Measures for the Core Outcome Set for Research Evaluating Interventions to Prevent and/or Treat Delirium in Critically Ill Adults: An International Consensus Study (Del-COrS).

UNLABELLED: To gain consensus on measurement methods for outcomes (delirium occurrence, severity, time to resolution, mortality, health-related quality of life [HrQoL], emotional distress including anxiety, depression, acute stress, and post-traumatic stress disorder, and cognition) of our Core Outcome Set (COS) for trials of interventions to prevent and/or treat delirium in critically ill adults. DESIGN: International consensus process. SETTING: Three virtual meetings (April 2021). PATIENTS/SUBJECTS: Critical illness survivors/family, clinicians, and researchers from six Countries. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measures (selected based on instrument validity, existing recommendations, and feasibility) and measurement time horizons were discussed. Participants voted on instruments and measurement timing (a priori consensus threshold ≥ 70%). Eighteen stakeholders (28% ICU survivors/family members) participated. We achieved consensus on the Confusion Assessment Method-ICU or Intensive Care Delirium Screening Checklist to measure delirium occurrence and delirium resolution (100%), Hospital Anxiety and Depression Scale for emotional distress (71%), and Montreal Cognitive Assessment-Blind for cognition (83%). We did not achieve consensus on EQ-5D five-level for HrQoL (69%) or its measurement at 6 months. We also did not achieve consensus on the Impact of Event Scale (IES)-Revised or IES-6 for post-traumatic stress (65%) or on measurement instruments for delirium severity incorporating delirium-related emotional distress. We were unable to gain consensus on when to commence and when to discontinue assessing for delirium occurrence and time to resolution, when to determine mortality. We gained consensus that emotional distress and cognition should be measured up to 12 months from hospital discharge. CONCLUSIONS: Consensus was reached on measurement instruments for four of seven outcomes in the COS for delirium prevention or treatment trials for critically ill adults. Further work is required to validate instruments for delirium severity that include delirium-related emotional distress

Expert consensus and recommendations on safety criteria for active mobilization of mechanically ventilated critically ill adults

Introduction: The aim of this study was to develop consensus recommendations on safety parameters for mobilizing adult, mechanically ventilated, intensive care unit (ICU) patients. Methods: A systematic literature review was followed by a meeting of 23 multidisciplinary ICU experts to seek consensus regarding the safe mobilization of mechanically ventilated patients. Results: Safety considerations were summarized in four categories: respiratory, cardiovascular, neurological and other. Consensus was achieved on all criteria for safe mobilization, with the exception being levels of vasoactive agents. Intubation via an endotracheal tube was not a contraindication to early mobilization and a fraction of inspired oxygen less than 0.6 with a percutaneous oxygen saturation more than 90% and a respiratory rate less than 30 breaths/minute were considered safe criteria for in- and out-of-bed mobilization if there were no other contraindications. At an international meeting, 94 multidisciplinary ICU clinicians concurred with the proposed recommendations. Conclusion: Consensus recommendations regarding safety criteria for mobilization of adult, mechanically ventilated patients in the ICU have the potential to guide ICU rehabilitation whilst minimizing the risk of adverse events

Trust in financial services: the influence of demographics and dispositional characteristics

So far, very little attention has been paid to examining consumer perceptions of trust from an interdisciplinary perspective. The purpose of this study is to examine how consumer trusting belief and disposition to trust within the financial services sector vary on the basis of individual demographic differences in trust. The research provides new insights into how consumers with higher dispositional trust have higher institutional trust and higher trusting belief and how consumers’ trusting belief significantly differs according to their demographic background in terms of age, marital status, ethnicity and gross annual income. The findings offer useful insights for the managers in financial institutions to carefully consider the impact of the influence of these individual differences on consumer behaviour in order to serve the needs of consumers in their target market and be able to design financial products and develop trust building strategies to attract and retain them. They also call for the action of the regulators and the financial institutions to play their part in building strong institutional systems that contribute to engendering higher levels of consumer trust

A vibrational circular dichroism implementation within a Slater-type-orbital based density functional framework and its application to hexa- and hepta-helicenes

