2 Minute Medicine Rewind October 17, 2016

A population-based study of cardiovascular mortality following early-stage breast cancer

The disease-specific survival for women treated for early-stage breast cancer (EBC) has improved substantially. However, there is overlap between risk factors for breast cancer and cardiovascular disease, and treatments for the former have been associated with adverse cardiovascular effects. In this population-based cohort study, 98,999 women diagnosed with EBC were followed up to determine the incidence of cardiovascular-related death in this patient population. Among the women that formed the cohort, 43.2% were younger than 66 years with no prior cardiovascular disease, diabetes or hypertension. Researchers found that breast cancer was the most common cause of death, accounting for 49.9% of all deaths in the cohort. However, cardiovascular disease accounted for 16.3% of all deaths in the cohort, with 89.6% of these deaths occurring among women age 66 years and older at the time of breast cancer diagnosis. Among women age 66 years and older, the risk of breast cancer death and cardiovascular death at 10 years were 11.9% (95% CI 11.6% to 12.3%) and 7.6% (95% CI 7.3% to 7.9%), respectively. In addition, among patients with prior cardiovascular disease, the risk of death from breast cancer and cardiovascular disease were nearly equivalent for the first 5 years at 12.4% and 12.6%, respectively, after which deaths from cardiovascular causes were more frequent. Specifically, the 10-year cumulative incidence of cardiovascular-related death was 16.9% (95% CI: 16.0% to 17.8%) compared to 14.6% (95% CI: 13.7% to 15.4%) for breast-cancer-related death. In women age 66 years and older that survived 5 years or more after being diagnosed with breast cancer, cardiovascular disease exceeded breast cancer as the leading cause of death at 10 years after diagnosis. This study therefore shows that cardiovascular death is an important competing risk for older women with EBC and women with a prior history of cardiovascular disease. The identification of women with EBC that may benefit from cardiovascular disease prevention strategies may attenuate the risk of cardiovascular-related outcomes in this patient population.

A randomized, controlled trial of ZMapp for Ebola virus infection

Data from studies in non-human primates have suggested that the triple monoclonal antibody cocktail ZMapp may represent a promising immune-based treatment for Ebola virus disease (EVD). In this randomized controlled trial, 72 patients with EVD were randomized to receive 3 intravenous infusions of ZMapp in addition to the current standard of care, or current standard of care alone. Researchers found that, of the 71 patients who could be evaluated, 21 died, representing an overall case fatality rate of 30%. Specifically, death occurred in 13 of 35 patients (37%) who received the current standard of care alone, compared to 8 of 36 patients (22%) who received ZMapp. These differences in mortality rate corresponded to a 91.2% posterior probability that ZMapp plus the current standard of care was superior to current standard of care alone. This was, however, below the pre-specified probability threshold (97.5%) for declaring superiority of the investigational treatment. Subgroup analyses defined according to age, geographic location of enrollment and baseline viral load (cycle-threshold value) also demonstrated mortality differences favoring ZMapp recipients. This study therefore shows that ZMapp may be beneficial in the treatment of EVD, although its estimated effect did not meet the pre-specified statistical threshold for efficacy.

Chronic kidney disease progression and cardiovascular outcomes following cardiac catheterization – a population-controlled study

