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BACKGROUND AND AIMS: Small-bowel neuroendocrine tumors (NETs) are slow growing, clinically silent tumors whose prognosis depends on disease stage. Members of kindreds with a familial form of small intestinal NETs (SI-NETs) represent a high-risk population for whom early detection improves disease outcome. Our aim was to determine the utility of small-bowel capsule endoscopy (SB-CE) for screening high-risk asymptomatic relatives from kindreds with familial carcinoid. METHODS: One hundred seventy-four asymptomatic subjects with a family history (≥2 family members) of SI-NETs were screened under Protocol NCT00646022, Natural History of Familial Carcinoid Tumor at the National Institutes of Health. All patients were imaged with SB-CE and 18fluoro-dihydroxphenylalanine (18F-DOPA) positron emission tomography (PET)/CT, and results were independently analyzed. Patients with a positive imaging study underwent surgical exploration. RESULTS: Thirty-five of 174 asymptomatic subjects screened for SI-NETs were positive on either SB-CE or 18F-DOPA PET. Thirty-two of 35 patients with a positive study were confirmed at surgery. SB-CE was positive in 28 of 32 patients with confirmed tumors for a per-patient sensitivity of 87.5%. SB-CE had a specificity of 97.3% and a negative predictive value of 96.5%. The average tumor number and size were 7.7 and 5.0 mm, respectively, and 81.2% of patients had multiple tumors. 18F-DOPA PET/CT had a similar sensitivity of 84% versus surgery. CONCLUSIONS: SB-CE is a sensitive and specific method comparable with 18F-DOPA PET/CT for screening high-risk patients with familial SI-NET. (Clinical trial registration number: NCT00646022.).
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Endoscopía Capsular , Tumor Carcinoide , Dihidroxifenilalanina/análogos & derivados , Tumores Neuroendocrinos , Humanos , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Tumor Carcinoide/diagnóstico por imagenRESUMEN
Lumbar interbody fusion procedures have seen a significant evolution over the years, with various approaches being developed to address spinal pathologies and instability, including posterior lumbar interbody fusion (PLIF), transforaminal lumbar interbody fusion (TLIF), anterior lumbar interbody fusion (ALIF), and lateral lumbar interbody fusion (LLIF). LLIF, a pivotal technique in the field, initially emerged as extreme/direct lateral interbody fusion (XLIF/DLIF) before the development of oblique lumbar interbody fusion (OLIF). To ensure comprehensive circumferential stability, LLIF procedures are often combined with posterior stabilization (PS) using pedicle screws. However, achieving this required repositioning of the patient during the surgical procedure. The advent of single-position surgery (SPS) has revolutionized the procedure by eliminating the need for patient repositioning. With SPS, LLIF along with PS can be performed either in the lateral or prone position, resulting in significantly reduced operative time. Ongoing research endeavors are dedicated to further enhancing LLIF procedures making them even safer and easier. Notably, the integration of robotic technology into SPS has emerged as a game-changer, simplifying surgical processes and positioning itself as a vital asset for the future of spinal fusion surgery. This literature review aims to provide a succinct summary of the evolutionary trajectory of lumbar interbody fusion techniques, with a specific emphasis on its recent advancements.
