Burning for Treatment: Impact of Staff Education on Asymptomatic Bacteriuria Management in the Elderly.

BACKGROUND: Studies indicate that elderly patients are often inappropriately treated with antimicrobials for asymptomatic bacteriuria (ASB). Interprofessional education may help improve the assessment and management of ASB. METHODS: Retrospective chart audits were conducted on two cohorts of positive urine cultures (n = 201) obtained from a geriatric acute care unit to determine the incidence of treated ASB. The first cohort (n = 101) was analyzed from January to July 2017. Education was provided to unit staff (e.g., nurses, physicians, pharmacists) in Fall 2017. The second cohort (n = 100) was analyzed from January to July 2018. Descriptive statistics were used to summarize and compare the results from the cohorts. RESULTS: 152 patients (n = 201 positive urine cultures) were reviewed: 74% (159) of positive urine cultures were ASB and 21% (42) were urinary tract infections. The incidence of treated ASB was 15% (30) and untreated ASB was 65% (129). The incidence of UTI, treated ASB, and untreated ASB were not significantly different between the two cohorts examined. CONCLUSION: The implementation of education did not result in lasting changes in ASB management. Our study suggests that future systemic solutions are necessary to reduce the incidence of treated ASB in the geriatric population.

Outcome reporting bias in Cochrane systematic reviews: a cross-sectional analysis.

BACKGROUND: Discrepancies in outcome reporting (DOR) between protocol and published studies include inclusions of new outcomes, omission of prespecified outcomes, upgrade and downgrade of secondary and primary outcomes, and changes in definitions of prespecified outcomes. DOR can result in outcome reporting bias (ORB) when changes in outcomes occur after knowledge of results. This has potential to overestimate treatment effects and underestimate harms. This can also occur at the level of systematic reviews when changes in outcomes occur after knowledge of results of included studies. The prevalence of DOR and ORB in systematic reviews is unknown in systematic reviews published post-2007. OBJECTIVE: To estimate the prevalence of DOR and risk of ORB in all Cochrane reviews between the years 2007 and 2014. METHODS: A stratified random sampling approach was applied to collect a representative sample of Cochrane systematic reviews from each Cochrane review group. DOR was assessed by matching outcomes in each systematic review with their respective protocol. When DOR occurred, reviews were further assessed if there was a risk of ORB (unclear, low or high risk). We classified DOR as a high risk for ORB if the discrepancy occurred after knowledge of results in the systematic review. RESULTS: 150 of 350 (43%) review and protocol pairings contained DOR. When reviews were further scrutinised, 23% (35 of 150) of reviews with DOR contained a high risk of ORB, with changes being made after knowledge of results from individual trials. CONCLUSIONS: In our study, we identified just under a half of Cochrane reviews with at least one DOR. Of these, a fifth were at high risk of ORB. The presence of DOR and ORB in Cochrane reviews is of great concern; however, a solution is relatively simple. Authors are encouraged to be transparent where outcomes change and to describe the legitimacy of changing outcomes in order to prevent suspicion of bias.

Evaluation of Collaborative Medication Reviews for High-Risk Older Adults.

BACKGROUND: Despite the widespread use of medication reviews, many older adults are still exposed to the risks of polypharmacy. OBJECTIVES: To quantify and describe the drug therapy problems identified and interventions undertaken by pharmacists before and after implementation (on July 1, 2015) of collaborative medication review for high-risk older adult patients (> 80 years of age). METHODS: A retrospective single-centre pre-post cohort study was conducted between July 1, 2014, and July 31, 2016, to characterize the impact of collaborative medication reviews-consisting of a thorough medication review by a pharmacist and care conferences with the hospitalist and family physician-on prescribing patterns in an Acute Care for Elders unit. A standardized template was used to conduct medication reviews for the post-implementation group, whereas a chart review was conducted for the pre-implementation group. The primary outcomes were the number of drug therapy problems identified by the clinical pharmacists and the associated interventions by the pharmacists, which were categorized as clinical or compliance interventions. Secondary outcomes included the number of medications at discharge, the rate of hospital readmission within 30 days, and the length of hospital stay. RESULTS: A total of 137 patients were identified for inclusion in either the pre-implementation group (n = 70) or the post-implementation group (n = 67). After implementation of collaborative medication reviews, there were statistically significant increases in the mean number of drug therapy problems identified (p < 0.001), the mean number of interventions undertaken (p = 0.004), and the median length of hospital stay (p < 0.001). There was no difference between the 2 groups in the number of medications at discharge, the proportion of patients taking more than 5 medications at discharge, or readmission within 30 days. CONCLUSION: At the study institution, implementation of a quality improvement program that included pharmacist-led medication reviews and collaborative care conferences involving community and hospital care providers helped to improve documentation by clinical pharmacists of potential medication-related problems and led to more interventions to optimize patients' medication regimens.

