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PURPOSE: We compared new cases detected per index case in familial hypercholesterolemia (FH) families with or without an identifiable monogenic etiology. METHODS: We enrolled 52 FH probands with a pathogenic variant (FHg+) in LDLR, APOB, or PCSK9 and 73 probands without such a variant (FHg-). After direct contact by the study team, family members (FMs) of FHg+ probands could opt-in for genetic testing and FMs of FHg- probands were asked to provide a lipid profile. New cases were defined as presence of a pathogenic variant in FHg+ families and as low-density lipoprotein cholesterol ≥155 mg/dL in FHg- families. RESULTS: Of 71 FHg+ probands seen by a genetic counselor, 52 consented and identified 253 FMs (111 consented and were tested, yielding 48 new cases). Of 101 FHg- probands who received counseling, 73 consented and identified 295 FMs (63 consented and were tested, yielding 17 new cases). New case detection per index case was significantly greater in FHg+ than in FHg- families (0.92 vs 0.23), a result of higher cascade testing uptake (43.9 vs 21.4%) and yield (43.2 vs 27.0%) in the former. CONCLUSION: New case detection rate was significantly higher in FH families with a monogenic etiology than in those without such an etiology owing to greater uptake and yield of cascade testing.
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Hiperlipoproteinemia Tipo II , Proproteína Convertasa 9 , Humanos , Proproteína Convertasa 9/genética , Receptores de LDL/genética , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , LDL-ColesterolRESUMEN
BACKGROUND: Dyad learning has been shown to be an effective tool for teaching procedural skills, but little is known about how dyad learning may impact the stress, anxiety, and cognitive load that a student experiences when learning in this manner. In this pilot study, we investigate the relationship between dyad training on stress, anxiety, cognitive load, and performance in a simulated bradycardia scenario. METHODS: Forty-one fourth-year medical school trainees were randomized as dyads (n = 24) or individuals (n = 17) for an education session on day 1. Reassessment occurred on day 4 and was completed as individuals for all trainees. Primary outcomes were cognitive load (Paas scale), stress (Cognitive Appraisal Ratio), and anxiety levels (abbreviated State-Trait Anxiety Inventory). Secondary outcomes were time-based performance metrics. RESULTS: On day 1 we observed significant differences for change in anxiety and stress measured before and after the training scenario between groups. Individuals compared to dyads had larger mean increases in anxiety, (19.6 versus 7.6 on 80-point scale, p = 0.02) and stress ratio (1.8 versus 0.9, p = 0.045). On the day 4 post-intervention assessment, no significant differences were observed between groups. Secondary outcomes were significant for shorter time to diagnosis of bradycardia (p = 0.01) and time to initiation of pacing (p = 0.04) in the dyad group on day 1. On day 4, only time to recognizing the indication for pacing was significantly shorter for individual training (hazard ratio [HR] = 2.26, p = 0.02). CONCLUSIONS: Dyad training results in lower stress and anxiety levels with similar performance compared to individual training.
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Entrenamiento Simulado , Ansiedad/terapia , Competencia Clínica , Cognición , Humanos , Aprendizaje , Proyectos PilotoRESUMEN
Platelet transmission electron microscopy (PTEM) is considered the gold standard test for assessing distinct ultrastructural abnormalities in inherited platelet disorders (IPDs). Nevertheless, PTEM remains mainly a research tool due to the lack of standardized procedures, a validated dense granule (DG) count reference range, and standardized image interpretation criteria. The aim of this study was to standardize and validate PTEM as a clinical laboratory test. Based on previously established methods, we optimized and standardized preanalytical, analytical, and postanalytical procedures for both whole mount (WM) and thin section (TS) PTEM. Mean number of DG/platelet (plt), percentage of plts without DG, platelet count (PC), mean platelet volume (MPV), immature platelet fraction (IPF), and plt light transmission aggregometry analyses were measured on blood samples from 113 healthy donors. Quantile regression was used to estimate the reference range for DG/plt, and linear regression was used to assess the association of DG/plt with other plt measurements. All PTEM procedures were standardized using commercially available materials and reagents. DG interpretation criteria were established based on previous publications and expert consensus, and resulted in improved operator agreement. Mean DG/plt was stable for 2 days after blood sample collection. The median within patient coefficient of variation for mean DG/plt was 22.2%; the mean DG/plt reference range (mid-95th %) was 1.2-4.0. Mean DG/plt was associated with IPF (p = .01, R2 = 0.06) but not age, sex, PC, MPV, or plt maximum aggregation or primary slope of aggregation (p > .17, R2 < 0.02). Baseline ultrastructural features were established for TS-PTEM. PTEM was validated using samples from patients with previously established diagnoses of IPDs. Standardization and validation of PTEM procedures and interpretation, and establishment of the normal mean DG/plt reference range and PTEM baseline ultrastructural features, will facilitate implementation of PTEM as a valid clinical laboratory test for evaluating ultrastructural abnormalities in IPDs.