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Tornillos Pediculares , Fusión Vertebral , Humanos , Vértebras Lumbares/cirugía , Fusión Vertebral/métodos , Región Lumbosacra , Estudios RetrospectivosRESUMEN
Red blood cell transfusion independence (RBC-TI) is an important goal in treating lower-risk myelodysplastic syndromes with ring sideroblasts. In the phase 3 MEDALIST study, RBC-TI of ≥ 8 weeks was achieved by significantly more luspatercept- versus placebo-treated patients in the first 24 weeks of treatment. In this post hoc analysis, we evaluated RBC transfusion units and visits based on patients' baseline transfusion burden level and the clinical benefit of luspatercept treatment beyond week 25 in initial luspatercept nonresponders (patients who did not achieve RBC-TI ≥ 8 weeks by week 25) but continued luspatercept up to 144 weeks. RBC transfusion burden, erythroid response, serum ferritin levels, and hemoglobin levels relative to baseline were evaluated. Through week 25, fewer RBC transfusion units and visits were observed in luspatercept-treated patients versus placebo, regardless of baseline transfusion burden. This continued through 144 weeks of luspatercept treatment, particularly in patients with low baseline transfusion burden. Sixty-eight patients were initial nonresponders at week 25 but continued treatment; most (81%) received the maximum dose of luspatercept (1.75 mg/kg). Sixteen percent achieved RBC-TI for ≥ 8 weeks during weeks 25-48, 26% had reduced RBC transfusion burden, 10% achieved an erythroid response, 44% had reduced serum ferritin, and hemoglobin levels increased an average of 1.3 g/dL from baseline. These data have implications for clinical practice, as transfusion units and visits are less in luspatercept-treated patients through week 25 regardless of baseline transfusion burden, and continuing luspatercept beyond week 25 can potentially provide additional clinical benefits for initial nonresponders. Trial registration: NCT02631070.
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Síndromes Mielodisplásicos , Humanos , Ferritinas , Hemoglobinas/análisis , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Síndromes Mielodisplásicos/tratamiento farmacológicoRESUMEN
BACKGROUND: Patients with transfusion-dependent (TD) ß-thalassemia require long-term red blood cell transfusions (RBCTs) that lead to iron overload, impacting health-related quality of life (HRQoL). METHODS: The impact of luspatercept, a first-in-class erythroid maturation agent, versus placebo on HRQoL of patients with TD ß-thalassemia was evaluated in the phase 3 BELIEVE trial. HRQoL was assessed at baseline and every 12 weeks using the 36-item Short Form Health Survey (SF-36) and Transfusion-dependent Quality of Life questionnaire (TranQol). Mean change in HRQoL was evaluated from baseline to week 48 for patients receiving luspatercept + best supportive care (BSC) and placebo + BSC and between luspatercept responders and non-responders. RESULTS: Through week 48, for both groups, mean scores on SF-36 and TranQol domains were stable over time and did not have a clinically meaningful change. At week 48, more patients who achieved clinical response (≥50% reduction in RBCT burden over 24 weeks) in the luspatercept + BSC group had improvement in SF-36 Physical Function compared with placebo + BSC (27.1% vs. 11.5%; p = .019). CONCLUSIONS: Luspatercept + BSC reduced transfusion burden while maintaining patients' HRQoL. HRQoL domain improvements from baseline through 48 weeks were also enhanced for luspatercept responders.
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Talasemia beta , Humanos , Receptores de Activinas Tipo II/uso terapéutico , Talasemia beta/tratamiento farmacológico , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Calidad de VidaRESUMEN
Aim: To assess real-world ruxolitinib treatment patterns and outcomes in patients diagnosed with primary or secondary myelofibrosis. Materials & methods: Patient medical records were reviewed in six countries. Results: Eligible patients (n = 469) had a mean age of 63.5 years, and most were male (66.5%) with primary myelofibrosis (78.5%). Median duration of ruxolitinib treatment was 13.1 months; 40% of patients initiated treatment at the recommended dose. The Kaplan-Meier estimate of median survival from ruxolitinib initiation was 44.4 months (95% CI, 38.8-50.2 months). Approximately one quarter (23%) of patients continued ruxolitinib after progression. Conclusion: These results suggest an unmet need for more effective treatments for patients with myelofibrosis who failed ruxolitinib.
