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Leading historians, anthropologists, educators and designers explore the role of materiality in medical education. With a broad focus, international scope and experimental format, this is the first book to seriously reflect on the material relationship between the medical school and reproduction of medical knowledge.&nbsp

Background Estimating glomerular filtration rate (GFR) in acute kidney injury (AKI) is challenging, with limited data comparing estimated and gold standard methods to assess GFR. The objective of our study was to assess the performance of the kinetic estimated GFR (KeGFR) and Jelliffe equations to estimate GFR in AKI, using a radioisotopic method (technetium-diethylenetriaminepentaacetic acid) as a reference measure. Methods We conducted a prospective multicenter observational study in hospitalized patients with AKI. We computed the Jelliffe and KeGFR equations to estimate GFR and compared these estimations to measured GFR (mGFR) by a radioisotopic method. The performances were assessed by correlation, Bland–Altman plots and smoothed and linear regressions. We conducted stratified analyses by age and chronic kidney disease (CKD). Results The study included 119 patients with AKI, mostly from the intensive care unit (63%) and with Stage 1 AKI (71%). The eGFR obtained from the Jelliffe and KeGFR equations showed a good correlation with mGFR (r = 0.73 and 0.68, respectively). The median eGFR by the Jelliffe and KeGFR equations was less than the median mGFR, indicating that these equations underestimated the mGFR. On Bland–Altman plots, the Jelliffe and KeGFR equations displayed a considerable lack of agreement with mGFR, with limits of agreement >40 mL/min/1.73 m2. Both equations performed better in CKD and the KeGFR performed better in older patients. Results were similar across AKI stages. Conclusions In our study, the Jelliffe and KeGFR equations had good correlations with mGFR; however, they had wide limits of agreement. Further studies are needed to optimize the prediction of mGFR with estimatation equations.

Chronic kidney disease (CKD) is a major health issue and cardiovascular risk factor. Validity assessment of administrative data for the detection of CKD in research for drug benefit and risk using real-world data is important. Existing algorithms have limitations and we need to develop new algorithms using administrative data, giving the importance of drug benefit/risk ratio in real world.The aim of this study was to validate a predictive algorithm for CKD GFR category 4-5 (eGFR30 mL/min/1.73 mThis is a retrospective cohort study using chart collection and administrative databases.The study was conducted in a community outpatient medical clinic and pre-dialysis outpatient clinic in downtown Montreal and rural area.Patient medical files with at least 2 serum creatinine measures (up to 1 year apart) between September 1, 2013, and June 30, 2015, were reviewed consecutively (going back in time from the day we started the study). We excluded patients with end-stage renal disease on dialysis. The study was started in September 2013.Glomerular filtration rate was estimated using the CKD Epidemiological Collaboration (CKD-EPI) from each patient's file. Several algorithms were developed using 3 administrative databases with different combinations of physician claims (diagnostics and number of visits) and hospital discharge data in the 5 years prior to the cohort entry, as well as specific drug use and medical intervention in preparation for dialysis in the 2 years prior to the cohort entry.Chart data were used to assess eGFR. The validity of various algorithms for detection of CKD groups was assessed with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).A total of 434 medical files were reviewed; mean age of patients was 74.2 ± 10.6 years, and 83% were older than 65 years. Sensitivity of algorithm #3 (diagnosis within 2-5 years and/or specific drug use within 2 years and nephrologist visit ≥4 within 2-5 years) in identification of CKD G4-5ND ranged from 82.5% to 89.0%, specificity from 97.1% to 98.9% with PPV and NPV ranging from 94.5% to 97.7% and 91.1% to 94.2%, respectively. The subsequent subgroup analysis (diabetes, hypertension, and65 and ≥65 years) and also the comparisons of predicted prevalence in a cohort of older adults relative to published data emphasized the accuracy of our algorithm for patients with severe CKD (CKD G4-5ND).Our cohort comprised mostly older adults, and results may not be generalizable to all adults. Participants with CKD without 2 serum creatinine measurements up to 1 year apart were excluded.The case definition of severe CKD G4-5ND derived from an algorithm using diagnosis code, drug use, and nephrologist visits from administrative databases is a valid algorithm compared with medical chart reviews in older adults.L’insuffisance rénale chronique (IRC) est un problème de santé majeur et un facteur de risque cardiovasculaire. La validité de la détection de l’IRC à partir des bases de données administratives est importante pour les études évaluant en situation réelle les bénéfices et les risques des médicaments. Les algorithmes existants comportent des limites et, compte tenu de l’importance revêtue par ce rapport bénéfices/risques, le développement de nouveaux algorithmes utilisant les bases de données administratives s’avère essentiel.Valider le pouvoir prédictif d’un algorithme pour détecter l’insuffisance rénale chronique sévère (DFGe30 mL/min/1.73 mÉtude de cohorte rétrospective réalisée à partir des dossiers médicaux et de données administratives.Des cliniques médicales communautaires et de protection rénale de Montréal et des régions rurales périphériques.Les dossiers médicaux de patients avec au moins deux mesures de la créatinine sérique (en moins d’un an) entre le 1er septembre 2013 et le 30 juin 2015 ont été revus consécutivement, en reculant dans le temps. Les patients avec insuffisance rénale terminale et dialysés ont été exclus. L’étude a débuté en septembre 2013.Le DFG a été estimé à l’aide de la formule CKD Epidemiological Collaboration (CKD-EPI) à partir du dossier médical de chaque patient. Nous avons développé différents algorithmes en utilisant trois banques de données administratives avec différentes combinaisons de facturations médicales (diagnostics et nombre de visites en néphrologie) et de données colligées au congé de l’hôpital dans les cinq ans précédant l’entrée dans la cohorte, de même qu’avec la consommation de certains médicaments et les interventions médicales subies en préparation à la dialyse dans les deux ans précédant l’entrée dans la cohorte.Les données des dossiers médicaux ont été utilisées pour définir le DFGe. La validité des algorithmes développés a été évaluée en utilisant la sensibilité, la spécificité, la valeur prédictive positive (VPP) et la valeur prédictive négative (VPN).En tout, 434 dossiers médicaux ont été revus; l’âge moyen des patients était de 74.2 ± 10.6 ans et 83% avaient plus de 65 ans. La sensibilité de l’algorithme no.3 (diagnostic dans un délai de 2 à 5 ans et/ou l’usage de médicaments spécifiques dans un délai de 2 ans, et au moins quatre visites médicales en néphrologie dans les 2 à 5 ans précédant la date d’entrée dans la cohorte) dans l’identification d’une insuffisance rénale sévère (CKD G4-5ND) variait de 82.5% à 89.0%. La spécificité de ce même algorithme variait de 97.1% à 98.9% avec une PPV et une NPV allant respectivement de 94.5.% à 97.7% et de 91.1% à 94.2%. L’analyse de sous-groupes (patients diabétiques, hypertendus, âgés de moins de 65 ans ou âgés de 65 ans et plus) ainsi que la comparaison de la prévalence prédite dans une cohorte de patients âgés par rapport aux données de la littérature font valoir la précision de notre algorithme pour les patients avec insuffisance rénale sévère (CKD G4-5ND).Notre cohorte était composée essentiellement de sujets âgées, les résultats pourraient ne pas s’appliquer à tous les adultes. Les patients n’ayant pas eu deux mesures de la créatinine sérique à l’intérieur d’un an ont été exclus.Chez les personnes âgées, la définition de cas pour une insuffisance chronique rénale sévère (CKD G4-5ND) estimée par un algorithme utilisant les codes diagnostic, la consommation de médicaments spécifiques et les services médicaux de néphrologie tirés des données administratives s’avère un algorithme valide comparativement à l’examen du dossier médical.

