Venous Access: National Guideline and Registry Development (VANGUARD): Advancing Patient-Centered Venous Access Care Through the Development of a National Coordinated Registry Network.

There are over 8 million central venous access devices inserted each year, many in patients with chronic conditions who rely on central access for life-preserving therapies. Central venous access device-related complications can be life-threatening and add tens of billions of dollars to health care costs, while their incidence is most likely grossly mis- or underreported by medical institutions. In this communication, we review the challenges that impair retention, exchange, and analysis of data necessary for a meaningful understanding of critical events and outcomes in this clinical domain. The difficulty is not only with data extraction and harmonization from electronic health records, national surveillance systems, or other health information repositories where data might be stored. The problem is that reliable and appropriate data are not recorded, or falsely recorded, at least in part because policy, payment, penalties, proprietary concerns, and workflow burdens discourage completeness and accuracy. We provide a roadmap for the development of health care information systems and infrastructure that address these challenges, framed within the context of research studies that build a framework of standardized terminology, decision support, data capture, and information exchange necessary for the task. This roadmap is embedded in a broader Coordinated Registry Network Learning Community, and facilitated by the Medical Device Epidemiology Network, a Public-Private Partnership sponsored by the US Food and Drug Administration, with the scope of advancing methods, national and international infrastructure, and partnerships needed for the evaluation of medical devices throughout their total life cycle.

Comparison of Unibody and Non-Unibody Endografts for Abdominal Aortic Aneurysm Repair in Medicare Beneficiaries: The SAFE-AAA Study.

BACKGROUND: Concerns have been raised about the long-term performance of aortic stent grafts for the treatment of abdominal aortic aneurysms, in particular, unibody stent grafts (eg, Endologix AFX AAA stent grafts). Only limited data sets are available to evaluate the long-term risks related to these devices. The SAFE-AAA Study (Comparison of Unibody and Non-Unibody Endografts for Abdominal Aortic Aneurysm Repair in Medicare Beneficiaries Study) was designed with the Food and Drug Administration to provide a longitudinal assessment of the safety of unibody aortic stent grafts among Medicare beneficiaries. METHODS: The SAFE-AAA Study was a prespecified, retrospective cohort study evaluating whether unibody aortic stent grafts are noninferior to non-unibody aortic stent grafts with respect to the composite primary outcome of aortic reintervention, rupture, and mortality. Procedures were evaluated from August 1, 2011, through December 31, 2017. The primary end point was evaluated through December 31, 2019. Inverse probability weighting was used to account for imbalances in observed characteristics. Sensitivity analyses were used to evaluate the effect of unmeasured confounding, including assessment of the falsification end points heart failure, stroke, and pneumonia. A prespecified subgroup included patients treated from February 22, 2016, through December 31, 2017, corresponding to the market release of the most contemporary unibody aortic stent grafts (Endologix AFX2 AAA stent graft). RESULTS: Of 87 163 patients who underwent aortic stent grafting at 2146 US hospitals, 11 903 (13.7%) received a unibody device. The average age of the total cohort was 77.0±6.7 years, 21.1% were female, 93.5% were White, 90.8% had hypertension, and 35.8% used tobacco. The primary end point occurred in 73.4% of unibody device-treated patients versus 65.0% of non-unibody device-treated patients (hazard ratio, 1.19 [95% CI, 1.15-1.22]; noninferior P value of 1.00; median follow-up, 3.4 years). Falsification end points were negligibly different between groups. In the subgroup treated with contemporary unibody aortic stent grafts, the cumulative incidence of the primary end point occurred in 37.5% of unibody device-treated patients and 32.7% of non-unibody device-treated patients (hazard ratio, 1.06 [95% CI, 0.98-1.14]). CONCLUSIONS: In the SAFE-AAA Study, unibody aortic stent grafts failed to meet noninferiority compared with non-unibody aortic stent grafts with respect to aortic reintervention, rupture, and mortality. These data support the urgency of instituting a prospective longitudinal surveillance program for monitoring safety events related to aortic stent grafts.

The Usefulness of Spectroscopic Simulations.

