Implementing a pharmacogenomic-driven algorithm to guide antiplatelet therapy among Caribbean Hispanics: a non-randomised clinical trial.

OBJECTIVES: To assess whether genotype-guided selection of oral antiplatelet drugs using a clinical decision support (CDS) algorithm reduces the rate of major adverse cardiovascular and cerebrovascular events (MACCEs) among Caribbean Hispanic patients, after 6 months. DESIGN: An open-label, multicentre, non-randomised clinical trial. SETTING: Eight secondary and tertiary care hospitals (public and private) in Puerto Rico. PARTICIPANTS: 300 Caribbean Hispanic patients on clopidogrel, both genders, underwent percutaneous coronary intervention (PCI) for acute coronary syndromes, stable ischaemic heart disease and documented extracardiac vascular diseases. INTERVENTIONS: Patients were separated into standard-of-care (SoC) and genotype-guided (pharmacogenetic (PGx)-CDS) groups (150 each) and stratified by risk scores. Risk scores were calculated based on a previously developed CDS risk prediction algorithm designed to make actionable treatment recommendations for each patient. Individual platelet function, genotypes, clinical and demographic data were included. Ticagrelor was recommended for patients with a high-risk score ≥2 in the PGx-CDS group only, the rest were kept or de-escalated to clopidogrel. The intervention took place within 3-5 days after PCI. Adherence medication score was also measured. PRIMARY AND SECONDARY OUTCOMES: The occurrence rate of MACCEs (primary) and bleeding episodes (secondary). Statistical associations between patient time free of events and predictor variables (ie, treatment groups, risk scores) were tested using Kaplan-Meier survival analyses and Cox proportional-hazards regression models. RESULTS: The genotype-guided group had a clinically lower but not significantly different risk of MACCEs compared with the SoC group (8.7% vs 10.7%, p=0.56; HR=0.56). Among high-risk score patients, genotype-driven guidance of antiplatelet therapy showed superiority over SoC in reducing MACCE incidence 6 months postcoronary stenting (adjusted HR=0.104; p< 0.0001). CONCLUSIONS: The potential benefit of implementing our PGx-CDS algorithm to significantly reduce the incidence rate of MACCEs in post-PCI Caribbean Hispanic patients on clopidogrel was observed exclusively among high-risk patients, with apparently no evident effect in other patient groups. TRIAL REGISTRATION NUMBER: NCT03419325.

Association Between Concurrent Use of Benzodiazepines and Opioids and Health Care Utilization Among Patients With Cancer in Puerto Rico.

PURPOSE: To evaluate the association between concurrent use of opioids and benzodiazepines (BZDs) and emergency room (ER) visits and hospital admissions in patients with cancer. METHODS: Data were obtained from the Puerto Rico Central Cancer Registry-Health Insurance Linkage. Odds ratios (ORs) with 95% CIs and incidence rate ratio (IRR) were estimated using logistic and negative binomial regression analyses to assess the association between concurrent use of opioids and BZDs (overlap of at least 7 days) and ER visits and hospital admissions. RESULTS: A total of 9,259 patients were included in the main analysis. The logistic regression results showed a significant association between concurrent use of opioids and BZDs and at least one ER visit (OR, 1.28 [95% CI, 1.07 to 1.54]) or hospital admission (OR, 1.42 [95% CI, 1.18 to 1.71]) compared with individuals with BZDs alone, after adjusting for age, sex, comorbidity index, cancer stage, health insurance, and health region. Compared with individuals with opioid use alone, the association did not reach significance. In the negative binomial regression, a significant association was observed for ER visits (IRR, 1.52 [95% CI, 1.31 to 1.76]) and hospitalizations (IRR, 1.34 [95% CI, 1.20 to 1.50]) when compared with individuals with BZDs alone. Compared with individuals with opioids alone, it only reached significance for ER visits (IRR, 1.39 [95% CI, 1.20 to 1.61]). CONCLUSION: Careful evaluation must be done before prescribing concurrent opioids and BZDs in patients with cancer, as the results suggest that coprescribing may increase the odds of ER visits and hospitalizations.

Experiences and Preferences of Opioid-Use-Disorder Patients Who Switched from Brand to Generic Buprenorphine/Naloxone Films: A Case Series.