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Plaquetas/metabolismo , Microscopía Electrónica de Transmisión/métodos , Valores de Referencia , HumanosRESUMEN
BACKGROUND: The aim of this study was to evaluate the use of a glucose meter with surgical patients under general anesthesia in the operating room. METHODS: Glucose measurements were performed intraoperatively on 368 paired capillary and arterial whole blood samples using a Nova StatStrip (Nova Biomedical, USA) glucose meter and compared with 368 reference arterial whole blood glucose measurements by blood gas analyzer in 196 patients. Primary outcomes were median bias (meter minus reference), percentage of glucose meter samples meeting accuracy criteria for subcutaneous insulin dosing as defined by Parkes error grid analysis for type 1 diabetes mellitus, and accuracy criteria for intravenous insulin infusion as defined by Clinical and Laboratory Standards Institute guidelines. Time under anesthesia, patient position, diabetes status, and other variables were studied to determine whether any affected glucose meter bias. RESULTS: Median bias (interquartile range) was -4 mg/dl (-9 to 0 mg/dl), which did not differ from median arterial meter bias of -5 mg/dl (-9 to -1 mg/dl; P = 0.32). All of the capillary and arterial glucose meter values met acceptability criteria for subcutaneous insulin dosing, whereas only 89% (327 of 368) of capillary and 93% (344 of 368) arterial glucose meter values met accuracy criteria for intravenous insulin infusion. Time, patient position, and diabetes status were not associated with meter bias. CONCLUSIONS: Capillary and arterial blood glucose measured using the glucose meter are acceptable for intraoperative subcutaneous insulin dosing. Whole blood glucose on the meter did not meet accuracy guidelines established specifically for more intensive (e.g., intravenous insulin) glycemic control in the acute care environment.
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Anestesia General , Glucemia , Monitoreo Intraoperatorio/instrumentación , Monitoreo Intraoperatorio/métodos , Anciano , Arterias , Capilares , Femenino , Humanos , Masculino , Persona de Mediana Edad , Quirófanos , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Automated external defibrillators can provide life-saving therapies to treat ventricular fibrillation. We developed a prototype unit that can deliver a unique shock waveform produced by four independent capacitors that is delivered through two shock vectors, with the rationale of providing more robust shock pathways during emergent defibrillation. We describe the initial testing and feasibility of this unique defibrillation unit, features of which may enable downsizing of current defibrillator devices. METHODS: We tested our defibrillation unit in four large animal models (two canine and two swine) under general anesthesia. Experimental defibrillation thresholds (DFT) were obtained by delivery of a unique waveform shock pulse via a dual-vector pathway with four defibrillation pads (placed across the chest). DFTs were measured and compared with those of a commercially available biphasic defibrillator (Zoll M series, Zoll Medical, Chelmsford, MA, USA) tested in two different vectors. Shocks were delivered after 10 seconds of stable ventricular fibrillation and the output characteristics and shock outcome recorded. Each defibrillation series used a step-down to failure protocol to define the defibrillation threshold. RESULTS: A total of 96 shocks were delivered during ventricular fibrillation in four large animals. In comparison to the Zoll M series, which delivered a single-vector, biphasic shock, the energy required for successful defibrillation using the unique dual-vector biphasic waveform did not differ significantly (P = 0.65). CONCLUSIONS: Our early findings support the feasibility of a unique external defibrillation unit using a dual-vector biphasic waveform approach. This warrants further study to leverage this unique concept and work toward a miniaturized, portable shock delivery system.
