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In Canada, there were over 60,000 long-term care facility patient transfers to emergency departments (EDs) in 2014, with up to a quarter of them being potentially preventable. Each preventable transfer exposes the patient to transport- and hospital-related complications, contributes to ED crowding, and adds significant costs to the health care system. There have been many proposed and studied interventions aimed at alleviating the issue, but few attempts to assess and evaluate different interventions across institutions.
A systematic search of MEDLINE, CINAHL, and EMBASE for studies describing the impact of interventions aimed at reducing preventable transfers from long-term care facilities to EDs on ED transfer rate. Two independent reviewers screened the studies for inclusion and completed a quality assessment. A tabular and narrative synthesis was then completed. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) guidelines.
A total of 26 studies were included (Cohen's k = 0.68). One was of low quality (Cohen's k = 0.58). Studies were summarized into five themes based on intervention type: Telemedicine, Outreach Teams, Interdisciplinary Care, Integrated Approaches, and Other. Effective interventions reported reductions in ED transfer rates post intervention ranging from 10 to 70%. Interdisciplinary health care teams staffed within long-term care facilities were the most effective interventions.
There are several promising interventions that have successfully reduced the number of preventable transfers from long-term care facilities to EDs in a variety of health care settings. Widespread implementation of these interventions has the potential to reduce ED crowding in Canada.
Assessing impact of treatment from the patient perspective provides additional information about treatment efficacy in major depressive disorder (MDD) trials.
Pooled data from three identically designed clinical trials showed aripiprazole adjunctive to antidepressant therapy (ADT) was effective in treating MDD.1
Patients who completed an 8-week prospective ADT phase with inadequate response were randomized double-blind to 6-weeks adjunctive treatment with aripiprazole or placebo. The Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) is a 16-item, self-report measure to evaluate daily functioning, with higher scores indicating better satisfaction. Comparisons of mean change from baseline (Week 8) to Week 14 in Q-LES-Q-SF items and general subscores were performed using ANCOVA (LOCF).
There was significant improvement in the Q-LES-Q-SF Overall-General subscore (total of items 1-14 expressed as a percentage of the maximum possible score) in the aripiprazole-treatment group (9.49% [n=507]) vs placebo (5.71% [n=492] p< 0.001). Placebo was significantly higher than aripiprazole in Physical Ability (placebo 0.13 vs aripiprazole 0.02, p=0.020). Aripiprazole was significantly higher than placebo in all other items except Physical Health and Vision. Aripiprazole also produced significant increases in both the Satisfaction with Medication (Item 15) (aripiprazole 0.36 vs placebo 0.20, p< 0.01) and Overall Satisfaction (Item 16) (aripiprazole 0.61 vs placebo 0.35, p< 0.001) scores.
Results emphasize that assessment of patient functioning and quality of life may have utility both in clinical trials and clinical practice.2
To evaluate the efficacy of aripiprazole adjunctive antidepressant therapy (ADT) with regard to functioning in patients with major depressive disorder (MDD) who did not achieve an adequate response with standard ADT.
Pooled data were analyzed from three nearly identically designed randomized, double-blind, placebo-controlled trials: CN138-139, CN138-163 and CN138-165. These included patients with MDD, without psychotic features, who had failed at least one ADT treatment in the present episode. Patients completing an 8-week prospective ADT phase with inadequate response were randomized to 6-weeks’ treatment with adjunctive aripiprazole (n=508) or placebo (n=494). Functioning was assessed using the Sheehan Disability Scale (SDS). Comparisons of mean change from baseline in total SDS score, and domains of family life, social life and work/school were performed using ANCOVA.
Adjunctive aripiprazole produced significant improvements in total SDS (-1.2 on an adjusted scale of 1-10, with 10=worst level of functioning/1=best) vs adjunctive placebo (-0.7, p< 0.001). Adjunctive aripiprazole produced significant changes in the family life domain (-1.4 for adjunctive aripiprazole vs -0.7 for adjunctive placebo, p< 0.001) and the social life domain (-1.4 for adjunctive aripiprazole vs -0.7 for adjunctive placebo, p< 0.001). No difference between groups was observed on the work/school domain (-0.8 for adjunctive aripiprazole and -0.6 for adjunctive placebo, p=0.34).
