Predictors of survival after haemorrhagic stroke in a multi-ethnic population: the South London Stroke Register (SLSR).

OBJECTIVES: To identify the predictors of long-term survival after haemorrhagic stroke. METHODS: Data were collected within the population-based South London Stroke Register covering a multiethnic source population of 271,817 inhabitants (2001) in South London. Death data were collected at post-stroke follow-up. The impact of patients' demographic and clinical characteristics, ethnic origin, pre-stroke risk factors and acute treatment on long-term survival were investigated. Survival methods included Kaplan-Meier curves and Cox's proportional hazards model. RESULTS: Between January 1995 and December 2004, a total of 566 patients with first-ever haemorrhagic stroke (395 primary intracerebral haemorrhage; 171 subarachnoid haemorrhage) were registered. Mean age was 62.3 years; 365 (64.5%) were white, 132 (23.3%) were black and 69 (12.2%) were other or unknown ethnic origin; there were 1340 person-years of follow-up. After multivariable adjustment, age (p<0.001) and having diabetes (hazard ratio (HR), 1.69; 95% CI 1.06-2.70) were associated with increased risk of death. Patients with severe stroke (Glasgow Coma Scale (GCS) <9) had an increased risk of death (HR 6.5; 95% CI 4.68 to 8.90) compared with those with mild stroke (GCS >12). Treatment on a stroke unit reduced the long-term risk of death (HR 0.70; 95% CI 0.50 to 0.98). Black patients had a reduced risk of death (HR 0.62; 95% CI 0.42 to 0.92) compared with white patients. CONCLUSIONS: Age, diabetes, stroke severity and stroke unit care influenced the long-term risk of death after haemorrhagic stroke. An independent survival advantage was observed in black patients. These factors can be utilised for clinical predictions but the cause of the observations in black patients remains unclear.

Long-term outcome after stroke: does dysphagia matter?

BACKGROUND: swallowing problems (dysphagia) are common following acute stroke and are independent predictors of short-term outcome. It is uncertain as to whether these swallowing problems are associated with outcome in the longer-term. AIM: insert to determine whether dysphagia present in the first week of acute stroke associated with long-term outcome. METHODS: a population-based long-term follow-up of people with first in a life-time stroke. Dysphagia was assessed within 1 week of stroke and patients were followed up at 3 months and yearly for 5 years by face-to-face interview. Outcome was defined by survival and place of residence, using multinomial logistic regression. Barthel Scores were divided into the two groups 15-20 and 0-14, and modelled using multiple logistic regression. RESULTS: there were 567 patients with dysphagia (mean age 74.3 years) and 621 with a safe swallow (mean age 69.6 years). Following multinomial logistic regression, residence in a nursing home was more likely to occur in those who failed the swallow test during the first week of their stroke; however, this only reached statistical significance at 3 months (relative risk ratio (RRR)=1.73; 95% confidence interval (CI) 1.02 to 2.95), and years 4 (RRR 3.35, 1.37-8.19) and 5 (RRR 3.06, 1.06-8.83). There was also a significant association with increased mortality only during the first three months (RRR 2.03, 1.12 to 3.67). CONCLUSION: this study confirms that the presence of dysphagia during the acute phase of stroke is associated with poor outcome during the subsequent year, particularly at 3 months, and is associated with increased institutionalisation rate in the long term.

The early origins hypothesis with an emphasis on growth rate in the first year of life and asthma: a prospective study in Chile.

