Delirium in the intensive care unit and its importance in the post-operative context: A review

The burden of delirium in the intensive care setting is a global priority. Delirium affects up to 80% of patients in intensive care units; an episode of delirium is often distressing to patients and their families, and delirium in patients within, or outside of, the intensive care unit (ICU) setting is associated with poor outcomes. In the short term, such poor outcomes include longer stay in intensive care, longer hospital stay, increased risk of other hospital-acquired complications, and increased risk of hospital mortality. Longer term sequelae include cognitive impairment and functional dependency. While medical category of admission may be a risk factor for poor outcomes in critical care populations, outcomes for surgical ICU admissions are also poor, with dependency at hospital discharge exceeding 30% and increased risk of in-hospital mortality, particularly in vulnerable groups, with high-risk procedures, and resource-scarce settings. A practical approach to delirium prevention and management in the ICU setting is likely to require a multi-faceted approach. Given the good evidence for the prevention of delirium among older post-operative outside of the intensive care setting, simple non-pharmacological interventions should be effective among older adults post-operatively who are cared for in the intensive care setting. In response to this, the future ICU environment will have a range of organizational and distinct environmental characteristics that are directly targeted at preventing delirium

Functional Movement Screen Task Scores and Joint Range-of-motion: A Construct Validity Study

Little is known about the construct validity of the Functional Movement Screen (FMS). We aimed to assess associations between FMS task scores and measures of maximum joint range-of-motion (ROM) among university varsity student-athletes from 4 sports (volleyball, basketball, ice hockey, and soccer). Athletes performed FMS tasks and had their maximum ankle, hip and shoulder ROM measured. Multivariable linear regression was used to estimate associations between FMS task scores and ROM measurements. 101 university student-athletes were recruited (52 W/49 M; mean age 20.4±1.9 years). In general, athletes with higher FMS task scores had greater ROM compared to those with lower task scores. For example, athletes who scored 2 on the FMS squat task had 4° (95% CI, 1° to 7°) more uni-articular ankle dorsiflexion ROM compared with those who scored 1, while those who scored 3 on the FMS squat task had 10° (4° to 17°) more uni-articular ankle dorsiflexion ROM compared with those who scored 1. Large variation in ROM measurements was observed. In sum, substantial overlap in joint ROM between groups of athletes with different FMS task scores weakens the construct validity of the FMS as an indicator of specific joint ROM

The burden of peripheral intravenous catheters in older hospital inpatients : a national cross-sectional study part of the One Million Global Peripheral Intravenous Catheters Collaboration

Objectives: To investigate the burden of peripheral intravenous catheters (PIVCs) in older hospitalised patients. Methods: A cross-sectional prospective observational study (2014/2015) to describe the characteristics, indications and outcomes of PIVCs among patients aged ≥65 from 65 Australian hospitals. Results: Amongst 2179 individual PIVCs (in 2041 patients, mean age 77.6 years, 45% female, 58% in NSW), 43% were inserted by doctors and 74% used that day, meaning 25% were ‘idle’. Overall, 18% (393/2179) exhibited signs of PIVC-related complications. Most commonly exhibited PIVC-related complications were tenderness (4.1%) and local redness (1.8%). Nearly one in three (29.1%) dressings was soiled, loosened or had come off, and only 36.8% had the time and date documented on the dressing. Both infusing IV medications (aOR 1.74, 95% CI 1.28–2.38, p 84 years) was independently associated with lower likelihood of a high score (aOR 0.71, 95% CI 0.54–0.94, p = 0.02). Conclusions: Given 1 in 5 PIVCs were identified with having complications, further research should focus on optimising PIVC use in older patients

High-content siRNA screening of the kinome identifies kinases involved in Alzheimer's disease-related tau hyperphosphorylation

<p>Abstract</p> <p>Background</p> <p>Neurofibrillary tangles (NFT), a cardinal neuropathological feature of Alzheimer's disease (AD) that is highly correlated with synaptic loss and dementia severity, appear to be partly attributable to increased phosphorylation of the microtubule stabilizing protein tau at certain AD-related residues. Identifying the kinases involved in the pathologic phosphorylation of tau may provide targets at which to aim new AD-modifying treatments.</p> <p>Results</p> <p>We report results from a screen of 572 kinases in the human genome for effects on tau hyperphosphorylation using a loss of function, high-throughput RNAi approach. We confirm effects of three kinases from this screen, the eukaryotic translation initiation factor 2 α kinase 2 (EIF2AK2), the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A), and the A-kinase anchor protein 13 (AKAP13) on tau phosphorylation at the 12E8 epitope (serine 262/serine 356). We provide evidence that EIF2AK2 effects may result from effects on tau protein expression, whereas DYRK1A and AKAP13 are likely more specifically involved in tau phosphorylation pathways.</p> <p>Conclusions</p> <p>These findings identify novel kinases that phosphorylate tau protein and provide a valuable reference data set describing the kinases involved in phosphorylating tau at an AD-relevant epitope.</p

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Research priorities for non-pharmacological therapies for common musculoskeletal problems: nationally and internationally agreed recommendations

