A retrospective cohort study of prescription drug use among youth with intellectual/developmental disabilities in British Columbia.

BACKGROUND: People with intellectual/developmental disabilities (IDD) are known to have high rates of prescription drug use, particularly for psychotropic medications. This is of concern due to the many side effects associated with these medications and because of the risks of polypharmacy. In this paper we compare the most commonly dispensed drugs and all psychotropic medications for youth with IDD compared with youth without IDD. METHODS: Using population-level administrative health data over a 10-year period, this study examined medications dispensed to youth with an IDD aged 15-24 years compared with youth without an IDD. The most common medications dispensed and the number of youth they were dispensed to were determined. As well a wide variety of psychotropic medications were examined. RESULTS: There were a total of 20 591 youth with IDD and 1 293 791 youth without IDD identified. Youth with IDD had higher odds of being dispensed pain medications, amoxicillin, salbutamol, levothyroxine and all the psychotropic medications (antidepressants, antipsychotics, anxiolytics, anti-adrenergic agents, mood stabilisers and stimulants). For youth with IDD, 6558 (31.85%) were dispensed two or more different psychotropic medications within a year, compared with 75 963 (5.87%) of youth without IDD. DISCUSSION: Compared to youth without IDD, youth with IDD had significantly higher odds of being dispensed most of the prescription medications studied, including all of the psychotropic medications. They were also twice as likely to be dispensed two or more medications from different classes of psychotropic drugs within the same year. These findings have important implications for the health of people with IDD and for their health care providers.

Population Data BC: Supporting population data science in British Columbia.

BACKGROUND: Population Data BC (PopData) was established as a multi-university data and education resource to support training and education, data linkage, and access to individual level, de-identified data for research in a wide variety of areas including human and community development and well-being. APPROACH: A combination of deterministic and probabilistic linkage is conducted based on the quality and availability of identifiers for data linkage. PopData utilizes a harmonized data request and approval process for data stewards and researchers to increase efficiency and ease of access to linked data. Researchers access linked data through a secure research environment (SRE) that is equipped with a wide variety of tools for analysis. The SRE also allows for ongoing management and control of data. PopData continues to expand its data holdings and to evolve its services as well as governance and data access process. DISCUSSION: PopData has provided efficient and cost-effective access to linked data sets for research. After two decades of learning, future planned developments for the organization include, but are not limited to, policies to facilitate programs of research, access to reusable datasets, evaluation and use of new data linkage techniques such as privacy preserving record linkage (PPRL). CONCLUSION: PopData continues to maintain and grow the number and type of data holdings available for research. Its existing models support a number of large-scale research projects and demonstrate the benefits of having a third-party data linkage and provisioning center for research purposes. Building further connections with existing data holders and governing bodies will be important to ensure ongoing access to data and changes in policy exist to facilitate access for researchers.

Development of comparable algorithms to measure primary care indicators using administrative health data across three Canadian provinces.

INTRODUCTION: Performance measurement has been recognized as key to transforming primary care (PC). Yet, performance reporting in PC lags behind even though high-performing PC is foundational to an effective and efficient health care system. OBJECTIVES: We used administrative data from three Canadian provinces, British Columbia, Ontario and Nova Scotia, to: 1) identify and develop a core set of PC performance indicators using administrative data and 2) examine their ability to capture PC performance. METHODS: Administrative data used included Physician Billings, Discharge Abstract Database, the National Ambulatory Care and Reporting System database, Census and Vital Statistics. Indicators were compiled based on a literature review of PC indicators previously developed with administrative data available in Canada (n=158). We engaged in iterative discussions to assess data conformity, completeness, and plausibility of results in all jurisdictions. Challenges to creating comparable algorithms were examined through content analysis and research team discussions, which included clinicians, analysts, and health services researchers familiar with PC. RESULTS: Our final list included 21 PC performance indicators pertaining to 1) technical care (n=4), 2) continuity of care (n=6), and 3) health services utilization (n=11). Establishing comparable algorithms across provinces was possible though time intensive. A major challenge was inconsistent data elements. Ease of data access, and a deep understanding of the data and practice context, was essential for selecting the most appropriate data elements. CONCLUSIONS: This project is unique in creating algorithms to measure PC performance across provinces. It was essential to balance internal validity of the indicators within a province and external validity across provinces. The intuitive desire of having the exact same coding across provinces was infeasible due to lack of standardized PC data. Rather, a context-tailored definition was developed for each jurisdiction. This work serves as an example for developing comparable PC performance indicators across different provincial/territorial jurisdictions.

