Summary Background The Confidential Inquiry into premature deaths of people with intellectual disabilities in England was commissioned to provide evidence about contributory factors to avoidable and ...premature deaths in this population. Methods The population-based Confidential Inquiry reviewed the deaths of people with intellectual disabilities aged 4 years and older who had been registered with a general practitioner in one of five Primary Care Trust areas of southwest England, who died between June 1, 2010, and May 31, 2012. A network of health, social-care, and voluntary-sector services; community contacts; and statutory agencies notified the Confidential Inquiry of all deaths of people with intellectual disabilities and provided core data. The Office for National Statistics provided data about the coding of individual cause of death certificates. Deaths were described as avoidable (preventable or amenable), according to Office for National Statistics definitions. Contributory factors to deaths were identified and quantified by the case investigator, verified by a local review panel meeting, and agreed by the Confidential Inquiry overview panel. Contributory factors were grouped into four domains: intrinsic to the individual, within the family and environment, care provision, and service provision. The deaths of a comparator group of people without intellectual disabilities but much the same in age, sex, and cause of death and registered at the same general practices as those with intellectual disabilities were also investigated. Findings The Confidential Inquiry reviewed the deaths of 247 people with intellectual disabilities. Nearly a quarter (22%, 54) of people with intellectual disabilities were younger than 50 years when they died, and the median age at death was 64 years (IQR 52–75). The median age at death of male individuals with intellectual disabilities was 65 years (IQR 54–76), 13 years younger than the median age at death of male individuals in the general population of England and Wales (78 years). The median age at death of female individuals with intellectual disabilities was 63 years (IQR 54–75), 20 years younger than the median age at death for female individuals in the general population (83 years). Avoidable deaths from causes amenable to change by good quality health care were more common in people with intellectual disabilities (37%, 90 of 244) than in the general population of England and Wales (13%). Contributory factors to premature deaths in a subset of people with intellectual disabilities compared with a comparator group of people without intellectual disabilities included problems in advanced care planning (p=0·0003), adherence to the Mental Capacity Act (p=0·0008), living in inappropriate accommodation (p<0·0001), adjusting care as needs changed (p=0·009), and carers not feeling listened to (p=0·006). Interpretation The Confidential Inquiry provides evidence of the substantial contribution of factors relating to the provision of care and health services to the health disparities between people with and without intellectual disabilities. It is imperative to examine care and service provision for this population as potentially contributory factors to their deaths—factors that can largely be ameliorated. Funding Department of Health for England.
The risk of sudden infant death syndrome (SIDS) among infants who co-sleep in the absence of hazardous circumstances is unclear and needs to be quantified.
Combined individual-analysis of two ...population-based case-control studies of SIDS infants and controls comparable for age and time of last sleep.
Parents of 400 SIDS infants and 1386 controls provided information from five English health regions between 1993-6 (population: 17.7 million) and one of these regions between 2003-6 (population:4.9 million).
Over a third of SIDS infants (36%) were found co-sleeping with an adult at the time of death compared to 15% of control infants after the reference sleep (multivariate OR = 3.9 95% CI: 2.7-5.6). The multivariable risk associated with co-sleeping on a sofa (OR = 18.3 95% CI: 7.1-47.4) or next to a parent who drank more than two units of alcohol (OR = 18.3 95% CI: 7.7-43.5) was very high and significant for infants of all ages. The risk associated with co-sleeping next to someone who smoked was significant for infants under 3 months old (OR = 8.9 95% CI: 5.3-15.1) but not for older infants (OR = 1.4 95% CI: 0.7-2.8). The multivariable risk associated with bed-sharing in the absence of these hazards was not significant overall (OR = 1.1 95% CI: 0.6-2.0), for infants less than 3 months old (OR = 1.6 95% CI: 0.96-2.7), and was in the direction of protection for older infants (OR = 0.1 95% CI: 0.01-0.5). Dummy use was associated with a lower risk of SIDS only among co-sleepers and prone sleeping was a higher risk only among infants sleeping alone.
These findings support a public health strategy that underlines specific hazardous co-sleeping environments parents should avoid. Sofa-sharing is not a safe alternative to bed-sharing and bed-sharing should be avoided if parents consume alcohol, smoke or take drugs or if the infant is pre-term.
Sudden infant death syndrome (SIDS) is a leading cause of postneonatal infant mortality. Our previous meta-analyses showed that any breastfeeding is protective against SIDS with exclusive ...breastfeeding conferring a stronger effect.The duration of breastfeeding required to confer a protective effect is unknown.
To assess the associations between breastfeeding duration and SIDS.
Individual-level data from 8 case-control studies.
Case-control SIDS studies with breastfeeding data.
Breastfeeding variables, demographic factors, and other potential confounders were identified. Individual-study and pooled analyses were performed.
