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Biomedical subjects

R N MacDonald

Publications and source records attributed to R N MacDonald.

At least 19 recordsLinked to original sources
PubMed1997

A randomized, controlled trial of intravenous clodronate in patients with metastatic bone disease and pain.

To evaluate the effectiveness of intravenous clodronate in ameliorating refractory bone pain in patients with metastatic bone disease, 60 patients with established osseous metastases and persistent bone pain were randomized to receive either clodronate (600 mg or 1500 mg in 500 mL of normal saline) or 500 mL of saline as placebo. After 2 weeks, the patients were crossed over to receive the alternate treatment. After another 2 weeks, each patient and investigator made a blinded choice. Daily visual analogue scales (VAS) and analgesic diaries were recorded throughout the study period. Forty-six patients were evaluable (77%). A treatment x period interaction was identified in the VAS and daily morphine equivalent dose (DMED) scores. First period analysis of the VAS scores for general pain, pain at rest, and pain upon movement demonstrated an average reduction of 13, 14, and 24 mm, respectively, from baseline, but were not significantly different from changes following placebo. The average change in DMED was -6.4 (SE = 2.9) following clodronate and was +24.6 (SE = 14.9) following placebo (p = 0.03). In the blinded choice of which agent resulted in improvement in pain, 26 (57%) patients chose clodronate, 12 (26%) chose placebo, and eight (17%) had no preference (p = 0.0021). For the investigators who also made a blinded selection, clodronate was chosen in 30 (65%) patients, placebo in ten (22%) patients, and no difference was apparent in six (13%) (p < 0.0001). Intravenous clodronate appeared to have analgesic effect in patients with refractory bone pain due to metastatic bone disease. The optimal dose and duration of effect require further evaluation, particularly in patients with stable disease and persistent bone pain.

Adult↗
PubMed1994

Comparison of the efficacy, safety, and pharmacokinetics of controlled release and immediate release metoclopramide for the management of chronic nausea in patients with advanced cancer.

BACKGROUND: The short elimination half-life of metoclopramide necessitates frequent administration for optimal relief of nausea. This study compares a newly developed controlled release preparation of metoclopramide (CRM) and immediate release metoclopramide (IRM) with respect to efficacy, safety, and pharmacokinetics in patients with chronic nausea associated with advanced cancer. METHODS: Thirty-four patients with advanced cancer with nausea lasting more than 1 month and with no evidence of involvement of the gastrointestinal tract, peptic ulcer or gastritis, brain metastases, or metabolic abnormalities were randomized, in a double-blind cross-over study, to receive 40 mg of CRM every 12 hours or 20 mg of IRM every 6 hours for 3 days. Nausea, food intake, and side effects were assessed four times daily. On Day 3, sequential venous samples were taken (12 patients) to determine plasma metoclopramide concentrations. RESULTS: In 29 evaluable patients, the intensity of nausea on Day 3, measured by a 0-100-mm visual analogue scale and 0-3 categoric scale was 15 +/- 17 and 0.6 +/- 0.6 after IRM, versus 8 +/- 9 (P = 0.033) and 0.4 +/- 0.5 (P = 0.055) after CRM, respectively. Visual analogue scale nausea scores recorded by time of day and by day for the 3 treatment days were significantly lower for patients who received CRM compared with those who received IRM (P = 0.047 and P = 0.043, respectively), but categoric nausea scores were not significantly different between treatments by time of day and by day across the 3 treatment days. No differences were observed in caloric intake or side effects between treatments. In a pharmacokinetic analysis, the CRM/IRM ratio for area under the curve0-12 (microgram x hours x L-1), Cmax (microgram/L), and Tmax (hours) was 100%, 98%, and 2.3 fold, respectively. CONCLUSION: Controlled release metoclopramide is safe and effective in managing chronic nausea in patients with advanced cancer. Future studies should focus on characterizing this syndrome more clearly and on determining the optimal dose of metoclopramide and the effects of drug combinations that have proven to be useful in managing chemotherapy-induced emesis (i.e., metoclopramide plus corticosteroids).

Chronic Disease↗
PubMed1992

A double-blind, crossover trial of intravenous clodronate in metastatic bone pain.

