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PURPOSE OF REVIEW: The polypill strategy, originally developed to improve medication adherence, has demonstrated efficacy in improving baseline systolic blood pressures and cholesterol levels in multiple clinical trials. However, the long-term clinical impact of improved major cardiovascular events (MACE) outcomes by the polypill remains uncertain. RECENT FINDINGS: Recent trials with long-term follow-up, which included minority groups and people with low socioeconomic status, have shown non-inferiority with no difference in adverse effects rates for the secondary prevention of MACE. Although the polypill strategy was initially introduced to improve adherence to guideline-directed medical therapy (GDMT) for cardiovascular complications, the strategy has surpassed standard medical treatment for secondary prevention of MACE outcomes. Studies also showed improved medication compliance in underserved populations.
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Doenças Cardiovasculares , Adesão à Medicação , Prevenção Secundária , Humanos , Doenças Cardiovasculares/prevenção & controle , Prevenção Secundária/métodos , Combinação de Medicamentos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Anticolesterolemiantes/uso terapêutico , Anticolesterolemiantes/administração & dosagemRESUMO
Eligible persons with HIV infection can receive client-centered case management to coordinate medical and social services. Novel mobile health interventions could improve effective case management and retention in care, an important goal to help end the HIV epidemic. Using a hybrid type I effectiveness-implementation design, we assessed whether access to bidirectional, free-draft secure text messaging with a case manager and clinic pharmacist could improve client satisfaction and care retention in a Southern academic HIV clinic. Sixty-four clients enrolled between November 2019 and March 2020, had a median age of 39 years, and were mostly male, single, and African-American. Heavy app users texted over 100 times (n = 6) over the course of the 12-month intervention while others never texted (n = 12). App usage peaked during months of clinic closure due to COVID-19. Most participants reported high satisfaction with the app and planned continued usage after study completion. Changes in clinic retention and virologic suppression rates were not observed, a result confounded by practice changes due to COVID-19. High usage and satisfaction of free-draft text messaging in case-managed HIV clients supports inclusion of this communication option in routine HIV clinical care.
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COVID-19 , Telefone Celular , Infecções por HIV , Retenção nos Cuidados , Envio de Mensagens de Texto , Humanos , Masculino , Adulto , Feminino , Infecções por HIV/terapiaRESUMO
Spontaneous coronary artery dissection (SCAD) is a rare clinical entity, often presenting similar to atherosclerotic acute coronary syndrome (ACS), although it is a non-atherosclerotic, non-traumatic, and non-iatrogenic coronary artery pathology. We report the case of a 36-year-old woman who presented with substernal, pressure-like chest pain without aggravating, alleviating, or associated symptoms. Initial evaluation revealed elevated troponin levels which peaked at 8.71 ng/mL. Electrocardiogram showed borderline J point elevation in the lateral leads. A transthoracic echocardiography revealed mild left ventricular dysfunction with an estimated ejection fraction of 45% to 50%, an akinetic apex with hyperdynamic basal segments, suggestive of stress cardiomyopathy. However, a left anterior descending artery (LAD) infarction could not be excluded. Emergent coronary angiography revealed SCAD of the LAD. No coronary interventions were performed. The patient was managed medically with dual antiplatelet therapy and beta-blockers. Given the high suspicion for fibromuscular dysplasia (FMD), computed tomographic angiography (CTA) of the head to pelvis was performed. The CTA neck showed bilateral focal areas of mild stenosis and dilation of the distal cervical internal carotid artery, and CTA abdomen revealed multiple splenic artery aneurysms, diagnostic of FMD. Unlike atherosclerotic ACS, our patient was managed medically without percutaneous intervention. This case illustrates the rare occurrence of myocardial injury due to SCAD which results in spontaneous intramural hematoma formation rather than atherosclerotic plaque rupture typically seen in ACS. FMD remains the most commonly associated condition with SCAD.
