Risk and Timing of Major Bleeding Complications Requiring Intervention of the Percutaneous Kidney Biopsy With a Short Observation Protocol: A Retrospective Chart Review.

Background: We previously published a retrospective study of kidney biopsies performed in a tertiary care hospital in London, Ontario from 2012 to 2017. This study resulted in a change of practice in our institution to shorter postbiopsy monitoring for outpatients as well as the development of a risk calculator to predict serious bleeding complications. Objective: The primary objective of this study was to determine whether this shorter monitoring time is adequate in the outpatient setting. A secondary objective was to validate the bleeding risk calculator in both inpatients and outpatients. Design: This was a retrospective chart review. Setting: This study was performed at a tertiary academic hospital in London, Ontario, Canada. Participants: This was a retrospective study of 400 adult patients who underwent kidney biopsy between April 30, 2018 and February 25, 2022 at a tertiary academic hospital in London, Canada. Methods: We retrospectively assessed frequency and timing of major bleeding complications in patients who underwent kidney biopsy. In secondary analyses, we examined the prediction performance of the risk calculator in discrimination and calibration. Results: Major bleeding occurred in 7 patients (1.8%). Five of these patients required blood transfusions (1.3%) and 2 required embolization (0.5%). In the outpatient setting, any major bleeding events were identified immediately (1 patient) or on the routine 2-hour ultrasounds (1 patient). The risk calculator showed good discrimination (C-statistic, 0.91, 95% confidence interval [CI] = [0.84 to 0.95]) and calibration (slope, 1.10, 95% CI = [0.47 to 1.74]; intercept, 95% CI = -0.02 [-0.79 to 0.75]), but with much uncertainty in the estimates. Limitations: The occurrence of only a few major bleeding events limits the reliability of our assessment of our risk calculator. Conclusions: There appears to be little yield in extending observation beyond 2 hours after an outpatient kidney biopsy with the use of immediate and 2-hour postbiopsy ultrasounds. The bleeding risk calculator (http://perioperativerisk.com/kbrc) warrants further validation.

Contexte: Nous avons publié précédemment une étude rétrospective des biopsies rénales effectuées entre 2012 et 2017 dans un hôpital de soins tertiaires de London, en Ontario. Les résultats de cette précédente étude ont entraîné un changement de pratique dans notre établissement, soit une réduction de la durée de la surveillance post-biopsie pour les patients ambulatoires, et la mise au point d'un calculateur de risque permettant de prédire les complications hémorragiques graves. Objectifs: L'objectif principal de l'étude en cours était de vérifier si ce temps de surveillance plus court est adéquat pour les patients ambulatoires. Un deuxième objectif était de valider le calculateur de risque d'hémorragie chez les patients hospitalisés et les patients ambulatoires. Conception: Étude rétrospective des dossiers médicaux. Cadre: Étude réalisée dans un hôpital de soins tertiaires de London, en Ontario (Canada). Sujets: Cette étude rétrospective portait sur 400 patients adultes ayant subi une biopsie rénale entre le 30 avril 2018 et le 25 février 2022 dans un centre hospitalier universitaire de soins tertiaires de London, au Canada. Méthodes: Nous avons procédé à un examen rétrospectif de la fréquence des complications hémorragiques graves, et du moment où celles-ci surviennent, chez les patients ayant subi une biopsie rénale. Dans les analyses secondaires, nous avons examiné la puissance prédictive du calculateur de risque en matière de discrimination et d'étalonnage. Résultats: Sept patients (1,75 %) ont subi une hémorragie majeure; de ces patients, cinq ont eu besoin de transfusions sanguines (1,3 %) et deux, d'une embolisation (0,5 %). En contexte ambulatoire, tous les événements hémorragiques graves ont été détectés immédiatement (un patient) ou lors de l'échographie de routine à deux heures (un patient). Le calculateur de risque a montré une bonne discrimination (statistique C : 0,91 [IC 95 % : 0,84 à 0,95]) et un bon étalonnage (pente : 1,10 [0,47 à 1,74]; point d'intersection : -0,02 [-0,79 à 0,75]), mais une grande incertitude dans les estimations. Limitations: La fiabilité de l'évaluation de notre calculateur de risque est limitée par le très faible échantillon d'événements hémorragiques graves étant survenus. Conclusion: Il semble y avoir peu d'intérêt à prolonger la surveillance au-delà de deux heures après une biopsie rénale chez les patients ambulatoires lorsqu'une échographie est pratiquée immédiatement après la procédure et deux heures plus tard. Le calculateur de risque d'hémorragie (http://perioperativerisk.com/kbrc) nécessite une validation plus approfondie.

