Effectiveness of emergency surgery for five common acute conditions: an instrumental variable analysis of a national routine database.

The effectiveness of emergency surgery vs. non-emergency surgery strategies for emergency admissions with acute appendicitis, gallstone disease, diverticular disease, abdominal wall hernia or intestinal obstruction is unknown. Data on emergency admissions for adult patients from 2010 to 2019 at 175 acute National Health Service hospitals in England were extracted from the Hospital Episode Statistics database. Cohort sizes were: 268,144 (appendicitis); 240,977 (gallstone disease); 138,869 (diverticular disease); 106,432 (hernia); and 133,073 (intestinal obstruction). The primary outcome was number of days alive and out of hospital at 90 days. The effectiveness of emergency surgery vs. non-emergency surgery strategies was estimated using an instrumental variable design and is reported for the cohort and pre-specified sub-groups (age, sex, number of comorbidities and frailty level). Average days alive and out of hospital at 90 days for all five cohorts were similar, with the following mean differences (95%CI) for emergency surgery minus non-emergency surgery after adjusting for confounding: -0.73 days (-2.10-0.64) for appendicitis; 0.60 (-0.10-1.30) for gallstone disease; -2.66 (-15.7-10.4) for diverticular disease; -0.07 (-2.40-2.25) for hernia; and 3.32 (-3.13-9.76) for intestinal obstruction. For patients with 'severe frailty', mean differences (95%CI) in days alive and out of hospital for emergency surgery were lower than for non-emergency surgery strategies: -21.0 (-27.4 to -14.6) for appendicitis; -5.72 (-11.3 to -0.2) for gallstone disease, -38.9 (-63.3 to -14.6) for diverticular disease; -19.5 (-26.6 to -12.3) for hernia; and - 34.5 (-46.7 to -22.4) for intestinal obstruction. For patients without frailty, the mean differences (95%CI) in days alive and out of hospital were: -0.18 (-1.56-1.20) for appendicitis; 0.93 (0.48-1.39) for gallstone disease; 5.35 (-2.56-13.28) for diverticular disease; 2.26 (0.37-4.15) for hernia; and 18.2 (14.8-22.47) for intestinal obstruction. Emergency surgery and non-emergency surgery strategies led to similar average days alive and out of hospital at 90 days for five acute conditions. The comparative effectiveness of emergency surgery and non-emergency surgery strategies for these conditions may be modified by patient factors.

Ethnic variations in the risk of hypoglycaemia among people with Type 2 diabetes prescribed insulins and/or sulfonylureas: a historical cohort study using general practice-recorded data.

AIM: To identify ethnic differences in hypoglycaemic risk among people with Type 2 diabetes prescribed insulins and/or sulfonylureas in community settings. METHODS: Using routine general practice-recorded data, two cohorts of adults with Type 2 diabetes from east London were studied between January 2013 and December 2015: (1) adults prescribed insulins ± other antidiabetes medications (n=7269) and (2) adults prescribed sulfonylureas ± other antidiabetes medications excluding insulins (n=12 502). Incidence rate ratios of hypoglycaemia by ethnicity, adjusting for age, sex, socio-economic status and clustering within Clinical Commissioning Groups, were estimated using random effects Poisson regression. RESULTS: Compared with white British people prescribed insulins, those of black Caribbean ethnicity were at increased hypoglycaemic risk [adjusted incidence rate ratio 1.56 (95% CI 1.21,2.01)], while Bangladeshi people had a lower risk [adjusted incidence rate ratio 0.49 (95% CI, 0.38,0.64)]. In the sulfonylurea cohort, black Caribbean, black African and Indian people all had increased risks of hypoglycaemia compared with white British people [adjusted incidence rate ratios 1.63 (95% CI 1.15,2.29), 1.90 (95% CI 1.32,2.75) and 1.93 (95% CI 1.39,2.69), respectively]. CONCLUSION: The differences in hypoglycaemic risk among people with Type 2 diabetes prescribed insulin and/or sulfonylureas warrant further investigation of any differing biological responses and/or cultural attitudes to antidiabetes therapy among ethnic groups, and should be considered by clinicians evaluating the treatment goals of people with Type 2 diabetes using insulins or sulfonylureas.