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Síndrome Coronariana Aguda , Displasia Fibromuscular , Feminino , Humanos , Adulto , Displasia Fibromuscular/complicações , Displasia Fibromuscular/diagnóstico , Displasia Fibromuscular/epidemiologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Angiografia Coronária , Dor no Peito/etiologiaRESUMO
BACKGROUND: Patterns and disparities in guideline-directed medical therapy (GDMT) uptake for heart failure with reduced ejection fraction (HFrEF) across rural vs urban regions are not well described. OBJECTIVES: This study aims to evaluate patterns, prognostic implications, and rural-urban differences in GDMT use among Medicare beneficiaries following new-onset HFrEF. METHODS: Patients with a diagnosis of new-onset HFrEF in a 5% Medicare sample with available data for Part D medication use were identified from January 2015 through December 2020. The primary exposure was residence in rural vs urban zip codes. Optimal triple GDMT was defined as ≥50% of the target daily dose of beta-blockers, ≥50% of the target daily dose of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker or any dose of sacubitril/valsartan, and any dose of mineralocorticoid receptor antagonist. The association between the achievement of optimal GDMT over time following new-onset HFrEF diagnosis and risk of all-cause mortality and subsequent HF hospitalization was also evaluated using adjusted Cox models. The association between living in rural vs urban location and time to optimal GDMT achievement over a 12-month follow-up was assessed using cumulative incidence curves and adjusted Fine-Gray subdistribution hazard models. RESULTS: A total of 41,296 patients (age: 76.7 years; 15.0% Black; 27.6% rural) were included. Optimal GDMT use over the 12-month follow-up was low, with 22.5% initiated on any dose of triple GDMT and 9.1% on optimal GDMT doses. Optimal GDMT on follow-up was significantly associated with a lower risk of death (HR: 0.89 [95% CI: 0.85-0.94]; P < 0.001) and subsequent HF hospitalization (HR: 0.93 [95% CI: 0.87-0.98]; P = 0.02). Optimal GDMT use at 12 months was significantly lower among patients living in rural (vs urban) areas (8.4% vs 9.3%; P = 0.02). In adjusted analysis, living in rural (vs urban) locations was associated with a significantly lower probability of achieving optimal GDMT (HR: 0.92 [95% CI: 0.86-0.98]; P = 0.01 Differences in optimal GDMT use following HFrEF diagnosis accounted for 16% of excess mortality risk among patients living in rural (vs urban) areas. CONCLUSIONS: Use of optimal GDMT following new-onset HFrEF diagnosis is low, with substantially lower use noted among patients living in rural vs urban locations. Suboptimal GDMT use following new-onset HFrEF was associated with an increased risk of mortality and subsequent HF hospitalization.
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BACKGROUND: Influenza disproportionately affects individuals with underlying comorbidities. Long-term follow-up studies have shown that patients with cancer with influenza have higher mortality. However, very little is known about the in-hospital mortality and cardiovascular outcomes of influenza infection in cancer hospitalisations. METHODS: We compared the in-hospital mortality and cardiovascular outcomes in patients with cancer with and without influenza by screening the National Inpatient Sample from 2015 to 2017. A total of 9 443 421 hospitalisations with any cancer were identified, out of which 14 634 had influenza while 9 252 007 did not. A two-level hierarchical multivariate logistic regression analysis adjusted for age, sex, race, hospital type and relevant comorbidities was performed. RESULTS: The group with cancer and influenza had higher in-hospital mortality (OR 1.08; 95% CI 1.003 to 1.16; p=0.04), acute coronary syndromes (OR 1.74; 95% CI 1.57 to 1.93; p<0.0001), atrial fibrillation (OR 1.24; 95% CI 1.18 to 1.29; p<0.0001) and acute heart failure (OR 1.41; 95% CI 1.32 to 1.51; p<0.0001). CONCLUSION: Patients with cancer affected by influenza have higher in-hospital mortality and a higher prevalence of acute coronary syndrome, atrial fibrillation and acute heart failure.
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Síndrome Coronariana Aguda , Fibrilação Atrial , Insuficiência Cardíaca , Influenza Humana , Neoplasias , Humanos , Influenza Humana/complicações , Influenza Humana/epidemiologia , Pacientes Internados , Fatores de Risco , Neoplasias/complicações , Neoplasias/epidemiologia , Mortalidade HospitalarRESUMO
Background: The use of cannabis has massively increased among younger patients due to increasing legalization and availability. Methods: We performed a retrospective nationwide study using the Nationwide inpatient sample (NIS) database to analyze the trends of acute myocardial infarction (AMI) in young cannabis users and related outcomes among patients aged 18-49 years from 2007 to 2018, using ICD-9 and ICD-10 codes. Results: Out of 819,175 hospitalizations, 230,497 (28%) admissions reported using cannabis. There was a significantly higher number of males (78.08% vs. 71.58%, p < 0.0001) and African Americans (32.22% vs. 14.06%, p < 0.0001) admitted with AMI and reported cannabis use. The incidence of AMI among cannabis users consistently increased from 2.36% in 2007 to 6.55% in 2018. Similarly, the risk of AMI in cannabis users among all races increased, with the biggest increase in African Americans from 5.69% to 12.25%. In addition, the rate of AMI in cannabis users among both sexes showed an upward trend, from 2.63% to 7.17% in males and 1.62%-5.12% in females. Conclusion: The incidence of AMI in young cannabis users has increased in recent years. The risk is higher among males and African Americans.