Identification and Prioritization of Canadian Society of Nephrology Clinical Practice Guideline Topics With Multidisciplinary Stakeholders and People Living With Kidney Disease: A Clinical Research Protocol.

Background: Despite efforts to provide evidence-based care for people living with kidney disease, health care provider goals and priorities are often misaligned with those of individuals with lived experience of disease. Coupled with competing interests of time, resources, and an abundance of suitable guideline topics, identifying and prioritizing areas of focus for the Canadian nephrology community with a patient-oriented perspective is necessary and important. Similar priority-setting exercises have been undertaken to establish research priorities for kidney disease and to standardize outcomes for kidney disease research and clinical care; however, research priorities are distinct from priorities for guideline development. Inclusion of people living with health conditions in the selection and prioritization of guideline topics is suggested by patient engagement frameworks, though the process to operationalizing this is variable. We propose that the Canadian Society of Nephrology Clinical Practice Guideline Committee (CSN CPGC) takes the opportunity at this juncture to incorporate evidence-based prioritization exercises with involvement of people living with kidney disease and their caregivers to inform future guideline activities. In this protocol, we describe our planned research methods to address this. Objective: To establish consensus-based guideline topic priorities for the CSN CPGC using a modified Delphi survey with involvement of multidisciplinary stakeholders, including people living with kidney disease and their caregivers. Study design: Protocol for a Modified Delphi Survey. Setting: Pilot-tested surveys will be distributed via email and conducted using the online platform SurveyMonkey, in both French and English. Participants: We will establish a group of multidisciplinary clinical and research stakeholders (both within and outside CSN membership) from Canada, in addition to people living with kidney disease and/or their caregivers. Methods: A comprehensive literature search will be conducted to generate an initial list of guideline topics, which will be organized into three main categories: (1) International nephrology-focused guidelines that may require Canadian commentary, (2) Non-nephrology specific guidelines from Canada that may require CSN commentary, and (3) Novel topics for guideline development. Participants will engage in a multi-round Modified Delphi Survey to prioritize a set of "important guideline topics." Measures: Consensus will be reached for an item based on both median score on the Likert-type scale (≥ 7) and the percentage agreement (≥ 75%); the Delphi process will be complete when consensus is reached on each item. Guideline topics will then be given a priority score calculated from the total Likert ratings across participants, adjusted for the number of participants. Limitations: Potential limitations include participant response rates and compliance to survey completion. Conclusions: We propose to incorporate evidence-based prioritization exercises with the engagement of people living with kidney disease and their caregivers to establish consensus-based guideline topics and inform future guidelines activities of the CSN CPGC.