This article presents a method for extracting the optical constants of homogeneous isotropic materials using the infrared spectra of that material. The method is based on using the harmonic oscillator model of molecular polarizability to obtain optical constants, then calculating the spectrum, comparing the calculated spectrum to an experimental spectrum of the material, and adjusting the model parameters until a close fit between the spectra is obtained. Corrections that need to be made to the experimental spectra in order to remove instrumental distortions are also briefly described. The remainder of the article centers on describing how the optical constants can be used to simulate spectra of that material in different experimental arrangements and the benefits that spectral simulations afford to experimentalists.

Causes of death in 184 patients with type 1 Gaucher disease from the United States who were never treated with enzyme replacement therapy.

Treatment for type 1 Gaucher disease (GD1) decreases morbidity from hematological cytopenias, hepatosplenomegaly and bone complications. Consequently, untreated symptomatic patients for study of late outcomes are hard to find. We identified 184 untreated GD1 patients (67.4% Ashkenazi; splenectomy 51.1%) who died between 1950 and 2010. Here, we report confirmed causes of death for these patients compared with the overall US population. Median age of death 66years (2-97years); causes of death (COD) with a high proportional mortality rate (PMR) included malignancies (PMR 1.57), suicide/drug overdose (PMR 3.86), liver disease (PMR 4.76) and septicemia (PMR 9.22). PMRs for CNS/gastrointestinal bleeding, pulmonary hypertension, post-splenectomy complications and Parkinsonism were also increased. PMR for heart disease (0.33) was significantly decreased. Average age at death was normal for heart disease, septicemia, suicide, and malignancies but younger for liver disease and Parkinsonism. COD more prevalent in splenectomy patients included liver disease, septicemia, pulmonary hypertension and GI bleeding. With timely diagnosis, improved risk assessment and obsolescence of splenectomy, GD1-associated malignancies, liver disease, septicemia, pulmonary hypertension, suicide and drug dependency may decrease with early institution of appropriate treatment. Our population of untreated patients is a valuable historical control for studies of the effect of GD1 treatment on premature mortality.

FDA Regulatory Perspectives for Studies on Hemodialysis Vascular Access.

In an effort to foster innovation and new product development, the American Society of Nephrology and the US Food and Drug Administration partnered to form the Kidney Health Initiative in 2012. Part of the Kidney Health Initiative's mission is to foster development of therapies by creating a collaborative environment where the US Food and Drug Administration and the greater nephrology community can interact to optimize product evaluation. This particular Kidney Health Initiative project focused on products related to hemodialysis vascular access, with the goal of clarifying appropriate trial end points that could subsequently inform clinical, regulatory, and coverage decisions. Both the lack of common definitions and the lack of consensus on trial end points have been viewed as barriers to innovation in this area. Toward this end, the Kidney Health Initiative convened teams of expert stakeholders to address these issues for each major vascular access category (arteriovenous grafts, arteriovenous fistulas, and central venous catheters), and each team provided recommendations. This commentary provides an overview of the US Food and Drug Administration centers that regulate hemodialysis vascular access and certain laws and regulations that affect these products as well as our perspectives on some of the issues raised and end points proposed by the Kidney Health Initiative teams. The standardized definitions and clinical trial end points proposed by the teams represent an important step forward to improve innovation in this area.

Causes of death due to hematological and non-hematological cancers in 57 US patients with type 1 Gaucher Disease who were never treated with enzyme replacement therapy.

