Influence of abiotic factors on diapause termination and temperature requirements for postdiapause development in the European red mite, Panonychus ulmi (Acari: Tetranychidae).

The European red mite Panonychus ulmi (Koch) is widely distributed and it can severely affect pome fruit crops, particularly apple. Pest outbreaks are related to an overuse of non-selective pesticide treatments that lead to the development of resistance and the absence of natural enemies in the orchard. A key aspect to optimize the use of pesticide treatments in the context of IPM is to increase the knowledge on the biology and ecology of the pest to better predict population dynamics and outbreaks. For the European red mite, knowledge on the conditions that lead to diapause breaking by winter eggs is essential to model population dynamics. To increase this knowledge, winter eggs were collected during field surveys in northen Spain during three years and egg hatching was monitored under controlled temperature and photoperiod conditions in the laboratory. The "number of days exposed to cold temperatures" was the most significant factor that positively affected hatching of overwintering eggs. The time required for 50% of the egg population to hatch (T50%) was also negatively modulated by the duration of exposure to cold temperature. The temperature threshold for postdiapause eggs development collected from the field was estimated between 5 and 6 ºC in 2005 and 2007, respectively. Moreover, the degree-days required for post diapause development were estimated between 263.2 and 270.3, depending on the year of collection. Collectively, we provide additional information on the diapause termination and postdiapause development of the European red mite that may effectively contribute to optimize pest population models.

Vaginal collagen I and III changes after carbon dioxide laser application in postmenopausal women with the genitourinary syndrome: a pilot study.

OBJECTIVE: The aim of the study was to evaluate the clinical response and collagen remodeling in the vaginal wall after three sessions of carbon dioxide (CO2) laser application. METHODS: Fourteen postmenopausal women with vulvovaginal atrophy, aged 45-65 years and sexually active, were evaluated with clinical questionnaires, gynecological examinations and histological techniques before and after 20 weeks of treatment (ClinicalTrials.gov NCT03939078). Treatment consisted of 3-monthly sessions of the CO2 laser. Clinical questionnaires included the Vaginal Health Index, the Female Sexual Function Index and the International Consultation on Incontinence Questionnaires Short Form. Biopsies were taken from the lateral vaginal wall at week 0 (left wall) and week 20 (right wall). Tissue samples were stained with hematoxylin and eosin, Periodic Acid-Schiff, Picrosirius Red Stain and Orcein dyes. Immunohistochemical study was used to quantify collagens I and III in the samples. RESULTS: The mean age was 54.4 ± 4.5 years, and the average time of amenorrhea was 7.6 ± 5.1 years. The Female Sexual Function Index and the Vaginal Health Index Score values increased while the International Consultation on Incontinence Questionnaire Short Form score decreased after the programmed treatment. There was no significant change in vaginal pH. Histological studies showed increases in the total and superficial epithelial cell layers, and type III collagen fibers (from 10.86 ± 7.66 to 16.87 ± 3.96, p < 0.05), and immunohistochemical studies confirmed the significant increase in collagen III. CONCLUSION: Histological findings revealed epithelial atrophy reversal and collagen remodeling of the vaginal wall. Immunohistochemical analysis showed an increase in collagen type III fibers.

Preventive dental management of osteonecrosis of the jaws related to zoledronic acid treatment.

OBJECTIVE: To evaluate the effect of preventive dental management on reducing the incidence and delaying the onset of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients treated with intravenous zoledronic acid (ZA). MATERIALS AND METHODS: This single-center clinical study included 255 patients with cancer monitored over a 6-year period. Patients received dental treatment prior to (group A) or after (group B) the initiation of ZA therapy. Dental treatments performed, incidence proportion (IP), and incidence rate (IR) in both groups were analyzed using significance tests. BRONJ onset was estimated using the Kaplan-Meier estimator and log-rank test. Independent risk factors to develop BRONJ were evaluated using Cox regression analysis models. RESULTS: Thirty-seven patients suffered from BRONJ (IP = 14.5%), 7.3% in group A and 36.5% in group B (p = .000). The IR was 0.007 patients/month in group B and 0.004 in group A. BRONJ-free survival at 3 years was 97% in group A and 66% in group B. Survival curves were significant (p = .056) according to log-rank test. Multivariate Cox models showed that dental extractions (p = .000) were significant. CONCLUSIONS: BRONJ occurred significantly in patients who underwent dental extractions after the initiation of ZA and did not accomplish a preventive dental program.

