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2.
J Robot Surg ; 18(1): 191, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38693330

RESUMEN

Robotic surgery has become increasingly prevalent in general surgery practice. While previous studies have shown the safety and efficacy of robotic assistance in laparoscopic general surgery procedures, few studies have evaluated the temporal and regional trends in implementation. In our retrospective population-based study, we aim to evaluate the national trends in robotic surgery. National Inpatient Database (NIS 2009-2014) was used to identify adults who underwent robotic assisted surgery (ICD 9 codes 17.41 to 17.49). Robotic procedures related to seven abdominal organ systems were compared against the trends of Urology, Gynaecologic, and Orthopedic robotic procedures. Discharge weights were applied to calculate National temporal trends separated by hospital size, teaching status and US geographic region. 894,163 patients received a robotic assisted procedure between 2009 and 2014 with 64% increase in utilization. The largest percent change was witnessed in biliary robotic procedures with 2984% change in utilization, followed by hernia (1376%). Lowest percent change was witnessed in esophageal procedures with 114% increase. Medium sized hospitals had the largest change in robotic utilization (41%), with large institutions seeing 18% decrease. Gastric procedures were the most common robotic procedure performed at small institutions (7917 total cases; 316%). Large institutions saw an overall decrease in gastric (- 47%), esophageal (- 17%), small and large intestinal (-16%), and hepatic (- 7%) robotic procedures. Rural non-teaching hospitals saw the largest increase in robotic surgery (274%). Urban non-teaching hospitals saw a decrease of 29%. While urban teaching institutions saw a 20% and 6% increase in gynecological and urological procedures, an overall decrease was seen in esophageal (- 10%), gastric (- 12%), intestinal (- 11%), hepatic (- 17%), biliary (- 10%), pancreatic (- 11%) and hernia procedures (- 14%). Biliary procedures saw the largest increase in rural institutions (740 cases; 392%), followed by hernia (144% increase). South region of the nation had the largest increase in robotic procedures (23%). No change was seen in the use of robotic surgery in the northeast region with the midwest and west seeing an overall decrease (- 4% and - 22%, respectively). Our study highlights the increase in use of robotics for both general and specialty surgery, with an increase in utilization over time. Increased incidence of robotic surgery in smaller, rural institutions with overall decrease in larger, urban teaching hospitals suggests increasing comfort in robotic surgery in the community setting. Further studies are necessary to evaluate the factors associated with increased utilization in smaller institutions.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricos , Procedimientos Quirúrgicos Robotizados/tendencias , Procedimientos Quirúrgicos Robotizados/métodos , Humanos , Estudios Retrospectivos , Estados Unidos , Femenino , Masculino , Adulto , Persona de Mediana Edad
3.
Clin Gerontol ; : 1-9, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38469621

RESUMEN

OBJECTIVES: To investigate indicators of potentially hazardous alcohol use among older adults living in a region with high substance use stigma. METHODS: Patients at a university-affiliated geriatrics clinic in the Deep South of theUS completed behavioral health screenings including self-reported alcohol use, symptoms of depression or anxiety, and cognitive functioning between 2018 and 2022. RESULTS: Participants (N = 278) averaged 76.04 years of age (SD = 9.25), were predominantly female (70.9%), and non-Hispanic white (84.5%), with an averageof 6.08 comorbid diagnoses (SD = 2.86). Race/ethnicity, age, and symptoms of anxiety were associated with alcohol use and hazardous alcohol use, with non-Hispanic whites, younger individuals, and those with more anxiety symptoms reporting more alcohol use. Notably, alcohol use and hazardous alcohol use were associated with cognitive functioning in the dementia range. CONCLUSION: Self-reported alcohol use is low in geriatric primary care in the Deep South, US, differs by race/ethnicity, and is predictive of cognitive impairment when alcohol use is hazardous. Issues of trust and stigma may play a role in self-report ofstigmatized behaviors. CLINICAL IMPLICATIONS: Self-reported alcohol intake must be considered within the cultural context of regional stigma. Recommendations to address this are provided.

