Showing papers in "BMJ in 1994"

Collaborative overview of randomized trials of antiplatelet therapy .1. prevention of death, myocardial-infarction, and stroke by prolonged antiplatelet therapy in various categories of patients

Abstract: Abstract Objective: To determine the effects of “prolonged” antiplatelet therapy (that is, given for one month or more) on “vascular events” (non-fatal myocardial infarctions, non-fatal strokes, or vascular deaths) in various categories of patients. Design: Overviews of 145 randomised trials of “prolonged” antiplatelet therapy versus control and 29 randomised comparisons between such antiplatelet regimens. Setting: Randomised trials that could have been available by March 1990. Subjects: Trials of antiplatelet therapy versus control included about 70 000 “high risk” patients (that is, with some vascular disease or other condition implying an increased risk of occlusive vascular disease) and 30 000 “low risk” subjects from the general population. Direct comparisons of different antiplatelet regimens involved about 10 000 high risk patients. Results: In each of four main high risk categories of patients antiplatelet therapy was definitely protective. The percentages of patients suffering a vascular event among those allocated antiplatelet therapy versus appropriately adjusted control percentages (and mean scheduled treatment durations and net absolute benefits) were: (a) among about 20 000 patients with acute myocardial infarction, 10% antiplatelet therapy v 14% control (one month benefit about 40 vascular events avoided per 1000 patients treated (2P< 0.00001)); (b) among about 20 000 patients with a past history of myocardial infarction, 13% antiplatelet therapy v 17% control (two year benefit about 40/1000 (2P<0.00001)); (c) among about 10 000 patients with a past history of stroke or transient ischaemic attack, 18% antiplatelet therapy v 22% control (three year benefit about 40/1000 (2P<0.00001)); (d) among about 20 000 patients with some other relevant medical history (unstable angina, stable angina, vascular surgery, angioplasty, atrial fibrillation, valvular disease, peripheral vascular disease, etc), 9% v 14% in 4000 patients with unstable angina (six month benefit about 50/1000 (2P<0.00001)) and 6% v 8% in 16 000 other high risk patients (one year benefit about 20/1000 (2P<0.00001)). Reductions in vascular events were about one quarter in each of these four main categories and were separately statistically significant in middle age and old age, in men and women, in hypertensive and normotensive patients, and in diabetic and non: diabetic patients. Taking all high risk patients together showed reductions of about one third in non-fatal myocardial infarction, about one third in non-fatal stroke, and about one sixth in vascular death (each 2P<0.00001). There was no evidence that non-vascular deaths were increased, so in each of the four main high risk categories overall mortality was significantly reduced. The most widely tested antiplatelet regimen was “medium dose” (75-325 mg/day) aspirin. Doses throughout this range seemed similarly effective (although in an acute emergency it might be prudent to use an initial dose of 160-325 mg rather than about 75 mg). There was no appreciable evidence that either a higher aspirin dose or any other antiplatelet regimen was more effective than medium dose aspirin in preventing vascular events. The optimal duration of treatment for patients with a past history of myocardial infarction, stroke, or transient ischaemic attack could not be determined directly because most trials lasted only one, two, or three years (average about two years). Nevertheless, there was significant (2P<0.00001) further benefit between the end of year 1 and the end of year 3, suggesting that longer treatment might well be more effective. Among low risk recipients of “primary prevention” a significant reduction of one third in non: fatal myocardial infarction was, however, accompanied by a non-significant increase in stroke. Furthermore, the absolute reduction in vascular events was much smaller than for high risk patients despite a much longer treatment period (4.4% antiplatelet therapy v 4.8% control; five year benefit only about four per 1000 patients treated) and was not significant (2P=0.09). Conclusions: Among a much wider range of patients at high risk of occlusive vascular disease than is currently treated routinely, some years of antiplatelet therapy - with aspirin 75-325 mg/day or some other antiplatelet regimen (provided there are no contraindications) - offers worthwhile protection against myocardial infarction, stroke, and death. Significant benefit is evident not only among patients with unstable angina, suspected acute myocardial infarction, or a past history of myocardial infarction, stroke, or transient ischaemic attack, but also among many other categories of high risk patients (such as those having vascular procedures and those with stable angina or peripheral vascular disease). There is as yet, however, no clear evidence on the balance of risks and benefits of antiplatelet therapy in primary prevention among low risk subjects.