A total of 2267 SIDS cases and 6837 control infants were included. In multivariable pooled analysis, breastfeeding for <2 months was not protective (adjusted odds ratio aOR: 0.91, 95% confidence interval CI: 0.68-1.22). Any breastfeeding ≥2 months was protective, with greater protection seen with increased duration (2-4 months: aOR: 0.60, 95% CI: 0.44-0.82; 4-6 months: aOR: 0.40, 95% CI: 0.26-0.63; and >6 months: aOR: 0.36, 95% CI: 0.22-0.61). Although exclusive breastfeeding for <2 months was not protective (aOR: 0.82, 95% CI: 0.59-1.14), longer periods were protective (2-4 months: aOR: 0.61, 95% CI: 0.42-0.87; 4-6 months: aOR: 0.46, 95% CI: 0.29-0.74).
The variables collected in each study varied slightly, limiting our ability to include all studies in the analysis and control for all confounders.
Breastfeeding duration of at least 2 months was associated with half the risk of SIDS. Breastfeeding does not need to be exclusive to confer this protection.
Despite the fall in numbers of unexpected infant deaths that followed the ‘Back to Sleep’ campaigns in the early 1990s in the UK and many other countries, such deaths remain one of the largest single ...groups of deaths in the postneonatal period in many Western countries. Changes in the ways in which unexpected infant deaths are categorised by pathologists and coroners, and increasing reluctance to use the term ‘sudden infant death syndrome’, make assessment of nationally and internationally collected data on incidence potentially inaccurate and confusing. In this paper, we review current understanding of the epidemiology and aetiology of unexpected deaths in infancy, and current hypotheses on the pathophysiology of the processes that may lead to death. We also review interventions that have been adopted, with variable degrees of effectiveness in efforts to reduce the numbers of deaths, and new approaches that offer the possibility of prevention in the future.
The genetic differences between human papilloma virus (HPV)-positive and -negative head and neck squamous cell carcinomas (HNSCC) remain largely unknown. To identify differential biology and novel ...therapeutic targets for both entities, we determined mutations and copy-number aberrations in a large cohort of locoregionally advanced HNSCC.
We performed massively parallel sequencing of 617 cancer-associated genes in 120 matched tumor/normal samples (42.5% HPV-positive). Mutations and copy-number aberrations were determined and results validated with a secondary method.
The overall mutational burden in HPV-negative and HPV-positive HNSCC was similar with an average of 15.2 versus 14.4 somatic exonic mutations in the targeted cancer-associated genes. HPV-negative tumors showed a mutational spectrum concordant with published lung squamous cell carcinoma analyses with enrichment for mutations in TP53, CDKN2A, MLL2, CUL3, NSD1, PIK3CA, and NOTCH genes. HPV-positive tumors showed unique mutations in DDX3X, FGFR2/3 and aberrations in PIK3CA, KRAS, MLL2/3, and NOTCH1 were enriched in HPV-positive tumors. Currently targetable genomic alterations were identified in FGFR1, DDR2, EGFR, FGFR2/3, EPHA2, and PIK3CA. EGFR, CCND1, and FGFR1 amplifications occurred in HPV-negative tumors, whereas 17.6% of HPV-positive tumors harbored mutations in fibroblast growth factor receptor genes (FGFR2/3), including six recurrent FGFR3 S249C mutations. HPV-positive tumors showed a 5.8% incidence of KRAS mutations, and DNA-repair gene aberrations, including 7.8% BRCA1/2 mutations, were identified.
The mutational makeup of HPV-positive and HPV-negative HNSCC differs significantly, including targetable genes. HNSCC harbors multiple therapeutically important genetic aberrations, including frequent aberrations in the FGFR and PI3K pathway genes. See related commentary by Krigsfeld and Chung, p. 495.
To provide reference data on sleep duration throughout childhood and explore the demographic characteristics associated with sleep.
Population-based prospective longitudinal birth-cohort study.
...South-West England, children born in 1991-1992 and followed since birth.
Eleven thousand five hundred children with repeat measures of sleep from birth based on parent-reported questionnaires. Data on daytime and nighttime sleep duration and timings and night awakenings at 8 timepoints from age 6 months to 11 years.
Total sleep duration steadily fell from 13 hours and 12 minutes during infancy to 9 hours and 49 minutes at 11 years of age. Compared with earlier studies, the younger children in this cohort slept for a shorter period. The variation in sleep duration was very wide: from 10 to 17 hours in early infancy, narrowing to 8.5 to 11 hours at 11 years. Half of the children at preschool age woke at least once during the night, but frequent waking (> 3 times) peaked in infancy (10% of all infants) and steadily declined in the preschool-aged years. Despite going to bed at the same time, girls slept consistently longer than boys (by 5-10 minutes). Children from low-income families went to bed later and woke up later, but there was little difference in total sleep duration. Children of younger mothers (< 21 years) slept longer, whereas children of older mothers (> 35 years) slept persistently less. Children in larger families tended to go to bed later, as did the minority group of non-White children in the cohort.