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Mielofibrosis Primaria , Femenino , Humanos , Masculino , Registros Médicos , Persona de Mediana Edad , Nitrilos/uso terapéutico , Mielofibrosis Primaria/tratamiento farmacológico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Resultado del TratamientoRESUMEN
Unlocking the potential of personalized medicine in point-of-care settings requires a new generation of biomarker and proteomic assays. Ideally, assays could inexpensively perform hundreds of quantitative protein measurements in parallel at the bedsides of patients. This goal greatly exceeds current capabilities. Furthermore, biomarker assays are often challenging to translate from benchtop to clinic due to difficulties achieving and assessing the necessary selectivity, sensitivity, and reproducibility. To address these challenges, we developed an efficient (<5â min), robust (comparatively lower CVs), and inexpensive (decreasing reagent use and cost by >70 %) immunoassay method. Specifically, the immunoblot membrane is dotted with the sample and then developed in a vortex fluidic device (VFD) reactor. All assay steps-blocking, binding, and washing-leverage the unique thin-film microfluidics of the VFD. The approach can accelerate direct, indirect, and sandwich immunoblot assays. The applications demonstrated include assays relevant to both the laboratory and the clinic.
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Microfluídica , Proteómica , Aceleración , Humanos , Inmunoensayo , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: This study utilized a population-based claims database to identify patients with beta-thalassemia and evaluate associations between transfusion burden, healthcare resource utilization (HCRU), and complications. STUDY DESIGN AND METHODS: Taiwan's National Health Insurance Research Database was used to identify patients with beta-thalassemia (ICD-10 D56.1) in 2016. Patients with a beta-thalassemia claim in 2016 were indexed into the study at their first claim on or after January 1, 2001 in the dataset through to December 31, 2016 and followed until the end of study. During the follow-up period, red blood cell transfusion (RBCT) units, HCRU, iron chelation therapy use, and beta-thalassemia-related complications incidence were recorded. Patients were grouped into transfusion burden severity cohorts based on average number of RBCT units per 12 weeks during follow-up: 0 RBCT units, >0 to <6 RBCT units (mild), ≥6 to <12 RBCT units (moderate), and ≥12 RBCT units (severe). RESULTS: A total of 2984 patients were included with mean follow-up of 6.95 years. Of these, 1616 (54.2%) patients had no claims for RBCT units, 1112 (37.3%) had claims for >0 to <6 RBCT units, 112 (3.8%) for ≥6 to <12 RBCT units, and 144 (4.8%) for ≥12 RBCT units per 12 weeks. Transfused patients had significantly more all-cause HCRU and iron chelation therapy compared with non-transfused patients during follow-up. Thalassemia-related HCRU and risk of liver, endocrine, cardiac, and renal complications were significantly and positively correlated with increases of RBCT units. DISCUSSION: Clinical and healthcare resource burden of patients with beta-thalassemia is closely related to transfusion burden.
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Transfusión Sanguínea , Talasemia beta/terapia , Adulto , Transfusión de Eritrocitos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud , Estudios Retrospectivos , Taiwán/epidemiología , Adulto Joven , Talasemia beta/epidemiologíaRESUMEN
Myelodysplastic syndromes (MDS) are a group of malignant hematologic diseases characterized by ineffective hematopoiesis, which may lead to chronic anemia and transfusion dependency, with up to 30% of patients progressing to acute myeloid leukemia (AML). Studies suggest transfusion dependency may impact overall survival (OS); however, there is a lack of evidence concerning the association between transfusion status (TS) and OS in patients with MDS who become transfusion independent (TI) after treatment. In addition, the holistic impact of TS on other clinical, economic, and humanistic outcomes has not been well understood. We conducted a systematic literature review (SLR) to understand this impact. Ten studies were included and showed consistent decrease in OS in transfusion dependent (TD) compared with TI patients. These findings were confirmed by a meta-analysis (MA) reporting better OS prognosis for TI patients. A second SLR was conducted to understand the association between TS and other clinical, economic, and humanistic outcomes. Twenty-eight studies were included and showed better prognosis for other outcomes, including AML progression and leukemia-free survival for TI patients. Risk of AML progression and cumulative non-leukemic death assessed by the MA showed a trend toward worse prognosis and higher risk of AML progression for TD patients. Lower healthcare resource utilization, better quality of life, and reduced non-leukemic death for TI patients were observed. Studies not eligible for MA also showed better clinical, economic, and humanistic outcomes for TI patients. These findings contribute to understanding the association between transfusion dependence and OS among other outcomes in patients with MDS.
