Polymorphisms of the farnesyl diphosphate synthase gene modulate bone changes in response to atorvastatin

Although their primary therapeutic indications are different, aminobisphosphonates and statins target enzymes in the mevalonate pathway, which is critical for bone homeostasis. Previous studies have shown that some polymorphisms of the gene encoding farnesyl diphosphate synthase (FDPS), the main target of aminobisphosphonates, modulate the response to these drugs. In this study, we explored whether those single nucleotide polymorphisms (SNPs) also influence the changes in bone mineral density (BMD) following therapy with statins. Sixty-six patients with coronary heart disease were studied at baseline and after 1-year therapy with atorvastatin. BMD was measured by DXA. Three SNPs of the FDPS gene (rs2297480, rs11264359 and rs17367421) were analyzed by using Taqman assays. The results showed that there was no association between the SNPs and basal BMD. However, rs2297480 and rs11264359 alleles, which are in linkage disequilibrium, were associated with changes in hip BMD following atorvastatin therapy. Thus, patients with AA genotype at the rs2297480 locus had a 0.8 ± 0.8 % increase in BMD at the femoral neck, whereas in patients with AC/CC genotypes, BMD showed a 2.3 ± 0.8 % decrease (p = 0.02). Similar results were obtained regarding changes of BMD at the femoral trochanter and when alleles at the rs11264359 locus were analyzed. However, there was no association between BMD and rs17367421 alleles. In conclusion, these results suggest that polymorphisms of the FDPS gene may influence the bone response to various drugs targeting the mevalonate pathway, including not only aminobisphosphonates but also statins.     

Combined alcohol septal ablation and transcatheter aortic valve replacement: Drunk and playing with fire

• Evaluation of the severity of aortic stenosis in the presence of dynamic left ventricular outflow (LVOT) obstruction is challenging.
• Invasive hemodynamic assessment with provocative maneuvers can be useful to differentiate of the relative components of obstruction.
• In patients with both dynamic LVOT obstruction and aortic stenosis, surgical myectomy and concurrent surgical aortic valve replacement is the optimal treatment strategy; combined alcohol septal ablation and transcatheter aortic valve replacement should only be considered for very high surgical risk patients.

     

Reductions in Children’s Vicariously Learnt Avoidance and Heart Rate Responses Using Positive Modeling

Recent research has indicated that vicarious learning can lead to increases in children’s fear beliefs and avoidance preferences for stimuli and that these fear responses can subsequently be reversed using positive modeling (counterconditioning). The current study investigated children’s vicariously acquired avoidance behavior, physiological responses (heart rate), and attentional bias for stimuli and whether these could also be reduced via counterconditioning. Ninety-six (49 boys, 47 girls) 7- to 11-year-olds received vicarious fear learning for novel stimuli and were then randomly assigned to a counterconditioning, extinction, or control group. Fear beliefs and avoidance preferences were measured pre- and post-learning, whereas avoidance behavior, heart rate, and attentional bias were all measured post-learning. Control group children showed increases in fear beliefs and avoidance preferences for animals seen in vicarious fear learning trials. In addition, significantly greater avoidance behavior, heart rate responding, and attentional bias were observed for these animals compared to a control animal. In contrast, vicariously acquired avoidance preferences of children in the counterconditioning group were significantly reduced post-positive modeling, and these children also did not show the heightened heart rate responding to fear-paired animals. Children in the extinction group demonstrated comparable responses to the control group; thus the extinction procedure showed no effect on any fear measures. The findings suggest that counterconditioning with positive modelling can be used as an effective early intervention to reduce the behavioral and physiological effects of vicarious fear learning in childhood.     

Osteoporotic Vertebral Fractures are Common in Hip Fracture Patients and are Under-recognized

Introduction: The vertebrae are the most common site for osteoporotic fracture. While they can result in disability and increased mortality, only one-third present clinically. People with multiple fractures are at greater risk of future fractures. Most hip fracture patients are neither diagnosed nor treated for their underlying osteoporosis. Computed tomography (CT) studies are often performed on hospitalised patients, can be used to diagnose osteoporosis and are gaining popularity for opportunistic osteoporosis screening by measuring BMD and other bone strength indices. The aim of this study was to assess the prevalence of vertebral fractures on CT pulmonary angiograms (CTPA) in a cohort of hip fracture patients and whether this increased their diagnosis and treatment rates. Methods: We retrospectively identified all hip fractures admitted to our institution between 2010 and 2017 to identify those who underwent CTPA scans. An independent, blinded consultant musculoskeletal radiologist reviewed the images for vertebral fractures and quantified severity using Genant criteria. Results were compared to the original radiology report, discharge diagnoses and treatment rates for osteoporosis. Results:Eleven percent (225/2122) of patients had CTPA images available. Seventy percent (158) were female with a mean age of 78 years (SD: 11). The median length of stay for all patients was 16 days (1–301). Forty percent (90) of patients had at least one vertebral fracture present and 20% (46) had more than one fracture. Only one in 5 radiology reports noted the fractures. 24% of subjects had osteoporosis treatment recorded at hospital discharge and there was no difference between those with vertebral fractures to those without. Conclusion: Many hip fracture patients have undiagnosed spine fractures. A screening strategy which evaluates CT scans for fractures has potential to increase diagnosis and treatment rates of osteoporosis. However, more work is needed to increase awareness.     

Immediate Post-Abortion Insertion of Intrauterine Contraceptives (IUC) in a Diverse Urban Population

Ethnic minority women have a higher incidence of unintended pregnancy and abortion than Caucasian women, with significant individual and social implications. Post-abortion intrauterine contraceptive (IUC) use may reduce future unintended pregnancy. This was a retrospective review of 265 women undergoing abortion at a Los Angeles County Reproductive Options Clinic. Demographic factors, reproductive history, and post-abortion contraceptive choice were evaluated and analyzed. The population was predominantly Latina (73 %) and single, with a mean age of 27. Immediate post-abortion IUC insertion was chosen by 48 % overall and more frequently by Latinas (55 %) than by African Americans (33 %) or Asians (43 %) (p = 0.02). IUC use increased with age, undesired future fertility, increasing gravidity, and history of previous abortion in univariate analysis. In multivariate analysis, IUC use increased with Latina ethnicity and increasing gravidity. In a clinic serving low-income urban women in Los Angeles, post-abortal IUC uptake is highest among Latinas and those with prior pregnancies. Future research should examine reasons for and barriers to IUC uptake in diverse communities and methods to improve post-abortion IUC uptake to prevent subsequent unintended pregnancies.