2 Minute Medicine Rewind January 11, 2016


Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies

The cause of peripartum cardiomyopathy remains unknown and it has been hypothesized in the literature that it may have a significant genetic component. It shares many clinical similarities to idiopathic dilated cardiomyopathy. Using this association, the authors of this paper sequenced 43 genes from 172 women with peripartum cardiomyopathy to identify variants that have been associated with dilated cardiomyopathy including mutations in TTN (which encodes the sarcomere protein titin). The authors found the prevalence of truncating variants (26 in 172) was similar to that in a cohort of patients with dilated cardiomyopathy (55 of 332 patients, p = 0.81). Comparing it to the reference population, they found these truncating variants were significantly higher (4.7%, p=1.3×10−7).  In addition, two thirds of identified truncating variants were in TTN, as seen in 10% of the patients compared to 1.4% in the reference population. When comparing the clinical relevance of TTN truncating variants, the authors found it was significantly correlated with a lower cardiac ejection fraction at 1-year follow up (p=0.005). Therefore, this study provides evidence that the distribution of truncating variants in women with diagnosed peripartum cardiomyopathy is similar to patients with idiopathic dilated cardiomyopathy. This may have future implications for targeted screening of this select population.

Long-term effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: follow-up of the CoBalT randomised controlled trial

Cognitive behavioral therapy (CBT) has been demonstrated to be an effective stand-alone treatment or in conjunction with antidepressants in patients suffering major depression. In this study the authors evaluate the cost-effectiveness of CBT as an adjunct to antidepressant over a 3-5year time period in patients with treatment-resistant depression from the randomized controlled CoBalT trial. In the CoBalT trial patients were randomized to receive either usual care with antidepressants or usual care plus CBT. The primary outcome was self-reported depressive symptoms evaluated by the Beck Depression Inventory (BDI)-II score (range 0–63). Cost-utility analysis compared health and social care costs with quality-adjusted life-years (QALYs). At follow-up (median 45.5 months) the authors found the CBT plus antidepressant group had a mean BDI-II score of 19.2 (SD 13.8) compared with a mean BDI-II score of 23.4 (SD 13.2) for the group only on antidepressants (difference in means –4·7 [95% CI –6.4 to –3.0, p<0.001]). In terms of cost, the average annual cost of CBT per participant was £343 (SD 129). Using the incremental cost-effectiveness ratio (ICER) to determine whether this intervention is considered cost-effective, the authors found the ICER to be £5374 per QALY gain (National Institute for Health and Care Excellence QALY threshold of £20 000). This is considered cost-effective and represents a 92% probability of being cost effective at the above used threshold. Therefore, using CBT in conjunction with antidepressants is considered cost-effective over the long-term in patients who have not responded to antidepressants.

How temporal evolution of intracranial collaterals in acute stroke affects clinical outcomes

Collateral intracranial vessels play an important role in functional outcome after an acute ischemic stroke. In order to determine their temporal evolution, CT angiograms at one academic institution between the years of 2010-2013 were analyzed to compare prior to treatment with IV tissue plasminogen activator (tPA) and repeat on day 2 post ischemic stroke. Collaterals on imaging were evaluated by two independent neuroradiologists using three predefined criteria which included: 1) the Miteff system, the Maas system, and 20-point collateral scale by the Alberta Stroke Program Early CT Score methodology. The primary endpoint for 209 patients was functional outcome at 3 months which was defined using the modified Rankin Scale (mRS). A score of 0 or 1 was considered a good outcome. The authors found that all 3 of the scoring systems showed that collateral recruitment on follow-up CTA from baseline of poor collateral state was significantly associated with poor outcome and increased bleeding risk. If the primary vessel remained occluded, collateral recruitment was also associated with significantly worse outcome. In addition, on two of the three grading systems used, collateral recruitment with significantly associated with increased mortality. This means that collateral recruitment is not always beneficial. The timing of collateral recruitment is a determinant of outcome. Delayed collateral recruitment compared to early (within first 24 hours) results in worse outcomes.

Aerobic Interval Training Reduces the Burden of Atrial Fibrillation in the Short Term: A Randomized Trial

It is recommended that patients with atrial fibrillation (AF) increase their levels of physical activity because of the comorbidities associated with AF. The effect of exercise on AF burden is however unclear and there are no current guideline recommendations. The purpose of this study was to determine the effect of aerobic interval training (AIT) on AF burden, cardiac symptoms and function, exercise capacity, quality of life, lipid profile and the need for health care services. A total of 51 patients were randomized to AIT or control, which consisted of regular exercise habits. AIT consisted of four 4-minute intervals at 85-95% of peak heart rate 3 times a week for 12 weeks. A loop recorder was implanted to record AF burden for a total of 8 weeks (4 weeks prior to starting intervention and 4 weeks post-intervention). The authors found in the AIT group mean time in AF decreased from 8.1% to 4.8% in the exercise group and increased from 10.4% to 14.6% in the control group (p=0.001 between groups). In addition, AF symptom frequency (p=0.006) and AF symptoms severity (p=0.009) were decreased after AIT. AIT improved the rest of the variables studied. It improved VO2peak, left atrial and ventricular ejection fraction, quality of life measures vitality and lipid values. Moreover, there was a trend toward fewer cardioversions and hospital admissions with AIT. Therefore, this study provides evidence that aerobic exercise for 12 weeks will reduce overall AF burden and consequently should be recommended for patients.

Familial Risk and Heritability of Cancer Among Twins in Nordic Countries

Cancer places a large societal burden at both the individual and population level. Screening and potentially preventing cancer has important economic implications. The aim of this prospective longitudinal study was to estimate the familial risk and heritability of cancer using a twin cohort in Denmark, Finland, Norway and Sweden from 1943 to 2010. There were a total of 80,309 monozygotic twins and 123,382 monozygotic twins. The main outcome was cancer incidence and time-to-event analyses were used to estimate familial risk and heritability. The authors found the same cancer diagnosed in 38% of monozygotic and 26% of dizygotic twins. If one twin was diagnosed with cancer, the cumulative risk of the other twin developing cancer was an absolute 5% (95% CI, 4%-6%) higher in dizygotic (37%; 95% CI, 36%-38%) and an absolute 14% (95% CI, 12%-16%) higher in monozygotic twins (46%; 95% CI, 44%-48%) compared with the cumulative risk in the overall cohort, which was 32%. For most cancers there were significant familiar risks and for monozygotic twins the cumulative risk was higher compared to dizygotic twins. Specifically, there was significant heritability for skin melanoma, prostate, non-melanoma skin, ovary, kidney, breast and corpus uteri cancers. Overall, this long-term study provides evidence that there is significant familiar risk for cancer.

Image: PD

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