Validation of an Inhaled Therapy Beliefs Questionnaire in Patients with Chronic Obstructive Pulmonary Disease.

Background: To carry out a validation questionnaire that assesses beliefs about inhaled treatments in patients with chronic obstructive pulmonary disease (COPD), as knowing patients' beliefs could help to improve medication adherence and health outcomes. Methods: We evaluated data from 260 COPD patients from electronic medical record databases from five primary healthcare centers, in a descriptive, cross-sectional study with a sample size calculated for a 10-item questionnaire, with an estimated Cronbach's alpha of 0.70 and a 95% confidence level. Study participants were selected via systematic random sampling. Variables: Ten-item Inhaled Therapy Beliefs Questionnaire, CCTI-Questionnaire v.2.0, time for completion, age, sex, educational level, spirometry severity (GOLD criteria), exacerbations (previous year), characteristics of inhaled treatment, and smoking habit. A two-year follow-up in a subsample of 77 patients from one health center was utilized. The Morisky-Green test, pharmacy dispensing data, test-retest (kappa coefficient), and an exploratory analysis of the adherence-belief relationship (ji-squared) were measured. Results: The 10-item questionnaire showed good viability (3 min completion time) when performed face-to-face or telephonically; its psychometric properties were acceptable, with an internal consistency (Cronbach's alpha) score of 0.613. Three factors explained 47.58% of the total variance (p < 0.0001): use (factor 1), effects (factor 2), and objectives (factor 3) of inhalers. The two-year follow-up ultimately considered 58 out of the 77 patients (10 deceased, 4 unlocated, 2 mistakes, 2 no inhaled treatment, and 1 withdrawal). Non-adherence was 48.3% in terms of the Morisky-Green test; 31% in terms of pharmacy dispensing data; and 40.4% considering both methods. There was low test-retest reliability, indicated by items 4, 8, and 9 of the CCTI-Questionnaire (Kappa = 0.4, 0.26, and 0.34; p-value < 0.0001, 0.008, and 0.001, respectively). There was mild correlation between beliefs and adherence. Conclusions: The ten-item CCTI-Questionnaire v.2.0 demonstrated acceptable psychometric properties regarding feasibility, reliability, and content validity.

Genome-wide CRISPR screens identify novel regulators of wild-type and mutant p53 stability.

Tumor suppressor p53 (TP53) is frequently mutated in cancer, often resulting not only in loss of its tumor-suppressive function but also acquisition of dominant-negative and even oncogenic gain-of-function traits. While wild-type p53 levels are tightly regulated, mutants are typically stabilized in tumors, which is crucial for their oncogenic properties. Here, we systematically profiled the factors that regulate protein stability of wild-type and mutant p53 using marker-based genome-wide CRISPR screens. Most regulators of wild-type p53 also regulate p53 mutants, except for p53 R337H regulators, which are largely private to this mutant. Mechanistically, FBXO42 emerged as a positive regulator for a subset of p53 mutants, working with CCDC6 to control USP28-mediated mutant p53 stabilization. Additionally, C16orf72/HAPSTR1 negatively regulates both wild-type p53 and all tested mutants. C16orf72/HAPSTR1 is commonly amplified in breast cancer, and its overexpression reduces p53 levels in mouse mammary epithelium leading to accelerated breast cancer. This study offers a network perspective on p53 stability regulation, potentially guiding strategies to reinforce wild-type p53 or target mutant p53 in cancer.

Analysis of the circumstances associated with death and predictors of mortality in Spanish adults with Down syndrome, 1997-2014.

