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ABSTRACT: Delirium is a highly prevalent and deleterious disorder in terminally ill cancer patients. We assessed whether a multicomponent preventive intervention was effective in decreasing delirium incidence and severity among cancer patients receiving end-of-life care.
A cohort of 1516 patients was followed from admission to death at seven Canadian palliative care centers. In two of these centers, routine care included a delirium preventive intervention targeting physicians (written notice on selective delirium risk factors and inquest on intended medication changes), patients, and their family (orientation to time and place, information about early delirium symptoms). Delirium frequency and severity were compared between patients at the intervention (N = 674) and usual-care (N = 842) centers based on thrice-daily symptom assessments with the Confusion Rating Scale.
The overall rate of adherence to the intervention was 89.7%. The incidence of delirium was 49.1% in the intervention group, compared with 43.9% in the usual-care group (odds ratio [OR] 1.23, P = 0.045). When confounding variables were controlled for, no difference was observed between the intervention and the usual-care groups in delirium incidence (OR 0.94, P = 0.66), delirium severity (1.83 vs. 1.92; P = 0.07), total days in delirium (4.57 vs. 3.57 days; P = 0.63), or duration of first delirium episode (2.9 vs. 2.1 days; P = 0.96). Delirium-free survival was similar in the two groups.
A simple multicomponent preventive intervention was ineffective in reducing delirium incidence or severity among cancer patients receiving end-of-life care. Delirium prevention remains a difficult challenge in terminally ill cancer patients.
Psycho-Oncology 02/2012; 21(2):187-94. · 3.34 Impact Factor
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ABSTRACT: Delirium is the most frequent neuropsychiatric disorder that affects the advanced cancer population who are receiving palliative care. There is limited evidence and much debate about the role of hydration in delirium management at the end of life. The purpose of this article is to review the literature on delirium management with regards to pharmacological management and hydration.
Pharmacological management is the first line of treatment for delirium, whereby antipsychotics are the medication of choice. However, they have not been approved by the United States Food and Drug Administration for delirium management as there is insufficient evidence supporting their use. Hydration is a believed to be a key component of delirium reversibility; yet there are conflicting results on its efficacy as an intervention for delirium management. As there are few studies of good methodological quality on the topic and large variations in practice, the effectiveness of hydration as an alternative management option for delirium is unclear.
More work is required to assess the role of hydration in delirium at the end of life. Given the lack of evidence-based research on hydration, more randomized clinical trials are needed to elucidate the effects of hydration as a delirium intervention.
Current opinion in supportive and palliative care 06/2011; 5(2):169-73.
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ABSTRACT: Several in vitro studies have indicated that metformin may reduce the risk of prostate cancer; however, epidemiologic studies have been inconclusive. The objective of this study was to determine whether metformin decreases the risk of prostate cancer in patients with type 2 diabetes.
A nested case-control analysis was conducted within a population-based cohort from the UK General Practice Research Database. The cohort included patients over the age of 40 who were prescribed a first oral hypoglycemic agent (OHA) between 1988 and 2009. Cases of prostate cancer were matched up to ten controls on year of birth, date of cohort entry, and duration of follow-up. Adjusted rate ratios (RR) were estimated using conditional logistic regression.
The cohort included 63,049 incident users of OHAs, in which 739 cases of prostate cancer were matched to 7,359 controls. Metformin use did not decrease the risk of prostate cancer (RR: 1.23, 95% CI: 0.99-1.52). In secondary analyses, prostate cancer risk was found to increase as a function of the number of metformin prescriptions received (one to seven prescriptions: RR: 1.05, 95% CI: 0.80-1.37; seven to eighteen prescriptions: RR: 1.29, 95% CI: 0.99-1.69; eighteen to thirty-six prescriptions: RR: 1.37, 95% CI: 1.04-1.81; more than thirty-six prescriptions: RR: 1.40, 95% CI: 1.03-1.89).
The results of this study indicate that metformin does not reduce the risk of prostate cancer in patients with type 2 diabetes.
The secondary analyses need to be interpreted with caution given the inverse association between type 2 diabetes and prostate cancer.
Cancer Epidemiology Biomarkers & Prevention 03/2011; 20(2):337-44. · 4.12 Impact Factor
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The Journal of neuropsychiatry and clinical neurosciences 01/2011; 23(2):E18. · 2.34 Impact Factor
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ABSTRACT: To review the research about psychostimulant effects on cognitive functions in end-of-life patients diagnosed with hypoactive delirium or cognitive disorders.