BACKGROUND: There is uncertainty about the impact of the programming hypothesis in terms of nutritional status at birth, rate of growth in the first year of life, length of gestation, breast feeding, and episodes of illness on asthma. An analysis was therefore carried out to test this hypothesis. METHODS: Data were collected on 1232 children born between 1974 and 1978 in a semi-rural area of Chile. Measurements at birth and growth in the first year of life were obtained from a birth registry and clinical notes. Information on asthma was collected using the European Community Respiratory Health Survey questionnaire. Sensitisation to eight allergens and bronchial hyperresponsiveness (BHR) to methacholine were determined. All other information was obtained using a questionnaire. Polytomous logistic analyses were carried out to explore the association of factors at birth and during the first year of life with asthma symptoms, atopy, and BHR. RESULTS: Weight and length gain in the first year were positively associated with wheeze (odds ratio (OR) 1.004, 95% CI 1.001 to 1.007 and OR 1.11, 95% CI 0.98 to 1.25, respectively). A higher body mass index (BMI) at birth was protective in subjects reporting both wheeze and waking with breathlessness (OR 0.54, 95% CI 0.35 to 0.84). Length rate in tertiles divided by length at birth in tertiles was related to asthma symptoms (OR 1.68, 95% CI 1.19 to 2.37). Most other assessments were not associated with asthma. CONCLUSION: These results show promising but inconclusive evidence that a rapid rate of growth in length, especially in newborn infants of low length, might be involved in the aetiology of asthma.

Onychomycosis: the development of a clinical diagnostic aid for toenail disease. Part I. Establishing discriminating historical and clinical features.

BACKGROUND: The ideal method for diagnosing onychomycosis is unclear. Mycological investigation is currently the method of choice, although there is a false-negative culture rate of at least 30%. OBJECTIVES: To establish a clinical diagnostic aid which may be used alongside laboratory-based mycological tests and in epidemiological studies. METHODS: Patients with nail disease (n = 209) were enrolled in the study. The examining clinician completed a questionnaire containing four historical questions and 21 questions related to the clinical findings. All patients had samples taken for mycological analysis. The gold standard for the diagnosis of onychomycosis was a positive result on both direct microscopy and culture of nail samples. Following exclusions, questionnaire responses from 169 patients were analysed using Stata. Multiple logistic regression with forward stepwise selection of variables was performed. RESULTS: Both microscopy and culture results were positive in 32% of cases and negative in 42%. Dermatophytes formed the majority of isolates. Four parameters were found to be significantly related to positive mycology results: a history of tinea pedis in the last year, scaling on one or both soles, white crumbly patches on the nail surface, and an abnormal colour of the nail plate. CONCLUSIONS: Our results have shown one historical feature and three clinical features to be strongly associated with onychomycosis. The questionnaire has been revised to include only these stems and is being tested further with the aim of achieving a binary definition.

Degloving of the inferior turbinates: pilot study to assess the effectiveness of a new technique in turbinate reduction.

A pilot study to assess the safety and efficacy of 'degloving' of the inferior turbinate is described. This prospective study reports on the effectiveness of the technique in 37 patients with nasal obstruction due to inferior turbinate hypertrophy. Both objective and subjective measurements of nasal patency were made pre-operatively, and repeated at six weeks, six months and two years post-operatively using nasal inspiratory peak flow rates, saccharin clearance time and an end referenced visual analogue scale to record nasal symptoms. There was a significant improvement in the peak inspiratory flow at six weeks (96.4 to 151.2 l/min) and at six months (148.4 l/min), which was sustained at two years (117.1 l/min, p<0.001). There was an overall improvement in patient satisfaction with nasal symptoms (23.4 to 76.7, 76.8 and 66.8 at six weeks, six months and two years, p<0.001) and a decrease in the sensation of nasal obstruction (71.9 to 21.5, 32.9 and 29.8, p<0.001), which was also sustained. Rhinorrhoea was reduced, and sense of smell increased across the group, but the improvements did not reach statistical significance. The results for postnasal drip and saccharin clearance did not show a significant change over the period of the study. There were no haemorrhagic complications in the group studied. This pilot study demonstrates a new surgical technique for reduction of the inferior turbinates, that yields significant improvement in nasal obstruction, an acceptably low complication rate and is well tolerated by patients. A randomized controlled trial is being planned.

Observer agreement in recording the clinical signs of nail disease and the accuracy of a clinical diagnosis of fungal and non-fungal nail disease.