Influence of surgical rate on patients' reported clinical need and outcomes in English NHS.

BACKGROUND: To determine if higher rates of surgery are associated with lower levels of need (patients' pre-operative reports of their symptoms, functional status and quality of life) and with less benefit (patients' post-operative reports). METHODS: Patient-reported outcome measures (PROMs) collected before and after joint replacement, hernia repair or varicose vein (VV) surgery in National Health Service (NHS)-funded patients (2009/11). Regression analysis for associations between 10% increase in rates and mean PROM score for Primary Care Trust (PCT) populations. RESULTS: National rate for hip and knee replacement increased by 6%, unchanged for hernia repair and decreased by 26% for VV surgery. Changes in PCT rates varied but had little or no association with the mean level of need of patients: 10% increase in the rate was associated with only 0.3% decline in the pre-operative PROM score for knee replacement (P < 0.05) and VV surgery (P < 0.001) and no significant change for other procedures. There was no significant association between a 10% change in the rate and the amount of benefit from surgery apart from a slight reduction (0.46%; P < 0.001) in the disease-specific PROM score for VV surgery. CONCLUSION: Policies by commissioners to reduce surgical rates in the English NHS cannot be justified on the grounds of avoiding inappropriate operations or increasing cost-utility.

An Approach for Combining Clinical Judgment with Machine Learning to Inform Medical Decision Making: Analysis of Nonemergency Surgery Strategies for Acute Appendicitis in Patients with Multiple Long-Term Conditions.

BACKGROUND: Machine learning (ML) methods can identify complex patterns of treatment effect heterogeneity. However, before ML can help to personalize decision making, transparent approaches must be developed that draw on clinical judgment. We develop an approach that combines clinical judgment with ML to generate appropriate comparative effectiveness evidence for informing decision making. METHODS: We motivate this approach in evaluating the effectiveness of nonemergency surgery (NES) strategies, such as antibiotic therapy, for people with acute appendicitis who have multiple long-term conditions (MLTCs) compared with emergency surgery (ES). Our 4-stage approach 1) draws on clinical judgment about which patient characteristics and morbidities modify the relative effectiveness of NES; 2) selects additional covariates from a high-dimensional covariate space (P > 500) by applying an ML approach, least absolute shrinkage and selection operator (LASSO), to large-scale administrative data (N = 24,312); 3) generates estimates of comparative effectiveness for relevant subgroups; and 4) presents evidence in a suitable form for decision making. RESULTS: This approach provides useful evidence for clinically relevant subgroups. We found that overall NES strategies led to increases in the mean number of days alive and out-of-hospital compared with ES, but estimates differed across subgroups, ranging from 21.2 (95% confidence interval: 1.8 to 40.5) for patients with chronic heart failure and chronic kidney disease to -10.4 (-29.8 to 9.1) for patients with cancer and hypertension. Our interactive tool for visualizing ML output allows for findings to be customized according to the specific needs of the clinical decision maker. CONCLUSIONS: This principled approach of combining clinical judgment with an ML approach can improve trust, relevance, and usefulness of the evidence generated for clinical decision making. HIGHLIGHTS: Machine learning (ML) methods have many potential applications in medical decision making, but the lack of model interpretability and usability constitutes an important barrier for the wider adoption of ML evidence in practice.We develop a 4-stage approach for integrating clinical judgment into the way an ML approach is used to estimate and report comparative effectiveness.We illustrate the approach in undertaking an evaluation of nonemergency surgery (NES) strategies for acute appendicitis in patients with multiple long-term conditions and find that NES strategies lead to better outcomes compared with emergency surgery and that the effects differ across subgroups.We develop an interactive tool for visualizing the results of this study that allows findings to be customized according to the user's preferences.

Socioeconomic differences in patient-reported outcomes after a hip or knee replacement in the English National Health Service.