OBJECTIVES: Characterise the circumstances associated with death during admission of adults with Down syndrome (DS) and to identify predictors of mortality. PATIENTS AND METHODS: Observational study based on data on all emergent admissions of adults with DS to hospitals of the Spanish National Health System between 1997 and 2014. We analysed epidemiological and clinical variables. RESULTS: We analysed admissions of 11,594 adults with DS, mean age 47 years. 1715 patients died (15%), being the highest mortality (35%) in individuals aged 50-59. A past medical history of cerebrovascular disease (aOR 2.95 [2.30-3.77]) or cancer (aOR 2.79 [2.07-3.75]), gross aspiration's admission (aOR 2.59 [2.20-3.04]), immobility (aOR 2.31 [1.46-3-62]), and readmission within 30 days (aOR 2.43 [2.06-2.86]) were identified as predictors of mortality. CONCLUSIONS: Adults with DS have a high in-hospital mortality rate. The main predictors of death were cerebrovascular disease, cancer, early readmission, and conditions commonly associated with advanced dementia.

What brings adults with Down syndrome to the hospital? A retrospective review of a Spanish cohort between 1997 and 2014.

OBJECTIVES: To describe the clinical and epidemiological characteristics of adult patients with Down syndrome admitted to Spanish hospitals between 1997 and 2014. Secondary goals were to study trend changes over time, and to analyse differences between patients admitted to medical and surgical departments. PATIENTS AND METHODS: Retrospective observational study on data collected from the Minimum Basic Dataset (MBDS, Conjunto Mínimo Básico de Datos [CMBD]) of admissions of adults with Down syndrome to hospitals belonging to the Spanish National Health System from 1 January 1997 through 31 December 2014. We analysed epidemiological and clinical variables. RESULTS: We analysed 28,716 admissions of 16,874 adult patients with Down syndrome. Men accounted for 58.2% of the sample, and the mean age on admission was 41 ± 13 years, with an 11-year increase in mean age during the study period. Admissions among persons with Down syndrome increased by 5% during the study period, with a noticeable rise in admissions of older adults and to medical departments. Almost one-third of patients (31.8%) were admitted more than once. Age-adjusted mortality was 15.7%. The most common comorbid conditions were chronic obstructive pulmonary disease (25%), hypothyroidism (18.6%), and epilepsy (14.3%). The departments with the highest numbers of admissions were internal medicine (26.3%), pulmonary medicine (6.9%), and general surgery (5.25%). CONCLUSION: Hospital admissions among Spanish adults with Down syndrome have increased in recent decades, especially in older patients. We identified substantial differences between patients admitted to medical and surgical departments.

Development and feasibility of 4 checklists for the evaluation of comorbidity in patients with rheumatoid arthritis, axial spondyloarthritis and psoriatic arthritis: GECOAI Project.

OBJECTIVE: To develop and assess the feasibility in daily practice of four comorbidity checklists, for common use in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). METHODS: A multidisciplinary panel of experts on comorbidity was established. Data from the GECOAR, GECOAX and GECOAP projects were analysed and a narrative literature review in Medline on RA, axSpA and PsA comorbidity was performed in order to select the most relevant and common comorbidities across the three diseases. With these results and those obtained from a focus group of patients, in a nominal group meeting, the experts generated preliminary checklists. These were afterwards modified by an external evaluation by two associations, a patients' association and an association of health professionals related to rheumatology. As a result, the final checklists were generated. A cross-sectional study was conducted to test the feasibility of three of the checklists in daily practice, in which eight health professionals evaluated the checklists in five patients with RA, five with axSpA and five with SpA. RESULTS: Four comorbidity checklists were designed, three for health professionals (one to assess current comorbidity, one on prevention/health promotion and one with the referral criteria to other health professionals), and another for patients. The feasibility study showed them to be simple, clear, and useful for use in routine clinical practice. CONCLUSIONS: The use of specific and common checklists for patients with RA, axSpA and PsA is feasible and might contribute favorably to their prognosis as well as in daily practice.