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Desfibriladores , Electrodos , Terapia Asistida por Computador/instrumentación , Fibrilación Ventricular/prevención & control , Animales , Perros , Diseño de Equipo , Análisis de Falla de Equipo , Estudios de Factibilidad , Humanos , Miniaturización , Proyectos Piloto , Porcinos , Evaluación de la Tecnología Biomédica , Terapia Asistida por Computador/métodos , Resultado del TratamientoRESUMEN
Severe hypercholesterolemia/possible familial hypercholesterolemia (FH) is relatively common but underdiagnosed and undertreated. We investigated whether implementing clinical decision support (CDS) was associated with lower low-density lipoprotein cholesterol (LDL-C) in patients with severe hypercholesterolemia/possible FH (LDL-C ≥ 190 mg/dL). As part of a pre-post implementation study, a CDS alert was deployed in the electronic health record (EHR) in a large health system comprising 3 main sites, 16 hospitals and 53 clinics. Data were collected for 3 months before ('silent mode') and after ('active mode') its implementation. Clinicians were only able to view the alert in the EHR during active mode. We matched individuals 1:1 in both modes, based on age, sex, and baseline lipid lowering therapy (LLT). The primary outcome was difference in LDL-C between the two groups and the secondary outcome was initiation/intensification of LLT after alert trigger. We identified 800 matched patients in each mode (mean ± SD age 56.1 ± 11.8 y vs. 55.9 ± 11.8 y; 36.0% male in both groups; mean ± SD initial LDL-C 211.3 ± 27.4 mg/dL vs. 209.8 ± 23.9 mg/dL; 11.2% on LLT at baseline in each group). LDL-C levels were 6.6 mg/dL lower (95% CI, -10.7 to -2.5; P = 0.002) in active vs. silent mode. The odds of high-intensity statin use (OR, 1.78; 95% CI, 1.41-2.23; P < 0.001) and LLT initiation/intensification (OR, 1.30, 95% CI, 1.06-1.58, P = 0.01) were higher in active vs. silent mode. Implementation of a CDS was associated with lowering of LDL-C levels in patients with severe hypercholesterolemia/possible FH, likely due to higher rates of clinician led LLT initiation/intensification.
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Background: Customized and standard automated insulin delivery (AID) systems for use in pregnancies of women with preexisting type 1 diabetes (T1D) are being developed and tested to achieve pregnancy appropriate continuous glucose monitoring (CGM) targets. Guidance on the use of CGM for treatment decisions during pregnancy in the United States is limited. Methods: Ten pregnant women with preexisting T1D participated in a trial evaluating at-home use of a pregnancy-specific AID system. Seven-point self-monitoring of blood glucose (SMBG) was compared to the closest sensor glucose (Dexcom G6 CGM) value biweekly to assess safety and reliability based on the 20%/20â mg/dL criteria. Results: All participants completed the study with 7 participants satisfying the safety and reliability criteria with a mean absolute relative difference of 10.3%. Three participants did not fulfill the criteria, mainly because the frequency of SMBG did not meet the requirements. Conclusion: Dexcom G6 CGM is safe and accurate in the real-world setting for use in pregnant women with preexisting T1D with reduced SMBG testing as part of a pregnancy-specific AID system.
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Anderson, Paul J., Christina M. Wood-Wentz, Kent R. Bailey, and Bruce D. Johnson. Objective versus self-reported sleep quality at high altitude. High Alt Med Biol. 24:144-148, 2023. Background: Previous studies have found little relationship between polysomnography and a diagnosis of acute mountain sickness (AMS) using the Lake Louise Symptom Questionnaire (LLSQ). The correlation between sleep question responses on the LLSQ and polysomnography results has not been explored. We compared LLSQ sleep responses and polysomnography data from our previous study of workers rapidly transported to the South Pole. Methods: Sixty-three subjects completed a 3-hour flight from sea level to the South Pole (3200 m, 9800 ft). Participants completed limited overnight polysomnography on their first night and completed LLSQ upon awakening. We compared polysomnography results at the South Pole with sleep question responses on the LLSQ to assess their degree of correspondence. Results: Twenty-two (30%) individuals reported no sleep problems whereas 20 (32%) reported some problems and 20 (33%) individuals reported poor sleep and 1 reported no sleep (n = 1). Median sleep efficiency was (94%) among response groups and mean overnight oxygen saturation was 81%. Median apnea hypopnea index (AHI; events/hour) was 10.2 in those who reported no problems sleeping, 5.1 in those reporting some problems sleeping, and 13.7 in those who reported poor sleep. These differences were not statistically significant. Conclusion: Self-reported sleep quality varied but there were no associated significant differences in sleep efficiency, overnight oxygen saturation, nor AHI. Studies that explore the role of objective sleep quality in the development of AMS should remove the sleep question on the LLSQ from AMS scoring algorithms.
