Accuracy of clinical signs, SEP, and EEG in predicting outcome of hypoxic coma: a meta-analysis.

OBJECTIVE: Accurate prediction of neurologic outcome after hypoxic coma is important. Previous systematic reviews have not used summary statistics to summarize and formally compare the accuracy of different prognostic tests. We therefore used summary receiver operating characteristic curve (SROC) and cluster regression methods to compare motor and pupillary responses with sensory evoked potential (SEP) and EEG in predicting outcome after hypoxic coma. METHODS: We searched PubMed, MEDLINE, and Embase (1966-2007) for reports in English, German, and French and identified 25 suitable studies. An SROC was constructed for each marker (SEP, EEG, M1 and M < or = 3), and the area under the curve (AUC), a measure of diagnostic accuracy, was determined. For comparison, we calculated the differences between the AUC for each test and M1 reference standard. RESULTS: The AUC for absent SEP was larger than those for M1, M < or = 3, absent pupillary response, and EEG when the examinations were performed within the first 24 hours. The difference between the AUC for SEP (AUC 0.891) and that for M1 (AUC 0.786) was small (0.105, 95% confidence interval 0.023-0.187), only reaching significance on day 1 after coma onset. The use of M < or = 3 improved the diagnostic accuracy of motor signs. CONCLUSIONS: This study demonstrated that sensory evoked potential (SEP) is marginally better than M1 at predicting outcome after hypoxic coma. However, the superiority of SEP diminishes after day 1 and when M < or = 3 is used. The findings therefore caution against the tendency to generalize that SEP is a better marker than clinical signs.

Validation of linear cerebral atrophy markers in multiple sclerosis.

Linear measures of cerebral ventricular enlargement may act as surrogate measures of cerebral atrophy in multiple sclerosis (MS). Linear atrophy markers were measured from routine MRI scans during a population survey of 171 Tasmanian MS patients and 91 healthy controls. Thirty-five Victorian MS clinic patients were recruited as a validation cohort with 14 of these re-assessed 4 years later. In the population survey, we measured three linear brain atrophy markers: inter-caudate distance (ICD), third ventricle width (TVW) and frontal horn width (FHW). TVW (OR 2.0, p=0.001) and ICD (OR 16.1, p<0.001) differentiated between MS cases and controls. In the validation study, we correlated the intercaudate ratio (ICR=ICD/brain width) and third ventricular ratio (TVR=TVW/brain width) with brain parenchymal volume. Cross-sectionally, ICR (R=-0.453, p<0.01) and TVR (R=-0.653, p<0.01) were correlated with brain parenchymal volume. Longitudinally, brain parenchymal volume loss was inversely correlated with increased ICD (R=-0.77, p<0.01) and TVW (R=-0.71, p<0.01). This study shows that ICD measurements obtained from clinical MRI scans are valid brain atrophy measures for use in monitoring MS progression.

Health Watch exposure estimates: do they underestimate benzene exposure?

A nested case-control study found that the excess of leukemia, identified among the male members of the Health Watch cohort, was associated with benzene exposure. Exposure had been retrospectively estimated for each individual occupational history using an algorithm in a relational database. Benzene exposure measurements, supplied by Australian petroleum companies, were used to estimate exposure for specific tasks. The tasks carried out within each job, the products handled, and the technology used, were identified from structured interviews with contemporary colleagues. More than half of the subjects started work after 1965 and had an average exposure period of 20 years. Exposure was low; nearly 85% of the cumulative exposure estimates were at or below 10 ppm-years. Matched analyses showed that leukemia risk increased with increasing cumulative benzene exposures and with increasing exposure intensity of the highest-exposed job. Non-Hodgkin lymphoma and multiple myeloma were not associated with benzene exposure. A reanalysis reported here, showed that for the 7 leukemia case-sets with greater than 16 ppm-years cumulative exposure, the odds ratio was 51.9 (5.6-477) when compared to the 2 lowest exposed categories combined to form a new reference category. The addition of occasional high exposures, e.g. as a result of spillages, increased exposure for 25% of subjects but for most, the increase was less than 5% of total exposure. The addition of these exposures reduced the odds ratios. Cumulative exposures did not range as high as those in comparable studies; however, the recent nature of the cohort and local handling practices can explain these differences.