Patients with type 1 Gaucher disease (GD1) have increased risk of developing myeloma, other hematological cancers, hepatocellular carcinoma, and other solid tumors. Patient awareness of the GD1-cancer association causes anxiety and fear. Little is known about cancer as a cause of death in GD1, especially in patients never treated with GD1-specific therapies. Consequently, the effect of treatment on cancer mortality in GD1 patients is difficult to evaluate. In this review, starting with a population of 184 GD1 cases never treated, we annotate and analyze the causes of death of 57 GD1 patients who died of cancer. The proportional mortality ratio (PMR) for all malignancies in patients with GD1 is 1.57 (p = 0.0002), but it is much higher for myeloma (PMR = 9.66) and other hematological cancers, hepatocellular carcinoma, and kidney cancer (PMR = ≍4). However, deaths from colorectal and pancreatic cancers were not more frequent than expected, and deaths from lung, breast, gynecological, and prostate cancer occurred less than anticipated. Herein, we discuss whether GD1 is truly a hereditary cancer syndrome and the problem of comorbidities and cancer risk assessment, and we speculate as to whether the variability in death by cancer type might be attributable to biochemical sequelae of tumor cell and macrophage/stromal cell GBA1 mutation affecting signals for metastasis, the process most closely associated with cancer mortality.

Nonalcoholic steatohepatitis (NASH) does not increase complications after laparoscopic bariatric surgery.

BACKGROUND: Advanced liver disease is associated with increased risk for postoperative complications. It is not well known whether the presence of nonalcoholic steatohepatitis (NASH) in morbidly obese patients contributes to the rate of postoperative complications. The main objective was to study the association between NASH and postoperative complications in bariatric patients. METHODS: A total of 340 contemporary sequential patients who underwent laparoscopic bariatric operations and who had intraoperative liver biopsies were studied. The rates of severe postoperative complications were compared across three patient groups-those with (1) no liver disease or with simple steatosis, (2) mild nonalcoholic NASH [steatosis with necroinflammation and mild fibrosis (stage 0-1)], and (3) advanced NASH [steatosis, necroinflammation, and more advanced fibrosis (stage ≥ 2)]. RESULTS: Of 340 patients, 141 (42%) had no NASH, and 151 (44%) and 48 (14%) had mild and advanced NASH, respectively. Superobesity (P = 0.037), diabetes (P < 0.001), and cerebrovascular disease (P = 0.013) had highest frequencies in patients with advanced NASH. Hypertension was highly prevalent in cohort (57%) but similarly distributed across three groups. Forty-five patients experienced at least one complication (pulmonary 4, cardiovascular 8, surgical 16, and acute kidney injury 21). The complications rate did not differ significantly across NASH categories. Median hospital stay was 3 days (IQR 2, 3), and it was not associated with NASH severity. There were no 30-day postoperative deaths. CONCLUSIONS: Despite the high prevalence of NASH among morbidly obese surgical patients, this condition was not associated with increased risk for postoperative complications. Postoperative acute kidney injury was the most frequent single complications.

The doctoral education of professional marriage and family therapists.

The professional practice of marriage and family therapy (MFT) scholarship is regulated at the master's level in the United States. Consequently, contemporary curricular issues have largely been focused on what is to be achieved within the master's degree, with an emphasis on clinical practice. We consider here what value may and should be added through the doctoral degree in marriage and family therapy. Doctoral programs are the developmental stage wherein we should seek to transmit the specialized knowledge and skills germane to MFT scholarship and practice in diverse settings, e.g., clinical and research intensive university, family law, health care, child development and education, child welfare, juvenile justice, faith based, and business. However, underlying this specialty education are three transcendental goals: sophistication of family systems scholarship, socialization into the profession of MFT, and cultivation of professional maturity.

Differences in antioxidant levels of fresh, frozen and freeze-dried strawberries and strawberry jam.

The present study was conducted to determine differences in antioxidant levels of fresh, frozen, and freeze-dried strawberries, and strawberry jam. Hydrophilic antioxidant activity (HAA) and lipophilic antioxidant activity (LAA) were measured using the ABTS/H2O2/HRP decoloration method. HAA and LAA were then summed to calculate the total antioxidant activity (TAA). Mean differences in HAA and LAA were analyzed using one-way analysis of variance and Dunnett's T3 pairwise comparisons. The mean TAA for freeze-dried strawberries based on an 'as consumed' weight (95% confidence interval [CI]: 29.58, 30.58) was significantly higher than for fresh (95% CI: 3.18, 3.66), frozen (95% CI: 2.58, 2.79), and jam (95% CI: 1.10, 1.22). The mean TAA based on dry weight for fresh strawberries (95% CI: 40.48, 46.67) was significantly higher than for freeze-dried (95% CI: 29.58, 30.58), frozen (95% CI: 24.62, 26.59), and jam (95% CI: 1.48, 1.64). Results agree with previous studies reporting that strawberries are a valuable source of antioxidants for consumers.

