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Anne Campbell and Duncan Campbell illustrate the ethical, moral and personal concerns that can arise when baptism is performed as part of a holistic nursing care for seriously ill infants and children. [ABSTRACT FROM AUTHOR]

Background: There is widespread belief in a 'cycle' of child sexual abuse, but little empirical evidence for this belief.Aims: To identify perpetrators of such abuse who had been victims of paedophilia and/or incest, in order to: ascertain whether subjects who had been victims become perpetrators of such abuse; compare characteristics of those who had and had not been victims; and review psychodynamic ideas thought to underlie the behaviour of perpetrators.Method: Retrospective clinical case note review of 843 subjects attending a specialist forensic psychotherapy centre.Results: Among 747 males the risk of being a perpetrator was positively correlated with reported sexual abuse victim experiences. The overall rate of having been a victim was 35% for perpetrators and 11% for non-perpetrators. Of the 96 females, 43% had been victims but only one was a perpetrator. A high percentage of male subjects abused in childhood by a female relative became perpetrators. Having been a victim was a strong predictor of becoming a perpetrator, as was an index of parental loss in childhood.Conclusions: The data support the notion of a victim-to-victimiser cycle in a minority of male perpetrators but not among the female victims studied. Sexual abuse by a female in childhood may be a risk factor for a cycle of abuse in males. [ABSTRACT FROM AUTHOR]

Presents several correspondences related to medicine in Great Britain. Discussion on birth trauma in vaginal breech delivery; Information on the heritability of blood pressure; Effectiveness of needle tracheostomy in the management of acute upper airway obstruction.

Introduction and Objectives Many people with severe asthma experience frequent debilitating symptoms and treatment side effects, both of which can have a significant impact on their quality of life. While previous qualitative studies have investigated attitudes to healthcare usage among people with severe asthma symptoms, there is relatively little evidence about how people with ongoing severe asthma cope with its broader impact on their lives. This study sought to examine how people with severe asthma and their families view the impact of the condition and how this affects their approach to its management. Methods Eight focus groups were held in five tertiary centres around the UK in 2010. Participants were grouped into young people with severe asthma (N=8), adults with severe asthma (N=26) and parents of children with severe asthma (N=17). Discussion guides were initially structured around the revised health belief model (Rosenstock IM, Strecher VJ and Becker MH. Social Learning Theory and the Health Belief Model. Health Educ Behav 1988;15:175-183) which suggests that health behaviours are driven e by perceptions in four areas: illness threat, costs and barriers to action, self-efficacy and value of reduced threat. A grounded theory approach was adopted, with concurrent data collection and analysis and adaptations made to the discussion guide in line with emerging themes (Charmaz K. Constructing Grounded Theory. London: Sage, 2006). Results Many people felt relatively powerless to improve their ongoing health-related quality of life, because the perceived threats to it posed by their asthma were closely matched by perceived threats of treatment side-effects. Coping strategies to improve quality of life were therefore often targeted at social interactions, rather than improving asthma control. The revised health belief model appeared to be relevant to people affected by severe asthma. Conclusions Social support for people with severe asthma may facilitate improved quality of life and interventions that deliver this should be investigated. [ABSTRACT FROM AUTHOR]

