Optimising antiplatelet utilisation in the acute care setting: a novel threshold for medical intervention in suspected acute coronary syndromes.

OBJECTIVES: To construct a model to optimise and personalise recommendations for antiplatelet prescription for patients with suspected acute coronary syndrome (ACS). Acknowledging that emergency physicians work with diagnostic uncertainty, we sought to identify the point at which the probability of ACS is sufficiently high that the benefits of antiplatelet treatment outweigh the risks. Second, we evaluated the projected clinical impact of this approach by using a clinical prediction model (Troponin-only Manchester Acute Coronary Syndromes (T-MACS)) to calculate the probability of ACS. METHODS: We conducted three systematic reviews, quantifying the effects of ticagrelor, clopidogrel or aspirin-alone treatment strategies for ACS (November 2017). We extracted data for (a) clinical outcomes and (b) weighted patient preferences (utilities) for each outcome. We then constructed utilitarian models, simulating the probability of clinical outcomes with different treatment strategies. This identified the threshold probability of ACS at which each treatment strategy became superior.We validated this approach in a prospective diagnostic study including patients with suspected ACS that was conducted at two large UK teaching hospitals (St George's Hospital London recruited October 2015 to June 2017 and Manchester Royal Infirmary: February 2015 to August 2017). We calculated the probability of ACS using T-MACS. The diagnosis of ACS was adjudicated based on serial high-sensitivity troponin testing and 30-day follow-up. RESULTS: We constructed three models using data from six studies. Prescribing ticagrelor had greatest overall benefit when the probability of ACS exceeded 8.0%. Below that threshold, aspirin alone yielded greater benefit. The validation study included 660 patients, of which 87 (13.2%) had ACS. Prescription of combined antiplatelet strategy to patients with >8% probability of ACS had greater utility than aspirin alone. CONCLUSION: Treatment with ticagrelor appears to yield greater net benefit for patients when the probability of ACS >8%. The clinical and cost-effectiveness of this 'precision medicine' approach warrants further study.

European guidelines on perioperative venous thromboembolism prophylaxis: Aspirin.

: There is a good rationale for the use of aspirin in venous thromboembolism prophylaxis in some orthopaedic procedures, as already proposed by the 9th American College of Chest Physicians' guidelines (Grade 1C). We recommend using aspirin, considering that it may be less effective than or as effective as low molecular weight heparin for prevention of deep vein thrombosis and pulmonary embolism after total hip arthroplasty, total knee arthroplasty and hip fracture surgery (Grade 1C). Aspirin may be less effective than or as effective as low molecular weight heparins for prevention of deep vein thrombosis and pulmonary embolism after other orthopaedic procedures (Grade 2C). Aspirin may be associated with a low rate of bleeding after total hip arthroplasty, total knee arthroplasty and hip fracture surgery (Grade 1B). Aspirin may be associated with less bleeding after total hip arthroplasty, total knee arthroplasty and hip fracture surgery than other pharmacological agents (Grade 1B). No data are available for other orthopaedic procedures. We do not recommend aspirin as thromboprophylaxis in general surgery (Grade 1C). However, this type of prophylaxis could be interesting especially in low-income countries (Grade 2C) and adequate large-scale trials with proper study designs should be carried out (Grade 1C).

Effect of Antithrombotic Therapy and Long Endoscopic Submucosal Dissection Procedure Time on Early and Delayed Postoperative Bleeding.

BACKGROUND: Recent updated guidelines of the Japanese Society of Gastroenterology recommend the use of a single dose of antiplatelet agents in patients undergoing endoscopic submucosal dissection (ESD). However, the postoperative bleeding risk after gastric ESD associated with the continuation or interruption of antithrombotic therapy remains controversial. We aimed to evaluate whether certain factors including interrupted antithrombotic therapy could affect early and delayed post-ESD bleeding risk. METHODS: Three hundred sixty-four patients with gastric neoplasms were treated with ESD at our hospital between October 2005 and December 2012. Seventy-four patients with interrupted antithrombotic therapy were undertaken with ESD. Early and delayed postoperative bleeding patterns were estimated. Various clinical characteristics such as gender, age, tumor location, tumor size, ESD procedure time, platelet count, and comorbidity were evaluated. RESULTS: There was a significant difference (p = 0.042) in the ESD procedure time between the patients with postoperative bleeding and those without it. There was no significant difference in postoperative bleeding between the patients on antithrombotic therapy and not on it. Moreover, interrupted antithrombotic therapy and platelet count were significantly (p = 0.0461 and p = 0.0059, respectively) associated with early postoperative bleeding in multivariate analysis. In addition, in univariate analysis, ESD procedure time was significantly (p = 0.041) associated with delayed postoperative bleeding. CONCLUSIONS: Antithrombotic therapy and prolonged ESD procedure time were significantly associated with early and delayed postoperative bleeding, respectively.

