Treatment of chronic pain in osteoarthritis: Do opioids have a clinical role?

Pain is the most prominent symptom and clinical finding in osteoarthritis (OA). Acetaminophen and nonsteroidal anti-inflammatory drug (NSAID) therapy are the mainstays of OA analgesia, but other drug and non-drug therapy, joint injections, and surgery may be needed to provide reasonable quality of life. Regularly scheduled, low-dose opioids can produce good relief of chronic nonmalignant pain including pain caused by OA. This paper reviews the potential risks and benefits of opioids, the evidence supporting their use in OA pain, and guidelines for their use in OA pain.     

Do white matter changes have clinical significance in Alzheimer's disease?

BACKGROUND: Although white matter changes visible with MRI are generally considered to result from ischemia, it has become clear that these changes also appear in patients with Alzheimer's disease (AD). However, their significance in AD is unknown. OBJECTIVE: We evaluated the clinical significance of white matter changes in AD. METHODS: Ninety-six AD patients (79.4 +/- 5.92 years old) and 48 age-matched control subjects (80.0 +/- 7.03 years old) participated in the study. Three neuroradiologists assessed the degree of periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH) using a modified Fazekas' rating scale. We examined whether there was a difference in the severity and the histogram pattern of the white matter changes, or in vascular factors (hypertension, diabetes mellitus, and ischemic heart disease) between the two groups. We also analyzed the association between the severity of the white matter changes and the degree of dementia (MMSE score and disease duration). RESULTS: There were no differences in the vascular factors between AD and control subjects. The degree of PVH in AD was severe compared with that in the control subjects. In histograms of the number of subjects with each degree of PVH severity, the distribution of AD patients had peaks at both the low and intermediate degrees of PVH, while most of the controls had a low degree of PVH. There was no difference in the degree or the histogram pattern of DWMH between the two groups. The severity of white matter changes was not associated with severity of dementia in AD. CONCLUSIONS: Although PVH might have several causative factors, and may have some clinical significance, the change itself does not contribute to the progression of AD.     

Overview of recent clinical trials in heart failure: what is the current standard of care?

Heart failure develops as a consequence of cardiac injury. As the heart begins to fail to meet the body's metabolic demands, the renin angiotensin aldosterone system (RAAS) and the sympathetic nervous system are activated. These interrelated systems act in concert to facilitate cardiac output and tissue perfusion. Though these neurohormonal systems are initially compensatory, evidence suggests that they promote deleterious cardiac remodeling and myocyte destruction. Recent studies in patients with heart failure have targeted the RAAS and sympathetic nervous system for therapeutic intervention. This article reviews major recent multicenter, randomized, double-blind, and placebo-controlled trials in heart failure that have resulted in a new standard of care for patients with this devastating disease.     

Do the pleiotropic effects of statins have a clinical significance?

The effectiveness of statins in the treatment of hypercholesterolaemia and the reduction in cardiovascular risk have now been clearly demonstrated. While their beneficial effects on the reduction of atherosclerosis and its clinical manifestations occur mainly due to the reduction in LDL-cholesterol, some pleiotropic actions which are independent of LDL-cholesterol have frequently been put forward in recent years. In effect, an improvement in endothelial function (increased vasodilatation in particular), an in vitro reduction in smooth muscle cell proliferation, a reduction in thrombosis, promotion of fibrinolysis and positive effects on atheromatous plaque stabilisation have been observed. Elsewhere, some anti-oxidant and anti-inflammatory properties have been attributed to statins. However, many of the described 'pleiotropic' effects are not due to the direct action of statins, but occur with the reduction in LDL-cholesterol. Furthermore, certain in vitro effects only occur at much higher than therapeutic doses. These considerations have therefore caused doubt about the clinical significance of the statins' pleiotropic effects. Finally, analysis of the results of human clinical trials on statins have proved that their effectiveness relies on the reduction in LDL-cholesterol and that the pleiotropic effects do not actually have a clinical implication.     

Do statins cause cancer? A meta-analysis of large randomized clinical trials

PURPOSE: Although the short-term safety and tolerability of statins has been well established, their potential carcinogenicity in the long term is still debated. The goal of this study was to determine whether long-term treatment with statins is associated with an increased risk of fatal and nonfatal cancers.

METHODS: We searched the Medline database between January 1966 and December 1999 for randomized, controlled trials of human subjects in which monotherapy with a statin was compared with placebo. No language restrictions were applied. Only trials with a minimum treatment duration of 4 years and a minimum of 1,000 subjects were included. Studies that did not provide information on fatal or nonfatal cancers were excluded. Data on fatal and nonfatal cancers and all-cause mortality were extracted by a single nonblinded reviewer. Overall crude estimates of risk difference were computed by summing the numerators and denominators of trial-specific risk estimates.