Given the wide natural variation of sleep in the childhood population, any recommendations on optimal sleep duration at any age must take into account considerable individual variability.
The association between upper respiratory tract microbial positivity and illness prognosis in children is unclear. This impedes clinical decision-making and means the utility of upper respiratory ...tract microbial point-of-care tests remains unknown. We investigated for relationships between pharyngeal microbes and symptom severity in children with suspected respiratory tract infection (RTI).
Baseline characteristics and pharyngeal swabs were collected from 2,296 children presenting to 58 general practices in Bristol, UK with acute cough and suspected RTI between 2011-2013. Post-consultation, parents recorded the severity of six RTI symptoms on a 0-6 scale daily for ≤28 days. We used multivariable hurdle regression, adjusting for clinical characteristics, antibiotics and other microbes, to investigate associations between respiratory microbes and mean symptom severity on days 2-4 post-presentation.
Overall, 1,317 (57%) children with complete baseline, microbiological and symptom data were included. Baseline characteristics were similar in included participants and those lacking microbiological data. At least one virus was detected in 869 (66%) children, and at least one bacterium in 783 (60%). Compared to children with no virus detected (mean symptom severity score 1.52), adjusted mean symptom severity was 0.26 points higher in those testing positive for at least one virus (95% CI 0.15 to 0.38, p<0.001); and was also higher in those with detected Influenza B (0.44, 0.15 to 0.72, p = 0.003); RSV (0.41, 0.20 to 0.60, p<0.001); and Influenza A (0.25, -0.01 to 0.51, p = 0.059). Children positive for Enterovirus had a lower adjusted mean symptom severity (-0.24, -0.43 to -0.05, p = 0.013). Children with detected Bordetella pertussis (0.40, 0.00 to 0.79, p = 0.049) and those with detected Moraxella catarrhalis (-0.76, -1.06 to -0.45, p<0.001) respectively had higher and lower mean symptom severity compared to children without these bacteria.
There is a potential role for upper respiratory tract microbiological point-of-care tests in determining the prognosis of childhood RTIs.
Patients with acute heart failure (AHF) require urgent in‐hospital treatment for relief of symptoms. The main reason for hospitalization is congestion, rather than low cardiac output. Although ...congestion is associated with a poor prognosis, many patients are discharged with persistent signs and symptoms of congestion and/or a high left ventricular filling pressure. Available data suggest that a pre‐discharge clinical assessment of congestion is often not performed, and even when it is performed, it is not done systematically because no method to assess congestion prior to discharge has been validated. Grading congestion would be helpful for initiating and following response to therapy. We have reviewed a variety of strategies to assess congestion which should be considered in the care of patients admitted with HF. We propose a combination of available measurements of congestion. Key elements in the measurement of congestion include bedside assessment, laboratory analysis, and dynamic manoeuvres. These strategies expand by suggesting a routine assessment of congestion and a pre‐discharge scoring system. A point system is used to quantify the degree of congestion. This score offers a new instrument to direct both current and investigational therapies designed to optimize volume status during and after hospitalization. In conclusion, this document reviews the available methods of evaluating congestion, provides suggestions on how to properly perform these measurements, and proposes a method to quantify the amount of congestion present.
Respiratory tract infections (RTIs) are common in children and generally self-limiting, yet often result in consultations to primary care. Frequent consultations divert resources from care for ...potentially more serious conditions and increase the opportunity for antibiotic overuse. Overuse of antibiotics is associated with adverse effects and antimicrobial resistance, and has been shown to influence how patients seek care in ensuing illness episodes.
We conducted a systematic review and meta-analysis to assess the effectiveness of interventions directed towards parents or caregivers which were designed to influence consulting and antibiotic use for respiratory tract infections (RTIs) in children in primary care. Main outcomes were parental consulting rate, parental knowledge, and proportion of children subsequently consuming antibiotics. Of 5,714 references, 23 studies (representing 20 interventions) met inclusion criteria. Materials designed to engage children in addition to parents were effective in modifying parental knowledge and behaviour, resulting in reductions in consulting rates ranging from 13 to 40%. Providing parents with delayed prescriptions significantly decreased reported antibiotic use (Risk Ratio (RR) 0.46 (0.40, 0.54); moreover, a delayed or no prescribing approach did not diminish parental satisfaction.
IN ORDER TO BE MOST EFFECTIVE, INTERVENTIONS TO INFLUENCE PARENTAL CONSULTING AND ANTIBIOTIC USE SHOULD: engage children, occur prior to an illness episode, employ delayed prescribing, and provide guidance on specific symptoms. These results support the wider implementation of interventions to reduce inappropriate antibiotic use in children.
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