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1.
PLoS One ; 19(1): e0297208, 2024.
Article in English | MEDLINE | ID: mdl-38285682

ABSTRACT

BACKGROUND: Prior studies have shown disparities in the uptake of cardioprotective newer glucose-lowering drugs (GLDs), including sodium-glucose cotranwsporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1a). This study aimed to characterize geographic variation in the initiation of newer GLDs and the geographic variation in the disparities in initiating these medications. METHODS: Using 2017-2018 claims data from a 15% random nationwide sample of Medicare Part D beneficiaries, we identified individuals diagnosed with type 2 diabetes (T2D), who had ≥1 GLD prescriptions, and did not use SGLT2i or GLP1a in the year prior to the index date,1/1/2018. Patients were followed up for a year. The cohort was spatiotemporally linked to Dartmouth hospital-referral regions (HRRs), with each patient assigned to 1 of 306 HRRs. We performed multivariable Poisson regression to estimate adjusted initiation rates, and multivariable logistic regression to assess racial disparities in each HRR. RESULTS: Among 795,469 individuals with T2D included in the analyses, the mean (SD) age was 73 (10) y, 53.3% were women, 12.2% were non-Hispanic Black, and 7.2% initiated a newer GLD in the follow-up year. In the adjusted model including clinical factors, compared to non-Hispanic White patients, non-Hispanic Black (initiation rate ratio, IRR [95% CI]: 0.66 [0.64-0.68]), American Indian/Alaska Native (0.74 [0.66-0.82]), Hispanic (0.85 [0.82-0.87]), and Asian/Pacific islander (0.94 [0.89-0.98]) patients were less likely to initiate newer GLDs. Significant geographic variation was observed across HRRs, with an initiation rate spanning 2.7%-13.6%. CONCLUSIONS: This study uncovered substantial geographic variation and the racial disparities in initiating newer GLDs.


Subject(s)
Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor , Healthcare Disparities , Medicare Part D , Sodium-Glucose Transporter 2 Inhibitors , Aged , Female , Humans , Male , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/ethnology , Glucose , Healthcare Disparities/ethnology , Healthcare Disparities/statistics & numerical data , Hispanic or Latino , Racial Groups/statistics & numerical data , United States , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Middle Aged , Aged, 80 and over , Black or African American , White , Asian American Native Hawaiian and Pacific Islander , American Indian or Alaska Native , Glucagon-Like Peptide-1 Receptor/agonists
2.
Cancer Epidemiol Biomarkers Prev ; 32(12): 1675-1682, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37788369

ABSTRACT

BACKGROUND: Supportive care medication use differences may contribute to racial disparities observed in health-related quality of life in patients with pancreatic cancer. METHODS: In this observation study using the Surveillance, Epidemiology, and End Results-Medicare linked database, we sought to examine supportive care medication use disparities in patients with pancreatic cancer from 2005 to 2017 by race and ethnicity. RESULTS: Among 74,309 patients included in the final analysis, racial and ethnic disparities in the use of supportive care medications were identified. After adjustment for confounding factors and compared with non-Hispanic Whites, minorities had significantly less use of opioids [Black: adjusted OR (aOR), 0.84; 95% confidence interval (CI), 0.79-0.88; Asian: aOR, 0.84; 95% CI, 0.79-0.90), and skeletomuscular relaxants (Black: aOR, 0.90; 95% CI, 0.82-0.99; Hispanic: aOR, 0.82; 95% CI, 0.74-0.91; Asian: aOR, 0.59; 95% CI, 0.51-0.68), and increased use of non-opioid analgesics (Hispanic: aOR, 1.16; 95% CI, 1.01-1.14; Asian: aOR, 1.37; 95% CI, 1.26-1.49). Racial and ethnic minorities had less use of antidepressants (Black: aOR, 0.56; 95% CI, 0.53-0.59; Hispanic: aOR, 0.77; 95% CI, 0.73-0.82; Asian: aOR, 0.47; 95% CI, 0.44-0.51), anxiolytics (Black: aOR, 0.78; 95% CI, 0.74-0.82; Hispanic: aOR, 0.66; 95% CI, 0.62-0.71; Asian: aOR, 0.52; 95% CI, 0.48-0.57), and antipsychotics (Hispanic: aOR, 0.90; 95% CI, 0.82-0.99; Asian: aOR, 0.84; 95% CI, 0.74-0.95). CONCLUSIONS: Racial and ethnic disparities in the use of supportive care medications among patients with pancreatic cancer were observed, with the differences unexplained by sociodemographic factors. IMPACT: Future studies should identify strategies to promote equitable use of supportive care medications among racial minorities and explore factors that may influence their use in these populations.