After a baseline symptom and laboratory assessment, 24 patients with metastatic bone disease and pain were randomized to receive either a 4-hr intravenous infusion of 2-dichloromethylene bisphosphonate (Cl2MDP), 600 mg in 500 mL of normal saline, or a 4-hr placebo infusion, 500 mL of normal saline. The administration was double blind. After 1 wk, the assessment was repeated and the patients were crossed over to the alternate treatment. After 1 more wk, a final assessment and blinded choice by the patient and investigator took place. Of the 21 evaluable patients, 12 (57%) chose the Cl2MDP and 4 (19%) chose the placebo; 5 (24%) patients did not have a specific preference (p = NS). The investigator chose the Cl2MDP in 14 (67%) cases, placebo in 6 (29%) cases and was unable to discern a difference in 1 (5%) case (p less than 0.05). The patients and investigator made similar selections in 16 (76%) instances. On the visual analogue scale assessments, a significant decrease in pain scores was observed following the Cl2MDP infusion (p less than 0.01) and an increase in activity scores was also demonstrated (p less than 0.01). No significant difference in the daily oral morphine equivalent analgesic requirement was demonstrated for either arm. No difference in clinical and laboratory parameters of toxicity was evident between the placebo and Cl2MDP arms of the trial. Our preliminary findings suggest that Cl2MDP is safe, and has analgesic properties that may prove to be useful in the management of metastatic bone pain.

Adult↗
PubMed1990

A controlled trial of megestrol acetate on appetite, caloric intake, nutritional status, and other symptoms in patients with advanced cancer.

This double-blind, cross-over trial was designed to assess the effects of megestrol acetate (MA) on cancer-induced cachexia. Forty consecutive malnourished patients with advanced non-hormone-responsive tumors receiving no antineoplastic treatment were randomized to receive MA 480 mg/day versus placebo for 7 days. During day 8, a cross-over was made until day 15. Appetite, pain, nausea, depression, energy, and well-being were assessed with a visual analog scale (0 to 100 mm) at 9:00 AM and 4:00 PM during days 6, 7, 13, and 14. Weight (W;kg), tricep skinfold (TS; mm), arm circumference (AC; cm), and calf circumference (CC; cm) were measured at days 1, 8, and 15. Caloric intake (CI; Kcal/day) was determined during days 6, 7, 13, and 14. In 31 evaluable patients, the percentual difference in appetite at 9:00 AM, appetite at 4:00 PM, energy, and well-being after MA was +15.1, +14, +3.2, and +5.2, versus -12 (P = 0.03), -5.1 (P = 0.015), -10 (P = 0.024), and -8.3 (not significant) after placebo. Percentual difference in W, TS, AC, and CC after MA was +0.2, +1, -0.1, and +0.4 versus -0.8 (P = 0.03), -0.8 (P = 0.001), -0.3 (not significant), and -0.5 (P = 0.04) after placebo. CI during MA was 3480 +/- 1574 (48-hour intake), versus 2793 +/- 1542 (P less than 0.001) during placebo. Patients and investigators blindly chose MA in 20 (66%, P = 0.023) and 28 cases (92%, P less than 0.001), placebo in eight and two cases, and made no choice in three and one cases, respectively. Toxicity consisted of mild edema and nausea in three and two cases, respectively. After mean follow-up of 27 +/- 13 days, on an open basis, an average increase in W and AC of 4.8 +/- 1.7 kg and 2.8 +/- 1.7 cm was observed, respectively. The authors conclude that MA is a powerful appetite stimulant with subjective and objective effects on nutritional status.

Appetite↗
PubMed1990

Effects of morphine on the dyspnea of terminal cancer patients.

