Louise Linsell

Schizophrenia and Violence: Systematic Review and Meta-Analysis

Seena Fazel and colleagues investigate the association between schizophrenia and other psychoses and violence and violent offending, and show that the increased risk appears to be partly mediated by substance abuse comorbidity.

Perinatal and maternal outcomes by planned place of birth for healthy women with low risk pregnancies: The Birthplace in England national prospective cohort study

Objective To compare perinatal outcomes, maternal outcomes, and interventions in labour by planned place of birth at the start of care in labour for women with low risk pregnancies. Design Prospective cohort study. Setting England: all NHS trusts providing intrapartum care at home, all freestanding midwifery units, all alongside midwifery units (midwife led units on a hospital site with an obstetric unit), and a stratified random sample of obstetric units. Participants 64 538 eligible women with a singleton, term (≥37 weeks gestation), and “booked” pregnancy who gave birth between April 2008 and April 2010. Planned caesarean sections and caesarean sections before the onset of labour and unplanned home births were excluded. Main outcome measure A composite primary outcome of perinatal mortality and intrapartum related neonatal morbidities (stillbirth after start of care in labour, early neonatal death, neonatal encephalopathy, meconium aspiration syndrome, brachial plexus injury, fractured humerus, or fractured clavicle) was used to compare outcomes by planned place of birth at the start of care in labour (at home, freestanding midwifery units, alongside midwifery units, and obstetric units). Results There were 250 primary outcome events and an overall weighted incidence of 4.3 per 1000 births (95% CI 3.3 to 5.5). Overall, there were no significant differences in the adjusted odds of the primary outcome for any of the non-obstetric unit settings compared with obstetric units. For nulliparous women, the odds of the primary outcome were higher for planned home births (adjusted odds ratio 1.75, 95% CI 1.07 to 2.86) but not for either midwifery unit setting. For multiparous women, there were no significant differences in the incidence of the primary outcome by planned place of birth. Interventions during labour were substantially lower in all non-obstetric unit settings. Transfers from non-obstetric unit settings were more frequent for nulliparous women (36% to 45%) than for multiparous women (9% to 13%). Conclusions The results support a policy of offering healthy women with low risk pregnancies a choice of birth setting. Women planning birth in a midwifery unit and multiparous women planning birth at home experience fewer interventions than those planning birth in an obstetric unit with no impact on perinatal outcomes. For nulliparous women, planned home births also have fewer interventions but have poorer perinatal outcomes.

Effects of Hypothermia for Perinatal Asphyxia on Childhood Outcomes

BACKGROUND In the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY), newborns with asphyxial encephalopathy who received hypothermic therapy had improved neurologic outcomes at 18 months of age, but it is uncertain whether such therapy results in longer-term neurocognitive benefits. METHODS We randomly assigned 325 newborns with asphyxial encephalopathy who were born at a gestational age of 36 weeks or more to receive standard care alone (control) or standard care with hypothermia to a rectal temperature of 33 to 34°C for 72 hours within 6 hours after birth. We evaluated the neurocognitive function of these children at 6 to 7 years of age. The primary outcome of this analysis was the frequency of survival with an IQ score of 85 or higher. RESULTS A total of 75 of 145 children (52%) in the hypothermia group versus 52 of 132 (39%) in the control group survived with an IQ score of 85 or more (relative risk, 1.31; P=0.04). The proportions of children who died were similar in the hypothermia group and the control group (29% and 30%, respectively). More children in the hypothermia group than in the control group survived without neurologic abnormalities (65 of 145 [45%] vs. 37 of 132 [28%]; relative risk, 1.60; 95% confidence interval, 1.15 to 2.22). Among survivors, children in the hypothermia group, as compared with those in the control group, had significant reductions in the risk of cerebral palsy (21% vs. 36%, P=0.03) and the risk of moderate or severe disability (22% vs. 37%, P=0.03); they also had significantly better motor-function scores. There was no significant between-group difference in parental assessments of childrens health status and in results on 10 of 11 psychometric tests. CONCLUSIONS Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood. (Funded by the United Kingdom Medical Research Council and others; TOBY ClinicalTrials.gov number, NCT01092637.).

Self-harm in prisons in England and Wales: an epidemiological study of prevalence, risk factors, clustering, and subsequent suicide

