Identifying subgroups with differential response to CBASP versus Escitalopram during the first eight weeks of treatment in outpatients with persistent depressive disorder.

There exists little empirical evidence helping clinicians to select the most effective treatment for individual patients with persistent depressive disorder (PDD). This study identifies and characterizes subgroups of patients with PDD who are likely to benefit more from an acute treatment with psychotherapy than from pharmacotherapy and vice versa. Non-medicated outpatients with PDD were randomized to eight weeks of acute treatment with the Cognitive Behavioral Analysis System of Psychotherapy (CBASP; n = 29) or escitalopram plus clinical management (ESC/CM; n = 31). We combined several baseline variables to one composite moderator and identified two subgroups of patients: for 56.0%, ESC/CM was associated with a greater reduction in depression severity than CBASP, for the remaining 44.0%, it was the other way around. Patients likely to benefit more from ESC/CM were more often female, had higher rates of moderate-to-severe childhood trauma, more adverse life events and more previous suicide attempts. Patients likely to benefit more from CBASP were older, had more often an early illness onset and more previous treatments with antidepressants. Symptomatic response, remission, and reductions in symptom severity occurred more often in those patients treated with their likely more effective treatment condition. The findings suggest that the baseline phenotype of patients with PDD moderates their benefit from acute treatment with CBASP relative to ESC/CM. Once confirmed in an independent sample, these results could serve to guide the choice between primarily psychotherapeutic or pharmacological treatments for outpatients with PDD.

The impact of childhood maltreatment on the differential efficacy of CBASP versus escitalopram in patients with chronic depression: A secondary analysis.

Childhood maltreatment (CM) has been indicated as a predictor of a differential response to antidepressant treatment with psychotherapy compared to medication. In this secondary analysis, we investigated whether the presence of CM results in a differential indication for the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) or escitalopram plus clinical management (ESC). Sixty patients with chronic depression were randomized to either 22 sessions of CBASP or ESC over the course of 8 weeks of acute and 20 weeks of extended treatment at 2 German treatment sites. CM was assessed using the Childhood Trauma Questionnaire and the clinician rated Early Trauma Inventory. Intention-to-treat analyses were used to examine the impact of CM on depression, global functioning, and quality of life. The presence of CM did not result in significant differences in treatment response to CBASP or ESC on any outcome measure after 28 weeks of treatment independent of the type of CM assessment. After 8 weeks, a significant CM × treatment interaction was found for scores on the Montgomery-Asberg Depression Rating Scale. Patients with a history of CM receiving CBASP had a significantly lower response rate compared to patients without CM and to those receiving ESC after 8 weeks. Conclusively, CBASP and ESC are equally effective treatment options for the difficult to treat subgroup of patients with chronic depression and a history of CM. CM may be a predictor of a longer latency of treatment response in the case of psychotherapy. KEY PRACTITIONER MESSAGE: CBASP and escitalopram are equally effective treatment options for chronic depression. Both treatments are also equally effective for the difficult to treat subgroup of patients with chronic depression and a history of childhood maltreatment. Childhood maltreatment may result in a longer latency of treatment response in the case of psychotherapy.

An Evaluation of Medication Reconciliation in an Outpatient Nephrology Clinic.

Background: Accreditation Canada recognizes medication reconciliation as a key required organizational practice (ROP) to enhance patient safety. Patients with chronic kidney disease (CKD) carry a high risk for adverse drug events due to multiple co-morbidities, using many medications, and being cared for by many practitioners. Data evaluating the benefits of ambulatory medication reconciliation (AmbMR) in patients with advanced CKD is limited. Methods: We retrospectively evaluated types and rates of medication discrepancies and their potential index for patient harm using the Cornish classification system in a cohort of consecutive non-dialysis-dependent CKD stage 5 patients who received AmbMR. Results: AmbMR was conducted 225 times on 115 patients during the study period. One hundred eighty medication discrepancies were identified. The most common discrepancy identified was incorrect drug followed by discrepant dose, discrepant frequency, and drug omission. Sixty-three percent of discrepancies were classified as unlikely to cause patient discomfort or clinical deterioration, 36% were classified as likely to cause moderate harm, and one percent was classified as potential to cause serious harm. Conclusion: Medication discrepancies are common in patients with advanced CKD. Nearly a quarter of patients may experience moderate discomfort or clinical deterioration from discrepancies. Our study showed that in patients with non-dialysis-dependent CKD stage 5, the risk of patient harm associated with medication discrepancies can be reduced by conducting AmbMR.

Stimulus-dependent amygdala involvement in affective theory of mind generation.