We report an open, uncontrolled study designed to assess the effects of subcutaneous (SC) morphine on dyspnea of terminal cancer. Twenty patients with dyspnea caused by restrictive respiratory failure received an SC dose of morphine of 5 mg (5 patients who were not receiving narcotics), or equivalent to 2.5 times their regular dose (15 patients who were receiving narcotics for pain). Dyspnea (D) and pain (15 cases) were measured before the dose and every 15 min for 150 min after the injection using a visual analog scale 0-100. Respiratory rate (RR), respiratory effort (RE) (score 1-6), arterial saturation of O2 (SO2) and end-tidal PACO2 were determined before and 45 min after SC morphine. D, RR, RE, SO2, and PACO2 were 68 +/- 32, 32 +/- 7; 3.5 +/- 1.8, 87 +/- 10, and 31 +/- 12, respectively, before SC morphine, and 34 +/- 25 (P less than 0.001), 31 +/- 9 (P:NS), 3.2 +/- 1.9 (P:NS), 86 +/- 11 (P:NS), and 33 +/- 9 (P:NS), respectively, 45 min after SC morphine. Nineteen of 20 patients (95%) reported improved dyspnea after morphine. We conclude that morphine appears to improve dyspnea without causing a significant deterioration in respiratory function in terminal cancer patients. Double-blind placebo controlled studies are needed in this population.

Aged↗
PubMed1990

Palliative care in a cancer center: results in 1984 versus 1987.

We reviewed the charts of 48 consecutive patients treated by our Palliative Care Team (PCT) during 1984 and compared these results with 50 consecutive patients treated during 1987. The composition of the PCT did not change between 1984 and 1987. The median equivalent daily dose of parenteral morphine (MEDD) before referral, after initial treatment by the PCT, and at the maximum prescribed by the PCT were 43 mg, 48 mg, and 96 mg in 1984, respectively, versus 60 mg (p less than 0.03), 60 mg (p less than 0.03), and 120 mg (p less than 0.12) in 1987, respectively. Seventeen of 43 patients were receiving mild narcotics in 1984 versus 7 of 48 patients in 1987 (p less than 0.01). Parenteral narcotics were used initially in 2% of patients in 1984 versus 46% of patients in 1987 (p less than 0.001). Poor pain control after the initial treatment was observed in 42% of patients in 1984 versus 26% in 1987 (p less than 0.01). Our results suggest that patients are being treated more aggressively by their physicians before referral to the PCT in 1987, that our PCT is using more aggressive initial treatment than in 1984, and that, notwithstanding these changes, there is still a significant proportion of patients in whom pain cannot be controlled before death. These results suggest that more research is necessary to better define intractable pain syndromes and develop adequate treatments for them.

Alberta↗
PubMed1990

Treatment of pain and other symptoms in cancer patients: patterns in a North American and a South American hospital.

The charts of 200 consecutive patients with cancer pain admitted to a major teaching hospital in Edmonton, Canada (n = 100) and in Buenos Aires, Argentina (n = 100) were reviewed to assess the differences between North American (NA) and South American (SA) facilities in patterns of treatment of pain and other symptoms. Criteria for eligibility and methods were identical in both hospitals. Characteristics of patients (age, sex, primary tumor, reason for admission) and attending staff were similar between both hospitals. Mean daily equivalent doses of parenteral morphine (mg) were 44 +/- 26 and 9 +/- 10 in NA and SA, respectively (p less than 0.001). Patients in NA, received narcotics every 4 hr and on a regular basis more frequently than in SA. The types of narcotics and the use of adjuvant drugs were significantly different between NA and SA. Nonpharmacologic treatments, antiemetics, and laxatives were more frequently used in NA. These results suggest that there are significant differences in symptomatic management of advanced cancer between institutions in NA and SA.

Adult↗
PubMed1989

The Edmonton staging system for cancer pain: preliminary report.

Fifty-six consecutive patients with pain due to cancer were admitted to a prospective study designed to test a clinical staging system for cancer pain. The system classifies patients in stage 1 (good prognosis) to stage 3 (poor prognosis) according to the mechanism of pain, characteristics of pain, previous narcotic exposure, cognitive function, psychological distress, tolerance and past history of drug addiction or alcoholism. During day 1 patients were staged after being seen by one of the investigators. Patients were treated for 21 days, when a final diagnosis of pain control was made. Eighteen of 22 patients in stage 1 achieved good pain control (82%) vs. 2/22 patients in stage 3 (10%; P less than 0.01). Sensitivity, specificity and negative predictive value of the system were 0.75, 0.86 and 0.80, respectively. We conclude that this is a simple and reliable system for clinical staging that can be used for clinical research and management of patients with cancer pain.

