ABSTRACT
Colfax, Louisiana hosts a commercial hazardous waste thermal treatment (TT) facility, which treats fireworks, explosives, and military ordnances by open-burn/open-detonation one mile from the edge of the nearest community. Seventy-one percent of Colfax's residents are Black, and forty-six percent live below poverty, indicating the community's structural vulnerability. This community-based study originated at the behest of Colfax community members. We hypothesized that the close relationships among members of this enclave may have enhanced the community's ability to mobilize in opposition to the TT facility. We conducted semi-structured oral history interviews with nineteen community members and examined the social and interorganizational networks used by the Colfax community to claim its role in decision-making regarding the TT facility after years of exclusion from this process. Interview transcripts were analyzed through the lens of community capacity theory to gain insight into how interactions among community members about the environmental hazards led to social mobilization and improved participation in the decision-making process using codes for communication, organization, and outcome. Additionally, we reviewed Louisiana Department of Environmental Quality records for complaints about the facility to gauge public participation. One notable theme across several interviews was exclusion from the initial decision-making process related to the facility. However, interviewees noted a sustained effort was made among community members to educate themselves about the facility, organize a response through neighbor-to-neighbor contact, and take action by submitting formal complaints and participating in public hearings. Through the lens of environmental justice, this study illustrates an evolving condition of procedural justice.
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BACKGROUND: Little is known about the multi-dimensional nature of traumatic duty-related events encountered by firefighters in relation to their post-traumatic stress disorder (PTSD) risk. AIMS: To describe the types of duty-related events encountered by career firefighters and explore if years in the fire service or total event load moderated the association of trauma exposure to PTSD symptoms. METHODS: Participants included 755 career, male firefighters (19% of the department's firefighters and 76% of those who accessed the electronic anonymous survey). The Duty-Related Incident Stressors scale was used to assess exposure to 25 potentially traumatic events (event load) and self-appraisal of the stress associated with these events, grouped by type of event (indirect, direct and colleague-related). The Post-Traumatic Stress Disorder Checklist was used to assess PTSD symptoms. RESULTS: Firefighters rated colleague-related events as the most stressful, followed by indirect and direct events. Event load (râ =â 0.25) and indirect, direct and colleague-related events stress (râ =â 0.32-0.35) were positively associated with PTSD symptoms. Results of moderation analyses indicated that event load served as a risk factor in the relation of indirect events stress to PTSD symptoms, and as a buffer in the relation of direct events stress to PTSD symptoms. Years in the fire service were not associated with PTSD symptoms nor moderated the relation of event stress to PTSD symptoms. CONCLUSIONS: Findings underscored the importance of considering the differential effects that types of duty-related traumatic events and cumulative exposure to trauma may have on firefighters' PTSD symptoms.
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PURPOSE: To utilize data mining for analysis of corneal transplantations (CT) in Florida from 2005-2014, segmented by demographics, geography, and transplantation technique. METHODS: A retrospective, database study was performed utilizing data queried from the Healthcare and Cost Utilization Project using Current Procedural Terminology codes for lamellar keratoplasty (ALK), endothelial keratoplasty (EK), and penetrating keratoplasty (PKP). Payer status, ethnic group, age, gender, and geography (urban versus rural) was extracted from each surgical encounter and reconfigured to provide a "clean", congruous dataset for statistical analysis. This Institutional Review Board-approved study did not utilize identifiable patient information; thus, individual informed consent was not required. RESULTS: From 2005-2014, CT (n=28,607) represented less than 1% of the total ambulatory surgeries (n=12,695,932) performed in Florida. EK volume increased while PKP and ALK volume decreased, year-over-year. Statistical significance was found between transplantation technique by sex (P<0.001) and ethnic group (P<0.001). The largest sex discrepancy was EK (59% female, 41% male). White patients underwent relatively fewer PKP than EK (71% vs. 83% of totals), while Black patients underwent relatively more PKP than EK (14% vs 6% of totals). Statistical significance was found between techniques by payer (P<0.001). Medicare was the most common payer for all techniques, but ALK and PKP had higher percentages of private insurance and self-pay. No statistical significance was found between techniques by geographic location. Corneal edema (22.4%), endothelial dystrophy (17.5%), and bullous keratopathy (10.9%) were erroneously coded as indications for ALK. Corneal scars (2.5%) and corneal opacity (1.7%) were erroneously coded as indications for EK. CONCLUSIONS: CT rates in Florida appear to overrepresent the female sex and underrepresent ethnic minorities, with propensities between PKP and African Americans, EK and female patients, and EK and Medicare reimbursement. Our study further confirms the utility of data mining for providing efficient, detailed, and practical insights into ophthalmology procedures, while highlighting the intrinsic challenges of large datasets.