Systematic Reviews: Identifying relevant studies for systematic reviews

Abstract: Objective : To examine the sensitivity and precision of Medline searching for randomised clinical trials. Design - Comparison of results of Medline searches to a “gold standard” of known randomised clinical trials in ophthalmology published in 1988; systematic review (meta-analysis) of results of similar, but separate, studies from many fields of medicine. Populations : Randomised clinical trials published in in 1988 in journals indexed in Medline, and those not indexed in Medline and identified by hand search, comprised the gold standard. Gold standards for the other studies combined in the meta-analysis were based on: randomised clinical trials published in any journal, whether indexed in Medline or not; those published in any journal indexed in Medline; or those published in a selected group of journals indexed in Medline. Main outcome measure - Sensitivity (proportion of the total number of known randomised clinical trails identified by the search) and precision (proportion of publications retrieved by Medline that were actually randomised clinical trials) were calculated for each study and combined to obtain weighted means. Searches producing the “best” sensitivity were used for sensitivity and precision estimates when multiple searches were performed. Results : The sensitivity of searching for ophthalmology randomised clinical trials published in 1988 was 82%, when the gold standard was for any journal, 87% for any journal indexed in Medline, and 88% for selected journals indexed in Medline. Weighted means for sensitivity across all studies were 51%, 77%, and 63%, respectively. The weighted mean for precision was 8% (median 32.5%). Most searchers seemed not to use freetext subject terms and truncation of those terms. Conclusion - Although the indexing terms available for searching Medline for randomised clinical trials have improved, sensitivity still remains unsatisfactory. A mechanism is needed to “register” known trials, preferably by retrospective tagging of Medline entries, and incorporating trials published before 1966 and in journals not indexed by Medline into the system.

Diagnostic tests. 1: Sensitivity and specificity.

Abstract: The simplest diagnostic test is one where the results of an investigation, such as an x ray examination or biopsy, are used to classify patients into two groups according to the presence or absence of a symptom or sign For example, the table shows the relation between the results of a test, a liver scan, and the correct diagnosis based on either necropsy, …

ABC of breast diseases. Breast cancer--epidemiology, risk factors and genetics.

Abstract: With 1 million new cases in the world each year, breast cancer is the commonest malignancy in women and comprises 18% of all female cancers In the United Kingdom, where the age standardised incidence and mortality is the highest in the world, the incidence among women aged 50 approaches two per 1000 women per year, and the disease is the single commonest cause of death among women aged 40-50, accounting for about a fifth of all deaths in this age group There are more than 14 000 deaths each year, and the incidence is increasing particularly among women aged 50-64, probably because of breast screening in this age group #### Worldwide incidence of cancers in women (1980) View this table: Worldwide incidence of cancers in women (1980) Of every 1000 women aged 50, two will recently have had breast cancer diagnosed and about 15 will have had a diagnosis made before the age of 50, giving a prevalence of breast cancer of nearly 2% ### Age The incidence of breast cancer increases with age, doubling about every 10 years until the menopause, when the rate of increase slows dramatically Compared with lung cancer, the incidence of breast cancer is higher at younger ages In some countries there is a flattening of the age-incidence curve after the menopause Percentage of all deaths in women attributable to breast cancer Standardised mortality for breast cancer in different countries ### Geographical variation Age adjusted incidence and mortality for breast cancer varies by up to a factor of five between countries The difference between Far Eastern and Western countries is diminishing but is still about fivefold Studies of migrants from Japan to Hawaii show that the rates of breast cancer in migrants assume the rate in the host country within one or two generations, indicating that environmental factors are of greater importance than genetic factors Age specific incidence and mortality for …

Diagnostic tests 2: Predictive values.

Abstract: The whole point of a diagnostic test is to use it to make a diagnosis, so we need to know the probability that the test will give the correct diagnosis. The sensitivity and specificity1 do not give us this information. Instead we must approach the data from the direction of the test results, using predictive values. Positive predictive value is the proportion of patients with positive test results who are correctly diagnosed. Negative predictive value is the proportion of patients with negative test results who are correctly diagnosed. Using the same data as in the previous note,1 we know that 231 of 263 patients with abnormal liver scans had abnormal pathology, giving the proportion of correct diagnoses as 231/263 = 0.88. …

Incidence and recognition of malnutrition in hospital

Abstract: Objectives : To determine incidence of malnutrition among patients on admission to hospital, to monitor their changes in nutritional status during stay, and to determine awareness of nutrition in different clinical units. Design : Prospective study of consecutive admissions. Setting : Acute teaching hospital. Subjects : 500 patients admitted to hospital: 100 each from general surgery, general medicine, respiratory medicine, orthopaedic surgery, and medicine for the elderly. Main outcome measures: Nutritional status of patients on admission and reassessment on discharge, review of case notes for information about nutritional status. Results : On admission, 200 of the 500 patients were undernourished (body mass index less than 20) and 34% were overweight (body mass index >25). The 112 patients reassessed on discharge had mean weight loss of 5.4% with greatest weight loss in those initially most undernourished. But the 10 patients referred for nutritional support showed mean weight gain of 7.9%. Review of case notes revealed that, of the 200 undernourished patients, only 96 had any nutritional information documented. Conclusion : Malnutrition remains a largely unrecognised problem in hospital and highlights the need for education on clinical nutrition.

Rationale for systematic reviews.

