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.     

Intussusception in a premature neonate: A rare and often misdiagnosed clinical entity

Intussusception is a very rare cause of intestinal obstruction in neonates. It is of extremely rare occurrence among premature neonates. We present a case of 11-day-old premature neonate who presented with abdominal distension, intolerance to feeds, vomiting, significant bilious aspirate and bleeding per rectum. The initial diagnosis of necrotizing enterocolitis (NEC) led to a delay in the diagnosis. On exploratory laparotomy, it turned out to be a case of ileo-colic intussusception with Meckel''s diverticulum as a lead point. This site of intussusception (ileo-colic) and presence of a lead point among premature neonate is of exceedingly rare occurrence and very few such cases have been reported.In this article, the published work about clinical features and management on intussusceptions in premature neonates has been reviewed. The authors intend to highlight the difficulty in distinguishing the NEC and intussusception. Subtle clinical and radiological features which can help in differentiating the two conditions have been emphasized. This can avoid the delay in diagnosis and management which can prove critical. High index of suspicion with timely intervention is the key for optimizing outcome. A diagnosis of intussusception should always be considered in any preterm infant with suspected NEC.     

A process evaluation of implementing a vocational enablement protocol for employees with hearing difficulties in clinical practice

Objective: A multidisciplinary vocational rehabilitation programme, the Vocational Enablement Protocol (VEP) was developed to address the specific needs of employees with hearing difficulties. In the current study we evaluated the process of implementing the VEP in audiologic care among employees with hearing impairment. Design: In conjunction with a randomized controlled trial, we collected and analysed data on seven process parameters: recruitment, reach, fidelity, dose delivered, dose received and implemented, satisfaction, and perceived benefit. Study sample: Sixty-six employees with hearing impairment participated in the VEP. The multidisciplinary team providing the VEP comprised six professionals. Results: The professionals performed the VEP according to the protocol. Of the recommendations delivered by the professionals, 31% were perceived as implemented by the employees. Compliance rate was highest for hearing-aid uptake (51%). Both employees and professionals were highly satisfied with the VEP. Participants rated good perceived benefit from it. Conclusions: Our results indicate that the VEP could be a useful treatment for employees with hearing difficulties from a process evaluation perspective. Implementation research in the audiological setting should be encouraged in order to further provide insight into parameters facilitating or hindering successful implementation of an intervention and to improve its quality and efficacy.     

The role of vessel wall physiology in predicting coronary bypass graft patency

Pulmonary hamartomas are usually an incidental finding and range in size from 1 cm to 8 cm in diameter in various series. We report a case of a massive pulmonary hamartoma (size 25.5 × 17.5 × 6.5 cm and weighing 1134 g) in a 61 year old male who presented with a short history of breathlessness. The tumour was arising from the medial border of the right lung and occupying most of the right chest extending in to the anterior mediastinum. The tumour was compressing the right lung and there was no evidence of infiltration into the surrounding structures. It was successfully treated by surgical resection and final histology was pulmonary hamartoma with predominantly adipose and leiomyomatous differentiation.     

Bipolar disorders: treatment options and patient satisfaction

Functional recovery, the goal of treatment, has long been overlooked in the assessment of effectiveness of pharmacological treatments. However, with the recent shift in paradigm, from syndromal–symptomatic recovery to functional recovery, there appears to be a new interest in the definition and evaluation of functional recovery. Since functional recovery lags symptomatic recovery, sometimes by months or years, the attainment of functional recovery will be determined by both efficacy and long-term compliance. Quetiapine, due to its efficacy in both mania and depression, and effect on cognition may lead to improved functioning in patients with bipolar disorder.     

Pulmonary effects of exposure to pig barn air

Swine production has undergone rapid transformation from family owned operation to a large scale industrial enterprise. Since increasing number of pigs are reared on a large scale in confined buildings, some of the swine barn workers may be employed to work eight hours per day. Swine barn workers suffer from higher incidences of impaired air flow and lung inflammation, which is attributed to high intensity and interrupted exposures to pig barn air. The air in these barns contains gases, dust, microbes and endotoxin with endotoxin being the major suspect as the cause of lung dysfunction. This review attempts to describe the current state of knowledge of incidences and mechanisms of pulmonary dysfunction following exposure to the barn air.     

Hypohiderotic ectodermal dysplasia.

We report a case of a six years age girl who presented to our out patients department with the history and findings suggestive of recurrent respiratory tract infections. She was also noticed to have; non homogeneous hyper- pigmented patches on the face since three months of age, sparse hair on the scalp and eyebrows, conical peg like teeth and delayed dentition, prominent and low set ears, perpetually flexed third toe bilaterally. Axillary skin biopsy showed adenexal structures and eccrine glands in subcutaneous fat which were reduced in number. The diagnosis made was: Anhydrotic/ Hypohidrotic type of ectodermal dysplasia. Key words: Ectodermal Dysplasia, Anhidreotic, Hypohidrotic.     

Additive Effects of Sevoflurane and Propofol on γ-Aminobutyric Acid Receptor Function

Background: Previous studies have shown that propofol and sevoflurane enhance the function of [gamma]-aminobutyric acid type A (GABAA) receptors. However, it is not known whether these two drugs modulate the same molecular pathways. In addition, little is known about receptor function in the presence of both propofol and sevoflurane. The aim of this study was to better understand the interactions of propofol and sevoflurane with the GABAA receptor.

Methods: Wild-type [alpha]1, [beta]2, [gamma]2s GABAA receptor subunit complementary DNAs were transfected into human embryonic kidney cells grown on glass coverslips using a calcium phosphate transfection method. After transfection (36-72 h), cells were whole cell patch clamped and exposed to combinations of the following: 0.3-1,000 [mu]m [gamma]-aminobutyric acid (GABA), 0-10 [mu]m propofol, and 0-1,650 [mu]m sevoflurane. Chemicals were delivered to the cells using two 10-channel infusion pumps and a rapid solution exchanger.

Results: Both propofol and sevoflurane alone enhanced the amplitude of GABAA receptor responses to submaximal concentrations of GABA in a dose-dependent manner. The enhancement was underpinned by an increase in the apparent affinity of the receptor for GABA. Coapplication of both anesthetics further enhanced the apparent affinity of the receptor for GABA.     

Cervical necrotizing fasciitis in an uncontrolled type II diabetic patient

We report a case of cervical necrotizing fasciitis (CNF) in a female having uncontrolled type II diabetes mellitus. The patient was presented to us after 20 days of preliminary symptoms. The aetiology of microbial inoculation in subdermal tissue was not known. The isolate was Staphylococcus aureus. In spite of the delay in presentation, the patient was successfully treated with combined antimicrobial and surgical intervention.