OBJECTIVES: (1) To evaluate the association between acute kidney injury (AKI) in the PICU and long-term mortality and (2) to determine the extent to which adding the urine output (UO)–defined AKI alters the association. METHODS: A 2-center retrospective cohort study of children (≤18 years old) admitted to the PICU between 2003 and 2005 for noncardiac surgery, with follow-up until 2010. Patients with end stage renal disease, no provincial health insurance number, who died during hospitalization, or could not be linked to administrative data were excluded. One hospitalization per patient was included. AKI was defined by using serum creatinine criteria and/or UO criteria. Mortality was ascertained by using administrative data. Cox regression analysis was performed to evaluate the association between AKI and long-term mortality. RESULTS: The study population included 2041 patients (55.7% male, mean admission age 6.5 ± 5.8 years). Of 2041 hospital survivors, 9 (0.4%) died within 30 days, 51 (2.5%) died within 1 year, and 118 (5.8%) died within 5 to 7 years postdischarge. AKI was independently associated with 5- to 7-year mortality (adjusted hazard ratio [95% confidence interval]: 3.10 [1.46–6.57] and 3.38 [1.63–7.02], respectively). Including UO did not strengthen the association. CONCLUSIONS: AKI is associated with 5- to 7-year mortality. Because this is an observational study we cannot determine if AKI is causative of mortality or of the pathophysiology. However, patients with AKI represent a high-risk group. It is reasonable that these patients be considered for targeted follow-up until future researchers better elucidate these relationships

Background and objectives Little is known about the long-term burden of AKI in the pediatric intensive care unit. We aim to evaluate if pediatric AKI is associated with higher health service use post–hospital discharge. Design, setting, participants, & measurements This is a retrospective cohort study of children (≤18 years old) admitted to two tertiary centers in Montreal, Canada. Only the first admission per patient was included. AKI was defined in two ways: serum creatinine alone or serum creatinine and/or urine output. The outcomes were 30-day, 1-year, and 5-year hospitalizations, emergency room visits, and physician visits per person-time using provincial administrative data. Univariable and multivariable Poisson regression were used to evaluate AKI associations with outcomes. Results A total of 2041 children were included (56% male, mean admission age 6.5±5.8 years); 299 of 1575 (19%) developed AKI defined using serum creatinine alone, and when urine output was included in the AKI definition 355 of 1622 (22%) children developed AKI. AKI defined using serum creatinine alone and AKI defined using serum creatinine and urine output were both associated with higher 1- and 5-year hospitalization risk (AKI by serum creatinine alone adjusted relative risk, 1.42; 95% confidence interval, 1.12 to 1.82; and 1.80; 1.54 to 2.11, respectively [similar when urine output was included]) and higher 5-year physician visits (adjusted relative risk, 1.26; 95% confidence interval, 1.14 to 1.39). AKI was not associated with emergency room use after adjustments. Conclusions AKI is independently associated with higher hospitalizations and physician visits postdischarge.

To develop a pediatric-specific hypertension algorithm using administrative data and use it to evaluate the association between acute kidney injury (AKI) in the intensive care unit (ICU) and hypertension diagnosis 5 years post-discharge. Two-center retrospective cohort study of children (≤ 18 years old) admitted to the pediatric ICU in Montreal, Canada, between 2003 and 2005 and followed until 2010. Patients with a valid healthcare number and without end-stage renal disease were included. Patients who could not be merged with the provincial database, did not survive admission, underwent cardiac surgery, had pre-existing renal disease associated with hypertension or a prior diagnosis of hypertension were excluded. AKI defined using the Kidney Disease: Improving Global Outcomes (KDIGO) definition. Using diagnostic codes and medications from administrative data, novel pediatric-specific hypertension definitions were designed. Both the evaluation of the prevalence of hypertension diagnosis and the association between AKI and hypertension occurred. Nineteen hundred and seventy eight patients were included (median age at admission [interquartile range] 4.3 years [1.1–11.8], 44% female, 325 (16.4%) developed AKI). Of these patients, 130 (7%) had a hypertension diagnosis 5 years after discharge. Patients with AKI had a higher prevalence of hypertension diagnosis [non-AKI: 84/1653 (5.1%) vs. AKI: 46/325 (14.2%), p

The progression from acute kidney injury (AKI) to chronic kidney disease (CKD) is not well understood in children.We aimed to develop a pediatric CKD definition using administrative data and use it to evaluate the association between AKI in critically ill children and CKD 5 years after hospital discharge.Retrospective cohort study using chart collection and administrative data.Two-center study in Montreal, Canada.Children (≤18 years old) admitted to two pediatric intensive care units (ICUs) between 2003 and 2005. We a priori excluded patients with end-stage renal disease or no health care number. Only the first admission during the study period was included. We excluded patients who could not be linked to administrative data, did not survive hospitalization, or had preexisting renal disease.Acute kidney injury was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patients were defined as having CKD 5 years post-discharge if they had ≥1 CKD diagnostic code or ≥1 CKD-specific medication prescription.Chart data used to define the exposure (AKI) were merged with provincial administrative data used to define the outcome (CKD). Cox regression was used to evaluate the AKI-CKD association.A total of 2235 (56% male) patients were included, and the median admission age was 3.7 years. A total of 464 (21%) patients developed AKI during pediatric ICU admission. At 5 years post-discharge, 43 (2%) patients had a CKD diagnosis. Patients with both stage 1 and stage 2-3 AKI had increased risk of a CKD diagnosis, with the adjusted hazard ratios (95% confidence intervals) of 2.2 (1.1-4.5) and 2.5 (1.1-5.7), respectively (Results may not be generalizable to non-ICU patients. We were not able to control for post-discharge variables; future research should try to explore these additional potential risk factors further.Acute kidney injury is associated with 5-year post-discharge CKD diagnosis defined by administrative health care data.Chez l’enfant, la progression de l’insuffisance rénale aigüe (IRA) vers l’insuffisance rénale chronique (IRC) est encore mal connue.Nous souhaitions élaborer une définition de l’IRC pédiatrique à partir des données administratives, et l’employer pour évaluer l’association entre l’IRA chez les enfants gravement malades et un diagnostic d’IRC cinq ans après leur sortie de l’hôpital.Étude de cohorte rétrospective réalisée à partir des dossiers médicaux et des données administratives.Deux centres hospitaliers de Montréal (Canada).L’étude porte sur des enfants (≤18 ans) admis à deux unités de soins intensifs (USI) pédiatriques entre 2003 et 2005. Les patients atteints d’insuffisance rénale terminale ou sans numéro d’assurance-maladie ont été exclus d’emblée. Seule la première admission survenue au cours de l’étude a été retenue. Les patients n’ayant pu être reliés aux données administratives, n’ayant pas survécu à l’hospitalisation ou souffrant d’une néphropathie préexistante ont été exclus.L’IRA a été définie selon les critères KDIGO (Les données des dossiers médicaux, utilisées pour définir l’exposition (IRA), ont été couplées aux données administratives provinciales, utilisées pour définir le résultat (IRC). Un modèle de régression de Cox a servi à établir l’association entre IRA et IRC.Ont été inclus 2 235 patients (56 % de garçons), dont l’âge médian à l’admission était de 3,7 ans. De ce nombre, 464 (21 %) ont développé une IRA en cours d’hospitalisation à l’USI pédiatrique. Cinq ans après leur sortie de l’hôpital, 43 patients (2 %) avaient reçu un diagnostic d’IRC. Les patients atteints d’une IRA de stade 1 et de stade 2-3 ont présenté un plus grand risque de progresser vers l’IRC (rapport de risque ajusté [IC à 95 %] 2,2 [1,1 – 4,5] et 2,5 [1,1 – 5,7] respectivement,Les résultats pourraient ne pas s’appliquer aux patients non admis aux USI pédiatriques. Nous n’avons pu ajuster les résultats avec les variables après la sortie de l’hôpital. Des études futures devraient examiner plus attentivement ces potentiels facteurs de risque supplémentaires.L’IRA chez l’enfant a été associée à une progression vers l’IRC cinq ans après la sortie de l’hôpital, telle que définie par les données administratives de santé.

