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PubMed2006

The obesity-driven rising costs of type 2 diabetes in Australia: projections from the Fremantle Diabetes Study.

BACKGROUND: The cost of diabetes is high for both the individual and society. Future health-care planning requires patient-level diabetes-attributable health-care cost data that have not previously been available for Australia. AIM: To determine Australian national direct diabetes-attributable health-care costs for known type 2 diabetes in 2000 and project these to 2051. METHODS: A total of 1294 patients with type 2 diabetes was recruited to the Fremantle Diabetes Study between 1993 and 1996. A bottom-up, prevalence-based approach using diabetes-attributable costs provided average annual per patient health-care costs (in year 2000 A$). Costs were extrapolated to 2051 using Australian type 2 diabetes prevalence figures and Australian Bureau of Statistics population projections, assuming that prevalence rates (i) remain at current levels and (ii) rise steadily. RESULTS: Total annual direct diabetes-attributable health-care costs in 2000 in Australia for people > or =25 years with known type 2 diabetes were estimated at A$636 million. As a result of ageing, the number of people with type 2 diabetes will double between 2000 and 2051 with a 2.5-fold increase in diabetes-attributable health-care costs. If obesity and inactivity prevalence rates continue to rise, prevalence rates of type 2 diabetes will further increase. The number of people with type 2 diabetes in 2051 may be 3.5 times higher than in 2000 with a 3.7-fold cost increase. CONCLUSIONS: The financial burden of treating type 2 diabetes could quadruple by 2051 unless more is done to prevent type 2 diabetes and its complications. A smaller proportion of the population will have the capacity to fund these rising health-care costs.

Adult↗
PubMed1992

Bladder cancer mortality in The Netherlands, 1955-1988.

In 1955, 234 men and 116 women died from bladder cancer in the Netherlands. In 1988 the numbers were 794 and 317 respectively. After adjusting for the ageing of the Dutch population since 1955, female mortality rates per 10(5) person-years appear to be very stable: 2.9 from 1955 to 1959 and 3.0 from 1985 to 1988. By contrast, an increasing trend exists in males. From 1955 to 1959 and from 1985 to 1988, bladder cancer mortality rates per 10(5) person-years were 7.5 and 12.4 respectively. For men in particular, increasing mortality (and incidence) rates are seen all over the world. In many cases this increasing trend is thought to originate from a higher risk of dying from bladder cancer in successive birth cohorts rather than from a higher risk in successive calendar periods. This so-called cohort effect is explained by changes in smoking behaviour in the male population. Statistical modelling of bladder cancer mortality data from 1955 to 1988 in the Netherlands shows that the increasing temporal trend in men can also be described as a cohort effect. The risk of dying from bladder cancer increases from the 1875 birth cohort to the 1910 birth cohort, but decreases thereafter. It is concluded that this decreasing risk for generations born after 1910 will probably result in a decreasing trend in mortality in the near future, when more and more of these "youngsters" reach the age of 70+.

Age Factors↗
PubMed1991

Effect of p-chlorophenylalanine on release of 5-hydroxytryptamine from the rat frontal cortex in vivo.

