2 Minute Medicine Rewind September 27, 2021

The effect of adiposity on cardiovascular function and myocardial fibrosis in patients with Duchenne muscular dystrophy

1. In a cohort of patients with Duchenne muscular dystrophy, adiposity was associated with cardiac dysfunction.

Evidence Rating Level: 2 (Good)

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease that leads to the absence of dystrophin, causing fibrofatty replacement of the myocardium and subsequent cardiomyopathy. Patients with DMD are at high risk of developing increased adiposity due to decreased mobility and corticosteroid use. Furthermore, long-term corticosteroid therapy is also associated with endocrine side effects, such as obesity and growth deceleration, which further contribute to adiposity levels in this population. This study sought to determine if adiposity is associated with the development of cardiac dysfunction in patients with DMD. The authors conducted a retrospective chart review of patients with DMD who underwent clinical cardiac magnetic resonance (CMR) studies from January 1, 2006, to December 31, 2018 and had at least 1 dual-energy x-ray absorptiometry (DXA) scan performed within a year of their CMR. Patients’ demographic information, medical histories, medications, heights, and functional mobility scores were collected. The CMR imaging parameters included presence of late gadolinium enhancement (LGE positive [LGE+]) and left ventricular ejection fraction. The adiposity indices, measured by DXA scans, included percentage of body fat (PBF), whole body fat mass indexed to height (WBF), and body mass index (BMI). A total of 324 patients with DMD were included in the study. On last CMR, 164 patients (52%) had LGE+ and 116 patients (36%) had cardiac dysfunction (left ventricular ejection fraction <55%). High PBF and WBF were associated with LGE+ on univariate analysis (mean difference between patients with and without LGE+: +2.0 kg/m, P=0.02; and +2.4%, P=0.02, respectively). Additionally, patients with cardiac dysfunction had higher WBF and BMI on univariate analysis (mean difference between patients with and without cardiac dysfunction: +2.9 kg/m, P=0.001; and +1.5 kg/m2P=0.03, respectively). These associations held true on multivariate analysis. In all, this study demonstrated an independent association of adiposity with cardiac dysfunction in patients with DMD.


Maternal cardiovascular disease after twin pregnancies complicated by hypertensive disorders of pregnancy: A population-based cohort study

1. Hypertensive disorders of pregnancy (HDP), such as pre-eclampsia and gestational hypertension, in twin gestations were a weaker risk factor for future cardiovascular disease than HDP in singleton pregnancies.

Evidence Rating Level: 2 (Good)

Cardiovascular disease (CVD) is the leading cause of death in women. It has been demonstrated that people whose singleton pregnancy is affected by hypertensive disorders of pregnancy (HDP), such as pre-eclampsia and gestational hypertension, are at risk of future CVD. A person who is pregnant with twins has a 3-4 times higher risk of HDP than a person who is pregnant with a single child. However, it is unclear whether the association between HDP and future CVD seen in singleton pregnancies also occurs in twin pregnancies. Consequently, this study aimed to conduct a population-based retrospective cohort study to compare the association between HDP and future CVD after singleton and twin pregnancies. Eligible participants were nulliparous people aged 18-45 years who had a singleton or twin hospital live birth between April 1, 1992 and March 31, 2017 in Ontario, Canada. People with any recognized form of CVD within 2 years before the conception date of the index pregnancy were excluded. The future CVD risk among pregnant people from 4 groups, namely i) singleton birth, no HDP; ii) singleton birth with HDP (defined as either pre-eclampsia or gestational hypertension at the index birth); iii) twin birth, no HDP; and iv) twin birth with HDP, were compared. The primary outcome measure was a CVD composite of any future hospital admission for heart failure, cardiac dysrhythmia, coronary artery disease, cerebrovascular disease, or peripheral artery disease. The study included 1,431,651 pregnant people in the singleton birth without HDP group, 98,631 singleton birth with HDP, 21,046 twin birth without HDP, and 4,283 twin birth with HDP. The median (interquartile range) duration of follow-up was 13 (7-20) years. The incidence rate of CVD was lowest among those with a singleton or twin pregnancy without HDP (0.72 and 0.74 per 1,000 person-years, respectively). Compared with people with a singleton birth without HDP, the risk of CVD was highest among those with a singleton pregnancy and HDP (1.47 per 1,000 person-years; adjusted hazard ratio [HR] 1.81 [95% confidence interval (CI) 1.72–1.90]), followed by those with a twin pregnancy and HDP ((1.07 per 1,000 person-years; adjusted HR 1.36 [95% CI 1.04–1.77]). When compared directly, future CVD risk was lower after a twin birth with HDP than a singleton birth with HDP (adjusted HR 0.74 [95% CI 0.57-0.97]), suggesting a weaker association between HDP and future CVD in twin gestations. Findings from this study can be used to further aid practitioners in the risk stratification of CVD for mothers of twin pregnancies.


