Randomized controlled pilot trial with ion-exchange water softeners to prevent eczema (SOFTER trial).

BACKGROUND: Observational studies suggest an increased risk of eczema in children living in hard versus soft water areas, and there is, therefore, an interest in knowing whether softening water may prevent eczema. We evaluated the feasibility of a parallel-group assessor-blinded pilot randomized controlled trial to test whether installing a domestic ion-exchange water softener before birth in hard water areas reduces the risk of eczema in infants with a family history of atopy. METHODS: Pregnant women living in hard water areas (>250 mg/L calcium carbonate) in and around London UK, were randomized 1:1 antenatally to either have an ion-exchange water softener installed in their home or not (ie to continue to receive usual domestic hard water). Infants were assessed at birth and followed up for 6 months. The main end-points were around feasibility, the primary end-point being the proportion of eligible families screened who were willing and able to be randomized. Clinical end-points were evaluated including frequency of parent-reported doctor-diagnosed eczema and visible eczema on skin examination. Descriptive analyses were conducted, and no statistical testing was performed as this was a pilot study. RESULTS: One hundred and forty-nine families screened were eligible antenatally and 28% (41/149) could not have a water softener installed due to technical reasons or lack of landlord approval. Eighty of 149 (54%) were randomized, the primary end-point. Two participants withdrew immediately after randomization, leaving 39 participants in each arm (78 total). Attrition was 15% (12/78) by 6 months postpartum. All respondents (n = 69) to the study acceptability questionnaire reported that the study was acceptable. Fifty-six of 708 (7.9%) water samples in the water softener arm were above the hard water threshold of 20 mg/L CaCO3 . At 6 months of age 27/67 infants (40%) developed visible eczema, 12/36 (33%) vs. 15/31 (48%) in the water softener and control groups, respectively, difference -15% (95% CI -38, 8.3%), with most assessments (≥96%) remaining blinded. Similarly, a lower proportion of infants in the water softener arm had parent-reported, doctor-diagnosed eczema by 6 months compared to the control arm, 6/17 (35%) versus 9/19 (47%), difference -12% (95% CI -44, 20%). CONCLUSION: A randomized controlled trial of water softeners for the prevention of atopic eczema in high-risk infants is feasible and acceptable. TRIAL REGISTRATION: NCT03270566 (clinicaltrials.gov).

Cost-Effectiveness Analysis of Stereotactic Ablative Body Radiation Therapy Compared With Surgery and Radiofrequency Ablation in Two Patient Cohorts: Metastatic Liver Cancer and Hepatocellular Carcinoma.

AIMS: To compare the cost-effectiveness of stereotactic ablative body radiation therapy (SABR) with radiofrequency ablation and surgery in adult patients with metastatic liver cancer and hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Two patient cohorts were assessed: liver oligometastases and HCC. For each patient cohort, a decision analytic model was constructed to assess the cost-effectiveness of interventions over a 5-year horizon. A Markov process was embedded in the decision model to simulate the possible prognosis of cancer. Data on transition probabilities, survival, side-effects, quality of life and costs were obtained from published sources and the SABR Commissioning through Evaluation (CtE) scheme. The primary outcome was the incremental cost-effectiveness ratio with respect to quality-adjusted life-years. The robustness of the results was examined in a sensitivity analysis. Analyses were conducted from a National Health Service and Personal Social Services perspective. RESULTS: In the base case analysis, which assumed that all three interventions were associated with the same cancer progression rates and mortality rates, SABR was the most cost-effective intervention for both patient cohorts. This conclusion was sensitive to the cancer progression rate, mortality rate and cost of interventions. Assuming a willingness-to-pay threshold of £20 000 per quality-adjusted life-year, the probability that SABR is cost-effective was 57% and 50% in liver oligometastases and HCC, respectively. CONCLUSIONS: Our results indicate a potential for SABR to be cost-effective for patients with liver oligometastases and HCC. This finding supports further investigation in clinical trials directly comparing SABR with surgery and radiofrequency ablation.

An observational study to compare the utilisation of computed tomography colonography with optical colonoscopy as the first diagnostic imaging tool in patients with suspected colorectal cancer.

