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PubMed1999

Continuity of care and readmission in two service systems: a comparative Victorian and Groningen case-register study.

OBJECTIVE: We compared service consumption, continuity of care and risk of readmission in a record linkage follow-up study of cohorts of patients with schizophrenia and related disorders in Victoria (Australia) and in Groningen (The Netherlands). These areas are interesting to compare because mental health care is in a different stage of deinstitutionalization. More beds are available in Groningen and more community resources are available in Victoria. METHOD: The cohorts were followed for 4 years, since discharge from inpatient services using record linkage data available in the psychiatric case-registers in both areas. Survival analysis was used to study continuity of care and risk of readmission. RESULTS: Available indicators showed a higher level of continuity of care in Victoria. While the relative risk of readmission was the same in both areas and not affected by aftercare contact after discharge, the number of days spent in hospital was much higher in the Groningen register area. CONCLUSION: These findings provide further support for earlier reports that the risk of readmission is predominantly affected by attributes of mental illness. However, the duration of admissions, is strongly affected by service system variables, including the provision of continuity of care.

Adolescent↗
PubMed1998

Genetic aspects of dental disorders.

This paper reviews past and present applications of quantitative and molecular genetics to dental disorders. Examples are given relating to craniofacial development (including malocclusion), oral supporting tissues (including periodontal diseases) and dental hard tissues (including defects of enamel and dentine as well as dental caries). Future developments and applications to clinical dentistry are discussed. Early investigations confirmed genetic bases to dental caries, periodontal diseases and malocclusion, but research findings have had little impact on clinical practice. The complex multifactorial aetiologies of these conditions, together with methodological problems, have limited progress until recently. Present studies are clarifying previously unrecognized genetic and phenotypic heterogeneities and attempting to unravel the complex interactions between genes and environment by applying new statistical modelling approaches to twin and family data. Linkage studies using highly polymorphic DNA markers are providing a means of locating candidate genes, including quantitative trait loci (QTL). In future, as knowledge increases; it should be possible to implement preventive strategies for those genetically-predisposed individuals who are identified to be at risk.

Chromosome Mapping↗
PubMed1966

Isolation of a Mutant of Escherichia coli with a Temperature-sensitive Fructose-1,6-Diphosphate Aldolase Activity.

Böck, August (Purdue University, Lafayette, Ind.), and Frederick C. Neidhardt. Isolation of a mutant of Escherichia coli with a temperature-sensitive fructose-1,6-diphosphate aldolase activity. J. Bacteriol. 92:464-469. 1966.-A mutant of Escherichia coli was isolated which was able to grow in rich medium at 30 C but not at 40 C. Upon exposure to 40 C, the cells immediately stopped ribonucleic acid (RNA) and deoxyribonucleic acid synthesis, but protein synthesis continued at a diminished rate for a short time. Addition of chloramphenicol did not release RNA synthesis from inhibition at 40 C. Synthesis of beta-galactosidase could be induced at high temperature despite the presence of glucose in the medium, indicating a lesion in glucose catabolism. Of many catabolic enzymes tested in cell-free extracts, only fructose-1,6-diphosphate aldolase activity appeared to be altered in the mutant cells. No activity was demonstrable in extracts of mutant cells grown at either 30 or 40 C, but determination of glucose-oxidation patterns revealed that the enzyme is probably active in vivo at 30 C. Temperature-resistant secondary mutants were found to have partially or fully restored aldolase activity, and temperature-resistant recombinants had normal aldolase activity, indicating that the growth pattern and the altered aldolase had a common genetic basis. Linkage data permitted the assignment of an approximate map location for the mutated aldolase gene.

Journal Article↗
PubMed1986

PEP4 gene of Saccharomyces cerevisiae encodes proteinase A, a vacuolar enzyme required for processing of vacuolar precursors.

