Clustering long-term health conditions among 67728 people with multimorbidity using electronic health records in Scotland.

There is still limited understanding of how chronic conditions co-occur in patients with multimorbidity and what are the consequences for patients and the health care system. Most reported clusters of conditions have not considered the demographic characteristics of these patients during the clustering process. The study used data for all registered patients that were resident in Fife or Tayside, Scotland and aged 25 years or more on 1st January 2000 and who were followed up until 31st December 2018. We used linked demographic information, and secondary care electronic health records from 1st January 2000. Individuals with at least two of the 31 Elixhauser Comorbidity Index conditions were identified as having multimorbidity. Market basket analysis was used to cluster the conditions for the whole population and then repeatedly stratified by age, sex and deprivation. 318,235 individuals were included in the analysis, with 67,728 (21·3%) having multimorbidity. We identified five distinct clusters of conditions in the population with multimorbidity: alcohol misuse, cancer, obesity, renal failure, and heart failure. Clusters of long-term conditions differed by age, sex and socioeconomic deprivation, with some clusters not present for specific strata and others including additional conditions. These findings highlight the importance of considering demographic factors during both clustering analysis and intervention planning for individuals with multiple long-term conditions. By taking these factors into account, the healthcare system may be better equipped to develop tailored interventions that address the needs of complex patients.

Which young women are not being vaccinated against HPV? Cross-sectional analysis of a UK national cohort study.

OBJECTIVES: HPV vaccination is highly effective in preventing HPV-associated disease, including cervical cancer, which disproportionately affects women from disadvantaged and minority ethnic backgrounds. We examined inequalities in initiation of the HPV vaccination schedule among young women in the UK and reasons given by their parents for non-initiation. DESIGN: Cross sectional analyses of a prospective nationally representative cohort study. SETTING: Four UK countries. PARTICIPANTS: 5,695 young women (39.9% from households in lowest income quintiles, 5.1% ever excluded from school, 0.5% not attending school) whose parents (14.3% from minority ethnic backgrounds; 54.1% with no stated religious faith) took part in interviews conducted when their daughters were 14 years old. MAIN OUTCOME MEASURES: Parent-reported initiation of HPV vaccination and reasons for non-initiation. The adjusted odds (aORs) and 95% Confidence Intervals (CI) of initiating HPV vaccination were estimated using logistic regression after mutual adjustment for household income, school exclusion, school attendance and parental ethnic background and religious faith. RESULTS: 92.3% (5265) had initiated HPV vaccination at time of interview. Initiation was less likely among those living in the poorest households (aOR; 95% CI: 0.44; 0.30 to 0.64 for those in lowest household income quintile), who did not attend school (0.11; 0.04 to 0.33), had ever been excluded from school (0.47; 0.29 to 0.76), or whose parents were from Black African (0.49; 0.26 to 0.95) or Any Other (0.34; 0.17 to 0.66) ethnic backgrounds. A reason consistent with a conscious or practical decision was reported by 53.3% (219) and 24.1% (90) parents respectively. CONCLUSIONS: Although most young women are immunised, marked social inequalities in access to HPV vaccination initiation remain. Practical steps to address this are possible and should be implemented to reduce inequalities in primary prevention of cancers and to ensure equitable access to this important public health intervention.

Newborn Screening for Primary Congenital Hypothyroidism: Estimating Test Performance at Different TSH Thresholds.

