To update the 2005 Cancer Care Ontario practice guidelines for the diagnosis and treatment of adult patients with a suspected or confirmed diagnosis of extradural malignant spinal cord compression (MESCC).
A review and analysis of data published from January 2004 to May 2011. The systematic literature review included published randomized control trials (RCTs), systematic reviews, meta-analyses, and prospective/retrospective studies.
An RCT of radiation therapy (RT) with or without decompressive surgery showed improvements in pain, ambulatory ability, urinary continence, duration of continence, functional status, and overall survival. Two RCTs of RT (30 Gy in eight fractions vs. 16 Gy in two fractions; 16 Gy in two fractions vs. 8 Gy in one fraction) in patients with a poor prognosis showed no difference in ambulation, duration of ambulation, bladder function, pain response, in-field failure, and overall survival. Retrospective multicenter studies reported that protracted RT schedules in nonsurgical patients with a good prognosis improved local control but had no effect on functional or survival outcomes.
If not medically contraindicated, steroids are recommended for any patient with neurologic deficits suspected or confirmed to have MESCC. Surgery should be considered for patients with a good prognosis who are medically and surgically operable. RT should be given to nonsurgical patients. For those with a poor prognosis, a single fraction of 8 Gy should be given; for those with a good prognosis, 30 Gy in 10 fractions could be considered. Patients should be followed up clinically and/or radiographically to determine whether a local relapse develops. Salvage therapies should be introduced before significant neurologic deficits occur.
Several large epidemiological studies in the Nordic countries have failed to confirm an association between age at first birth and breast cancer independent of parity. To assess whether lack of power or heterogeneity between the countries could explain this, a meta-analysis was performed of 8 population-based studies (3 cohort and 5 case-control) of breast cancer and reproductive variables in the Nordic countries, including a total of 5,568 cases. It confirmed that low parity and late age at first birth are significant and independent determinants of breast-cancer risk. Nulliparity was associated with a 30% increase in risk compared with parous women, and for every 2 births, the risk was reduced by about 16%. There was a significant trend of increasing risk with increasing age at first birth, women giving first birth after the age of 35 years having a 40% increased risk compared to those with a first birth before the age of 20 years. Tests for heterogeneity between studies were not significant for any of the examined variables. In the absence of bias, this suggests that several individual Nordic studies may have had too little power to detect the weak effect of age at first birth observed in the meta-analysis.
Age-related macular degeneration, AMD, is the commonest cause of legal blindness in the industrialised world. Epidemiological data suggest that in Denmark more than 80,000 persons suffer impaired vision in at least one eye, because of AMD. More than 4000 are legally blind owing to this disease. AMD has two major phenotypes: wet and dry. Most severe visual losses are caused by wet AMD, where new blood vessels form under the macula. A new treatment of this condition is now available. Photodynamic therapy with verteporfin has been investigated in a double-blind, randomised clinical trial with more than 600 patients. This study has been scrutinised by a Cochrane review, which has recommended criteria for the treatment. For eyes meeting these inclusion criteria, photodynamic therapy can reduce the occurrence of moderate and severe visual loss over a two-year period by more than 60%. It is estimated that around 1000 eyes in Denmark will meet the inclusion criteria for photodynamic therapy.
In order to demonstrate how possible causal relationships are critically evaluated in epidemiologic research, literature on the association between alcohol and breast cancer is reviewed and discussed. A cause can be defined as a factor which, in combination with other factors, known and unknown, is sufficient to produce an effect. Since the hypothesis-generating study was published in 1977, a total of 34 positive and 16 negative studies have been published. Methodological problems, such as chance, bias and confounding, cannot be considered as plausible explanations for the above majority of positive findings. The question of causality was then evaluated using the guidelines developed by Bradford Hill in 1965. Among these, the strength of the association, consistency, temporality, biological gradient and biological plausibility, are the most important. In spite of the relatively weak association and somewhat inconsistent results, it is concluded that alcohol consumption should be considered as a cause of breast cancer. It is estimated that in Norway, between 24 and 180 cases of breast cancer may be attributed to alcohol consumption. Future research should focus on the question of effect-modification and on the possible implications of different patterns of alcohol consumption.
The determinants of personal injury road accidents and their severity are studied by means of generalized Poisson regression models estimated on the basis of combined cross-section/time-series data. Monthly data have been assembled for 18 Norwegian counties (every county but one), covering the period from January 1974 until December 1986. A rather wide range of potential explanatory factors are taken into account, including road use (exposure), weather, daylight, traffic density, road investment and maintenance expenditure, accident reporting routines, vehicle inspection, law enforcement, seat belt usage, proportion of inexperienced drivers, and alcohol sales. Separate probability models are estimated for the number of personal injury accidents, fatal accidents, injury victims, death victims, car occupants injured, and bicyclists and pedestrians injured. The fraction of personal injury accidents that are fatal is interpreted as an average severity measure and studied by means of a binomial logit model.
