Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression.

BACKGROUND: In treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high. The efficacy and safety of esketamine nasal spray as compared with extended-release quetiapine augmentation therapy, both in combination with ongoing treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), in patients with treatment-resistant depression are unknown. METHODS: In an open-label, single-blind (with raters unaware of group assignments), multicenter, phase 3b, randomized, active-controlled trial, we assigned patients, in a 1:1 ratio, to receive flexible doses (according to the summary of product characteristics) of esketamine nasal spray (esketamine group) or extended-release quetiapine (quetiapine group), both in combination with an SSRI or SNRI. The primary end point was remission, defined as a score of 10 or less on the Montgomery-Åsberg Depression Rating Scale (MADRS), at week 8 (scores range from 0 to 60, with higher scores indicating more severe depression). The key secondary end point was no relapse through week 32 after remission at week 8. All patients were included in the analysis; patients who discontinued the trial treatment were considered as having had an unfavorable outcome (i.e., they were grouped with patients who did not have remission or who had a relapse). Analyses of the primary and key secondary end points were adjusted for age and number of treatment failures. RESULTS: Overall, 336 patients were assigned to the esketamine group and 340 to the quetiapine group. More patients in the esketamine group than in the quetiapine group had remission at week 8 (91 of 336 patients [27.1%] vs. 60 of 340 patients [17.6%]; P = 0.003) and had no relapse through week 32 after remission at week 8 (73 of 336 patients [21.7%] vs. 48 of 340 patients [14.1%]). Over 32 weeks of follow-up, the percentage of patients with remission, the percentage of patients with a treatment response, and the change in the MADRS score from baseline favored esketamine nasal spray. The adverse events were consistent with the established safety profiles of the trial treatments. CONCLUSIONS: In patients with treatment-resistant depression, esketamine nasal spray plus an SSRI or SNRI was superior to extended-release quetiapine plus an SSRI or SNRI with respect to remission at week 8. (Funded by Janssen EMEA; ESCAPE-TRD ClinicalTrials.gov number, NCT04338321.).

The American Association for the Surgery of Trauma (AAST) Liver Injury Grade Does Not Equally Predict Interventions in Blunt and Penetrating Trauma.

INTRODUCTION: The AAST liver injury grade has a validated association with mortality and need for operation. AAST liver injury grade is the same regardless of the mechanism of trauma. METHODS: A 5-year retrospective review of all liver injuries at an urban, level-one trauma center was performed. RESULTS: Totally, 315 patients were included (29% blunt, 71% penetrating). In blunt trauma, AAST grade was associated with need for laparotomy (0%, 7%, 5%, 33%, 29%, Grade 1-5, p = 0.01), angiography (0%, 7%, 25%, 40%, 57%, p < 0.001), embolization (0%, 7%, 15%, 33%, 43%, p = 0.01), and percutaneous drainage procedures (13% use in Grade 4, otherwise 0%, p = 0.04), but not ERCP (0% for all grades). In penetrating trauma, AAST grade was associated with need for angiography (7%, 4%, 15%, 24%, 30%, p < 0.01) and percutaneous drainage (7%, 2%, 14%, 18%, 26%, p = 0.03) and had a marginal association with embolization (0%, 4%, 11%, 13%, 22%, p = 0.06). Laparotomy, ERCP, sphincterotomy, and stenting rates increased with AAST grade, but this was not statistically significant. CONCLUSION: AAST grade is associated with the need for surgical hemostasis, angioembolization, and percutaneous drainage in both penetrating and blunt trauma. Operative, endoscopic, and percutaneous procedures are utilized more in penetrating trauma. Angioembolization was used more in blunt trauma. Mechanism should be considered when using AAST grade to guide management of liver injuries.

Association between Torso Gunshot Wound Volumes of Trauma Centers and Outcomes of Torso Gunshot Wound Patients. A Propensity-Matched Nationwide Cohort Study.