Contexte: Malgré les efforts déployés pour fournir aux personnes atteintes de néphropathies des soins fondés sur les données probantes, il s'avère que les objectifs et priorités des prestataires de soins de santé sont souvent mal alignés avec ceux des personnes qui ont une expérience concrète de la maladie. Compte tenu des intérêts concurrents en matière de temps et de ressources, et de l'abondance de sujets pertinents pour l'élaboration de lignes directrices, il est nécessaire et important d'identifier et de hiérarchiser les domaines prioritaires pour la communauté néphrologique canadienne dans une perspective orientée vers le patient. Des exercices semblables pour la définition des priorités ont été entrepris afin d'établir les priorités de la recherche sur les maladies rénales et normaliser les soins cliniques et les résultats de la recherche sur les maladies rénales. Or, les priorités de la recherche diffèrent des priorités pour l'élaboration des lignes directrices. Bien que les façons de procéder varient, les cadres d'engagement des patients suggèrent que des personnes vivant avec des problèmes de santé soient incluses dans la sélection et la hiérarchisation des sujets des lignes directrices. À cet égard, nous proposons que le Comité sur les lignes directrices de pratique clinique de la Société canadienne de néphrologie (CSN CPGC ­ Canadian Society of Nephrology Clinical Practice Guideline Committee) profite de l'occasion pour intégrer des exercices d'établissement des priorités fondés sur des données probantes et impliquer des personnes vivant avec une néphropathie et des soignants afin de guider les futures activités d'élaboration de lignes directrices. Dans ce protocole, nous décrivons la méthodologie de recherche que nous suivrons pour y remédier. Objectif: Établir des priorités consensuelles en matière de sujets de lignes directrices pour le CSN CPGC à l'aide d'une enquête Delphi modifiée et avec la participation d'intervenants multidisciplinaires, notamment des personnes vivant avec une néphropathie et leurs soignants. Conception: Protocole pour une enquête Delphi modifiée. Cadre: Des sondages pilotes, en anglais et en français, seront distribués par courriel et réalisés à l'aide de la plateforme en ligne SurveyMonkey. Participants: Nous créerons un groupe d'intervenants multidisciplinaires canadiens œuvrant en clinique et en recherche (à la fois des membres et des non membres de la SCN) auquel s'ajouteront des personnes atteintes d'une néphropathie et/ou leurs soignants. Méthodologie: Une recherche exhaustive sera effectuée dans la littérature afin de constituer une première liste de sujets de lignes directrices, laquelle sera divisée en trois catégories principales: (1) lignes directrices internationales axées sur la néphrologie et pouvant nécessiter des commentaires canadiens, (2) lignes directrices canadiennes non spécifiquement liées à la néphrologie et pouvant nécessiter des commentaires de la SCN, (3) nouveaux sujets pour l'élaboration de lignes directrices. Les participants s'engageront dans une enquête Delphi modifiée à plusieurs tours afin de hiérarchiser un ensemble de « sujets importants pour l'élaboration de lignes directrices ¼. Mesures: Un consensus sera atteint pour un énoncé s'il atteint à la fois un score médian (≥7) sur l'échelle de Likert et le pourcentage d'accord établi (≥ 75 %); le processus Delphi sera terminé lorsque le consensus sera atteint pour chaque énoncé. Les sujets pour l'élaboration de lignes directrices recevront ensuite une cote de priorité calculée à partir du total des scores des participants sur l'échelle Likert et ajustée en fonction du nombre de participants. Limites: L'étude pourrait être limitée par le taux de réponse des participants et leur engagement à compléter toutes les étapes de l'enquête. Conclusion: Nous proposons d'intégrer des exercices de définition des priorités fondés sur des données probantes et impliquant la participation de personnes vivant avec une néphropathie et de leurs soignants afin de déterminer des sujets consensuels pour l'élaboration de lignes directrices et de guider les futures activités du CSN CPGC en lien avec ce processus.

Cognitive Impairment Early After Initiating Maintenance Hemodialysis: A Cross Sectional Study.

Background: Abnormalities in cognitive function are almost universal in patients receiving hemodialysis (HD) and are associated with worse quality of life, impaired decision making, increased healthcare utilization and mortality. While cognitive impairment in the HD population is increasingly recognized, it is unclear how quickly it develops after starting HD. Methods: This was a cross-sectional study of a cohort of low dialysis vintage HD patients (<12 months). We used the validated Cambridge Brain Science (CBS) battery of web-based tests to evaluate cognition compared to age- and sex matched controls across three cognitive domains: verbal processing, reasoning and short-term memory. Results: Forty-nine HD patients were included in this study; 43 completed the full battery of tests. The average scores for HD patients were consistently below the age and sex-matched controls. Fifty-five percent of HD patients had cognitive impairment in verbal skills, 43% in reasoning and 18% in short-term memory. Conclusions: There is a high prevalence of CI evident early after starting HD, with the largest deficits seen in reasoning and verbal processing. These deficits may be attributable to the HD treatment itself. Further studies are needed to characterize the natural history of CI in this patient population and to test interventions aimed at preventing or slowing its progression.

A Higher Concentration of Dialysate Magnesium to Reduce the Frequency of Muscle Cramps: A Narrative Review.