Subject(s)
Pain Management , Pancreatic Neoplasms , Humans , Aged , United States/epidemiology , Quality of Life , Healthcare Disparities , Medicare , Death , Pancreatic Neoplasms/drug therapy
3.
Article in English | MEDLINE | ID: mdl-37835151

ABSTRACT

Historically, pharmacists in independent community pharmacies have been pivotal in promoting community health. During the COVID-19 pandemic, they demonstrated their commitment by advocating for vaccination and providing accessible care, particularly in underserved communities. By addressing disparities, implementing strategies like mobile clinics and community outreach, and fostering trust and engagement, independent community pharmacists played a crucial role in bridging gaps in healthcare access for vulnerable populations and mitigating the impact of the COVID-19 pandemic.


Subject(s)
COVID-19 , Community Pharmacy Services , Pharmacies , Pharmacy , Humans , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Pandemics/prevention & control , Professional Role , Pharmacists , Vaccination
4.
Cancer Control ; 30: 10732748231197878, 2023.
Article in English | MEDLINE | ID: mdl-37703814

ABSTRACT

INTRODUCTION: The Florida-California Cancer Research, Education, and Engagement (CaRE2) Health Equity Center is a triad partnership committed to increasing institutional capacity for cancer disparity research, the diversity of the cancer workforce, and community empowerment. This article provides an overview of the structure, process innovations, and initial outcomes from the first 4 years of the CaRE2 triad partnership. METHODS: CaRE2 serves diverse populations in Florida and California using a "molecule to the community and back" model. We prioritize research on the complex intersection of biological, environmental, and social determinants health, working together with scientific and health disparities communities, sharing expertise across institutions, bidirectional training, and community outreach. Partnership progress and outcomes were assessed using mixed methods and four Program Steering Committee meetings. RESULTS: Research capacity was increased through development of a Living Repository of 81 cancer model systems from minority patients for novel cancer drug development. CaRE2 funded 15 scientific projects resulting in 38 publications. Workforce diversity entailed supporting 94 cancer trainees (92 URM) and 34 ESIs (32 URM) who coauthored 313 CaRE2-related publications and received 48 grants. Community empowerment was promoted via outreaching to more than 3000 individuals, training 145 community cancer advocates (including 28 Community Scientist Advocates), and publishing 10 community reports. CaRE2 members and trainees together have published 639 articles, received 61 grants, and 57 awards. CONCLUSION: The CaRE2 partnership has achieved its initial aims. Infrastructure for translational cancer research was expanded at one partner institution, and cancer disparities research was expanded at the two cancer centers.


Subject(s)
Health Equity , Neoplasms , Humans , California , Florida , Minority Groups , Neoplasms/therapy
5.
Am J Pharm Educ ; 87(12): 100551, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37336326