To provide context in oncology for the significance of the benefits and cost of combined androgen blockade (CAB) in the treatment of advanced prostate cancer.
Canadian drug costs for the survival benefit with CAB in advanced prostate cancer were compared with the costs of benefit with new treatments in advanced non-small-cell lung cancer (NSCLC), metastatic colorectal cancer, and metastatic breast cancer. Clinical toxicities were also compared.
The survival benefit with CAB in advanced prostate cancer appears to be approximately 3 months. The survival benefit with the addition of vinorelbine to cisplatin for the treatment of advanced NSCLC is approximately 2 months, and the survival benefit with the addition of irinotecan to fluorouracil (and leucovorin) for the treatment of metastatic colorectal cancer is approximately 2 to 3 months. The survival benefit with anastrozole or exemestane in advanced breast cancer, or with the addition of trastuzumab to standard chemotherapy in metastatic breast cancer that overexpresses human epidermal growth factor receptor 2 (HER2), is approximately 4 to 5 months. The calculated cost per month of survival benefit with bicalutamide in CAB for prostate cancer is 437 US dollars to 1107 US dollars. The cost per month of survival benefit with vinorelbine for NSCLC is 1241 US dollars and with irinotecan for colorectal cancer is 6812 to 11,214 US dollars. The calculated cost per month of survival benefit with anastrozole for breast cancer is 170 US dollars, for exemestane is 185 US dollars, and the cost per month with the addition of trastuzumab is 5230 US dollars. Vinorelbine and irinotecan are associated with severe grade 3 or 4 clinical toxicities, and an increased frequency of heart failure has been observed when trastuzumab is added to anthracyclines. Anastrozole, exemestane and nonsteroidal antiandrogens are associated with mild to moderate side effects.
The advantages offered by CAB (including the cost per month of survival benefit and minimal associated clinical toxicities) are comparable to the reported advantages of new treatments for other common cancers such as NSCLC, colorectal cancer, and breast cancer.
Pharmacotherapy for anxiety disorders is an active area of research. A variety of drug groups have been shown to be effective in treating many of the anxiety disorders, with selective serotonin reuptake inhibitors (SSRIs) being considered first-line agents for virtually all anxiety disorders. There is a clinical need for alternative drug treatments, as many patients do not achieve a complete response and experience significant adverse effects. The successful use of antiepileptic drugs in mood disorders has led clinicians and researchers to investigate their potential efficacy in other psychiatric disorders, particularly in anxiety disorders. There have been a number of investigations conducted in the form of case reports, case series and open-label trials, suggesting the potential usefulness of antiepileptic drug treatment in a variety of anxiety disorders. More reliable evidence for the use of antiepileptic drugs in anxiety disorders can be gleaned from recent placebo-controlled trials. Thus far, the strongest placebo-controlled evidence has demonstrated the efficacy of pregabalin in treating social phobia and generalised anxiety disorder, while smaller or less robust controlled trials have suggested the potential efficacy of gabapentin in social phobia, lamotrigine in post-traumatic stress disorder, and valproic acid in panic disorder. Antiepileptic drugs may have a place in the treatment of anxiety disorders; however, further investigation is warranted to determine in what circumstances they should be used as monotherapy or as augmenting agents in individuals who are partially or non-responsive to conventional therapy.
One in five Canadians has high blood pressure. The prevalence is as high as 58% in women between the ages of 65 and 74 years. Approximately 40% of stroke cases, 39% of myocardial infarction cases and 28% of end stage renal diseases are attributable to hypertension. Despite the burden that hypertension places on women, the effect of antihypertensive therapy on cardiovascular complications has not been well established. To address this knowledge gap, two meta-analyses with sex-specific results, including the most current randomized, controlled trials to evaluate hypertension treatment, were reviewed. The Individual Data Analysis of Antihypertensive (INDANA) intervention trials group and Quan and colleagues analyzed treatment benefits in 23,000 women and 19,975 men according to subgroup meta-analyses from 12 randomized, controlled trials that compared antihypertensive drug therapy with placebo. The meta-analyses demonstrated a statistically significant treatment benefit for all of the reported clinical outcomes in men of all ages and in black women. In women over the age of 54 years, antihypertensive treatment was associated with a significant reduction of fatal and nonfatal stroke, cardiovascular events and cardiovascular mortality. Overall, there was no significant difference in the relative treatment benefit in women and men; however, the absolute treatment benefit was lower in women than in men. Thus, the number needed to treat for the end points of fatal stroke, nonfatal stroke and cardiovascular events was one- to threefold higher for women than for men. Furthermore, white women between the ages of 30 and 54 years showed no treatment benefit or harm. Data from the 6.7-year follow-up in the Hypertension Detection and Follow-up Program (HDFP) trial suggested that this group of younger women might benefit from a longer duration of treatment. Indications for pharmacological intervention seem quite clear for all subgroups, excluding these younger women. Until further evidence is available for this low risk subgroup, the current recommendations for lifestyle modification cannot be challenged.