2 Minute Medicine Rewind July 8, 2019

2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: long-term follow-up of a multicentre, randomised trial

The ideal surgical excision margin for patients with thick (>2 mm) localized cutaneous melanomas is unclear, where the risk of recurrence must be weighed against excess morbidity resulting from larger skin defects with wide excision. In this randomized controlled trial, 936 clinically staged patients were recruited and randomly assigned to a 4-cm (n=465) or 2-cm excision margin (n=471) and followed up for a median of 19.6 years to compare melanoma-specific and overall survival. Researchers found that the overall death rate was highest during the first 5 years of follow-up, and comparable between groups. Over the course of the follow-up period 621 deaths were reported, where there were 304 deaths (49%) in the 2-cm group and 317 deaths (51%) in the 4-cm group (HR 0.98, 95% CI 0.83 to 1.14, p=0.75). Of these deaths, 397 were attributed to cutaneous melanoma, with 192 deaths (48%) occurring in the 2-cm excision margin group and 205 deaths (52%) in the 4-cm excision margin group (HR 0.95, 95% CI 0.78 to 1.16, p=0.61). This study therefore shows that a 2-cm excision margin in patients with thick, localized cutaneous melanoma confers similar melanoma-specific and overall survival when compared to a more extensive 4-cm excision margin. This has important implications in mitigating the morbidity associated with surgical management of melanoma.

Disclosure of infant unsafe sleep practices by African American mothers in primary care settings

African American infants from low socioeconomic backgrounds remain at an increased risk of sleep-related death. In this study, 46 African American mothers were surveyed on their infants’ sleep practices on 3 different encounters on the same day, specifically during a well-baby visit with the pediatrician, safe sleep discussion with a health educator, and with a research assistant, to assess disclosure rates for unsafe sleep practices. With the pediatrician, participants were asked to provide a comprehensive medical history in addition to infant examination in keeping with professional guidelines. This included the provision of age-appropriate anticipatory guidance topics, such as safe sleep. During the encounter with the research assistant, participating mothers were asked about co-sleeping, sleeping with objects (i.e. blanket, wedge, pillow), whether their infant was put to sleep on the side of stomach, or slept on an adult bed. The mean age of participating mothers was 26 years (SD 5.6 years). The majority of participants (91%) had received or applied for medical assistance, and 46% had some schooling experience beyond high school. Researchers found that mothers disclosed unsafe sleep practices more often to the research assistant (30%) than to the health educator (13%) or pediatrician (0%). Researchers attributed these differences in disclosures rates to the number and specificity of questions asked. In light of the persistently high rates of infant sleep-related deaths in this patient population, this points to a need for increased clinician education on sleep practices, as part of emphasizing sleep safety.

Association between androgen deprivation therapy use and diagnosis of dementia in men with prostate cancer

Androgen deprivation therapy (ADT) is used in the treatment of prostate cancer, either alone or in combination with other treatment modalities. ADT, however, is not without long-term effects, with patients commonly experiencing sexual dysfunction, in addition to conferring an increased risk of cardiovascular events. ADT exposure may also increase the risk of cognitive dysfunction. In this retrospective cohort study, 154,089 elderly men diagnosed with prostate cancer (1996-2003) were identified through the National Cancer Institute’s Surveillance, Epidemiology and End Results-Medicare linked database, and followed up to assess the association between ADT exposure and the diagnosis of Alzheimer disease or dementia in this patient population. Researchers found that ADT exposure was associated with a diagnosis of Alzheimer’s disease (difference 3.7%, 95% CI 3.3% to 3.9%, p<0.001; HR 1.20, 95% CI 1.17 to 1.24) and dementia (difference 5.8%, 95% CI 5.4% to 6.2%, p <0 .001; HR, 1.20, 95% CI 1.17 to 1.24). Based on survival analyses, there was also evidence of a dose-dependent association, where the time to outcome was relatively decreased in patients that received 1 to 4 doses of ADT (HR 1.19, 95% CI 1.15 to 1.24 for Alzheimer disease; HR 1.19, 95% CI 1.15 to 1.23 for dementia) compared to those that received 5 to 8 doses of ADT (HR 1.28, 95% CI 1.22 to 1.35 for Alzheimer disease; HR 1.24, 95% CI 1.19 to 1.29 for dementia). This study therefore shows that in elderly patients with prostate cancer, ADT exposure may be associated with an increased risk of Alzheimer’s disease or dementia in later life.

Trends in diverting loop ileostomy vs. total abdominal colectomy as surgical management for Clostridium Difficile colitis

Fulminant Clostridium difficile colitis (FCDC) is a major complication of C. difficile colitis that has not responded to non-invasive interventions, and is ultimately treated with laparotomy, total abdominal colectomy (TAC), and end-ileostomy. Diverting loop ileostomy and colonic lavage, however, represents another surgical option in the management of FCDC, with prior studies suggesting a lower associated mortality when compared to TAC. In this retrospective cohort study, 2408 patients who underwent surgery for C. difficile colitis (2011-2015) were followed up to compare outcomes of diverting loop ileostomy versus abdominal colectomy in the management of FCDC. Overall, 613 patients (20.28%) underwent diverting loop ileostomy without TAC. Over the course of the study period, the annual proportion of patients undergoing diversion increased from 11.6% in 2011 to 25.30% in 2015. Rates of in-hospital mortality did not significantly differ between the two groups (p=0.28). There was also no difference observed in the length of stay when comparing the two groups (p=0.99). Of note, however, there were higher rates of operative wound disruption (p=0.04) and surgical site infection (p=0.01) in patients that underwent diverting loop ileostomy, as compared to TAC. This study shows no significant difference in mortality rate between diverting loop ileostomy and TAC in the management of FCDC on retrospective analysis, and as such, the former may represent a reasonable surgical alternative to TAC. The increased risks of surgical site infection and wound disruption with diverting loop ileostomy, however, should be considered as well as differences in patient selection.

Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial

In this randomized controlled trial, 605 patients with moderate-to-severe chronic plaque psoriasis were assigned to receive 150 mg risankizumab subcutaneously at weeks 0 and 4, or 80 mg of adalimumab subcutaneously, and then 40 mg at weeks 1, 3, 5 and every other week thereafter during a 16-week treatment period to evaluate the efficacy and safety of risankizumab compared with adalimumab in this patient population. After 16 weeks, adalimumab intermediate responders were re-randomized to receive either continue 40 mg adalimumab or to switch to 150 mg risankizumab. Researchers found that at 16 weeks of follow-up, a 90% reduction in Psoriasis Area and Severity Index (PASI-90) was achieved in 72% of patients in the risankizumab group and in 47% of patients given adalimumab (difference 24.9%, 95% CI 17.5% to 32.4%, p<0.0001). In addition sPGA (static Physician Global Assessment) scores of 0 or 1 were achieved in 84% of patients given risankizumab, compared to 60% of patients in the adalimumab group (difference 23.3%, 95% CI 16.6% to 30.1%, p<0.0001). In the second part of the study, PASI-90 was observed in 66% of patients that switched to risankizumab versus 21% of patients that continued with adalimumab at 44 weeks of follow-up (difference 45.0%, 95% CI 28.9 to 61.1%, p<0.0001). The incidence of adverse events was comparable between groups. This study therefore shows that risankizumab demonstrates significantly greater efficacy compared to adalimumab in patients with moderate-to-severe plaque psoriasis, with comparable safety profile.

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