Geographic and facility variation in initial use of non-tunneled catheters for incident maintenance hemodialysis patients.

BACKGROUND: Non-tunneled (temporary) hemodialysis catheters (NTHCs) are the least-optimal initial vascular access for incident maintenance hemodialysis patients yet little is known about factors associated with NTHC use in this context. We sought to determine factors associated with NTHC use and examine regional and facility-level variation in NTHC use for incident maintenance hemodialysis patients. METHODS: We analyzed registry data collected between January 2001 and December 2010 from 61 dialysis facilities within 12 geographic regions in Canada. Multi-level models and intra-class correlation coefficients were used to evaluate variation in NTHC use as initial hemodialysis access across facilities and geographic regions. Facility and patient characteristics associated with the lowest and highest quartiles of NTHC use were compared. RESULTS: During the study period, 21,052 patients initiated maintenance hemodialysis using a central venous catheter (CVC). This included 10,183 patients (48.3 %) in whom the initial CVC was a NTHC, as opposed to a tunneled CVC. Crude variation in NTHC use across facilities ranged from 3.7 to 99.4 % and across geographic regions from 32.4 to 85.1 %. In an adjusted multi-level logistic regression model, the proportion of total variation in NTHC use explained by facility-level and regional variation was 40.0 % and 34.1 %, respectively. Similar results were observed for the subgroup of patients who received greater than 12 months of pre-dialysis nephrology care. Patient-level factors associated with increased NTHC use were male gender, history of angina, pulmonary edema, COPD, hypertension, increasing distance from dialysis facility, higher serum phosphate, lower serum albumin and later calendar year. CONCLUSIONS: There is wide variation in NTHC use as initial vascular access for incident maintenance hemodialysis patients across facilities and geographic regions in Canada. Identifying modifiable factors that explain this variation could facilitate a reduction of NTHC use in favor of more optimal initial vascular access.

Rationale for a home dialysis virtual ward: design and implementation.

BACKGROUND: Home-based renal replacement therapy (RRT) [peritoneal dialysis (PD) and home hemodialysis (HHD)] offers independent quality of life and clinical advantages compared to conventional in-center hemodialysis. However, follow-up may be less complete for home dialysis patients following a change in care settings such as post hospitalization. We aim to implement a Home Dialysis Virtual Ward (HDVW) strategy, which is targeted to minimize gaps of care. METHODS/DESIGN: The HDVW Pilot Study will enroll consecutive PD and HHD patients who fulfilled any one of our inclusion criteria: 1. following discharge from hospital, 2. after interventional procedure(s), 3. prescription of anti-microbial agents, or 4. following completion of home dialysis training. Clinician-led telephone interviews are performed weekly for 2 weeks until VW discharge. Case-mix (modified Charlson Comorbidity Index), symptoms (the modified Edmonton Symptom Assessment Scale) and patient satisfaction are assessed serially. The number of VW interventions relating to eight pre-specified domains will be measured. Adverse events such as re-hospitalization and health-services utilization will be ascertained through telephone follow-up after discharge from the VW at 2, 4, 12 weeks. The VW re-hospitalization rate will be compared with a contemporary cohort (matched for age, gender, renal replacement therapy and co-morbidities). Our protocol has been approved by research ethics board (UHN: 12-5397-AE). Written informed consent for participation in the study will be obtained from participants. DISCUSSION: This report serves as a blueprint for the design and implementation of a novel health service delivery model for home dialysis patients. The major goal of the HDVW initiative is to provide appropriate and effective supports to medically complex patients in a targeted window of vulnerability. TRIAL REGISTRATION: (NCT01912001).

Health information technology tools to accelerate gastrointestinal evaluation in patients with iron deficiency anaemia: a cluster randomised controlled trial.

