Cost-Effectiveness of HIV Screening in Emergency Departments: Results From the Pragmatic Randomized HIV Testing Using Enhanced Screening Techniques in Emergency Departments Trial.

STUDY OBJECTIVE: Identification of HIV remains a critical health priority for which emergency departments (EDs) are a central focus. The comparative cost-effectiveness of various HIV screening strategies in EDs remains largely unknown. The goal of this study was to compare programmatic costs and cost-effectiveness of nontargeted and 2 forms of targeted opt-out HIV screening in EDs using results from a multicenter, pragmatic randomized clinical trial. METHODS: This economic evaluation was nested in the HIV Testing Using Enhanced Screening Techniques in Emergency Departments (TESTED) trial, a multicenter pragmatic clinical trial of different ED-based HIV screening strategies conducted from April 2014 through January 2016. Patients aged 16 years or older, with normal mental status and not critically ill, or not known to be living with HIV were randomized to 1 of 3 HIV opt-out screening approaches, including nontargeted, enhanced targeted, or traditional targeted, across 4 urban EDs in the United States. Each screening method was fully integrated into routine emergency care. Direct programmatic costs were determined using actual trial results, and time-motion assessment was used to estimate personnel activity costs. The primary outcome was newly diagnosed HIV. Total annualized ED programmatic costs by screening approach were calculated using dollars adjusted to 2023 as were costs per patient newly diagnosed with HIV. One-way and multiway sensitivity analyses were performed. RESULTS: The trial randomized 76,561 patient visits, resulting in 14,405 completed HIV tests, and 24 (0.2%) new diagnoses. Total annualized new diagnoses were 12.9, and total annualized costs for nontargeted, enhanced targeted, and traditional targeted screening were $111,861, $88,629, and $70,599, respectively. Within screening methods, costs per new HIV diagnoses were $20,809, $23,554, and $18,762, respectively. Enhanced targeted screening incurred higher costs but with similar annualized new cases detected compared with traditional targeted screening. Nontargeted screening yielded an incremental cost-effectiveness ratio of $25,586 when compared with traditional targeted screening. Results were most sensitive to HIV prevalence and costs of HIV tests. CONCLUSION: Nontargeted HIV screening was more costly than targeted screening largely due to an increased number of HIV tests performed. Each HIV screening strategy had similar within-strategy costs per new HIV diagnosis with traditional targeted screening yielding the lowest cost per new diagnosis. For settings with budget constraints or very low HIV prevalences, the traditional targeted approach may be preferred; however, given only a slightly higher cost per new HIV diagnosis, ED settings looking to detect the most new cases may prefer nontargeted screening.

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Heat Illness: 2024 Update.

The Wilderness Medical Society (WMS) convened an expert panel in 2011 to develop a set of evidence-based guidelines for the recognition, prevention, and treatment of heat illness. The current panel retained 5 original members and welcomed 2 new members, all of whom collaborated remotely to provide an updated review of the classifications, pathophysiology, evidence-based guidelines for planning and preventive measures, and recommendations for field- and hospital-based therapeutic management of heat illness. These recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks or burdens for each modality. This is an updated version of the WMS clinical practice guidelines for the prevention and treatment of heat illness published in Wilderness & Environmental Medicine. 2019;30(4):S33-S46.

Accelerated Cr (VI) removal by a three-dimensional electro-Fenton system using green iron nanoparticles.