The proteinase A structural gene of Saccharomyces cerevisiae was cloned by using an immunological screening procedure that allows detection of yeast cells which are aberrantly secreting vacuolar proteins (J. H. Rothman, C. P. Hunter, L. A. Valls, and T. H. Stevens, Proc. Natl. Acad. Sci. USA, 83:3248-3252, 1986). A second cloned gene was obtained on a multicopy plasmid by complementation of a pep4-3 mutation. The nucleotide sequences of these two genes were determined independently and were found to be identical. The predicted amino acid sequence of the cloned gene suggests that proteinase A is synthesized as a 405-amino-acid precursor which is proteolytically converted to the 329-amino-acid mature enzyme. Proteinase A shows substantial homology to mammalian aspartyl proteases, such as pepsin, renin, and cathepsin D. The similarities may reflect not only analogous functions but also similar processing and intracellular targeting mechanisms for the two proteins. The cloned proteinase A structural gene, even when it is carried on a single-copy plasmid, complements the deficiency in several vacuolar hydrolase activities that is observed in a pep4 mutant. A strain carrying a deletion in the genomic copy of the gene fails to complement a pep4 mutant of the opposite mating type. Genetic linkage data demonstrate that integrated copies of the cloned proteinase A structural gene map to the PEP4 locus. Thus, the PEP4 gene encodes a vacuolar aspartyl protease, proteinase A, that is required for the in vivo processing of a number of vacuolar zymogens.

Amino Acid Sequence↗
PubMed2006

Uptake of screening for breast cancer in patients with mental health problems.

OBJECTIVES: Mental illness is associated with physical illness and mortality from a variety of causes including cancer. There is little information on screening attendance among the mentally ill population. An audit was conducted of a breast screening service in inner London to determine uptake rates in women with mental illness. DESIGN: Cross sectional data linkage study of the local screening register and patients of the local psychiatric units. Screening uptake rates in all patients, those with a history of multiple detention in hospital, and those with psychosis were compared with the local reference population. SETTING: Women in three inner London boroughs. PARTICIPANTS: Screening records for 933 psychiatric patients and 44 195 women without mental health problems aged 50 to 64 years. MAIN RESULTS: Overall, psychiatric patients were as likely as the reference group to attend breast screening. Patients with a history of multiple detention were significantly less likely to attend (OR = 0.40, 0.29 to 0.55; p<0.001), as were patients with a diagnosis of psychosis (OR = 0.33, 0.18 to 0.61; p<0.01). Increasing age, a history of detention in hospital, and social deprivation remained independent predictors for non-attendance. CONCLUSION: Women with severe mental health problems may be less likely to attend national screening programmes such as breast screening, and action should be taken to overcome the barriers to attendance.

Breast Neoplasms↗
PubMed1991

Confirmation of linkage of hyperkalaemic periodic paralysis to chromosome 17.

Linkage studies were performed in six European families with hyperkalaemic periodic paralysis (PPII) with myotonia, an autosomal dominantly inherited disorder characterised by episodic weakness. The weakness is caused by non-inactivating sodium channels of reduced single channel conductance of the muscle fibre membrane. Recently, portions of the gene coding for the alpha subunit of the sodium channel of the adult human skeletal muscle (h-Na2) have been cloned and localised on chromosome 17q with no recombinants to the human growth hormone locus (GH1). Linkage between these two chromosome 17 markers and the disease was shown in our families (Z = 7.14, 0 = 0.00). These results, combined with the linkage data of a single large American family, suggest that the disease is caused by dominant mutations of the adult sodium channel, and that it is probably a genetically homogeneous disorder. Hyperkalaemic periodic paralysis is the first non-progressive myotonic disorder to be localised on the human genome.

Chromosomes, Human, Pair 17↗
PubMed1986

Formaldehyde and the risk of squamous cell carcinoma of the sinonasal cavities.

A study of 759 histologically verified cancers of the nasal cavity (287 cases), paranasal sinuses (179 cases), and nasopharynx (293 cases) and 2465 cancer controls diagnosed in Denmark between 1970 and 1982 was conducted to investigate the importance of occupational exposure to formaldehyde. Information on job history for cases and controls was derived from a national data linkage system and exposure to formaldehyde and wood dust was assessed by industrial hygienists unaware of the case-control status of the patients. The exposure rates for formaldehyde among male and female controls were 4.2% and 0.1%, respectively. After proper adjustment for contemporary wood dust exposure, relative risks of 2.3 (95% CI = 0.9-5.8) for squamous cell carcinoma and 2.2 (95% CI = 0.7-7.2) for adenocarcinoma of the nasal cavity and paranasal sinuses were detected among men who have ever been exposed to formaldehyde in their job compared with those never exposed. The introduction of a 10 year latency period did not change the risk estimates substantially. It was considered unlikely that the results were due to bias or misclassification of exposure although the effect of chance could not be excluded.

Adenocarcinoma↗
PubMed1999

Mortality in a cohort of licensed pesticide applicators in Florida.