BACKGROUND: Onychomycosis is increasing in incidence. To date, no studies have examined the detection of abnormalities of the nail apparatus, nor the accuracy of a clinical diagnosis of onychomycosis and non-fungal nail disease. OBJECTIVES: To assess the agreement between and within different groups of observers in detecting signs of nail disease, and to obtain information regarding clinical diagnostic skills. METHODS: An observational study was performed. Nine observers, including dermatologists, mycologists, general practitioners and a dermatology clinical assistant, completed a questionnaire containing 21 clinical signs of nail disease during examination of nine patients, five with onychomycosis and four with non-fungal nail disease. Observers were additionally requested to suggest the most likely underlying diagnosis for the nail dystrophy. Mean pair observer agreement values were calculated for each of the clinical signs, between all observers and within groups of observers. The chance-corrected agreement index, kappa, was determined. From the clinical diagnoses given, the positive predictive value of a diagnosis of fungal and non-fungal nail disease was calculated. RESULTS: There was substantial between-observer agreement on only three clinical signs: abnormal nails on both hands, abnormal toenails and abnormal fingernails. More specific signs of nail disease such as onycholysis elicited weaker agreement. All observers showed accuracy in making a clinical diagnosis of fungal nail disease, with a mean positive predictive value of 0.91, compared with 0.77 for non-fungal nail disease. CONCLUSIONS: Our results showed that agreement between observers, in recording signs of nail disease, was generally poor. The clinical diagnosis of onychomycosis was highly likely to be correct, suggesting that other criteria are being employed by individuals in reaching the diagnosis.

Isolated echogenic foci in the fetal heart as marker of chromosomal abnormality.

OBJECTIVE: To assess the effect of echogenic foci in the fetal heart on the risk for Down's syndrome. DESIGN: Prospective evaluation of fetal echocardiograms at a fetal cardiology referral center and systematic postnatal follow-up. A relative risk was calculated from the prevalence of echogenic foci in fetuses subsequently demonstrated to have trisomy 21 divided by that in normal fetuses. For a subgroup of 548 fetuses with echogenic foci but otherwise normal detailed anomaly scans, the expected number of trisomy 21 fetuses calculated from maternal age risks was compared with the observed number to derive a relative risk for isolated echogenic foci. RESULTS: Echogenic foci occurred in 905 of 6904 fetuses scanned, but after excluding those referred specifically because of an echogenic focus and those with heart defects, the incidence was 9.5%. Overall, echogenic foci were more frequent in fetuses with trisomy 21 than those without by a factor of 2.93. For the 548 fetuses with echogenic foci but otherwise normal detailed anomaly scans, the actual number of trisomy 21 fetuses exceeded that expected on the basis of maternal age risks by a factor of 5.54. Combination with data from several previous studies suggests a consensus relative risk of about 3.0. CONCLUSIONS: Echogenic foci are associated with increased risk of trisomy 21 even when present as an isolated finding. Their significance in an individual should be interpreted in the light of prior risk assessment based on maternal age and results of any first-trimester screening tests. We suggest that the prior risk is increased by a factor of 3.0.

Mechanism for the transit-induced increase in colonic deoxycholic acid formation in cholesterol cholelithiasis.