BACKGROUND: We investigated socioeconomic differences in patient-reported outcomes after a hip or knee replacement and the contribution of health differences beforehand. METHODS: Our sample included 121 983 patients in England who had an operation in 2009-2011. Socioeconomic status was measured with quintiles of the ranking of areas by the English Index of Multiple Deprivation. Outcomes at 6 months were the Oxford hip or knee score (OHS or OKS) that measure pain and disability on a scale from 0 (worst) to 48 (best), and the percentage reporting no improvement in problems. Adjustment was made for age, sex, ethnicity, comorbidity, general health, revision surgery, primary diagnosis, preoperative OHS or OKS and having longstanding problems. RESULTS: Comparing the most- with the least-deprived group, the mean OHS was 5.0 points lower and the OKS 5.4 lower. Adjusted differences, reflecting the differences in improvement in the condition, were 2.8 [95% confidence interval (CI): 2.5-3.0] on OHS and 2.4 (95% CI: 2.2-2.7) on OKS. Adjusted odds ratios for reporting no improvement were 1.4 (1.2-1.6) for the hip and 1.4 (1.3-1.5) for the knee. CONCLUSIONS: On average, patients living in socioeconomically deprived areas had worse outcomes after surgery, partly related to preoperative differences in health and disease severity and partly to less postoperative improvement.

Sociodemographic differences in the severity and duration of disease amongst patients undergoing hip or knee replacement surgery.

BACKGROUND: Differences in the use of hip and knee replacement by sex, age, ethnicity or socioeconomic status may lead to differences in disease severity between those who have surgery. METHODS: Analyses used data collected from 117,736 patients in 2009-10 via the Patient Reported Outcome Measures (PROMs) programme in England. Adjusted differences were estimated in the Oxford Hip Score (OHS) or the Oxford Knee Score (OKS), both expressed on a scale from 0 to 48, and the proportion with longstanding problems (>5 years), expressed as odds ratios (ORs). RESULTS: Women had more severe pain and disability than men on average (difference OHS 2.3 and OKS 3.3), but less often longstanding problems. Compared with white patients, average severity was higher in South Asian patients (difference OHS 2.7 and OKS 3.0) and in black patients (difference OHS 0.9 and OKS 1.6), who also more often had longstanding problems (OR 1.40 for hip and 1.54 for knee). Patients from deprived areas had more severe disease (difference OHS 3.6 and OKS 3.3 between least and most deprived quintile). CONCLUSIONS: There is evidence that non-white and deprived patients tend to have hip and knee replacement surgery at a later stage in the course of their disease.

Local Instrumental Variable Methods to Address Confounding and Heterogeneity when Using Electronic Health Records: An Application to Emergency Surgery.

BACKGROUND: Electronic health records (EHRs) offer opportunities for comparative effectiveness research to inform decision making. However, to provide useful evidence, these studies must address confounding and treatment effect heterogeneity according to unmeasured prognostic factors. Local instrumental variable (LIV) methods can help studies address these challenges, but have yet to be applied to EHR data. This article critically examines a LIV approach to evaluate the cost-effectiveness of emergency surgery (ES) for common acute conditions from EHRs. METHODS: This article uses hospital episodes statistics (HES) data for emergency hospital admissions with acute appendicitis, diverticular disease, and abdominal wall hernia to 175 acute hospitals in England from 2010 to 2019. For each emergency admission, the instrumental variable for ES receipt was each hospital's ES rate in the year preceding the emergency admission. The LIV approach provided individual-level estimates of the incremental quality-adjusted life-years, costs and net monetary benefit of ES, which were aggregated to the overall population and subpopulations of interest, and contrasted with those from traditional IV and risk-adjustment approaches. RESULTS: The study included 268,144 (appendicitis), 138,869 (diverticular disease), and 106,432 (hernia) patients. The instrument was found to be strong and to minimize covariate imbalance. For diverticular disease, the results differed by method; although the traditional approaches reported that, overall, ES was not cost-effective, the LIV approach reported that ES was cost-effective but with wide statistical uncertainty. For all 3 conditions, the LIV approach found heterogeneity in the cost-effectiveness estimates across population subgroups: in particular, ES was not cost-effective for patients with severe levels of frailty. CONCLUSIONS: EHRs can be combined with LIV methods to provide evidence on the cost-effectiveness of routinely provided interventions, while fully recognizing heterogeneity. HIGHLIGHTS: This article addresses the confounding and heterogeneity that arise when assessing the comparative effectiveness from electronic health records (EHR) data, by applying a local instrumental variable (LIV) approach to evaluate the cost-effectiveness of emergency surgery (ES) versus alternative strategies, for patients with common acute conditions (appendicitis, diverticular disease, and abdominal wall hernia).The instrumental variable, the hospital's tendency to operate, was found to be strongly associated with ES receipt and to minimize imbalances in baseline characteristics between the comparison groups.The LIV approach found that, for each condition, there was heterogeneity in the estimates of cost-effectiveness according to baseline characteristics.The study illustrates how an LIV approach can be applied to EHR data to provide cost-effectiveness estimates that recognize heterogeneity and can be used to inform decision making as well as to generate hypotheses for further research.

