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Biomedical subjects

N Hagen

Publications and source records attributed to N Hagen.

At least 19 recordsLinked to original sources

Palliative radiotherapy improves pain and reduces functional interference in patients with painful bone metastases: a quality assurance study.

AIMS: To characterise the effect of palliative radiotherapy treatment outcomes as evaluated by the Brief Pain Inventory within a radiotherapy clinic, as a quality assurance initiative. MATERIALS AND METHODS: Tumour and treatment parameters of patients with painful bone metastases treated through a dedicated bone pain radiotherapy clinic have been prospectively recorded since 2002. One hundred and nine ambulatory patients provided pre- and post-treatment pain assessments at 4-6 weeks after palliative radiotherapy. The self-administered Brief Pain Inventory questionnaire was completed by patients during their visits. Changes in pain and seven-item functional interference scores were analysed. RESULTS: Most of the patients had prostate (n=42) or breast (n=42) cancer. The mean Karnofsky performance score was 70 before palliative radiation therapy. Sixty-eight per cent of patients were treated with a single fraction (6-8 Gy) and 25% received 20 Gy/five fractions. The overall response (reduction in worst pain by > or = 2/10) was 72%. Sixty-one per cent of patients had stable or reduced consumption of opioid analgesics. A significant reduction for all seven functional interference items was seen after treatment, the greatest improvement being general activity (-2.4/10). There was significant correlation between pain reduction and improvement in functional interference. CONCLUSION: This quality assurance initiative showed that palliative radiotherapy reduced both pain and its interference on function among ambulatory patients with symptomatic bone metastases. The reduction in pain was correlated with reductions in functional interference. Clinical trials of palliative radiotherapy should provide data that allow an evaluation of various domains of chronic pain.

Adult↗

Characterization of mixtures of recombinant human cytochrome p450s as a screening model for metabolic stability in drug discovery.

1. Recombinant human cytochrome p450 (rhCYP) has become an important screening model in drug metabolism studies due to the high cost of human and animal hepatic tissue. Until now, rhCYPs have been evaluated and used as separate forms, but a mixture of CYP forms comparable with the human liver could be of value in early drug discovery. 2. In the present study, rhCYP2C9, rhCYP2D6 and rhCYP3A4 co-expressed with reductase in Escerichia coli were mixed and evaluated with regards to kinetic properties (K(m) and V(max)). Furthermore, antioxidant was added to investigate whether a free radical scavenger would affect the kinetic parameters. Results were compared with data obtained in human liver microsomes (HLM). 3. Results showed a good correlation between mixed rh CYP data and HLM data for K(m) and V(max). K(m) varied < 3-fold between matrices for CYP2C9 and CYP3A4, whereas the K(m) for CYP2D6 varied up to 4.5-fold. V(max) differed up to 3-fold between matrices for the CYP forms investigated. However, the discrepancy in V(max) may depend on the anticipated level of each form in HLM. The addition of antioxidant increased V(max) for CYP2C9 and CYP2D6 by 75 and 50%, respectively, whereas V(max) for CYP3A4 was unchanged. 4. In conclusion, the rhCYP mixture shows promising results as a predictor of CYP kinetic parameters. Furthermore, addition of antioxidant can in certain cases increase catalytic activity.

Antioxidants↗

Computerized quality-of-life screening in a cancer pain clinic.

METHODS: To determine the utility and acceptability to patients and staff of a computerized quality-of-life (QOL) screening program in a tertiary ambulatory cancer pain clinic, patients were administered the computerized EORTC-QLQ-C30 questionnaire. A report summarizing this QOL information was given to clinic staff prior to each patient's appointment. Both the patient and the clinical staff were surveyed afterwards. RESULTS: Although more than half of the 46 patients had never used a computer before, almost all reported that the program was easy to use and understand, enjoyable, helpful, and quick. Their attitudes toward computers significantly improved from pre- to post-assessment. Staff found the QOL information to be appropriate and useful. CONCLUSIONS: The computerized questionnaire was readily used by patients and was helpful to pain clinic staff, making it an appropriate tool for identifying important QOL problems and issues in busy clinical settings, even for inexperienced computer users with significant functional impairment.

Activities of Daily Living↗

The Canadian Palliative Care Education Group.

The Canadian Palliative Care Education Group, a committee of the Canadian Society of Palliative Care Physicians, carries out surveys from time to time on the status of palliative care education in Canadian medical schools. We describe the organization of the Canadian Palliative Care Education Group and report on a survey carried out in the 1996-97 academic year. Our data suggest that the emphasis on palliative care varies widely amongst the 16 Canadian medical schools, in concert with the availability of academic staff positions in palliative care. We conclude that the need for palliative care education is supported by rhetoric which remains to be matched by proportionate tangible investment.