BACKGROUND & AIMS: Many patients with cholesterol gallbladder stones (GBS) have a high percentage of deoxycholic acid (DCA) in gallbladder bile (all of which are in the conjugated form), probably as a result of prolonged large bowel transit times (LBTT). However, whether the prolonged LBTT increases DCA formation, solubilization, or absorption (or all 3) is not known. METHODS: In 40 subjects (20 with GBS; age range, 24-74 years), we measured LBTT using radiopaque markers, and intestinal luminal pH by radiotelemetry. We also measured quantitative anaerobic bacteriology and the activities of 2 bile acid-metabolizing enzymes in fresh cecal aspirates obtained during clinically indicated unprepared colonoscopy, and related these results to the percentage of DCA in fasting serum measured by gas chromatography-mass spectrometry. RESULTS: Compared with controls, GBS patients had longer LBTT (mean 23.1 +/- SEM 2.8 h vs. 36.5 +/- 3.3 h; P < 0.01); more total (2.7 +/- 0.6 x 10(9) vs. 5.9 +/- 1.5 x 10(9) cfu/mL) and Gram-positive (9.5 +/- 3.1 x 10(8) vs. 18.0 +/- 4.1 x 10(8) cfu/mL; P < 0.05) anaerobes; and greater 7alpha-dehydroxylating (7alpha-DH) activity (3.39 +/- 0.59 vs. 10.37 +/- 1.15 x 10(-4) U/mg protein) in the cecal aspirates. They also had higher intracolonic pH values (P < 0.02) and increased percentages of DCA in fasting serum (13.4% +/- 1.52% vs. 21.8% +/- 2. 19%; P < 0.005). Results of univariate and multivariate analyses confirmed that LBTT was critical in determining the percentage of DCA in serum and showed that 7alpha-DH activity and apparent distal colonic pH were also significant independent variables. CONCLUSIONS: Slow colonic transit (more time), increased Gram-positive anaerobes (more bacteria), and greater 7alpha-DH activity (more enzyme) favor enhanced DCA formation; transit-induced increases in distal colonic luminal pH favor enhanced DCA solubilization/bioavailability; and increases in LBTT (more time) again favor DCA absorption.

Atrioventricular septal defects diagnosed in fetal life: associated cardiac and extra-cardiac abnormalities and outcome.

OBJECTIVES: We sought to establish the outlook for fetuses diagnosed with atrioventricular septal defect (AVSD) prenatally and its relation to additional cardiac, extracardiac and chromosomal abnormalities. BACKGROUND: Prediction of likely outcome of AVSD presenting prenatally is complicated by the wide variation in associated features. METHODS: Computerized records from 14,726 pregnancies referred to a fetal cardiology center were reviewed retrospectively. Pathological reports, postnatal records, follow-up inquiries and review of echocardiographic video recordings supplemented analysis of the records for all those with AVSD. RESULTS: Atrioventricular septal defect was confirmed in 301 fetuses. Eighty-six (39%) of the 218 with known karyotype had trisomy 21, and 21/218 (10%) had other chromosome abnormalities. Right isomerism occurred in 37/301 (12%) fetuses, left isomerism in 62 (20%), mirror image atrial arrangement in 2 (1%), and 200 (67%) had usual arrangement. Atrioventricular septal defect occurred without any other intracardiac abnormality in 155 fetuses (51%). Extracardiac abnormalities and nonkaryotypic syndromes were evident in 40 fetuses (13%, confidence interval [CI] 9.5-17.1%). Uncomplicated cardiac anatomy was significantly associated with the presence of karyotype abnormality (p < 0.0001). Parents opted for termination of pregnancy in 175/298 (58.5%). For the continuing pregnancies, Kaplan-Meier estimates for live birth, survival past the neonatal period and survival to three years were 82% (CI 75.3-88.9%), 55% (CI 46.0%-0/64.3%) and 38% (CI 27.1-48.6%), respectively. Fetal hydrops and earlier year of diagnosis were independent variables with adverse influence on survival. CONCLUSIONS: Despite some improvements in the outlook for AVSD diagnosed prenatally, the overall prognosis remains considerably poorer than that implied from surgical series. The detection of associated cardiac and extracardiac abnormalities is important in order to give the best indication of the likely outcome when counseling parents.

Estimating the prevalence of malformation of the heart in the first year of life using capture-recapture methods.

