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Background: This experimental research aimed to determine whether No-ozone Cold Plasma (NCP) has regenerative effect on crushed injured sensory nerves in a rat model (Wistar A) and to evaluate whether NCP can be used as an alternative treatment method for sensory nerve injury in the oral-maxillofacial region. Methods: A total of 10 Wistar A rats were used for this experiment. They were divided into three groups according to whether the mental nerve of the left mandible was injured and NCP was applied or not: group 1 (n=3) (non-mental nerve damage, non-MD) - the left mental nerve was exposed and non-damaged; group 2 (n=3) (mental nerve damage, MD) - the left mental nerve was exposed and damaged, NCP was not applied; and group 3 (n=4) (mental nerve damage and NCP, MD-NCP) - the left mental nerve was exposed and damaged, NCP was applied with regular intervals (three times a week). Results: For the behavior analysis, von Frey test was used. Furthermore, the nerve tissues were examined with hematoxylin and eosin (H&E) staining, and the extent of neurorecovery was evaluated with the immunofluorescence staining of certain markers. The behavioral analysis showed that the function recovery sensory nerve was faster in group 3 (MD-NCP). In the histomorphologic and immunofluorescence analyses, the expression of the factors involved in neurorecovery was much higher in group 3 than in group 2 (MD). Conclusions: The expeditious recovery of sensory nerve function as well as the higher expression of the factors indicating nerve function recovery in the NCP-treated group suggest that NCP has a positive effect on regeneration after sensory nerve crushing injury. Therefore, in the case of sensory impairment of the oral-maxillofacial region, no-ozone cold plasma can be applied for therapeutic effect.
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Lesões por Esmagamento , Traumatismos do Nervo Mandibular , Ozônio , Traumatismos dos Nervos Periféricos , Gases em Plasma , Ratos , Animais , Nervo Isquiático/lesões , Regeneração Nervosa , Gases em Plasma/uso terapêutico , Ozônio/farmacologia , Ozônio/uso terapêutico , Ratos Wistar , Traumatismos dos Nervos Periféricos/tratamento farmacológicoRESUMO
BACKGROUND: Mobocertinib, an EGFR exon 20 insertion (Ex20ins)-specific tyrosine kinase inhibitor has been used for treatment of advanced/metastatic EGFR Ex20ins-mutant non-small cell lung cancer (NSCLC). However, resistance mechanisms to EGFR Ex20ins-specific inhibitors and the efficacy of subsequent amivantamab treatment is unknown. METHODS: To investigate resistance mechanisms, tissue and cfDNA samples were collected before treatment initiation and upon development of resistance from NSCLC patients with EGFR Ex20ins mutations received mobocertinib, poziotinib, and amivantamab treatments. Genetic alterations were analyzed using whole-genome and targeted sequencing, and in vitro resistant cell lines were generated for validation. RESULTS: EGFR amplification (n = 6, including 2 broad copy number gain) and EGFR secondary mutation (n = 3) were observed at the resistance of mobocertinib. One patient had both EGFR secondary mutation and high EGFR focal amplification. In vitro models harboring EGFR alterations were constructed to validate resistance mechanisms and identify overcoming strategies to resistance. Acquired EGFR-dependent alterations were found to mediate resistance to mobocertinib in patients and in vitro models. Furthermore, two of six patients who received sequential amivantamab followed by an EGFR tyrosine kinase inhibitor had MET amplification and showed partial response. CONCLUSIONS: Our study revealed EGFR-dependent and -independent mechanisms of mobocertinib resistance in patients with advanced EGFR Ex20ins-mutant NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Éxons , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Humanos , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Mutação , Mutagênese Insercional , Linhagem Celular TumoralRESUMO
Dozens of frameworks have been proposed to assess evidence for digital health interventions (DHIs), but existing frameworks may not facilitate DHI evidence reviews that meet the needs of stakeholder organizations including payers, health systems, trade organizations, and others. These organizations may benefit from a DHI assessment framework that is both rigorous and rapid. Here we propose a framework to assess Evidence in Digital health for EFfectiveness of INterventions with Evaluative Depth (Evidence DEFINED). Designed for real-world use, the Evidence DEFINED Quick Start Guide may help streamline DHI assessment. A checklist is provided summarizing high-priority evidence considerations in digital health. Evidence-to-recommendation guidelines are proposed, specifying degrees of adoption that may be appropriate for a range of evidence quality levels. Evidence DEFINED differs from prior frameworks in its inclusion of unique elements designed for rigor and speed. Rigor is increased by addressing three gaps in prior frameworks. First, prior frameworks are not adapted adequately to address evidence considerations that are unique to digital health. Second, prior frameworks do not specify evidence quality criteria requiring increased vigilance for DHIs in the current regulatory context. Third, extant frameworks rarely leverage established, robust methodologies that were developed for non-digital interventions. Speed is achieved in the Evidence DEFINED Framework through screening optimization and deprioritization of steps that may have limited value. The primary goals of Evidence DEFINED are to a) facilitate standardized, rapid, rigorous DHI evidence assessment in organizations and b) guide digital health solutions providers who wish to generate evidence that drives DHI adoption.