Hemiagenesia tiroidea: caso clínico y revisión de la literatura / Thyroid hemiagenesis: clinical case and review of the literature

La hemiagenesia tiroidea representa un trastorno congénito caracterizado por la ausencia de desarrollo de uno de los lóbulos tiroideos, asociado o no a ausencia del istmo. Es más frecuente en las mujeres y por lo general se presenta como falta del lóbulo izquierdo, con hipertrofia compensatoria del lóbulo contralateral. Su diagnóstico es generalmente incidental o por manifestaciones del lóbulo tiroideo presente. Se hizo una revisión bibliografía, en donde no se encontraron casos reportados en Venezuela de hemiagenesia o agenesia tiroidea, describiéndose el siguiente. Presentamos a una paciente de 50 años de edad, conocida con hipotiroidismo desde los 31 años, negando cualquier cirugía en el área de cabeza y cuello. Desde febrero 2019 presentó aumento progresivo de volumen en región anterior de cuello. Al examen físico se observó aumento de volumen en región anterior derecha del cuello, palpándose lóbulo tiroideo derecho aumentado de tamaño, de aspecto nodular, no doloroso. En ecosonograma tiroideo se concluyó como bocio tiroideo derecho de aspecto multinodular, con ausencia del lóbulo izquierdo. Perfil tiroideo dentro de límites normales. Se lleva a mesa operatoria corroborándose ausencia del lóbulo izquierdo y presentado en la biopsia definitiva hiperplasia nodular en el lóbulo derecho. Se discute su frecuencia, la forma de presentación y se hace revisión de la literatura(AU)

Thyroid hemiagenesis represents a congenital disorder characterized by the absence of development of one of thyroid lobes, associated or not with absence of isthmus. It is more frequent in women and generally presents as absence of the left lobe, with compensatory hypertrophy of the contralateral lobe. Its diagnosis is generally incidental or by manifestations of the present thyroid lobe. A bibliography review was made, where no cases reported in Venezuela of hemiagenesis or thyroid agenesis were found, describing the following. We present a 50-year-old patient, known with hypothyroidism since she was 31, denying any surgery in the head and neck area. Since February 2019, presented a progressive increase in volume in the anterior neck region. On physical examination, an increase in volume was observed in right anterior region of the neck, palpating an enlarged right thyroid lobe, with a nodular appearance and not painful. In a thyroid echo-sonogram, it was concluded as a right thyroid goiter with a multinodular appearance, with the absence of the left lobe. Thyroid profile within normal limits. It is taken to the operating table, confirming the absence of the left lobe and presented in the definitive biopsy nodular hyperplasia in the right lobe. Its frequency, form of presentation, and literature review are discussed(AU)

Development and feasibility of 4 checklists for the evaluation of comorbidity in patients with rheumatoid arthritis, axial spondyloarthritis and psoriatic arthritis: GECOAI Project. / Desarrollo y viabilidad de cuatro checklists para la evaluación de la comorbilidad en pacientes con artritis reumatoide, espondiloartritis axial y artritis psoriásica: Proyecto GECOAI.

OBJECTIVE: To develop and assess the feasibility in daily practice of four comorbidity checklists, for common use in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). METHODS: A multidisciplinary panel of experts on comorbidity was established. Data from the GECOAR, GECOAX and GECOAP projects were analysed and a narrative literature review in Medline on RA, axSpA and PsA comorbidity was performed in order to select the most relevant and common comorbidities across the three diseases. With these results and those obtained from a focus group of patients, in a nominal group meeting, the experts generated preliminary checklists. These were afterwards modified by an external evaluation by two associations, a patients' association and an association of health professionals related to rheumatology. As a result, the final checklists were generated. A cross-sectional study was conducted to test the feasibility of three of the checklists in daily practice, in which eight health professionals evaluated the checklists in five patients with RA, five with axSpA and five with SpA. RESULTS: Four comorbidity checklists were designed, three for health professionals (one to assess current comorbidity, one on prevention/health promotion and one with the referral criteria to other health professionals), and another for patients. The feasibility study showed them to be simple, clear, and useful for use in routine clinical practice. CONCLUSIONS: The use of specific and common checklists for patients with RA, axSpA and PsA is feasible and might contribute favorably to their prognosis as well as in daily practice.

Predictors of pre-rehabilitation exercise capacity in elderly European cardiac patients - The EU-CaRE study.

