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.

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.

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.

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.

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.

Lymphocytic adenohypophysitis of pregnancy with complete recovery.

A case of lymphocytic adenohypophysitis in a postpartum woman who became symptomatic during her 8th month of pregnancy is presented. The clinical presentation, endocrine findings, pathological findings, and operative management are discussed. Transient hypopituitarism is documented. Unlike most previously published cases, this woman had complete recovery of anterior pituitary function.

Ventriculoatrial shunt distal catheter placement using transesophageal echocardiography: technical note.

Accurate placement of the distal end of a ventriculoatrial shunt at the cavo-atrial junction is important for long-term shunt function as well as for avoiding cardiac arrhythmias, thrombus formation, and damage to myocardial tissue. Standard methods of intraoperative localization, including chest x-ray, pressure measurements, and electrocardiogram recording, can be inaccurate. By using intraoperative transesophageal echocardiography, the distal end of the catheter can be localized to the cavo-atrial junction.

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.

Aneurysm of the ICA petrous segment treated by balloon entrapment after EC-IC bypass. Case report.

A 44-year-old man experienced the sudden onset of horizontal diplopia and hemifacial numbness. Arteriography demonstrated a left intrapetrous carotid artery aneurysm. The patient was successfully treated with a left superficial temporal artery to middle cerebral artery bypass followed by balloon entrapment of the aneurysm. There have been at least 40 previously reported cases of aneurysms of the petrous portion of the carotid artery. These aneurysms can be mycotic, traumatic, or developmental in origin. They can present with massive otorrhagia or epistaxis from acute rupture or with decreased hearing and paresis of the fifth through eighth cranial nerves and, less frequently, of the ninth, 10th, and 12th cranial nerves caused by direct pressure. They can also produce pulsatile tinnitus, and sometimes they are discovered as a retrotympanic vascular mass during otological examination. The treatment of choice is carotid artery occlusion. Trapping of the aneurysm by detachable balloons eliminates immediately the risk of hemorrhage, offers the possibility of test occlusion of the internal carotid artery with the patient awake prior to permanent occlusion, and should also reduce the risk of thromboembolism. It should be preceded by a bypass procedure when preliminary evaluation indicates that the patient will not tolerate internal carotid artery occlusion.

Intracranial dissection of the distal middle cerebral artery as an uncommon cause of distal cerebral artery aneurysm. Case report.

An aneurysmal dissection of a right middle cerebral artery (MCA) branch is described in a 56-year-old woman. The abnormality was an incidental finding on computerized tomography and subsequently appeared on magnetic resonance imaging performed to evaluate the patient for subjective pulsatile tinnitus. The intracranial aneurysm was documented to have enlarged on serial angiography over a 6-week interval. Treatment was believed to be necessary because of the unknown etiology of the aneurysm, with the differential diagnosis including mycotic or neoplastic aneurysm with a risk of hemorrhage. The lesion was excised and flow to the distal MCA branch was preserved with an anastomosis of the superficial temporal artery to the MCA. The aneurysm, which developed at the level of the sylvian fissure, proved on pathological study to be related to a focal dissection of the MCA branch. The radiographic appearance and pathological findings are presented. Focal dissection must henceforth be included in the differential diagnosis of peripheral cerebral artery aneurysms.

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.

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.

Intraoperative use of electroencephalography as an assessment of cerebral blood flow.

The electroencephalogram (EEG) is exquisitely sensitive to decreases in cerebral blood flow (CBF). The EEG can detect cerebral ischemia in the awake and generally anesthetized patient. EEG monitoring of CBF during carotid endarterectomy alerts the surgeon to the need for a shunt. In the surgery of intracranial aneurysms, it can detect cerebral ischemia secondary to temporary vessel occlusion or determine the optimal anesthetic doses for brain protection.

The surgical management of benign intracranial meningiomas and acoustic neuromas in patients 70 years of age and older.

Over a 22-year-period (1967-1989) 80 patients 70 years of age and older underwent surgery for resection of a benign intracranial tumor. This group included 56 meningiomas and 24 acoustic neuromas. Forty-five of the tumors were completely excised, whereas 35 were partially removed. Tumor regrowth was documented in seven patients during the follow-up period, five of whom underwent additional surgery for resection of recurrent tumor. Thirty-six (64.3%) of the patients with meningiomas had only a minimal or no preoperative neurologic deficit, whereas twenty (35.7%) had a major deficit. Fifty-three (94.6%) patients who underwent surgery for resection of their meningioma made a good recovery (48 were improved or unchanged and five had minimal nonincapacitating worsening), one (1.8%) was worse, and two (3.6%) died. Fourteen (58.3%) of the patients with acoustic neuromas had only a minimal or no preoperative neurologic deficit, whereas 10 (41.7%) had a major deficit. Twenty-two (91.7%) of the patients who underwent surgery for resection of their acoustic neuroma made a good recovery (18 were improved or unchanged and four had minimal nonincapacitating worsening), two (8.3%) were worse, and none died. We conclude that, when indicated, surgery for intracranial meningiomas and schwannomas can be offered to patients 70 years of age and older with acceptable morbidity and mortality.

Subdural empyema complicating bacterial meningitis in a child: enhancement of membranes with gadolinium on magnetic resonance imaging in a patient without enhancement on computed tomography.

Subdural empyema is a known yet infrequent complication of bacterial meningitis. Subdural effusions occur frequently with meningitis in children and usually resolve spontaneously or with subdural taps. Subdural empyema should be suspected when a patient fails to respond to antibiotic therapy or worsens neurologically. Computed tomography (CT) scans with contrast often show enhancement of subdural collections when an empyema exists. However, this is not true all of the time. We present a case of subdural empyema complicating bacterial meningitis in a 4 month old in which CT enhancement was not present yet magnetic resonance imaging (MRI) scans with gadolinium demonstrated intense enhancement. For comparison, we present a second case of a child with sterile subdural effusions due to meningitis that demonstrates an absence of contrast enhancement on MRI studies. MRI scans with contrast may offer a more sensitive means of making an early diagnosis of subdural empyema.