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The WHO's definition of health transcends the mere absence of disease, emphasizing physical, mental, and social well-being. As this perspective is being increasingly applied to the management of chronic diseases, research on gut microbiota (GM) is surging, with a focus on its potential for persistent and noninvasive dietary therapeutics. In patients with epilepsy (PWE), a chronic lack of seizure control along with often neglected psychiatric comorbidities greatly disrupt the quality of life. Evidence shows that GM-derived short chain fatty acids (SCFAs) may impact seizure susceptibility through modulating (1) excitatory/inhibitory neurotransmitters, (2) oxidative stress and neuroinflammation, and (3) psychosocial stress. These functions are also connected to shared pathologies of epilepsy and its two most common psychiatric consequences: depression and anxiety. As the enhancement of SCFA production is enabled through direct administration, as well as probiotics and prebiotics, related dietary treatments may exert antiseizure effects. This paper explores the potential roles of SCFAs in the context of seizure control and its mental comorbidities, while analyzing existing studies on the effects of pro/prebiotics on epilepsy. Based on currently available data, this study aims to interpret the role of SCFAs in epileptic treatment, extending beyond the absence of seizures to target the health of PWE.
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Epilepsia , Probióticos , Ácidos Graxos Voláteis , Humanos , Neurotransmissores , Prebióticos , Probióticos/uso terapêutico , Qualidade de Vida , ConvulsõesRESUMO
BACKGROUND: The purpose of this study was to measure the time of the conventional surgical planning (CSP) and virtual surgical planning (VSP) in orthognathic surgery and to compare them in terms of cost. MATERIAL AND METHOD: This is a retrospective study of the patients who underwent orthognathic surgery at the OOOOO University Dental Hospital from December 2017 to August 2018. All the patients were analyzed through both CSP and VSP, and all the surgical stents were fabricated through manual and 3-dimensional (3D) printing. The predictor variables were the planning method (CSP vs. VSP) and the surgery type (group I: Le Fort I osteotomy+bilateral sagittal split osteotomy [LFI+BSSO] or group II: only bilateral sagittal split osteotomy [BSSO]), and the outcomes were the time and cost. The results were analyzed using paired t test. RESULTS: Thirty patients (12 females, 18 males) met the inclusion criteria, and 17 patients were excluded from the study due to missing or incomplete data. There were 20 group I patients (LFI+BSSO regardless of genioplasty) and 10 group II patients (BSSO regardless of genioplasty). The average time of CSP for group I was 385±7.8 min, and that for group II was 195±8.33 min. The time reduction rate of VSP compared with CSP was 62.8% in group I and 41.5% in group II. On the other hand, there was no statistically significant cost reduction. CONCLUSIONS: The time investment in VSP in this study was significantly smaller than that in CSP, and the difference was greater in group I than in group II.