CONTEXTE: Malgré l'utilisation répandue des revues des médicaments, bon nombre de personnes âgées sont encore exposées à des risques causés par la polypharmacie. OBJECTIF: Quantifier et décrire les problèmes pharmacothérapeutiques repérés et les interventions effectuées par les pharmaciens avant et après la mise en place (le 1er juillet 2015) d'une revue collaborative des médicaments chez les patients âgés (de plus de 80 ans) à haut risque. MÉTHODES: Une étude de cohorte rétrospective avant-après menée dans un seul centre entre le 1er juillet 2014 et le 31 juillet 2016 dans le but d'offrir un portrait de l'influence des revues collaboratives des médicaments (qui se résument en une évaluation complète des médicaments par un pharmacien et des discussions sur les soins avec le médecin hospitalier et le médecin de famille) sur les habitudes de prescription dans une unité de soins de courte durée pour aînés. Un modèle standardisé a servi pour effectuer les revues des médicaments auprès du groupe d'après mise en place alors qu'une analyse des dossiers médicaux a été menée auprès du groupe d'avant mise en place. Les principaux critères d'évaluation étaient le nombre de problèmes pharmacothérapeutiques décelés par les pharmaciens cliniciens et les interventions connexes effectuées par les pharmaciens, qui ont été classées de type soit clinique soit conformité. Les critères d'évaluation secondaires comprenaient le nombre de médicaments au congé, les taux de réadmission dans les 30 jours suivant le congé et la durée du séjour à l'hôpital. RÉSULTATS: Au total, 137 patients répondaient aux critères d'admissibilité pour le groupe d'avant mise en place (n = 70) ou pour le groupe d'après mise en place (n = 67). Après la mise en place des revues collaboratives des médicaments, on a observé une augmentation statistiquement significative dans le nombre moyen de problèmes pharmacothérapeutiques décelés (p < 0,001), le nombre moyen d'interventions effectuées (p = 0,004) et la durée médiane du séjour à l'hôpital (p < 0,001). Aucune différence n'a été remarquée entre les deux groupes quant au nombre de médicaments au congé, à la proportion de patients prenant plus de cinq médicaments au congé et au taux de réadmission dans les 30 jours suivant le congé. CONCLUSION: À l'établissement où s'est déroulée l'étude, on a mis en place un programme d'amélioration de la qualité comprenant des revues des médicaments dirigées par des pharmaciens et des discussions sur les soins en collaboration avec des fournisseurs de soins communautaires et hospitaliers. Le programme a aidé à améliorer la consignation par les pharmaciens cliniciens de potentiels problèmes liés à la pharmacothérapie et a mené à un plus grand nombre d'interventions visant à optimiser la pharmacothérapie des patients.

Managing the incidence of selective reporting bias: a survey of Cochrane review groups.

BACKGROUND: Selective reporting bias (SRB), the incomplete publication of outcomes measured or of analyses performed in a study, may lead to the over- or underestimation of treatment effects or harms. Cochrane systematic reviews of interventions are required to assess the risk of SRB, achieved in part by applying the Cochrane risk of bias tool to each included randomised trial. The Cochrane Handbook outlines strategies for a comprehensive risk of bias assessment, but the extent to which these are followed by Cochrane review groups (CRGs) has not been assessed to date. The objective of this study was to determine the methods which CRGs require of their authors to address SRB within systematic reviews, and how SRB risk assessments are verified. METHODS: A cross-sectional survey was developed and distributed electronically to the 52 CRGs involved in intervention reviews. RESULTS: Responses from 42 CRGs show that the majority refer their authors to the Cochrane Handbook for specific instruction regarding assessments of SRB. The handbook strategies remain variably enforced, with 57 % (24/42) of CRGs not requiring review authors to search for included trial protocols and 31 % (13/42) not requiring that contact with individual study authors be attempted. Only half (48 %, 20/42) of the groups consistently verify review authors' assessments of the risk of SRB to ensure completeness. CONCLUSIONS: A range of practices are used by CRGs for addressing SRB, with many steps outlined in the Cochrane Handbook being encouraged but not required. The majority of CRGs do not consider their review authors to be sufficiently competent to assess for SRB, yet risk of bias assessments are not always verified by editors before publication. The implications of SRB may not be fully appreciated by all CRGs, and resolving the identified issues may require an approach targeting several steps in the systematic review process.

Measuring anti-factor xa activity to monitor low-molecular-weight heparin in obesity: a critical review.