Adjunctive aripiprazole showed significant improvements in overall SDS scores, and family and social life domains. Less change was observed in the work/school domain. The results emphasize that assessment of patient functioning may have utility both in clinical trials and clinical practice.
Single nucleotide polymorphisms (SNPs) contribute small increases in risk for late-onset Alzheimer's disease (LOAD). LOAD SNPs cluster around genes with similar biological functions (pathways). Polygenic risk scores (PRS) aggregate the effect of SNPs genome-wide. However, this approach has not been widely used for SNPs within specific pathways.
We investigated whether pathway-specific PRS were significant predictors of LOAD case/control status.
We mapped SNPs to genes within 8 pathways implicated in LOAD. For our polygenic analysis, the discovery sample comprised 13,831 LOAD cases and 29,877 controls. LOAD risk alleles for SNPs in our 8 pathways were identified at a P-value threshold of 0.5. Pathway-specific PRS were calculated in a target sample of 3332 cases and 9832 controls. The genetic data were pruned with R2 > 0.2 while retaining the SNPs most significantly associated with AD. We tested whether pathway-specific PRS were associated with LOAD using logistic regression, adjusting for age, sex, country, and principal components. We report the proportion of variance in liability explained by each pathway.
The most strongly associated pathways were the immune response (NSNPs = 9304, = 5.63 × 10−19, R2 = 0.04) and hemostasis (NSNPs = 7832, P = 5.47 × 10−7, R2 = 0.015). Regulation of endocytosis, hematopoietic cell lineage, cholesterol transport, clathrin and protein folding were also significantly associated but accounted for less than 1% of the variance. With APOE excluded, all pathways remained significant except proteasome-ubiquitin activity and protein folding.
Genetic risk for LOAD can be split into contributions from different biological pathways. These offer a means to explore disease mechanisms and to stratify patients.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Infants undergoing stage 1 palliation for hypoplastic left heart syndrome may have post-operative feeding difficulties. Although the cause of feeding difficulties in these patients is multi-factorial, residual arch obstruction may affect gut perfusion, contributing to feeding intolerance. We hypothesised that undergoing arch reintervention following stage 1 palliation would be associated with post-operative feeding difficulties.
This was a retrospective cohort study. We analysed data from the National Pediatric Cardiology Quality Improvement Collaborative, which maintains a multicentre registry for infants with hypoplastic left heart syndrome discharged home following stage 1 palliation. Patients who underwent arch reintervention (percutaneous or surgical) prior to discharge following stage 1 palliation were compared with those who underwent non-aortic arch interventions after stage 1 palliation and those who underwent no intervention. Median post-operative days to full enteral feeds and weight for age z-scores were compared. Predictors of post-operative days to full feeds were identified.
Among patients who underwent arch reintervention, post-operative days to full enteral feeds were greater than for those who underwent non-aortic arch interventions (25 versus 16, p = 0.003) or no intervention (median days 25 versus 12, p < 0.001). Arch intervention, multiple interventions, gestational age, and the presence of a gastrointestinal anomaly were predictors of days to full feeds.
Repeat arch intervention is associated with a longer time to achieve full enteral feeding in patients with hypoplastic left heart syndrome after stage 1 palliation. Further investigation of this association is needed to understand the role of arch obstruction in feeding problems in these patients.
Modern humans evolved in Africa approximately 200,000 years ago (Campbell and Tishkoff 2010). As groups migrated out of Africa they underwent bottlenecks leading to sharp reductions in population size and genetic diversity (Amos and Hoffman 2010; Harpending and Rogers 2000; Ramachandran et al. 2005). To this day, African populations retain the most genetic diversity globally (Auton et al. 2015). In order to survive both within and out of Africa, early human populations had to adapt to their novel environments, including new food resources, colder climates, higher altitudes, and, especially, infectious diseases (Balaresque et al. 2007; Fumagalli et al. 2011). These adaptive requirements, facilitated by natural selection, led to an increased frequency of alleles that were beneficial in that environment. Due to the fact that these adaptive requirements were driven by local environmental pressures, some of these evolutionarily advantageous alleles display geographic and ancestral specificity, as observed in the genomes of present-day humans (Fumagalli et al. 2011).