4.
Animal ; 17 Suppl 5: 100921, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37659911

RESUMEN

Nowadays, vast amounts of data representing feed intake, growth, and environmental impact of individual animals are being recorded in on-farm settings. Despite their apparent use, data collected in real-world applications often have missing values in one or several variables, due to reasons including human error, machine error, or sampling frequency misalignment across multiple variables. Since incomplete datasets are less valuable for downstream data analysis, it is important to address the missing value problem properly. One option may be to reduce the dataset to a subset that contains only complete data, but considerable data may be lost via this process. The current study aimed to compare imputation methods for the estimation of missing values in a raw dataset of dairy cattle including 454 553 records collected from 629 cows between 2009 and 2020. The dataset was subjected to a cleaning process that reduced its size to 437 075 observations corresponding to 512 cows. Missing values were present in four variables: concentrate DM intake (CDMI, missing percentage = 2.30%), forage DM intake (FDMI, 8.05%), milk yield (MY, 15.12%), and BW (64.33%). After removing all missing values, the resulting dataset (n = 129 353) was randomly sampled five times to create five independent subsets that exhibit the same missing data percentages as the cleaned dataset. Four univariate and nine multivariate imputation methods (eight machine learning methods and the MissForest method) were applied and evaluated on the five repeats, and average imputation performance was reported for each repeat. The results showed that Random Forest was overall the best imputation method for this type of data and had a lower mean squared prediction error and higher concordance correlation coefficient than the other imputation methods for all imputed variables. Random Forest performed particularly well for imputing CDMI, MY, and BW, compared to imputing FDMI.


Asunto(s)
Leche , Proyectos de Investigación , Humanos , Femenino , Bovinos , Animales , Aprendizaje Automático , Ingestión de Alimentos , Granjas
5.
Animal ; 17 Suppl 5: 100874, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37394324

RESUMEN

Within poultry production systems, models have provided vital decision support, opportunity analysis, and performance optimization capabilities to nutritionists and producers for decades. In recent years, due to the advancement of digital and sensor technologies, 'Big Data' streams have emerged, optimally positioned to be analyzed by machine-learning (ML) modeling approaches, with strengths in forecasting and prediction. This review explores the evolution of empirical and mechanistic models in poultry production systems, and how these models may interact with new digital tools and technologies. This review will also examine the emergence of ML and Big Data in the poultry production sector, and the emergence of precision feeding and automation of poultry production systems. There are several promising directions for the field, including: (1) application of Big Data analytics (e.g., sensor-based technologies, precision feeding systems) and ML methodologies (e.g., unsupervised and supervised learning algorithms) to feed more precisely to production targets given a 'known' individual animal, and (2) combination and hybridization of data-driven and mechanistic modeling approaches to bridge decision support with improved forecasting capabilities.


Asunto(s)
Macrodatos , Aves de Corral , Animales , Aprendizaje Automático , Algoritmos , Tecnología
6.
Aging Ment Health ; 27(3): 453-465, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35168415

RESUMEN

OBJECTIVES: Psychological flexibility/inflexibility (PF/PI) is a core component of the acceptance and commitment therapy (ACT) model, which is gaining more attention in the geropsychological literature. This scoping review examines the size and scope of the research on PF/PI in older adulthood related to age differences between older adult and younger samples, correlates relevant to psychological health, and changes with ACT. METHODS: A systematic literature search was conducted using PubMed, CINAHL, and PsycINFO. Peer-reviewed articles available in English were included that: had a mean age ≥65 and a minimum age ≥60; and reported self-report measures of PF/PI. We categorized PF/PI into three domains: open, aware, and engaged. RESULTS: Forty-six articles were included. Most studies measured open or aware domains; few measured the engaged domain. Older adults evidenced greater awareness compared to younger adults (9 of 13 analyses were significant). Openness and awareness consistently yielded medium to large correlations with anxiety and depression. PF/PI did not relate with positive affect and inconsistently correlated with quality of life measures. CONCLUSION: Despite emerging trends, variability and limitations were evident in the literature. Specifically, measurement issues, lack of conceptual clarity, and the omission of values and behavioral measures require future attention.


