Negative symptoms in the clinic: we treat what we can describe.

Recent research has led to important changes in the concepts and assessment of negative symptoms in schizophrenia. We review current negative symptom concepts and their clinical implications, as well as new methods of assessing these symptoms. These changes hold promise for improving our understanding and treatment of negative symptoms.

Reduced willingness to expend effort for rewards is associated with risk for conversion and negative symptom severity in youth at clinical high-risk for psychosis.

BACKGROUND: Schizophrenia (SZ) is typically preceded by a prodromal (i.e. pre-illness) period characterized by attenuated positive symptoms and declining functional outcome. Negative symptoms are prominent among individuals at clinical high-risk (CHR) for psychosis (i.e. those with prodromal syndromes) and predictive of conversion to illness. Mechanisms underlying negative symptoms are unclear in the CHR population. METHODS: The current study evaluated whether CHR participants demonstrated deficits in the willingness to expend effort for rewards and whether these impairments are associated with negative symptoms and greater risk for conversion. Participants included 44 CHR participants and 32 healthy controls (CN) who completed the Effort Expenditure for Reward Task (EEfRT). RESULTS: Compared to CN, CHR participants displayed reduced likelihood of exerting high effort for high probability and magnitude rewards. Among CHR participants, reduced effort expenditure was associated with greater negative symptom severity and greater probability of conversion to a psychotic disorder on a cross-sectional risk calculator. CONCLUSIONS: Findings suggest that effort-cost computation is a marker of illness liability and a transphasic mechanism underlying negative symptoms in the SZ spectrum.

Efficacy of a transdiagnostic, prevention-focused program for at-risk young adults: a waitlist-controlled trial.

BACKGROUND: Prevention programs that are 'transdiagnostic' may be more cost-effective and beneficial, in terms of reducing levels of psychopathology in the general population, than those focused on a specific disorder. This randomized controlled study evaluated the efficacy of one such intervention program called Resilience Training (RT). METHODS: College students who reported mildly elevated depressive or subclinical psychotic symptoms ('psychotic experiences' (PEs)) (n = 107) were randomized to receiving RT (n = 54) or to a waitlist control condition (n = 53). RT consists of a four-session intervention focused on improving resilience through the acquisition of mindfulness, self-compassion, and mentalization skills. Measures of symptoms and these resilience-enhancing skills were collected before and after the 4-week RT/waitlist period, with a follow-up assessment 12-months later. RESULTS: Compared to the waitlist control group, RT participants reported significantly greater reductions in PEs, distress associated with PEs, depression, and anxiety, as well as significantly greater improvements in resilience, mindfulness, self-compassion, and positive affect, following the 4-week RT/waitlist period (all p < 0.03). Moreover, improvements in resilience-promoting skills were significantly correlated with symptom reductions (all p < 0.05). Lastly, the RT-related reductions in PEs and associated distress were maintained at the 12-month follow-up assessment. CONCLUSIONS: RT is a brief, group-based intervention associated with improved resilience and reduced symptoms of psychopathology, with sustained effects on PEs, in transdiagnostically at-risk young adults. Follow-up studies can further assess the efficacy of RT relative to other interventions and test whether it can reduce the likelihood of developing a serious mental illness.

Environmental context predicts state fluctuations in negative symptoms in youth at clinical high risk for psychosis.

BACKGROUND: Negative symptoms (avolition, anhedonia, asociality) are a prevalent symptom in those across the psychosis-spectrum and also occur at subclinical levels in the general population. Recent work has begun to examine how environmental contexts (e.g. locations) influence negative symptoms. However, limited work has evaluated how environments may contribute to negative symptoms among youth at clinical high risk for psychosis (CHR). The current study uses Ecological Momentary Assessment to assess how four environmental contexts (locations, activities, social interactions, social interaction method) impact state fluctuations in negative symptoms in CHR and healthy control (CN) participants. METHODS: CHR youth (n = 116) and CN (n = 61) completed 8 daily surveys for 6 days assessing negative symptoms and contexts. RESULTS: Mixed-effects modeling demonstrated that negative symptoms largely varied across contexts in both groups. CHR participants had higher negative symptoms than CN participants in most contexts, but groups had similar symptom reductions during recreational activities and phone call interactions. Among CHR participants, negative symptoms were elevated in several contexts, including studying/working, commuting, eating, running errands, and being at home. CONCLUSIONS: Results demonstrate that negative symptoms dynamically change across some contexts in CHR participants. Negative symptoms were more intact in some contexts, while other contexts, notably some used to promote functional recovery, may exacerbate negative symptoms in CHR. Findings suggest that environmental factors should be considered when understanding state fluctuations in negative symptoms among those at CHR participants.