Large studies evaluating pediatric acute kidney injury (AKI) epidemiology and outcomes are lacking, partially due to underuse of large administrative health care data.To assess the diagnostic accuracy of administrative health care data-defined AKI in children admitted to the pediatric intensive care unit (PICU).Retrospective cohort study utilizing chart and administrative data.Children admitted to the PICU at 2 centers in Montreal, QC.Patients between 0 and 18 years old with a provincial health insurance number, without end-stage renal disease and admitted to the PICU between January 1, 2003, and March 31, 2005, were included.The AKI was defined from chart data using the Kidney Disease: Improving Global Outcomes (KDIGO) definition (Chart-AKI). The AKI defined using administrative health data (Admin-AKI) was based onData available from retrospective chart review, including baseline and PICU patient characteristics, and serum creatinine (SCr) and urine output (UO) values during PICU admission, were merged with provincial administrative health care data containing diagnostic and procedure codes used for ascertaining Admin-AKI. Sensitivity, specificity, positive, and negative predictive value of Admin-AKI compared with Chart-AKI (reference standard) were calculated. Univariable associations between Admin-AKI and hospital mortality were evaluated.A total of 2051 patients (55% male, mean age at admission 6.1 ± 5.8 years, 355 cardiac surgery, 1696 noncardiac surgery) were included. The AKI defined by SCr or UO criteria occurred in 52% of cardiac surgery patients and 24% of noncardiac surgery patients. Overall, Admin-AKI detected Chart-AKI with low sensitivity, but high specificity in cardiac and noncardiac surgery patients. Sensitivity increased by 1.5 to 2 fold with each increase in AKI severity stage. Admin-AKI was associated with hospital mortality (13% in Admin-AKIThese data were generated in a PICU population; future research should study non-PICU populations.Use of administrative health care data to define AKI in children leads to AKI incidence underestimation. However, for detecting more severe AKI, sensitivity is higher, while maintaining high specificity.On dispose de peu d’études à grande échelle évaluant l’épidémiologie et l’évolution de l’insuffisance rénale aigüe (IRA) chez les enfants, notamment en raison d’une sous-utilisation des données administratives du système de santé.Évaluer la précision diagnostique de l’IRA définie à partir des données administratives en santé chez des enfants admis aux unités de soins intensifs pédiatriques (USIP).Une étude de cohorte rétrospective utilisant des données administratives et les données provenant des dossiers médicaux.Les USIP de deux centres hospitaliers de Montréal, au Canada.Ont été inclus les patients âgés de 0 à 18 ans possédant un numéro d’assurance-maladie provincial qui ont été admis aux USIP entre le 1er janvier 2003 et le 31 mars 2005 avec une insuffisance rénale non terminale.L’IRA-Dos a été définie à partir des dossiers médicaux en utilisant les critères du KDIGO (Kidney Disease: Improving Global Outcomes). L’IRA-Admin a été définie à partir des données administratives en santé avec les codes d’IRA de la neuvième révision de la Classification internationale des maladies (CIM-9).Les données tirées de l’examen rétrospectif des dossiers médicaux, soit les valeurs de créatinine sérique (SCr) et de diurèse pendant le séjour aux USIP et les caractéristiques des patients, initiales et à l’admission, ont été fusionnées aux données administratives provinciales en santé contenant les codes de diagnostic et de procédure utilisés pour établir l’IRA-Admin. La sensibilité, la spécificité et les valeurs prédictives négative et positive de l’IRA-Admin, en comparaison à l’IRA-Dos (standard de référence), ont été calculées. L’association univariée entre l’IRA-Admin et la mortalité à l’hôpital a également été évaluée.Un total de 2 051 patients ont été inclus (355 ayant subi une cardiochirurgie et 1 696 non opérés). L’âge moyen des sujets à l’admission était de 6,1 ± 5,8 ans et 55 % étaient des garçons. L’IRA définie par les critères de SCr et de diurèse a été diagnostiquée chez 52 % des patients opérés et chez 24 % des patients non opérés. Pour l’ensemble de la cohorte (patients opérés ou non), l’IRA-Admin a détecté l’IRA-Dos avec une faible sensibilité, mais avec une spécificité élevée. La sensibilité s’est accrue de 1,5 à 2 fois pour chaque passage à un stade supérieur de gravité de l’IRA. Enfin, l’IRA-Admin a été associée à un taux plus élevé de mortalité à l’hôpital (13 % des patients IRA-AdminCes résultats concernent une population de patients hospitalisés aux USIP. Des études futures devraient inclure des populations non admises aux USIP.L’utilisation des données administratives en santé pour définir l’IRA chez les enfants a mené à une sous-estimation de son incidence. Cependant, la méthode montre une plus grande sensibilité dans la détection des cas plus graves d’IRA, tout en conservant une spécificité élevée.

Background Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes.Methods We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18-85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25-75 mL/min per 1.73 m(2) of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g who had received maximum labelled or tolerated renin-angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0.75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0.75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for >= 30 days) or end-stage kidney disease (eGFR = 90 days, chronic dialysis for >= 90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials. gov, number NCT01858532.Findings Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2.2 years (IQR 1.4-2.9). 79 (6.0%) of 1325 patients in the atrasentan group and 105 (7.9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0.65 [95% CI 0.49-0.88]; p=0.0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3.5%) of 1325 patients in the atrasentan group and 34 (2.6%) of 1323 patients in the placebo group (HR 1.33 [95% CI 0.85-2.07]; p=0.208). 58 (4.4%) patients in the atrasentan group and 52 (3.9%) in the placebo group died (HR 1.09 [95% CI 0.75-1.59]; p=0.65).Interpretation Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

