Cost-effectiveness analysis when the WTA is greater than the WTP.

The incremental cost effectiveness ratio has long been the standard parameter of interest in the assessment of the cost-effectiveness of a new treatment. However, due to concerns with interpretability and statistical inference, authors have suggested using the willingness-to-pay for a unit of health benefit to define the incremental net benefit as an alternative. The incremental net benefit has a more consistent interpretation and is amenable to routine statistical procedures. These procedures rely on the fact that the willingness-to-accept compensation for a loss of a unit of health benefit (at some cost saving) is the same as the willingness-to-pay for it. Theoretical and empirical evidence suggest, however, that in health care the willingness-to-accept is about twice as much as the willingness-to-pay. We use Bayesian methods to provide a statistical procedure for the cost-effectiveness comparison of two arms of a randomized clinical trial that allows the willingness-to-pay and the willingness-to-accept to have different values. An example is provided.

Analysis, sample size, and power for estimating incremental net health benefit from clinical trial data.

Stinnett and Mullahy recently introduced the concept of net health benefit as an alternative to cost-effectiveness ratios for the statistical analysis of patient-level data on the costs and health effects of competing interventions. Net health benefit addresses a number of problems associated with cost-effectiveness ratios by assuming a value for the willingness-to-pay for a unit of effectiveness. We extend the concept of net health benefit to demonstrate that standard statistical procedures can be used for the analysis, power, and sample size determinations of cost-effectiveness data. We also show that by varying the value of the willingness-to-pay, the point estimate and confidence interval for the incremental cost-effectiveness ratio can be determined. An example is provided.

Incremental net benefit in randomized clinical trials.

There are three approaches to health economic evaluation for comparing two therapies. These are (i) cost minimization, in which one assumes or observes no difference in effectiveness, (ii) incremental cost-effectiveness, and (iii) incremental net benefit. The latter can be expressed either in units of effectiveness or costs. When analysing data from a clinical trial, expressing incremental net benefit in units of cost allows the investigator to examine all three approaches in a single graph, complete with the corresponding statistical inferences. Furthermore, if costs and effectiveness are not censored, this can be achieved using common two-sample statistical procedures. The above will be illustrated using two examples, one with censoring and one without.

Cancer care workers in Ontario: prevalence of burnout, job stress and job satisfaction.

BACKGROUND: Cancer Care Ontario's Systemic Therapy Task Force recently reviewed the medical oncology system in the province. There has been growing concern about anecdotal reports of burnout, high levels of stress and staff leaving or decreasing their work hours. However, no research has systematically determined whether there is evidence to support or refute these reports. To this end, a confidential survey was undertaken. METHODS: A questionnaire was mailed to all 1016 personnel of the major providers of medical oncology services in Ontario. The questionnaire consisted of the Maslach Burnout Inventory, the 12-item General Health Questionnaire, a questionnaire to determine job satisfaction and stress, and questions to obtain demographic characteristics and to measure the staff's consideration of alternative work situations. RESULTS: The overall response rate was 70.9% (681 of 961 eligible subjects): by group it was 63.3% (131/207) for physicians, 80.9% (314/388) for allied health professionals and 64.5% (236/366) for support staff. The prevalence of emotional exhaustion were significantly higher among the physicians (53.3%) than among the allied health professionals (37.1%) and the support staff (30.5%) (p < or = 0.003); the same was true for feelings of depersonalization (22.1% v. 4.3% and 5.5% respectively) (p < or = 0.003). Feelings of low personal accomplishment were significantly higher among physicians (48.4%) and allied health professionals (54.0%) than among support staff (31.4%) (p < or = 0.002). About one-third of the respondents in each group reported that they have considered leaving for a job outside the cancer care system. Significantly more physicians (42.6%) than allied health professionals (7.6%) or support staff (4.5%) stated that they have considered leaving for a job outside the province. INTERPRETATION: The findings support the concern that medical oncology personnel are experiencing burnout and high levels of stress and that large numbers are considering leaving or decreasing their work hours. This is an important finding for the cancer care system, where highly trained and experienced health care workers are already in short supply.