1. Rats were given p-chlorophenylalanine (PCPA, 150 mg kg-1, i.p.) to inhibit partially 5-hydroxytryptamine (5-HT) synthesis so that its concentration in the frontal cortex fell by about half. The effects of this treatment on frontal cortex dialysate 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined before and after stimulation by increasing K+ concentration in the perfusion fluid by 100 mM for 20 min. Rates of 5-HT synthesis as indicated by the effects of 3-hydroxybenzylhydrazine (NSD 1015, 150 mg kg-1, i.p.) on frontal cortex tissue and dialysate 5-hydroxytryptophan (5-HTP) and dialysate 5-HIAA were also measured in rats that had not been stimulated with K+. 2. Dialysate 5-HT and 5-HIAA concentrations of both vehicle- and PCPA-treated rats fell into major (group 1) and minor (group 2) populations statistically distinguishable from each other by the high 5-HT and low 5-HIAA values of the latter group. 3. In group 1 animals, PCPA decreased both the dialysate 5-HT concentration and its rise following stimulation by K+ in proportion with the decrease of 5-HT in frontal cortex tissue. 5-HIAA fell more markedly than 5-HT and in similar proportion in both tissue and dialysate. The fall of dialysate 5-HIAA on stimulation by K+ was also attenuated to the same degree. The elevated 5-HT/5-HIAA ratios after PCPA treatment imply increased conservation of the depleted 5-HT stores. 4. PCPA decreased the above 5-HIAA values and the effects of NSD 1015 on tissue 5-HTP or dialysate 5-HIAA concentrations in similar proportion. However, PCPA had little effect on corresponding dialysate 5-HTP values. 5. The results are discussed with respect to relationships between synthesis, storage and release of 5-HT. They indicate that (under the conditions of the present study) the availability of 5-HT to receptors is directly proportional to total vesicular stores under both basal conditions and during neuronal firing.

5-Hydroxytryptophan↗
PubMed1981

The future for the elderly.

This tentative look into the future for the elderly covers such aspects as population statistics, the unique role of Medicine in contributing to the quality of life, the problems engendered by dementia patients and the "staff factor" involved in their care. The development of personality in the aged is stressed. Being attractive to others in the time of disability and old age is a valuable asset. There is great need for education of the public about the elderly.

Aged↗
PubMed1993

HLA class II polymorphism and IDDM susceptibility in the Greek population.

The frequencies of HLA-DQA1, DQB1 and DRB1 alleles were compared between 50 Insulin-Dependent Diabetes Melitus (IDDM) patients and 49 healthy controls in the Greek population. Statistically significant difference in the frequencies of HLA-DQA1*0501-DQB1*0201 (P = 10(-4)), DQA1*0301-DQB1*0201 (P = 0.01) and DQA1*0301-DQB1*0302 (P = 0.001) were observed. The DRB1*0405-DQA1*0301-DQB1*0201 was the only DR, DQ combination significantly associated with the disease. The unexpected increase of DRB1*0405 observed in the Greek IDDM may suggest as reported in Chinese and Japanese IDDM a contribution of DR beta and DQ alpha in susceptibility. Moreover, in contrast to the Asians, in the Greek, the DR beta, DQ alpha are found with the usual DQ beta 57-ve.

Adolescent↗
PubMed2004

On the noise variance of a digital mammography system.

A recent paper by Cooper et al. [Med. Phys. 30, 2614-2621 (2003)] contains some apparently anomalous results concerning the relationship between pixel variance and x-ray exposure for a digital mammography system. They found an unexpected peak in a display domain pixel variance plot as a function of 1/mAs (their Fig. 5) with a decrease in the range corresponding to high display data values, corresponding to low x-ray exposures. As they pointed out, if the detector response is linear in exposure and the transformation from raw to display data scales is logarithmic, then pixel variance should be a monotonically increasing function in the figure. They concluded that the total system transfer curve, between input exposure and display image data values, is not logarithmic over the full exposure range. They separated data analysis into two regions and plotted the logarithm of display image pixel variance as a function of the logarithm of the mAs used to produce the phantom images. They found a slope of minus one for high mAs values and concluded that the transfer function is logarithmic in this region. They found a slope of 0.6 for the low mAs region and concluded that the transfer curve was neither linear nor logarithmic for low exposure values. It is known that the digital mammography system investigated by Cooper et al. has a linear relationship between exposure and raw data values [Vedantham et al., Med. Phys. 27, 558-567 (2000)]. The purpose of this paper is to show that the variance effect found by Cooper et al. (their Fig. 5) arises because the transformation from the raw data scale (14 bits) to the display scale (12 bits), for the digital mammography system they investigated, is not logarithmic for raw data values less than about 300 (display data values greater than about 3300). At low raw data values the transformation is linear and prevents over-ranging of the display data scale. Parametric models for the two transformations will be presented. Results of pixel variance measurements made on raw data images will be presented. The experimental data are in good agreement with those of Cooper et al. It will be shown that the slope of 0.6 found by Cooper et al. for the log-log plot at low exposure is not due to transfer function nonlinearity, it occurs because of an additive variance term-possibly due to electronic noise. It will also be shown, using population statistics from clinical images, that raw data values below 300 are rare in tissue areas. Those tissue areas with very low raw data values are within about a millimeter of the chest wall or in very dense muscle at comers of images.

