Les critères STOPP/START.v2 : adaptation en langue française. [STOPP/START.v2 criteria: Adaptation into French language]

Objectif STOPP/START est un outil de détection de la prescription médicamenteuse potentiellement inappropriée chez la personne de 65 ans ou plus. La version initiale de 2008 vient d'être mise à jour et améliorée par ses auteurs. Nous en présentons l'adaptation et la validation en langue française. Méthodes L'adaptation en français de l'outil STOPP/START.v2 a été réalisée par deux experts, confirmée par la méthode de traduction-inverse, et finalisée d'après les commentaires de neufs évaluateurs francophones, gériatres, pharmaciens cliniciens, et médecin généraliste de quatre pays (France, Belgique, Suisse, Canada). La validation a été complétée par une analyse de concordance inter-juge (CCI) des critères STOPP/START.v2 appliqués à dix vignettes cliniques standardisées. Résultats Les 115 critères de STOPP/START.v2 en français sont, par rapport à la version originale anglaise, identiques par leur classification mais adaptés en termes de présentation (critères START.v2 commençant par la condition clinique, et accompagnés par une justification du caractère inapproprié de l'omission) voire de formulation de certains critères. Cette adaptation en français est validée par (i) la traduction-inverse montrant le respect du sens clinique de la version originale, (ii) l'identification semblable des critères lorsque appliqués à dix vignettes cliniques par les neuf évaluateurs, et (iii) le haut niveau de concordance de ces neuf évaluations tant pour STOPP.v2 (CCI 0,849) que pour START.v2 (CCI 0,921). Conclusion L'adaptation en langue française des critères STOPP/START.v2 fournit aux cliniciens un outil de détection de la prescription médicamenteuse potentiellement inappropriée chez les personnes de 65 ans et plus qui est logique, fiable et facile à utiliser. Objective STOPP/START is a screening tool to detect potentially inappropriate prescribing in persons aged 65 or older. Its Irish authors recently updated and improved the initially published version of 2008. We present the adaptation and validation into French language of this updated tool. Methods STOPP/START.v2 was adapted into French by two experts, then confirmed by a translation-back translation method and finalised according to the comments of nine French-speaking assessors - geriatricians, pharmacologists and a general physician - from four countries (France, Belgium, Switzerland, and Canada). The validation was completed by an inter-rater reliability (IRR) analysis of the STOPP/START.v2 criteria applied to 10 standardized clinical vignettes. Results In comparison to the original English version, the 115 STOPP/START.v2 criteria in French language classify in identical manner, but the presentation has been adjusted (START.v2 first specifies the clinical condition followed by an explanation of the inappropriateness of the prescription or omission). This adaptation into French language was validated by means of (i) the translation/back-translation, which showed that the French version complied with the clinical meaning of the original criteria; (ii) the similar screening results when applied by the nine specialists to the 10 cases; and (iii) the high level of inter-rater reliability of these 9 evaluations, for both STOPP (IRR 0.849) and START.v2 (IRR 0.921). Conclusion The adaptation into French of the STOPP/START.v2 criteria provides clinicians with a screening tool to detect potentially inappropriate prescribing in patients aged 65 and older that is more logical, more reliable and easier to use.

Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General Population.

BACKGROUND AND OBJECTIVES: Allelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointerstitial kidney disorders and risk of CKD and hypertension in the general population. The factors associated with uromodulin excretion in the normal population remain largely unknown, and were therefore explored in this study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Urinary uromodulin excretion was measured using a validated ELISA in two population-based cohorts that included more than 6500 individuals. The Swiss Kidney Project on Genes in Hypertension study (SKIPOGH) included 817 adults (mean age±SD, 45±17 years) who underwent renal ultrasonography and performed a 24-hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age, 53±11 years) with fresh spot morning urine samples. We calculated eGFRs using the CKD-Epidemiology Collaboration formula and by 24-hour creatinine clearance. RESULTS: In both studies, positive associations were found between uromodulin and urinary sodium, chloride, and potassium excretion and osmolality. In SKIPOGH, 24-hour uromodulin excretion (median, 41 [interquartile range, 29-57] mg/24 h) was positively associated with kidney length and volume and with creatinine excretion and urine volume. It was negatively associated with age and diabetes. Both spot uromodulin concentration and 24-hour uromodulin excretion were linearly and positively associated (multivariate analyses) with eGFR<90 ml/min per 1.73 m(2). CONCLUSION: Age, creatinine excretion, diabetes, and urinary volume are independent clinical correlates of urinary uromodulin excretion. The associations of uromodulin excretion with markers of tubular functions and kidney dimensions suggest that it may reflect tubule activity in the general population.