OBJECTIVES: Although the primary hazard to humans associated with pesticide exposure is acute poisoning, there has been considerable concern surrounding the possibility of cancer and other chronic health effects in humans. Given the huge volume of pesticides now used throughout the world, as well as environmental and food residue contamination leading to chronic low level exposure, the study of possible chronic human health effects is important. METHODS: This was a retrospective cohort study, analysed by general standardised mortality ratio (SMR) of licensed pesticide applicators in Florida compared with the general population of Florida. A cohort of 33,658 (10% female) licensed pesticide applicators assembled through extensive data linkages yielded 1874 deaths with 320,250 person-years from 1 January 1975 to 31 December 1993. RESULTS: The pesticide applicators were consistently and significantly healthier than the general population of Florida. As with many occupational cohorts, the risks of cardiovascular disease and of diseases associated with alcohol and tobacco use were significantly lower, even in the subpopulations--for example, men, women, and licence subcategories. Among male applicators, prostate cancer mortality (SMR 2.38 (95% confidence interval (95% CI) 1.83 to 3.04) was significantly increased. No cases of soft tissue sarcoma were confirmed in this cohort, and non-Hodgkin's lymphoma was not increased. The number of female applicators was small, as were the numbers of deaths. Mortality from cervical cancer and breast cancer was not increased. Additional subcohort and exposure analyses were performed. CONCLUSIONS: Consistent with previous publications on farmers but at odds with current theories about the protective effects of vitamin D, prostate cancer was increased in these pesticide applicators. Female breast cancer was not increased despite theories linking risk of breast cancer with exposure to oestrogen disruptors--such as the organochlorines. The lack of cases of soft tissue sarcoma is at odds with previous publications associating the use of the phenoxy herbicides with an increased risk of these cancers.

Adult↗
PubMed2003

Under-ascertainment of multiple myeloma among participants in UK atmospheric atomic and nuclear weapons tests.

An inter-comparison of cases of multiple myeloma among UK participants in the UK's atmospheric atomic and nuclear weapons tests ascertained by direct follow up methods detected at least a third more cases than a strategy relying solely on data linkage between the Office of National Statistics and the Service Records Offices. These finding have implications for the conduct and robustness of follow up studies of long term health effects among participants in nuclear weapons tests.

Air Pollutants, Radioactive↗
PubMed2006

Independent effects of waist circumference and physical activity on all-cause mortality in Canadian women.

The purpose of this study was to determine the independent effects of waist circumference (WC) and physical inactivity on the risk of mortality in women. This prospective cohort study included 5421 female participants 20-69 years of age in the 1981 Canada Fitness Survey. WC was measured with an anthropometric tape and leisure-time physical activity levels over the previous 12 months were assessed with a questionnaire. Mortality surveillance was conducted by data linkage with the Canadian Mortality Database through 31 December, 1993. The hazard ratios (HR) of mortality were estimated using Cox proportional hazards regression with age, smoking status, and alcohol consumption included as covariates in all models. A total of 225 deaths occurred over an average of 12.4 years of follow up (67 500 person-years of follow up). Physical activity (HR = 0.78; 95% C.I.: 0.64-0.95) and WC (HR = 1.17; 95% C.I.: 1.05-1.31) were associated with mortality when included in separate regression models. When included in the same model, both physical activity (HR = 0.79; 95% CI: 0.65-0.96) and WC (HR = 1.16; 95% C.I.: 1.04-1.30) remained independent significant predictors of mortality. In conclusion, physical inactivity and high WC have significant independent risks of premature mortality among women.

Adiposity↗
PubMed2001

Socioeconomic inequalities in injury: critical issues in design and analysis.

Injuries continue to place a tremendous burden on the public's health and rates vary widely among different groups in the population. Increasing attention has recently been given to the effects of socioeconomic status (SES) as a determinant of health among both individuals and communities. However, relatively few studies have focused on the influence of SES and injuries. Furthermore, those that have, and the other injury studies that have included measures of SES in their analysis, have varying degrees of conceptual and methodological rigor in their use of this measure. Recent advances in data linkage and analytic techniques have, however, provided new and improved methods to assess the relationship between SES and injuries. This review summarizes the relevant literature on SES and injuries, with particular attention to study design, and the measurement and interpretation of SES. We found that increasing SES has a strong inverse association with the risk of both homicide and fatal unintentional injuries, although the results for suicide were mixed. However, the relationship between SES and nonfatal injuries was less consistent than for fatal injuries. We offer potential explanatory mechanisms for the relationship between SES and injuries and make recommendations for future research in this area.

Adult↗
PubMed2006

Combined work and leisure physical activity and risk of stroke in men and women in the European prospective investigation into Cancer-Norfolk Prospective Population Study.

