Can pharmacological, psychological and non-invasive brain stimulation interventions prevent depression after stroke? A cochrane review summary with commentary

BACKGROUND: Depression is very common in patients after a stroke and it can impact recovery. OBJECTIVE: The Cochrane Review aimed to determine whether psychological therapy, pharmacological interventions, non-invasive brain stimulation, or their combination can prevent depression after stroke. METHODS: The population addressed were patients who suffered from a stroke and had no previous diagnosis of depressive disorders. Studies comparing pharmacological intervention to placebo, psychological therapy to usual care, and non-invasive brain stimulation to sham stimulation or usual care were included. RESULTS: Outcome information was available for nine pharmacological and two psychological trials, showing favorable treatment effects. CONCLUSIONS: The available evidence suggests that pharmacological interventions and psychological therapy may prevent depression and improve mood after stroke. Although, the current evidence is of very low quality resulting in serious uncertainties about the estimates of effect observed.

Judgments in causal chains: The impact of positive and negative motives and outcomes on lay attributions

<p>Research on attributions about several events in causal chains has focused on chains ending in negative outcomes and has not examined positive outcomes and actions (e.g., Hilton, McClure, & Sutton, 2010; Lagnado & Channon, 2008; McClure, Hilton, & Sutton, 2007). On the other hand, research on attributions for positive and negative events has examined judgments about one event in the chain and has not examined effects on other causes in the chain or made comparative judgments about physical causes that produce similar effects to actions (e.g., Alicke, 1992; Alicke, Rose, & Bloom, 2011). This thesis integrates these two lines of research. Six studies examined judgments about two consecutive events (intentional actions and physical events) in chains leading to positive as well as negative outcomes. The intentional action was the same action (e.g. a man started a fire) that differed in motive (positive or negative). The physical event had the same causal effect as the action (e.g., a lightning strike started a fire), or was a physical event (e.g., strong wind) that occurred later in the causal chain. The results replicate previous findings that when both actions and outcomes are negative, participants rate intentional actions more causal and blameworthy than physical events. However, when the intended outcomes fail to eventuate or positively motivated actions pre-empt positive outcomes, two distinct patterns emerged: A mismatch effect that explains the cause of the outcome; and a motive effect that explains judgments of culpability (measured by judgments of blame and punitiveness in these studies). Specifically, judgments of cause, responsibility, intentionality and foresight follow the same pattern that reflects the congruence between the valence of the agent‟s motive and the outcome. In contrast, judgments of culpability follow a different pattern where motive and outcome information have independent effects. Notably, it is the moral intent of actions that primarily determines judgments of culpability. The valence of the outcome plays a secondary role and amplifies ratings. These results show that the important psychological and legal concepts of intentionality, abnormality, foresight, proximity, and outcome information are core determinants in lay attributions (e.g., Hart & Honoré, 1985; Heider, 1958; Kelley, 1973; Weiner, 1995). But it is valence that plays the critical role in shaping lay reasoning. Several theoretical approaches applied in previous research on causal chains are examined, for example, Alicke's (2000) culpable control model, Tetlock's (2002) social functionalist model, and Spellman's (1997) crediting causality model. Yet none of the theories are able to account for the findings for chains that include positive actions or positive outcomes. The theoretical scope of this thesis was expanded in Study 6 to include research on the folk concept of intentionality, hindsight, and actor-observer biases (Fischhoff, 1975; Kashima, McKintyre, & Clifford, 1998; Malle & Knobe, 1997; Malle, Knobe, & Nelson, 2007). The results are interpreted in terms of Sloman, Fernbach and Ewings' (2012) causal model of intentionality.</p>

Judgments in causal chains: The impact of positive and negative motives and outcomes on lay attributions