ALDH1A3 is epigenetically regulated during melanocyte transformation and is a target for melanoma treatment.

Despite the promising targeted and immune-based interventions in melanoma treatment, long-lasting responses are limited. Melanoma cells present an aberrant redox state that leads to the production of toxic aldehydes that must be converted into less reactive molecules. Targeting the detoxification machinery constitutes a novel therapeutic avenue for melanoma. Here, using 56 cell lines representing nine different tumor types, we demonstrate that melanoma cells exhibit a strong correlation between reactive oxygen species amounts and aldehyde dehydrogenase 1 (ALDH1) activity. We found that ALDH1A3 is upregulated by epigenetic mechanisms in melanoma cells compared with normal melanocytes. Furthermore, it is highly expressed in a large percentage of human nevi and melanomas during melanocyte transformation, which is consistent with the data from the TCGA, CCLE and protein atlas databases. Melanoma treatment with the novel irreversible isoform-specific ALDH1 inhibitor [4-dimethylamino-4-methyl-pent-2-ynthioic acid-S methylester] di-methyl-ampal-thio-ester (DIMATE) or depletion of ALDH1A1 and/or ALDH1A3, promoted the accumulation of apoptogenic aldehydes leading to apoptosis and tumor growth inhibition in immunocompetent, immunosuppressed and patient-derived xenograft mouse models. Interestingly, DIMATE also targeted the slow cycling label-retaining tumor cell population containing the tumorigenic and chemoresistant cells. Our findings suggest that aldehyde detoxification is relevant metabolic mechanism in melanoma cells, which can be used as a novel approach for melanoma treatment.

Temporal association between home nursing and hospital costs at end of life in three provinces.

BACKGROUND: Research has demonstrated that increases in palliative homecare nursing are associated with a reduction in the rate of subsequent hospitalizations. However, little evidence is available about the cost-savings potential of palliative nursing when accounting for both increased nursing costs and potentially reduced hospital costs. METHODS: Our retrospective cohort study included cancer decedents from British Columbia, Ontario, and Nova Scotia who received any palliative nursing in the last 6 months of life. A Poisson regression analysis was used to determine the association of increased nursing costs (in 2-week blocks) on the relative average hospital costs in the subsequent 2-week block and on the overall total cost (hospital costs plus nursing costs in the preceding 2-week block). RESULTS: The cohort included 58,022 cancer decedents. Results of the analysis for the last month of life showed an association between increased nursing costs and decreased relative hospital costs in comparisons with a reference group (>0 to 1 hour nursing in the block): the maximum decrease was 55% for Ontario, 31% for British Columbia, and 38% for Nova Scotia. Also, increased nursing costs in the last month were almost always associated with lower total costs in comparison with the reference. For example, cost savings per person-block ranged from $376 (>10 nursing hours) to $1,124 (>4 to 6 nursing hours) in British Columbia. CONCLUSIONS: In the last month of life, increased palliative nursing costs (compared with costs for >0 to 1 hour of nursing in the block) were associated with lower relative hospital costs and a lower total cost in a subsequent block. Our research suggests a cost-savings potential associated with increased community-based palliative nursing.

Mobilization without immune depletion fails to restore immunological tolerance or preserve beta cell function in recent onset type 1 diabetes.

Granulocyte colony-stimulating factor (G-CSF) has been used to restore immune competence following chemoablative cancer therapy and to promote immunological tolerance in certain settings of autoimmunity. Therefore, we tested the potential of G-CSF to impact type 1 diabetes (T1D) progression in patients with recent-onset disease [n = 14; n = 7 (placebo)] and assessed safety, efficacy and mechanistic effects on the immune system. We hypothesized that pegylated G-CSF (6 mg administered subcutaneously every 2 weeks for 12 weeks) would promote regulatory T cell (Treg) mobilization to a degree capable of restoring immunological tolerance, thus preventing further decline in C-peptide production. Although treatment was well tolerated, G-CSF monotherapy did not affect C-peptide production, glycated haemoglobin (HbA1c) or insulin dose. Mechanistically, G-CSF treatment increased circulating neutrophils during the 12-week course of therapy (P < 0·01) but did not alter Treg frequencies. No effects were observed for CD4(+) : CD8(+) T cell ratio or the ratio of naive : memory (CD45RA(+)/CD45RO(+)) CD4(+) T cells. As expected, manageable bone pain was common in subjects receiving G-CSF, but notably, no severe adverse events such as splenomegaly occurred. This study supports the continued exploration of G-CSF and other mobilizing agents in subjects with T1D, but only when combined with immunodepleting agents where synergistic mechanisms of action have previously demonstrated efficacy towards the preservation of C-peptide.

