2 Minute Medicine Rewind February 6, 2017

Intra-articular corticosteroids versus intra-articular corticosteroids plus methotrexate in oligoarticular juvenile idiopathic arthritis: a multicentre, prospective, randomised, open-label trial

Juvenile idiopathic arthritis (JIA) is a heterogeneous disease and a major cause of acquired disability. It is sub-classified on the basis of clinical and laboratory features presenting in the first 6 months of illness, with oligoarticular JIA being defined as an arthritis affecting four or fewer joints during the first 6 months of illness. In this subgroup, structural joint damage is frequent and the probability of remission is low. While intra-articular corticosteroid injections are widely used in the management of oligoarticular JIA, this induces only short-term relief of inflammatory symptoms, obviating a need for regular systemic therapy. On the basis of randomized controlled trials, methotrexate has been used in the management of patients with polyarthritis, with use in oligoarticular JIA reserved for those that fail to respond to non-steroidal anti-inflammatory drugs (NSAIDs) or intra-articular steroids. In this randomized controlled trial, 207 children with oligoarticular JIA were randomized to receive intra-articular corticosteroids and methotrexate or intra-articular corticosteroids alone to assess whether the concomitant administration of methotrexate augments the rate and duration of arthritis remission. Based on an intention-to-treat analysis, researchers found that the proportion of patients achieving remission of arthritis in all injected joints at 12 months was comparable between the two treatment arms, with 39% of patients assigned to the methotrexate and intra-articular corticosteroids group and 34% of patients assigned to the control group achieving these outcomes (p = 0.48). This study therefore shows that concomitant administration of methotrexate does not augment the effectiveness of intra-articular corticosteroid therapy in patients with oligoarticular JIA.

Association between mentally stimulating activities in late life and the outcome of incident mild cognitive impairment, with an analysis of the APOE genotype

Few studies have investigated whether cognitive activities are related to the outcome of mild cognitive impairment (MCI), the intermediate zone between normal cognitive aging and dementia. In this population-based cohort study, 1,929 cognitively normal individuals ages 70 years and older were followed up to assess whether an association exists between mentally stimulating activities in late life and the risk of incident MCI. As apolipoprotein E (APOE) carrier status is a well-known risk factor for MCI and dementia, the authors also conducted a stratified analysis by APOE genotype. Over a median follow-up time of 4.0 years, researchers found that playing games (HR 0.78, 95% CI 0.65 to 0.95), engaging in craft activities (HR 0.72, 95% CI 0.57 to 0.90), computer use (HR 0.70, 95% CI 0.57 to 0.85) and social activities (HR 0.77, 95% CI 0.63 to 0.94) were associated with a decreased risk of incident MCI. Upon stratifying research participants by APOE carrier status, non-carriers of the genotype that engaged in craft activities (HR 0.65, 95%CI 0.49 to 0.85) and computer use (HR 0.73, 95% CI 0.58 to 0.93) had a significantly decreased risk of incident MCI. Conversely, among APOE carriers, those that engaged in computer use (HR 0.65, 95% CI 0.46 to 0.92) and social activities (HR 0.62, 95% CI 0.43 to 0.89) had a decreased risk of incident MCI. Patients at highest risk of incident MCI among APOE carriers were those who do not engage in mentally stimulating activities. This study therefore shows that older adults with normal cognitive status may decrease their risk of incident MCI by engaging in mentally-stimulating activities in later life.

Promoting end-of-life discussions in advanced cancer: effects of patient coaching and question prompt lists