Context: Active surveillance of primary congenital hypothyroidism (CH) in a multiethnic population with established newborn bloodspot screening. Objective: To estimate performance of newborn screening for CH at different test thresholds and calculate incidence of primary CH. Design: Prospective surveillance from June 2011 to June 2012 with 3-year follow-up of outcomes. Relative likelihood ratios (rLRs) estimated to compare bloodspot TSH test thresholds of 6 mU/L and 8 mU/L, with the nationally recommended standard of 10 mU/L for a presumptive positive result. Setting: UK National Health Service. Patients: Clinician notification of children aged <5 years investigated following clinical presentation or presumptive positive screening result. Main Outcome Measure(s): Permanent primary CH status determined by clinician report of continuing T4 requirement at 3-year follow-up. Results: A total of 629 newborns (58.3% girls; 58.7% white ethnicity) were investigated following presumptive positive screening result and 21 children (52.4% girls; 52.4% white) after clinical presentation; 432 remained on treatment at 3-year follow-up. Permanent CH incidence was 5.3 (95% CI, 4.8 to 5.8) per 10,000 infants. With use of locally applied thresholds, sensitivity, specificity, and positive predictive value were 96.76%, 99.97%, and 66.88%, respectively. Compared with a TSH threshold of 10 mU/L, positive rLRs for 8 mU/L and 6 mU/L were 1.20 (95% CI, 0.82 to 1.75) and 0.52 (95% CI, 0.38 to 0.72), and negative rLRs were 0.11 (95% CI, 0.03 to 0.36) and 0.11 (95% CI, 0.06 to 0.20), respectively. Conclusions: Screening program performance is good, but a TSH threshold of 8 mU/L appears superior to the current national standard (10 mU/L) and requires further evaluation. Further research should explore the implications of transient CH for screening policy.

Predictors of non-response in a UK-wide cohort study of children's accelerometer-determined physical activity using postal methods.

OBJECTIVES: To investigate the biological, social, behavioural and environmental factors associated with non-consent, and non-return of reliable accelerometer data (≥2 days lasting ≥10 h/day), in a UK-wide postal study of children's activity. DESIGN: Nationally representative prospective cohort study. SETTING: Children born across the UK, between 2000 and 2002. PARTICIPANTS: 13 681 7 to 8-year-old singleton children who were invited to wear an accelerometer on their right hip for 7 consecutive days. Consenting families were posted an Actigraph GT1M accelerometer and asked to return it by post. PRIMARY OUTCOME MEASURES: Study consent and reliable accelerometer data acquisition. RESULTS: Consent was obtained for 12 872 (94.5%) interviewed singletons, of whom 6497 (50.5%) returned reliable accelerometer data. Consent was less likely for children with a limiting illness or disability, children who did not have people smoking near them, children who had access to a garden, and those who lived in Northern Ireland. From those who consented, reliable accelerometer data were less likely to be acquired from children who: were boys; overweight/obese; of white, mixed or 'other' ethnicity; had an illness or disability limiting daily activity; whose mothers did not have a degree; who lived in rented accommodation; who exercised once a week or less; who had been breastfed; were from disadvantaged wards; had younger mothers or lone mothers; or were from households with just one, or more than three children. CONCLUSIONS: Studies need to encourage consent and reliable data return in the wide range of groups we have identified to improve response and reduce non-response bias. Additional efforts targeted at such children should increase study consent and data acquisition while also reducing non-response bias. Adjustment must be made for missing data that account for missing data as a non-random event.

Radiographic measurements of hip dysplasia at skeletal maturity--new reference intervals based on 2,038 19-year-old Norwegians.

OBJECTIVE: Normative references for radiographic measurements commonly used in the diagnosis of developmental dysplasia of the hip at skeletal maturity are incomplete. The present study therefore aimed to establish new gender-specific standards for measurements reflecting the acetabular morphology, namely Sharp's angle, the acetabular roof angle of Tönnis (AA) and the acetabular depth-width ratio (ADR), and measurements reflecting the position of the femoral head related to the acetabulum, namely the center-edge (CE) angle of Wiberg, the refined CE angle of Ogata, and the femoral head extrusion index (FHEI). The joint space width (JSW) is also reported. MATERIALS AND METHODS: The population-based 1989 Bergen Birth Cohort (n = 3,935) was invited at age 19 years to a follow-up during 2007-09, of which 2,038 (52 %) attended. A standardized antero-posterior radiograph was assessed. The normative references are presented as mean ± standard deviation (SD) and 2.5-97.5 percentiles with 95 % confidence intervals. RESULTS: A total of 2,011 (841 males, 1,170 females, mean age 18.6 (SD 0.6)) radiographs were analyzed. Sharp's angle was 38.8° ± 3.5° in males and 40.7° ± 3.5° in females, with 97.5 percentiles of 46° and 47°, respectively. The CE angle was 32.1° ± 6.1° in males and 31.0° ± 6.1° in females, with 2.5 percentiles of 21° and 20°, respectively. The FHEI was 86.0 % ± 6.3 % in males and 85.6 % ± 6.6 % in females, with 2.5 percentiles of 74° and 73°, respectively. CONCLUSIONS: Updated gender-specific reference ranges for radiographic measurements commonly used for hip dysplasia at skeletal maturity are reported, similar to or slightly wider than those described in the literature. Statistically significant gender differences have been confirmed for most of the measurements.