AIMS: Functional capacity is an important endpoint for therapies oriented to older adults with cardiovascular diseases. The literature on predictors of exercise capacity is sparse in the elderly population. In a longitudinal European study on effectiveness of cardiac rehabilitation of seven European countries in elderly (>65 years) coronary artery disease or valvular heart disease patients, predictors for baseline exercise capacity were determined, and reference ranges for elderly cardiac patients provided. METHODS: Mixed models were performed in 1282 patients (mean age 72.9 ± 5.4 years, 79% male) for peak oxygen consumption relative to weight (peak VO2; ml/kg per min) with centre as random factor and patient anthropometric, demographic, social, psychological and nutritional parameters, as well as disease aetiology, procedure, comorbidities and cardiovascular risk factors as fixed factors. RESULTS: The most important predictors for low peak VO2 were coronary artery bypass grafting or valve surgery, low resting forced expiratory volume, reduced left ventricular ejection fraction, nephropathy and peripheral arterial disease. Each cumulative comorbidity or cardiovascular risk factors reduced exercise capacity by 1.7 ml/kg per min and 1.1 ml/kg per min, respectively. Males had a higher peak VO2 per body mass but not per lean mass. Haemoglobin was significantly linked to peak VO2 in both surgery and non-surgery patients. CONCLUSIONS: Surgical procedures, cumulative comorbidities and cardiovascular risk factors were the factors with the strongest relation to reduced exercise capacity in the elderly. Expression of peak VO2 per lean mass rather than body mass allows a more appropriate comparison between sexes. Haemoglobin is strongly related to peak VO2 and should be considered in studies assessing exercise capacity, especially in studies on patients after cardiac surgery.

Barley-ß-glucans reduce systemic inflammation, renal injury and aortic calcification through ADAM17 and neutral-sphingomyelinase2 inhibition.

In chronic kidney disease (CKD), hyperphosphatemia-induced inflammation aggravates vascular calcification (VC) by increasing vascular smooth muscle cell (VSMC) osteogenic differentiation, ADAM17-induced renal and vascular injury, and TNFα-induction of neutral-sphingomyelinase2 (nSMase2) to release pro-calcifying exosomes. This study examined anti-inflammatory ß-glucans efficacy at attenuating systemic inflammation in health, and renal and vascular injury favoring VC in hyperphosphatemic CKD. In healthy adults, dietary barley ß-glucans (Bßglucans) reduced leukocyte superoxide production, inflammatory ADAM17, TNFα, nSMase2, and pro-aging/pro-inflammatory STING (Stimulator of interferon genes) gene expression without decreasing circulating inflammatory cytokines, except for γ-interferon. In hyperphosphatemic rat CKD, dietary Bßglucans reduced renal and aortic ADAM17-driven inflammation attenuating CKD-progression (higher GFR and lower serum creatinine, proteinuria, kidney inflammatory infiltration and nSMase2), and TNFα-driven increases in aortic nSMase2 and calcium deposition without improving mineral homeostasis. In VSMC, Bßglucans prevented LPS- or uremic serum-induced rapid increases in ADAM17, TNFα and nSMase2, and reduced the 13-fold higher calcium deposition induced by prolonged calcifying conditions by inhibiting osteogenic differentiation and increases in nSMase2 through Dectin1-independent actions involving Bßglucans internalization. Thus, dietary Bßglucans inhibit leukocyte superoxide production and leukocyte, renal and aortic ADAM17- and nSMase2 gene expression attenuating systemic inflammation in health, and renal injury and aortic calcification despite hyperphosphatemia in CKD.

Perforación no traumática del íleon terminal. A propósito de un caso / Nontraumaticperforationofthe terminal ileum. About a case / Perfuraçãonão traumática do íleo terminal. Sobre um caso