Subject(s)
Corneal Diseases , Corneal Transplantation , Aged , Algorithms , Corneal Diseases/epidemiology , Corneal Diseases/surgery , Corneal Transplantation/methods , Data Mining , Female , Humans , Keratoplasty, Penetrating/methods , Male , Medicare , Receptor Protein-Tyrosine Kinases , Retrospective Studies , United StatesABSTRACT
Advances in immunology support the understanding that precise structural epitopes on the antibody-accessible region of the HLA molecule determine antigenicity and challenge the need for identity across the full HLA molecule to minimize graft immunogenicity. Retrospective studies confirm that quantitative measurement of epitope-level mismatching between donor and recipient is an informative marker of graft rejection and survival and suggest that prospective allocation of donor organs based on this principle may improve graft survival. Here we describe the process for rigorous prospective evaluation of this hypothesis in a formal national proof-of-concept program for epitope-based matching. This encompasses broad societal consultation to engage the public, patients and providers; the development of clear allocation policies with strategies to support candidates who may be difficult to match; molecular and sequencing methods and web-based calculators enabling rapid epitope typing and recipient selection; precise immunological monitoring of the graft response; information systems permitting real-time monitoring of clinical outcomes; and assessment of health benefit and economic cost. The results of this objective evaluation can then be provided to payers and policy-makers for review, and adoption if of proven benefit.
Subject(s)
Kidney Transplantation , Epitopes , Graft Rejection/prevention & control , Graft Survival , HLA Antigens/genetics , Histocompatibility Testing/methods , Humans , Precision Medicine , Retrospective StudiesABSTRACT
INTRODUCTION: Ketamine is a vital component for acute pain management in emergency trauma care for both civilian and military hospitals. This preliminary analysis examined whether combat-injured US service members sustaining traumatic brain injuries (TBI) experienced increased odds of ketamine side effects compared with those without TBI. METHODS: This preliminary analysis included combat-injured service members, ages ≥18 years with documented pain scores during the 24 hours before and 48 hours after receiving an intravenous ketamine infusion at Walter Reed National Military Medical Center (WRNMMC) between 2007 and 2014. Logistic regression modeling examined the association between TBI and ketamine side effects (eg, hallucinations, nightmares, dysphoria, nausea, decreased oxygen saturation) during hospitalisation. RESULTS: Of the 77 patients, 62% presented with a documented TBI. Side effects were documented for 18.8% of those without TBI and 24.4% of those with TBI. Analyses were unable to find evidence against the null hypothesis with the current sample size, even when adjusting for injury characteristics and preinfusion opioid doses (adjusted OR=0.90 (95% CI 0.26 to 3.34), p=0.87). CONCLUSION: In this small sample of combat-injured service members, we were unable to detect a difference in ketamine-related side effects by documented TBI status. These hypothesis-generating findings support the need for future studies to examine the use of intravenous ketamine infusions for pain management, and subsequent care outcomes in patients who experience polytraumatic trauma inclusive of TBI.
