Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a secondary analysis of the PITCHES trial.

OBJECTIVE: To evaluate whether a particular group of women with intrahepatic cholestasis of pregnancy (ICP), based on their presenting characteristics, would benefit from treatment with ursodeoxycholic acid (UDCA). DESIGN: Secondary analysis of the PITCHES trial (ISRCTN91918806). SETTING: United Kingdom. POPULATION OR SAMPLE: 527 women with ICP. METHODS: Subgroup analyses were performed to determine whether baseline bile acid concentrations or baseline itch scores moderated a woman's response to treatment with UDCA. MAIN OUTCOME MEASURES: Bile acid concentration and itch score. RESULTS: In women with baseline bile acid concentrations less than 40 µmol/l, treatment with UDCA resulted in increased post-randomisation bile acid concentrations (geometric mean ratio 1.19, 95% CI 1.00-1.41, P = 0.048). A test of interaction showed no significance (P = 0.647). A small, clinically insignificant difference was seen in itch response in women with a high baseline itch score (-6.0 mm, 95% CI -11.80 to -0.21, P = 0.042), with a test of interaction not showing significance (P = 0.640). Further subgroup analyses showed no significance. Across all women there was a weak relationship between bile acid concentrations and itch severity. CONCLUSIONS: There was no subgroup of women with ICP in whom a beneficial effect of treatment with UDCA on bile acid concentration or itch score could be identified. This confirms that its routine use in women with this condition for improvement of bile acid concentration or itch score should be reconsidered. TWEETABLE ABSTRACT: PITCHES: No group of women with ICP has been found in whom UDCA reduces bile acid concentrations or pruritus.

An international comparison of retinopathy of prematurity grading performance within the Benefits of Oxygen Saturation Targeting II trials.

PurposeTo investigate whether the observed international differences in retinopathy of prematurity (ROP) treatment rates within the Benefits of Oxygen Saturation Targeting (BOOST) II trials might have been caused by international variation in ROP disease grading.MethodsGroups of BOOST II trial ophthalmologists in UK, Australia, and New Zealand (ANZ), and an international reference group (INT) used a web based system to grade a selection of RetCam images of ROP acquired during the BOOST II UK trial. Rates of decisions to treat, plus disease grading, ROP stage grading, ROP zone grading, inter-observer variation within groups and intra-observer variation within groups were measured.ResultsForty-two eye examinations were graded. UK ophthalmologists diagnosed treat-requiring ROP more frequently than ANZ ophthalmologists, 13.9 (3.49) compared to 9.4 (4.46) eye examinations, P=0.038. UK ophthalmologists diagnosed plus disease more frequently than ANZ ophthalmologists, 14.1 (6.23) compared to 8.5 (3.24) eye examinations, P=0.021. ANZ ophthalmologists diagnosed stage 2 ROP more frequently than UK ophthalmologists, 20.2 (5.8) compared to 12.7 (7.1) eye examinations, P=0.026. There were no other significant differences in the grading of ROP stage or zone. Inter-observer variation was higher within the UK group than within the ANZ group. Intra-observer variation was low in both groups.ConclusionsWe have found evidence of international variation in the diagnosis of treatment-requiring ROP. Improved standardisation of the diagnosis of treatment-requiring ROP is required. Measures might include improved training in the grading of ROP, using an international approach, and further development of ROP image analysis software.

Caesarean section surgical techniques: 3 year follow-up of the CORONIS fractional, factorial, unmasked, randomised controlled trial.