Green-synthesized iron nanoparticles (GAP-FeNP) were used as particle electrodes in a three-dimensional electro-Fenton (3DEF) process to accelerate the removal of hexavalent chromium [Cr (VI)]. Removal was evaluated by varying the pH (3.0, 6.0, and 9.0) and initial Cr (VI) concentrations (10, 30, and 50 mg/L) at 5 and 25 min. These results demonstrated that GAP-FeNP/3DEF treatment achieved more than 94% Cr (VI) removal under all tested conditions. Furthermore, it was observed that Cr (VI) removal exceeded 98% under pH 9.0 in all experimental parameters tested. The results of the response surface methodology (RSM) determined two optimal conditions: the first, characterized by a pH of 3.0, Cr (VI) concentration at 50 mg/L, and 25 min, yielded a Cr (VI) removal of 99.7%. The second optimal condition emerged at pH 9.0, with Cr (VI) concentrations of 10 mg/L and 5 min, achieving a Cr (VI) removal of 99.5%. This study highlights the potential of the GAP-FeNP to synergistically accelerate Cr (VI) removal by the 3DEF process, allowing faster elimination and expansion of the alkaline (pH 9.0) applicability. PRACTITIONER POINTS: The required time for >99% of Cr (VI) removal by the GAP-FeNP/3DEF process was shortened from 25 to 5 min. EF process with GAP-FeNP reduces the time necessary for Cr (VI) removal, which is 67% faster than conventional methods. EF process using GAP-FeNP removed >94% of Cr (VI) after 25 min for all initial Cr (VI) concentrations and pH treatments. Cr (VI) removal by the GAP-FeNP/3DEF process was >98% at a pH of 9.0, widening the solution pH applicability.

The Liver in Hemophagocytic Lymphohistiocytosis: Not an Innocent Bystander.

Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystemic hyperinflammatory disease commonly associated with hepatic dysfunction. Liver injury is mediated by unchecked antigen presentation, hypercytokinemia, dysregulated cytotoxicity by natural killer and CD8 T cells, and disruption of intrinsic hepatic metabolic pathways. Over the past decade, there have been significant advances in diagnostics and expansion in therapeutic armamentarium for this disorder allowing for improved morbidity and mortality. This review discusses the clinical manifestations and pathogenesis of HLH hepatitis in both familial and secondary forms. It will review growing evidence that the intrinsic hepatic response to hypercytokinemia in HLH perpetuates disease progression and the novel therapeutic approaches for patients with HLH-hepatitis/liver failure.

The RAG1 Ubiquitin Ligase Domain Stimulates Recombination of TCRß and TCRα Genes and Influences Development of αß T Cell Lineages.

RAG1/RAG2 (RAG) endonuclease-mediated assembly of diverse lymphocyte Ag receptor genes by V(D)J recombination is critical for the development and immune function of T and B cells. The RAG1 protein contains a ubiquitin ligase domain that stabilizes RAG1 and stimulates RAG endonuclease activity in vitro. We report in this study that mice with a mutation that inactivates the Rag1 ubiquitin ligase in vitro exhibit decreased rearrangements and altered repertoires of TCRß and TCRα genes in thymocytes and impaired thymocyte developmental transitions that require the assembly and selection of functional TCRß and/or TCRα genes. These Rag1 mutant mice present diminished positive selection and superantigen-mediated negative selection of conventional αß T cells, decreased genesis of invariant NK T lineage αß T cells, and mature CD4+ αß T cells with elevated autoimmune potential. Our findings reveal that the Rag1 ubiquitin ligase domain functions in vivo to stimulate TCRß and TCRα gene recombination and influence differentiation of αß T lineage cells, thereby establishing replete diversity of αß TCRs and populations of αß T cells while restraining generation of potentially autoreactive conventional αß T cells.

Caracterización colorimétrica del proceso termogravimétrico de la deshidroxilación de caolín hidrotermal y de toba / Colorimetric characterization of thermogravimetric process for dehydroxilation of hydrothermal and tuff kaolins