Subject(s)
Brain Injuries, Traumatic , Ketamine , Military Personnel , Adolescent , Analgesics, Opioid , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/drug therapy , Hospitals, Military , Humans , Ketamine/adverse effects , United StatesABSTRACT
Biological treatments such as enzyme-replacement therapies (ERT) can generate anti-drug antibodies (ADA), which may reduce drug efficacy and impact patient safety and consequently led to research to mitigate ADA responses. Transient low-dose methotrexate (TLD-MTX) as a prophylactic ITI regimen, when administered concurrently with ERT, induces long-lived reduction of ADA to recombinant human alglucosidase alfa (rhGAA) in mice. In current clinical practice, a prophylactic ITI protocol that includes TLD-MTX, rituximab and intravenous immunoglobulin (optional), successfully induced lasting control of ADA to rhGAA in high-risk, cross-reactive immunological material (CRIM)-negative infantile-onset Pompe disease (IOPD) patients. More recently, evaluation of TLD-MTX demonstrated benefit in CRIM-positive IOPD patients. To more clearly understand the mechanism for the effectiveness of TLD-MTX, non-targeted transcriptional and proteomic screens were conducted and revealed up-regulation of erythropoiesis signatures. Confirmatory studies showed transiently larger spleens by weight, increased spleen cellularity and that following an initial reduction of mature red blood cells (RBCs) in the bone marrow and blood, a significant expansion of Ter-119+ CD71+ immature RBCs was observed in spleen and blood of mice. Histology sections revealed increased nucleated cells, including hematopoietic precursors, in the splenic red pulp of these mice. This study demonstrated that TLD-MTX induced a transient reduction of mature RBCs in the blood and immature RBCs in the bone marrow followed by significant enrichment of immature, nucleated RBCs in the spleen and blood during the time of immune tolerance induction, which suggested modulation of erythropoiesis may be associated with the induction of immune tolerance to rhGAA.
Subject(s)
Cell Differentiation/drug effects , Cell Proliferation/drug effects , Erythroblasts/drug effects , Immune Tolerance/drug effects , Methotrexate/administration & dosage , Animals , Cell Differentiation/genetics , Cell Differentiation/immunology , Dose-Response Relationship, Drug , Erythroblasts/cytology , Erythroblasts/metabolism , Erythrocytes/drug effects , Erythrocytes/immunology , Erythrocytes/metabolism , Erythropoiesis/drug effects , Erythropoiesis/genetics , Erythropoiesis/immunology , Female , Gene Expression Profiling/methods , Humans , Immune Tolerance/genetics , Immune Tolerance/immunology , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/immunology , Methotrexate/immunology , Mice, Inbred C57BL , Proteomics/methods , Spleen/drug effects , Spleen/immunology , Spleen/metabolism , alpha-Glucosidases/administration & dosageABSTRACT
Infections of the male and female reproductive system can lead to significant morbidity and mortality. This article will review the relevant embryology and anatomy of the male and female reproductive systems and will discuss the imaging findings of different infections. An understanding of the clinical presentation and imaging findings of infections of the reproductive system is critical in order to allow for prompt and accurate diagnosis. A delay in diagnosis for these infections can have significant morbidity, and occasional mortality.
Subject(s)
Genital Diseases, Female/diagnostic imaging , Genital Diseases, Female/microbiology , Genital Diseases, Male/diagnostic imaging , Genital Diseases, Male/microbiology , Genitalia, Female/anatomy & histology , Genitalia, Male/anatomy & histology , Infections/diagnostic imaging , Infections/microbiology , Diagnosis, Differential , Female , Genitalia, Female/embryology , Genitalia, Male/embryology , Humans , MaleABSTRACT
Acute urinary tract infection diagnosis is primarily performed on clinical grounds. Diagnostic imaging is, however, often necessary as part of the workup for poor response to treatment, to evaluate causative or contributory factors, complicated infections and chronic presentations. Appropriate knowledge of the most relevant radiological findings in urinary tract infections provides pertinent differential diagnosis and guides clinical management, including emergent and aggressive interventions. In this article we review ultrasound and CT imaging findings of acute and chronic urinary tract infections.
