Previous studies have shown that benzodiazepine use in early pregnancy is associated with spontaneous abortion (SA). The association between specific benzodiazepines and the risk of SA, however, has not been investigated. In this nested case-control study based in Montreal, Quebec, Canada, cases defined as any pregnancy loss between the beginning of the sixth week of gestation and the 19th completed week of pregnancy were matched to controls by gestational age and calendar year (1998-2015) to quantify the risk of SA associated with gestational incident benzodiazepine use by drug class, duration of action, and specific benzodiazepine agent. Of the 442,066 pregnancies included in the Quebec Pregnancy Cohort, 27,149 (6.1%) ended with SA. Of these pregnancies, 1.4% occurred in women exposed to benzodiazepines in early pregnancy; this was compared to 0.6% amongst matched controls (OR 2.39, 95% CI 2.10 to 2.73). This association persisted after adjustment for maternal mood and anxiety disorders before pregnancy (OR 1.85, 95% CI 1.61 to 2.12). Interestingly, the risk conferred with benzodiazepine use was comparable in women that used either short- (OR 1.81, 95% CI 1.55 to 2.12) or long-acting (OR 1.73, 95% CI 1.31 to 2.28) benzodiazepines. This study therefore shows that incident benzodiazepine use in early pregnancy may be associated with an increased risk of SA.
Roux-en-Y gastric bypass (RYGB) is associated with significant bone loss and may increase fracture risk as a result. This is in contrast to other bariatric procedures, such as adjustable gastric banding (AGB), which has not been found to confer the same fracture risk to date. In this retrospective cohort study, 42,345 severely obese adults that underwent either RYGB or AGB were followed up using Medicare claims (2006-2014), to compare fracture risk after RYGB and AGB procedures. Of note, 78.5% of participants were women, with a mean age of 51 years. Researchers found that the fracture incidence rate was 6.6 (95% CI 6.0 to 7.2) after RYGB as compared to 4.6 (95% CI 3.9 to 5.3) after AGB (HR 1.73, 95% CI 1.45 to 2.08). Skeletal site-specific analyses demonstrated an increased risk of fracture at the hip (HR 2.81, 95% CI 1.82 to 4.49), wrist (HR 1.70, 95% CI 1.33 to 2.14), and pelvis (HR 1.48, 95% CI 1.08 to 2.07) among RYGB recipients. In a subgroup analysis of patients age 65 years and older, researchers also found that the incidence rate for any non-vertebral fracture was 9.9 per 1000 person-years (95% CI 7.6 to 11.7) in patients from the RYGB group, compared to 5.3 per 1000 person-years (95% CI 3.6 to 6.7) in patients who underwent AGB. This study therefore shows that when compared to those undergoing AGB, patients undergoing RYGB are at a significantly increased risk of fracture.
Breast cancer is the most common cancer seen in females, though it is rare in males. Transgender individuals experience incongruence between the sex assigned to them at birth and their experienced or expressed gender. Within this patient population, there has been an increase in the number of referrals for endocrine treatment, where patients can receive gender-affirming hormones, inducing desired physical changes (i.e. body hair, body composition). In trans women who are assigned male sex at birth but identify as female, this typically consists of anti-androgens and estrogens. In trans men, treatment usually consists of testosterone. In addition, while it has been established that sex steroids induce changes in breast tissue, it is not clear whether the receipt of exogenous sex steroids influences breast cancer risk in the transgender population. In this retrospective, nationwide, cohort study, 2260 adult trans women and 1229 adult trans men who received gender-affirming hormone treatment were followed-up to investigate the incidence and characteristics of breast cancer in transgender people in the Netherlands as compared to the general Dutch population. Researchers found that over the course of 33,991 person-years, there were 15 cases of invasive breast cancer in the trans women group. The median duration of hormone treatment in these patients was 18 years (range 7 to 37 years). When compared to cisgender men in the general population, this was 46-fold higher (RR 46.7, 95% CI 27.2 to 75.4), but lower than that observed in cisgender women (RR 0.3, 95% CI 0.2 to 0.4). Of these tumors, most were of ductal origin, estrogen and progesterone receptor positive, and 8.3% were HER2 positive. In the trans men subgroup, 4 cases of invasive breast cancer were identified, with a significantly decreased risk when compared to cisgender women (RR 0.2, 95% CI 0.1 to 0.5). The median duration of hormone treatment in these patients was 15 years (range 2 to 17 years). This study therefore shows that trans women receiving gender-affirming hormone treatment have an increased risk of breast cancer compared to cisgender men. This has important implications for breast cancer screening in trans women.