Background: Critical care beds are a limited resource, yet research indicates that recommendations for postoperative critical care admission based on patient-level risk stratification are not followed. It is unclear how prioritisation decisions are made in real-world settings and the effect of this prioritisation on outcomes., Methods: This was a prespecified analysis of an observational cohort study of adult patients undergoing inpatient surgery, conducted in 274 hospitals across the UK and Australasia during 2017. The primary outcome was postoperative morbidity at day 7. Logistic regression models were used to evaluate the relationship between critical care admission and patient and health system factors. The causal effect of critical care admission on outcome was estimated using variation in critical care occupancy as a natural experiment in an instrumental variable analysis., Results: A total of 19,491 patients from 248 hospitals were eligible for analysis, of whom 2107 were directly admitted to critical care postoperatively. Postoperative morbidity occurred in 2829/19,491 (15%) patients. Increasing surgical risk was associated with critical care admission, as was increased availability of critical care beds (odds ratio (95%CI) 1.04 (1.01-1.06), p = 0.002) per available bed; however, the probability of admission varied significantly between hospitals (median odds ratio 3.05). There was no evidence of a difference in postoperative morbidity with critical care admission (odds ratio (95%CI) 0.91 (0.57-1.45), p = 0.710)., Discussion: Postoperative critical care admission is variable and related to bed availability. Statistical methods that adjust for unobserved confounding lowered the estimates of harm previously reported to have been associated with postoperative critical care admission. Our findings provide a rationale for a clinical trial which would evaluate any potential benefits for postoperative critical care admission for patients in whom there is no absolute indication for admission., (© 2024 The Author(s). Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Objectives: Despite reported psychological hazards of information technology (IT) work, studies of diagnosed mental health conditions in IT workers are lacking. We investigated self-reported mental health outcomes and incident anxiety/depression in IT workers compared to others in employment in a large population-based cohort., Methods: We evaluated self-reported mental health outcomes in the UK Biobank cohort and incident diagnosed anxiety/depression through health record linkage. We used logistic regression and Cox models to compare the risks of prevalent and incident anxiety/depression among IT workers with all other employed participants. Furthermore, we compared outcomes within IT worker subgroups, and between these subgroups and other similar occupations within their major Standard Occupational Classification (SOC) group., Results: Of 112 399 participants analyzed, 4093 (3.6%) were IT workers. At baseline, IT workers had a reduced odds (OR = 0.66, 95%CI: 0.52-0.85) of anxiety/depression symptoms and were less likely (OR = 0.87, 95%CI: 0.83-0.91) to have ever attended their GP for anxiety/depression, compared to all other employed participants, after adjustment for confounders. The IT technician subgroup were more likely (OR = 1.22, 95%CI: 1.07-1.40) to have previously seen their GP or a psychiatrist (OR = 1.31, 95%CI: 1.06-1.62) for anxiety/depression than their SOC counterparts. IT workers had lower incident anxiety/depression (HR = 0.84, 95%CI 0.77-0.93) compared to all other employed participants, after adjustment for confounders., Conclusions: Our findings from this, the first longitudinal study of IT worker mental health, set the benchmark in our understanding of the mental health of this growing workforce and identification of high-risk groups. This will have important implications for targeting mental health workplace interventions., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Background: There are concerns that COVID-19 mitigation measures, including the 'lockdown', may have unintended health consequences. We examined trends in mental health and health behaviours in the UK before and during the initial phase of the COVID-19 lockdown and differences across population subgroups., Methods: Repeated cross-sectional and longitudinal analysis of the UK Household Longitudinal Study, including representative samples of over 27,000 adults (aged 18+) interviewed in four survey waves between 2015 and 2020. A total of 9748 adults had complete data for longitudinal analyses. Outcomes included psychological distress (General Health Questionnaire-12), loneliness, current cigarette smoking, use of e-cigarettes and