Asunto(s)
Terapia de Aceptación y Compromiso , Humanos , Anciano , Calidad de Vida , Ansiedad/terapia , Salud Mental
7.
ACS Chem Neurosci ; 13(17): 2658-2665, 2022 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-35946788

RESUMEN

Multiple sclerosis (MS) is an inflammatory disease characterized by damage to the myelin sheath surrounding axons in the central nervous system. While the exact mechanism of this destruction is unknown, excess nitric oxide (NO) and adenosine triphosphate (ATP) have been measured in tissues and fluids obtained from people with MS. Here, incubation of interferon-beta (IFN-ß), an MS drug with an unknown mechanism of action, with red blood cells (RBCs) obtained from people with MS provide evidence of a potential hypermetabolic state in the MS RBC that is decreased with IFN-ß intervention. Specifically, binding of all three components of an albumin/C-peptide/Zn2+ complex to MS RBCs was significantly increased in comparison to control RBCs. For example, the binding of C-peptide to MS RBCs was significantly increased (3.4 ± 0.1 nM) compared to control RBCs (1.6 ± 0.2 nM). However, C-peptide binding to MS RBCs was reduced to a value (1.6 ± 0.3 nM) statistically equal to that of control RBCs in the presence of 2 nM IFN-ß. Similar trends were measured for albumin and Zn2+ binding to RBCs when in the presence of IFN-ß. RBC function was also affected by incubation of cells with IFN-ß. Specifically, RBC-derived ATP and measurable membrane GLUT1 were both significantly decreased (56 and 24%, respectively) in the presence of IFN-ß. Collectively, our results suggest that IFN-ß inhibits albumin binding to the RBC, thereby reducing its ability to deliver ligands such as C-peptide and Zn2+ to the cell and normalizing the basal hypermetabolic state.


Asunto(s)
Interferón beta , Esclerosis Múltiple , Adenosina Trifosfato/metabolismo , Albúminas/metabolismo , Péptido C/metabolismo , Eritrocitos/metabolismo , Humanos , Interferón beta/metabolismo , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/metabolismo
8.
Endosc Int Open ; 10(1): E9-E18, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35047330

RESUMEN

Background and study aims Fujifilm has developed a novel ELUXEO 7000 endoscope system that employs light-emitting diodes (LEDs) at four different wavelengths as light sources that enable blue light imaging (BLI), linked color imaging (LCI), and high-definition white-light endoscopy (HD-WLE). The aim of this study was to address the diagnostic accuracy of real-time polyp characterization using BLI, LCI and HD-WLE (ELUXEO 7000 endoscopy system). Patients methods This is a prespecified post-hoc analysis of a prospective study in which 22 experienced endoscopists (> 2,000 colonoscopies) from eight international centers participated. Using a combination of BLI, LCI, and HD-WLE, lesions were endoscopically characterized including a high- or low-confidence statement. Per protocol, digital images were created from all three imaging modalities. Histopathology was the reference standard. Endoscopists were familiar with polyp characterization, but did not take dedicated training for purposes of this study. Results Overall, 341 lesions were detected in 332 patients. Of the lesions, 269 histologically confirmed polyps with an optical diagnosis were included for analysis (165 adenomas, 27 sessile serrated lesions, and 77 hyperplastic polyps). Overall, polyp characterization was performed with high confidence in 82.9 %. The overall accuracy for polyp characterization was 75.1 % (95 % confidence interval [CI] 69.5-80.1 %), compared with an accuracy of 78.0 % (95 % CI 72.0-83.2 %) for high confidence assignments. The accuracy for endoscopic characterization for diminutive polyps was 74.7 % (95 %CI 68.4-80.3 %), compared with an accuracy of 78.2 % (95 % CI 71.4-84.0 %) for high-confidence assignments. Conclusions The diagnostic accuracy of BLI, LCI, and HD-WLE by experienced endoscopist for real-time polyp characterization seems limited (NCT03344289).

