Community Pharmacists Identification of Gaps in Care - Statin Utilization for Primary Prevention.

Background: Statins are a highly effective lipid-lowering therapy associated with significant reductions in atherosclerotic cardiovascular disease (ASCVD) events and death. Despite these benefits, statins are underutilized. Pharmacist-led interventions to increase statin prescribing are effective. To our knowledge, no prior studies implemented a comprehensive cardiovascular risk assessment utilizing point-of-care (POC) testing in community pharmacies. Objectives: The primary objective was to determine if community pharmacists can be utilized to identify gaps in care regarding appropriate use of statin therapy for prevention of ASCVD events in HPSAs. Secondary objectives were to assess public interest in ASCVD risk assessment and statin prescribing by the pharmacist, and to identify factors associated with statin gaps in care. Methods: A cross-sectional study was conducted at three independent community pharmacies. Participants were identified based on age and medication history and were scheduled at their pharmacy to receive a comprehensive ASCVD risk screening consisting of POC measurement of a complete lipid panel, blood glucose or A1C, and blood pressure. Participants were informed of their statin candidacy at the screening. Participants completed a survey regarding perceptions of the services provided and opinions of statin prescribing by pharmacists. Results: Of the 57 participants, 43 (75.4%) were possible statin candidates. Most indicated trusting their pharmacist to prescribe a cholesterol-lowering medication and felt insurance should pay for these screenings. Conclusion: ASCVD risk assessment conducted within the community pharmacy setting can be utilized to identify treatment gaps in statin use. Participants indicated trusting pharmacists to provide this service and found the service valuable.

Pneumococcal Pure Polysaccharide Vaccination in Pediatric Patients With Chronic Heart Disease.

INTRODUCTION: This study aimed to describe pneumococcal polysaccharide vaccine-23 (PPSV23) vaccination use in high-risk pediatric patients with chronic heart disease (CHD). METHOD: This was a single-center retrospective cohort study. Patients were included if they were aged 2-18 years and were diagnosed with CHD. The primary outcome was PPSV23 vaccination. Secondary outcomes included missed opportunities and the incidence of infections. RESULTS: Three hundred ninety-two patients were included; the mean age was 8.8 years. Only 40 patients (10.2%) had documentation of PPSV23 vaccination. Patients had a median number of three clinic visits in 2019. There were 114 cases of pneumonia documented in patients before receiving PPSV23 and one case reported after PPSV23 vaccination. DISCUSSION: PPSV23 vaccination in high-risk pediatric patients with CHD was low, with many documented missed opportunities for vaccination. This may be attributed to the PPSV23 not being a routine vaccination on the pediatric schedule.

Retooling the Remediation Process: An Overview of One School's Process Overhaul.

OBJECTIVE: This article describes the process of review and modification of a Doctor of Pharmacy didactic course remediation process. A highlight of the new process includes early intervention with a Learning Specialist, creating the opportunity for students to address learning issues earlier in the courses. METHODS: Review of past remediation processes, student success, and pertinent literature related to remediation processes to allow for a new remediation process that supports students' learning and success. RESULTS: Creation of a new 2-phase process, including an early intervention and remediation process. The process includes a Learning Specialist position to focus on learning and barriers to academics. Remediation opportunities focus on proficiency in specific areas for each course. CONCLUSION: The new remediation policy provides greater support to students through the Learning Specialist. The new policy helps students connect with resources earlier in the program and provides multiple opportunities for assisting students during the semester. Over the past 4 years, the Learning Specialist has met with an average of 73 individual students per semester, while only an average of 25 students in the didactic portion of the curriculum (year 1-3) require remediation each semester.

Utilization rates and predictors of sodium glucose cotransporter 2 inhibitor use in patients with heart failure with or without type 2 diabetes.