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Transfusión de Eritrocitos/métodos , Eritrocitos/citología , Leucemia Mieloide Aguda/complicaciones , Síndromes Mielodisplásicos/terapia , Anemia/complicaciones , Teorema de Bayes , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Método de Montecarlo , Síndromes Mielodisplásicos/complicaciones , Fenotipo , Pronóstico , Calidad de Vida , Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of this study is to evaluate the content validity of the National Comprehensive Cancer Network - Functional Assessment of Cancer Therapy - Breast Cancer Symptom Index (NFBSI-16) and the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 10b among patients with hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. METHODS: Cognitive debriefing interviews sought to evaluate patients' ability to read, understand, and meaningfully respond to the questionnaires, as well as to evaluate the questionnaires' relevance in the target patient population. Interviews were conducted by telephone and lasted approximately 90 min. Audio recordings were transcribed, anonymized, and analyzed using qualitative data analysis software. RESULTS: Fifteen cognitive debriefing interviews were conducted with women (mean age 66.0 years [standard deviation = 12.4]). Patients reported metastases in the bone (86.7%), liver (20.0%), lung (13.3%), skin (6.7%), and lymph node (6.7%) (not mutually exclusive). All patients for whom data were available demonstrated understanding of the instructions and the recall period of the NFBSI-16 (n = 14/14, 100.0%) and the PROMIS (n = 14/14, 100.0%). Greater than 90% of patients demonstrated understanding of each of the items in the NFBSI-16 and the PROMIS. Greater than 70% of patients demonstrated understanding of the response options of the NFBSI-16, > 90% understood response options of PROMIS Items 1-6, and ≥ 50% understood response options of PROMIS Items 7-10. Conceptual relevance was supported for most items in both questionnaires based on patients' reports of experiencing the concepts as part of their breast cancer experience. CONCLUSIONS: The results of the cognitive debriefing interviews provide evidence that the NFBSI-16 and PROMIS Physical Function Short Form 10b have content validity in the HR+/HER2- advanced breast cancer patient population. Patients may benefit from additional instructions at the point the response options reverse direction in the PROMIS.
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Neoplasias de la Mama/psicología , Medición de Resultados Informados por el Paciente , Calidad de Vida , Actividades Cotidianas/psicología , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/terapia , Femenino , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND & AIMS: Small intestinal neuroendocrine tumors (SI-NETs) are serotonin-secreting well-differentiated neuroendocrine tumors believed to originate from enterochromaffin (EC) cells. Intestinal stem cell (ISC) are believed to contribute to the formation of SI-NETs, although little is known about tumor formation or development. We investigated the relationship between EC cells, ISCs, and SI-NETs. METHODS: We analyzed jejuno-ileal tissue specimens from 14 patients with familial SI-NETs enrolled in the Natural History of Familial Carcinoid Tumor study at the National Institutes of Health from January 2009 to December 2014. Frozen and paraffin-embedded tumor tissues of different stages and isolated crypts were analyzed by in situ hybridization and immunohistochemistry. Tumor clonality was assessed by analyses of mitochondrial DNA. RESULTS: We identified multifocal aberrant crypt-containing endocrine cell clusters (ACECs) that contain crypt EC cell microtumors in patients with familial SI-NETs. RNA in situ hybridization revealed expression of the EC cell and reserve stem cell genes TPH1, BMI1, HOPX, and LGR5(low), in the ACECs and more advanced extraepithelial tumor nests. This expression pattern resembled that of reserve EC cells that express reserve ISC genes; most reside at the +4 position in normal crypts. The presence of multifocal ACECs from separate tumors and in the macroscopic tumor-free mucosa indicated widespread, independent, multifocal tumorigenesis. Analyses of mitochondrial DNA confirmed the independent origin of the ACECs. CONCLUSIONS: Familial SI-NETs originate from a subset of EC cells (reserve EC cells that express reserve ISC genes) via multifocal and polyclonal processes. Increasing our understanding of the role of these reserve EC cells in the genesis of multifocal SI-NETs could improve diagnostic and therapeutic strategies for this otherwise intractable disease.