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BACKGROUND: Limited comparative data are available on the impact of systemic corticosteroid (SCS) use in children and adolescents. OBJECTIVE: To determine if asthmatic children and adolescents treated with SCS have a higher likelihood of developing complications versus those not receiving SCS and to examine health care resource utilization (HCRU) in this population. METHODS: A retrospective study of data from children and adolescents with persistent asthma retrieved from the MarketScan database, a large US health claims data set, for the period 2000 to 2017 was performed. Propensity score matching was used to pair patients in the SCS and control cohorts. For complications, SCS subgroups (≥4 or 1-3 annual prescriptions) were compared with asthmatic controls without SCS using logistic regression, and for HCRU, cohorts were compared using negative binomial regression. RESULTS: A total of 67,081 patients were included (SCS: 23,898; control: 43,183). The odds of having a complication were 2.9 (95% confidence interval [CI], 2.5-3.2; P < .001) and 1.6 (95% CI, 1.6-1.7; P < .001) times higher in the ≥4 and 1 to 3 SCS groups, respectively, in the first year of follow-up versus controls. For asthma-related hospitalizations, the incidence rate ratio (IRR) was 6.9 (95% CI, 5.6-8.6) and 3.1 (95% CI, 2.8-3.4) times greater in the ≥4 SCS and 1 to 3 SCS groups, respectively, versus controls; for asthma-related emergency department visits, IRR was 5.0 (95% CI, 4.4-5.6) and 2.9 (95% CI, 2.7-3.0) times greater, respectively, versus controls (all P < .01). CONCLUSION: Children and adolescents receiving SCS for persistent asthma have an increased risk of developing complications and have greater HCRU in the first year of follow-up versus those without SCS exposure.
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Asma , Adolescente , Corticosteroides/uso terapêutico , Asma/tratamento farmacológico , Asma/epidemiologia , Criança , Hospitalização , Humanos , Aceitação pelo Paciente de Cuidados de Saúde , Estudos RetrospectivosRESUMO
The EVIDENCE (EValuatIng connecteD sENsor teChnologiEs) checklist was developed by a multidisciplinary group of content experts convened by the Digital Medicine Society, representing the clinical sciences, data management, technology development, and biostatistics. The aim of EVIDENCE is to promote high quality reporting in studies where the primary objective is an evaluation of a digital measurement product or its constituent parts. Here we use the terms digital measurement product and connected sensor technology interchangeably to refer to tools that process data captured by mobile sensors using algorithms to generate measures of behavioral and/or physiological function. EVIDENCE is applicable to 5 types of evaluations: (1) proof of concept; (2) verification, (3) analytical validation, and (4) clinical validation as defined by the V3 framework; and (5) utility and usability assessments. Using EVIDENCE, those preparing, reading, or reviewing studies evaluating digital measurement products will be better equipped to distinguish necessary reporting requirements to drive high-quality research. With broad adoption, the EVIDENCE checklist will serve as a much-needed guide to raise the bar for quality reporting in published literature evaluating digital measurements products.
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Objective: Targeted care management for hospitalized patients with acute decompensated heart failure (ADHF) with reduced or preserved ejection fraction (HFrEF/HFpEF) who are at higher risk for post-discharge mortality may mitigate this outcome. However, identification of the most appropriate population for intervention has been challenging. This study developed predictive models to assess risk of 30 day and 1 year post-discharge all-cause mortality among Medicare patients with HFrEF or HFpEF recently hospitalized with ADHF.Methods: A retrospective study was conducted using the 100% Centers for Medicare Services fee-for-service sample with complementary Part D files. Eligible patients had an ADHF-related hospitalization and ICD-9-CM diagnosis code for systolic or diastolic heart failure between 1 January 2010 and 31 December 2014. Data partitioned into training (60%), validation (20%) and test sets (20%) were used to evaluate the three model approaches: classification and regression tree, full logistic regression, and stepwise logistic regression. Performance across models was assessed by comparing the receiver operating characteristic (ROC), cumulative lift, misclassification rate, the number of input variables and the order of selection/variable importance.Results: In the HFrEF (N = 83,000) and HFpEF (N = 123,644) cohorts, 30 day all-cause mortality rates were 6.6% and 5.5%, respectively, and 1 year all-cause mortality rates were 33.6% and 29.5%. The stepwise logistic regression models performed best across both cohorts, having good discrimination (test set ROC of 0.75 for both 30 day mortality models and 0.74 for both 1 year mortality models) and the lowest number of input variables (18-34 variables).Conclusions: Post-discharge mortality risk models for recently hospitalized Medicare patients with HFrEF or HFpEF were developed and found to have good predictive ability with ROCs of greater than or equal to 0.74 and a reasonable number of input variables. Applying this risk model may help providers and health systems identify hospitalized Medicare patients with HFrEF or HFpEF who may benefit from more targeted care management.