AIM: To evaluate the clinical and cost implications of using computed tomography colonography (CTC) compared to optical colonoscopy (OC) as the initial colonic investigation in patients with low-to-intermediate risk of colorectal cancer (CRC). MATERIALS AND METHODS: A non-randomised, prospective single-centre study recruited 180 participants to compare the cost implications of two clinical pathways used in the diagnosis of low-to-intermediate risk of CRC that differ in the initial diagnostic test, either CTC or OC. Costs were compared using generalised linear models (GLM) and combined with quality-adjusted life years (QALYs, based on the EQ-5D-5L) to estimate cost-effectiveness at 6 months post-recruitment. Secondary outcomes assessed access to care and patient satisfaction. RESULTS: Mean (SD, n) cost at 6 months post-recruitment per participant was £991 (£316, n=105) for the OC group and £645 (£607, n=68) for the CTC group, leading to an estimated cost difference of -£370 (95% CI: -£554, -£185, p<0.001). Assuming a £20,000 willingness-to-pay per QALY threshold, there was a 91.4% probability of CTC being cost-effective at month 6. The utilisation of CTC led to improved access to care, with a shorter mean time from referral from primary care to results (6.3 days difference, p=0.005). No differences in patient satisfaction were detected between both groups. CONCLUSION: The utilisation of CTC as the first-line investigation for patients with low-to-intermediate risk of CRC has the potential to release OC capacity, of pivotal importance for patients more likely to benefit from an invasive diagnostic approach.

Longitudinal analysis of the effect of water hardness on atopic eczema: evidence for gene-environment interaction.

BACKGROUND: Several studies have identified an association between water hardness and atopic eczema (AE); however, there is a paucity of longitudinal data in early life. OBJECTIVES: To examine whether water hardness is associated with an increased risk of AE and skin barrier dysfunction in infants and to assess effect modification by filaggrin (FLG) loss-of-function variants. METHODS: We performed a longitudinal analysis of data from infants in the Enquiring About Tolerance (EAT) study, who were enrolled at 3 months and followed up until 36 months of age. RESULTS: Of 1303 infants enrolled in the EAT study, 91·3% (n = 1189) attended the final clinic visit and 94·0% (n = 1225) of participants' families completed the 36-month questionnaire. In total, 761 (58·4%) developed AE by 36 months. There was no overall association between exposure to harder (> 257 mg L-1 CaCO3 ) vs. softer (≤ 257 mg L-1 CaCO3 ) water: adjusted hazard ratio (HR) 1·07, 95% confidence interval (CI) 0·92-1·24. However, there was an increased incidence of AE in infants with FLG mutations exposed to hard water (adjusted HR 2·72, 95% CI 2·03-3·66), and statistically significant interactions between hard water plus FLG and both risk of AE (HR 1·80, 95% CI 1·17-2·78) and transepidermal water loss (0·0081 g m-2 h-1 per mg L-1 CaCO3 , 95% CI 0·00028-0·016). CONCLUSIONS: There is evidence of an interaction between water hardness and FLG mutations in the development of infantile AE.

Epilepsy as a systemic condition: Link with somatic comorbidities.

BACKGROUND: People with epilepsy have more concomitant medical conditions than the general population; these comorbidities play an important role in premature mortality. We sought to generate explanatory hypotheses about the co-occurrence of somatic comorbidities and epilepsy, avoiding causal and treatment-resultant biases. METHODS: We collected clinical, demographic and somatic comorbidity data for 2016 consecutive adults with epilepsy undergoing assessment at a tertiary centre and in 1278 people with epilepsy in the community. Underlying causes of epilepsy were not classed as comorbidities. RESULTS: Somatic comorbidities were more frequent in the referral centre (49%) where people more frequently had active epilepsy than in the community (36%). Consistent risk factors for comorbidities were found in both cohorts. Using multivariable ordinal regression adjusted for age, longer epilepsy duration and an underlying brain lesion were independently associated with a smaller burden of somatic conditions. The treatment burden, measured by the number of drugs to which people were exposed, was not an independent predictor. Shorter epilepsy duration was a predictor for conditions that conceivably harbour significant mortality risks. CONCLUSIONS: Somatic comorbidities do not occur randomly in relation to epilepsy; having more severe epilepsy seems to be a risk factor. Independently from age, the early period after epilepsy onset appears to be at particular risk, although it is not clear whether this relates to an early mortality or to a later decrease in the burden of comorbidities. These results suggest that, for some people, epilepsy should be considered a systemic condition not limited to the CNS.