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Mal de Altura , Altitud , Humanos , Calidad del Sueño , Autoinforme , Mal de Altura/diagnóstico , Sueño/fisiología , Enfermedad AgudaRESUMEN
BACKGROUND: The performance of the American College of Cardiology/American Heart Association pooled cohort equation (PCE) for atherosclerotic cardiovascular disease (ASCVD) in real-world clinical practice has not been evaluated extensively. OBJECTIVES: The goal of this study was to test the performance of PCE to predict ASCVD risk in the community, and determine if including individuals with values outside the PCE range (ie, age, blood pressure, cholesterol) or statin therapy initiation over follow-up would significantly affect PCE predictive capabilities. METHODS: The PCE was validated in a community-based cohort of consecutive patients who sought primary care in Olmsted County, Minnesota, between 1997 and 2000, followed-up through 2016. Inclusion criteria were similar to those of PCE derivation. Patient information was ascertained by using the record linkage system of the Rochester Epidemiology Project. ASCVD events (nonfatal and fatal myocardial infarction and ischemic stroke) were validated in duplicate. Calculated and observed ASCVD risk and c-statistics were compared across predefined groups. RESULTS: This study included 30,042 adults, with a mean age of 48.5 ± 12.2 years; 46% were male. Median follow-up was 16.5 years, truncated at 10 years for this analysis. Mean ASCVD risk was 5.6% ± 8.73%. There were 1,555 ASCVD events (5.2%). The PCE revealed good performance overall (c-statistic 0.78) and in sex and race subgroups; it was highest among non-White female subjects (c-statistic 0.81) and lowest in White male subjects (c-statistic 0.77). Out-of-range values and initiation of statin medication did not affect model performance. CONCLUSIONS: The PCE performed well in a community cohort representing real-world clinical practice. Values outside PCE ranges and initiation of statin medication did not affect performance. These results have implications for the applicability of current strategies for the prevention of ASCVD.
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Aterosclerosis , Enfermedades Cardiovasculares , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Adulto , Estados Unidos/epidemiología , Humanos , Masculino , Femenino , Persona de Mediana Edad , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/tratamiento farmacológico , Factores de Riesgo , Medición de Riesgo/métodos , Aterosclerosis/tratamiento farmacológico , Factores de Riesgo de Enfermedad CardiacaRESUMEN
PURPOSE: To determine the outcome of ulnar head endoprostheses in the treatment of distal radioulnar joint instability, arthrosis, or both. METHODS: We conducted a retrospective review of 47 patients to analyze the outcome of a single ulnar head replacement over a 10-year period. All patients reported pain or instability at the distal radioulnar joint. Standardized assessments included a patient-rated pain score, forearm range of motion, grip strength, and Mayo wrist score. We examined preoperative and postoperative radiographs for final implant position, loosening, and osteolysis. RESULTS: We observed 47 patients for a median of 56 months (minimum, 16 mo). There was a statistically significant decrease in pain scores from 4.6 to 2.2 and improvement in the mean Mayo wrist score from 14 to 69 points after surgery. There was no significant improvement in forearm rotation and wrist function. Kaplan-Meier analysis demonstrated 83% survival at 6 years. A total of 14 patients (30%) required additional surgical procedures after primary arthroplasty. Risk factors for failure included history of previous surgery, use of an extended collar, lucency greater than 2 mm around the implant stem, and pedestal formation at the tip of the implant. CONCLUSIONS: Distal ulna implant arthroplasty reduces pain and improves function in patients with distal radioulnar joint instability, arthrosis, or both.