El metacaolín es el producto obtenido de la calcinación del caolín. La alta actividad puzolánica del metacaolín permite su utilización como un material sustituto del cemento en el concreto. Esta y otras propiedades fisicoquímicas se ven afectadas por las condiciones de procesamiento del caolín. Por lo tanto, este estudio tuvo como objetivo caracterizar los cambios del color y densidad de dos tipos de caolín (toba triturada e hidrotermal) por medio de un análisis termogravimétrico del proceso de calcinación. Para la evaluación de la densidad se empleó la norma ASTM C188, mientras que la valoración de los cambios de color utilizó un espectrofotómetro C I E - L* a * b* en conjunto con la norma UNE 80117. Asimismo, la pérdida de peso y la densidad se correlacionaron con las coordenadas de color mediante una regresión polinomial. Los resultados demostraron que la deshidroxi-lación de los caolines ocurrió entre 400 ºC y 650 ºC, caracterizándose por un máximo en el delta E* de 12.9 y 4.3 para el caolín hidrotermal y de toba, respectivamente. Además, el caolín de toba triturada presentó la máxima luminosidad (L* = 92.84) de todos los tratamientos a los 21 ºC. Este valor disminuyó 11.75% al incrementar la temperatura hasta 450 ºC. A partir de esta temperatura,L* incrementó linealmente hasta alcanzar un valor final de 87.3 a 900 ºC. La regresión polinomial obtenida explica en un 93% y 92% la variación del peso en función de los parámetros C I E - L* a * b* para el caolín de toba triturada e hidrotermal, respectivamente.

Metakaolin is a product of kaolin's calcination. The high pozzolanic activity of metakaolin allows its usage as supplementary cementitious material in concrete. This property and other physicochemical properties are affected by metakaolin's manufacturing conditions. Therefore, this study aims to characterize the changes in color and density of two types of kaolin (tuff and hydrothermal) through a thermogravimetric analysis of the calcina-tion process. Evaluation of density used ASTM C188, while the assessment of color changes used a CIE-L*a*b* spectrophotometer in conjunction with normative UNE 80117. In addition, weight loss and density were correlated with the color coordinates using polynomial regression. The results showed that kaolin dehydroxylation occurred at 450ºC and 650ºC, characterized by a maximum in delta E * of 12.9 and 4.3 for hydrothermal and tuff kaolin, respectively. In addition, the tuff kaolin presented the maximum luminosity (L * = 92.84) of all the treatments at 21ºC. This value decreased 11.75% during the temperature increment up to 450ºC. From this temperature, L * increased linearly until reaching a final value of 87.3 at 900ºC. The polynomial regression explained 93% and 92% of the weight variation as a function of the CIE-L*a*b* parameters for tuff and hydrothermal kaolin, respectively.

Photocatalytic activity, water absorption capacity, and thermal stability of white cement-based mortars with polysiloxane silicone and different doses of titanium dioxide nanoparticles / Actividad fotocatalítica, absorción de agua y estabilidad térmica de morteros a base de cemento blanco con silicona de polisiloxano y diferentes dosis de nanopartículas de dióxido de titanio

White cement-based mortars in urban areas are usually discolored and altered their esthetic properties due to air pollutants. The addition of nanoparticles in these mortars can provide photocatalytic properties that can decompose pollution agents. Likewise, other hydrophobic agents have been individually studied to improve outdoor building constructions. Therefore, this study presented the photocatalytic and hydrophobic effect of adding nano-TiO2and silicone hydrophobic powder (DOWSILTM) in a white cement matrix. The nano-TiO2 were characterized by X-Ray Diffraction (XRD); afterwards, the mortar was mixed with additions of nano-TiO2 (0.0, 0.5, 1.0, 3.0%) and DOWSILTM (0.0, 0.5%). The mortar's photocatalytic performance was evaluated using a modification of the standard Italian test Ente Nazionale Italiano di Unificazione 11259:2016 based on Rhodamine B (RhB) degradation on the sample exposed to UV irradiation. Therefore, mortar samples were subjected to UV irradiation to degrade the organic dye rhodamine B, monitoring their color variation using a C I E L* a* b* spectrophotometer. Moreover, the water permeability and the contact angle were evaluated. This research demonstrates that the white cement-based mortar samples added with nano-TiO2/DOWSILTM possess photocatalytic activity. The samples with the addition of 1.0%/0.5% and 3.0%/0.5% nano-TiO2/DOWSILTM showed a higher RhB degradation for R4 and R26. Therefore, these two materials can be employed in these proportions to improve the quality of the white cement-based mortars in urban constructions.

