Monitoring vaccine safety is a complex and shared responsibility. It can be carried out in many ways, one of which is the reporting of individual cases of adverse reactions thought to be due to vaccination. The task is difficult because ascribing causality to an individual case report is fraught with challenges. A standardized evaluation instrument--known as the causality assessment form--was therefore developed for use by an expert advisory committee to facilitate the process. By following the several sections in this form, the members of the committee are taken through a series of points to establish causality. These points include the basic criteria for causation such as biological plausibility, the time elapsed between the vaccine administration and the onset of the adverse event, and whether other factors (drugs, chemicals or underlying disease) could account for the adverse symptoms. The form concludes with a consensus assessment of causality, a commentary about the assessment, and advice for further study or follow-up. This method of assessing the more serious cases of adverse reaction reported to vaccination has proven useful in evaluating ongoing safety of vaccines in Canada. Through analyses such as this, new signals can be identified and investigated further.

Adverse Drug Reaction Reporting Systems↗

PubMed1999

Risk factors for resistance to "first-line" antimicrobials among urinary tract isolates of Escherichia coli in children.

BACKGROUND: There are increasing concerns regarding antimicrobial resistance in Canada. Data are limited on the prevalence, patterns of resistance and risk factors associated with resistant organisms, including coliforms, in children. This study was done to address these issues as they relate to urinary tract isolates of Escherichia coli in a tertiary care pediatric centre in Ottawa. METHODS: A surveillance study was conducted from December 1992 to December 1994. Susceptibility testing of urinary tract isolates of E. coli was performed using a panel of antimicrobial agents. A case-control study was also conducted for subjects with isolates resistant to trimethoprim-sulfamethoxazole (T-S), this drug being used a representative "first-line" agent. RESULTS: A total of 1636 consecutive isolates were obtained from 967 subjects. Of the 1636 isolates, 736 (45.0%) were resistant to ampicillin, 514 (31.4%) were resistant to T-S, 363 (22.2%) were resistant to both ampicillin and T-S, and 27 (1.7%) were resistant to both ampicillin and gentamicin. In the case-control study 274 children with isolates resistant to T-S were matched with 274 children who had T-S-sensitive isolates obtained during the study period or the preceding or subsequent 6 months. Multivariate analyses indicated that subjects who had received antimicrobials for more than 4 weeks in the previous 6 months were about 23 times more likely to have isolates resistant to T-S than were subjects without this risk factor (odds ratio [OR] 23.4, 95% confidence interval [CI] 12.0-47.6). Children with genitourinary tract abnormalities were 2.4 times more likely to have resistant isolates than those without such abnormalities (95% CI 1.2-4.5). Compared with children who had no hospital admissions in the previous year, those with 1 admission in that period were more likely to have resistant isolates (OR 2.3, 95% CI 1.4-7.5), as were those with 2 or more admissions in that period (OR 3.2, 95% CI 1.1-4.8). Compared with children aged 2-6 years, children under 2 years of age were less likely to have resistant isolates (OR 0.3, 95% CI 0.2-0.8). INTERPRETATION: Selective antimicrobial pressure and multiple admissions to hospital were among the risk factors associated with antimicrobial resistance. The finding of a low but definite level of resistance to both ampicillin and gentamicin is important for the selection of empiric therapy for sepsis in neonates. The role of inexpensive first-line agents in the outpatient treatment and prevention of urinary tract infections requires re-examination, particularly in children who have recently received antimicrobial therapy.

Anti-Bacterial Agents↗

PubMed1999

Screening for ovarian cancer: a pilot randomised controlled trial.

BACKGROUND: The value of screening for ovarian cancer is uncertain. We did a pilot randomised trial to assess multimodal screening with sequential CA 125 antigen and ultrasonography. METHODS: Postmenopausal women aged 45 years or older were randomised to a control group (n=10,977) or screened group (n=10,958). Women randomised to screening were offered three annual screens that involved measurement of serum CA 125, pelvic ultrasonography if CA 125 was 30 U/mL or more, and referral for gynaecological opinion if ovarian volume was 8.8 mL or more on ultrasonography. All women were followed up to see whether they developed invasive epithelial cancers of the ovary or fallopian tube (index cancers). FINDINGS: Of 468 women in the screened group with a raised CA 125, 29 were referred for a gynaecological opinion; screening detected an index cancer in six and 23 had false-positive screening results. The positive predictive value was 20.7%. During 7-year follow-up, ten further women with index cancers were identified in the screened group and 20 in the control group. Median survival of women with index cancers in the screened group was 72.9 months and in the control group was 41.8 months (p=0.0112). The number of deaths from an index cancer did not differ significantly between the control and screened groups (18 of 10,977 vs nine of 10,958, relative risk 2.0 [95% CI 0.78-5.13]). INTERPRETATION: These results show that a multimodal approach to ovarian cancer screening in a randomised trial is feasible and justify a larger randomised trial to see whether screening affects mortality.