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Insuficiência Cardíaca/mortalidade , Medicare , Medição de Risco , Volume Sistólico/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Masculino , Alta do Paciente , Estudos Retrospectivos , Estados UnidosRESUMO
OBJECTIVE: To investigate the clinical and health care burden of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) in the United States. STUDY DESIGN: Retrospective, cross-sectional design with analyses of patient visits from 2 databases. SETTING: National Ambulatory Medical Care Survey (NAMCS, 2012-2016) and State Ambulatory Surgery and Services Databases (SASD, 2012-2015) in available states. METHODS: In each analysis, we identified patients (≥18 years old) with a diagnosis of CRSwNP (ICD-9-CM: 471.x; ICD-10-CM: J33.x) in the visit record during the study period. CRS patients without polyps (CRSsNP: ICD-9-CM: 473.x, ICD-10-CM: J32.x; without CRSwNP codes) were identified for comparison. In the SASD, we focused on visits involving relevant sinus procedures. Outcomes included comorbidities, diagnostic testing, and prescribed medication (NAMCS) and surgery visit characteristics (SASD). RESULTS: We identified 2272 NAMCS records from physician offices (183 CRSwNP, 2089 CRSsNP). Most visits were for patients aged <65 years (78.8%, 80.6%) and privately insured (67.7%, 61.5%); CRSwNP visits had a male majority (56.3%, 35.4%). CRSwNP vs CRSsNP visits more often reported asthma (40.2%, 10.3%), allergic rhinitis (14.0%, 8.7%), and congestion (22.0%, 21.1%), with the use of glucocorticoids (21.0%, 17.7%) and nasal allergy medication (26.2%, 10.2%). In the SASD, 427,306 surgery visits were identified (71,195 CRSwNP, 356,111 CRSsNP); demographics were similar to NAMCS. CRSwNP surgeries involved more sinus types (59.3%, 41.4%). Surgeries were mostly elective (>99%) and completed quickly (<2 hours), without perioperative complications (>99%), followed by routine discharge (>91%); follow-up visits were common (14.9%, 13.9%). CONCLUSION: CRSwNP compared to CRSsNP patients have a distinct clinical experience, with moderately higher medication need and more extensive surgery.
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AIM: To understand the financial impact of health system adoption of novel heart failure medications under US alternative payment models (APMs). MATERIALS AND METHODS: This study used a decision tree model to assess the financial impact of health system adoption of sacubitril/valsartan to treat acute decompensated heart failure (ADHF). A comparator scenario modeled current health care utilization and cost for treating hospitalized ADHF patients with angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB). The study then measured the impact of adopting sacubitril/valsartan to treat ADHF on health system economic outcomes. Differences in treatment efficacy were based on the PIONEER-HF clinical trial. The financial impact of changes in patient outcomes under the sacubitril/valsartan and ACEi/ARB arms was assessed across three APMs: the Medicare Shared Savings Program, Bundled Payments for Care Improvement, and fee-for-service payments adjusted according to the Hospital Readmission Reduction Program. RESULTS: Sacubitril/valsartan reduced re-hospitalizations after an initial ADHF admission by 46.3% for individuals aged 18-64 years and 23.4% for individuals aged ≥65 years. Health systems' financial benefit of adopting sacubitril/valsartan was $740 per ADHF case per year (PCPY). Savings were larger for patients aged ≥65 years ($803 PCPY) compared to those <65 years ($653 PCPY). The majority of the health system financial benefit came from changes in APM bonus and penalty reimbursements. Value-based payments from the Hospital Readmission Reduction Program ($1,190 financial gain PCPY) and the Bundled Care Payment Improvement Initiative ($645 financial gain PCPY) produced larger financial benefits than participation in the Medicare Shared Savings Program ($253 financial gain PCPY). LIMITATIONS: The model uses clinical trial data, which may not reflect real-world outcomes. Further, the financial implications were modeled based only on three widely used APMs. CONCLUSION: Sacubitril/valsartan adoption decreased hospitalizations and led to a positive net financial impact on health systems after accounting for APM bonus payments.