Effect of smoking cessation on mortality after myocardial infarction: meta-analysis of cohort studies.

OBJECTIVE: To determine the effect of smoking cessation on mortality after myocardial infarction. DATA SOURCES: English- and non-English-language articles published from 1966 through 1996 retrieved using keyword searches of MEDLINE and EMBASE supplemented by letters to authors and searching bibliographies of reviews. STUDY SELECTION: Selection of relevant abstracts and articles was performed by 2 independent reviewers. Articles were chosen that reported the results of cohort studies examining mortality in patients who quit vs continued smoking after myocardial infarction. DATA EXTRACTION: Mortality data were extracted from the selected articles by 2 independent reviewers. DATA SYNTHESIS: Twelve studies were included containing data on 5878 patients. The studies took place in 6 countries between 1949 and 1988. Duration of follow-up ranged from 2 to 10 years. All studies showed a mortality benefit associated with smoking cessation. The combined odds ratio based on a random effects model for death after myocardial infarction in those who quit smoking was 0.54 (95% confidence interval, 0.46-0.62). Relative risk reductions across studies ranged from 15% to 61%. The number needed to quit smoking to save 1 life is 13 assuming a mortality rate of 20% in continuing smokers. The mortality benefit was consistent regardless of sex, duration of follow-up, study site, and time period. CONCLUSION: Results of several cohort studies suggest that smoking cessation after myocardial infarction is associated with a significant decrease in mortality.

Will the use of low-molecular-weight heparin (enoxaparin) in patients with acute coronary syndrome save costs in Canada?

BACKGROUND: One-year follow-up data from the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) trial show that use of low-molecular-weight heparin (enoxaparin) compared with unfractionated heparin in patients hospitalized with unstable angina or non-Q-wave myocardial infarction is associated with a 10% reduction in the cumulative 1-year risk of death, myocardial infarction, or recurrent angina. Given the higher acquisition cost of enoxaparin relative to unfractionated heparin, we assessed whether the reduced use of revascularization procedures and related care makes enoxaparin a cost-saving therapy in Canada. METHODS AND RESULTS: We analyzed cumulative 1-year resource use data on the 1259 ESSENCE patients enrolled in Canadian centers (40% of the total ESSENCE sample). Patient-specific data on use of drugs, diagnostic cardiac catheterization, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, and hospital days were available from the initial hospital stay and cumulative to 1 year. Hospital resources were costed with the use of data from a teaching hospital in southern Ontario that is a participant in the Ontario Case Costing Project. During the initial hospital stay, use of enoxaparin was associated with reduced use of diagnostic catheterization and revascularization procedures, with the largest effect being reduced use of percutaneous transluminal coronary angioplasty (15.0% vs 10.6%; P =.03). At 1 year, the reduced risk and costs of revascularization more than offset increased drug costs for enoxaparin, producing a cost-saving per patient of $1485 (95% confidence interval $-93 to $3167; P =.06). Sensitivity analysis with lower hospital per diem costs from a community hospital in Ontario still predicts cost savings of $1075 per patient over a period of 1 year. CONCLUSIONS: The acquisition and administration cost of enoxaparin is higher than for unfractionated heparin ($101 vs $39), but in patients with acute coronary syndrome, the reduced need for hospitalization and revascularization over a period of 1 year more than offsets this initial difference in cost. Evidence from this Canadian substudy of ESSENCE supports the view that enoxaparin is less costly and more effective than unfractionated heparin in this indication.

Treatment outcomes for squamous intraepithelial lesions.