Successful social interaction requires knowledge about another person's emotional states, represented in an affective theory of mind (ToM). This information can be acquired either directly or indirectly, i.e., by observing emotional facial expressions (EFE) or indirectly by inferring emotions through cognitive perspective taking. Therefore, it is of great interest how the function of the cortical ToM network and the limbic system in affective ToM depends on the presence of facial expressions. We addressed this question in a functional magnetic resonance imaging (fMRI) study. The experimental paradigm applied a well-established ToM cartoon task to test functional effects of EFE on the activation of the amygdala and the anterior ToM network during affective ToM judgments. During the task, 22 healthy participants had to judge the changes of the emotional state of the stories protagonist in the presence or absence of EFE. After quality control, 21 data sets entered the final analyses. The presence of EFE during affective ToM judgments was associated with shorter reaction times as well as increased activation of the right amygdala, most probably located in the basolateral nucleus (BLA), coincident with reduced activation of ToM-related regions of the prefrontal cortex. Psychophysiological interactions (PPI) revealed EFE-dependent modulation of connectivity between the right BLA and the contralateral ToM network regions. In combination with the functional interaction of EFE and affective ToM in the right amygdala, our data suggest a complementary but parallel organization of EFE processing and affective ToM. In this framework, the amygdala seems to act as an EFE detector when affective ToM judgments are demanded. Additionally, the facts that EFE induced exclusively right-sided amygdala activation and modulated the connectivity with the contralateral ToM network support the idea of a functional lateralization of stimulus driven components of affective ToM.

Cognitive Behavioral Analysis System of Psychotherapy versus Escitalopram in Chronic Major Depression.

BACKGROUND: A specific psychotherapy for chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), was compared to escitalopram (ESC). METHODS: Sixty patients with chronic major depression were randomized to 'CBASP' (22 sessions) or 'ESC plus clinical management' (ESC/CM) at two treatment sites. The primary outcome measure was the score on the Montgomery-Asberg Depression Rating Scale (MADRS) after 8 weeks of acute treatment assessed by blinded raters. In the case of nonimprovement (<20% reduction in the MADRS score), the other condition was augmented for the following 20 weeks of extended treatment. Secondary end points were, among others, depressive symptoms, remission (MADRS score of ≤9) and response rates (reduction of MADRS score of ≥50%) 28 weeks after randomization. RESULTS: An intent-to-treat analysis revealed that clinician-rated depression scores decreased significantly after 8 and 28 weeks with no significant differences between the groups. The response rates after 28 weeks of treatment were high (CBASP: 68.4%, ESC/CM: 60.0%), and the remission rates were moderate (CBASP: 36.8%, ESC/CM: 50.0%) with neither group being superior. Nonimprovers to the initial treatment caught up with the initial improvers in terms of depression scores and response and remission rates by the end of the treatment after being augmented with the respective other condition. CONCLUSIONS: CBASP and ESC/CM appear to be equally effective treatment options for chronically depressed outpatients. For nonimprovers to the initial treatment, it is efficacious to augment with medication in the case of nonresponse to CBASP and vice versa.

Behavioral evidence for an impairment of affective theory of mind capabilities in chronic depression.

BACKGROUND: The only treatment specifically developed for chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), is based amongst others on the hypothesis that chronically depressed patients (CD) show considerable deficits of affective theory of mind (ToM) capabilities. Data are scarce, however, and it remains unclear if ToM deficits are specific or if they arise from global cognitive deficits associated with depression. This study investigates the specific deficits of affective ToM abilities in CD. SAMPLING AND METHODS: ToM abilities were assessed in 26 medication-free CD and 26 matched healthy controls (HC) by means of a previously established false-belief ToM cartoon task. Since the task allowed an intern control for cognitive factors - operationalized in a visuospatial ToM task - it was possible to investigate specific affective ToM deficits. RESULTS: As hypothesized, the CD showed a significant specific slowdown of affective ToM compared to cognitive ToM (3rd person perspective) when compared to HC. Simultaneously, we observed a general deterioration of all ToM functions in CD. CONCLUSIONS: This study provides evidence that CD have a mentalization deficit, specifically for affective ToM functions. This deficit is combined with a general deterioration of ToM functions, most likely attributable to frequently described cognitive deficits in depression.

Pilot study evaluating intravenous amoxicillin-clavulanate as an alternative to piperacillin-tazobactam for general surgery patients.

In this point-prevalence survey followed by prospective audit and feedback at 4 tertiary-care hospitals in Calgary, Alberta, Canada, we evaluated whether intravenous amoxicillin-clavulanate may be used as a narrower-spectrum alternative to intravenous piperacillin-tazobactam for patients admitted to general surgery services.