The authors estimated the prevalence of heart malformation during the first year of life, using five data sets with varying degrees of completeness from two English regional health authorities. These areas covered a total population of 6,872,000. Analysis was carried out using capture-recapture methods, including log-linear modeling, on data collected between June 1993 and August 1994. A large number of cases in the community were unrecorded by any of the current sources of information. In South East Thames, where an antenatal training screening program for detecting heart malformations had been implemented in the late 1980s, the estimated prevalence rate varied from 5.5 per 1,000 births (95% confidence interval (CI): 3.5, 10.8) to 9.0 per 1,000 births (95% CI: 6.4, 14.2), depending on the assumptions in the model and the number of sources used in the analysis. In the Wessex region, which did not have a formal training program, prevalence was lower and varied little, from 4.3 per 1,000 (95% CI: 3.4, 6.0) to 5.1 per 1,000 (95% CI: 4.0, 7.2), according to assumptions. These two estimates were reasonable rates in comparison with reports in the literature. This analysis was helpful in demonstrating that the training program designed to identify severe heart malformations during the antenatal period in one of these regions had no lasting impact on prevalence.

Is involvement of the surgical margins of large loop excision of the cervical transformation zone specimens for cervical intraepithelial neoplasia III a risk factor for persistent cervical intraepithelial neoplasia?

We aimed to test the hypothesis that patients with cervical intraepithelial neoplasia (CIN) III treated by large loop excision of the cervical transformation zone (LLETZ) are more likely to suffer recurrence of cervical abnormalities if the CIN reaches the margins of the index specimen. Three hundred and forty-five women treated by LLETZ in 1991, and 1992, and in whom the histological diagnosis was CIN III, were studied. The reports were reviewed and the cases were categorised as completely excised, incompletely excised, or undetermined. Cytological follow-up, or in some cases histological follow-up in the same year and in each of the 5 following years was tabulated. Follow-up data were recorded from the same and also surrounding institutions. The chi-squared test was used to compare the differences in recurrence rates between the three groups at the various points in time. A small advantage was demonstrated for those cases where excision was complete. This was statistically significant in the third following year (P=0.022). The resection margin status of LLETZ specimens for CIN III has only a minor effect on the likelihood of recurrence. Nevertheless, recording the status may be important in case of unexpected invasion. The relative reassurance the information will provide when the lesion has been excised may also be seen as worthwhile.

Anxiety and depression in mothers related to severe malformation of the heart of the child and foetus.

The aim of the study was to assess levels of anxiety and depression in three groups: pregnant mothers referred to foetal cardiology, subdivided into those with a confirmed diagnosis and those for which no abnormality was detected, and mothers who had a child with a heart malformation. Psychological status was measured between 6 and 10 months after diagnosis using the Hospital Anxiety and Depression scale in 108 females. Levels of anxiety were higher in the two groups with a confirmed diagnosis in the antenatal period or after birth (62%) than in those who were screened positively but in whom no abnormality was found (30%) (p = 0.0055). Anxiety was the highest in young females who had a foetus with a heart malformation. Depression scores were higher in those who had a child with heart malformation (18%) than in the other two groups (5%). Mothers who terminated a pregnancy after diagnosis remained depressed long after the event. Younger mothers may be especially vulnerable to mood problems associated with a traumatic obstetric experience.

Epidemiological study of Guillain-Barré syndrome in south east England.

OBJECTIVES: To determine the incidence, treatment, and outcome of Guillain-Barré syndrome in south east England. METHODS: Patients presenting with confirmed Guillain-Barré syndrome between 1 July 1993 and 30 June 1994 were recruited via a voluntary reporting scheme coordinated by the British Neurological Surveillance Unit, hospital activity data collected from acute admitting hospitals within the South East and South West Thames Regional Health Authorities, death certificates, and a contemporary research study of Guillain-Barré syndrome and Campylobacter jejuni infection. All patients were followed up for one year to determine outcome. RESULTS: Seventy nine patients were recruited, 35 (44%) male, 44 (56%) female, including three children (two boys, one girl). The crude (95% confidence interval (95% CI)) annual incidence was 1.2 (0.9-1.4) cases/100000 population and 1.5 (1.3-1.8)/100000 when adjusted for undetected cases. Twenty (25%) patients required ventilation for an average (SD) of 42 (64) days. Thirty six (46%) patients received intravenous human immunoglobulin, five (6%) received plasma exchange, 11 (14%) both treatments, three (4%) steroids, and 25 (32%) no immunomodulatory treatment. One year later, six patients (8%) had died, all of whom were older than 60, three (4%) remained bedbound or ventilator dependent, seven (9%) were unable to walk unaided, 14 (17%) were unable to run, and 49 (62%) had made a complete or almost complete recovery. Increasing age was significantly associated with a poorer outcome at one year. CONCLUSIONS: Despite the frequent use of modern immunomodulatory treatments Guillain-Barré syndrome still carries considerable morbidity and mortality.