PURPOSE: Sodium glucose cotransporter 2 (SGLT2) inhibitors have been demonstrated to reduce cardiovascular deaths and heart failure (HF) hospitalizations in patients with HF. Despite this, utilization remains low. The purpose of this study was to characterize SGLT2 inhibitor utilization rates and predictors of use in a population of patients with or without type 2 diabetes (T2D). METHODS: This was a retrospective, single-center, descriptive chart review study. Individuals 18 years of age or older with HF were eligible for inclusion. Charts were reviewed between August 2021 and February 2022. The primary objective was to identify rates of SGLT2 inhibitor prescribing for patients with HF within a large academic medical center. Logistic regression analyses were conducted to identify potential SGLT2 inhibitor utilization predictors (demographic characteristics, medical history, laboratory results, specialty provider visits, medication use, and medication coverage). RESULTS: A total of 800 patients with HF were included: 377 with HF with reduced ejection fraction (HFrEF), 88 with mildly reduced EF, and 335 with preserved EF. Key baseline characteristics were as follows: 43% female; 47% Hispanic; 42% with T2D; 49% with established atherosclerotic cardiovascular disease; and mean age, 65 years. SGLT2 inhibitor utilization was 6.5% overall. Key predictors of utilization were as follows: T2D (odds ratio [OR], 33.4; 95% CI, 8.01-139.55), HFrEF (OR, 2.8; 95% CI, 1.45-5.51), HF clinic visit (OR, 2.5; 95% CI, 1.40-4.60), visit with pharmacist with prescriptive authority (OR, 5.8; 95% CI, 3.14-10.88), and enrollment in the hospital patient assistance program (OR, 2.3; 95% CI, 1.08-4.97). CONCLUSION: Despite guideline recommendations, SGLT2 inhibitors are underutilized in patients with HF with or without T2D.

Underprescribing of statin therapy in people with HIV at risk for atherosclerotic cardiovascular disease.

PURPOSE: People with HIV (PWH) are at increased risk for developing atherosclerotic cardiovascular disease (ASCVD). The primary objective of this study was to evaluate adherence to guideline recommendations on statin use in PWH for both primary and secondary ASCVD prevention in a single healthcare institution. METHODS: A retrospective chart review was performed to evaluate statin use for cardiovascular risk reduction in PWH 40 to 75 years of age at an HIV clinic over a 1-year evaluation period. The study included patients who met one of the 4 criteria for statin therapy defined in the "ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults." Patient demographics were collected and a 10-year ASCVD risk score was calculated. RESULTS: A total of 432 PWH were evaluated for statin therapy; 205 patients (47.5%) met criteria for statin therapy. The majority of patients were male, the average age was 58 years, and the average time since HIV diagnosis was 19 years. The mean ASCVD risk score was 14.2%. Only 79 patients (38.5%) who met criteria were prescribed statin therapy, and only 45 (56.9%) were prescribed statin therapy of appropriate intensity. Use of ART pharmacokinetic enhancer was low and did not affect statin prescribing. Multivariable analysis found that age, diabetes, clinical ASCVD, and an appointment with a pharmacist clinician prescriber predicted statin utilization. A high ASCVD risk score (>20%) did not predict statin treatment. CONCLUSION: Statin prescribing is low in PWH, who are at increased risk for ASCVD. Future research in PWH should focus on improving ASCVD risk assessment and exploring causes for statin underprescribing.

Symbiotic Modulation as a Driver of Niche Expansion of Coastal Plants in the San Juan Archipelago of Washington State.

Modern evolutionary theory and population genetics posit that adaptation and habitat expansion of plants result from processes exclusive to their genomes. Here, we present studies showing that plants can grow across complex habitat gradients by modulating symbiotic associations with Class 2 fungal endophytes. Endophyte analysis of three native (Leymus mollis, Distichlis spicata, and Salicornia pacifica) and one invasive (Spartina anglica) plant growing across adjacent microhabitats in the San Juan Archipelago altered associations with Class 2 fungal endophytes in response to soil salinity levels. At the microhabitat interfaces where the gradation of salinity varied, the plants were colonized by endophytes from both microhabitats. A reciprocal transplant study along a salt gradient demonstrated that Leymus mollis (dunegrass) required endophytes indigenous to each microhabitat for optimal fitness and/or survival. In contrast, when dunegrass and Grindelia integrifolia (gumweed) were found growing in low salinity, but high drought habitats, these plant species had their own unique dominant endophyte association regardless of geographic proximity and conferred drought but not high salt stress tolerance. Modulation of endophyte abundance occurred in planta based on the ability of the symbiont to confer tolerance to the stress imposed on plants. The ability of an endophyte to confer appropriate stress tolerance resulted in a significant increase of in planta fungal abundance. Conversely, the inability of an endophyte to confer stress tolerance resulted in a decrease of in planta fungal abundance. Our studies indicate that Class 2 fungal endophytes can provide a symbiotic mechanism for niche expansion and phenotypic plasticity across environmental gradients.