Mortality with congenital heart defects in England and Wales, 1959-2009: exploring technological change through period and birth cohort analysis.

BACKGROUND: Technological advances in surgery, intensive care and medical support have led to substantial decrease in mortality for children with congenital heart defects (CHDs) over the last 50 years. METHODS: Using routinely-collected mortality and population data for England and Wales from 1959 to 2009, the authors investigated age, period and birth cohort trends in child mortality attributable to CHDs. RESULTS: The total number of deaths with CHDs at all ages between 1959 and 2009 was 61 903 (33 929 (55%) males). Absolute numbers of CHD-related deaths in children (under age 15 years) fell from 1460 in 1959 to 154 in 2009. Infants (aged under 1 year) comprised over 60% of all deaths due to CHD during the 5-year period 1959-1963, but this fell to 22% by 2004-2008. Age-standardised death rates have declined for both sexes but, despite narrowing sex differences, males continue to have higher death rates. Successive birth cohorts have experienced improved death rates in the first year of life; however, declining mortality across all age-groups has only been observed for birth cohorts originating after 1989. Poisson regression modelling predicts continuing generational decline in mortality. CONCLUSIONS: Death rates attributable to CHDs have fallen dramatically with advances in paediatric cardiac surgery and intensive care, largely due to decreased mortality in infants aged under 1 year. Initially, mortality in later childhood rose as infant deaths fell, suggesting death was delayed beyond infancy. Children born within the last 20 years experienced lower mortality throughout childhood.

Seasonal variation in accelerometer-determined sedentary behaviour and physical activity in children: a review.

AIM: To undertake a review of the methods and findings of published research evaluating the influence of season on accelerometer-determined sedentary behaviour (SB) and physical activity (PA) in children. METHODS: A literature search was carried out using PubMed, Embase, Medline and Web of Science up to, and including, June 2011. The search strategy focused on four key elements: children, SB or PA, season and accelerometer. Articles were eligible for inclusion if they were published in English, included healthy study participants aged ≤ 18 years, reported at least one outcome variable derived from accelerometer-determined measurements, and compared SB or PA between two or more seasons, or controlled for season of measurement. Eligible papers were reviewed and evidence tables compiled reporting on publication year, country studied, study recruitment, consent rate, sample descriptives, study design, accelerometer protocol, valid accelerometer data receipt, season definition, statistical methods and key findings. RESULTS: Sixteen of 819 articles were eligible for inclusion: children aged two to five years, six to twelve, or six to 18 years were included in five, six and five articles respectively. Six articles were from the UK, six from other European countries, three from the USA and one from New Zealand. Study sample sizes ranged from 64 to 5595. PA was reported in all articles but SB in only three. Only four studies were longitudinal and none of these reported SB. Seasonal variation in PA was reported in all UK studies, being highest in summer and lowest in winter. In four non-UK studies seasonal variation in PA was not found. Findings were inconclusive for SB. CONCLUSION: There is sufficient evidence to support public health interventions aimed at increasing PA during winter in UK children. No conclusions can be drawn regarding the effect of season on children's SB reflecting few studies of small sample size, lack of repeat measures, incomparable definitions of season and inconsistent accelerometer protocols. Future research should determine factors that drive seasonal patterns in PA and SB in children such as age, sex, and geographic and climatic setting to inform interventions and target populations.

Newborns with sonographically dysplastic and potentially unstable hips: 6-year follow-up of an RCT.

