Timing of P2Y12 Inhibitor Administration in Patients With STEMI Undergoing Primary PCI.

BACKGROUND: The optimal timing of P2Y12 inhibitor administration in patients with ST-segment elevation myocardial infarction (STEMI) has not been completely elucidating. OBJECTIVES: This analysis from a prospective multicenter registry sought to assess the safety and effectiveness of P2Y12 inhibitor pretreatment in patients transferred for primary percutaneous coronary intervention (PCI) within a regional STEMI network. METHODS: Pretreatment was defined as P2Y12 inhibitor administration before coronary angiography. Endpoints were major adverse cardiac events (MACE), major bleeding, and net adverse clinical events, a composite of MACE or major bleeding, within 30 days of index admission. Association of P2Y12 inhibitor pretreatment with outcomes was modeled using doubly robust weighted estimators based on propensity score analysis. RESULTS: Of 1,624 patients included, 1,033 received P2Y12 inhibitors before angiography and 591 in the catheterization laboratory (cath lab). The non-pretreated cohort more often had history of coronary artery disease and were more likely to receive antiplatelet therapy before the index admission. After adjustment for confounding and dependent censoring, pretreatment with P2Y12 inhibitors predicted lower risk of MACE (adjusted HR: 0.53; 95% CI: 0.37-0.76), without increasing bleeding risk (adjusted HR: 0.62; 95% CI: 0.36-1.05), resulting in superior net clinical benefit (adjusted HR: 0.47; 95% CI: 0.26-0.86) compared with in-cath lab administration of P2Y12 inhibitors. There was a significant treatment-by-time interaction for MACE risk, whereby the observed benefits of pretreatment only became apparent when time between P2Y12 inhibitor administration and PCI was longer than 80 minutes. CONCLUSIONS: In contemporary patients with STEMI transferred for primary PCI, pretreatment with P2Y12 inhibitors was associated with a significant time-dependent reduction of 30-day MACE without increasing bleeding risk.

Nonadherence to ticagrelor versus clopidogrel and clinical outcomes in patients with ACS. Results from the CREA-ARIAM registry.

INTRODUCTION AND OBJECTIVES: Prior studies have not determined whether the effect of dual antiplatelet therapy (DAPT) cessation on the subsequent risk of major adverse cardiac events (MACE) varies by the choice of P2Y12-inhibitor after acute coronary syndrome (ACS). METHODS: We performed a prespecified subanalysis of a multicenter, prospective registry of ACS patients discharged on ticagrelor or clopidogrel between 2015 and2019. Nonadherence to DAPT was categorized as physician-guided discontinuation and disruption due to adverse effects, nonadherence, or bleeding. The association between DAPT cessation and 1-year MACE was analyzed using multivariate time-updated Cox models with inverse probability of censoring weighted estimators. RESULTS: Out of 2180 patients, 174 (8.3%) prematurely discontinued DAPT (physician-guided, n=126; disruption, n=48). Nonadherent patients were older and had more comorbidities than those on DAPT. Compared with physician-guided discontinuation, disruption occurred earlier after discharge and was more frequent with ticagrelor than with clopidogrel. In time-varying analysis, DAPT cessation was associated with an increased risk of MACE (adjusted HR, 1.32, 95%CI, 1.10-1.76), largely driven by disruption (adjusted HR, 1.47, 95%CI, 1.22-1.73). There was an exponential increase in MACE risk after DAPT cessation within 90 days after ACS, especially after disruption of ticagrelor compared with clopidogrel (Pinteraction<.001). After adjustment for DAPT duration, this interaction was not statistically significant on the additive scale (relative excess risk due to interaction 0.12, 95%CI,-0.99-1.24). CONCLUSIONS: In this all-comers registry, 1 in 12 patients prematurely discontinued DAPT within 1 year after ACS. Compared with physician-recommended discontinuation, disruption resulted in a significantly higher risk of MACE. After adjustment for DAPT duration, this association was not moderated by the choice of P2Y12-inhibitor. Clinical trial registered at ClinicalTrials.gov (Identifier: NCT02500290).

Risk Factors Involved in the High Incidence of Bladder Cancer in an Industrialized Area in North-Eastern Spain: A Case-Control Study.