Summary Background Self-harm and suicide are common in prisoners, yet robust information on the full extent and characteristics of people at risk of self-harm is scant. Furthermore, understanding how frequently self-harm is followed by suicide, and in which prisoners this progression is most likely to happen, is important. We did a case-control study of all prisoners in England and Wales to ascertain the prevalence of self-harm in this population, associated risk factors, clustering effects, and risk of subsequent suicide after self-harm. Methods Records of self-harm incidents in all prisons in England and Wales were gathered routinely between January, 2004, and December, 2009. We did a case-control comparison of prisoners who self-harmed and those who did not between January, 2006, and December, 2009. We also used a Bayesian approach to look at clustering of people who self-harmed. Prisoners who self-harmed and subsequently died by suicide in prison were compared with other inmates who self-harmed. Findings 139 195 self-harm incidents were recorded in 26 510 individual prisoners between 2004 and 2009; 5–6% of male prisoners and 20–24% of female inmates self-harmed every year. Self-harm rates were more than ten times higher in female prisoners than in male inmates. Repetition of self-harm was common, particularly in women and teenage girls, in whom a subgroup of 102 prisoners accounted for 17 307 episodes. In both sexes, self-harm was associated with younger age, white ethnic origin, prison type, and a life sentence or being unsentenced; in female inmates, committing a violent offence against an individual was also a factor. Substantial evidence was noted of clustering in time and location of prisoners who self-harmed (adjusted intra-class correlation 0·15, 95% CI 0·11–0·18). 109 subsequent suicides in prison were reported in individuals who self-harmed; the risk was higher in those who self-harmed than in the general prison population, and more than half the deaths occurred within a month of self-harm. Risk factors for suicide after self-harm in male prisoners were older age and a previous self-harm incident of high or moderate lethality; in female inmates, a history of more than five self-harm incidents within a year was associated with subsequent suicide. Interpretation The burden of self-harm in prisoners is substantial, particularly in women. Self-harm in prison is associated with subsequent suicide in this setting. Prevention and treatment of self-harm in prisoners is an essential component of suicide prevention in prisons. Funding Wellcome Trust, National Institute for Health Research, National Offender Management Service, and Department of Health.

Breast cancer awareness among older women

The aim of this study was to elicit the level of breast cancer awareness in older women. A cross-sectional study-specific questionnaire survey of 712 British women aged 67–73 years (response rate 83.8%), assessing knowledge of symptoms and risk and confidence to detect a change, was conducted. Over 85% of respondents were aware that a lump was a symptom of breast cancer but knowledge of non-lump symptoms was limited. Knowledge of risk was poor; 50% believed that the lifetime risk of developing breast cancer was less than 1 in 100 women and 75% were not aware that age is a risk factor. Thirty-one percent of women reported low levels of confidence to detect a breast change and 19% rarely or never checked their breasts. Those with fewer educational qualifications had poorer knowledge of symptoms, less awareness of lifetime and age-related risks, but were more likely to check their breasts than more highly educated women. This national survey demonstrates a significant lack of the prerequisite knowledge and confidence to detect a breast change. Raising breast cancer awareness and promoting early presentation among older women is important, as they are more at risk of breast cancer and more likely to delay seeking help with breast cancer symptoms than younger women.

Early or Delayed Enteral Feeding for Preterm Growth-Restricted Infants: A Randomized Trial

BACKGROUND: Growth-restricted preterm infants are at increased risk of developing necrotizing enterocolitis (NEC) and initiation of enteral feeding is frequently delayed. There is no evidence that this delay is beneficial and it might further compromise nutrition and growth. METHODS: Infants with gestation below 35 weeks, birth weight below the 10th centile, and abnormal antenatal umbilical artery Doppler waveforms were randomly allocated to commence enteral feeds “early,” on day 2 after birth, or “late,” on day 6. Gradual increase in feeds was guided by a “feeding prescription” with rate of increase the same for both groups. Primary outcomes were time to achieve full enteral feeding sustained for 72 hours and NEC. RESULTS: Four hundred four infants were randomly assigned from 54 hospitals in the United Kingdom and Ireland (202 to each group). Median gestation was 31 weeks. Full, sustained, enteral feeding was achieved at an earlier age in the early group: median age was 18 days compared with 21 days (hazard ratio: 1.36 [95% confidence interval: 1.11–1.67]). There was no evidence of a difference in the incidence of NEC: 18% in the early group and 15% in the late group (relative risk: 1.2 [95% confidence interval: 0.77–1.87]). Early feeding resulted in shorter duration of parenteral nutrition and high-dependency care, lower incidence of cholestatic jaundice, and improved SD score for weight at discharge. CONCLUSIONS: Early introduction of enteral feeds in growth-restricted preterm infants results in earlier achievement of full enteral feeding and does not appear to increase the risk of NEC.

Prognostic Factors for Poor Cognitive Development in Children Born Very Preterm or With Very Low Birth Weight: A Systematic Review.

