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Modified adriamycin-vincristine-dexamethasone (m-VAD) in primary refractory and relapsed plasma cell myeloma: an NCI (Canada) pilot study. The National Cancer Institute of Canada Clinical Trials Group.

The purpose of this single arm phase II study was to test a modified version of the three drug combination vincristine, adriamycin and dexamethasone (m-VAD), in which intravenous vincristine (0.4 mg/d) and adriamycin (9 mg/m2 per day) infusions are administered for only 2 h on days 1-4 of each 28 d cycle, in patients with refractory multiple myeloma. In addition, only two 4 d courses of dexamethasone 40 mg/d was given during each cycle. The entry criteria for 44 patients included plasma cell myeloma and a measurable monoclonal peak, either refractory to initial treatment with melphalan and prednisone, or resistant to melphalan and prednisone after initially responding (resistant relapsed disease, 27 patients). Patients treated previously with chemotherapy other than melphalan and prednisone were excluded. There were no complete responses. Of the 41 evaluable patients who completed at least one course of therapy 11 had a partial response (27%, 95% C.I. 14-40%). The response rates were 19% for primary refractory disease patients, and 32% for those with resistant relapsed disease. The median duration of response was 4 months. The median survival for all 44 patients was 7.6 months (5.5 months for primary refractory patients, and 10 months for relapsed resistant disease patients). Episodes of documented bacterial infection occurred in 12 patients, and 10 patients had minor viral infection. The dexamethasone dose was reduced in 12 patients. The median neutrophil nadir was 1.2 x 10(9)/l, and median platelet nadir was 147 x 10(9)/l. Five deaths were judged as treatment related and occurred during marrow cytopenia. The results of this modified form of VAD are inferior to that reported previously for 4 d continuous infusions of vincristine and doxorubicin. This could be related to either patient selection factors, or to a reduction of the efficacy of the drug combination produced by either the shortened intravenous infusions and/or omission of one 4 d course of dexamethasone.

Aged↗

Survey of blood stream infections attributable to gram-positive cocci: frequency of occurrence and antimicrobial susceptibility of isolates collected in 1997 in the United States, Canada, and Latin America from the SENTRY Antimicrobial Surveillance Program. SENTRY Participants Group.

The SENTRY Antimicrobial Surveillance Program was established in January, 1997 to monitor the predominant pathogens and antimicrobial resistance patterns of nosocomial and community-acquired infections via a network of sentinel hospitals in the United States (30 sites), Canada (eight sites), Latin America (10 sites), and Europe (24 sites). During the first 12-month study period (January to December, 1997), a total of 9519 blood stream infections (BSI) were reported by SENTRY participants in the U.S. (6150), Canada (1727), and Latin America (1642). The Gram-positive cocci, Staphylococcus aureus, coagulase-negative staphylococci (CoNS), enterococci, and streptococci accounted for 53.9% (5131 infections) of all BSI (56.5% U.S., 55.7% Canada, and 42.9% Latin America). The staphylococci, Enterococcus spp., S. pneumoniae, beta-hemolytic streptococci, and viridans group streptococci accounted for 6 of the top 11 BSI pathogens in the U.S. and Canada, whereas only S. aureus (1st), CoNS (3rd), and Enterococcus spp. (9th) were among the top 11 pathogens in Latin American hospitals. The results of this survey affirm the importance of Gram-positive cocci as causes of BSI in both North America and Latin America and demonstrate that important antimicrobial resistance exists among isolates of staphylococci, streptococci, and enterococci from all three geographic regions. This includes oxacillin-resistance among S. aureus (26.9% U.S., 29.2% Latin America, and 4.0% Canada) and CoNS (71.5% U.S., 68.4% Latin America, and 65.6% Canada), penicillin resistance among viridans group streptococci (48.5% U.S., 45.1% Canada, and 33.3% Latin America) and pneumococci (36.1% U.S., 27.5% Canada, and 65.6% Latin America), high-level resistance (HLR) to aminoglycosides among enterococci (27.2 to 70.1% U.S., 33.3 to 75.7% Canada and 16.7 to 51.5% Latin America), and macrolide resistance among beta-hemolytic streptococci (12.4 to 14.2% U.S., 10.5 to 12.3% Canada, and 0.0 to 4.0% Latin America), viridans group streptococci (32.4 to 39.7% U.S., 22.5-35.2% Canada, and 20.0% Latin America), and pneumococci (10.0 to 10.6% U.S., 9.8-10.8% Canada, and 9.4-18.7% Latin America). BSI isolates of Gram-positive cocci from the U.S. and Latin America were considerably more resistant than those from Canada. New agents with Gram-positive activity will be essential for optimal treatment of BSI attributable to Gram-positive cocci in both North and Latin America.