PURPOSE: Differences in the suppression of withdrawal symptoms have been observed in opioid-use-disorder (OUD) patients who were switched from Suboxone (the brand name of buprenorphine/naloxone sublingual films) to either 1 of 2 generic versions. These descriptive observations evidence the need to further assess the use of these generics and its impact on the adherence to and outcomes of OUD treatments. The objective of this case series was to describe patient and provider experiences, perceptions, and preferences when said patients were abruptly switched from Suboxone to one of the generic versions manufactured by Sandoz or Alvogen. PATIENTS AND METHODS: A retrospective chart review of 24 Suboxone-maintained OUD patients from a single clinic who were forced to switch to a generic was performed to collect withdrawal and craving symptoms that occurred after the switch, as well as toxicology results and changes in dose (documented by the provider). RESULTS: The medical records of 9 (37.5%) of the 24 patients showed that they were suffering from withdrawal symptoms and/or cravings, had had their doses adjusted, and/or had had a positive urine toxicology screen. All 9 subjects communicated a preference for the brand formulation over that of either of the generic versions; few expressed a preference for one generic formulation over the other. None of patients were able to switch back to the brand formulation, nor were any of them able to choose the generic that worked best for them. Insomnia, muscle pain, and gooseflesh skin were the most common withdrawal symptoms reported by the patients using the generics. Better outcomes were observed in patients who received a buprenorphine dose increase (2 mg) to suppress the withdrawal symptoms experienced while using the generics. CONCLUSION: Our study serves as a reference to prescribers regarding approaches (eg, a small dose adjustment) that may potentially encourage OUD treatment adherence and even improve outcomes in patients who appear to be decompensating after the brand-to-generic switch.

Factors Associated with Intention to Receive Vaccination against COVID-19 in Puerto Rico: An Online Survey of Adults.

We conducted an online survey among adults in Puerto Rico to identify factors associated with the intention to receive vaccination against COVID-19. Sociodemographic variables were analyzed independently for association with intent to receive vaccination. Significant associations were included in the multivariate logistic regression analysis. A total of 1016 responses were available for analysis. In the bivariate analysis, younger age, higher education, pre-COVID-19 employment, male sex, gay/bisexual identity, and single marital status were associated with increased intent to receive the vaccination. In the multivariate logistic regression, younger, male respondents, and those with higher educational attainment reported higher intent to receive the vaccination. Lower-income and living outside the San Juan metro region were associated with lower intent to receive the vaccination. National and international health organizations were identified as the most reliable sources of information, followed by healthcare professionals. These findings highlight the importance of considering sociodemographic characteristics and using trusted sources of information when designing COVID-19 vaccination public messaging.

Pharmacogenomic polygenic risk score for clopidogrel responsiveness among Caribbean Hispanics: A candidate gene approach.

This multicenter clinical study was aimed at conducting a targeted pharmacogenomic association analysis of residual on-clopidogrel platelet reactivity in 474 Caribbean Hispanic patients. Platelet reactivity was measured using the VerifyNow P2Y12 assay and clopidogrel resistance was defined as P2Y12 reaction units (PRUs) greater than or equal to 208. Genotyping was performed using the whole-genome Infinium MEGA BeadChip array. An ancestry-adjusted, weighted polygenic risk score (wPGxRS) was developed to account for the effect of multiple variants on PRU and compared between clopidogrel responders and nonresponders. The mean PRU across the study cohort was 173.8 ± 68.5 and 33.5% of patients were defined as clopidogrel resistant. Multivariate linear regression showed that 19% of PRU variability was attributed to nine independent predictors, with CYP2C19*2 (rs4244285) accounting for ~ 7% of observed PRU variation (p < 0.001). PON1 rs662, ABCB1/MDR1 rs2032582, PEAR1 rs12041331 carrier status, and the interaction between African ancestry and rs12041331 carriers also predicted PRU among the participants (p ≤ 0.05). A clear gene-dose effect was detected between PRU and CYP2C19*2 genotype, consistent with previous studies in European patient populations, as well as rs12777823. Importantly, a significant positive correlation was detected between our novel wPGxRS (4 variants) and PRU among the Hispanic patient population (rp  = 0.35, p < 0.001). Moreover, the wPGxRS discriminated between nonresponders and responders (p = 0.003), indicating that this multigene-based score is a useful predictor of clopidogrel resistance among Caribbean Hispanics. Taken together, these results help close the gap of knowledge on clopidogrel pharmacogenomics and its potential clinical implementation in this under-represented population.

