2 Minute Medicine Rewind May 16, 2016

Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study

Numerous studies have shown that women using combined oral contraceptives are at an increased risk of venous thromboembolism. This risk varies according to the type of progesterone, and is increased with higher estrogen dose and in long-term users. While the risk of stroke and myocardial infarction should also be taken into account when selecting the most appropriate oral contraceptive, few studies have examined this relation. In this large cohort study, 4,945,088 French women age 15-49 years using oral contraceptives were followed to quantify the risk of pulmonary embolism, ischemic stroke and myocardial infarction associated with 8 oral contraceptives, with varying doses of estrogen and progesterone. Women were identified using the national health insurance database, and followed up using data from the linked hospital discharge database. Researchers found that adjusting for the type of progesterone, age and other medical risk factors, women using an oral contraceptive with a low-dose estrogen (20 mg) were less likely to experience pulmonary embolism (RR 0.75, 95% CI 0.67 to 0.85), ischemic stroke (RR 0.82, 95% CI 0.70 to 0.96) or myocardial infarction (RR 0.56, 95% CI 0.39 to 0.79), compared to women receiving a higher dose of estrogen (30-40 mg). In comparing different types of progesterone (levonorgestrel, desogestrel, gestodene), researchers found that relative to levonorgestrel, the risk of pulmonary embolism, but not ischemic stroke or myocardial infarction was increased in women using desogestrel (RR 2.16, 95% CI 1.93 to 2.41), orgestodene (RR 1.63, 95% CI 1.34 to 1.97). This study therefore shows that, among women using oral contraceptives, the risk of experiencing a serious thromboembolic event is decreased in those on a lower dose of estrogen. This risk can be further reduced by selecting combined oral contraceptives with levonorgestrel, as the use of other forms of progesterone (i.e. desogestrel, gestodene) also confer a higher risk of pulmonary embolism.

Association of environmental contamination in the home with the risk for recurrent community-associated methicillin-resistant Staphylococcus aureus infection

Over the last several decades, the number of methicillin-resistance Staphylococcus aureus (MRSA) infections in community settings has increased dramatically. While most infections involve the skin and soft tissues, 5-10% of infections are life threatening. Interestingly, studies have indicated that the household is the primary reservoir for S. aureus in the community. As such, environmental contamination has been increasingly recognized for its possible role in S. aureus transmission and infection within households. In this prospective cohort study, 82 patients with skin or soft tissue infection, as well as positive cultures (blood, urine or sputum) for MRSA were followed-up to determine whether environmental contamination of the household increases the risk of recurrent infection among individuals with a community acquired MRSA infection. In all households, a standardized list of environmental items (i.e. door knobs, toilet seats, kitchen appliance handles) were sampled through swabbing. Researchers found that among the 82 households in which a patient had an index MRSA infection, the clinical isolate was present in the environment in 20 (24.4%) and not found in 62 (75.6%). Over the course of follow-up, 35 patients (42.7%) reported a recurrent infection. In examining household exposure, researchers found that 13 recurrent infections were from the 20 households with environmental contamination (65.0%), while the remaining 22 recurrent infections came from the 62 (35.5%) households without environmental contamination. In other words, environmental contamination increased the rate of index recurrent infection (incident rate ratio (IRR) 2.05, 95% CI 1.03 to 4.10, p = 0.04). This study therefore shows that household environmental contamination is associated with an increased risk of recurrent MRSA infection. As such, environmental decontamination should be considered in the prevention of future MRSA infections, particularly among households where an infection has occurred.