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Carcinogénesis/genética , Neoplasias del Íleon/genética , Neoplasias del Yeyuno/genética , Familia de Multigenes/genética , Tumores Neuroendocrinos/genética , Células Enterocromafines/metabolismo , Proteínas de Homeodominio/genética , Humanos , Hibridación in Situ , Intestino Delgado/citología , Complejo Represivo Polycomb 1/genética , Receptores Acoplados a Proteínas G/genética , Células Madre/metabolismo , Triptófano Hidroxilasa/genética , Proteínas Supresoras de Tumor/genéticaRESUMEN
PURPOSE OF REVIEW: Helicobacter pylori (HP) infection is known to be a significant risk factor in the development of certain gastric conditions, such as ulcers, gastritis, and malignancy. Recently, however, the systemic effect of HP infection on other organ systems has come to be appreciated. In this review, we will explore the association between HP infection and nonalcoholic fatty liver disease (NAFLD), the hepatic component of metabolic syndrome. RECENT FINDINGS: The possible association between HP infection and NAFLD initially stemmed from the isolation of HP bacteria in the livers of patients with NAFLD. Although there have been conflicting results, several subsequent clinical trials have demonstrated a higher rate of fatty liver and NASH in HP-positive patients compared to HP-negative patients; in addition, small trials examining the effect of HP eradication have shown improvement in markers of NAFLD activity, further supporting a link between these two conditions. The pathophysiology behind the possible association between HP infection and NAFLD has yet to be fully elucidated; several possible mechanisms include induction of a pro-inflammatory state that shifts the body toward a more lipogenic profile, and a hormonal shift that favors progression toward insulin resistance and fibrosis. The association between HP infection and NAFLD has been demonstrated in several clinical trials, including small trials evaluating the effect of HP eradication on NAFLD. Future studies examining the pathophysiology behind this association are the next step in characterizing the relationship between these two conditions.
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Infecciones por Helicobacter/complicaciones , Helicobacter pylori/aislamiento & purificación , Enfermedad del Hígado Graso no Alcohólico/microbiología , Infecciones por Helicobacter/fisiopatología , Humanos , Enfermedad del Hígado Graso no Alcohólico/fisiopatologíaAsunto(s)
Migración de Cuerpo Extraño/etiología , Balón Gástrico , Enfermedades del Íleon/etiología , Válvula Ileocecal , Obstrucción Intestinal/etiología , Femenino , Migración de Cuerpo Extraño/diagnóstico por imagen , Migración de Cuerpo Extraño/terapia , Humanos , Enfermedades del Íleon/diagnóstico por imagen , Enfermedades del Íleon/terapia , Válvula Ileocecal/diagnóstico por imagen , Obstrucción Intestinal/diagnóstico por imagen , Obstrucción Intestinal/terapia , Tomografía Computarizada por Rayos XAsunto(s)
Enfermedades del Colon/diagnóstico , Endometriosis/complicaciones , Hemorragia Gastrointestinal/diagnóstico , Adulto , Biopsia , Colectomía , Enfermedades del Colon/etiología , Enfermedades del Colon/cirugía , Colonoscopía , Diagnóstico Diferencial , Endometriosis/diagnóstico , Femenino , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/cirugía , Humanos , Laparotomía/métodosRESUMEN
OBJECTIVE: To evaluate the impact of urinary incontinence (UI) on healthcare resource utilization (HRU), health-related quality of life (HRQoL) and productivity measures in patients with overactive bladder (OAB). PATIENTS AND METHODS: This retrospective, cross-sectional study used data from the Adelphi OAB/UI Disease Specific Programme, a multinational survey of patient- and physician-reported data, fielded between November 2010 and February 2011. The primary patient groups of interest were those with OAB, both with and without UI. Health-related quality of life and productivity measures were derived from the EuroQoL-5D, the Incontinence Quality of Life questionnaire, the Overactive Bladder Questionnaire, and the Work Productivity and Activity Impairment Questionnaire. Measures of HRU included OAB-related surgeries, OAB-related hospitalizations, incontinence pads, anticholinergic use and physician visits. Multivariate linear regression models and literature-based minimal clinically important differences were used to assess statistically significant and clinically meaningful differences in HRQoL and productivity measures between patients with OAB with UI and those without UI. RESULTS: A total of 1 730 patients were identified, with a mean age of 60.7 years, and 77.0% of them were women, 84.2% were non-Hispanic whites, and 71% were incontinent. Bivariate analyses showed that HRU was significantly higher among patients with OAB with UI than among those without UI in all categories except for the number of OAB-related physician visits. In both bivariate and multivariate analyses, incontinent patients presented with clinically and statistically significantly lower HRQoL and productivity measures with respect to all study endpoints, except for percentage of work time missed due to their OAB/UI. CONCLUSIONS: Urinary incontinence was associated with significantly higher HRU and lower HRQoL and productivity in this population of patients with OAB from five different countries. In addition to clinical considerations, the economic and humanistic impact of UI should be taken into account when evaluating treatment options for patients with OAB.