PURPOSE OF REVIEW: Strategies to mitigate muscle cramps are a top research priority for patients receiving hemodialysis. As hypomagnesemia is a possible risk factor for cramping, we reviewed the literature to better understand the physiology of cramping as well as the epidemiology of hypomagnesemia and muscle cramps. We also sought to review the evidence from interventional studies on the effect of oral and dialysate magnesium-based therapies on muscle cramps. SOURCES OF INFORMATION: Peer-reviewed articles. METHODS: We searched for relevant articles in major bibliographic databases including MEDLINE and EMBASE. The methodological quality of interventional studies was assessed using a modified version of the Downs and Blacks criteria checklist. KEY FINDINGS: The etiology of muscle cramps in patients receiving hemodialysis is poorly understood and there are no clear evidence-based prevention or treatment strategies. Several factors may play a role including a low concentration of serum magnesium. The prevalence of hypomagnesemia (concentration of <0.7 mmol/L) in patients receiving hemodialysis ranges from 10% to 20%. Causes of hypomagnesemia include a low dietary intake of magnesium, use of medications that inhibit magnesium absorption (eg, proton pump inhibitors), increased magnesium excretion (eg, high-dose loop diuretics), and a low concentration of dialysate magnesium. Dialysate magnesium concentrations of ≤0.5 mmol/L may be associated with a decrease in serum magnesium concentration over time. Preliminary evidence from observational and interventional studies suggests a higher dialysate magnesium concentration will raise serum magnesium concentrations and may reduce the frequency and severity of muscle cramps. However, the quality of evidence supporting this benefit is limited, and larger, multicenter clinical trials are needed to further determine if magnesium-based therapy can reduce muscle cramps in patients receiving hemodialysis. In studies conducted to date, increasing the concentration of dialysate magnesium appears to be well-tolerated and is associated with a low risk of symptomatic hypermagnesemia. LIMITATIONS: Few interventional studies have examined the effect of magnesium-based therapy on muscle cramps in patients receiving hemodialysis and most were nonrandomized, pre-post study designs.

CONTEXTE MOTIVANT LA REVUE: Les stratégies visant à atténuer les crampes musculaires sont parmi les principales priorités de recherche des patients hémodialysés. L'hypomagnésémie étant un possible facteur de risque, nous avons procédé à une revue de la littérature afin de mieux en comprendre l'épidémiologie, et d'examiner la physiologie et l'épidémiologie des crampes musculaires. Nous souhaitions également examiner les données probantes issues d'études interventionnelles portant sur l'effet des thérapies à base de dialysat de magnésium et de magnésium oral sur les crampes musculaires. SOURCES: Articles examinés par les pairs. MÉTHODOLOGIE: Nous avons cherché les articles pertinents dans les principales bases de données bibliographiques, notamment MEDLINE et EMBASE. La qualité méthodologique a été évaluée à l'aide d'une version modifiée des critères de contrôle de la qualité des études de Downs et Black. PRINCIPAUX RÉSULTATS: L'étiologie des crampes musculaires chez les patients hémodialysés est mal comprise et il n'existe aucune stratégie de prévention ou traitement clairement fondé sur des données probantes. Plusieurs facteurs pourraient jouer un rôle, notamment de faibles concentrations sériques de magnésium. La prévalence de l'hypomagnésémie (concentration inférieure à 0,7 mmol/L) chez les patients hémodialysés variait de 10 à 20 %. Une faible consommation de magnésium dans l'alimentation, la prise de médicaments inhibant l'absorption du magnésium (ex. les inhibiteurs de la pompe à protons), l'excrétion accrue du magnésium (ex. dose élevée de diurétiques de l'anse) et une faible concentration de dialysat de magnésium figuraient parmi les causes d'hypomagnésémie. Un taux de dialysat de magnésium inférieur ou égal à 0,5 mmol/L pourrait être associé à une diminution de la concentration sérique de magnésium au fil du temps. Les résultats préliminaires de certaines études observationnelles et interventionnelles suggèrent qu'une concentration sérique plus élevée de magnésium dans le dialysat augmenterait les concentrations sériques de magnésium et pourrait réduire la fréquence et la sévérité des épisodes de crampes musculaires. La qualité des preuves appuyant ce bienfait est cependant limitée. Des essais multicentriques et à plus vaste échelle sont nécessaires pour juger si un traitement à base de magnésium peut véritablement réduire les crampes musculaires chez les patients hémodialysés. Dans les études menées jusqu'à maintenant, l'augmentation de la concentration de dialysat de magnésium semblait bien tolérée et a été associée à un faible risque d'hypermagnésémie symptomatique. LIMITES: Peu d'études interventionnelles ont examiné l'effet de la prise de magnésium sur les crampes musculaires des patients hémodialysés, et la plupart de celles-ci constituaient des plans pré- ou post-études non randomisées.

Frequency, Timing, and Prediction of Major Bleeding Complications From Percutaneous Renal Biopsy.