IMPORTANCE Cognitive delay is the most common form of impairment among children born very preterm (VPT) at 32 weeks or less or with very low birth weight (VLBW) of 1250 g or less. It is important to identify factors that are robust predictors of long-term outcome because the ability to predict future prognosis will assist in health care and educational service planning and provision. OBJECTIVE To identify prognostic factors for poor cognitive development in children born VPT or with VLBW. EVIDENCE REVIEW A systematic review was conducted using MEDLINE, EMBASE, and PyscINFO databases to identify studies published between January 1, 1990, and June 1, 2014, reporting multivariable prediction models for neurodevelopment in VPT or VLBW children. Thirty-one studies comprising 98 risk factor models for cognitive outcome were identified. Two independent reviewers extracted key information on study design, outcome definition, risk factor selection, model development, and reporting and conducted a risk-of-bias assessment. FINDINGS There was evidence that male sex, nonwhite race/ethnicity, lower level of parental education, and lower birth weight were predictive of global cognitive impairment in children younger than 5 years. In older children, only the influence of parental education was sustained. Male sex was also predictive of language impairment in early infancy, but not in middle childhood. Gestational age was a poor predictor of cognitive outcome, probably because of a reduced discriminatory power in cohorts restricted to a narrow gestational age range. The prognostic value of neonatal brain injury was unclear; however, studies adopted mixed strategies for managing children with physical or neurosensory disability. CONCLUSIONS AND RELEVANCE The influence of perinatal risk factors on cognitive development of VPT or VLBW children appears to diminish over time as environmental factors become more important. It is difficult to isolate cognitive outcomes from motor and neurosensory impairment, and the strategy for dealing with untestable children has implications for risk prediction.

Implementation and Conduct of Therapeutic Hypothermia for Perinatal Asphyxial Encephalopathy in the UK – Analysis of National Data

Background Delay in implementing new treatments into clinical practice results in considerable health and economic opportunity costs. Data from the UK TOBY Cooling Register provides the opportunity to examine how one new effective therapy for newborn infants suspected of suffering asphyxial encephalopathy – therapeutic hypothermia- was implemented in the UK. Methodology/Principal Findings We analysed returned data forms from inception of the Register in December 2006 to the end of July 2011. Data forms were received for 1384 (67%) of the 2069 infants registered. The monthly rate of notifications increased from median {IQR} 18 {15–31} to 33 {30–39} after the announcement of the results of the recent TOBY trial, and to 50 {36–55} after their publication. This rate further increased to 70 {64–83} following official endorsement of the therapy, and is now close to the expected numbers of eligible infants. Cooling was started at 3.3 {1.5–5.5} hours after birth and the time taken to achieve the target 33–34°C rectal temperature was 1 {0–3} hours. The rectal temperature was in the target range in 83% of measurements. From 2006 to 2011 there was evidence of extension of treatment to slightly less severely affected infants. 278 of 1362 (20%) infants died at 2.9 {1.4–4.1} days of age. The rates of death fell slightly over the period of the Register and, at two years of age cerebral palsy was diagnosed in 22% of infants; half of these were spastic bilateral. Factors independently associated with adverse outcome were clinical seizures prior to cooling (p<0.001) and severely abnormal amplitude integrated EEG (p<0.001). Conclusions/Significance Therapeutic hypothermia was implemented appropriately within the UK, with significant benefit to patients and the health economy. This may be due in part to participation by neonatal units in clinical trials, the establishment of the national Register, and its endorsement by advisory bodies.

Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial

Summary Background Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. Methods Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36–43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. Findings The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference −0·01, 95% CI −0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. Interpretation Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia. Funding UK Medical Research Council.

Geographical distribution of variant CJD in the UK (excluding Northern Ireland)

BACKGROUND The agent that causes variant Creutzfeldt-Jakob disease (variant CJD) is indistinguishable from the causative agent of bovine spongiform encephalopathy (BSE). The transmission route by which human beings are infected has not been established. One hypothesis is that cases of variant CJD have resulted from exposure to the BSE agent via rendering plants involved in the production of meat and bone meal, the main vehicle of the BSE epidemic. METHODS We identified cases of variant CJD through the National CJD Surveillance Unit, and obtained lifetime residential histories of cases by interviewing a relative. The addresses of all rendering plants in the UK (excluding Northern Ireland) in production in 1988 were available from a survey done in that year. We calculated the distance between each cases place of residence on Jan 1, 1988, and the nearest rendering plant from postcode data, and used data from the 1991 UK census to estimate the population living within various distances of rendering plants. We compared the observed number of cases of variant CJD within a particular distance of a rendering plant with the number expected if there is no association between residential proximity to a rendering plant and the risk of developing variant CJD. FINDINGS Up to Aug 31, 1998, 26 cases of variant CJD with onset in the UK (Northern Ireland not included) had been identified. The observed and expected numbers of variant CJD cases living within a specified distance of any rendering plant up to 50 km were almost the same. Two plants in the county of Kent each had four cases within 50 km in 1988, significantly more cases than expected (plant A, 1.04 expected; plant B, 0.74 expected). Multiple significance tests were done, so some tests would be expected to appear significant by chance alone. Computer simulations suggested that the observation of four cases of variant CJD living in an area with a population of 1.5 million (the size of Kent) is not unexpected. INTERPRETATION There is no evidence that people with variant CJD tended to live closer than the population as a whole to rendering plants in the 1980s. The reported cluster of variant CJD cases in Kent is most probably a chance finding.