ABSTRACT

OBJECTIVE: This study aimed to describe trends in social vulnerability (SV) among pharmacy students at a large public college of pharmacy, and to describe differences in SV by race and ethnicity using the Centers for Disease Control and Prevention Social Vulnerability Index (SVI). METHODS: The SVI was determined for each student admitted between Fall 2017 and Fall 2022 using the submitted permanent address for each student in a deidentified fashion. International students and students not from the 50 US states were excluded from the analysis. RESULTS: During the study period, 1427 pharmacy students met the study inclusion criteria and were included in the final analysis. Students from historically minoritized populations accounted for 53.4% (n = 763/1427) of students. The median SVI score for all students was 0.4091 (interquartile range [IQR]: 0.2091-0.6395), which is consistent with low/moderate SV risk. When considering SVI by race, students from historically minoritized populations had a higher median SVI (0.4807 [IQR: 0.2791-0.7071] vs 0.3562 [IQR: 0.1561-0.5523]), and were more likely to come from moderate/high SV regions compared with White students (odds ratio 2.00 [95% confidence interval: 1.609-2.486]). CONCLUSION: Among pharmacy students at a large public university, a substantial proportion of students had moderate/high SV risk, particularly those from historically minoritized backgrounds. Colleges and schools of pharmacy need to consider the unique needs of students from high SV backgrounds and provide intentional equity-based mitigation strategies to maximize the potential for student success for all.


Subject(s)
Education, Pharmacy , Students, Pharmacy , Humans , Universities , Social Vulnerability , Schools, Pharmacy
6.
Curr Pharm Teach Learn ; 15(4): 329-333, 2023 04.
Article in English | MEDLINE | ID: mdl-37105797

ABSTRACT

INTRODUCTION: There is a long-standing commitment in higher education to provide parallel experiences for students with disabilities, including those with hearing disabilities or impairments. The commitment remains the same in professional pharmacy school education, with the objective to train competent clinical pharmacy practitioners. COMMENTARY: Limited literature exists to provide schools and colleges of pharmacy (S/COP) with best practices when accommodating students who are deaf or hard of hearing (DHOH) in the didactic pharmacy curriculum. The authors will examine practices implemented at the COP to accommodate students with either a DHOH disability. IMPLICATIONS: Students who are DHOH in didactic pharmacy education require individualized assistance to help ensure success throughout the program. A collaborative approach between the student, disability resources, student affairs office, faculty, and staff help ensure accommodations are met and fosters a culture of inclusiveness.


Subject(s)
Hearing Loss , Pharmacy , Humans , Curriculum , Educational Status , Hearing
7.
Ann Pharmacother ; 57(6): 653-661, 2023 06.
Article in English | MEDLINE | ID: mdl-36154486

ABSTRACT

BACKGROUND: Sepsis and septic shock are associated with significant morbidity and mortality. Rapid initiation of appropriate antibiotic therapy is essential, as inadequate therapy early during septic shock has been shown to increase the risk of mortality. However, despite the importance of appropriate antibiotic initiation, in clinical practice, concerns for renal dysfunction frequently lead to antibiotic dose reduction, with scant evidence on the impact of this practice in septic shock patients. OBJECTIVE: The purpose if this article is to investigate the rate and impact of piperacillin-tazobactam dose adjustment in early phase septic shock patients using real-world electronic health record (EHR) data. METHODS: A multicenter, observational, retrospective cohort study was conducted of septic shock patients who received at least 48 hours of piperacillin-tazobactam therapy and concomitant receipt of norepinephrine. Subjects were stratified into 2 groups according to their cumulative 48-hour piperacillin-tazobactam dose: low piperacillin-tazobactam dosing (LOW; <27 g) group and normal piperacillin-tazobactam dosing (NORM; ≥27 g) group. To account for potential confounding variables, propensity score matching was used. The primary study outcome was 28-day norepinephrine-free days (NFD). RESULTS: In all, 1279 patients met study criteria. After propensity score matching (n = 608), the NORM group had more median NFD (23.9 days [interquartile range, IQR: 0-27] vs 13.6 days [IQR: 0-27], P = 0.021). The NORM group also had lower rates of in-hospital mortality/hospice disposition (25.9% [n = 79] vs 35.5% [n = 108]), P = 0.014). Other secondary outcomes were similar between the treatment groups. CONCLUSIONS AND RELEVANCE: In the propensity score-matched cohort, the NORM group had significantly more 28-day NFD. Piperacillin-tazobactam dose reduction in early phase septic shock is associated with worsened clinical outcomes. Clinicians should be vigilant to avoid piperacillin-tazobactam dose reduction in early phase septic shock.