Subject(s)
Urinary Tract Infections/diagnostic imaging , Diagnosis, Differential , Humans , Tomography, X-Ray Computed , Ultrasonography , Urinary Tract Infections/microbiologyABSTRACT
BACKGROUND: Little is known regarding the mental health of women firefighters. AIMS: To identify demographic, work-related and mental health characteristics associated with post-traumatic stress disorder (PTSD) symptoms and lifetime suicidal ideation in female firefighters compared with male colleagues. METHODS: Participants were firefighters (75 women and 2564 men) employed in a large urban fire department in the USA. Chi-square, correlations, t-tests and analyses of variance were conducted to examine the predictors of PTSD symptoms and lifetime suicide ideation in men and women. RESULTS: Approximately 20% of women scored positively for PTSD and 30% reported lifetime suicidal ideation. Women with PTSD symptoms were more likely to be in their mid-career years (11-20) than in their first 10 years (87% versus 44%; χ2 = 8.77, P < 0.05) and to have received counselling (53% versus 14%; χ2 = 8.11, P < 0.01). Being single (73% versus 58%; χ2 = 6.02, P < 0.05), having a second job (68% versus 38%; χ2 = 5.79, P < 0.05) and having received counselling (41% versus 11%; χ2 = 8.51, P < 0.01) predicted suicide ideation. Depression and general stress positively predicted PTSD symptoms and suicide ideation. PTSD also predicted suicide ideation. CONCLUSIONS: Compared to male firefighters, women were at high risk for PTSD symptoms and suicide ideation. Particularly for women, few socio-demographic and work-related variables were associated with these outcomes. Mental health variables predicted depression and suicide ideation for both gender groups. Therefore, in screening and intervention efforts, it may be most fruitful to focus on mental health risk correlates of PTSD and suicide ideation.
Subject(s)
Firefighters/psychology , Stress Disorders, Post-Traumatic/psychology , Suicidal Ideation , Adult , Aged , Depression/epidemiology , Female , Humans , Male , Marital Status , Middle Aged , Risk Factors , Sex Factors , Stress Disorders, Post-Traumatic/epidemiology , Surveys and Questionnaires , United States/epidemiologyABSTRACT
BACKGROUND: The Concord Health and Ageing in Men Project (CHAMP) is a cohort study of the health of a representative sample of older Australian men. The aim of this paper is to describe the oral health behaviours and dental service use of CHAMP participants and explore associations between oral health behaviours with and general health status. METHOD: Information collected related to socio-demographics, general health, oral health service-use and oral health behaviours. Key general health conditions were ascertained from the health questionnaire and included physical capacity and cognitive status. RESULTS: Fifty-seven percent of the men reported visiting a dental provider at least once or more a year and 56.7% did so for a "dental check-up". Of those with some natural teeth, 59.3% claimed to brush their teeth at least twice or more a day. Most men (96%) used a standard fluoride toothpaste. Few participants used dental floss, tooth picks or mouth-rinses to supplement oral hygiene. Cognitive status and self-rated general health were associated with dental visiting patterns and toothbrushing behaviour. CONCLUSIONS: Most older men in CHAMP perform favourable oral health behaviours. Smoking behaviour is associated with less favourable dental visiting patterns, and cognitive status with toothbrushing behaviour.
Subject(s)
Health Behavior , Oral Health , Toothbrushing , Aged , Aging , Australia , Cohort Studies , Humans , MaleABSTRACT
BACKGROUND: Human polyomaviruses (HPyVs) are small, nonenveloped, double-stranded DNA viruses that express tumour antigen proteins. Fourteen species of polyomaviruses have been discovered in humans, and since the 2008 discovery of the first cutaneous polyomavirus - Merkel cell polyomavirus (MCPyV) - six more species have been detected in the skin: trichodysplasia spinulosa-associated polyomavirus (TSPyV), HPyV6, HPyV7, HPyV9, HPyV10 and HPyV13. Of these cutaneous species, only MCPyV, TSPyV, HPyV6 and HPyV7 have been definitively associated with diseases of the skin, most commonly in immunocompromised individuals. MCPyV is a predominant aetiology in Merkel cell carcinomas. TSPyV is one of the aetiological factors of trichodysplasia spinulosa. HPyV6 and HPyV7 have been recently linked to pruritic skin eruptions. The roles of HPyV9, HPyV10 and HPyV13 in pathogenesis, if any, are still unknown, but their molecular features have provided some insight into their functional biology. RESULTS: In this review, we summarize the known molecular mechanisms, clinical presentation and targeted therapies of each of the eight cutaneous HPyVs. CONCLUSIONS: We hope that heightened awareness and clinical recognition of HPyVs will lead to increased reports of HPyV-associated diseases and, consequently, a more robust understanding of how to diagnose and treat these conditions.
