Trajectories of post-traumatic stress in sepsis survivors two years after ICU discharge: a secondary analysis of a randomized controlled trial.

BACKGROUND: Post-traumatic stress has been identified as a frequent long-term complication in survivors of critical illnesses after sepsis. Little is known about long-term trajectories of post-traumatic stress and potentially modifiable risk factors following the ICU stay. Study objective was to explore and compare different clinical trajectories of post-traumatic stress symptoms in sepsis survivors up to two years after discharge from ICU. METHODS: Data on post-traumatic stress symptoms by means of the Post-traumatic Symptom Scale (PTSS-10) were collected in sepsis survivors at one, six, 12 and 24 months after discharge from ICU. Data on chronic psychiatric diagnoses prior ICU were derived from the primary care provider's health records, and data on intensive care treatment from ICU documentation. Trajectories of post-traumatic symptoms were identified ex post, discriminating patterns of change and k-means clustering. Assignment to the trajectories was predicted in multinomial log-linear models. RESULTS: At 24 months, all follow-up measurements of the PTSS-10 were completed in N = 175 patients. Three clusters could be identified regarding clinical trajectories of PTSS levels: stable low symptoms (N = 104 patients [59%]), increasing symptoms (N = 45 patients [26%]), and recovering from symptoms (N = 26 patients [15%]). Patients with initially high post-traumatic symptoms were more likely to show a decrease (OR with 95% CI: 1.1 [1.05, 1.16]). Females (OR = 2.45 [1.11, 5.41]) and patients reporting early traumatic memories of the ICU (OR = 4.04 [1.63, 10]) were at higher risk for increasing PTSS levels. CONCLUSION: Post-traumatic stress is a relevant long-term burden for sepsis patients after ICU stay. Identification of three different trajectories within two years after ICU discharge highlights the importance of long-term observation, as a quarter of patients reports few symptoms at discharge yet an increase in symptoms in the two years following. Regular screening of ICU survivors on post-traumatic stress should be considered even in patients with few symptoms and in particular in females and patients reporting traumatic memories of the ICU.

Being mindful does not always benefit everyone: mindfulness-based practices may promote alienation among psychologically vulnerable people.

A growing number of interventions have sought to cultivate mindfulness, an accepting awareness of body and mind experiences. A great deal of prior research has shown mostly beneficial effects of mindfulness interventions. However, cultivating mindfulness may not always be beneficial for everyone. Two studies examined whether mindfulness may have alienating effects among people high in state orientation (i.e. low self-regulatory abilities). Participants were randomly assigned to either a 90-minute mindfulness training plus 5-minute retreatment or a waiting list control group (Study 1 N = 54, Study 2 N = 155). Alienation was operationalised as false self-ascriptions (FSA rate) of extrinsic goals that were allegedly recommended by experts. Participants high (versus low) in state orientation had significantly higher FSA rates in the mindfulness (versus control) condition. These results suggest that mindfulness training may alienate psychologically vulnerable populations (e.g. state-oriented people) from their intrinsic emotional preferences.

Every look matters: appraisals of faces follow distinct rules of information integration under arousing versus non-arousing conditions.

In this research, we investigated whether appraisals of faces follow distinct rules of information integration under arousing versus non-arousing conditions. Support for this prediction was found in four experiments in which participants observed angry (and fearful) faces that were presented with a direct versus an averted gaze (Experiments 1a, b), on a red versus a grey background (Experiment 2), and after performing a motor exercise versus no exercise (Experiment 3). Under arousing conditions, participants' appraisals of faces reflected summation (i.e. extremely negative encounters were strengthened by moderately negative encounters) whereas, under non-arousing conditions, appraisals did not reflect summation (i.e. extremely negative encounters were weakened by moderately negative encounters) and could instead be accounted for by three alternative rules of information integration based on averaging, mere exposure, or the number of strong stimuli.

Do positive illusions of control foster happiness?