Los morteros a base de cemento blanco generalmente se decoloran y alteran sus propiedades estéticas debido a los contaminantes del aire en las áreas urbanas. Nanopartículas añadidas a estos morteros pueden proporcionar propiedades fotocatalíticas que descomponen estos contaminantes. Asimismo, otros agentes hidrofóbicos se han estu-diado individualmente para mejorar las construcciones a la intemperie. Por lo tanto, se presenta el efecto fotocatalítico e hidrofóbico al incorporar nano-TiO2 y silicona hidrofóbica de polisiloxano (DOWSILTM) en una matriz de cemento blanco. El nano-TiO2 se caracterizó por medio de Difracción de Rayos X (DRX); luego, el mortero se mezcló con adiciones de nano-TiO2 (0.0, 0.5, 1.0, 3.0%) y DOWSILTM (0.0, 0.5%). Los morteros se sometieron a irradiación UV, para degradar el colorante orgánico rodamina B, monitoreando su variación de color usando un espectrofotómetro C I E L* a* b*. La eficiencia fotocatalítica del mortero se evaluó utilizando una modificación de la norma italiana Ente Nazionale Italiano di Unificazione 11259:2016 basada en la degradación de la rodamina B (RhB) en el mortero expuesto a la radiación UV. Además, se evaluó la permeabilidad al agua y el ángulo de contacto. Esta investigación demostró que el mortero de cemento con nano-TiO2/ DOWSILTM posee actividad fotocatalítica. Las muestras con 1.0%/0.5% y 3.0%/0.5% nano-TiO2/DOWSILTM mostraron una mayor eficiencia de degradación de RhB para R4 y R26. Por lo tanto, estos materiales tienen potencial para mejorar la calidad de los morteros en construcciones urbanas.

Efecto de las membranas con Cu(II) sobre el proceso de filtración y capacidad de biocida contra Escherichia coli / Effect of Cu(II) membranes on the filtration process and biocide capacity against Escherichia coli

Esta investigación estudió la preparación de membranas compuestas de celulosa y quitosano entrecruzadas con Cu(II) para determinar su efecto biocida y eficiencia en la remoción deEscherichia coli. Las membranas de quitosano se obtuvieron por medio de la técnica de evaporación del solvente. Propiedades de absorción de agua, degradación térmica y mecánicas de las membranas fueron evaluadas con el propósito de modificar la estructura química, la superficie y estudiar su impacto como agente biocida. Los resultados muestran que el Cu(II) interactúa con los grupos iónicos de las membranas que inducen un cambio estructural produciendo un aumento de 190% en el módulo G*. Además, el catión provee estabilidad térmica a temperaturas menores de 200 ºC y produce cambios superficiales a la membrana, especialmente a la membrana de celulosa. Adicionalmente, la membrana de celulosa-Cu(II) aumentó su efecto biocida contraE. colihasta un 96%. El proceso de remoción por medio de la filtración aumentó 41% con la incorporación del catión. Esta investigación muestra el efecto de la interacción del catión con grupos iónicos en la membrana que mejoran las propiedades de filtración y efecto biocida contra esta enterobacteria que puede llegar a ser patógena para el ser humano.

This research studied the membrane preparation of Cu(II) crosslinked membranes composed of cellulose and chitosan to determine its biocidal effect and efficiency to remove Escherichia coli. Water absorption, thermal degradation, and G* modulus evaluated the Cu(II) impact on the equilibrium, thermal and mechanical properties. These results showed that Cu(II) incorporation interacts with the ionic groups, inducing a structural change increasing the G* modulus by 190%. Moreover, the cation provides thermal stability at temperatures below 200 ºC and produced surface changes to the membrane, especially to the cellulose mekkmbrane. Additionally, the cellulose-Cu(II) membranes increased 96% their biocidal effect against E. coli. Enterobacter filtration process increased 41% with the cation incorporation into the cellulose membrane. Therefore, this research showed the cation effect on the ionic groups in the membrane that improve the filtration properties and biocidal effect against harmful enterobacteria to humans.

Lumbar Spine Fusion and Symptoms of Leg Length Discrepancy After Hip Arthroplasty.