Mortality due to injuries by place of occurrence in the European region: analysis of data quality in the WHO mortality database.

BACKGROUND AND OBJECTIVE: The 10th revision of the International Classification of Diseases (ICD-10) has codes for the place of occurrence of external causes of mortality. The purpose of this study was to investigate the quality of data available in the World Health Organization (WHO) mortality database on the place of occurrence of fatal injuries in the European region. METHODS: Data on external causes of mortality from countries in the European region according to the ICD-10 with four-character subdivision, between the years 1998 and 2003, were analysed. The quality of ICD-10 place of occurrence data was analysed for each country, based on the completeness, coverage and percentage of unspecified place of injury occurrence. RESULTS: Only three countries in the European region (Hungary, Iceland and Lithuania) had high quality of data on place of occurrence of injuries, and six had medium-quality data. CONCLUSIONS: Few countries in the European region have injury mortality data of adequate quality by place of occurrence.

Tension pneumothorax secondary to automatic mechanical compression decompression device.

The details are presented of the first published case of a tension pneumothorax induced by an automatic compression-decompression (ACD) device during cardiac arrest. An elderly patient collapsed with back pain and, on arrival of the crew, was in pulseless electrical activity (PEA) arrest. He was promptly intubated and correct placement of the endotracheal tube was confirmed by noting equal air entry bilaterally and the ACD device applied. On the way to the hospital he was noted to have absent breath sounds on the left without any change in the position of the endotracheal tube. Needle decompression of the left chest caused a hiss of air but the patient remained in PEA. Intercostal drain insertion in the emergency department released a large quantity of air from his left chest but without any change in his condition. Post-mortem examination revealed a ruptured abdominal aortic aneurysm as the cause of death. Multiple left rib fractures and a left lung laceration secondary to the use of the ACD device were also noted, although the pathologist felt that the tension pneumothorax had not contributed to the patient's death. It is recommended that a simple or tension pneumothorax should be considered when there is unilateral absence of breath sounds in addition to endobronchial intubation if an ACD device is being used.

Is intimal hyperplasia a marker of neuro-ophthalmic complications of giant cell arteritis?

OBJECTIVE: The ischaemic complications of giant cell arteritis (GCA) such as blindness and stroke may result from luminal narrowing of the affected arteries. This study focuses on the association between the severity of intimal proliferation on temporal artery biopsy (TAB) histology and neuro-ophthalmic complications (NOCs) of GCA. METHOD: We identified 30 cases of biopsy-proven temporal arteritis. One histopathologist (blinded to the clinical details) evaluated the TAB specimens and categorized the degree of maximum stenosis due to intimal hyperplasia into four grades: grade 1 is <50% luminal occlusion due to intimal hyperplasia, grade 2 is 50-75%, grade 3 is >75% and grade 4 is complete luminal occlusion. A second histopathologist (also blinded to the clinical details) independently evaluated the TAB specimens using the same grading system. The NOCs in these patients were noted after a case record review. RESULTS: Of the 30 patients, 12 had NOC-10 with eye complications (complete visual loss, anterior ischaemic neuropathy, visual field defects), one patient had cerebral infarcts and one had both cerebral infarcts and vision loss. There was evidence for a statistically significant trend of NOC associated with higher intimal hyperplasia scores (P = 0.001). The scores of the histopathologists agreed for 23 (77%) patients and differed by 1 category for the remaining 7 (kappa-statistic 0.88). CONCLUSIONS: Our study suggests that the degree of intimal hyperplasia on TAB histology (routinely available to all hospital units) seems to be closely associated with NOCs of GCA. The study highlights the possible prognostic as well as diagnostic role of the biopsy. We feel that intimal hyperplasia noted in biopsy specimens may help us in the risk stratification of GCA patients and targeting of appropriate and novel therapies.

