Primary Prevention of Sudden Cardiac Death: Can We Afford the Cost of Cardioverter-Defibrillators? Data from the Search-MI Registry-Italian Sub-study

Background: Large randomized trials show that in appropriately selected patients with left ventricular dysfunction, implantable cardioverter-defibrillators (ICDs) can improve overall survival at 2–5 years. Since direct implementation of the criteria used in the MADIT II and SCD-HeFT will lead to a marked rise in ICD implants, there is a growing fear that increased use of ICDs may cause a dramatic burden to health care systems. The ICD has traditionally been seen as an expensive form of treatment, which is difficult to accept at the first look. This is mainly due to the nonlinear character of the ICD investment, characterized by high initial expenditure, followed by a deferred pay-off in terms of clinical benefits. Cost-effectiveness analysis may help provide a different perspective on the problem of ICD cost, as may estimation of the daily cost of ICD treatment, assuming a time horizon of 5–7 years—a particularly interesting subject for further registry studies.
Methods and Results: Based on real expenditure data from 2002 to 2005, as recorded in the Search-MI Registry-Italian Sub-study of patients implanted on MADIT II indications, we estimated the daily costs associated with the device and leads. Over a 5–7 year time horizon, the average daily cost was estimated to be €4.60–€6.70. Translation of these figures into U.S. market conditions suggests a daily cost of around $7.90–$11.40.
Conclusions: These findings appear useful to help evaluate the affordability of ICD in comparison with other therapeutic options in a context of limited available economic resources.     

Synthesis of TPH-13, a new tridecapeptide from Phyllomedusa rohdei

The synthesis of TPH-13 (Glp-Glu-Lys-Pro-Tyr-Trp-Pro-Pro-Pro-Ile-Tyr-Pro-Met-OH), a tridecapeptide isolated from the skin of the South American frog Phyllomedusa rohdei, is described and alternative approaches are discussed.     

Allogeneic bone marrow transplantation versus chemotherapy in high-risk childhood acute lymphoblastic leukaemia in first remission

We compared the outcome of children with high-risk acute lymphoblastic leukaemia (HR-ALL) in first complete remission (first CR) treated with chemotherapy (CHEMO) or with allogeneic bone marrow transplantation (BMT) in a multicentre study.   All children treated by the Italian Paediatric Haematology Oncology Association for HR-ALL in first CR between 1986 and 1994 were eligible for the study. 30 children were given BMT at a median of 4 months from first CR, with preparative regimens including total-body irradiation ( n  =25/30). 130 matched controls for BMT patients were identified among 397 HR-ALL CHEMO patients. Matching on main prognostic factors and duration of first CR was adopted to control the selection and time-to-transplant biases. The comparative analysis was based on the results of a stratified Cox model. The estimated hazard ratios of BMT versus CHEMO at 6 months, 1 year and 2 years after CR were 1.38 (CI 0.59–3.24), 0.69 (CI 0.27–1.77) and 0.35 (CI 0.06–1{\raise 5mu ..91), with an overall non-significant difference between the two groups ( P  = 0.34). With a median follow-up of 4 years, the disease-free survival was 58.5% (SE 9.3) in the BMT group and 47.7% (SE 4.8) in the CHEMO group, at 4 years from CR. Non-leukaemic death occurred in 4% of CHEMO and 10% of BMT patients. In the BMT group the estimated cumulative incidence of relapse at 1.5 years from CR was 31.5% (SE 8.8) and did not change thereafter, whereas in the CHEMO group the corresponding figure was 29.2% (SE 4.1) and the incidence continued to increase thereafter (48.2% (SE 4.8) at 4 years from CR).   The results of this study suggest that, with respect to the CHEMO group, the higher risk of early failure in the BMT group is outweighed by the lower risk of relapse after 1 year. Results prompt the need for a prospective study, in order to demonstrate the likely advantage of BMT in HR childhood ALL in first CR.     

