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1.
Nat Immunol ; 24(8): 1382-1390, 2023 08.
Article in English | MEDLINE | ID: mdl-37500887

ABSTRACT

Microglia, the macrophages of the brain parenchyma, are key players in neurodegenerative diseases such as Alzheimer's disease. These cells adopt distinct transcriptional subtypes known as states. Understanding state function, especially in human microglia, has been elusive owing to a lack of tools to model and manipulate these cells. Here, we developed a platform for modeling human microglia transcriptional states in vitro. We found that exposure of human stem-cell-differentiated microglia to synaptosomes, myelin debris, apoptotic neurons or synthetic amyloid-beta fibrils generated transcriptional diversity that mapped to gene signatures identified in human brain microglia, including disease-associated microglia, a state enriched in neurodegenerative diseases. Using a new lentiviral approach, we demonstrated that the transcription factor MITF drives a disease-associated transcriptional signature and a highly phagocytic state. Together, these tools enable the manipulation and functional interrogation of human microglial states in both homeostatic and disease-relevant contexts.


Subject(s)
Alzheimer Disease , Induced Pluripotent Stem Cells , Neurodegenerative Diseases , Humans , Microglia , Alzheimer Disease/genetics , Brain
2.
Intern Med J ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963005

ABSTRACT

BACKGROUND: Despite common global usage, fluoropyrimidine (FP; 5-flurouracil and capecitabine)-related chemotherapy toxicity is poorly reported in the literature, with serious toxicity ranging from 10% to 40% and early toxicity (within 60 days of exposure) quoted at 14%. Data reflecting the incidence of Grades 3-5 FP-related toxicity in Australian cancer patients is scant, despite the significant impact of toxicity on patients (hospitalisations, intensive care unit (ICU) admissions and even death). AIMS: This retrospective audit evaluated Grades 3-5 toxicities in a contemporaneous cohort of 500 patients receiving FP chemotherapies within the Hunter-New England Local Health District from June 2020 to June 2022. Data were extracted from public hospital records and oncology-specific e-records to determine rates of toxicity and associated hospitalisations, intensive care admissions and deaths that occurred within 60 days of first exposure to FP chemotherapy-containing regimens. RESULTS: One hundred and fifty incidents of Grades 3-4 toxicity in the first 60 days led to 87 patients presenting to hospital (87/500, 17.4%). The most common serious toxicities were diarrhoea (39.3%), nausea and vomiting (22.7%) and febrile neutropaenia (10%). Four patients were admitted to the ICU, and four patients died of toxicity. Within the first 60 days, 22.2% of patients required treatment delays, 21.4% required dose reductions, and 7.8% of patients ceased treatment because of toxicities. DISCUSSION AND CONCLUSION: Our experience reflects international reports and is likely generalisable to the Australian population. These data are a basis to understand the potential benefits of precision medicine strategies such as pharmacogenomic screening to improve patient tolerability and the cost-effectiveness of FP chemotherapy prescribing.

3.
J Am Pharm Assoc (2003) ; 63(4): 1180-1184, 2023.
Article in English | MEDLINE | ID: mdl-37149140

ABSTRACT

BACKGROUND: No published data exist regarding per diem pay differences between the 50 United States Boards of Pharmacy. OBJECTIVES: The purpose of this study was to quantify and compare the per diem pay rate of Board of Pharmacy members for each state in the U.S. Compensation for mileage and meals, as well as demographic information regarding U.S. Board of Pharmacy members, was also evaluated. METHODS: In June 2022, each state Board of Pharmacy was contacted to gather data including per diem pay, mileage and meal compensation, number of meetings per year, number and gender of Board members, length of appointment, and regulatory statutes. RESULTS: The average per diem pay for Board members was $75.86 (median = $50.00, range = $0.00-$250.00, n = 48 states). Most states report paying Board members for mileage (95.1%, n = 39 of 41) and meals (80.0%, n = 28 of 35). On average, Boards are composed of 8.3 members (median = 7.5, range = 5-17, n = 50), meet 8.3 times annually (median = 8, range = 3-16, n = 47), and have a 4.5-year length of appointment (median = 4, range = 3-6, n = 47). Men represented 61.2% of occupied Board positions, and pharmacists accounted for 74.2% of all positions. The average year for per diem pay statute update was 2002. CONCLUSION: The per diem pay for U.S. Board of Pharmacy members varies from state to state, ranging from unpaid (n = 8 states) up to $250.00 per diem. Fair compensation, increased pharmacy technician and women representation, and more timely pharmacy statute updates are necessary in order to achieve inclusion, diversity, and equity across state Boards of Pharmacy.