Quality of end-of-life cancer care in Canada: a retrospective four-province study using administrative health care data.

BACKGROUND: The quality of data comparing care at the end of life (eol) in cancer patients across Canada is poor. This project used identical cohorts and definitions to evaluate quality indicators for eol care in British Columbia, Alberta, Ontario, and Nova Scotia. METHODS: This retrospective cohort study of cancer decedents during fiscal years 2004-2009 used administrative health care data to examine health service quality indicators commonly used and previously identified as important to quality eol care: emergency department use, hospitalizations, intensive care unit admissions, chemotherapy, physician house calls, and home care visits near the eol, as well as death in hospital. Crude and standardized rates were calculated. In each province, two separate multivariable logistic regression models examined factors associated with receiving aggressive or supportive care. RESULTS: Overall, among the identified 200,285 cancer patients who died of their disease, 54% died in a hospital, with British Columbia having the lowest standardized rate of such deaths (50.2%). Emergency department use at eol ranged from 30.7% in Nova Scotia to 47.9% in Ontario. Of all patients, 8.7% received aggressive care (similar across all provinces), and 46.3% received supportive care (range: 41.2% in Nova Scotia to 61.8% in British Columbia). Lower neighbourhood income was consistently associated with a decreased likelihood of supportive care receipt. INTERPRETATION: We successfully used administrative health care data from four Canadian provinces to create identical cohorts with commonly defined indicators. This work is an important step toward maturing the field of eol care in Canada. Future work in this arena would be facilitated by national-level data-sharing arrangements.

The quick and the dead: "managing" inpatient care in British Columbia hospitals, 1969-1995/96.

OBJECTIVE: To examine changes in hospital use in British Columbia during a decade of capacity reductions. DATA SOURCES/STUDY SETTING: The data used are all separation records for British Columbia hospitals for the years 1969, 1978, 1985/86, 1993/94, and 1995/96. Separation records include acute care, rehabilitation, extended care, and surgical day care hospital encounters in British Columbia that were concluded during the years of interest. STUDY DESIGN: Analyses were based on per capita use of services for five-year age groups of the population to ages 90+; the emphasis was on looking at changes in the use of specific types of hospital services over the 26 years of study, with a particular focus on the most recent decade. DATA COLLECTION/EXTRACTION METHODS: Data were extracted from hospital separations files owned by the British Columbia Ministry of Health and housed at the Centre for Health Services and Policy Research. All separation records for the years of interest were included in the study. PRINCIPAL FINDINGS: Acute care use continued to fall over the last decade. The rate of decline increased during the last time period of study and affected seniors to the same degree as younger patients. At the same time, use of extended care decreased, compared to steady increases in earlier years. The result was that by 1995/96 nearly 40 percent of inpatient days were used by people who died in hospital, compared to 9 percent in 1969. These people, however, still represent a small proportion of separations. CONCLUSIONS: The "bed blocker" problem common to many hospital systems appears to have been largely alleviated in British Columbia over the decade 1985-95. The concurrent decrease in extended care use, however, makes it difficult to say where and how these people are now being cared for. Care for the dying has become a bigger issue for hospitals, but whether this is because of heroic interventions at the end of life is not clear. A "top-down," capacity-driven management approach to hospital use in British Columbia has produced effects that may seem familiar to those involved in more "bottom-up" managed care approaches in the United States.

Prescription of methylphenidate to children and youth, 1990-1996.