Subject(s)
Piperacillin , Shock, Septic , Humans , Piperacillin/adverse effects , Tazobactam , Shock, Septic/drug therapy , Retrospective Studies , Penicillanic Acid/adverse effects , Anti-Bacterial Agents/therapeutic use , Piperacillin, Tazobactam Drug Combination
8.
Clin Pharmacol Ther ; 113(3): 615-623, 2023 03.
Article in English | MEDLINE | ID: mdl-36306392

ABSTRACT

Black patients suffer worse outcomes after percutaneous coronary intervention (PCI) than White patients. Inequities in antiplatelet prescribing may contribute to this health disparity. We compared P2Y12 inhibitor prescribing by race following CYP2C19 genotyping to guide antiplatelet therapy selection after PCI. Patients from 9 sites that performed clinical CYP2C19 genotyping after PCI were included. Alternative therapy (e.g., prasugrel or ticagrelor) was recommended for CYP2C19 no-function allele carriers, in whom clopidogrel is predicted to be less effective. The primary outcome was choice of P2Y12 inhibitor (clopidogrel vs. alternative therapy) based on genotype. Of 3,342 patients included, 2,448 (73%) were White, and 659 (20%) were Black. More Black than White patients had a no-function allele (34.3% vs. 29.7%, P = 0.024). At hospital discharge following PCI, 44.2% of Black and 44.0% of White no-function allele carriers were prescribed alternative therapy. At the time of the last follow-up within 12 months, numerically fewer Black (51.8%) than White (56.7%) no-function allele carriers were prescribed alternative therapy (P = 0.190). However, the difference was not significant after accounting for other factors associated with P2Y12 inhibitor selection (odds ratio 0.79, 95% confidence interval 0.58-1.08). Alternative therapy use did not differ between Black (14.3%) and White (16.7%) patients without a no-function allele (P = 0.232). Among real-world patients who received CYP2C19 testing after PCI, P2Y12 inhibitor prescribing rates did not differ between Black and White patients. Our data suggest an absence of racial disparity in genotype-guided antiplatelet prescribing among patients receiving CYP2C19 testing.


Subject(s)
Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Humans , Clopidogrel/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Percutaneous Coronary Intervention/adverse effects , Cytochrome P-450 CYP2C19/genetics , Ticagrelor/therapeutic use , Genotype , Cytochrome P-450 CYP2C19 Inhibitors , Purinergic P2Y Receptor Antagonists/adverse effects
9.
J Am Coll Clin Pharm ; 5(12): 1284-1296, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36844700

ABSTRACT

There is surmounting levels of evidence on the health disparities within cancer treatment in the United States (US). Most of the research focused on cancer specific factors including anticancer incidence, screening, treatment and follow-up, and clinical outcomes such as overall survival (OS). Less is known about the disparities present with supportive care medication use in cancer patients. Supportive care utilization during cancer treatment has been linked to improved quality of life (QoL) and OS among patients. The goal of this scoping review is to summarize findings of current literature on the relationship between race and ethnicity and the receipt of supportive care medications during cancer treatment for pain and chemotherapy-induced nausea and vomiting (CINV). This scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA-ScR) guidelines. Our literature search included quantitative studies, qualitative studies, and grey literature written in the English language with clinically relevant outcomes pertaining to pain and CINV management in cancer treatment published from 2001-2021. Articles that met the predefined inclusion criteria were considered for inclusion in the analysis. The initial search yielded 308 studies. Following de-duplication and screening, 14 studies met the predefined inclusion criteria, with majority of the studies being quantitative studies (n=13). Collectively, results were mixed results regarding the presence of racial disparities for supportive care medication use. Half of the studies (n=7) supported this finding whereas, the other half (n=7) did not identify any racial disparities. In our review, multiple studies illustrate the existence of disparities in the use of supportive care medications in some cancer types. Clinical pharmacists should strive to eliminate supportive medication use disparities as part of a multidisciplinary team. In order to develop strategies to prevent supportive care medication use disparities in this population, further research and analysis of external factors that influence them are needed.