Randomized clinical trial of comprehensive geriatric assessment and optimization in vascular surgery.

BACKGROUND: Increasing numbers of older patients are undergoing vascular surgery. Inadequate preoperative assessment and optimization may contribute to increased postoperative morbidity and mortality. METHODS: Patients aged at least 65 years scheduled for elective aortic aneurysm repair or lower-limb arterial surgery were enrolled in an RCT of standard preoperative assessment or preoperative comprehensive geriatric assessment and optimization. Randomization was stratified by sex and surgical site (aorta/lower limb). Primary outcome was length of hospital stay. Secondary outcome measures included new medical co-morbidities, postoperative medical or surgical complications, discharge to a higher level of dependency and 30-day readmission rate. RESULTS: A total of 176 patients were included in the final analysis (control 91, intervention 85). Geometric mean length of stay was 5·53 days in the control group and 3·32 days in the intervention group (ratio of geometric means 0·60, 95 per cent c.i. 0·46 to 0·79; P < 0·001). There was a lower incidence of delirium (11 versus 24 per cent; P = 0·018), cardiac complications (8 versus 27 per cent; P = 0·001) and bladder/bowel complications (33 versus 55 per cent; P = 0·003) in the intervention group compared with the control group. Patients in the intervention group were less likely to require discharge to a higher level of dependency (4 of 85 versus 12 of 91; P = 0·051). CONCLUSION: In this study of patients aged 65 years or older undergoing vascular surgery, preoperative comprehensive geriatric assessment was associated with a shorter length of hospital stay. Patients undergoing assessment and optimization had a lower incidence of complications and were less likely to be discharged to a higher level of dependency. Registration number: ISRCTN23142588 (http://www.controlled-trials.com).

How should a district general hospital immunology service screen for anti-nuclear antibodies? An 'in-the-field' audit.

Anti-nuclear antibody (ANA) testing assists in the diagnosis of several immune-mediated disorders. The gold standard method for detection of these antibodies is by indirect immunofluorescence testing on human epidermoid laryngeal carcinoma (HEp-2) cells. However, many laboratories test for these antibodies using solid-phase assays such as enzyme-linked immunosorbent assay (ELISA), which allows for higher throughput testing at reduced cost. In this study, we have audited the performance of a previously established ELISA assay to screen for ANA, making comparison with the gold standard HEp-2 immunofluorescence test. A prospective and unselected sample of 89 consecutive ANA test requests by consultant rheumatologists were evaluated in parallel over a period of 10 months using both tests. ELISA and HEp-2 screening assays yielded 40 (45%) and 72 (81%) positive test results, respectively, demonstrating lack of concordance between test methods. Using standard and clinical samples, it was demonstrated that the ELISA method did not detect several ANA with nucleolar, homogeneous and speckled immunofluorescence patterns. None of these ELISA(NEG) HEp-2(POS) ANA were reactive with a panel of six extractable nuclear antigens or with double-stranded DNA. Nonetheless, 13 of these samples (15%) originated from patients with recognized ANA-associated disease (n = 7) or Raynaud's phenomenon (n = 6). We conclude that ELISA screening may fail to detect clinically relevant ANA that lack defined specificity for antigen.

Estimating dichotomised outcomes in two groups with unequal variances: a distributional approach.

Dichotomisation in medical research is sometimes necessary for decision-making or communication purposes. This practice has been criticised in the case of continuous data, and it has been said that means should be compared instead. However when the two groups have unequal variances, comparing means might not show the whole picture as a particular group with a risk defined by a threshold in an outcome may have been affected differently by an intervention than when there is a simple shift of distribution. A statistically sound method using a distributional approach for the dichotomisation of normally distributed outcomes has been described under the assumption of equal variances. This assumption is not sustainable in some situations, and in this work, we develop the method further to cover the case of unequal variances. Through examples from the literature and our own data, we illustrate the effect of unequal variance on dichotomised estimates and present a validation of the method through simulations.