Objective: The number and type of patients treated by trauma centers can vary widely because of a number of factors. There might be trauma centers with a high volume of torso GSWs that are not designated as high-level trauma centers. We proposed that, for torso gunshot wounds (GSWs), the treating hospital's trauma volume and not its trauma center level designation drives patient prognosis.Methods: The National Trauma Data Bank was queried for torso GSWs. The characteristics of torso GSWs in trauma centers with different volumes of torso GSWs were compared. The association between torso GSW volumes of trauma centers and the outcomes of torso GSWs were evaluated with propensity score matching (PSM) and multivariate logistic regression (MLR) analysis.Results: There were 618 trauma centers that treated 14,804 torso GSW patients in two years (2014-2015). In 191 level I trauma centers, 82 of them (42.9%, 82/191) treated <1 torso GSW per month. After well-balanced PSM, patients who were treated in higher volume trauma centers (≥9 torso GSWs/month) had a significantly lower mortality rate (7.9% vs. 9.7%). Patients treated in trauma centers with ≥9 torso GSWs/month had a 30.9% (odds ratio = 0.764) lower probability of death than if sent to trauma centers with <9 torso GSWs/month. Treatment in level I or II trauma centers did not significantly affect mortality.Conclusion: There is an uneven distribution of torso GSWs among trauma centers. Torso GSWs treated in trauma centers with ≥9 torso GSWs/month have significantly superior outcomes with regard to survival.

Obesity May Require a Higher Level of Trauma Care: A Propensity-Matched Nationwide Cohort Study.

OBJECTIVE: Stable patients with less severe injuries are not necessarily triaged to high-level trauma centers according to current guidelines. Obese patients are prone to comorbidities and complications. We hypothesized that stable obese patients with low-energy trauma have lower mortality and fewer complications if treated at Level-I/II trauma centers. Methods: Blunt abdominal trauma (BAT) patients with systolic blood pressures ≥90mmHg, Glasgow coma scale ≥14, and respiratory rates at 10-29 were derived from the National Trauma Data Bank between 2013-2015. Per current triage guidelines, these patients are not necessarily triaged to high-level trauma centers. The relationship between obesity and mortality of stable BAT patients was analyzed. A subset analysis of patients with injury severity scores (ISS) <16 was performed with propensity score matching (PSM) to evaluate outcomes between Level-I/II and Level-III/IV trauma centers. Outcomes of obese patients were compared between Level-I/II and Level-III/IV trauma centers. Non-obese patients were analyzed as a control group using a similar PSM cohort analysis. Results: 48,043 stable BAT patients in 707 trauma centers were evaluated. Non-survivors had a significantly higher body mass index (BMI) (28.7 vs. 26.9, p < 0.001) and higher proportion of obesity (35.6% vs. 26.5%, p < 0.001) than survivors. After a PSM (1,502 obese patients: 751 in Level-I/II trauma centers and 751 in Level-III/IV trauma centers), obese patients treated in Level-I/II trauma centers had significantly lower complication rates than obese patients treated in other trauma centers (20.2% vs. 26.6%, standardized difference = 0.151). The complication rate of obese patients treated at Level-I/II trauma centers was 20.6% lower than obese patients treated at other trauma centers. Conclusion: Obesity plays a role in the mortality of stable BAT patients. Obese patients with ISS < 16 have lower complication rates at Level-I/II trauma centers compared to obese patients treated at other trauma centers. Obesity may be a consideration for triaging to Level-I/II trauma centers.

Prevalence and sort of pharmacokinetic drug-drug interactions in hospitalized psychiatric patients.