BACKGROUND: The choice of whether to monitor anti-factor Xa (anti-Xa) activity in patients who are obese and who are receiving low-molecular-weight heparin (LMWH) therapy is controversial. To the authors' knowledge, no systematic review of monitoring of anti-Xa activity in such patients has been published to date. OBJECTIVE: To systematically ascertain the utility of monitoring anti-Xa concentrations for LMWH therapy in obese patients. DATA SOURCES: MEDLINE (1946 to September 2014), the Cochrane Database of Systematic Reviews, Embase (1974 to September 2014), PubMed (1947 to September 2014), International Pharmaceutical Abstracts (1970 to September 2014), and Scopus were searched using the terms obesity, morbid obesity, thrombosis, venous thrombosis, embolism, venous thromboembolism, pulmonary embolism, low-molecular weight heparin, enoxaparin, dalteparin, tinzaparin, anti-factor Xa, anti-factor Xa monitoring, anti-factor Xa activity, and anti-factor Xa assay. The reference lists of retrieved articles were also reviewed. STUDY SELECTION AND DATA EXTRACTION: English-language studies describing obese patients treated with LMWH or reporting anti-Xa activity were reviewed using a 9-step decision-making algorithm to determine whether monitoring of LMWH therapy by means of anti-Xa activity in obesity is warranted. Studies published in abstract form were excluded. DATA SYNTHESIS: The analysis showed that anti-Xa concentrations are not strongly associated with thrombosis or hemorrhage. In clinical studies of LMWH for thromboprophylaxis in bariatric surgery, orthopedic surgery, general surgery, and medical patients, and for treatment of venous thrombo embolism and acute coronary syndrome, anti-Xa activity can be predicted from dose of LMWH and total body weight; no difference in clinical outcome was found between obese and non-obese participants. CONCLUSIONS: Routinely determining anti-Xa concentrations in obese patients to monitor the clinical effectiveness of LMWH is not warranted on the basis of the current evidence. Circumstances where measurement of anti-Xa concentration may help in clinical decision-making in either obese or non-obese patients would be cases where elimination of LMWH is impaired or there is an unexpected clinical response, as well as to confirm compliance with therapy or to identify deviation from predicted pharmacokinetics.

CONTEXTE: Choisir d'effectuer ou non une surveillance de l'activité de l'anti-facteur Xa (anti-Xa) chez le patient obèse qui reçoit un traitement par héparine de bas poids moléculaire (HBPM) est controversé. À la connaissance des auteurs, aucune analyse systématique de la surveillance de l'activité anti-Xa chez ce type de patient n'a été publiée à ce jour. OBJECTIF: Établir systématiquement l'utilité de la surveillance des concentrations d'anti-Xa pour le traitement par HBPM chez le patient obèse. SOURCES DES DONNÉES: Les bases de données MEDLINE (de 1946 à septembre 2014), Cochrane Database of Systematic Reviews, Embase (de 1974 à septembre 2014), PubMed (de 1947 à septembre 2014), International Pharmaceutical Abstracts (de 1970 à septembre 2014) et Scopus ont été interrogées à l'aide des termes obésité, obésité morbide, thrombose, thrombose veineuse, embolie, événement thromboembolique veineux, embolie pulmonaire, héparine de bas poids moléculaire, énoxaparine, daltéparine, tinzaparine, anti-facteur Xa, surveillance de l'anti-facteur Xa, activité anti-facteur Xa et analyse de l'activité anti-facteur Xa. Un examen des bibliographies des articles extraits a aussi été réalisé. SÉLECTION DES ÉTUDES ET EXTRACTION DES DONNÉES: Les études en anglais présentant des patients obèses traités par HBPM ou signalant l'activité anti-Xa ont été examinées à l'aide d'un algorithme de prise de décision à neuf étapes dans le but de déterminer s'il est justifié de réaliser une surveillance des HBPM en mesurant l'activité anti-Xa dans les cas d'obésité. Les études publiées sous forme de résumé étaient exclues. SYNTHÈSE DES DONNÉES: Les concentrations d'anti-Xa ne sont pas fortement associées aux thromboses ou aux hémorragies. Dans les études cliniques sur la thromboprophylaxie en chirurgie bariatrique, en chirurgie orthopédique, en chirurgie générale et chez le patient médical, et sur le traitement de la thromboembolie veineuse et du syndrome coronarien aigu, l'activité anti-Xa peut être prédite à l'aide de la dose de HBPM et du poids total du patient. Aucune différence dans les résultats cliniques entre les sujets obèses et non obèses n'a été trouvée. CONCLUSIONS: À la lumière des données probantes actuelles, il n'est pas justifié d'effectuer une analyse systématique des concentrations d'anti-Xa chez le patient obèse afin de surveiller l'efficacité clinique des HBPM. Il reste tout de même des situations pour lesquelles l'analyse des concentrations d'anti-Xa chez le patient obèse ou non obèse pourrait aider à prendre une décision clinique : présence d'une élimination déficiente des HBPM, survenue d'une réaction clinique inattendue, confirmation de l'observance du traitement ou explication d'un écart de la pharmacocinétique prévue.