Inappropriate Use of Aspirin in Real-Life Cardiology Practice: Results from the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study (ASSOS) Study.

BACKGROUND: Indications and appropriateness of aspirin use have not been well investigated in Turkey. AIMS: To investigate the prescription patterns and appropriateness of aspirin in a real-world clinical setting. STUDY DESIGN: Cross-sectional study. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study (ASSOS) is a cross-sectional and multicenter study that included 5007 consecutive patients aged 18 or over who presented to 30 different cardiology outpatient clinics from 14 cities throughout Turkey. Only patients using aspirin (80-325 mg) were included. The study population was divided into 2 groups regarding the use of aspirin: primary prevention (PP) group and secondary prevention (SP) group. The indication of aspirin use was evaluated following the 2016 European Society of Cardiology (ESC) and the 2016 United States Preventative Services Task Force (USPTF) guidelines in the PP group. RESULTS: A total of 5007 patients (mean age 62.15 ± 11.05, 39% female) were enrolled. The PP group included 1132 (22.6%) patients, and the SP group included 3875 (77.4%) patients. Of the 1132 patients, inappropriate use of aspirin was determined in 100% of the patients according to the ESC guidelines, and 71% of the patients according to the USPTF guidelines. Multivariate logistic regression analysis showed age OR: 0.98 CI (0.97-0.99) P = .037, smoking OR: 0.60 CI (0.44-0.82) P = .001, heart failure OR: 2.11 CI (1.14-3.92) P = .017, hypertension OR: 0.51 CI (0.36-0.74) P < .001, diabetes mellitus OR: 0.34 CI (0.25-0.47) P < .001, oral anticoagulant use OR: 3.01 CI (1.10-8.25) P = .032, and female sex OR: 2.73 CI (1.96-3.80) P < .001 were independent predictors of inappropriate aspirin use in PP patients. CONCLUSION: Although there are considerable differences between the USPTF and the ESC guidelines with respect to recommendations for aspirin use in PP, inappropriate use of aspirin in Turkey is frequent in real-world practice for both guidelines. Besides, heart failure, oral anticoagulant use, and the female sex of the patients were independent predictors of inappropriate use of aspirin.

Aspirin in primary prevention: the triumph of clinical judgement over complex equations.

Aspirin, in 2017, has celebrated its 120th birthday. The efficacy and safety of low-dose aspirin in secondary prevention of cardiovascular disease is well supported by many studies, instead in primary prevention it remains controversial, especially in the aftermath of the publication in 2018 of three novel primary prevention randomized clinical trials, showing that the benefit of low-dose aspirin, although additive to that of statin, is counterbalanced by an excess of (mainly gastrointestinal) bleeding events. The signal for a net benefit seems to be even more controversial in the elderly starting aspirin after the age of 70 years. While international guidelines have promptly downgraded their recommendations to more conservative indications, the practicing clinician is called to make the effort to individualize the treatment, after careful evaluation of the haemorrhagic risk vis-a-vis the risk to develop, in the mid-term and long-term follow-up, major cardiovascular events or cancer. This is a particularly complex task, given the different immediate and long-term impact of diverse outcomes on health, the dynamic nature over time of the benefit/risk balance, prompting periodic re-assessments of its indication, and the interindividual variability in aspirin response. The chemopreventive properties of aspirin, anticipated by a large body of epidemiological and mechanistic evidence, are awaiting their final confirmation by the long-term follow-up of the latest trials specifically designed to assess this endpoint, with the expectation to subvert the delicate benefit/risk balance of aspirin in primary prevention. This review is intended to provide an interpretation of past and current evidence to guide clinical decision making on the contemporary patient.

ACOG Committee Opinion No. 743 Summary: Low-Dose Aspirin Use During Pregnancy.