Validation of the Spanish version of the Franciscan Hospital for Children Oral Health-Related Quality of Life questionnaire.

BACKGROUND: The Franciscan Hospital for Children Oral Health-Related Quality of Life questionnaire (FHC-OHRQOL-Q) is an instrument designed specifically for parents and caregivers of patients with special needs that has not yet been applied in Spain. The aim of this study was to adapt it to Spanish and evaluate its reliability and validity in patients with intellectual disability (ID) treated under general anesthesia. MATERIAL AND METHODS: The study was conducted in two different stages: a) cross-cultural adaptation of the original questionnaire, and b) cross-sectional study on 100 parents and caregivers who completed the piloted FHC-OHRQOL-Q. The patients were examined according to the WHO methodology. Dental treatments performed were recorded. Statistical tests were used to evaluate reliability (internal consistency) and validity (content, criterion, construct and discriminant) of the instrument. RESULTS: The mean age was 24 years (range=4-71 years). The most frequent causes of ID were psychomotor retardation (25%) and cerebral palsy (24%). The items most frequently answered by parents and caregivers were eating and nutrition problems (80%) and bad breath/taste (57%). Reliability (Cronbach's alpha coefficient) was considered excellent (alpha=0.80-0.95). The analysis of the factorial validity yielded similar results to the original questionnaire. The high response rate of items (>96%) allowed content validity. Criterion validity was confirmed by a significant correlation with questions on oral health and oral well-being. Discriminant validity was demonstrated by the significant association of ≥21.5 years of age with worse oral symptoms (p=0.034) and parental concerns (p=0.005), DMFT index ≥3 with daily life problems (p=0.02), ≥4 decayed teeth with daily life problems (p=0.001), and >2 dental extractions with oral symptoms (p=0.000), daily life problems (p=0.002) and parent's perceptions (p=0.043). CONCLUSIONS: The FHC-OHRQOL-Q in Spanish is a reliable and valid instrument to apply in clinical practice to evaluate the impact of OHRQOL in mostly adult patients with ID, accessible to Spanish-speaking parents and caregivers.

Use of Torulaspora delbrueckii and Saccharomyces cerevisiae in semi-industrial sequential inoculation to improve quality of Palomino and Chardonnay wines in warm climates.

AIMS: We have evaluated for the first time the impact of two commercial yeast strains (Torulaspora delbrueckii TD291 and Saccharomyces cerevisiae QA23) inoculated sequentially in musts of Chardonnay and Palomino Fino grape varieties grown under warm climate (South-west of Spain). METHODS AND RESULTS: Semi-industrial scale alcoholic fermentations (AF) were performed during the 2011 and 2012 harvests. Implantation analyses demonstrated that T. delbrueckii is the predominant strain until the end of the AF phase. Wines with sequential inoculation (SI) resulted in the production of low levels of acetic acid (which gives wine an undesirable 'vinegary' character), low acetaldehyde in Chardonnay and high in Palomino wines. The most salient attributes that contribute to the quality of the Chardonnay and Palomino wines produced were aroma intensity, fresh and tropical fruit character. CONCLUSIONS: This study demonstrated that SI of T. delbrueckii and S. cerevisiae contribute significantly to the improvement of Chardonnay wine aromas and the creation of new styles of wine for Palomino. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has generated new knowledge about the biotechnological potential of T. delbrueckii (TD219) and S. cerevisiae (QA23) for improving the organoleptic properties of Chardonnay and Palomino wines.

Individual and regional factors of access to the renal transplant waiting list in france in a cohort of dialyzed patients.

Several studies have investigated geographical variations in access to renal transplant waiting lists, but none has assessed the impact on these variations of factors at both the patient and geographic levels. The objective of our study was to identify medical and non-medical factors at both these levels associated with these geographical variations in waiting-list placement in France. We included all incident patients aged 18-80 years in 11 French regions who started dialysis between January 1, 2006, and December 31, 2008. Both a multilevel Cox model with shared frailty and a competing risks model were used for the analyses. At the patient level, old age, comorbidities, diabetic nephropathy, non-autonomous first dialysis, and female gender were the major determinants of a lower probability of being waitlisted. At the regional level, the only factor associated with this probability was an increase in the number of patients on the waiting list from 2005 to 2009. This finding supports a slight but significant impact of a regional organ shortage on waitlisting practices. Our findings demonstrate that patients' age has a major impact on waitlisting practices, even for patients with no comorbidity or disability, whose survival would likely be improved by transplantation compared with dialysis.