Psychiatric patients are high-risk patients for the development of pharmacokinetic drug-drug interactions (DDIs), leading to highly variable (victim) drug serum concentrations. Avoiding and targeting high-risk drug combinations could reduce preventable adverse drug reactions (ADRs). Pharmacokinetic cytochrome P450 (CYP)-mediated DDIs are often predictable and, therefore, preventable. The retrospective, longitudinal analysis used informations from a large pharmacovigilance study (Optimization of pharmacological treatment in hospitalized psychiatric patients study, study number 01VSF16009, 01/2017), conducted in 10 psychiatric hospitals in Germany. Medication data were examined for the co-prescription of clinically relevant CYP inhibitors or inducers and substrates of these enzymes (victim drugs). In total, data from 27,396 patient cases (45.6% female) with a mean (mean ± standard deviation (SD)) age of 47.3 ± 18.3 years were available for analysis. CYP inhibitors or inducers were at least once prescribed in 14.4% (n = 3946) of the cases. The most frequently prescribed CYP inhibitors were melperone (n = 2504, 28.1%) and duloxetine (n = 1324, 14.9%). Overall, 51.0% of the cases taking melperone were combined with a victim drug (n = 1288). Carbamazepine was the most frequently prescribed CYP inducer (n = 733, 88.8%). Combinations with victim drugs were detected for 58% (n = 427) of cases on medication with carbamazepine. Finally, a DDI was detected in 43.6% of the cases in which a CYP inhibitor or inducer was prescribed. The frequency of CYP-mediated DDI is considerably high in the psychiatric setting. Physicians should be aware of the CYP inhibitory and inducing potential of psychotropic and internistic drugs (especially, melperone).

Obesity is Associated with Worse Outcomes Among Abdominal Trauma Patients Undergoing Laparotomy: A Propensity-Matched Nationwide Cohort Study.

INTRODUCTION: Obesity is associated with increased morbidity and mortality in abdominal trauma patients. The characteristics of abdominal trauma patients with poor outcomes related to obesity require evaluation. We hypothesize that obesity is related to increased mortality and length of stay (LOS) among abdominal trauma patients undergoing laparotomies. METHODS: Abdominal trauma patients were identified from the National Trauma Data Bank between 2013 and 2015. Patients who received laparotomies were analyzed using propensity score matching (PSM) to evaluate the mortality rate and LOS between obese and non-obese patients. Patients without laparotomies were analyzed as a control group using PSM cohort analysis. RESULTS: A total of 33,798 abdominal trauma patients were evaluated, 10,987 of them received laparotomies. Of these patients, the proportion of obesity in deceased patients was significantly higher when compared to the survivors (33.1% vs. 26.2%, p < 0.001). Elevation of one kg/m2 of body mass index independently resulted in 2.5% increased odds of mortality. After a well-balanced PSM, obese patients undergoing laparotomies had significantly higher mortality rates [3.7% vs. 2.4%, standardized difference (SD) = 0.241], longer hospital LOS (11.1 vs. 9.6 days, SD = 0.135), and longer intensive care unit LOS (3.5 vs. 2.3 days, SD = 0.171) than non-obese patients undergoing laparotomies. CONCLUSIONS: Obesity is associated with increased mortality in abdominal trauma patients who received laparotomies versus those who did not. Obesity requires a careful evaluation of alternatives to laparotomy in injured patients.

Drug-Induced Liver Injury (DILI) in Patients with Depression Treated with Antidepressants: A Retrospective Multicenter Study.

INTRODUCTION: Drug-induced liver injury (DILI) is the 4th most common cause of liver damage in Western countries and can be caused by antidepressants. METHODS: Against the background of increasing antidepressant prescriptions and increasing use of polypharmacy, we analyzed administered antidepressants and other pharmacological substances, liver toxicity, comorbid somatic secondary diseases together with the occurrence of DILI in a patient population of 6 centers throughout Germany. RESULTS: The majority of the enrolled 329 patients received polypharmacological treatment in an inpatient setting. During antidepressant treatment 5.1% of the patients had elevated serum transaminase levels, whereby exactly and not more than 1 criterion proposed to be indicative for DILI, was fulfilled by 3 patients (0.9%). DISCUSSION: During patient characterization it becomes clear that a sensitization for relevant risk constellations causing liver injury in MDD patients is relevant to prevent further serious adverse events.

Morbid Obesity's Silver Lining: An Armor for Hollow Viscus in Blunt Abdominal Trauma.