RESUMEN Introducción: la perforación del íleon terminal es una causa de la peritonitis oscura, anunciado por la exacerbación del dolor abdominal asociado con la defensa muscular y la rigidez más pronunciado sobre la fosa ilíaca derecha. Sin embargo, muchos pacientes, en un estado tóxico grave, pueden ser no clásicas sus características clínicas y conllevar a demoras en el diagnóstico y la intervención quirúrgica adecuada Presentación de caso: se presenta el caso de una paciente operada de urgencias en la capital de las Islas Seychelles con diagnóstico de perforación no traumática del íleon terminal. Se realizó resección intestinal con anastomosis término lateral en dos planos con evolución favorable. Discusión: el desbridamiento simple y el cierre primario de la perforación es el procedimiento más comúnmente empleado, pero en casos en los que, además, se encuentra una contaminación importante con íleon terminal friable (causado por una presentación tardía, perforaciones múltiples o por peritonitis fecaloidea), se hace obviamente necesario algo más que el mero cierre de la perforación para reducir la incidencia de complicaciones mortales como la fístula fecaloidea. Conclusiones: los tempranos diagnóstico y tratamiento evitan procederes más complicados, y también están asociados a una menor morbilidad y mortalidad en estos pacientes, y en el paciente quirúrgico en general.

ABSTRACT Introduction: perforation of the terminal ileum is a cause of the dark peritonitis, announced by the exacerbation of the abdominal pain associated with the muscular defense and the more pronounced rigidity on the right iliac fossa. However, many patients, in a severe toxic state, may be non-classical clinical characteristics and lead to delays in diagnosis and appropriate surgical intervention. Case presentation: the case of an emergency operated patient is presented in the capital of the Seychelles Islands with a diagnosis of non-traumatic perforation of the terminal ileum. Intestinal resection was performed with lateral term anastomosis in two planes with favorable evolution. Discussion: simple debridement and primary closure of the perforation is the most commonly used procedure, but in cases in which there is also significant contamination with friable terminal ileum (caused by late presentation, multiple perforations or fecaloid peritonitis). ), something more than the mere closure of the perforation is obviously necessary to reduce the incidence of fatal complications such as the fecaloid fistula. Conclusions: early diagnosis and treatment avoid more complicated procedures, and they are also associated with lower morbidity and mortality in these patients, 3 and in the surgical patient in general.

RESUMO Introdução: a perfuração terminal do íleo é uma causa do peritonitis escuro, anunciada pela exacerbação da dor abdominal associadacom a defesa do músculo e a rigidez mais pronunciada sobre o poço ilíaco direito. Entretanto, muitos pacientes, emum estado tóxico severo, podem ser não-Classicalsuas características clínicas e conduziraos atrasos no diagnóstico e à intervençãocirúrgicaapropriada Apresentação do caso: o exemplo de um paciente emergência-operado no capital das ilhas de Seychelles comum diagnóstico da puncturanão-traumático do drenagem terminal é apresentado. A ressecção intestinal com anastomose de termo lateral foi realizada emdois planos comevoluçãofavorável. Discussão: o desbridamento simples e o fechamento preliminar da perfuraçãosão o procedimento o maisgeralmente usado, mas nos casos onde, além, a contaminação significativa com o drenagem terminal friável é encontrada (causada por umaapresentação atrasada, perfuraçõesmúltiplasou pelo peritonitis restos), torna-se obviamente necessáriomais do que apenas fechando a perfuração para reduzir a incidência de complicaçõesfataistais como a fístula restos. Conclusões: o diagnóstico precoce e o tratamentoevitamaçõesmais complicadas, e tambémestãoassociadoscom menor morbidade e mortalidadenesses pacientes3, e no paciente cirúrgicoemgeral.

Use of lip photoprotection in patients suffering from actinic cheilitis.

BACKGROUND: Actinic cheilitis (AC) is a chronic condition that affects mainly the lower lip. OBJECTIVES: To investigate the use of lip photoprotection in patients with AC. MATERIALS AND METHODS: A cross-sectional multicentre study of patients, ≥45 years of age, was performed in eight dermatology departments in the Galicia region over a period of one year. From 1,239 patients included in the study, 410 were diagnosed with AC and complete data were available for 408. An analysis of lip photoprotection habits and possible associations in patients with AC is reported. RESULTS: Mean age of patients with AC was 71.9 years and 53.8% were women. More than 90% of AC patients (370/408) had never used lip photoprotection. In the group of patients who used it, 62.16% of them had only used a single stick within the previous year. The only variable significantly associated with the use of lip sun protection was low Fitzpatrick's skin types I and II (p=0.039). Study limitations include the inclusion of patients 45 years or older and the use of a semiquantitative scale for measuring the frequency of application of lip photoprotection. CONCLUSION: To our knowledge, this is the first European study focused on lip photoprotection in patients suffering from AC. Only a minority of AC patients protect their lips from UV radiation. Specific lip sun protection recommendations should be promoted, especially in high-risk populations.