BACKGROUND: Hip length discrepancy (HLD) is common after total hip arthroplasty (THA); however, the effect of spinal fusion on perceived leg length discrepancy (LLD) symptoms after THA has not been examined. This study tested the hypothesis that LLD symptoms are increased in patients who underwent lumbar spinal fusion and THA, compared with patients with THA only. METHODS: This retrospective cohort study included 67 patients who underwent lumbar spinal fusion and THA, along with 78 matched control patients who underwent THA only. Hip and spine measurements were taken on postoperative, standing anterior-posterior pelvic, lateral lumbar, and anterior-posterior lumbar spinal radiographs. Perceived LLD symptoms were assessed via telephone survey. RESULTS: Between the spinal fusion and control groups, there was no significant difference in HLD (M = 7.10 mm, SE = 0.70 and M = 5.60 mm, SE = 0.49) (P = .403). The spinal fusion patients reported more frequently noticing a difference in the length of their legs than the control group (P = .046) and reported limping "all the time" compared with the control group (P = .001). Among all patients with an HLD ≤10 mm, those in the spinal fusion group reported limping at a higher frequency than patients in the control group (P = .008). Patients in the spinal fusion group were also more likely to report worsened back pain after THA (P = .011) than the control group. CONCLUSION: Frequencies of a perceived LLD, limping, and worsened back pain after THA were increased in patients with THA and a spinal fusion compared with patients who had THA only, even in a population with HLD traditionally considered to be subclinical. The results indicate that in patients with prior spinal fusion, precautions should be taken to avoid even minor LLD in the setting of THA.

Impact of HIV-1 Infection and Antigen Class on T Follicular Helper Cell Responses to Pneumococcal Polysaccharide-Protein Conjugate Vaccine-13.

Pneumococcal infections are common and serious complications of HIV-1 disease. Prevention has been compromised by the limited magnitude and quality of Ab responses to T cell-independent type 2 pneumococcal capsular polysaccharides (PPS). The pneumococcal polysaccharide-protein conjugate vaccine-13 (PCV-13) contains PPS conjugated to the T cell-dependent protein (diphtheria toxoid [DT] [CRM197]). We investigated the differential response to PPS and DT by human Ab-secreting B cells (ASC) after immunization with PCV-13 in newly diagnosed healthy HIV+ and control adults. The numbers of PPS-specific IgG ASC increased significantly and similarly in HIV+ and controls. However, DT-specific IgG ASC increased in controls but not HIV+ subjects. To determine the cellular basis of these disparate responses to DT and PPS, we characterized the frequency and activation of T follicular helper (Tfh) cells, the predominant T cell subset providing B cell help. Expression of inducible T cell costimulator (ICOS), which sustains Tfh function and phenotype, increased significantly among controls, when compared with the HIV+ group. Increases in ICOS+ Tfh correlated with changes in T-dependent, DT-specific IgG ASC in controls but not in HIV+ In contrast, ICOS expression did not correlate with T cell-independent type 2 PPS-specific ASC in either group. Of note, upon optimized ex vivo stimulation, CD4 T cells from HIV+ subjects differentiated into Tfh cells and formed synapses with Raji B cells at frequencies similar to that of controls. In summary, PCV-13-induced increase in ICOS expression on Tfh was associated with responses to DT, which was compromised in recently diagnosed healthy HIV+ adults and can be restored ex vivo by providing effective Tfh-differentiating signals.

Effect of sulfonated block copolymer on the equilibrium and thermal properties of sulfonated fluoroblock copolymer blend membrane / Efecto del copolímero en bloque sulfonado sobre las propiedades térmicas y de equilibrio de una membrana sulfonada mezclada con un fluoropolímero en bloque