Modelling the hierarchical structure in datasets with very small clusters: a simulation study to explore the effect of the proportion of clusters when the outcome is continuous.

In cluster-randomised trials, the problem of non-independence within clusters is well known, and appropriate statistical analysis documented. Clusters typically seen in cluster trials are large in size and few in number, whereas datasets of preterm infants incorporate clusters of size two (twins), size three (triplets) and so on, with the majority of infants being in 'clusters' of size one. In such situations, it is unclear whether adjustment for clustering is needed or even possible. In this paper, we compared analyses allowing for clustering (linear mixed model) with analyses ignoring clustering (linear regression). Through simulations based on two real datasets, we explored estimation bias in predictors of a continuous outcome in different size datasets typical of preterm samples, with varying percentages of twins. Overall, the biases for estimated coefficients were similar for linear regression and mixed models, but the standard errors were consistently much less well estimated when using a linear model. Non-convergence was rare but was observed in approximately 5% of mixed models for samples below 200 and percentage of twins 2% or less. We conclude that in datasets with small clusters, mixed models should be the method of choice irrespective of the percentage of twins. If the mixed model does not converge, a linear regression can be fitted, but standard error will be underestimated, and so type I error may be inflated.

Dichotomising continuous data while retaining statistical power using a distributional approach.

Dichotomisation of continuous data is known to be hugely problematic because information is lost, power is reduced and relationships may be obscured or changed. However, not only are differences in means difficult for clinicians to interpret, but thresholds also occur in many areas of medical practice and cannot be ignored. In recognition of both the problems of dichotomisation and the ways in which it may be useful clinically, we have used a distributional approach to derive a difference in proportions with a 95% CI that retains the precision and the power of the CI for the equivalent difference in means. In this way, we propose a dual approach that analyses continuous data using both means and proportions to replace dichotomisation alone and that may be useful in certain situations. We illustrate this work with examples and simulations that show good performance of the parametric approach under standard distributional assumptions from our own research and from the literature.

Premature mortality in refractory partial epilepsy: does surgical treatment make a difference?

BACKGROUND: Epilepsy carries an increased risk of premature death. For some people with intractable focal epilepsy, surgery offers hope for a seizure-free life. The authors aimed to see whether epilepsy surgery influenced mortality in people with intractable epilepsy. METHODS: The authors audited survival status in two cohorts (those who had surgery and those who had presurgical assessment but did not have surgery). RESULTS: There were 40 known deaths in the non-surgical group (3365 person years of follow-up) and 19 in the surgical group (3905 person-years of follow-up). Non-operated patients were 2.4 times (95% CI 1.4 to 4.2) as likely to die as those who had surgery. They were 4.5 times (95% CI 1.9 to 10.9) as likely to die a probable epilepsy-related death. In the surgical group, those with ongoing seizures 1 year after surgery were 4.0 (95% CI 1.2 to 13.7) times as likely to die as those who were seizure-free or who had only simple partial seizures. Time-dependent Cox analysis showed that the yearly outcome group did not significantly affect mortality (HR 1.3, 95% CI 0.9 to 1.8). CONCLUSION: Successful epilepsy surgery was associated with a reduced risk of premature mortality, compared with those with refractory focal epilepsy who did not have surgical treatment. To some extent, the reduced mortality is likely to be conferred by inducing freedom from seizures. It is not certain whether better survival is attributable only to surgery, as treatment decisions were not randomised, and there may be inherent differences between the groups.

To close or not to close? A systematic review and a meta-analysis of peritoneal non-closure and adhesion formation after caesarean section.