Anti-Bacterial Agents↗

A comparison of delays in the treatment of cancer with radiation in Canada and the United States.

PURPOSE: Waiting lists for medical care in Canada have been used as an argument against the single-payer option for health care reform in the United States, but there have been no direct comparisons of access to care in these two health care systems. The objective of this study was to compare how long cancer patients wait for radiotherapy in Canada and the USA. METHODS AND MATERIALS: Heads of radiation oncology at all cancer centers listed by the International Union Against Cancer (UICC) in Canada and the United States were sent a questionnaire that asked how long their patients waited for radiotherapy, and how long they though it was acceptable for patients to wait, in six clinical situations. RESULTS: Ninety-two of 97 eligible centers responded (95%). Median waiting times to start of radiotherapy were as follows: carcinoma of the larynx (T2,N0,M0), 29 days in Canada, 10 days in the USA; carcinoma of the lung (Stage IIIb, squamous), 34 days in Canada, 9 days in the USA; carcinoma of the prostate (Stage B2), 40 days in Canada, 11 days in the USA; carcinoma of the breast (T2,N0,M0) referred 1 month after lumpectomy, 43 days in Canada, 10 days in the USA; carcinoma of the prostate with painful bone metastases, 17 days in Canada, 5 days in the USA; carcinoma of the prostate with spinal cord compression, < 1 day in Canada, < 1 day in the USA. The differences in waiting times between Canada and the USA were all statistically significant (p < 0.0001), except in the case of emergency treatment for cord compression. The majority of radiation oncologists in both Canada and the USA regarded the delays reported by Canadian departments as medically unacceptable. CONCLUSIONS: Patients almost everywhere in Canada wait longer for radiotherapy than they do almost anywhere in the United States.

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Factors influencing the emigration of physicians from Canada to the United States.

OBJECTIVE: To determine whether location of postgraduate medical training and other factors are associated with the emigration of physicians from Canada to the United States. DESIGN: Case-control study, physicians were surveyed with the use of a questionnaire mailed in May 1994 (with a reminder sent in September 1994), responses to which were accepted until Dec. 31, 1994. PARTICIPANTS: Physicians randomly selected from the CMA database, 4000 with addresses in Canada and 4000 with current addresses in the United States and previous addresses in Canada. OUTCOME MEASURES: Sex, age, location of undergraduate and postgraduate medical training, qualifications, practice location, opinions concerning residence decisions, current satisfaction and plans. RESULTS: The overall response rate was 49.6% (50.0% among physicians in the United States and 49.2% among those in Canada). Age and sex distributions were similar among the 8000 questionnaire recipients and the nearly 4000 respondents. Physicians living in the United States were more likely to be older (mean 53.2 v. 49.6 years of age), male (87% v. 75%) and specialists (79% v. 52%) than those practising in Canada. Postgraduate training in the United States was associated with subsequent emigration (odds ratio 9.2, 95% confidence interval 7.8 to 10.7). However, in rating the importance of nine factors in the decision to emigrate or remain in Canada, there was no significant difference between the two groups in the rating assigned to location of postgraduate training. Professional factors rated most important by most physicians in both groups were professional/clinical autonomy, availability of medical facilities and job availability. Remuneration was considered an equally important factor by those in Canada and in the United States. Six of seven personal/family factors were rated as more important to their choice of practice location by respondents in Canada than by those in the United States. Current satisfaction was significantly higher among respondents in the United States. Most physicians in each group planned to continue practising at their current location. Of Canadian respondents, 22% indicated that they were more likely to move to the United States than they were a year beforehand, whereas 4% of US respondents indicated that they were more likely to return to Canada. CONCLUSIONS: Factors affecting the decision to move to the United States or remain in Canada can be categorized as "push" factors (e.g., government involvement) and "pull" factors (e.g., better geographic climate in the US). Factors can also be categorized by whether they are amenable to change (e.g., availability of medical facilities) or cannot be managed (e.g., proximity of relatives). An understanding of the reasons why physicians immigrate to the United States or remain in Canada is essential to planning physician resources nationally.