Does the decline in road traffic injury in London vary by ethnicity?

OBJECTIVE: To examine ethnic variations in trends in road traffic injuries in London. DESIGN: Analysis of STATS19 data comparing trends in road traffic casualty rates by ethnic group. SETTING: London, 2001-6. SUBJECTS: Children (or=15 years). MAIN OUTCOME MEASURES: Annual casualty rates in white, black, and Asian pedestrians, cyclists, and car occupants. RESULTS: Casualty rates in London declined each year between 2001 and 2006 by an average of 8.8% (95% CI 8.5% to 9.0%). After adjustment for area-level deprivation, there was good evidence that the average annual reduction in injury rates in car occupants was significantly less in Asian than in white adults (10.9% vs 14.4%, p<0.001). There was some evidence that average annual reductions in injury rates were lower in black than in white adult pedestrians (7.4% vs 9.3%, p = 0.041) and car occupants (13.2% vs 14.4%, p = 0.03). CONCLUSIONS: Casualty rates in London have declined for pedestrians, cyclists, and car occupants in three broad ethnic groups. Asian car drivers appear to have benefited least from these reductions.

Increased risk of tuberculosis among health care workers in Samara Oblast, Russia: analysis of notification data.

SETTING: Samara Oblast, Russia. OBJECTIVE: To compare the rates of tuberculosis (TB) in health care workers (HCWs) working in TB services, general health services (GHS) and the general population in a region of the Russian Federation. DESIGN: Analysis of notification rates of TB among HCWs, GHS workers and the general population during the 9-year period from 1994 to 2002. RESULTS: During 1994-2002, TB incidence among staff employed at the TB services in Samara Oblast was ten times higher than among the general population, reaching 741.6/100 000 person years at risk. Staff working at in-patient TB facilities were found to be at highest risk, with an incidence rate ratio of 17.7 (95% CI 11.6-27.0) compared to HCWs at the GHS. CONCLUSIONS: HCWs at TB services in the Russian Federation are at substantially increased risk for TB, suggesting significant risks from nosocomial transmission. Control of institutional spread of TB in the Russian Federation is an area that requires urgent attention, especially given the epidemic of human immunodeficiency virus that Russia is currently witnessing.

A Systematic Review of the Burden of Pancreatic Cancer in Europe: Real-World Impact on Survival, Quality of Life and Costs.

PURPOSE: The purpose of this study was to assess the overall burden of pancreatic cancer in Europe, with a focus on survival time in a real-world setting, and the overall healthy life lost to the disease. METHODS: Real-world data were retrieved from peer-reviewed, observational studies identified by an electronic search. We performed two de novo analyses: a proportional shortfall analysis to quantify the proportion of healthy life lost to pancreatic cancer and an estimation of the aggregate life-years lost annually in Europe. RESULTS: Ninety-one studies were included. The median, age-standardised incidence of pancreatic cancer per 100,000 was 7.6 in men and 4.9 in women. Overall median survival from diagnosis was 4.6 months; median survival was 2.8-5.7 months in patients with metastatic disease. The proportional shortfall analysis showed that pancreatic cancer results in a 98 % loss of healthy life, with a life expectancy at diagnosis of 4.6 months compared to 15.1 years for an age-matched healthy population. Annually, 610,000-915,000 quality-adjusted life-years (QALYs) are lost to pancreatic cancer in Europe. Patients had significantly lower scores on validated health-related quality of life instruments versus population norms. CONCLUSIONS: To the best of our knowledge, this is the first study to systematically review real-world overall survival and patient outcomes of pancreatic cancer patients in Europe outside the context of clinical trials. Our findings confirm the poor prognosis and short survival reported by national studies. Pancreatic cancer is a substantial burden in Europe, with nearly a million aggregate life-years lost annually and almost complete loss of healthy life in affected individuals.

Increased costimulatory responses in African-American kidney allograft recipients.