BACKGROUND: The CORONIS trial reported differences in short-term maternal morbidity when comparing five pairs of alternative surgical techniques for caesarean section. Here we report outcomes at 3 years follow-up. METHODS: The CORONIS trial was a pragmatic international 2 × 2 × 2 × 2× 2 non-regular fractional, factorial, unmasked, randomised controlled trial done at 19 sites in Argentina, Chile, Ghana, India, Kenya, Pakistan, and Sudan. Pregnant women were eligible if they were to undergo their first or second caesarean section through a planned transverse abdominal incision. Women were randomly assigned by a secure web-based allocation system to one intervention from each of the three assigned pairs. All investigators, surgeons, and participants were unmasked to treatment allocation. In this follow-up study, we compared outcomes at 3 years following blunt versus sharp abdominal entry, exteriorisation of the uterus for repair versus intra-abdominal repair, single versus double layer closure of the uterus, closure versus non-closure of the peritoneum, and chromic catgut versus polyglactin-910 for uterine repair. Outcomes included pelvic pain; deep dyspareunia; hysterectomy and outcomes of subsequent pregnancies. Outcomes were assessed masked to the original trial allocation. This trial is registered with the Current Controlled Trials registry, number ISRCTN31089967. FINDINGS: Between Sept 1, 2011, and Sept 30, 2014, 13,153 (84%) women were followed-up for a mean duration of 3·8 years (SD 0·86). For blunt versus sharp abdominal entry there was no evidence of a difference in risk of abdominal hernias (adjusted RR 0·66; 95% CI 0·39-1·11). We also recorded no evidence of a difference in risk of death or serious morbidity of the children born at the time of trial entry (0·99, 0·83-1·17). For exteriorisation of the uterus versus intra-abdominal repair there was no evidence of a difference in risk of infertility (0·91, 0·71-1·18) or of ectopic pregnancy (0·50, 0·15-1·66). For single versus double layer closure of the uterus there was no evidence of a difference in maternal death (0·78, 0·46-1·32) or a composite of pregnancy complications (1·20, 0·75-1·90). For closure versus non-closure of the peritoneum there was no evidence of a difference in any outcomes relating to symptoms associated with pelvic adhesions such as infertility (0·80, 0·61-1·06). For chromic catgut versus polyglactin-910 sutures there was no evidence of a difference in the main comparisons for adverse pregnancy outcomes in a subsequent pregnancy, such as uterine rupture (3·05, 0·32-29·29). Overall, severe adverse outcomes were uncommon in these settings. INTERPRETATION: Although our study was not powered to detect modest differences in rare but serious events, there was no evidence to favour one technique over another. Other considerations will probably affect clinical practice, such as the time and cost saving of different approaches. FUNDING: UK Medical Research Council and the Department for International Development.

The effect of oxygen saturation targeting on retinal blood vessel growth using retinal image data from the BOOST-II UK Trial.

PURPOSE: Retinopathy of prematurity (ROP) is a disorder of developing retinal blood vessels in preterm infants. The purpose of this nested study was to investigate the effects of higher (91-95%) and lower (85-89%) oxygen saturation (SpO2) targeting on retinal blood vessel growth in preterm infants. METHODS: Retinal blood vessel growth in the higher (91-95%) and lower (85-89%) oxygen saturation (SpO2) targeting groups was compared. Suitable RetCam (Clarity, Pleasanton, CA, USA) images collected in the BOOST-II UK trial were used. The distances between the centre of the optic disc and the ROP ridge in the temporal and nasal retina were measured in pixel units. RESULTS: Images from 38 infants were studied, 20 from the higher SpO2 target group and 18 from the lower SpO2 target group. On average, temporal blood vessels extended further from the optic disc than nasal blood vessels, mean (standard deviation (SD)) 463.39 (55.05) pixels compared with 360.13 (44.47) pixels, respectively, P<0.0001. Temporal blood vessels extended less far from the optic disc in the higher SpO2 target group than in the lower SpO2 target group: mean (SD) 449.83 (56.16) pixels compared with 480.02 (49.94), respectively, P=0.055. Nasal retinal blood vessel measurements were broadly similar in the higher and lower SpO2 target groups; mean (SD) 353.96 (41.95) compared with 370.00 (48.82) pixels, respectively, P=0.38. CONCLUSIONS: Relatively high oxygen saturation targeting (91-95%) was associated with a trend (P=0.055) towards reduced retinal blood vessel growth in this study of preterm infants.