Subject(s)
Pharmaceutical Services , Pharmacies , Pharmacy , Male , United States , Humans , Female , Pharmacists , Pharmacy Technicians
4.
Ann Surg ; 272(1): 24-29, 2020 07.
Article in English | MEDLINE | ID: mdl-32209893

ABSTRACT

OBJECTIVE: To determine the representation of Black/AA women surgeons in academic medicine among U.S. medical school faculty and to assess the number of NIH grants awarded to Black/AA women surgeon-scientists over the past 2 decades. SUMMARY OF BACKGROUND DATA: Despite increasing ethnic/racial and sex diversity in U.S. medical schools and residencies, Black/AA women have historically been underrepresented in academic surgery. METHODS: A retrospective review of the Association of American Medical Colleges 2017 Faculty Roster was performed and the number of grants awarded to surgeons from the NIH (1998-2017) was obtained. Data from the Association of American Medical Colleges included the total number of medical school surgery faculty, academic rank, tenure status, and department Chair roles. Descriptive statistics were performed. RESULTS: Of the 15,671 U.S. medical school surgical faculty, 123 (0.79%) were Black/AA women surgeons with only 11 (0.54%) being tenured faculty. When stratified by academic rank, 15 (12%) Black/AA women surgeons were instructors, 73 (59%) were assistant professors, 19 (15%) were associate professors, and 10 (8%) were full professors of surgery. Of the 372 U.S. department Chairs of surgery, none were Black/AA women. Of the 9139 NIH grants awarded to academic surgeons from 1998 and 2017, 31 (0.34%) grants were awarded to fewer than 12 Black/AA women surgeons. CONCLUSION: A significant disparity in the number of Black/AA women in academic surgery exists with few attaining promotion to the rank of professor with tenure and none ascending to the role of department Chair of surgery. Identifying and removing structural barriers to promotion, NIH grant funding, and academic advancement of Black/AA women as leaders and surgeon-scientists is needed.


Subject(s)
Black or African American , Faculty, Medical/supply & distribution , Physicians, Women/supply & distribution , Research Support as Topic , Surgeons/supply & distribution , Adult , Female , Humans , Retrospective Studies , Schools, Medical , United States
6.
Clin Microbiol Rev ; 28(1): 80-94, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25567223

ABSTRACT

Despite significant improvements in leprosy (Hansen's disease) treatment and outlook for patients since the introduction of multidrug therapy (MDT) 3 decades ago, the global incidence remains high, and patients often have long-term complications associated with the disease. In this article, we discuss recent findings related to genetics, susceptibility, and disease reservoirs and the implications of these findings for Hansen's disease control and health outcomes for patients. We describe the continued difficulties associated with treatment of inflammatory episodes known as "leprosy reactions," which cause much of the disability associated with the disease and can affect people for many years after MDT is complete. We also discuss some of the contemporary challenges for physicians and patients, including international and internal migration of people affected by the disease. We suggest some important areas of focus for future Hansen's disease research.