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Candida empyema is a rare presentation seen in immunocompromised patients, with a high mortality rate if not treated appropriately. We present a rare case of Candida albicans empyema in a patient with gastric cancer undergoing chemotherapy who recently underwent cholecystectomy, successfully treated with fluconazole and drainage. This case not only highlights an unusual presentation of a common pathogen but stresses the fact that when patients with malignancy, present with pleural effusion, candida should be in the differential. Early detection is key in such cases, as outcomes are poor if diagnosis and treatment are delayed.
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PURPOSE OF REVIEW: Atherosclerosis is the largest cause of death in the western world with the role of sex yet to be determined. The purpose of this review is to investigate the role sex may play in the development of atherosclerosis. RECENT FINDINGS: Differences in plaque burden play a role in atherosclerotic outcome. Men have a higher prevalence of plaque burden, while women have less plaque rupture, necrotic core, and calcium. Differences in hormones, vascular anatomy, and overall lifestyle all play a role. Estrogen's cardioprotective effect is well known, but there is a lack of consensus on testosterone's role. There are varying rates of atherosclerosis between the sexes. Studies have also shown varying differences in the progression of plaque and the type of plaques between sexes. Further investigations need to be done to solidify the role sex may play as a variable in the development of atherosclerosis and how that may impact future treatment goals.
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Aterosclerose , Doença da Artéria Coronariana , Placa Aterosclerótica , Masculino , Feminino , Humanos , Doença da Artéria Coronariana/terapia , Fatores de RiscoRESUMO
Herpes zoster (HZ) is a common illness caused by the reactivation of latent varicella zoster virus (VZV) due to waning immunity, often secondary to old age or an underlying immunocompromised state. Its complications can manifest in variety of ways, including persistent neuralgias, vasculopathies, and stroke. Here, we describe a case of a 45-year-old man with a history of cryptogenic stroke and smoldering myeloma who was admitted with sacral HZ complicated by right lumbosacral radiculopathy and myelitis, otherwise known as Elsberg syndrome (ES). He was found to have an enhancing lesion in the peripheral conus medullaris on magnetic resonance imaging (MRI) with nonspecific inflammation and necrosis on biopsy pathology and cerebrospinal fluid (CSF) polymerase chain reaction (PCR) positive for VZV. The patient was initially treated with intravenous acyclovir and dexamethasone and discharged with a steroid taper and indefinite valacyclovir therapy. Twelve months postdischarge, the patient's right lumbosacral radiculopathy and myelitis had almost completely resolved; however, he continued to require bladder self-catheterization. We believe that the patient's underlying smoldering myeloma lead to an immunocompromised state, allowing for reactivation of latent VZV, resulting in both the patient's cryptogenic stroke years earlier and recent ES.
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Herpes Zoster , Mielite , Radiculopatia , Mieloma Múltiplo Latente , Assistência ao Convalescente , Herpes Zoster/complicações , Herpes Zoster/diagnóstico , Herpes Zoster/tratamento farmacológico , Herpesvirus Humano 3 , Humanos , Masculino , Pessoa de Meia-Idade , Mielite/etiologia , Alta do Paciente , Radiculopatia/etiologiaRESUMO
BACKGROUND: Influenza disproportionately affects individuals with underlying comorbidities. Long-term follow-up studies have shown that patients with cancer with influenza have higher mortality. However, very little is known about the in-hospital mortality and cardiovascular outcomes of influenza infection in cancer hospitalisations. METHODS: We compared the in-hospital mortality and cardiovascular outcomes in patients with cancer with and without influenza by screening the National Inpatient Sample from 2015 to 2017. A total of 9 443 421 hospitalisations with any cancer were identified, out of which 14 634 had influenza while 9 252 007 did not. A two-level hierarchical multivariate logistic regression analysis adjusted for age, sex, race, hospital type and relevant comorbidities was performed. RESULTS: The group with cancer and influenza had higher in-hospital mortality (OR 1.08; 95% CI 1.003 to 1.16; p=0.04), acute coronary syndromes (OR 1.74; 95% CI 1.57 to 1.93; p<0.0001), atrial fibrillation (OR 1.24; 95% CI 1.18 to 1.29; p<0.0001) and acute heart failure (OR 1.41; 95% CI 1.32 to 1.51; p<0.0001). CONCLUSION: Patients with cancer affected by influenza have higher in-hospital mortality and a higher prevalence of acute coronary syndrome, atrial fibrillation and acute heart failure.