Ticagrelor versus aspirin in acute stroke or transient ischemic attack

Patients that have experienced ischemic stroke or a transient ischemia attack (TIA) are at a high risk of experiencing subsequent ischemic events in the 90 days following an index event. While aspirin has been historically used in the prevention of secondary ischemic stroke, studies have shown that aspirin confers limited benefit to these patients. In addition, even moderate doses of aspirin are associated with an increased risk of hemorrhage events, including gastrointestinal bleeding. Ticagrelor is a potent antiplatelet that reversibly binds and inhibits the P2Y12 receptor on platelets and is direct-acting. In this randomized controlled trial, 13,199 patients that experienced a non-severe ischemic stroke or high-risk TIA, and had not been administered thrombolysis were randomized to receive either ticagrelor (90 mg twice daily for 90 days) or aspirin (100 mg daily for 90 days) to determine whether ticagrelor can be used to effectively prevent major vascular events (stroke, myocardial infarction or death) in patients with acute cerebral ischemia. Researchers found that over the course of 90 days, 6.7% and 7.5% of patients in the ticagrelor and aspirin groups experienced a major vascular event, respectively (HR 0.89, 95% CI 0.78 to 1.01, p=0.07). In addition, when assessing rates of ischemic stroke specifically, researchers found that patients receiving ticagrelor did not confer a significant benefit compared to patients treated with aspirin (HR 0.87, 95% CI 0.76 to 1.00). Similar rates of major bleeding, intracranial hemorrhage and fatal bleeding were noted between the two treatment arms. This study therefore shows that ticagrelor may not be superior to aspirin in reducing the rate of stroke, myocardial infarction or death at 90 days.

Association between artificially sweetened beverage consumption during pregnancy and infant body mass index

Over 20% of preschool children are considered overweight or obese, indicating the presence of important risk factors for obesity in early life. In recognizing the relationship between high sugar intake and obesity, sugar replacements or non-nutritive sweeteners (NNS) have become increasingly popular. Paradoxically, a growing body of literature suggests that chronic NNS consumption may increase the risk of obesity and metabolic diseases. Little, however, is known about the effect of NNS exposure during pregnancy on offspring. In this cohort study, 2413 mother-infant dyads from the Canadian Healthy Infant Longitudinal Development (CHILD) Study were followed up to determine whether maternal consumption of artificially-sweetened beverages during pregnancy, based on a food frequency questionnaire, is associated with infant body mass index (BMI). Researchers found that 29.5% of the women forming the cohort consumed artificially sweetened beverage during pregnancy. Compared to women who consumed less than 1 artificially sweetened beverage per month, daily consumption was associated with a 0.20-unit increase in infant BMI z-score (95% CI 0.02 to 0.38). Infants born to mothers who consumed artificially sweetened beverages daily were also more likely to be overweight at 1 year of age (OR 2.19, 95% CI 1.23 to 3.88). This study therefore shows that maternal consumption of artificial sweeteners during pregnancy may influence infant BMI.

Initiating Antiretroviral Therapy for HIV at a Patient’s First Clinic Visit: The RapIT Randomized Controlled Trial

One of the most persistent operational challenges facing antiretroviral therapy (ART) programs for HIV/AIDS in sub-Saharan Africa is late presentation of patients for care and high rates of attrition from the time of HIV testing to ART initiation. While many of patients that drop out of care prior to ART initiation seek care at a later time, many have significantly lower CD4 cell counts and more symptoms of illness than when they first tested positive. In this randomized controlled trial, 377 patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation, to determine whether “same-day initiation” of ART increases the number of patients starting treatment and improves overall health outcomes, compared to current practices. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (400 copies/ml) within 10 months of study enrollment. Researchers found that by 90 days after study enrollment 97% of participants in the rapid group, compared to 72% of participants in the standard group had initiated ART (RR 1.36, 95% CI 1.24 to 1.49). In addition, at 10 months, 64% of patients from the rapid group that had initiated treatment were virally suppressed, compared to 51% in the group (RR 1.26, 95% CI 1.05 to 1.50), indicating that earlier or rapid intervention led to improved health outcomes. Retention in care was also improved among patients in the rapid arm, where 81% of patients of patients had made at least 1 clinic visit between months 5 and 10 after study enrollment, compared to just 64% in the standard arm (RR 1.27, 95% CI 1.12 to 1.44). This study therefore shows that offering single-visit ART initiation to adult patients may significantly increase uptake of ART and viral suppression.

Image: PD

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