Subject(s)
Leprosy/epidemiology , Leprosy/pathology , Animals , Armadillos/microbiology , Disease Reservoirs , Disease Susceptibility , Humans , Incidence , Leprosy/genetics , Leprosy/prevention & control , Leprosy/transmission , Risk Factors
7.
Glob Public Health ; 18(1): 2261773, 2023 01.
Article in English | MEDLINE | ID: mdl-37750403

ABSTRACT

Climate change is an important driver of migration, but little research exists on whether migrant communities in the U.S. identify climate change-related factors as reasons for migrating. In 2021, we conducted a multidisciplinary, collaborative project to better understand the nexus of climate change and immigrant health in the Atlanta area. This paper presents one arm of this collaboration that explored both the role of climate change in decisions to immigrate to Georgia and the ways that climate change intersects with other possible drivers of migration. First generation migrants from Latin America were recruited primarily through CPACS Cosmo Health Center and were invited to participate in an intake survey and an in-depth interview. Results were analyzed using descriptive statistics and thematic analysis. Findings suggest that while participants may not have explicitly identified climate change as a primary reason for migration, in both surveys and in-depth interviews, participants reported multiple and intersecting social, economic, political, and environmental factors that are directly or indirectly influenced by climate change and that are involved in their decisions to migrate. The narratives that emerged from in-depth interviews further contextualised survey data and elucidated the complex nexus of climate change, migration, and health.


Subject(s)
Emigrants and Immigrants , Transients and Migrants , Humans , Latin America , Climate Change , Health Facilities
8.
Am J Trop Med Hyg ; 2022 Feb 07.
Article in English | MEDLINE | ID: mdl-35130490

ABSTRACT

The new Lancet Commission on water, sanitation, and hygiene (WASH) hopes to reimagine and guide global WASH efforts. This comes at a time when unequal living conditions and global disparities in response and recovery have been highlighted by the COVID-19 pandemic and recent large impact trials have delivered mostly disappointing results suggesting the need for radically more effective interventions to improve global public health. We find ourselves at an inflection point in global WASH with an opportunity to build new approaches with potentially more equitable, cost-effective, and scalable solutions. Mobile health (mHealth) technology is an important and innovative tool for WASH advances. Yet, the use of mHealth has not been equally distributed in terms of its benefits nor is its impact guaranteed. In resource-constrained settings, where technology can increase inequalities, special attention should be paid to structural and systemic hierarchies during the development of mHealth programs along with the acknowledgment and understanding how these systems can reinforce the systematic exclusion of those most vulnerable. The WASH sector needs to adapt to a future that is innovative and inclusive with a commitment to rethinking the resources needed to enhance scope and impact. We highlight urban sanitation in Brazil as a case study to demonstrate that mHealth can support and enhance publicly funded infrastructure and to help reimagine WASH for postpandemic and beyond.

9.
Am J Surg ; 223(1): 146-150, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34340862

ABSTRACT

BACKGROUND: Enoxaparin is the recommended agent for deep vein thrombosis (DVT) chemoprophylaxis in trauma patients. Current literature suggests weight-based dosing is superior to standard dosing for adequate chemoprophylaxis. Literature regarding the use of weight-based enoxaparin in the setting of traumatic brain injury (TBI) however is limited. METHODS: A retrospective analysis of adult trauma patients admitted between January 1, 2018 to February 28, 2019 was performed. Sixty-six patients with TBI receiving weight-based enoxaparin met inclusion criteria. Incidence of intracranial hemorrhage (ICH) expansion was the primary endpoint. Newly diagnosed venous thromboembolism (VTE) and death were secondary endpoints. RESULTS: Two patients, out of sixty-six, had progression of their TBI requiring surgical intervention. Newly diagnosed VTE occurred in one patient. No deaths were due to ICH expansion or VTE. CONCLUSIONS: Use of weight-based enoxaparin dosing in the setting of TBI shows promise without an increased incidence of ICH expansion when compared to other studies. Level of Evidence and Study Type: Level IV, Therapeutic.


