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N S Rawson

Publications and source records attributed to N S Rawson.

At least 19 recordsLinked to original sources

Hospitalizations for aplastic anemia and agranulocytosis in Saskatchewan: incidence and associations with antecedent prescription drug use.

A population-based study to estimate the incidence of hospitalizations for aplastic anemia and agranulocytosis and to evaluate associations between these disorders and antecedent prescription drug use was performed using the Saskatchewan administrative health care databases. Hospital charts and cancer registration data were utilized to apply strict diagnostic criteria to case identification. Estimates of the annual incidence of aplastic anemia and agranulocytosis were 2.7 and 3.0 per million, which are similar to those from other recent population-based studies with comparable case identification criteria. Only a small number of cases were available to evaluate potential drug causes, leading to an analysis of limited power. Nevertheless, significant associations were found between aplastic anemia and tocainide, gold salts, and antidepressants; and between agranulocytosis and anti-thyroids, trimethoprim-sulfamethoxazole, beta-lactams, sulfasalazine, chlorpromazine, carbamazepine, glyburide, and procainamide, although the associations with antibiotics may indicate a response to the disorders rather than a possible cause. These findings are generally consistent with the results of other case-control investigations.

Adolescent

Reliability of the recording of schizophrenia and depressive disorder in the Saskatchewan health care datafiles.

Administrative data have long been used in psychiatric epidemiology and outcomes evaluation. This article examines the reliability of the recording of schizophrenia and depressive disorder in three Saskatchewan administrative health care utilization datafiles. Due to their comprehensive nature, these datafiles have been used in a wide range of epidemiologic studies. Close agreement was found between hospital computer data and patients' charts for personal and demographic factors (> or = 94.7%). Diagnostic concordance between computerized hospital data and medical charts was very good for schizophrenia (94%) but poor for depressive disorder (58%). Appropriate physician services were identified for 60% and 72% of hospital discharges for schizophrenia and depressive disorder, respectively, and exact diagnostic agreement between hospital and physician datafiles was 62% for schizophrenia and 66% for depressive disorder. Appropriate provincial mental health branch services were found for 83% and 38% of hospital discharges for schizophrenia and depressive disorder, respectively; exact diagnostic concordance between these datafiles was 75% for schizophrenia and 0% for depressive disorder. A significant number of patients with major or neurotic depression appeared to be wrongly coded as having depressive disorder in the hospital file. The differences in diagnostic agreement may also be partly a function of how the two conditions are differentially treated in the health system. These findings suggest that more specific and severe psychiatric diagnoses are likely to be recorded accurately and consistently in the Saskatchewan datafiles. However, disorders with multiple manifestations or those for which there are several possible codes should be examined with caution and ways sought to validate them. Attention should also be paid to which service sectors are involved in the treatment of specific disorders.

Adolescent

Letter and category fluency in community-dwelling Canadian seniors: a comparison of normal participants to those with dementia of the Alzheimer or vascular type.

Measures of letter (FAS) and category (Animal Naming) fluency were completed by community-dwelling, cognitively normal seniors (n = 635), and by individuals diagnosed with dementia of the Alzheimer type (DAT) (n = 155), or with vascular dementia (n = 39). Among normal seniors, category, but not letter fluency, declined with age, females performed better than males on letter but not on category fluency, and performance increased with education on both tasks. Among participants with DAT, letter fluency was influenced by level of education, whereas category fluency was education-, age-, and gender-invariant. Both measures differentiated normal seniors from those with dementia. Category fluency was more impaired than letter fluency at both mild and moderate stages of dementia, but neither task differentiated DAT from vascular dementia.

Aged

Reliability of the recording of hysterectomy in the Saskatchewan health care system.