Onset seizures independently predict poor outcome after subarachnoid hemorrhage.

OBJECTIVE: To determine whether onset seizures after subarachnoid hemorrhage (SAH) carry independent prognostic information and to investigate the risk factors for late seizures after SAH. BACKGROUND: Modern management of SAH, including early operation, has substantially reduced mortality. No study has adequately assessed the importance of onset seizures in a contemporary SAH cohort. METHODS: The authors analyzed the records and initial CT scans of 412 consecutive patients with aneurysmal or nonaneurysmal SAH admitted to the Royal Melbourne Hospital from 1990 to 1996. Each patient with an onset seizure (n = 32, 7.8% of cohort) was age and sex matched to two nonseizure patients of the same cohort. Each patient with a late seizure (n = 17, 5.1% of cohort) was matched to five control subjects of the same cohort. RESULTS: With use of logistic regression analysis, onset seizures correlated with the sum score of blood on initial CT scan (OR = 1.1, p = 0.05), but there was no significant correlation with duration of loss of consciousness at onset, Glasgow Coma Score (GCS), presence of aneurysm, or past history of hypertension or epilepsy. Disability 6 weeks after SAH according to the Glasgow Outcome Scale was independently predicted by initial GCS of <6 (OR = 13.7, p < 0.01) and onset seizure (OR = 7.8, p = 0.04). Late seizures within the first 6 weeks were independently related to rebleeding (OR = 94, p < 0.01) and onset seizures (OR = 27, p < 0.01) but not to other onset variables, development of hydrocephalus, or vasospasm. CONCLUSION: In this single-institution cohort of patients with SAH, onset seizures were an independent risk factor for late seizures and a predictor of poor outcome.

Stigma and Alzheimer's disease: causes, consequences and a constructive approach.

The term 'Alzheimer's disease' has entered the vocabulary of ordinary people. This has been useful, encouraging patients and families to seek medical help for conditions that were previously neglected as inevitable consequences of old age. Yet Alzheimer's itself can carry negative connotations. Some people who believe they have Alzheimer's disease are suffering from less sinister and more easily treated conditions. Even when the diagnosis is confirmed, many months of happy and worthwhile life continue for most patients and families if they are given appropriate information and support. It is important that neither families nor clinicians see life with presumed Alzheimer's disease as of no value.

Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2. Australian Breast Cancer Family Study.

The average breast cancer risk for carriers of a germ-line mutation in BRCA1 or BRCA2 (penetrance) has been estimated from the multiple-case families collected by the Breast Cancer Linkage Consortium (BCLC) to be approximately 80% to age 70. However, women now being tested for these mutations do not necessarily have the intense family history of the BCLC families. Testing for protein-truncating mutations in exons 2, 11, and 20 of BRCA1 and exons 10 and 11 of BRCA2 was conducted in a population-based sample of 388 Australian women with breast cancer diagnosed before age 40. Onset of breast cancer was analyzed in the known and potential mutation-carrying first- and second-degree female relatives of cases found to carry a mutation. Of the 18 mutation-carrying cases (9 BRCA1 and 9 BRCA2), only 5 (1 BRCA1 and 4 BRCA2) had at least one affected relative, so family history of breast cancer was not a strong predictor of mutation status in this setting. The risk in mutation carriers was, on average, 9 times the population risk [95% confidence interval (CI), 4-23; P < 0.001]. Penetrance to age 70 was 40% (95% CI, 15-65%), about half that estimated from BCLC families. By extrapolation, approximately 6% (95% CI, 2-20%) of breast cancer before age 40 may be caused by protein-truncating mutations in BRCA1 or BRCA2. Breast cancer risk in BRCA1 or BRCA2 mutation carriers may be modified by other genetic or environmental factors. Genetic counselors may need to take into account the family history of the consultand.

Gender, isolation, work patterns and stress among old age psychiatrists.

