Joe Kossowsky

The Influence of the Patient-Clinician Relationship on Healthcare Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective To determine whether the patient-clinician relationship has a beneficial effect on either objective or validated subjective healthcare outcomes. Design Systematic review and meta-analysis. Data Sources Electronic databases EMBASE and MEDLINE and the reference sections of previous reviews. Eligibility Criteria for Selecting Studies Included studies were randomized controlled trials (RCTs) in adult patients in which the patient-clinician relationship was systematically manipulated and healthcare outcomes were either objective (e.g., blood pressure) or validated subjective measures (e.g., pain scores). Studies were excluded if the encounter was a routine physical, or a mental health or substance abuse visit; if the outcome was an intermediate outcome such as patient satisfaction or adherence to treatment; if the patient-clinician relationship was manipulated solely by intervening with patients; or if the duration of the clinical encounter was unequal across conditions. Results Thirteen RCTs met eligibility criteria. Observed effect sizes for the individual studies ranged from d = −.23 to .66. Using a random-effects model, the estimate of the overall effect size was small (d = .11), but statistically significant (p = .02). Conclusions This systematic review and meta-analysis of RCTs suggests that the patient-clinician relationship has a small, but statistically significant effect on healthcare outcomes. Given that relatively few RCTs met our eligibility criteria, and that the majority of these trials were not specifically designed to test the effect of the patient-clinician relationship on healthcare outcomes, we conclude with a call for more research on this important topic.

The separation anxiety hypothesis of panic disorder revisited: a meta-analysis.

OBJECTIVE Evidence suggests that childhood separation anxiety disorder may be associated with a heightened risk for the development of other disorders in adulthood. The authors conducted a meta-analysis to examine the relationship between childhood separation anxiety disorder and future psychopathology. METHOD PubMed, PsycINFO, and Embase were searched for studies published through December 2011. Case-control, prospective, and retrospective cohort studies comparing children with and without separation anxiety disorder with regard to future panic disorder, major depressive disorder, any anxiety disorder, and substance use disorders were included in the analysis. Effects were summarized as pooled odds ratios in a random-effects model. RESULTS Twenty-five studies met all inclusion criteria (14,855 participants). A meta-analysis of 20 studies indicated that children with separation anxiety disorder were more likely to develop panic disorder later on (odds ratio=3.45; 95% CI=2.37-5.03). Five studies suggested that a childhood diagnosis of separation anxiety disorder increases the risk of future anxiety (odds ratio=2.19; 95% CI=1.40-3.42). After adjusting for publication bias, the results of 14 studies indicated that childhood separation anxiety disorder does not increase the risk of future depression (odds ratio=1.06; 95% CI=0.78-1.45). Five studies indicated that childhood separation anxiety disorder does not increase the risk of substance use disorders (odds ratio=1.27; 95% CI=0.80-2.03). Of the subgroup analyses performed, differences in comparison groups and sample type significantly affected odds ratio sizes. CONCLUSIONS A childhood diagnosis of separation anxiety disorder significantly increases the risk of panic disorder and any anxiety disorder. These results support a developmental psychopathology conceptualization of anxiety disorders.

Children suffering from separation anxiety disorder (SAD) show increased HPA axis activity compared to healthy controls

RESEARCH QUESTIONS Separation anxiety disorder (SAD) is one of the most common mental disorders in childhood, and one of the earliest emerging. Little is known about the association between SAD and the hypothalamic-pituitary-adrenocortical (HPA) axis activity. Therefore, the present study aimed at investigating this association in children suffering from separation anxiety compared to healthy controls. METHODS A total of 31 children with diagnosed SAD (mean age: 8.45; 17 females, 14 males) and 25 healthy controls (HC; mean age: 9.74; 12 females, 13 males) took part in the study. All participants underwent psycho-physiological testing for HPA axis challenge. Testing consisted of a separation and a social exposure paradigm. Saliva samples to assess HPA axis-related cortisol secretion were gathered in parallel. RESULTS Compared to healthy controls, children with SAD showed greatly increased HPA axis activity, as reflected by an increased cortisol secretion throughout the entire period of investigation. The rise of cortisol was already observed in anticipation of, but not following the separation paradigm. No gender-related differences of cortisol secretion were observed. CONCLUSIONS Separation anxiety disorder (SAD) in children is reflected in greatly increased HPA axis activity. Compared to healthy controls, children with SAD showed increased cortisol values from the beginning of, and throughout, the entire investigation. This pattern of results suggests that both the anticipation of a separation and a persistent hyperactivity of the HPA axis system leads to an increased cortisol secretion.