Female↗
PubMed1989

Influence of the pain and symptom control team (PSCT) on the patterns of treatment of pain and other symptoms in a cancer center.

To assess the influence of a pain and symptom control team on the pattern of prescription of pharmacologic and nonpharmacologic treatments for cancer pain, we reviewed the charts of 100 consecutive patients admitted to the Cross Cancer Institute during 1987 and 100 patients admitted during 1984. The average daily dose of parenteral morphine per patient was 44 +/- 26 mg in 1987 versus 34 +/- 38 mg in 1984 (p less than 0.05). In 1987 and 1984, only 31 and 22% of the analgesics were ordered around the clock respectively (P:NS). Approximately half of the patients in 1987 and 1984 were prescribed antiemetics and two-thirds of the patients were prescribed laxatives. Parenteral narcotics were prescribed subcutaneously in 0/52 cases in 1984 versus 21/63 cases in 1987 (33%, p less than 0.01). The pattern of prescription of narcotics by residents changed significantly during the last four weeks of rotation as compared to the first four weeks. We conclude that there have been some changes in the modality of treatment of pain that are probably due to changes in the pattern of prescription by the residents and continued improvement in assessment of pain by nurses. However, in several areas of treatment the impact of a pain and symptom control team remains minimal.

Adult↗
PubMed1988

Patient-controlled subcutaneous hydromorphone versus continuous subcutaneous infusion for the treatment of cancer pain.

Twenty-five patients with pain due to advanced cancer were randomized to receive patient-controlled sc injections (PCIs) of hydromorphone (HM) versus continuous sc infusion (CSCI) of HM by means of a Pharmacia 5200 pump. Each self-injection of HM during PCI was equivalent to 4 hours of CSCI. After 3 days, a crossover occurred, and patients received the alternate treatment for 3 days. During both phases of the study, patients could request extra doses of HM from their nurses. In 22 patients able to be evaluated, pain intensity (visual analogue, 0-100 mm) at 9:00 a.m. and 4:00 p.m. was 31 +/- 23 and 28 +/- 18 mm, respectively, on PCI versus 28 +/- 18 and 27 +/- 17 mm, respectively, on CSCI [P = not significant (NS)]. The total dose of HM was 168 +/- 197 and 181 +/- 234 mg on PCI and CSCI, respectively (P = NS). No significant difference was found in nausea, drowsiness, or number of hours of sleep. The total number of extra doses of HM was 6 +/- 7 on CSCI versus 2 +/- 3 on PCI (P = .007). At the end of the study, patients chose PCI and CSCI in seven and 10 cases, respectively (P = NS; 5 patients expressed no preference). We conclude that both methods were similar in regard to effectiveness and toxic effects in short-term hospital use.

Female↗
PubMed1988

Muscle electrophysiology in patients with advanced breast cancer.

Sixty-one consecutive patients with advanced breast cancer (defined as metastatic disease) and 20 normal age- and sex-matched controls were admitted to a prospective study designed to assess muscle electrophysiology. Nutritional status, lean body mass, and ultrasonographic measurement of the triceps brachialis, sternomastoid, and adductor pollicis muscles were determined in patients and controls. In addition, tumor mass and performance status were determined in the patient group. Electrophysiology of the adductor pollicis muscle was assessed during isometric voluntary maximum effort and during electrical stimulation via the ulnar nerve (80-120 V, 50-100 msec). Nutritional status, lean body mass, and ultrasonographic measurements of the triceps brachialis, sternomastoid, and adductor pollicis were not significantly different between patients and controls. Maximum strength after supramaximal stimulation at 50 Hz was 34 +/- 15 N in patients, versus 40 +/- 9 (P less than .01) N in controls. Relaxation velocity was 336 +/- 149 N/sec in patients, versus 507 +/- 251 (P = .02) N/sec in controls. Fatigue (% of initial strength after 30 sec of stimulation) was 67% +/- 22% in patients, versus 79% +/- 17% (P = .03) in controls. Muscle electrophysiology did not correlate with tumor mass or performance status. It was concluded that patients with advanced breast cancer have abnormal muscle electrophysiology that is not due to abnormal nutritional status or decreased muscle mass. More research is needed to better characterize this disorder and to better define its cause.

Aged↗