Metformin presents better survival rates than other oral antidiabetics in the treatment of type 2 diabetes. However, these benefits may be dampened by inadequate treatment adherence.We aimed to investigate the relationship between adherence level to metformin therapy and all-cause mortality over 10 years in incident metformin users.A nested case-control study was conducted using a large cohort of beneficiaries of the Quebec public drug insurance plan, aged 45 to 85 years, who initiated metformin between 2000 and 2009. Each case of all-cause death during follow-up was matched with up to 10 controls. Adherence to metformin was measured using the medication possession ratio (MPR). Conditional logistic regression models were used to estimate rate ratios (RRs) for mortality between adherent (MPR ≥ 80%) and nonadherent patients (MPR80%). Subgroup analyses were conducted according to age (45-64 and 65-85 years) and comedication use (antihypertensive/cardiovascular drugs and statins).The cohort included 82 720 incident metformin users, followed up for 2.4 [0.8-4.4] years (median [interquartile range]) and 4747 cases of all-cause deaths. Analyses revealed decreased mortality risks after long-term adherence to metformin. Specifically, RRs were 0.84 (95% CI = [0.71-0.98]) and 0.69 [0.57-0.85] after 4 to 6 and ≥6 years of adherence to metformin, respectively. Survival benefits of long-term adherence (≥4 years) were also observed across most subgroups and particularly in patients using neither antihypertensive/cardiovascular drugs nor statins (0.57 [0.41-0.77]).Long-term adherence to metformin is associated with decreased risks of all-cause mortality in incident metformin users. Further research should investigate whether survival benefits vary according to the comorbidity burden of patients.

Background: Hypertension holds a unique place in population health and health care because it is the leading cause of cardiovascular disease and the most common noncommunicable condition seen in primary care worldwide. Without effective prevention and control, raised blood pressure significantly increases the risk of stroke, myocardial infarction, chronic kidney disease, heart failure, dementia, renal failure, and blindness. There is an urgent need for stakeholders—including individuals and families—across the health system, researchers, and decision makers to work collaboratively for improving prevention, screening and detection, diagnosis and evaluation, awareness, treatment and medication adherence, management, and control for people with or at high risk for hypertension. Meeting this need will help reduce the burden of hypertension-related disease, prevent complications, and reduce the need for hospitalization, costly interventions, and premature deaths. Objective: This review aims to synthesize evidence on the epidemiological landscape and control of hypertension in Cameroon, and to identify elements that could potentially inform interventions to combat hypertension in this setting and elsewhere in sub-Saharan Africa. Methods: The full search process will involve several steps, including selecting relevant databases, keywords, and Medical Subject Headings (MeSH); searching for relevant studies from the selected databases; searching OpenGrey and the Grey Literature Report for gray literature; hand searching in Google Scholar; and soliciting missed publications (if any) from relevant authors. We will select qualitative, quantitative, or mixed-methods studies with data on the epidemiology and control of hypertension in Cameroon. We will include published literature in French or English from electronic databases up to December 31, 2016, and involving adults aged 18 years or older. Both facility and population-based studies on hypertension will be included. Two reviewers of the team will independently search, screen, extract data, and assess the quality of selected studies using suitable tools. Selected studies will be analyzed by narrative synthesis, meta-analysis, or both, depending on the nature of the data retrieved in line with the review objectives. Results: This review is part of an ongoing research program on disease prevention and control in the context of the dual burden of communicable and noncommunicable diseases in Africa. The first results are expected in 2017. Conclusions: This review will provide a comprehensive assessment of the burden of hypertension and control measures that have been designed and implemented in Cameroon. Findings will form the knowledge base relevant to stakeholders across the health system and researchers who are involved in hypertension prevention and control in the community and clinic settings in Cameroon, as a yardstick for similar African countries. Trial Registration: PROSPERO registration number: CRD42017054950; http://www.crd.york.ac.uk/PROSPERO/ display_record.asp?ID=CRD42017054950 (Archived by WebCite at http://www.webcitation.org/6qYSjt9Jc) [JMIR Res Protoc 2017;6(5):e102]

The use of an extracorporeal treatment (ECTR) in a poisoned patient may be life-saving in a limited number of scenarios. The decision-processes surrounding the use of ECTR in poisoning is complex: most nephrologists are not trained to assess a poisoned patient while clinical toxicologists rarely prescribe ECTRs. Deciding on which ECTR is most appropriate for a poison requires a good understanding of the poison's physicochemical and pharmacokinetic properties. Further, a detailed understanding of the capabilities and limitations of the different ECTRs can be useful to select the most appropriate ECTR for a given clinical situation. This manuscript provides a stepwise approach to assess the usefulness of ECTRs in poisoning.

Isot/Jasts Abstract 2016Isot/Jasts Abstract 2016; International audience; Bitter compounds induced innate aversion which was reflected in loss of appetite and decreased fat depositionin a pig model reported by our group. However, the mechanism remains unclear. We hypothesized that bittercompounds would reduce gastric emptying and slow down intestinal peristalsis in the pig. Based on previous invivo trial and known molecular mechanisms, caffeine and quinine were the two bitter compounds selected. Bothcompounds are known agonists of human bitter taste receptors (hT2R) with high homology with the porcine T2Rs: Tas2r4, Tas2r7, Tas2r10, Tas2r20 and Tas2r39. Real-time PCR was used to study the expression ofporcine bitter taste receptor genes in the stomach and duodenum that related to the tested bitter compounds.The results showed high expression both in the stomach and duodenum and that the expression level was mostsignificant in the epithelium relative to the smooth muscle layer. The non-invasive scintigraphy imaging datashowed that caffeine and quinine mixed feed significantly (P

Montague W M Hadley (“Monty”) was born in Inverness, after a prenatal dash by his dentist mother from West Bromwich to ensure her child's Scottish and Inverness heritage. During his medical residency at Inverness Royal Infirmary, Monty met fellow resident Dorothy Reside, who would later become his wife. He joined the Royal Army Medical Corps in 1945 and was posted to Ranchi, India, for two …

Cardiovascular diseases (CVD) represent a heavy economic burden on individuals, health services, and society. Low adherence to antihypertensive (AH) agents is acknowledged as a major contributor to the lack of blood pressure control, and may have a significant impact on clinical outcomes and healthcare costs.To evaluate the impact of low adherence to AH agents on cardiovascular outcomes and hospitalization costs.A cohort of 59,647 patients with essential hypertension was reconstructed from the Régie de l'assurance maladie du Québec and Med-Echo databases. Subjects included were between 45 and 85 years of age, without any evidence for symptomatic CVD, newly treated with AH agents between 1999 and 2002 and followed-up for a 3-year period. Adherence to AH agents was categorized asor=80% or80%. The adjusted odds ratio (OR) for CVD events between the 2 adherence groups was estimated using a polytomous logistic analysis. A 2-part model was applied for hospitalization costs.Patients with low adherence were more likely to have coronary disease (OR, 1.07; 95% confidence interval [CI], 1.00-1.13), cerebrovascular disease (OR, 1.13; 95% CI, 1.03-1.25), and chronic heart failure (OR, 1.42; 95% CI, 1.27-1.58) within the 3-year follow-up period. Among hospitalized patients, low adherence to AH therapy was associated with increased costs by approximately $3574 (95% CI, $2897-$4249) per person within a 3-year period.Low adherence to AH agents is correlated with a higher risk of vascular events, hospitalization, and greater healthcare costs. An increased level of adherence to AH agents should provide a better health status for individuals and a net economic gain.