alcohol consumption. Cross-sectional prevalence estimates were calculated and multilevel Poisson regression assessed associations between time period and the outcomes of interest, as well as differential associations by age, gender, education level and ethnicity., Results: Psychological distress increased 1 month into lockdown with the prevalence rising from 19.4% (95% CI 18.7% to 20.1%) in 2017-2019 to 30.6% (95% CI 29.1% to 32.3%) in April 2020 (RR=1.3, 95% CI 1.2 to 1.4). Groups most adversely affected included women, young adults, people from an Asian background and those who were degree educated. Loneliness remained stable overall (RR=0.9, 95% CI 0.6 to 1.5). Smoking declined (RR=0.9, 95% CI=0.8,1.0) and the proportion of people drinking four or more times per week increased (RR=1.4, 95% CI 1.3 to 1.5), as did binge drinking (RR=1.5, 95% CI 1.3 to 1.7)., Conclusions: Psychological distress increased 1 month into lockdown, particularly among women and young adults. Smoking declined, but adverse alcohol use generally increased. Effective measures are required to mitigate negative impacts on health., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Preoperative risk prediction is important for guiding clinical decision-making and resource allocation. Clinicians frequently rely solely on their own clinical judgement for risk prediction rather than objective measures. We aimed to compare the accuracy of freely available objective surgical risk tools with subjective clinical assessment in predicting 30-day mortality., Methods and Findings: We conducted a prospective observational study in 274 hospitals in the United Kingdom (UK), Australia, and New Zealand. For 1 week in 2017, prospective risk, surgical, and outcome data were collected on all adults aged 18 years and over undergoing surgery requiring at least a 1-night stay in hospital. Recruitment bias was avoided through an ethical waiver to patient consent; a mixture of rural, urban, district, and university hospitals participated. We compared subjective assessment with 3 previously published, open-access objective risk tools for predicting 30-day mortality: the Portsmouth-Physiology and Operative Severity Score for the enUmeration of Mortality (P-POSSUM), Surgical Risk Scale (SRS), and Surgical Outcome Risk Tool (SORT). We then developed a logistic regression model combining subjective assessment and the best objective tool and compared its performance to each constituent method alone. We included 22,631 patients in the study: 52.8% were female, median age was 62 years (interquartile range [IQR] 46 to 73 years), median postoperative length of stay was 3 days (IQR 1 to 6), and inpatient 30-day mortality was 1.4%. Clinicians used subjective assessment alone in 88.7% of cases. All methods overpredicted risk, but visual inspection of plots showed the SORT to have the best calibration. The SORT demonstrated the best discrimination of the objective tools (SORT Area Under Receiver Operating Characteristic curve [AUROC] = 0.90, 95% confidence interval [CI]: 0.88-0.92; P-POSSUM = 0.89, 95% CI 0.88-0.91; SRS = 0.85, 95% CI 0.82-0.87). Subjective assessment demonstrated good discrimination (AUROC = 0.89, 95% CI: 0.86-0.91) that was not different from the SORT (p = 0.309). Combining subjective assessment and the SORT improved discrimination (bootstrap optimism-corrected AUROC = 0.92, 95% CI: 0.90-0.94) and demonstrated continuous Net Reclassification Improvement (NRI = 0.13, 95% CI: 0.06-0.20, p < 0.001) compared with subjective assessment alone. Decision-curve analysis (DCA) confirmed the superiority of the SORT over other previously published models, and the SORT-clinical judgement model again performed best overall. Our study is limited by the low mortality rate, by the lack of blinding in the 'subjective' risk assessments, and because we only compared the performance of clinical risk scores as opposed to other prediction tools such as exercise testing or frailty assessment., Conclusions: In this study, we observed that the combination of subjective assessment with a parsimonious risk model improved perioperative risk estimation. This may be of value in helping clinicians allocate finite resources such as critical care and to support patient involvement in clinical decision-making., Competing Interests: The authors have declared that no competing interests exist.