<p>Research on attributions about several events in causal chains has focused on chains ending in negative outcomes and has not examined positive outcomes and actions (e.g., Hilton, McClure, & Sutton, 2010; Lagnado & Channon, 2008; McClure, Hilton, & Sutton, 2007). On the other hand, research on attributions for positive and negative events has examined judgments about one event in the chain and has not examined effects on other causes in the chain or made comparative judgments about physical causes that produce similar effects to actions (e.g., Alicke, 1992; Alicke, Rose, & Bloom, 2011). This thesis integrates these two lines of research. Six studies examined judgments about two consecutive events (intentional actions and physical events) in chains leading to positive as well as negative outcomes. The intentional action was the same action (e.g. a man started a fire) that differed in motive (positive or negative). The physical event had the same causal effect as the action (e.g., a lightning strike started a fire), or was a physical event (e.g., strong wind) that occurred later in the causal chain. The results replicate previous findings that when both actions and outcomes are negative, participants rate intentional actions more causal and blameworthy than physical events. However, when the intended outcomes fail to eventuate or positively motivated actions pre-empt positive outcomes, two distinct patterns emerged: A mismatch effect that explains the cause of the outcome; and a motive effect that explains judgments of culpability (measured by judgments of blame and punitiveness in these studies). Specifically, judgments of cause, responsibility, intentionality and foresight follow the same pattern that reflects the congruence between the valence of the agent‟s motive and the outcome. In contrast, judgments of culpability follow a different pattern where motive and outcome information have independent effects. Notably, it is the moral intent of actions that primarily determines judgments of culpability. The valence of the outcome plays a secondary role and amplifies ratings. These results show that the important psychological and legal concepts of intentionality, abnormality, foresight, proximity, and outcome information are core determinants in lay attributions (e.g., Hart & Honoré, 1985; Heider, 1958; Kelley, 1973; Weiner, 1995). But it is valence that plays the critical role in shaping lay reasoning. Several theoretical approaches applied in previous research on causal chains are examined, for example, Alicke's (2000) culpable control model, Tetlock's (2002) social functionalist model, and Spellman's (1997) crediting causality model. Yet none of the theories are able to account for the findings for chains that include positive actions or positive outcomes. The theoretical scope of this thesis was expanded in Study 6 to include research on the folk concept of intentionality, hindsight, and actor-observer biases (Fischhoff, 1975; Kashima, McKintyre, & Clifford, 1998; Malle & Knobe, 1997; Malle, Knobe, & Nelson, 2007). The results are interpreted in terms of Sloman, Fernbach and Ewings' (2012) causal model of intentionality.</p>

COVID-19 Infection in Fingolimod- or Siponimod-Treated Patients

Background and ObjectivesA descriptive analysis of COVID-19 infection in patients with multiple sclerosis (MS) receiving fingolimod or siponimod.MethodsWe reviewed the cases of COVID-19 from postmarketing or ongoing clinical trials reported to Novartis through December 27, 2020.ResultsAs of December 27, 2020, 283 cases had been reported in fingolimod-treated patients. The mean age was 44 years (from n = 224; range 11–69 years), and 190 were women. Of 161 cases with available information, 138 were asymptomatic (6), mild (100), or moderate (32); 50 cases required hospitalization. At the last follow-up, 140 patients were reported as recovered/recovering, condition was unchanged in 22, and deteriorated in 3 patients; 4 patients had a fatal outcome. Information was not available for 114 patients. Of the 54 cases of COVID-19 reported in siponimod-treated patients, 45 were from the postmarketing setting and 9 from an ongoing open-label clinical trial. The mean age was 54 years (from n = 45; range 31–70), and 30 were women. Of 28 cases with available information, 24 were asymptomatic (2), mild (17), or moderate (5); 9 cases required hospitalization. At the last follow-up, 27 patients were reported as recovered/recovering, condition remained unchanged for 1, and 3 patients had a fatal outcome. Information was not available for 23 patients.DiscussionBased on a review of available information, the risk of more severe COVID-19 in patients receiving fingolimod or siponimod seems to be similar to that reported in the general population and the MS population with COVID-19. However, limitations of spontaneous reporting, especially missing data, should be considered in the interpretation of these observations.

A Goal-Directed Account of Action Slips: The Reliance on Old Contingencies

People often keep engaging in behaviors that used to be successful in the past but which are knowingly no longer effective in the current situation, so called action slips. Such action slips are often explained with stimulus-driven processes in which behavior is caused by a stimulus-response association and without information about the outcome of the behavior. This process is contrasted with a goal-directed process in which behavior is selected because it is expected to lead to a desired outcome. Failing to act in line with changes in the outcome, is taken as evidence for stimulus-driven processes. Stimulus-driven processes are assumed to get installed after overtraining and to be deployed under poor operating conditions. In line with this, previous research has found that action slips are more likely to occur after extensive training and when under time pressure. We propose an alternative goal-directed explanation according to which action slips are not caused by a stimulus-driven process, but rather by a goal-directed process that relies on old, no longer accurate, outcome information. In the current study, participants learned four stimulus-response-outcome contingencies during a single (i.e., moderate training) or a four-day training schedule (i.e., extensive training). Afterwards two contingencies were reversed. Results show that after extensive training and when under time pressure, participants not only committed more action slips but also reported more old response-outcome contingencies in line with these action slips. This is consistent with the goal-directed explanation that action slips result from a reliance on old, no longer accurate outcome information.