Patients are often misinformed regarding their cancer survival and curability. As a result, those with over-optimistic prognosis estimates are more likely to die in hospital and receive futile care towards the end of life. This occurs despite most patients indicating that they desire honest communication surrounding end-of-life issues. Much of this discord is likely the result of patients not disclosing their concerns or indicating how much information they want to know about their disease, prognosis and treatment options, but also physicians not knowing or enacting patient preferences around these issues. Randomized controlled trials have shown that question prompt lists (QPLs) help patients and their caregivers ask more questions. However, there have been no randomized trials to date evaluating interventions directed towards both oncologists and their patients with advanced cancer who are not yet receiving palliative or hospice care. In this cluster randomized controlled trial, 170 patients with advanced cancer received either a pre-visit individualized communication coaching session incorporating a QPL, or no intervention, with oncologists in the intervention group also receiving individualized communication training. The goal of this study was to determine how the intervention affects the number and nature of topics brought up during an oncology office visit. The QPL used in the study was adapted from a QPL designed for patients with cancer in palliative care. Researchers found patients and caregivers in the intervention group were significantly more likely to bring up QPL-related topics during their audio-recorded oncology visit compared to controls (70.2% vs. 32.6%, p<0.001). The most commonly selected QPL-related topics were about cancer treatment, current cancer state and concerns or preferences about care at the end of life. Patients in the intervention group were more also more likely to ask about prognosis (16.7% vs. 5.8%, p=0.03). This study therefore shows that a combined coaching and QPL intervention effectively assists patients with advanced cancer identify and discuss topics of concern during oncology visits.

Radiation with or without antiandrogen therapy in recurrent prostate cancer

Over 30% of patients that undergo radical prostatectomy for localized prostatic cancer experience biochemical recurrence, signaled by a rising serum level of prostate-specific antigen (PSA). Radiation therapy and either androgen-deprivation therapy or antiandrogen therapy prolongs survival among some men with an intact prostate. In this randomized, double-blind trial, 760 patients that had undergone radical prostatectomy were randomized to receive salvage radiation therapy and antiandrogen therapy or radiation therapy alone, to determine whether the addition of antiandrogen therapy prolongs overall survival. Antiandrogen therapy consisted of bicalutamide 150 mg daily. Researchers found that the actuarial rate of overall survival at 12 years was 76.3% in the bicalutamide group, compared to 71.3% in the radiation-only group (HR 0.77, 95% CI 0.59 to 0.99, two-sided p = 0.04). The 12-year mortality rate due to prostate cancer was 5.8% in the bicalutamide group, compared to 13.4% in the placebo group (HR 0.49, 95% CI 0.32 to 0.74, p<0.001). Furthermore, the cumulative incidence of distant metastases at 12 years was 14.5% in the bicalutamide group, as compared with 23.0% in the placebo group (HR 0.63, 95% CI 0.46 to 0.87, p<0.005). The cumulative incidence of a second biochemical recurrence at 12 years was 44.0% in the bicalutamide group, compared to 67.9% in the control group (HR 0.48, 95% CI 0.40 to 0.58, p<0.001). This study therefore shows that the addition of 24 months of antiandrogen therapy with bicalutamide to salvage radiation therapy results in significantly higher rates of long-term survival, with lower incidences of metastatic prostate cancer and death from prostate cancer when compared to radiation therapy alone.

Comparative Effectiveness and Risks of Bowel Preparation Before Elective Colorectal Surgery

Surgical site infection (SSI) is the most common hospital-acquired infection, representing a significant source of postoperative morbidity. Elective colorectal resections, in particular, are associated with high rates of SSI. Recognizing this, mechanical bowl preparation (MBP) has long been used to decrease fecal mass within the large bowel to, theoretically, decrease bacterial load within the operative field. However, numerous studies have shown and continue to show that MBP does not in fact bacterial load or SSI rates. In this cohort study, 32,359 patients undergoing elective colorectal resections were followed up to determine relative effectiveness of MBP, oral antibiotics (OA), and MBP + OA in reducing SSI. Consistent with previous studies, researchers found that MBP was not associated with a decreased risk of SSI when compared to no bowel preparation (p=0.10). In contrast, researchers found that patients that received MBP and OA (OR 0.45, 95% CI 0.40 to 0.50), or OA alone (OR 0.49, 95% CI 0.38 to 0.64) had a decreased risk of SSI when compared to patients that received no bowel preparation. Patients that received OA and MBP, or OA alone, were also less likely to experience anastomotic leaks, postoperative ileus, readmission, and had shorter lengths of hospital stay (p<0.05). This study therefore shows that MBP + OA and OA alone confer decreased risks of SSI without increased risk of other adverse outcomes, when compared to no bowel preparation. This is contrast to the use of MBP alone, which continues to prove ineffective in preventing SSI.

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