Patients' perception of using telehealth for consultation: insights after pandemic and development of an online calculator platform to predict acceptance of remote consultation: the TELEMED international study.

The COVID-19 pandemic has led to a change in healthcare models. The aim of this study was to evaluate patient acceptance of telehealth as an alternative to physical consultations, and to identify factors predicting higher satisfaction. This was an observational, cross-sectional, multi-center, international study. All consecutive patients for whom telehealth was used in consultations between April and July 2020 were considered for inclusion. The validated Telehealth Usability Questionnaire (TUQ) was used as a model to measure patient acceptance. Overall, 747 patients were observed, of whom 721 agreed to participate (96·5%). The TUQ showed that 86·9% of patients agreed that telehealth was useful; 85·2% supported the interface quality and 81·4% endorsed the interaction quality. Patients aged > 60 y were less likely to agree with the use of telehealth (p < 0·05). A web-based prediction tool was generated to calculate global satisfaction and to identify patients more likely to feel comfortable with telehealth. Telehealth is feasible and allows consultations that are satisfactory for patients. Technological advancements could ease safe implementation of telehealth into everyday practice. Adequate patient selection can be useful to ensure that the ideal strategy is used for each individual during and after the pandemic.

Assessment of Body Composition as an Indicator of Early Peripheral Parenteral Nutrition Therapy in Patients Undergoing Colorectal Cancer Surgery in an Enhanced Recovery Program.

BACKGROUND: A poor body composition (BC) has been identified as a risk factor for patients with colorectal cancer (CRC). This study was performed to assess the effect of early peripheral parenteral nutrition (PPN) on BC in patients undergoing CCR surgery within an enhanced recovery program. METHODS: Patients with normal nutritional status were prospectively included between October 2016 and September 2019, randomized into two groups (PPN with periOlimel N4-E versus conventional fluid therapy) and subsequently classified according to their preoperative CT scan into high- or low-risk BC groups. Postoperative complications and length of hospital stay (LOS) were assessed. RESULTS: Of the 156 patients analyzed, 88 patients (56.4%) were classified as having high-risk BC according to CT measurements. PPN led to a 15.4% reduction in postoperative complications in high-risk vs. 1.7% in low-risk BC patients. In the multivariate analysis, high-risk BC was related to an OR (95% CI) of 2 (p = 0.044) of presenting complications and of 1.9 (p = 0.066) for major complications, and was associated with an increase in LOS of 3.6 days (p = 0.039). CONCLUSIONS: The measurement of patients' BC can allow for the identification of target patients where PPN has been proven to be an effective tool to improve postoperative outcomes.

Key factors affecting people's unwillingness to be confined during the COVID-19 pandemic in Spain: a large-scale population study.

Population confinements have been one of the most widely adopted non-pharmaceutical interventions (NPIs) implemented by governments across the globe to help contain the spread of the SARS-CoV-2 virus. While confinement measures have been proven to be effective to reduce the number of infections, they entail significant economic and social costs. Thus, different policy makers and social groups have exhibited varying levels of acceptance of this type of measures. In this context, understanding the factors that determine the willingness of individuals to be confined during a pandemic is of paramount importance, particularly, to policy and decision-makers. In this paper, we study the factors that influence the unwillingness to be confined during the COVID-19 pandemic by the means of a large-scale, online population survey deployed in Spain. We perform two types of analyses (logistic regression and automatic pattern discovery) and consider socio-demographic, economic and psychological factors, together with the 14-day cumulative incidence per 100,000 inhabitants. Our analysis of 109,515 answers to the survey covers data spanning over a 5-month time period to shed light on the impact of the passage of time. We find evidence of pandemic fatigue as the percentage of those who report an unwillingness to be in confinement increases over time; we identify significant gender differences, with women being generally less likely than men to be able to sustain long-term confinement of at least 6 months; we uncover that the psychological impact was the most important factor to determine the willingness to be in confinement at the beginning of the pandemic, to be replaced by the economic impact as the most important variable towards the end of our period of study. Our results highlight the need to design gender and age specific public policies, to implement psychological and economic support programs and to address the evident pandemic fatigue as the success of potential future confinements will depend on the population's willingness to comply with them.

Bone toxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the retinoid system: A causality analysis anchored in osteoblast gene expression and mouse data.