Impact of Baseline Characteristics on the Effectiveness of Disorder-Specific Cognitive Behavioral Analysis System of Psychotherapy (CBASP) and Supportive Psychotherapy in Outpatient Treatment for Persistent Depressive Disorder.

Importance: In the treatment of persistent depressive disorder (PDD), disorder-specific Cognitive Behavioral Analysis System of Psychotherapy (CBASP) has been shown to be superior to Supportive Psychotherapy (SP) in outpatients. It remains to clear which subgroups of patients benefit equally and differentially from both psychotherapies. Objective: To identify those patient-level baseline characteristics that predict a comparable treatment effectiveness of CBASP and SP and those that moderate the differential effectiveness of CBASP compared to SP. Design, setting and participants: In this analysis of a 48-week multicenter randomized clinical trial comparing CBASP to SP in adult antidepressant-free outpatients with early-onset PDD, we evaluated baseline variables from the following domains as potential predictors and moderators of treatment effectiveness: socio-demography, clinical status, psychosocial and global functioning, life quality, interpersonal problems, childhood trauma, treatment history, preference for psychotherapy, and treatment expectancy. Interventions: A 48-week treatment program with 32 sessions of either CBASP or SP. Main outcomes and measures: Depression severity measured by the 24-item Hamilton Rating Scale for Depression (HRSD-24) at week 48. Results: From N = 268 randomized outpatients, N = 209 completed the 48-week treatment program. CBASP completers had significantly lower post-treatment HRSD-24 scores than SP completers (meanCBASP=13.96, sdCBASP= 9.56; meanSP= 16.69, sdSP= 9.87; p = 0.04). A poor response to both therapies was predicted by higher baseline levels of clinician-rated depression, elevated suicidality, comorbid anxiety, lower social functioning, higher social inhibition, moderate-to-severe early emotional or sexual abuse, no preference for psychotherapy, and the history of at least one previous inpatient treatment. Moderator analyses revealed that patients with higher baseline levels of self-rated depression, comorbidity of at least one Axis-I disorder, self-reported moderate-to-severe early emotional or physical neglect, or at least one previous antidepressant treatment, had a significantly lower post-treatment depression severity with CBASP compared to SP (all p < 0.05). Conclusions and relevance: A complex multifactorial interaction between severe symptoms of depression, suicidality, and traumatic childhood experiences characterized by abuse, social inhibition, and anxiety may represent the basis of non-response to psychotherapy in patients with early onset PDD. Specific psychotherapy with CBASP might, however, be more effective and recommendable for a variety of particularly burdened patients compared to SP.

Combining baseline characteristics to disentangle response differences to disorder-specific versus supportive psychotherapy in patients with persistent depressive disorder.

Does the pre-treatment profile of individuals with persistent depressive disorder (PDD) moderate their benefit from disorder-specific Cognitive Behavioral System of Psychotherapy (CBASP) versus supportive psychotherapy (SP)? We investigated this question by analyzing data from a multi-center randomized clinical trial comparing the effectiveness of 48 weeks of CBASP to SP in n  =  237 patients with early-onset PDD who were not taking antidepressant medication. We statistically developed an optimal composite moderator as a weighted combination of 13 preselected baseline variables and used it for identifying and characterizing subgroups for which CABSP may be preferable to SP or vice versa. We identified two distinct subgroups: 58.65% of the patients had a better treatment outcome with CBASP, while the remaining 41.35% had a better outcome with SP. At baseline, patients responding more favorably to CBASP were more severely depressed and more likely affected by moderate-to-severe childhood trauma including early emotional, physical, or sexual abuse, as well as emotional or physical neglect. In contrast, patients responding more favorably to SP had a higher pre-treatment global and social functioning level, a higher life quality and more often a recurrent illness pattern without complete remission between the episodes. These findings emphasize the relevance of considering pre-treatment characteristics when selecting between disorder-specific CBASP and SP for treating PDD. The practical implementation of this approach would advance personalized medicine for PDD by supporting mental health practitioners in their selection of the most effective psychotherapy for an individual patient.

Outcomes Associated with Reducing the Urine Alkalinization Threshold in Patients Receiving High-Dose Methotrexate.