OBJECTIVE: System-level safety measures do not exist to ensure that patients with iron deficiency anaemia (IDA) undergo proper diagnostic evaluations. We sought to determine if a set of EHR (electronic health record) tools and an expedited referral workflow increase short-term completion of bidirectional endoscopy in higher risk patients with IDA. MATERIALS AND METHODS: We conducted a pragmatic, cluster-randomised trial randomised by primary care physician (PCP) that included 16 PCPs and 316 patients with IDA. Physicians were randomised to intervention or control groups. Intervention components included a patient registry visible within the EHR, point-of-care alert and expedited diagnostic evaluation workflow for IDA. Outcomes were assessed at 120 days. The primary outcome was completion of bidirectional endoscopy. Secondary outcomes were any endoscopy completed or scheduled, gastroenterology consultation completed, and gastroenterology referral or endoscopy ordered or completed. RESULTS: There were no differences in the primary or secondary outcomes. At 120 days, the primary outcome had occurred for 7 (4%) of the intervention group and 5 (3.5%) of the control group. For the three secondary outcomes, rates were 15 (8.6%), 12 (6.9%) and 39 (22.4%) for the immediate intervention group and 10 (7.0%), 9 (6.3%) and 25 (17.6%) for the control group, respectively, p>0.2. Lack of physician time to use the registry tools was identified as a barrier. DISCUSSION AND CONCLUSION: Providing PCPs with lists of patients with IDA and a pathway for expedited evaluation did not increase rates of completing endoscopic evaluation in the short term. TRIAL REGISTRATION NUMBER: NCT05365308.

Seamless Integration of Computer-Adaptive Patient Reported Outcomes into an Electronic Health Record.

BACKGROUND: Patient-reported outcome (PRO) measures have become an essential component of quality measurement, quality improvement, and capturing the voice of the patient in clinical care. In 2004, the National Institutes of Health endorsed the importance of PROs by initiating the Patient-Reported Outcomes Measurement Information System (PROMIS), which leverages computer-adaptive tests (CATs) to reduce patient burden while maintaining measurement precision. Historically, PROMIS CATs have been used in a large number of research studies outside the electronic health record (EHR), but growing demand for clinical use of PROs requires creative information technology solutions for integration into the EHR. OBJECTIVES: This paper describes the introduction of PROMIS CATs into the Epic Systems EHR at a large academic medical center using a tight integration; we describe the process of creating a secure, automatic connection between the application programming interface (API) which scores and selects CAT items and Epic. METHODS: The overarching strategy was to make CATs appear indistinguishable from conventional measures to clinical users, patients, and the EHR software itself. We implemented CATs in Epic without compromising patient data security by creating custom middleware software within the organization's existing middleware framework. This software communicated between the Assessment Center API for item selection and scoring and Epic for item presentation and results. The middleware software seamlessly administered CATs alongside fixed-length, conventional PROs while maintaining the display characteristics and functions of other Epic measures, including automatic display of PROMIS scores in the patient's chart. Pilot implementation revealed differing workflows for clinicians using the software. RESULTS: The middleware software was adopted in 27 clinics across the hospital system. In the first 2 years of hospital-wide implementation, 793 providers collected 70,446 PROs from patients using this system. CONCLUSION: This project demonstrated the importance of regular communication across interdisciplinary teams in the design and development of clinical software. It also demonstrated that implementation relies on buy-in from clinical partners as they integrate new tools into their existing clinical workflow.

Temporary hemodialysis catheter placement by nephrology fellows: implications for nephrology training.

The insertion of temporary hemodialysis catheters is considered to be a core competency of nephrology fellowship training. Little is known about the adequacy of training for this procedure and the extent to which evidence-based techniques to reduce complications have been adopted. We conducted a web-based survey of Canadian nephrology trainees regarding the insertion of temporary hemodialysis catheters. Responses were received from 45 of 68 (66%) eligible trainees. The median number of temporary hemodialysis catheters inserted during the prior 6 months of training was 5 (IQR, 2-11), with 9 (20%) trainees reporting they had inserted none. More than one-third of respondents indicated that they were not adequately trained to competently insert temporary hemodialysis catheters at both the femoral and internal jugular sites. These findings are relevant to a discussion of the current adequacy of procedural skills training during nephrology fellowship. With respect to temporary hemodialysis catheter placement, there is an opportunity for increased use of simulation-based teaching by training programs. Certain infection control techniques and use of real-time ultrasound should be more widely adopted. Consideration should be given to the establishment of minimum procedural training requirements at the level of both individual training programs and nationwide certification authorities.

The British Columbia Nephrologists' Access Study (BCNAS) - a prospective, health services interventional study to develop waiting time benchmarks and reduce wait times for out-patient nephrology consultations.