Brand-to-Generic Substitution of Buprenorphine/Naloxone Sublingual Film in Puerto Rico: A Case Study.

A 56-year-old patient with a 1-year history of stable maintenance treatment with Suboxone for opioid use disorder (OUD) was switched to a generic formulation in May of 2019. The patient reported experiencing-over the course of the following 3 months-withdrawal symptoms when switched to the Alvogen-produced generic formulation in May of 2019 and then to the Sandoz-produced version in July of that same year, she also was positive for fentanyl during that time. As a result, the buprenorphine dose was increased, and the patient was stable at this new dose using the generic versions. Blood levels pre- and post-change (not reported in previous case reports) showed maximum buprenorphine concentration being reached more quickly when the brand-name drug was used. Additionally, the area under the curve (AUC) values indicate that the generic formulation had higher exposures than the brand-name drug. Based on the clinical impact of the brand-to generic switch in this patient, further research in this area is warranted. In the meantime, clinicians should carefully monitor their patients so that, if warranted, dose adjustments can be made quickly and safely to minimize negatively impacting the OUD therapy outcomes of patients.

Socially distant and out of reach: Unintended consequences of COVID-19 prevention efforts on transgender and gender non-binary populations in Puerto Rico.

Substance use disorders in the United States disproportionately affect minorities and socially vulnerable populations, particularly those at the intersection of racial and sexual minority status. Preceded by over a century-long subjugation to the U.S. government, a recent financial crisis, the devastating hurricanes of 2017, and a string of earthquakes at the end of 2019 and early 2020, the current COVID-19 pandemic is only the most recent disaster to disrupt the local health care system in Puerto Rico. However, the effects of the current emergency and imposed social distancing measures have only exacerbated the underlying vulnerabilities of the transgender and gender non-conforming (GNC) population made bare during these other recent disasters. Clinics and providers who treat patients with opioid use disorder (OUD) in Puerto Rico have had to develop their own safety protocols to limit the spread of the virus while trying to optimize current treatment protocols to maintain the stability of their patients. Despite these measures, we have observed a reduction in the ability of local organizations to outreach to already disconnected transgender and GNC individuals with OUD. For example, due to the government-imposed curfew that began March 15, 2020, some providers engaged in outreach with transgender and GNC sex workers have eliminated nighttime outreach completely. Additionally, a research project surveying all buprenorphine prescribers in Puerto Rico has found that few have received training in treating this vulnerable population, and even fewer report that they are currently providing treatment for transgender or GNC individuals. If Puerto Rico is to address this problem of gross under-representation of a population known to be disproportionately affected by substance use disorders, Puerto Rico must address structural factors to prevent this disparity from widening further during the inevitable future disasters our health care system will face.

Treating Opioid Use Disorder in Puerto Rico During the COVID-19 Pandemic: Providers' Leadership Efforts in Unprecedented Times.

Opioid use disorder (OUD) is an unprecedented medical and public health issue both in Puerto Rico (PR) and the greater US with an increase incidence of opioid use every year. Unprecedented and compounded emergencies in PR such as those caused by hurricanes, earthquakes, and the COVID-19 pandemic coupled with limited national and local governmental support, has forced most clinics in PR to take action to be able to continue providing care. This commentary summarizes the leadership and clinical initiatives of 3 community organizations in PR to maintain services for people with OUD during the COVID-19 pandemic. Local legislation that supported the continuity of OUD care is summarized, along with unique experiences specific to each organization. In addition, the vulnerability of economically disadvantaged people or experiencing homelessness as well as those affected by these compounded events in PR is discussed, with an emphasis on how some challenges were addressed and future directions for continuity of care as our country adjusts to new demands caused by the COVID-19 pandemic.

Community Pharmacy Operations in Puerto Rico During the 2017 Hurricane Season: A Descriptive Analysis of Rx Open Data.