Use of metformin to prolong gestation in preterm pre-eclampsia: Randomized, double blind, placebo controlled trial

1. Extended release metformin prolonged gestation in women with pre-term pre-eclampsia when compared with placebo.

Evidence Rating Level: 1 (Excellent)

Pre-term pre-eclampsia, a severe variant of pre-eclampsia, is a major cause of maternal and neonatal morbidity and mortality, particularly in South Africa. Pre-term pre-eclampsia often requires premature delivery for maternal indications, significantly increasing risk of neonatal disability and death. Metformin has been identified as a possible treatment for pre-eclampsia, potentially slowing its progression and reducing complications of severe prematurity. This study evaluated whether extended release metformin can prolong gestation among women with a diagnosis of pre-term pre-eclampsia. The authors conducted a double-blind, placebo-controlled clinical trial among 180 women with a diagnosis of pre-term pre-eclampsia (defined according to the International Society for the Study of Hypertension in Pregnancy Classification) at 26+0 to 31+6 weeks’ gestation at Tygerberg Hospital in Cape Town, South Africa. The women were randomly assigned to receive either 3 g of oral extended release metformin or placebo daily, in divided doses, until delivery. The primary outcome measure was prolongation of gestation. Of 180 participants, one woman in the metformin arm delivered before taking any trial drug and was therefore excluded. Subsequently, two women in the metformin arm and four women in the placebo arm were discharged home as it was decided they did not meet study criteria. One woman in the metformin arm and one woman in the placebo arm withdrew before delivery. Among those who continued to take the trial drug at any dose, the median prolongation of gestation in the metformin arm was 17.5 days (interquartile range 5.4-28.7; N=76) compared with 7.9 days (interquartile range 3.0-22.2; N=74) days in the placebo arm, a median difference of 9.6 days (geometric mean ratio 1.67, 90% CI 1.16 to 2.42). Among those who took the full dosage, the median prolongation of gestation in the metformin arm was 16.3 days (interquartile range 4.8-28.8; N=40) compared with 4.8 days (interquartile range 2.5-15.4; N=61) in the placebo arm, a median difference of 11.5 days (geometric mean ratio 1.85, 95% CI 1.14 to 2.88). In all, this trial suggests that medical treatment of pre-term pre-eclampsia with extended release metformin is possible.


Does seniority always correlate with simulated intubation performance? Comparing endotracheal intubation performance across medical students, residents, and physicians using a high-fidelity simulator

1. Seniority correlated with intubation success rate and use of certain devices, but not other intubation-related skills.

Evidence Rating Level: 2 (Good)

Endotracheal intubation is crucial for maintaining a clear and secure airway in emergency medical care and anesthesia. It is an invasive procedure requiring rapid assessment of patient and situational factors and complex psychomotor skills. Generally, the success of intubation is attributed in part to the operator’s level of competence. As such, seniority (often considered a proxy for expertise or proficiency) is usually a requirement for performing difficult airway management. Research evaluating the association between seniority and intubation success rate has generated mixed results. This cross-sectional study explored differences in intubation success rate and other skills during intubation between medical trainees and senior physicians. 50 participants, including final-year medical students (UGY’ N=7), postgraduate year physicians (PGY; N=18), residents (R; N=18), and attending physicians (VS; N=7), completed a 90-minute-long airway management course. Subsequently, each participant performed 12 intubations (i.e. 3 devices x 4 scenarios) on a high-fidelity simulator. Primary outcome measures included intubation success rate (i.e., intubation time within 30 s and ventilation of both lungs) and intubation time. Success rate differed by seniority (χ2(3) = 15.1, p < 0.01). 63% of VS were able to achieve first pass success compared with 44% of PGY, 43% of UGY, and 38% of R. Although the main effect of seniority was not significant for intubation time (F(3, 46) = 1.89, p = 0.15), VS (m = 31.2s, 95% CI 15.8–46.6; m = 26.2s, 95% CI 17.5–35.0) required significantly less time when using direct laryngoscopy and Glidescope than UGY (m = 71.6s, 95% CI 56.2–87.0; m = 50.6s, 95% CI 41.8–59.3). Overall, it was found that seniority correlates with intubation success rate and use of certain devices, but not other intubation-related skills. Developing new airway management tools and training programs that place an emphasis on efficiency and practice will likely benefit the education of junior trainees.


The risk of COVID-19 in survivors of domestic violence and abuse

1. Women exposed to domestic violence and abuse were at a higher risk of suspected or confirmed COVID-19 compared to unexposed women.

Evidence Rating Level: 2 (Good)

Public health restrictions for containing the spread of SARS-CoV-2 have inadvertently resulted in a “shadow pandemic” of domestic violence and abuse (DVA). Many countries have implemented policies to allow free movement of DVA survivors in an attempt to minimize their exposure to abusive environments and better facilitate access to support. However, freedom of travel can potentially increase risk of COVID-19 exposure for this vulnerable group. Conducted between January 31, 2020 and February 28, 2021, this retrospective cohort study sought to compare the risk of developing suspected or confirmed COVID-19 in women (aged 16+ years) exposed to DVA against age-sex-matched unexposed controls. “The Health Improvement Network” (THIN) database was used to identify 10,462 eligible women exposed to DVA who were matched to 41,467 similarly-aged unexposed women. The primary outcome of interest was the presence of a GP-recorded diagnosis of suspected or confirmed COVID-19. Following adjustment, women exposed to DVA were found to be at an increased risk (aHR 1.57; 95% CI 1.29–1.90) of suspected/confirmed COVID-19 compared to unexposed women. These findings provide support for positive policy action improving DVA surveillance and prioritizing survivors for COVID-19 vaccination.

Image: PD

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