BACKGROUND: Early referral and management of high-risk chronic kidney disease may prevent or delay the need for dialysis. Automatic eGFR reporting has increased demand for out-patient nephrology consultations and in some cases, prolonged queues. In Canada, a national task force suggested the development of waiting time targets, which has not been done for nephrology. METHODS: We sought to describe waiting time for outpatient nephrology consultations in British Columbia (BC). Data collection occurred in 2 phases: 1) Baseline Description (Jan 18-28, 2010) and 2) Post Waiting Time Benchmark-Introduction (Jan 16-27, 2012). Waiting time was defined as the interval from receipt of referral letters to assessment. Using a modified Delphi process, Nephrologists and Family Physicians (FP) developed waiting time targets for commonly referred conditions through meetings and surveys. Rules were developed to weigh-in nephrologists', FPs', and patients' perspectives in order to generate waiting time benchmarks. Targets consider comorbidities, eGFR, BP and albuminuria. Referred conditions were assigned a priority score between 1-4. BC nephrologists were encouraged to centrally triage referrals to see the first available nephrologist. Waiting time benchmarks were simultaneously introduced to guide patient scheduling. A post-intervention waiting time evaluation was then repeated. RESULTS: In 2010 and 2012, 43/52 (83%) and 46/57 (81%) of BC nephrologists participated. Waiting time decreased from 98(IQR44,157) to 64(IQR21,120) days from 2010 to 2012 (p = <.001), despite no change in referral eGFR, demographics, nor number of office hrs/wk. Waiting time improved most for high priority patients. CONCLUSIONS: An integrated, Provincial initiative to measure wait times, develop waiting benchmarks, and engage physicians in active waiting time management associated with improved access to nephrologists in BC. Improvements in waiting time was most marked for the highest priority patients, which suggests that benchmarks had an influence on triaging behavior. Further research is needed to determine whether this effect is sustainable.

Double-Positive Anti-Glomerular Basement Membrane Antibody and Myeloperoxidase Antineutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis Post COVID-19 mRNA vaccine: A Case Series of 4 Patients.

Rationale: Vaccines remain central to the management of COVID-19 pandemic, including the need for repeat doses of vaccines to boost immunity. There has been an accumulating case count of glomerulopathies temporally associated with COVID-19 vaccination. This case series presents 4 patients who developed double-positive anti-glomerular basement membrane antibody (anti-GBM) and myeloperoxidase (MPO) antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis after COVID-19 mRNA vaccination. This report contributes to our collective knowledge about the pathophysiology and clinical outcomes associated with this rare complication. Presenting Concerns of the Patient: Four patients developed nephritic syndrome within 1 to 6 weeks after receiving a COVID-19 mRNA vaccine (3 post Pfizer-BioNTech and 1 post Moderna vaccination). Three of the 4 patients also had hemoptysis. Diagnosis: Three of the 4 patients had double-positive serology, whereas the fourth patient had renal biopsy findings consistent with double-positive disease, although anti-GBM serology was negative. All patients had renal biopsy findings consistent with double-positive anti-GBM and ANCA-associated glomerulonephritis. Interventions: All 4 patients were treated with pulse steroids, cyclophosphamide, and plasmapheresis. Outcomes: Of the 4 patients, 1 demonstrated complete remission, 2 remained dialysis-dependent, and the fourth is deceased. Of the 2 patients who received repeat vaccination with COVID-19 mRNA vaccine, 1 patient had second serologic flare of anti-GBM in response to the vaccine. Novel Findings: This case series reinforces growing evidence that COVID-19 mRNA vaccine-induced glomerulonephritis is a rare but real phenomenon. Dual ANCA and anti-GBM nephritis can present after the first dose of COVID-19 mRNA vaccine or after several administrations of the vaccine. We are the first to report cases of double-positive MPO ANCA and anti-GBM nephritis after Pfizer-BioNTech vaccination. To our knowledge, we are also the first to report outcomes of repeat COVID-19 vaccination in patients with de novo flare of ANCA and anti-GBM nephritis temporally associated with COVID-19 vaccination.

Current state of intensive hemodialysis: a comparative review of benefits and barriers.

