U.S. Filipino Adults Have Elevated Prevalence of Hypertension Across the Adult Lifespan: Findings From a Cross-Sectional Electronic Health Record Study.

Introduction: The prevalence of hypertension increases with age and differs by race and ethnicity. Among U.S. Asian adults, prevalence is higher for Filipino adults than for other major Asian subgroups, but whether this disparity exists across the adult lifespan is unknown. This study examined hypertension prevalence by age decade, comparing Filipino adults with South Asian, Chinese, Black, Hispanic, and White adults. Methods: This cross-sectional study used 2015-2016 electronic health record data from a Northern California integrated healthcare delivery system for 1,839,603 adults aged 30-79 years, including 128,124 Filipino adults. Hypertension was defined by diagnosis codes. Sex-specific prevalence was calculated by race and ethnicity overall and by 10-year age decade from ages 30-39 years to 70-79 years. The prevalence of hypertension among 5 racial and ethnic groups was compared within each decade (with Filipino as the reference), adjusting for age, English language, diabetes, smoking, and weight category. Results: Decade-specific prevalence of hypertension among Filipino men and women, respectively, was 9.7% and 8.5% for ages 30-39 years, 26.0% and 23.9% for ages 40-49 years, 45.9% and 44.4% for ages 50-59 years, 65.4% and 63.9% for ages 60-69 years, and 82.1% and 82.9% for ages 70-79 years. Across all age decades, hypertension prevalence among Filipino adults largely tracked with Black adults and was much higher than among South Asian, Chinese, White, and Hispanic adults. This pattern remained after adjusting for covariates, with the largest differences observed for adults aged <60 years. Conclusions: Similar to Black adults, Filipino adults have persistently higher hypertension prevalence than South Asian, Chinese, Hispanic, and White adults across the adult lifespan. These findings underscore the importance of surveillance and prevention efforts for this high-risk Asian group beginning in early adulthood.

Clinical presentation of group B Streptococcus-infected diabetic foot ulcers.

OBJECTIVE: Group B Streptococcus (GBS) is a common pathogen in diabetic foot ulcers (DFUs), where it has been found to result in higher rates of soft tissue infection and amputation despite appropriate treatment. In this study, we aim to investigate clinical characteristics and prognosis of GBS DFU infections, especially those with tenosynovial involvement. We hypothesise that GBS-infected DFUs with tenosynovial involvement leads to an increased number of recurrent infections and unexpected returns to the operating room. METHOD: Data were retrospectively collected from GBS-infected DFU patients surgically treated by an orthopaedic foot and ankle surgeon over a four-year period. Demographics, comorbidities, initial laboratory values and culture results from infected bone samples were recorded. Clinical outcome was assessed by recurrent infection and unplanned reoperation(s) within 3 months following the initial surgery. RESULTS: In total, 72 patients were treated for GBS-infected DFUs. Intra-operative culture of infected bone identified GBS in 16 patients (22.2%). Significantly more black patients (p=0.017) were afflicted by GBS DFUs. Patients with GBS DFUs had higher initial haemoglobin A1C levels (p=0.019), and those with tenosynovial involvement were likely to require reoperation (p=0.036) and had a greater total number of surgeries (p=0.015) than those without. CONCLUSION: GBS-infected DFUs are more common in black patients and those with elevated haemoglobin A1Cs. GBS infections with tenosynovial involvement are particularly destructive and require aggressive treatment by surgeons.

Clinical Improvement Following Operative Management of Ankle Fractures Among Patients With and Without Moderate to High Depressive Symptoms: An Analysis Using PROMIS.