OBJECTIVE: To investigate work patterns and stress in consultant old age psychiatrists over a period of 1 week and to attempt to identify areas amenable to change. DESIGN: Postal survey. PARTICIPANTS: Full-time old age psychiatrists on the list held by the Faculty of Old Age Psychiatry, Royal College of Psychiatrists. MAIN OUTCOME MEASURES: Hours spent on different work activities during a period of 1 week, Stress Checklist score, stressors perceived by respondents. MAIN RESULTS: Men and women doctors did not differ in numbers of hours worked. Consultants working with colleagues worked similar hours to single-handed consultants. Community activity was greater among consultants working with colleagues than among single-handed doctors, whose work was based more in outpatient clinics. For the whole group, time in acute ward rounds correlated positively with stress score and time spent on research at home correlated negatively with stress score. CONCLUSIONS: Doctors spending more than 50 hours at work might be advised to review their work pattern. Excessive time on administrative activities should be reduced. Peer support should be encouraged. Consultants and managers should be sensitive to work patterns and possible sources of stress.

Inter-hospital comparison of mortality rates.

OBJECTIVE: To compare crude and adjusted in-hospital mortality rates after prostatectomy between hospitals using routinely collected hospital discharge data and to illustrate the value and limitations of using comparative mortality rates as a surrogate measure of quality of care. METHODS: Mortality rates for non-teaching hospitals (n = 21) were compared to a single notional group of teaching hospitals. Patients age, disease (comorbidity), length of stay, emergency admission, and hospital location were identified using ICD-9-CM coded Victorian hospital morbidity data from public hospitals collected between 1987/88 and 1994/95. Comparisons between hospitals were based on crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) derived using univariate and multivariate logistic regression. Model fit was evaluated using receiver operating characteristic curve i.e. statistic, Somer's D, Tau-a, and R2. RESULTS: The overall crude mortality rates between hospitals achieved borderline significance (alpha2=31.31; d.f.=21; P=0.06); these differences were no longer significant after adjustment (chi2=25.68; P=0.21). On crude analysis of mortality rates, four hospitals were initially identified as 'low' outlier hospitals; after adjustment, none of these remained outside the 95% CI, whereas a new hospital emerged as a 'high' outlier (OR=4.56; P= 0.05). The adjusted ORs between hospitals compared to the reference varied from 0.21 to 5.54, ratio = 26.38. The model provided a good fit to the data (c=0.89; Somer's D= (0.78; Tau-a = 0.013; R2= 0.24). CONCLUSIONS: Regression adjustment of routinely collected data on prostatectomy from the Victorian Inpatient Minimum Database reduced variance associated with age and correlates of illness severity. Reduction of confounding in this way is a move in the direction of exploring differences in quality of care between hospitals. Collection of such information over time, together with refinement of data collection would provide indicators of change in quality of care that could be explored in more detail as appropriate in the clinical setting.

Design and analysis issues in a population-based, case-control-family study of the genetic epidemiology of breast cancer and the Co-operative Family Registry for Breast Cancer Studies (CFRBCS).

BACKGROUND: Historically, studies of the "genetic epidemiology" of cancer have used nonsystematically sampled kindreds with numerous cases of cancer across multiple generations. From the epidemiologic viewpoint, it is difficult to extrapolate findings to the population because of the ad hoc ascertainment of these atypical, ill-defined families. Since 1992, we have been conducting a population-based, case-control-family study of breast cancer. METHODS: Families are identified through a single, population-sampled proband, who is either affected or unaffected, making adjustment for ascertainment straightforward. Administered questionnaires and blood samples are sought from cases, controls, and specified sets of relatives. From 1996 through 1999, a further 1200 case families have been recruited as part of the Co-operative Family Registry for Breast Cancer Studies (CFRBCS). Issues relevant to the study design and analysis are discussed. RESULTS: Epidemiologic and genetic findings published to date are summarized. In particular, this population-based study has shown that the so-called "high-risk" families containing multiple cases of breast cancer are not typical of families in the general population in which BRCA1 or BRCA2 mutations are segregating. Most "hereditary" cancers are "sporadic." CONCLUSION: The collection of DNA, as well as data on disease status and risk factors, from population-sampled sets of relatives provides a powerful resource for addressing genetic and environmental determinants of cancer. A population-based multicenter, multidisciplinary enterprise, such as has been developed by the CFRBCS, may become a model for future research in cancer epidemiology, allowing genetic and environmental risk factors to be put into a proper population perspective.

Adverse events after prostatectomy in Victorian public hospitals.

