Premature Ticagrelor Discontinuation in Secondary Prevention of Atherosclerotic CVD: JACC Review Topic of the Week

Ticagrelor is a cornerstone of modern antithrombotic therapy alongside aspirin in patients with acute coronary syndrome and after percutaneous coronary intervention. Adverse effects such as bleeding and dyspnea have been associated with premature ticagrelor discontinuation, which may limit any potential advantage of ticagrelor over clopidogrel. The randomized trials of ticagrelor captured adverse events, offering the opportunity to more precisely quantify these effects across studies. Therefore, a meta-analysis of 4 randomized clinical trials of ticagrelor conducted between January 2007 and June 2017 was performed to quantify the incidence and causes of premature ticagrelor discontinuation. Among 66,870 patients followed for a median 18 months, premature ticagrelor discontinuation was seen in 25%; bleeding was the most common cause of discontinuation followed by dyspnea. Versus the comparators, the relative risk of dyspnea-related discontinuation during follow-up was 6.4-fold higher, the relative risk of bleeding was 3.2-fold higher, and the relative risk of discontinuation due to any adverse event was 59% higher for patients receiving ticagrelor. Understanding these potential barriers to adherence to ticagrelor is crucial for informed patient-physician decision making and can inform future efforts to improve ticagrelor adherence. This review discusses the incidence, causes, and biological mechanisms of ticagrelor-related adverse effects and offers strategies to improve adherence to ticagrelor.     

Robotic surgery does not affect upstaging of T1 renal masses

Partial nephrectomy is the mainstay of treatment for localized kidney cancer. A proportion of patients are upstaged post-operatively to locally advanced di     

Genetics of epilepsy: epilepsy research foundation workshop report.

The Sixth Epilepsy Research Foundation workshop, held in Oxford in March 2006, brought together basic scientists, geneticists, epidemiologists, statisticians, pharmacologists and clinicians to consider progress, issues and strategies for harnessing genetics to improve the understanding and treatment of the epilepsies. General principles were considered, including the fundamental importance of clear study design, adequate patient numbers, defi ned phenotypes, robust statistical data handling, and follow-up of genetic discoveries. Topics where some progress had been made were considered including chromosomal abnormalities, neurodevelopment, hippocampal sclerosis, juvenile myoclonic epilepsy, focal cortical dysplasia and pharmacogenetics. The ethical aspects of epilepsy genetics were reviewed. Principles and limitations of collaboration were discussed. Presentations and their matched discussions are produced here. There was optimism that further genetic research in epilepsy was not only feasible, but might lead to improvements in the lives of people with epilepsy.     

Assessment of the durability of robot-assisted laparoscopic sacrocolpopexy for treatment of vaginal vault prolapse

Transabdominal sacrocolpopexy has been shown, in multiple long-term studies of its success and durability, to be the definitive treatment option for post-hysterectomy vaginal vault prolapse. It is, however, associated with greater morbidity than vaginal repair. We describe a minimally invasive technique for vaginal vault prolapse repair and present our experience with a minimum of one-year follow-up. The surgical technique involves five laparoscopic ports—three for the da Vinci robot and two for the assistant. After appropriate dissection a polypropylene mesh is attached to the sacral promontory and to the vaginal apex by use of Gore-Tex sutures. The mesh material is then covered by the peritoneum. Patient analysis focused on complications, urinary continence, patient satisfaction, and morbidity, with a minimum of 12 months follow-up. Forty-two patients with post-hysterectomy vaginal vault prolapse underwent robot-assisted laparoscopic sacrocolpopexy at our institute and 35 have a minimum of 12 months follow-up, with a mean follow-up of 36 months (range 12–48) in the group. Mean age was 67 (47–83) years and mean operating time was 3.1 (2.15–4.75) h for the entire cohort. All but one patient were discharged home on postoperative day one; one patient left on postoperative day two. One developed recurrent grade three rectocele, one had recurrent vault prolapse, and two suffered from vaginal extrusion of mesh. All patients were satisfied with their outcome. The robot-assisted laparoscopic sacrocolpopexy is a minimally invasive technique for vaginal vault prolapse repair, combining the advantages of open sacrocolpopexy with the reduced morbidity of laparoscopy. We observed reduced hospital stay, low occurrence of complications, and high patient satisfaction, with a minimum of 1-year follow-up. Most importantly, the long-term results of the robotic repair are similar to those of open repair, but with significantly less morbidity.     

Capillary gas chromatographic assay of camphor and m-cresol in dermatological creams

Camphor and m-cresol mixtures are used in antiseptic and anti-itching creams. No compendial method exists for these preparations. This paper reports a capillary gas chromatographic method using FID detection with 2,6-di-tert-butyl-4-methylphenol as internal standard on a 30 m×0.32 mm Supelcowax®-10 column (0.25 μm film) with helium as carrier gas. Ramped temperature programming was applied. The method allows simultaneous quantitation of camphor and m-cresol in the presence of o- and p-cresols, calamine and zinc oxide. Overall percent recoveries (±SD, n=9) of camphor, o-, p- and m-cresol from spiked placebo creams, at a labeled amount of 10 (w/w)% were 96.9±0.6, 98.2±0.6, 99.2±0.5 and 101.0±0.9%, respectively, and at a labeled amount of 1% were 96.7±0.6, 97.8±0.9, 97.8±0.6, and 100.3±1.0%, respectively. The recovery studies were carried out at ±30% of the labeled amounts. Linear peak area or height ratios were obtained (r>0.999) for camphor, o-, p- and m-cresol covering a concentration range of 10–200% of the labeled amount. Linearity (r>0.999) was also obtained for m-cresol when the relative concentration of o- and p-cresol was varied from 5 to 100% of the m-cresol concentration. The resolution between the ‘critical pair’ of p- and m-cresol was ≥1.1. The limit of quantitation was 23 pg for m-cresol and 9.3 pg for camphor using an injection split of 1:50. The repeatability (%RSD) for all compounds were <2% for peak area and <1.4% for peak height ratios. System suitability and robustness of the method were established. The method was successively applied to the assay of available commercial products and allows assay of camphor and the three cresol isomers.     