Background: We aimed to estimate the causal effect of health conditions and risk factors on social and socioeconomic outcomes in UK Biobank. Evidence on socioeconomic impacts is important to understand because it can help governments, policy makers and decision makers allocate resources efficiently and effectively., Methods: We used Mendelian randomization to estimate the causal effects of eight health conditions (asthma, breast cancer, coronary heart disease, depression, eczema, migraine, osteoarthritis, type 2 diabetes) and five health risk factors [alcohol intake, body mass index (BMI), cholesterol, systolic blood pressure, smoking] on 19 social and socioeconomic outcomes in 336 997 men and women of White British ancestry in UK Biobank, aged between 39 and 72 years. Outcomes included annual household income, employment, deprivation [measured by the Townsend deprivation index (TDI)], degree-level education, happiness, loneliness and 13 other social and socioeconomic outcomes., Results: Results suggested that BMI, smoking and alcohol intake affect many socioeconomic outcomes. For example, smoking was estimated to reduce household income [mean difference = -£22 838, 95% confidence interval (CI): -£31 354 to -£14 321] and the chance of owning accommodation [absolute percentage change (APC) = -20.8%, 95% CI: -28.2% to -13.4%], of being satisfied with health (APC = -35.4%, 95% CI: -51.2% to -19.5%) and of obtaining a university degree (APC = -65.9%, 95% CI: -81.4% to -50.4%), while also increasing deprivation (mean difference in TDI = 1.73, 95% CI: 1.02 to 2.44, approximately 216% of a decile of TDI). There was evidence that asthma decreased household income, the chance of obtaining a university degree and the chance of cohabiting, and migraine reduced the chance of having a weekly leisure or social activity, especially in men. For other associations, estimates were null., Conclusions: Higher BMI, alcohol intake and smoking were all estimated to adversely affect multiple social and socioeconomic outcomes. Effects were not detected between health conditions and socioeconomic outcomes using Mendelian randomization, with the exceptions of depression, asthma and migraines. This may reflect true null associations, selection bias given the relative health and age of participants in UK Biobank, and/or lack of power to detect effects., (© The Author(s) 2020. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objectives: This project explored the deployment of pharmacy assistants to inpatient wards in a new role as 'medicines assistants' (MA)., Methods: Ward-based MAs were introduced to six wards across two UK hospitals to support medicines administration. Each 30-bed ward delivered acute inpatient services with MAs supporting typical nursing medication administration rounds to 15 patients. Data were collected using activity diaries, observations, clinical audit and semistructured interviews with pharmacy assistants, pharmacy technicians, clinical pharmacists, nurses, ward managers and pharmacy managers. Thematic analysis, descriptive statistics and the Mann-Whitney U test were used to analyse qualitative and quantitative data, respectively., Results: MAs were able to act as a point of contact between the ward and the pharmacy department and were perceived to save nursing time. A statistically significant reduction in the length of time to complete morning medication administration to 15 patients was observed (mean 74.5 vs 60.8 min per round, p<0.05). On average, 17.4 hours of medicines-related activity per ward per week was carried out by MAs rather than by nursing staff. Participants identified broader training and clarity was needed in relation to the accountability and governance of patient-facing roles., Conclusion: Pharmacy assistants deployed as MAs can contribute to saving nursing time and bridge the gap between nursing and pharmacy professionals., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Ivacaftor is the first in a class of drugs, CFTR modulators, that target the underlying defect in cystic fibrosis (CF). This long-term observational safety study evaluated CF disease progression in patients treated with ivacaftor in a real-world setting for up to 5 years., Methods: Data from existing US and UK CF patient registries were used to assess longitudinal patterns in lung function, nutritional status, pulmonary exacerbations and hospitalizations, CF-related diabetes (CFRD), and Pseudomonas aeruginosa in ivacaftor-treated vs untreated comparator cohorts matched by age, sex, and disease severity., Results: US analyses included 635 ivacaftor-treated patients and 1874 comparators followed for 5 years from year 1 of market availability (2012-2016). Evaluation of outcome patterns