BACKGROUND AND OBJECTIVES: The risk and timing of bleeding events following ultrasound-guided percutaneous renal biopsy are not clearly defined. DESIGN SETTING PARTICIPANTS AND MEASUREMENTS: We performed a retrospective study of 617 consecutive adult patients who underwent kidney biopsy between 2012 and 2017 at a tertiary academic hospital in London, Canada. We assessed frequency and timing of minor (not requiring intervention) and major (requiring blood transfusion, surgery, or embolization) bleeds and developed a personalized risk calculator for these. RESULTS: Bleeding occurred in 79 patients (12.8%; 95% confidence interval [CI]: 10.4%-15.7%). Minor bleeding occurred in 67 patients (10.9%; 95% CI: 8.6%-13.6%). Major bleeding occurred in 12 patients (1.9%; 95% CI: 1.1%-3.4%); 2 required embolization or surgery (0.3%; 95% CI: 0.09%-1.2%) and 10 required blood transfusion (1.6%; 95% CI: 0.9%-3.0%). Seventy-three of 79 events were identified immediately on post-procedure ultrasound (92.4% of cases; 95% CI: 84.4%-96.5%). Four of 617 patients experienced a minor event not detected immediately (0.6%; 95% CI: 0.3%-1.7%). Two patients (0.3%; 95% CI: 0.09%-1.2%) suffered a major complication that was not recognized immediately; both required blood transfusions only. There were no deaths or nephrectomies. A risk calculator using age, body mass index, platelet count, hemoglobin concentration, size of the target kidney, and whether the kidney is native, or an allograft predicted minor (C-statistic, 0.70) and major bleeding (C-statistic, 0.83). CONCLUSIONS: This retrospective study of 617 patients who had percutaneous ultrasound-guided renal biopsies supports the safety of short post-biopsy monitoring for most patients. A risk calculator can further personalize estimates of complication risk (http://perioperativerisk.com/kbrc).

CONTEXTE: Les risques d'hémorragie et le moment où surviennent ces événements après une biopsie rénale percutanée échoguidée ne sont pas clairement définis. MÉTHODOLOGIE: Nous avons procédé à une étude rétrospective sur 617 patients adultes consécutifs ayant subi une biopsie rénale entre 2012 et 2017 dans un center hospitalier universitaire de soins tertiaires de London, au Canada. Nous avons analysé la fréquence des saignements et le moment où est survenue une hémorragie mineure (ne nécessitant aucune intervention) ou majeure (nécessitant une transfusion sanguine, une chirurgie ou une embolisation). Un calculateur de risque a ultérieurement été développé pour chacun. RÉSULTATS: Des 617 patients étudiés, 79 (12,8 %; IC 95 % : 10,4 %-15,7 %) ont vécu un événement hémorragique mineur (n=67 [10,9 %]; IC 95 % : 8,6 %-13,6 %) ou majeur (n=12 [1,9 %]; IC 95 % : 1,1 %-3,4 %). Deux hémorragies majeures ont nécessité une embolisation ou une chirurgie (0,3 %; IC 95 % : 0,09 %-1,2 %), les dix autres ayant été traitées par transfusion sanguine (1,6 %; IC 95 % : 0,9 %-3,0 %). Des 79 événements rapportés, 73 ont été détectés à l'échographie immédiatement après l'intervention (92,4 % des cas; IC 95 % : 84,4 %-96,5 %). Quatre patients (0,6 %; IC 95 % : 0,3 %-1,7 %) ont subi une complication mineure n'ayant pas été détectée immédiatement après la biopsie. Deux patients (0,3 %; IC 95 % : 0,09 %-1,2 %) ont souffert d'une complication majeure n'ayant pas été reconnue immédiatement, mais qui n'a nécessité que des transfusions sanguines. Aucun décès ou néphrectomie n'a été rapporté. Un calculateur du risque d'hémorragie utilisant l'âge, l'indice de masse corporelle, la numération plaquettaire, le taux d'hémoglobine, la taille du rein biopsié, et tenant compte du fait que le rein est natif ou une allogreffe, a pu prédire un événement mineur (statistique C = 0,70) ou majeur (statistique C = 0,83). CONCLUSION: Cette étude rétrospective sur 617 patients confirme qu'il serait prudent d'assurer une surveillance de courte durée pour la plupart des patients qui subissent une biopsie percutanée échoguidée. L'emploi d'un calculateur du risque d'hémorragie précise davantage le risque de complications estimé (http://perioperativerisk.com/kbrc).