Bladder cancer (BC) is the most common of the malignancies affecting the urinary tract. Smoking and exposure to occupational and environmental carcinogens are responsible for most cases. Vallès Occidental is a highly industrialized area in north-eastern Spain with one of the highest incidences of BC in men. We carried out a case-control study in order to identify the specific risk factors involved in this area. Three hundred and six participants were included (153 cases BC and 153 controls matched for age and sex): in each group, 89.5% (n = 137) were male and the mean age was 71 years (range 30-91; SD = 10.6). There were no differences between groups in family history, body mass index, or dietary habits. Independent risk factors for CV were smoking (OR 2.08; 95% CI 1.30-3.32; p = 0.002), the use of analgesics in nonsmokers (OR 10.00; 95% CI 1.28-78.12; p = 0.028), and profession (OR: 8.63; 95% CI 1.04-71.94; p = 0.046). The consumption of black and blond tobacco, the use of analgesics in nonsmokers, and occupational exposures are risk factors for the development of BC in this area, despite the reduction in smoking in the population and the extensive measures taken in the last few decades in major industries to prevent exposure to occupational carcinogens.

Validation of a Set of Instruments to Assess Patient- and Caregiver-Oriented Measurements in Spinal Muscular Atrophy: Results of the SMA-TOOL Study.

INTRODUCTION: Outcome measures traditionally used in spinal muscular atrophy (SMA) clinical trials are inadequate to assess the full range of disease severity. The aim of this study was to assess the psychometric properties of a set of existing questionnaires and new items, gathering information on the impact of SMA from the patient and caregiver perspectives. METHODS: This was a multicenter, prospective, noninterventional study including patients with a confirmed diagnosis of 5q-autosomal-recessive SMA aged 8 years and above, or their parents (if aged between 2 and 8 years). The set of outcome measurements included the SMA Independence Scale (SMAIS) patient and caregiver versions, the Neuro-QoL Fatigue Computer Adaptive Test (CAT), the Neuro-QoL Pain Short Form-Pediatric Pain, the PROMIS adult Pain Interference CAT, and new items developed by Fundación Atrofia Muscular España: perceived fatigability, breathing and voice, sleep and rest, and vulnerability. Reliability, construct validity, discriminant validity, and sensitivity to change (4 months from baseline) were measured. RESULTS: A total of 113 patients were included (59.3% 2-17 years old, 59.3% male, and 50.4% with SMA type II). Patients required moderate assistance [mean patient and caregiver SMAIS (SD) scores were 31.1 (12.8) and 7.6 (11.1), respectively]. Perceived fatigability was the most impacted domain, followed by vulnerability. Cronbach's alpha coefficient for perceived fatigability, breathing and voice, and vulnerability total scores were 0.92, 0.88, and 0.85, respectively. The exploratory factor analysis identified the main factors considered in the design, except in the sleep and rest domain. All questionnaires were able to discriminate between the Clinical Global Impression-Severity scores and SMA types. Sensitivity to change was only found for the SMAIS caregiver version and vulnerability items. CONCLUSIONS: This set of outcome measures showed adequate reliability, construct validity, and discriminant validity and may constitute a valuable option to measure symptom severity in patients with SMA.

Environmental Factors Involved in the High Incidence of Bladder Cancer in an Industrialized Area in North-Eastern Spain.