9.
Mindfulness (N Y) ; 13(10): 2448-2460, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36938380

RESUMEN

Objectives: This study evaluates the effects of treatment with mindfulness-based stress reduction (MBSR) compared to the active control, present-centered group therapy (PCGT), on morning plasma cortisol, interleukin-6 (IL-6), and C-reactive protein (CRP) in veterans diagnosed with post-traumatic stress disorder (PTSD). Methods: In a post hoc exploratory analysis, we pooled biomarkers and clinical outcomes of mindfulness, PTSD, and depression from two randomized controlled trials comparing MBSR (n = 104) to PCGT (n = 106) in U.S. military veterans diagnosed with PTSD. Linear mixed-effects modeling was used to evaluate associations between changes in biomarkers and clinical outcomes from baseline to 9-week primary endpoint and 16-week follow-up endpoint. Results: Cortisol levels were inversely related to self-reported PTSD symptoms at baseline (p = 0.02). Cortisol increased from baseline to 9-week endpoint for both groups, but significantly less so in the MBSR group compared to PCGT group (mean difference 1.69 ± 0.8 SE; p = 0.035). Changes in IL-6 and CRP did not differ between groups at either baseline or week 9. From baseline to week 9, increased mindfulness was significantly associated with increased cortisol (p = 0.02) and decreased PTSD and depression severity (p < 0.01). Increased IL-6 and CRP were significantly associated with decreased PTSD severity (p < 0.05), but not depression. Pooled analysis corroborated earlier findings that MBSR is significantly better than PCGT in improving clinical outcomes. Increased mindfulness was strongly associated with improved symptoms. Conclusions: Increased mindfulness is associated with a recalibration of cortisol levels which may be indicative of therapeutic response, especially in patients with lower baseline cortisol. Furthermore, mindfulness-based practices improve symptoms of PTSD and depression in a significant correlation with self-reported levels of mindfulness. Clinical Trial Registration clinicaltrialsgov: NCT01532999 and NCT01548742.

10.
Glob Heart ; 16(1): 80, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34900571

RESUMEN

Background: Cardiovascular disease reflects a major burden of non-communicable disease in Sub-Saharan Africa (SSA). Early detection and treatment of atrial fibrillation (AF), as a preventive measure against stroke, is currently not in the scope of the World Health Organization recommendation to reduce cardiovascular disease. Objective: We hypothesized that screening for AF would be an important approach to determine the true AF prevalence in the general population in African countries and to identify asymptomatic AF patients at risk for stroke to optimize prevention. Methods: A decision analytic model was developed to study the health-economic impact of AF screening in Nigeria over a life-time horizon. The patient population explored in the model was a population of newly detected AF cases that would be diagnosed with a one-time systematic screening for AF with a single lead ECG device in community health centres across Nigeria. Conclusions: The health gain per newly detected AF patient (N = 31,687) was 0.41 QALY at a cost of $5,205 per patient with 100% NOAC use, leading to an ICER of $12,587 per QALY gained. The intervention was cost-effective with a 99.9% warfarin use with an ICER of $1,363 per QALY gained. The total cost of a single screening session was $7.3 million for the total screened population in Nigeria or $1.60 per patient screened. Screening for AF to detect AF patients in need for stroke prevention can be a cost-effective intervention in the Sub-Saharan region, depending on type of anticoagulant used and drug costs.


Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular , Anticoagulantes/uso terapéutico , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Análisis Costo-Beneficio , Estudios de Factibilidad , Humanos , Tamizaje Masivo , Nigeria/epidemiología , Años de Vida Ajustados por Calidad de Vida , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control
11.
J Clin Psychol Med Settings ; 28(4): 897-908, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34596823

RESUMEN

Quality improvement (QI) work is increasingly necessary to ensure healthcare is delivered safely, efficiently, and equitably. As geropsychologists play an increasingly vital role in healthcare service delivery for older adults, it is imperative that they develop professional competence in QI, yet there is little formal QI training aimed at geropsychologists or to graduate students pursuing geropsychology. This article aims to elucidate the importance of QI education and training in geropsychology. In line with the Pikes Peak model for training in professional geropsychology, we outline QI knowledge and skills competencies for geropsychology training and suggest a rubric for integrating QI education into academic and clinical training from graduate school to professional practice. We provide recommended readings that geropsychology educators can read to become familiar with QI or use as part of a syllabus. Finally, we offer some recommendations for how current and future geropsychologists can be leaders in quality improvement work.