OBJECTIVES: This article aims to: (1) describe the 'Return to Open Pharmacy Operations' in Puerto Rico following the hurricanes Irma and Maria in the 2017 hurricane season, and (2) compare the recovery rate (Return to Open Pharmacy Operations) during the 2017 hurricane season between the US Commonwealth of Puerto Rico and the state of Florida. METHODS: We performed a cross-sectional study of pharmacy operations in Puerto Rico utilizing Rx Open data for pharmacies in Puerto Rico during the 2017 hurricane season. To compare open rates of pharmacy operations over time in different contexts, we also analyzed Rx Open data for the state of Florida for Hurricane Irma. RESULTS: Only 11.1% of pharmacies remained open in Puerto Rico 3 days after Hurricane Maria made landfall, and Puerto Rico pharmacy operations recovered slowly, at an average daily rate of 3.9% before reaching pre-landfall baseline operations. Puerto Rico pharmacy operations after Hurricane Maria recovered 10 times slower on average, compared to pharmacy operations in Florida after Hurricane Irma which reached baseline operations less than 1 week following Hurricane Irma's landfall. CONCLUSION: Our results demonstrate the unique severity of Hurricane Maria's impacts on Puerto Rico's health system.

Pharmacokinetic Characterization and External Evaluation of a Quantitative Framework of Sublingual Buprenorphine in Patients with an Opioid Disorder in Puerto Rico.

BACKGROUND: The aim of this analysis was to characterize the pharmacokinetics (PK) of sublingual buprenorphine (BUP) and its metabolites (buprenorphine glucuronide; BUP-g, norbuprenorphine; Nor-BUP, and norbuprenorphine glucuronide; Nor-BUP-g) in opioid use disorder (OUD) patients in Puerto Rico (PR) as a first step of evidence-based BUP dosing strategies in this population. METHODS: BUP and metabolites concentrations were measured from 0 to 8 h after the administration of sublingual buprenorphine/naloxone films in 12 stable OUD subjects. RESULTS: PK non-compartmental characteristics showed considerable variability in parameters between the subjects over the 8-h sampling time (tmax = 1.5 ± 0.7 h, Co = 1.6 ± 1.4 ng/mL, Cmax= 7.1 ± 6 ng/mL, and AUC0-8h = 26.8 ± 17.8 h·ng/mL). Subjects had a significantly higher tendency towards CYP-mediated N-demethylation, with the AUC0-8h ratios of the molar concentrations of [Nor-BUP + Nor-BUP-g] to BUP being (3.4 ± 1.9) significantly higher compared with BUP-g to BUP (0.19 ± 0.2). A two-compartment population-PK model with linear absorption (ka = 2.54 h-1), distribution (k12= 2.34 h-1, k14 = 1.29 h-1), metabolism (k24 = 1.28 × 10-1 h-1, k23 = 6.43 × 10-2 h-1, k35 = 1.23 × 10-1 h-1, k45 = 8.73 × 10-1 h-1), and elimination (k30 = 3.81 × 10-3 h-1, k50 = 1.27 × 10-1 h-1) adequately described the time-course of BUP and its metabolites, which has been externally validated using published data. CONCLUSIONS: Although limited in sampling time and number of recruited subjects, this study presents specific BUP PK characteristics that evidenced the need for additional PK studies and subsequent modeling of the data for the development of evidence-based dosing approaches in Puerto Rico.

Physicochemical Evaluation of Compounded Oral Preparations for Respiratory Illnesses, also known as Mezclitas.

OBJECTIVE: Compounded oral solutions for respiratory illnesses such as the common cold and cough are commonly prepared and dispensed by licensed pharmacists in the United States and Puerto Rico (PR). Standard protocols for their preparation and quality assessment and for patient counseling are available for most of the prescribed compounded solutions. However, in PR there is a common prescription approach colloquially referred to as "mezclitas": mixtures of antitussives, expectorants, decongestants, and other active ingredients available in commercial solutions for which there are no science-driven compounding guidelines for local pharmacists. METHODS: This study evaluated the physicochemical stability of a commonly dispensed compounded preparation (containing guaifenesin, dextromethorphan, and dexamethasone) that is used for the treatment of respiratory illnesses in PR. The stability indicators tested included clarity, odor, pH, and viscosity. Changes in stability indicators were evaluated for different storage conditions (ambient temperature and refrigerated) over a period of 6 months. RESULTS: The samples exhibited small changes in color, odor, and viscosity. Although the observed changes were small, they may be indicative of chemical and/or physical transformations that occurred over time. A survey of local pharmacists also evidenced the absence of standardized protocols for the preparation and dispensation of the mezclitas in PR. CONCLUSION: In spite of the absence of protocols for compounding oral solutions for respiratory illnesses, our study suggests that the stability of such solutions is not heavily compromised. However further chemical and physical testing is needed and the findings of such testing used to develop standardized protocols for the compounding of oral solutions for respiratory illnesses.