Dalteparin sodium, a low-molecular-weight heparin, is indicated for prevention of clotting in the extracorporeal circuit during hemodialysis (HD). Product labeling recommends a fixed single-bolus dose of 5000 international units (IU) for HD sessions lasting up to 4 hours, but adjustable dosing may be beneficial in clinical practice.The aim of the PARROT study was to investigate the safety and efficacy of an adjustable dose of dalteparin in patients with end-stage renal disease requiring 3 to 4 HD sessions per week.A 7-week, open-label, multicenter study with a single treatment arm, conducted between October 2013 and March 2016.Ten sites in Canada.A total of 152 patients with end-stage renal disease requiring 3 to 4 HD sessions per week.The primary outcome was the proportion of HD sessions completed without premature termination due to inadequate anticoagulation.All participants initially received a dose of 5000 IU dalteparin, which could be adjusted at subsequent HD sessions when clinically indicated, by increment or decrement of 500 or 1000 IU, with no specified dose limits.Patients were followed for 256 patient-months. Nearly all (99.9%; 95% confidence interval [CI]: 99.7-100) evaluable HD sessions were completed without premature clotting. Dose was adjusted for more than half (52.3%) of participants, mostly owing to clotting or access compression time10 minutes. Median dalteparin dose was 5000 IU (range: 500-13 000 IU). There were no major bleeds, and minor bleeding was reported in 2.3% of all HD sessions. There was no evidence of bioaccumulation.This short-term study, with a single treatment arm, was designed to optimize dalteparin dose using a flexible dosing schedule; it was not designed to specifically evaluate dalteparin dose minimization, provide a direct comparison of dalteparin versus unfractionated heparin, or provide information on long-term safety for flexible dalteparin dosing. Patients were excluded if they were at high risk of bleeding, including those on anticoagulants and those on antiplatelet agents other than aspirin100 mg/d.Overall, an adjustable dalteparin sodium dose regimen allowed safe completion of HD, with clinical benefits over fixed dosing.ClinicalTrials.gov NCT01879618, registered June 13, 2013.La daltéparine sodique, une héparine de faible poids moléculaire, est indiquée pour prévenir la formation de caillots dans le circuit extracorporel durant l’hémodialyse (HD). Pour une séance de dialyse d’une durée maximale de quatre heures, l’étiquette du produit recommande une dose fixe de 5 000 unités internationales (U.I.) administrée en bolus. Cependant, il est possible qu’il puisse être bénéfique d’ajuster la dose en pratique.Le but de l’étude PARROT était d’analyser l’innocuité et l’efficacité d’une dose ajustable de daltéparine chez des patients atteints d’insuffisance rénale terminale (IRT) et nécessitant trois à quatre séances d’HD par semaine.Il s’agit d’une étude ouverte et multicentrique à traitement unique d’une durée de sept semaines couvrant la période entre octobre 2013 et mars 2016.L’étude a eu lieu dans dix centres de dialyse au Canada.L’étude a inclus 152 patients atteints d’IRT et nécessitant trois à quatre séances d’HD par semaine.Le résultat principal était la proportion de séances d’HD complétées, non interrompues de manière prématurée en raison d’une anticoagulation inadéquate.Tous les participants ont initialement reçu 5000 U.I. de daltéparine, dose qui a pu être ajustée lors des séances subséquentes, lorsqu’indiqué par le contexte clinique, à raison d’augmentation ou de réduction de 500 ou 1 000 U.I., sans spécification quant aux doses limites.Les patients ont été suivis sur une période de 256 mois-patients. Pratiquement toutes les séances d’HD évaluables (99,9 %; IC 95 % : 99,7-100) ont été complétées sans coagulation prématurée. La dose de daltéparine a été ajustée pour plus de la moitié (52,3 %) des participants, essentiellement en raison de coagulation ou d’un besoin de procéder à une compression de l’accès vasculaire au-delà de 10 minutes. La dose médiane de daltéparine était de 5 000 U.I. (entre 500 et 13 000 U.I.). Aucune hémorragie majeure n’a été rapportée, mais une hémorragie mineure est survenue dans 2,3 % de toutes les séances d’HD analysées. Aucune bioaccumulation n’a été détectée.Cette étude de courte durée à traitement unique a été conçue pour optimiser le dosage de daltéparine à l’aide d’un schéma de posologie flexible. Elle ne visait pas à évaluer spécifiquement la minimisation de la dose ou à fournir des informations sur l’innocuité à long terme d’une posologie flexible pour la daltéparine. Également, les patients à haut risque d’hémorragie ont été exclus de l’étude, notamment ceux qui prenaient des anticoagulants ou des antiplaquettaires autres qu’une dose quotidienne de moins de 100 mg d’aspirine.Dans l’ensemble, un schéma posologique flexible pour la daltéparine sodique a permis de compléter les séances d’HD de façon sécuritaire, en plus de fournir des avantages cliniques par rapport à une dose fixe.

Lithium (Li) is a first-line treatment for bipolar disorder but has a narrow therapeutic index. Treatment of Li toxicity includes supportive measures and hemodialysis in severe cases, but this modality is not always immediately available. Sodium polystyrene sulfonate (SPS, Kayexalate), a cation exchanger, has been promising in animal models and human reports to reduce absorption and enhance elimination of Li.A retrospective cohort study was conducted. All cases of chronic Li intoxication were reviewed in two adult-care hospitals from 2000 to 2009. A group comparison and a within-patient comparison were performed to compare the effect of SPS on the median Li half-life (T(1/2)). For this study, at least three serum Li levels were required for T(1/2) calculations.Forty-eight patients met inclusion requirements, 12 of whom had taken SPS. Median Li T(1/2) in the treated and control groups was 20.5 and 43.2 hours, respectively (p = 0.0006). In the 12 treated patients, Li T(1/2) during SPS was on average 48.9% shorter than without SPS. Furthermore, in one subject in whom urinary Li data were available, Li clearance with SPS was superior to Li renal clearance. Prolonged constipation was noted in one patient whereas mild hypokalemia was noted in six patients treated with SPS.This study shows that SPS reduced Li T(1/2) and suggests that SPS is capable of promoting Li elimination in chronic intoxications. These results warrant a prospective trial looking at the use of SPS in the treatment of Li overdose as an adjunct to supportive measures and hemodialysis.

Les années 80 ont vu naître au Québec un bon nombre de réseaux de femmes de carrière. Tantôt bien structurés, tantôt plutôt informels, ces réseaux permettent aux femmes qui occupent des postes d’influence de s’apporter mutuellement diverses formes d’appui et de rayonner plus largement auprès des autres femmes. Cette note d’action rappelle d’abord quelques expériences antérieures de réseautage féminin puis elle présente les caractéristiques des regroupements contemporains. Trois réseaux sont décrits plus en profondeur par l’une de leurs membres : Les filles du Ritz (maintenant appelées « Les amies d’affaires »), le réseau International Women’s Forum et l’Association des femmes en finance du Québec. Des réflexions générales sont tirées de ces histoires de cas qui peuvent inciter les jeunes femmes à participer activement à des réseaux existants ou à créer elles-mêmes de nouveaux groupes., The 80’s have seen the rise in Quebec of a great number of networks of career women. Sometimes well structured, sometimes rather informal, these networks allow women who hold down a job of influence to bring each other diverse forms of support and to reach out to the other women. This action report foremostly recalls past experiences of feminine networking then presents contemporary gathering attributes. Three networks are portrayed in depth by one of their members: « Les filles du Ritz » (now called « Les amies d’affaires »), the International Women’s Forum network and the Financial Women’s Association of Quebec. General reflections are drawn from these stories that may prompt young women to create new groups and to actively participate in existing networks.