Subject(s)
Anticoagulants/administration & dosage , Brain Injuries, Traumatic/complications , Enoxaparin/administration & dosage , Intracranial Hemorrhages/epidemiology , Venous Thrombosis/prevention & control , Adult , Aged , Anticoagulants/adverse effects , Body Weight , Brain Injuries, Traumatic/blood , Brain Injuries, Traumatic/drug therapy , Drug Dosage Calculations , Enoxaparin/adverse effects , Female , Humans , Incidence , Intracranial Hemorrhages/chemically induced , Male , Middle Aged , Retrospective Studies , Venous Thrombosis/epidemiology , Venous Thrombosis/etiology
10.
Clin Pharmacol Ther ; 112(4): 791-802, 2022 10.
Article in English | MEDLINE | ID: mdl-35607723

ABSTRACT

Fluoropyrimidines (FP; 5-fluorouracil, capecitabine, and tegafur) are a commonly prescribed class of antimetabolite chemotherapies, used for various solid organ malignancies in over 2 million patients globally per annum. Dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene, is the critical enzyme implicated in FP metabolism. DPYD variant genotypes can result in decreased DPD production, leading to the development of severe toxicities resulting in hospitalization, intensive care admission, and even death. Management of toxicity incurs financial burden on both patients and healthcare systems alike. Upfront DPYD genotyping to identify variant carriers allows an opportunity to identify patients who are at high risk to suffer from serious toxicities and allow prospective dose adjustment of FP treatment. This approach has been shown to reduce patient morbidity, as well as improve the cost-effectiveness of managing FP treatment. Upfront DPYD genotyping has been recently endorsed by several countries in Europe and the United Kingdom. This review summarizes current knowledge about DPD deficiency and upfront DPYD genotyping, including clinical and cost-effectiveness outcomes, with the intent of supporting implementation of an upfront DPYD genotyping service with individualized dose-personalization.


Subject(s)
Dihydropyrimidine Dehydrogenase Deficiency , Antimetabolites, Antineoplastic/adverse effects , Dihydropyrimidine Dehydrogenase Deficiency/drug therapy , Dihydropyrimidine Dehydrogenase Deficiency/genetics , Dihydrouracil Dehydrogenase (NADP)/genetics , Dihydrouracil Dehydrogenase (NADP)/metabolism , Fluorouracil , Genotype , Humans , Prospective Studies
11.
J Trauma Acute Care Surg ; 93(4): 439-445, 2022 10 01.
Article in English | MEDLINE | ID: mdl-35788582

ABSTRACT

BACKGROUND: Acute care surgeons are prone to burnout because of heavy workload, concurrent clinical responsibilities, and busy in-house call. Modifiable burnout factors have been identified, but few studies have looked for longitudinal effects after change is implemented. We hypothesized that optimizing faculty workflow could decrease burnout without compromising productivity. METHODS: We streamlined the faculty schedule at our institution to eliminate 24-hour call by creating weekly blocks of 12-hour day and night call, free from other clinical obligations. Protected academic time was added. The Maslach Burnout Inventory and Areas of Worklife Survey for health care providers were given to faculty, as well as close friends or family, at baseline, 6 months, and 12 months. Maslach Burnout Inventory and Areas of Worklife Survey proprietary formulas were used to assess change in factors contributing to burnout. Our primary outcome measure was the presence of factors contributing to burnout. Chart delinquency, relative value units, and academic projects were secondary outcome measures assessing clinical productivity change. RESULTS: Survey completion rates were 92% for faculty and 80% for family. All burnout risk factors improved at 6 and 12 months. In surgeon and family groups, the following improvements were noted in the mean scores of risk factors at 1 year: workload (74%, 68%), control (38%, 16%), reward (14%, 24%), fairness (69%, 22%), emotional exhaustion (27.5%, 24%), depersonalization (37.5%, 14%), personal accomplishment (12.5%, 2%), community (3%, 5%), values (10%, 15%), and over-all burnout (12.5%, 23.3%). There was a reduction in charts reaching delinquent status. Relative value unit production did not decrease. CONCLUSION: This study demonstrates that implementing a weekly, 12-hour call schedule can improve factors leading to burnout. Improvements were noted in surgeon and family groups alike, signifying both subjective improvements and observed change in the surgeons' behavior, without compromising clinical productivity. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.