Readiness to provide pharmaceutical care to transgender patients: Perspectives from pharmacists and transgender individuals.

OBJECTIVES: The objectives of this study were (1) to assess pharmacist readiness to provide pharmaceutical care for transgender patients through measuring both pharmacists' knowledge and attitudes towards transgender patients, (2) to assess transgender patients' perception of pharmacist readiness to provide them pharmaceutical care through measuring both pharmacists' knowledge and attitudes toward them, and (3) to compare pharmacist readiness to provide pharmaceutical care for transgender patients and patient perception of this readiness. DESIGN: The study used a descriptive, cross-sectional design. The pharmacist's readiness and the transgender patient's perception of their readiness, defined as a combination of knowledge and attitude, were evaluated. Two separate, validated questionnaires with dichotomous, multiple choice, and open-ended questions were used to measure both constructs among both populations. SETTING: Community-based research. PARTICIPANTS: Pharmacists practicing in Puerto Rico were provided the questionnaire by e-mail or in person. Transgender participants in Puerto Rico were recruited through health clinics and community partners and were surveyed in person. The analysis included responses from 96 pharmacists and 31 transgender participants. RESULTS: The majority of the pharmacists' knowledge scores (90%) were found in the low (0-5) and moderate (6-10) ranges, with a mean score of 7.23 out of a total possible score of 16 (SD ±2.36). For the attitude construct, most of the scores (81%) were found in the high (18-26) range, with a mean score of 19.63 out of a total possible score of 26 (SD ±3.65). For both constructs, transgender patient perceptions echoed the results of the pharmacists, indicating several perceived knowledge deficits in combination with mostly positive attitudes. CONCLUSION: The majority of pharmacists demonstrated positive attitudes toward caring for transgender patients, and transgender patients also perceived these positive attitudes from pharmacists. However, the measured and perceived knowledge deficits observed in this study suggest the need for educational interventions to improve pharmacist readiness to provide care for transgender patients.

Description of Patients Medications Needs and the Community Pharmacist's Role in Puerto Rico Following a Natural Disaster.

BACKGROUND: In September 2017, Puerto Rico was hit by Hurricane Maria, a natural disaster that caused devastation. Initial reports of disruption to the health care system were later followed by increases in the death toll in Puerto Rico. OBJECTIVE: This project assessed patient medications needs, level of satisfaction with community pharmacy services, and perceptions about the role of the pharmacist during the emergency following Hurricane Maria in Puerto Rico. METHODOLOGY: The investigation utilized a descriptive, cross-sectional design. Data were collected at 3 community pharmacies located in San Juan, Puerto Rico: Walgreens (Specialty Pharmacy and Store 891) and Farmacia Caridad #9. Patients receiving care at these locations were invited to complete a 10-item questionnaire. These were provided with an information sheet describing details of the study prior to participation. RESULTS: Sixty-five patients participated in the study, with an average age of 59 years. The majority (77%) of the respondents reported problems related to their medications and nearly half (47.7%) reported having trouble either contacting or getting to their pharmacy following the hurricane. Regarding the role of pharmacists following a natural disaster, 94% of respondents reported the pharmacist was available to help them and 95% reported the information provided by the pharmacist was "trustworthy/very trustworthy." CONCLUSION: Although the challenges reported in Puerto Rico with regard to medications following Hurricane Maria were significant, patients reported a high level of confidence in the ability of community pharmacists to help them.

A Preliminary Assessment of Selected Social Determinants of Health in a Sample of Transgender and Gender Nonconforming Individuals in Puerto Rico.