The current interest in intensive hemodialysis (HD) was born out of the impasse in an effort to improve survival and quality of life (QOL) in patients with end-stage renal disease. In this review, we have summarized the emerging data of intensive HD on (i) survival, (ii) cardiovascular outcomes, (iii) phosphate balance and (iv) QOL. Although there is a consistent and compelling signal favoring intensive HD, it is important to balance the enthusiasm with the significant amount of perceived and actual barriers for our patients to overcome to receive or perform intensive HD. For an individual patient, the answer to the question 'What is the best form of intensive hemodialysis?' should be a consideration between the benefits sought and the obstacles in attaining intensive HD. In the future, changes in dialysis technology, healthcare delivery and education strategy are needed to allow the majority of patients to receive optimal renal replacement therapy.

Dendritic spikes amplify the synaptic signal to enhance detection of motion in a simulation of the direction-selective ganglion cell.

The On-Off direction-selective ganglion cell (DSGC) in mammalian retinas responds most strongly to a stimulus moving in a specific direction. The DSGC initiates spikes in its dendritic tree, which are thought to propagate to the soma with high probability. Both dendritic and somatic spikes in the DSGC display strong directional tuning, whereas somatic PSPs (postsynaptic potentials) are only weakly directional, indicating that spike generation includes marked enhancement of the directional signal. We used a realistic computational model based on anatomical and physiological measurements to determine the source of the enhancement. Our results indicate that the DSGC dendritic tree is partitioned into separate electrotonic regions, each summing its local excitatory and inhibitory synaptic inputs to initiate spikes. Within each local region the local spike threshold nonlinearly amplifies the preferred response over the null response on the basis of PSP amplitude. Using inhibitory conductances previously measured in DSGCs, the simulation results showed that inhibition is only sufficient to prevent spike initiation and cannot affect spike propagation. Therefore, inhibition will only act locally within the dendritic arbor. We identified the role of three mechanisms that generate directional selectivity (DS) in the local dendritic regions. First, a mechanism for DS intrinsic to the dendritic structure of the DSGC enhances DS on the null side of the cell's dendritic tree and weakens it on the preferred side. Second, spatially offset postsynaptic inhibition generates robust DS in the isolated dendritic tips but weak DS near the soma. Third, presynaptic DS is apparently necessary because it is more robust across the dendritic tree. The pre- and postsynaptic mechanisms together can overcome the local intrinsic DS. These local dendritic mechanisms can perform independent nonlinear computations to make a decision, and there could be analogous mechanisms within cortical circuitry.

Outreach to Promote Management of Cardiovascular Risk in Primary Care Among Patients With Rheumatoid Arthritis Seen in Rheumatology Practice.

OBJECTIVE: Rheumatoid arthritis (RA) confers a 1.5- to 2.0-fold increased risk of cardiovascular disease (CVD). A prior multifaceted quality improvement approach to improving CVD preventive care increased CVD risk factor assessments, but there was no significant effect on the management of risk factors. We tested the impact of adding a proactive outreach strategy promoting primary care treatment of CVD risk factors among patients with RA through their rheumatology practice. METHODS: Through electronic health record searches, we identified patients with RA who were potential candidates for hypertension treatment initiation or intensification, statin therapy, or a smoking-cessation intervention. A nonclinician care manager contacted patients by phone and mail on behalf of the rheumatologists, provided information about the identified risk factor(s), recommend follow-up with primary care physicians (PCPs), sent correspondence to PCPs, and followed up with patients to see what actions had been taken. We measured preventive cardiology quality indicators and compared preintervention and intervention time periods using interrupted time series methods. RESULTS: During the 6-month intervention period, the proportion of patients prescribed at least moderate-intensity statin treatment for primary prevention rose from 18.4% to 23.8%. The rate of increase was 1.06% greater per month than during the preceding period (P < 0.001). Rates of increase in hypertension diagnosis and control improved more rapidly during this phase (P < 0.001 for each) and reversed preceding negative trends. CONCLUSION: Implementing proactive nonclinician outreach to encourage primary care-based treatment of CVD risk factors was associated with increases in statin prescribing and in hypertension diagnosis and control. Smoking was not affected.