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Antagonistas de Receptores de Angiotensina , Insuficiência Cardíaca , Idoso , Aminobutiratos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Medicare , Estados Unidos , ValsartanaRESUMO
BACKGROUND: Opioids and sedatives are commonly prescribed in chronic obstructive pulmonary disease (COPD) patients for symptoms of dyspnoea, pain, insomnia, depression and anxiety. Older adults are advised to avoid these medications due to increased adverse events, including respiratory events. This study examines respiratory event risks associated with concomitant opioid and sedative use compared with opioid use alone in older adults with COPD. METHODS: A 5% nationally representative sample of Medicare beneficiaries with COPD and opioid use between 2009 and 2013 was used for this retrospective cohort study. Current and past concomitant use were identified using drug dispensed within 7 days from the censored date: at respiratory event, at death, or at 12 months post index. Concomitant opioid and sedative use were categorised into no overlap (opioid only), 1 to 10, 11 to 30, 31 to 60 and >60 days of total overlap. The primary outcome was hospitalisation or emergency department (ED) visits for respiratory events (COPD exacerbations or respiratory depression). Propensity score matching was implemented and semi-competing risk models were used to address competing risk by death. RESULTS: Among 48 120 eligible beneficiaries, 1810 (16.7%) concomitant users were matched with 9050 (83.3%) opioid only users. Current concomitant use of 1 to 10, 11 to 30 and 31 to 60 days was associated with increased respiratory events (HRs (95% CI): 2.8 (1.2 to 7.3), 9.3 (4.9 to 18.2) and 5.7 (2.5 to 12.5), respectively), compared with opioid only use. Current concomitant use of >60 days or past concomitant use of ≤60 days was not significantly associated with respiratory events. Consistent findings were found in sensitivity analyses, including in subgroup analysis of non-benzodiazepine sedatives. Additionally, current concomitant use significantly increased risk of death. CONCLUSION: Short-term and medium-term current concomitant opioid and sedative use significantly increased risk of respiratory events and death in older COPD Medicare beneficiaries. Long-term past concomitant users, however, demonstrated lower risks of these outcomes, possibly reflecting a healthy user effect or developed tolerance to the effects of these agents.
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Analgésicos Opioides/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Medicare , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/mortalidade , Insuficiência Respiratória/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Serviço Hospitalar de Emergência , Feminino , Hospitalização , Humanos , Masculino , Pontuação de Propensão , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos Retrospectivos , Risco , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: The purpose of this study was to identify the characteristics of supernumerary teeth, analyze the associated complications, and to present new clinical knowledge on surgical interventions for supernumerary teeth. STUDY DESIGN: This retrospective cohort study was based on the medical records and radiographic records of patients who underwent surgical extraction of supernumerary teeth. The relationships among the patient's age, gender, anatomic features of supernumerary teeth, and presence and type of complications (i.e., spacing, rotation, delayed eruption of the adjacent tooth, cyst formation.) were investigated. The groups were compared by using the Mann-Whitney U test, the Kolmogorov-Smirnov test, and multiple logistic regression analysis (P < .05). RESULTS: The study population consisted of 705 participants who underwent extraction for 1036 supernumerary teeth. The mean age of the participants was 11.5 years, and 73.5% of the participants were males. The complication rate was 55.6%. Variables associated with an increased risk of complications were the patient's age, dentition, tuberculate shape, and horizontal direction of eruption (P < .05). CONCLUSIONS: An increase in the patient's age or abnormalities in the shape and direction of eruption of supernumerary teeth was associated with complications. These parameters should be considered while formulating the treatment plan.