Microwave plasma chemical vapor deposition (MPCVD) was used to diffuse boron into tantalum using plasma initiated from a feedgas mixture containing hydrogen and diborane. The role of substrate temperature and substrate bias in influencing surface chemical structure and hardness was investigated. X-ray diffraction shows that increased temperature results in increased TaB2 formation (relative to TaB) along with increased strain in the tantalum body-centered cubic lattice. Once the strained tantalum becomes locally supersaturated with boron, TaB and TaB2 precipitate. Additional boron remains in a solid solution within the tantalum. The combination of precipitation and solid solution hardening along with boron-induced lattice strain may help explain the 40 GPa average hardness measured by nanoindentation. Application of negative substrate bias did not further increase the hardness, possibly due to etching from increased ion bombardment. These results show that MPCVD is a viable method for synthesis of superhard borides based on plasma-assisted diffusion.
Glucose intolerance during pregnancy – a major driver of gestational diabetes mellitus (GDM) – has significant short- and long-term health consequences for both the mother and child. As GDM prevalence continues to escalate, there is growing need for preventative strategies. There is limited but suggestive evidence that myo-inositol (MI) and probiotics (PB) could improve glucose tolerance during pregnancy. The present study tested the hypothesis that MI and/or PB supplementation would reduce the risk of glucose intolerance during pregnancy. Female C57BL/6 mice were randomised to receive either no treatment, MI, PB (Lactobacillus rhamnosus and Bifidobacterium lactis) or both (MIPB) for 5 weeks. They were then provided with a high-fat diet for 1 week before mating commenced and throughout mating/gestation, while remaining on their respective treatments. An oral glucose tolerance test occurred at gestational day (GD) 16·5 and tissue collection at GD 18·5. Neither MI nor PB, separately or combined, improved glucose tolerance. However, MI and PB both independently increased adipose tissue expression of Ir, Irs1, Akt2 and Pck1, and PB also increased Pparγ. MI was associated with reduced gestational weight gain, whilst PB was associated with increased maternal fasting glucose, total cholesterol and pancreas weight. These results suggest that MI and PB may improve insulin intracellular signalling in adipose tissue but this did not translate to meaningful differences in glucose tolerance. The absence of fasting hyperglycaemia or insulin resistance suggests this is a very mild model of GDM, which may have affected our ability to assess the impact of these nutrients.
Papillon treatment is a form of contact X-ray brachytherapy (CXB) which is used as an alternative to surgery for rectal cancer. This study aimed to audit patients who were referred for and treated with CXB over a 6-year period against guidelines derived from a critical review of the evidence base.
Materials and methods:
Patient demographics, tumour characteristics and outcome data were gathered for 31 patients referred for CXB. A critical review of the evidence identified consensus referral criteria and outcome data against which to audit patients.
Referral criteria were derived from six published studies. These applied to patients unfit for surgery or stoma-averse. All referred patients had a visible tumour or scar with a tumour size under 3 cm and sited less than 12 cm from the anal verge. Nodal status varied from N0 to N2, but there was no metastatic disease present. The audited cohort demonstrated demographic equivalence, while the initial clinical complete response and recurrence rates were also comparable.
This audit confirmed the validity of referral and treatment protocols and should guide future referrals until evidence from ongoing studies becomes available. These findings should contribute to the development of robust national guidelines.
The psychedelic research renaissance is gaining traction. Preliminary clinical studies of the hallucinogenic fungi, psilocybin, with psychological support, have indicated improvements in mood, anxiety and quality of life. A seminal, open-label study demonstrated marked reductions in depression symptoms in participants with treatment-resistant depression (TRD). The associated neurobiological processes involve alterations in brain connectivity, together with altered amygdala and default mode network activity. At the cellular level, psychedelics promote synaptogenesis and neural plasticity. Prompted by the promising preliminary studies, a randomized, double-blind trial has recently been launched across Europe and North America to investigate the efficacy of psilocybin in TRD. One of these centres is based in Ireland – CHO Area 7 and Tallaght University Hospital. The outcome of this trial will determine whether psilocybin with psychological support will successfully translate into the psychiatric clinic for the benefit of patients.
Medical residents are an important group for antimicrobial stewardship programs (ASPs) to target with interventions aimed at improving antibiotic prescribing. In this study, we compared antimicrobial prescribing practices of 2 academic medical teams receiving different ASP training approaches along with a hospitalist control group.
Retrospective cohort study comparing guideline-concordant antibiotic prescribing for 3 common infections among a family medicine (FM) resident service, an internal medicine (IM) resident service, and hospitalists.