Urine Fetuin-A is a biomarker of autosomal dominant polycystic kidney disease progression.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by numerous fluid-filled cysts that frequently result in end-stage renal disease. While promising treatment options are in advanced clinical development, early diagnosis and follow-up remain a major challenge. We therefore evaluated the diagnostic value of Fetuin-A as a new biomarker of ADPKD in human urine. RESULTS: We found that renal Fetuin-A levels are upregulated in both Pkd1 and Bicc1 mouse models of ADPKD. Measurement by ELISA revealed that urinary Fetuin-A levels were significantly higher in 66 ADPKD patients (17.5 ± 12.5 μg/mmol creatinine) compared to 17 healthy volunteers (8.5 ± 3.8 μg/mmol creatinine) or 50 control patients with renal diseases of other causes (6.2 ± 2.9 μg/mmol creatinine). Receiver operating characteristics (ROC) analysis of urinary Fetuin-A levels for ADPKD rendered an optimum cut-off value of 12.2 μg/mmol creatinine, corresponding to 94% of sensitivity and 60% of specificity (area under the curve 0.74 ; p = 0.0019). Furthermore, urinary Fetuin-A levels in ADPKD patients correlated with the degree of renal insufficiency and showed a significant increase in patients with preserved renal function followed for two years. CONCLUSIONS: Our findings establish urinary Fetuin-A as a sensitive biomarker of the progression of ADPKD. Further studies are required to examine the pathogenic mechanisms of elevated renal and urinary Fetuin-A in ADPKD.

Sociodemographic, behavioral and genetic determinants of allostatic load in a Swiss population-based study.

Allostatic load (AL) is a marker of physiological dysregulation which reflects exposure to chronic stress. High AL has been related to poorer health outcomes including mortality. We examine here the association of socioeconomic and lifestyle factors with AL. Additionally, we investigate the extent to which AL is genetically determined. We included 803 participants (52% women, mean age 48±16years) from a population and family-based Swiss study. We computed an AL index aggregating 14 markers from cardiovascular, metabolic, lipidic, oxidative, hypothalamus-pituitary-adrenal and inflammatory homeostatic axes. Education and occupational position were used as indicators of socioeconomic status. Marital status, stress, alcohol intake, smoking, dietary patterns and physical activity were considered as lifestyle factors. Heritability of AL was estimated by maximum likelihood. Women with a low occupational position had higher AL (low vs. high OR=3.99, 95%CI [1.22;13.05]), while the opposite was observed for men (middle vs. high OR=0.48, 95%CI [0.23;0.99]). Education tended to be inversely associated with AL in both sexes(low vs. high OR=3.54, 95%CI [1.69;7.4]/OR=1.59, 95%CI [0.88;2.90] in women/men). Heavy drinking men as well as women abstaining from alcohol had higher AL than moderate drinkers. Physical activity was protective against AL while high salt intake was related to increased AL risk. The heritability of AL was estimated to be 29.5% ±7.9%. Our results suggest that generalized physiological dysregulation, as measured by AL, is determined by both environmental and genetic factors. The genetic contribution to AL remains modest when compared to the environmental component, which explains approximately 70% of the phenotypic variance.

CYP17A1 Enzyme activity is linked to ambulatory blood pressure in a family-based population study.

BACKGROUND: Genome-wide association studies have linked CYP17A1 coding for the steroid hormone synthesizing enzyme 17α-hydroxylase (CYP17A1) to blood pressure (BP). We hypothesized that the genetic signal may translate into a correlation of ambulatory BP (ABP) with apparent CYP17A1 activity in a family-based population study and estimated the heritability of CYP17A1 activity. METHODS: In the Swiss Kidney Project on Genes in Hypertension, day and night urinary excretions of steroid hormone metabolites were measured in 518 participants (220 men, 298 women), randomly selected from the general population. CYP17A1 activity was assessed by 2 ratios of urinary steroid metabolites: one estimating the combined 17α-hydroxylase/17,20-lyase activity (ratio 1) and the other predominantly 17α-hydroxylase activity (ratio 2). A mixed linear model was used to investigate the association of ABP with log-transformed CYP17A1 activities exploring effect modification by urinary sodium excretion. RESULTS: Daytime ABP was positively associated with ratio 1 under conditions of high, but not low urinary sodium excretion (P interaction <0.05). Ratio 2 was not associated with ABP. Heritability estimates (SE) for day and night CYP17A1 activities were 0.39 (0.10) and 0.40 (0.09) for ratio 1, and 0.71 (0.09) and 0.55 (0.09) for ratio 2 (P values <0.001). CYP17A1 activities, assessed with ratio 1, were lower in older participants. CONCLUSIONS: Low apparent CYP17A1 activity (assessed with ratio 1) is associated with elevated daytime ABP when salt intake is high. CYP17A1 activity is heritable and diminished in the elderly. These observations highlight the modifying effect of salt intake on the association of CYP17A1 with BP.

