2 Minute Medicine Rewind October 1, 2018

Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark: prospective, nationwide cohort study

Worldwide, more than 100 million women use hormonal methods of contraception. Combined oral contraceptives have previously shown an inverse relationship with ovarian cancer risk. However, changes in the formulations of these contraceptives, including decreases in estrogen dosing, as well as the utilization of newer progestogens, necessitates a re-assessment of the effects of combined oral contraceptives being used today. This prospective, nationwide cohort study enrolled and followed up 1,879,227 Danish women age 15 to 49 years, recording their contraceptive type and history (never users, current users or those that had used contraception within the past year, and former users) to investigate the association between contemporary combined hormonal contraceptives and ovarian cancer risk. Researchers found that current or recent use of contraception was associated with a significantly decreased risk of ovarian cancer (RR 0.58, 95% CI 0.49 to 0.68). Former use of contraception was also associated with a significantly reduced risk of ovarian cancer (RR 0.77, 95% CI 0.66 to 0.91). There was a significant decrease with increasing duration of use of the contraception (p<0.001 for trend). No significant difference was seen between risk estimates with varying progestogen contents across contraceptives. There was also a significant decrease in risk associated with progestogen-only contraceptives (RR 0.72, 95% CI 0.55 to 0.95), though investigators noted this may be secondary to previous combined oral contraceptive use and concluded there is insufficient evidence to determine the effects. This study therefore shows that the use of contemporary combined hormonal contraceptives are associated with a reduction in ovarian cancer risk in women of reproductive age.

First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer

The current standard of care for the treatment of advanced small-cell lung cancer (SCLC) includes a regimen of either cisplatin or carboplatin, along with etoposide. Atezolizumab is a monoclonal antibody that targets programmed death ligand 1 (PD-L1). In this phase 3 randomized controlled trial, 403 patients with extensive-stage SCLC who had not previously received treatment were randomized to receive induction and maintenance chemotherapy with etoposide, carboplatin, and either atezolizumab or placebo to investigate the efficacy of atezolizumab when used with carboplatin and etoposide. Patients were treated until it was determined that they had unacceptable side effects, were receiving no clinical benefit, or had disease progression. Researchers found that median overall survival was significantly increased in the group treated with atezolizumab, as compared to the group treated with the current standard-of-care (12.3 months versus 10.3 months, HR 0.70, 95% CI 0.54 to 0.91, p=0.007). The progression-free survival was also significantly increased in the group treated with atezolizumab (5.2 months versus 4.3 months, HR 0.77, 95% CI 0.62 to 0.96, p=0.02). The adverse effects were consistent with previous reports of the safety profile of each individual medication, with the most common grade 3 or 4 adverse effects in the atezolizumab group being anemia, neutropenia, and decreased neutrophil count. Investigators therefore concluded that the addition of atezolizumab to the current standard-of-care for extensive-stage small-cell lung cancer prolongs overall and progression-free survival.

Blinded outcomes and angina assessment of coronary bioresorbable scaffolds: 30-day and 1-year results from the ABSORB IV randomised trial

Coronary bioresorbable vascular scaffolds (BVS) are devices that provide mechanical support, similar to a stent, for approximately 1 year after implantation. These devices subsequently resorb over of the course of several years. While randomized controlled trials initially demonstrated non-inferiority for composite adverse events at 1 year with BVS when compared to metallic drug-eluting stents, one randomized trial reported lower rates of recurrent angina with BVS before the time of its complete bioresorption. These findings, however, have not been replicated. In addition to angina not being a prespecified or adjudicated endpoint in prior trials, this may have been due to a narrow study population not including patients with thrombotic ACS, and suboptimal scaffold implant techniques leading to scaffold thrombosis. In this international randomized controlled trial, (ABSORB IV), 2604 patients with stable coronary artery disease or acute coronary syndromes were randomized to receive either a polymeric everolimus-eluting BVS or a cobalt-chromium everolimus-eluting stent (EES) to establish whether improved BVS implantation technique in an expanded population is non-inferior when compared to contemporary metallic DES with respect to early and late outcomes. Researchers found that at 30 days of follow-up, BVS was non-inferior to EES in terms of the primary end-point of target lesion failure, including target-vessel myocardial infarction, ischemia-driven target-vessel revascularization, or cardiac death (p=0.0244 for non-inferiority). At 1 year of follow-up, BVS was also non-inferior in terms of the primary outcome p=0.0006 for non-inferiority). The rates of angina between the two groups also showed that BVS was non-inferior (p)= 0.008 for non-inferiority). No significant difference was observed with respect to device thrombosis. Investigators therefore concluded that polymeric BVS implanted with optimized technique is non-inferior to metallic DES when comparing rates of target lesion failure at 30 days and 1 year of follow-up.

Phase 2b controlled trial of M72/ASO1E vaccine to prevent tuberculosis

Tuberculosis is the leading infectious cause of death worldwide, responsible for an estimated 1.7 million deaths in 2016. Currently, there is a need for a vaccine to interrupt transmission of infection and prevent active pulmonary disease. This randomized, double-blind, phase 2b trial assigned human immunodeficiency virus (HIV) negative adults with latent mycobacterium tuberculosis infection (n=3573) to receive either two intramuscular doses of the M72/ASO1_E tuberculosis vaccine or receive two intramuscular placebo injections to evaluate M72/AS01 _E in preventing bacteriologically-confirmed pulmonary tuberculosis in this patient population. Researchers found that after a mean of 2.3 years of follow-up, the rate of bacteriologically confirmed active pulmonary tuberculosis, as determined by sputum polymerase chain reaction or mycobacterial culture, was significantly lower in the intervention group (0.3 per 100 person-years versus 0.6 per 100-person years), resulting in an efficacy of 54% (95% CI 2.9% to 78.2%, p=0.03). Adverse reactions were reported at a higher rate in the group treated with the vaccine (67.4% versus 45.4%), but were largely related to injection site reactions and flu-like symptoms. Death and serious adverse events occurred at a similar rate in the two groups. Investigators therefore concluded that the M72/ASO1_E vaccine provide protection for those with latent mycobacterial tuberculosis with an efficacy of 54% in preventing active pulmonary tuberculosis disease.

Association between physician US News and World Report medical school ranking and patient outcomes and costs of care: observational study

Variations in practice patterns among internists has been demonstrated in the past, but it is currently unknown whether or not the ranking, as determined by the US News and World Report, of a physician’s medical school has an effect on patient outcomes or healthcare spending. In this observational study of a random sample of Medicare fee-for-service beneficiaries age 65 years or older, 996,212 admissions treated by 30,322 general internists were followed for patients’ 30-day mortality and re-admission rates. Additionally, the internists’ Medicare Part B spending, adjusted for the patient, physician, and hospital characteristics, was documented. Researchers found that physicians from the top 10 ranked schools, as based on primary care US News and World Report rankings, had lower 30-day re-admission rates, as compared to schools ranked 50 or above (adjusted risk difference 0.4%, 95% CI 0.1% to 0.8%, p=0.005 for trend). Additionally, the physicians from the top 10 schools from primary care rankings spent significantly less through Medicare Part B (adjusted difference $36, 95% CI $20 to $52, p<0.001 for trend). No differences were observed in mortality among patients treated by these groups of physicians. When using US News and World Report research rankings, as opposed to primary care, no significant trends were observed for patient mortality or re-admission, though the lower spending among physicians from top 10 schools was again observed. Investigators therefore concluded that the ranking of a physician’s medical school has no effect on 30-day mortality and little effect on 30-day readmission, although physicians from top-ranked medical schools did account for less healthcare spending.

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