BACKGROUND: A retrospective analysis of data from the Victorian Inpatient Minimum Database (VIMD) was conducted to analyse trends in prostatectomy rates in Victorian public acute-care hospitals from 1989/90 to 1994/95. The study also sought to identify predictors of adverse events (AE) after prostatectomy, and to compare in-hospital complications between open prostatectomy and transurethral resection of prostate (TURP). METHODS: All patients who had undergone any prostatectomy were identified according to the relevant ICD-9-CM procedure codes (60.2-60.4) documented in the VIMD. The main outcome measures, AE, were identified using the ICD-9-CM supplementary classification of external cause of injury (E850-858, E870-876, E878-879, E930-949). The variables used as predictors were year of prostatectomy, type of admission (planned, emergency), location of the hospital (rural, metropolitan), type of procedure (TURP, open), and teaching status of the hospital. Crude and adjusted odds ratios (OR) were based on univariate and multivariate logistic regression. RESULTS: The rates of prostatectomies have significantly increased over the 6-year study period (P for trend < 0.0001). The percentage of AE after prostatectomy increased simultaneously from 6.1 to 12.9% (P < 0.0001). During the same period, the in-hospital mortality rate after prostatectomy decreased from 1.2 to 0.5%, and length of stay decreased from 10.3 to 6.1 days (Kruskal-Wallis P < 0.0001). The significant predictors of outcome were year of prostatectomy (P for trend < 0.0001), emergency admissions (OR = 1.57; P < 0.0001), metropolitan hospitals (OR = 0.81; P = 0.0003), non-teaching hospitals (OR = 0.78; P < 0.0001), and open prostatectomy (OR = 1.52; P = 0.04). More in-hospital complications were associated with open prostatectomy than with TURP. CONCLUSIONS: The rise in AE rate after prostatectomy is unlikely to reflect poor quality of care, because in the same period there was a significant decrease in in-hospital mortality after prostatectomy. A more likely explanation is heightened awareness of AE with a lower threshold for reporting such events. Important factors other than variations in quality of care can result in an increase in AE. Hence the reported increase should be interpreted with caution before attempting to conclude that changes in clinical practice could have a direct impact on these rates.

Effectiveness of needle-exchange programmes for prevention of HIV infection.

BACKGROUND: Needle-exchange programmes (NEPs) are potentially a key strategy for containing the spread of HIV infection among injecting drug users, but their implementation has been limited by uncertainty about their effectiveness. We used an ecological study design to compare changes over time in HIV seroprevalence in injecting drug users worldwide, for cities with and without NEPs. METHODS: Published reports of HIV seroprevalence in injecting drug users were identified, and unpublished information on HIV seroprevalence for injecting drug users entering drug treatment in the USA between 1988 and 1993 was obtained from the Centers for Disease Control and Prevention. Details of the implementation of NEPs were obtained from published reports and experts. For each of the 81 cities with HIV seroprevalence data from more than 1 year and NEP implementation details, the rate of change of seroprevalence was estimated by regression analysis. The average difference in this rate for cities with and without NEPs was calculated. FINDINGS: On average, seroprevalence increased by 5.9% per year in the 52 cities without NEPs, and decreased by 5.8% per year in the 29 cities with NEPs. The average annual change in seroprevalence was 11% lower in cities with NEPs (95% CI -17.6 to -3.9, p = 0.004). INTERPRETATION: A plausible explanation for this difference is that NEPs led to a reduction in HIV incidence among injecting drug users. Despite the possibility of confounding, our results, together with the clear theoretical mechanisms by which NEPs could reduce HIV incidence, strongly support the view that NEPs are effective.

The everyday work of geriatric psychiatrists.

A workload questionnaire, detailing activities undertaken over a specified 7-day period, was circulated by post to geriatric psychiatrists on the list held by the Section of Old Age Psychiatry, Royal College of Psychiatrists. One hundred and thirty-eight responses have been analysed to show patterns of work over the days of the week. Much of the respondents' time is concentrated on clinical work. Administration and committee work extends into every day of the week, but personal study and research are only reported by small numbers of respondents.

Postoperative complications of cholecystectomy in Victorian public hospitals.