Dioxin exposures impact on bone quality and osteoblast differentiation, as well as retinoic acid metabolism and signaling. In this study we analyzed associations between increased circulating retinol concentrations and altered bone mineral density in a mouse model following oral exposure to 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD). Additionally, effects of TCDD on differentiation marker genes and genes involved with retinoic acid metabolism were analysed in an osteoblast cell model followed by benchmark dose-response analyses of the gene expression data. Study results show that the increased trabecular and decreased cortical bone mineral density in the mouse model following TCDD exposure are associated with increased circulating retinol concentrations. Also, TCDD disrupted the expression of genes involved in osteoblast differentiation and retinoic acid synthesis, degradation, and nuclear translocation in directions compatible with increasing cellular retinoic acid levels. Further evaluation of the obtained results in relation to previously published data by the use of mode-of-action and weight-of-evidence inspired analytical approaches strengthened the evidence that TCDD-induced bone and retinoid system changes are causally related and compatible with an endocrine disruption mode of action.

Effect of Early Peripheral Parenteral Nutrition Support in an Enhanced Recovery Program for Colorectal Cancer Surgery: A Randomized Open Trial.

BACKGROUND: Peripheral parenteral nutrition allows repletion of acute nutrient deficiencies and could prevent further nutrition deficits before and after colorectal surgery. A randomized open study was performed to evaluate the effect of perioperative peripheral parenteral nutrition (PPN) support on postoperative morbidity after colorectal cancer surgery within an enhanced recovery program. METHODS: Patients were randomized into two groups: peripheral parenteral nutrition (PPN) (with Peri-Olimel N4-E) versus conventional fluid therapy (FT). Ninety-day postoperative complications, laboratory parameters, length of hospital stay, and compliance with the ERAS protocol were assessed. RESULTS: A total of 158 patients were analysed. The overall 90-day complication rate was 38.6% (61 patients), and 24 patients had major complications (Clavien-Dindo III-V) (15.2%). In the multivariate analysis, the intervention (PPN vs. FC) showed a protective effect against postoperative complications (p = 0.0031, OR = 0.2 (CI: 0.08-0.87)). Following ordinal regression, PPN and early oral tolerance showed a protective effect, being less likely to develop complications or to move from minor to major complications. In patients with low compliance to ERAS during the first postoperative day, PPN showed a protective effect, preventing 28% of morbidity. CONCLUSIONS: Perioperative peripheral parenteral nutrition (PPN) support with Peri-Olimel N4-E in colorectal cancer surgery associated with early oral intake could reduce postoperative complications.

Assessing the Impact of the COVID-19 Pandemic in Spain: Large-Scale, Online, Self-Reported Population Survey.

BACKGROUND: Spain has been one of the countries most impacted by the COVID-19 pandemic. Since the first confirmed case was reported on January 31, 2020, there have been over 405,000 cases and 28,000 deaths in Spain. The economic and social impact is without precedent. Thus, it is important to quickly assess the situation and perception of the population. Large-scale online surveys have been shown to be an effective tool for this purpose. OBJECTIVE: We aim to assess the situation and perception of the Spanish population in four key areas related to the COVID-19 pandemic: social contact behavior during confinement, personal economic impact, labor situation, and health status. METHODS: We obtained a large sample using an online survey with 24 questions related to COVID-19 in the week of March 28-April 2, 2020, during the peak of the first wave of COVID-19 in Spain. The self-selection online survey method of nonprobability sampling was used to recruit 156,614 participants via social media posts that targeted the general adult population (age >18 years). Given such a large sample, the 95% CI was ±0.843 for all reported proportions. RESULTS: Regarding social behavior during confinement, participants mainly left their homes to satisfy basic needs. We found several statistically significant differences in social behavior across genders and age groups. The population's willingness to comply with the confinement measures is evident. From the survey answers, we identified a significant adverse economic impact of the pandemic on those working in small businesses and a negative correlation between economic damage and willingness to stay in confinement. The survey revealed that close contacts play an important role in the transmission of the disease, and 28% of the participants lacked the necessary resources to properly isolate themselves. We also identified a significant lack of testing, with only 1% of the population tested and 6% of respondents unable to be tested despite their doctor's recommendation. We developed a generalized linear model to identify the variables that were correlated with a positive SARS-CoV-2 test result. Using this model, we estimated an average of 5% for SARS-CoV-2 prevalence in the Spanish population during the time of the study. A seroprevalence study carried out later by the Spanish Ministry of Health reported a similar level of disease prevalence (5%). CONCLUSIONS: Large-scale online population surveys, distributed via social media and online messaging platforms, can be an effective, cheap, and fast tool to assess the impact and prevalence of an infectious disease in the context of a pandemic, particularly when there is a scarcity of official data and limited testing capacity.