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Artroplastia de Reemplazo/métodos , Prótesis Articulares , Cúbito/cirugía , Articulación de la Muñeca/cirugía , Adulto , Anciano , Femenino , Fuerza de la Mano/fisiología , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Complicaciones Posoperatorias , Modelos de Riesgos Proporcionales , Diseño de Prótesis , Radiografía , Rango del Movimiento Articular/fisiología , Recuperación de la Función , Reoperación , Estudios Retrospectivos , Rotación , Resultado del Tratamiento , Cúbito/diagnóstico por imagen , Articulación de la Muñeca/diagnóstico por imagenRESUMEN
Importance: US rural vs nonrural populations have striking disparities in diabetes care. Whether rurality contributes to disparities in diabetes mortality is unknown. Objective: To examine rates and trends in diabetes mortality based on county urbanization. Design, Setting, and Participants: In this observational, cross-sectional study, the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database was searched from January 1, 1999, to December 31, 2018, for diabetes as a multiple cause and the underlying cause of death among residents aged 25 years or older in US counties. County urbanization was categorized as metro, medium-small, and rural. Weighted multiple linear regression models and jackknife resampling, with a 3-segment time component, were used. The models included exposures with up to 3-way interactions and were age standardized to the 2009-2010 population. The analyses were conducted from July 1, 2020, to February 1, 2022. Exposures: County urbanization (metro, medium-small, or rural), gender (men or women), age group (25-54, 55-74, or ≥75 years), and region (Midwest, Northeast, South, or West). Main Outcomes and Measures: Annual diabetes mortality rate per 100â¯000 people. Results: From 1999-2018, based on 4â¯022â¯238â¯309 person-years, diabetes was a multiple cause of death for 4â¯735â¯849 adults aged 25 years or older. As a multiple cause, diabetes mortality rates in 2017-2018 vs 1999-2000 were highest and unchanged in rural counties (157.2 [95% CI, 150.7-163.7] vs 154.1 [95% CI, 148.2-160.1]; P = .49) but lower in medium-small counties (123.6 [95% CI, 119.6-127.6] vs 133.6 [95% CI, 128.4-138.8]; P = .003) and urban counties (92.9 [95% CI, 90.5-95.3] vs 109.7 [95% CI, 105.2-114.1]; P < .001). In 2017-2018 vs 1999-2000, mortality rates were higher in rural men (+18.2; 95% CI, 14.3-22.1) but lower in rural women (-14.0; 95% CI, -17.7 to -10.3) (P < .001 for both). In the 25- to 54-year age group, mortality rates in 2017-2018 vs 1999-2000 showed a greater increase in rural counties (+9.4; 95% CI, 8.6-10.2) compared with medium-small counties (+4.5; 95% CI, 4.0-5.0) and metro counties (+0.9; 95% CI, 0.4-1.4) (P < .001 for all). Of all regions and urbanization levels, the mortality rate in 2017-2018 vs 1999-2000 was higher only in the rural South (+13.8; 95% CI, 7.6-20.0; P < .001). Conclusions and Relevance: In this cross-sectional study, US rural counties had the highest overall diabetes mortality rate. The determinants of persistent rural disparities, in particular for rural men and for adults in the rural South, require investigation.
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Diabetes Mellitus , Población Rural , Adulto , Estudios Transversales , Diabetes Mellitus/epidemiología , Femenino , Humanos , MasculinoRESUMEN
Background: Contemporary prevalence, awareness, and control of severe hypercholesterolemia (SH) and familial hypercholesterolemia (FH) and the associated atherosclerotic cardiovascular disease risk in the US are unknown. Method: Using electronic health records, we assessed the burden of SH and FH in Olmsted County, Minnesota, US, between 2004 and 2015. We defined SH as low-density lipoprotein cholesterol (LDL-C) level ≥190 mg/dl without secondary causes of hypercholesterolemia and FH as a Dutch Lipid Clinic Network score ≥6. Controls were age- and sex-matched individuals with LDL-C level <190 mg/dl. Results: The age- and sex-adjusted point and period prevalence (age-recursive method) of SH was 4.44% and 8.95%, respectively; 1 in 21 had FH (â¼1:233 adults), and 46.2% had a recorded diagnosis. Guideline recommended targets (LDL-C <100 mg/dl and <70 mg/dl in the primary and secondary prevention settings, respectively) were achieved in 33.1% and 21.2% of SH cases, with less women overall achieving the target than men (18.6% vs. 23.7%, p=0.022). After adjustment for conventional risk factors, the hazard ratio for incident coronary heart disease (CHD) in those with SH was 1.21 (1.05-1.39; p=0.010), in those with SH and a family history of CHD was 2.16 (1.57-2.96; p<0.001) and in those with FH was 4.61 (2.66-7.97; p<0.001). The association of SH with CHD was modified by age (p-interaction = 0.015), such that the risk was greater at younger ages. Conclusions: SH was prevalent and an independent risk factor for incident CHD. Awareness and control were low, highlighting a treatment gap (more prominent in women) that needs to be addressed.