Breast Neoplasms↗
PubMed2001

Genetic discrimination and mental illness: a case report.

With advances in genetic technology, there are increasing concerns about the way in which genetic information may be abused, particularly in people at increased genetic risk of developing certain disorders. In a recent case in Hong Kong, the court ruled that it was unlawful for the civil service to discriminate in employment, for the sake of public safety, against people with a family history of mental illness. The plaintiffs showed no signs of any mental health problems and no genetic testing was performed. This was the first case concerning genetic discrimination in common law jurisdictions, therefore the court's judgment has implications for how genetic discrimination cases may be considered in the future. The court considered it inappropriate to apply population statistics or lifetime risks to individuals while examining fitness for work. It recommended an individualised assessment of specific risks within the job, relative to other risks posed by that workplace.

Adult↗
PubMed1986

Cancer mortality in the British rubber industry: 1946-80.

The mortality experienced by a cohort of 36445 rubber workers during 1946-80 has been investigated. These workers were all male operatives first employed in any one of the 13 participating factories in 1946-60; all had worked continuously in the industry for a minimum period of one year. Compared with the general population, statistically significant excesses relating to cancer mortality were found for cancer of the stomach (E = 245.9, O = 282, SMR = 115), primary cancer of the liver (E = 12.8, O = 22, SMR = 172), cancer of the lung (E = 892.7, O = 1191, SMR = 133), and all neoplasms (E = 2165.2, O = 2487, SMR = 115). Statistically significant deficits were found for cancer of the prostate (E = 79.7, O = 59, SMR = 74) and cancer of the testis (E = 10.3, O = 4, SMR = 39). The method of regression models in life tables (RMLT) was used to compare the duration of employment in the industry, the duration in "dust exposed" jobs, and the duration in "fume and/or solvent exposed" jobs of those dying from causes of interest with those of all matching survivors. Significant positive associations were found only for cancer of the stomach and cancer of the lung. The results of the RMLT analysis are independent of those from the SMR analysis, and the study has provided further evidence of a causal association between the risks of lung and stomach cancer and certain occupational exposures in the rubber industry.

Adolescent↗
PubMed1989

Mortality in the British rubber industry 1946-85.

The mortality experienced by a cohort of 36,691 rubber workers during 1946-85 has been investigated. These workers were all male operatives first employed in any one of the 13 participating factories in 1946-60; all had worked continuously in the industry for a minimum period of one year. Compared with the general population, statistically significant excesses relating to cancer mortality were found for cancer of the pharynx (E = 20.2, O = 30, SMR = 149), oesophagus (E = 87.6, O = 107, SMR = 122), stomach (E = 316.5, O = 359, SMR = 113), lung (E = 1219.2, O = 1592, SMR = 131), and all neoplasms (E = 2965.6, O = 3344, SMR = 113). Statistically significant deficits were found for cancer of the prostate. (E = 128.2, O = 91, SMR = 71), testis (E = 11.0, O = 4, SMR = 36), and Hodgkin's disease (E = 26.9, O = 16, SMR = 59). Involvement of occupational exposures was assessed by the method of regression models and life tables (RMLT). This method was used to compare the duration of employment in the industry, the duration in "dust exposed" jobs, and the duration in "fume and/or solvent exposed" jobs of those dying from causes of interest with those of all matching survivors. Positive associations (approaching formal levels of statistical significance) were found only for cancers of the stomach and the lung. The results of the RMLT analysis are independent of those from the SMR analysis, and the study continues to provide limited evidence of a causal association between the risks of stomach cancer and dust exposures, and the risks of lung cancer and fume or solvent exposures in the rubber industry during the period under study.