Subject(s)
Burnout, Professional , Surgeons , Burnout, Professional/epidemiology , Burnout, Professional/prevention & control , Faculty , Humans , Surveys and Questionnaires , Tertiary Care Centers , Workload
12.
Epigenetics ; 17(12): 1701-1714, 2022 12.
Article in English | MEDLINE | ID: mdl-35345970

ABSTRACT

Chimpanzees have consistent individual differences in behaviour, also referred to as personality. Similar to human personality structure, five dimensions are commonly found in chimpanzee studies that show evidence for convergent and predictive validity (Dominance, Openness, Extraversion, Agreeableness, and Reactivity/Undependability). These dimensions are to some extent heritable, indicating a genetic component that explains part of the variation in personality scores, but are also influenced by environmental factors, such as the early social rearing background of the individuals. In this study, we investigated the role of epigenetic modification of the dopamine receptor D2 gene (DRD2) as a potential mechanism underlying personality variation in 51 captive chimpanzees. We used previously collected personality trait rating data and determined levels of DRD2 CpG methylation in peripheral blood samples for these same individuals. Results showed that DRD2 methylation is most strongly associated with Extraversion, and that varying methylation levels at specific DRD2 sites are associated with changes in Extraversion in nursery-reared, but not mother-reared, individuals. These results highlight the role of dopaminergic signalling in chimpanzee personality, and indicate that environmental factors, such as social experiences early in life, can have long-lasting behavioural effects, potentially through modification of the epigenome. These findings add to the growing evidence demonstrating the importance of the experience-dependent methylome for the development of complex social traits like personality.


Subject(s)
Epigenesis, Genetic , Extraversion, Psychological , Pan troglodytes , Receptors, Dopamine D2 , Animals , DNA Methylation , Pan troglodytes/genetics , Personality/genetics , Receptors, Dopamine D2/genetics
13.
JAMA Surg ; 157(4): 327-334, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35138327

ABSTRACT

IMPORTANCE: The lack of underrepresented in medicine physicians within US academic surgery continues, with Black surgeons representing a disproportionately low number. OBJECTIVE: To evaluate the trend of general surgery residency application, matriculation, and graduation rates for Black trainees compared with their racial and ethnic counterparts over time. DESIGN, SETTING, AND PARTICIPANTS: In this nationwide multicenter study, data from the Electronic Residency Application Service (ERAS) for the general surgery residency match and Graduate Medical Education (GME) surveys of graduating general surgery residents were retrospectively reviewed and stratified by race, ethnicity, and sex. Analyses consisted of descriptive statistics, time series plots, and simple linear regression for the rate of change over time. Medical students and general surgery residency trainees of Asian, Black, Hispanic or Latino of Spanish origin, White, and other races were included. Data for non-US citizens or nonpermanent residents were excluded. Data were collected from 2005 to 2018, and data were analyzed in March 2021. MAIN OUTCOMES AND MEASURES: Primary outcomes included the rates of application, matriculation, and graduation from general surgery residency programs. RESULTS: Over the study period, there were 71 687 applicants, 26 237 first-year matriculants, and 24 893 graduates. Of 71 687 applicants, 24 618 (34.3%) were women, 16 602 (23.2%) were Asian, 5968 (8.3%) were Black, 2455 (3.4%) were Latino, and 31 197 (43.5%) were White. Women applicants and graduates increased from 29.4% (1178 of 4003) to 37.1% (2293 of 6181) and 23.5% (463 of 1967) to 33.5% (719 of 2147), respectively. When stratified by race and ethnicity, applications from Black women increased from 2.2% (87 of 4003) to 3.5% (215 of 6181) (P < .001) while applications from Black men remained unchanged (3.7% [150 of 4003] to 4.6% [284 of 6181]). While the matriculation rate for Black women remained unchanged (2.4% [46 of 1919] to 2.3% [52 of 2264]), the matriculation rate for Black men significantly decreased (3.0% [57 of 1919] to 2.4% [54 of 2264]; P = .04). Among Black graduates, there was a significant decline in graduation for men (4.3% [85 of 1967] to 2.7% [57 of 2147]; P = .03) with the rate among women remaining unchanged (1.7% [33 of 1967] to 2.2% [47 of 2147]). CONCLUSIONS AND RELEVANCE: Findings of this study show that the underrepresentation of Black physicians at every stage in surgical training pipeline persists. Black men are especially affected. Identifying factors that address intersectionality and contribute to the successful recruitment and retention of Black trainees in general surgery residency is critical for achieving racial and ethnic as well as gender equity.