Background: Understanding the recovery trajectory following operative management of ankle fractures can help surgeons guide patient expectations. Further, it is beneficial to consider the impact of mental health on the recovery trajectory. Our study aimed to address the paucity of literature focused on understanding the recovery trajectory following surgery for ankle fractures, including in patients with depressive symptoms. Methods: From February 2015 to March 2020, patients with isolated ankle fractures were asked to complete Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF), Pain Interference (PI), and Depression questionnaires as part of routine care at presentation and follow-up time points. Linear mixed effects regression models were used to evaluate the patient recovery pattern, comparing the preoperative time point to <3 months, 3-6 months, and >6 months across all patients. Additional models that included the presence of depression symptoms as a covariate were then used. Results: A total of 153 patients met inclusion criteria. By 3-6 months, PROMIS PF (ß: 9.95, 95% CI: 7.97-11.94, P < .001), PI (ß: -10.30, 95% CI: -11.87 to -8.72, P < .001), and Depression (ß: -5.60, 95% CI: -7.01 to -4.20, P < .001) improved relative to the preoperative time point. This level of recovery was sustained thereafter. When incorporating depressive symptoms into our model as a covariate, the moderate to high depressive symptoms were associated with significantly and clinically important worse PROMIS PF (ß: -4.00, 95% CI: -7.00 to -1.00, P = .01) and PI (ß: 3.16, 95% CI: -0.55 to 5.76, P = .02) scores. Conclusion: Following ankle fracture surgery, all patients tend to clinically improve by 3-6 months postoperatively and then continue to appreciate this clinical improvement. Although patients with moderate to high depressive symptoms also clinically improve following the same trajectory, they tend to do so to a lesser level than those who have low depressive symptoms. Level of Evidence: Level III, case-control study.

Building a strong foundation from the ground up: the impact of a medical student substance use disorder organization on curriculum and community.

Due to the increasing rates of substance use disorders (SUDs), accidental overdoses, and associated high mortality rates, there is an urgent need for well-trained physicians who can grasp these complex issues and help struggling patients. Preparing these physicians occurs through targeted education and clinical exposure in conjunction with medical school curricula in the field of addiction medicine. Medical students can often feel overwhelmed by the medical school curriculum and changes to the curriculum take time, money, and administrative commitment to ratify. Implementing a student organization dedicated to SUD education can be a solution to provide clinical exposure, education and student autonomy in their medical school experience. At Wayne State University School of Medicine, Detroit vs. Addiction (DvA) is a student-run organization that is filling the gap in SUD education for medical students whilst providing assistance to the community. DvA not only extends clinical education for physicians in training, but it also provides the medical school with an opportunity to allow students to create a blueprint for education initiatives that can be incorporated as a mainstay in the school's technical trainings. Herein, we describe the evolution of this organization and its activities.

Eight-hour medication-assisted treatment waiver training for opioid use disorder: integration into medical school curriculum.

Background: The opioid epidemic is a growing problem in the USA. Use of medication-assisted treatment (MAT) has been effective in treating patients with opioid use disorders (OUD) and maintaining sobriety; however, there is a significant shortage of physicians formally trained in MAT. Objective: Wayne State University School of Medicine integrated the 8-hour MAT waiver training into its Internal Medicine clerkship curriculum. The objectives of integrating this into the curriculum were to (1) introduce opioid use education during students' Internal Medicine clerkship and (2) assess whether the curriculum prepares students to feel more comfortable evaluating and treating patients with OUD. Design: MAT training specifically for medical students was provided free online by the Providers Clinical Support System (PCSS). All students on the Internal Medicine clerkship were required to complete the training. A 7-question pre-survey and post-survey assessed students' comfort in evaluating and treating OUD. Significant changes were assessed with a paired McNemar Bowker Test. Results: Medical students (n = 141) completed the pre-survey and post-survey. After the MAT training, students' perspective of their clinical knowledge about OUD, familiarity with MAT, and likelihood to utilize MAT for their patients significantly differed, with increased proportions of medical students in agreement across 6 of 7 pre-post survey items (p <.0001). Conclusions: Online MAT waiver training is a low-cost (free) way to introduce MAT education into the undergraduate clinical curriculum. Upon completing of the training, medical students self-reported improvements in their knowledge and attitudes about OUD and the different treatment options. Our hope is that MAT waiver training will allow for graduation of medical students who are ready to care for patients with OUD during residency and as practitioners upon completion of their residency.