Ocular myasthenia gravis and risk factors for developing a secondary generalisation: description of a Spanish series.

INTRODUCTION: Ocular myasthenia gravis (MG) is the most common phenotype of MG at onset. A variable percentage of these patients develop secondary generalisation; the risk factors for conversion and the protective effect of immunosuppressive treatment are currently controversial. PATIENTS AND METHODS: We designed a retrospective single-centre study with the aim of describing the demographic, clinical, and laboratory characteristics of a Spanish cohort of patients with ocular MG from Hospital Universitario de Albacete from January 2008 to February 2020. RESULTS: We selected 62 patients with ocular MG from a cohort of 91 patients with MG (68.1%). Median age at diagnosis was 68 (IQR, 52-75.3), and men accounted for 61.3% of the sample (n = 38). Most patients presented very late-onset ocular MG (n = 34, 54.8%). Binocular diplopia was the most frequent initial symptom (51.7%). The rate of progression to generalised MG was 50% (n = 31), with a median time of 6 months (IQR, 2-12.8). Female sex (OR: 5.46; 95% CI, 1.16-25-74; P= .03) and anti-acetylcholine receptor antibodies (OR: 8.86; 95% CI, 1.15-68.41; P = .04) were significantly associated with the risk of developing generalised MG. CONCLUSIONS: The conversion rate observed in our series is relatively high. Generalisation of MG mainly occurs during the first 2 years of progression, and is strongly associated with female sex and especially with the presence of anti-acetylcholine receptor antibodies.

Compatibility of the entomopathogenic fungus Beauveria bassiana with flufenoxuron and azadirachtin against Tetranychus urticae.

Laboratory studies were developed to evaluate the compatibility of flufenoxuron and azadirachtin with Beauveria bassiana against Tetranychus urticae larvae along with the required Probit analysis of the involved chemicals on all of the life stages of this mite. Flufenoxuron displayed parallel regression lines for the mortality of eggs, deutonymphs and adults. Larvae and protonymphs were the most susceptible life stages. Protonymphs were 35 times more sensitive than eggs and adults. Azadirachtin gave equal mortality on proto- and deutonymphs. The response of eggs and adults was equivalent when treated with azadirachtin. The regression lines for proto- and deutonymphs were parallel to those of adults and eggs yet three times more sensitive. The effects of separate combinations of the entomopathogenic fungus Beauveria bassiana at its LC(20) with flufenoxuron and azadirachtin at their corresponding LC(40) were evaluated on mite larvae. The application of flufenoxuron with B. bassiana revealed a clear synergy. While the combination of azadirachtin and B. bassiana had an additive effect. These combinations with B. bassiana could improve mite control by contributing to a decline in the likelihood of resistance so often described in the literature.

Deterioration of graffiti spray paints applied on granite after a decade of natural environment.

Graffiti spray paints are commonly used in contemporaneous mural paintings in public spaces, contributing to the transformation of sites and urban life. These outdoor artworks are now beginning to show different deterioration forms, such as physical-mechanical alteration (loss of material and cohesion, etc.) and chromatic changes. However, the deterioration has not been formally characterized, and the influence of the paint composition and underlying substrate are not known. In this study, three non-metallic (red, blue and black) alkyd graffiti spray paints and one metallic (silver) polyethylene graffiti spray paint were applied to two granite stones with different mineralogy and texture and exposed to a natural urban-marine environment near Vigo (NW Spain) for one decade (2010-2020). Physical changes were evaluated by stereomicroscopy, colour spectrophotometry, measurements of gloss, surface roughness and static contact angle, and peeling test. Mineralogical changes were determined by x-ray diffraction and molecular changes by Fourier transform infrared spectroscopy. Moreover, micromorphological and chemical characterization of the surfaces was conducted by scanning electron microscopy. Physical-mechanical changes, such as craquelure and paint loss, depended on the texture of the granite. More specifically, paint on the granite with the finest grain size showed most intense cracking and loss of material. Chemical changes, which were not related to the granite substrate, were most intense in the red and silver paint coatings. In the red paint, loss of binder was accompanied by an intense fading of the colour (due to titanium dioxide relative enrichment), while in the silver paint coating, chemical changes occurred in both the organic binder and aluminium particles, thus darkening the colour. Fewer chemical changes were observed in the blue and black paints. Physical and chemical changes detected in these paints were not correlated.