Separation anxiety disorder in children: disorder‐specific responses to experimental separation from the mother

BACKGROUND Separation anxiety disorder (SAD) is one of the most common anxiety disorders in childhood and is predictive of adult anxiety disorders, especially panic disorder. However, the disorder has seldom been studied and the attempt to distinguish SAD from other anxiety disorders with regard to psychophysiology has not been made. We expected exaggerated anxiety as well as sympathetic and respiratory reactivity in SAD during separation from the mother. METHOD Participants were 49 children with a principal diagnosis of SAD, 21 clinical controls (CC) with a principal diagnosis of anxiety disorder other than SAD, and 39 healthy controls (HC) not meeting criteria for any current diagnosis. Analyses of covariance controlling for age were used to assess sympathetic and parasympathetic activation (preejection period and respiratory sinus arrhythmia) as well as cardiovascular (heart rate, mean arterial pressure, total peripheral resistance), respiratory (total breath time, minute ventilation, tidal volume, end-tidal CO(2) , respiratory variability), electrodermal, and self-report (anxiety, cognitions, symptoms) variables during baseline, 4-min separation from, and reunion with the mother. RESULTS Children with a diagnosis of SAD were characterized by elevated self-reported anxiety responses to separation and increased sympathetic reactivity compared with CC and HC groups. The SAD group also displayed greater vagal withdrawal and higher reactivity in multiple cardiovascular, respiratory, and electrodermal measures compared with the HC group, while corresponding responses were less in the CC group and not significantly different from the other groups. CONCLUSIONS Separation from the mother elicits greater autonomic, respiratory, and experiential responses in children with SAD. Our findings based on brief experimental separation demonstrate differential subjective and physiological manifestations of specific anxiety diagnoses, thus supporting the validity of the diagnostic category of SAD.

Oxytocin and Autism Spectrum Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Aim: Oxytocin presents an exciting potential to target the core symptoms of autism spectrum disorder (ASD) pharmacologically in an easily administered, cost-effective form with possibly minimal adverse effects. But, there are still major gaps in this area of research. This paper reviewed randomized controlled trials (RCTs) examining the effects of oxytocin administration on social cognition and restricted, repetitive behaviors in individuals with an ASD. Method: Electronic literature searches were conducted from PsycINFO, PubMed, Web of Knowledge, and EMBASE for RCTs published through June 2015. Results: 12 RCTs were included in this review. 7 out of the 11 studies that examined social cognition reported improvements. Additionally, one out of the 4 studies on restricted, repetitive behaviors, reported improvements following oxytocin administration. However, results from our meta-analyses suggest that oxytocin has no significant effect on these 2 domains. Conclusion: Previous evidence revealed mixed findings about the effects of oxytocin on ASD. Given the limited number of RCTs, our summary of findings on the effectiveness of oxytocin on ASD should still be considered tentative.

Efficacy and Safety of Selective Serotonin Reuptake Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors, and Placebo for Common Psychiatric Disorders Among Children and Adolescents: A Systematic Review and Meta-analysis