Caesarean section surgical techniques (CORONIS): a fractional, factorial, unmasked, randomised controlled trial.

BACKGROUND: Variations exist in the surgical techniques used for caesarean section and many have not been rigorously assessed in randomised controlled trials. We aimed to assess whether any surgical techniques were associated with improved outcomes for women and babies. METHODS: CORONIS was a pragmatic international 2×2×2×2×2 non-regular fractional, factorial, unmasked, randomised controlled trial that examined five elements of the caesarean section technique in intervention pairs. CORONIS was undertaken at 19 sites in Argentina, Chile, Ghana, India, Kenya, Pakistan, and Sudan. Each site was assigned to three of the five intervention pairs: blunt versus sharp abdominal entry; exteriorisation of the uterus for repair versus intra-abdominal repair; single-layer versus double-layer closure of the uterus; closure versus non-closure of the peritoneum (pelvic and parietal); and chromic catgut versus polyglactin-910 for uterine repair. Pregnant women were eligible if they were to undergo their first or second caesarean section through a planned transverse abdominal incision. Women were randomly assigned by a secure web-based number allocation system to one intervention from each of the three assigned pairs. All investigators, surgeons, and participants were unmasked to treatment allocation. The primary outcome was the composite of death, maternal infectious morbidity, further operative procedures, or blood transfusion (>1 unit) up to the 6-week follow-up visit. Women were analysed in the groups into which they were allocated. The CORONIS Trial is registered with Current Controlled Trials: ISRCTN31089967. FINDINGS: Between May 20, 2007, and Dec 31, 2010, 15 935 women were recruited. There were no statistically significant differences within any of the intervention pairs for the primary outcome: blunt versus sharp entry risk ratio 1·03 (95% CI 0·91-1·17), exterior versus intra-abdominal repair 0·96 (0·84-1·08), single-layer versus double-layer closure 0·96 (0·85-1·08), closure versus non-closure 1·06 (0·94-1·20), and chromic catgut versus polyglactin-910 0·90 (0·78-1·04). 144 serious adverse events were reported, of which 26 were possibly related to the intervention. Most of the reported serious adverse events were known complications of surgery or complications of the reasons for the caesarean section. INTERPRETATION: These findings suggest that any of these surgical techniques is acceptable. However, longer-term follow-up is needed to assess whether the absence of evidence of short-term effects will translate into an absence of long-term effects. FUNDING: UK Medical Research Council and WHO.

Pre-clinical and preliminary dose-finding and safety studies to identify candidate antivenoms for treatment of envenoming by saw-scaled or carpet vipers (Echis ocellatus) in northern Nigeria.

The aim of this study was to identify candidate antivenoms with specific activity against the venom of the saw-scaled or carpet viper (Echis ocellatus) in northern Nigeria, where bites by this species cause great morbidity and mortality but where effective antivenoms have become scarce and unaffordable. Selected antivenoms were destined to be compared by randomised controlled clinical trials (RCTs). Standard pre-clinical neutralisation assays were carried out in rodents. We included two licensed antivenoms of established clinical efficacy and 6 candidate antivenoms. Although 6 of the tested antivenoms showed promising efficacy, all but 3 were excluded from further study because of inadequate pre-clinical efficacy or because they were unavailable or unaffordable for the anticipated RCTs. Median effective doses (ED(50)) of the remaining three candidate antivenoms suggested that the following doses might neutralise the maximum observed venom yield of 24.8 mg (dry weight) of venom milked from captive E. ocellatus: 10 ml of MicroPharm "EchiTAb G" (ET-G) antivenom; 30 ml of Instituto Clodomiro Picado "EchiTAb-Plus-ICP" (ET-Plus) antivenom; 50 ml of VacSera, Cairo "EgyVac" antivenom. A preliminary clinical dose-finding and safety study of these three antivenoms was carried out in 24 patients with incoagulable blood after E. ocellatus bites who were not severely envenomed. A 3+3 dose escalation design was employed. Initial doses of 10 ml ET-G and 30 ml ET-Plus restored blood coagulability in groups of 6 patients with early mild reactions (pruritus only) in not more than one third of them. EgyVac antivenom did not fulfil efficacy or safety criteria in 12 patients. On the basis of these results, ET-G and ET-Plus were selected for comparison in a RCT.