<p>Abstract</p> <p>Background</p> <p>Musculoskeletal problems such as low back pain, neck, knee and shoulder pain are leading causes of disability and activity limitation in adults and are most frequently managed within primary care. There is a clear trend towards large, high quality trials testing the effectiveness of common non-pharmacological interventions for these conditions showing, at best, small to moderate benefits. This paper summarises the main lessons learnt from recent trials of the effectiveness of non-pharmacological therapies for common musculoskeletal conditions in primary care and provides agreed research priorities for future clinical trials.</p> <p>Methods</p> <p>Consensus development using nominal group techniques through national (UK) and international workshops. During a national Clinical Trials Thinktank workshop in April 2007 in the UK, a group of 30 senior researchers experienced in clinical trials for musculoskeletal conditions and 2 patient representatives debated the possible explanations for the findings of recent high quality trials of non-pharmacological interventions. Using the qualitative method of nominal group technique, these experts developed and ranked a set of priorities for future research, guided by the evidence from recent trials of treatments for common musculoskeletal problems. The recommendations from the national workshop were presented and further ranked at an international symposium (hosted in Canada) in June 2007.</p> <p>Results</p> <p>22 recommended research priorities were developed, of which 12 reached consensus as priorities for future research from the UK workshop. The 12 recommendations were reduced to 7 agreed priorities at the international symposium. These were: to increase the focus on implementation (research into practice); to develop national musculoskeletal research networks in which large trials can be sited and smaller trials supported; to use more innovative trial designs such as those based on stepped care and subgrouping for targeted treatment models; to routinely incorporate health economic analysis into future trials; to include more patient-centred outcome measures; to develop a core set of outcomes for new trials of interventions for musculoskeletal problems; and to focus on studies that advance methodological approaches for clinical trials in this field.</p> <p>Conclusion</p> <p>A set of research priorities for future trials of non-pharmacological therapies for common musculoskeletal conditions has been developed and agreed through national (UK) and international consensus processes. These priorities provide useful direction for researchers and research funders alike and impetus for improvement in the quality and methodology of clinical trials in this field.</p

A Phosphatidylinositol 3-Kinase/Protein Kinase B-independent Activation of Mammalian Target of Rapamycin Signaling Is Sufficient to Induce Skeletal Muscle Hypertrophy

Overexpression of Rheb activates mTOR signaling via a PI3K/PKB-independent mechanism and is sufficient to induce skeletal muscle hypertrophy. The hypertrophic effects of Rheb are driven through a rapamycin-sensitive (RS) mechanism, mTOR is the RS element that confers the hypertrophy and the kinase activity of mTOR is necessary for this event

Quantifying sources of variability in infancy research using the infant-directed-speech preference

Psychological scientists have become increasingly concerned with issues related to methodology and replicability, and infancy researchers in particular face specific challenges related to replicability: For example, high-powered studies are difficult to conduct, testing conditions vary across labs, and different labs have access to different infant populations. Addressing these concerns, we report on a large-scale, multisite study aimed at (a) assessing the overall replicability of a single theoretically important phenomenon and (b) examining methodological, cultural, and developmental moderators. We focus on infants’ preference for infant-directed speech (IDS) over adult-directed speech (ADS). Stimuli of mothers speaking to their infants and to an adult in North American English were created using seminaturalistic laboratory-based audio recordings. Infants’ relative preference for IDS and ADS was assessed across 67 laboratories in North America, Europe, Australia, and Asia using the three common methods for measuring infants’ discrimination (head-turn preference, central fixation, and eye tracking). The overall meta-analytic effect size (Cohen’s d) was 0.35, 95% confidence interval = [0.29, 0.42], which was reliably above zero but smaller than the meta-analytic mean computed from previous literature (0.67). The IDS preference was significantly stronger in older children, in those children for whom the stimuli matched their native language and dialect, and in data from labs using the head-turn preference procedure. Together, these findings replicate the IDS preference but suggest that its magnitude is modulated by development, native-language experience, and testing procedure. (This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 798658.

The clinical course of low back pain: a meta-analysis comparing outcomes in randomised clinical trials (RCTs) and observational studies.

BACKGROUND: Evidence suggests that the course of low back pain (LBP) symptoms in randomised clinical trials (RCTs) follows a pattern of large improvement regardless of the type of treatment. A similar pattern was independently observed in observational studies. However, there is an assumption that the clinical course of symptoms is particularly influenced in RCTs by mere participation in the trials. To test this assumption, the aim of our study was to compare the course of LBP in RCTs and observational studies. METHODS: Source of studies CENTRAL database for RCTs and MEDLINE, CINAHL, EMBASE and hand search of systematic reviews for cohort studies. Studies include individuals aged 18 or over, and concern non-specific LBP. Trials had to concern primary care treatments. Data were extracted on pain intensity. Meta-regression analysis was used to compare the pooled within-group change in pain in RCTs with that in cohort studies calculated as the standardised mean change (SMC). RESULTS: 70 RCTs and 19 cohort studies were included, out of 1134 and 653 identified respectively. LBP symptoms followed a similar course in RCTs and cohort studies: a rapid improvement in the first 6 weeks followed by a smaller further improvement until 52 weeks. There was no statistically significant difference in pooled SMC between RCTs and cohort studies at any time point:- 6 weeks: RCTs: SMC 1.0 (95% CI 0.9 to 1.0) and cohorts 1.2 (0.7to 1.7); 13 weeks: RCTs 1.2 (1.1 to 1.3) and cohorts 1.0 (0.8 to 1.3); 27 weeks: RCTs 1.1 (1.0 to 1.2) and cohorts 1.2 (0.8 to 1.7); 52 weeks: RCTs 0.9 (0.8 to 1.0) and cohorts 1.1 (0.8 to 1.6). CONCLUSIONS: The clinical course of LBP symptoms followed a pattern that was similar in RCTs and cohort observational studies. In addition to a shared 'natural history', enrolment of LBP patients in clinical studies is likely to provoke responses that reflect the nonspecific effects of seeking and receiving care, independent of the study design