Geographic and Racial Disparities in Infant Hearing Loss.

OBJECTIVE: Approximately 1 to 2 of every 1000 American newborns has hearing loss identified by newborn screening. This study was designed to determine if infant hearing loss is more common in socioeconomically disadvantaged communities. STUDY DESIGN: In this retrospective study, we analyzed electronic medical record data using geostatistical models. SETTING: Infants were residents of Durham County, North Carolina, born in 2 hospitals of the Duke University Health System. This county includes the city of Durham and surrounding suburban and rural communities. SUBJECTS AND METHODS: Subjects were hearing-screened newborns, born between 2005 and 2016, whose residential address was in Durham County, North Carolina. This was a retrospective study using medical record data. We used Bayesian regression models with smoothing of coordinate date to identify both spatial and nonspatial predictors of infant hearing loss. RESULTS: We identified 19,348 infants from Durham County, of whom 675 had failed initial hearing screening and 191 had hearing loss confirmed on follow-up. Hearing loss was significantly associated with minority race (odds ratio [OR], 2.45; 95% confidence interval, 1.97-3.06), as well as lower gestational age and maternal sexually transmitted infections. We identified significant geographic heterogeneity, with a higher probability of hearing loss in poorer urban neighborhoods (local OR range, 0.59-1.39). Neighborhood disadvantage was a significant predictor of hearing loss, as was high local seroprevalence of cytomegalovirus (CMV) among pregnant women. CONCLUSIONS: Urban, low-income neighborhoods have a high prevalence of infant hearing loss compared with more affluent surrounding communities, particularly among minorities. This distribution may be attributable to congenital CMV infection.

Prediction of long-term outcomes of HIV-infected patients developing non-AIDS events using a multistate approach.

OBJETIVES: Outcomes of people living with HIV (PLWH) developing non-AIDS events (NAEs) remain poorly defined. We aimed to classify NAEs according to severity, and to describe clinical outcomes and prognostic factors after NAE occurrence using data from CoRIS, a large Spanish HIV cohort from 2004 to 2013. DESIGN: Prospective multicenter cohort study. METHODS: Using a multistate approach we estimated 3 transition probabilities: from alive and NAE-free to alive and NAE-experienced ("NAE development"); from alive and NAE-experienced to death ("Death after NAE"); and from alive and NAE-free to death ("Death without NAE"). We analyzed the effect of different covariates, including demographic, immunologic and virologic data, on death or NAE development, based on estimates of hazard ratios (HR). We focused on the transition "Death after NAE". RESULTS: 8,789 PLWH were followed-up until death, cohort censoring or loss to follow-up. 792 first incident NAEs occurred in 9.01% PLWH (incidence rate 28.76; 95% confidence interval [CI], 26.80-30.84, per 1000 patient-years). 112 (14.14%) NAE-experienced PLWH and 240 (2.73%) NAE-free PLWH died. Adjusted HR for the transition "Death after NAE" was 12.1 (95%CI, 4.90-29.89). There was a graded increase in the adjusted HRs for mortality according to NAE severity category: HR (95%CI), 4.02 (2.45-6.57) for intermediate-severity; and 9.85 (5.45-17.81) for serious NAEs compared to low-severity NAEs. Male sex (HR 2.04; 95% CI, 1.11-3.84), age>50 years (1.78, 1.08-2.94), hepatitis C-coinfection (2.52, 1.38-4.61), lower CD4 cell count at cohort entry (HR 2.49; 95%CI 1.20-5.14 for CD4 cell count below 200 and HR 2.16; 95%CI 1.01-4.66 for CD4 cell count between 200-350, both compared to CD4 cell count higher than 500) and concomitant CD4<200 cells/mL (2.22, 1.42-3.44) were associated with death after NAE. CD4 count and HIV-1 RNA at engagement, previous AIDS and hepatitis C-coinfection predicted mortality in NAE-free persons. CONCLUSION: NAEs, including low-severity events, increase prominently the risk for mortality in PLWH. Prognostic factors differ between NAE-experienced and NAE-free persons. These findings should be taken into account in the clinical management of PLWH developing NAEs and may permit more targeted prevention efforts.