OBJECTIVE: To determine the validity of data pertaining to hysterectomy in the Saskatchewan health care utilisation datafiles. DESIGN: Retrospective analysis of routinely collected data covering hospital discharge records and practitioner claims for reimbursement of services, together with a review of clinical charts. SETTING: Province of Saskatchewan, Canada. SAMPLE: All 1905 cases of hysterectomy in one calendar year for analysis of datafiles and a random sample of 227 clinical charts for review. METHOD: Information in the hospitalisation datafile was validated through an external comparison with data extracted from a review of clinical charts, as well as an internal comparison with independent data from the practitioner claims file. Corresponding context data on drug use and performance of related procedures were also analysed. RESULTS: Concordance between hospital data and clinical charts was greater than 95% for those items of an administrative nature as well as type of hysterectomy and was around 85% for the diagnoses. When hospitalisation and practitioner claims data were compared, the concordance was 98% for type of hysterectomy but only 56% for diagnoses. CONCLUSIONS: The agreement between hospital data and clinical charts was excellent. The concordance between hospitalisation and practitioner claims data was almost exact for type of hysterectomy, while discrepancies in diagnoses between these files were mostly explainable on the basis of accepted clinical practice. Saskatchewan health care utilisation datafiles provide a source of valid data for research and evaluation studies.

Adolescent

Validity of the recording of ischaemic heart disease and chronic obstructive pulmonary disease in the Saskatchewan health care datafiles.

The internal validity of the recording of information about ischaemic heart disease (IHD) and chronic obstructive pulmonary disease (COPD) in the administrative health care datafiles of the Canadian province of Saskatchewan is investigated. Comparisons between hospital data and medical charts for acute myocardial infarction and chronic airways obstruction patients showed excellent diagnostic agreement: 97 per cent and 94 per cent, respectively. Appropriate physician service claims were identified for 89 per cent of hospitalizations for IHD and COPD and exact concordance between diagnoses in the two datafiles varied between 15 per cent for acute/sub-acute IHD and 80 per cent for asthma; including any physician diagnosis within the same broad category (IHD or COPD) increased concordance to 79-94 per cent for IHD and 64-88 per cent for COPD. Contextual information related to the hospitalizations was clinically and epidemiologically realistic.

Adolescent

The timeliness of new drug approvals in Canada.

In a recent article, Lexchin asks "who needs faster drug approval times in Canada?" and, on the basis of extremely limited and selective data, draws the conclusion that neither the public nor the pharmaceutical industry does. Whether the Canadian system is really slower is investigated by comparing Canadian and U.S. marketing approval dates and by using information on regulatory approval times from the two countries and elsewhere. Marketing approval dates in Canada are significantly later than those in the United States, although not consistently across all therapeutic categories; anti-cancer and gastrointestinal drugs have earlier approval dates in Canada. However, Canadian and U.S. regulatory approval times are not significantly different, indicating that marketing applications are submitted later in Canada, but both are considerably longer than those in the United Kingdom. The evidence shows that Canadians need faster drug approval times if individuals requiring the medications are not to suffer unnecessarily. A significant decrease in drug approval times and the establishment of comprehensive and effective postmarketing surveillance would reduce the time it takes for new drugs to be made available to Canadians while, at the same time, providing a high level of drug safety.

Canada

Unlocking datasets.

Explore the source record for details and available documents.

Costs and Cost Analysis

Serum markers for primary and recurrent breast cancer: BCM-EIA, CAM 26 and CAM 29.

Three sandwich enzyme immunoassays were used to evaluate serum from 93 women: 20 normal, 20 with benign breast disease, 22 with primary and 31 with recurrent breast cancer. Using the three assays, breast cancer mucin enzyme immunoassay (BCM-EIA) carcinoma-associated mucin antigen (CAM) 26 and CAM 29, both singly and in combination, we were unable to establish meaningful cut-offs to differentiate between patients with or without breast cancer. The sensitivity and specificity for BCM-EIA were 90% and 40%, for CAM 26, 89% and 42%, and for CAM 29, 91% and 66%, respectively. Serial serum specimens from 29 patients with recurrent breast cancer were assayed. At recurrence, an increase of 25% or more in marker level over the previous value was found in 24/29 (83%) BCM results, 14/29 (48%) CAM 26 results and 12/29 (41%) CAM 29 results. Prior to clinical detection of recurrence, stepwise increases in BCM and CAM 26 marker levels were seen up to 299 days prior to clinical detection of recurrence. We conclude that these markers may help in the early detection of recurrent breast cancer.