Polymeric membrane technologies demand the synthesis of new polymers to enhance their equilibrium, thermal, and transport properties. Therefore, the focus of this investigation was the evaluation of the equilibrium and thermal properties of a sulfonated fluoroblock copolymer blend membrane composed of sulfonated poly(styre-ne-isobutylene-styrene) (SIBS SO3H) and a novel sulfonated fluoroblock copolymer composed of poly(4-fluo-rostyrene) (P4FS), poly(styrene) (PS) and poly(isobutylene) (PIB). The fluoroblock copolymer was synthesized using Atom Transfer Radical Polymerization (ATRP) and cationic polymerization. First, the molecular weight and the thermal stability of the block copolymer were determined using Gel Permeation Chromatography (GPC) and Thermogravimetric Analysis (TGA). Second, the chemical composition was monitored utilizing Fourier Transform Infrared spectroscopy (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopy. The molecular weight of P4FS-b-PS was Mn ~ 36,100; this value increased 8% after the cationic polymerization. The equilibrium properties of the membrane were evaluated using the water uptake and Ion-Exchange Capacity. The degradation behavior and the thermal transitions were determined using TGA and Differential Scanning Calorimetry (DSC), respectively. This newly membrane exhibited water uptake higher than 608% related to the improvement of 36% in the ion-exchange capacity and the increment of 25.31% and 25.24% in the energy required to produce the thermal transitions induced by the addition of the sulfonated fluoroblock copolymer.

La tecnología de membranas poliméricas requiere de la síntesis de nuevos polímeros que mejoren sus propiedades de equilibrio, térmicas y de transporte. Esta investigación tuvo como objetivo determinar las pro-piedades de equilibrio y térmicas de una membrana compuesta de poli(estireno-isobutileno-estireno) sulfonado (SIBS SO3H) y un fluoropolímero en bloque sulfonado compuesto de poli(4-fluorostireno) (P4FS), poli(estireno) (PS) y poli(isobutileno) (PIB). El fluoropolímero en bloque se sintetizó utilizando la técnica de polimerización radical por transferencia atómica (ATRP por sus siglas en inglés) y polimerización catiónica. El peso molecular y la estabilidad térmica del fluoropolímero en bloque fueron determinadas por medio de Cromatografía de Permeación en Gel (GPC) y un análisis termogravimétrico (TGA). La composición química se monitorizó utilizando espectroscopía infrarroja por transformada de Fourier (FTIR) y espectroscopía de Resonancia Magnética Nuclear (RMN). El peso molecular de P4FS-b-PS fue Mn ~ 36,100; este valor aumentó un 8% después de la polimerización catiónica. Las propiedades de equilibrio de la membrana fueron evaluadas por medio de la absorción de agua y la capacidad de intercambio iónico. El comportamiento de degradación y las transiciones térmicas se determinaron utilizando TGA y Calorimetría Diferencial de Barrido (DSC). Esta nueva membrana exhibió una absorción de agua mayor del 608% relacionada con la mejora del 36% en la capacidad de intercambio iónico y el incremento en 25.31% y 25.24% en la energía requerida para producir las transiciones termales inducidas por la adición del fluoropolímero sulfonado en bloque.

Cannabis sativa extracts protect LDL from Cu2+-mediated oxidation.

BACKGROUND: Multiple therapeutic properties have been attributed to Cannabis sativa. However, further research is required to unveil the medicinal potential of Cannabis and the relationship between biological activity and chemical profile. OBJECTIVES: The primary objective of this study was to characterize the chemical profile and antioxidant properties of three varieties of Cannabis sativa available in Uruguay during progressive stages of maturation. METHODS: Fresh samples of female inflorescences from three stable Cannabis sativa phenotypes, collected at different time points during the end of the flowering period were analyzed. Chemical characterization of chloroform extracts was performed by 1H-NMR. The antioxidant properties of the cannabis sativa extracts, and pure cannabinoids, were measured in a Cu2+-induced LDL oxidation assay. RESULTS: The main cannabinoids in the youngest inflorescences were tetrahydrocannabinolic acid (THC-A, 242 ± 62 mg/g) and tetrahydrocannabinol (THC, 7.3 ± 6.5 mg/g). Cannabinoid levels increased more than twice in two of the mature samples. A third sample showed a lower and constant concentration of THC-A and THC (177 ± 25 and 1 ± 1, respectively). The THC-A/THC rich cannabis extracts increased the latency phase of LDL oxidation by a factor of 1.2-3.5 per µg, and slowed down the propagation phase of lipoperoxidation (IC50 1.7-4.6 µg/mL). Hemp, a cannabidiol (CBD, 198 mg/g) and cannabidiolic acid (CBD-A, 92 mg/g) rich variety, also prevented the formation of conjugated dienes during LDL oxidation. In fact, 1 µg of extract was able to stretch the latency phase 3.7 times and also to significantly reduce the steepness of the propagation phase (IC50 of 8 µg/mL). Synthetic THC lengthened the duration of the lag phase by a factor of 21 per µg, while for the propagation phase showed an IC50 ≤ 1 µg/mL. Conversely, THC-A was unable to improve any parameter. Meanwhile, the presence of 1 µg of pure CBD and CBD-A increased the initial latency phase 4.8 and 9.4 times, respectively, but did not have an effect on the propagation phase. CONCLUSION: Cannabis whole extracts acted on both phases of lipid oxidation in copper challenged LDL. Those effects were just partially related with the content of cannabinoids and partially recapitulated by isolated pure cannabinoids. Our results support the potentially beneficial effects of cannabis sativa whole extracts on the initial phase of atherosclerosis.