Purpose: Transgender and gender nonconforming (GNC) people continue to experience suboptimal health care, social exclusion, and lower quality of life. Globally, lack of access to services, institutional violence, and public harassment have been reported. However, there is limited data on transgender health in Puerto Rico and the Caribbean. The purpose of this study is to assess the social determinants of health and wellbeing of transgender and GNC people living in Puerto Rico. Methods: Utilizing a community-based participatory research approach, 52 self-identified transgender and GNC individuals living in Puerto Rico completed a survey, which included questions on access to health care services, social support, and violence, among others. Data were collected from March to Ma y of 2015 and descriptive statistical analysis was conducted. Results: Most of the participants reported experiences of discrimination across multiple social settings, most commonly at school (70.6%) and work (67.4%). Regarding experiences of violence, more than half (65.4%) had been verbally attacked in a public space. Many reported that access to gender-affirming health care services is difficult in Puerto Rico (88.5%) due to lack of knowledgeable providers (59.6%) and discomfort during the encounter (55.8%). The main perceived priority for their wellbeing was a transgender health care center. Conclusion: Although the LGBT equality movement has reached great milestones, access to gender-affirming health services and safe educational and work spaces are still needed. Findings from the study provide guidance for actions to reduce health disparities by addressing the needs for health and wellbeing among transgender and GNC individuals.

Community Pharmacy Response in the Aftermath of Natural Disasters: Time-Sensitive Opportunity for Research and Evaluation.

One year ago, Hurricane Maria passed over the archipelago of Puerto Rico, leaving widespread disruption of nearly all human services, including the health care sector. In the aftermath of the hurricane, limited access to medical care and prescription medications presented a serious challenge to maintaining control of preexisting chronic diseases. Many patients did not have access to refrigeration for heat-sensitive medications. Significant dietary changes due to the limited availability of shelf-stable foods further exacerbated chronic conditions such as heart failure and diabetes. The role of community pharmacists following a natural disaster has previously been documented, and may include the triage of evacuees, assessment of immunization needs, and provision of prescription medications under a collaborative practice agreement. However, our experience in Puerto Rico demonstrated a variety of barriers limited pharmacists' ability to adequately respond to the magnitude of this disaster. These included medication shortages, extended loss of power, and limited telecommunications for contacting prescribers, disaster relief agencies, and third-party payers. Ultimately, the lack of preexisting emergency protocols made overcoming such barriers difficult. As the first and sometimes only accessible health care provider to many patients following a natural disaster, we must build a solid evidence base and better understanding of the individual, interpersonal, and environmental factors that contribute to the community pharmacist response. To date, however, a paucity of data exists on both the pharmacist and patient factors, which may contribute to an effective immediate response to patient needs at the community pharmacy following a natural disaster. Future research must focus on these multi-level factors to better inform public policy and effective disaster planning. Ultimately, such research and planning will lead to increased resiliency in our primary health care systems in the face of future disasters.

Knowledge and Perceptions of E-cigarettes and the Motivations for their Use: Talking to Smokers (E-cigarettes and/or Conventional Cigarettes) and Non-smokers in Puerto Rico.

OBJECTIVE: The awareness and use of e-cigarettes have been increasing in recent years. The World Health Organization recently reported that regulations are needed to impede the promotion of e-cigarettes to young people, prohibit unproven health claims about them (including those regarding smoking-cessation efficacy), minimize potential health risks to e-cigarette users and non-users, and protect existing tobacco controls. The study described herein explored e-cigarette knowledge, perceptions, and usage motivations among a group of adults in Puerto Rico. METHODS: This research study used a validated questionnaire with closed-ended questions to gather data. Non-inferential and inferential statistics were used to characterize smokers (of e-cigarettes, of conventional cigarettes, and of both) and non-smokers. RESULTS: A total of 415 respondents took part; they were evenly distributed by gender, age, and socioeconomic status; all were residents of Puerto Rico at the time of the survey. The overall awareness of e-cigarettes was high, but knowledge of nicotine content and regulations was limited. Asked whether e-cigarettes contain nicotine (they do not), approximately two thirds stated either that they do or that they didn't know; asked whether e-cigarettes are regulated as a tobacco product (they are in Puerto Rico), 84% stated either that they are not or that they didn't know. Common perceptions of e-cigarettes are that they are harmful to health and that they are no less harmful than cigarettes are. However, a significant portion of the respondents perceived e-cigarettes to be less addictive than conventional cigarettes are. Overall, the respondents were divided on the efficacy of e-cigarettes for smoking cessation. Nonetheless, the most common motivation for their use, according to both current users and potential future users, is to aid in smoking cessation or reduction. CONCLUSION: The majority of individuals surveyed were aware of e-cigarettes but had limited knowledge of their contents or regulation. As an aid in smoking cessation was the most commonly mentioned motivation for e-cigarette use.