Human papillomavirus in oropharyngeal cancer in Canada: analysis of 5 comprehensive cancer centres using multiple imputation.

BACKGROUND: The incidence of oropharyngeal cancer has risen over the past 2 decades. This rise has been attributed to human papillomavirus (HPV), but information on temporal trends in incidence of HPV-associated cancers across Canada is limited. METHODS: We collected social, clinical and demographic characteristics and p16 protein status (p16-positive or p16-negative, using this immunohistochemistry variable as a surrogate marker of HPV status) for 3643 patients with oropharyngeal cancer diagnosed between 2000 and 2012 at comprehensive cancer centres in British Columbia (6 centres), Edmonton, Calgary, Toronto and Halifax. We used receiver operating characteristic curves and multiple imputation to estimate the p16 status for missing values. We chose a best-imputation probability cut point on the basis of accuracy in samples with known p16 status and through an independent relation between p16 status and overall survival. We used logistic and Cox proportional hazard regression. RESULTS: We found no temporal changes in p16-positive status initially, but there was significant selection bias, with p16 testing significantly more likely to be performed in males, lifetime never-smokers, patients with tonsillar or base-of-tongue tumours and those with nodal involvement (p < 0.05 for each variable). We used the following variables associated with p16-positive status for multiple imputation: male sex, tonsillar or base-of-tongue tumours, smaller tumours, nodal involvement, less smoking and lower alcohol consumption (p < 0.05 for each variable). Using sensitivity analyses, we showed that different imputation probability cut points for p16-positive status each identified a rise from 2000 to 2012, with the best-probability cut point identifying an increase from 47.3% in 2000 to 73.7% in 2012 (p < 0.001). INTERPRETATION: Across multiple centres in Canada, there was a steady rise in the proportion of oropharyngeal cancers attributable to HPV from 2000 to 2012.

Distress levels in patients with oropharyngeal vs. non-oropharyngeal squamous cell carcinomas of the head and neck over 1 year after diagnosis: a retrospective cohort study.

BACKGROUND: Human papillomavirus (HPV)-related cancers have been associated with different demographic profiles and disease characteristics than HPV-unrelated cancers in head and neck patients, but distress and other symptoms have not been compared. The aim of this study was to assess whether distress levels, fatigue, pain, anxiety, depression, and common psychological and practical problems differ between head and neck cancer patients with HPV-related vs. HPV-unrelated carcinomas (using oropharyngeal carcinoma (OPC) and non-OPC cancers as surrogates for HPV status). METHODS: Distress, depression, anxiety, fatigue, pain, and common problems were examined in 56 OPC and 90 non-OPC patients at 4 timepoints during the first year following diagnosis. Two-level hierarchical linear modeling was used to examine effects. RESULTS: The HPV-related OPC group was more likely to be younger (p = 0.05), Caucasian (p = 0.001), non-smokers (p = 0.01), earn more (p = 0.04), and present with more advanced stage (p < 0.0001). At baseline, OPC patients reported only higher pain scores (p = 0.01) than non-OPC patients. Total problems decreased more in the OPC group (p = 0.08) than the non-OPC group from baseline to 12-month follow-up. In both groups, scores on distress, depression, psychosocial problems, and practical problems decreased similarly over time. CONCLUSIONS: Despite a difference in the clinico-demographic characteristics of HPV-related vs. HPV-unrelated patients, only baseline pain levels and total problems over time differed between the two groups.

Structural basis for antibody recognition in the receptor-binding domains of toxins A and B from Clostridium difficile.

Clostridium difficile infection is a serious and highly prevalent nosocomial disease in which the two large, Rho-glucosylating toxins TcdA and TcdB are the main virulence factors. We report for the first time crystal structures revealing how neutralizing and non-neutralizing single-domain antibodies (sdAbs) recognize the receptor-binding domains (RBDs) of TcdA and TcdB. Surprisingly, the complexes formed by two neutralizing antibodies recognizing TcdA do not show direct interference with the previously identified carbohydrate-binding sites, suggesting that neutralization of toxin activity may be mediated by mechanisms distinct from steric blockage of receptor binding. A camelid sdAb complex also reveals the molecular structure of the TcdB RBD for the first time, facilitating the crystallization of a strongly negatively charged protein fragment that has resisted previous attempts at crystallization and structure determination. Electrospray ionization mass spectrometry measurements confirm the stoichiometries of sdAbs observed in the crystal structures. These studies indicate how key epitopes in the RBDs from TcdA and TcdB are recognized by sdAbs, providing molecular insights into toxin structure and function and providing for the first time a basis for the design of highly specific toxin-specific therapeutic and diagnostic agents.