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In India, bee stings are very common, seen mainly in farmers and honey collectors. Usually, it presents with local reactions and anaphylaxis. It rarely requires urgent hospitalisation. Other major complications seen are acute renal failure, intravascular coagulation, rhabdomyolysis and acute pulmonary oedema. Stroke as a presentation is uncommon. We report a case of a 45-year-old man presenting with right-sided hemiplegia and aphasia due to multiple bee stings. Diffusion MRI showed left middle cerebral artery territory hyperacute infarct.
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Anafilaxia , Venenos de Abelha , Mordeduras e Picadas de Insetos , Acidente Vascular Cerebral , Animais , Abelhas , Imagem de Difusão por Ressonância Magnética , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/etiologia , Mordeduras e Picadas de Insetos/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologiaRESUMO
STUDY DESIGN: This was a retrospective cohort analysis. OBJECTIVE: To identify the impact of Parkinson disease (PD) on 2-year postoperative outcomes following cervical spine surgery (CSS). SUMMARY OF BACKGROUND DATA: (PD) patients are prone to spine malalignment and surgical interventions, yet little is known regarding outcomes of CSS among PD patients. MATERIALS AND METHODS: All patients from the Statewide Planning and Research Cooperative System with cervical radiculopathy or myelopathy who underwent CSS were included; among these, those with PD were identified. PD and non-PD patients (n=64 each) were 1:1 propensity score-matched by age, sex, race, surgical approach, and Deyo-Charlson Comorbidity Index (DCCI). Demographics, hospital-related parameters, and adverse postoperative outcomes were compared between cohorts. Logistic regression identified predictive factors for outcomes. RESULTS: Overall, patient demographics were comparable between cohorts, except that DCCI was higher in PD patients (1.28 vs. 0.67, P=0.028). PD patients had lengthier mean hospital stays than non-PD patients (6.4 vs. 4.1 d, P=0.046). PD patients also incurred comparable total hospital expenses ($69,565 vs. $57,388, P=0.248). Individual medical complication rates were comparable between cohorts; though PD patients had higher rates of postoperative altered mental status (4.7% vs. 0%, P=0.08) and acute renal failure (10.9% vs. 3.1%, P=0.084), these differences were not significant. Yet, PD patients experienced higher rates of overall medical complications (35.9% vs. 18.8%, P=0.029). PD patients had comparable rates of individual and overall surgical complications. The PD cohort underwent higher reoperation rates (15.6% vs. 7.8%, P=0.169) compared with non-PD patients, though this difference was not significant. Of note, PD was not a significant predictor of overall 2-year complications (odds ratio=1.57, P=0.268) or reoperations (odds ratio=2.03, P=0.251). CONCLUSION: Overall medical complication rates were higher in patients with PD, while individual medical complications as well as surgical complication and reoperation rates after elective CSS were similar in patients with and without PD, though PD patients required longer hospital stays. Importantly, a baseline diagnosis of PD was not significantly associated with adverse two-year medical and surgical complications. This data may improve counseling and risk-stratification for PD patients before CSS. LEVEL OF EVIDENCE: Level III.