CA-125 Antigen↗

PubMed1999

Increased mortality in postmenopausal women with serum CA125 elevation.

OBJECTIVES: Serum CA125 is used in monitoring treatment and detecting recurrence in ovarian cancer (OC). We have also shown that CA125 can be used with ultrasound for the early detection of OC. However, physiological, benign, and malignant conditions are also associated with CA125 elevation. The aim of the study was to determine the prognostic implications of CA125 elevation in asymptomatic postmenopausal women. METHODS: The study involved 771 volunteers in an OC screening trial of 22,000 women who had elevated serum CA125 levels (>/=30 U/ml). The control group consisted of an equal number of volunteers with normal levels. Survival was analyzed from the first point of CA125 elevation. Univariate analyses utilized the log-rank chi2 test. A logistic model was constructed for the multivariate analyses. RESULTS: The mean duration of follow-up was 1614 days (SD 897 days). Eighty-four women died (elevated CA125 group-62, control group-22). Univariate analyses showed that mortality in the elevated CA125 group was significantly greater (log-rank chi2 = 23.556, P < 0.0001, RR = 2.76), even when preexisting morbid conditions were excluded (log-rank chi2 = 14.644, P = 0.0001, RR = 2.4). Multivariate analysis showed that CA125 elevation, age (>60 years), and a prior history of cancer were associated with a poor prognosis. CONCLUSIONS: Serum CA125 elevation is associated with a significantly increased risk of death from all causes in the next 5 years. These findings may have implications for asymptomatic postmenopausal women with CA125 elevation.

CA-125 Antigen↗

PubMed1999

Palliative care education: a global imperative.

Explore the source record for details and available documents.

Curriculum↗

PubMed1999

A comparison of national cancer registry and direct follow-up in the ascertainment of ovarian cancer.

The National Health Service Central Register (NHSCR) and direct follow-up were used to document ovarian and fallopian tube cancers in 22000 women from 1986 to 1993. Direct follow-up identified 47/49 cases (96%) and the NHSCR 38/49 (78%). NHSCR ascertainment was incomplete and direct follow-up provided additional information. These findings have implications for interpretation of national cancer statistics and for use of the NHSCR in research trials.

Cohort Studies↗

PubMed1999

Epidemiological features of pertussis in hospitalized patients in Canada, 1991-1997: report of the Immunization Monitoring Program--Active (IMPACT).

To assess the morbidity associated with the continued high levels of pertussis, we studied all children <2 years of age who were admitted to the 11 Immunization Monitoring Program--Active (IMPACT) centers, which constitute 85% of Canada's tertiary care pediatric beds. In the 7 years preceding implementation of acellular pertussis vaccine, a total of 1,082 pertussis cases were reported, of which 49.1% were culture-confirmed. The median age of the patients was 12.4 weeks; 78.9% of cases were in children <6 months of age. Complications of pertussis were common: pneumonia was reported in 9.4% of cases, new seizures in 2.3%, and encephalopathy in 0.5%. There were 10 deaths (0.9%), all in children < or =6 months of age. Duration of hospitalization was longer (9.3 days vs. 4.9 days; P = .001) and intensive care was required more frequently (19.2% vs. 4.9%; P = .001) in infants under <6 months of age than in those > or =6 months. Pertussis continues to cause significant morbidity and occasional mortality in Canada, particularly in young infants.

Canada↗

PubMed1999

Cost of chickenpox in Canada: part I. Cost of uncomplicated cases.