Adolescent↗
PubMed1999

Mortality among residents near cokeworks in Great Britain.

OBJECTIVES: To investigate whether residents near cokeworks have a higher standardised mortality than those further away, particularly from cardiovascular and respiratory causes, which may be associated with pollution from cokeworks. METHOD: Cross sectional small area study with routinely collected postcoded mortality data and small area census statistics. Populations within 7.5 km of 22 cokeworks in Great Britain, 1981-92. Expected numbers of deaths within 2 and 7.5 km of cokeworks, and in eight distance bands up to 7.5 km of cokeworks, were calculated by indirect standardisation from national rates stratified for age and sex and a small area deprivation index, and adjusted for region. Age groups examined were all ages, 1-14, 15-64, 65-74, > or = 75. Only the 1-14 and 15-44 age groups were examined for asthma mortality. RESULTS: There was a 3% (95% confidence interval (95% CI) 1% to 4%) excess of all deaths within 2 km of cokeworks, and a significant decline in mortality with distance from cokeworks. The excess of deaths within 2 km was slightly higher for females and elderly people, but excesses within 2 km and declines in risk with distance were significant for all adult age groups and both sexes. The size of the excess within 2 km was 5% (95% CI 3% to 7%) for cardiovascular causes, 6% (95% CI 3% to 9%) for ischaemic heart disease, and 2% (95% CI -2% to 6%) for respiratory deaths, with significant declines in risk with distance for all these causes. There was a non-significant 15% (95% CI -1% to 101%) excess in asthma mortality in the 15-44 age group. There were no significant excesses in mortality among children but 95% CIs were wide. Within 2 km of cokeworks, the estimated additional excess all cause mortality for all ages combined related to region and mainly to the greater deprivation of the population over national levels was 12%. CONCLUSIONS: A small excess mortality near cokeworks as found in this study is plausible in the light of current evidence about the health impact of air pollution. However, in this study the effects of pollution from cokeworks, if any, are outweighed by the effects of deprivation on weighed by the effects of deprivation on mortality near cokeworks. It is not possible to confidently exclude socioeconomic confounding or biases resulting from inexact population estimation as explanations for the excess found.

Adolescent↗
PubMed1997

The significance of neural ensemble codes during behavior and cognition.

The development of techniques to record from populations of neurons has made it possible to ask questions concerning the encoding of task-relevant information in awake, behaving animals. The issue of how groups of neurons within different brain structures register and retrieve representations of behaviorally significant events can now be addressed using multineuron-recording techniques. This review examines recent studies employing simultaneous recording of ten or more individual neurons in the mammalian brain. A major issue discussed is whether ensemble information content reconstructed from single-neuron recordings may be underestimated if compared to ensembles where those same neurons were recorded simultaneously. The mechanics of ensemble information encoding in the hippocampus is illustrated from population statistical analyses of ensemble activity during performance of a delay task. Detailed descriptions of methods of extracting ensemble information, as well as cross-correlational analyses, are discussed in the context of emergent issues regarding interpretation of ensemble data.

Animals↗
PubMed1990

Variability of pulmonary function in alpha-1-antitrypsin deficiency: residual family resemblance beyond the effect of the Pi locus.

To gain insight into the variable expression of lung disease in alpha 1-antitrypsin deficiency, two pulmonary function tests, FEV1 and FEF25-75, were examined in alpha 1-antitrypsin-deficient individuals and their families. The mean and variance effects of Pi type, age, and sex on the pulmonary function variables were removed by stepwise multiple regression, and the residual phenotypes were analyzed. Path analysis of the residual phenotypes with environmental indices in 46 nuclear families demonstrated highly significant cultural inheritance. Significant polygenic inheritance was not demonstrated for FEV1 but was shown for FEF25-75. For FEV1, adjustment for the significant interaction between Pi type and pack-years of smoking tended to increase the estimated contribution of polygenic inheritance and to decrease the estimated contribution of cultural inheritance. Segregation analysis of the residual phenotypes in 44 nuclear families was carried out to determine whether another major gene, other than the Pi locus, may be influencing pulmonary function in this population. Statistical evidence was found for an additional major gene influencing FEV1; however, the evidence diminished after adjusting for the effects of pack-years and the interaction between Pi type and pack-years. This apparent drop in the importance of genetic factors would not be surprising if the effect of the putative major gene is to enhance susceptibility to effects of cigarette smoking. Finally, our investigation demonstrates the feasibility of dissecting residual familial effects on complex multifactorial traits.