Corticosteroids are frequently used in the treatment of acute chronic obstructive pulmonary disease (COPD) exacerbations. However, the use of systemic corticosteroids is not without its risks. As such, strategies to limit systemic corticosteroid exposure are needed. In this multicenter randomized controlled trial, 318 patients age 40 years and older with known airflow limitation (post-bronchodilator FEV1/FVC £0.7) and established COPD were randomized to either eosinophil-guided therapy or standard therapy with systemic corticosteroids to determine whether an algorithm using blood eosinophil counts could safely reduce systemic corticosteroid exposure in patients admitted for the treatment of acute COPD exacerbation. All patients received 80 mg of intravenous methylprednisolone on the first day of admission. From the second day onwards, patients assigned to the eosinophil-guided group were given 37.5 mg of oral prednisolone daily, up to a maximum of 4 days, when their blood eosinophil count was at least 0.3 x 109 cells/L. On days where the eosinophil count did not meet this threshold, prednisolone was not administered. If a patient was discharged during the treatment period, a discharge prescription for the remaining days within a 5-day period was based on the last measured eosinophil count. The standard therapy group received 37.5 mg of oral prednisolone daily from the second day for 4 days. The primary outcome measure was the number of days alive and out of hospital within 14 days after recruitment. Researchers found that there was no between-group difference for days alive and out of hospital within 14 days after recruitment (p=0.34). Treatment failure at 30 days was also comparable between groups (p=0.90). At 30 days of follow-up, 6% of patients in the eosinophil-guided group and 4% of patients in the control group had died (p=0.43). The median duration of systemic corticosteroid therapy, however, was lower in the intervention group (p<0.0001). This study therefore shows that although eosinophil-guided therapy does reduce systemic corticosteroid exposure, this strategy may not confer a benefit in terms of the number of days alive and out of hospital. Further studies are needed in assessing eosinophil-guided therapy and other long-term outcomes.
Patients with colorectal cancer (CRC) are 2-4 times more likely to develop cardiovascular disease, as compared to individuals without a history of cancer. With survival rates increasing significantly over the last 4 decades, this has important implications in patients that are now more susceptible to competing causes of morbidity and mortality, including cardiovascular disease. In this retrospective cohort study, 2839 patients with CRC treated with curative intent were followed up to quantify the incidence of cardiovascular events up to 10 years after CRC diagnosis (2006-2011), and determine which measures of body composition are associated with major adverse cardiovascular events (MACEs) in patients with CRC. Researchers found that the cumulative incidence of MACE 10 years after CRC diagnosis was 19.1%. Of note, a considerable number of patients were former (40%) or current smokers (12%), had hypertension (55%), hyperlipidemia (49%) and type 2 diabetes (20%). Body mass index (BMI) was not correlated with MACE; however, researchers found that visceral adipose tissue area was associated with MACE, where in contrasting the highest and lowest quintiles, HR was 1.54 (95% CI 1.02 to 2.31, p=0.04). Subcutaneous adipose tissue area was not associated with MACE (p=0.92). Contrasting the highest (i.e. less lipid stored in the muscle) to lowest quintile of muscle radiodensity, the multivariable-adjusted cause-specific HR for MACE was 0.67 (95% CI, 0.44 to 1.03, p=0.02 for trend). This study therefore shows that visceral adiposity and muscle radiodensity may be risk factors for MACE in patients previously diagnosed with CRC. The results of this study also indicated that BMI likely has limited utility in determining cardiovascular risk in this patient population.
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