Many gynaecologists do not currently close the peritoneum after caesarean section (CS). Recently, several studies examining adhesion formation after repeat CS appear to favour closure of the peritoneum after caesarean section. We performed a systematic review of the current available evidence with regard to the long-term outcome, mainly in terms of adhesion formation after closure versus non-closure of peritoneum during CS. We undertook a literature search between January 1995 and February 2008 using MEDLINE, Pubmed, EMBASE, Cochrane central controlled trials register and Cochrane pregnancy and childbirth group trials register. We also had searched all the references cited in the relevant studies. Both English and non-English language papers were included. Prospective studies which compared peritoneal closure versus non-closure during CS in terms of adhesion formation were included. Studies were included if they had a primary objective to examine adhesion formation in a repeat caesarean section, had a clear study design, had an adhesion scoring system, excluded patients who had adhesions in the primary caesarean section or interim surgeries after the primary caesarean section, and had no usage of anti-adhesion agents in the primary caesarean section. Retrospective studies which were performed by case-notes review alone, were excluded. Eleven studies were identified via our search strategy. Five were retrospective and six were prospective. Out of the eleven studies, three satisfied the inclusion criteria and were included (n=249); two studies were follow-ups of RCTs and one was not randomised. Out of 249 women included in the analysis, 110 had peritoneal closure during CS whereas the other 139 did not have peritoneal closure. Meta-analysis was performed using the two randomised studies plus (i) the unadjusted estimate from the non-randomised study and (ii) the reported adjusted estimate, adjusted for baseline differences in the groups. Non-closure of the peritoneum during CS resulted in a significantly increased likelihood of adhesion formation in both meta-analyses--OR (95% CI): (i) 2.60 (1.48-4.56) and (ii) 4.23 (2.06-8.69). This systematic review has demonstrated that according to current data in the literature, there is some evidence to suggest that non-closure of the peritoneum after caesarean section is associated with more adhesion formation compared to closure.

Randomised trial of high frequency oscillatory ventilation or conventional ventilation in babies of gestational age 28 weeks or less: respiratory and neurological outcomes at 2 years.

BACKGROUND: The long term outcome of children entered into neonatal trials of high frequency oscillatory ventilation (HFOV) or conventional ventilation (CV) has been rarely studied. OBJECTIVE: To evaluate respiratory and neurodevelopmental outcomes for children entered into the United Kingdom Oscillation Study, which was designed to evaluate these outcomes. METHODS: Surviving infants were followed until 2 years of age corrected for prematurity. Study forms were completed by local paediatricians at routine assessments, and parents were asked to complete a validated neurodevelopmental questionnaire. RESULTS: Paediatricians' forms were returned for 73% of the 585 surviving infants. Respiratory symptoms were common in all infants, and 41% had received inhaled medication. Mode of ventilation had no effect on frequency of any symptoms. At 24 months of age, severe neurodevelopmental disability was present in 9% and other disabilities in 38% of children, but the prevalence of disability was similar in children who received HFOV or CV (relative risk 0.93; 95% confidence interval 0.74 to 1.16). The prevalence of disability did not vary by gestational age, but boys were more likely to have overall disability. Developmental scores were unaffected by mode of ventilation (relative risk 1.13; 95% confidence interval 0.78 to 1.63) and were lower in infants born before 26 weeks gestation compared with babies born at 26-28 weeks. CONCLUSIONS: Initial mode of ventilation in very preterm infants has no impact on respiratory or neurodevelopmental morbidity at 2 years. HFOV and CV appear equally effective for the early treatment of respiratory distress syndrome.

Respiratory function of very prematurely born infants at follow up: influence of sex.

OBJECTIVE: To test the hypothesis that male compared with female prematurely born infants would have worse lung function at follow up. DESIGN: Prospective follow up study. SETTING: Tertiary neonatal intensive care units PATIENTS: Seventy six infants, mean (SD) gestational age 26.4 (1.5) weeks, from the United Kingdom oscillation study. INTERVENTIONS: Lung function measurements at a corrected age of 1 year. MAIN OUTCOME MEASURES: Airways resistance (Raw) and functional residual capacity (FRC(pleth)) measured by whole body plethysmography, specific conductance (sGaw) calculated from Raw and FRC(pleth), and FRC measured by a helium gas dilution technique (FRC(He)). RESULTS: The 42 male infants differed significantly from the 34 female infants in having a lower birth weight for gestation, requiring more days of ventilation, and a greater proportion being oxygen dependent at 36 weeks postmenstrual age and discharge. Furthermore, mean Raw and FRC(pleth) were significantly higher and mean sGaw significantly lower. After adjustment for birth and current size differences, the sex differences in FRC(pleth) and sGaw were 15% and 26% respectively and remained significant. CONCLUSION: Lung function at follow up of prematurely born infants is influenced by sex.

