To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
To evaluate the impact of changes to urine testing orderables in computerized physician order entry (CPOE) system on urine culturing practices.
Retrospective before-and-after study.
A 1,250-bed academic tertiary-care referral center.
Hospitalized adults who had ≥1 urine culture performed during their stay.
The intervention (implemented in April 2017) consisted of notifications to providers, changes to order sets, and inclusion of the new urine culture reflex tests in commonly used order sets. We compared the urine culture rates before the intervention (January 2015 to April 2016) and after the intervention (May 2016 to August 2017), adjusting for temporal trends.
During the study period, 18,954 inpatients (median age, 62 years; 68.8% white and 52.3% female) had 24,569 urine cultures ordered. Overall, 6,662 urine cultures (27%) were positive. The urine culturing rate decreased significantly in the postintervention period for any specimen type (38.1 per 1,000 patient days preintervention vs 20.9 per 1,000 patient days postintervention; P < .001), clean catch (30.0 vs 18.7; P < .001) and catheterized urine (7.8 vs 1.9; P < .001). Using an interrupted time series model, urine culture rates decreased for all specimen types (P < .05).
Our intervention of changes to order sets and inclusion of the new urine culture reflex tests resulted in a 45% reduction in the urine cultures ordered. CPOE system format plays a vital role in reducing the burden of unnecessary urine cultures and should be implemented in combination with other efforts.
To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.
In the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.
Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.
343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.
Patients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.
In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.
Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).
343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.
These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
To describe the frequency of urine cultures performed in inpatients without additional testing for pyuria
Retrospective cohort study
A 1,250-bed academic tertiary referral center
This study included urine cultures drawn on 4 medical and 2 surgical wards from 2009 to 2013 and in the medical and surgical intensive care units (ICUs) from 2012 to 2013. Patient and laboratory data were abstracted from the hospital’s medical informatics database. We identified catheter-associated urinary tract infections (CAUTIs) in the ICUs by routine infection prevention surveillance. Cultures without urinalysis or urine microscopy were defined as “isolated.” The primary outcome was the proportion of isolated urine cultures obtained. We used multivariable logistic regression to assess predictors of isolated cultures.
During the study period, 14,743 urine cultures were obtained (63.5 cultures per 1,000 patient days) during 11,820 patient admissions. Of these, 2,973 cultures (20.2%) were isolated cultures. Of the 61 CAUTIs identified, 31 (50.8%) were identified by an isolated culture. Predictors for having an isolated culture included male gender (adjusted odds ratio [aOR], 1.22; 95%; confidence interval [CI], 1.11–1.35], urinary catheterization (aOR, 2.15; 95% CI, 1.89–2.46), ICU admission (medical ICU aOR, 1.72; 95% CI, 1.47–2.00; surgical ICU aOR, 1.82; 95% CI, 1.51–2.19), and obtaining the urine culture ≥1 calendar day after admission (1–7 days aOR, 1.91; 95% CI. 1.71–2.12; >7 days after admission aOR, 2.81; 95% CI, 2.37–3.34).
Isolated urine cultures are common in hospitalized patients, particularly in patients with urinary catheters and those in ICUs. Interventions targeting inpatient culturing practices may improve the diagnosis of urinary tract infections.
Objectives: We examined florbetapir positron emission tomography (PET) amyloid scans across stages of preclinical Alzheimer’s disease (AD) in cortical, allocortical, and subcortical regions. Stages were characterized using empirically defined methods. Methods: A total of 312 cognitively normal Alzheimer’s Disease Neuroimaging Initiative participants completed a neuropsychological assessment and florbetapir PET scan. Participants were classified into stages of preclinical AD using (1) a novel approach based on the number of abnormal biomarkers/cognitive markers each individual possessed, and (2) National Institute on Aging and the Alzheimer’s Association (NIA-AA) criteria. Preclinical AD groups were compared to one another and to a mild cognitive impairment (MCI) sample on florbetapir standardized uptake value ratios (SUVRs) in cortical and allocortical/subcortical regions of interest (ROIs). Results: Amyloid deposition increased across stages of preclinical AD in all cortical ROIs, with SUVRs in the later stages reaching levels seen in MCI. Several subcortical areas showed a pattern of results similar to the cortical regions; however, SUVRs in the hippocampus, pallidum, and thalamus largely did not differ across stages of preclinical AD. Conclusions: Substantial amyloid accumulation in cortical areas has already occurred before one meets criteria for a clinical diagnosis. Potential explanations for the unexpected pattern of results in some allocortical/subcortical ROIs include lack of correspondence between (1) cerebrospinal fluid and florbetapir PET measures of amyloid, or between (2) subcortical florbetapir PET SUVRs and underlying neuropathology. Findings support the utility of our novel method for staging preclinical AD. By combining imaging biomarkers with detailed cognitive assessment to better characterize preclinical AD, we can advance our understanding of who is at risk for future progression. (JINS, 2016, 22, 978–990)
Materials diagnostic techniques are the principal tools used in the development of low-cost, high-performance electrodes for next-generation lithium-based energy storage technologies. This review highlights the importance of materials diagnostic techniques in unraveling the structure and the structural degradation mechanisms in high-voltage, high-capacity oxides that have the potential to be implemented in high-energy-density lithium-ion batteries for transportation that can use renewable energy and is less-polluting than today.