Awareness, perceptions, and attitudes toward community pharmacist clinical services: An analysis of data from 2004 and 2018.

OBJECTIVE: This study aimed to describe and compare the public's change in awareness and perceptions of, willingness to use, willingness to pay, and interest in insurance coverage for community pharmacist prescriptive authority services and point of care testing over a time span of 14 years. METHODS: This was a retrospective review of anonymous questionnaires administered by student pharmacists in 2004 and in 2018. Questionnaires were administered to individuals who presented to University of New Mexico College of Pharmacy sponsored health fair screenings and at various community pharmacies throughout the state of New Mexico (NM). RESULTS: In total, 545 (2004) and 659 (2017-2018) participants completed the questionnaire. Awareness of community pharmacist clinical services increased from 2004 to 2018. In 2018, awareness of newer prescriptive authority services provided by pharmacists in NM was low relative to the services assessed in previous years. Most respondents indicated a willingness to use and pay for pharmacist-provided clinical services and felt that pharmacists should receive compensation by their insurance for these services. Trust in pharmacist advice grew from 2004 to 2018. CONCLUSION: Overall rates of awareness of community pharmacist clinical services were low with the exception of immunizations; however, most participants indicated interest in and willingness to use these services. Most participants believed pharmacists should receive reimbursement from insurance companies for clinical services and were also willing to pay a copay or out-of-pocket cost for these services.

Curricular-driven screening for atrial fibrillation at community pharmacies.

BACKGROUND: Atrial fibrillation (AF) increases the risk of stroke. It can be asymptomatic and patients may be unaware they have AF. Therefore, there is a need to develop a sustainable community model to screen for unrecognized AF. OBJECTIVE: The objective is to assess a curriculum driven model developed by the University of New Mexico College of Pharmacy (UNM-CoP) to evaluate AF screening at 3 community pharmacy sites. METHODS: Screenings and education for AF were performed by fourth year pharmacy students during their advanced pharmacy practice experience (APPE) community rotation at pre-selected independent pharmacies. Patients were screened using the KardiaMobile device (AliveCor®, Mountain View, CA), an FDA-cleared device that interprets a medical-grade ECG in 30 seconds. All screening materials and devices were provided by UNM-CoP. Semi-structured interviews with each targeted pharmacy were conducted to assess the logistics, value, and sustainability of the program (N=5 pharmacists). RESULTS: AF assessment was performed over a 7-month period by 8 students at three pharmacies. Students screened a total of 63 patients (62% female, 56 ± 14 years of age) with 92% of the encounters taking less than 10 minutes to complete. Three patients (4.7%) were found to have possible AF. Positive scores were noted when assessing value to the pharmacy (8.8 ± 0.8, scale 1-10 with 10 being high value) and professionally (9.7 ± 0.6). DISCUSSION: Student-pharmacists provides a likely pathway for sustainability for this clinical initiative and provides for a novel and measurable APPE patient interaction. CONCLUSION: Curricular driven AF assessment in community pharmacies was shown to be a feasible model. Additional studies are needed to assess whether population-based real-time assessment and detection of AF can reduce the risk of stroke in previously undetected AF. If stroke reduction is realized, reimbursement for service is likely and can contribute to further sustainability.

Awareness and perceptions of advanced practice pharmacists among health care providers in New Mexico.