Asunto(s)
Geriatría , Mejoramiento de la Calidad , Anciano , Competencia Clínica , Atención a la Salud , Geriatría/educación , Humanos
12.
Clin Gerontol ; 44(5): 536-543, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34028341

RESUMEN

Objectives: Suicide Awareness for Veterans Exiting Community Living Centers (SAVE-CLC) is a brief intervention to standardize suicide-risk screening and clinical follow-up after VA nursing home discharge. This paper examines the outcomes of SAVE-CLC compared to care as usual.Methods: A quasi-experimental evaluation was conducted (N = 124) with SAVE-CLC patients (n = 62) matched 1:1 to a pre-implementation comparison group. Data were obtained through VA Corporate Data Warehouse resources and chart reviews. Outcomes examined (within 30/90 days of discharge) included mortality rates, frequency of outpatient mental health visits, emergency department visits, rehospitalizations, depression screens (PHQ-2), and the latency period for outpatient mental health care.Results: A greater portion of SAVE-CLC patients received a depression screen after discharge, n = 42, 67.7% versus n = 8, 12.9%, OR = 14.2 (5.7, 35.3), p < .001. The number of days between discharge and first mental health visit was also substantially shorter for SAVE-CLC patients, M = 8.9, SD = 8.2 versus M = 17.6, SD = 9.1; t = 2.47 (122), p = .02. Significant differences were not observed in emergency department visits, hospitalizations, or mortality.Conclusions: SAVE-CLC is a time-limited intervention for detecting risk and speeding engagement in mental health care in the immediate high-risk post-discharge period.Clinical Implications: Care transitions present an important opportunity for addressing older adults' suicide risk; brief telephone-based interventions like SAVE-CLC may provide needed support to individuals returning home.


Asunto(s)
Alta del Paciente , Prevención del Suicidio , Cuidados Posteriores , Anciano , Estudios de Seguimiento , Humanos , Casas de Salud
13.
Gerontol Geriatr Educ ; 42(2): 277-296, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33939939

RESUMEN

A shortage of individuals in academic geropsychology positions further perpetuates the shortage of clinicians trained to meet the needs of the aging population. Barriers to recruiting geropsychology trainees into academia and what attracts trainees into career paths within geropsychology are not understood. The current mixed-methods study examined 1) geropsychology trainees' (n = 28) knowledge and attitudes toward work in clinical or academic positions and 2) professional geropsychologists (n = 67) activities, career expectations, ideal activities, and work/life balance. We asked geropsychology trainees to estimate the amount of time their supervisors spent in clinical, research, education, and administrative activities, and professional geropsychologists reported how they currently spent their time in these same activities. We conducted qualitative interviews asking geropsychology trainees about experiences in academic or clinical settings and geropsychologists about career expectations, opportunities, and work/life balance. Geropsychology trainees had less accurate estimates of academic work time compared to clinically focused work time. Trainee interviews revealed negative perceptions of the university system, including bureaucracy, low salary, and perceived workload. Professional geropsychologists reported high agreement between actual and ideal work time with some individual differences. Each group discussed work-life balance, based on career stage or work setting. Interventions for recruiting more geropsychology trainees into academic jobs are discussed.


Asunto(s)
Geriatría , Anciano , Envejecimiento , Selección de Profesión , Geriatría/educación , Humanos
15.
Arch Orthop Trauma Surg ; 141(4): 637-643, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32710342

RESUMEN

INTRODUCTION: Older hip fracture patients are still challenging in daily clinical practice. Due to the high prevalence of osteoporosis and atrial fibrillation in this age group, the number of fragility fracture patients under oral anticoagulation (OAC) increases. The outcome is still disappointing, short- and long-term mortality and morbidity is high. The impact of pre-existing OAC is not yet clear, especially regarding new OAC drugs like Factor Xa inhibitors (FXa). The purpose of our study was to compare the short-term outcome of older hip fracture patients, without OAC (controls), on Vitamin K antagonists (VKA) and on FXa. MATERIALS AND METHODS: The study is a retrospective case-control study including patients older than 70 years who sustained hip fractures caused by an inadequate trauma and treated at a level 1 trauma center from February 2017 to June 2018. Patient's information was taken from patient's charts. 102 cases were analysed, 61 controls, 41 on OAC (15 on VKA and 26 on FXa). As outcome parameter we defined mortality, perioperative complications, bleeding, need of blood supplements, delay of surgery, length of stay, and a combined outcome parameter (mortality, myocardial infarction, stroke, thromboembolic events, blood preservations, re-vision surgery, major bleeding and decline of hemoglobin). RESULTS: Eight patients died during hospital stay, in-hospital mortality was 7.8%. The highest mortality rate was found in patients on VKA (20%), compared to patients on FXa (3.8%) and controls (6.6%). However, mortality rate did not differ significantly within the groups. The combined endpoint was significantly more frequently seen in patients on OAC compared to controls (p = 0.006). No difference was observed between patients on VKA or FXa. Mean time to surgery and LOS was significantly longer in patients on OAC compared to controls. No significant differences were seen between VKA and FXa. CONCLUSIONS: In our study OAC was significantly associated with worse outcome compared to controls. Marginal differences were observed between patients on FXa or VKA. Further studies involving a higher number of patients are necessary to confirm our results. At that time, some our results have to interpreted carefully and need confirmation.