from pretreatment baseline (2011) through year 5 (2016), showed that relative to comparators, ivacaftor-treated patients had better preserved lung function (mean change in percent predicted FEV 1 , -0.7 percentage points with ivacaftor vs -8.3 percentage points in comparators) and improved nutritional status (mean body mass index change +2.4 kg/m 2 with ivacaftor vs +1.6 kg/m 2 in comparators). US patients treated with ivacaftor had significantly lower frequencies of exacerbations and hospitalizations in each of the 5 years of follow-up relative to pretreatment baseline and comparators. Favorable trends in CFRD and P. aeruginosa prevalence were also observed. Findings from the smaller UK registry were directionally similar to and consistent with US findings., Conclusions: This observational study represents the largest longitudinal analysis of patients treated with ivacaftor in a real-world setting. The findings support disease modification by CFTR modulation with ivacaftor., Competing Interests: Conflict of interest statement All authors received nonfinancial support (assistance with manuscript preparation) from ArticulateScience LLC, which received funding from Vertex Pharmaceuticals. Additional disclosures are as follows: NV, KM, JE, DC, ST, CS, and MH: employee of Vertex Pharmaceuticals and may own stock or stock options in Vertex Pharmaceuticals. MWK: grants, personal fees, and nonfinancial support from Vertex Pharmaceuticals, during the course of the study; grants and nonfinancial support from the Cystic Fibrosis Foundation (CFF); grants, personal fees, and nonfinancial support from Corbus, Laurent, PTC, and Savara; personal fees and nonfinancial support from Chiesi, Celtaxsys, Genentech, and Merck; personal fees from Albumedix, Anthera, Ionis, Paranta, Protalix, and Santhera outside the submitted work. GSS: grants and personal fees from Vertex Pharmaceuticals outside the submitted work. AE and BCM: other support from several pharmaceutical companies during the conduct of the study (The CFF has entered into therapeutic development award agreements and licensing agreements to assist with the development of CFTR modulators that may result in intellectual property rights, royalties and other fees provided to CFF by various pharmaceutical companies). SCC: service agreement between Vertex Pharmaceuticals and Cystic Fibrosis Services Limited for statistical analysis. DB: member of the Steering Committee of the UK CF Registry, which provided data for this study., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To explore how prolonged hospitalisation of a child with a neurological condition influences the dietary habits of parents, taking account of their attitudes and perceptions of this experience., Design: Qualitative study using semi-structured interviews and inductive thematic analysis., Subjects: Fifteen parents of children (aged 2-16 years) with a neurological condition resulting in prolonged periods of hospitalisation were recruited., Results: Mothers (n=13) and fathers (n=2) who were interviewed experienced frequent hospital visits brought about by their child's condition, or associated medical complications. Dietary habits of parents were affected throughout their time in hospital. Three key themes were identified relating to how hospitalisation influenced this: (1) access to food, (2) emotional and physical well-being and (3) impact on eating patterns and food choice., Conclusions: Findings from this study suggest that parents in these circumstances need to be better supported within the hospital setting as a number of barriers exist when it comes to accessing food in hospital and making healthy food choices. Additionally, having a child in hospital has a considerable effect on a parent's emotional well-being, which further impacts on their dietary habits. The long-term physical and mental health implications of this may influence their ability to care for the sick child., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The 'GP check' at 6-8 weeks forms part of the selective surveillance system for developmental dysplasia of the hip (DDH) in the UK. It is imperative to pick up DDH within the first months of life to allow for non-invasive treatment and the avoidance of surgery. We aim to investigate the effectiveness of hip examination at 6-8 weeks., Methods: This is a longitudinal observational study including all infants born in our region in the 5 years following 2006. Early presentation was defined as diagnosis within 14 weeks of birth and late presentation after 14 weeks. Treatment records for early and late DDH as well as referrals for ultrasound (US) following examination at 6-8 weeks were analysed. Attendance of the examination at 6-8 weeks in those patients who went on to present with a late DDH was also analysed., Results: 23 112 live births occurred during the study period. There were 141 confirmed cases of DDH. 400 referrals for US were received following examination at 6-8 weeks; 6 of these had a positive finding of DDH. 27 patients presented after 14 weeks and were classified as late presentations. 