Drug interactions between antiplatelet or novel oral anticoagulant medications and antiretroviral medications.

OBJECTIVE: To review potential drug interactions between antiretroviral (ARV) medications and antiplatelets or novel oral anticoagulants (NOACs). DATA SOURCES: A literature search of MEDLINE, PubMed, EMBASE, International Pharmaceutical Abstracts, and Google Scholar was performed using the search terms (1) clopidogrel or ticagrelor or prasugrel, (2) dabigatran or rivaroxaban or apixaban, and (3) antiretrovirals. STUDY SELECTION AND DATA EXTRACTION: Any English language study or case report describing a drug interaction between an ARV and an antiplatelet or NOAC was included. Additional information was taken from pharmacokinetic studies of individual agents alone or information from similar drug interactions. RESULTS: Two studies were identified through the literature search: one reporting an in vivo interaction between ritonavir and prasugrel and the other an in vitro interaction between efavirenz and clopidogrel. A case report describing a drug interaction between nevirapine and rivaroxaban was also located. Information from pharmacokinetic studies and from similar drug interactions allowed for a comprehensive review of potential drug interactions. CONCLUSIONS: There are potential drug interactions between ARVs, antiplatelet agents or NOACs. Management of these interactions may include selecting ARVs with a lower potential for drug interactions or choosing antiplatelet agents or NOACs least likely to interact with ARVs. With protease inhibitors or cobicistat, clopidogrel and dabigatran do not appear to have clinically significant interactions. Nonnucleoside reverse transcriptase inhibitors have a low potential for interactions with prasugrel and dabigatran. Clinically significant drug interactions are unlikely to occur between antiplatelet agents or NOACs and nucleoside reverse transcriptase inhibitors raltegravir, dolutegravir, or maraviroc.

Visually evoked responses in extrastriate area MT after lesions of striate cortex in early life.

Lesions of striate cortex [primary visual cortex (V1)] in adult primates result in blindness. In contrast, V1 lesions in neonates typically allow much greater preservation of vision, including, in many human patients, conscious perception. It is presently unknown how this marked functional difference is related to physiological changes in cortical areas that are spared by the lesions. Here we report a study of the middle temporal area (MT) of adult marmoset monkeys that received unilateral V1 lesions within 6 weeks of birth. In contrast with observations after similar lesions in adult monkeys, we found that virtually all neurons in the region of MT that was deprived of V1 inputs showed robust responses to visual stimulation. These responses were very similar to those recorded in neurons with receptive fields outside the lesion projection zones in terms of firing rate, signal-to-noise ratio, and latency. In addition, the normal retinotopic organization of MT was maintained. Nonetheless, we found evidence of a very specific functional deficit: direction selectivity, a key physiological characteristic of MT that is known to be preserved in many cells after adult V1 lesions, was absent. These results demonstrate that lesion-induced reorganization of afferent pathways is sufficient to develop robust visual function in primate extrastriate cortex, highlighting a likely mechanism for the sparing of vision after neonatal V1 lesions. However, they also suggest that interactions with V1 in early postnatal life are critical for establishing stimulus selectivity in MT.

Does outcome reporting bias "cause" cancer? Risks associated with hidden data on Angiotensin receptor blockers.

Conflicting reports have been published regarding the influence of angiotensin receptor blockers (ARBs) on the incidence of cancer. One meta-analysis reported a 1% absolute increase in the incidence of cancer associated with ARBs over 4 years. Contrasting findings were reported in an industry-sponsored meta-analysis and in another meta-analysis, both of which showed no difference in the incidence of cancer in ARB treatment groups relative to control groups. The US Food and Drug Administration has recently asserted that evidence does not support an association between ARBs and the development of cancer. The current review compares the 3 published meta-analyses assessing the association between ARBs and cancer and shows that outcome reporting bias contributed to the conflicting results. Given the prevalence of this form of bias in the scientific literature, the processes for systematic reviews and meta-analyses are under siege, and there is an important role for health care regulators to play. If all outcome data from clinical trials were to be reported in the public domain, independent analyses could be performed and the results of industry-sponsored trials verified. Furthermore, if regulators were to mandate the publication, in the public domain, of all clinical outcomes collected in clinical trials, outcome reporting bias could be eliminated.