Acute kidney injury (AKI) following a percutaneous coronary intervention (PCI) is a serious procedure-related complication. In this retrospective cohort study, 24,405 patients undergoing PCI were followed up and compared to 24,405 matched population controls, to examine the association between PCI, AKI and chronic kidney disease (CKD) progression using laboratory data. Cardiac catheterization-associated AKI (CCA-AKI) was defined as an absolute creatinine of 0.5mg/dL or greater, a relative increase of 25% or more from the last serum creatinine, or new onset of dialysis up to 7 days post-PCI. Researchers found that the incidence of CKD progression following PCI complicated by CCA-AKI, following uncomplicated coronary interventions, and in matched controlled was 28.66, 11.15 and 6.81 per 100-person-years, respectively. PCI also increased the likelihood of CKD progression, both in the presence of AKI (HR 5.02, 95% CI: 4.68 to 5.39) and in the absence of AKI (HR 1.76, 95% CI: 1.70 to 1.86) when compared to controls. Researchers also found that, compared to controls, PCI complicated by CCA-AKI increased the likelihood of dialysis over 5 years by nearly 8-fold (HR 7.83, 95% CI: 6.24 to 9.83, p<0.001). PCI uncomplicated by overt CCA-AKI increased this risk by over 2-fold (HR 2.15, 95% CI: 1.72 to 2.68, p<0.001). This study therefore shows that CCA-AKI after PCI is associated with increased chronic kidney development.

Orthostatic hypotension and the long-term risk of dementia: a population-based study

Orthostatic hypotension (OH) is a common cause of transient cerebral hypoperfusion, associated with subclinical brain disease and an increased risk of stroke. In this prospective cohort study, 6204 community-dwelling adults age 55 years and older were followed up to determine the association between OH and the risk of developing dementia in the general population. OH was defined as a drop in systolic blood pressure (SBP) or 20 mmHg or more, or a drop in diastolic blood pressure (DBP) of 10 mmHg or more, within 3 minutes from postural change. Researchers found that OH was associated with an increased risk of dementia (HR 1.15, 95% CI: 1.00 to 1.34, p = 0.05). Greater SBP variability with postural change was also associated with an increased risk of dementia (HR 1.08, 95% CI: 1.01 to 1.16, p = 0.02). The risk of dementia was particularly increased among individuals with OH that lacked a compensatory increase in heart rate (HR for lowest quartile of heart rate response 1.39, 95% CI 1.04 to 1.85, p-interaction = 0.05). This study therefore shows that transient cerebral hypoperfusion or OH may be associated with an increased risk of developing dementia.

Receipt of antibiotics in hospitalized patients and risk for Clostridium difficile infection in subsequent patients who occupy the same bed

Clostridium difficile infection (CDI) is the most common cause of diarrhea in hospitals, associated with significant morbidity and mortality in susceptible patients. Exposure to C. difficile is common in the hospital as spores are capable of persisting in the environment for months. In fact, C. difficile can be readily cultured from the beds, bed rails, floors and walls of hospital rooms where prior occupants have had CDI. While it is known that the most important host-related risk factor for CDI is exposure to antibiotics, it is uncertain how antibiotics or other CDI risk factors in a given patient increase the risk for CDI in another patient that subsequently shares the same hospital environment. In this retrospective cohort study, 100,615 pairs of patients who sequentially occupied a given hospital bed were studied to assess whether the receipt of non-CDI antibiotics by prior hospital bed occupants is associated with increased risk for CDI in subsequent patients who occupy the same bed. Researchers found that the receipt of antibiotics in prior patients was significantly associated with incident CDI in subsequent patients (p < 0.01). Based on the final multivariate analysis conducted for this study, this was also the only prior bed occupant risk factor that was significantly associated with CDI in subsequent patients (HR 1.22, 95% CI 1.02 to 1.45). The relationship between the receipt of antibiotics by prior patients and risk for CDI in subsequent patients remained unchanged in a sensitivity analysis where pairs in which the prior patient had recent CDI were excluded (HR 1.20, 95% CI: 1.01 to 1.43). Subsequent patient risk factors that emerged as significant in the multivariate analysis included the receipt of antibiotics (HR 4.20, 95% CI 3.52 to 5.02), the presence of a contemporaneous patient with CDI on the ward (HR 3.99, 95% CI 3.31 to 4.81), receipt of acid suppression medications (HR 2.14, 95% CI 1.75 to 2.61), and hospitalization in the ICU (HR 1.94, 95% CI 1.57 to 2.40). This study therefore shows that the receipt of antibiotics by prior bed occupants is associated with an increased risk for CDI in subsequent patients.

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