Subject(s)
Internship and Residency , Surgeons , Education, Medical, Graduate , Female , Humans , Intersectional Framework , Male , Retrospective Studies , Surgeons/education , United States
14.
Lepr Rev ; 82(2): 147-54, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21888139

ABSTRACT

If it can be argued that no single attribute or condition (leprosy included) is inherently or universally considered to be 'deeply discrediting,' to quote Goffman, then we must consider how external factors shape stigma associated with that condition in different cultural and socioeconomic contexts. Often, an analysis of what is perceived to be stigma towards people affected by leprosy uncovers other prejudices or stigmatising attitudes associated with class, gender, and/or ethnic inequalities in that society. The movement of people across international borders adds new dimensions to the experience of leprosy, as affected individuals confront different sets of understandings of the disease among healthcare professionals, friends, family, and employers in host and sending countries. Preconceptions of the immigrant 'other' in host countries may be bound up with notions of disease and danger, further complicating the experience of leprosy treatment for immigrants. Drawing on the work of others and on early stage qualitative research on leprosy among Brazilian immigrants to the United States, this paper will consider the ways in which immigration and transnational processes could affect the experience of stigma among immigrants affected by leprosy.


Subject(s)
Emigration and Immigration , Leprosy/psychology , Prejudice , Stereotyping , Aged , Brazil/ethnology , Discrimination, Psychological , Focus Groups , Humans , Leprosy/ethnology , Male , Mexico/ethnology , Middle Aged , Social Perception , United States , Vietnam/ethnology , Work
15.
J Trauma ; 70(3): 705-9, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21610362

ABSTRACT

BACKGROUND: Many surgeons avoid the damage-control techniques of intrathoracic packing and temporary chest wall closure after thoracotomy for trauma because of concerns about packing's effects on intrathoracic pressure and infectious risks. We hypothesized that temporary chest closure with or without intrathoracic packing (TCC-P) as a method of thoracic damage control would yield higher than expected survival rates for trauma thoracotomy patients with metabolic exhaustion, whereas traditional definitive chest closure (DEF) would exhibit predicted survival rates. METHODS: This was a retrospective cohort study by two urban Level I trauma centers on patients who (1) underwent emergent thoracotomy for trauma, (2) received ≥10 units (U) packed red blood cells and/or sustained a cardiac arrest before starting chest closure, and (3) survived to intensive care unit arrival. Demographic/physiologic data, chest closure method, and thoracic complications were gathered. Trauma injury severity scores (TRISS) were used to calculate survival probability for TCC-P and DEF. Nonparametric statistics were used for all comparisons. All values are expressed as medians and interquartile ranges (IQR). RESULTS: Sixty-one patients met inclusion criteria. Both TCC-P (n = 17) and DEF (n = 44) were severely injured (ISS=35 [IQR, 25-42] vs. 29 [IQR 19-45] and packed red blood cells = 16.5 U [IQR, 12.3-25.5 U] vs. 15 U [IQR, 11-23 U], respectively; p=ns). Patient demographics were similar except for the findings that the TCC-P cohort had higher rates of cardiac arrest before starting chest closure (TCC-P 82% vs. DEF 48%, p=0.04), significantly more severe abdominal injuries, and less severe head injuries than the DEF group. No significant differences were observed in survival of the overall samples (TCC-P=47% vs. DEF=57%), nor for observed:expected (O:E) survival ratio in 13 patients with TCC-P and 30 with DEF meeting criteria for TRISS calculation (TCC-P O:E, 46%:39%; DEF O:E, 53%:57%). No significant differences were found for TCC-P and DEF thoracic infectious (24% vs. 25%) or hemorrhagic (18% vs. 14%) complications. Surprisingly, peak inspiratory pressures on intensive care unit arrival were markedly better after TCC-P (20 cm H2O [IQR, 18-31 cm H2O]) than after DEF (32.5 cm H2O [IQR, 28-37.5 cm H2O], p=0.003). CONCLUSION: Concerns about TCC-P are not borne out as thoracic infection rates are unaffected and peak pressures are actually lower, possibly due to greater pleural volume from an open chest wall and skin-only closure. However, no significant survival benefit was seen with TCC-P.