Asunto(s)
Anticoagulantes/efectos adversos , Inhibidores del Factor Xa/efectos adversos , Fracturas de Cadera , Vitamina K/antagonistas & inhibidores , Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Estudios de Casos y Controles , Inhibidores del Factor Xa/uso terapéutico , Fracturas de Cadera/complicaciones , Fracturas de Cadera/epidemiología , Fracturas de Cadera/mortalidad , Fracturas de Cadera/cirugía , Humanos , Estudios Retrospectivos , Resultado del Tratamiento
16.
Gerontol Geriatr Educ ; 42(2): 268-276, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-31173565

RESUMEN

Assessment of decision-making capacity of older adults is a growing area of practice but training opportunities are lacking. We present a needs assessment, program characteristics, pilot clinic process (n= 52 referrals) and outcome training (n= 4 interns) data for a capacity training clinic. Process data reveal that the training clinic provided consistent referrals (1 per week) across multiple capacity domains (independent living, treatment consent, and financial capacities), with 27% of referrals providing opportunities for training in protective services. Outcome data found three of the four interns reported proficient skills in capacity assessment, as well as improved skills in six areas related to capacity assessment: knowledge of limitations of assessment methods, person-environment interaction, identifying and applying ethical and legal standards, utilizing cognitive assessments, communicating results and recommendations, and assessing risk. The discussion shares lessons learned for the development of future training rotations and clinics in the capacity assessment.


Asunto(s)
Geriatría , Internado y Residencia , Anciano , Competencia Clínica , Curriculum , Geriatría/educación , Humanos , Pacientes Ambulatorios
17.
Regul Toxicol Pharmacol ; 117: 104767, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32866543

RESUMEN

Skin sensitising substances that induce contact allergy and consequently risk elicitation of allergic contact dermatitis (ACD) remain an important focus regarding the replacement of animal experimentation. Current in vivo methods, notably the local lymph node assay (LLNA) refined and reduced animal usage and led to a marked improvement in hazard identification, characterisation and risk assessment. Since validation, regulatory confidence in the LLNA approach has evolved until it became the first choice assay in most regulated sectors. Currently, hazard identification using the LLNA is being actively replaced by a toolbox of non-animal approaches. However, there remains a need to increase confidence in the use of new approach methodologies (NAMs) as replacements for LLNA sensitiser potency estimation. The EPAA Partners Forum exchanged the current state of knowledge on use of NAMs in various industry sectors and regulatory environments. They then debated current challenges in this area and noted several ongoing needs. These included a requirement for reference standards for potency, better characterisation of applicability domains/technical limitations of NAMs, development of a framework for weight of evidence assessments, and an increased confidence in the characterisation of non-sensitisers. Finally, exploration of an industry/regulator cross-sector user-forum on skin sensitisation was recommended.