Simultaneous detection of anti-C1q and anti-double stranded DNA autoantibodies in lupus nephritis: predictive value for renal flares.

Clinical difficulties in predicting systemic lupus erythematosus (SLE) renal flares are still encountered. Biological markers such as autoantibodies (aAbs) may be of major interest for clinicians in the follow-up of SLE patients. The aim of our study was to investigate the clinical utility of one of these biological markers, anti-C1q aAbs, in predicting renal flares of SLE nephritis in comparison with the 'gold standard' anti-double stranded DNA (anti-dsDNA) aAbs. Anti-C1q aAbs and anti-dsDNA aAbs were analysed through a longitudinal retrospective study of 23 SLE patients presenting with one or more renal flares. Anti-C1q and/or anti-dsDNA aAbs were found in 20 (87%) of 23 patients, of whom 16 (69%) displayed both. Thirty-three renal flares occurred during the course of the study, and anti-C1q aAbs and anti-dsDNA aAbs were positive in 25 (76%) and 24 (73%) of these flares respectively. The sensitivity of anti-C1q and/or anti-dsDNA aAbs in predicting renal flares reached 85%. The specificity of anti-C1q aAbs was 84%, of anti-dsDNA aAbs 77% and of both aAbs 97%. Positive and negative predictive values were as follows: 56% and 70% for anti-C1q aAbs, 53% and 72% for anti-dsDNA aAbs. The combination of both aAbs had the highest positive predictive value (69%), whereas absence of both aAbs was associated with the highest negative predictive value (74%). In conclusion, our results confirm that anti-C1q aAbs are present in a significant percentage of SLE patients with active renal involvement, suggesting that these aAbs could be a useful additional marker. The presence of anti-C1q and anti-dsDNA aAbs was associated with a high risk of renal flare, whereas the absence of both aAbs excluded such an event. These data confirm that systematic detection of anti-C1q and anti-dsDNA aAbs is of interest for the follow-up in SLE patients with renal involvement.

The immediate effects of diacutaneous fibrolysis on pain and mobility in patients suffering from painful shoulder: a randomized placebo-controlled pilot study.

OBJECTIVES: To describe the immediate effects of diacutaneous fibrolysis on pain and mobility in patients suffering from painful shoulder, and to assess the ability of the placebo technique to blind participants to group allocation. DESIGN: A double-blind before-after randomized placebo-controlled pilot study. SETTING: Two public centres of Primary Health Care of the Spanish National Health System. PARTICIPANTS: Fifty patients (29 women, 21 men) with a diagnosis of painful shoulder of subacromial origin were included. INTERVENTION: Participants were randomly allocated to one of two groups. The intervention group (N = 25) was actually treated with diacutaneous fibrolysis, while the placebo group (N = 25) was treated with placebo diacutaneous fibrolysis. MEASUREMENTS: Active range of motion (flexion, abduction, extension, external and internal rotation) and pain intensity in the hand-behind-back position were measured. Participants were also asked about their perception in terms of comfort of the technique and results obtained. RESULTS: Between-groups differences were significant in flexion (mean 11.4 degrees; 95% confidence interval (CI) 5.7-17.1), abduction (mean 7.2 degrees; 95% CI 2.0-12.5) and internal rotation movements (mean 3.1 cm; 95% CI 0.1-6.1). There were no significant differences between groups in pain intensity, extension or external rotation movements. The placebo technique showed its ability to blind participants to group allocation. None of the participants suffered any adverse effects from diacutaneous fibrolysis. CONCLUSION: Diacutaneous fibrolysis may be an effective and safe therapeutic option to improve active range of motion in patients suffering from painful shoulder.

Determination of the melatonin content of different varieties of tomatoes (Lycopersicon esculentum) and strawberries (Fragariaananassa).