Treatment of asphyxiated newborns with moderate hypothermia in routine clinical practice: how cooling is managed in the UK outside a clinical trial.

BACKGROUND: This is a phase 4 study of infants registered with the UK TOBY Cooling Register from December 2006 to February 2008. The registry was established on completion of enrolLment to the TOBY randomised trial of treatment with whole body hypothermia following perinatal asphyxia at the end of November 2006. METHODS: We collected information about patient characteristics, condition at birth, resuscitation details, severity of encephalopathy, hourly temperature record, clinical complications and outcomes before hospital discharge. RESULTS: 120 infants born at a median of 40 (IQR 38-41) weeks' gestation and weighing a median of 3287 (IQR 2895-3710) g at birth were studied. Cooling was started at a median of 3 h 54 min (IQR 2 h-5 h 32 min) after birth. All but three infants underwent whole body cooling. The mean (SD) rectal temperature from 6 to 72 h of the cooling period was 33.57 degrees C (0.51 degrees C). The daily encephalopathy score fell: median (IQR) 11 (6-15), 9.7 (5-14), 8 (5-13) and 7 (2-12) on days 1-4 after birth, respectively. 51% of the infants established full oral feeding at a median (range) of 9 (4-24) days. 26% of the study infants died. MRI was consistent with hypoxia-ischaemia in most cases. Clinical complications were not considered to be due to hypothermia. CONCLUSION: In the UK, therapeutic hypothermia following perinatal asphyxia is increasingly being provided. The target body temperature is successfully achieved and the clinical complications observed were not attributed to hypothermia. Treatment with hypothermia may have prevented the worsening of the encephalopathy that is commonly observed following asphyxia.

Compression stockings for preventing deep vein thrombosis in airline passengers.

BACKGROUND: Air travel might increase the risk of deep vein thrombosis (DVT). It has been suggested that wearing compression stockings might reduce this risk. OBJECTIVES: To assess the effects of wearing compression stockings versus not wearing them among people travelling on flights lasting at least four hours. SEARCH STRATEGY: We searched the Cochrane Peripheral Vascular Diseases Group's Specialized Register (January 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library, Issue 4, 2005), MEDLINE (January 1966 to November 2005), EMBASE (January 1980 to December 2005) and several other electronic or grey literature sources, detailed in full in the review. The most recent searches were done in January 2006. SELECTION CRITERIA: Randomized trials of compression stockings versus no stockings in passengers on flights lasting at least four hours. Trials in which passengers wore a stocking on one leg but not the other, or those comparing stockings and another intervention were also eligible. DATA COLLECTION AND ANALYSIS: At least two authors independently assessed the quality of each study and extracted data. We sought additional information from trialists. MAIN RESULTS: Ten randomized trials (n = 2856) were included; nine (n = 2821) compared wearing stockings on both legs versus not wearing them, and one (n = 35) compared wearing a stocking on one leg for the outbound flight and on the other leg on the return flight. Of the nine trials, seven included people judged to be at low or medium risk (n = 1548) and two included high risk participants (n = 1273). All flights lasted at least seven hours. Fifty of 2637 participants with follow-up data available in the trials of wearing stockings on both legs had a symptomless DVT; three wore stockings, 47 did not (odds ratio 0.10, 95% confidence interval 0.04 to 0.25, P < 0.00001). There were no symptomless DVTs in three trials. No deaths, pulmonary emboli or symptomatic DVTs were reported. Wearing stockings had a significant impact in reducing oedema (based on six trials). No significant adverse effects were reported. AUTHORS' CONCLUSIONS: Airline passengers similar to those in this review can expect a substantial reduction in the incidence of symptomless DVT and leg oedema if they wear compression stockings. We cannot assess the effect of wearing stockings on death, pulmonary embolus or symptomatic DVT because no such events occurred in these trials. Randomized trials to assess these outcomes would need to include a very large number of people.