OBJECTIVE: To examine the long-term outcome of early abduction splinting versus active sonographic surveillance in newborns with mildly dysplastic hips. PATIENTS AND METHODS: Between 1997 and 2003, 128 newborns with mildly dysplastic and potentially unstable hips on ultrasound (43° ≤ α-angle < 50°) were randomly assigned to immediate abduction treatment or sonographic surveillance. All were invited for a radiographic follow-up at 6 years. The radiographs were analyzed by a single radiologist masked to the randomization allocation, and markers of hip dysplasia (acetabular index, center-edge angle of Wiberg) and avascular necrosis were reported. RESULTS: Eighty-three participants (65%) agreed to participate in the follow-up (42 participants from the treatment group). The mean acetabular index was 14.7° (SD: 5.6°) for the treatment group and 13.9° (SD: 3.9°) for the control group (mean difference: -0.8° [95% confidence interval: -2.9° to 1.3°]). Values were within normal ranges for age for all participants except for 1 female subject from the treatment group. The mean center edge was 26.6° for those treated and 26.4° for the active surveillance group (mean difference: -0.3° [95% confidence interval: -2.5° to 2.0°]). None had markers suggestive of avascular necrosis. CONCLUSIONS: We found no difference in radiographic outcome at 6 years of age between children allocated to initial splintage for 6 weeks and those offered active sonographic surveillance. The delayed acetabular ossification or persistent dysplasia seen in a third of infants from both groups at 1 year of age had completely resolved in all but 1 of the female subjects from the treatment group.

Immediate treatment versus sonographic surveillance for mild hip dysplasia in newborns.

OBJECTIVE: We conducted a blinded, randomized, controlled trial to examine whether mildly dysplastic but stable or instable hips would benefit from early treatment, as compared with watchful waiting. PATIENTS AND METHODS: A total of 128 newborns with mild hip dysplasia (sonographic inclination angle [alpha angle] of 43 degrees -49 degrees ) and stable or instable but not dislocatable hips were randomly assigned to receive either 6 weeks of abduction treatment (immediate-treatment group) or follow-up alone (active-sonographic-surveillance group). The main outcome measurement was the acetabular inclination angle, measured by radiograph, at 1 year of age. RESULTS: Both groups included 64 newborns, and there was no loss to follow-up. With the exception of a small but statistically significant excess of girls in the active-sonographic-surveillance group, there were no statistically significant differences in baseline characteristics between the 2 groups. The mean inclination angle at 12 months was 24.2 degrees for both groups (difference: 0.1 [95% confidence interval (CI): -0.8 to 0.9]), and all children had improved and were without treatment. The mean alpha angle was 59.7 degrees in the treatment group and 57.1 degrees in the active-surveillance group for a difference of 2.6 degrees evaluated after 1.5 and 3 months (95% CI: 1.8 to 3.4; P < .001). At 1.5 months of age, the hips had improved in all treated children but not in 5 children under active surveillance (P = .06). Among the sonographic-surveillance group, 47% received treatment after the initial surveillance period of 1.5 months. CONCLUSIONS: Active-sonographic-surveillance halved the number of children requiring treatment, did not increase the duration of treatment, and yielded similar results at 1-year follow-up. Given a reported prevalence of 1.3% for mildly dysplastic but stable hips, a strategy of active surveillance would reduce the overall treatment rate by 0.6%. Our results may have important implications for families as well as for health care costs.

Developmental dysplasia of the hip.

In its severest form, developmental dysplasia of the hip is one of the most common congenital malformations. The pathophysiology and natural history of the range of morphological and clinical disorders that constitute developmental dysplasia of the hip are poorly understood. Neonatal screening programmes, based on clinical screening examinations, have been established for more than 40 years but their effectiveness remains controversial. Whereas systematic sonographic imaging of newborn and young infants has afforded insights into normal and abnormal hip development in early life, we do not clearly understand the longer-term outcomes of developmental hip dysplasia, its contribution to premature degenerative hip disorders in adult life, and the benefits and harms of newborn screening. High quality studies of the adult outcomes of developmental hip dysplasia and the childhood origins of early degenerative hip disease are needed, as are randomised trials to assess the effectiveness and safety of neonatal screening and early treatment.

Differences in risk factors for partial and no immunisation in the first year of life: prospective cohort study.