Plethysmograph and interrupter resistance measurements in prematurely born young children.

BACKGROUND: Airways obstruction in premature infants is often assessed by plethysmography, which requires sedation. The interrupter (Rint) technique does not require sedation, but has rarely been examined in children under 2 years of age. OBJECTIVE: To compare Rint results with plethysmographic measurements of airway resistance (Raw) in prematurely born, young children. DESIGN: Prospective study. SETTING: Infant and Paediatric Lung Function Laboratories. PATIENTS: Thirty children with a median gestational age of 25-29 weeks and median postnatal age of 13 months. INTERVENTIONS AND MAIN OUTCOME MEASURES: The infants were sedated, airway resistance was measured by total body plethysmography (Raw), and Rint measurements were made using a MicroRint device. Further Raw and Rint measurements were made after salbutamol administration if the children remained asleep. RESULTS: Baseline measurements of Raw and Rint were obtained from 30 and 26 respectively of the children. Mean baseline Rint values were higher than mean baseline Raw results (3.45 v 2.84 kPa/l/s, p = 0.006). Limits of agreement for the mean difference between Rint and Raw were -1.52 to 2.74 kPa/l/s. Ten infants received salbutamol, after which the mean Rint result was 3.6 kPa/l/s and mean Raw was 3.1 kPa/l/s (limits of agreement -0.28 to 1.44 kPa/l/s). CONCLUSION: The poor agreement between Rint and Raw results suggests that Rint measurements cannot substitute for plethysmographic measurements in sedated prematurely born infants.

Changes in the emergency workload of the London Ambulance Service between 1989 and 1999.

OBJECTIVES: To examine changes in the emergency workload of the London Ambulance Service (LAS) between 1989 and 1999. METHODS: All emergency responses by the LAS during week 16 in each of 1989, 1996, and 1999 were studied. For each week, 999 call responses were analysed by time and day of call, and age/sex of the patient. Call response rates were calculated using age/sex census population estimates for London. Changes in call rates over time were calculated as rate ratios. RESULTS: Emergency responses increased from 6624 to 13 178 in the index weeks of 1989-1999. The ratio of response rates (1999/1989) was 1.91 (95% CI: 1.85 to 1.96). The proportion of out of hours calls increased significantly, from 68.8% in 1989 to 71.3% in 1999 (p = 0.0003). Response rates rose significantly more steeply for male patients than female patients from 1989 to 1999: rate ratio (95% CI); male patients 2.00 (1.91 to 2.08), female patients 1.69 (1.62 to 1.77), p<0.0001. Response rates varied by age in each of the three years investigated. Rates were consistently highest for patients aged 75 and above, and lowest for those aged 5-14. However, there was no evidence that call rates had increased disproportionately in any particular age group (p = 0.79). CONCLUSIONS: Demand for emergency ambulance services in London has doubled in a decade. This increase is similar for all age groups, with no evidence of a greater rise in demand among older people. Call rates have increased more steeply in men than in women. Demographic changes do not explain the observed increases in demand.

Associations between perinatal interventions and hospital stillbirth rates and neonatal mortality.

BACKGROUND: Previous studies suggest that high risk and low birthweight babies have better outcomes if born in hospitals with level III neonatal intensive care units. Relations between obstetric care, particularly intrapartum interventions and perinatal outcomes, are less well understood, however. OBJECTIVE: To investigate effects of obstetric, paediatric, and demographic factors on rates of hospital stillbirths and neonatal mortality. METHODS: Cross sectional data on all 65 maternity units in all Thames Regions, 1994-1996, covering 540 834 live births and stillbirths. Hospital level analyses investigated associations between staffing rates (consultant/junior paediatricians, consultant/junior obstetricians, midwives), facilities (consultant obstetrician/anaesthetist sessions, delivery beds, special care baby unit, neonatal intensive care unit cots, etc), interventions (vaginal births, caesarean sections, forceps, epidurals, inductions, general anaesthetic), parental data (parity, maternal age, social class, deprivation, multiple births), and birthweight standardised stillbirth rates and neonatal mortality. RESULTS: Unifactorial analyses showed consistent negative associations between measures of obstetric intervention and stillbirth rates. Some measures of staffing, facilities, and parental data also showed significant associations. Scores for interventional, organisational, and parental variables were derived for multifactorial analysis to overcome the statistical problems caused by high intercorrelations between variables. A higher intervention score and higher number of consultant obstetricians per 1000 births were both independently and significantly associated with lower stillbirth rates. Organisational and parental factors were not significant after adjustment. Only Townsend deprivation score was significantly associated with neonatal mortality (positive correlation). CONCLUSIONS: Birthweight adjusted stillbirth rates were significantly lower in units that took a more interventionalist approach and in those with higher levels of consultant obstetric staffing. There were no apparent associations between neonatal death rates and the hospital factors measured here.