11.
Front Neurosci ; 15: 590775, 2021.
Article in English | MEDLINE | ID: mdl-33897340

ABSTRACT

The overarching goal was to resolve a major barrier to real-life prosthesis usability-the rapid degradation of prosthesis control systems, which require frequent recalibrations. Specifically, we sought to develop and test a motor decoder that provides (1) highly accurate, real-time movement response, and (2) unprecedented adaptability to dynamic changes in the amputee's biological state, thereby supporting long-term integrity of control performance with few recalibrations. To achieve that, an adaptive motor decoder was designed to auto-switch between algorithms in real-time. The decoder detects the initial aggregate motoneuron spiking activity from the motor pool, then engages the optimal parameter settings for decoding the motoneuron spiking activity in that particular state. "Clear-box" testing of decoder performance under varied physiological conditions and post-amputation complications was conducted by comparing the movement output of a simulated prosthetic hand as driven by the decoded signal vs. as driven by the actual signal. Pearson's correlation coefficient and Normalized Root Mean Square Error were used to quantify the accuracy of the decoder's output. Our results show that the decoder algorithm extracted the features of the intended movement and drove the simulated prosthetic hand accurately with real-time performance (<10 ms) (Pearson's correlation coefficient >0.98 to >0.99 and Normalized Root Mean Square Error <13-5%). Further, the decoder robustly decoded the spiking activity of multi-speed inputs, inputs generated from reversed motoneuron recruitment, and inputs reflecting substantial biological heterogeneity of motoneuron properties, also in real-time. As the amputee's neuromodulatory state changes throughout the day and the electrical properties and ratio of slower vs. faster motoneurons shift over time post-amputation, the motor decoder presented here adapts to such changes in real-time and is thus expected to greatly enhance and extend the usability of prostheses.

12.
Curr Pharm Teach Learn ; 13(2): 152-158, 2021 02.
Article in English | MEDLINE | ID: mdl-33454072

ABSTRACT

BACKGROUND AND PURPOSE: Team-based learning (TBL) has been successfully applied to multiple healthcare education disciplines. A primary tenet of TBL is the development of solutions leveraging the collective knowledge of a team rather than the individual competency of any one student. In an effort to enhance individual student accountability, an individual verbal defense (IVD) format was implemented in a multi-campus TBL-based pharmacotherapeutics course. The study sought to investigate the use of TBL-IVD embedded within a traditional TBL format on student engagement, teaching style preferences, and exam performance compared to a TBL-only format. EDUCATIONAL ACTIVITY AND SETTING: In this cross-sectional study, second-year pharmacy students enrolled in a pharmacotherapeutics course during fall 2019 completed an 11-item survey. The survey was designed to assess TBL-IVD on student engagement and teaching style preference. Free-response qualitative feedback was solicited to assess positive-negative themes related to the activity. Aggregate exam performance for community-acquired pneumonia (CAP) related content was compared to historical exam data to assess the impact on student performance. FINDINGS: The majority of students (72%, n = 54) preferred the TBL-IVD compared to a TBL-only format. Students reported higher engagement with TBL-IVD (84%, n = 63). Correct exam responses for CAP related content were higher in the TBL-IVD group (67% vs. 55%, P < .001). Positive themes included an increased opportunity to defend recommendations verbally and increased interaction with an on-campus faculty member. SUMMARY: The study demonstrates the addition of IVD can enhance student perceptions, confidence, and performance within a large, multi-campus, TBL-based pharmacotherapeutics course.