BACKGROUND: Morbid obesity is usually accompanied by both subcutaneous and visceral fat accumulation. Fat can mimic an air bag, absorbing the force of a collision. We hypothesized that morbid obesity is mechanically protective for hollow viscus organs in blunt abdominal trauma (BAT). METHODS: The National Trauma Data Bank (NTDB) was queried for BAT patients from 2013 to 2015. We looked at the rate of gastrointestinal (GI) tract injuries in all BAT patients with different BMIs. A subset analysis of BAT patients with operative GI tract injuries was performed to evaluate the need for abdominal operation. Multivariate analyses were carried out to identify factors independently associated with increased GI tract injuries and associated abdominal operations. RESULTS: A total of 100,459 BAT patients were evaluated in the NTDB. Patients with GI tract injury had a lower proportion of morbidly obese patients [body weight index (BMI) ≥ 40 kg/m2)] (3.7% vs. 4.2%, p = 0.015) and instead had more underweight patients (BMI < 18.5) (5.9% vs. 5.0%, p < 0.001). The risk of GI tract injury decreased 11.6% independently in morbidly obese patients and increased 15.7% in underweight patients. Of the patients with GI tract injuries (N = 11,467), patients who needed a GI operation had a significantly lower proportion of morbidly obese patients (3.2% vs. 5.3%, p < 0.001). The risk of abdominal operation for GI tract injury decreased 57.3% independently in morbidly obese patients. Compared with underweight patients, morbidly obese patients had significantly less GI tract injury (6.0% vs. 13.3%, p < 0.001) and associated abdominal operation rates (65.2% vs. 73.3%, p < 0.001). CONCLUSION: Obesity is protective in BAT. This translates into lower rates of GI tract injury and operation in morbidly obese patients. In contrast, underweight patients appear to suffer a higher rate of GI tract injury and associated GI operations.

The Efficacy of Tiapride and Carbamazepine Combination Therapy in Reducing Alcohol Withdrawal Symptoms: A Systematic Review and Meta-Analysis.

The combination of tiapride (TIA) and carbamazepine (CBZ) as an alternative treatment option to benzodiazepines and clomethiazole has been investigated by several investigations. We performed a systematic review and meta-analysis to further explore the efficacy of this combination in order to render more definite answers whether this combination can be recommendable in the clinical practice. We systematically searched electronic databases including PubMed (MEDLINE), EMBASE, OVID, Cochrane, Google Scholar, and Scopus for human studies. Statistical homogeneity was checked by χ2 test and I2 using Cochran heterogeneity statistic. Our analysis showed a significant efficacy of the combination of TIA and CBZ in reducing alcohol withdrawal syndrome (AWS) (p<0.0001, z-value: 4.07). The cumulative analysis illustrated that the favorable efficacy of this combination therapy has been consistent over time. Our study shows that the combination of TIA/CBZ is an effective treatment in management of AWS in patients with alcohol abstinence. However, the safety of this combination could not be proven, so we recommend its prescription after an informed consent.

[Therapeutic drug monitoring in neuropsychopharmacology : Summary of the consensus guidelines 2017 of the TDM task force of the AGNP]. / Therapeutisches Drug-Monitoring in der Neuropsychopharmakologie : Zusammenfassung der Konsensusleitlinien 2017 der TDM-Arbeitsgruppe der AGNP.

Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood serum or plasma to optimize pharmacological therapy. TDM is an instrument with which the high interindividual variability of pharmacokinetics of patients can be identified and therefore enables a personalized pharmacotherapy. In September 2017 the TDM task force of the Working Group for Neuropsychopharmacology and Pharmacopsychiatry (AGNP) published an update of the consensus guidelines on TDM published in 2011. This article summarizes the essential statements for the clinical practice in psychiatry and neurology.

Mobility behaviour and driving status of patients with mental disorders - an exploratory study.