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Dente Supranumerário , Criança , Humanos , Masculino , Projetos de Pesquisa , Estudos Retrospectivos , Erupção DentáriaRESUMO
NRAS mutation is rarely observed in non-small cell lung cancer (NSCLC) patients, and there are no approved treatments for NRAS-mutant NSCLC. Here, we evaluated the effect of pan-RAF inhibitors on human NRAS-mutant NSCLC cell lines and performed high-throughput screening using human kinome small interfering (si)RNA or CRISPR/Cas9 libraries to identify new targets for combination NSCLC treatment. Our results indicate that human NRAS-mutant NSCLC cells are moderately sensitive to pan-RAF inhibitors. High-throughput kinome screenings further showed that G2/M arrest, particularly following knockdown of polo-like kinase 1 (PLK1), can inhibit the growth of human NRAS-mutant NSCLC cells and those treated with the type II pan-RAF inhibitor LXH254. In addition, treatment with volasertib plus LXH254, resulting in dual blockade of PLK1 and pan-RAF, was found to be more effective than LXH254 monotherapy for inhibiting long-term cell viability, suggesting that this combination therapeutic strategy may lead to promising results in the clinic.
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Carcinoma Pulmonar de Células não Pequenas/genética , GTP Fosfo-Hidrolases/genética , Neoplasias Pulmonares/genética , Proteínas de Membrana/genética , Mutação , Inibidores de Proteínas Quinases/farmacologia , Pteridinas/farmacologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas de Ciclo Celular/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Ensaios de Triagem em Larga Escala , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Quinase 1 Polo-LikeRESUMO
Importance: There are major gaps in use of guideline-directed medical therapy (GDMT) for patients with heart failure (HF). Patient-reported data outlining patient goals and preferences associated with GDMT are not available. Objective: To survey patients with chronic HF to better understand their experiences and perceptions of living with HF, including their familiarity and concerns with important GDMT therapies. Design, Setting, and Participants: Study participants were recruited from the GfK KnowledgePanel, a probability-sampled online panel representative of the US adult population. English-speaking adults who met the following criteria were eligible if they were (1) previously told by a physician that they had HF; (2) currently taking medications for HF; and (3) had no history of left ventricular assist device or cardiac transplant. Data were collected between October and November 2018. Analysis began in December 2018. Main Outcomes and Measures: The survey included 4 primary domains: (1) relative importance of disease-related goals, (2) challenges associated with living with HF, (3) decision-making process associated with HF medication use, and (4) awareness and concerns about available HF medications. Results: Of 30â¯707 KnowledgePanel members who received the initial survey, 15â¯091 (49.1%) completed the screening questions, 440 were eligible and began the survey, and 429 completed the survey. The median (interquartile range) age was 68 (60-75) years and most were white (320 [74.6%]), male (304 [70.9%]), and had at least a high school education (409 [95.3%]). Most survey responders reported familiarity with ß-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics. Overall, 107 (24.9%) reported familiarity with angiotensin receptor-neprilysin inhibitors or mineralocorticoid receptor antagonists. Overall, 136 patients (42.5%) reported have safety concerns regarding angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and 133 (38.5%) regarding ß-blockers, 35 (37.9%) regarding mineralocorticoid receptor antagonists, 38 (36.5%) regarding angiotensin receptor-neprilysin inhibitors, and 123 (37.2%) regarding diuretics. Between 27.7% (n = 26) and 38.5% (n = 136) reported concerns regarding the effectiveness of ß-blockers, angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, or diuretics, while 41% (n = 132) were concerned with the effectiveness of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Conclusions and Relevance: In this survey study, many patients were not familiar with GDMT for HF, with familiarity lowest for angiotensin receptor-neprilysin inhibitors and mineralocorticoid receptor antagonists. Among patients not familiar with these therapies, significant proportions questioned their effectiveness and/or safety. Enhanced patient education and shared decision-making support may be effective strategies to improve the uptake of GDMT for HF in US clinical practice.