OBJECTIVE: To compare demographic, social, maternal, and infant related factors associated with partial immunisation and no immunisation in the first year of life in the United Kingdom. DESIGN: Prospective cohort study. SETTING: Sample of electoral wards in England, Wales, Scotland, and Northern Ireland, stratified by measures of ethnic composition and social disadvantage. PARTICIPANTS: 18,488 infants born between September 2000 and January 2002, resident in the UK and eligible to receive child benefit (a universal benefit available to all families) at age 9 months. MAIN OUTCOME MEASURE: Immunisation status at 9 months of age, defined as fully immunised, partially immunised, or not immunised. RESULTS: Overall in the UK, 3.3% of infants were partially immunised and 1.1% were unimmunised; these rates were highest in England (3.6% and 1.3%, respectively; P < 0.01). Residence in ethnic or disadvantaged wards, larger family size, lone or teenaged parenthood, maternal smoking in pregnancy, and admission to hospital by 9 months of age were independently associated with partial immunisation status. In contrast, a higher proportion of mothers of unimmunised infants were educated to degree level or above (1.9%), were older (3.1%), or were of black Caribbean ethnicity (4.7%). CONCLUSIONS: Mothers of unimmunised infants differ in terms of age and education from those of partially immunised infants. Interventions to reduce incomplete immunisation in infancy need different approaches.

Economic evaluation of ultrasonography in the diagnosis and management of developmental hip dysplasia in the United Kingdom and Ireland.

BACKGROUND: Clinical neonatal hip screening is performed to identify hip instability and the increased risk of later hip subluxation and dislocation. However, there is minimal information regarding the costs of such screening to parents and health services. The aim of this study was to assess these costs in association with the use of ultrasonography for the diagnosis and management of neonatal hip instability. METHODS: We conducted a prospective economic analysis in conjunction with a randomized clinical trial (the Hip Trial), for which 629 patients were recruited from thirty-three centers in the United Kingdom and Ireland to be randomized to undergo either ultrasonographic hip examination (314 patients) or clinical assessment alone (315 patients). Information on clinical outcomes was obtained from hospital records and records from the Hip Trial. Resource information was obtained from hospital records and from repeated periodic cross-sectional surveys of the families. Typical unit costs were applied to resource information to obtain a cost per patient, and the mean costs in the two study groups were calculated and compared. RESULTS: The average overall health-service cost per patient (and standard deviation) was $1298 +/- $2168 in the ultrasonography group and $1488 +/- $2912 in the group that underwent clinical assessment alone, a net difference of -$190 (95% confidence interval, -$630 to $250). Families in which the infant was examined with ultrasonography had significantly lower costs associated with splinting: $92 compared with $118 in the group that underwent clinical assessment alone, a mean difference of -$26 (95% confidence interval, -$46 to -$6). Costs associated with surgery and total costs to the family were also slightly, but not significantly, lower in the ultrasonography group. CONCLUSIONS: Our results suggest that use of ultrasonography in the management of neonates with clinical hip instability is unlikely to impose an increased cost burden and may reduce costs to health services and families.

The evolution of airway function in early childhood following clinical diagnosis of cystic fibrosis.

This study aimed to investigate the evolution of airway function in infants newly diagnosed with cystic fibrosis (CF). FEV(0.5) was measured soon after diagnosis (median age of 28 weeks) and 6 months later in subjects with CF and on two occasions 6 months apart (median ages of 7.4 and 33.7 weeks) in healthy infants, using the raised-volume technique. Repeated measurements were successful in 34 CF and 32 healthy subjects. After adjustment for age, length, sex, and exposure to maternal smoking, mean FEV(0.5) was significantly lower in infants with CF both shortly after diagnosis and at the second test, with no significant difference in rate of increase in FEV(0.5) with growth between the two groups. When compared with published reference data, FEV(0.5) was reduced by an average of two z scores on both test occasions in those with CF, with 72% of individuals having an FEV(0.5) of less than 1.64 z-scores (i.e., less than the fifth percentile) on one or both test occasions. On longitudinal analysis, subjects with CF experienced a mean (95% confidence interval) reduction in FEV(0.5) of 20% (11, 28). Airway function is diminished soon after diagnosis in infants with CF and does not catch up during infancy and early childhood. These findings have important implications for early interventions in CF.

The effect of parental smoking on lung function and development during infancy.

