclusion and socio-economic position that made their use untenable in the present project. We were, however, able to use the new field-generated estimates of eligibility to: (1) update our previous work on estimating future need for adult social care services for people with learning disabilities; and (2) extend this work to estimating future need for adult social care services for people with physical disabilities (including sensory impairment) in the age range 19-30. To estimate future need beyond this age point would require making important assumptions about the annual age-specific incidence (onset) of serious physical and sensory impairments in adults. There is, at present, insufficient information to make these assumptions with any degree of confidence. However, such information will become available in the near future with the release of Wave 2 data from the Office for Disability Issues’ longitudinal Life Opportunities Survey.1 All of the scenarios included in our estimation procedures suggested sustained growth in the need for social care services for adults with physical or learning disabilities over the time period 2012-2030. • For younger adults with physical disabilities compound annual growth rates vary from 1.8% to 6.5%. A ‘no growth’ scenario in the number of users of adult social care services for young adults with physical disabilities could only be achieved by either cutting services to existing users or by rationing access to services to young adults with physical disabilities with ‘critical’ need and 61% of those with ‘substantial’ need. • For adults with learning disabilities compound annual growth rates vary from 2.0% to 2.7%. A ‘no growth’ scenario in the number of users of adult social care services for adults with learning disabilities could only be achieved by either cutting services to existing users or by rationing access to services to young people with learning disabilities with ‘critical’ need and just 25% of those with substantial need. As we have argued above, rationing social care to people with critical or substantial needs is inconsistent with the policy objective strongly emphasised in Putting People First2 of adopting a more preventative approach to social care.3-5 There are a number of factors that would have an impact on future need that we were not able to take into account. These included: • Effects due to international migration; • Changes in the incidence of disability over time; • Changes in mortality rates among people with disabilities over time. It must be stressed that our predictions are based on estimates of ‘need’ rather than ‘demand’. Changes in demand are likely to outstrip changes in need due to a variety of factors combining to reduce the capacity of informal support networks to provide care, networks that have primarily relied on the unpaid labour of women. These factors include: • Increases in lone parent families6 • Increasing rates of maternal employment6 • Increases in the percentage of older people with learning disabilities (whose parents are likely to have died or be very frail)7 8 • Changing expectations among families regarding the person’s right to an independent life

Self-Reported Participation in Sport/Exercise Among Adolescents and Young Adults With and Without Mild to Moderate Intellectual Disability

Physical inactivity is a leading risk factor for mortality. Adults with intellectual disability are extremely inactive, but less is known about physical activity levels in children and youth with intellectual disability. This paper examines the participation by adolescents and young adults with and without mild to moderate intellectual disability in sport/exercise. Methods: Secondary analysis was undertaken of Next Steps, an annual panel study that followed a cohort from early adolescence into adulthood. Participants with mild to moderate intellectual disability were identified through data linkage with educational records. Results: Sport/exercise participation rates were consistently lower for adolescents and young people with mild to moderate intellectual disability than for their peers without intellectual disability. Matching participants on between-group differences in exposure to extraneous risk factors did not impact on these between-group differences in participation in sport/exercise. Conclusion: The results support limited existing evidence regarding the low level of participation of children and young people with intellectual disability in sport/exercise compared with their peers. Future work on promoting sport/exercise and physical activity in children and young people with intellectual disability may play a role in helping to reduce the health inequalities experienced by people with intellectual disability

Predictors of self-reported alcohol use and attitudes toward alcohol among 11 year old British children with and without intellectual disability

Background Reducing harmful levels of alcohol consumption among children is an important public health concern internationally and in many high income countries. Little is known about levels and predictors of alcohol use among children with intellectual disability. Method Secondary analysis of child self-report data at age 11 years collected in the UK’s Millennium Cohort Study. Results Children with intellectual disability were significantly more likely to: have used alcohol in the last four weeks; to have had five or more alcoholic drinks on one occasion; to have had five or more alcoholic drinks or been intoxicated on one occasion; to have more positive attitudes about the psychological and social benefits of drinking; to have less negative attitudes about the social and physical costs of drinking. Potentially harmful levels of drinking (intoxication or 5+ alcoholic drinks on one occasion) among children with intellectual disability were associated with child smoking, having friends who use alcohol, reporting that drinking makes it easier to make friends and reporting that drinking reduces worrying. Children with intellectual disability accounted for 9% of all children with potentially harmful levels of drinking. Conclusion Public health interventions to reduce potentially harmful drinking among children in general must recognise that children with intellectual disability are a potentially high risk group and ensure that interventions are appropriately adjusted to take account of their particular needs and situation. Future research in this area is needed to untangle the causal pathways between attitudes toward alcohol and alcohol use among children with intellectual disability and the extent to which levels of alcohol use and predictors of alcohol use may be moderated by severity of intellectual disability