Canada↗

Patient-identified needs for hormone replacement therapy counseling: a qualitative study.

BACKGROUND: Numerous medical organizations, including the American College of Physicians, have recommended that women be counseled about postmenopausal hormone replacement therapy (HRT). Patients' perspectives on their counseling needs, however, have not been integrated into most counseling guides. OBJECTIVE: To use patient self-reports to identify needs for HRT counseling. DESIGN: Individual, in-depth patient interviews. SETTING: Managed care organization. PATIENTS: 26 women who had received an initial prescription for HRT. MEASUREMENTS: Qualitative, consensus review of the content of interview transcripts. RESULTS: On average, women reported 15 factors (range, 6 to 24 factors) as critical to their decision-making process. Although most women cited their physician's opinion (96%), reports in the media (81%), and experiences and opinions of friends (77%) as critical to their decisions about HRT, counseling recommendations address none of these concerns. CONCLUSIONS: Many women in a managed care organization who accepted a prescription for HRT identified counseling needs that are not included in widely used HRT guidelines.

Adult↗

Alternative therapy use in neurologic diseases: use in brain tumor patients.

BACKGROUND: The extent of alternative therapy use in brain tumor patients is unknown, but it may be frequent and seems important to those who use it. OBJECTIVE: To characterize alternative therapy use in brain tumor patients. METHODS: Prospective questionnaire-based survey of 167 brain tumor patients who attended a cancer center in Southern Alberta. Physicians completed forms describing clinical information such as disease status. RESULTS: The response rate was 91% (167/184). Twenty-four percent of patients used alternative therapies and often more than one therapy at the same time. Motivation to use these therapies was influenced by the desire for patient-focused treatment and a perceived need to take charge. Alternative therapy users were younger (p = 0.04) and more likely to be on sick or disability leave (p = 0.02), to come in for repeat visits (p = 0.05), and to have received conventional treatments (p = 0.01). Users tended to have lower quality of life with respect to physical well-being, functional well-being, and a specific brain tumor subscale. Clinical variables, such as disease status, tumor type, and Karnofsky Performance Score, were not related to alternative therapy use. Major changes in number and types of alternative therapy use occurred during the study period. No major side effects or tumor responses were seen with alternative therapies. CONCLUSIONS: Alternative therapy use in brain tumor patients is common and may reflect unmet patient needs with respect to their cancer care within the current model of health care delivery.

Adult↗

Effectiveness of megestrol acetate in patients with advanced cancer: a randomized, double-blind, crossover study.

PURPOSE: To evaluate the effect of megestrol acetate at a lower dose than previously investigated on the symptoms of cachexia in patients with advanced cancer. METHODS: A total of 84 patients with advanced, solid tumours not responsive to hormone therapy were enrolled in this double-blind, crossover study. During phase 1, patients were randomly assigned to receive megestrol acetate (160 mg 3 times daily) for 10 days or placebo. During phase 2, after a 2-day washout period, patients received the alternate treatment for 10 days. Patients underwent daily assessments of activity, nausea, appetite and well-being by means of a visual analogue scale (VAS). In addition, nutritional status (weight, tricep skinfold measure, arm muscle circumference), energy intake, fatigue (Piper Fatigue Scale) and quality of life (Functional Living Index-Cancer [FLIC]) were assessed. RESULTS: Among the 53 evaluable patients megestrol acetate resulted in a significant improvement in appetite (p = 0.005), activity (p = 0.007) and well-being (p = 0.03). There was no significant change in the intensity of nausea, nutritional parameters, energy intake or FLIC scores. There was a significant improvement in 2 of the 3 factors measured by the Piper Fatigue Scale and in the overall fatigue score. Upon completion of the study, while still blind to the treatment condition, 30 patients indicated that they felt better overall after megestrol, 15 said they felt better after placebo, and 10 indicated no preference (p = 0.001). CONCLUSION: Treatment with megestrol acetate results in rapid and significant improvement of symptoms in terminally ill patients at lower doses than previously reported. The effects are not secondary to nutritional changes. The FLIC quality-of-life questionnaire was unable to detect these changes.

Adult↗

Strychnine-like multifocal myoclonus and seizures in extremely high-dose opioid administration: treatment strategies.

While occasional myoclonic jerks are prevalent in cancer patients receiving opioids, severe myoclonic jerks and seizures due to opioids are uncommon. In this retrospective case series, we describe five cancer patients with refractory cancer pain and severe neuroexcitatory toxicity associated with extremely high-dose opioid therapy to characterize better the syndrome, its treatment, and its outcome. Two patients died following seizures, but three patients recovered following prompt treatment with parenteral midazolam infusions and rotation to alternative opioids. Possible mechanisms and treatment options for this potentially lethal clinical syndrome are reviewed. The authors conclude that severe multifocal myoclonus and seizures associated with extremely high-dose opioid therapy are life-threatening, and respond to parenteral midazolam infusion, rotation to alternative opioids, and aggressive supportive care.