Most studies to date support a protective role of physical activity in reducing stroke risk. However, they were not able to take into account combined work and leisure activity. We prospectively followed up 22,602 men and women aged 40-79 years, who had no history of stroke and myocardial infarction at baseline, participating in the European Prospective Investigation into Cancer-Norfolk. Participants were categorized into four levels of physical activity based on a validated self-reported questionnaire, which assesses combined work and leisure activities, at baseline during the period from 1993 to 1997. Stroke incidence was ascertained by death certificate and hospital record linkage data up to 2004, average 8.6 years of follow-up. We used the Cox proportional hazards model. There were 361 incident strokes during follow-up (total person years = 195,092). After adjusting for age, sex, systolic blood pressure, body mass index, cholesterol, history of diabetes and smoking, men and women who were physically active were less likely to have a stroke (relative risk = 0.70, 95% CI: 0.49-0.99, p = 0.024) compared to those who were inactive. This highlights the fact that efforts to increase physical activity in both the work place and in leisure time should be encouraged.

Adult↗
PubMed2004

Significant nonsurgical risk factors for endophthalmitis after cataract surgery: EPSWA fourth report.

PURPOSE: Endophthalmitis remains a devastating complication of cataract surgery, despite improved methods of prophylaxis and surgical technique. The current study was conducted to identify sociodemographic, environmental, and clinical risk factors for the development of postoperative endophthalmitis, using population-based administrative data from Western Australia. METHODS: The Western Australian Data Linkage System identified all patients who underwent cataract surgery, along with those in whom postoperative endophthalmitis subsequently developed, from 1980 to 2000 inclusive. Cases of endophthalmitis were cross-referenced with other sources and validated by medical record review. After selection and preliminary analysis of potential risk factors, multivariate logistic regression modeling was used to estimate odds ratios for the selected variables. RESULTS: Over the 21 years, 210 cases of endophthalmitis occurred after 117,083 cataract procedures, yielding a cumulative incidence rate of 1.79 per 1000 procedures. The incidence of endophthalmitis decreased for extracapsular extraction over the whole period, but not for phacoemulsification over the recent 12 years. There was no risk-adjusted difference in the incidence rate of endophthalmitis for the various cataract surgery procedure types. However, a significantly higher risk was found in patients aged over 80 years, in having surgery in private hospitals, and to a lesser degree in having same-day surgery and surgery in winter. Cataract surgery with lacrimal or eyelid procedures dramatically increased the risk of endophthalmitis. CONCLUSIONS: It may be possible to reduce the incidence rate of postoperative endophthalmitis by almost 80% with a systematic approach to the management of elderly patients, hospital stay, and clinical protocols.

Age Factors↗
PubMed2005

Posterior polymorphous corneal dystrophy in Czech families maps to chromosome 20 and excludes the VSX1 gene.

PURPOSE: Posterior polymorphous corneal dystrophy (PPCD) is an autosomal dominant disorder, affecting both the corneal endothelium and Descemet's membrane. In the Czech Republic, PPCD is one of the most prevalent corneal dystrophies. The purpose of this study was to determine the chromosomal locus of PPCD in two large Czech families, by using linkage analysis. METHODS: Linkage analysis was performed on 52 members of two Czech families with PPCD and polymorphic microsatellite markers and lod scores were calculated. The candidate gene VSX1 was also screened for mutations. RESULTS: Significant lod scores were obtained with microsatellite markers on chromosome 20. Linkage analysis delineated the Czech PPCD locus to a 2.7-cM locus on chromosome 20, region p11.2, between flanking markers D20S48 and D20S139, which excluded VSX1 as the disease-causing gene in both families. In addition, the exclusion of VSX1 was confirmed by sequence analysis. CONCLUSIONS: This study reports the localization of PPCD in patients of Czech origin to chromosome 20 at p11.2. Linkage data and sequence analysis exclude VSX1 as causative of PPCD in two Czech families. This refined locus for PPCD overlaps the congenital hereditary endothelial dystrophy (CHED1) disease interval, and it is possible that these corneal dystrophies are allelic.

Chromosome Mapping↗
PubMed2005

First report of donor cell-derived acute leukemia as a complication of umbilical cord blood transplantation.