Importance Depressive disorders (DDs), anxiety disorders (ADs), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) are common mental disorders in children and adolescents. Objective To examine the relative efficacy and safety of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and placebo for the treatment of DD, AD, OCD, and PTSD in children and adolescents. Data Sources PubMed, EMBASE, PsycINFO, Web of Science, and Cochrane Database from inception through August 7, 2016. Study Selection Published and unpublished randomized clinical trials of SSRIs or SNRIs in youths with DD, AD, OCD, or PTSD were included. Trials using other antidepressants (eg, tricyclic antidepressants, monoamine oxidase inhibitors) were excluded. Data Extraction and Synthesis Effect sizes, calculated as standardized mean differences (Hedges g) and risk ratios (RRs) for adverse events, were assessed in a random-effects model. Main Outcomes and Measures Primary outcomes, as defined by authors on preintervention and postintervention data, mean change data, and adverse event data, were extracted independently by multiple observers following PRISMA guidelines. Results Thirty-six trials were eligible, including 6778 participants (3484 [51.4%] female; mean [SD] age, 12.9 [5.1] years); 17 studies for DD, 10 for AD, 8 for OCD, and 1 for PTSD. Analysis showed that SSRIs and SNRIs were significantly more beneficial compared with placebo, yielding a small effect size (g = 0.32; 95% CI, 0.25-0.40; P < .001). Anxiety disorder (g = 0.56; 95% CI, 0.40-0.72; P < .001) showed significantly larger between-group effect sizes than DD (g = 0.20; 95% CI, 0.13-0.27; P < .001). This difference was driven primarily by the placebo response: patients with DD exhibited significantly larger placebo responses (g = 1.57; 95% CI, 1.36-1.78; P < .001) compared with those with AD (g = 1.03; 95% CI, 0.84-1.21; P < .001). The SSRIs produced a relatively large effect size for ADs (g = 0.71; 95% CI, 0.45-0.97; P < .001). Compared with participants receiving placebo, patients receiving an antidepressant reported significantly more treatment-emergent adverse events (RR, 1.07; 95% CI, 1.01-1.12; P = .01 or RR, 1.49; 95% CI, 1.22-1.82; P < .001, depending on the reporting method), severe adverse events (RR, 1.76; 95% CI, 1.34-2.32; P < .001), and study discontinuation due to adverse events (RR, 1.79; 95% CI, 1.38-2.32; P < .001). Conclusions and Relevance Compared with placebo, SSRIs and SNRIs are more beneficial than placebo in children and adolescents; however, the benefit is small and disorder specific, yielding a larger drug-placebo difference for AD than for other conditions. Response to placebo is large, especially in DD. Severe adverse events are significantly more common with SSRIs and SNRIs than placebo.

Focusing on the adult attachment style in schizophrenia in community mental health centres: validation of the Psychosis Attachment Measure (PAM) in a German-speaking sample.

Background: Assessing attachment style in people with schizophrenia may be important to identify a risk factor in building a strong therapeutic relationship and so indirectly to understand the development of mal-compliance as one of the major obstacles in the treatment of schizophrenia. Aims: The present study analysed the psychometric properties of the German version of the Psychosis Attachment Measure (PAM), which assesses avoidant and anxious attachment style. Methods: A sample of 127 patients suffering from chronic schizophrenia or schizoaffective disorder participated in this study. In testing discriminant validity, we assessed psychopathology, depression, therapeutic relationship and service engagement. Internal consistency, test-retest reliability and factor structure were analysed. Results: The German version of PAM exhibited acceptable to good internal and test-retest reliabilities and the two-factor structure of the English version could be replicated. Avoidant attachment style was related to higher levels of positive symptoms and to a poorer therapeutic relationship. In the context of external validation, a regression analysis revealed that a poor therapeutic relationship correlated with avoidant attachment style, independent of anxious attachment style and depressive symptoms. Anxious attachment was associated with higher treatment adherence. Both insecure attachment styles (avoidant and anxious) were found to be correlated with higher levels of depression, but only attachment anxiety had an independent predictive value for self-reported depression in regression analysis. Conclusions: The German version of PAM displayed satisfactory psychometric properties and seems to be a reliable measure for assessing attachment style in individuals with schizophrenia. Validation of PAM led to the finding that only the avoidant attachment style might be a risk factor when building a strong therapeutic relationship in schizophrenia. In future studies, other factors influencing therapeutic relationship should be taken into account. Anxious attachment style may be a risk factor for depression, but it also has an enhancing effect on treatment adherence.