The rapid increase in glomerular filtration rate in a normal contralateral kidney after uninephrectomy is well known in living kidney donors but much less well described in chronic kidney disease (CKD). The purpose of this study is to determine the magnitude of this initial compensatory capacity in (CKD) groups 3 to 5 (G3 to G5) patients undergoing uninephrectomy and the clinical factors predicting it. This is a retrospective study of all cases (142) of uninephrectomy in patients with estimated glomerular filtration rate (eGFR; with MDRD equation)60 ml/min/1.73 m(2), between 2003 and 2010, in two University of Montreal-affiliated teaching hospitals.Baseline eGFR, patients' comorbidities, and surgical characteristics and complications were noted. The change of eGFR after nephrectomy was evaluated; moreover, the expected post-op eGFR, i.e. without compensation by the contralateral kidney following surgery, was estimated in a sub-group of patients who had a preoperative renal scintigraphy and compared to the actual eGFR at hospital discharge.The mean change of eGFR from baseline to hospital discharge was -5 ± 12 ml/min/1.73 m(2) (-11 %; 95 % CI -16 to -6 %; P 0.001). In univariate and multivariate analyses, baseline eGFR did not influence significantly these results. However, in the multivariate model, radical nephrectomy vs. partial nephrectomy and preoperative hypertension predicted a worse renal outcome. In the sub-group of patients with preoperative renal scintigraphy, the actual eGFR at hospital discharge was also higher than expected from the renal split function (13 ml/min/1.73 m(2); 95 % CI 10 to 16; P 0.001).After uninephrectomy, the contralateral kidney in patients with CKD G3 to G5 still has a clinically significant initial compensatory capacity. The compensation is statistically smaller if the patient had hypertension or a radical uninephrectomy. This initial compensation is rapid and most probably haemodynamic (hyperfiltration). However, most of the included patients had a CKD G3, limiting the strength of the conclusion for the G4 toG5 patients; the length of observation covers the early postoperative period, i.e. less than 2 weeks, in more than half of the cohort.L’accroissement rapide du débit de filtration glomérulaire du rein controlatéral à la suite d’une uninéphrectomie (uniNPX) est bien connu pour les donneurs de rein vivants, mais est beaucoup moins bien documenté dans le cas des patients souffrant d’une insuffisance rénale chronique (IRC).L’étude avait pour objectif principal de déterminer à quel point la capacité de compensation initiale du rein controlatéral est maintenue chez les patients souffrant d’IRC de stade 3 à 5 après une NPX et quels facteurs cliniques sont susceptibles d’aider à prévoir la perte d’activité fonctionnelle du rein.Il s’agit d’une étude rétrospective de 142 cas de NPX pratiquées entre 2003 et 2010 au sein de deux centres hospitaliers universitaires affiliés à l’Université de Montréal, sur des patients présentant un débit de filtration glomérulaire estimé (DFGe) par l’équation MDRD, inférieur à 60 ml/min/1.73 mLa mesure du débit de filtration glomérulaire préopératoire, les maladies concomitantes inscrites au dossier, les particularités de la chirurgie ainsi que les complications survenues par la suite, ont été notées pour chaque patient. La variation du DFG a été évaluée après la chirurgie. De plus, le DFG post-op attendu, calculé en ne tenant pas en compte la compensation offerte par le rein controlatéral après la chirurgie, a été estimé pour un sous-groupe de patients qui avaient subi une scintigraphie rénale préopératoire et comparé à la mesure du DFG faite au moment de la sortie de l’hôpital.La variation moyenne du DFG entre les mesures prises avant la chirurgie et celles prises lors de la sortie de l’hôpital était de −5 ± 12 ml/min/1.73 mÀ la suite d’une néphrectomie, le rein controlatéral des patients atteints d’insuffisance rénale chronique de stade 3 à 5 possède toujours une capacité compensatoire significative du point de vue clinique. Par contre, la compensation est moindre si le patient souffre d’hypertension avant la chirurgie ou lorsqu’il subit une uniNPX radicale, elle est également rapide et probablement hémodynamique (hyperfiltration). Il importe également de noter que la majorité des patients ayant participé à l’étude avait une IRC de stade 3 et que ceci ne permet pas de tirer des conclusions sans équivoque pour les patients de stades 4 et 5. De plus, les observations se sont déroulées sur une très courte période, moins de deux semaines pour plus de la moitié de la cohorte, immédiatement après la chirurgie.

According to the theory on which the Script Concordance Test (SCT) is based, scripts contain expectations on features that are associated with each illness and about the range of values that are typical, atypical, or incompatible.To document the construct validity of the SCT, we investigated the theory prediction that once a script is activated, new incoming information (e.g., additional clinical features) is processed faster if it is typical for that script than if it is atypical. If it is incompatible, processing time falls in between.We presented 2 groups of participants (30 fourth-year medical students and 30 full-time geriatricians) with 64 clinical vignettes (divided over 5 types of prevalent clinical presentations in geriatrics), each accompanied by a diagnostic hypothesis aimed to instantiate an appropriate script. Next, we presented a new finding, which could be typical, atypical, or incompatible given the hypothesis. Participants had to decide as quickly and accurately as possible whether the new finding increased, decreased, of did not affect the likelihood of the diagnostic hypothesis. We administered the test on a computer. The dependent variable was processing time. We analyzed data with a repeated measure 2 x 3 analysis of variance.Typical information was processed faster than atypical and incompatible information (M = 10.6 sec vs. 19.2 sec and 16.4 sec, respectively; p lt; .001 for both). Incompatible information was processed faster than atypical information (16.4 sec vs. 19.2; p.001). There was no significant difference between the groups of geriatricians and students.It is possible to predict what kind of information will be processed faster depending of the typicality and compatibility of clinical data for given hypotheses. Results support SCT construct validity.

Background: To separate non-(1–84)parathyroid hormone [non-(1–84)PTH] from PTH(1–84), we developed new HPLC gradients and observed that the peak coeluting with hPTH(1–84) could be separated into two entities recognized by a cyclase-activating PTH (CA-PTH) assay that reacts with the first four amino acids of the PTH structure.Methods: Sera from six healthy individuals and five patients with primary hyperparathyroidism, and eight pools of sera from patients in renal failure were fractionated by HPLC. A total (T)-PTH assay reacting with the (15–20) region, the CA-PTH assay, and a COOH-terminal (C)-PTH assay with a (65–84) structure requirement were used to measure basal and fractionated PTH values.Results: T-PTH was higher than CA-PTH in all healthy controls [mean (SD), 3.13 (0.37) vs 2.29 (0.33) pmol/L; P Conclusions: This new molecular form of PTH has structural integrity of the (1–4) region but presumably is modified in the region (15–20), which is usually recognized by the T-PTH assay. Its clinical implications remain to be defined.