Positive emotions have been shown to benefit from optimistic perceptions, even if these perceptions are illusory (Seligman & Csikszentmihalyi, 2000). The current research investigated the effects of increases and decreases in illusory control on positive and negative emotions. In two studies we experimentally induced changes in illusory perceptions of control (increase vs. decrease of illusory control) and assessed the extent to which these changes, in turn, influenced participants' emotions. Extending prior research, the results of both studies revealed that whereas illusions of personal control over environmental outcomes mitigated the experience of negative emotions, they did not foster positive emotions. Perceiving a loss of illusory control, however, significantly reduced the experience of positive emotions, but had no effect on negative emotions. Implications for emotion theory and intervention programs are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Prediction of response to targeted and immune checkpoint therapies.

Targeted therapies continue to be key components of cancer treatment. New approaches to detection of acquired resistance at the genomic level, in combination with new therapies, help to overcome the challenges that are seen frequently, rapidly and broadly across tumor pathologies, and provide opportunities for cancer management. In the last several years, a new breed of modalities called immune checkpoint inhibitors have come to the forefront of clinically effective treatments. A plethora of rapid approvals and early access initiatives have seen anti-cytotoxic T-lymphocyte-associated antigen-4, and particularly anti-programmed death receptor-1 therapies, deployed in a number of tumor indications of high unmet need. With the rise of immune checkpoint inhibition, and the broader resurgence in the immuno-oncology field, we are facing challenges in the prediction of response.

Quadriceps performance under activation of foot dorsal extension in healthy volunteers: an interventional cohort study.

BACKGROUND: The m. quadriceps femoris is the strongest muscle in the human body and plays an important role in sports, activities of daily living and independence. Two older studies showed increased electromyographic (EMG) activity of the quadriceps when the dorsal extensors of the foot were pre-activated. The aim was to physiologically replicate this finding by EMG and to verify it functionally by single leg hop. METHODS: EMG activity (root mean square, RMS) was tested on the leg press at the isometric load of the individual 12-repetition-maximum (12RM) weight (on average 79.7 kg) at 45° and 90° knee flexion. Single leg hop distance was measured between the tests. Intra-individual changes between with and without dorsal foot extension were quantified and compared by standardized response means (SRM). RESULTS: Thirty-five healthy subjects between 21 and 57 years were included. The m. vastus medialis was activated on average to an RMS of 32.4 µV without and 53.7 µV with dorsal foot extension (SRM = 1.39, p < 0.001) at 45° knee flexion and an RMS of 124.9 µV versus 152.8 µV (SRM = 1.08, p < 0.001) at 90°. The corresponding data for the rectus femoris were 9.4 µV versus 18.9 µV (SRM = 0.71, p < 0.001) at 45° and 77.8 µV versus 135.3 µV (SRM = 0.89, p < 0.001) at 90°. Mean single leg hop distance was 169.8 cm without versus 178.9 cm with dorsal foot extension (SRM = 1.09, p < 0.001). CONCLUSIONS: Pre-activation of dorsal foot extensors significantly increased EMG activity in the m. quadriceps femoris and single leg hop distance. It can therefore be used to improve functional quadriceps muscle performance and knee joint stability in training and rehabilitation.

A perspective analysis: companion diagnostics: an evolving paradigm in 21st century healthcare.

Medical history has not wandered far from its original aspirations of being personalized. Diagnostic capability has evolved from the metaphysical to the anatomical to the cellular and ultimately to the molecular level. Now that diseases can be subclassified into categories that indicate the course of disease and in some cases its likely response to treatment, there is a responsibility to act on that information. As more predictive biomarkers become clinically validated and as more targeted therapies become available, single marker companion diagnostics for specific drugs will be replaced by multiplex and multiparameter diagnostics that may be applicable across disease entities preserving sample, time, money and enabling rapid molecular taxonomy. We call this an ensemble relationship model between diagnostics and medicines.

Aligning the economic value of companion diagnostics and stratified medicines.

The twin forces of payors seeking fair pricing and the rising costs of developing new medicines has driven a closer relationship between pharmaceutical companies and diagnostics companies, because stratified medicines, guided by companion diagnostics, offer better commercial, as well as clinical, outcomes. Stratified medicines have created clinical success and provided rapid product approvals, particularly in oncology, and indeed have changed the dynamic between drug and diagnostic developers. The commercial payback for such partnerships offered by stratified medicines has been less well articulated, but this has shifted as the benefits in risk management, pricing and value creation for all stakeholders become clearer. In this larger healthcare setting, stratified medicine provides both physicians and patients with greater insight on the disease and provides rationale for providers to understand cost-effectiveness of treatment. This article considers how the economic value of stratified medicine relationships can be recognized and translated into better outcomes for all healthcare stakeholders.