25 of these patients had attended examination at 6-8 weeks and no abnormality had been identified., Conclusions: The sensitivity of examination at 6-8 weeks was only 19.4%, its specificity was 98% and it had a positive predictive value of 1.5%. For many years the check at 6-8 weeks has been thought of as a means to identify those children not identified as neonates; however, we found that four out of five children with DDH were not identified by the check at 6-8 weeks. Unfortunately, we conclude that the presumed safety net of the examination in its current form is not reliable., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Decisions to admit high-risk postoperative patients to critical care may be affected by resource availability. We aimed to quantify adult ICU/high-dependency unit (ICU/HDU) capacity in hospitals from the UK, Australia, and New Zealand (NZ), and to identify and describe additional 'high-acuity' beds capable of managing high-risk patients outside the ICU/HDU environment., Methods: We used a modified Delphi consensus method to design a survey that was disseminated via investigator networks in the UK, Australia, and NZ. Hospital- and ward-level data were collected, including bed numbers, tertiary services offered, presence of an emergency department, ward staffing levels, and the availability of critical care facilities., Results: We received responses from 257 UK (response rate: 97.7%), 35 Australian (response rate: 32.7%), and 17 NZ (response rate: 94.4%) hospitals (total 309). Of these hospitals, 91.6% reported on-site ICU or HDU facilities. UK hospitals reported fewer critical care beds per 100 hospital beds (median=2.7) compared with Australia (median=3.7) and NZ (median=3.5). Additionally, 31.1% of hospitals reported having high-acuity beds to which high-risk patients were admitted for postoperative management, in addition to standard ICU/HDU facilities. The estimated numbers of critical care beds per 100 000 population were 9.3, 14.1, and 9.1 in the UK, Australia, and NZ, respectively. The estimated per capita high-acuity bed capacities per 100 000 population were 1.2, 3.8, and 6.4 in the UK, Australia, and NZ, respectively., Conclusions: Postoperative critical care resources differ in the UK, Australia, and NZ. High-acuity beds may have developed to augment the capacity to deliver postoperative critical care., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Ivacaftor is generally safe and effective in patients aged 2 years and older who have cystic fibrosis and specific CFTR mutations. We assessed its use in children aged 12 to <24 months., Methods: The ARRIVAL study is a phase 3, single-arm, two-part, multicentre study. Eligible children were aged 12 to <24 months at enrolment and had a confirmed diagnosis of cystic fibrosis and a CFTR gating mutation on at least one allele and could participate in one or both parts of the study. Children received 50 mg (bodyweight 7 to <14 kg) or 75 mg (bodyweight ≥14 to <25 kg) ivacaftor orally every 12 h. In study part A, children received ivacaftor for 3 days plus one morning. In study part B, children received 24 weeks of treatment. Children were enrolled into part A at seven sites in Australia (one site), the UK (one), and the USA (five) and into part B at 13 sites in Australia (two sites), Canada (one), the UK (three), and the USA (seven). Primary endpoints were pharmacokinetics (part A) and safety (parts A and B) in children who received at least one dose of ivacaftor. Secondary endpoints in part B were pharmacokinetics in children who received at least one dose of ivacaftor and absolute change from baseline in sweat chloride concentration. We also explored changes in growth parameters and markers of pancreatic function. This study is registered with ClinicalTrials.gov, number NCT02725567., Findings: Children aged 12 to <24 months were enrolled between Aug 25, 2016, and Nov 1, 2017. Seven children were enrolled in part A, of whom five received 50 mg and two received 75 mg ivacaftor. All completed treatment. Of 19 children enrolled in part B, including one from part A, all received 50 mg ivacaftor and 18 completed treatment (one withdrew because of difficulty with blood draws). All children received at least one dose of ivacaftor. Pharmacokinetics indicated exposure was similar to that in children aged 2 to <6 years and adults. No children discontinued