Melatonin has recently been detected in various plants and foods. However, data regarding the food composition of melatonin are too scarce to evaluate dietary intake. This paper aims to identify melatonin unequivocally using LC-MS in a wide set of varieties of tomatoes (Lycopersicon esculentum) and strawberry (Fragariaananassa). Furthermore, a validated LC fluorescence was developed. This is the first time melatonin has been identified in Bond, Borsalina, Catalina, Gordal, Lucinda, Marbone, Myriade, Pitenza, Santonio, Perlino, Platero, and RAF varieties of tomatoes, as well as in strawberry (Fragaria ananassa): Camarosa, Candonga, Festival, and Primoris. Melatonin concentration was shown to vary greatly depending on the tomato varieties and harvests (2009, 2010), ranging from 4.11ng/g to 114.52ng/g fresh weight. However, the four varieties of strawberries collected during the two harvests showed greater similarity in melatonin (1.38-11.26ng/g fresh weight).

[Non-drug treatments for chronic non-malignant pain: patients' perceptions].

BACKGROUND: The prevalence of chronic pain in Spain is 17%. There is a need for more scientific data on non-drug treat-ments that can be effectively used to treat chronic pain. The aim of this study is to analyze how patients with chronic non-malignant pain perceive non-drug approaches. METHOD: Mixed, descriptive and phenomenological study. Nineteen patients enrolled in a workshop on pain management and non-drug treatments that consisted of four sessions (one session a week). Each session lasted four hours. The patients then participated in a reflective writing activity about their personal experiences. Data from this activity was then ana-lyzed. Atlas.ti 8 software was used for the qualitative data analysis. RESULTS: Sixteen participants tried an alternative therapy and fourteen assessed its benefits. The participants' expecta-tions were divided into three groups of similar size: relief from physical pain, emotional pain management and tools for use in daily life. All the participants were satisfied with the workshop. Perceived personal benefits were better pain and sleep management, reduced fatigue, reduced drug consumption; a more positive approach to life, better mood, more positive energy, more motivation and improved capacity to cope. CONCLUSIONS: The participants commented that the workshop had helped them to reduce pain levels and consume to fewer analgesics, and had reduced other symptoms associated with chronic disease, thus improving their perceived health. They also expressed great satisfaction with the organization and teachers.

Acceptability and tolerability of levetiracetam oral solution for the treatment of partial-onset seizures: the SOLUCIÓN study.

This cross-sectional, observational study evaluated the use of levetiracetam oral solution in usual clinical practice. Patients ≥ 16 years with partial-onset seizures (had received levetiracetam oral solution for ≥ 28 days) completed a study questionnaire assessing overall acceptability of levetiracetam oral solution, specific organoleptic characteristics (taste, taste intensity, aftertaste), ease of use and convenience. Tolerability was assessed by evaluating adverse events. Of 389 patients, 92.8% (361/389) were evaluable for acceptability, all (389) for tolerability; 65.3% (236/361) rated levetiracetam oral solution very acceptable or acceptable, 41.5% (150/361) pleasant or very pleasant, 54.3% (196/361) neither strong nor mild taste intensity and indicated the drug left an aftertaste (most stated aftertaste did not bother them), 75.3% very easy or easy to use and 61.8% very convenient or convenient to use. There was a positive relationship between overall acceptability of levetiracetam oral solution and favorable responses for organoleptic characteristics, ease of use, convenience and patients' evaluation of treatment compliance (P < 0.0001 for each). Of the 176/353 who previously received another antiepileptic drug and reported preference for a medication, 72.2% (127/176) preferred levetiracetam oral solution and 39/389 (10%) reported adverse events. Levetiracetam oral solution demonstrated a high degree of patient acceptability in adult patients with partial-onset seizures and was well tolerated.

Ocular myasthenia gravis and risk factors for developing a secondary generalisation: Description of a Spanish series. / Miastenia gravis ocular y factores asociados al desarrollo de una generalización secundaria: descripción de una serie española.