We describe the implementation of the rotational strengths for vibrational circular dichroism (VCD) in the Slater-type orbital based Amsterdam Density Functional (ADF) package. We show that our implementation, which makes use of analytical derivative techniques and London atomic orbitals, yields origin independent rotational strengths. The basis set dependence in the particular case of Slater-type basis functions is also discussed. It turns out that the triple zeta STO basis sets with one set of polarization functions (TZP) are adequate for VCD calculations. The origin- dependence of the atomic axial tensors is checked by a distributed origin gauge implementation. The distributed and common origin gauge implementations yield virtually identical atomic axial tensors with the Slater-type basis sets employed here, proving that our implementation yields origin independent rotational strengths. We verify the implementation for a set of benchmark molecules, for which the dependence of the VCD spectra on the particular choice of the exchange–correlation functional is studied. The pure functionals BP86 and OLYP show a particularly good performance. Then, we apply this approach to study the VCD spectra of hexa- and hepta- helicenes. In particular we focus on relationships between the sign of the rotational strengths of the two helicenes

A Qualitative Exploration of Patient and Clinician Views on Patient Reported Outcome Measures in Child Mental Health and Diabetes Services

Patient Reported Outcome Measures (PROMs) are increasingly being recommended for use in both mental and physical health services. The present study is a qualitative exploration of the views of young people, mothers, and clinicians on PROMs. Semi-structured interviews were conducted with a sample of n = 10 participants (6 young people, 4 clinicians) from mental health services and n = 14 participants (4 young people, 7 mothers, 3 clinicians) from a diabetes service. For different reasons, young people, mothers, and clinicians saw feedback from PROMs as having the potential to alter the scope of clinical discussions

Occurrence of delirium is severely underestimated in the ICU during daily care

Delirium is associated with prolonged intensive care unit (ICU) stay and higher mortality. Therefore, the recognition of delirium is important. We investigated whether intensivists and ICU nurses could clinically identify the presence of delirium in ICU patients during daily care. All ICU patients in a 3-month period who stayed for more than 48 h were screened daily for delirium by attending intensivists and ICU nurses. Patients were screened independently for delirium by a trained group of ICU nurses who were not involved in the daily care of the patients under study. The Confusion Assessment Method for the ICU (CAM-ICU) was used as a validated screening instrument for delirium. Values are expressed as median and interquartile range (IQR; P25-P75). During the study period, 46 patients (30 male, 16 female), median age 73 years (IQR = 64-80), with an ICU stay of 6 days (range 4-11) were evaluated. CAM-ICU scores were obtained during 425 patient days. Considering the CAM-ICU as the reference standard, delirium occurred in 50% of the patients with a duration of 3 days (range 1-9). Days with delirium were poorly recognized by doctors (sensitivity 28.0%; specificity 100%) and ICU nurses (sensitivity 34.8%; specificity 98.3%). Recognition did not differ between hypoactive or active status of the patients involved. Delirium is severely under recognized in the ICU by intensivists and ICU nurses in daily care. More attention should be paid to the implementation of a validated delirium-screening instrument during daily ICU car

Evidence For Genetic Heterogeneity Between Clinical Subtypes of Bipolar Disorder

We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P = 3.28 × 10 − 8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia (SCZ) and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I h2 = 0.35; BD II h2 = 0.25; P = 0.02) with a genetic correlation between BD I and BD II of 0.78,compared with a genetic correlation of 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for SCZ and BD in patients with BD I compared with patients with BD II, and a greater load of SCZ risk alleles in the bipolar type of schizoaffective disorder (SAB) compared with both other BD subtypes. These results point to a partial difference in genetic architecture of BD subtypes, and are suggestive of a molecular correlate for the clinical division of BD into subtypes

A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPreviously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.info:eu-repo/grantAgreement/EC/FP7/21807

miR-210: fine-tuning the hypoxic response

Hypoxia is a central component of the tumor microenvironment and represents a major source of therapeutic failure in cancer therapy. Recent work has provided a wealth of evidence that noncoding RNAs and, in particular, microRNAs, are significant members of the adaptive response to low oxygen in tumors. All published studies agree that miR-210 specifically is a robust target of hypoxia-inducible factors, and the induction of miR-210 is a consistent characteristic of the hypoxic response in normal and transformed cells. Overexpression of miR-210 is detected in most solid tumors and has been linked to adverse prognosis in patients with soft-tissue sarcoma, breast, head and neck, and pancreatic cancer. A wide variety of miR-210 targets have been identified, pointing to roles in the cell cycle, mitochondrial oxidative metabolism, angiogenesis, DNA damage response, and cell survival. Additional microRNAs seem to be modulated by low oxygen in a more tissue-specific fashion, adding another layer of complexity to the vast array of protein-coding genes regulated by hypoxia