Quiste de Mesenterio. Presentación de un caso / Mesentery cyst. Presentation of a case / Cisto de mesentério. Apresentação de um caso

RESUMEN Se presenta el caso de un paciente masculino de 9 años, ingresado en los servicios de pediatría y cirugía del Hospital General Peltier de la República de Djibouti, con diagnóstico de tumor abdominal gigante, el cual es intervenido quirúrgicamente y se realiza escisión completa del tumor quístico. El estudio anatomopatológico mostró quiste del mesenterio. Se revisa la literatura y se ofrecen consideraciones.

ABSTRACT We present the case of a 9-year-old male patient, admitted to the pediatrics and surgery departments of the Peltier General Hospital of the Republic of Djibouti, with a diagnosis of a giant abdominal tumor, which is operated on and a complete excision of the cystic tumor is performed. The anatomopathological study showed cyst of the mesentery. The literature is reviewed and considerations are offered.

RESUMO Apresentamos o caso de um paciente do sexo masculino, 9 anos, internado nos departamentos de pediatria e cirurgia do Hospital Geral de Peltier, República de Djibuti, com diagnóstico de tumor abdominal gigante, que é operado e completa excisão do tumor cístico. . O estudo anatomopatológico mostrou cisto do mesentério. A literatura é revisada e considerações são oferecidas.

Actinic Cheilitis Prevalence and Risk Factors: A Cross-sectional, Multicentre Study in a Population Aged 45 Years and Over in North-west Spain.

Actinic cheilitis is thought to be a premalignant lesion or a superficial squamous cell carcinoma. The prevalence of actinic cheilitis in Europe is unknown. The aim of this study was to determine the prevalence of actinic cheilitis in the Galicia region (north-west Spain). Secondary objectives were the description of risk factors of actinic cheilitis. A cross-sectional multicentre study in patients ≥ 45 years of age was performed in 8 dermatology departments in Galicia region during a 1-year period. The prevalence of actinic cheilitis was 31.3%. Significant and independent risk factors of actinic cheilitis after multivariate analysis were age ≥ 60 years, Fitzpatrick skin phototype II, outdoor working for more than 25 years, and previous history of non-melanoma skin cancer. This is the first cross-sectional multicentre study of the prevalence of actinic cheilitis in Europe. Actinic cheilitis was present in almost one-third of the screened patients. Lip examination should be performed in all patients with chronic actinic damage.

A Mutation in the UL24 Gene Abolishes Expression of the Newly Identified UL24.5 Protein of Herpes Simplex Virus 1 and Leads to an Increase in Pathogenicity in Mice.