Subject(s)
Education, Pharmacy , Students, Pharmacy , Cross-Sectional Studies , Educational Measurement , Humans , Problem-Based Learning
13.
Front Cell Dev Biol ; 9: 803419, 2021.
Article in English | MEDLINE | ID: mdl-35127720

ABSTRACT

Regenerative processes depend on the interpretation of signals to coordinate cell behaviors. The role of ubiquitin-mediated signaling is known to be important in many cellular and biological contexts, but its role in regeneration is not well understood. To investigate how ubiquitylation impacts tissue regeneration in vivo, we are studying planarians that are capable of regenerating after nearly any injury using a population of stem cells. Here we used RNAi to screen RING/U-box E3 ubiquitin ligases that are highly expressed in planarian stem cells and stem cell progeny. RNAi screening identified nine genes with functions in regeneration, including the spliceosomal factor prpf19 and histone modifier rnf2; based on their known roles in developmental processes, we further investigated these two genes. We found that prpf19 was required for animal survival but not for stem cell maintenance, suggesting a role in promoting cell differentiation. Because RNF2 is the catalytic subunit of the Polycomb Repressive Complex 1 (PRC1), we also examined other putative members of this complex (CBX and PHC). We observed a striking phenotype of regional tissue misspecification in cbx and phc RNAi planarians. To identify genes regulated by PRC1, we performed RNA-seq after knocking down rnf2 or phc. Although these proteins are predicted to function in the same complex, we found that the set of genes differentially expressed in rnf2 versus phc RNAi were largely non-overlapping. Using in situ hybridization, we showed that rnf2 regulates gene expression levels within a tissue type, whereas phc is necessary for the spatial restriction of gene expression, findings consistent with their respective in vivo phenotypes. This work not only uncovered roles for RING/U-box E3 ligases in stem cell regulation and regeneration, but also identified differential gene targets for two putative PRC1 factors required for maintaining cell-type-specific gene expression in planarians.

15.
J Neurophysiol ; 123(4): 1380-1391, 2020 04 01.
Article in English | MEDLINE | ID: mdl-32073942

ABSTRACT

Experimental, methodological, and biological variables must be accounted for statistically to maximize accuracy and comparability of published neuroscience data. However, accounting for all variables is nigh impossible. Thus we aimed to identify particularly influential variables within published neurological data, from cat, rat, and mouse studies, via a robust statistical process. Our goal was to develop tools to improve rigor in the collection and analysis of data. We strictly constrained experimental and methodological variables and then assessed four key biological variables within motoneuron research: species, age, sex, and cell type. We quantified intraexperimental and interexperimental variances in 11 commonly reported electrophysiological properties of spinal motoneurons. We first assessed variances without accounting for biological variables and then reassessed them while accounting for all four variables. We next assessed variances with all possible combinations of these four variables. We concluded that some motoneuron properties have low intraexperimental, but high interexperimental, variance; that individual motoneuron properties are impacted differently by biological variables; and that some unexplained variances still remain. We report here the optimal combinations of biological variables to reduce interexperimental variance for all 11 parameters. We also rank each parameter by intra- and interexperimental consistency. We expect these results to assist with design of experimental and analytical methods, and to support accuracy in simulations. Furthermore, although demonstrated on spinal motoneuron electrophysiology literature, our approach is applicable to biological data from all fields of neuroscience. This approach represents an important aid to experimental design, comparison of reported data, and reduction of unexplained variance in neuroscience data.NEW & NOTEWORTHY Our meta-analysis shows the impact of species, age, sex, and cell type on lumbosacral motoneuron electrophysiological properties by thoroughly quantifying variances across literature for the first time. We quantify the variances of 11 motoneuron properties with consideration of biological variables, thus providing specific insights for motoneuron modelers and experimenters, and providing a general methodological template for the quantification of variance in neurological data with the consideration of any experimental, methodological, or biological variables of interest.


Subject(s)
Data Interpretation, Statistical , Electrophysiological Phenomena/physiology , Electrophysiology/methods , Motor Neurons/physiology , Research Design , Spinal Cord/physiology , Animals , Cats , Electrophysiology/standards , Mice , Rats , Research Design/standards , Research Design/statistics & numerical data
16.
Clin Ther ; 41(12): 2594-2610, 2019 12.
Article in English | MEDLINE | ID: mdl-31668356