Background: Bladder cancer (BC) is the most common of those affecting the urinary tract, and a significant proportion of the cases are attributable to tobacco use as well as occupational and environmental factors. Objective: The aim of this study is to estimate the current incidence of BC in an industrialized area in northeastern Spain and to analyze its time trends over three decades from an ecological perspective. Methods: Patients diagnosed with histologically confirmed primary BC, during 2018-2019, in an area in northeastern Spain (430,883 inhabitants) were included. Crude and age-standardized incidence rates were estimated per 100,000 person-years based on the number of individuals getting their first diagnosis. An exploratory time trend analysis was carried out to describe the evolution in tobacco use and occupational or environmental risk factors and the incidence of BC in the same area from the 1990s. Results: 295 patients were included (age 72.5 ± 10.3 years; 89.8% men). The crude rate was 62.6 (95% CI: 51.9-73.2) for men and 6.8 (95% CI: 3.4-10.3) for women. The annual rate adjusted to the European Standard Population was 85.3 (95% CI:75.0-95.5) for men and 7.0 (95% CI:4.5-9.5) for women. From 1994 to 2018, the prevalence of smokers decreased in men (42.3% to 30.9%) as well as in the active population working in the industry (44.36% to 22.59%). Nevertheless, the car fleet, especially diesel, has increased considerably. The annual mean concentrations of air (PM10, PM2.5, O3, and NO2) and water (nitrates, arsenic, trihalomethanes) pollutants were within the regulatory limit values, but not the maximum levels. Conclusions: The incidence of BC is one of the highest in men but not in women, despite the decrease in tobacco use and industrial activity (perhaps related to high latency after carcinogen exposure cessation) and despite the control of environmental pollution (the maximum regulatory limit probably needs to be lowered). Finally, a similar exposure to the carcinogen would result in a gender-specific differential incidence.

Comparative Safety and Effectiveness of Ticagrelor versus Clopidogrel in Patients With Acute Coronary Syndrome: An On-Treatment Analysis From a Multicenter Registry.

Background: The net clinical benefit of ticagrelor over clopidogrel in acute coronary syndrome (ACS) has recently been questioned by observational studies which did not account for time-dependent confounders. We aimed to assess the comparative safety and effectiveness of ticagrelor vs. clopidogrel accounting for non-adherence in a real-life setting. Methods: This is a prospective, multicenter cohort study of patients with ACS discharged on ticagrelor or clopidogrel between 2015 and 2019. Major exclusions were previous intracranial bleeding, and the use of prasugrel or oral anticoagulation. Association of P2Y12 inhibitor therapy with 1-year risk of Bleeding Academic Research Consortium Type 3 or 5 bleeding; major adverse cardiac events (MACEs), a composite endpoint of all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, or urgent target lesion revascularization; definite/probable stent thrombosis; vascular death; and net adverse clinical event (a composite endpoint of major bleeding and MACE) were analyzed according to the "on-treatment" principle, using fully adjusted Cox and Fine-Gray regression models with doubly robust inverse probability of censoring weighted estimators. Results: Among 2,070 patients (mean age 63 years, 27% women, 62.5% ST-elevation MI), 1,035 were discharged on ticagrelor and clopidogrel, respectively. Ticagrelor-treated patients were younger and had few comorbidities, but high rates of medication non-compliance, compared with clopidogrel users. After comprehensive multivariate adjustments, ticagrelor did not increase the risk of major bleeding compared with clopidogrel [subhazard ratio, 1.40; 95% confidence interval (CI), 0.96-2.05], while proved superior in reducing MACE (hazard ratio 0.62; 95% CI, 0.43-0.90), vascular death (subhazard ratio, 0.71; 95% CI, 0.52-0.97) and definite/probable stent thrombosis (subhazard ratio, 0.54; 95% CI, 0.30-0.79); thereby resulting in a favorable net clinical benefit (hazard ratio 0.78; 95% CI, 0.60-0.98) compared with clopidogrel. Results from sensitivity analyses were consistent with those from the primary analysis, whereas those from the intention-to-treat (ITT) analysis went in the opposite direction. Conclusion: Among all-comers with ACS, ticagrelor did not significantly increase the risk of major bleeding, while resulting in a net clinical benefit compared with clopidogrel. Further research is warranted to confirm these findings in high bleeding risk populations. CREA-ARIAM Andalucía: (ClinicalTrials.gov Identifier: NCT02500290); Current pre-specified analysis (ClinicalTrials.gov Identifier: NCT04630288).

Toxic Metals (Al, Cd, Pb) and Trace Element (B, Ba, Co, Cu, Cr, Fe, Li, Mn, Mo, Ni, Sr, V, Zn) Levels in Sarpa Salpa from the North-Eastern Atlantic Ocean Region.