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Tomada de Decisões , Objetivos , Conhecimentos, Atitudes e Prática em Saúde , Insuficiência Cardíaca/terapia , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Diuréticos/uso terapêutico , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Neprilisina/antagonistas & inibidores , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The purpose of this study was to measure the time of the conventional surgical planning (CSP) and virtual surgical planning (VSP) in orthognathic surgery and to compare them in terms of cost. MATERIAL AND METHOD: This is a retrospective study of the patients who underwent orthognathic surgery at the Pusan National University Dental Hospital from December 2017 to August 2018. All the patients were analyzed through both CSP and VSP, and all the surgical stents were fabricated through manual and three-dimensional (3D) printing. The predictor variables were the planning method (CSP vs. VSP) and the surgery type (group I: Le Fort I osteotomy + bilateral sagittal split osteotomy [LFI+BSSO] or group II: only bilateral sagittal split osteotomy [BSSO]), and the outcomes were the time and cost. The results were analyzed using the paired t test. RESULTS: Thirty patients (12 females, 18 males) met the inclusion criteria, and 17 patients were excluded from the study due to missing or incomplete data. There were 20 group I patients (LFI+BSSO regardless of genioplasty) and 10 group II patients (BSSO regardless of genioplasty). The average time of CSP for group I was 385 ± 7.8 min, and that for group II was 195 ± 8.33 min. The time reduction rate of VSP compared with CSP was 62.8% in group I and 41.5% in group II. On the other hand, there was no statistically significant cost reduction. CONCLUSIONS: The time investment in VSP in this study was significantly smaller than that in CSP, and the difference was greater in group I than in group II.
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INTRODUCTION: Pain control is one of the most important aspects of rheumatoid arthritis (RA) management from the patient's perspective. Newer generations of RA treatment including tumor necrosis factor inhibitor (TNFi) have the potential to alleviate pain and thus reduce opioid utilization. However, patterns of opioid utilization before and after TNFi initiation have not been well characterized. This study aims to examine multiple measures of change in opioid utilization after the initiation of TNFi. METHODS: Patients aged ≥ 18 years with RA and 24 months continuous enrollment between January 2007 and December 2015 who newly initiated a TNFi in IQVIA™ Health Plan Claims Data were included in our study. Opioid utilization at baseline and during follow-up were identified and compared. RESULTS: Of 2330 patients with RA that were included in the study, 38.8% of patients used opioids in both baseline and follow-up periods. From pre-index to post-index, the proportion of patients receiving any opioid decreased from 54.0 to 51.0%. In addition, the proportion of those who received ≥ 50 mg median daily MED decreased from 12.6 to 10.6% during pre-post periods. CONCLUSIONS: This real-world study of commercially insured patients with RA suggests that opioid use among these patients is prevalent. There was a small decrease in overall opioid utilization after TNFi initiation.