The MEDLINE (1966-March 2008), Embase (1974-March 2008), PsycINFO (1806-March 2008), IPA (1970-March 2008), CINAHL (1982-March 2008), ISI Web of Science (1945-March 2008), Current Contents (March 2007-March 2008), Access Medicine (2001-March 2008), and ProQuest Dissertations & Theses (1980-March 2008) databases were searched with keywords related to delirium, cognition, psychostimulants, and palliative care for French or English articles in a dementia-free and hyperactive delirium-free end-of-life population. Cognitive functions had to be assessed before and after initiation of the psychostimulant treatment. Moreover, treatment had to be initiated after the onset of cognitive impairments.
A total of 173 studies were screened. Five studies on methylphenidate and 1 study on caffeine met inclusion criteria and were included in this review. Two studies were case reports, 2 were open-label trials, and 2 were double-blind, crossover randomized placebo-controlled trials. Three studies were conducted with hypoactive delirium patients and all studies were conducted in an advanced cancer patient population.
The reviewed studies support the use of methylphenidate to improve end-of-life patient cognitive functions, particularly in the case of hypoactive delirium. Caffeine seems to have beneficial effects on psychomotor activity. Further well-designed studies are needed to consolidate these findings.
Canadian journal of psychiatry. Revue canadienne de psychiatrie 06/2010; 55(6):386-93. · 2.42 Impact Factor
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James R Wright,
Yee C Ung,
Jim A Julian,
Kathleen I Pritchard,
Timothy J Whelan,
Column Smith,
Barbara Szechtman,
Wilson Roa,
Liam Mulroy,
Leona Rudinskas, Bruno Gagnon,
Gord S Okawara,
Mark N Levine
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ABSTRACT: Previous trials have suggested a quality-of-life (QOL) improvement for anemic cancer patients treated with erythropoietin, but few used QOL as the primary outcome. We designed a trial to investigate the effects of epoetin alfa therapy on the QOL of anemic patients with advanced non-small-cell carcinoma of the lung (NSCLC).
A multicenter, randomized, double-blind, placebo-controlled trial was conducted. The proposed sample size was 300 patients. Eligible patients were required to have NSCLC unsuitable for curative therapy and baseline hemoglobin (Hgb) levels less than 121 g/L. Patients were assigned to 12 weekly injections of subcutaneous epoetin alpha or placebo, targeting Hgb levels between 120 and 140 g/L. The primary outcome was the difference in the change in Functional Assessment of Cancer Therapy-Anemia scores between baseline and 12 weeks.
Reports of thrombotic events in other epoetin trials prompted an unplanned safety analysis after 70 patients had been randomly assigned (33 to the active arm and 37 to the placebo arm). This revealed a significant difference in the median survival in favor of the patients on the placebo arm of the trial (63 v 129 days; hazard ratio, 1.84; P = .04). The Steering Committee closed the trial. Patient numbers compromised the interpretation of the QOL analysis, but a positive Hgb response was noted with epoetin alfa treatment.
An unplanned safety analysis suggested decreased overall survival in patients with advanced NSCLC treated with epoetin alfa. Although infrequent, other similar reports highlight the need for ongoing trials evaluating erythropoietin receptor agonists to ensure that overall survival is monitored closely.
Journal of Clinical Oncology 04/2007; 25(9):1027-32. · 18.37 Impact Factor
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ABSTRACT: The objective of this population-based observational cohort study was to estimate the extent to which the inclusion/exclusion of transferred patients with acute myocardial infarction (AMI) impacts on hospital performance rankings.
The authors studied 91,633 adult patients admitted to 116 acute care hospitals in Quebec, Canada, with a primary diagnosis of AMI between 1992 and 1999.
Hospital performance ranks, based on 30-day AMI mortality rates, were estimated with hierarchical models and compared using 3 different methods for handling transferred patients (exclude all transfers; include transfers and assign outcome to the referring hospital; include transfers and assign outcome to the receiving hospital). The explanatory variable of interest was the hospital to which the patient's outcome was attributed.
Using the 3 methods, 4 hospitals were ranked "best performers" once, and 1 hospital ranked among the best in 2 of the 3 analyses performed. Nine hospitals were ranked "worst performers" at least once (4 of which ranked among the "worst" once only, 2 ranked among the "worst" twice, and 3 were consistently ranked "worst performers" in all analyses). There was significant variation in mortality rates among hospitals, and the difference in the rates between the highest and lowest ranking hospitals exceeded the clinically relevant benchmark of 1%.