OBJECTIVE: The purpose of this study was to evaluate health care provider awareness and perceptions of the 2 types of advanced practice pharmacists (APPhs) in New Mexico: pharmacist clinicians (PhCs) and community pharmacists with independent prescriptive authority (iRPhs). METHODS: A cross-sectional electronic survey was administered to health care providers in New Mexico to describe awareness and perceptions of APPhs and benefits and barriers to collaborative practice with APPhs. RESULTS: A total of 5905 providers received the emailed survey, and 634 (11%) completed the survey, with 68% of the respondents indicating that they were not aware of the 2 types of APPhs in New Mexico. The top benefits of working with a PhC identified by the respondents were access to medication knowledge, enhanced clinical outcomes, and increased access to patient care. The barriers to employing a PhC at their practice included cost, difficulty in billing for services, and limited reimbursement. Importantly, 80% of the respondents felt that PhCs should be recognized as providers for insurance reimbursement. Awareness of iRPhs varied by prescriptive authority service, ranging from 34% for tuberculin skin testing to 84% for adult vaccinations. Overall, 80%-92% indicated that iRPhs should be reimbursed, depending on the prescriptive authority service. CONCLUSION: Provider awareness of APPhs in New Mexico was low; however, the willingness to refer patients to APPhs for clinical services was high. Cost, difficulty in billing for services, and reimbursement for PhC services were the primary identified barriers to adding a PhC into practice. Most of the respondents indicated that both types of APPhs should be granted provider status and reimbursed by third-party payers for their services.

Interactive Effects of Omega-3 Polyunsaturated Fatty Acids and Secondhand Smoke in Mice and Human Subjects.

Active smoking and secondhand smoke (SHS) exposure increase the risk of cardiovascular morbidity and mortality. Active smoking is associated with reduced levels of omega-3 polyunsaturated fatty acids (n-3 PUFA) and studies show that n-3 PUFA supplementation can improve smoking-induced vascular dysfunction. However, the relationship between n-3 PUFA and SHS exposure has not been studied. Fat-1 transgenic mice, which convert n-6 to n-3 PUFA, were fed diets with n-3 PUFA or without (n-6 PUFA diet), exposed to air or SHS for 4 weeks, and vasoreactivity, antioxidant indices, and omega-3 index (percent eicosapentaenoic + docosahexaenoic acids in RBC) measured. Compared to air-exposed mice, SHS-enhanced aortic constriction in mice fed the n-6 PUFA diet (omega-3 index, 5.9 ± 0.2%; mean ± SE), but not in mice fed the n-3 PUFA diet (omega-3 index, 7.8 ± 0.6%). SHS also significantly induced mRNA expression of cytochrome P4501A1, NADPH:quinone oxidoreductase, heme oxygenase-1, and angiotensinogen in adipose tissue, and increased antioxidant capacity only in mice on the n-6 PUFA diet. Notably, SHS reduced the omega-3 index by 1.0 percentage point (p = 0.003), compared to air-exposed mice irrespective of diet. Additionally, we recruited human nonsmokers (NS) with and without SHS exposure (n = 40) 19-40 years old and measured the omega-3 index and antioxidant capacity. In human subjects SHS exposure was associated with a significantly lower omega-3 index (NS, 4.4 ± 1.1%; NS + SHS, 3.2 ± 1.0%; mean ± SD, p = 0.002) and higher antioxidant capacity (p < 0.001) than unexposed NS. Thus, SHS exposure is associated with lower levels of n-3 PUFA in mice and humans; however, an omega-3 index of ~ 8% in mice has vasoprotective and antioxidant properties.

Development of a bead-based assay for detection and differentiation of field strains and four vaccine strains of type 2 porcine reproductive and respiratory syndrome virus (PRRSV-2) in the USA.

Porcine reproductive and respiratory syndrome (PRRS) remains one of the most economically devastating diseases in swine population in the United States of America. Due to high mutation rate of the PRRS virus (PRRSV) genome, it is difficult to develop an accurate diagnostic assay with high strain coverage. Differentiation of field strains from the four vaccines that have been used in the USA, namely Ingelvac PRRS MLV, Ingelvac ATP, Fostera PRRS and Prime Pac PRRS, adds an additional challenge. It is difficult to use current real-time PCR systems to detect and differentiate the field strains from the vaccine strains. Luminex xTAG technology allows us to detect more molecular targets in a single reaction with a cost similar to a single real-time PCR reaction. By analysing all available 678 type 2 PRRSV (PRRSV-2) complete genome sequences, including the 4 vaccine strains, two pairs of detection primers were designed targeting the conserved regions of ORF4-ORF7, with strain coverage of 98.8% (670/678) based on in silico analysis. The virus strains sharing ≥98% identity of the complete genomes with the vaccine strains were considered vaccine or vaccine-like strains. One pair of primers for each vaccine strain were designed targeting the nsp2 region. In silico analysis showed the assay matched 94.7% (54/57) of Ingelvac PRRS® MLV (MLV) strain and the MLV-like strains, and 100% of the other three vaccine strains. Analytical sensitivity of the Luminex assay was one to two logs lower than that of the reverse transcription real-time PCR assay. Evaluated with 417 PRRSV-2 positive clinical samples, 95% were detected by the Luminex assay. Compared to ORF5 sequencing results, the Luminex assay detected 92.4% (73/79) of MLV strains, 78.3% (18/23) of Fostera strains and 50% (2/4) of ATP strains. None of the 472 samples were the Prime Pac strain tested by either ORF5 sequencing or the Luminex assay.