OBJECTIVE: To assess the effectiveness of cone biopsy, cryotherapy, laser ablation and the loop electrosurgical procedure in the treatment of squamous intraepithelial lesions. METHOD: Systematic review of randomized controlled trials in subjects who underwent treatment of low- and high-grade squamous intraepithelial lesions with these modalities. Main outcome measures included the following: percent resolution and persistence of a lesion and notable complications for each procedure. RESULT: Pooled rates of resolution for low-grade, high-grade, or combined squamous intraepithelial lesions were similar across the different treatment modalities (range 85.2-94.7%), with substantial overlap among the 95% confidence intervals. Significant hemorrhage occurred most frequently in subjects who received cone biopsy (4.6%) (95% CI: 2.15, 6.99), followed by laser ablation (1.75%) (95% CI: 0.70, 2.81), and LEEP (1.35%) (95% CI: 0.24, 2.47). No hemorrhages were reported among subjects who received cryotherapy. Study sample sizes were relatively small. There were no reported cases of progression to invasive cancer, but duration of follow-up (median follow-up time for all eligible studies = 12 months) was not sufficient to evaluate long-term outcomes. CONCLUSIONS: There were no substantive differences in outcomes regarding persistence and resolution in the treatment of squamous intraepithelial lesions for subjects receiving cone biopsy, cryotherapy, laser ablation, or LEEP.

Mastectomy or lumpectomy? Helping women make informed choices.

PURPOSE: To develop an instrument to help clinicians inform their patients about surgical treatment options for the treatment of breast cancer and to evaluate the impact of the instrument on the clinical encounter. METHODS: We developed an instrument, called the Decision Board, to present information regarding the benefits and risks of breast-conserving therapy (lumpectomy plus radiation therapy) and mastectomy to women with early-stage breast cancer to enable them to express a preference for the type of surgery. Seven surgeons from different communities in Ontario administered the instrument to women with newly diagnosed clinical stage I or II breast cancer over an 18-month period. Patients and surgeons were interviewed regarding acceptability of the instrument. The rates of breast-conserving surgery performed by surgeons before and after the introduction of the instrument were compared. RESULTS: The Decision Board was administered to 175 patients; 98% reported that the Decision Board was easy to understand, and 81% indicated that it helped them make a decision. The average score on a true/false test of comprehension was 11.8 of 14 (84%) (range, 6 to 14). Surgeons found the Decision Board to be helpful in presenting information to patients in 91% of consultations. The rate of breast-conserving surgery decreased when the Decision Board was introduced (88% v 73%, P =.001) CONCLUSION: The Decision Board is a simple method to improve communication and facilitate shared decision making. It was well accepted by patients and surgeons and easily applied in the community.

Sample size and power issues in estimating incremental cost-effectiveness ratios from clinical trials data.

It is becoming increasingly more common for a randomized controlled trial of a new therapy to include a prospective economic evaluation. The advantage of such trial-based cost-effectiveness is that conventional principles of statistical inference can be used to quantify uncertainty in the estimate of the incremental cost-effectiveness ratio (ICER). Numerous articles in the recent literature have outlined and compared various approaches for determining confidence intervals for the ICER. In this paper we address the issue of power and sample size in trial-based cost-effectiveness analysis. Our approach is to determine the required sample size to ensure that the resulting confidence interval is narrow enough to distinguish between two regions in the cost-effectiveness plane: one in which the new therapy is considered to be cost-effective and one in which it is not. As a result, for a given sample size, the cost-effectiveness plane is divided into two regions, separated by an ellipse centred at the origin, such that the sample size is adequate only if the truth lies on or outside the ellipse.

Health care professionals' familiarity with non-pharmacological strategies for managing cancer pain.

Many studies have confirmed unnecessary suffering among cancer patients, due to the inadequate use of analgesic medication and other effective interventions. While pharmacological treatments are appropriately the central component of cancer pain management, the under-utilization of effective nonpharmacological strategies (NPS) may contribute to the problem of pain and suffering among cancer patients. The purpose of this study was to determine health care professionals' familiarity with, and perceptions regarding, NPS for managing cancer pain, and to assess their interest in learning more about NPS as adjuncts to pharmacological analgesics. Two-hundred and fourteen health care professionals were surveyed at two cancer treatment centres in Ontario, Canada. The self-report questionnaire included questions regarding 11 psychological strategies (e.g. imagery) and eight other NPS (e.g. acupuncture). The response rate was 67% (141/214). Subjects were found to be the least familiar with autogenic training, operant conditioning, and cognitive therapy. Other than radiation and surgery, subjects most commonly reported recommending support groups (67%), imagery (54%), music or art therapy (49%) and meditation (43%) for managing cancer pain. Participants were most interested in learning more about acupuncture, massage therapy, therapeutic touch, hypnosis, and biofeedback. Participants were somewhat familiar with most of the 19 NPS presented; however, they use or recommend few NPS for managing cancer pain. Health professionals' interest in NPS has important implications for the supportive care of cancer patients.