Adult↗

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↗

Pain in Guillain-Barré syndrome.

OBJECTIVES: To determine the character, intensity and frequency of pain in Guillain-Barré syndrome (GBS) and to evaluate the response to treatment. DESIGN: A prospective longitudinal study. SETTING: Academic hospital-based practices. PATIENTS: Fifty-five consecutive patients with GBS. INTERVENTIONS: Patients were evaluated on admission and at 2, 4, 8, 16, and 24 weeks. MAIN OUTCOME MEASURES: Character of pain, pain intensity using Visual Analogue Scale ([VAS] 0 to 10 cm) and Present Pain Intensity of McGill Pain Questionnaire, pain relief (VAS 0 to 10 cm), Disability Grading Scale for GBS. RESULTS: Forty-nine patients (89.1%) described pain during the course of their illness. On admission, mean pain intensity (VAS) was 4.7 +/- 3.3. However, 26 patients (47.3%) described pain that was either distressing, horrible, or excruciating (mean VAS, 7.0 +/- 2.0). The most common pain syndromes observed were deep aching back and leg pain and dysesthetic extremity pain. Pain intensity on admission correlated poorly with neurologic disability on admission (r = 0.26, p = 0.06) and throughout the period of study (r < 0.20, p > 0.10). Forty-one patients (74.5%) required opioid analgesics, with 16 (29.0%) receiving parenteral morphine to provide adequate pain relief. CONCLUSIONS: Moderate to severe pain is a common and early symptom of GBS and requires aggressive treatment. Pain intensity on admission is not a predictor of poor prognosis. Back and leg pain usually resolves over the first 8 weeks, but dysesthetic extremity pain may persist longer in 5 to 10% of patients despite motor recovery and the use of adjuvant analgesics.

Back↗

Focal midbrain glioma: long term survival in a cohort of 16 patients and the implications for management.

BACKGROUND: Focal gliomas involving the midbrain tectum and tegmentum have been identified as having a better prognosis than diffuse tumors affecting the brain stem. However, only limited information is available concerning treatment effectiveness and long term outcome for these patients. METHODS: A retrospective, population-based cancer registry survey was performed to assess the clinical features and treatment courses of patients with focal midbrain tumors. RESULTS: Sixteen patients with midbrain gliomas were identified; eight had tectal gliomas and eight tegmental gliomas. Thirteen patients presented with symptoms related to hydrocephalus, and 12 required a ventriculoperitoneal shunt. Seven patients underwent surgery directed at the tumor. Eight patients underwent initial radiation therapy and none had initial chemotherapy. One patient diagnosed at age 18 months had a rapidly growing tumor after 14 months of follow up which has responded to chemotherapy. The mean survival of this patient population was 84 months (range 3-280 months) after diagnosis, with only one tumor related death occurring (280 months after diagnosis). Survival was not affected by tumor location within the midbrain (tegmental or tectal) or by whether radiation therapy was or was not administered. CONCLUSIONS: Patients with focal midbrain gliomas require symptom control aimed at treatment of hydrocephalus, or mass effect from the tumor. However the extended survival of this population suggests that routine aggressive surgical debulking is often not required. Furthermore, the routine use of radiation therapy or chemotherapy for all such patients is questioned.

Adolescent↗

Diffusion of standards of care for cancer pain.

The authors report the results of a symposium on improving the standards of care for patients with cancer pain. The symposium was sponsored by the Advisory Committee on Cancer Control of the National Cancer Institute of Canada and was held Apr. 8 to 10, 1994, in Toronto. Participants included experts on control of cancer pain and on diffusion techniques, patients with cancer and representatives of regulatory agencies. They suggested the following strategies to improve outcomes in patients with cancer pain. Processes for accreditation of health care institutions should require documentation of cancer pain, its treatment and its outcome. Tertiary care facilities that provide cancer treatment should have expert, subspecialty, multidisciplinary programs for pain control and should provide adequate psychosocial support to patients suffering cancer pain. The Canadian Cancer Society should conduct a public-education campaign to encourage patients to report pain to health care providers. The National Cancer Institute of Canada should foster research on cancer pain by restructuring its process for review of pain-research protocols. Examinations for professionals who care for patients with cancer should include a defined number of questions concerning pain and symptom control. Provincial programs to monitor prescribing through the use of triplicate prescription pads should have an educational as well as regulatory purpose.