Contribution of Oxidative Stress to Non-AIDS Events in HIV-Infected Patients.

OBJECTIVE: Recognition of potentially modifiable mechanisms implicated in the pathogenesis of non-AIDS events (NAEs) might help improve outcomes of HIV-infected individuals. HIV infection has been associated with increased oxidative stress. We assessed the association between F2-isoprostanes and serious NAEs, and whether they improve the predictive performance of inflammation and coagulation biomarkers. METHODS: Prospective multicenter cohort. Individuals who had an incident serious NAE and 2 sex- and age-matched participants with no events were selected. Measurement of F2-isoprostanes, highly sensitive C-reactive protein, interleukin-6, D-dimer, sCD14, sCD40, sCD163, and neopterin levels was performed in successive plasma samples collected from cohort inclusion. RESULTS: Biomarkers were measured in 78 participants developing serious NAEs or death, and 151 subjects with no events. Adjusted levels of F2-isoprostanes, and also of highly sensitive C-reactive protein, sCD14, and D-dimer were higher in individuals who developed serious NAEs, including or not non-AIDS deaths. The same results were observed when only samples collected since the time of achieving virological suppression were analyzed. The additive incorporation of each biomarker, ending with F2-isoprostanes, in an adjusted model was associated with a graded and significant increase in the quality of model fitting, and 94% sensitivity, 33% specificity, and 0.77 accuracy to predict serious NAEs including non-AIDS-related death. CONCLUSION: Oxidative stress is associated with a higher risk of serious NAEs, including non-AIDS deaths. This effect is independent and additive to biomarkers of inflammation, monocyte activation, and coagulation. Our results suggest that oxidative stress should be included among mechanisms to deal with to improve prognosis of HIV-infected individuals.

Modelling the presence of disease under spatial misalignment using Bayesian latent Gaussian models.

Modelling patterns of the spatial incidence of diseases using local environmental factors has been a growing problem in the last few years. Geostatistical models have become popular lately because they allow estimating and predicting the underlying disease risk and relating it with possible risk factors. Our approach to these models is based on the fact that the presence/absence of a disease can be expressed with a hierarchical Bayesian spatial model that incorporates the information provided by the geographical and environmental characteristics of the region of interest. Nevertheless, our main interest here is to tackle the misalignment problem arising when information about possible covariates are partially (or totally) different than those of the observed locations and those in which we want to predict. As a result, we present two different models depending on the fact that there is uncertainty on the covariates or not. In both cases, Bayesian inference on the parameters and prediction of presence/absence in new locations are made by considering the model as a latent Gaussian model, which allows the use of the integrated nested Laplace approximation. In particular, the spatial effect is implemented with the stochastic partial differential equation approach. The methodology is evaluated on the presence of the Fasciola hepatica in Galicia, a North-West region of Spain.

Comparative Impact of Suppressive Antiretroviral Regimens on the CD4/CD8 T-Cell Ratio: A Cohort Study.