Natural history of cervical squamous intraepithelial lesions: a meta-analysis.

OBJECTIVE: To define the strengths and weaknesses of existing research on the natural history of cervical squamous intraepithelial lesions (SIL) and to estimate rates of progression and regression without treatment. DATA SOURCES: Studies of women whose cervical smears showed squamous atypia or worse and who were observed for a minimum of 6 months were identified by a search of MEDLINE from 1966 to 1996, Current Contents, the Federal Research in Progress database, and references of review articles and identified studies, and by experts in the field. METHODS OF STUDY SELECTION: Fifteen of 81 studies were eligible for data extraction. To be eligible, studies had to report a minimum of 6 months' follow-up without treatment; relate entry cytologic findings to outcomes; and report entry cytologic findings so that the study population could be stratified into categories of atypical cells of undetermined significance (ASCUS), low-grade SIL, or high-grade SIL. Studies published before 1970 were excluded. TABULATION, INTEGRATION, AND RESULTS: Eligible studies, representing 27,929 patients, were stratified according to entry cytologic findings. The following rates of progression to high-grade SIL at 24 months were found: ASCUS, 7.13% (95% confidence interval [CI] 0.8%, 13.5%); low-grade SIL, 20.81% (6.08%, 35.55%); and high-grade SIL, 23.37% (12.82%, 32.92%). The following rates of invasive cancer at 24 months were found: ASCUS, 0.25% (0%, 2.25%); low-grade SIL, 0.15% (0%, 0.71%); and high-grade SIL, 1.44% (0%, 3.95%). The following rates of regression to normal were found: ASCUS, 68.19% (57.51%, 78.86%); low-grade SIL, 47.39% (35.92%, 58.86%); and high-grade SIL, 35.03% (16.57%, 53.49%). Study heterogeneity was not explained by regression analysis of study level variables. CONCLUSION: Our findings for borderline and low-grade abnormal cervical cytologic results suggest a relatively low risk of invasive cervical cancer with observation up to 24 months and support the clinical policy of early colposcopy for high-grade lesions.

Evaluation of a patient file folder to improve the dissemination of written information materials for cancer patients.

BACKGROUND: Many cancer centers make available to patients written information material to supplement verbal information provided by clinicians. Randomized trials have demonstrated that providing such information can increase patient knowledge and satisfaction. However, little data are available regarding effective means of dissemination of such materials. The purpose of this study was to determine whether providing patients with a personal file folder after their first clinic appointment would improve the dissemination of written information materials and increase patient satisfaction. METHODS: A before/after study was performed. Consecutive patients with newly diagnosed cancer attending the Hamilton Regional Cancer Centre were selected randomly and interviewed by telephone within 1-2 weeks of the first clinic appointment regarding the number of information pamphlets received, patient satisfaction, and general preference for written information materials. The preintervention evaluation (T1) occurred over a 4-month period followed by the introduction of the personal file folder into the clinical practice. Six weeks after its introduction, the postintervention (T2) evaluation took place over the ensuing 4 months. RESULTS: A total of 300 patients completed the evaluation (150 each in T1 and T2). Responding patients in the two time periods were comparable with respect to background demographic variables. The mean number of information pamphlets received by patients increased with the introduction of the personal file folder from 2.4+/-2.0 standard deviations (SD) in T1 to 3.6+/-2.5 SD in T2 (P=0.0001). The percentage of patients planned for treatment who received treatment-related information increased from 36% (42 of 116 patients) in T1 to 65% (68 of 105 patients) in T2 (P=0.002). Mean patient satisfaction increased from 3.3+/-1.1 SD to 3.8+/-1.0 SD over the 2 time periods (P=0.0001). The majority of patients (87%) believed it was important to receive written information materials. CONCLUSIONS: The patient file folder increased the dissemination of written information materials and currently is being incorporated into routine practice.

Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.

PURPOSE: To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. PATIENTS AND METHODS: The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. RESULTS: The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). CONCLUSION: A treatment that reduces symptoms and improves quality of life has the potential to reduce costs in other areas. Economic factors should not influence the clinical decision as to whether to use M + P in a symptomatic patient.

Impact of age and cranial irradiation on radiographic skeletal pathology in children with acute lymphoblastic leukemia.

BACKGROUND: Symptomatic osteopenia is a common form of morbidity in children with acute lymphoblastic leukemia (ALL) before, during, and after treatment. A causal role for corticosteroids has been proposed, but other investigators have suggested that cranial irradiation is an important factor contributing to this disorder. PROCEDURE: In this study of children with ALL, all of whom received steroids, skeletal morbidity was assessed radiographically by an observer who was blinded to the ages of the children, their risk categorization (and related treatment), and the timing of the assessments with respect to the administration of therapy. DISCUSSION: Skeletal morbidity was most prevalent in older subjects who had been given cranial radiotherapy. However, there was no difference in the frequency of fractures in two groups of younger children (< or = 9 years of age), one irradiated and the other not. CONCLUSIONS: It is likely that corticosteroid therapy plays an important part in the pathogenesis of this disorder. The role played by cranial irradiation is much less certain.

The supportive care needs of newly diagnosed cancer patients attending a regional cancer center.

BACKGROUND: The objective of this study was to examine the physical and emotional health status, self-perceived problems, and needs of newly diagnosed cancer patients to determine and plan supportive care strategies. METHODS: A cross-sectional survey of newly diagnosed cancer patients attending a regional cancer center during a 6-month period was performed. Patients with breast, colorectal, head and neck, lung, and prostate carcinoma as well as nonmelanoma of the skin were selected randomly. Patients were interviewed prior to their first appointment at the clinic. Physical health status was assessed using the Symptom Distress Scale, psychologic health status was assessed with the General Health Questionnaire (GHQ), day-to-day functioning with the Rapid Disability Scale, and social support with the modified Sarason's Social Support Scale. Perceived needs were assessed in a number of ways, including identification of patients' specific social concerns and informational needs, and by asking them to list their current problems or concerns. RESULTS: Of 156 eligible patients, 134 completed the interview. One hundred and twenty-nine patients (96%) reported current symptoms that included fatigue (66%), worried outlook (61%), difficulty sleeping (48%), and pain (42%). Forty-four patients (33%) were identified as psychologically distressed with a GHQ score of > or = 6. One hundred and fourteen patients (85%) had informational needs, 89 (66%) indicated > or = 1 social concerns, and 55 (41%) reported a need for assistance with day-to-day living. CONCLUSIONS: Patients with newly diagnosed cancer commonly report symptoms related to fatigue, pain, and psychologic distress. Other frequently reported issues relate to the need for information and social concerns regarding the patients' ability to take care of their home and maintain family and other relationships. Awareness of these issues is important for planning supportive care interventions for newly diagnosed cancer patients.

Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. Ontario Clinical Oncology Group.