Abstract: Systematic literature reviews including meta-analyses are invaluable scientific activities. The rationale for such reviews is well established. Health care providers, researchers, and policy makers are inundated with unmanageable amounts of information; they need systematic reviews to efficiently integrate existing information and provide data for rational decision making. Systematic reviews establish whether scientific findings are consistent and can be generalised across populations, settings, and treatment variations, or whether findings vary significantly by particular subsets. Meta-analyses in particular can increase power and precision of estimates of treatment effects and exposure risks. Finally explicit methods used in systematic reviews limit bias and, hopefully, will improve reliability and accuracy of conclusions. Systematic literature review is a fundamental scientific activity. Its rationale is grounded firmly in several premises. Firstly, large quantities of information must be reduced into palatable pieces for digestion. Over two million articles are published annually in the biomedical literature in over 20 000 journals1 - literally a small mountain of information. For example, about 4400 pages were devoted to approximately 1100 articles in the BMJ and New England Journal of Medicine, combined, in 1992. In a stack, two million such articles would rise 500 m. Clearly, systematic literature review is needed to refine these unmanageable amounts of information. Through critical exploration, evaluation, and synthesis the systematic review separates the insignificant, unsound, or redundant deadwood in the medical literature from the salient and critical studies that are worthy of reflection.2 Secondly, various decision makers need to integrate the critical pieces of available biomedical information. Systematic reviews are used by more specialised integrators, such as economic and decision analysts, to estimate the variables and outcomes that are included in their evaluations. Both systematic and more specialised integrations are used by clinicians to keep abreast of the primary literature in a given field …

Mortality in relation to consumption of alcohol: 13 years' observations on male British doctors

Abstract: Objective : To assess the risk of death associated20with various patterns of alcohol consumption. Design - Prospective study of mortality in relation to alcohol drinking habits in 1978, with causes of death sought over the next 13 years (to 1991). Subjects : 12 321 British male doctors born between 1900 and 1930 (mean 1916) who replied to a postal questionnaire in 1978. Those written to in 1978 were the survivors of a long running prospective study of the effects of smoking that had begun in 195120and was still continuing. Results - Men were divided on the basis of their response to the 1978 questionnaire into two groups according to whether or not they had ever had any type of vascular disease, diabetes, or “life threatening disease” and into seven groups according to the amount of alcohol they drank. By 1991 almost a third had died. All statistical analyses of mortality were standardised for age, calendar year, and smoking habit. There was a U shaped relation between all cause mortality and the average amount of alcohol reportedly drunk; those who reported drinking 8-14 units of alcohol a week (corresponding to an average of one to two units a day) had the lowest risks. The causes of death were grouped into three main categories: “alcohol augmented” causes (6% of all deaths: cirrhosis, liver cancer, upper aerodigestive (mouth, oesophagus, larynx, and pharynx) cancer, alcoholism, poisoning, or injury), ischaemic heart disease (33% of all deaths), and other causes. The few deaths from alcohol augmented causes showed, at least among regular drinkers, a progressive trend, with the risk increasing with dose. In contrast, the many deaths from ischaemic heart disease showed no significant trend among regular drinkers, but there were significantly lower rates in regular drinkers than in non-drinkers. The aggregate of all other causes showed a U shaped dose-response relation similar to that for all cause mortality. Similar differences persisted irrespective of a history of previous disease, age (under 75 or 75 and older), and period of follow up (first five and last eight years). Some, but apparently not much, of the excess mortality in non-drinkers could be attributed to the inclusion among them of a small proportion of former drinkers. Conclusion : The consumption of alcohol appeared to reduce the risk of ischaemic heart disease, largely irrespective of amount. Among regular drinkers mortality from all causes combined increased progressively with amount drunk above 21 units a week. Among British men in middle or older age the consumption of an average of one or two units of alcohol a day is associated with significantly lower all cause mortality than is the consumption of no alcohol, or the consumption of substantial amounts. Above about three units (two American20units) of alcohol a day, progressively greater levels of consumption are associated with progressively higher all cause mortality.

By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease

Abstract: Objective : To estimate by how much and how quickly a given reduction in serum cholesterol concentration will reduce the risk of ischaemic heart disease. Design : Data on the incidence of ischaemic heart disease and serum cholesterol concentration were analysed from 10 prospective (cohort) studies, three international studies in different communities, and 28 randomised controlled trials (with mortality data analysed according to allocated treatment to ensure the avoidance of bias). Main outcome measure - Decrease in incidence of ischaemic heart disease or mortality for a 0.6 mmol/l (about 10%) decrease in serum cholesterol concentration. Results : For men results from the cohort studies showed that a decrease of serum cholesterol concentration of 0.6 mmol/l (about 10%) was associated with a decrease in incidence of ischaemic heart disease of 54% at age 40 years, 39% at age 50, 27% at 60, 20% at 70, and 19% at 80. The combined estimate from the three international studies (for ages 55-64 years) was 38% (95% confidence interval 33% to 42%), somewhat greater than the cohort study estimate of 27%. The reductions in incidence of ischaemic heart disease in the randomised trials (for ages 55-64 years) were 7% (0 to 14%) in the first two years, 22% (15% to 28%) from 2.1-5 years, and 25% (15% to 35%) after five years, the last estimate being lose to the estimate of 27% for the long term reduction from the cohort studies. The data for women are limited but indicate a similar effect. Conclusions - The results from the cohort studies, international comparisons, and clinical trials are remarkably consistent. The cohort studies, based on half a million men and 18 000 ischaemic heart disease events, estimate that a long term reduction in serum cholesterol concentration of 0.6 mmol/l (10%), which can be achieved by moderate dietary change,lowers the risk of ischaemic heart disease by 50% at age 40, falling to 20% at age 70. The randomised trials, based on 45 000 men and 4000 ischaemic heart disease events show that the full effect of the reduction in risk is achieved by five years.