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OBJECTIVES: Although lymphatic spread is common in intrahepatic cholangiocarcinoma (ICC), lymphadenectomy is not widely performed as part of operative resection in this disease. The objectives of this study were to assess national trends for lymphadenectomy and its impact on survival in patients with ICC. METHODS: The National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) registry was queried to identify patients with ICC (n=4893) reported during 1988-2007. Kaplan-Maier and Cox proportional hazards regression were used to analyse survival. RESULTS: Five-year overall survival (OS) was 5.2%. Lymph node (LN) status was available for 48.9% (n=2391) of patients. Histologic LN evaluation was performed in 13.5% (n=658) of patients for a median of two (interquartile range: 1-3) LNs. During the study period, the frequency of histologic LN assessment (P=0.78) did not change in liver resection patients. In the 733 resected patients, positive vs. negative LN status was associated with worse 5-year OS of 8.4% vs. 25.9%, respectively (hazard ratio=1.8; P<0.001). CONCLUSIONS: Nodal status is an important prognostic factor for survival in patients diagnosed with ICC. In the USA, few patients undergo hepatic resection with lymphadenectomy; therefore, the clinical benefit of formal lymphadenectomy in ICC remains unknown.
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Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos/patología , Conductos Biliares Intrahepáticos/cirugía , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Hepatectomía , Escisión del Ganglio Linfático , Anciano , Neoplasias de los Conductos Biliares/mortalidad , Colangiocarcinoma/mortalidad , Femenino , Hepatectomía/mortalidad , Hepatectomía/tendencias , Humanos , Estimación de Kaplan-Meier , Modelos Lineales , Modelos Logísticos , Escisión del Ganglio Linfático/mortalidad , Escisión del Ganglio Linfático/tendencias , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Selección de Paciente , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Programa de VERF , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
Background Hypertriglyceridemia is associated with increased risk of coronary heart disease but the association is often attributed to concomitant metabolic abnormalities. We investigated the epidemiology of primary isolated hypertriglyceridemia (PIH) and associated cardiovascular risk in a population-based setting. Methods and Results We identified adults with at least one triglyceride level ≥500 mg/dL between 1998 and 2015 in Olmsted County, Minnesota. We also identified age- and sex-matched controls with triglyceride levels <150 mg/dL. There were 3329 individuals with elevated triglyceride levels; after excluding those with concomitant hypercholesterolemia, a secondary cause of high triglycerides, age <18 years or an incomplete record, 517 patients (49.4±14.0 years, 72.0% men) had PIH (triglyceride 627.6±183.6 mg/dL). The age- and sex-adjusted prevalence of PIH in adults was 0.80% (0.72-0.87); the diagnosis was recorded in 60%, 46% were on a lipid-lowering medication for primary prevention and a triglyceride level <150 mg/dL was achieved in 24.1%. The association of PIH with coronary heart disease was attenuated but remained significant after adjustment for demographic, socioeconomic, and conventional cardiovascular risk factors (hazard ratio [HR], 1.53; 95% CI, 1.06-2.20; P= 0.022). There was no statistically significant association between PIH and cerebrovascular disease (HR, 1.06; 95% CI, 0.65-1.73, P= 0.813), peripheral artery disease (HR, 1.27; 95% CI, 0.43-3.75; P= 0.668), or the composite end point of all 3 (HR, 1.28; 95% CI, 0.92-1.80; P=0.148) in adjusted models. Conclusions PIH was associated with incident coronary heart disease events (although there was attenuation after adjustment for conventional risk factors), supporting a causal role for triglycerides in coronary heart disease. The condition is relatively prevalent but awareness and control are low.
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Enfermedad Coronaria/epidemiología , Hipertrigliceridemia/complicaciones , Vigilancia de la Población , Medición de Riesgo/métodos , Triglicéridos/sangre , Biomarcadores/sangre , Enfermedad Coronaria/sangre , Enfermedad Coronaria/etiología , Femenino , Humanos , Hipertrigliceridemia/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Minnesota/epidemiología , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
This study aimed to determine if there is a co-elevation of human blood arsenic and mercury levels in the Midwestern population of the United States (U.S.) and to determine any geographical patterns and variation of arsenic and mercury that may exist in Michigan. 58,800 blood specimens along with associated demographic/geographic data from the contiguous United States were reviewed. Univariate and multivariable logistic regression were used to analyze demographic/geographic variables associated with elevated arsenic concentrations. Furthermore, blood data from patients in Michigan were aggregated to the ZIP code tabulation area (ZCTA) in order to assess geographic variation using spatial regression models. SaTScan software was also used to analyze potential clustering of arsenic and mercury across Michigan ZCTAs. Within the contiguous United States, elevated mercury blood concentrations, older age, female sex, and coastal status were all associated with elevated arsenic blood concentrations (elevated mercury odds ratio (OR) 3.18 (3.04-3.33); female sex OR 1.06 (1.02-1.11); +10 yr age OR 1.12 (1.11-1.14); coastal state OR 1.33 (1.27-1.40). Within the state of Michigan, as with the continuous U.S., elevated mercury blood concentrations and older age were associated with elevated arsenic blood concentrations (elevated mercury OR 2.75 (2.38-3.18); female sex OR 1.06 (0.95-1.19); +10 yr age OR 1.10 (1.06-1.13). Using spatial regression, it was determined that within Michigan, economic inequality (measured via the Gini coefficient) was also associated with elevated concentrations of mercury in the blood. Clinical reference laboratory data, in conjunction with spatial analysis methods, may enhance our understanding of how elemental exposure affects human health and should be considered for studying how environmental contaminants, socioeconomics and geography affect the health of populations.