BACKGROUND: Breast-conservation surgery is now commonly used to treat breast cancer. Postoperative breast irradiation reduces cancer recurrence in the breast. There is still controversy concerning the necessity of irradiation of the breast in all patients. PURPOSE: We present an update of results from a randomized clinical trial designed to examine the efficacy of breast irradiation following conservation surgery in the treatment of women with axillary lymph node-negative breast cancer. The patients were enrolled from April 1984 through February 1989. Initial results were published in 1992 after a median follow-up time of 43 months. It was reported that recurrence of cancer in the breast occurred in 5.5% of the patients who received breast irradiation compared with 25.7% of those who did not. No difference in survival was detected between the two treatment groups. Now that the median patient follow-up has reached 7.6 years, the trial end points have been re-examined and an attempt has again been made to identify a group of patients at low risk for recurrence of cancer in the breast. METHODS: Eight hundred thirty-seven patients with node-negative breast cancer were randomly assigned to receive either radiation therapy (n = 416) or no radiation therapy (n = 421) following lumpectomy and axillary lymph node dissection. The cumulative local recurrence rate as a first event, distant recurrence (i.e., occurrence of metastasis) rate, and overall mortality rate for the treatment groups were described by the Kaplan-Meier method and compared with the use of the logrank test. The Cox proportional hazards model was used to adjust the observed treatment effect for the influence of various prognostic factors (patient age, tumor size, estrogen receptor level, and tumor histology) at study entry on the outcomes of local breast recurrence, distant recurrence, and overall mortality. All P values resulted from the use of two-tailed statistical tests. RESULTS: One hundred forty eight (35%) of the nonirradiated patients and 47 (11%) of the irradiated patients developed recurrent cancer in the breast (relative risk for patients in the former versus the latter group = 4.0; 95% confidence interval = 2.83-5.65; P < .0001). Ninety-nine (24%) of the patients in the former group have died compared with 87 (21%) in the latter group. Age (< 50 years), tumor size (> 2 cm), and tumor nuclear grade (poor) continued to be important predictors for local breast relapse. On the basis of these factors, we were unable to identify a subgroup of patients with a very low risk for local breast cancer recurrence. Tumor nuclear grade, as previously reported, and tumor size were important predictors for mortality. CONCLUSIONS: Breast irradiation was shown to reduce cancer recurrence in the breast, but there was no statistically significant reduction in mortality. A subgroup of patients with a very low risk for local breast recurrence who might not require radiation therapy was not identified.

Design considerations in crossover trials with a single interim analysis and serial patient entry.

A two-stage sequential design is presented to facilitate a single interim analysis in crossover trials with serial patient entry. The interim analysis is based on a linear statistic that combines data from individuals observed for only one treatment period with data from those observed for both periods (Cook, R. J., 1995, Biometrics 51, 932-945). The final analysis is based on the usual test statistic used in crossover trials. The size of this procedure is controlled by partitioning the experimental type I error rate over the two analyses and deriving the appropriate critical values. We investigate the design implications of adopting this procedure over the usual analysis for crossover trials by examining the necessary sample size inflation factors to maintain power, and indicate the expected savings in terms of the number of responses required. Data from a study designed to compare two antiemetic therapies for previously untreated chemotherapy patients (Osaba, D., et al., 1986, Clinical and Investigative Medicine 9, 225-231) are used to illustrate the procedure.

A randomised trial of two information packages distributed to new cancer patients before their initial appointment at a regional cancer centre.

The purpose of this study was to evaluate the extent to which a new patient information package (NPIP) or a mini version of the same package (mini-NPIP) reduces emotional distress and meets the informational needs of patients arriving at a tertiary cancer centre for the first time. A comprehensive package, NPIP, consisting of procedural information regarding cancer centre location, description of the health care team, treatment services, research, educational activities, accommodation and community services provided at the centre; and a condensed version of the same package, mini-NPIP, were developed. Consecutive patients with newly diagnosed breast, gynaecological, lung and prostate cancer, referred to the centre for the first time were prerandomised to receive NPIP, mini-NPIP or no information package. Patients randomised to NPIP or mini-NPIP were mailed the information package at least one week before their first appointment. On arrival at the centre, patients were administered the Brief Symptom Inventory (BSI) which measures psychological distress, and interviewed regarding preferences for information and acceptability of the information packages. Of 465 randomised patients, 161 were excluded post-randomisation and 304 completed the entire interview: 100 were randomised to the NPIP, 102 to the mini-NPIP and 102 to the control group. Emotional distress as measured by the BSI was similar for all groups (P = 0.98). Most patients preferred to receive the information (98%), receive it before the first appointment (84%) and by mail (79%). These preferences were more evident for those given the information packages. The majority of patients found the information packages easy to understand (88%) and useful (89%), and no differences were detected between packages. The cost of production and dissemination of NPIP was more than double the cost for mini-NPIP: $ 8.93 vs $ 3.98 (Canadian dollars) per patient. For patients presenting to a cancer centre for the first time, packages of procedural information do not appear to reduce psychological distress, but are preferred by patients. Given the cost of producing NPIP, mini-NPIP is the preferred approach.