Development of a differential multiplex real-time PCR assay for porcine circovirus type 2 (PCV2) genotypes PCV2a, PCV2b and PCV2d.

A multiplex quantitative real-time polymerase chain reaction (mqPCR) assay was developed and validated for detection and differentiation of porcine circovirus type 2 (PCV2) genotypes, PCV2a, PCV2b and PCV2d. Single nucleotide polymorphism in primers or probes was deployed for different genotype detections, while conserved sequence in the 3' end of a primer and in the middle of a probe was used for the targeted genotype. In silico analysis of 2601 PCV2 ORF2 sequences showed that the predicted strain coverage of the assay was 93.4 % (409/438) for PCV2a, 95.1 % (1161/1221) for PCV2b and 93.6 % (882/942) for PCV2d strains. The PCR amplification efficiencies were 94.5 %, 100.2 %, and 99.2 % for PCV2a, PCV2b and PCV2d, respectively, with correlation coefficients >0.995 for all genotypes. The limits of detection (LOD) were 1.58 × 10-4 TCID50/mL for PCV2a, 5.62 × 10-4 TCID50/mL for PCV2b, and 3.16 × 10-3 TCID50/mL for PCV2d. Sanger sequencing of 74 randomly selected PCV2 positive clinical samples confirmed the genotypes of strains identified by the mqPCR. Validation with clinical samples co-positive for target and non-target pathogens demonstrated that the mqPCR assay specifically detected targeted viruses without cross reacting to each other or to other common porcine viruses.

Effects of medium chain fatty acids as a mitigation or prevention strategy against porcine epidemic diarrhea virus in swine feed.

Feed has been shown to be a vector for viral transmission. Four experiments were conducted to: 1) determine if medium chain fatty acids (MCFA) are effective mitigants when applied to feed both pre- and post-porcine epidemic diarrhea virus (PEDV) inoculation measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR), 2) evaluate varying levels and combinations of MCFA measured by qRT-PCR, and 3) evaluate selected treatments in bioassay to determine infectivity. In exp. 1, treatments were arranged in a 2 × 2 + 1 factorial with main effects of treatment (0.3% commercial formaldehyde [CF] product, Sal CURB [Kemin Industries, Inc.; Des Moines, IA], or 1% MCFA blend (Blend) of 1:1:1 C6:C8:C10 [PMI, Arden Hills, MN]) and timing of application (pre- or post-inoculation with PEDV) plus a positive control (PC; feed inoculated with PEDV and no treatment). All combinations of treatment and timing decreased detectable PEDV compared with the PC (P < 0.05). Pre-inoculation treatment elicited decreased magnitude of PEDV detection (cycle threshold value) compared with post-inoculation (P = 0.009). Magnitude of PEDV detection was decreased for CF compared with Blend (P < 0.0001). In exp. 2, pre-inoculation treatments consisted of: 1) PC, 2) 0.3% CF, 3 to 5) 0.125% to 0.33% C6:0, 6 to 8) 0.125% to 0.33% C8:0, 9 to 11) 0.125% to 0.33% C10:0, and 12 to 15) 0.125% to 0.66% C5:0. Treating feed with 0.33% C8:0 resulted in decreased (P < 0.05) PEDV detection compared with all other treatments. Increasing concentration of each individual MCFA decreased PEDV detectability (P < 0.042). In exp. 3, pre-inoculation treatments consisted of: 1) PC, 2) 0.3% CF, 3 to 7) 0.25% to 1% Blend, 8 to 10) 0.125% to 0.33% C6:0 + C8:0, 11 to 13) 0.125% to 0.33% C6:0 + C10:0, and 14 to 16) 0.125% to 0.33% C8:0 + C10:0. Treating feed with CF, 0.5% Blend, 0.75% Blend, 1% Blend, all levels of C6:0+C8:0, 0.25% C6:0 + 0.25% C10:0, 0.33% C6:0 + 0.33% C10:0, 0.25% C8:0 + 0.25% C10:0, or 0.33% C8:0 + 0.33% C10:0 elicited decreased detection of PEDV compared with PC (P < 0.05). Increasing concentration of each MCFA combination decreased PEDV detectability (linear, P < 0.012). In exp. 4, feed was treated pre-inoculation with: 1) no treatment (PC), 2) 0.3% CF, 3) 0.5% Blend, or 4) 0.3% C8:0 and analyzed via qRT-PCR and bioassay. Adding 0.5% Blend or 0.3% C8:0 resulted in decreased PEDV compared with PC and only PC resulted in a positive bioassay. Therefore, MCFA can decrease detection of PEDV in feed. Further, inclusion of lower levels of MCFA than previously evaluated are effective against PEDV.