Sarpa salpa is a fish belonging to the Sparidae family and is usually found in local markets. Toxic metals such as aluminum (Al), cadmium (Cd), lead (Pb) and trace elements such as boron (B), barium (Ba), cobalt (Co), copper (Cu), chromium (Cr), iron (Fe), lithium (Li), manganese (Mn), molybdenum (Mo), nickel (Ni), strontium (Sr), vanadium (V) and zinc (Zn) are incorporated into fish tissues and remain there. The liver has the highest concentrations of all the analyzed toxic metals and almost all the analyzed trace elements. The consumption of 100 g/day of S. salpa muscle tissue does not pose a health risk. However, 100 g/day of liver consumption may pose a serious health risk due to the intake of Cd (572% of the tolerable weekly intake for adults with a body weight of 68.48 kg) and Pb (117% of the tolerable daily intake for adults weighing 68.48 kg). The consumption of liver of this species is not recommended due to its possible harmful effects on health.

Metal Contents in the Most Widely Consumed Commercial Preparations of Four Different Medicinal Plants (Aloe, Senna, Ginseng, and Ginkgo) from Europe.

Medicinal plants like Aloe barbadensis, Ginkgo biloba, Panax ginseng, and Cassia angustifolia are being increasingly used but self-medication is a major public health challenge because of their numerous interactions. Furthermore, dietary exposure to metals through the consumption of these commercial preparations should be evaluated. Some of these metals may have a nutritional interest but others are metals of toxicological relevance. The content of essential and toxic metals has been analyzed by inductively coupled plasma optical emission spectrometry (ICP-OES) in 80 samples of both organically and conventionally grown aloe, senna, ginseng, and ginkgo pharmaceutical formats to establish their metallic profile, to evaluate their nutritional value and to assess the toxic metal risk resulting from their consumption. Ca (9181 mg/kg ww) in senna, Fe (30.0 mg/kg ww) in ginseng, and Al (15.7 mg/kg ww) in ginseng are noteworthy. The consumption of 9 g/day of ginkgo represents 6.44% of the RDI set for Ca. The consumption of 25 mL/day of aloe syrup is 3.06% (men) and 1.52% (women) of the RDI of Fe. Al exposure from 25 mL/day of aloe consumption is 2.71% of its TDI. Considering the dosages recommended by the manufacturers, the intake of toxic metals does not pose a health risk but the intake of essential metals is worth mentioning.

Metals in Diplodus sargus cadenati and Sparisoma cretense-a risk assessment for consumers.

The increases in urbanization, demography and industrial activity, along with growing human needs which exploit the resources of the planet, have exponentially exacerbated pollution. In particular, the discharge of heavy metals into the marine ecosystem is a problem of global magnitude, as this may damage the diversity of marine species and ecosystems because of their toxicity, long persistence and bioaccumulation. Consequently, it is necessary to carry out an assessment of the risk of human exposure from the consumption of marine species potentially exposed to this type of pollutants. In the present study, the levels of toxic heavy metals (Cd, Pb and Al) as well as trace and essential metals (B, Ba, Co, Cu, Cr, Fe, Li, Mn, Mo, Ni, Sr, V and Zn) and macronutrients (Ca, K, Mg, Na) have been quantified in two species of fish for human consumption. In order to do this, a total of 80 muscle samples and 80 liver samples, belonging to two species of osteichthyes (bony fish), Diplodus sargus cadenati and Sparisoma cretense, were analyzed. The specimens studied were captured on the north coast of Gran Canaria (Canary Islands) using recreational fishing techniques. As they caught from the shore, the data obtained respond to the need to assess the toxic levels in two representative species of artisanal and recreational fishing in the area. The risk assessment indicated that these two fish species are safe for the average consumer; however, if the livers are frequently consumed, there may be potential risks because they exceed the Admissible Daily Intakes for Pb and Cd.

Determination of toxic metals, trace and essentials, and macronutrients in Sarpa salpa and Chelon labrosus: risk assessment for the consumers.