Donor cell leukemia is a rare complication after allogeneic hematopoietic stem cell transplantation. A 12-month-old boy underwent unrelated donor umbilical cord blood transplant (UCBT) for refractory Langerhan's cell histiocytosis. Forty months after transplantation, he developed acute myeloid leukemia. Cytogenetic and molecular analysis confirmed donor cell origin. The Cord Blood Bank (CBB) contacted the donor's family and established that the child, now 7 years old, was healthy. This represents the first reported case of donor cell leukemia following UCBT. This case illustrates that donor cell leukemia is a rare but real event after UCBT as with other stem cell sources and highlights the need for CBBs to maintain linkage data between donors and recipients.

Acute Disease↗
PubMed2006

Respiratory tract infections and subsequent risk of chronic lymphocytic leukemia.

Recent evidence suggests that chronic lymphocytic leukemia (CLL) might occur following a response to an infectious agent. We conducted a population-based study including 4249 CLL patients diagnosed in Denmark from 1977 to 1997 and 15 690 frequency-matched controls to quantify risk of CLL following various airway infections. Through data linkage we gathered information on hospital inpatient/outpatient discharges that listed infections present at least 1 year prior to CLL. Using logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Personal history of pneumonia was associated with significantly increased CLL risk (OR = 1.4; 1.2-1.8); risk was restricted to 1 to 4.99 years prior to CLL diagnosis (OR = 1.6; 1.2-2.0). Individuals with 3 or more prior pneumonia events had a significant 2.5-fold (1.1-5.6) elevated CLL risk, and risk increased with the number of pneumonia episodes (P(trend) < .001). None of 9 other respiratory-tract infections was significantly associated with CLL risk. Pneumonia might be a potential CLL trigger or it could represent premalignant immune disruption preceding CLL.

Aged↗
PubMed2004

On modeling locus heterogeneity using mixture distributions.

BACKGROUND: Locus heterogeneity poses a major difficulty in mapping genes that influence complex genetic traits. A widely used approach to deal with this problem involves modeling linkage data in terms of finite mixture distributions. In its simplest setup, also known as the admixture approach, a single parameter is used to model the probability that the disease-causing gene of a family is linked to a reference marker. This parameter is usually interpreted as the overall proportion of linked families. RESULTS: In this article, we address two issues regarding the admixture approach. First, we tackle the question of whether the single parameter of linked proportion is well defined in general. By formulating the likelihood under a classification scheme based on distributions, we show that such a parameter is meaningful only when a certain well-characterized condition is met. Second, we study a condition given in the literature for validating the admixture approach. A counter example is constructed to illustrate that the condition does not necessarily lead to valid estimates. CONCLUSIONS: Estimators from the admixture approach may be inconsistent. This holds even if a condition given in the literature to validate the approach is satisfied.

Chromosome Mapping↗
PubMed2005

The use of end-quintile comparisons to identify under-servicing of the poor and over-servicing of the rich: a longitudinal study describing the effect of socioeconomic status on healthcare.

BACKGROUND: To demonstrate the use of end-quintile comparisons in assessing the effect of socio-economic status on hospital utilisation and outcomes in Western Australia. METHODS: Hospital morbidity records were extracted from the WA Data Linkage System for the period 1994-99, with follow-up to the end of 2000. Multivariate modelling was used to estimate the effect of socio-economic status on hospital admission rates, average and total length of stay (LOS), cumulative incidence of readmission at 30 days and one year, and case fatality at one year. RESULTS: The study demonstrated higher rate ratios of hospital admission in the more disadvantaged quintiles: rate ratios were 1.31 (95% CI 1.25-1.37) and 1.32 (1.26-1.38) in the first quintile (most disadvantaged) and the second quintile respectively, compared with the fifth quintile (most advantaged). There was a longer total LOS in the most disadvantaged quintile compared with quintile 5 (LOS ratio 1.24; 1.23-1.26). The risk of readmission at 30 days and one year and the risk of death at one year were also greater in those with greater disadvantage: the hazard ratios for quintiles 1:quintile 5 were 1.07 (1.05-1.09), 1.17 (1.16-1.18) and 1.10 (1.07-1.13) respectively. In contradiction to the trends towards higher hospital utilisation and poorer outcomes with increasing social disadvantage, in some MDC's the rate ratio of quintile 1:quintile 2 was less than 1, and quintile 4:quintile 5 was greater than 1. For all surgical admissions the most disadvantaged had a significantly lower admission rate than the second quintile. CONCLUSION: This study has shown that the disadvantaged within Western Australia are more intensive users of hospital services but their outcomes following hospitalisation are worse, consistent with their health status. Instances of overuse in the least disadvantaged and under use in the most disadvantaged have also been identified.

Adolescent↗