Link between diet and cardiovascular disease in Latin America and the Caribbean using geographic information systems / Vinculación de la dieta con la enfermedad cardiovascular en América Latina y el Caribe mediante sistemas de información geográfica

OBJECTIVE: To determine the visual, spatial, and/or statistical relationships between food availability/dietary patterns and cardiovascular disease (CVD) in Latin America and the Caribbean (LAC). METHODS: CVD mortality rates and diet information (the number of kilocalories and amount of alcohol, fats, fish, fruits, meats, sugars, and vegetables available per person daily) were obtained from internationally available databases. The analyses included 32 LAC countries with sufficient data (15 of 47 had been excluded for incomplete data). Pearson's correlations (r) were used to determine relationships between diet and CVD mortality, and multiple linear regression analysis was conducted to identify predictors of mortality. ArcGIS version 9.2 (Environmental Systems Research Institute, Inc., Redlands, California, United States) was used to construct maps to explore visual relationships between CVD and diet. RESULTS: No relationships were found between CVD and alcohol, fruit, meat, sugar, or vegetable intake. Statistically significant, positive correlations were found between oil-crops (r = 0.680, P = 0.000) and fish and seafood (r = 0.411, P = 0.019) and CVD mortality. Regression analysis revealed that high kilocalorie availability was a predictor of low CVD mortality (P = 0.020). High oil-crop availability was a predictor of high CVD mortality (P = 0.000). Maps constructed show visual relationships between availability of fish and seafood, kilocalories, and oil-crops, and CVD mortality. CONCLUSIONS: Fish and seafood, kilocalorie, and oil-crop availability appear to be related to CVD mortality, but further investigation is needed. Associations between diet and CVD mortality create the opportunity to target specific countries for nutrition education and CVD prevention programs.

OBJETIVOS: Determinar la relación visual, espacial y estadística entre los patrones dietéticos y de disponibilidad alimentaria, y la enfermedad cardiovascular (ECV) en América Latina y el Caribe. MÉTODOS: Las kilocalorías y la cantidad de alcohol, grasas, pescado, frutas, carnes, azúcar y vegetales disponibles por persona diariamente, las tasas de mortalidad por ECV y la información dietética se obtuvieron de bases de datos internacionales. El análisis abarcó 32 de los 47 países latinoamericanos y caribeños con datos suficientes (se excluyeron 15 países por datos incompletos). Se determinó la relación entre la dieta y la mortalidad por ECV mediante el análisis de correlación de Pearson (r) y se identificaron los factores de predicción de la mortalidad mediante el análisis de regresión lineal múltiple. Se elaboraron mapas para explorar las relaciones visuales entre la ECV y la dieta con el programa ArcGIS 9.2 (Environmental Systems Research Institute, Inc., Redlands, California, Estados Unidos de América). RESULTADOS: No se encontró relación entre la ECV y el consumo de alcohol, frutas, carnes, azúcar o vegetales. Se observó una correlación directa significativa entre la mortalidad por ECV y el consumo de cultivos oleaginosos (r = 0,680; P < 0,001) y pescados y mariscos (r = 0,411; P = 0,019). El análisis de regresión reveló que la elevada disponibilidad calórica fue un factor de predicción de baja mortalidad por ECV (P = 0,020), mientras la alta disponibilidad de cultivos oleaginosos fue un factor de predicción de elevada mortalidad por ECV (P < 0,001). Los mapas elaborados mostraron relaciones visuales entre la disponibilidad de pescados y mariscos, kilocalorías y cultivos oleaginosos, por una parte, y la mortalidad por ECV por la otra. CONCLUSIONES: La disponibilidad de pescados y mariscos, kilocalorías y cultivos oleaginosos parece estar relacionada con la mortalidad por ECV, pero se necesitan estudios adicionales. Las asociaciones ...