ABSTRACT

PURPOSE: Angiotensin II (ATII) is a potent endogenous vasoconstrictor that has recently garnered regulatory approval for the treatment of distributive shock, including septic shock. Traditional vasoactive substances used in the management of distributive shock include norepinephrine, epinephrine, phenylephrine, and vasopressin. However, their use can be associated with deleterious adverse drug effects, such as splanchnic vasoconstriction and associated hypoperfusion. The purpose of this review is to describe ATII, including its pharmacologic mechanisms, pharmacokinetic profile, evidence of efficacy and tolerability, and potential role in contemporary critical care practice. METHODS: Peer-reviewed clinical trials and relevant treatment guidelines published from 1966 to September 14, 2019, were identified from Medline/PubMed using the following search terms: angiotensin II OR angiotensin 2 AND shock OR septic shock OR vasodilatory shock. Pertinent review articles were reviewed for additional studies for inclusion and discussion. The final decision on the inclusion of studies in the current review was based on the expert opinion of the authors. FINDINGS: On the basis of the available evidence, ATII is effective at elevating blood pressure in patients with distributive shock and appears to reduce the dose of concurrent vasopressors to maintain adequate blood pressure. ATII has been investigated for other causes of shock; however, robust evidence of off-label indications is lacking and is much needed. Clinical and cost benefits compared with traditional vasopressors have yet to be established. IMPLICATIONS: ATII represents a welcome addition to the armamentarium of critical care clinicians. Enthusiasm for the use of ATII should be balanced with the current gaps in our understanding of ATII in patients with shock. Until further evidence provides more clinically meaningful benefits, as well as cost-effectiveness compared with currently available vasopressors, critical care clinicians should reserve ATII for salvage therapy in patients with septic shock.


Subject(s)
Angiotensin II , Shock/drug therapy , Vasoconstrictor Agents , Critical Care , Humans
17.
Infect Dis Ther ; 8(4): 671-686, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31392580

ABSTRACT

INTRODUCTION: Methicillin-susceptible Staphylococcus aureus (MSSA) is a common cause of infection in humans. Beta-lactam antibiotics are the preferred agents, with anti-staphylococcal penicillins (ASPs) or the first-generation cephalosporin, cefazolin, favored by clinicians. Recent studies comparing the two strategies suggest similar outcomes between the agents. The purpose of this meta-analysis was to explore differences between cefazolin and ASPs for the treatment of MSSA infections. METHODS: We performed a meta-analysis with trial sequential analysis (TSA) of observational or cohort studies using a random-effects model. Two blinded reviewers independently assessed studies for inclusion, risk of bias, and data extraction. The primary outcome was all-cause mortality. Secondary outcomes included clinical failure, infection recurrence, and antibiotic discontinuation due to adverse events. Subgroup analyses were conducted for the primary outcome by type of ASP, studies with a high percentage of deep-seated infections, and studies of low to moderate risk of bias. RESULTS: After performing a comprehensive search of the literature, and screening for study inclusion, 19 studies (13,390 patients) were included in the final meta-analysis. Fifteen of the 19 studies (79%) were judged as having a low or moderate risk of bias. Use of cefazolin was associated with lower all-cause mortality [odds ratio (OR) 0.71, 95% confidence interval (CI) 0.56-0.91, p = 0.006, I2 = 28%], clinical failure (OR 0.55, 95% CI 0.41-0.74, p < 0.001, I2 = 0%), and antibiotic discontinuation due to adverse events (OR 0.25, 95% CI 0.16-0.39, p < 0.001, I2 = 23%). Infection recurrence was higher in the cefazolin patients (OR 1.41, 95% CI 1.04-1.93, p = 0.03, I2 = 0%). CONCLUSION: This meta-analysis demonstrated that the use of cefazolin was associated with significant reductions in all-cause mortality, clinical failure, and discontinuation due to adverse events, but was associated with an increased risk of infection recurrence. FUNDING: University of Florida Open Access Publishing Fund funded the Rapid Service Fees. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews (study ID: CRD42018106442).