Technique Survival and Determinants of Technique Failure in In-Center Nocturnal Hemodialysis: A Retrospective Observational Study.

BACKGROUND: Long-duration (7-8 hours) hemodialysis provides benefits compared with conventional thrice-weekly, 4-hour sessions. Nurse-administered, in-center nocturnal hemodialysis (INHD) may expand the population to whom an intensive dialysis schedule can be offered. OBJECTIVE: The primary objective of this study was to determine predictors of INHD technique failure, disruptions, and technique survival. DESIGN: This study used retrospective chart and database review methodology. SETTING: This study was conducted at a single Canadian INHD program operating in Victoria, British Columbia, within a tertiary care hospital. Our program serves a catchment population of approximately 450 000 people. PATIENTS/SAMPLE/PARTICIPANTS: Forty-three consecutive incident INHD patients took part in the INHD program of whom 42 provided informed consent to participate in this study. METHODS: We conducted a retrospective observational study including incident INHD patients from 2015 to 2017. The primary outcome was technique failure ≤6 months (TF ≤6). Secondary outcomes included technique survival and reasons for/predictors of INHD discontinuation or temporary disruption. Predictors of each outcome included demographics, comorbidities, and Clinical Frailty Scale (CFS) scoring. RESULTS: Among 42 patients, mean (SD) age, dialysis vintage, CFS score, and follow-up were 63 (16) years, 46 (55) months, 4 (1), and 11 (9) months, respectively. 52% were aged ≥65 years. TF ≤6 occurred in 12 (29%) patients. One-year technique survival censored for transplants and home dialysis transitions was 60%. Discontinuation related to insomnia (32%), medical status change (27%), and vascular access (23%). In unadjusted Cox survival analysis, 1-point increases in CFS score associated with a higher risk of technique failure (hazard ratio: 2.04, 95% confidence interval [CI]: 1.26-3.31). In an adjusted analysis, higher frailty severity also associated with temporary INHD disruptions (incidence rate ratio: 2.64, 95% CI: 1.55-4.50, comparing CFS of ≥4 to 1-3). LIMITATIONS: The retrospective, observational design of this study resulted in limited ability to control for confounding factors. In addition, the relatively small number of events observed owing to a small sample size diminished statistical power to inform study conclusions. Use of a single physician to determine the clinical frailty score is another limitation. Finally, the use of a single center for this study limits generalizability to other programs and clinic settings. CONCLUSIONS: INHD is a sustainable modality, even among older patients. Higher frailty associates with INHD technique failure and greater missed treatments. Inclusion of a CFS threshold of ≤4 into INHD inclusion criteria may help to identify individuals most likely to realize the long-term benefits of INHD. TRIAL REGISTRATION: Due to the retrospective and observational design of this study, trial registration was not necessary.

