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1.
J Am Heart Assoc ; 9(17): e016552, 2020 09.
Article in English | MEDLINE | ID: mdl-32844723

ABSTRACT

Background Despite reductions in door-to-balloon times for primary coronary intervention, mortality from ST-segment-elevation myocardial infarction has plateaued. Early pre-primary coronary intervention treatment of ST-segment-elevation myocardial infarction with glycoprotein IIb/IIIa inhibitors improves pre-primary coronary intervention coronary flow, limits infarct size, and improves survival. We report the first human use of a novel glycoprotein IIb/IIIa inhibitor designed for subcutaneous first point-of-care ST-segment-elevation myocardial infarction treatment. Methods and Results Healthy volunteers and patients with stable coronary artery disease receiving aspirin received escalating doses of RUC-4 or placebo in a sentinel-dose, randomized, blinded fashion. Inhibition of platelet aggregation (IPA) to ADP (20 µmol/L), RUC-4 blood levels, laboratory evaluations, and clinical assessments were made through 24 hours and at 7 days. Doses were increased until reaching the biologically effective dose (the dose producing ≥80% IPA within 15 minutes, with return toward baseline within 4 hours). In healthy volunteers, 15 minutes after subcutaneous injection, mean±SD IPA was 6.9%+7.1% after placebo and 71.8%±15.0% at 0.05 mg/kg (n=6) and 84.7%±16.7% at 0.075 mg/kg (n=6) after RUC-4. IPA diminished over 90 to 120 minutes. In patients with coronary artery disease, 15 minutes after subcutaneous injection of placebo or 0.04 mg/kg (n=2), 0.05 mg/kg (n=6), and 0.075 mg/kg (n=18) of RUC-4, IPA was 14.6%±11.7%, 53.6%±17.0%, 76.9%±10.6%, and 88.9%±12.7%, respectively. RUC-4 blood levels correlated with IPA. Aspirin did not affect IPA or RUC-4 blood levels. Platelet counts were stable and no serious adverse events, bleeding, or injection site reactions were observed. Conclusions RUC-4 provides rapid, high-grade, limited-duration platelet inhibition following subcutaneous administration that appears to be safe and well tolerated. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NTC03844191.


Subject(s)
Aspirin/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Pyrimidinones/therapeutic use , ST Elevation Myocardial Infarction/drug therapy , Thiadiazoles/therapeutic use , Adult , Aged , Case-Control Studies , Coronary Artery Disease/drug therapy , Female , Humans , Injections, Subcutaneous , Male , Middle Aged , Placebos/administration & dosage , Platelet Count/statistics & numerical data , Point-of-Care Systems/standards , Pyrimidinones/administration & dosage , Pyrimidinones/adverse effects , Pyrimidinones/pharmacokinetics , Thiadiazoles/administration & dosage , Thiadiazoles/adverse effects , Thiadiazoles/pharmacokinetics , Treatment Outcome , Young Adult
2.
Acta Orthop Belg ; 84(3): 284-291, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30840570

ABSTRACT

Pressure ulcers (PUs) are highly frequent in hip fractured elderly patients. This issue has a direct impact in quality of life, mortality as well as healthcare costs. Handgrip strength (HGS) is an efficient, low-cost and straightfoward method to measure functional capacity, as well as the global muscle strength of elderly patients. In this research we are aiming to analyze if low HGS is associated with higher incidence of pressure ulcers within a population of elderly patients with hip fracture from a tertiary hospital from Monterrey, Mexico. This research, designed as an observational-longi- tudinal cohort, included 462 patients admitted at the Hip and Pelvic Surgery Department of the Hospital of Traumatology and Orthopedics No. 21, of the Mexican Institute of the Social Security (IMSS), in Monterrey, Mexico. HGS measurement was performed by a trained physician, using a Jamar® Hydraulic Hand DynamometerPatients were grouped into tertiles according to their grip strength measurement and sex. Every patient was evaluated for presence or absence of PUs during hospital admission and followed until discharge. The general incidence of PUs was 25.7%. The incidence was higher in the weaker subjects (Tertile one 33%, Tertile two 30%, and Tertile three 15%, P=0.001). Pre-fracture Barthel's index, and Mini Nutritional Assessment Scores were lower among participants with PUs. After multivariate analysis, only HGS remained associated with PUs incidence. Low handgrip strength is associated with a higher incidence of pressure ulcers.


Subject(s)
Hand Strength , Hip Fractures/surgery , Postoperative Complications/epidemiology , Pressure Ulcer/epidemiology , Aged , Aged, 80 and over , Female , Humans , Longitudinal Studies , Male , Mexico/epidemiology , Risk Assessment
3.
Aging Clin Exp Res ; 28(5): 901-8, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26646253

ABSTRACT

BACKGROUND: The aging population in Latin America is characterized by not optimal conditions for good health, experiencing high burden of comorbidity, which contribute to increase the frequency of frailty; thus, identification should be a priority, to classify patients at high risk to develop its negative consequences. AIM: The objective of this analysis was to validate the FRAIL instrument to measure frailty in Mexican elderly population, from the database of the Mexican Health and Aging Study (MHAS). MATERIALS AND METHODS: Prospective, population study in Mexico, that included subjects of 60 years and older who were evaluated for the variables of frailty during the year 2001 (first wave of the study). Frailty was measured with the five-item FRAIL scale (fatigue, resistance, ambulation, illnesses, and weight loss). The robust, pre-frail or intermediate, and the frail group were considered when they had zero, one, and at least two components, respectively. Mortality, hospitalizations, falls, and functional dependency were evaluated during 2003 (second wave of the study). Relative risk was calculated for each complications, as well as hazard ratio (for mortality) through Cox regression model and odds ratio with logistic regression (for the rest of the outcomes), adjusted for covariates. RESULTS: The state of frailty was independently associated with mortality, hospitalizations, functional dependency, and falls. The pre-frailty state was only independently associated with hospitalizations, functional dependency, and falls. CONCLUSIONS: Frailty measured through the FRAIL scale, is associated with an increase in the rate of mortality, hospitalizations, dependency in activities of daily life, and falls.


Subject(s)
Aging/physiology , Fatigue/epidemiology , Frail Elderly , Hospitalization/statistics & numerical data , Accidental Falls/statistics & numerical data , Aged , Aged, 80 and over , Comorbidity , Female , Health Status , Health Surveys , Humans , Logistic Models , Male , Mexico , Middle Aged , Odds Ratio , Proportional Hazards Models , Prospective Studies , Walking/physiology
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