Subject(s)
Communicable Diseases, Emerging/virology , Polyomavirus Infections/virology , Polyomavirus/physiology , Skin Diseases, Viral/virology , Tumor Virus Infections/virology , Carcinogenesis , Communicable Diseases, Emerging/therapy , Humans , Immunocompromised Host , Polyomavirus/genetics , Polyomavirus Infections/therapy , Skin Diseases, Viral/therapy , Tumor Virus Infections/therapyABSTRACT
BACKGROUND: The aim of this study was to compare the crown preparation dimensions produced from two different techniques of preparation for posterior all-ceramic crowns. METHODS: Twenty-four fourth year dental students undertook a course of advanced simulation training involving education in an alternative technique of preparation for a 36 all-ceramic crown. Crown preparations performed using the traditional technique were compared with an alternative technique for total occlusal convergence (TOC) and reduction difference (RD) using digital scanning and comparative software. RESULTS: Groups that spent the most time performing the alternative technique produced crown preparations with significantly lower buccolingual (BL) TOC. The training resulted in crown preparations that were closer to ideal TOC and RD measurements. CONCLUSIONS: The alternative technique of crown preparation for a posterior all-ceramic crown showed initial promise in creating a less buccolingually tapered and more ideally occlusally reduced crown preparation.
Subject(s)
Clinical Competence , Crowns , Dental Porcelain , Tooth Preparation, Prosthodontic , Computer Simulation , Curriculum , Dental Prosthesis Design , Education, Dental , Humans , Program Evaluation , Students, DentalABSTRACT
A 12-year-old neutered male pug suffered cardiac arrest and died under general anaesthesia during diagnostic imaging for evaluation of exercise intolerance and respiratory crisis. Histopathological evaluation revealed two types of storage material, glycolipid and lipopigment, having differential distributions in multiple organs. The heart was most strikingly affected and other less affected tissues included the liver, brain, kidneys and skin. Cardiomyocytes were swollen with extensive sarcoplasmic vacuolation together with coalescing areas of myocardial fibrosis. Transmission electron microscopy revealed irregular myelin-like structures and complex concentric lamellar bodies dominating the sarcoplasm and displacing myofibrils. These findings were consistent with a lysosomal storage disease (LSD) as the cause of cardiac disease and death. The unique clinical presentation, histomorphology and ultrastructural features of the material suggested a glycolipid storage disease most closely resembling Anderson-Fabry (Fabry) disease in man. Fabry disease is a LSD that can present in later life and is characterized by loss of α-galactosidase A function and, often, accumulation of glycosphingolipids in tissues including the heart, kidneys, vascular endothelium and smooth muscle.
Subject(s)
Cardiomyopathies/veterinary , Fabry Disease/veterinary , Swine Diseases/pathology , Animals , Male , Microscopy, Electron, Transmission , Myocytes, Cardiac/pathology , SwineABSTRACT
STUDY DESIGN: Meta-analysis. OBJECTIVES: Although the association between modifiable psychosocial factors and spinal cord injury (SCI) pain has been identified, the full range of psychological and social difficulties for those who experience acute and/or persistent pain remains unclear. This meta-analysis consolidates the available evidence, using the International Classification of Functioning, Disability and Health (ICF) as a reference framework. METHODS: Nineteen studies that examined persistent neuropathic, nociceptive or mixed pain subtypes in adults with a SCI (newly acquired and chronic; Nparticipants=2934) were identified from electronic database searches. Standardised mean differences between SCI pain and no-pain groups on self-reported psychosocial outcomes were calculated, along with 95% confidence intervals, fail-safe Ns and heterogeneity statistics. RESULTS: Twenty individual outcomes were grouped into nine ICF-related categories. Emotional functions were the most frequent (100%) psychosocial outcomes assessed, with pain contributing to heightened stress (d=-0.85), depression (d=-2.49) anxiety (d range=-0.85 to -1.45), poor self-efficacy (d=-0.77), lowered wellbeing (d range=-0.67 to -1.02) and decreased use of adaptive coping, such as illness acceptance (d=-0.85). Activity limitations and participation restriction were examined by seven studies (43%), although these findings were largely characterised by single studies. CONCLUSIONS: Multicomponent treatments that target mood disturbance and foster community connections are important in SCI pain management. However, to improve the comparability of future studies, SCI pain research must adopt definitions of pain consistent with the International Spinal Cord Injury Pain Classification along with validated outcomes that map onto the ICF framework.