STUDY OBJECTIVES: Urine alkalinization increases methotrexate (MTX) solubility and reduces the risk of nephrotoxicity. The objectives of this study were to determine whether a reduction in the urine pH threshold from 8 to 7 in patients receiving high-dose methotrexate (HDMTX) results in a shorter length of hospital stay, delayed MTX clearance, or higher rates of nephrotoxicity; and to determine whether specific factors were associated with prolonged MTX clearance. DESIGN: Retrospective cohort study. SETTING: Hematology service of a large university-affiliated teaching hospital in Ottawa, Canada. PATIENTS: Sixty-five adults with 150 HDMTX exposures who had elective admissions for HDMTX between September 1, 2014, and December 18, 2015, were included. Thirty-four patients (with 79 HDMTX exposures) had their urine alkalinized to a pH of 8 or higher, and 31 patients (with 71 HDMTX exposures) had their urine alkalinized to a pH of 7 or higher, after an institutional change in the urine pH threshold from 8 to 7 was implemented on May 1, 2015. MEASUREMENTS AND MAIN RESULTS: Data related to patient demographics, urine alkalinization, MTX serum concentration monitoring, hospital length of stay, and renal function were collected retrospectively from patients' electronic health records. Lowering the urine pH threshold from 8 to 7 did not significantly affect hospital length of stay (absolute difference 3.5 hrs, 95% confidence interval -4.0 to 10.9) or clearance of MTX (elimination rate constant 0.058 in the pH of 7 or higher group vs 0.064 in the pH of 8 or higher group, p=0.233). Nephrotoxicity rates were similar between groups (15.5% in the pH of 7 or higher group vs 10.1% in the pH of 8 or higher group, p=0.34). Higher MTX dose and interacting medications (e.g., proton pump inhibitors and sulfonamide antibiotics) were significantly associated with delayed MTX elimination. CONCLUSION: No significant differences in HDMTX-associated hospital length of stay, MTX clearance, or rates of nephrotoxicity were noted between patients in the urine pH of 7 or higher and 8 or higher groups. Interacting medications and higher MTX dose were associated with delayed MTX elimination, suggesting that a closer review of interacting medications before HDMTX administration may be warranted.

Comparison of intensive versus standard hemodialysis central venous catheter dysfunction protocol using rt-PA: a quality assurance initiative.

PURPOSE: Catheter locking solutions such as recombinant tissue plasminogen activator (rt-PA) are used to treat and prevent clotting of hemodialysis (HD) catheters during HD treatments and the interdialytic period. However, evidence to guide the use of rt-PA for catheter dysfunction is limited. METHODS: We evaluated outcomes using two catheter dysfunction protocols in a cohort of consecutive prevalent dialysis patients (Jan 2013 to Sep 2014) undergoing HD with a tunneled catheter. In the intensive protocol, rt-PA was administered to all catheters based on blood flow and/or line reversal. In the standard protocol, rt-PA administration was based only on blood flow. The primary outcome was the rate of rt-PA use for catheter malfunction (rt-PA treatment days/1000 total line days; [TLD]). Secondary outcomes included the cost of rt-PA/TLD and the rate of catheter-related bacteremia. RESULTS: There were 26 and 35 patients managed by the intensive and standard protocols, respectively. The rate of rt-PA use was 52/1000 TLD (intensive) versus 39/1000 TLD (standard) (rate ratio 1.30, 95% CI 1.12-1.52 CI, p<0.001). The rate of bacteremia was 0.43 and 0.22/1000 TLD for the intensive and standard protocols, respectively (p = 0.491). The cost of rt-PA was CDN $5.58 and CDN $6.15 per TLD for the intensive protocol and standard protocol groups (p<0.001). CONCLUSIONS: Managing catheter dysfunction based on line reversal and blood flow as opposed to only blood flow was associated with a higher rate of rt-PA use, but at a reduced overall cost.

Functional Correlates of childhood maltreatment and symptom severity during affective theory of mind tasks in chronic depression.

Among multiple etiological factors of depressive disorders, childhood maltreatment (CM) gains increasing attention as it confers susceptibility for depression and predisposes to chronicity. CM assumedly inhibits social-cognitive development, entailing interactional problems as observed in chronic depression (CD), especially in affective theory of mind (ToM). However, the extent of CM among CD patients varies notably as does the severity of depressive symptoms. We tested whether the extent of CM or depressive symptoms correlates with affective ToM functions in CD patients. Regional brain activation measured by functional magnetic resonance imaging during an affective ToM task was tested for correlation with CM, assessed by the Childhood Trauma Questionnaire (CTQ), and symptom severity, assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS), in 25 unmedicated CD patients (mean age 41.52, SD 11.13). Amygdala activation during affective ToM correlated positively with CTQ total scores, while (para)hippocampal response correlated negatively with MADRS scores. Our findings suggest that differential amygdala activation in affective ToM in CD is substantially modulated by previous CM and not by the pathophysiological equivalents of current depressive symptoms. This illustrates the amygdala's role in the mediation of CM effects. The negative correlation of differential (para)hippocampal activation and depressive symptom severity indicates reduced integration of interactional experiences during depressive states.