Differential Diagnosis of Diarrhea in Patients With Neuroendocrine Tumors.

Patients with neuroendocrine tumors (NETs) and carcinoid syndrome experience diarrhea that can have a debilitating effect on quality of life. Diarrhea also may develop in response to other hormonal syndromes associated with NETs, surgical complications, medical comorbidities, medications, or food sensitivities. Limited guidance on the practical approach to the differential diagnosis of diarrhea in these patients can lead to delays in appropriate treatment. This clinical review and commentary underscore the complexity in identifying the etiology of diarrhea in patients with NETs. Based on our collective experience and expertise, we offer a practical algorithm to guide medical oncologists and other care providers to expedite effective management of diarrhea and related symptoms in patients with NETs.

Predicting Renal Cancer Recurrence: Defining Limitations of Existing Prognostic Models With Prospective Trial-Based Validation.

PURPOSE: To validate currently used recurrence prediction models for renal cell carcinoma (RCC) by using prospective data from the ASSURE (ECOG-ACRIN E2805; Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma) adjuvant trial. PATIENTS AND METHODS: Eight RCC recurrence models (University of California at Los Angeles Integrated Staging System [UISS]; Stage, Size, Grade, and Necrosis [SSIGN]; Leibovich; Kattan; Memorial Sloan Kettering Cancer Center [MSKCC]; Yaycioglu; Karakiewicz; and Cindolo) were selected on the basis of their use in clinical practice and clinical trial designs. These models along with the TNM staging system were validated using 1,647 patients with resected localized high-grade or locally advanced disease (≥ pT1b grade 3 and 4/pTanyN1Mo) from the ASSURE cohort. The predictive performance of the model was quantified by assessing its discriminatory and calibration abilities. RESULTS: Prospective validation of predictive and prognostic models for localized RCC showed a substantial decrease in each of the predictive abilities of the model compared with their original and externally validated discriminatory estimates. Among the models, the SSIGN score performed best (0.688; 95% CI, 0.686 to 0.689), and the UISS model performed worst (0.556; 95% CI, 0.555 to 0.557). Compared with the 2002 TNM staging system (C-index, 0.60), most models only marginally outperformed standard staging. Importantly, all models, including TNM, demonstrated statistically significant variability in their predictive ability over time and were most useful within the first 2 years after diagnosis. CONCLUSION: In RCC, as in many other solid malignancies, clinicians rely on retrospective prediction tools to guide patient care and clinical trial selection and largely overestimate their predictive abilities. We used prospective collected adjuvant trial data to validate existing RCC prediction models and demonstrate a sharp decrease in the predictive ability of all models compared with their previous retrospective validations. Accordingly, we recommend prospective validation of any predictive model before implementing it into clinical practice and clinical trial design.

Spatio-temporal modelling of Leishmania infantum infection among domestic dogs: a simulation study and sensitivity analysis applied to rural Brazil.