Subject(s)
Thoracic Injuries/surgery , Thoracic Wall/surgery , Thoracotomy/methods , Adult , Erythrocyte Transfusion , Female , Humans , Injury Severity Score , Male , Retrospective Studies , Statistics, Nonparametric , Survival Rate , Thoracic Injuries/mortality
16.
Pharmacotherapy ; 41(6): 508-514, 2021 06.
Article in English | MEDLINE | ID: mdl-33864688

ABSTRACT

STUDY OBJECTIVE: The purpose of this study was to evaluate the utility of routine anti-Xa peak monitoring for trauma patients initiated on weight-based enoxaparin for venous thromboembolism (VTE) prophylaxis and identify patient populations where monitoring is necessary. DESIGN: Retrospective study. SETTING: Augusta University (AU) Medical Center in Augusta, Georgia, a level 1 trauma center. PATIENTS: Adult patients admitted to the trauma surgery service requiring chemical VTE prophylaxis. INTERVENTION: At least three consecutive doses of enoxaparin 0.5 mg/kg subcutaneously every 12 hour for VTE prophylaxis prior to an anti-Xa peak as the initial chemical VTE prophylaxis strategy. MEASUREMENTS: The primary end point was the percentage of patients who achieved goal anti-Xa peak of 0.2-0.6 unit/ml. The incidence of newly diagnosed VTE and clinically significant bleeding were assessed as secondary end points. MAIN RESULTS: From January 1, 2018, through February 28, 2019, 300 patients met inclusion criteria. Anti-Xa peaks were within goal in 91% of all patients, 7.7% were below goal, and 1.3% were above goal. For patients who did not meet the goal, dose adjustments were made in 70.4% of patients. New levels were obtained in 73.7% of those patients, and all repeat levels was within goal. Clinically significant bleeding occurred in 5.3% of patients. Newly diagnosed VTE occurred in 1.7% of patients. CONCLUSIONS: The use of initial weight-based enoxaparin dosing in trauma patients routinely achieved the prespecified target anti-Xa goal. In conclusion, anti-Xa levels are not necessary for routine monitoring of weight-based enoxaparin for VTE prophylaxis in trauma patients. Incidence of clinically significant bleeding and newly diagnosed VTE were similar to previous studies.


Subject(s)
Enoxaparin , Venous Thromboembolism , Wounds and Injuries , Adult , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Enoxaparin/administration & dosage , Enoxaparin/adverse effects , Factor Xa Inhibitors , Goals , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Heparin, Low-Molecular-Weight , Humans , Retrospective Studies , Venous Thromboembolism/epidemiology , Venous Thromboembolism/prevention & control , Wounds and Injuries/drug therapy
17.
Pharmgenomics Pers Med ; 14: 1603-1617, 2021.
Article in English | MEDLINE | ID: mdl-34916829

ABSTRACT

Pharmacogenomic screening can identify patients with gene variants that predispose them to the development of severe toxicity from fluoropyrimidine (FP) chemotherapy. Deficiency of the critical metabolic enzyme dihydropyrimidine dehydrogenase (DPD) leads to excessive toxicity on exposure to fluoropyrimidine chemotherapy. This can result in hospitalisation, intensive care admissions and even death. Upfront screening of the gene that encodes for DPD (DPYD) has recently been implemented in regions throughout Europe and the United Kingdom. Current screening evaluates DPYD variants that are well described within Caucasian patient populations and provides genotyped-guided dose adjustment recommendations based upon the presence of these variants. This article reviews the differences in DPYD gene variants within non-Caucasian populations compared to Caucasian populations, with regard to the implications for clinical tolerance of fluoropyrimidine chemotherapies and genotype guided dose adjustment guidelines.