Adult↗

Field evaluation of lead effects on Canada geese and mallards in the Coeur d'Alene River Basin, Idaho.

Hatch year (HY) mallards (Anas platyrhynchos) in the Coeur d'Alene (CDA) River Basin had higher concentrations of lead in their blood than HY Western Canada geese (Branta canadensis moffitti) (geometric means 0.98 versus 0.28 microg/g, wet weight). The pattern for adults of both species was similar, although geometric means (1.77 versus 0. 41 microg/g) were higher than in HY birds. HY mallards captured in the CDA River Basin in 1987 contained significantly lower lead concentrations in their blood than in 1994-95 (0.36 versus 0.98 microg/g); however, some very young mallards were sampled in 1987, and concentrations in adults were not significantly different in 1987, 1994, or 1995 (1.52, 2.07, 1.55 microg/g, respectively). Both species in the CDA River Basin in 1994-95 showed significantly reduced red blood cell delta-aminolevulinic acid dehydratase (ALAD) activity compared to the reference areas: Canada geese (HY -65.4 to -86.0%, adults -82.3%), and mallards (HY -90.7 to -95.5%, adults -94. 1%). Canada goose goslings were divided into size classes, and the two smaller classes from the CDA River Basin had significantly elevated free erythrocyte protoporphyrin (protoporphyrin) levels compared to the reference area (15.2x and 6.9x). HY and adult mallards both had significantly elevated protoporphyrin (5.9x and 7. 5x). Recognizing that interspecific differences exist in response and sensitivity to lead, it appears (at least for hemoglobin and hematocrit) that Canada geese were more sensitive to lead than mallards, i.e., adverse hematologic effects occur at lower blood lead concentrations. Only Canada geese from the CDA River Basin, in spite of lower blood lead concentrations, had significantly reduced mean hemoglobin and hematocrit values. No euthanized Canada geese (all HYs) from CDA River Basin were classified as clinically lead poisoned, but 38 Canada geese found dead in the CDA River Basin during a concurrent study succumbed to lead poisoning between 1992 and 1997. Only 6 (15.8%) of these 38 contained ingested lead shot, which contrasts greatly with the 75-94% incidence of ingested lead shot when mortality was due to lead shot ingestion. Lead from other contaminated sources (i.e., sediments and vegetation) in the CDA River Basin was strongly implicated in most Canada goose deaths. Based on the 31 live mallards and Canada geese collected in the CDA River Basin, which were representative of the live populations blood sampled only, the prevalence of subclinical and clinical lead poisoning (as determined by liver lead concentrations, excluding birds with ingested lead shot) was higher in mallards: subclinical (4 of 8, 50% HYs and 6 of 11, 55% adults); clinical (0% HYs and 4 of 11, 36% adults), with less data available for Canada geese (only 1 of 9, 11% HYs marginally subclinical). The clinically lead-poisoned mallards had extremely high concentrations of lead in blood (2.69-8. 82 microg/g) and liver (6.39-17.89 microg/g). Eight mallards found dead in the CDA River Basin during a concurrent study were diagnosed as lead poisoned, and only one (12.5%) contained ingested lead shot, which again strongly implicates other lead sources. The finding of dead lead poisoned Canada geese together with the high percentage of live mallards classified as subclinically or clinically lead poisoned, in combination with the low incidence of ingested lead shot causes us concern for both of these species, which live in association with lead-contaminated sediment in the CDA River Basin.

Animals↗