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Doença de Parkinson , Radiculopatia , Doenças da Medula Espinal , Fusão Vertebral , Vértebras Cervicais/cirurgia , Seguimentos , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/cirurgia , Complicações Pós-Operatórias/etiologia , Radiculopatia/etiologia , Radiculopatia/cirurgia , Estudos Retrospectivos , Doenças da Medula Espinal/cirurgiaRESUMO
BACKGROUND: Patient-provider communication is critical for engaging and retaining people living with HIV in care, especially among medically case-managed patients in need of service coordination and adherence support. Expanding patient-provider communication channels to include mobile health modalities, such as text messaging and video calling, has the potential to facilitate communication and ultimately improve clinical outcomes. However, the implementation of these communication modalities in clinical settings has not been well characterized. OBJECTIVE: The purpose of this study is to understand patient and provider perspectives on the acceptability of and preferences for using text messaging and video calling as a means of communication; perceived factors relevant to adoption, appropriateness, and feasibility; and organizational perspectives on implementation within an HIV clinic in South Carolina. METHODS: We conducted 26 semistructured in-depth interviews among patients receiving case management services (n=12) and clinic providers (n=14) using interview guides and content analysis informed by the Proctor taxonomy of implementation outcomes and the Consolidated Framework for Implementation Research. Participants were purposefully sampled to obtain maximum variation in terms of age and gender for patients and clinic roles for providers. The data were analyzed using quantitative and qualitative content analyses. RESULTS: Most patients (11/12, 92%) and providers (12/14, 86%) agreed that they should have the capacity to text message and/or video call each other. Although consensus was not reached, most preferred using a secure messaging app rather than standard text messaging because of the enhanced security features. Perceived benefits to adoption included the added convenience of text messaging, and potential barriers included the cost and access of smartphone-based technology for patients. From an organizational perspective, some providers were concerned that offering text messaging could lead to unreasonable expectations of instant access and increased workload. CONCLUSIONS: Patients and providers perceived text messaging and video calling as acceptable, appropriate, and feasible and felt that these expanded modes of communication could help meet patients' needs while being safe and not excessively burdensome. Although patients and providers mostly agreed on implementation barriers and facilitators, several differences emerged. Taking both perspectives into account when using implementation frameworks is critical for expanding mobile health-based communication, especially as implementation requires active participation from providers and patients.
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Mice and mouse platelets are major experimental models for hemostasis and thrombosis; however, important physiological data from this model has received little to no quantitative, 3D ultrastructural analysis. We used state-of-the-art, serial block imaging scanning electron microscopy (SBF-SEM, nominal Z-step size was 35 nm) to image resting platelets from C57BL/6 mice. α-Granules were identified morphologically and rendered in 3D space. The quantitative analysis revealed that mouse α-granules typically had a variable, elongated, rod shape, different from the round/ovoid shape of human α-granules. This variation in length was confirmed qualitatively by higher-resolution, focused ion beam (FIB) SEM at a nominal 5 nm Z-step size. The unexpected α-granule shape raises novel questions regarding α-granule biogenesis and dynamics. Does the variation arise at the level of the megakaryocyte and α-granule biogenesis or from differences in α-granule dynamics and organelle fusion/fission events within circulating platelets? Further quantitative analysis revealed that the two major organelles in circulating platelets, α-granules and mitochondria, displayed a stronger linear relationship between organelle number/volume and platelet size, i.e., a scaling in number and volume to platelet size, than found in human platelets suggestive of a tighter mechanistic regulation of their inclusion during platelet biogenesis. In conclusion, the overall spatial arrangement of organelles within mouse platelets was similar to that of resting human platelets, with mouse α-granules clustered closely together with little space for interdigitation of other organelles.
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Plaquetas/ultraestrutura , Imageamento Tridimensional/métodos , Animais , Humanos , CamundongosRESUMO
Topical analgesics and topical rubefacients are widely used to control acute as well as chronic pain every day. Due to their availability without a prescription, consumers often overlook any potentially harmful effects and consider them largely benign. Here, we present a rare case of chemical burn triggered by a typical over-the-counter (OTC) analgesic containing menthol and methyl salicylate resulting in chemical burn, complicated by necrotizing infection treated by below the knee amputation.
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The canalicular system (CS) has been defined as: 1) an inward, invaginated membrane connector that supports entry into and exit from the platelet; 2) a static structure stable during platelet isolation; and 3) the major source of plasma membrane (PM) for surface area expansion during activation. Recent analysis from STEM tomography and serial block face electron microscopy has challenged the relative importance of CS as the route for granule secretion. Here, We used 3D ultrastructural imaging to reexamine the CS in mouse platelets by generating high-resolution 3D reconstructions to test assumptions 2 and 3. Qualitative and quantitative analysis of whole platelet reconstructions, obtained from immediately fixed or washed platelets fixed post-washing, indicated that CS, even in the presence of activation inhibitors, reorganized during platelet isolation to generate a more interconnected network. Further, CS redistribution into the PM at different times, post-activation, appeared to account for only about half the PM expansion seen in thrombin-activated platelets, in vitro, suggesting that CS reorganization is not sufficient to serve as a dominant membrane reservoir for activated platelets. In sum, our analysis highlights the need to revisit past assumptions about the platelet CS to better understand how this membrane system contributes to platelet function.