The rise in CO2 concentration in the earth’s atmosphere due to the use of petroleum products in vehicles and the dramatic increase in the cost of gasoline demand the replacement of current internal combustion engines in our vehicles with environmentally friendly, carbon free systems. Therefore, vehicles powered fully/partially by electricity are being introduced into today’s transportation fleet. As power requirements in all-electric vehicles become more demanding, lithium-ion battery (LiB) technology is now the potential candidate to provide higher energy density. Discovery of layered high-voltage lithium-manganese–rich (HV-LMR) oxides has provided a new direction toward developing high-energy-density LiBs because of their ability to deliver high capacity (∼250 mA h/g) and to be operated at high operating voltage (∼4.7 V). Unfortunately, practical use of HV-LMR electrodes is not viable because of structural changes in the host oxide during operation that can lead to fundamental and practical issues. This article provides the current understanding on the structure and structural degradation pathways in HV-LMR oxides, and manifests the importance of different materials diagnostic tools to unraveling the key mechanism(s). The fundamental insights reported, might become the tools to manipulate the chemical and/or structural aspects of HV-LMR oxides for low cost, high-energy-density LiB applications.
Background: Metacognition has been described as the knowledge of our own cognitive processes. Metacognitive deficits are common in schizophrenia, but little is known about metacognition before the onset of full-blown psychosis. Aims: This study aimed to longitudinally characterize metacognition in a sample of individuals at clinical high risk (CHR) for psychosis, and to determine if metacognition was related to later conversion to psychosis. Method: Participants (153 CHR individuals; 68 help seeking controls, HSC) were part of the large multi-site PREDICT study, which sought to determine predictors of conversion to psychosis. They were tested at baseline and 6 months using the Meta-Cognitions Questionnaire (MCQ) that has five sub-scales assessing different domains of metacognition. Results: Results of the mixed-effect models demonstrated significantly poorer scores at baseline for the CHR group compared to the HSC group in Negative beliefs about uncontrollability, Negative beliefs and the overall MCQ score. At the 6-month assessment, no difference was observed in metacognition between the two groups, but both groups showed improvement in metacognition over time. Those who later converted to psychosis had poorer performance on metacognitive beliefs at baseline. Conclusions: A poorer performance in metacognition can be seen as a marker of developing a full blown psychotic illness and confirms the potential value of assessing metacognitive beliefs in individuals vulnerable for psychosis.
Libon et al. (2010) provided evidence for three statistically determined clusters of patients with mild cognitive impairment (MCI): amnesic (aMCI), dysexecutive (dMCI), and mixed (mxMCI). The current study further examined dysexecutive impairment in MCI using the framework of Fuster's (1997) derailed temporal gradients, that is, declining performance on executive tests over time or test epoch. Temporal gradients were operationally defined by calculating the slope of aggregate letter fluency output across 15-s epochs and accuracy indices for initial, middle, and latter triads from the Wechsler Memory Scale-Mental Control subtest (Boston Revision). For letter fluency, slope was steeper for dMCI compared to aMCI and NC groups. Between-group Mental Control analyses for triad 1 revealed worse dMCI performance than NC participants. On triad 2, dMCI scored lower than aMCI and NCs; on triad 3, mxMCI performed worse versus NCs. Within-group Mental Control analyses yielded equal performance across all triads for aMCI and NC participants. mxMCI scored lower on triad 1 compared to triads 2 and 3. dMCI participants also performed worse on triad 1 compared to triads 2 and 3, but scored higher on triad 3 versus triad 2. These data suggest impaired temporal gradients may provide a useful heuristic for understanding dysexecutive impairment in MCI. (JINS, 2012, 18, 20–28)