The myocardial performance index during low-dose dobutamine echocardiography in control subjects and patients with a recent myocardial infarction: a new index of left ventricular functional reserve?

BACKGROUND: Wall-motion analysis during low-dose dobutamine echocardiography (LDDE) is a semiquantitative measure of left ventricular contractile reserve after myocardial infarction (MI). The Doppler echocardiographic myocardial performance index (MPI) is a quantitative measure of combined left ventricular systolic and diastolic function. We sought to characterize the changes in MPI during LDDE in control subjects and patients with MI, and to describe the relation of these changes to changes in regional systolic function. METHODS: MPI was obtained at rest and during LDDE (10 microg/kg/min) in 25 healthy volunteers (group 1) and 50 patients with a recent MI. Patients were divided into two subsets; those with (n = 23; group 2A) and those without (n = 27; group 2B) a contractile reserve defined as an improvement of wall motion in more than two contiguous infarct-zone segments during LDDE. DeltaMPI was defined as the change from rest to LDDE. RESULTS: MPI decreased significantly during LDDE in groups 1 and 2A, whereas MPI increased in group 2B (DeltaMPI = 0.12 +/- 0.04 and 0.10 +/- 0.08 vs -0.03 +/- 0.08, P <.0001). On multivariate analysis, Deltawall-motion score index predicted DeltaMPI (beta = 0.65, P <.0001) independently of age, sex, and the dobutamine-induced change in heart rate and systolic blood pressure. CONCLUSIONS: Data suggest that the change in MPI during LDDE may provide a simple and quantitative measure of overall left ventricular functional reserve in patients with a recent MI.     

Death anxiety in patients with epilepsy.

PURPOSE: Whereas the relationship between epilepsy and anxiety has received much attention, less is known about the relationship between death anxiety and this disorder. The objective of this study was to assess death anxiety among epileptic patients who attended the outpatient neurology clinic at the Salmaniya Medical Complex, Kingdom of Bahrain. METHODS: Ninety-two patients (48 males and 44 females) completed a death anxiety scale. The scale items were adopted from already published surveys and adjusted to suit epilepsy patients. RESULTS: Results showed that the mean death anxiety score was moderate (2.75+/-1.35), with 26.09% of patients reporting high levels of death anxiety. Period of illness and educational level were significant predictors of death anxiety. Female patients, generalized type of epilepsy, the short duration of the illness and low level of education were associated with higher death anxiety scores. CONCLUSION: This study highlights the need for developing treatment strategies, counseling therapies and social support for people with epilepsy to decrease their death anxiety and improve their quality of life.     

Evaluation of the behaviour of a thermal diffusion sensor in a high field strength magnetic resonance system: an experimental study.

Patients with acute brain pathology requiring ferromagnetic bio-medical implants for on-going invasive monitoring are largely excluded from the benefits of MRI scanning. We evaluated the behaviour of a thermal diffusion cortical blood flow (TD-CBF) sensor both in vitro (phantom gelatin model) and in vivo environments in a high field strength MRI system.Two baboons underwent cranial subdural implantation of 2 TD-CBF sensors/hemisphere and a single left parietal sensor was implanted subcortically to determine any deleterious effects. Using standard MRI sequences, artefact size, thermal effects, current generation, movement and reliability of recordings were assessed during scanning.The deflection forces were negligible, no observable thermal effects were demonstrated, while wide fluctuations in cerebral blood flow recordings were recorded. Mean image artefact size for implanted sensors was 6 times larger than in vitro. Patients with an implanted TD-CBF sensor may be safely imaged provided the device is disconnected. The MRI images obtained are of an acceptable quality.     

Combined sclerotherapy and operation for the treatment of bleeding oesophageal varices.

OBJECTIVE--To identify prognostic factors in a consecutive series of patients with bleeding oesophageal varices and develop an optimum regimen of treatment. DESIGN--Retrospective review. SETTING--I Department of Surgery, University Hospital, Vienna, Austria. PATIENTS--301 consecutive patients with bleeding oesophageal varices. OUTCOME MEASURES--Median survival and survival at one year after sclerotherapy alone (n = 213), or sclerotherapy with portosystemic shunt (n = 54), Hassab's devascularisation (n = 29), or liver transplantation (n = 5). RESULTS--Prognosis was dependent on the severity of liver damage at the start of treatment. Median survival for Child's class A was 47 months, for Child's class B 54 months, and for Child's class C 2 months. The overall one year survival for patients in Child's class C was 33%, for sclerotherapy alone 28%, and for sclerotherapy and portosystemic shunt 42%, Hassab's devascularisation 50%, and liver transplantation 80%. CONCLUSION--Despite the small number of patients who underwent liver transplantation and their poor initial prognosis (Child's class C, n = 4; class B, n = 1) our results suggest that liver transplantation should be considered for the treatment of patients with end stage cirrhosis and bleeding varices.