Cooking does not decrease hydrophilic antioxidant capacity of wild blueberries.

The present study examined the effects of domestic cooking methods on the hydrophilic antioxidant activity (HAA) of wild blueberries. Baked, microwaved, simmered, and pan-fried frozen wild blueberries, and a thawed uncooked control, were analyzed for HAA using an ABTS/H(2)O(2)/HRP decoloration method. All cooking treatments were derived from recipes using wild blueberries, and were performed in triplicate. A randomized block design was used to determine whether there were statistical differences in antioxidant content after cooking and between each of the trials. There were no statistically significant decreases after cooking the thawed berries. On both a fresh weight and a dry weight basis, pan-fried blueberries had significantly higher HAA than baked, simmered, and control blueberries (P<0.05). Antioxidants in wild blueberries appear to be heat stable since cooked berries retained significant HAA. Cooked wild blueberries can be recommended as a good source of dietary antioxidants.

Link between diet and cardiovascular disease in Latin America and the Caribbean using geographic information systems.

OBJECTIVE: To determine the visual, spatial, and/or statistical relationships between food availability/dietary patterns and cardiovascular disease (CVD) in Latin America and the Caribbean (LAC). METHODS: CVD mortality rates and diet information (the number of kilocalories and amount of alcohol, fats, fish, fruits, meats, sugars, and vegetables available per person daily) were obtained from internationally available databases. The analyses included 32 LAC countries with sufficient data (15 of 47 had been excluded for incomplete data). Pearson's correlations (r) were used to determine relationships between diet and CVD mortality, and multiple linear regression analysis was conducted to identify predictors of mortality. ArcGIS version 9.2 (Environmental Systems Research Institute, Inc., Redlands, California, United States) was used to construct maps to explore visual relationships between CVD and diet. RESULTS: No relationships were found between CVD and alcohol, fruit, meat, sugar, or vegetable intake. Statistically significant, positive correlations were found between oil-crops (r = 0.680, P = 0.000) and fish and seafood (r = 0.411, P = 0.019) and CVD mortality. Regression analysis revealed that high kilocalorie availability was a predictor of low CVD mortality (P = 0.020). High oil-crop availability was a predictor of high CVD mortality (P = 0.000). Maps constructed show visual relationships between availability of fish and seafood, kilocalories, and oil-crops, and CVD mortality. CONCLUSIONS: Fish and seafood, kilocalorie, and oil-crop availability appear to be related to CVD mortality, but further investigation is needed. Associations between diet and CVD mortality create the opportunity to target specific countries for nutrition education and CVD prevention programs.

Implementation of a semi-automated post-processing system for parametric MRI mapping of human breast cancer.

Magnetic resonance imaging (MRI) investigations of breast cancer incorporate computationally intense techniques to develop parametric maps of pathophysiological tissue characteristics. Common approaches employ, for example, quantitative measurements of T (1), the apparent diffusion coefficient, and kinetic modeling based on dynamic contrast-enhanced MRI (DCE-MRI). In this paper, an integrated medical image post-processing and archive system (MIPAS) is presented. MIPAS demonstrates how image post-processing and user interface programs, written in the interactive data language (IDL) programming language with data storage provided by a Microsoft Access database, and the file system can reduce turnaround time for creating MRI parametric maps and provide additional organization for clinical trials. The results of developing the MIPAS are discussed including potential limitations of the use of IDL for the application framework and how the MIPAS design supports extension to other programming languages and imaging modalities. We also show that network storage of images and metadata has a significant (p < 0.05) increase in data retrieval time compared to collocated storage. The system shows promise for becoming both a robust research picture archival and communications system working with the standard hospital PACS and an image post-processing environment that extends to other medical image modalities.

Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b.