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Eficiencia , Recursos en Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos , Calidad de Vida , Vejiga Urinaria Hiperactiva/terapia , Incontinencia Urinaria/terapia , Adulto , Anciano , Estudios de Casos y Controles , Costo de Enfermedad , Europa (Continente) , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: Neurogenic detrusor overactivity (NDO) leads to impaired health-related quality of life (HRQoL), productivity, and greater healthcare resource burden. The humanistic and economic burden may be more apparent in NDO patients with urinary incontinence (UI). The objective of this study was to compare the HRQoL, productivity, and health resource use (HRU) between continent and incontinent NDO patients. METHODS: A retrospective database analysis was conducted using the Adelphi Overactive Bladder (OAB)/UI Disease Specific Programme, a multi-national, cross-sectional survey reported from both patients' and physicians' perspectives. The population for this analysis included NDO patients with or without UI. General and disease-specific HRQoL were assessed using the EuroQoL-5D (EQ-5D), Incontinence Quality of Life questionnaire (I-QOL), and the Overactive Bladder Questionnaire (OAB-q). Productivity and daily activity impairment were measured using the Work Productivity and Activity Impairment (WPAI) questionnaire. HRU indicators included OAB-related surgery, OAB-related hospitalizations, incontinence pad usage, switching anticholinergics used for OAB due to inadequate response or adverse effects, and OAB-related physician visits. Bivariate analyses, multivariate ordinary least squares (OLS) regression analyses and published minimal clinically important differences (MCID) were used to assess relationships between incontinent status and the aforementioned outcome measures. RESULTS: A total of 324 NDO patients with or without urinary incontinence were included, averaging 54 years of age (SD 16), of whom 43.8 percent were male. Bivariate analyses detected no significant relationship between incontinent status and HRU variables. Regression analyses revealed that incontinent patients had clinically and statistically lower disease-specific HRQoL and greater impairment in daily activities as compared to continent patients. On average, incontinent patients scored 10 points lower on the I-QOL total score, 9 points lower on the OAB-q HRQoL score, 15 points higher on OAB-q symptom severity, and experienced 8.2 percent higher activity impairment due to their bladder condition (all p < 0.001). CONCLUSIONS: Incontinent NDO patients experience significantly lower HRQoL and activity impairment as compared to continent NDO patients.