INTRODUCTION: Ocular myasthenia gravis (MG) is the most common phenotype of MG at onset. A variable percentage of these patients develop secondary generalisation; the risk factors for conversion and the protective effect of immunosuppressive treatment are currently controversial. PATIENTS AND METHODS: We designed a retrospective single-centre study with the aim of describing the demographic, clinical, and laboratory characteristics of a Spanish cohort of patients with ocular MG from Hospital Universitario de Albacete from January 2008 to February 2020. RESULTS: We selected 62 patients with ocular MG from a cohort of 91 patients with MG (68.1%). Median age at diagnosis was 68 (IQR, 52-75.3), and men accounted for 61.3% of the sample (n = 38). Most patients presented very late-onset ocular MG (n = 34, 54.8%). Binocular diplopia was the most frequent initial symptom (51.7%). The rate of progression to generalised MG was 50% (n = 31), with a median time of 6 months (IQR, 2-12.8). Female sex (OR: 5.46; 95% CI, 1.16-25-74; p = .03) and anti-acetylcholine receptor antibodies (OR: 8.86; 95% CI, 1.15-68.41; p = .04) were significantly associated with the risk of developing generalised MG. CONCLUSIONS: The conversion rate observed in our series is relatively high. Generalisation of MG mainly occurs during the first 2 years of progression, and is strongly associated with female sex and especially with the presence of anti-acetylcholine receptor antibodies.

Effect of type 2 diabetes on mortality risk associated with end-stage kidney disease.

AIMS/HYPOTHESIS: Patients with end-stage kidney disease (ESKD) and patients with diabetes mellitus experience higher mortality rates than the general population. Whether ESKD imparts the same excess in mortality risk for those with diabetes as it does for those without diabetes is unknown. METHODS: Included in the study were all white patients aged > or =25 years with incident ESKD and type 2 diabetes (n = 4,141) or with incident ESKD but without diabetes (n = 13,289) in Australia from 1991 to 2005, and all the individuals aged > or =25 years without ESKD and with type 2 diabetes (n = 909) or without ESKD without diabetes (n = 10,302) enrolled in the AusDiab Study--a nationwide Australian representative cohort--from 1999 to 2005. Excess mortality was analysed in patients with ESKD by diabetes status, using age-, sex- and diabetes-status-specific standardised mortality ratios (SMRs) in the first 8 years after first renal replacement therapy among ANZDATA patients relative to AusDiab participants. RESULTS: The SMRs in patients with ESKD were, in non-diabetic patients and in those with type 2 diabetes, respectively: 14.2 (95% CI 13.9-14.6) and 10.8 (95% CI 10.4-11.2) (p < 0.01); in people aged <60 years, 28.7 (95% CI 27.2-30.4) and 18.6 (95% CI 17.1-20.4) (p < 0.01); in people aged > or =60 years, 12.5 (95% CI 12.1-12.9) vs 9.7 (95% CI 9.3-10.1) (p < 0.01); in men, 11.0 (95% CI 10.7-11.4) vs 8.9 (95% CI 8.4-9.3) (p < 0.01); and in women, 23.4 (95% CI 22.5-24.3) vs 16.2 (95% CI 15.2-17.3) (p < 0.01). CONCLUSIONS/INTERPRETATION: ESKD was associated with a greater relative increase in mortality in the non-diabetic study populations than in the type 2 diabetes population. Excess mortality was greater among younger people and women.

The Impact of type 2 diabetes on mortality in end-stage renal disease patients differs between genders.

BACKGROUND/AIMS: In diabetics with end-stage renal disease (ESRD), risk of death has been reported to be non-constant after the first dialysis, and different outcomes have been observed between genders. We assessed the impact of type 2 diabetes (T2DM) on mortality in dialysis regarding its differential effect by gender using time-dependent analyses. METHODS: All T2DM and non-diabetic (no-DM) patients who started dialysis in two renal units in Lyon, France, between January 1, 1995, and December 31, 2007, were included. In multivariate analyses, the Cox model and Shoenfeld residual approach were used to assess the effect of T2DM on dialysis mortality by gender. RESULTS: We included 235 T2DM (males: 57.9%) and 480 no-DM (males: 65.6%) patients. In males, the adjusted hazard ratio (aHR) for death in T2DM versus no-DM was 0.83 (p = 0.20) and was constant over time after the first renal replacement therapy (RRT) (p = 0.88). In females, aHR for death in T2DM versus no-DM patients was not constant over time (p = 0.002). It was 0.64 (p = 0.13) within the first year after the first RRT and 2.10 (p = 0.002) after the first year. Evolutions with time of these aHR by gender were significantly different (p = 0.009). CONCLUSIONS: T2DM was associated with death only in females. This association was not constant over time after the first dialysis.

A Simple Modeling-free Method Provides Accurate Estimates of Sensitivity and Specificity of Longitudinal Disease Biomarkers.