CONTEXTE: L'hémodialyse prolongée (7-8 heures) offre des avantages comparativement aux séances habituelles de quatre heures, administrées trois fois par semaine. L'hémodialyse nocturne en centre (HDNC), administrée par une infirmière, pourrait permettre de proposer un programme de dialyse prolongée à davantage de patients. OBJECTIF: L'étude visait principalement à déterminer les prédicteurs de l'échec, de l'interruption temporaire ou du succès de la modalité HDNC. TYPE D'ÉTUDE: Une méthodologie rétrospective a été employée pour examiner les dossiers médicaux et bases de données. CADRE: Étude menée dans le seul programme canadien d'HDNC, soit celui du centre de soins tertiaires de Victoria, en Colombie-Britannique. Ce programme dessert un bassin d'environ 450 000 personnes. SUJETS: Un total de 43 patients incidents consécutifs ont pris part au programme d'HDNC; 42 ont donné leur consentement éclairé pour participer à l'étude. MÉTHODOLOGIE: Nous avons procédé à une étude observationnelle rétrospective examinant les résultats de patients incidents sous HDNC entre 2015 et 2017. L'échec de la modalité dans les six premiers mois constituait l'issue principale. La réussite de la modalité et les prédicteurs d'une interruption temporaire ou complète de l'HDNC constituaient les issues secondaires. Les prédicteurs pour chaque résultat incluaient les données démographiques, les maladies concomitantes et le score sur l'échelle CFS (Clinical Frailty Scale) mesurant la fragilité clinique. RÉSULTATS: L'étude porte sur 42 sujets dont l'âge moyen s'établissait à 63 ans (ET: 16 ans); 52 % étaient âgés de 65 ans et plus. En moyenne, les patients étaient dialysés depuis 46 (55) mois, suivis depuis 11 (9) mois et présentaient un score CFS de 4 (1). L'échec de la modalité est survenu dans les six premiers mois pour 12 patients (29 %). La réussite de la modalité après 1 an, censurée pour les transplantations et les transitions vers la dialyse à domicile, était de 60 %. Les interruptions étaient liées à l'insomnie (32 %), au changement de statut médical (27 %) et à l'accès vasculaire (23 %). Dans l'analyse de survie de Cox non corrigée, des augmentations d'un point au score CFS étaient associées à un plus grand risque d'échec (RR: 2,04; IC à 95 %: 1,26-3,31). Dans l'analyse corrigée, l'augmentation de la fragilité a également été associée à une interruption temporaire de l'HDNC (rapport du taux d'incidence: 2,64; IC à 95 %: 1,55-4,50; comparaison d'un score CFS entre 1 et 3 à un score CFS égal ou supérieur à 4). LIMITES: La conception rétrospective et observationnelle de l'étude a limité le contrôle des facteurs confusionnels. De plus, le nombre relativement faible d'événements observés (échantillon de petite taille) a diminué la puissance statistique permettant d'étayer les conclusions. Enfin, l'étude est monocentrique, ce qui limite sa généralisabilité à d'autres programmes et contextes cliniques, et un seul médecin a déterminé les scores de fragilité clinique. CONCLUSION: L'HDNC s'avère une modalité viable, même pour les patients plus âgés. L'accroissement de la fragilité a été associé à un risque accru d'échec de la modalité et à davantage de traitements manqués. L'ajout d'un seuil de fragilité clinique (score ≤ 4) aux critères d'inclusion pour l'HDNC pourrait aider à identifier les personnes les plus susceptibles de profiter des avantages à long terme de cette modalité. ENREGISTREMENT DE L'ESSAI: Non nécessaire puisqu'il s'agit d'une étude rétrospective et observationnelle.

Measured Performance and Vaccine Administration After Decision Support and Office Workflow Changes for Influenza Vaccination.

Influenza vaccination is underused. We examined changes in vaccination following decision support and workflow changes in a cross-sectional analysis of three vaccination seasons among adult primary care patients from 21 practices. Interventions included clinical decision support changes to facilitate documentation; changes to rooming workflow for medical assistants and licensed practical nurses to promote vaccination, prepare orders, document care done elsewhere; and record patient refusals. We measured rates for a national vaccination performance measure and receipt of onsite vaccination. Approximately 120,000 patients were eligible each season. Performance on the quality measure increased each year (40.6% to 62.5% to 76.4%). Corresponding rates of onsite vaccination were 27.7%, 28.8%, and 31.5%. The adjusted odds ratio for onsite vaccination in the second season compared with the first was 0.94 (95% confidence interval [CI] 0.92, 0.96). Onsite vaccination was more likely in the third season compared with either previous season-adjusted odds ratio for third versus second 1.14 (95% CI, 1.12, 1.16) or adjusted odds ratio for third versus first 1.07 (95% CI 1.05-1.09). Sequential changes in decision support and patient rooming process workflows were associated with large improvements in measured performance and with a significant increase in clinic-administered influenza vaccination by the third season.

The epidemiology of medication errors: how many, how serious?

1. Errors will always occur in any system, but it is essential to identify causes and attempt to minimize risks. 2. Although it is difficult to quantify precisely the extent of medication errors, they are clearly frequent and often avoidable, representing a major threat to patient safety. 3. Many of the consequences of these errors can be prevented by the intervention of pharmacists. 4. Some errors are due to the conditions under which prescribers work; where possible these should be improved (for example, low staffing levels). 5. Computerized prescribing can help but can also generate its own inherent errors. 6. Improved training of prescribers at the undergraduate and postgraduate levels is vital, a fact that is now being belatedly recognized.

Medication errors: problems and recommendations from a consensus meeting.