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Actividades Cotidianas , Calidad de Vida , Incontinencia Urinaria/complicaciones , Femenino , Recursos en Salud/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Vejiga Urinaria Hiperactiva/complicacionesRESUMEN
PURPOSE: Identify predictors of quality of life (QOL) in patients with any form of cardiac arrhythmia (CA). METHODS: Data from the Medical Panel Expenditure Survey were analyzed from 2004 to 2009. Patients aged ≥18 with any form of CA (identified via ICD-9-CM codes) were included. Primary outcomes included the physical and mental component scores (PCS and MCS) of the Short-Form 12 version 2 (SF-12) and EuroQoL-5D (EQ-5D) utility scores (US version). Patient demographics included insurance status, urban status, geographical region, federal poverty level, education, comorbidities, and disease-related risk factors of CA. RESULTS: Approximately 5,750,440 individuals had CA. Non-Hispanic Whites had the highest SF-12 MCS (mean 50.9; p < 0.001 across racial groups) and utility scores (mean 0.76; p < 0.001 across racial groups). Patients with both private and public insurance had significantly higher PCS (p = 0.001) and MCS (p < 0.001) in comparison with patients only covered by public insurance. Patients on antiarrhythmic agents had higher SF-12 MCS (51.4 vs. 48.4; p < 0.001) compared to individuals not on antiarrhythmic agents. CONCLUSIONS: Significantly lower QOL existed in specific subpopulations (e.g., patients with only public health insurance, racial/ethnic minorities, and those not exposed to antiarrhythmic agents) within the CA population.
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Arritmias Cardíacas/psicología , Indicadores de Salud , Calidad de Vida , Adolescente , Adulto , Anciano , Antiarrítmicos/uso terapéutico , Arritmias Cardíacas/tratamiento farmacológico , Arritmias Cardíacas/epidemiología , Estudios de Cohortes , Comorbilidad , Bases de Datos Factuales , Etnicidad/estadística & datos numéricos , Femenino , Gastos en Salud , Humanos , Masculino , Persona de Mediana Edad , Características de la Residencia/estadística & datos numéricos , Estudios Retrospectivos , Factores Socioeconómicos , Resultado del Tratamiento , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: There is a lack of established clinical outcomes for patients with myelofibrosis (MF) receiving fedratinib following ruxolitinib failure. This study examined real-world patient characteristics, treatment patterns, and clinical outcomes of patients with MF treated with fedratinib following ruxolitinib failure in US clinical practice. PATIENTS AND METHODS: This retrospective patient chart review included adults with a physician-reported diagnosis of MF, who initiated fedratinib after discontinuing ruxolitinib. Descriptive analyses characterized patient characteristics, clinical outcomes, and treatment patterns from MF diagnosis through ruxolitinib and fedratinib treatment. RESULTS: Twenty-four physicians abstracted data for 150 eligible patients. Approximately 55.3% of the patients were male, 68.0% were White, and median age at MF diagnosis was 68 (range, 35-84) years. Median duration of ruxolitinib therapy was 7.6 (range, 0.7-65.5) months. At initiation of fedratinib, 88.0% of patients had palpable spleen and a mean spleen size of 16.0 (standard deviation [SD], 5.9) cm. Spleen size decreased by 19.4% to 13.2 (SD, 7.9) cm at month 3 (P = .0001) and by 53.4% to 7.2 (SD, 7.4) cm at month 6 (P = .01) of fedratinib treatment, respectively. Almost one-third (26.8%) of patients had achieved ≥ 50% spleen reduction by month 6. Mean number of symptoms also decreased significantly at month 3 (P < .0001) and month 6 (P = .01). CONCLUSION: Fedratinib appears to deliver spleen and symptom benefits in real-world patients with MF previously treated with ruxolitinib.
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Nitrilos , Mielofibrosis Primaria , Pirazoles , Pirimidinas , Adulto , Humanos , Masculino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/tratamiento farmacológico , Estudios Retrospectivos , Inhibidores de Proteínas Quinasas , Pirrolidinas/uso terapéutico , Sulfonamidas/uso terapéuticoRESUMEN
Resistance to immune checkpoint therapy (ICT) presents a growing clinical challenge. The tumor microenvironment (TME) and its components, namely tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), play a pivotal role in ICT resistance; however, the underlying mechanisms remain under investigation. In this study, we identify expression of TNF-Stimulated Factor 6 (TSG-6) in ICT-resistant pancreatic tumors, compared to ICT-sensitive melanoma tumors, both in mouse and human. TSG-6 is expressed by CAFs within the TME, where suppressive macrophages expressing Arg1, Mafb, and Mrc1, along with TSG-6 ligand Cd44, predominate. Furthermore, TSG-6 expressing CAFs co-localize with the CD44 expressing macrophages in the TME. TSG-6 inhibition in combination with ICT improves therapy response and survival in pancreatic tumor-bearing mice by reducing macrophages expressing immunosuppressive phenotypes and increasing CD8 T cells. Overall, our findings propose TSG-6 as a therapeutic target to enhance ICT response in non-responsive tumors.