Aims Quinine is often used to prevent muscle cramps in patients with chronic renal failure. A standard dose of 300 mg at bedtime is usually recommended, but little is known about the pharmacokinetics of quinine in the presence of renal failure. Methods We studied the pharmacokinetics of quinine in eight normal subjects and eight patients with chronic renal failure on haemodialysis after a single oral dose of quinine sulphate (300 mg). Results The concentration of a 1 -acid glycoprotein (AAG), the major binding protein for quinine, was increased in haemodialysis patients compared with control subjects (1.52 g l - 1 vs 0.63 g l - 1 [mean difference 1.033; 95% CI 0.735, 1.330]) whereas albumin levels were decreased (30 g l - 1 vs 40 g l - 1 [mean difference 9.5; 95% CI 3.048, 15.952]). Accordingly, the free fraction of quinine was decreased (0.024 vs 0.063 [mean difference 0.0380; 95% CI 0.0221, 0.0539]) and the apparent volume of distribution tended to decrease (0.95 l kg - 1 vs 1.43 l kg - 1 [mean difference 0.480; 95% CI 0.193, 1.154]). The quinine binding ratio correlated with the plasma concentration of AAG but not that of albumin. The clearance of free (unbound) quinine was increased in haemodialysis patients compared with controls (67.9 ml min - 1 kg - 1 vs 41.1 ml min - 1 kg - 1 [mean difference - 26.8; 95% CI, ‐56.994, 3.469]), and the area under the curve (AUC) of the two main metabolites, 3hydroxyquinine and 10,11-dihydroxydihydroquinine were increased. Conclusions In patients with chronic renal failure, there is an increase in plasma protein binding and in the clearance of free drug, resulting in lower plasma concentration of free quinine.

A population-based cohort study design was used to estimate persistence rate, re-initiation rate after discontinuation, and adherence level among incident users of oral antidiabetics (OADs), and to investigate predictors of non-persistence and non-adherence.Incident OAD users were identified using healthcare databases of residents covered by the public drug insurance plan of the Province of Quebec, Canada. Patients initiated OAD therapy between January 2000 and October 2009 and were aged 45-85 years at cohort entry. Persistence rate, re-initiation after discontinuation, and adherence level were assessed over 2 years. Predictors of non-persistence and non-adherence were analyzed using Cox and logistic regression models, respectively.The cohort included 160,231 incident OAD users at entry. One year after OAD initiation, persistence rate was 51 % and adherence level 67 %. Among those deemed non-persistent, 80.6 % re-initiated OAD therapy within 12 months of discontinuation; a proportion increasing with primary persistence duration. The 1-year persistence rate varied according to OAD classes; being the highest for thiazolidinediones (62 %) and the lowest for alpha-glucosidase inhibitors (30 %). The likelihood for non-persistence was 39-54 % higher when drug copayments were required. Conversely, OAD discontinuation was least likely for patients with schizophrenia [hazard ratio 0.70 (95 % CI 0.67-0.73)], dyslipidemia [0.85 (0.84-0.87)], anticoagulation [0.86 (0.83-0.88)], hypertension [0.87 (0.85-0.88)], and ≥7 medications [0.90 (0.88-0.91)]. Predictors of non-adherence were similar.Non-persistence and non-adherence to OAD therapy were common, although re-initiation rate was high. OAD classes, drug copayments, comorbidities and co-medications may help identifying those who were more likely to benefit from counseling.

A role for nephrologists in the management of a poisoned patient involves evaluating the indications for, and methods of, enhancing the elimination of a poison. Nephrologists are familiar with the various extracorporeal treatments (ECTRs) used in the management of impaired kidney function, and their respective advantages and disadvantages. However, these same skills and knowledge may not always be considered, or applicable, when prescribing ECTR for the treatment of a poisoned patient. Maximizing solute elimination is a key aim of such treatments, perhaps more so than in the treatment of uremia, because ECTR has the potential to reverse clinical toxicity and shorten the duration of poisoning. This manuscript reviews the various principles that govern poison elimination by ECTR (diffusion, convection, adsorption, and centrifugation) and how components of the ECTR can be adjusted to maximize clearance. Data supporting these recommendations will be presented, whenever available.

Background: The appropriate observation period, rate and risk factors of complications after a percutaneous renal biopsy remain debated. Methods: We retrospectively studied native kidney biopsies performed in our institution between January 2007 and July 2011. Outpatients had either an 8- (67%) or a 24-hour (33%) observation period. Results: 312 biopsies were reviewed (287 patients), 51% of patients were female and the mean age was 54 ± 15 years. Half of these biopsies were performed in outpatients. A total of 15% of patients developed a symptomatic hematoma, 9% received a red blood cell transfusion and 1% required an angio-intervention. Eighty-four percent of the complications manifested within the first 8 h, 86% at 12 h and 94% at 24 h. Outpatients experienced significantly less complications, all manifesting within the first 8 h, 14% required an observation period longer than planned. The risk of symptomatic hematoma increased to 11, 20, 35 and 40% in patients with >200, 140-200, 100-140 and 9/l platelets, respectively (p = 0.002). It also increased in hemodialysis patients (29% compared to 14%, p = 0.02). We found no association of risk with the number of biopsy passes and only a trend with needle size. Conclusion: Symptomatic hematomas occurred in 15% of kidney biopsies and were strongly associated with platelet count and hemodialysis. Outpatients experienced fewer complications; therefore, we can conclude that same-day discharge in selected patients is safe.

Objectives: To assess the effects of nonpharmacologic approaches to pain relief during labor, according to their endogenous mechanism of action, on obstetric interventions, maternal, and neonatal outcomes. Data source: Cochrane library, Medline, Embase, CINAHL and the MRCT databases were used to screen studies from January 1990 to December 2012. Study selection: According to Cochrane criteria, we selected randomized controlled trials that compared nonpharmacologic approaches for pain relief during labor to usual care, using intention-to-treat method. Results: Nonpharmacologic approaches, based on Gate Control (water immersion, massage, ambulation, positions) and Diffuse Noxious Inhibitory Control (acupressure, acupuncture, electrical stimulation, water injections), are associated with a reduction in epidural analgesia and a higher maternal satisfaction with childbirth. When compared with nonpharmacologic approaches based on Central Nervous System Control (education, attention deviation, support), usual care is associated with increased odds of epidural OR 1.13 (95% CI 1.05-1.23), cesarean delivery OR 1.60 (95% CI 1.18-2.18), instrumental delivery OR 1.21 (95% CI 1.03-1.44), use of oxytocin OR 1.20 (95% CI 1.01-1.43), labor duration (29.7 min, 95% CI 4.5-54.8), and a lesser satisfaction with childbirth. Tailored nonpharmacologic approaches, based on continuous support, were the most effective for reducing obstetric interventions. Conclusion: Nonpharmacologic approaches to relieve pain during labor, when used as a part of hospital pain relief strategies, provide significant benefits to women and their infants without causing additional harm. (BIRTH 41:2 June 2014)

Background: Commercial intact parathyroid hormone (I-PTH) assays detect molecular form(s) of human PTH, non-(1-84) PTH, different from the 84-amino acid native molecule. These molecular form(s) accumulate in hemodialyzed patients. We investigated the importance of non-(1-84) PTH in the interpretation of the increased I-PTH in progressive renal failure.Methods: Five groups were studied: 26 healthy individuals, 12 hemodialyzed patients, and 31 patients with progressive renal failure subdivided according to their glomerular filtration rate (GFR) into 11 with a GFR between 60 and 100 mL · min−1 · 1.73 m−2, 12 with a GFR between 30 and 60 mL · min−1 · 1.73 m−2, and 8 with a GFR between 5 and 30 mL · min−1 · 1.73 m−2. We evaluated indicators of calcium and phosphorus metabolism and creatinine clearance (CrCl) in the progressive renal failure groups, and the HPLC profile of I-PTH and C-terminal PTH in all groups.Results: Only patients with a GFR Conclusions: As I-PTH increases progressively with GFR decrease, part of the increase is associated with the accumulation of non-(1-84) PTH, particularly when the GFR is

