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.
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.
Long-term institutionalization is no longer the preferred treatment for the severely mentally ill. Several models for outpatient treatment of the severely mentally ill have been developed, among them Assertive Community Treatment (ACT). The literature on this model is reviewed in a Cochrane review and in randomized trials comparing ACT with hospital admission. ACT is a clinically effective approach to managing the care of severely ill people in the community. ACT, if correctly targeted on high users of in-patient-care, can substantially reduce costs of hospital care whilst improving outcome and patient and relatives satisfaction. Setting up ACT teams should be supported by politicians, professionals and consumers.
We reported earlier that two mitochondrial gene polymorphisms, UCP2 -866 G/A (rs659366) and mtDNA nt13708 G/A (rs28359178), are associated with multiple sclerosis (MS). Here we aim to investigate whether these functional polymorphisms contribute to other eight chronic inflammatory diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Wegener' granulomatosis (WG), Churg-Strauss syndrome (CSS), Crohn's disease (CD), ulcerative colitis (UC), primary sclerosing cholangitis (PSC) and psoriasis. Compared with individual control panels, the UCP2 -866 G/A polymorphism was associated with RA and SLE, and the mtDNA nt13708 G/A polymorphism with RA. Compared with combined controls, the UCP2 -866 G/A polymorphism was associated with SLE, WG, CD and UC. When all eight disease panels and the original MS panel were combined in a meta-analysis, the UCP2 was associated with chronic inflammatory diseases in terms of either alleles (odds ratio (OR)=0.91, 95% confidence interval (95% CI): 0.86-0.96), P=0.0003) or genotypes (OR=0.88, (95% CI: 0.82-0.95), P=0.0008), with the -866A allele associated with a decreased risk to diseases. As the -866A allele increases gene expression, our findings suggest a protective role of the UCP2 protein in chronic inflammatory diseases.
Apolipoprotein E (APOE) genotypes are associated with cardiovascular disease (CVD) and lipid levels. In rheumatoid arthritis (RA), an association has been found with disease activity. We examined the associations between APOE genotypes and disease susceptibility and markers of disease severity in RA, including radiographic joint damage, inflammatory markers, lipid levels and cardiovascular markers.
A Norwegian cohort of 945 RA patients and 988 controls were genotyped for two APOE polymorphisms. We examined longitudinal associations between APOE genotypes and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) as well as hand radiographs (van der Heijde Sharp Score(SHS)) in 207 patients with 10 year longitudinal data. Lipid levels, cardiovascular markers and history of CVD were compared across genotypes in a cross sectional study of 136 patients. Longitudinal radiological data of cohorts from Lund and Leiden were available for replication. (N = 935, with 4799 radiographs).
In the Norwegian cohort, associations between APOE genotypes and total cholesterol (TC) and low-density lipoproteins (LDL) were observed (e2
Cites: Ann Rheum Dis. 2008 Jun;67(6):794-80017981915
Cites: Ann Rheum Dis. 2008 Feb;67(2):212-717526555
Cites: Lancet. 2009 Feb 21;373(9664):659-7219157532
Maternal asthma has been associated with adverse pregnancy outcomes. Little is known about the influence of other atopic diseases on pregnancy outcomes. We assessed how various maternal atopic diseases might affect preterm birth, stillbirth, and neonatal death.
By linking Norwegian national registries, we acquired information on maternal health, socio-demographic factors, pregnancy, birth, and neonatal outcome on all births in Norway from 1967 to 2003.
A total of 1?974?226 births were included. Of these, 1.8% had a record of maternal asthma, 3.4% of maternal atopic dermatitis, and 0.4% of maternal allergic rhinoconjunctivitis. Overall rates of preterm birth, stillbirth, and neonatal death were 6.0%, 0.6%, and 0.5%, respectively. After adjustments for possible confounders, maternal asthma was associated with increased risk of preterm birth (relative risk (RR), 1.15, [95% confidence interval (CI) 1.10, 1.21]). In contrast, maternal atopic dermatitis was associated with decreased risk of preterm birth (RR 0.90, [95% CI 0.86, 0.93]), stillbirth (RR 0.70, [95% CI 0.62, 0.79]), and neonatal death (RR 0.76, [95% CI 0.65, 0.90]). Similarly, maternal allergic rhinoconjunctivitis was associated with decreased risk of preterm birth (RR 0.84, [95% CI 0.76, 0.94]) and stillbirth (RR 0.40, [95% CI 0.25, 0.66]).
We confirmed the previously reported association of maternal asthma with increased risk for preterm birth. Unexpectedly, maternal atopic dermatitis and allergic rhinoconjunctivitis were associated with decreased risk of preterm birth and stillbirth. Mechanisms for these protective associations are unclear, and our findings require confirmation in further studies.