Asunto(s)
Fibroblastos Asociados al Cáncer , Moléculas de Adhesión Celular , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pancreáticas , Microambiente Tumoral , Animales , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Humanos , Microambiente Tumoral/inmunología , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/efectos de los fármacos , Ratones , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Línea Celular Tumoral , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/genética , Células Mieloides/metabolismo , Células Mieloides/inmunología , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/efectos de los fármacos , Ratones Endogámicos C57BL , Femenino , Resistencia a Antineoplásicos , Macrófagos/inmunología , Macrófagos/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismoRESUMEN
Introduction: To date, there is limited literature to guide emergency providers (EPs) on the proper dosing of prescription opioids. Our study aims to assess the self-reported opioid use, storage, and disposal practices of patients presenting to the emergency department (ED) with acute pain. Methods: This prospective cohort study employed a validated, cross-sectional survey of subjects identified using electronic medical records. The survey link was e-mailed to a continuous sample of eligible participants 3-4 weeks following ED discharge. Nonrespondents were surveyed through telephone after 1 week. We used descriptive and nonparametric statistics to report survey results. Results: Of 500 eligible subjects, 97 completed the questionnaire. Only 28% of respondents reported that they took all of the prescribed pills. Of the remaining responses, 20% stated that they did not take any pills, 33% took about one-fourth, 7.2% took about half, and 12.4% took about three-fourths of the pills. Among those who did not take any pills, 42% filled the prescription. Most (71.2%) reported storing their leftover pills; among those who stored their pills, less than one-fourth (23.8%) used a locked storage location. Conclusions: Our findings suggest that less than one-third of patients who receive prescriptions in the ED for acute pain use all of their prescribed pills, suggesting that many patients are unnecessarily prescribed opioids for acute conditions. The findings of this study also suggest that many patients with unused prescription opioids do not practice safe storage or proper disposal of leftover pills. This represents a potential opportunity for EPs to improve medication safety by educating patients on proper storage and disposal practices. Limitations include low response rate and the use of self-reporting.
RESUMEN
OBJECTIVE: Blood supply shortages may create unnecessary burden, including treatment delay, worsened quality of life, or increased healthcare resource utilization in patients with myelodysplastic syndromes (MDS). This study examined physicians' experience with blood supply shortages in the MDS population. Additionally, physicians' perspectives on the factors that impact clinical, economic, and humanistic outcomes of patients with MDS were investigated. METHODS: A total of 378 physicians primarily specializing in hematology/oncology across the UK, France, Germany, Italy, and Spain completed the survey (n ≈ 75 in each country). Physicians answered questions regarding adequacy of blood supply for patients with MDS who require red blood cell (RBC) transfusions and identified factors impacting the clinical, economic, and humanistic outcomes in the MDS population. RESULTS: Over 65% of physicians reported that their patients with MDS requiring RBC transfusions encountered RBC transfusion delays due to blood supply shortage. Among physicians who reported delays, 13.8% of patients were impacted, ranging from 11.0% in Spain to 19.4% in Italy. On average, patients experienced a 4.2-day delay in receiving RBC transfusions due to blood supply shortages, and 16.7% of patients required additional healthcare provider visits. Eastern Cooperative Oncology Group performance status, threshold hemoglobin levels, and age were the top factors reported by more than two-thirds of physicians that impact outcomes of patients with MDS. CONCLUSION: Our findings support the need for new treatments in MDS that reduce transfusions and thus blood supply needs, and that would have a beneficial effect on clinical, humanistic, and economic outcomes.