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BACKGROUND: Real-world analyses of treatments for patients with metastatic breast cancer are limited. We evaluated the comparative effectiveness of nab-paclitaxel vs. paclitaxel in patients with metastatic breast cancer using data from an electronic medical record database from community practices across the USA. METHODS: We performed a retrospective cohort study using fully de-identified data from an independent US electronic medical record platform of patients with metastatic breast cancer initiating single-agent nab-paclitaxel or paclitaxel as a first- or second-line treatment from December 1, 2010 to October 6, 2014. The clinical efficacy objectives were time to treatment discontinuation (TTD) and time to next treatment (TTNT). Subgroup analyses were performed in patients with 2 types of metastatic breast cancer as follows: 1) hormone receptor-positive and human epidermal growth factor receptor 2 negative, and 2) triple-negative disease. RESULTS: This analysis included 925 patients. Patients receiving nab-paclitaxel vs. paclitaxel had significantly longer TTD (median 4.2 vs. 2.8 months, P<0.0001) and TTNT (median 6.0 vs. 4.2 months, P<0.0001); similar outcomes were observed for patients with hormone receptor-positive/human epidermal growth factor receptor 2 negative disease. Compared with paclitaxel, nab-paclitaxel was associated with significantly longer TTD in patients with triple-negative disease. nab-Paclitaxel was associated with significantly less all-grade neuropathy, anemia, pain, and diarrhea than paclitaxel. Antiemetic and antihistamine use were significantly less frequent with nab-paclitaxel vs. paclitaxel, whereas use of granulocyte colony-stimulating factor, hydrating agents, and bone-directed therapy to decrease skeletal-related events were more frequent. CONCLUSION: nab-Paclitaxel demonstrated improved clinical effectiveness compared with paclitaxel when examining TTD and TTNT in patients with metastatic breast cancer in a real-world setting.
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Endotracheal intubation is commonly associated with laryngeal injury that often resolves spontaneously without any complication. However, stenosis or granulomatous lesions are generally found on the tracheal wall or vocal process at the tube cuff level, caused by excessive cuff pressure. We present a case of fatal vocal cord granuloma leading to dyspnea following orthognathic surgery and sustained intubation for 14 hours.
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INTRODUCTION: Despite a clinically relevant, statistically significant survival benefit with nab-paclitaxel plus gemcitabine and FOLFIRINOX vs single-agent gemcitabine for metastatic pancreatic cancer (mPC), little is known regarding their real-world effectiveness. We analyzed patients with mPC using a nationally representative electronic medical records database to address this unmet need. METHODS: This retrospective analysis of the Navigating Cancer database compared outcomes among patients who received first-line nab-paclitaxel plus gemcitabine, FOLFIRINOX, or gemcitabine for mPC. Effectiveness, safety, and supportive care use were examined. nab-Paclitaxel plus gemcitabine was the reference for statistical comparisons. RESULTS: Baseline characteristics were similar except age (oldest patients were in the gemcitabine cohort followed by nab-paclitaxel plus gemcitabine, then FOLFIRINOX). Patients receiving nab-paclitaxel plus gemcitabine (n=122) demonstrated similar time to treatment discontinuation (TTD; median, 3.4 vs 3.8 months; P=0.947) and database persistence (DP; median, 8.6 vs 8.6 months; P=0.534) vs FOLFIRINOX (n=80); however, TTD (median, 3.4 vs 2.2 months; P<0.001) and DP (median, 8.6 vs 5.3 months; P=0.030) were significantly longer with nab-paclitaxel plus gemcitabine vs gemcitabine (n=46). There were more any-grade adverse events with FOLFIRINOX or gemcitabine vs nab-paclitaxel plus gemcitabine (95% or 89% vs 84%, respectively). CONCLUSION: This real-world analysis confirms the phase III MPACT trial findings and demonstrates that nab-paclitaxel plus gemcitabine has effectiveness similar to that of FOLFIRINOX but greater tolerability for treating mPC despite younger patients being in the FOLFIRINOX cohort. These findings support nab-paclitaxel plus gemcitabine as an appropriate first-line treatment option for patients with mPC.
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Cells interact with various nanoscaled topographical and biochemical cues in their cellular macromolecular environment. Nanotopography recreates or mimic the cellular macromolecular environment in vitro. The influence of material surface topography on the behavior of adherent cells has been studied. Current techniques enable various kinds of nanopatterned surface to be generated and applied to cells. The purpose of this review is to provide an overview of nanotopography and its surface patterns, and introduce nanotopography effects on cell behavior including cell attachment, proliferation, and cell differentiation with particular emphasis on musculoskeletal regeneration.