BACKGROUND: Driving is an important activity of daily life and an integral part of mobility. However, impact of mental illness on road mobility is widely unexplored. METHOD: Driving status in 1497 psychiatric inpatients (PPs) and a clinical control group of 313 neurological inpatients (NPs) was investigated using a brief questionnaire. RESULTS: 67% of PPs (89% NPs) reported to have a valid driver's licence and 77% of them (92% NPs) reported to regularly use their cars. Within driver's license holders, patients with organic mental disorder (32%), substance dependence (37%) and psychotic disorder (40%) had the lowest proportion of current drivers. Higher educational qualification (odds ratio [OR] from 2.978 to 17.036) and being married/partnered (OR 3.049) or divorced (OR 4.840) significantly advanced the probability of possession of a driving license. Predictive factors for driving cessation were being female, an older age, drawing a pension and having an organic mental disease or schizophrenic disorder. CONCLUSION: Mental disease has a negative impact on driving status and this is especially true for illnesses frequently being accompanied by distinct cognitive impairments. Factors predicting road mobility elucidate the strong relationship with psychosocial status indicating that recovery of driving competence should be an integral goal of treatment strategies.

Excess after stress-A three-study validation of the salzburg stress drinking scale as a new tool to measure the stress-drinking relationship.

Stress frequently influences a person's propensity to drink alcohol. Inter-individual differences in such stress-related drinking can be assessed through psychometric scales; however, available questionnaires conflate stress- with emotion-related reasons to drink and ignore evidence of decreased alcohol consumption in response to stress. Therefore, we developed a genuine stress-drinking scale (Salzburg Stress Drinking Scale; SSDS), adapted from the Salzburg Stress Eating Scale, and assessed its psychometric properties. In study 1 (n = 639), the SSDS was found to have a one-factor structure, excellent internal consistency, and acceptable test-retest reliability. SSDS scores were significantly correlated with other measures assessing emotional drinking, but uncorrelated with general alcohol pathology and other health-relevant consummatory behaviors such as stress-related eating or nicotine consumption. In addition, no significant sex differences arose. In study 2 (n = 42) patients with an alcohol use disorder or addiction scored significantly higher on the SSDS compared to healthy controls. In an Ecological Momentary Assessment study 3 (n = 67), the SSDS showed partial ecological validity through significant relationships with daily alcohol consumption, but not daily stress-drinking relationships. In sum, the SSDS represents a psychometrically sound tool for the measurement of stress-related drinking and complements a battery of stress-related changes in health-relevant behaviors.

Osteopathic Manipulative Treatment During Post-operative Recovery: A Scoping Review.

Surgery is a common and often necessary treatment option for a wide range of medical conditions, with an estimated 40 to 50 million surgeries performed in the US alone each year. While the various types of surgeries performed may be effective in treating or managing different conditions, the post-operative period can be challenging for patients. Osteopathic manipulative treatment (OMT) is a hands-on approach to medical care that seeks to restore balance and harmony to the body from the lens of an interconnected mind, body, and spirit. Given the potential for adverse events in patients following surgical treatments, OMT may be a viable adjunct post-operatively to enhance patient care and recovery. The purpose of this scoping review is to evaluate the state of current research examining the effectiveness of OMT in improving outcomes in post-operative patients. Three hundred articles were collected; 53 duplicates were removed. Eleven independent reviewers evaluated all 247 articles. Thirty articles were identified, including nine in general surgery, six in cardiothoracic surgery, five in orthopedic surgery, four in spinal surgery, three in neurosurgery, and three others (otolaryngology, oral/maxillofacial, and gynecologic surgery). Post-operative patients were treated with various OMT techniques with myofascial release and muscle energy being some of the most common treatments utilized in all surgical fields. Many studies demonstrated the benefits of OMT usage including significant pain relief, improved and earlier bowel function, and decreased lengths of hospital stay. This study demonstrates how OMT can be effective in reducing post-operative pain, reducing the incidence of post-operative ileus, and shortening the length of stay. Further research into the utilization of OMT in post-operative patients should be considered a potential adjunct to surgical intervention, especially in vulnerable patient populations.

Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment.