RESULTS: Five trials met the inclusion criteria. The estimated differences in absolute risk between treatment and placebo were as follows (negative risks indicate that treatment was safer than placebo): all nonfatal cancers, 0.0% (95% confidence interval [CI]: –0.8% to 0.8%); all fatal cancers, –0.1% (95% CI: –0.7% to 0.4%); all fatal and nonfatal cancers combined, –0.1% (95% CI: –1.0% to 0.7%); and all-cause mortality, –1.5% (95% CI: 2.8% to 0.2%).

CONCLUSION: This study demonstrates no association between statin use over a 5-year period and the risk of fatal and nonfatal cancers. This conclusion is limited by the relatively short follow-up of the studies analyzed. Similar analyses of data from studies with longer follow-up periods would be valuable.     

Is it ethical to use placebos in osteoporosis clinical trials?

Because there are now effective agents for treatment of osteoporosis, the question is being raised as to whether or not it is ethical to have placebo-controlled trials of new agents. It is ethical for patients who are at low risk of serious or irreversible harm to participate in placebo-controlled trials as long as they provide informed consent. Morbidity, mortality, and future fracture risk correlate with the presence of previous fractures, the number of previous fractures, whether or not the fracture is recent, and whether or not the fracture is clinically recognized. Lower-risk subjects who may be allowed to participate in placebo-controlled trials include those with low bone density but without a previous vertebral fracture, those with a single vertebral deformity that was not clinically recognized, and those with a vertebral fracture more than 2 years before. Higher-risk subjects who do not tolerate proven drugs or who have not responded to proven drugs may also participate. Even though it may be ethical for selected subjects to participate in placebo-controlled trials of new therapies for osteoporosis, steps should be taken to minimize their exposure (eg, unbalanced randomization, integration of outcomes, and powering trials to actual events rather than a projected number over 3 years), and treating patients who fracture or who fail to respond.     

Do young patients have different clinical presentation of colorectal cancer causing delay in diagnosis?

Purpose

The incidence of colorectal cancer is increasing among young patients. In these patients, colorectal cancer is believed to have a poorer prognosis because it is more aggressive and diagnosed at later stages; however, the behavior of these tumors in young patients remains to be elucidated. We investigated the impact of time interval between onset of symptoms and diagnosis (TISD) at the pathologic stage of colorectal cancer in young patients.

Methods

The medical records of 215 patients with colorectal adenocarcinoma were reviewed. Patients were divided into two groups according to age. The young group (age?<?50 years) consisted of 66 patients, and the older group (age?≥?50 years) of 149 patients. Clinical variables, TISD, pathologic stage, operative mortality, and oncologic outcomes were compared between groups.

Results

The older group had less abdominal pain (74.0 vs. 56.0 %, p?=?0.0129). In multivariate analysis, the following variables were independently associated with tumor pathologic stage: personal history of inflammatory bowel disease (p?<?0.0001), family history of familial adenomatous polyposis (p?=?0.00100), and smoking (p?=?0.0070). Both groups had similar rates regarding pathologic stage (I, 15 vs. 22 %; II, 22 vs. 24 %; III, 27 vs. 16 %; IV, 37 vs. 38 %, p?=?0.3380). There was no difference in overall survival [45 (69 %) vs. 84 (61 %), p?=?0.2482] and cancer-free survival [36 (63 %) vs. 83 (62 %), p?=?0.9218] between groups.

Conclusions

Young patients with colorectal cancer had clinical and pathological presentation similar to that of older patients.     

Is stroke unit care portable? A systematic review of the clinical trials

BACKGROUND: It is not known if mobile stroke teams can achieve the good results seen in trials of geographically discrete stroke wards (stroke units). OBJECTIVE: To establish the effectiveness of mobile stroke teams. DESIGN: Systematic review of controlled clinical trials that compared peripatetic systems of organised stroke care (stroke team care) with alternative hospital services. METHODS: Systematic review and meta-analysis (using Cochrane Collaboration methodology and involving the primary trialists).Clinical outcomes included death, dependency, the need for institutional care and measures of the process of care such as the delivery of key investigations and treatments. RESULTS: Six clinical trials (1,085 patients) were identified; five (781 patients) compared some form of stroke team care with conventional care in general medical wards and one (304 patients) compared team care with a comprehensive stroke unit.Compared with care in general wards, stroke team care improved some aspects of the process of care, but clinical outcomes were similar. Compared with a comprehensive stroke unit, stroke team patients were significantly less likely to survive (P <0.001), return home (P < 0.001) or regain independence (P < 0.0001). Most aspects of the process of care were also poorer than in the stroke unit. CONCLUSIONS: Care from a mobile stroke team had no major impact on death, dependency or the need for institutional care.