BACKGROUND: The issue of racial differences in immune responses has been seldom investigated, despite the increased incidence of transplant rejection and inferior allograft outcomes in African-Americans (AA). We previously reported significantly increased expression of costimulatory molecules on peripheral blood cells from healthy adult AA compared with Caucasian (CS) volunteers. This report extends the study to pediatric kidney allograft recipients. METHODS: Surface antigen expression by peripheral blood mononuclear cells (MNC) from AA and CS transplant patients was determined by flow cytometry, after staining with specific antibodies. In vitro proliferation, in a one-way mixed lymphocyte response (MLR), was measured after stimulation with allogeneic irradiated mononuclear cells. The concentration of cyclosporine (CsA) achieving 50% inhibition (IC50) of in vitro proliferative responses to PHA and OKT3 was calculated. RESULTS: MNC from AA patients were shown to have significantly higher expression of CD80 (CS 5.2% +/- 0.6, AA 9.6% +/- 1.2, P < 0.0001) than cells from CS patients. Additionally, the cells from AA transplant recipients proliferated significantly more in an MLR (stimulation index: CS 8 +/- S2, AA 25 +/- 8, P < 0.05), and the CsA IC50 values, during proliferation to PHA and OKT3, were significantly higher in AA compared to CS patients. CONCLUSIONS: Although socioeconomic factors and therapeutic compliance are undoubtedly important issues in long-term allograft survival, our data suggest that AA patients mount more vigorous immune responses to antigens. The increased requirement for immunosuppression may be linked to racial variations in costimulatory molecule expression on antigen-presenting cells.

Light and electron microscopic studies of cellular localization of oPL with monoclonal and polyclonal antibodies.

Accurate knowledge of placental lactogen localization is fundamental to any hypothesis of its synthesis and secretion. We used locally generated monoclonal and polyclonal antibodies from three separate sources to localize ovine placental lactogen immunoreactivity on light and electron microscope Lowicryl K4M sections of ovine placentomes of 97-145 days of gestation, using immunogold techniques. All antibodies demonstrated that immunoreactivity was exclusively localized in the trophoectoderm binucleate cell Golgi body and granules and in granules in the syncytium derived from binucleate cell migration. No evidence was found to support a recent claim that monoclonal antibodies to oPL that were produced in Canada indicated a predominant localization of ovine placental lactogen to uninucleate trophectodermal cells.

A panel of monoclonal antibodies to ovine placental lactogen.

A panel of 11 rat monoclonal antibodies (mAbs) has been raised to ovine placental lactogen (PL). By competitive enzyme-linked immunoabsorbent assay (ELISA), confirmed by two-site ELISA, the antibodies were shown to recognize six antigenic determinants on the ovine PL molecule, two of which overlap. One antigenic determinant (designated 1) was shared by other members of the prolactin/growth hormone (GH)/PL family in ruminants, humans and rodents. The binding of (125)I-labelled ovine PL to crude receptor preparations from sheep liver (somatotrophic) or rabbit mammary gland (lactogenic) was inhibited by mAbs recognizing antigenic determinants 2-6. Both types of receptor preparation were affected similarly. In the local in vivo pigeon crop sac assay, mAbs directed against determinants 3 and 6 enhanced the biological activity of ovine PL.

Inappropriate requests for serum anti-epileptic drug levels in hospital practice.