Performance evaluation studies that compare hospital mortality rates typically exclude transferred patients. However, methods used to deal with AMI patient transfers influenced hospital ranks when comparing 30-day mortality rates. Excluding transfers may lead to an inaccurate depiction of the quality of healthcare services in regionalized healthcare systems that call for the timely interhospital transfer of patients with AMI.
Medical Care 08/2006; 44(7):664-70. · 3.41 Impact Factor
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ABSTRACT: Palliative care is an essential component of cancer care, and population-based research is needed to monitor its impact. Administrative databases are the cornerstone of health services research. Their limitation is that cause of death is not sufficient to readily classify decedents as terminally ill for the study of the health services they received at the end of life. The study purpose is to develop and test the validity of an algorithm allowing the classification of the decedents as dying of breast cancer (BC), using administrative data.
Validation was carried out through a chart review of 119 BC decedents extracted from hospital-based databases. This algorithm was applied to 3,384 deceased women with BC representative of the whole population. The effect of the classification by the algorithm was illustrated by the shift in the distributions of age and place of death.
The validation showed a sensitivity of 95%, a specificity of 89%, a positive predictive value of 98%, and negative predictive value of 77% for the classification of women dying of BC. Of the 3,384 decedents, 2,293 were classified as dying of, and 1,091 as not dying of BC. Women dying of BC were younger, died less often at home (6.9% v 17.9%), and in chronic care institutions (4.1% v 14.8%), and more often in acute-care beds (69.9% v 57.1%).
This novel way to classify decedents is conceptually based and empirically validated through chart review and impact on distribution of age and place of death.
Journal of Clinical Oncology 03/2006; 24(6):856-62. · 18.37 Impact Factor
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ABSTRACT: To assess the efficacy of intermittent androgen ablation (IAA) in patients with biochemical failure after radiotherapy for prostate cancer.
Thirty-nine patients received a luteinizing hormone-releasing hormone analog every 2 months for a total of 4 doses. IAA was then discontinued if serum prostate-specific antigen (PSA) fell to a normal level with a castrate level of testosterone. Therapy was restarted when the serum PSA level reached > or = 10 ng/mL and was discontinued if hormone resistance or unacceptable toxicity occurred.
Median PSA was 9.1 ng/mL at the time of first IAA. The median time between the first and the second cycles was 20.1 months, decreasing to 15.5 months between the third and fourth cycles. Two patients discontinued the treatment because of severe hot flushes. Four patients developed hormone resistance. With a median follow-up of 56.4 months, 5-year survival is 92.3%. Three patients died of unrelated causes. The incidence of distant metastasis is 6.8%.
The use of IAA seems to be a safe and effective treatment for patients with biochemical failure post radiotherapy and no evidence of metastatic disease. The use of IAA limits hormone-related side effects and health care costs without an apparent increase in the risk for the development of metastatic disease.
International Journal of Radiation OncologyBiologyPhysics 03/2006; 64(3):842-8. · 4.11 Impact Factor
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ABSTRACT: To investigate the clinical improvement observed in patients with advanced cancer and hypoactive delirium after the administration of methylphenidate hydrochloride.
Fourteen patients with advanced cancer and hypoactive delirium were seen between March 1999 and August 2000 at the Palliative Care Day Hospital and the inpatient Tertiary Palliative Care Unit of Montreal General Hospital, Montreal. They were chosen for inclusion in a prospective clinical study on the basis of (1) cognitive failure documented by the Mini-Mental State Examination (MMSE), (2) sleep-wake pattern disturbances, (3) psychomotor retardation, (4) absence of delusions or hallucinations, and (5) absence of an underlying cause to explain the delirium. All patients were treated with methylphenidate, and changes in their cognitive function were measured using the MMSE.
All 14 patients showed improvement in their cognitive function as documented by the MMSE. The median pretreatment MMSE score (maximum score 30) was 21 (mean 20.9, standard deviation [SD] 4.9), which improved to a median of 27 (mean 24.9, SD 4.7) after the first dose of methylphenidate (p < 0.001, matched, paired Wilcoxon signed rank test). One patient died before reaching a stable dose of methylphenidate. In the other 13 patients, the median MMSE score further improved to 28 (mean 27.8, SD 2.4) (p = 0.02 compared with the median MMSE score documented 1 hour after the first dose of methylphenidate). All patients showed an improvement in psychomotor activities.
Hypoactive delirium that cannot be explained by an underlying cause (metabolic or drug-induced) in patients with advanced cancer appears to be a specific syndrome that could be improved by the administration of methylphenidate.