Although different factors have been implicated in the CD4/CD8 T-cell ratio recovery in HIV-infected patients who receive effective antiretroviral therapy (ART), limited information exists on the influence of the regimen composition. A longitudinal study carried out in a prospective, single-center cohort of HIV-infected patients. ART regimens including non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), or integrase strand transfer inhibitors (INSTI) from patients who achieved long-term (≥6-month duration) virological suppression (HIV-RNA < 400 copies/mL) from January 1998 to June 2014 were analyzed. The impact of ART composition on the changes of the CD4/CD8 T-cell ratio was modeled using a mixed linear approach with adjustment for possible confounders. A total of 1068 ART regimens from 570 patients were analyzed. Mean (SD) age of the patients was 42.15 (10.68) years and 276 (48.42%) had hepatitis C virus (HCV) coinfection. Five hundred fifty-eight (52.25%) regimens were PI-based, 439 (40.10%) NNRTI-based, and 71 (6.65%) INSTI-based; 487 (45.60%) were initial regimens, 476 (44.57%) simplification, and 105 (9.83%) salvage regimens. Median (IQR) number of regimens was 1 (1-2) per patient, of 29 (14-58) months duration, and 4 (3-7) CD4/CD8 measurements per regimen. The median baseline CD4/CD8 ratio was 0.42, 0.50, and 0.54, respectively, with the PI-, NNRTI-, and INSTI-based regimens (P = 0.0073). Overall median (IQR) increase of CD4/CD8 ratio was 0.0245 (-0.0352-0.0690) per year, and a CD4/CD8 ratio ≥1 was achieved in 19.35% of the cases with PI-based, 25.97% with NNRTI-based, and 22.54% with INSTI-based regimens (P = 0.1406). In the adjusted model, the mean CD4/CD8 T-cell ratio increase was higher with NNRTI-based regimens compared for PI-based (estimated coefficient for PI [95% CI], -0.0912 [-0.1604 to -0.0219], P = 0.009). Also, a higher CD4/CD8 baseline ratio was associated with higher CD4/CD8 increase in the adjusted model (P = 0.001); by contrast, higher age (P = 0.020) and simplification of ART regimen (P = 0.003) had a negative impact on the CD4/CD8 ratio. Antiretroviral regimen composition has a differential impact on the CD4/CD8 T-cell ratio; NNRTI-based regimens are associated with enhanced CD4/CD8 T-cell ratio recovery compared to PI-based antiretroviral regimens.

Aluminium, nickel, cadmium and lead in candy products and assessment of daily intake by children in Spain.

Aluminium (Al), nickel (Ni), cadmium (Cd) and lead (Pb) levels in a total of 263 samples of 12 types of candies widely consumed in Spain, were evaluated. Samples were analysed using an ICP-MS method after acidic sample mineralization. Concentration ranges of Al, Ni, Cd and Pb were 21.28-62.91 µg g(-1), 0.40-1.27 µg g(-1), 0.12-1.01 µg g(-1) and 1.03-7.14 µg g(-1), respectifgvely. Statistically significant positive correlations were calculated between concentrations of Ni-Al and Pb-Cd (p-values < 0.05). Taking into consideration the relatively high metal content, together with the high caloric density of these products, as well as high content of particular nutrients such as sugars that can induce development of certain pathologies like obesity and caries, indicate that frequent consumption of candy products is not recommended.

Gestational and lactational exposure to the polychlorinated biphenyl mixture Aroclor 1254 modulates retinoid homeostasis in rat offspring.

Polychlorinated biphenyls (PCBs) induce a broad spectrum of biochemical and toxic effects in mammals including alterations of the vital retinoid (vitamin A) system. The aim of this study was to characterize alterations of tissue retinoid levels in rat offspring and their dams following gestational and lactational exposure to the PCB mixture Aroclor 1254 (A1254) and to assess the interrelationship of these changes with other established sensitive biochemical and toxicological endpoints. Sprague-Dawley rat dams were exposed orally to 0 or 15 mg/kg body weight/day of A1254 from gestational day 1 to postnatal day (PND) 23. Livers, kidneys and serum were collected from the offspring on PNDs 35, 77 and 350. Tissue and serum retinoid levels, hepatic cytochrome P450 (CYP) enzymes and serum thyroid hormones were analyzed. A multivariate regression between A1254 treatment, hepatic retinoid levels, hepatic CYP enzymes activities, thyroid hormone levels and body/liver weights was performed using an orthogonal partial least-squares (PLS) analysis. The contribution of dioxin-like (DL) components of A1254 to the observed effects was also estimated using the toxic equivalency (TEQ) concept. In both male and female offspring short-term alterations in tissue retinoid levels occurred at PND35, i.e. decreased levels of hepatic retinol and retinoic acid (RA) metabolite 9-cis-4-oxo-13,14-dihydro-RA with concurrent increases in hepatic and renal all-trans-RA levels. Long-term changes consisted of decreased hepatic retinyl palmitate and increased renal retinol levels that were apparent until PND350. Retinoid system alterations were associated with altered CYP enzyme activities and serum thyroid hormone levels as well as body and liver weights in both offspring and dams. The estimated DL activity was within an order of magnitude of the theoretical TEQ for different endpoints, indicating significant involvement of DL congeners in the observed effects. This study shows that tissue retinoid levels are affected both short- and long-term by developmental A1254 exposure and are associated with alterations of other established endpoints of toxicological concern.

