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.     

Predictors of long-term survival in patients with gallbladder cancer

The aim of this study was to examine the predictors of long-term survival (>24 months) in patients with gall bladder cancer. A retrospective review of 117 cases of gall bladder cancer resected between 1989 and 2000. The resections included 80 simple cholecystectomies and 37 extended procedures. Patients with survival >24 months (n=44) were compared with those having survival <24 months (n=73) for 17 prognostic factors. Overall median survival was 16 months with a 5-year survival of 27%. T status (P=.000) and adjuvant chemoradiotherapy (P=.001) were independent predictors of long-term survival. Survival advantage was seen in T3N+ve disease (P=.007) with extended procedures. Complete (R0) resection was attained in 30 patients with a 5-year survival advantage of 30% as compared with incomplete (R1) resection (P=.0002). Adjuvant chemoradiotherapy improved survival in simple cholecystectomy group (P=.0008) but no advantage was seen after extended procedures. Stage III (P=.001) and node-positive disease (P=.0005) had significant benefit with adjuvant therapy. Poor differentiation and vascular invasion were associated with poor long-term survival. R0 resection was associated with prolonged survival. Extended procedures improved survival in patients with T3N+ve disease. Addition of chemoradiotherapy made significant improvement in long-term survival in stage III and node-positive lesions and in patients undergoing simple cholecystectomy. R0 resection predicted long-term survival in gall bladder cancer. T3 N+ve disease had better survival after extended procedures. Adjuvant chemoradiotherapy improved survival in stage III and node-positive disease. Poor differentiation and vascular invasion were adverse predictors of survival.     

Autoimmune hepatitis: a study of 50 patients.

INTRODUCTION: Autoimmune hepatitis (AIH) is a well-defined entity in the West but there are sparse Indian data on this disease. AIM: To study the clinical profile and response to treatment of Indian patients with AIH. METHODS: This is a part retrospective and part prospective study of 50 patients (median age 48 years, range 11-82; 43 women) seen between 1995 to 2001, diagnosed to have AIH as per the revised scoring system. Clinical and laboratory profile, response to treatment, and complications of treatment were analyzed. RESULTS: AIH accounted for 6% of all patients with liver disease seen during the period. The presenting symptoms were gastrointestinal in 43 and non-gastrointestinal in 7, with median symptom duration of 6 months (range 2 weeks to 40 years). Forty patients (80%) had chronic liver disease. Associated illnesses were present in 28 patients. Twenty-six patients were classified as definite and the rest as probable AIH. Forty-nine patients had Type 1 AIH. Five patients had overlap syndrome. Forty-five patients (90%) received immunosuppressive therapy. Twelve of 18 patients receiving only prednisolone and 21 of 27 patients receiving prednisolone and azathioprine combination responded. Thirteen (26%) patients had therapy-related complications (infectious 5, non infectious 8) with two treatment-related deaths. CONCLUSION: Type 1 AIH was the predominant type of AIH. The majority of patients with AIH presented with chronic liver disease. There was good response to immunosuppressive therapy. Therapy-related complications occurred in one-fourth of patients.     

Serotonergic interhemispheric asymmetry: Neurochemical and pharmaco-EEG evidence

1. Postmortem neurochemical investigations revealed interhemispheric asymmetry in the mediofrontal region of human brain. Significantly higher right hemisphere serotonin metabolite (5HIAA) content as well as increased maximal imipramine binding (IB) were found in the right hemisphere than in the left side.

2. IB did not show a gender difference in the mediofrontal area. However, women had higher IB in the right orbital frontal cortex than did men.

3. In vivo pharmaco-EEG results tend to support the postmortem neurochemical data. Intravenous chlorimipramine resulted in an asymmetric topographic distribution of the P300 auditory evoked potential, peak amplitudes were shifted to the right hemisphere.     

Effect of local mupirocin application on exit-site infection and peritonitis in an Indian peritoneal dialysis population.