To evaluate myocardial contractility during ST segment depression in healthy parturients during Cesarean section (CS).Forty-seven consecutive term parturients undergoing elective CS under spinal anesthesia were studied. The ST segment was recorded continuously on leads II and V5 using a Holter monitor. Myocardial performance was evaluated by measuring cardiac index (CI), heart rate (HR), pre-ejection period (PEP), ventricular ejection time (VET), systolic time ratio (STR, PEP/VET), and ejection fraction (EF) with an impedance cardiograph.Fourteen patients (30%) developed ST segment depression within 15 min after delivery and the remaining 33 (70%) did not (controls). Seven patients developed a 1 mm change, five patients a 2 mm change and the remaining two a 3 mm change in the ST segment. Compared with pre-anesthesia values, the mean HR increased from 103 +/- 10 to 116 +/- 10 (ISD) bpm (P = 0.001), CI from 4.7 +/- 0.7 to 5.6 +/- 1.7 L.min-1 (P = 0.01), EF from 0.58 +/- 0.08 to 0.66 +/- 0.05 (P = 0.01) and STR decreased from 0.26 +/- 0.06 to 0.2 +/- 0.04 (P = 0.01) during ST segment depression. At this time, CI, HR and EF were greater and STR smaller than values obtained 15 min after delivery in the control subjects.ST-segment depression occurring during CS is associated with a hyperkinetic myocardial contractile state.

A gas chromatographic–mass spectrometric method was used to separate quinine and its metabolites present in urine after oral dosing of 300 mg quinine in humans. The technique allowed the separation of quinine and ten metabolites. Four of these metabolites were definitely identified as 3-hydroxyquinine, 2′-quinone, O-desmethylquinine and 10,11-dihydroxydihydroquinine, by comparing their methane chemical ionization mass spectra with those of authentic standards prepared by organic synthesis. Six other metabolites are described for the first time in human urine. From their electron impact and chemical ionization mass spectra, we propose these compounds to be 3-hydroxy-2′-quinone, O-desmethyl-2′-quinone, O-desmethyl-3-hydroxyquinine, O-desmethyl-3-hydroxy-2′-quinone, 10,11-dihydroxydihydro-2′-quinone and 10,11-dihydroxydihydro-O-desmethylquinine. These secondary metabolites probably arose from further biotransformation of the four primary metabolites.

Capillary electrophoresis (CE) and reverse phase HPLC were used to analyse Maillard reaction products (MRPs) formed in refluxed, aqueous xylose—glycine and glucose—glycine model systems. CE was shown to resolve many more components than reverse phase HPLC. Ultrafiltration was used to separate the MRPs into three molecular weight fractions, nominally > 3000, between 3000 and 1000, and

Cisapride (Propulsid) is a gastrointestinal prokinetic agent commonly used to treat nocturnal heartburn as well as a variety of other gastrointestinal disorders. The use of cisapride has been associated with acquired long QT syndrome and ventricular arrhythmias such as torsades de pointes which produces sudden cardiac death. These cardiotoxic effects can be due to blockade of one or more types of K+ channel currents in the human heart. For this reason we compared the effects of cisapride on two cloned human cardiac K+ channels, Kv1.5 and the human ether-a-go-go-related gene (HERG) stably transfected into mammalian cells. Using patch clamp electrophysiology, we found that cisapride was a potent inhibitor of HERG displaying an IC50 value of 44.5 nmol/l when tail currents at −40 mV were measured following a 2 s test depolarization to +20 mV. When HERG currents were measured at the end of prolonged (20 s) depolarizing steps to +20 mV, the apparent affinity of cisapride was increased and measured 6.70 nmol/l. The main effect of cisapride was to enhance the rate of HERG current decay thereby reducing current at the end of the voltage clamp pulse. Furthermore, the potency of cisapride for the HERG channel was similar to that observed for the class III antiarrhythmic agent dofetilide (IC50=15.3 nmol/l) and the nonsedating antihistamine terfenadine (IC50=56.0 nmol/l). In contrast to its effects on HERG, cisapride inhibited Kv1.5 channel currents weakly displaying an IC50 value of 21.2 μmol/l. It is concluded that cisapride displays specific, high affinity block of the human cardiac K+ channel HERG. It is likely that this interaction underlies the proarrhythmic effects of the drug observed under certain clinical settings.

Ascites becomes refractory to medical treatment in nearly 10% of cirrhotic patients, who then require repeated large-volume paracentesis. In this prospective study we evaluated the use of transjugular intrahepatic portosystemic shunt (TIPS) in 30 patients with refractory ascites. TIPS was successful in all and resulted in a 54% reduction in portacaval gradient (from 22.8 +/- 0.8 to 10.4 +/- 0.6 mm Hg). Ascites became easily controlled with diuretics in 26 patients following TIPS. Ascites recurrence associated with shunt stenosis was observed during follow-up in eight patients; revision could be undertaken in five of them and resulted in good control of ascites. In responders, a marked decrease in plasma aldosterone and renin activity, a reduction in serum creatinine, and a rise in urinary sodium excretion were observed. Creatinine and inulin clearances improved significantly; PAH clearance remained unchanged. However, new-onset or worsening hepatic encephalopathy was seen in 14 patients. Severe disabling chronic encephalopathy occurred in five patients; it could be reversed successfully by balloon occlusion of the shunt in three. The cumulative survival rate was 41 and 34% at 1 and 2 years, respectively. In summary, TIPS can control refractory ascites in a majority of patients but is associated with a high rate of chronic disabling HE. In addition, the survival rate is poor. Randomized trials are needed to evaluate the exact role of TIPS in the management of refractory ascites. It is unlikely to improve survival but can ameliorate quality of life in nontransplant candidates and be useful as a bridge to transplantation, in particular, to improve denutrition associated with longstanding tense ascites.

Purpose. To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of acetazolamide (ACTZ) in peritoneal dialysis patients, ACTZ 500 mg was administered intravenously to 7 healthy subjects (HV) and 8 peritoneal dialysis patients (CAPD). Methods. Population PK/PD modeling was performed with ACTZ serum (total and unbound), urine and dialysate concentrations, intra-ocular pressure (IOP) and covariates. A multi-compartment PK model (accounting for non-linear protein binding) and an inhibitory Emax (maximal change in IOP) PD model were selected. Results. As expected, renal clearance (which almost equals total body clearance) was severely decreased in CAPD (1.2 vs 80.3 L/h) and the elimination half-life of total ACTZ was prolonged (20.6 vs 3.4 hours). The protein binding was significantly altered with a mean free fraction 4.2% in HV and 8.6% in CAPD. Moreover protein binding of ACTZ was concentration dependent in both HV and CAPD. Despite a higher free fraction of ACTZ, the Emax was lower in CAPD: 4.4±1.4 vs 7.4±2.8 mmHg. Conclusion. Both PK and PD are significantly altered in dialysis patients. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.