Herpes simplex virus 1 (HSV-1) infects the host via epithelia and establishes latency in sensory neurons. The UL24 gene is conserved throughout the Herpesviridae family, and the UL24 protein is important for efficient viral replication and pathogenesis. Multiple transcripts are expressed from the UL24 gene. The presence of a transcription initiation site inside the open reading frame of UL24 and an ATG start codon in the same open reading frame led us to suspect that another protein was expressed from the UL24 locus. To test our hypothesis, we constructed a recombinant virus that expresses a hemagglutinin tag at the C terminus of UL24. Western blot analysis revealed the expression of an 18-kDa protein that is not a degradation product of the full-length UL24, which we refer to as UL24.5. Ectopically expressed UL24.5 did not induce the dispersal of nucleolar proteins, as seen for UL24. In order to characterize the role of UL24.5, we constructed a mutant virus encoding a substitution of the predicted initiation methionine to a valine. This substitution eliminated the expression of the 18-kDa polypeptide. Unlike the UL24-null mutant (UL24X), which exhibits reduced viral yields, the UL24.5-null mutant exhibited the same replication phenotype in cell culture as the parental strain. However, in a murine ocular infection model, we observed an increase in the incidence of neurological disorders with the UL24.5 mutant. Alignment of amino acid sequences for various herpesviruses revealed that the initiation site of UL24.5 is conserved among HSV-1 strains and is present in many herpesviruses.IMPORTANCE We discovered a new HSV-1 protein, UL24.5, which corresponds to the C-terminal portion of UL24. In contrast to the replication defects observed with HSV-1 strains that do not express full-length UL24, the absence of UL24.5 did not affect viral replication in cell culture. Moreover, in mice, the absence of UL24.5 did not affect viral titers in epithelia or trigeminal ganglia during acute infection; however, it was associated with a prolonged persistence of signs of inflammation. Strikingly, the absence of UL24.5 also led to an increase in the incidence of severe neurological impairment compared to results for wild-type control viruses. This increase in pathogenicity is in stark contrast to the reduction in clinical signs associated with the absence of full-length UL24. Bioinformatic analyses suggest that UL24.5 is conserved among all human alphaherpesviruses and in some nonhuman alphaherpesviruses. Thus, we have identified UL24.5 as a new HSV-1 determinant of pathogenesis.

Post-operative stress hyperglycemia is a predictor of mortality in liver transplantation.

BACKGROUND: A significant association is known between increased glycaemic variability and mortality in critical patients. To ascertain whether glycaemic profiles during the first week after liver transplantation might be associated with long-term mortality in these patients, by analysing whether diabetic status modified this relationship. METHOD: Observational long-term survival study includes 642 subjects undergoing liver transplantation from July 1994 to July 2011. Glucose profiles, units of insulin and all variables with influence on mortality are analysed using joint modelling techniques. RESULTS: Patients registered a survival rate of 85% at 1 year and 65% at 10 years, without differences in mortality between patients with and without diabetes. In glucose profiles, however, differences were observed between patients with and without diabetes: patients with diabetes registered lower baseline glucose values, which gradually rose until reaching a peak on days 2-3 and then subsequently declined, diabetic subjects started from higher values which gradually decreased across the first week. Patients with diabetes showed an association between mortality and age, Model for End-Stage Liver Disease score (MELD) score and hepatitis C virus; among non-diabetic patients, mortality was associated with age, body mass index, malignant aetiology, red blood cell requirements and parenteral nutrition. Glucose profiles were observed to be statistically associated with mortality among patients without diabetes (P = 0.022) but not among patients who presented with diabetes prior to transplantation (P = 0.689). CONCLUSIONS: Glucose profiles during the first week after liver transplantation are different in patients with and without diabetes. While glucose profiles are associated with long-term mortality in patients without diabetes, after adjusting for potential confounding variables such as age, cause of transplantation, MELD, nutrition, immunosuppressive drugs, and units of insulin administered, this does not occur among patients with diabetes.

Bootstrap-based procedures for inference in nonparametric receiver-operating characteristic curve regression analysis.

Prior to using a diagnostic test in a routine clinical setting, the rigorous evaluation of its diagnostic accuracy is essential. The receiver-operating characteristic curve is the measure of accuracy most widely used for continuous diagnostic tests. However, the possible impact of extra information about the patient (or even the environment) on diagnostic accuracy also needs to be assessed. In this paper, we focus on an estimator for the covariate-specific receiver-operating characteristic curve based on direct regression modelling and nonparametric smoothing techniques. This approach defines the class of generalised additive models for the receiver-operating characteristic curve. The main aim of the paper is to offer new inferential procedures for testing the effect of covariates on the conditional receiver-operating characteristic curve within the above-mentioned class. Specifically, two different bootstrap-based tests are suggested to check (a) the possible effect of continuous covariates on the receiver-operating characteristic curve and (b) the presence of factor-by-curve interaction terms. The validity of the proposed bootstrap-based procedures is supported by simulations. To facilitate the application of these new procedures in practice, an R-package, known as npROCRegression, is provided and briefly described. Finally, data derived from a computer-aided diagnostic system for the automatic detection of tumour masses in breast cancer is analysed.