In utero and lactational exposure to a mixture of environmental contaminants detected in Canadian Arctic human populations alters retinoid levels in rat offspring with low margins of exposure.

Arctic inhabitants are highly exposed to persistent organic pollutants (POP), which may produce adverse health effects. This study characterized alterations in tissue retinoid (vitamin A) levels in rat offspring and their dams following in utero and lactational exposure to the Northern Contaminant Mixture (NCM), a mixture of 27 contaminants including polychlorinated biphenyls (PCB), organochlorine (OC) pesticides, and methylmercury (MeHg), present in maternal blood of the Canadian Arctic Inuit population. Further, effect levels for retinoid system alterations and other endpoints were compared to the Arctic Inuit population exposure and their interrelationships were assessed. Sprague-Dawley rat dams were dosed with NCM from gestational day 1 to postnatal day (PND) 23. Livers, kidneys and serum were obtained from offspring on PND35, PND77, and PND350 and their dams on PND30 for analysis of tissue retinoid levels, hepatic cytochrome P-450 (CYP) enzymes, and serum thyroid hormones. Benchmark doses were established for all endpoints, and a partial least-squares regression analysis was performed for NCM treatment, hepatic retinoid levels, CYP enzyme induction, and thyroid hormone levels, as well as body and liver weights. Hepatic retinoid levels were sensitive endpoints, with the most pronounced effects at PND35 though still apparent at PND350. The effects on tissue retinoid levels and changes in CYP enzyme activities, body and liver weights, and thyroid hormone levels were associated and likely driven by dioxin-like compounds in the mixture. Low margins of exposure were observed for all retinoid endpoints at PND35. These findings are important for health risk assessment of Canadian Arctic populations and further support the use of retinoid system analyses in testing of endocrine-system-modulating compounds.

Estudio comparativo de las 2 versiones de un inmunoanálisis comercializado para la monitorización terapéutica de adalimumab en artritis reumatoide / Comparative study of both versions of an immunoassay commercialized for therapeutic drug monitoring of adalimumab in rheumatoid arthritis

Objetivo: Describir los resultados del estudio comparativo entre las 2 versiones de un inmunoanálisis comercializado para la monitorización terapéutica de adalimumab (ADA) en artritis reumatoide (AR). Material y métodos: Se han analizado 140 muestras de suero de pacientes con AR tratados con ADA 40 mg cada 14 días con las 2 versiones del ensayo (V1 o anterior y V2 o actualizada). Resultados: Se obtuvo una buena correlación con las dos versiones. En general, V2 proporciona resultados más altos de concentración de ADA que V1 y presenta una mayor precisión en el rango de concentraciones próximas al nivel de decisión clínica, ajustándose más a la concentración real del fármaco en sangre. Además, permite la automatización completa, lo cual simplifica mucho el análisis, y reduce significativamente la variabilidad. Conclusión: La monitorización de ADA con la versión actualizada demostró tener ventajas técnicas significativas, pudiendo ser una herramienta más práctica para la toma de decisiones terapéuticas en pacientes con AR (AU)

Objective: To describe the results of the comparative study between both versions of an immunoassay commercialized for therapeutic drug monitoring of adalimumab (ADA) in rheumatoid arthritis (AR). Material and methods: 140 samples of patients with RA treated with ADA 40 mg every 14 days were analyzed by both versions of the test (V1 or previous and V2 or updated). Results: A good correlation was obtained by both versions. In general V2 provides higher results of ADA’s concentration than V1 and presents greater precision in the range of concentrations for clinical decisions, adjusting for the real concentration of the drug in blood. In addition, V2 allows for complete automation, which simplifies the analysis and reduces significantly the variability. Conclusion: ADA’s monitoring with the updated version demonstrated to have technical significant advantages, constituting a more practical tool for therapeutic decisions in patients with RA (AU)

Comparative study of both versions of an immunoassay commercialized for therapeutic drug monitoring of adalimumab in rheumatoid arthritis.