Expression of a peptide epitope of the colonic mucin MUC2 in precursor lesions to gastric carcinoma.

Previous histochemical studies have shown that changes occur in the composition of mucins both in preneoplastic and neoplastic lesions of the gastric mucosa. Since monoclonal antibodies are now available which recognize the protein product of distinct mucin genes, they are likely to provide useful tools for evaluating these changes. Thus, a monoclonal antibody 996/1 raised against a peptide epitope of the colonic mucin MUC2 was examined for its potential as a prognostic indicator in gastric cancer. 996/1 works well on formalin-fixed paraffin sections and shows good staining of the colonic goblet cells in the region of the golgi, while there is no staining of normal control gastric mucosa. The epitope was detected in all cases of intestinal metaplasia (44 samples) and some but not all cases of dysplasia (26 samples) and gastric carcinoma (74 samples). There was no significant difference between the positivity of the tumours according to their classification, stage and lymph node status. These results unfortunately gave little indication that this antibody would be a useful prognostic tool in gastric cancer. However, the pattern of 996/1 staining provides useful information about the molecular changes in mucin expression that occur in gastric carcinogenesis.

Gastroesophageal reflux in patients with angiographically normal coronary arteries: an uncommon cause of exertional chest pain.

OBJECTIVES: To investigate the association between exertional chest pain and gastroesophageal reflux in patients with normal coronary angiograms and in controls by measuring oesophageal pH during treadmill exercise tests and to compare the results with routine ambulatory monitoring. DESIGN: Case control study. SETTING: Tertiary referral cardiac unit. PATIENTS: 50 consecutive patients with chest pain and completely normal coronary angiograms and 16 controls with coronary artery stenoses. MAIN OUTCOME MEASURES: Episodes of acid reflux and chest pain during treadmill exercise; a symptom index expressing the percentage of episodes of pain related to acid reflux during ambulatory monitoring. RESULTS: Four (8%) patients and two (12%) controls had reflux during treadmill exercise (NS). 32 (64%) and 16 (100%) reported chest pain, but only three (6%) and two (12%) had coincident reflux (NS). Reflux was as frequent before, during, and after treadmill exercise (five (8%) v six (9%) v two (3%)) in the 66 subjects; (NS). 19 (38%) patients and three (19%) controls had abnormal reflux on ambulatory monitoring (NS). Eight (16%) and three (19%) had a symptom index > 50%, but six and two of these reported pain without coincident reflux during treadmill exercise. CONCLUSION: There are many potential causes of chest pain in patients with angiographically normal coronary arteries. Although gastroesophageal reflux is commonly implicated and many patients have a high incidence of spontaneous reflux during ambulatory monitoring, it rarely occurs during exertion and the association with chest pain is poor.

Improving the quality of teaching: staff responses to students' views.

This paper describes the use of a questionnaire designed to enable students to comment on aspects of the teaching they received from their tutor during the preclinical course in Conservative Dentistry. The information was subsequently used by the teachers themselves, to modify their performance.

QT interval in anorexia nervosa.