BACKGROUND: The parasite Leishmania infantum causes zoonotic visceral leishmaniasis (VL), a potentially fatal vector-borne disease of canids and humans. Zoonotic VL poses a significant risk to public health, with regions of Latin America being particularly afflicted by the disease. Leishmania infantum parasites are transmitted between hosts during blood-feeding by infected female phlebotomine sand flies. With a principal reservoir host of L. infantum being domestic dogs, limiting prevalence in this reservoir may result in a reduced risk of infection for the human population. To this end, a primary focus of research efforts has been to understand disease transmission dynamics among dogs. One way this can be achieved is through the use of mathematical models. METHODS: We have developed a stochastic, spatial, individual-based mechanistic model of L. infantum transmission in domestic dogs. The model framework was applied to a rural Brazilian village setting with parameter values informed by fieldwork and laboratory data. To ensure household and sand fly populations were realistic, we statistically fitted distributions for these entities to existing survey data. To identify the model parameters of highest importance, we performed a stochastic parameter sensitivity analysis of the prevalence of infection among dogs to the model parameters. RESULTS: We computed parametric distributions for the number of humans and animals per household and a non-parametric temporal profile for sand fly abundance. The stochastic parameter sensitivity analysis determined prevalence of L. infantum infection in dogs to be most strongly affected by the sand fly associated parameters and the proportion of immigrant dogs already infected with L. infantum parasites. CONCLUSIONS: Establishing the model parameters with the highest sensitivity of average L. infantum infection prevalence in dogs to their variation helps motivate future data collection efforts focusing on these elements. Moreover, the proposed mechanistic modelling framework provides a foundation that can be expanded to explore spatial patterns of zoonotic VL in humans and to assess spatially targeted interventions.

Association of calpain and calpastatin activity to postmortem myofibrillar protein degradation and sarcoplasmic proteome changes in bovine Longissiumus lumborum and Triceps brachii.

The aim of this study was to determine the extent to which calpastatin (CASN) variants (based on two chromatographic peaks; CASN-P1 and CASN-P2) explain variation in µ-calpain autolysis, protein degradation, and changes in the sarcoplasmic proteome observed during postmortem aging of beef. The Longissimus lumborum (LL) and Triceps brachii (TB) muscles were obtained from six crossbred steers and samples prepared from day 0, 1 and 7 postmortem (pm). The decline of CASN activity during aging was due to decrease of CASN-P2 in both muscles. The CASN-P2:µ-calpain ratio at day 0 was greater for TB, which presented lesser calpain autolysis, myofibrillar protein degradation, and fewer sarcoplasmic proteome changes during aging. Changes in abundance of Heat shock protein 70 family in the sarcoplasmic fraction were positively associated to proteolysis during aging, with greater differences in LL.

Novel Opioid Safety Clinic Initiative to Deliver Guideline-Concordant Chronic Opioid Therapy in Primary Care.

OBJECTIVE: To develop and evaluate a novel Opioid Safety Clinic (OSC) initiative to enhance adherence to guidelines on the assessment and monitoring of patients prescribed chronic opioid therapy (COT). PATIENTS AND METHODS: The OSC was developed at an urban Federally Qualified Health Center to provide guideline-concordant care for COT, standardize workflows, and efficiently use clinic staff. We evaluated the OSC using a matched cohort study. Five hundred thirty-nine patients participated in the clinic between July 1, 2014, and March 31, 2016. Of these, 472 clinic participants were matched to 472 nonparticipants by sex and age on the date of the OSC visit. The OSC was evaluated by its completion rates of standardized pain assessments, urine toxicology, and naloxone dispensings. We conducted logistic regression comparing OSC participants to OSC nonparticipants. RESULTS: A total of 539 patients attended an OSC visit, representing approximately 53% of patients in the chronic opioid registry. The OSC participants were more likely than nonparticipants to have completed a pain assessment (adjusted odds ratio [aOR], 169.8; 95% CI, 98.3-293.5), completed a urine toxicology (aOR, 46.1; 95% CI, 30.4-69.9), or had naloxone dispensed (aOR, 2.8; 95% CI, 1.9-4.3) over 12 months of follow-up. CONCLUSION: The OSC model improved adherence to guideline-concordant COT in primary care. Future research is needed to assess the impact of these interventions on pain, quality of life, and adverse events from opioid analgesics.