Antigens, Neoplasm

Estrogen and progesterone receptors in the normal female breast.

We have studied estrogen receptor (ER) and progesterone receptor (PR) in normal breast by immunocytochemistry using tissue biopsies and fine needle aspirates (FNA) and, in the case of ER, by enzyme immunoassay. For ER we found a high degree of reproducibility for biopsies taken from the upper outer quadrant: FNA, r = 0.56 (P less than 0.002); tissue section immunocytochemistry, r = 0.89 (P less than 0.0001); and enzyme immunoassay, r = 0.76 (P less than 0.0001). For PR, FNA (r = 0.56, P less than 0.002) and tissue section (r = 0.97, P less than 0.0001) were also found to be reproducible techniques. Using enzyme immunoassay, we were able to measure ER accurately in normal breast tissue. In 59 samples we found a range of 0-37 fmol/mg cytosol protein (mean, 4 fmol/mg). In an age-matched group of 126 women with breast cancer, we found a significantly higher ER [range, 0-139 fmol/mg; mean, 37 fmol/mg (P less than 0.001)]. We then analyzed the ER and PR content of FNAs obtained from the upper outer quadrant of the normal breast in 143 normal women. We found that in only 23 of 143 samples (16%) were greater than or equal to 50% epithelial cells stained. There was a relationship between ER and PR (P = 0.03) and a higher ER content in European women than in non-European women (P less than 0.03). The PR content was related to high body mass index (P less than 0.02) and family history of breast cancer (P = 0.04). Samples tended to be more frequently ER positive by FNA if taken in the follicular phase of the menstrual cycle. We conclude that, although the levels of ER and PR are low in normal breast, they can be accurately measured. There is significant variation of ER and PR with several clinical parameters.

Adolescent

Randomised trial of epirubicin alone versus 5-fluorouracil, epirubicin and mitomycin C in locally advanced and metastatic carcinoma of the pancreas.

Sixty-nine unselected patients with locally advanced and metastatic carcinoma of the pancreas, who had not received previous chemotherapy or radiotherapy were randomised to receive either 5-fluorouracil, epirubicin and mitomycin C (FEM) or epirubicin. Survival was not significantly different in the two arms. Toxic reactions (WHO grade greater than 3) in the FEM and epirubicin arm respectively included nausea (2), (4), severe alopecia (1) (3) and leucopenia (1), (5), none of these were statistically significant. We therefore suggest that combination chemotherapy should not be used in preference to single agent chemotherapy as standard treatment for locally advanced or metastatic cancer of the pancreas.

Antineoplastic Agents

Prescription-event monitoring of 10,895 patients treated with alprazolam.

'Prescription-event monitoring' (PEM) is one of two national systems of post-marketing surveillance in operation in Britain. It identified 22,065 patients who had received NHS prescriptions for alprazolam, and data available on 10,895 of these were analysed. The main reasons for treatment with alprazolam were anxiety and depression. The patients provided 3360 patient-years of treatment and 7540 patient-years of follow-up. No serious events clearly associated with treatment were recorded. The main events reported during treatment, albeit infrequently, were drowsiness and depression, although depression is more likely to be due to the disorder being treated than to the drug. Some of the other alleged unwanted effects of alprazolam in published reports were not encountered. Since PEM is unable to determine the dependence potential of alprazolam, further evaluation of this problem is called for.

Adult

Sedative-hypnotic drug use in Canada.

Although many studies of sedative-hypnotic drug use have been performed in Canada, there has been no national study of the use of these drugs. We have attempted to correct this deficit in our knowledge by using data from an international survey of health care utilization performed in 1968-9 and from the Canada Health Survey (1978-9), the Health Promotion Survey (1985) and the National Alcohol and Other Drugs Survey (1989) to examine sedative-hypnotic use among individuals aged 15 or more. The results suggest that the use of these drugs in Canada is about average for an industrialized society. Several socioeconomic and health care correlates of sedative-hypnotic use were found. The rate of use of these drugs was higher among women, the elderly, separated, divorced or widowed individuals, those who had a secondary school education or less, individuals with a low family income, the retired, and the unemployed. Among women, higher rates of use were reported by those whose main activity was keeping house (as compared with those who were employed outside the home) and by those who lived alone. Higher rates of use were also found for individuals who had consulted a physician or been hospitalized recently, individuals taking multiple drugs, those who scored highly on an anxiety scale, persons in whom negative feelings predominated, and those who had experienced a high frequency of psycho-physiological symptoms of anxiety and depression. From a regional point of view, the highest rates of use for women were consistently reported from Quebec, while the lowest were consistently found in the Prairie provinces. No consistent pattern was found for men.