18.
Lepr Rev ; 81(1): 17-26, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20496566

ABSTRACT

Leprosy, or Hansen's disease, continues to be feared and poorly understood in the United States, where knowledge of the disease is limited and prevalence is low. The presence of leprosy among immigrants, however, provides fuel for those with an anti-immigration agenda. In recent years, there have been several examples of popular media distortions of statistics and of information on leprosy's properties and contagiousness. As in previous eras of U.S. history, public fears about leprosy seem to be related to anti-immigration or nativist sentiment, which often mask underlying concerns about the potential economic threat of immigrant populations. In this article, I analyse the role of the U.S. media and other stakeholders who may have an interest in generating public fear associated with leprosy, in presenting and at times manipulating data about the disease to create an association between leprosy and undocumented immigration.


Subject(s)
Emigration and Immigration , Leprosy/diagnosis , Prejudice , Emigrants and Immigrants , Fear , History, 21st Century , Humans , Mass Media , Politics , United States
19.
Glob Public Health ; 15(7): 956-967, 2020 07.
Article in English | MEDLINE | ID: mdl-32202468

ABSTRACT

For over half a century, many public health campaigns related to infectious disease have focused on disease 'eradication,' rather than 'control' or 'management.' In this article, I will focus on the example of a recent global leprosy (Hansen's Disease) control campaign, Triple Zero. Drawing on examples from other public health initiatives, this article explores how the language of 'zero disease' or 'endgame strategies' is appealing to certain audiences but how it can also be misleading and have unexpected and unintended consequences. Depending on the specific characteristics of the disease, the disease vectors, and the circumstances of transmission, 'zero' disease is rarely an achievable goal. In addition, when a disease is said to reach 'zero,' it is important to consider the possible implications for people with social, physical, or emotional sequeläe from the disease and who still may require follow-up treatment and care.


Subject(s)
Disease Eradication , Leprosy , Disease Eradication/methods , Health Promotion , Humans , Leprosy/epidemiology , Leprosy/prevention & control , Public Health
20.
Philos Trans R Soc Lond B Biol Sci ; 375(1811): 20190616, 2020 11 09.
Article in English | MEDLINE | ID: mdl-32951551

ABSTRACT

Methylation levels have been shown to change with age at sites across the human genome. Change at some of these sites is so consistent across individuals that it can be used as an 'epigenetic clock' to predict an individual's chronological age to within a few years. Here, we examined how the pattern of epigenetic ageing in chimpanzees compares with humans. We profiled genome-wide blood methylation levels by microarray for 113 samples from 83 chimpanzees aged 1-58 years (26 chimpanzees were sampled at multiple ages during their lifespan). Many sites (greater than 65 000) showed significant change in methylation with age and around one-third (32%) of these overlap with sites showing significant age-related change in humans. At over 80% of sites showing age-related change in both species, chimpanzees displayed a significantly faster rate of age-related change in methylation than humans. We also built a chimpanzee-specific epigenetic clock that predicted age in our test dataset with a median absolute deviation from known age of only 2.4 years. However, our chimpanzee clock showed little overlap with previously constructed human clocks. Methylation at CpGs comprising our chimpanzee clock showed moderate heritability. Although the use of a human microarray for profiling chimpanzees biases our results towards regions with shared genomic sequence between the species, nevertheless, our results indicate that there is considerable conservation in epigenetic ageing between chimpanzees and humans, but also substantial divergence in both rate and genomic distribution of ageing-associated sites. This article is part of the theme issue 'Evolution of the primate ageing process'.


Subject(s)
Aging , Blood/metabolism , Epigenesis, Genetic/physiology , Pan troglodytes/genetics , Animals , Humans , Methylation
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