Subject(s)
Pain/etiology , Pain/psychology , Spinal Cord Injuries/complications , Activities of Daily Living , Adaptation, Psychological , Databases, Bibliographic/statistics & numerical data , Humans , Mood Disorders/etiology , Pain/complications , Pain ManagementABSTRACT
Mcl-1 has recently emerged as an attractive target to expand the armamentarium in the war on cancer. Using structure-based design, 3-carboxy-substituted 1,2,3,4-tetrahydroquinolines were developed as a new chemotype to inhibit the Mcl-1 oncoprotein. The most potent compound inhibited Mcl-1 with a Ki of 120 nM, as determined by a fluorescence polarization competition assay. Direct binding was confirmed by 2D (1)H-(15)N HSQC NMR spectroscopy with (15)N-Mcl-1, which indicated that interactions with R263 and T266, and occupation of the p2 pocket are likely responsible for the potent binding affinity. The short and facile synthetic chemistry to access target molecules is expected to mediate lead optimization.
Subject(s)
Drug Design , Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors , Quinolines/chemistry , Quinolines/pharmacology , Molecular Docking Simulation , Myeloid Cell Leukemia Sequence 1 Protein/chemistry , Myeloid Cell Leukemia Sequence 1 Protein/metabolism , Protein Conformation , Quinolines/metabolism , Structure-Activity RelationshipABSTRACT
OBJECTIVE: The goal of this study was to determine the prevalence of asthma in school children in the tri-island Caribbean nation of Grenada. SETTING, PARTICIPANTS AND OUTCOMES: This was a self-report study provided to the guardians of all primary school children between ages 6 and 7 throughout Grenada, Carriacou and Petite Martinique in 2013. Of the 2362 surveys provided, 1374 were returned, resulting in a response rate of 58.2%. Only responders listing birthdays between 1 January 2006 and 31 December 2007 were included in the analysis, resulting in 1165 qualifying responders. Asthma diagnosis was based on previous physician diagnosed asthma and/or self-reported presence of wheeze in the past 12â months (current wheeze). Severity of asthma, medication usage, environmental exposures, physician and emergency department visits were compared among respondents. RESULTS: The prevalence of wheezing in the past year was 30.5±1.8%, and of these 68.4% were previously diagnosed with asthma. Of the current wheeze participants, 39.9±9.2% reported moderate to severe asthma symptoms and increased exposure to cigarette smoke, excessive dust, burning brush and landfills. Carriacou and Petite Martinique, the two smaller islands, had a lower incidence of current wheeze (14.1±7.7%) and exposure rates to cigarette smoke and burning brush as compared to the larger, denser island of Grenada. Although 65.7% of respondents diagnosed with asthma reported taking medication, the number of annual doctor and emergency department visits were high (2.82 and 0.86, respectively). Respondents with the most severe asthma symptoms reported the most emergency department visits with an average of 1.05 visits annually, whereas respondents with moderate asthma symptoms had the most doctor visits with an average of 3.33 visits annually. CONCLUSIONS: This study indicates that the prevalence of childhood asthma in Grenada is very high and warrants policy consideration in public health and education to decrease its morbidity.