Low-dose aspirin has been used during pregnancy, most commonly to prevent or delay the onset of preeclampsia. The American College of Obstetricians and Gynecologists issued the Hypertension in Pregnancy Task Force Report recommending daily low-dose aspirin beginning in the late first trimester for women with a history of early-onset preeclampsia and preterm delivery at less than 34 0/7 weeks of gestation, or for women with more than one prior pregnancy complicated by preeclampsia. The U.S. Preventive Services Task Force published a similar guideline, although the list of indications for low-dose aspirin use was more expansive. Daily low-dose aspirin use in pregnancy is considered safe and is associated with a low likelihood of serious maternal, or fetal complications, or both, related to use. The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine support the U.S. Preventive Services Task Force guideline criteria for prevention of preeclampsia. Low-dose aspirin (81 mg/day) prophylaxis is recommended in women at high risk of preeclampsia and should be initiated between 12 weeks and 28 weeks of gestation (optimally before 16 weeks) and continued daily until delivery. Low-dose aspirin prophylaxis should be considered for women with more than one of several moderate risk factors for preeclampsia. Women at risk of preeclampsia are defined based on the presence of one or more high-risk factors (history of preeclampsia, multifetal gestation, renal disease, autoimmune disease, type 1 or type 2 diabetes, and chronic hypertension) or more than one of several moderate-risk factors (first pregnancy, maternal age of 35 years or older, a body mass index greater than 30, family history of preeclampsia, sociodemographic characteristics, and personal history factors). In the absence of high risk factors for preeclampsia, current evidence does not support the use of prophylactic low-dose aspirin for the prevention of early pregnancy loss, fetal growth restriction, stillbirth, or preterm birth.

ACOG Committee Opinion No. 743: Low-Dose Aspirin Use During Pregnancy.

Low-dose aspirin has been used during pregnancy, most commonly to prevent or delay the onset of preeclampsia. The American College of Obstetricians and Gynecologists issued the Hypertension in Pregnancy Task Force Report recommending daily low-dose aspirin beginning in the late first trimester for women with a history of early-onset preeclampsia and preterm delivery at less than 34 0/7 weeks of gestation, or for women with more than one prior pregnancy complicated by preeclampsia. The U.S. Preventive Services Task Force published a similar guideline, although the list of indications for low-dose aspirin use was more expansive. Daily low-dose aspirin use in pregnancy is considered safe and is associated with a low likelihood of serious maternal, or fetal complications, or both, related to use. The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine support the U.S. Preventive Services Task Force guideline criteria for prevention of preeclampsia. Low-dose aspirin (81 mg/day) prophylaxis is recommended in women at high risk of preeclampsia and should be initiated between 12 weeks and 28 weeks of gestation (optimally before 16 weeks) and continued daily until delivery. Low-dose aspirin prophylaxis should be considered for women with more than one of several moderate risk factors for preeclampsia. Women at risk of preeclampsia are defined based on the presence of one or more high-risk factors (history of preeclampsia, multifetal gestation, renal disease, autoimmune disease, type 1 or type 2 diabetes, and chronic hypertension) or more than one of several moderate-risk factors (first pregnancy, maternal age of 35 years or older, a body mass index greater than 30, family history of preeclampsia, sociodemographic characteristics, and personal history factors). In the absence of high risk factors for preeclampsia, current evidence does not support the use of prophylactic low-dose aspirin for the prevention of early pregnancy loss, fetal growth restriction, stillbirth, or preterm birth.

[Current problems in the quality control of pharmaceutical preparations manufactured in pharmacies II. Paracetamol contraining preparations]. / Magisztráilis gyógyszerkészítmények minoségellenorzésének aktuális kérdései II. Paracetamol tartalmú készítmények tartalmi meghatározáisi lehetoségei.

In our previous paper identification methods using chemical reactions and TLC are described for the active ingredients of pharmaceutical preparations in Formula Normales (FoNo VII.). Present paper introduces the development and validation of analytical methods suitable for quantitative determination of paracetamol containing dosage forms in FoNo VII. Titrimetric methods, UV spectroscopy and HPLC are used for assay of paracetamol and accompanying components (e.g. codeine, papaverine, caffeine and acetylsalicylic acid) in these preparations.

Expert position paper on prolonged dual antiplatelet therapy in secondary prevention following myocardial infarction.

The protective effect of dual antiplatelet therapy (DAPT) following acute coronary syndrome is undisputed, but its duration is subject of debate. Several studies show that prolonged therapy provides a clinical benefit in patients following acute coronary syndrome. The aim of this position paper authored by Austrian experts is to outline the current evidence and provide an overview of recent studies. It is also intended to serve as a practical guide to identify those patients who may benefit from prolonged DAPT.

Reporting on the Strategies Needed to Implement Proven Interventions: An Example From a "Real-World" Cross-Setting Implementation Study.