Studying the relationship between a woman's reproductive lifespan and age at menarche using a Bayesian multivariate structured additive distributional regression model.

Studies addressing breast cancer risk factors have been looking at trends relative to age at menarche and menopause. These studies point to a downward trend of age at menarche and an upward trend for age at menopause, meaning an increase of a woman's reproductive lifespan cycle. In addition to studying the effect of the year of birth on the expectation of age at menarche and a woman's reproductive lifespan, it is important to understand how a woman's cohort affects the correlation between these two variables. Since the behavior of age at menarche and menopause may vary with the geographic location of a woman's residence, the spatial effect of the municipality where a woman resides needs to be considered. Thus, a Bayesian multivariate structured additive distributional regression model is proposed in order to analyze how a woman's municipality and year of birth affects a woman's age of menarche, her lifespan cycle, and the correlation of the two. The data consists of 212,517 postmenopausal women, born between 1920 and 1965, who attended the breast cancer screening program in the central region of Portugal.

Identification and management of comorbidity in psoriatic arthritis: evidence- and expert-based recommendations from a multidisciplinary panel from Spain.

The objective is to establish recommendations, based on evidence and expert opinion, for the identification and management of comorbidities in patients with psoriatic arthritis (PsA). The following techniques were applied: discussion group, systematic review, and Delphi survey for agreement. A panel of professionals from four specialties defined the users, the sections of the document, possible recommendations, and what systematic reviews should be performed. A second discussion was held with the results of the systematic reviews. Recommendations were formulated in the second meeting and voted online from 1 (total disagreement) to 10 (total agreement). Agreement was considered if at least 70% voted ≥7. The level of evidence and grade of recommendation were assigned using the Oxford Centre for Evidence-Based Medicine guidance. The full document was critically appraised by the experts, and the project was supervised at all times by a methodologist. In a final step, the document was reviewed and commented by a patient and a health management specialist. Fourteen recommendations were produced, together with a checklist to facilitate the implementation. The items with the largest support from evidence were those related to cardiovascular disease and risk factors. The panel recommends paying special attention to obesity, smoking, and alcohol consumption, as they are all modifiable factors with an impact on treatment response or complications of PsA. Psychological and organizational aspects were also deemed important. We herein suggest practical recommendations for the management of comorbidities in PsA based on evidence and expert opinion.

Glycemic Variability and Its Association With Demographics and Lifestyles in a General Adult Population.

OBJECTIVE: The objective was to investigate glycemic variability indices in relation to demographic factors and common environmental lifestyles in a general adult population. METHODS: The A Estrada Glycation and Inflammation Study is a cross-sectional study covering 1516 participants selected by sampling of the population aged 18 years and over. A subsample of 622 individuals participated in the Glycation project, which included continuous glucose monitoring procedures. Five glycemic variability indices were analyzed, that is, SD, MAGE, MAG, CONGA1, and MODD. RESULTS: Participants had a mean age of 48 years, 62% were females, and 12% had been previously diagnosed with diabetes. In the population without diabetes, index distributions were not normal but skewed to the right. Distributional regression models that adjusted for age, gender, BMI, alcohol intake, smoking status, and physical activity confirmed that all indices were positively and independently associated with fasting glucose levels and negatively with heavy drinking. SD, MAGE, and CONGA1 were positively associated with aging, and MAG was negatively associated with BMI. None of the GVI studied were influenced by physical activity. Age-group-specific reference values are given for the indices. CONCLUSIONS: This study yielded age-specific reference values for glucose variability indices in a general adult population. Significant increases were observed with aging. Heavy drinking of more than 140 g/week was associated with significant decreases in variability indices. No differences were found between males and females. These normative ranges provide a guide for clinical care, and may offer an alternative treatment target among persons with diabetes.