Here we discuss 15 recommendations for reducing the risks of medication errors: 1. Provision of sufficient undergraduate learning opportunities to make medical students safe prescribers. 2. Provision of opportunities for students to practise skills that help to reduce errors. 3. Education of students about common types of medication errors and how to avoid them. 4. Education of prescribers in taking accurate drug histories. 5. Assessment in medical schools of prescribing knowledge and skills and demonstration that newly qualified doctors are safe prescribers. 6. European harmonization of prescribing and safety recommendations and regulatory measures, with regular feedback about rational drug use. 7. Comprehensive assessment of elderly patients for declining function. 8. Exploration of low-dose regimens for elderly patients and preparation of special formulations as required. 9. Training for all health-care professionals in drug use, adverse effects, and medication errors in elderly people. 10. More involvement of pharmacists in clinical practice. 11. Introduction of integrated prescription forms and national implementation in individual countries. 12. Development of better monitoring systems for detecting medication errors, based on classification and analysis of spontaneous reports of previous reactions, and for investigating the possible role of medication errors when patients die. 13. Use of IT systems, when available, to provide methods of avoiding medication errors; standardization, proper evaluation, and certification of clinical information systems. 14. Nonjudgmental communication with patients about their concerns and elicitation of symptoms that they perceive to be adverse drug reactions. 15. Avoidance of defensive reactions if patients mention symptoms resulting from medication errors.

In vivo Calcium Imaging Reveals That Cortisol Treatment Reduces the Number of Place Cells in Thy1-GCaMP6f Transgenic Mice.

The hippocampus, a structure essential for spatial navigation and memory undergoes anatomical and functional changes during chronic stress. Here, we investigate the effects of chronic stress on the ability of place cells to encode the neural representation of a linear track. To model physiological conditions of chronic stress on hippocampal function, transgenic mice expressing the genetically encoded calcium indicator GCaMP6f in CA1 pyramidal neurons were chronically administered with 40 µg/ml of cortisol for 8 weeks. Cortisol-treated mice exhibited symptoms typically observed during chronic stress, including diminished reward seeking behavior and reduced adrenal gland and spleen weights. In vivo imaging of hippocampal cellular activity during linear track running behavior revealed a reduced number of cells that could be recruited to encode spatial position, despite an unchanged overall number of active cells, in cortisol-treated mice. The properties of the remaining place cells that could be recruited to encode spatial information, however, was unperturbed. Bayesian decoders trained to estimate the mouse's position on the track using single neuron activity data demonstrated reduced performance in a cue richness-dependent fashion in cortisol-treated animals. The performance of decoders utilizing data from the entire neuronal ensemble was unaffected by cortisol treatment. Finally, to test the hypothesis that an antidepressant drug could prevent the effects of cortisol, we orally administered a group of mice with 10 mg/kg citalopram during cortisol administration. Citalopram prevented the cortisol-induced decrease in single-neuron decoder performance but failed to significantly prevent anhedonia and the cortisol-induced reduction in the proportion place cells. The dysfunction observed at the single-neuron level indicates that chronic stress may impair the ability of the hippocampus to encode individual neural representations of the mouse's spatial position, a function pivotal to forming an accurate navigational map of the mouse's external environment; however, the hippocampal ensemble as a whole is resilient to any cortisol-induced insults to single neuronal place cell function on the linear track.

Self-face recognition and theory of mind in patients with schizophrenia and first-degree relatives.