Daytime continuous polysomnography predicts MSLT results in hypersomnias of central origin

In the diagnostic work‐up of hypersomnias of central origin, the complaint of excessive daytime sleepiness should be objectively confirmed by MSLT findings. Indeed, the features and diagnostic utility of spontaneous daytime sleep at 24 h continuous polysomnography (PSG) have never been investigated. We compared daytime PSG features to MSLT data in 98 consecutive patients presenting with excessive daytime sleepiness and with a final diagnosis of narcolepsy with cataplexy/hypocretin deficiency (n = 39), narcolepsy without cataplexy (n = 7), idiopathic hypersomnia without long sleep time (n = 19), and ‘hypersomnia’ with normal sleep latency at MSLT (n = 33). Daytime sleep time was significantly higher in narcolepsy‐cataplexy but similar in the other groups. Receiver operating characteristics (ROC) curves showed that the number of naps during daytime PSG predicted a mean sleep latency ≤8 min at MSLT with an area under the curve of 0.67 ± 0.05 (P = 0.005). The number of daytime sleep‐onset REM periods (SOREMPs) in spontaneous naps strikingly predicted the scheduled occurrence of two or more SOREMPs at MSLT, with an area under the ROC curve of 0.93 ± 0.03 (P < 10^?12). One spontaneous SOREMP during daytime had a sensitivity of 96% with specificity of 74%, whereas two SOREMPs had a sensitivity of 75%, with a specificity of 95% for a pathological REM sleep propensity at MSLT. The features of spontaneous daytime sleep well correlated with MSLT findings. Notably, the occurrence of multiple spontaneous SOREMPs during daytime clearly identified patients with narcolepsy, as well as during the MSLT.     

Low‐Dose Heparin for Elective Percutaneous Coronary Intervention

Objectives

We evaluated the safety and efficacy of low‐dose heparin (40 IU/kg) for elective percutaneous coronary intervention (PCI).

Background

Current guidelines recommend a 70–100 IU/kg bolus of heparin for elective PCI, but this dose may be associated with increased bleeding risk. Low‐dose heparin may have an advantage in this regard, but has not been well studied.

Methods

From January 2008 to October 2012, 300 patients underwent elective transfemoral PCI and were treated with an initial bolus of 40 IU/kg of heparin at the UCLA Medical Center. Dual antiplatelet therapy with clopidogrel and aspirin was administered prior to or just after diagnostic coronary angiography. The primary end‐point was the composite of cardiac death, myocardial infarction, urgent target vessel revascularization for ischemia, or major bleeding within 30 days after PCI.

Results

The mean activating clotting time was 233 ± 28 seconds. The primary end‐point occurred in 2.3%. The cardiac death rate was 0.3% but was not related to the PCI. The myocardial infarction rate was 1.3%. Urgent target vessel revascularization occurred in 1 patient (0.3%). The major bleeding rate was 0.3%. No stent thrombosis occurred.

Conclusion

Using a lower dose of heparin with dual antiplatelet therapy is safe and is associated with a low bleeding risk after transfemoral PCI while providing suppression of ischemic events. This may also represent a cost savings compared with other antithrombotic strategies. A randomized clinical trial comparing low‐dose heparin with bivalirudin in patients is required to determine the optimal anticoagulation strategy. (J Interven Cardiol 2014;27:58–62)

     

The effect of glycerol on the guinea-pig hydropic ear

The aim of this paper was to investigate the effect of glycerol on experimental endolymphatic hydrops in guinea-pigs. The right endolymphatic sac and duct were obliterated through an extradural posterior fossa approach. Some animals received a 3 g/kg dose of glycerol for a period of 7 days, whereas others received the same dose for 30 days. The activity of glycerol was studied by investigating the volumetric changes in the scala media determined with a computerized planimeter. Glycerol induced a significant reduction of the hydrops showing its effectiveness and suggesting a strial metabolic response.