Parent satisfaction in a nurse led clinic compared with a paediatric gastroenterology clinic for the management of intractable, functional constipation.

AIMS: To assess parent satisfaction with a nurse led clinic for children with intractable, functional constipation compared with a paediatric gastroenterology outpatient clinic. METHODS: A validated questionnaire covering six separate domains in 48 statements (provision of information, empathy with the patient, technical quality and competence, attitude towards the patient, access to and continuity with the caregiver, and overall satisfaction) was employed. For all outcomes, the data were analysed on an intention-to-treat basis. RESULTS: 90/107 (84%) questionnaires were returned: 40/51 (78%) from the paediatric gastroenterology clinic and 50/56 (89%) from the nurse led clinic. Results indicated a high "total" satisfaction with the clinical care, but these were statistically significantly higher in the nurse led clinic compared with the paediatric gastroenterology clinic (median score 8.7 and 7.3 respectively, out of a maximum score of 10). This difference was consistent across all domains when the scores from those attending the nurse led clinic were compared with those attending the paediatric gastroenterology clinic (information median score 8.7 v 7.5; empathy 9.0 v 7.3; competence 9.1 v 8.0; attitude 8.7 v 7.3; access 8.2 v 6.7). All comparisons were highly statistically significant. CONCLUSION: These results provide firm evidence that parents of children with intractable constipation are satisfied with the care they receive in both the paediatric and nursing clinic setting. Parent satisfaction, however, was significantly higher in those attending the nurse led clinic. This study adds further support to the development of a nurse led service to manage intractable, functional constipation in children.

Nurse management of intractable functional constipation: a randomised controlled trial.

AIMS: To evaluate the effectiveness of a nurse led clinic (NLC) compared with a consultant led paediatric gastroenterology clinic (PGC) in the management of chronic constipation. METHODS: Children (age 1-15 years) with functional constipation were randomised following a detailed medical assessment to follow up in either the NLC or PGC. An escalating algorithm of treatment was used as the basis of management in both the NLC and PGC. Main outcome measures were: time to cure at last visit or later confirmed by telephone; time to cure at last visit; and time to prematurely leaving the study. RESULTS: A total of 102 children were recruited, of whom 52 were randomly assigned to NLC and 50 to PGC. Outcome assessment showed that 34 children in the NLC and 25 children in the PGC were confirmed cured at their last visit or later confirmed by telephone. The median time to cure was 18.0 months in the NLC and 23.2 months in the PGC. The probability of being cured was estimated as 33% higher in the NLC compared to PGC (hazard ratio 1.33). Attending the NLC hastened time to cure by an estimated 18.4%. CONCLUSION: Children who attend an NLC are equally as, if not more likely to be cured of intractable constipation, than those attending a PGC and on average their cure will occur sooner. Results suggest that an NLC can significantly improve follow up for children with intractable constipation and highlight the important role for clinic nurse specialists in management of children with gastrointestinal disease.

An investigation of risk factors for symptomatic osteoarthritis of the knee in women using a life course approach.

STUDY OBJECTIVE: To explore risk factors for symptomatic knee osteoarthritis (OAK) in women, which included wearing high heeled shoes. DESIGN: Matched case-control study. Exposure information obtained by interview, included details about past footwear. Self reported weight and height data obtained representing when women left school, were aged 36-40 and were aged 51-55. Regular work activities (including periods when homemaker or carer), smoking, and hormone related data gathered using a life-grid. SETTING: Interviews in participants' homes. Cases identified from orthopaedic hospital surgical waiting list, controls identified by general practitioners (GPs) PARTICIPANTS: Women aged 50 to 70 years. Cases awaiting knee replacement surgery. Controls, who had no past knee surgery and no knee pain in the past three years, were matched for age and GP. Altogether 111 eligible women were interviewed (29 cases, 82 controls). MAIN RESULTS: Univariate analyses identified several significant associations with OAK including past knee injury, arthritis of the feet, heavy smoking, being overweight (BMI 25 or above) and various occupational activities. Virtually all measures of high heeled shoes use were associated with reduced risk of OAK, although none of these findings were statistically significant. In multivariate analysis only BMI 25 or above at age 36-40 remained significantly associated with OAK (OR 36.4, 95% CI 3.07 to 432, p=0.004), although weak evidence suggested certain occupational activities might increase risk. Weight gain in early adult life was particularly pronounced among cases. CONCLUSIONS: Being overweight before the age of 40 considerably increased the risk of subsequent symptomatic OAK in women. Wearing high heeled shoes did not.