Administration, Oral↗

Steady-state pharmacokinetics of hydromorphone and hydromorphone-3-glucuronide in cancer patients after immediate and controlled-release hydromorphone.

Although the pharmacokinetics of oral hydromorphone has been evaluated in healthy volunteers after small single oral doses, data are not available regarding the disposition of hydromorphone and its principal metabolite, hydromorphone-3-glucuronide (H3G), at steady-state and after large oral doses. The authors studied the pharmacokinetics of hydromorphone and H3G after oral administration of an immediate-release (IR) and controlled-release (CR) formulation of hydromorphone at a daily dose of 48 +/- 11 mg (range 6-216 mg) in a randomized, double-blind, steady-state, two-way crossover evaluation in 18 patients with chronic cancer pain. Controlled-release hydromorphone demonstrated equivalent bioavailability and acceptable CR characteristics, when compared with IR hydromorphone (CR vs. IR: AUC0-12 123.10 +/- 20.38 vs. 118.98 +/- 20.92 ng.hr.mL-1, P = NS, Cmax 17.76 +/- 3.07 vs. 19.70 +/- 4.04 ng.mL-1, P = NS, Cmin 6.04 +/- 1.01 vs. 5.28 +/- 1.000 ng.mL-1, P = NS, and Tmax 4.78 +/- 0.78 vs. 1.47 +/- 0.22 hr, P = 0.0008). A significant linear relationship existed between hydromorphone dose and hydromorphone AUC (r = 0.8315, P = 0.0001) and between hydromorphone AUC and H3G AUC (r = 0.8048, P = 0.0001) over a wide dose range. The steady-state molar ratio of H3G to hydromorphone was 27:1. The authors conclude that CR hydromorphone provides a pharmacokinetic profile consistent with 12 hourly dosing and that at steady state, oral hydromorphone is extensively metabolized to H3G, although the pharmacologic activity of this metabolite remains unknown.

Administration, Oral↗

Comparative clinical efficacy and safety of immediate release and controlled release hydromorphone for chronic severe cancer pain.

BACKGROUND: The short elimination half-life of hydromorphone necessitates 4-hourly dosing to maintain optimal levels of analgesia in patients with chronic cancer pain. The purpose of this study was to compare the clinical efficacy and safety of controlled release hydromorphone administered every 12 hours and immediate release hydromorphone administered every 4 hours in patients with chronic severe cancer pain. METHODS: Forty-eight patients with stable chronic severe cancer pain were randomized, in a double-masked crossover study, to controlled release hydromorphone every 12 hours or immediate release hydromorphone every 4 hours for 7 days each. Pain intensity was assessed using a visual analog scale (VAS) and the Present Pain Intensity Index of the McGill Pain Questionnaire. Nausea and sedation were also assessed using a VAS. Assessments were made by the patient four times a day at 7:00 a.m., 11:00 a.m., 3:00 p.m., and 7:00 p.m. Use of rescue hydromorphone also was recorded by the patient. RESULTS: Forty-five patients completed the study (26 women, 19 men; mean age, 57.1 +/- 13.6 years) and received a mean daily dose of 76 +/- 133 mg (range, 6-768 mg). There were no significant differences between controlled release hydromorphone and immediate release hydromorphone in overall VAS pain intensity scores (19 +/- 14 vs. 20 +/- 14 mm), ordinal pain intensity scores (1.2 +/- 0.8 vs. 1.2 +/- 0.8) and pain scores by day of treatment or time of day. The daily rescue analgesic consumption during controlled release hydromorphone and immediate release hydromorphone did not differ significantly overall (1.1 +/- 1.1 vs. 1.0 +/- 1.1 doses per day) or with respect to time of day. There were no significant differences in overall VAS sedation scores (18 +/- 18 mm vs. 19 +/- 18 mm) and in overall mean VAS nausea scores (12 +/- 15 mm vs. 11 +/- 14 mm) between controlled release hydromorphone and immediate release hydromorphone. CONCLUSIONS: Controlled release hydromorphone administered every 12 hours is as effective as immediate release hydromorphone administered every 4 hours in the management of patients with chronic severe cancer pain. The benefits of controlled release hydromorphone lie in the convenience of its capsule formulation, which can be sprinkled on soft food, and its 12-hour duration of action, which allows patients uninterrupted sleep and improved compliance.

Chronic Disease↗

Proximal muscle weakness in a patient with hepatocellular carcinoma.

Asthenia and generalized weakness are common in cancer patients. There are multiple causes for these symptoms. We describe a case of rapid onset of proximal muscle weakness in a patient with hepatocellular carcinoma. The differential diagnosis of muscle weakness in the palliative care patient is reviewed. The discussion centers on steroid myopathy and its treatment.

Asthenia↗