Asunto(s)
Alérgenos/toxicidad , Alternativas a las Pruebas en Animales/normas , Congresos como Asunto/normas , Ensayo del Nódulo Linfático Local , Informe de Investigación/normas , Piel/efectos de los fármacos , Alternativas a las Pruebas en Animales/métodos , Animales , Bélgica/epidemiología , Dermatitis Alérgica por Contacto/diagnóstico , Dermatitis Alérgica por Contacto/epidemiología , Humanos , Medición de Riesgo/métodos , Medición de Riesgo/normas
18.
Artículo en Inglés | MEDLINE | ID: mdl-32513802

RESUMEN

Experiments were conducted with polymyxin B and two Klebsiella pneumonia isogenic strains (the wild type, KP_WT, and its transconjugant carrying the mobile colistin resistance gene, KP_MCR-1) to demonstrate that conducting two consecutive time-kill experiments (sequential TK) represents a simple approach to discriminate between pharmacokinetics/pharmacodynamics models with two heterogeneous subpopulations or adaptive resistance.


Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana , Infecciones por Klebsiella , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Colistina/farmacocinética , Colistina/farmacología , Farmacorresistencia Bacteriana/genética , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella pneumoniae/genética , Pruebas de Sensibilidad Microbiana
19.
Trials ; 21(1): 334, 2020 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-32299515

RESUMEN

BACKGROUND: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. METHODS/DESIGN: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. DISCUSSION: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018.


Asunto(s)
Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/terapia , Implementación de Plan de Salud , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/terapia , Calidad de Vida , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos del Sistema Biliar , Carcinoma Ductal Pancreático/epidemiología , Niño , Preescolar , Análisis por Conglomerados , Drenaje , Terapia de Reemplazo Enzimático , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Terapia Neoadyuvante , Países Bajos/epidemiología , Cuidados Paliativos , Neoplasias Pancreáticas/epidemiología , Pancreaticoduodenectomía , Cooperación del Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto , Stents , Resultado del Tratamiento , Adulto Joven
20.
Dis Esophagus ; 33(9)2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32129453

RESUMEN

Barrett's esophagus (BE) is a metaplastic condition of the distal esophagus, resulting from longstanding gastroesophageal reflux disease (GERD). BE predisposes for the highly malignant esophageal adenocarcinoma (EAC). Both BE and EAC have the highest frequencies in white males. Only a subset of patients with GERD develop BE, while <0.5% of BE will progress to EAC. Therefore, it is most likely that the development of BE and EAC is associated with underlying genetic factors. We hypothesized that in white males, Y-chromosomal haplogroups are associated with BE and EAC. To investigate this we conducted a multicenter study studying the frequencies of the Y-chromosomal haplogroups in GERD, BE, and EAC patients. We used genomic analysis by polymerase chain reaction and restriction fragment length polymorphism to determine the frequency of six Y-chromosomal haplogroups (DE, F(xJ,xK), K(xP), J, P(xR1a), and R1a) between GERD, BE, and EAC in a cohort of 1,365 white males, including 612 GERD, 753 BE patients, while 178 of the BE patients also had BE-associated EAC. Univariate logistic regression analysis was used to compare the outcomes. In this study, we found the R1a (6% vs. 9%, P = 0.04) and K (3% vs. 6%, P = 0.035) to be significantly underrepresented in BE patients as compared to GERD patients with an odds ratio (OR) of 0.63 (95% CI 0.42-0.95, P = 0.03) and of 0.56 (95% CI 0.33-0.96, P = 0.03), respectively, while the K haplogroup was protective against EAC (OR 0.30; 95% CI 0.07-0.86, P = 0.05). A significant overrepresentation of the F haplogroup was found in EAC compared to BE and GERD patients (34% vs. 27% and 23%, respectively). The F haplogroup was found to be a risk factor for EAC with an OR of 1.5 (95% CI 1.03-2.19, P = 0.03). We identified the R1a and K haplogroups as protective factors against development of BE. These haplogroups have low frequencies in white male populations. Of importance is that we could link the presence of the predominantly occurring F haplogroup in white males to EAC. It is possible that this F haplogroup is associated to genetic variants that predispose for the EAC development. In future, the haplogroups could be applied to improve stratification of BE and GERD patients with increased risk to develop BE and/or EAC.


Asunto(s)
Adenocarcinoma , Esófago de Barrett , Cromosomas Humanos Y/genética , Neoplasias Esofágicas , Adenocarcinoma/genética , Esófago de Barrett/genética , Cromosomas , Neoplasias Esofágicas/genética , Haplotipos , Humanos , Masculino , Factores de Riesgo
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