Impact of concomitant use of proton pump inhibitors and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome

Background There is great debate on the possible adverse interaction between proton pump inhibitors (PPIs) and clopidogrel. In addition, whether the use of PPIs affects the clinical efficacy of ticagrelor remains less known. We aimed to determine the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods We retrospectively analyzed data from a “real world”, international, multi-center registry between 2003 and 2014 (n = 15,401) and assessed the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year composite primary endpoint (all-cause death, re-infarction, or severe bleeding) in patients with ACS after PCI. Results Of 9,429 patients in the final cohort, 54.8% (n = 5165) was prescribed a PPI at discharge. Patients receiving a PPI were older, more often female, and were more likely to have comorbidities. No association was observed between PPI use and the primary endpoint for patients receiving clopidogrel (adjusted HR: 1.036; 95% CI: 0.903–1.189) or ticagrelor (adjusted HR: 2.320; 95% CI: 0.875–6.151) (P_interaction = 0.2004). Similarly, use of a PPI was not associated with increased risk of all-cause death, re-infarction, or a decreased risk of severe bleeding for patients treated with either clopidogrel or ticagrelor. Conclusions In patients with ACS following PCI, concomitant use of PPIs was not associated with increased risk of adverse outcomes in patients receiving either clopidogrel or ticagrelor. Our findings indicate it is reasonable to use a PPI in combination with clopidogrel or ticagrelor, especially in patients with a higher risk of gastrointestinal bleeding.     

Administration of pegylated recombinant human megakaryocyte growth and development factor to humans stimulates the production of functional platelets that show no evidence of in vivo activation

This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status.     

Asthma Severity and Control and Their Association With Perinatal Mental Illness

ObjectiveGrowing evidence suggests asthma increases perinatal mental illness risk, but few studies have explored the impact of asthma severity and control. Our objective was to explore the association between asthma severity and control and perinatal mental illness risk and the impact of asthma exacerbations during pregnancy on postpartum mental illness risk.MethodsThis was a population-based retrospective cohort study of all women in Ontario, Canada, from 2005 to 2015 with a singleton live birth who used public drug insurance, excluding women with recent history of mental illness. We constructed modified Poisson regression models to assess the risk of perinatal mental illness, defined as a mood or anxiety, psychotic or substance use disorder, self-harm or other mental illness diagnosed from conception to 365 days postnatally. Models controlled for socio-demographic factors and medical history.ResultsThere were 62,583 women in the cohort (46.7% between 15 − 24 years), of whom 22.7% had asthma (94.3% mild, 5.7% moderate/severe; 86.5% controlled and 13.5% uncontrolled). After adjustment, there was increased risk of perinatal mental illness with mild asthma (adjusted relative risk [RR]: 1.12; 95% confidence interval [CI], 1.09 to 1.16) and moderate/severe asthma (aRR: 1.16; 95% CI, 1.04 to 1.30) compared to no asthma. Controlled asthma (aRR: 1.11; 95% CI, 1.08 to 1.15) and uncontrolled asthma (aRR: 1.19; 95% CI, 1.11 to 1.27) were also associated with increased perinatal mental illness risk compared to no asthma. Women with worsened asthma during pregnancy had the highest risk of postpartum mental illness compared to no change in asthma status (by severity: aRR: 1.57; 95% CI, 1.36 to 1.80; by control: aRR: 1.37; 95% CI, 1.22 to 1.54).ConclusionAsthma is associated with increased risk of perinatal mental illness, particularly in the presence of asthma exacerbations in pregnancy. The results support multidisciplinary collaborative care programmes throughout the perinatal period, especially among women with asthma exacerbations during pregnancy.     

Rapid assessment of blood pressure in the obstetric day unit using Microlife MaM technology.

OBJECTIVE: To compare MaM technology with current methods of assessing blood pressure (BP) over time on the obstetric day unit. BACKGROUND: It is recommended that the average of repeated measures is used to confirm hypertension in pregnancy. The Microlife 3AC1 is a validated oscillometric device featuring "MaM" mode using the average of at least 3 BP readings 15 seconds apart. This allows rapid assessment of BP. The difference between each measurement is calculated and influences the percentage contribution to the final average reading. We compared MaM with readings taken in a conventional manner. METHODS: Blood pressure was measured in 30 hypertensive pregnant patients recruited from the obstetric day unit of a large teaching hospital. Single BP measurements were taken at 0, 15, 30, 60, and 90 minutes using the Microlife BP 3BT0-A[2]. Simultaneous measurements (in the opposite arm) were also taken at 0 and 90 minutes using MaM technology. RESULTS: Systolic BP fell over 90 minutes (p = 0.035) compared with the first single reading, but diastolic BP did not (p = 0.54). The difference between the first MaM and the first single reading was significantly different for systolic BP (5.6 mm Hg, p = 0.017), but not for diastolic (0.6 mm Hg, p = 0.39). The mean of all single readings and the first MaM reading were similar for both systolic and diastolic BP (SBP:0.3 mm Hg, p = 0.75, DBP: 0.2 mm Hg, p = 0.87). Conclusions: White-coat hypertension exists for systolic BP in the obstetric day unit. The MaM technology allows rapid and accurate characterization of blood pressure equivalent to repeated measures over 90 minutes.     

Epidemiology of tuberculosis and HIV coinfections in Singapore, 2000–2014

Cross‐matching of records between Singapore's tuberculosis and HIV registries showed that 3.3% of individuals with tuberculosis (TB) were coinfected with HIV (2000?2014), the TB incidence among individuals with HIV infection was 1.65 per 100 person‐years, and 53% of coinfections were diagnosed within 1 month of each other. The findings supported joint prevention programmes for early diagnosis and treatment.     

One-stage repair of cardiac and arch anomalies without circumlatory arrest

Indian Journal of Thoracic and Cardiovascular Surgery -