A mobile-bearing total knee prosthesis compared with a fixed-bearing prosthesis. A multicentre single-blind randomised controlled trial.

Before proceeding to longer-term studies, we have studied the early clinical results of a new mobile-bearing total knee prosthesis in comparison with an established fixed-bearing device. Patients requiring bilateral knee replacement consented to have their operations under one anaesthetic using one of each prosthesis. They also agreed to accept the random choice of knee (right or left) and to remain ignorant as to which side had which implant. Outcomes were measured using the American Knee Society Score (AKSS), the Oxford Knee Score (OKS), and determination of the range of movement and pain scores before and at one year after operation. Preoperatively, there was no systematic difference between the right and left knees. One patient died in the perioperative period and one mobile-bearing prosthesis required early revision for dislocation of the meniscal component. At one year the mean AKSS, OKS and pain scores for the new device were slightly better (p < 0.025) than those for the fixed-bearing device. There was no difference in the range of movement. We believe that this is the first controlled, blinded trial to compare early function of a new knee prosthesis with that of a standard implant. It demonstrates a small but significant clinical advantage for the mobile-bearing design.

Impact of feeding problems on nutritional intake and growth: Oxford Feeding Study II.

Poor nutritional status and growth failure are common in children with cerebral palsy (CP). The aim of this study was to assess, within a subgroup of a large and clearly defined population of children with disabilities, the impact of feeding difficulties on (1) the quality (micronutrient intake) and quantity (macronutrient intake) of their diet and (2) their growth. One hundred children with disabilities (40 females, 60 males; mean age 9 years, SD 2 years 5 months; range 4 years 6 months to 13 years 7 months) underwent a detailed dietetic analysis and a comprehensive anthropometric assessment. Diagnostic categories of disability were: CP (n=90); global developmental delay (n=3); Marfan syndrome (n=1); intractable epilepsy (n=2); agenesis of the corpus callosum (n=2); methyl malonic aciduria (n=1); and congenital rubella (n=1). Neurological impairment was classified according to difficulty with mobility which was graded as mild (little or no difficulty walking), moderate (difficulty walking but does not need aids or a helper), and severe (needs aids and/or a helper or cannot walk). Results confirmed the significant impact of neurological impairment in children on body growth and nutritional status becoming worse in those with a greater degree of motor impairment. The major nutritional deficit was in energy intake, with only one fifth reportedly regularly achieving over 100% estimated average requirement (EAR), whilst micronutrient intake was less markedly impaired and protein intake was normal in this group (96% above EAR). Many children with neurological impairment would benefit from individual nutritional assessment and management as part of their overall care.

Effect of death of Diana, princess of Wales on suicide and deliberate self-harm.

BACKGROUND: The death of the Princess of Wales in 1997 was followed by widespread public mourning. Such major events may influence suicidal behaviour. AIMS: To assess the impact of the Princess's death on suicide and deliberate self-harm (DSH). METHOD: Analysis, using Poisson regression, of the number of suicides and open verdicts ('suicides') in England and Wales following the Princess's death compared to the 3 months beforehand, and the equivalent periods in 1992-1996. Similar analysis on DSH presentations to a general hospital. RESULTS: Suicides increased during the month following the Princess's funeral (+17.4%). This was particularly marked in females (+33.7%), especially those aged 25-44 years (+45.1%). Suicides did not fall in the week between the death and the funeral. Presentations for DSH increased significantly during the week following the death (+44.3%), especially in females (+65.1%). Examination of case notes suggested that the influence of the death was largely through amplification of personal losses or exacerbation of existing distress. CONCLUSIONS: The death of a major public figure can influence rates of suicidal behaviour. For DSH, the impact may be immediate, but for suicide it may be delayed.