UNLABELLED: The objective of this study was to empirically demonstrate the use of a new framework for describing the strategies used to implement quality improvement interventions and provide an example that others may follow. Implementation strategies are the specific approaches, methods, structures, and resources used to introduce and encourage uptake of a given intervention's components. Such strategies have not been regularly reported in descriptions of interventions' effectiveness, or in assessments of how proven interventions are implemented in new settings. This lack of reporting may hinder efforts to successfully translate effective interventions into "real-world" practice. A recently published framework was designed to standardize reporting on implementation strategies in the implementation science literature. We applied this framework to describe the strategies used to implement a single intervention in its original commercial care setting, and when implemented in community health centers from September 2010 through May 2015. Per this framework, the target (clinic staff) and outcome (prescribing rates) remained the same across settings; the actor, action, temporality, and dose were adapted to fit local context. The framework proved helpful in articulating which of the implementation strategies were kept constant and which were tailored to fit diverse settings, and simplified our reporting of their effects. Researchers should consider consistently reporting this information, which could be crucial to the success or failure of implementing proven interventions effectively across diverse care settings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02299791.

Near-infrared chemical imaging (NIR-CI) as a process monitoring solution for a production line of roll compaction and tableting.

In the present study the application of near-infrared chemical imaging (NIR-CI) supported by chemometric modeling as non-destructive tool for monitoring and assessing the roller compaction and tableting processes was investigated. Based on preliminary risk-assessment, discussion with experts and current work from the literature the critical process parameter (roll pressure and roll speed) and critical quality attributes (ribbon porosity, granule size, amount of fines, tablet tensile strength) were identified and a design space was established. Five experimental runs with different process settings were carried out which revealed intermediates (ribbons, granules) and final products (tablets) with different properties. Principal component analysis (PCA) based model of NIR images was applied to map the ribbon porosity distribution. The ribbon porosity distribution gained from the PCA based NIR-CI was used to develop predictive models for granule size fractions. Predictive methods with acceptable R(2) values could be used to predict the granule particle size. Partial least squares regression (PLS-R) based model of the NIR-CI was used to map and predict the chemical distribution and content of active compound for both roller compacted ribbons and corresponding tablets. In order to select the optimal process, setting the standard deviation of tablet tensile strength and tablet weight for each tablet batch was considered. Strong linear correlation between tablet tensile strength and amount of fines and granule size was established, respectively. These approaches are considered to have a potentially large impact on quality monitoring and control of continuously operating manufacturing lines, such as roller compaction and tableting processes.

Aspirin--a national survey III: Determination of impurities in bulk aspirin and aspirin formulations by high-pressure liquid chromatography and spectrophotometry.

A quantitative high-pressure liquid chromatographic method, using a reversed-phase column and an aqueous acetic acid-methanol solution as the mobile phase, was employed for the determination of O-acetyl-O-salicylsalicylic acid and O-salicylsalicylic acid in pharmaceutical aspirin preparations. The aspirin was dissolved, filtered, and injected into the chromatograph. The absorbance of the impurities was measured at 254 nm. Acetylsalicylic anhydridge was determined by a spectrophotometric method. The aspirin was dissolved in pH 11.3 buffer and extracted with benzene. An aliquot of the benzene was evaporated, and the residue was dissolved in alpha-benzamidocinnamate-pyridine reagent. The acetylsalicylic anhydride was measured using the difference between the absorbance at 362 and 372 nm. Possible interference of aspirin with the procedure is discussed. Thirty-four bulk aspirin and 172 tablet formulations were examined. Results for O-acetyl-O-salicylsalicylic acid, O-salicylsalicylic acid and acetylsalicylic anhydride are given.

Aspirin--a national survey V: Determination of aspirin and impurities in enteric coated tablets and suppository formulations and in vitro dissolution of enteric coated tablets.

The results of a national survey on the quality of enteric coated aspirin tablets and aspirin suppositories are presented. The tablets were analyzed for strength, salicylic acid content, in vitro dissolution rate, and related aspirin impurities. The suppositories were analyzed for strength and salicylic acid content. The methods of analysis and validation of data are also presented.

Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: defining the role of gastroprotective agents.