BACKGROUND: Staphylococcus aureus-associated peritonitis and catheter exit-site infections (ESIs) are important causes of hospitalization and catheter loss in patients undergoing chronic peritoneal dialysis. Intranasal and topical use of mupirocin has been found to be an effective strategy in decreasing S. aureus-related infectious complications in persons who are carriers of S. aureus; however, there is no consensus regarding the prophylactic use of mupirocin irrespective of carrier status. We aimed to determine the potential effectiveness of application of mupirocin cream at the catheter exit site in preventing ESI and peritonitis irrespective of carrier status in a tropical country such as India. METHODS: This prospective historically controlled study was done in a total of 40 patients. From August 2003, all patients, incident and prevalent, were instructed to apply 2% mupirocin cream daily to the exit site instead of the older practice of povidone-iodine and gauze dressing. Patients were not screened to determine whether they were S. aureus carriers. The infection-related data for 1 year, until July 2004, were compared with the historical control, which was infection-related data for the year preceding the year of mupirocin application. RESULTS: Mean age of the study population was 62 years, with 61.8% being male and 64.3% being diabetic. Local application of mupirocin led to a significant reduction in the incidence density per patient-month of both ESI and peritonitis compared to controls (0.15 vs 0.37 and 0.37 vs 0.67, p = 0.01 for both). This amounted to a relative reduction of 60.5% and 55% respectively. ESI and peritonitis due to S. aureus were also significantly lower in the study group compared to controls (incidence density per patient-month 0.05 vs 0.13 and zero vs 0.17 respectively, p < 0.01 for both). There occurred no catheter removal due to infection-related complications during the study period compared to two during the control period. None of the patients reported a mupirocin-related adverse effect. CONCLUSIONS: Daily application of mupirocin at the exit site is a well-tolerated and effective strategy in reducing the incidence of ESI and peritonitis in a tropical country such as India. It can thus significantly reduce morbidity, catheter loss, and transfer to hemodialysis in peritoneal dialysis patients.     

Return of fertility following discontinuation of an injectable contraceptive — Norethisterone oenanthate (NET EN) 200mg dose

The return of fertility following discontinuation of norethisterone oenanthate (NET EN) 200 mg injectable contraceptive after use for a minimum period of six months or more was studied in 69 women who discontinued the method for planning pregnancy. Former users of copper intra-uterine device (CuT 200) were enrolled as a control group. Another 161 women who had discontinued NET EN due to other reasons (e.g. amenorrhoea, excessive bleeding or personal reasons) were also studied for return of fertility after ensuring that they were not using any other method of contraception and were exposed to the risk of pregnancy. The subjects from both groups were followed for a period of one year. The cumulative conception rates at one year were 72.5 and 83.6 per 100 subjects for ex-NET EN and ex-CuT 200 users who had discontinued the method for planning pregnancy and this difference was not statistically significant (P > 0.05). The median time for conception for ex-NET EN users was 7.8 months as compared to 3.7 months in ex-CuT 200 users but the cumulative conception rates at the end of one year show that future return of fertility in NET EN users does not appear to be adversely affected.

In 51 subjects who had discontinued NET EN due to amenorrhoea, the return of fertility was predictably slower and less. The return of fertility in subjects who discontinued NET EN for other reasons (e.g. excessive bleeding and other personal reasons) was similar to ex-NET EN and ex-CuT 200 users.     

CT appearances of hydatid disease at various locations

Hydatid disease has characteristic imaging features on CT, which allow accurate preoperative diagnosis in most cases. However, when it occurs at unusual locations the diagnosis is often difficult, especially as the imaging appearance varies at different sites. In this article we have presented a pictorial review of the CT features of disease due to Echinococcus granulosus at various sites in the human body.     

Studies on the optimal conditions for inactivation of Bordetella pertussis organisms with glutaraldehyde for preparation of a safe and potent pertussis vaccine

The optimal conditions for inactivation of Bordetella pertussis organisms with glutaraldehyde for the production of a safe and potent whole cell pertussis vaccine were investigated. Two bacterial harvests from B. pertussis strain 10536 were treated with glutaraldehyde, each with 0.025, 0.05 and 0.1% concentrations of glutaraldehyde for 10, 60 and 120 min. The nine types of glutaraldehyde-inactivated pertussis vaccine (GIPV) and conventional heat-inactivated pertussis vaccine (HIPV) preparations made from two bacterial harvests were comparatively evaluated for the mouse weight gain test (MWGT), potency, and the histamine-sensitization (HS) and leucocytosis-promoting-factor (LPF) tests. The minimum period for killing the B. pertussis organisms with glutaraldehyde was>10 min for 0.025%, 10 min for 0.05% and 5 min for 0.1% concentration. The average loss in opacity varied from 5 to 10% for GIPV preparations and was 14% for HIPV preparations. The GIPV preparations except those inactivated with 0.025% glutaraldehyde for 10 min (GIPV-A) were much less toxic than the HIPV preparations in the MWGT. The GIPV-A preparations did not pass the MWGT. The GIPV preparations were also much less toxic in HS and LPF tests than the HIPV preparation. The potency of GIPV preparations inactivated with 0.05% glutaraldehyde for 10 min (GIPV-D) was similar to that of HIPV preparations. The prolonged treatments with glutaraldehyde reduced the potency. The GIPV-D preparation with good potency and less toxicity was found to be inactivated with glutaraldehyde under optimal conditions. All the preparations were innocuous in the abnormal toxicity test.