Subject(s)
Asthma/epidemiology , Respiratory Sounds/etiology , Ambulatory Care/statistics & numerical data , Asthma/drug therapy , Child , Cross-Sectional Studies , Environmental Exposure , Female , Grenada/epidemiology , Humans , Male , Risk Factors , Self Report , Severity of Illness IndexABSTRACT
Much of the focus in evolutionary biology has been on the adaptive differentiation among organisms. It is equally important to understand the processes that result in similarities of structure among systems. Here, we discuss examples of similarities occurring at different ecological scales, from predator-prey relations (attack rates and handling times) through communities (food-web structures) to ecosystem properties. Selection among systemic configurations or patterns that differ in their intrinsic stability should lead generally to increased representation of relatively stable structures. Such nonadaptive, but selective processes that shape ecological communities offer an enticing mechanism for generating widely observed similarities, and have sparked new interest in stability properties. This nonadaptive systemic selection operates not in opposition to, but in parallel with, adaptive evolution.
Subject(s)
Biological Evolution , Ecological and Environmental Phenomena , Ecosystem , Adaptation, Physiological , Animals , Food Chain , Population Dynamics , Predatory BehaviorABSTRACT
AIM: This was a retrospective cohort study that evaluated the differences in glycated haemoglobin (HbA1c) and body mass index (BMI) in veterans with type 2 diabetes mellitus (T2DM), prescribed exenatide twice daily (BID) versus long-acting insulin analog (LAIA) two years after initiation in the United States (US) veteran population. MATERIALS AND METHODS: Patients were included if they were ≥ 18 years old with T2DM, and initiated exenatide BID or LAIA at the Veterans Health Administration between January 1, 2006 and December 31, 2010. Multivariate models were used to evaluate the changes in HbA1c and BMI between groups, controlling for potential confounders. Logistic regression was used to evaluate the odds of achieving ≥ 0.5% HbA1c reduction based on baseline HbA1c stratifications: low,<7%; moderate, 7% to<9%; and high,≥ 9%. RESULTS: A total of 446 exenatide BID and 51,531 LAIA patients met inclusion/exclusion criteria. On average, exenatide BID patients were significantly older (64 versus 60 years) with a higher BMI (37.8 versus 32.9 kg/m(2)). Baseline HbA1c was 8.2% and 8.8% for exenatide BID and LAIA patients, respectively (P<0.001); otherwise, patients were similar for all other characteristics. Exenatide BID treatment was significantly associated with a 0.32% (95%CI: 0.18-0.47%) greater reduction in HbA1c at two years compared with LAIA. Similar findings were observed for BMI reduction (0.68 kg/m(2); 95%CI: 0.42-0.95 kg/m(2)). Exenatide BID patients with moderate baseline HbA1c had significantly higher odds of achieving ≥ 0.5% HbA1c reduction compared with LAIA patients (OR=1.5; 95%CI: 1.2-2.0). CONCLUSIONS: Veterans treated with exenatide BID had significantly greater reduction in HbA1c and BMI compared with patients treated with LAIA patients two years after initiation.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin, Long-Acting/administration & dosage , Peptides/administration & dosage , Venoms/administration & dosage , Veterans , Aged , Cohort Studies , Diabetes Mellitus, Type 2/blood , Exenatide , Female , Glycated Hemoglobin/metabolism , Humans , Male , Middle Aged , Retrospective Studies , United States , Veterans HealthABSTRACT
WHAT IS KNOWN AND OBJECTIVE: Based on in vitro assays and select animal models, buprenorphine is commonly called a 'partial agonist'. An implication is that it should produce less analgesic effect in humans than so-called 'full agonists' such as morphine or fentanyl. However, buprenorphine has a multimechanistic pharmacology, and thus partial agonism at a specific receptor is not particularly relevant to its overall analgesic action. We review published clinical trials that directly compared the magnitude of buprenorphine's analgesic effect to analgesics commonly considered full agonists. COMMENT: Due to different signal transduction pathways, a drug can be a full agonist on one endpoint and a partial agonist on another. Therefore, we limited the present review to buprenorphine's analgesic effect. WHAT IS NEW AND CONCLUSION: Twenty-four controlled clinical trials were identified, plus a case report and dose-response curve. Based on complete or comparable pain relief, in buprenorphine had full clinical analgesic efficacy in 25 of the 26 studies.