Cholecystectomies in Victorian public hospitals were evaluated by analysis of hospital morbidity data. The Victorian Inpatient Minimum Dataset (VIMD) contains data on postoperative complications from all cholecystectomies in Victorian public hospitals. Hospital separations associated with cholecystectomy were identified according to Australian national diagnosis-related groups and the procedures were grouped as open, laparoscopic or conversion from laparoscopic to open cholecystectomy (conversion). Postoperative complications were identified by ICD9-CM external-cause codes (E-codes) in the VIMD. The 35593 cholecystectomies performed between 1987-88 and 1993-94 were analysed. A further detailed analysis of all cholecystectomies performed in 1993 was based on logistic regression. This identified the adjusted odds (AOR) of occurrence of complications and included covariates of age, sex, admission type, diagnosis-related group and hospital identification code. The annual frequency of cholecystectomy increased after introduction of laparoscopic cholecystectomy in 1990, and was associated with an increase in rates of separations having adverse events, but laparoscopic cholecystectomy had the lowest rate (66.7 per 1000 separations). Adverse-event rates for open procedures increased to 157.5 per 1000 in 1993-94, and for conversions to 290.0 per 1000. Of 5627 cholecystectomies in 1993, 74.4 per cent were laparoscopic, 21.5 per cent open and 4.1 per cent conversions. Postoperative complications were more likely in males (AOR 1.67, 95 per cent confidence interval (CI) 1.38 to 2.04), in patients admitted as an emergency (1.27, CI 1.01 to 1.60), and in those having open cholecystectomies (2.25, 1.78 to 2.85) or conversions (4.29, 3.05 to 6.03). Analysis of the VIMD has provided information for the evaluation of cholecystectomy. The VIMD is a useful tool for monitoring postoperative complications and the quality of care in Victorian hospitals.

Socioeconomic deprivation and notification rates for tuberculosis in London during 1982-91.

OBJECTIVES: To investigate the association between four sociodemographic measures (unemployment, overcrowding, low social class, and the proportion of migrants from areas of high prevalence of tuberculosis) and average level and rate of change of notification rates for tuberculosis. DESIGN: Ecological analysis of both the average and the rate of change of standardised annual notification rates for tuberculosis from 1982-91 and sociodemographic measures from the 1981 and 1991 censuses. SETTING: 32 London boroughs. SUBJECTS AND DATA: Sociodemographic measures from the 1981 and 1991 censuses and tuberculosis notification rates for 1982-91. MAIN OUTCOME MEASURES: A measure of the association between average levels and rate of change in tuberculosis notification rates and four sociodemographic measures in 1981 and between the rate of change in tuberculosis notification rates between 1981 and 1991 and changes in sociodemographic measures between 1981 and 1991. RESULTS: The average level of notifications was correlated with overcrowding and the proportion of migrants but not with unemployment or social class. No significant association was found between the rate of change in notification rates and sociodemographic measures in 1981. An association was found between increases in unemployment and the rate of change in notification rates, but the effect was small. Changes in the levels of unemployment explained 23% of the variation between boroughs in the rate of change in their notification rates. CONCLUSION: The average tuberculosis notification rates were related to overcrowding and the proportion of migrants in 1981. Only increases in unemployment from 1981 to 1991, however, were significantly associated with the rate of change in notifications over the same period.

One hundred cases of suicide in elderly people.

BACKGROUND: The White Paper The Health of the Nation targets a reduction in suicide rates. Preventive strategies must be guided by an understanding of the demography and antecedents of suicide. These issues are examined in relation to suicide by old people in Manchester. METHOD: One hundred consecutive coroners' inquisitions on people aged over 65 occurring between 1980 and 1991 in which the verdict was suicide were scrutinised and related to Health Service notes. RESULTS: Suicides were rare, numbers ranging from 0 to seven per annum per Health District. Rates did not vary between district but did within smaller sub-populations. Most individuals died at home; 65% were physically ill, of whom 23% had been hospitalised within the previous year. At least 60% were clinically depressed, with 25% being prescribed antidepressants. A total of 43% had seen their general practitioner in the previous month but only 14% were in contact with psychiatric services. CONCLUSIONS: Many elderly people who commit suicide are not in close contact with primary care services; those who are may not be prescribed appropriate treatment, and few are referred for specialist care. Specialist services will fail to reduce suicide rates unless they embark upon programmes to increase public awareness of therapeutic possibilities and work more closely with primary care agencies to realise these possibilities.