Treatment with anti-inflammatory drugs and the analgesic efficacy of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are compromised by a two- to fourfold increased risk of gastrointestinal complications. This increased risk has resulted in an increasing use of the new selective cyclooxygenase-2 inhibitors or coxibs, which, in clinical trials and outcomes studies, reduced gastrointestinal adverse events by 50% to 65% compared with conventional NSAIDs. However, the coxibs are not available to all patients who need them, and NSAIDs are still widely used. Moreover, treatment with a coxib cannot heal pre-existing gastrointestinal lesions, and cotherapy with an anti-secretory drug or mucosal protective agent may be required. This paper addresses the management of patients with risk factors for gastrointestinal complications who are taking NSAIDs and makes recommendations for the appropriate use of 'gastroprotective' agents (GPAs) in patients who need to take an NSAID or a coxib. When economically possible, a coxib alone is preferable to a conventional NSAID plus a GPA to minimize exposure to potential gastrointestinal damage and avoid unnecessary dual therapy. Patients at high risk require a GPA in addition to a coxib.

Comparison of fluorimetric, voltammetric and biosensor methods for the determination of total antioxidant capacity of drug products containing acetylsalicylic acid.

Antioxidant capacity of several drug specialities containing as mean component acetylsalicylic acid were experimentally evaluated using an enzymatic electrode, recently developed by the present authors, based on superoxide dismutase (SOD) enzyme. The precision of this method of analysis was found to be good (for drug samples RSD < or = 5%). The results were also compared with those ones by a traditional spectrofluorimetric method and by two other methods, respectively, based on cyclic and pulsed voltammetry, recently trialled by the present authors.

Quality of pharmaceutical items available from drugstores in Phnom Penh, Cambodia.

Drugstores and drug outlets are the main sources of care for the majority of Cambodian citizens because of the availability of drugs, short waiting time, and ability to control the cost of treatment. Unfortunately, no enforcement of pharmacy regulations and little consumer and drugstore personnel education contribute to a potential harmful unregulated drug market resulting in high costs and prolonged illness. No study has looked at the quality of over-the-counter drugs, which would have the highest impact on the people. In this study, we were interested in exploring the quality of commonly used pharmaceutical items available from drugstores in Phnom Penh, Cambodia, using uncoated aspirin tablets as a case study. Factors relating to quality of the drug were also examined. This study was conducted by means of drug fishing method to obtain uncoated aspirin tablet samples from 96 drugstores in Phnom Penh. The quality of the samples was examined in six aspects: percent label amount, weight variation, hardness, percent friability, disintegration time, and dissolution rate. We found that only seven (7.3%) of the total 96 samples passed all six quality criteria. Dissolution test appeared to be the most critical step in determining aspirin quality. Factors that were statistically related to the quality of the sample were type of packaging. All the drugs that passed the six criteria were in bottles. Source of the medications was also significantly related to their quality. Among seven samples that passed the test, six were from Vietnam. Our study revealed that the quality of uncoated aspirin tablets was a serious problem. The vast majority of the samples did not meet the standard requirements. Type of packaging and source of medications were related to the quality of samples. This study has important implications for the Cambodian government regarding the control of the quality of pharmaceutical items available in drugstores.

Total organic carbon method for aspirin cleaning validation.

Cleaning validation is the process of assuring that cleaning procedures effectively remove the residue from manufacturing equipment/facilities below a predetermined level. This is necessary to assure the quality of future products using the equipment, to prevent cross-contamination, and as a World Health Organization Good Manufacturing Practices requirement. We have applied the Total Organic Carbon (TOC) analysis method to a number of pharmaceutical products. In this article we discuss the TOC method that we developed for measuring residual aspirin on aluminum, stainless steel, painted carbon steel, and plexiglass. These are all surfaces that are commonly found as part of pharmaceutical production equipment. The method offers low detection capability (parts per million levels) and rapid sample analysis time. The recovery values ranged from 25% for aluminum to about 75% for plexiglass with a precision of 13% or less. The results for the plexiglass tended to vary with the age of the surface making the determination of an accurate recovery value difficult for this type of surface. We found that the TOC method is applicable for determining residual aspirin on pharmaceutical surfaces and will be useful for cleaning validation.

Detection and determination of salicylic acid impurity in aspirin tablet formulations' by high performance liquid chromatography.

Salicylic acid is a major hydrolytic degradation product of aspirin, responsible especially for gastric irritation during oral aspirin administration. This impurity was investigated in 12 different brands of aspirin formulation readily available in our locality. A simple, rapid and sensitive high performance liquid chromatographic method was adopted for this investigation. The mobile phase was methanol/water (20/80, v/v) adjusted to pH 2.5 with phosphoric acid and was run on a 50 mm reversed-phase column monitored at 240 nm. The limit of detection for salicylic acid was 5 ng. Only three of these formulations showed the presence of salicylic acid impurity and all these contained salicylic acid in excess of the USP 1980 limit of 0.3% salicylic acid per tablet.