BACKGROUND: Serum anti-epileptic drug (AED) levels are indicated to assess AED adherence or toxicity, and are applicable to only a few AEDs. Expert consensus views on the clinical role of serum AED levels are summarized in the evidence-based guidelines published by the Scottish Intercollegiate Guidelines Network. AIM: To examine local compliance with these guidelines. DESIGN: Retrospective case-note audit. METHODS: We included all serum AED level measurements requested from our hospital over two months. Our audit standards were first, that serum AED levels should be requested only for suspicion of poor AED adherence or toxicity ('indication-compliant'), and secondly, for 'full compliance', that 'indication-compliant' requests should be made only for AEDs with established dose-response and dose-toxicity relationships (phenytoin, carbamazepine, phenobarbitone). RESULTS: There were 114 measurements in 102 patients. Serum AED level requests were for phenytoin (n = 50), valproate (n = 27), carbamazepine (n = 22), lamotrigine (n = 8), phenobarbitone (n = 7), and were made by physicians (n = 46), paediatricians (n = 30), neurologists (n = 15), neurosurgeons (n = 14), psychiatrists (n = 7), and intensivists (n = 2). AED toxicity was queried in 29 requests (25%), and adherence in 10 (9%); thus 34% of requests were 'indication-compliant'. However, 16 of these were for valproate or lamotrigine; thus only 23 requests (20%) were 'fully compliant'. Clinical management changed in only 17 of the 47 patients whose levels fell outside target ranges, and only two of these followed indication-compliant AED measurement. DISCUSSION: The audit identified a failure locally to comply with standard evidence-based guidelines. If, as is likely, this reflects practice elsewhere in the UK, there are potentially major clinical management and resource implications.

Prostacyclin release stimulated by thrombin or bradykinin in porcine endothelial cells cultured from aorta and umbilical vein.

We have investigated the responsiveness of porcine endothelial cells, cultured from aorta or umbilical vein, to bradykinin and thrombin. Aortic cells studied in situ, in primary culture and in subculture responded to both agents with an increase in prostacyclin (PGI2) release; the increase was greater with bradykinin than with thrombin. Umbilical vein cells in primary culture or in subculture also responded to bradykinin and to thrombin; bradykinin was again more effective than thrombin. For both cell types there was a rapid quantitative decline in their ability to be stimulated by either agent with increasing passage number, so that by passage 8 stimulation of PGI2 release could no longer be detected from monolayers cultured under conventional conditions. The presence of a stimulatory response was still, however, easily demonstrable in subcultured cells when they were grown on microcarrier beads, packed in small columns, and perfused. Under these conditions greater than 10-fold stimulation above baseline levels was often found, while the conventional monolayer culture technique gave a smaller maximum stimulation even in primary cultures.

Reduction in the use of surgery for glue ear: did national guidelines have an impact?

BACKGROUND: It is widely accepted that the passive dissemination of national clinical guidance has little or no impact on practice. OBJECTIVE: To assess the impact in England of an Effective Health Care bulletin on childhood surgery for glue ear issued in 1992 and to understand the reasons for any change (or lack of change) in practice that ensued. METHOD: Time series analysis of the rate of use of surgery by children under 10 years of age from 1975 to 1997/8 in 13 English health districts. RESULTS: Following a rise in the rate of surgery in public (National Health Service) hospitals from 1975 to 1985, the rate declined by 1.6% a year from 1986 to 1992/3. Following publication of the guidelines in November 1992, the rate of decline increased to 10.1% a year. Even after allowing for a slight increase in the use of independent (private) hospitals between 1992/3 and 1997/8, the overall rate of decline was at least 7.9%. It appears that the rate of referral of cases by primary care physicians (general practitioners) halved during this period. Several contextual factors are thought to have contributed to the effect of the guidelines, including pre-existing professional concern about the value of surgery, the introduction of an internal market into the NHS, and growing apprehension among parents fuelled by scepticism in the mass media. During this unprecedented period of rapid change in usage, staff delivering the service remained unaware of the alterations in their own practice. CONCLUSIONS: Passive dissemination of national guidelines can accelerate an existing trend in clinical practice if the context is hospitable. Policy makers should identify and target such situations.

Occupational exposure of midwives to nitrous oxide on delivery suites.

AIMS: To compare environmental and biological monitoring of midwives for nitrous oxide in a delivery suite environment. METHODS: Environmental samples were taken over a period of four hours using passive diffusion tubes. Urine measurements were taken at the start of the shift and after four hours. RESULTS: Environmental levels exceeded the legal occupational exposure standards for nitrous oxide (100 ppm over an 8 hour time weighted average) in 35 of 46 midwife shifts monitored. There was a high correlation between personal environmental concentrations and biological uptake of nitrous oxide for those midwives with no body burden of nitrous oxide at the start of a shift, but not for others. CONCLUSIONS: Greater engineering control measures are needed to reduce daily exposure to midwives to below the occupational exposure standard. Further investigation of the toxicokinetics of nitrous oxide is needed.