Hostile Hartlepool and genteel Guildford: hostility and health in 10 English towns.

Research from the USA suggests that cities with high mortality rates have high levels of hostility. Our aim was to replicate this research in English towns. A telephone questionnaire, based on the Cook-Medley hostility scale, was administered to random samples of adults in 10 English towns: five with high standardized mortality ratios (SMR) and five with low SMRs. The point estimate for the age-sex-weighted mean hostility score of high SMR towns was higher than that of low SMR towns (mean difference 0.2). However, the 95% confidence interval on the estimate included no difference between the two groups (-0.3-0.8). Our study does not confirm beyond doubt the findings of earlier research in the USA.

Frequent wheeze at follow up of very preterm infants: which factors are predictive?

OBJECTIVE: To determine if chest radiograph appearance at 28 days or 36 weeks postmenstrual age (PMA) can predict recurrent wheeze or cough at follow up in prematurely born infants more effectively than readily available clinical data. DESIGN: Chest radiographs of infants entered into the UKOS trial, who had had a chest radiograph at 28 days and 36 weeks PMA and completed six months of follow up, were assessed for the presence of fibrosis, interstitial shadows, cystic elements, and hyperinflation. At 6 months of corrected age, the occurrence and frequency of wheeze and cough since discharge were determined using a symptom questionnaire. PATIENTS: A total of 185 infants with a median gestational age of 26 (range 23-28) weeks. RESULTS: Thirty seven infants wheezed more than once a week, compared with the rest of the cohort. These infants had significantly higher chest radiograph scores at 28 days (p = 0.020) and 36 weeks PMA (p = 0.005), with significantly higher scores at 28 days for fibrosis (p = 0.017) and at 36 weeks PMA for fibrosis (p = 0.001) and cystic elements (p = 0.0007). They had also been ventilated for longer (p = 0.013). Forty four infants coughed more than once a week; they did not differ significantly from the rest of the cohort. An abnormal chest radiograph score at 36 weeks PMA had the largest area under the receiver operator characteristic curve with regard to prediction of frequent wheeze. CONCLUSION: An abnormal chest radiograph appearance at 36 weeks PMA predicts frequent wheeze at follow up and appears to be a better predictor than readily available clinical data.

Electrical treatment of tibial non-union: a prospective, randomised, double-blind trial.

Electrical stimulation in the treatment of bony non-union has been used in different forms for many years. However, there is still a lot of uncertainty about its efficacy. We, therefore, undertook a prospective, randomised, double-blind trial to try and determine its effect. Over a period of 5 years, 34 consecutive patients with a tibial non-union met our "criteria for inclusion". Each patient had an oblique fibular osteotomy, followed by a unilateral external fixator. They were then randomly allocated one of two machines. Group 1, the active group, received electrical stimulation from an active machine. Group 2, the dummy group, had an identical machine but without any current passing through the active coils. They were then followed up for 6 months and evaluated clinically and radiologically for bony union. Unfortunately, there was by chance, an imbalance in smoking habit between the two groups. The union rate in the subgroup that smoked was 75% (6/8) in the active group as compared to 46% (6/13) in the dummy group. The active group of non-smokers had 100% (10/10) union rate, compared to 67% (2/3) in the dummy group. Overall 24 out of the 34 patients progressed to union. Out of 18, 16 (89%) in the active group showed bony union as compared to 8/16 (50%) in the dummy. There was, thus, a statistically significant positive association between tibial union and electrical stimulation (odds ratio 8, 95% CI: 1.5-41, P=0.02).