BACKGROUND: There are concerns about the frequency and appropriateness of psychostimulant drug prescription to children. In order to identify unusual or unexpected patterns of use or prescribing, we reviewed prescription of methylphenidate (Ritalin) to children and adolescents aged 19 years or less in British Columbia between 1990 and 1996. METHODS: We obtained information about patients, physicians and prescriptions from British Columbia's Triplicate Prescription Program database for controlled drugs. Prescription data were available for the period Jan. 1, 1990, to Dec. 31, 1996. Linkage with the BC Linked Health Dataset provided additional demographic and health information. RESULTS: In 1990, 1715 children received at least 1 prescription for methylphenidate (1.9 per 1000 children). By 1996, the number had increased to 10,881 children (11.0 per 1000). Because some children were prescribed methylphenidate in more than 1 year, we also calculated the frequency with which the drug was prescribed to children who had never received it before. This rate increased from 1.0 per 1000 children in 1990 to 4.7 per 1000 in 1995; the rate fell in 1996 to 3.5 per 1000. The number of children receiving methylphenidate varied across health regions of the province, from 12.0 to 35.4 per 1000. Use also varied by socioeconomic status quintile: in the 2 lowest (least privileged) quintiles, 21.6 per 1000 children received methylphenidate, compared with 18.4 per 1000 in the 3 highest quintiles (relative risk 1.2, 95% confidence interval 1.1-1.2). Pediatricians and psychiatrists wrote 23% and 21% of all prescriptions respectively. General practitioners accounted for 56% of all prescriptions and 41% of initial methylphenidate prescriptions. A claim for prior specialist consultation was found in 30% of such cases. Many of the children who received more than 10 prescriptions had seen 4 or more physicians. The average daily dosage prescribed differed little among general practitioners, pediatricians and psychiatrists, unlike the mean interval between successive prescriptions: 89.9 (standard deviation [SD] 68.2), 99.8 (SD 64.1) and 75.9 (SD 70.2) days respectively. Persistence with therapy was more likely when a psychiatrist provided the initial prescription, or with involvement of more than one specialty. INTERPRETATION: Many trends and practices in the prescription of methylphenidate to children in British Columbia are consistent with other settings and accepted standards. Some aspects warrant closer investigation, including regional and socio-economic discrepancies in the distribution of patients, the relative involvement of primary and specialist care providers, continuity of care issues and time intervals between prescriptions.

Hospital downsizing and trends in health care use among elderly people in British Columbia.

BACKGROUND: There has been considerable downsizing of acute care services in British Columbia over the past 2 decades. In this population-based study we examined changes in the proportion of elderly people who used acute care, long-term care and home care services between 1986-1988 and 1993-1995 to explore whether the downsizing has influenced use. Changes in death rates were also examined. METHODS: The British Columbia Linked Health Database was used to select all British Columbia residents aged 65 years, 75-76 years, 85-87 years or 90-93 years as of Jan. 1, 1986 (cohort 1), and Jan. 1, 1993 (cohort 2). Each person was assigned to 1 of 6 mutually exclusive categories of health care use reflecting different intensities of use (i.e., hospital, long-term or home care). The proportions of people within each category were compared between the 2 periods, as were the age-standardized death rates. RESULTS: There were 79,175 people in cohort 1 and 92,320 in cohort 2. Overall, the relative proportion of people in each use category was similar between the 2 study periods. The most substantial changes were an increase of 2 percentage points in the proportion of people who received no facility or home care services and a decrease of 2 to 3 percentage points in the proportion who received some acute care but no facility-based continuing care. The age-adjusted all-cause death rates for the earlier and later cohorts were virtually identical (15.7% and 15.8% respectively), although the rate increased from 63.6% to 70.1% among those in the "full-time facility with acute care" group. INTERPRETATION: Overall changes in health care use were small, which suggests that the repercussions of the decline in acute care services for elderly people have been minimal. The higher age-adjusted death rates in the later cohort in full-time care suggests that long-term stays are becoming reserved for a sicker group of elderly people than in the past.

Age, costs of acute and long-term care and proximity to death: evidence for 1987-88 and 1994-95 in British Columbia.

BACKGROUND: the consequences of ageing populations for health care costs have become a concern for governments and health care funders in most countries. However, there is increasing evidence that costs are more closely related to proximity to death than to age. This means that projections using age-specific costs will exaggerate the impact of ageing. Previous studies of the relationship of age, proximity to death and costs have been restricted to acute medical care. OBJECTIVE: to assess the effects of age and proximity to death on costs of both acute medical care and nursing and social care, and to assess if this relationship was stable in a time of rapid change in health care expenditure. DESIGN AND METHODS: we compared all decedents in the chosen age categories for the years 1987-88 and 1994-95 with all survivors in the same age groups. We measured use of health and social care for each individual using the British Columbia linked data, and costs of care assessed by multiplying the number of services by the unit cost of each service. SETTING: the Province of British Columbia. SUBJECTS: all decedents in 1987-88 and 1994-95 in British Columbia in the chosen age groups, and all survivors in the same age groups. RESULTS: costs of acute care rise with age, but the proximity to death is a more important factor in determining costs. The additional costs of dying fall with age. In contrast, costs of nursing and social care rise with age, but additional costs for those who are dying increase with age. Similar patterns were found for the two cohorts. CONCLUSIONS: age is less important than proximity to death as a predictor of costs. However, the pattern of social and nursing care costs is different from that for acute medical care. In planning services it is important to take into account the relatively larger impact of ageing on social and nursing care than on acute care.

Mortality rates after cataract extraction.