The Duffy antigen receptor for chemokines regulates asthma pathophysiology.

BACKGROUND: The Duffy antigen receptor for chemokines (DARC) is an atypical receptor that regulates pro-inflammatory cytokines. However, the role of DARC in asthma pathophysiology is unknown. OBJECTIVE: To determine the role of DARC in allergic airways disease in mice, and the association between DARC single nucleotide polymorphisms (SNPs) and clinical outcomes in patients with asthma. METHODS: Mice with targeted disruption of the Darc gene (Darc∆E2 ) or WT mice were challenged over 3 weeks with house dust mite (HDM) antigen. Allergic airways disease was assessed 24 hours and 7 days following the final challenge. Additionally, associations between DARC SNPs and clinical outcomes were analysed in a cohort of poorly controlled asthmatics. RESULTS: Total airway inflammation following HDM did not differ between Darc∆E2 and WT mice. At 24 hours, Darc∆E2 mice had increased airway hyperresponsiveness; however, at 7 days airway hyperresponsiveness had completely resolved in Darc∆E2 but persisted in WT mice. In poorly controlled asthmatics, DARC SNPs were associated with worse asthma control at randomization and subsequent increased risk of healthcare utilization (odds ratio 3.13(1.37-7.27), P=.0062). CONCLUSIONS AND CLINICAL RELEVANCE: Our animal model and human patient data suggest a novel role for DARC in the temporal regulation in asthma pathophysiology and symptoms.

Genome-wide association study of leukotriene modifier response in asthma.

Heterogeneous therapeutic responses to leukotriene modifiers (LTMs) are likely due to variation in patient genetics. Although prior candidate gene studies implicated multiple pharmacogenetic loci, to date, no genome-wide association study (GWAS) of LTM response was reported. In this study, DNA and phenotypic information from two placebo-controlled trials (total N=526) of zileuton response were interrogated. Using a gene-environment (G × E) GWAS model, we evaluated 12-week change in forced expiratory volume in 1 second (ΔFEV1) following LTM treatment. The top 50 single-nucleotide polymorphism associations were replicated in an independent zileuton treatment cohort, and two additional cohorts of montelukast response. In a combined analysis (discovery+replication), rs12436663 in MRPP3 achieved genome-wide significance (P=6.28 × 10(-08)); homozygous rs12436663 carriers showed a significant reduction in mean ΔFEV1 following zileuton treatment. In addition, rs517020 in GLT1D1 was associated with worsening responses to both montelukast and zileuton (combined P=1.25 × 10(-07)). These findings implicate previously unreported loci in determining therapeutic responsiveness to LTMs.

Mechanisms of airway hyper-responsiveness in asthma: the past, present and yet to come.

Airway hyper-responsiveness (AHR) has long been considered a cardinal feature of asthma. The development of the measurement of AHR 40 years ago initiated many important contributions to our understanding of asthma and other airway diseases. However, our understanding of AHR in asthma remains complicated by the multitude of potential underlying mechanisms which in reality are likely to have different contributions amongst individual patients. Therefore, the present review will discuss the current state of understanding of the major mechanisms proposed to contribute to AHR and highlight the way in which AHR testing is beginning to highlight distinct abnormalities associated with clinically relevant patient populations. In doing so we aim to provide a foundation by which future research can begin to ascribe certain mechanisms to specific patterns of bronchoconstriction and subsequently match phenotypes of bronchoconstriction with clinical phenotypes. We believe that this approach is not only within our grasp but will lead to improved mechanistic understanding of asthma phenotypes and we hoped to better inform the development of phenotype-targeted therapy.

A genome-wide association study of bronchodilator response in asthmatics.