Factor Analysis, Statistical↗
PubMed1995

Study of aneurysmal subarachnoid hemorrhage in Izumo City, Japan.

BACKGROUND AND PURPOSE: Estimation of the actual incidence rate of subarachnoid hemorrhage and evaluation of the treatment require the inclusion of all patients in a defined geographic area. METHODS: During 1987 through 1992 in Izumo City, Japan, we estimated the incidence rate of subarachnoid hemorrhage by including dead-on-arrival patients and by further adding the results obtained after reviewing all death certificates registered in this city in the corresponding period. In addition, we compared the management and surgical outcomes in hospitalized patients from 1987 through 1992 with outcomes from 1980 through 1986. RESULTS: During 1987 through 1992, we diagnosed 123 patients as having subarachnoid hemorrhage. The crude and the age- and sex-adjusted incidence rates using the 1990 population statistics for Japan were 25 (95% confidence interval, 21 to 30) per 100,000/y and 23 (95% confidence interval, 19 to 28) per 100,000/y for all ages, respectively; these occurrences are the highest among those reported to date. Of these patients, 8% died before receiving medical attention, 27% in the first week, and 39% at 1 month. The survival curve for 2 years improved significantly from 1980-1986 to 1987-1992 in patients with admission grades 4 and 5 (P = .035) and in operated patients with preoperative grades 1 through 3 (P = .036). However, there was little improvement in the overall management results (P = .168), possibly because patients with high risk and/or old age were admitted and/or diagnosed more often in the latter period. CONCLUSIONS: The incidence rate of subarachnoid hemorrhage is much higher than that reported so far in the literature, and despite improvement of management and surgical therapy, the actual case-fatality rate is still high, mainly because of the high mortality rate directly associated with the primary bleeding.

Adult↗
PubMed2001

Trends in incidence and case fatality rates of aneurysmal subarachnoid hemorrhage in Izumo City, Japan, between 1980-1989 and 1990-1998.

BACKGROUND AND PURPOSE: With aging of the population, the profile of subarachnoid hemorrhage (SAH) is likely to change; however, evaluation of long-term trends for incidence and case fatality rates of SAH is still limited. METHODS: We compared the incidence and case fatality rates of aneurysmal SAH during the 9-year period 1990-1998 with those during the 10-year period 1980-1989 in Izumo City, Japan. RESULTS: During 1980-1989 and 1990-1998, we diagnosed 170 and 188 patients as having aneurysmal SAH, respectively. The percentage of very elderly patients aged >/=80 years increased from 5% (8 patients) during 1980-1989 to 18% (33 patients) during 1990-1998 (P<0.001). The age-specific incidence rate of SAH has a tendency to increase with increasing age. The crude and the age- and sex-adjusted incidence rates using the 1995 population statistics for Japan were 21 and 23 per 100 000/y for all ages during 1980-1989 and 25 and 23 per 100 000/y during 1990-1998, respectively. The 3-month case fatality rate of patients aged </=79 years decreased from 38% during 1980-1989 to 26% during 1990-1998 (P=0.021), whereas the case fatality rates in patients aged >/=80 years were very high (63% and 79%, respectively) regardless of study periods. Consequently, the overall case fatality rates for patients with SAH were similar for the 2 study periods (39% and 36%). CONCLUSIONS: The age- and sex-adjusted incidence rates of aneurysmal SAH were stable over the 19-year period since 1980 and, despite improvement of outcome in patients aged </=79 years, the overall case fatality rate was not lower because the improvements were counterbalanced by increasing numbers of very elderly patients

Adolescent↗
PubMed2006

Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics.