Don’t Throw Your Heart Away: Increased Transparency of Donor Utilization Practices in Transplant Center Report Cards Alters How Center Performance Is Evaluated

Background Publicly available report cards for transplant centers emphasize posttransplant survival and obscure the fact that some centers reject many of the donor organs they are offered (reflecting a conservative donor acceptance strategy), while others accept a broader range of donor offers (reflecting an open donor acceptance strategy). Objective We assessed how the provision of salient information about donor acceptance practices and waitlist survival rates affected evaluation judgments of hospital report cards given by laypeople and medical trainees. Methods We tested 5 different report card formats across 4 online randomized experiments ( n1 = 1,003, n2 = 105, n3 = 123, n4 = 807) in the same hypothetical decision. The primary outcome variable was a binary choice between transplant hospitals (one with an open donor acceptance strategy and the other with a conservative donor acceptance strategy). Results Report cards featuring salient information about donor organ utilization rates (transplant outcomes categorized by quality of donor offers accepted) or overall survival rates (outcomes from both waitlist and transplanted patients) led lay participants (studies 1, 3, and 4) and medical trainees (study 2) to evaluate transplant centers with open donor acceptance strategies more favorably than centers with conservative strategies. Limitations Due to the nature of the decision, a hypothetical scenario was necessary for both ethical and practical reasons. Results may not generalize to transplant clinicians or patients faced with the decision of where to join the transplant waitlist. Conclusions These findings suggest that performance evaluations for transplant centers may vary significantly based not only on what outcome information is presented in report cards but also how the information is displayed.

SDF4 Is a Prognostic Factor for 28-Days Mortality in Patients With Sepsis via Negatively Regulating ER Stress

Sepsis is a heterogeneous syndrome induced by infection and results in high mortality. Even though more than 100 biomarkers for sepsis prognosis were evaluated, prediction of patient outcomes in sepsis continues to be driven by clinical signs because of unsatisfactory specificity and sensitivity of these biomarkers. This study aimed to elucidate the key candidate genes involved in sepsis response and explore their downstream effects based on weighted gene co-expression network analysis (WGCNA). The dataset GSE63042 with sepsis outcome information was obtained from the Gene Expression Omnibus (GEO) database and then consensus WGCNA was conducted. We identified the hub gene SDF4 (stromal cell derived factor 4) from the M6 module, which was significantly associated with mortality. Subsequently, two datasets (GSE54514 and E-MTAB-4421) and cohort validation (n=89) were performed. Logistic regression analysis was used to build a prediction model and the combined score resulting in a satisfactory prognosis value (area under the ROC curve=0.908). The model was subsequently tested by another sepsis cohort (n=70, ROC= 0.925). We next demonstrated that endoplasmic reticulum (ER) stress tended to be more severe in patients PBMCs with negative outcomes compared to those with positive outcomes and SDF4 was related to this phenomenon. In addition, our results indicated that adenovirus-mediated Sdf4 overexpression attenuated ER stress in cecal ligation and puncture (CLP) mice lung. In summary, our study indicates that incorporation of SDF4 can improve clinical parameters predictive value for the prognosis of sepsis, and decreased expression levels of SDF4 contributes to excessive ER stress, which is associated with worsened outcomes, whereas overexpression of SDF4 attenuated such activation.

Clinico-Epidemiological Characteristics of Pediatric COVID-19 Patients in Bangladesh

Background To delineate the clinico-epidemiological characteristics of pediatric coronavirus disease-2019 (COVID-19) patients was the objective of the study. Method: This observational study included 290 pediatric patients with a definite diagnosis of COVID-19 admitted to Dhaka Shishu Hospital, Bangladesh, from April 2021 to October 2021. Clinical and epidemiological characteristics were analyzed based on demographic data, medical history, laboratory tests, and outcome information. Data analysis was performed with SPSS 26. Ethical measures were taken in compliance with the current declaration of Helsinki, and final analysis was performed using SPSS 26. Result Of all, 42 (14.5%) were neonates (< 28 days), 88 (30.3%) were infants (28 days to < 1 year) and 160 (55.2%) were children (1–17 years). The median age of the children was 18 (0.3–204) months, 58.3% were male, 62% had malnutrition, and presented with various clinical presentations. The main symptoms were fever (5.7%) and breathlessness (20%). Approximately 22% of children were asymptomatic, and 57% had at least one comorbidity. Fever and abdominal pain were predominant presenting symptoms in children compared with neonates and infants (p < .01 for both), while cough and breathlessness were more frequent in infants (p < .01 for both). The infants suffered significantly from neutropenia and lymphocytosis than neonates and children (p < .001 for both). The discharge and death rates were 77.8% with 6.9%. Overall case fatality was higher among neonates than others. Conclusion Compared to other pediatric groups, neonatal case fatality was higher, and COVID-19 in neonates, infants, and children has similar epidemiological and clinical manifestations. The findings from this study might help to guide the development of measures to prevent and treat this ongoing global pandemic of these particular age groups.