Reversibility of airway obstruction in response to ß2-agonists is highly variable among asthmatics, which is partially attributed to genetic factors. In a genome-wide association study of acute bronchodilator response (BDR) to inhaled albuterol, 534 290 single-nucleotide polymorphisms (SNPs) were tested in 403 white trios from the Childhood Asthma Management Program using five statistical models to determine the most robust genetic associations. The primary replication phase included 1397 polymorphisms in three asthma trials (pooled n=764). The second replication phase tested 13 SNPs in three additional asthma populations (n=241, n=215 and n=592). An intergenic SNP on chromosome 10, rs11252394, proximal to several excellent biological candidates, significantly replicated (P=1.98 × 10(-7)) in the primary replication trials. An intronic SNP (rs6988229) in the collagen (COL22A1) locus also provided strong replication signals (P=8.51 × 10(-6)). This study applied a robust approach for testing the genetic basis of BDR and identified novel loci associated with this drug response in asthmatics.

A polymorphism in the thyroid hormone receptor gene is associated with bronchodilator response in asthmatics.

A pro-asthmatic culture milieu and ß2-agonist (isoproterenol) were previously shown to regulate the expression of select transcription factors (TFs) within human airway epithelial and smooth muscle cells. This study tests 1116 single-nucleotide polymorphisms (SNPs) across 98 of these TF genes for association with bronchodilator response (BDR) in asthma patients. Genotyping was conducted using the Illumina HumanHap550v3 Beadchip in 403 non-Hispanic White asthmatic children and their parents. SNPs were evaluated for association with BDR using family and population-based analyses. Forty-two SNPs providing P-values <0.1 in both analyses were then genotyped in three adult asthma trials. One SNP 5' of the thyroid hormone receptor-ß gene was associated with BDR in the childhood population and two adult populations (P-value=0.0012). This investigation identified a novel locus for inter-individual variability in BDR and represents a translation of a cellular drug-response study to potential personalization of clinical asthma management.

HLA-DQ strikes again: genome-wide association study further confirms HLA-DQ in the diagnosis of asthma among adults.

BACKGROUND: Asthma is a common chronic respiratory disease in children and adults. An important genetic component to asthma susceptibility has long been recognized, most recently through the identification of several genes (e.g., ORMDL3, PDE4D, HLA-DQ, and TLE4) via genome-wide association studies. OBJECTIVE: To identify genetic variants associated with asthma affection status using genome-wide association data. METHODS: We describe results from a genome-wide association study on asthma performed in 3855 subjects using a panel of 455 089 single nucleotide polymorphisms (SNPs). RESULT: The genome-wide association study resulted in the prioritization of 33 variants for immediate follow-up in a multi-staged replication effort. Of these, a common polymorphism (rs9272346) localizing to within 1 Kb of HLA-DQA1 (chromosome 6p21.3) was associated with asthma in adults (P-value = 2.2E-08) with consistent evidence in the more heterogeneous group of adults and children (P-value = 1.0E-04). Moreover, some genes identified in prior asthma GWAS were nominally associated with asthma in our populations. CONCLUSION: Overall, our findings further replicate the HLA-DQ region in the pathogenesis of asthma. HLA-DQA1 is the fourth member of the HLA family found to be associated with asthma, in addition to the previously identified HLA-DRA, HLA-DQB1 and HLA-DQA2.

Personal exposure to aerosolized red tide toxins (brevetoxins).