Adolescent

Prescription-event monitoring: methodology and recent progress.

Event monitoring was first suggested 25 years ago as a way of detecting adverse reactions to drugs. Prescription-event monitoring (PEM), which has been developed by the Drug Safety Research Unit, is the first large-scale systematic post-marketing surveillance method to use event monitoring in the U.K. PEM identifies patients, who have been prescribed a particular drug, and their doctors from photocopies of National Health Service prescriptions which are processed centrally in England. A personalized follow-up questionnaire ("green form") is mailed to each patient's general practitioner, usually on the first anniversary of the initial prescription, asking for information about the patient, especially any "events" that he or she may have experienced since beginning treatment with the drug. The methodology of PEM is presented, together with examples of analyses that can be performed using results from recent studies. The problems and benefits of PEM are discussed.

Drug Prescriptions

An overview of prognostic factors in small cell lung cancer. A report from the Subcommittee for the Management of Lung Cancer of the United Kingdom Coordinating Committee on Cancer Research.

Several studies of small cell lung cancer (SCLC) treatments have been performed in the United Kingdom. In some, prognostic factor analyses were carried out but the results were not entirely consistent. The Lung Cancer Subcommittee of the United Kingdom Coordinating Committee on Cancer Research (UKCCCR) consequently initiated an overview of these studies with the aim of identifying the important prognostic factors using a large number of patients. Information on almost 4,000 patients was available, but it was necessary to perform analyses on smaller subsets because the variables recorded in individual studies were inconsistent. A number of variables contributed significantly to the prediction of likely survival over the 6 months after starting treatment, but performance status (PS), alkaline phosphatase (AlkP) and disease stage were shown to be the most important; aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) may also be useful. A prognostic index was devised for this initial period and validated using independent data. For patients who survived the first 6 months, the pre-treatment variables important for prognosis in the 6-24 month period were stage, PS and plasma sodium (Na). The Subcommittee recommends that performance status, disease stage, AlkP, Na, AST and LDH should be measured in all future SCLC studies to assist comparisons between studies and possibly the selection of patients for different treatment strategies. The additional recording of five other variables would allow a more definitive overview to be performed at some future date.

Adult

Adjuvant chemotherapy in head and neck cancer.

An overview is presented of 23 trials of adjuvant chemotherapy in squamous cell carcinoma of the head and neck. These were reviewed from the point of view of design of the trial, analysis of survival, response rates, meta-analysis, site of failure, toxicity and cost. The minimal increase in survival that could be detected ranged from 11 to 51%, with a median of 25%. No trial was big enough to detect the likely increase of survival, which is 5%. Many trials excluded some eligible patients before randomisation, the proportion being 21% in those series with details. A further 9% of treated patients were excluded from analysis. A response rate in four induction studies of 47% equated with a 6% increase in cancer mortality. Meta-analysis showed an insignificant overall improvement in cancer mortality of 0.5%. Induction chemotherapy, synchronous chemotherapy and induction/maintenance chemotherapy did not affect cancer mortality whereas synchronous/maintenance therapy did. Cisplatinum, methotrexate, bleomycin, 5-FU and a variety of other regimens did not affect the death rate from cancer, but the combination of VBM significantly increased it. Neither single agent nor combination chemotherapy produced a significant reduction of cancer deaths. The rate of locoregional failure was significantly lower in the treated arms, whereas the metastatic rate was similar in both arms. Only three papers gave full details of toxicity with grading: these showed a high toxicity rate. The mortality rate from chemotherapy in nine series averaged 6.5%.

Carcinoma, Squamous Cell