Community teaching hospital.
Adult patients admitted between July 1, 2016, and June 30, 2017, with a discharge diagnosis of pneumonia, cellulitis, and urinary tract infections were reviewed.
All 3 medical teams received identical baseline ASP education and daily antibiotic prescribing audit with feedback via clinical pharmacists. The FM resident service received an additional layer of targeted ASP intervention that included biweekly stewardship-focused rounds with an ASP physician and clinical pharmacist leadership. Guideline-concordant prescribing was assessed based on the institution’s ASP guidelines.
Of 1,572 patients, 295 (18.8%) were eligible for inclusion (FM, 96; IM, 69; hospitalist, 130). The percentage of patients receiving guideline-concordant antibiotic selection empirically was similar between groups for all diagnoses (FM, 87.5%; IM, 87%; hospitalist, 83.8%; P = .702). No differences were observed in appropriate definitive antibiotic selection among groups (FM, 92.4%; IM, 89.1%; hospitalist, 89.9%; P = .746). The FM resident service was more likely to prescribe a guideline-concordant duration of therapy across all diagnoses (FM, 74%; IM, 56.5%; hospitalist, 44.6%; P < .001).
Adding dedicated stewardship-focused rounds into the graduate medical curriculum demonstrated increased guideline adherence specifically to duration of therapy recommendations.
Computational acceleration of performance metric-based materials discovery via high-throughput screening and machine learning methods is becoming widespread. Nevertheless, development and optimization of the opto-electronic properties that depend on dilute concentrations of point defects in new materials have not significantly benefited from these advances. Here, the authors present an informatics and simulation suite to computationally accelerate these processes. This will enable faster and more fundamental materials research, and reduce the cost and time associated with the materials development cycle. Analogous to the new avenues enabled by current first-principles-based property databases, this type of framework will open entire new research frontiers as it proliferates.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Through autonomic and affective mechanisms, adverse childhood experiences (ACEs) may disrupt the capacity to regulate negative emotions, increasing craving and exacerbating risk for opioid use disorder (OUD) among individuals with chronic pain who are receiving long-term opioid analgesic pharmacotherapy. This study examined associations between ACEs, heart rate variability (HRV) during emotion regulation, and negative emotional cue-elicited craving among a sample of female opioid-treated chronic pain patients at risk for OUD. A sample of women (N = 36, mean age = 51.2 ± 9.5) with chronic pain receiving long-term opioid analgesic pharmacotherapy (mean morphine equivalent daily dose = 87.1 ± 106.9 mg) were recruited from primary care and pain clinics to complete a randomized task in which they viewed and reappraised negative affective stimuli while HRV and craving were assessed. Both ACEs and duration of opioid use significantly predicted blunted HRV during negative emotion regulation and increased negative emotional cue-elicited craving. Analysis of study findings from a multiple-levels-of-analysis approach suggest that exposure to childhood abuse occasions later emotion dysregulation and appetitive responding toward opioids in negative affective contexts among adult women with chronic pain, and thus this vulnerable clinical population should be assessed for OUD risk when initiating a course of extended, high-dose opioids for pain management.
Most current models of nonnative speech perception (e.g., extended perceptual assimilation model, PAM-L2, Best & Tyler, 2007; speech learning model, Flege, 1995; native language magnet model, Kuhl, 1993) base their predictions on the native/nonnative status of individual phonetic/phonological segments. This paper demonstrates that the phonotactic properties of Japanese influence the perception of natively contrasting consonants and suggests that phonotactic influence must be formally incorporated in these models. We first propose that by extending the perceptual categories outlined in PAM-L2 to incorporate sequences of sounds, we can account for the effects of differences in native and nonnative phonotactics on nonnative and cross-language segmental perception. In addition, we test predictions based on such an extension in two perceptual experiments. In Experiment 1, Japanese listeners categorized and rated vowel–consonant–vowel strings in combinations that either obeyed or violated Japanese phonotactics. The participants categorized phonotactically illegal strings to the perceptually nearest (legal) categories. In Experiment 2, participants discriminated the same strings in AXB discrimination tests. Our results show that Japanese listeners are more accurate and have faster response times when discriminating between legal strings than between legal and illegal strings. These findings expose serious shortcomings in currently accepted nonnative perception models, which offer no framework for the influence of native language phonotactics.