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Arsénico/análisis , Exposición a Riesgos Ambientales/análisis , Mercurio/análisis , Adulto , Anciano , Exposición a Riesgos Ambientales/estadística & datos numéricos , Femenino , Geografía , Humanos , Masculino , Michigan , Persona de Mediana Edad , Estados UnidosRESUMEN
OBJECTIVES: Expression of prostaglandin biosynthetic pathway enzymes in mucinous pancreatic cysts is unknown. Cyclooxygenase-2 (COX-2) inhibition is a potential cancer chemoprevention strategy for these lesions. We evaluated the expression of COX-2, cytosolic phospholipase A2 (cPLA2), and protein kinase B (AKT) in the epithelium of pancreatic cysts and correlated enzyme expression with aspirin (ASA) use and cyst fluid prostaglandin E2 (PGE2) concentration. METHODS: Pathology of 80 resected pancreatic cysts was reviewed. Expression of COX-2, cPLA2, and AKT was quantified by tissue immunohistochemistry immunoreactivity scores (IRSs). IRS values were compared between cyst types and (in 30 cases) with matched cyst fluid PGE2 concentrations. RESULTS: The mean IRS was higher in the epithelium of mucinous vs nonmucinous cysts for COX-2 (6.1 ± 4.7 vs 3.2 ± 2.8, P = 0.01) and cPLA2 (6.9 ± 3.0 vs 2.9 ± 2.9, P < 0.001). Cyst epithelial COX-2 expression was higher in mucinous cysts with low-grade dysplasia vs those with high-grade dysplasia or invasive carcinoma (IRS 8.0 ± 3.9 vs 1.5 ± 2.9, P < 0.001), whereas the opposite was found for cPLA2 (6.2 ± 3.0 vs 8.6 ± 2.3, P = 0.005). Cyst fluid PGE2 concentrations did not correlate with either the IRS or a history of low- to moderate-dose ASA use. CONCLUSIONS: COX-2 and cPLA2 are overexpressed in the epithelium of mucinous pancreatic cysts. COX-2 and/or cPLA2 inhibition might prevent the emergence or progression of mucinous pancreatic cysts, but higher doses of ASA or nonsteroidal anti-inflammatory drugs may be necessary to substantially inhibit cyst epithelial COX-2 activity.
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Carcinoma Ductal Pancreático/patología , Ciclooxigenasa 2/metabolismo , Quiste Pancreático/patología , Neoplasias Pancreáticas/patología , Fosfolipasas A2 Citosólicas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Aspirina/farmacología , Aspirina/uso terapéutico , Carcinoma Ductal Pancreático/prevención & control , Inhibidores de la Ciclooxigenasa/farmacología , Inhibidores de la Ciclooxigenasa/uso terapéutico , Líquido Quístico/química , Dinoprostona/análisis , Dinoprostona/metabolismo , Epitelio/efectos de los fármacos , Epitelio/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Páncreas/efectos de los fármacos , Páncreas/patología , Quiste Pancreático/tratamiento farmacológico , Neoplasias Pancreáticas/prevención & control , Proteínas Proto-Oncogénicas c-akt/metabolismo , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: To analyze consistency of reference limits and widths of reference intervals (RIs) calculated by six procedures and evaluate a protocol for merging intrainstitutional reference data. METHODS: The differences between reference limits were compared with "optimal" bias goals. Also, widths of the RIs were compared. RIs were calculated using Mayo-SAS quantile, EP Evaluator, and four International Federation of Clinical Chemistry and Laboratory Medicine methods: parametric and nonparametric (NP) with and without latent abnormal values exclusion (LAVE). Regression parameters from cotested samples were evaluated for harmonizing intrainstitutional reference data. RESULTS: Mayo-SAS quintile, LAVE(-)NP, and EP Evaluator generated similar RIs, but these RIs often were wider than RIs from parametric procedures. LAVE procedures generated narrower RIs for nutritional and inflammatory markers. Transformation with regression parameters did not ensure homogeneity of merged data. CONCLUSIONS: Parametric methods are recommended when inappropriate values cannot be excluded. The nonparametric procedures may generate wider RIs. Data sets larger than 200 are recommended for robust estimates. Caution should be exercised when merging intrainstitutional data.