The Handbook of Research Synthesis

Abstract: Ed Harris Cooper, Larry V Hedges, Russell Sage Foundation, $49.95, pp 573 ISBN 0-87154-226-9 Methods for combining results across different studies have existed since the early ‘thirties, but the use of quantitative techniques for synthesising research results was rare until about 15 years ago. Meta- analysis, as the statistical analysis of a large collection of results from individual studies is called, has now achieved a status of respectability in medicine. This respectability, when combined with the slight hint of mystique …

Why sources of heterogeneity in meta-analysis should be investigated.

Abstract: Although meta-analysis is now well established as a method of reviewing evidence, an uncritical use of the technique can be very misleading One common problem is the failure to investigate appropriately the sources of heterogeneity, in particular the clinical differences between the studies included This paper distinguishes between the concepts of clinical and statistical heterogeneity and exemplifies the importance of investigating heterogeneity by using published meta-analyses of epidemiological studies of serum cholesterol concentration and clinical trials of its reduction Although not without some dangers of speculative conclusions, prompted by overzealous inspection of the data to hand, a sensible investigation of sources of heterogeneity should increase both the scientific and the clinical relevance of the results of meta-analyses

Eclampsia in the United Kingdom

Abstract: Objectives: To measure the incidence of eclampsia, establish how often it is preceded by signs of pre-eclampsia, document the morbidity associated with eclampsia, and determine the maternal case fatality rates. Design: A prospective, descriptive study of every case of eclampsia in the United Kingdom in 1992. Information was collected from reviews of hospital case notes and questionnaires to general practitioners. Setting: All 279 hospitals in the United Kingdom with a consultant obstetric unit. Results: Obstetricians and midwives notified 582 possible cases, and 383 were confirmed as eclampsia. The national incidence of eclampsia was 4.9/10000 maternities (95% confidence interval 4.5 to 5.4). Most convulsions occurred despite antenatal care (70%) and within one week of the woman9s last visit to a doctor or midwife (85%). Three quarters of first seizures occurred in hospital, of which 38% developed before both proteinuria and hypertension had been documented. Forty four per cent of cases occurred postpartum, more than a third (38%) antepartum, and the remainder (18%) intrapartum. Nearly one in 50 women (1.8%) died, and 35% of all women had at least one major complication. The rate of stillbirths and neonatal deaths was 22.2/1000 and 34.1/1000, respectively. Preterm eclampsia occurred more commonly antepartum and was associated with more maternal complications and fetuses that were small for gestational age, as well as with higher rates of stillbirth and neonatal mortality. Antepartum eclampsia, which was more likely to occur preterm, was associated with a higher rate of maternal complications and a higher neonatal mortality. Both factors (gestational prematurity and antepartum occurrence) contributed independently to the severity of the outcome. Conclusion: Eclampsia occurs in nearly one in 2000 maternities in the United Kingdom and is associated with high maternal morbidity and fatality in cases. It may present unheralded by warning signs. Preterm and antenatal eclampsia seem to be particularly severe.

Medical ethics : four principles plus attention to scope

Abstract: The “four principles plus scope” approach provides a simple, accessible, and culturally neutral approach to thinking about ethical issues in health care. The approach, developed in the United States, is based on four common, basic prima facie moral commitments - respect for autonomy, beneficence, non-maleficence, and justice - plus concern for their scope of application. It offers a common, basic moral analytical framework and a common, basic moral language. Although they do not provide ordered rules, these principles can help doctors and other health care workers to make decisions when reflecting on moral issues that arise at work. Nine years ago the BMJ allowed me to introduce to its readers1 an approach to medical ethics developed by the Americans Beauchamp and Childress,2 which is based on four prima facie moral principles and attention to these principles' scope of application. Since then I have often been asked for a summary of this approach by doctors and other health care workers who find it helpful for organising their thoughts about medical ethics. This paper, based on the preface of a large multiauthor textbook on medical ethics,3 offers a brief account of this “four principles plus scope” approach. The four principles plus scope approach claims that whatever our personal philosophy, politics, religion, moral theory, or life stance, we will find no difficulty in committing ourselves to four prima facie moral principles plus a reflective concern about their scope of application. Moreover, these four principles, plus attention to their scope of application, encompass most of the moral issues that arise in health care. The four prima facie principles are respect for autonomy, beneficence, non-maleficence, and justice. “Prima facie,” a term introduced by the English philosopher W D Ross, means that the principle is binding unless it conflicts with another moral principle …

Complementary medicine in Europe.