The association between obesity and back pain in nine countries: a cross-sectional study

BACKGROUND: The association between obesity and back pain has mainly been studied in high-income settings with inconclusive results, and data from older populations and developing countries are scarce. The aim of this study was to assess this association in nine countries in Asia, Africa, Europe, and Latin America among older adults using nationally-representative data. METHODS: Data on 42116 individuals ≥50 years who participated in the Collaborative Research on Ageing in Europe (COURAGE) study conducted in Finland, Poland, and Spain in 2011-2012, and the World Health Organization's Study on Global Ageing and Adult Health (SAGE) conducted in China, Ghana, India, Mexico, Russia, and South Africa in 2007-2010 were analysed. Information on measured height and weight available in the two datasets was used to calculate Body Mass Index (BMI). Self-reported back pain occurring in the past 30 days was the outcome. Multivariable logistic regression analysis was used to assess the association between BMI and back pain. RESULTS: The prevalence of back pain ranged from 21.5% (China) to 57.5% (Poland). In the multivariable analysis, compared to BMI 18.5-24.9 kg/m(2), significantly higher odds for back pain were observed for BMI ≥35 kg/m(2) in Finland (OR 3.33), Russia (OR 2.20), Poland (OR 2.03), Spain (OR 1.56), and South Africa (OR 1.48); BMI 30.0-34.0 kg/m(2) in Russia (OR 2.76), South Africa (OR 1.51), and Poland (OR 1.47); and BMI 25.0-29.9 kg/m(2) in Russia (OR 1.51) and Poland (OR 1.40). No significant associations were found in the other countries. CONCLUSIONS: The strength of the association between obesity and back pain may vary by country. Future studies are needed to determine the factors contributing to differences in the associations observed.

Länsimaisten naisten sosiaalihistoriaa norjaksi

Kirjallisuusarvostelu

Kansainvälisen politiikan käytöstä ja kutsumuksesta

Laajennettu ja nootitette versio professoriluennosta, Turun yliopisto 9.2.2011.

Liver regeneration with l-glutamine supplemented diet: experimental study in rats

OBJECTIVE: To assess liver regeneration in rats after 60% hepatectomy with and without supplementation of L-glutamine through liver weight changes, laboratory parameters and histological study.METHODS: 36 male rats were divided into two groups: glutamine group and control group. Each group was subdivided into three subgroups, with death in 24h, 72h and seven days. The glutamine group received water and standard diet supplemented with L-glutamine, and the control recieved 0.9% saline. In all subgroups analysis of liver regeneration was made by the Kwon formula, study of liver function (AST, ALT, GGT, total bilirubin, indirect and indirect bilirubin and albumin) and analysis of cell mitosis by hematoxylin-eosin.RESULTS: In both groups there was liver regeneration by weight gain. Gamma-GT increased significantly in the control group (p < 0.05); albumin increased in the glutamine group. The other indicators of liver function showed no significant differences. Histological analysis at 72h showed a higher number of mitoses in the glutamine group, with no differences in other subgroups.CONCLUSION: Diet supplementation with L glutamine is beneficial for liver regeneration.

Conventional cytogenetic characterization of a new cell line, ACP01, established from a primary human gastric tumor

Gastric cancer is the second most frequent type of neoplasia and also the second most important cause of death in the world. Virtually all the established cell lines of gastric neoplasia were developed in Asian countries, and western countries have contributed very little to this area. In the present study we describe the establishment of the cell line ACP01 and characterize it cytogenetically by means of in vitro immortalization. Cells were transformed from an intestinal-type gastric adenocarcinoma (T4N2M0) originating from a 48-year-old male patient. This is the first gastric adenocarcinoma cell line established in Brazil. The most powerful application of the cell line ACP01 is in the assessment of cytotoxicity. Solid tumor cell lines from different origins have been treated with several conventional and investigational anticancer drugs. The ACP01 cell line is triploid, grows as a single, non-organized layer, similar to fibroblasts, with focus formation, heterogeneous division, and a cell cycle of approximately 40 h. Chromosome 8 trisomy, present in 60% of the cells, was the most frequent cytogenetic alteration. These data lead us to propose a multifactorial triggering of gastric cancer which evolves over multiple stages involving progressive genetic changes and clonal expansion.

Ristiretkeläisten, pakanoiden ja saraseenien kohtaamisia

Kirjallisuusarvostelu

Association of postalimentary lipemia with atherosclerotic manifestations

We identified different lipemic and metabolic responses after the ingestion of a standardized meal by healthy adults and related them to atherosclerotic markers. Samples from 60 normolipidemic adults were collected before and after a liquid meal (40 g fat/m² body surface) at 0, 2, 4, 6, and 8 h for measurements of lipids, free fatty acids (FFA), insulin, cholesteryl ester transfer protein (CETP), autoantibodies to epitopes of oxidized LDL (oxLDL Ab), lipolytic activities, and apolipoprotein E polymorphism. Mean carotid intima-media thickness (cIMT) was determined by Doppler ultrasound. The volunteers were classified into early (N = 39) and late (N = 31) triacylglycerol (TAG) responders to the test meal. Late responders showed lower HDL cholesterol concentration at fasting and in the TAG peak, lower insulin and higher FFA concentrations compared to early responders. Multivariate regression analyses showed that mean cIMT was associated with gender (male) and age in early responders and by cholesterol levels at the 6th hour in late responders. oxLDL Ab were explained by lipoprotein lipase and negatively by hepatic lipase and oxLDL Ab (fasting period) by CETP (negative) and FFA (positive). This study is the first to identify a postalimentary insulin resistance state, combined with a reduced CETP response exclusively among late responders, and the identification of the regulators of postalimentary atherogenicity. Further research is required to determine the metabolic mechanisms described in the different postalimentary phenotypes observed in this study, as well as in different pathological states, as currently investigated in our laboratory.