Ardeparin (low-molecular-weight heparin) vs graduated compression stockings for the prevention of venous thromboembolism. A randomized trial in patients undergoing knee surgery.

BACKGROUND: Deep vein thrombosis is common in patients undergoing major knee surgery. Static graduated compression stockings effectively prevent venous thrombosis in general surgery. Because of the demonstrated prophylactic efficacy of pneumatic compression in knee surgery, the similar efficacy of static graduated compression and pneumatic compression in neurosurgery, and the easier use of static graduated compression in knee surgery, graduated static compression stockings were used as the control arm in our clinical trial. Although low-molecular-weight heparin had been shown to be effective in general surgery and hip replacement, its efficacy was unproved in knee surgery. METHODS: A double-blind, randomized trial compared the combination of low-molecular-weight heparin and graduated compression stockings with graduated compression stockings alone in patients undergoing major knee surgery. Patients received either ardeparin (Normiflo) (low-molecular-weight heparin), 0.005 mL/kg (50 anti-Xa U/Kg), or placebo. Both were administered subcutaneously twice daily commencing 12 to 24 hours after surgery and continued for 14 days or until discharge, if sooner. Both study groups wore graduated compression stockings. Bilateral venography was performed on day 14, or sooner if the patient was ready for discharge. RESULTS: One hundred twenty-two patients were allocated to receive ardeparin and 124 received placebo. Ninety-six patients in the ardeparin group and 103 in the placebo group had evaluable venograms. Deep vein thrombosis was detected in 28 patients in the ardeparin group and in 60 in the placebo group. Proximal deep vein thrombosis was detected in two patients who received ardeparin and 16 who received placebo. One patient in each group, both of whom did not have venography, experienced pulmonary embolism. Thus, deep vein thrombosis or pulmonary embolism was detected in 29 (29.9%) of the 97 patients in the ardeparin group and in 61 (58.7%) of the 104 patients in the placebo group, a relative risk reduction of 49% (P < 00.1). The rate of major bleeding in the ardeparin group was 2.5%, compared with 2.4% in the placebo group. CONCLUSION: Ardeparin administered postoperatively twice daily is effective and safe for the prevention of venous thrombosis in patients undergoing major knee surgery. Whereas graduated compression stockings have been shown to be effective prophylactic agents in general surgery and neurosurgery, they have little effect in knee surgery.

Argon green vs. krypton red laser photocoagulation for extrafoveal choroidal neovascularization secondary to age-related macular degeneration: 3-year results of a multicentre randomized trial. Canadian Ophthalmology Study Group.

OBJECTIVE: To determine whether argon green laser (AGL) or krypton red laser (KRL) is superior for the treatment of well-defined extrafoveal choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) after 3 years of follow-up. DESIGN: Multicentre randomized clinical trial. SETTING: University-based referral practices in Canada. PARTICIPANTS: Among 210 patients selected by ophthalmologists at 13 participating centres there were 191 eligible patients aged 50 years or more with angiographically proven CNV whose posterior edge was 200 to 2500 microns from the foveal avascular zone. Other inclusion criteria included the presence of drusen in either eye, a best corrected visual acuity in the study eye of at least 35 letters on the Early Treatment Diabetic Retinopathy Study chart (equivalent of 20/200 or better on the Snellen chart) and no prior photocoagulation in the study eye. The patients were randomly assigned to receive either AGL (96 patients) or KRL (95 patients) treatment. INTERVENTIONS: Treatment with 200-microns spots of 0.2 to 0.5 seconds' exposure to produce a homogeneous grey white lesion that completely covered the CNV. OUTCOME MEASURES: Change from baseline in visual acuity at 1, 2 and 3 years (primary measure), development of persistent or recurrent CNV (secondary measure). RESULTS: There were no significant differences between the treatment groups in drop-out rates. No significant differences were found between the two groups in loss of visual acuity or angiographic evidence of persistent or recurrent CNV. CONCLUSION: KRL is no better than AGL in preserving vision and preventing loss of visual acuity in patients with AMD with well-defined extrafoveal CNV followed for 3 years.