Abstract: Complementary or unconventional treatments are used by many doctors and other therapists throughout Europe. The major forms are acupuncture, homoeopathy, manual therapy or manipulation, and phytotherapy or herbal medicine. The relative popularity of therapies differs between countries, but public demand is strong and growing. Regulation of practitioners varies widely: in most countries only registered health professionals may practice, but in the United Kingdom practice is virtually unregulated. Germany and some Scandinavian countries have intermediate systems. Legal reforms are in progress in the Netherlands and the United Kingdom. European institutions are starting to influence the development of complementary medicine. Harmonisation of training and regulation of practitioners is the challenge for the future. To speak of “alternative” medicine is, as Pietroni has pointed out, like talking about foreigners—both terms are vaguely pejorative and refer to large, heterogeneous categories defined by what they are not rather than by what they are.1 The analogy is apt: the current worldwide trend away from suspicion and hostility between “orthodox” and “alternative” medicine towards investigation, understanding, and consumer protection can be compared with the process by which Europeans have learnt to view each other as partners rather than foreigners. This shift in attitude is evident in the BMA's recent publication, Complementary Medicine: New Approaches to Good Practice,2 and in the use of the term “complementary” rather than “alternative.” We welcome this new spirit and believe it will benefit patients. Even the term complementary medicine is not entirely satisfactory, lumping together as it does a wide range of methods with little in common except that they are outside the mainstream of medicine. The most accurate term is perhaps “unconventional therapeutic methods.” Consumer surveys consistently show positive public attitudes to complementary medicine, with about 60% of the public in the Netherlands3 and Belgium4 declaring themselves …

Prevalence of headache and migraine in schoolchildren.

Abstract: Objectives: To determine the prevalence rates of the various causes of severe headache in school-children, with special emphasis on migraine and its impact on school attendance. Design: Population based study in two stages, comprising an initial screening questionnaire followed by clinical interviews and examination of children with symptoms and a control group of asymptomatic children matched for age and sex. Setting: 67 primary and secondary schools in the city of Aberdeen. Subjects: 2165 children, representing a random sample of 10% of schoolchildren in Aberdeen aged 5-15 years. Main outcome measures: (a) the prevalence of20migraine (International Headache Society criteria) and of other types of headache; (b) the impact of migraine on school attendance. Results: The estimated prevalence rates of migraine and tension headache were 10.6% (95% confidence interval 9.1 to 12.3) and 0.9% (0.5 to 1.5) respectively. The estimated prevalence rates for migraine without aura and migraine with aura were 7.8% (95% confidence interval 6.5 to 9.3) and 2.8% (2.0 to 3.8) respectively. In addition, 10 children (0.7%) had headaches which, though lasting less than two hours, also fulfilled the International Headache Society criteria for migraine, 14 (0.9%) had tension headaches, and 20 (1.3%) had non-specific recurrent headache. The prevalence of migraine increased with age, with male preponderance in children under 12 and female preponderance thereafter. Children with migraine lost a mean of 7.8 school days a year due to all illnesses (2.8 days (range 0-80) due to headache) as compared with a mean of 3.7 days lost by controls. Conclusions: Migraine is a common cause of headache in children and causes significantly reduced school attendance.

Birth weight and non-insulin dependent diabetes: thrifty genotype, thrifty phenotype, or surviving small baby genotype?

Abstract: Objective : To determine the prevalence of diabetes in relation to birth weight in Pima Indians. Design : Follow up study of infants born during 1940-72 who had undergone a glucose tolerance test at ages 20-39 years. Setting : Gila River Indian community, Arizona. Subjects : 1179 American Indians. Main outcome measure: Prevalence of non-insulin dependent diabetes mellitus (plasma glucose concentration >=11.1 mmol/l two hours after ingestion of carbohydrate). Results : The prevalence was greatest in those with the lowest and highest birth weights. The age adjusted prevalences for birth weights =4500 g were 30%, 17%, and 32%, respectively. When age, sex, body mass index, maternal diabetes during pregnancy, and birth year were controlled for, subjects with birth weights =4500 g) was associated with maternal diabetes during pregnancy. Most diabetes, however, occurred in subjects with intermediate birth weights (2500-4500 g). Conclusions : The relation of the prevalence of diabetes to birth weight in the Pima Indians is U shaped and is related to parental diabetes. Low birth weight is associated with non-insulin dependent diabetes. Given the high mortality of low birthweight infants selective survival in infancy of those genetically predisposed to insulin resistance and diabetes provides an explanation for the observed relation between low birth weight and diabetes and the high prevalence of diabetes in many populations.

The scandal of poor medical research.

Abstract: We need less research, better research, and research done for the right reasons What should we think about a doctor who uses the wrong treatment, either wilfully or through ignorance, or who uses the right treatment wrongly (such as by giving the wrong dose of a drug)? Most people would agree that such behaviour was unprofessional, arguably unethical, and certainly unacceptable. What, then, should we think about researchers who use the wrong techniques (either wilfully or in ignorance), use the right techniques wrongly, misinterpret their results, report their results selectively, cite the literature selectively, and draw unjustified conclusions? We should be appalled. Yet numerous studies of the medical literature, in both general and specialist journals, have shown that all of the above phenomena are common.1 2 3 4 5 6 7 This is surely a scandal. When I tell friends outside medicine that many papers published in medical journals are misleading because of methodological weaknesses they are rightly shocked. Huge sums of money are spent annually on research that is seriously flawed through the use of inappropriate designs, unrepresentative samples, small samples, incorrect methods …

Third degree obstetric anal sphincter tears: risk factors and outcome of primary repair