Asunto(s)
Técnicas de Laboratorio Clínico/normas , Humanos , Valores de ReferenciaRESUMEN
OBJECTIVE: To understand why the population-based incidence of diverticulitis has increased over time, we studied temporal changes in age, body mass index (BMI), and diverticulitis in Olmsted County, Minnesota. PARTICIPANTS AND METHODS: We compared the BMIs of 2967 patients with diverticulitis and 9795 people without diverticulitis from January 1, 1980, through December 31, 2007. Because BMI is a surrogate for adipose tissue, computed tomographic estimations of abdominal fat content were compared between 381 diverticulitis cases and 381 age- and sex-matched controls. RESULTS: Between 1980 and 2007, the prevalence of obesity increased from 12% to 49% in the population and from 19% to 40% in patients with diverticulitis (P<.001 for both). Temporal trends in age, BMI, and the increased incidence of diverticulitis in people with normal BMI accounted for 48%, 47%, and 20%, respectively, of corresponding trends in diverticulitis. The secular decline in the proportion of people with normal BMI was partly offset by an increased incidence of diverticulitis in such people. In the case-control study, BMI was greater in cases than in controls (P=.001). However, after incorporating abdominal visceral (odds ratio [OR], 2.4; 95% CI, 1.6-3.7) and subcutaneous (OR, 2.9; 95% CI, 1.7-5.2) fat content (both associated with diverticulitis), BMI was associated with lower risk (OR, 0.8; 95% CI, 0.7-0.8) of diverticulitis. CONCLUSION: Aging, increasing obesity, and the increased incidence of diverticulitis in people with normal BMI account for the temporal increase in diverticulitis. Rather than BMI per se, increased abdominal visceral and subcutaneous fat are independently associated with diverticulitis. The incidence of diverticulitis, which is among the most common gastrointestinal diagnoses in hospitalized patients, has increased markedly since 2000. This study suggests that aging, increasing obesity, and the increased incidence of diverticulitis in people with normal BMI account for the temporal increase in diverticulitis.
Asunto(s)
Diverticulitis/epidemiología , Obesidad/complicaciones , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Estudios de Casos y Controles , Diverticulitis/etiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Minnesota/epidemiología , Obesidad/epidemiología , Dinámica Poblacional , Factores de RiesgoRESUMEN
BACKGROUND: Medication use in the intensive care unit (ICU) depends on creatinine-based glomerular filtration rate (GFR) estimates. Urine output deterioration may precede the creatinine rise resulting in delayed recognition of GFR reductions. Our objective was to quantify the disparity between estimated GFR (eGFR) and true GFR in ICU patients with hospital-acquired oligoanuric acute kidney injury (hAKI). METHODS: This single-center cohort study examined adults who met the Acute Kidney Injury Network stage III urine output criterion ≥48 hours after ICU admission. True GFR was ≤15 mL/min/1.73 m(2), and eGFR was described by 6 different creatinine-based equations. True GFR and eGFR were compared on the day of hAKI diagnosis and followed for 4 days using multivariable linear regression with generalized estimating equations, adjusting for day and method. RESULTS: Of the 691 patients screened, we enrolled 61 patients. After adjustment for multiple comparisons and day, there were significant differences in eGFR between the estimation methods and true GFR (P < .001). After day adjustment, eGFR overestimated true GFR by 17 to 50 mL/min/1.73 m(2) and overestimation persisted through the fourth day of hAKI (P ≤ .001). CONCLUSION: Creatinine-based equations overestimated GFR in ICU patients with hAKI. This study highlights a population at risk of medication misadventures in whom systems optimization should be considered.