Assessment of serum creatinine and kidney function among incident metformin users.

OBJECTIVE: Metformin is considered the first-line antihyperglycemic therapy for type 2 diabetes, but should be used with caution in people with renal insufficiency. Our study objective was to describe the proportion of patients who have an assessment of kidney function (serum creatinine [SCr] and estimated glomerular filtration rate [eGFR]) around the time of initiation of metformin in new users. METHODS: We used data from the Alberta Kidney Disease Network to identify patients with diabetes (age, ≥66 y) with a new prescription for metformin from November 1, 2002, to March 31, 2008. We assessed whether SCr measurement was completed before and after metformin initiation. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and categorized into CKD stages. Frequency of metformin use based on SCr measurement and CKD stage was reported using descriptive statistics. RESULTS: A total of 22 051 subjects were identified as new metformin users. Overall, 25.4% (n=5608) had no measurement of SCr or assessment of eGFR before metformin prescription. In addition, of patients with an eGFR measurement, 38.7% (n=8544) of individuals had an eGFR of less than 60 mL/min/1.73 m(2). CONCLUSIONS: One quarter of patients started on metformin did not have a SCr measurement completed beforehand. Also, metformin was used commonly among patients with diabetes and CKD, potentially putting these individuals at risk for adverse events.

The effect of nocturnal and conventional hemodialysis on markers of nutritional status: results from a randomized trial.

OBJECTIVE: More frequent dialysis may improve nutrition and remove dietary restrictions in hemodialysis (HD) patients. We present results from a trial comparing nutritional parameters between nocturnal hemodialysis (NHD) and conventional HD patients. METHODS: Patients were randomized to conventional thrice weekly HD or NHD for a 6-month study period. Dietary intake was recorded by patients using a 3-day food record at baseline and study exit. RESULTS: Of 51 patients, 23 completed baseline and exit food records and were included in the analysis. Although dietary intake of calcium, potassium, and lipids increased in the NHD group, serum levels of calcium and potassium remained within target limits. The majority of NHD subjects were able to reduce or discontinue their phosphate binders and maintain serum phosphate levels within target limits. Serum albumin improved among the NHD group (0.7 g/L) and declined for the conventional group (-1.6 g/L). None of the between group differences achieved statistical significance. CONCLUSIONS: As compared with conventional dialysis, NHD was associated with a nonstatistically significant increase in dietary intake for some nutrients, with maintenance of serum levels for potassium, calcium, and phosphorus. Whether increased dietary intake translates into improvement in morbidity and mortality remains to be determined.

Nocturnal hemodialysis does not improve overall measures of quality of life compared to conventional hemodialysis.

We conducted a randomized controlled trial to compare the quality of life of 52 patients undergoing nocturnal hemodialysis and conventional hemodialysis. Quality of life was measured using a number of established methods including the Kidney Disease Quality of Life Short Form and the preference-based Euroqol EQ-5D questionnaire (whose scores varied from 0 to 1). The primary outcome was a change in the Euroqol EQ-5D index scores between baseline and 6 months. We performed additional analyses comparing change in quality of life from pre-randomization (when patients were unaware of treatment allocation) to 6 months. Other analyses considered the impact of nocturnal hemodialysis on four pre-selected Kidney Disease Quality of Life Short Form domains, and the longer term impact of nocturnal hemodialysis on quality of life. Compared with conventional hemodialysis, nocturnal hemodialysis increased Euroqol-EQ-5D index scores by 0.05, which was not significantly different from baseline. When six-month values were compared with pre-randomization values rather than baseline values, the between group difference was larger (0.12) though it was still not statistically significant (P=.06). Nocturnal hemodialysis was associated with clinically and statistically significant improvements in selected kidney-specific quality of life domains (P=.01 for effects of kidney disease; P=.02 for burden of kidney disease). Our primary quality of life analysis did not demonstrate a statistically significant change between nocturnal hemodialysis and conventional hemodialysis, though statistically significant and clinically important changes in some secondary kidney-disease- specific measures were observed.