Florida red tides occur annually in the Gulf of Mexico from blooms of the marine dinoflagellate, Karenia brevis, which produces highly potent natural polyether toxins, brevetoxins. Several epidemiologic studies have demonstrated that human exposure to red tide aerosol could result in increased respiratory symptoms. Environmental monitoring of aerosolized brevetoxins was performed using a high-volume sampler taken hourly at fixed locations on Siesta Beach, Florida. Personal exposure was monitored using personal air samplers and taking nasal swab samples from the subjects who were instructed to spend 1 hr on Sarasota Beach during two sampling periods of an active Florida red tide event in March 2005, and in May 2008 when there was no red tide. Results showed that the aerosolized brevetoxins from the personal sampler were in modest agreement with the environmental concentration taken from a high-volume sampler. Analysis of nasal swab samples for brevetoxins demonstrated 68% positive samples in the March 2005 sampling period when air concentrations of brevetoxins were between 50 to 120 ng/m(3) measured with the high-volume sampler. No swab samples showed detectable levels of brevetoxins in the May 2008 study, when all personal samples were below the limit of detection. However, there were no statistical correlations between the amounts of brevetoxins detected in the swab samples with either the environmental or personal concentration. Results showed that the personal sample might provide an estimate of individual exposure level. Nasal swab samples showed that brevetoxins indeed were inhaled and deposited in the nasal passage during the March 2005 red tide event.

Routine histopathologic evaluation in hallux valgus surgery.

BACKGROUND: Anecdotal evidence suggests that specimens submitted for histopathologic assessment during hallux valgus surgery most commonly reveal degenerative changes. The purpose of this study was to evaluate the cost effectiveness of routine examination of tissue from hallux valgus procedures. We hypothesized that such examination rarely diagnoses a new condition and does not alter postoperative management. MATERIALS AND METHODS: Specimens from 315 consecutive primary hallux valgus reconstructions performed between November 1995 and August 2002 were retrospectively analyzed. Patient charts were reviewed to determine the number of cases in which new diagnoses were made or treatment altered based upon histopathologic examination. Cost effectiveness was assessed by identifying the reimbursement for professional fees charged for these analyses. The total reimbursement per new diagnosis made and per alteration of treatment were calculated. RESULTS: Degenerative changes were diagnosed in the majority of speciments (97.5%, 307 of 315). Other diagnoses included rheumatoid arthritis (1.3%, four of 315), gouty arthritis (1.0%, three of 315), and pseudogout (0.3%, one of 315). A new diagnosis was made only in the one patient (0.3%, one of 315) with pseudogout. Postoperative management was unchanged in every case. CONCLUSION: Routine submission of specimens obtained during hallux valgus surgery is not cost effective. New diagnoses are very rare and postoperative management did not change.

A polymorphism in the NPPA gene associates with asthma.

BACKGROUND: Atrial natriuretic peptide (ANP) plays an important role in the lung and in augmenting allergic inflammation in asthma. The gene encoding ANP, NPPA, is located on chromosome 1p36, a region that has been linked to asthma. OBJECTIVES: Determine associations between asthma and four common SNPs on the NPPA gene: C/G (rs13305986) in the promoter; G/A (rs5063) in Exon 1 resulting in NPPAMet32-->Val substitution; T/C (rs5065) in Exon 3 resulting in an Arg152-->Ter substitution; and T/C in the 3'UT region (rs5067). Methods A case-control design was used in White participants. The screening cohort consisted of 336 asthmatic cases who participated in a large clinical trial and 154, non-asthmatic controls. The replicate cohort consisted of 172 asthmatic cases from a second clinical trial and 115 healthy controls. Demographic characteristics were well matched for cases and controls in the screening cohort. Adjusted (age, gender, body mass index) odds ratio (OR) were calculated by chi(2) and logistic regression; a P-value of 0.0167 defined the threshold of significance. RESULTS: The C allele of rs5067 was associated with asthma in the screening and replicate cohorts: adjusted ORs (95% confidence intervals) 0.5 (0.29-0.84; P=0.009) and 0.24 (0.11-0.53; P<0.0001), respectively. The C allele of rs5065 was associated with asthma in the screening cohort but not in the replicate. The population-attributable risk for asthma in carriers of the C allele for rs5067 was 23.3%. CONCLUSIONS: For rs5067, the risks of asthma in carriers of the C allele in the screening and replicate cohorts were reduced by 50% and 76%, respectively. NPPA may be an important susceptibility gene for asthma.