OBJECTIVE: In many parts of the world, second-generation antipsychotics have largely replaced typical antipsychotics as the treatment of choice for schizophrenia. Consequently, trials comparing two drugs of this class--so-called head-to-head studies--are gaining in relevance. The authors reviewed results of head-to-head studies of second-generation antipsychotics funded by pharmaceutical companies to determine if a relationship existed between the sponsor of the trial and the drug favored in the study's overall outcome. METHOD: The authors identified head-to-head comparison studies of second-generation antipsychotics through a MEDLINE search for the period from 1966 to September 2003 and identified additional head-to-head studies from selected conference proceedings for the period from 1999 to February 2004. The abstracts of all studies fully or partly funded by pharmaceutical companies were modified to mask the names and doses of the drugs used in the trial, and two physicians blinded to the study sponsor reviewed the abstracts and independently rated which drug was favored by the overall outcome measures. Two authors who were not blinded to the study sponsor reviewed the entire report of each study for sources of bias that could have affected the results in favor of the sponsor's drug. RESULTS: Of the 42 reports identified by the authors, 33 were sponsored by a pharmaceutical company. In 90.0% of the studies, the reported overall outcome was in favor of the sponsor's drug. This pattern resulted in contradictory conclusions across studies when the findings of studies of the same drugs but with different sponsors were compared. Potential sources of bias occurred in the areas of doses and dose escalation, study entry criteria and study populations, statistics and methods, and reporting of results and wording of findings. CONCLUSIONS: Some sources of bias may limit the validity of head-to-head comparison studies of second-generation antipsychotics. Because most of the sources of bias identified in this review were subtle rather than compelling, the clinical usefulness of future trials may benefit from minor modifications to help avoid bias. The authors make a number of concrete suggestions for ways in which potential sources of bias can be addressed by study initiators, peer reviewers of studies under consideration for publication, and readers of published studies.

Antipsychotic Agents↗
PubMed2006

Dealing with missing data in a multi-question depression scale: a comparison of imputation methods.

BACKGROUND: Missing data present a challenge to many research projects. The problem is often pronounced in studies utilizing self-report scales, and literature addressing different strategies for dealing with missing data in such circumstances is scarce. The objective of this study was to compare six different imputation techniques for dealing with missing data in the Zung Self-reported Depression scale (SDS). METHODS: 1580 participants from a surgical outcomes study completed the SDS. The SDS is a 20 question scale that respondents complete by circling a value of 1 to 4 for each question. The sum of the responses is calculated and respondents are classified as exhibiting depressive symptoms when their total score is over 40. Missing values were simulated by randomly selecting questions whose values were then deleted (a missing completely at random simulation). Additionally, a missing at random and missing not at random simulation were completed. Six imputation methods were then considered; 1) multiple imputation, 2) single regression, 3) individual mean, 4) overall mean, 5) participant's preceding response, and 6) random selection of a value from 1 to 4. For each method, the imputed mean SDS score and standard deviation were compared to the population statistics. The Spearman correlation coefficient, percent misclassified and the Kappa statistic were also calculated. RESULTS: When 10% of values are missing, all the imputation methods except random selection produce Kappa statistics greater than 0.80 indicating 'near perfect' agreement. MI produces the most valid imputed values with a high Kappa statistic (0.89), although both single regression and individual mean imputation also produced favorable results. As the percent of missing information increased to 30%, or when unbalanced missing data were introduced, MI maintained a high Kappa statistic. The individual mean and single regression method produced Kappas in the 'substantial agreement' range (0.76 and 0.74 respectively). CONCLUSION: Multiple imputation is the most accurate method for dealing with missing data in most of the missind data scenarios we assessed for the SDS. Imputing the individual's mean is also an appropriate and simple method for dealing with missing data that may be more interpretable to the majority of medical readers. Researchers should consider conducting methodological assessments such as this one when confronted with missing data. The optimal method should balance validity, ease of interpretability for readers, and analysis expertise of the research team.

Alberta↗