Abstract: Objectives To determine (i) risk factors in the development of third degree obstetric tears and (ii) the success of primary sphincter repair. Design (i) Retrospective analysis of obstetric variables in 50 women who had sustained a third degree tear, compared with the remaining 8553 vaginal deliveries during the same period. (ii) Women who had sustained a third degree tear and had primary sphincter repair and control subjects were interviewed and investigated with anal endosonography, anal manometry, and pudendal nerve terminal motor latency measurements Setting: Antenatal clinic in teaching hospital in inner London. Subjects (i) All women (n=8603) who delivered vaginally over a 31 month period. (ii) 34 women who sustained a third degree tear and 88 matched controls. Main outcome measures : Obstetric risk factors, defaecatory symptoms, sonographic sphincter defects, and pudendal nerve damage. Results - (i) Factors significantly associated with development of a third degree tear were: forceps delivery (50% v 7% in controls; P=0.00001), primiparous delivery (85% v 43%; P=0.00001), birth weight >4 kg (P=0.00002), and occipitoposterior position at delivery (P=0.003). No third degree tear occurred during 351 vacuum extractions. Eleven of 25 (44%) women who were delivered without instruments and had a third degree tear did so despite a posterolateral episiotomy. (ii) Anal incontinence or faecal urgency was present in 16 women with tears and 11 controls (47% v 13%;20P=0.00001). Sonographic sphincter defects were identified in 29 with tears and 29 controls (85% v 33%; P=0.00001). Every symptomatic patient had persistent combined internal and external sphincter defects, and these were associated with significantly lower anal pressures. Pudendal nerve terminal motor latency measurements were not significantly different. Conclusions Vacuum, extraction is associated with fewer third degree tears than forceps delivery. An episiotomy does not always prevent a third degree tear. Primary repair is inadequate in most women who sustain third degree tears, most having residual sphincter defects and about half experiencing anal incontinence, which is caused by persistent mechanical sphincter disruption rather than pudendal nerve damage. Attention should be directed towards preventive obstetric practice and surgical techniques of repair.

Population based study of fatigue and psychological distress

Abstract: Objectives: To determine the prevalence of fatigue in the general population and the factors associated with fatigue. Design: Postal survey. Setting: Six general practices in southern England. Subjects: 31 651 men and women aged 18-45 years registered with the practices. Main outcome measures: Responses to the 12 item general health questionnaire and a fatigue questionnaire which included self reported measures of duration, severity, and causes of fatigue. Results - 15 283 valid questionnaires were returned, giving a response rate of 48.3%, (64% after adjustment for inaccuracies in the practice registers). 2798 (18.3%) of respondents reported substantial fatigue lasting six months or longer. Fatigue and psychological morbidity were moderately correlated (r=0.62). Women were more likely to complain of fatigue than men, even after adjustment for psychological distress. The commonest cited reasons for fatigue were psychosocial (40% of patients). Of 2798 patients with excessive tiredness, only 38 (1.4%) attributed this to the chronic fatigue syndrome. Conclusion: Fatigue is distributed as a continuous variable in the community and is closely associated with psychological morbidity.

Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women.

Abstract: We recently showed that daily supplementation with 12 g calcium and 800 IU cholecalciferol over 18 months substantially decreased the risk of hip fractures and other non-vertebral fractures in elderly women living in nursing homes1 We report the results of a further 18 months of treatment A total of 3270 mobile elderly women (mean age 84 (SD 6) years) living in 180 nursing homes were enrolled in the study Half the women received 12 g calcium daily in the form of tricalcium phosphate, together with 800 IU (20 μg) cholecalciferol; the other half received a double placebo All subjects were followed up every six months; biochemical variables were measured at baseline and every year in a subgroup of 52 women Hip fractures and all non-vertebral fractures were separately analysed using a log …

Abnormal bacterial colonisation of the genital tract and subsequent preterm delivery and late miscarriage

Abstract: Objective : To find out whether women with bacterial vaginosis detected early in pregnancy are at increased risk of preterm delivery. Design : Prospective description cohort study. Setting : Antenatal clinic in a district general hospital. Subjects : 783 women examined during their first antenatal clinic visit and screened for recognised risk factors for preterm delivery and the presence of bacterial vaginosis or intermediate abnormal flora detected by examination of a vaginal smear stained by Gram9s method. Main outcome measures : Gestational age at delivery classified as late miscarriage (16-24 weeks9 gestation), preterm delivery (24-37 weeks9 gestation), term delivery (>=37 weeks9 gestation). Results : Multiple logistic analysis showed that there was an increased incidence of preterm delivery in women with a previous preterm delivery (9/24; odds ratio 25; 95% confidence interval 9 to 70; P Conclusions : Late miscarriage and preterm delivery are associated with the presence of bacterial vaginosis in early pregnancy. This is independent of recognised risk factors such as previous preterm delivery.

Collaborative overview of randomised trials of antiplatelet therapy--III: Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. Antiplatelet Trialists' Collaboration.