OBJECTIVE: The hypothesized relationship between theory of mind (ToM) and self-face recognition as well as its potential genetic associations has not been previously explored in patients with schizophrenia and in first-degree relatives with schizotypal personality traits. METHOD: Ten patients diagnosed with schizophrenia, 10 of their first-degree relatives and 10 healthy controls were included. To assess self-face recognition (SFR), participants were presented images of faces of themselves and others and asked to make rapid 'unfamiliar', 'familiar' and 'self' judgments. As a measure of ToM, subjects were administered the Revised Mind in the Eyes Test (MET [Baron-Cohen, S., Wheelwright, S., Hill, J., Raste, Y., and Plumb, I., 2001. The "Reading the Mind in the Eyes" Test revised version: a study with normal adults, and adults with Asperger syndrome or high-functioning autism. J Child Psychol Psychiatry 42(2), 241-251.]). Schizotypal characteristics in relatives and controls were assessed using a modified version of the Schizotypal Personality Questionnaire (SPQ [Raine, A., 1991. The SPQ: a scale for the assessment of schizotypal personality based on DSM-III-R criteria. Schizophrenia Bulletin 17(4), 555-564.]). RESULTS: Patients took longer and were less accurate on the SFR task than their relatives who in turn performed worse than healthy controls. Specific ToM deficits in schizophrenia were replicated. There was a relationship between accuracy rates on the MET and SFR tasks. High levels of schizotypal traits such as social anxiety, constricted affect and no close friends were important for both tasks. CONCLUSIONS: Face recognition deficits and ToM deficits in schizophrenia are apparent. The critical influence of high levels of select schizotypal traits is also highlighted. A deficit in relatives of schizophrenia patients raises the possibility that ToM and face recognition deficits may be candidate endophenotypes for schizophrenia. Support for the hypothesized link between ToM and face recognition is provided.

Uric acid and hypertension.

Increased levels of uric acid are associated with cardiovascular disease and the metabolic syndrome. They may predict clinical outcomes and also the onset of hypertension, though it is less clear that hyperuricaemia can be regarded as an independent risk factor given its clustering with other well-recognised factors. Uric acid may increase as a result of pathophysiological processes such as impaired renal sodium handling but may also contribute to renal and vascular damage, particularly endothelial dysfunction. It is notable that the synthesis of uric acid may be associated with the generation of reactive oxygen species if the enzyme xanthine oxidorectase is converted to the oxidase, as may occur in ischaemia. It has been suggested that uric acid may play a role in the pathogenesis of early-onset hypertension but evidence for this is limited. There is also very limited data to suggest that in some circumstances lowering uric acid can lower blood pressure. In the metabolic syndrome, the presence of elevated uric acid concentrations is closely associated with raised triglyceride levels, for reasons that have not been clearly defined. It remains to be seen whether uric acid could or should be considered a specific therapeutic target in cardiovascular disease and especially in hypertension and if so what should be the optimal pharmacological approach to lowering serum urate levels.

Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update.

Statins are the treatment of choice for the management of hypercholesterolaemia because of their proven efficacy and safety profile. They also have an increasing role in managing cardiovascular risk in patients with relatively normal levels of plasma cholesterol. Although all statins share a common mechanism of action, they differ in terms of their chemical structures, pharmacokinetic profiles, and lipid-modifying efficacy. The chemical structures of statins govern their water solubility, which in turn influences their absorption, distribution, metabolism and excretion. Lovastatin, pravastatin and simvastatin are derived from fungal metabolites and have elimination half-lives of 1-3 h. Atorvastatin, cerivastatin (withdrawn from clinical use in 2001), fluvastatin, pitavastatin and rosuvastatin are fully synthetic compounds, with elimination half-lives ranging from 1 h for fluvastatin to 19 h for rosuvastatin. Atorvastatin, simvastatin, lovastatin, fluvastatin, cerivastatin and pitavastatin are relatively lipophilic compounds. Lipophilic statins are more susceptible to metabolism by the cytochrome P(450) system, except for pitavastatin, which undergoes limited metabolism via this pathway. Pravastatin and rosuvastatin are relatively hydrophilic and not significantly metabolized by cytochrome P(450) enzymes. All statins are selective for effect in the liver, largely because of efficient first-pass uptake; passive diffusion through hepatocyte cell membranes is primarily responsible for hepatic uptake of lipophilic statins, while hydrophilic agents are taken up by active carrier-mediated processes. Pravastatin and rosuvastatin show greater hepatoselectivity than lipophilic agents, as well as a reduced potential for uptake by peripheral cells. The bioavailability of the statins differs greatly, from 5% for lovastatin and simvastatin to 60% or greater for cerivastatin and pitavastatin. Clinical studies have demonstrated rosuvastatin to be the most effective for reducing low-density lipoprotein cholesterol, followed by atorvastatin, simvastatin and pravastatin. As a class, statins are generally well tolerated and serious adverse events, including muscle toxicity leading to rhabdomyolysis, are rare. Consideration of the differences between the statins helps to provide a rational basis for their use in clinical practice.