Due to increased environmental pollution, monitoring of contaminants in the environment and marine organisms is a fundamental tool for assessing the existence of risk from their consumption to human health. The levels of toxic heavy metals (Cd, Pb, and Al), trace and essential metals (B, Ba, Co, Cu, Cr, Fe, Li, Mn, Mo, Ni, Sr, V, and Zn), and macronutrients (Ca, K, Mg, Na) in two species of fish for human consumption were quantified in the present study. Eighty samples of muscle tissue and 80 samples of liver tissue belonging to two species of Osteichthyes fish; Sarpa salpa and Chelon labrosus were analyzed. The studied specimens were caught on the northern coast of Gran Canaria (Canary Islands) with fishing rods. As they caught from the shore, they are suitable samples for assessing the toxic levels of representative species caught by local amateur fishermen. The results show that both species are fit for human consumption since they have toxic levels of heavy metals (Cd, Pb, and Al) which are below the maximum established levels; however, the toxic levels of the liver samples are several orders of magnitude higher than the muscle samples, so we discourage their regular consumption. The risk assessment indicated that the two species of fish are safe for the average consumer; however, if the livers of these species are consumed, there could be risks because they exceed the PTWI for Pb and the TWI for Cd.

Metals in wheat flour; comparative study and safety control.

Cereal industry and its derived products have a big economic and social importance worldwide. Therefore, as wheat flour is a commodity for all bread and bakery industry, it is safety is of high nutrition and toxicological interest. In this investigation we intend to study and determine the content of twelve metals in 50 samples of wheat flour coming from a wheat flour industry. Macro elements sodium, potassium magnesium and calcium, micro elements manganese, iron, copper, zinc, chrome and nickel as well as toxic trace elements cadmium and lead have been analysed. The estimated diary intake of each metal and their contribution in percentage terms to the RDI (macro and micro elements) and to the PTWI (toxic elements) has been determined. Contribution of Cd and Pb to the PTWI was very low, a fact that shows safety in this wheat flour concerning toxic metals.

La industria de los cereales y sus derivados tiene una gran importancia económica y social en todo el mundo. Por ello, la seguridad de las harinas como materias primas de todas las industrias de panadería, bollería y repostería es de sumo interés nutricional y toxicológico. En este trabajo nos hemos propuesto estudiar y determinar el contenido de doce metales en 50 muestras de harina de trigo procedentes de una industria harinera. Se analizaron los macroelementos sodio, potasio, magnesio y calcio, los microelementos manganeso, hierro, cobre, zinc, cromo y níquel y los elementos traza tóxicos cadmio y plomo. Se determinó la ingesta diaria estimada de cada metal y su contribución porcentual a las IDRs (macro y microelementos) y a las PTWIs (elementos tóxicos). La contribución de las PTWIs para el Cd y Pb fue muy baja, lo que demuestra la seguridad de estas harinas en relación con estos metales tóxicos.

Metals in wheat flour; comparative study and safety control / Metales en harina de trigo; estudio comparativo y control de su seguridad

Cereal industry and its derived products have a big economic and social importance worldwide. Therefore, as wheat flour is a commodity for all bread and bakery industry, it is safety is of high nutrition and toxicological interest. In this investigation we intend to study and determine the content of twelve metals in 50 samples of wheat flour coming from a wheat flour industry. Macro elements sodium, potassium magnesium and calcium, micro elements manganese, iron, copper, zinc, chrome and nickel as well as toxic trace elements cadmium and lead have been analysed. The estimated diary intake of each metal and their contribution in percentage terms to the RDI (macro and micro elements) and to the PTWI (toxic elements) has been determined. Contribution of Cd and Pb to the PTWI was very low, a fact that shows safety in this wheat flour concerning toxic metals (AU)

La industria de los cereales y sus derivados tiene una gran importancia económica y social en todo el mundo. Por ello, la seguridad de las harinas como materias primas de todas las industrias de panadería, bollería y repostería es de sumo interés nutricional y toxicológico. En este trabajo nos hemos propuesto estudiar y determinar el contenido de doce metales en 50 muestras de harina de trigo procedentes de una industria harinera. Se analizaron los macroelementos sodio, potasio, magnesio y calcio, los microelementos manganeso, hierro, cobre, zinc, cromo y níquel y los elementos traza tóxicos cadmio y plomo. Se determinó la ingesta diaria estimada de cada metal y su contribución porcentual a las IDRs (macro y microelementos) y a las PTWIs (elementos tóxicos). La contribución de las PTWIs para el Cd y Pb fue muy baja, lo que demuestra la seguridad de estas harinas en relación con estos metales tóxicos (AU)