OBJECTIVE: The purpose of this study was to assess the direct medical costs and productivity losses associated with uncomplicated chickenpox (no hospitalization) in Canada. METHODS: A total of 179 otherwise healthy 1- to 9-year-old children with active chickenpox were recruited from schools, day care centers, and physician offices in 5 provinces. Direct medical (physician contacts, medication, and diagnostic tests) and nonmedical (personal expenses including child care) resources expended during the illness were determined by caregiver interview. Productivity losses attributable to the disease were determined by assessing caregiver time lost from work and daily activities. Unit costs for all resources were obtained from sources in 2 provinces, and per-patient treatment costs were determined from the patient, Ministry of Health, and societal perspectives. RESULTS: From a societal perspective, the per-case cost for children from 1 to 4 years of age and from 5 to 9 years of age was $370.2 and $236.5, respectively. Direct medical costs accounted for 10% of the total costs in both groups. The largest cost driver in patient care was caregiver productivity losses, which amounted to $316.5 in the younger age group and to $182.7 in the older age group. Based on an estimated yearly incidence of 344 656 cases of uncomplicated chickenpox in Canada, the total annual societal burden of the disease can be estimated at $109.2 million, with a cost to the Ministry of Health of $11.2 million. CONCLUSION: Chickenpox is one of the last common childhood diseases prevalent in Canada, and the uncomplicated disease, despite its rather benign course, imparts a large annual economic burden.

Canada↗

PubMed1999

Alopecia areata: identification and current treatment approaches.

Alopecia areata is a disease which occurs in 1.7% of the population (Safavi et al., 1995), often with devastating effects to patients and their families. In the past, this condition has been misunderstood and treated inadequately. New treatment modalities and support systems are offering hope to patients with alopecia areata.

Algorithms↗

PubMed1998

Bioethics for clinicians: 15. Quality end-of-life care.

A physician who receives a call from the emergency department to see a patient with heart failure will have a clear framework within which to approach this problem. The thesis of this article is that physicians do not have an analogous conceptual framework for approaching end-of-life care. The authors present and describe a framework for end-of-life care with 3 main elements: control of pain and other symptoms, the use of life-sustaining treatments and support of those who are dying and their families. This 3-part framework can be used by clinicians at the bedside to focus their effort in improving the quality of end-of-life care.

Advance Care Planning↗

PubMed1998

A march of folly.

Explore the source record for details and available documents.

Biomedical Research↗

PubMed1998

Palliative care--an essential component of cancer control.

Unlike in other nations, in Canada palliative care has its origins in university hospitals. It has subsequently developed in a few Canadian schools as an academic discipline closely linked with oncology programs. Although this model is successful, other faculties of medicine and cancer centres have been slow to emulate it. Today, the situation is rapidly changing, and both palliative care and oncology professionals are re-examining the manifest need for collaborative efforts in patient care, research and education. Palliative care must be regarded as an essential component of cancer care, its principles must be applied throughout the course of the illness and, as in other phases of cancer control, palliative care should be regarded as an exercise in prevention--prevention of suffering. This article discusses practical applications that flow from acceptance of these concepts.

Canada↗

PubMed1998

Transient renal failure due to simultaneous ibuprofen and aminoglycoside therapy in children with cystic fibrosis.

Explore the source record for details and available documents.

Adolescent↗

PubMed1998

Acute-phase neurologic complications of Haemophilus influenzae type b meningitis: association with developmental problems at school age.

The purposes of this study were to describe the incidence of acute-phase neurologic complications in a sample of 126 children with Haemophilus influenzae type b meningitis, and to determine if these complications were associated with higher rates of learning and behavior problems at school age. Risks were assessed by comparing rates of adverse psychoeducational outcomes in the 53 children in the sample with complications to corresponding outcome rates in the 67 children who were free of neurologic complications and who did not have abnormal electroencephalograms (EEGs) or computed tomographic (CT) scans. Comparisons were made by means of logistic regression analysis. Twenty-nine children (23% of the sample) had seizures, 16 (13%) were comatose or obtunded, 15 (12%) had sensorineural hearing loss, 8 (6%) had hemiparesis, and 7 (6%) had cranial nerve deficits other than hearing loss. Relative to children without complications, those with complications had higher rates of grade repetition and substandard performance on neuropsychological and achievement testing. Adverse outcomes, however, consisted primarily of more subtle cognitive and learning problems; only two of the children in the sample obtained prorated IQ scores below 70. Sequelae were associated with persistent neurologic deficits and bilateral hearing loss, as well as with transient symptoms including seizures, coma, and hemiparesis. While study findings argue against adverse consequences for the vast majority of children treated for this disease, the results clarify learning and behavior outcomes and indicate which children are at greatest risk.

Adolescent↗