Population screening for atrial fibrillation by student pharmacists at health fairs.

BACKGROUND: Individuals with unrecognized atrial fibrillation (AF) may be at an increased risk of stroke. There is a need to develop a sustainable and reproducible population-based screening model to identify unrecognized AF. OBJECTIVE: The objective of this study is to evaluate AF screening and education at student pharmacist-driven health fairs. METHODS: Screening for AF was performed by student members of the American Pharmacist Association Academy of Student Pharmacists with preceptor oversight. Participants were screened using the KardiaMobile device (AliveCor, Mountain View, CA), a Food and Drug Administration-cleared device that interprets a medical-grade electrocardiogram in 30 seconds. Student pharmacists also calculated a CHA2DS2-VASc score. Participant education was provided using an American Heart Association AF patient information sheet. Learning assessment was evaluated with 3 multiple choice questions. RESULTS: Students screened a total of 697 participants over a 6-month period at 13 health fairs. Overall, 71% of the participants were women aged 56 ± 15 years (mean ± SD). Sixteen of the participants (2.3%) who were screened received results indicating possible AF. None of the participants with a possible positive finding had symptoms suggestive of AF. Of these 16 participants, 11 (69%) had a CHA2DS2-VASc score greater than or equal to 2 (2.7 ± 0.7). Most participants answered each learning assessment question correctly. More than 95% of participants believed that screening for AF at health fairs was important or very important. CONCLUSION: Student pharmacist-driven health fairs were shown to be feasible models to screen for AF and were effective in providing AF education to the public. Student pharmacists also cultivated a clinical skill that is transferable to their future practice setting, including the community pharmacy setting. Additional studies are needed to assess whether population-based real-time assessment and detection of AF can reduce the risk of stroke in individuals with previously undetected AF.

Associations of medium and long chain omega-3 polyunsaturated fatty acids with blood pressure in Hispanic and non-Hispanic smokers and nonsmokers.

Epidemiology studies and clinical trials have shown that omega-3 polyunsaturated fatty acids (n-3 PUFAs) are inversely associated with blood pressure. We sought to determine the influence of cigarette smoking and Hispanic ethnicity on this association. Age- and sex-matched smokers and nonsmokers (n = 98) 19-50 years old lacking cardiovascular disease were recruited. Systolic and diastolic blood pressure (SBP, DBP), heart rate, HbA1c, lipids, BMI, and RBC fatty acids were measured. The omega-3 index (percent eicosapentaenoic and docosahexaenoic acid, EPA+DHA, in RBCs) was significantly lower in smokers (Smokers: 3.19 ± 0.86%; Nonsmokers, 3.88 ± 1.05%, p = 0.001) and Hispanics (Hispanic 3.32 ± 0.93%; Non-Hispanic, 3.82 ± 1.03%, p = 0.006). DHA exhibited a significant inverse association with BP in both smokers and nonsmokers, while alpha-linolenic acid (ALA) exhibited a significant positive association with BP only in smokers. Multiple regression analyses showed that BMI, DHA, smoking status, and smoking status*ALA interaction significantly predicted SBP (p < 0.0001, R2 = 0.44) and DBP (p < 0.0001, R2 = 0.33), while ethnicity had no effect. The observed lower BP when DHA levels are high suggests a possible protective role of DHA on BP in normotensive smokers and nonsmokers. Additionally, the observed higher BP when ALA levels are high only in smokers suggests that ALA may influence the BP-lowering effects of chronic smoking.