While the adverse effects of parental smoking on respiratory health during childhood are well recognized, its potential impact on early lung development is less clear. This review summarizes current evidence on the effect of parental smoking on lung function during infancy. It is difficult to separate the effects of pre- and postnatal exposure, since the majority of mothers who smoke in pregnancy (currently around 30% worldwide) continue to do so thereafter. Nevertheless, measurements undertaken prior to any postnatal exposure have consistently demonstrated significant changes in tidal flow patterns in infants whose mothers smoked in pregnancy. While there is, as yet, no convincing evidence from studies in human infants that smoking during pregnancy is associated with increased airway responsiveness at birth, many studies have demonstrated a reduction in forced expiratory flows (on average by 20%) in infants exposed to parental smoking. While maternal smoking during pregnancy remains the most significant source of such exposure and is likely to be responsible for diminished airway function in early life, continuing postnatal tobacco smoke exposure will increase the risk of respiratory infections, the combination of both being responsible for the two- to fourfold increased risk of wheezing illnesses observed during the first year of life in infants whose parents smoke. These findings emphasize the need to keep infants in a smoke-free environment both before and after birth, not least because of growing awareness that airway function in later life is largely determined by that during foetal development and early infancy.

Ultrasonography in the diagnosis and management of developmental hip dysplasia (UK Hip Trial): clinical and economic results of a multicentre randomised controlled trial.

BACKGROUND: Clinical screening aims to identify and treat neonatal hip instability associated with increased risk of hip displacement, but risks failures of diagnosis and treatment (abduction splinting), iatrogenic effects, and costs to parents and health services. Our objectives were to assess clinical effectiveness and net cost of ultrasonography compared with clinical assessment alone, to provide guidance for management of infants with clinical hip instability. METHODS: Infants with clinical hip instability were recruited from 33 centres in UK and Ireland and randomised to either ultrasonographic hip examination (n=314) or clinical assessment alone (n=315). The primary outcome was appearance on hip radiographs by 2 years. Secondary outcomes included surgical treatment, abduction splinting, level of mobility, resource use, and costs. Analysis was by intention to treat. FINDINGS: Protocol compliance was high, and radiographic information was available for 91% of children by 12-14 months and 85% by 2 years. By age 2 years, subluxation, dislocation, or acetabular dysplasia were identified by radiography on one or both hips of 21 children in each of the groups (relative risk 1.00; 95% CI 0.56-1.80). Fewer children in the ultrasonography group had abduction splinting in the first 2 years than did those in the no-ultrasonography group (0.78; 0.65-0.94; p=0.01). Surgical treatment was required by 21 infants in the ultrasonography group (6.7%) and 25 (7.9%) in the no-ultrasonography group (0.84; 0.48-1.47). One child from the ultrasonography group and four from the no-ultrasonography group were not walking by 2 years (0.25; 0.03-2.53; p=0.37). Infants in the ultrasonography group incurred significantly higher ultrasound costs over the first 2 years (pound 42 vs pound 23, mean difference pound 19, 95% CI 11-27); total hospital costs were lower for those infants, but the difference was not significant. INTERPRETATION: The use of ultrasonography in infants with screen-detected clinical hip instability allows abduction splinting rates to be reduced, and is not associated with an increase in abnormal hip development, higher rates of surgical treatment by 2 years of age, or significantly higher health-service costs.

Relative ability of full and partial forced expiratory maneuvers to identify diminished airway function in infants with cystic fibrosis.

The tidal and raised volume rapid thoracoabdominal compression techniques are increasingly used to detect diminished airway function in infancy. The aim of this study was to assess the relative ability of parameters measured by these techniques to identify diminished airway function in infants newly diagnosed with cystic fibrosis (CF) with and without clinical evidence of prior lower respiratory illness. A cross-sectional, prospective study design was used in which maximal flow at functional residual capacity (VmaxFRC) from the tidal technique and FVC, FEV0.5, FEF75, and FEF25-75 from the raised volume technique were measured in 47 infants with CF and 187 healthy infants of similar body size, sex distribution, ethnic group, and exposure to maternal smoking. Multiple linear regression was used to assess group differences and to calculate SD scores for each parameter for the infants with CF. Airway function was also compared with clinical assessments of respiratory status made by pediatric pulmonologists. FEV0.5 was significantly diminished in 13 infants with CF, of whom 4 had been identified by clinicians as having normal respiratory status. Only one infant with CF had a VmaxFRC below the estimated normal range. Airway function is diminished in infants with CF irrespective of prior lower respiratory illness and in those whose respiratory status is considered normal by pediatric pulmonologists. In infants with CF, the raised volume technique identified diminished airway function more frequently than the tidal technique.