Clinical Relevant Polymorphisms Affecting Clopidogrel Pharmacokinetics and Pharmacodynamics: Insights from the Puerto Rico Newborn Screening Program.

Background: Variations in several clopidogrel-pharmacogenes have been linked to clopidogrel response variability and clinical outcomes. We aimed to determine the frequency distribution of major polymorphisms on CYP2C19, PON1, ABCB1 and P2RY12 pharmacogenes in Puerto Ricans. Methods: This was a cross-sectional, population-based study of 200 unrelated "Guthrie" cards specimens from newborns registered in the Puerto Rican newborn screening program (PRNSP) between 2004 and 2014. Taqman® SNP assay techniques were used for genotyping. Results: Minor allele frequencies (MAF) were 46% for PON1 (rs662), 41% for ABCB1 (rs1045642), 14% for CYP2C19*17, 13% for CYP2C19*2, 12% for P2RY12-H2 and 0.3% for CYP2C19*4. No carriers of the CYP2C19*3 variants were detected. All alleles and genotype proportions were found to be in Hardy⁻Weinberg equilibrium (HWE). Overall, there were no significant differences between MAFs of these variants in Puerto Ricans and the general population (n = 453) of the 1000 Genome project, except when comparisons to each individual parental group were performed (i.e., Africans, Europeans and East-Asians; p < 0.05). As expected, the prevalence of these markers in Puerto Ricans most resembled those in the 181 subjects from reference populations of the Americas. Conclusions: These prevalence data provide a necessary groundwork for future clinical studies of clopidogrel pharmacogenetics in Caribbean Hispanics.

Effect of cilostazol on platelet reactivity among patients with peripheral artery disease on clopidogrel therapy.

BACKGROUND: Antiplatelet therapy with clopidogrel is recommended to reduce cardiovascular events in patients with peripheral artery disease (PAD); however, clopidogrel efficacy has not been adequately studied in this patient population. Therefore, we aimed to determine the effects of cilostazol therapy on platelet reactivity among PAD patients on clopidogrel. METHODS: We performed a cross-sectional pilot study of 46 Puerto Rican patients diagnosed with PAD. The cohort was divided based on use of clopidogrel and cilostazol (n=24) or clopidogrel alone (n=22). Platelet function was measured ex vivo using the VerifyNow P2Y12 assay. Genomic DNA was extracted from peripheral blood samples using the QIAamp DNA Blood Midi Kit, which was subjected to candidate variant genotyping (CYP2C19, ABCB1, PON1 and P2RY12) using TaqMan quantitative polymerase chain reaction assays. All analyses were performed using SAS version 9.4 (SAS Institute). RESULTS: Among all enrolled patients, 18 (39%) had high on-treatment platelet reactivity (HTPR). The mean platelet reactivity was 207±53 (range, 78-325) with higher P2Y12 reaction units in the non-cilostazol group, 224±45 vs. 191±55 on the cilostazol group (p=0.03). No significant differences were observed in the clinical or genetic variables between the two groups. A multiple regression analysis determined that history of diabetes mellitus (p=0.03), use of cilostazol (p=0.03) and hematocrit (p=0.02) were independent predictors of platelet reactivity. CONCLUSIONS: In Puerto Rican PAD patients on clopidogrel therapy, history of diabetes mellitus, use of cilostazol and hematocrit are independent predictors of platelet reactivity. Adjunctive cilostazol therapy may enhance clopidogrel efficacy among PAD patients with HTPR.

Lessons Learned From Hurricane Maria: Pharmacists' Perspective.

The destruction in Puerto Rico following Hurricane Maria brought an increased demand for health care services while severely limiting the health care system's ability to provide patient care. Immediately following the hurricane, countless patients found themselves in a situation without their medications for both acute and chronic conditions. Many of these patients turned first to community pharmacies for access to their medications. In this letter, we describe the response of pharmacists to the needs of their communities following the natural disaster, Hurricane Maria, and summarize some lessons learned from the experience that may be useful in future disaster planning.