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Imageamento Tridimensional/métodos , Ativação Plaquetária/fisiologia , Animais , Humanos , CamundongosRESUMO
INTRODUCTION: The current value-driven healthcare system encourages physicians to continuously optimize the value of the services they provide. Relative value units (RVUs) serve as the basis of a reimbursement model linking the concept that as the effort and value of services provided to patient's increases, physician reimbursement should increase proportionately. Spine surgery is particularly affected by these factors as there are multiple ways to achieve similar outcomes, some of which require more time, effort, and risk. Specifically, as the trend of spinal interbody fusion has increased over the past decade, the optimal approach to use-posterior versus anterior lumbar interbody fusion (PLIF vs. ALIF)-has been a source of controversy. Due to potential discrepancies in effort, one factor to consider is the correlation between RVUs and the time needed to perform a procedure. Therefore, the purpose of this study was to compare: 1) mean RVUs; 2) mean operative time; and 3) mean RVUs per unit of time between PLIF and ALIF with the utilization of a national surgical database. We also performed an individual surgeon cost benefit analysis for performing PLIF versus ALIF. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was utilized to identify 6,834 patients who underwent PLIF (CPT code: 22630) and 6,985 patients who underwent ALIF (CPT code: 22558) between 2008 and 2015. The mean operative times (in minutes), mean RVUs, and RVUs per minute were calculated and compared using the Student's t-tests. In addition, the reimbursement amount (in dollars) per minute, case, day, and year for an individual surgeon performing PLIF versus ALIF were also calculated and compared. A p-value of less than 0.05 was used as the threshold for statistical significance. RESULTS: Compared to ALIF cases, PLIF cases had longer mean operative times (203 vs. 212 minutes, p<0.001). However, PLIF cases were assigned lower mean RVUs than ALIF cases (22.08 vs. 23.52, p<0.001). Furthermore, PLIF had a lower mean RVU/minutes than ALIF cases (0.126 vs. 0.154, p<0.001). The reimbursement amounts calculated for PLIF versus ALIF were: $4.52 versus $5.53 per minute, $958.66 versus $1,121.95 per case, and $2,875.98 versus $3,365.86 per day. The annual cost difference was $78,380.92. CONCLUSION: The data from this study indicates a potentially greater annual compensation of nearly $80,000 for performing ALIF as opposed to PLIF due to a higher "hourly rate" for ALIF as is noted by the significantly greater RVU per minute (0.154 vs. 0.126 RVU/minutes). These results can be used by spine surgeons to design more appropriate compensation effective practices while still providing quality care.
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Fusão Vertebral , Custos e Análise de Custo , Humanos , Vértebras Lombares , Duração da Cirurgia , Fusão Vertebral/métodos , Coluna Vertebral/cirurgiaRESUMO
Platelet α-granule cargo release is fundamental to both hemostasis and thrombosis. Granule matrix hydration is a key regulated step in this process, yet its mechanism is poorly understood. In endothelial cells, there is evidence for 2 modes of cargo release: a jack-in-the-box mechanism of hydration-dependent protein phase transitions and an actin-driven granule constriction/extrusion mechanism. The third alternative considered is a prefusion, channel-mediated granule swelling, analogous to the membrane "ballooning" seen in procoagulant platelets. Using thrombin-stimulated platelets from a set of secretion-deficient, soluble N-ethylmaleimide factor attachment protein receptor (SNARE) mutant mice and various ultrastructural approaches, we tested predictions of these mechanisms to distinguish which best explains the α-granule release process. We found that the granule decondensation/hydration required for cargo expulsion was (1) blocked in fusion-protein-deficient platelets; (2) characterized by a fusion-dependent transition in granule size in contrast to a preswollen intermediate; (3) determined spatially with α-granules located close to the plasma membrane (PM) decondensing more readily; (4) propagated from the site of granule fusion; and (5) traced, in 3-dimensional space, to individual granule fusion events at the PM or less commonly at the canalicular system. In sum, the properties of α-granule decondensation/matrix hydration strongly indicate that α-granule cargo expulsion is likely by a jack-in-the-box mechanism rather than by gradual channel-regulated water influx or by a granule-constriction mechanism. These experiments, in providing a structural and mechanistic basis for cargo expulsion, should be informative in understanding the α-granule release reaction in the context of hemostasis and thrombosis.