OBJECTIVES: To determine the incidence of a long QT interval as a marker for sudden death in patients with anorexia nervosa and to assess the effect of refeeding. To define a long QT interval by linear regression analysis and estimation of the upper limit of the confidence interval (95% CI) and to compare this with the commonly used Bazett rate correction formula. DESIGN: Prospective case control study. SETTING: Tertiary referral unit for eating disorders. SUBJECTS: 41 consecutive patients with anorexia nervosa admitted over an 18 month period. 28 age and sex matched normal controls. MAIN OUTCOME MEASURES: maximum QT interval measured on 12 lead electrocardiograms. RESULTS: 43.6% of the variability in the QT interval was explained by heart rate alone (p < 0.00001) and group analysis contributed a further 5.9% (p = 0.004). In 6 (15%) patients the QT interval was above the upper limit of the 95% CI for the prediction based on the control equation (NS). Two patients died suddenly; both had a QT interval at or above the upper limit of the 95% CI. In patients who reached their target weights the QT interval was significantly shorter (median 9.8 ms; p = 0.04) relative to the upper limit of the 60% CI of the control regression line, which best discriminated between patients and controls. The median Bazett rate corrected QT interval (QTc) in patients and controls was 435 v 405 ms.s-1/2 (p = 0.0004), and before and after refeeding it was 435 v 432 ms.s1/2 (NS). In 14(34%) patients and three (11%) controls the QTc was > 440 ms.s-1/2 (p = 0.053). CONCLUSIONS: The QT interval was longer in patients with anorexia nervosa than in age and sex matched controls, and there was a significant tendency to reversion to normal after refeeding. The Bazett rate correction formula overestimated the number of patients with QT prolongation and also did not show an improvement with refeeding.

Observer variation in the assessment of dysplasia in ulcerative colitis.

Six histopathologists allocated 100 sections from patients with long-standing ulcerative colitis into four diagnostic categories, regular hyperplasia, reactive atypia, low-grade and high-grade dysplasia. Their allocations were analysed using kappa statistics, including Fleiss's multiple kappa for groups of observers, and agreement on specific diagnoses was explored by constructing a conditional probability matrix. The nature of their disagreements was investigated using coefficients for systematic and haphazard errors. Over the four diagnostic categories there was a wide range of pairwise agreement from a low of 49% up to 72% and kappa values were only 'fair' or 'moderate'. As expected, agreement over the two categories 'dysplasia' vs 'no dysplasia' was better, ranging from 68% to 84%, and for 'atypia present' (reactive atypia, low- and high-grade dysplasia) vs "no atypia' two pairings achieved over 90% and 11 pairings over 80% agreement. In view of its clinical importance, conditional agreement on high-grade dysplasia, pairwise agreement on this diagnosis ranged from 100% down to as low as 33%. However, most of these disagreements fell into the low-grade dysplasia category so that closer follow-up and further biopsies would still have been indicated. It is a truism that the basis for safe management is careful co-operation between clinicians and pathologists who have all the relevant facts and who know and trust one another's judgement. Thus, several aspects of the ideal diagnostic process cannot be evaluated in inter-observer studies and the element of artificiality should be borne in mind when applying the findings to diagnostic practice. Nevertheless, the low level of agreement on the diagnosis of high-grade dysplasia achieved by certain pairings of specialist pathologists is a disturbing outcome of this study. Inaccuracies should be minimized by a concensus approach and we therefore recommend referral of putative cases of dysplasia to interested pathologists for further opinions. We would also advocate that pathologists faced with appearances which are indefinite between reactive atypia and dysplasia, would do better to describe them in terms of "atypia, significance uncertain', so that closer surveillance is undertaken, rather than force them into more precise diagnostic categories which may be incorrect.

Distribution of episodes of mental illness in general practice: results from the Second National Morbidity Survey.

The Second National Morbidity Survey, conducted in England and Wales between 1970 and 1976, contains a unique body of information on episodes of mental illness experienced by individuals registered in a representative sample of general practices around the country. This information is used to construct the episode distribution among the individuals surveyed. The Poisson and negative binomial distributions are then used to model the episodes. The Poisson model gives a very poor fit but the negative binomial model is found to fit the data very well. Deviations of the observed data from this model are discussed. The possibility of applying this model at the local practice level is then considered.