Abstract: OBJECTIVE--To determine the efficacy of antiplatelet therapy as prophylaxis against deep venous thrombosis or pulmonary embolism in surgical and high risk medical patients. DESIGN--Overviews of all randomised trials of antiplatelet therapy that could have been available by March 1990 and in which deep venous thrombosis was assessed systematically. SETTING--53 trials (total 8400 patients) of an average of two weeks of antiplatelet therapy versus control in general or orthopaedic surgery; nine trials (600 patients) of antiplatelet therapy versus control in other types of immobility; 18 trials (1000 patients) of one antiplatelet regimen versus another. RESULTS--Overall, a few weeks of antiplatelet therapy produced a highly significant (2P < 0.00001) reduction in deep venous thrombosis. 25% of patients allocated antiplatelet therapy versus 34% of appropriately adjusted controls had deep venous thrombosis detected by systematic fibrinogen scanning or venography, representing prevention in about 90 patients per 1000 allocated antiplatelet therapy. There was an even greater proportional reduction in pulmonary embolism: such emboli were detected among 47 (1.0%) antiplatelet allocated patients versus an adjusted control total of 129 (2.7%), representing prevention among about 17 patients per 1000 treated (2P < 0.00001). In analyses confined to surgical trials, the proportional reductions were similar and separately significant for nonfatal pulmonary embolism (0.7% antiplatelet therapy v 1.8% control; 2P < 0.00001) and for deaths attributed to pulmonary embolism (0.2% v 0.9%; 2P = 0.0001). There was a slight but non-significant excess of deaths from other causes (1.0% v 0.7%), which made the difference in total mortality nonsignificant, though still favourable (1.2% v 1.5%). Information on adding antiplatelet therapy to heparin was limited but, at least for pulmonary embolism, suggested more protection from the combination than from heparin alone. The proportional reduction in the odds of suffering a deep venous thrombosis was roughly the same in patients having general surgery, traumatic orthopaedic surgery, and elective orthopaedic surgery (and in medical patients who were at increased risk of thromboembolism). For pulmonary embolism the numbers affected were smaller, but again the reductions were highly significant both in general surgery (16 (0.5%) v 58 (1.7%) pulmonary emboli; 2P < 0.0001) and in orthopaedic surgery (28 (2.7%) v 63 (6.1%) pulmonary emboli; 2P < 0.0002). CONCLUSION--It had previously been supposed that antiplatelet therapy did not influence venous thromboembolism, and many surgeons and physicians do not use it routinely for thromboprophylaxis, even for patients who are at substantial risk of deep venous thrombosis or pulmonary embolism. These results indicate that antiplatelet therapy--either alone or, for greater effect, in addition to other proved forms of thromboprophylaxis (such as subcutaneous heparin)--should be considered.

Diagnostic tests 3: receiver operating characteristic plots

Abstract: We have previously considered diagnosis based on tests that give a yes or no answer.1, 2 Many diagnostic tests, however, are quantitative, notably in clinical chemistry. The same statistical approach can be used only if we can select a cut off point to distinguish “normal” from “abnormal,” which is not a trivial problem. Firstly, we can investigate to what extent the test results differ among people who do or do not have the diagnosis of interest. The receiver operating characteristic (ROC) plot is one way to do this. These plots were developed in the 1950s for evaluating radar signal detection. Only recently have they become commonly used in medicine. We assume that high values are more likely …

Ethnicity as a variable in epidemiological research.

Abstract: Ethnicity is used increasingly as a key variable to describe health data, and ethnic monitoring in the NHS will further stimulate this trend. We identify four fundamental problems with ethnicity in this type of research: the difficulties of measurement, the heterogeneity of the populations being studied, lack of clarity about the research purpose of the research, and ethnocentricity affecting the interpretation and use of data. Ethnicity needs to be used carefully to be a useful tool for health research. We make nine recommendations for future practice, one of which is that ethnicity and race should be recognised and treated as distinct concepts. Epidemiology is the study of the distribution and determinants of disease. The main method of study, particularly for investigating the causes of disease, is to compare populations with different risks of disease. Ethnicity is a variable that is used increasingly to define populations for epidemiological studies. Differences by ethnicity in both the characteristics of populations and their experience of disease have been easy to describe, and the literature on ethnicity and health is large and growing.1 We consider here the nature of ethnicity, the attributes of sound epidemiological variables, the measurement and value of ethnicity as an epidemiological variable, and how ethnicity might best be used in future research. By reviewing critically ethnicity as a variable in epidemiology we hope to facilitate better research. This review is relevant to ethnic monitoring in the NHS. Ethnicity is derived from a Greek word meaning a people or tribe. The concept of ethnicity is neither simple nor precise,*RF 2-6* but it implies one or more of the following: shared origins or social background; shared culture and traditions that are distinctive, maintained between generations, and lead to a sense of identity and group; and a common language or religious tradition.*RF 3-6* …

Changing prevalence of asthma in Australian children

Abstract: Objective : To investigate whether prevalence of asthma in children increased in 10 years. Design : Serial cross sectional studies of two populations of children by means of standard protocol. Setting : Two towns in New South Wales: Belmont (coastal and humid) and Wagga Wagga (inland and dry). Subjects : Children aged 8-10 years: 718 in Belmont and 769 in Wagga Wagga in 1982; 873 in Belmont and 795 in Wagga Wagga in 1992. Main outcome measures : History of respiratory illness recorded by parents in self administered questionnaire; airway hyperresponsiveness by histamine inhalation test; atopy by skin prick tests; counts of house dust mites in domestic dust. Results : Prevalence of wheeze in previous 12 months increased in Belmont, from 10.4% (75/718) in 1982 to 27.6% (240/873) in 1992 (P Conclusions : We suggest that exposure to higher allergen levels has increased airway abnormalities in atopic children or that mechanisms that protected airways of earlier generations of children have been altered by new environmental fators.