because of adverse events or safety findings. In part A, three (43%) of seven children had treatment-emergent adverse events, all of which were mild and deemed not to be or unlikely to be related to ivacaftor. By 24 weeks in part B, treatment-emergent adverse events had been reported in 18 (95%) of 19 children, of which most were mild or moderate and the most frequent was cough (14 [74%] children). Two children in part B had four serious adverse events: one had constipation (possibly related to ivacaftor), distal intestinal obstruction syndrome, and eczema herpeticum, and one had persistent cough, all needing hospital admission. In five (28%) of 18 children aspartate or alanine aminotransferase concentrations rose to more than three times the upper limit of normal (to more than eight times in two children with concurrent infections). At week 24, the mean absolute change from baseline in sweat chloride concentration was -73·5 (SD 17·5) mmol/L. Growth parameters for age were normal at baseline and at week 24. At week 24, concentrations of faecal elastase-1 had increased and concentrations of immunoreactive trypsinogen had decreased from baseline. Mean serum lipase and amylase were raised at baseline and rapidly decreased after treatment was started., Interpretation: Ivacaftor was generally safe and well tolerated in children aged 12 to <24 months for up to 24 weeks and was associated with rapid and sustained reductions in sweat chloride concentrations. Improvements in biomarkers of pancreatic function suggest that ivacaftor preserves exocrine pancreatic function if started early. The study is continuing in infants younger than 12 months., Funding: Vertex Pharmaceuticals Incorporated., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The use of different limbs for the administration of sequential doses of an intradermal rabies vaccine was shown to result in reduced vaccine immunogenicity. We aimed to assess whether this phenomenon also occurs with routine infant vaccines., Methods: In this open-label, randomised, controlled study, eligible healthy infants 6-12 weeks of age recruited through five clinical trials units (four in the UK and one in Malta) were randomly assigned in a 1:1 ratio to two vaccination groups: consistent limb or alternating limb. Infants in the consistent limb group received the diphtheria-tetanus-acellular pertussis-inactived polio-Haemophilus influenzae type b combined vaccine (DTaP-IPV-Hib) at 2, 3, and 4 months of age, and the pneumococcal conjugate vaccine (PCV13) at 2, 4, and 12 months, all administered to the right leg. Infants in the alternating limb group received DTaP-IPV-Hib in the left leg at 2 months and in the right leg at 3 and 4 months; and PCV13 in the left leg at 2 months, in the right leg at 4 months, and in the left arm at 12 months. All infants in both groups received the combined H influenzae type b and capsular group C Neisseria meningitidis tetanus toxoid conjugate vaccine (Hib-MenC-TT), administered in the left leg at 12 months. Randomisation was achieved by randomly generated codes, with permuted block size of 30, and was stratified by study site. Group allocation was not masked from study staff and parents of participants after enrolment, but group allocation was masked from laboratory staff assessing blood samples. The current study was a prespecified secondary objective of a parent phase 4 trial that assessed the induction of immunity following varying schedules of vaccination with glyco-conjugate capsular group C Neisseria meningitidis (Men C) vaccines in infancy. The objective of the current study was to compare the immunogenicity and reactogenicity of vaccines delivered in either consistent or alternating limbs. Immunogenicity was assessed by comparing serum IgG geometric mean concentrations at 5, 12, 13, and 24 months, analysed per protocol. This study is registered with ClinicalTrials.gov, number NCT01129518., Findings: Between July 5, 2010, and Aug 1, 2013, we enrolled 509 infants and randomly allocated them to the consistent limb group (n=254) or the alternating limb group (n=255). Anti-H influenzae type b anti-polyribosylribitol phosphate IgG geometric mean concentrations were lower in the consistent limb group than in the alternating limb group at 5 months (consistent limb 0·41 μg/mL [95% CI 0·31-0·54] vs alternating limb 0·61 μg/mL [0·45-0·82]; p=0·0268) and at 12 months (0·35 μg/mL [0·28-0·43] vs 0·50 μg/mL [0·40-0·62]; p=0·0136). Anti-tetanus toxoid antibody IgG geometric mean concentrations were lower in the consistent limb group (1·63 IU/mL [95% CI 1·40-1·90]) than in the alternating limb group (2·30 IU/mL [1·97-2·68]) at 13 months (p=0·0008) and at 24 months (0·44 IU/mL [0·37-0·52] vs 0·61 IU/mL [0·51-0·73]; p=0·0074). Anti-pneumococcal IgG geometric mean concentrations were similar between both groups at all timepoints. The proportions of participants who had adverse events did not differ between the two groups., Interpretation: Use of different (alternating) limbs for sequential doses of routine infant vaccines does not reduce, and might enhance, immunogenicity. The underlying mechanism for this finding warrants further research., Funding: NIHR Oxford Biomedical Research Centre and GlaxoSmithKline Biologicals., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Recent studies have shown associations between size and body proportions at birth and health outcomes throughout the life cycle, but there are few data on how neonatal phenotype varies in different populations around the world., Methods: Data from the UK, Finland, India, Sri Lanka, China, DR Congo, Nigeria, and Jamaica (n=22,067) were used to characterize geographical differences in phenotype in singleton, live-born newborns. Measurements included birth weight, placental weight, length, head, chest, abdominal and arm circumferences, and skinfolds., Results: Neonates in Europe were the largest, followed by Jamaica, East Asia (China), then Africa and South Asia. Birth weight varied widely (mean values 2,730-3,570 g), but in contrast, head circumference was similar in all except China (markedly smaller). The main difference in body proportions between populations was the head to length ratio, with small heads relative to length in China and large heads relative to length in South Asia and Africa., Conclusions: These marked geographical differences in neonatal phenotype need to be considered when investigating determinants of fetal growth, and optimal phenotype for short-term and long-term outcomes.

Background: Size and body proportions at birth are partly determined by maternal body composition, but most studies of mother-baby relationships have only considered the effects of maternal height and weight on offspring birth weight, and few have examined the size of effects. Paternal size and body composition also play a role, primarily through the fetal genome, although few studies have investigated relationships with neonatal phenotype., Methods: Data from the UK, Finland, India, Sri Lanka, China, DR Congo, Nigeria and Jamaica were used to investigate the effects of maternal measures (derived at 30 weeks' gestation, n=16,418), and also paternal size (n=3,733) on neonatal phenotype, for singleton, live-born, term births., Results: After accounting for variation in maternal size and shape across populations, differences in neonatal phenotype were markedly reduced. Mother-baby relationships were similar across populations, although some were stronger in developing countries. Maternal height was generally the strongest predictor of neonatal length, maternal head circumference of neonatal head and maternal skinfold thickness of neonatal skinfolds. Relationships with maternal arm muscle area were generally weak. Effects of paternal height and body mass index were weaker than the equivalent maternal measurements in most studies., Conclusions: Differences in maternal body composition account for a large part of the geographical variation in neonatal phenotype. The size of the effects of all maternal measures on neonatal phenotype suggests that nutrition at every stage of the mother's life cycle may influence fetal growth. Further research is needed into father-baby relationships and the genetic mechanisms that influence fetal growth.

Anorexia nervosa (AN) is an enigmatic syndrome affecting approximately 0.1% of the at risk population in the UK which equates to approximately 70000 sufferers. Data from a number of studies have demonstrated the heritability of this disorder, however it is only in the last few years that studies have begun to determine the involvement of particular candidate genes in this genetic predisposition. In the current study we have used classical case-control association analysis to determine whether two highly polymorphic microsatellite markers, located within a 3-cM region of the UCP-2/UCP-3 locus, show involvement of this region of the human genome in the predisposition to AN. Analysis of a cohort of 170 female Caucasian anorexia nervosa sufferers and 150 normal female controls shows evidence of association with the marker D11S911 but not D11S916. Allele 13 of the marker D11S911 is significantly over represented in the anorexia nervosa population suggesting that a mutation in linkage disequilibrium with this locus may form part of the genetic component of AN. Further work is now required to try to reproduce these data in a second independent cohort and to further characterise this region of the human genome.