Obstetric complications and schizophrenia. Two case-control studies based on structured obstetric records.

BACKGROUND: Most previous case-control studies of obstetric complications in schizophrenia have been small scale and many have relied on retrospective information. AIMS: To determine which obstetric complications are more common in probands with schizophrenia than matched controls. METHOD: Two hundred and ninety-six probands with an in-patient diagnosis of schizophrenia who had been born in Scotland in 1971-74, and a further 156 born in 1975-78, were closely matched with controls and the incidence of obstetric complications in the two compared using obstetric data recorded in a set format shortly after birth. RESULTS: Not a single complication of pregnancy or delivery was significantly more common in the probands with schizophrenia than the controls in the 1971-74 birth cohort and only emergency Caesarean section and labour lasting over 12 hours were significantly more common in the schizophrenia probands in the 1975-78 cohort. CONCLUSION: The evidence that schizophrenia is associated with a raised incidence of obstetric complications is weaker than has recently been assumed.

Obstetric complications and affective psychoses. Two case-control studies based on structured obstetric records.

BACKGROUND: Unlike schizophrenia, little interest has been taken in the incidence of obstetric complications in affective psychoses. AIMS: To find out whether obstetric complications are more common in affective psychoses than matched controls. METHOD: Two hundred and seventeen probands with an in-patient diagnosis of affective psychosis who had been born in Scotland in 1971-74, and a further 84 born in 1975-78, were closely matched with controls and the incidence of obstetric complications in the two compared using obstetric data recorded in a set format shortly after birth. RESULTS: Abnormal presentation of the foetus was the only complication significantly more common in the affective probands in the 1971-74 birth cohort and artificial rupture of the membranes was the only event more common in the probands in the 1975-78 cohort. Both are probably chance findings. CONCLUSION: It is unlikely that the incidence of obstetric complications is raised in people with affective psychoses of early onset.

Pre- and perinatal risk factors for childhood leukaemia and other malignancies: a Scottish case control study.

A case control study of Scottish children aimed to identify risk factors for leukaemia and other cancers operating in the prenatal environment, during delivery and neonatally. Cases (0-14 years) were age-and sex- matched to two population-based controls and details abstracted from the mother's hospital obstetric notes. Analyses of 144 leukaemias (124 acute lymphoblastic leukaemias (ALL)), 45 lymphomas, 75 central nervous system (CNS) tumours and 126 'other solid tumours' were conducted using conditional logistic regression. The presence of a neonatal infection significantly reduced the risk of ALL (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26-0.95), particularly in 0- to 4-year-olds. Positive swab tests confirmed 47% of ALL cases with any infection and 46% of controls. This is consistent with the hypothesis that early exposure to infections may reduce the risk of childhood ALL. Asphyxia at birth significantly increased the risk of leukaemia, which was accounted for by ALL. For the 'other solid tumours' higher levels of maternal education were inversely associated with risk (OR 0.59, 95% CI 0.37-0.94) but positively associated with antibiotics (OR 2.16 95% CI 1.10-4.25) and respiratory tract infections (OR 14.1, 95% CI 1.76-113.7) in pregnancy. No obvious plausible patterns of risk were detected either within or across disease subgroups.

Neonatal mortality amongst Scottish preterm singleton births (1985-1994).