OBJECTIVE: To describe the results of the comparative study between both versions of an immunoassay commercialized for therapeutic drug monitoring of adalimumab (ADA) in rheumatoid arthritis (AR). MATERIAL AND METHODS: 140 samples of patients with RA treated with ADA 40mg every 14 days were analyzed by both versions of the test (V1 or previous and V2 or updated). RESULTS: A good correlation was obtained by both versions. In general V2 provides higher results of ADA's concentration than V1 and presents greater precision in the range of concentrations for clinical decisions, adjusting for the real concentration of the drug in blood. In addition, V2 allows for complete automation, which simplifies the analysis and reduces significantly the variability. CONCLUSION: ADA's monitoring with the updated version demonstrated to have technical significant advantages, constituting a more practical tool for therapeutic decisions in patients with RA.

Long-term safety and efficacy of etanercept in the treatment of ankylosing spondylitis.

To date, anti-tumor necrosis factor alfa (anti-TNF-α) therapy is the only alternative to nonsteroidal anti-inflammatory drugs for the treatment of ankylosing spondylitis. Etanercept is a soluble TNF receptor, with a mode of action and pharmacokinetics different to those of antibodies and distinctive efficacy and safety. Etanercept has demonstrated efficacy in the treatment of ankylosing spondylitis, with or without radiographic sacroiliitis, and other manifestations of the disease, including peripheral arthritis, enthesitis, and psoriasis. Etanercept is not efficacious in inflammatory bowel disease, and its efficacy in the treatment of uveitis appears to be lower than that of other anti-TNF drugs. Studies of etanercept confirmed regression of bone edema on magnetic resonance imaging of the spine and sacroiliac joint, but failed to reduce radiographic progression, as do the other anti-TNF drugs. It seems that a proportion of patients remain in disease remission when the etanercept dose is reduced or administration intervals are extended. Etanercept is generally well tolerated with an acceptable safety profile in the treatment of ankylosing spondylitis. The most common adverse effect of etanercept treatment is injection site reactions, which are generally self-limiting. Reactivation of tuberculosis, reactivation of hepatitis B virus infection, congestive heart failure, demyelinating neurologic disorders, hematologic disorders like aplastic anemia and pancytopenia, vasculitis, immunogenicity, and exacerbation or induction of psoriasis are class effects of all the anti-TNF drugs, and have been seen in patients with ankylosing spondylitis. However, etanercept is less likely to induce reactivation of tuberculosis than the other anti-TNF drugs and it has been suggested that etanercept might be less immunogenic, especially in ankylosing spondylitis. Acute uveitis, Crohn's disease, and sarcoidosis are other adverse events that have been rarely associated with etanercept therapy in patients with ankylosing spondylitis.

Serum tryptase levels and markers of renal dysfunction in a population with chronic kidney disease.

BACKGROUND: Mast cells (MCs) might play a pathogenetic role in renal fibrosis. Tryptase is a marker for activated MCs. Little is known about tryptase levels in the chronic renal disease population. METHODS: We examined serum MC tryptase concentrations in relation to specific laboratory abnormalities in 153 outpatients with chronic kidney disease (CKD) and in 35 hemodialysis (HD) patients. RESULTS: Here we found that tryptase mean values were higher in men than in women (12.4 +/- 7.6 microg/L vs. 10.2 +/- 8.4 microg/L; p<0.05). Tryptase levels were increased in CKD stages 4 and 5 and in HD patients, versus CKD stages 1 and 2: 12.7 +/- 7.3 microg/L, 13.8 +/- 7.8 microg/L, 15 +/- 8.9 microg/L vs. 6.7 +/- 5.1 microg/L (p<0.01). In univariate analysis, in the conservative treatment CKD population, tryptase was positively correlated with urea, creatinine, potassium, uric acid, phosphorus, parathyroid hormone, homocysteine, fibrinogen and proteinuria (p<0.01); tryptase was negatively correlated with calcium, albumin, creatinine clearance, estimated glomerular filtration rate (by abbreviated MDRD equation) and urine creatinine (p<0.01). In HD patients, the only significative correlation found was with systolic blood pressure and diastolic blood pressure (p<0.01). No significant correlations were found between tryptase and other parameters such as albumin, glucose, hemoglobin, leukocytes, immunoglobulins or C-reactive protein. Multiple regression analysis showed estimated glomerular filtration rate and proteinuria to be independent determinants of tryptase. CONCLUSIONS: This is the first study to determine that tryptase levels increase with higher degrees of kidney dysfunction. The association with markers of diminished renal function suggests impaired metabolism or a negative effect of inflammation on glomerular filtration rate. Further studies are required to ascertain the clinical implications of these findings.