18.
Biochem Mol Biol Educ ; 47(5): 547-559, 2019 09.
Article in English | MEDLINE | ID: mdl-31194289

ABSTRACT

Undergraduate research experiences are excellent opportunities to engage students in science alongside experienced scientists, but at large institutions, it is challenging to accommodate all students. To address and engage a larger number of students, we developed a modular laboratory course based on the course-based undergraduate research experiences model. This new course was integrated with the scientific aims of a research laboratory studying the cellular and molecular mechanisms underlying tissue regeneration in planarians. In this course, students were asked to identify genes with roles in planarian biology. Students analyzed and cloned an assigned gene, determined its expression pattern in situ and examined its function in regeneration. Additionally, we developed critical thinking and scientific communication skills by incorporating activities focused on critical concepts. Students obtained high quality primary data and were successful in completing and mastering the course learning outcomes. They benefitted by developing basic research skills, learning to perform, trouble-shooting experiments, reading and critically analyzing primary literature, and using the information to defend and explain their experimental results. Through this course, students also increased their confidence and ability to perform independent scientific research. The course was designed to make it accessible to the community to implement and adapt as appropriate in diverse institutions. © 2019 International Union of Biochemistry and Molecular Biology, 47(5):547-559, 2019.


Subject(s)
Laboratories , Learning , Planarians/genetics , Regeneration/genetics , Animals , Curriculum , Humans , Planarians/physiology , Students
19.
Semin Cell Dev Biol ; 87: 58-68, 2019 03.
Article in English | MEDLINE | ID: mdl-29705300

ABSTRACT

Most mammals cannot easily overcome degenerative disease or traumatic injuries. In contrast, an innate ability to regenerate is observed across animal phyla. Freshwater planarians are amongst the organisms that are capable of stem cell-mediated whole-body regeneration and have served as an exemplary model to study how pluripotency is maintained and regulated in vivo. Here, we review findings on the role of post-translational modifications and the genes regulating phosphorylation, ubiquitylation, and chromatin remodeling in planarian regeneration. Furthermore, we discuss how technological advances for identifying cellular targets of these processes will fill gaps in our knowledge of the signaling mechanisms that underlie regeneration in planarians, which should inform how tissue repair can be stimulated in non-regenerative model organisms and in humans.


Subject(s)
Protein Processing, Post-Translational/genetics , Animals , Planarians , Regeneration
20.
Ann Pharmacother ; 53(4): 385-395, 2019 04.
Article in English | MEDLINE | ID: mdl-30404539

ABSTRACT

OBJECTIVE: Describe recent developments in the pharmacological management of sepsis and septic shock, focusing on fluid resuscitation, vasopressors, and corticosteroids. DATA SOURCES: A literature search limited to randomized controlled trials written in the English language reporting mortality and other clinically relevant outcomes that were published from July 1, 2016, to August 31, 2018, in patients aged ≥ 18 years. Titles and abstracts were reviewed for relevance. References for pertinent review articles were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Relevant randomized controlled trials conducted in patients meeting the pre-defined inclusion criteria were considered for inclusion. DATA SYNTHESIS: From an initial search that identified 147 studies, 14 original research studies met inclusion criteria and were included in this review. Risk of bias (ROB) was assessed using the Revised Cochrane ROB assessment tool, with most included studies having a low ROB. Relevance to Patient Care and Clinical Practice: Sepsis and septic shock pose a significant burden on public health. Despite advances in our understanding of sepsis, mortality remains unacceptably high. Recent developments in the pharmacological management of septic shock have focused on determining optimal composition and dosage of fluid resuscitation, enhanced use of vasopressor therapy, and clarifying the role of corticosteroids. This systematic review will provide recommendations for application to practice focusing on recent research on these topics. CONCLUSIONS: Although recent developments in the pharmacological management of sepsis are encouraging, clinicians must be keen to utilize patient-specific factors to guide therapy and continue to strive to address the remaining unanswered questions.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Fluid Therapy/methods , Sepsis/therapy , Vasoconstrictor Agents/therapeutic use , Adrenal Cortex Hormones/administration & dosage , Humans , Practice Guidelines as Topic , Randomized Controlled Trials as Topic , Sepsis/drug therapy , Shock, Septic/drug therapy , Shock, Septic/therapy , Vasoconstrictor Agents/administration & dosage
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