The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant-dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs.

Effectiveness of antipsychotic maintenance therapy with quetiapine in comparison with risperidone and olanzapine in routine schizophrenia treatment: results of a prospective observational trial.

Objective of this observational trial is to examine the effects of quetiapine in comparison with olanzapine and risperidone on clinical outcomes and quality of life in patients with schizophrenia and schizoaffective disorder in routine care. 374 adult persons with schizophrenia or schizoaffective disorder prescribed antipsychotic maintenance therapy with quetiapine, olanzapine, or risperidone at discharge from inpatient treatment were included. Clinical and psychosocial outcomes were assessed before discharge and at 6, 12, 18, and 24 months. Statistical analyses were conducted by mixed-effects regression models for longitudinal data. The propensity score method was used to control for selection bias. Patients discharged on olanzapine had significantly lower hospital readmissions than those receiving quetiapine or risperidone. The average chlorpromazine equivalent dose of quetiapine was higher than in patients treated with olanzapine or risperidone. No further significant differences between treatment groups were found. Quetiapine and risperidone are less effective in preventing the need for psychiatric inpatient care than olanzapine, and higher chlorpromazine equivalent doses of quetiapine are needed to obtain clinical effects similar to those of olanzapine and risperidone.

Incidence, risk factors and clinical implications of postoperative urinary tract infection in geriatric hip fractures.

INTRODUCTION: Postoperative urinary tract infection (UTI) is common in geriatric patients; however, little is known about the impact of UTI in orthopedic trauma. The present study was designed to determine the risk factors and clinical impact of postoperative urinary tract infection (UTI) in acute geriatric hip fractures. PATIENTS AND METHODS: Geriatric patients (≥65 years of age) undergoing hip fracture surgery were identified within the American College of Surgeons National Surgical Quality Improvement Program between 2016 and 2019. Patients presenting with UTI at the time of surgery were excluded. Baseline characteristics and outcomes were compared between patients with and without postoperative UTI. Multivariate logistic regression was performed, controlling for potential confounders. RESULTS: A total of 46,263 patients included in the study. Overall, 1,397 (3.02%) patients had postoperative UTI. Patients who developed postoperative UTI had higher rates of pneumonia (6.44% vs. 3.76%, p < 0.001), DVT (2.22% vs. 1.04%, p < 0.001), sepsis (7.73% vs. 0.62%, p < 0.001), and more frequently experienced postoperative hospital lengths of stay exceeding 6 days (37.94% vs. 20.33%, p < 0.001). Hospital readmission occurred more frequently in patients with postoperative UTI (24.55% vs. 7.85%, p < 0.001), but surprisingly, these patients had a lower mortality rate (1.36% vs. 2.2%, p < 0.001). Adjusted analysis demonstrated the following variables associated with postoperative UTI: age ≥ 85 (OR = 1.37, 95%CI = 1.08 - 1.73), ASA class ≥ 3 (OR = 1.59, 95%CI = 1.21 - 2.08,), chronic steroid use (OR = 1.451, 95%CI = 1.05 - 1.89), blood transfusion (OR = 1.24, 95%CI = 1.05 - 1.48), and >2 days delay from admission to operation (OR = 1.37, 95%CI = 1.05 - 1.79). Postoperative UTI was significantly associated with sepsis (OR = 7.65, 95%CI = 5.72 - 10.21), postoperative length of stay >2 days (OR = 1.83, 95%CI = 1.07 - 3.13), and readmission (OR = 3, 95%CI = 2.54 - 3.55). CONCLUSIONS: In our study, postoperative UTI was found in 3% of geriatric hip fracture patients. Predictors of postoperative UTI were age ≥ 85, ASA class ≥ 3, chronic steroid use, blood transfusion, and time to operation > 2 days from admission. Results showed that postoperative UTI is independently associated with sepsis, postoperative length of stay beyond 2 days, and hospital readmission. To diminish the risk of UTI and its consequences, we recommend operating geriatric hip fractures in 24-48 hours after admission.