OBJECTIVE: To provide a valid estimate of singleton neonatal mortality based on birthweight and gestational age at delivery. DESIGN: Record linkage of maternity data and neonatal mortality data. SETTING: Scotland, UK. POPULATION: All singleton preterm deliveries from 24 to 36 weeks inclusive between 1985 and 1994. MAIN OUTCOME MEASURE: Neonatal death. RESULTS: There were 625,646 liveborn singleton deliveries over the study period, of which 33,912 were preterm (5.4%). The overall neonatal mortality in the preterm group was 41/1000 and the data have been presented by both gestational age and birthweight. The neonatal mortality rate fell with advancing gestation from 795/1000 live births at 24 weeks to 9/1000 live births at 36 weeks and was higher at the extremes of birthweight for a given gestational age. There was a significant increase in the proportion of babies delivered iatrogenically over the study period (chi test for trend P < 0.001). CONCLUSION: This is the largest recent series to consider neonatal mortality using both birthweight and gestational age. These figures will be of use in obstetric management when elective preterm delivery is considered, and for providing prognostic guidance following preterm delivery.

Case-control study of childhood leukaemia and cancer in Scotland: findings for neonatal intramuscular vitamin K.

OBJECTIVE: To test the hypothesis of an association between neonatal intramuscular vitamin K and childhood leukaemia and other cancers. DESIGN: Population based case-control study with data abstracted from hospital records. SETTING: Scotland. SUBJECTS: Children aged 0-14 years resident in Scotland from 1991-4 and diagnosed with leukaemia (150), lymphomas (46), central nervous system tumours (79), a range of other solid tumours (142), and a subset of acute lymphoblastic leukaemia (129). Controls were 777 children matched for age and sex, providing 417 matched sets (360 triplets and 57 pairs) for analysis. MAIN OUTCOME MEASURE: Odds ratios for the risk of childhood leukaemia and cancer and intramuscular vitamin K versus a combined group of oral doses, none, and no record. Results are given for information recorded in medical notes and data supplemented by hospital policy. RESULTS: Odds ratios based on medical record abstractions showed no significant positive association for leukaemias (odds ratio 1.30; 95% confidence interval 0.83 to 2.03), acute lymphoblastic leukaemia (1.21; 0.74 to 1.97), lymphomas (1.06; 0.46 to 2.42), central nervous system tumours (0.74; 0.40 to 1.34), and other solid tumours (0.59; 0.37 to 0.96). There was no association with acute lymphoblastic leukaemia in children aged 1 to 6 years. Imputation of exposure from hospital policy gave similar results. Adjustment for deprivation and type of delivery moved risk estimates closer to unity for all major diagnostic groups. CONCLUSIONS: The observation of an increased risk of childhood leukaemia and cancer associated with intramuscular vitamin K is not confirmed by this independent population based study.

Suicide in the 12 months after discharge from psychiatric inpatient care, Scotland 1968-92.

STUDY OBJECTIVE: To investigate the rate of suicide in the 12 months after discharge from psychiatric hospital and to determine its relationship to age, diagnosis, and period. DESIGN: Cohort study of patients discharged from psychiatric hospital. SETTING: Scotland. PARTICIPANTS: Altogether 159,742 men and 178,271 women, aged 15-84, who were discharged from Scottish psychiatric hospitals during 1968-92. MAIN RESULTS: During the 25 year period, 1212 male patients committed suicide in 198,059 person years at risk (612 per 100,000; 95% confidence interval (CI) 578,647) and 1099 female patients committed suicide in 228,993 person years at risk (480 per 100,000; 95% CI 452, 509). The overall standardised mortality ratio (general population rate = 1) was 27 (95% CI 26, 29) in men and 40 (95% CI 38, 43) in women. There were variations in the suicide rates in relation to age, diagnosis, and period. The ratio of the 1-28 day rate to the rate between days 29 and 365 over the whole study period was 1.7 (95% CI 1.4, 1.9) in men and 1.6 (95% CI 1.3, 1.8) in women. CONCLUSIONS: The variations in the post discharge suicide rate by age, sex, diagnosis, geographical location, and period suggest that there are several risk factors which vary in their distribution. Further study of these may lead to the development of effective interventions.