Monoclonal antibodies against the human somatostatin receptor subtypes 1-5: development and immunohistochemical application in neuroendocrine tumors.

BACKGROUND: Activation of somatostatin receptors (sstr1-5) by somatostatin and its analogues exerts an inhibitory effect on hormone secretion and provides the basis for the treatment of a range of endocrine diseases such as acromegaly, Cushing's disease and neuroendocrine tumors (NET). The lack of well-characterized commercially available sstr subtype-specific antibodies prevents routine identification of the sstr expression profile in patients. METHODS: We generated and characterized new mouse monoclonal antibodies (mAbs) targeting the five human sstr subtypes using ELISA and immunohistochemistry, and tested their suitability in formalin-fixed and paraffin-embedded (FFPE) human tissues and archival samples of normal pancreatic tissue and NET. RESULTS: All mAbs were highly specific with no cross-reactivity. The sstr1-5 immunoreactivity in gastrointestinal NET (n=67) was correlated with clinicopathologic data. With the exception of sstr3, NET were highly positive for all receptor subtypes (42, 63, 6, 32 and 65% of tumors were positive for sstr1, sstr2a, sstr3, sstr4 and sstr5, respectively). sstr1, sstr2a and sstr5 were present at the plasma membrane and in the cytoplasm of tumor cells, whereas sstr3 and sstr4 were almost exclusively cytoplasmic. Immunoreactivity of sstr1, sstr2a and sstr4 tended to decrease as tumor aggressiveness increased. sstr5 showed an opposite pattern, with higher staining in well-differentiated carcinomas compared with well-differentiated tumors. sstr5 immunoreactivity was correlated with the presence of metastases and angioinvasion, suggesting a possible association with more aggressive behavior. CONCLUSION: Determination of the sstr1-5 by immunohistochemistry using subtype-specific mAbs is feasible in FFPE tissue and may provide a tool for routine clinical practice.

Somatostatin receptors in non-neuroendocrine malignancies: the potential role of somatostatin analogs in solid tumors.

Somatostatin receptors (sstrs) are G-protein-coupled receptors that mediate various physiological effects when activated by the neuropeptide somatostatin or its synthetic analogs. In addition to the well-documented antisecretory effects of sstr(2)-preferential somatostatin analogs octreotide and lanreotide, ligand binding to sstr initiates an inhibitory action on tumor growth. This effect may result from both indirect actions (suppression of growth factors and growth-promoting hormones [e.g., GH/IGF-1 axis] and inhibition of angiogenesis) and direct actions (activation of antigrowth activities [e.g., apoptosis]). As solid tumor cells express multiple sstrs, there is a rationale to evaluate the potential antitumor effects of pasireotide (SOM230), a multireceptor-targeted somatostatin analog with high binding affinity for sstr(1-3) and sstr(5). Pasireotide reduces systemic IGF-1 levels more potently than currently available somatostatin analogs and has been well tolerated in clinical trials.

Origins of the sample-size effect in explicit evaluative judgment.

This research considers situations in which individuals explicitly form attitude judgments toward a target object after considering a sample of information. Previous research shows sample-size effects under such conditions: Increasing sample size can produce more extreme judgments. Commonly, these effects are attributed to summative processes in information integration. Alternatively, this research proposes that sample size affects perceived reliability of information, which in turn affects the extremity of the subsequent judgment. Three experiments were conducted to empirically substantiate this alternative account. Experiment 1 provides evidence that participants perceive larger samples as more reliable than smaller samples. Experiment 2 demonstrates that perceived reliability mediates the sample-size effect on judgments. Experiment 3 shows that other variables, such as variability, which lowers the perceived reliability, attenuate sample-size effects. The results are explained with reference to the value account model of attitude formation, stating that implicit and explicit modes of attitude formation are guided by different principles of information integration.