Trust in the health care professional and health outcome: A meta-analysis

Objective To examine whether patients’ trust in the health care professional is associated with health outcomes. Study selection We searched 4 major electronic databases for studies that reported quantitative data on the association between trust in the health care professional and health outcome. We screened the full-texts of 400 publications and included 47 studies in our meta-analysis. Data extraction and data synthesis We conducted random effects meta-analyses and meta-regressions and calculated correlation coefficients with corresponding 95% confidence intervals. Two interdependent researchers assessed the quality of the included studies using the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Results Overall, we found a small to moderate correlation between trust and health outcomes (r = 0.24, 95% CI: 0.19–0.29). Subgroup analyses revealed a moderate correlation between trust and self-rated subjective health outcomes (r = 0.30, 0.24–0.35). Correlations between trust and objective (r = -0.02, -0.08–0.03) as well as observer-rated outcomes (r = 0.10, -0.16–0.36) were non-significant. Exploratory analyses showed a large correlation between trust and patient satisfaction and somewhat smaller correlations with health behaviours, quality of life and symptom severity. Heterogeneity was small to moderate across the analyses. Conclusions From a clinical perspective, patients reported more beneficial health behaviours, less symptoms and higher quality of life and to be more satisfied with treatment when they had higher trust in their health care professional. There was evidence for upward bias in the summarized results. Prospective studies are required to deepen our understanding of the complex interplay between trust and health outcomes.

Is the rationale more important than deception? A randomized controlled trial of open-label placebo analgesia

Abstract Research on open-label placebos questions whether deception is a necessary characteristic of placebo effects. Yet, comparisons between open-label and deceptive placebos (DPs) are lacking. We therefore assessed effects of open-label placebos and DPs in comparison with no treatment (NT) with a standardized experimental heat pain paradigm in a randomized controlled trial in healthy participants. Participants (N = 160) were randomly assigned to NT, open-label placebo without rationale (OPR-), open-label placebo with rationale (OPR+), and DP. We conducted baseline and posttreatment measurements of heat pain threshold and tolerance. Apart from the NT, all groups received an application of a placebo cream. Primary outcomes were planned comparisons of heat pain tolerance and the corresponding intensity and unpleasantness ratings. Objective posttreatment pain tolerance did not differ among groups. However, for subjective heat pain ratings at the posttreatment tolerance level, groups with a rationale (OPR+ and DP) reported diminished heat pain intensity (t(146) = −2.15, P = 0.033, d = 0.43) and unpleasantness ratings (t(146) = −2.43, P = 0.016, d = 0.49) compared with the OPR-group. Interestingly, the OPR+ and the DP groups did not significantly differ in heat pain intensity (t(146) = −1.10, P = 0.272) or unpleasantness ratings (t(146) = −0.05, P = 0.961) at the posttreatment tolerance level. Our findings reveal that placebos with a plausible rationale are more effective than without a rationale. Even more, open-label placebos did not significantly differ in their effects from DPs. Therefore, we question the ubiquitously assumed necessity of concealment in placebo administration.

Immediate rescue designs in pediatric analgesic trials: a systematic review and meta-analysis.

Background:Designing analgesic clinical trials in pediatrics requires a balance between scientific, ethical, and practical concerns. A previous consensus group recommended immediate rescue designs using opioid sparing as a surrogate measure of analgesic efficacy. The authors summarize the performance of rescue analgesic designs in pediatric trials of four commonly used classes of analgesics: opioids, nonsteroidal antiinflammatory drugs, acetaminophen, and local anesthetics. Methods:MEDLINE, Embase, CINAHL, The Cochrane Library, and Web of science were searched in April 2013. The 85 studies selected were randomized or controlled clinical trials using immediate rescue paradigms in postoperative pain settings. A random-effects meta-analysis was used to synthesize predefined outcomes using Hedges’ g. Difference between the means of the treatment arms were also expressed as a percentage of the corresponding value in the placebo group (placebo-treatment/placebo). Distributions of pain scores in study and control groups and relationships between opioid sparing and pain scores were examined. Results:For each of the four study drug classes, significant opioid sparing was demonstrated in a majority of studies by one or more of the following endpoints: (1) total dose (milligram per kilogram per hour), (2) percentage of children requiring rescue medication, and (3) time to first rescue medication (minutes). Pain scores averaged 2.4/10 in study groups, 3.4/10 in control groups. Conclusions:Opioid sparing is a feasible pragmatic endpoint for pediatric pain analgesic trials. This review serves to guide future research in pediatric analgesia trials, which could test whether some specific design features may improve assay sensitivity while minimizing the risk of unrelieved pain.