OBJECTIVE: To assess the time-dependent accuracy of a continuous longitudinal biomarker used as a test for early diagnosis or prognosis. METHODS: A method for accuracy assessment is proposed taking into account the marker measurement time and the delay between marker measurement and outcome. It dealt with markers having interval-censored measurements and a detection threshold. The threshold crossing times were assessed by a Bayesian method. A numerical study was conducted to test the procedures that were later applied to PCR measurements for prediction of cytomegalovirus disease after renal transplantation. RESULTS: The Bayesian method corrected the bias induced by interval-censored measurements on sensitivity estimates, with corrections from 0.07 to 0.3. In the application to cytomegalovirus disease, the Bayesian method estimated the area under the ROC curve to be over 75% during the first 20 days after graft and within five days between marker measurement and disease onset. However, the accuracy decreased quickly as that delay increased and late after graft. CONCLUSIONS: The proposed Bayesian method is easy to implement for assessing the time-dependent accuracy of a longitudinal biomarker and gives unbiased results under some conditions.

Improving survival in end-stage renal disease: A case study.

Background: With the increase of life expectancy, *On behalf of the REIN registry. end-stage renal disease (ESRD) is affecting a growing number of people. Simultaneously, renal replacement therapies (RRTs) have considerably improved patient survival. We investigated the way current RRT practices would affect patients' survival. Methods: We used a multi-state model to represent the transitions between RRTs and the transition to death. The concept of "crude probability of death" combined with this model allowed estimating the proportions of ESRD-related and ESRD-unrelated deaths. Estimating the ESRD-related death rate requires comparing the mortality rate between ESRD patients and the general population. Predicting patients' courses through RRTs and Death states could be obtained by solving a system of Kolmogorov differential equations. The impact of practice on patient survival was quantified using the restricted mean survival time (RMST) which was compared with that of healthy subjects with same characteristics. Results: The crude probability of ESRD-unrelated death was nearly zero in the youngest patients (18-45 years) but was a sizeable part of deaths in the oldest (≥70 years). Moreover, in the oldest patients, the proportion of expected death was higher in patient without vs. with diabetes because the former live older. In men aged 75 years at first RRT, the predicted RMSTs in patients with and without diabetes were, respectively, 61% and 69% those of comparable healthy men. Conclusion: Using the concept of "crude probability of death" with multi-state models is feasible and useful to assess the relative benefits of various treatments in ESRD and help patient long-term management.

Promoting healthy lives and well-being for all: The contribution of the International College of Person-Centered Medicine (ICPCM).

This article defines the scope of Person-Centered Medicine, traces its roots in ancient conceptions, explains the reasons for the revival of this perspective in our times, and highlights the contribution of the International College of Person-Centered Medicine (ICPCM) in the promotion of the personcentered perspective in health and disease. The value of communication is underlined with reference to both diagnosis and treatment. The concept of Health is considered historically and the inclusiveness, holistic vista and positive health orientation of the WHO definition of Health (1948) is underlined. It is emphasized that Mental Health Promotion is differentiated conceptually from Disease Prevention in that promotion deals with health and prevention deals with illness, the relationship of Health Promotion with Salutogenesis (Antonovsky 1996) is noted and it is pointed out that among the targets of health promotion, preservation of peace is also included (WHO, 2004). In line with this, the ICPCM has supported and co-signed the Athens Anti-War Declaration (2016). Evaluating the impact of Health Promotion efforts is a necessary but difficult task as it requires targeted research and there are many inherent confounding factors. The social or environmental contexts of health behaviors should be taken into account as well as the subjective indicators of health. In an attempt to resolve the difficulties arising from this issue, the ICPCM has developed a prototype "Person-centered Care Index" (Kirisci et al 2016). With reference to Education it is pointed out that it is necessary for the educators to speak with the students rather than speak to them. Concerning research, the ICPCM in its 2013 Geneva Declaration has identified the main research areas in the person-centered field. The importance of assuring healthy lives and well-being for ALL is underlined and the difficulties associated with the achievement of this goal are noted. Lastly, the need to apply the principles of Person-centered Medicine to victims of natural, human-made and economic disasters (Christodoulou et al 2016) is underlined, especially in view of the frequent occurrence of these disasters in our times. In conclusion, the contribution of the ICPCM during the ten years of its existence, with reference to the sensitization of health professionals in the Person-centered approach is noted. This contribution has been carried out in line with the principles of the ICPCM and with its Geneva Declarations.