Recruitment activities and sociodemographic factors that predict attendance at a mammographic screening program.

A random sample of 2266 women aged 50 to 69 years was used to investigate factors that predict attendance at a free Australian mammographic screening program. The most important predictor was receipt of a personal invitation letter. A letter that included an appointment time increased attendance 132-fold initially and decreased to 20 times baseline after 14 days. A letter that did not include an appointment time increased attendance 12-fold, and a second letter to nonattenders increased attendance approximately 13-fold. Attendance declined with increasing distance from the program and with increases in the percentage of non-English speaking women in a neighborhood, but was higher in areas of higher socioeconomic status.

Effectiveness, costs, and cost-effectiveness of recruitment strategies for a mammographic screening program to detect breast cancer.

BACKGROUND AND PURPOSE: Since effective and affordable recruitment methods are essential for the widespread implementation of mammographic screening for detection of breast cancer, we studied the effectiveness, the costs, and the cost-effectiveness of various recruitment strategies in the population targeted by a pilot Australian program that offered free mammography screening between 1988 and 1990. METHODS: We evaluated three public recruitment strategies--local newspaper articles, community promotion, and promotion to physicians--and five personal strategies--invitation letters with or without specified appointment times, either alone or with a follow-up letter, or telephone call to nonattenders. The effectiveness of public recruitment strategies was estimated from monthly attendance rates by Poisson regression analysis, while the probability of attendance in response to personal strategies was calculated using logistic regression analysis. Costs were determined by resource usage studies. The cost-effectiveness ratios for personal strategies were determined using decision analysis. RESULTS: The costs in 1988-1989 Australian dollars per woman recruited were $22 for local newspaper articles and $106 for community promotion. No detectable increase in attendance resulted from promotion to physicians. When the cost of reserving an appointment was considered, the most cost-effective personal recruitment strategy was an invitation letter without a specified appointment time, followed by a second letter to nonattenders. This strategy recruited 35.6% of women in the sample targeted and cost $10.52 per attendee. In comparison, the most effective personal recruitment strategy was a letter with a specified appointment time followed by a second letter to nonattenders, which recruited 44.1% of women at an average cost of $19.99 and a marginal cost of $59.71 per additional attendee. CONCLUSIONS: Personal recruitment strategies were more cost-effective than public strategies. The most cost-effective personal strategy was an invitation letter without a specified appointment time, followed by a second letter to nonattenders.

Linking prescription and patient-identifying data: a pilot study.

OBJECTIVE: To link a Pharmaceutical Benefits Scheme (PBS) prescription data set with patient-identifying data held by the Health Insurance Commission (HIC) and to then determine the prevalence of prescribing of cardiovascular drugs, non-steroidal anti-inflammatory drugs, hypnotics and minor tranquillizers, and diuretics (prescribed without other cardiovascular drugs) by age and sex in two defined populations. DESIGN: Prescription data for a three-month period in 1985 were matched with patient-identifying information to obtain a database which included the patient's age, sex and an identifying number, for each prescription record. The percentages of the population taking a drug from each of the drug categories mentioned above were then determined and the effect of age, sex and region of residence on prescribing prevalence was investigated using logistic regression analysis. SETTING: Two rural regions of Australia with a total population of 65,087 residents. MEASUREMENTS AND MAIN RESULTS: Of the 101,383 prescriptions dispensed over the period 96% could be matched with HIC information. In the two regions combined, the percentages of the population taking a cardiovascular drug, non-steroidal anti-inflammatory drug, hypnotic or minor tranquilizer, or diuretic (without other cardiovascular drugs) were 10.4%, 5.8%, 3.5% and 2.5%, respectively. Prescribing rates were higher for females than males, increased with age and varied between the two regions. Approximately 5% of women aged 30-39 years were taking diuretics without other cardiovascular drugs, compared with only 0.2% of men in the same age group. CONCLUSIONS: This pilot study illustrates the use of a patient-identified prescription database for drug utilisation review, therapeutic audit and hypothesis generation.