Senile cataract may be a marker of generalized tissue aging. We examined this hypothesis using population-based linked health data. We hypothesized that any such association would diminish with increased use of cataract surgery. Mortality rates of those 50-95 years of age undergoing cataract surgery in British Columbia during either 1985 or 1989 were compared with the provincial population of comparable age who did not undergo cataract surgery during the study period. The 1985 cohort included 8,262 patients undergoing surgery and a comparison population of 804,303, and the 1989 cohort included 11,952 patients and a comparison population of 839,393. Using Cox regression, for the 1985 cohort, the hazard ratios for dying during follow-up were 3.2 for males 50-54.9 years of age [95% confidence limits (CL) = 2.0, 5.0] and 3.3 for females (95% CL = 1.9, 5.7). Hazard ratios for older age groups decreased with age. We also fit an additive risk model that produced excess mortalities that were less age dependent. In the 1985 analysis, these ranged from +7.1 per 1,000 (95% CL = +0.44, +13.76) to +20.3 (95% CL = +13.24, +27.36) for males and -17.5 (95% CL = -28.28, -6.72) to +2.0 (95% CL = -2.12, +6.12) for females. Findings for the 1989 analyses were similar, indicating that the association between cataracts and generalized aging remained constant despite a large increase in the use of cataract surgery.

Lung carcinoma presenting as metastasis to intracranial meningioma: case report and review of the literature.

Tumor-to-tumor metastasis is rare. The authors report a case of a 52-year-old man with a 1-year history of a right parasaggital meningioma, whose clinical signs were consistent with enlarging meningioma. In preparation for surgery, the routine preoperative chest radiograph revealed a lung mass. Fine-needle aspiration of the mass revealed adenocarcinoma. The patient underwent surgical excision of the intracranial mass, which was thought to be a meningioma. However, pathologic examination revealed a transitional meningioma extensively infiltrated with deposits of metastatic carcinoma from the patient's primary lung tumor. Metastasis to meningioma was therefore responsible for the rapid enlargement of the long-standing meningioma, and caused the first clinical manifestation of primary lung carcinoma. Recurrent metastasis developed at the surgical site 5 weeks later, requiring surgical excision and postoperative radiation to prevent further recurrence. This is a highly unusual presentation for lung carcinoma and, to the authors' best knowledge, is the first such case reported. A review of the published literature revealed 20 other cases of lung carcinoma metastatic to meningioma, which were incidentally discovered on surgery or autopsy.

Saphenous vein interposition graft for recurrent carotid stenosis after prior endarterectomy and stent placement. Case report.

Although the use of carotid artery stents is increasing, the management of recurrent stenosis after their placement is undefined. The authors report on a patient who underwent two left carotid endarterectomies followed by left carotid angioplasty and stent placement for recurrent stenosis. A third symptomatic recurrence was subsequently managed by placement of a saphenous vein interposition graft from the common carotid artery to the distal cervical internal carotid artery. The patient remained without hemispheric or retinal ischemia at his 5-month follow-up visit. Interposition grafting should be considered as a treatment option for carotid restenosis after initial endarterectomy and stent placement.

Socioeconomic status, mortality, and the development of cataract at a young age.

It has been hypothesized that senile cataract may serve as a marker for generalised tissue aging, since structural changes occurring in the proteins of the lens during cataract formation are similar to those which occur elsewhere as part of the aging process. An earlier analysis we carried out to test this hypothesis revealed a strong age-dependent relationship between undergoing cataract surgery and subsequent mortality. Relative risks for dying over 9 yr of follow-up were particularly increased for individuals who had developed cataract requiring operation between the ages of 50-65. This finding prompted us to test the hypothesis that younger patients undergoing surgery for cataract (those in which surgery was undertaken at 50-65 yr of age) would tend disproportionately to be resident in areas of generally lower socioeconomic status. A population-based linked health data resource containing data on all hospital separations in the province of British Columbia was used to examine this hypothesis. Linkage to Canadian census data was used to assign a socioeconomic decile to the area of residence for all individuals in British Columbia who either did, or did not, undergo cataract surgery over a 3 yr period, and were aged 50-95. Relative to those who resided in the highest socioeconomic areas, odds ratios for undergoing cataract surgery between 50 and 65 yr of age were significantly greater than 1 for the four lowest socioeconomic deciles. This association was observed despite a conservative bias in our setting that favoured those of higher socioeconomic status tending to receive earlier treatment. The results of this ecologic study prompt consideration of whether factors which have the dual attributes of being correlates of socioeconomic status and implicated in the development of cataract may play a role in mediating the processes involved in the well known association of socioeconomic status and mortality.