Regression towards the mean.

Abstract: The statistical term “regression,” from a Latin root meaning “going back,” was first used by Francis Galton in his paper “Regression towards Mediocrity in Hereditary Stature.”1 Galton related the heights of children to the average height of their parents, which he called the mid- parent height (figure). Children and parents had the same mean height of 68.2 inches. The ranges differed, however, because the mid-parent height was an average of two …

Cardiovascular disease and distribution of cognitive function in elderly people: the Rotterdam Study.

Abstract: Objective: To investigate the distribution of cognitive function in elderly people and to assess the impact of clinical manifestations of atherosclerotic disease on this distribution. Design: Single centre population based cross sectional door to door study. Setting: Ommoord, a suburb of Torrerdam, the Netherlands. Subjects: 4971 subjects aged 55 to 94 years. Main outcome measure: Cognitive function as measured by the mini mental state examination. Results: The overall participation rate in the study was 80%. Cognitive test data were available for 90% of the participants. Increasing age and lower educational level were associated with poorer cognitive function. Previous vascular events, presence of plaques in the carotid arteries, and presence of peripheral arterial atherosclerotic disease were associated with worse cognitive performance independent of the effects of age and education. On average the differences were moderate; however, they reflected the net result of a shift of the total population distribution of cognitive function towards lower values. Thereby, they resulted in a considerable increase in the proportion of subjects with scores indicative of dementia. Conclusions: These findings are compatible with the view that atherosclerotic disease accounts for considerable cognitive impairment in the general population.

Comparison of tests for glycated haemoglobin and fasting and two hour plasma glucose concentrations as diagnostic methods for diabetes

Abstract: Objective : To compare the ability of tests measuring two hour plasma glucose, fasting plasma glucose, and glycated haemoglobin concentrations in predicting the specific microvascular complications of non-insulin dependent diabetes mellitus. Design : Cross sectional and longitudinal analysis of the relation between complications and concomitant results of the three tests. Setting : Gila River Indian Community, Arizona. Subjects : Pima Indians (cross sectional, n=960),aged 25 years or above who were not receiving insulin or oral hypoglycaemic treatment at the baseline examination. Main outcome measures : Development of retinopathy and nephropathy. Results : Cross sectionally, frequency distributions of logarithms of the three sets of results were bimodal, with the prevalence of retinopathy and nephropathy being, respectively, 12.0-26.7 and 3.9-4.2 times as high above as below cut off points which minimised overlap (two hour plasma glucose concentration 12.6 mmol/l; fasting plasma glucose concentration 9.3mmol/l; glycated haemoglobin (HbA1c) concentration 7.8%). Longitudinally, each of the three measures of glycaemia significantly predicted the development of retinopathy (P Conclusions : These findings suggest that determination of glycated haemoglobin or fasting plasma glucose concentrations alone may be acceptable alternatives to measuring glucose concentration two hours after challenge with 75 g glucose for the diagnosis of diabetes.

Childhood antecedents of schizophrenia and affective illness: social adjustment at ages 7 and 11.

Abstract: OBJECTIVE: To investigate the social adjustment in childhood of people who as adults have psychiatric disorders. DESIGN: Subjects in a prospectively followed up cohort (the national child development study) who had been admitted as adults to psychiatric hospitals were compared with the rest of the cohort on ratings of social behaviour made by teachers at the ages of 7 and 11 years. SUBJECTS: 40 adult patients with schizophrenic illnesses, 35 with affective psychoses, and 79 with neurotic illness who had been admitted for psychiatric reasons by the age of 28. 1914 randomly selected members of the cohort who had never been admitted for psychiatric treatment. MAIN OUTCOME MEASURES: Overall scores and scores for overreaction (externalising behaviour) and underreaction (internalising behaviour) with the Bristol social adjustment guide at ages 7 and 11. RESULTS: At the age of 7 children who developed schizophrenia were rated by their teachers as manifesting more social maladjustment than controls (overall score 4.3 (SD 2.4) v 3.1 (2.0); P < 0.01). This was more apparent in the boys (5 (2.6)) than the girls (3.4 (1.8)) and related to overreactive rather than underreactive behaviour. At both ages prepsychotic (affective) children differed little from normal controls. By the age of 11 preneurotic children, particularly the girls, had an increased rating of maladjustment (including overreactions and underreactions). CONCLUSION: Abnormalities of social adjustment are detectable in childhood in some people who develop psychotic illness. Sex and the rate of development of different components of the capacity for social interaction are important determinants of the risk of psychosis and other psychiatric disorders in adulthood.