BACKGROUND: There have been indications that common Angiotensin Receptor Blockers (ARBs) may be exerting anti-inflammatory actions by directly modulating the immune system. We decided to use molecular modelling to rapidly assess which of the potential targets might justify the expense of detailed laboratory validation. We first studied the VDR nuclear receptor, which is activated by the secosteroid hormone 1,25-dihydroxyvitamin-D. This receptor mediates the expression of regulators as ubiquitous as GnRH (Gonadatrophin hormone releasing hormone) and the Parathyroid Hormone (PTH). Additionally we examined Peroxisome Proliferator-Activated Receptor Gamma (PPARgamma), which affects the function of phagocytic cells, and the C-CChemokine Receptor, type 2b, (CCR2b), which recruits monocytes to the site of inflammatory immune challenge. RESULTS: Telmisartan was predicted to strongly antagonize (Ki asymptotically equal to 0.04 nmol) the VDR. The ARBs Olmesartan, Irbesartan and Valsartan (Ki asymptotically equal to10 nmol) are likely to be useful VDR antagonists at typical in-vivo concentrations. Candesartan (Ki asymptotically equal to 30 nmol) and Losartan (Ki asymptotically equal to 70 nmol) may also usefully inhibit the VDR. Telmisartan is a strong modulator of PPARgamma (Ki asymptotically equal to 0.3 nmol), while Losartan (Ki asymptotically equal to 3 nmol), Irbesartan (Ki asymptotically equal to 6 nmol), Olmesartan and Valsartan (Ki asymptotically equal to 12 nmol) also seem likely to have significant PPAR modulatory activity. Olmesartan and Irbesartan (Ki asymptotically equal to 9 nmol) additionally act as antagonists of a theoretical model of CCR2b. Initial validation of this CCR2b model was performed, and a proposed model for the Angiotensin II Type1 receptor (AT2R1) has been presented. CONCLUSION: Molecular modeling has proven valuable to generate testable hypotheses concerning receptor/ligand binding and is an important tool in drug design. ARBs were designed to act as antagonists for AT2R1, and it was not surprising to discover their affinity for the structurally similar CCR2b. However, this study also found evidence that ARBs modulate the activation of two key nuclear receptors-VDR and PPARgamma. If our simulations are confirmed by experiment, it is possible that ARBs may become useful as potent anti-inflammatory agents, in addition to their current indication as cardiovascular drugs.

Sudanese refugee youth in foster care: the "lost boys" in America.

This study examined the resettlement experiences of unaccompanied Sudanese refugee youth placed in foster care from the perspectives of the youth, foster parents, and agency caseworkers. Youth experienced considerable success. The challenges of adjusting to school and family life, however, suggest a need for funding to support more intensive educational services, more cultural training and support for foster parents and school personnel, and flexibility to provide services in more culturally appropriate modalities.

Microdissection genotyping of archival fixative treated tissue for Gaucher disease.

The genetic diagnosis of Gaucher disease by molecular methods is complicated by the existence of a highly homologous transcribed pseudogene (96% identity) that is found in close proximity to the true gene on chromosome 1q21. In addition, the pseudogene sequence can mimic disease-causing mutations in the true gene. Selective polymerase chain reaction (PCR) amplification of the true gene can be accomplished in extracted DNA from fresh-frozen samples by designing oligonucleotide primers to hybridize to defined regions that are not present in the pseudogene. This standard molecular approach, which entails amplification of relatively long segments of intact DNA, is not feasible in archival, paraffin-embedded, solid-tissue specimens in which the negative effects of chemical fixation result in DNA strand scission and breakdown of nucleic acid. A novel approach, specifically created for use with archival, fixative-treated tissue specimens, was developed for detection and characterization of common mutations of Gaucher disease. Three separate robust PCR reactions were formulated, 2 for selective amplification of portions of only the true gene exons 2 and 9, with a third reaction targeting exon 10, wherein both the true and pseudogene were coamplified. In the latter, DNA sequencing was used to determine the presence of true and pseudogene allele content in addition to identification of base sequence alterations. This method, requiring a single, 4-microm-thick histologic section, was successfully applied to archival paraffin block tissue specimens that had been in storage for up to 75 years. It was capable of accurately genotyping common Gaucher disease mutations as well as discovering a novel mutation and genetic polymorphism. We recommend our approach when only fixative-treated tis sue is available for molecular genotyping.