Journal of psychiatry & neuroscience: JPN 03/2005; 30(2):100-7. · 5.34 Impact Factor
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ABSTRACT: In the last 40 years, palliative care has become the standard of care at the end of life. However, there are limited data about the degree of access to such care at the population level.
Using administrative databases, a care-oriented profile score was created to describe the care received during the last 6 months of life for 2,291 women who were dying of breast cancer in the province of Quebec, Canada, during the years 1992 to 1998. The care received was described through indicators of care that would reflect a palliative care philosophy. An ordinal score was developed for comparisons among age groups of women using a proportional odds ordinal regression model.
We found that only 6.9% of women died at home, while 69.6% of them died in acute care beds. While most women (75%) had few indicators indicating provision of palliative care during the last 6 months of life, younger women (< 50 years) were even less likely (odds ratio, 0.70; 95% CI, 0.54 to 0.90) to receive such care compared with middle aged women (50 to 59 years; serving as the reference group), while older women (> 70 years) were more likely (odds ratio, 1.85; 95% CI, 1.49 to 2.29).
Our study indicates that a sizeable proportion of women terminally ill from breast cancer do not have access to palliative care-an issue that health care policy makers may wish to explore further.
Journal of Clinical Oncology 09/2004; 22(17):3458-65. · 18.37 Impact Factor
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Aminah Jatoi,
Kendrith Rowland,
Charles L Loprinzi,
Jeff A Sloan,
Shaker R Dakhil,
Neil MacDonald, Bruno Gagnon,
Paul J Novotny,
James A Mailliard,
Teresita I L Bushey,
Suresh Nair,
Brad Christensen
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ABSTRACT: Studies suggest eicosapentaenoic acid (EPA), an omega-3 fatty acid, augments weight, appetite, and survival in cancer-associated wasting. This study determined whether an EPA supplement-administered alone or with megestrol acetate (MA)-was more effective than MA.
Four hundred twenty-one assessable patients with cancer-associated wasting were randomly assigned to an EPA supplement 1.09 g administered bid plus placebo; MA liquid suspension 600 mg/d plus an isocaloric, isonitrogenous supplement administered twice a day; or both. Eligible patients reported a 5-lb, 2-month weight loss and/or intake of less than 20 calories/kg/d.
A smaller percentage taking the EPA supplement gained >or= 10% of baseline weight compared with those taking MA: 6% v 18%, respectively (P =.004). Combination therapy resulted in weight gain of >or= 10% in 11% of patients (P =.17 across all arms). The percentage of patients with appetite improvement (North Central Cancer Treatment Group Questionnaire) was not statistically different: 63%, 69%, and 66%, in EPA-, MA-, and combination-treated arms, respectively (P =.69). In contrast, 4-week Functional Assessment of Anorexia/Cachexia Therapy scores suggested MA-containing arms experienced superior appetite stimulation compared with the EPA arm, with scores of 40, 55, and 55 in EPA-, MA-, and combination-treated arms, respectively (P =.004). Survival was not significantly different among arms. Global quality of life was not significantly different among groups. With the exception of increased impotence in MA-treated patients, toxicity was comparable.
This EPA supplement, either alone or in combination with MA, does not improve weight or appetite better than MA alone.
Journal of Clinical Oncology 06/2004; 22(12):2469-76. · 18.37 Impact Factor
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ABSTRACT: Methadone, being an N-Methyl-D-Aspartate receptor antagonist, may have a potential role in the treatment of neuropathic pain.
To evaluate the effect of methadone in the treatment of neuropathic pain and to estimate the possible dose ranges needed for pain control.
Methadone was offered as a treatment option to consecutive cancer and noncancer patients with neuropathic pain. Pain intensity was measured by the visual analogue scale (VAS) (0-10 cm where 0 = no pain and 10 = worst possible pain). Mechanical allodynia and paroxysmal (shooting) pain were assessed clinically. All assessments were collected prospectively before treatment and once a stable dose of methadone was reached.
A total number of 18 patients met our inclusion criteria. The mean pretreatment VAS +/- SD was 7.7+/-1.5 cm and this dropped significantly to 1.4+/-1.7 cm on a stable dose of methadone (P<0.0001). Nine of 13 patients (70 %) had a complete resolution of mechanical allodynia and all eight patients (100%) with shooting pain reported a complete response. The median stable dose of methadone was 15 mg per day.
Methadone at relatively low doses seems to be useful in the treatment of neuropathic pain.
Pain research & management: the journal of the Canadian Pain Society = journal de la societe canadienne pour le traitement de la douleur 01/2003; 8(3):149-54. · 1.97 Impact Factor