Identification of BVDV2b and 2c subgenotypes in the United States: Genetic and antigenic characterization.

Bovine viral diarrhea virus (BVDV), a ubiquitous pathogen of cattle, causes subclinical to severe acute disease. Two species of BVDV are recognized, BVDV1 and BVDV2 with BVDV1 divided into at least 21 subgenotypes and BVDV2 into 3-4 subgenotypes, most commonly using sequences from the 5' untranslated region (5' UTR). We report genomic sequencing of 8 BVDV2 isolates that did not segregate into the 2a subgenotype; but represented two additional BVDV2 subgenotypes. One BVDV2 subgenotype was previously recognized only in Asia. The other seven viruses fell into a second subgenotype that was first reported in Brazil and the U.S. in 2002. Neutralization assays using antiserum raised against vaccine strain BVDV2a 296c revealed varying degrees of neutralization of genetically diverse BVDV2 isolates. Neutralization titers decreased from 1.8 to more than a four log(2) decrease. This study illustrated the considerable genetic and antigenic diversity in BVDV2 circulating in the U.S.

Tissue localization, shedding, virus carriage, antibody response, and aerosol transmission of Porcine epidemic diarrhea virus following inoculation of 4-week-old feeder pigs.

We determined tissue localization, shedding patterns, virus carriage, antibody response, and aerosol transmission of Porcine epidemic diarrhea virus (PEDV) following inoculation of 4-week-old feeder pigs. Thirty-three pigs were randomly assigned to 1 of 3 groups for the 42-day study: inoculated (group A; n = 23), contact transmission (group B; n = 5), and aerosol transmission (group C; n = 5). Contact transmission occurred rapidly to group B pigs whereas productive aerosol transmission failed to occur to group C pigs. Emesis was the first clinical sign noted at 3 days postinoculation (dpi) followed by mild to moderate diarrhea lasting 5 more days. Real-time PCR detected PEDV in fecal and nasal swabs, oral fluids, serum, and gastrointestinal and lymphoid tissues. Shedding occurred primarily during the first 2 weeks postinoculation, peaking at 5-6 dpi; however, some pigs had PEDV nucleic acid detected in swabs collected at 21 and 28 dpi. Antibody titers were measurable between 14 and 42 dpi. Although feces and intestines collected at 42 dpi were PEDV negative by PCR and immunohistochemistry, respectively, small intestines from 70% of group A pigs were PCR positive. Although disease was relatively mild and transient in this age group, the results demonstrate that 4-week-old pigs are productively infected and can sustain virus replication for several weeks. Long-term shedding of PEDV in subclinically affected pigs should be considered an important source for PEDV transmission.

Treating Diuretic Resistance: An Overview.

Loop diuretics are central to the management of fluid overload in acute decompensated heart failure. However, a variance in the response to loop diuretics can alter a patient's clinical course and has an adverse effect on clinical outcomes. Thus, a diminished response to loop diuretics is an important clinical issue. Factors thought to contribute to diuretic resistance include erratic oral absorption in congested states and postdiuretic sodium retention. Further contributing to diuretic resistance in patients with advanced heart failure are decreases in renal perfusion and alterations in sodium handling that occur in an attempt to maintain circulatory homeostasis. Several pharmacologic interventions have been used to improve diuretic response. Intravenous diuretic administration, increasing diuretic doses, or changing diuretic agents can potentially overcome pharmacokinetic obstacles which contribute to drug resistance. Combination diuretic therapy may be useful to overcome increased sodium retention, dopamine may improve renal perfusion, and hypertonic saline may transiently increase intravascular volume and improve sodium delivery to the tubules of the nephron. Despite the prevalence of diuretic resistance, there remains a paucity of clinical trial evidence to help guide therapy in these patients.

PCSK9 Inhibitors: An Innovative Approach to Treating Hyperlipidemia.

Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are novel agents indicated for the treatment of hyperlipidemia. Inhibition of PCSK9 produces an increase in surface low-density lipoprotein (LDL) receptors and increases removal of LDL from the circulation. Alirocumab (Praluent; Sanofi/Regeneron, Bridgewater, NJ) and evolocumab (Repatha; Amgen, Thousand Oaks, CA) are currently available and approved for use in patients with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, and clinical atherosclerotic cardiovascular disease. Bococizumab (RN316; Pfizer, New York, NY) is currently being studied in similar indications, with an estimated approval date in late 2016. The pharmacodynamic effects of PCSK9 inhibitors have been extensively studied in various patient populations. They have been shown to produce significant reductions in LDL and are well tolerated in clinical studies, but they are very costly when compared with statins, the current mainstay of hyperlipidemia treatment. Clinical outcome studies are underway, but not yet available; however, meta-analyses have pointed to a reduction in cardiovascular death and cardiovascular events with the use of PCSK9 inhibitors. This review will discuss the novel mechanism of action of PCSK9 inhibitors, the results of clinical studies, and the clinical considerations of these agents in current therapy.

Ring test evaluation of the detection of influenza A virus in swine oral fluids by real-time reverse-transcription polymerase chain reaction and virus isolation.

The probability of detecting influenza A virus (IAV) in oral fluid (OF) specimens was calculated for each of 13 assays based on real-time reverse-transcription polymerase chain reaction (rRT-PCR) and 7 assays based on virus isolation (VI). The OF specimens were inoculated with H1N1 or H3N2 IAV and serially diluted 10-fold (10(-1) to 10(-8)). Eight participating laboratories received 180 randomized OF samples (10 replicates × 8 dilutions × 2 IAV subtypes plus 20 IAV-negative samples) and performed the rRT-PCR and VI procedure(s) of their choice. Analysis of the results with a mixed-effect logistic-regression model identified dilution and assay as variables significant (P < 0.0001) for IAV detection in OF by rRT-PCR or VI. Virus subtype was not significant for IAV detection by either rRT-PCR (P = 0.457) or VI (P = 0.101). For rRT-PCR the cycle threshold (Ct) values increased consistently with dilution but varied widely. Therefore, it was not possible to predict VI success on the basis of Ct values. The success of VI was inversely related to the dilution of the sample; the assay was generally unsuccessful at lower virus concentrations. Successful swine health monitoring and disease surveillance require assays with consistent performance, but significant differences in reproducibility were observed among the assays evaluated.

La probabilité de détecter le virus de l'influenza A (VIA) dans des échantillons de fluide oral (FO) a été calculée pour chacune des 13 épreuves basées sur une réaction d'amplification en chaine en temps réel utilisant la polymérase réverse (rRT-PCR) et 7 épreuves basées sur l'isolement viral (IV). Les échantillons de FO ont été inoculés avec du VIA H1N1 ou H3N2 et dilués en série par facteur de 10 (10−1 à 10−8). Huit laboratoires participants ont reçu 180 échantillons randomisés de FO (10 réplicats × 8 dilutions × 2 sous-types de VIA plus 20 échantillons témoins négatifs sans VIA) et ont réalisé la méthode de rRT-PCR et d'IV de leur choix. L'analyse des résultats à l'aide d'un modèle de régression logistique pour les effets mélangés a identifié la dilution et l'épreuve comme étant des variables significatives (P < 0,0001) pour la détection de VIA dans du FO par rRT-PCR ou IV. Le sous-type de virus n'était pas significatif pour la détection de VIA soit par rRT-PCR (P = 0,457) ou par IV (P = 0,101). Pour les épreuves rRT-PCR les valeurs seuils de cycle (Ct) augmentaient de manière constante avec la dilution mais variaient énormément. Ainsi, il n'était pas possible de prédire le succès de l'IV sur la base des valeurs de Ct. Le succès de l'IV était inversement relié à la dilution de l'échantillon; l'épreuve était généralement négative aux faibles concentrations de virus. Pour avoir du succès dans la surveillance des maladies et de la santé des porcs il est nécessaire d'avoir des épreuves avec des performances constantes, mais des différences significatives dans la reproductibilité ont été observées parmi les épreuves évaluées.(Traduit par Docteur Serge Messier).