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Plaquetas/metabolismo , Grânulos Citoplasmáticos/metabolismo , Proteínas SNARE/metabolismo , Animais , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Plaquetas/ultraestrutura , Membrana Celular/metabolismo , Células Endoteliais/metabolismo , Exocitose , Lisossomos/metabolismo , Fusão de Membrana , Camundongos , Microscopia Eletrônica , Proteínas SNARE/genética , Trombina/farmacologia , Corpos de Weibel-Palade/metabolismoRESUMO
BACKGROUND: Since it was introduced as an Olympic sport in 1998, snowboarding has drawn the participation of individuals of all ages. Despite the growing popularity of this sport, individuals can suffer from a number of musculoskeletal injuries. The specific goals of the study were to: (I) compare the number of injuries and trends of snowboarding injuries; (II) identify the injury occurrences, trends, and incidence of snowboarding-related fractures; and (III) identify the injury occurrences and trends of snowboarding-related fractures by body part. METHODS: The National Electronic Injury Surveillance System (NEISS) database was queried for snowboarding injuries and snowboarding-related fractures treated in US emergency departments (EDs) from 2010-2016. The weighted estimate of the number of injuries were obtained by using the NEISS statistical weight calculations that were provided in the data. An estimated total of 248,388 patients (mean age =20 years) experienced a snowboarding-related injury. Linear regression analysis was used to analyze annual trends of snowboarding-related fractures and the snowboarding-related fractures by body part; reported as the correlation coefficient (r) and the coefficient of determination (R2). RESULTS: The estimated annual number of injuries decreased from 56,223 injuries in 2010 to 17,667 injuries in 2016 (r=-0.967, R2=0.936, P<0.001). The most common types of injuries were fractures (31.7%), strains/sprains (25.2%), contusions (10.9%), concussions (10.0%), internal injuries (7.2%), and dislocations (4.0%). From 2010 to 2016, the estimated annual number of fractures decreased from 18,757 in 2010 to 4,539 in 2016 (r=-0.978, R2=0.957, P<0.001), and the annual incidence of snowboarding-related fractures decreased by 23.1%. The most common location of snowboarding-related fractures was the upper extremity, more specifically the wrist (32.3%). There was a decrease in the estimated annual number of fractures of the wrist (r=-0.965, R2=0.932, P<0.001), forearm (r=-0.821, R2=0.861, P=0.023), shoulder (r=-0.872, R2=0.760, P=0.011), elbow (r=-0.901, R2=0.813, P=0.006), and lower leg (r=-0.929, R2=0.864, P=0.002). CONCLUSIONS: With the growing popularity of snowboarding in the US, it is important to know the common types of injuries that occur. This study found that fractures were the most common injuries, especially of the upper extremity.
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Giant plasma membrane vesicles (GPMVs) are isolated directly from living cells and provide an alternative to vesicles constructed of synthetic or purified lipids as an experimental model system for use in a wide range of assays. GPMVs capture much of the compositional protein and lipid complexity of intact cell plasma membranes, are filled with cytoplasm, and are free from contamination with membranes from internal organelles. GPMVs often exhibit a miscibility transition below the growth temperature of their parent cells. GPMVs labeled with a fluorescent protein or lipid analog appear uniform on the micron-scale when imaged above the miscibility transition temperature, and separate into coexisting liquid domains with differing membrane compositions and physical properties below this temperature. The presence of this miscibility transition in isolated GPMVs suggests that a similar phase-like heterogeneity occurs in intact plasma membranes under growth conditions, albeit on smaller length scales. In this context, GPMVs provide a simple and controlled experimental system to explore how drugs and other environmental conditions alter the composition and stability of phase-like domains in intact cell membranes. This chapter describes methods to generate and isolate GPMVs from adherent mammalian cells and to interrogate their miscibility transition temperatures using fluorescence microscopy.