Global reward processing deficits predict negative symptoms transdiagnostically and transphasically in a severe mental illness-spectrum sample.

Reward processing impairments are a key factor associated with negative symptoms in those with severe mental illnesses. However, past findings are inconsistent regarding which reward processing components are impaired and most strongly linked to negative symptoms. The current study examined the hypothesis that these mixed findings may be the result of multiple reward processing pathways (i.e., equifinality) to negative symptoms that cut across diagnostic boundaries and phases of illness. Participants included healthy controls (n = 100) who served as a reference sample and a severe mental illness-spectrum sample (n = 92) that included psychotic-like experiences, clinical high-risk for psychosis, bipolar disorder, and schizophrenia participants. All participants completed tasks measuring four RDoC Positive Valence System constructs: value representation, reinforcement learning, effort-cost computation, and hedonic reactivity. A k-means cluster analysis of the severe mental illness-spectrum samples identified three clusters with differential reward processing profiles that were characterized by: (1) global reward processing deficits (22.8%), (2) selective impairments in hedonic reactivity alone (40.2%), and (3) preserved reward processing (37%). Elevated negative symptoms were only observed in the global reward processing cluster. All clusters contained participants from each clinical group, and the distribution of these groups did not significantly differ among the clusters. Findings identified one pathway contributing to negative symptoms that was transdiagnostic and transphasic. Future work further characterizing divergent pathways to negative symptoms may help to improve symptom trajectories and personalized treatments.

Network analysis of discrete emotional states measured via ecological momentary assessment in schizophrenia.

Prior studies demonstrate that schizophrenia (SZ) is associated with abnormalities in positive and negative emotional experience that predict clinical presentation. However, it is unclear whether specific discrete emotions within the broader positive/negative categories are driving those symptom associations. Further, it is also unclear whether specific emotions contribute to symptoms in isolation or via networks of emotional states that dynamically interact across time. The current study used network analysis to evaluate temporally dynamic interactions among discrete emotional states experienced in the real world as assessed via Ecological Momentary Assessment (EMA). Participants included 46 outpatients with chronic SZ and 52 demographically matched healthy controls (CN) who completed 6 days of EMA that captured reports of emotional experience and symptoms derived from monetary surveys and geolocation based symptom markers of mobility and home location. Results indicated that less dense emotion networks were associated with greater severity of negative symptoms, whereas more dense emotion networks were associated with more severe positive symptoms and mania. Additionally, SZ evidenced greater centrality for shame, which was associated with greater severity of positive symptoms. These findings suggest that positive and negative symptoms are associated with distinct profiles of temporally dynamic and interactive emotion networks in SZ. Findings have implications for adapting psychosocial therapies to target specific discrete emotional states in the treatment of positive versus negative symptoms.

Negative Schizotypy Mediates the Relationship Between Metacognition and Social Functioning in a Nonclinical Sample.

ABSTRACT: Reduced metacognitive abilities-difficulty making sense of and understanding oneself and others-have been found to be key predictors of social functioning across a range of clinical and nonclinical groups. However, the exact processes through which metacognition impacts social functioning are unclear. This study examined whether subclinical negative symptoms mediated the relationship between metacognition and social functioning in a nonclinical sample of young adults (n = 98). Results demonstrated that lower metacognitive mastery was found to be uniquely associated with greater subclinical negative symptoms, whereas higher subclinical negative symptoms were associated with reduced social functioning. Further, the effects of lower metacognition on reduced social function were mediated by subclinical negative symptoms and not positive or disorganized subclinical symptoms. Results suggest that subclinical negative symptoms may link reductions in metacognition with social functioning in nonclinical samples. Training aimed at enhancing metacognition may support normative social functioning in the general population.

Return to Activity After Arthroscopically Assisted Triangular Fibrocartilage Complex Repair: A Systematic Review.

OBJECTIVE: To evaluate patients' ability to return to preinjury activity level after arthroscopically assisted triangular fibrocartilage complex (TFCC) repair. DATA SOURCES: The PubMed electronic library was systematically searched from inception to August 2021 for any eligible articles using a combination of the phrases "TFCC," "return to sport," "return to work," and "athlete." RESULTS: Studies that evaluated patients who had undergone arthroscopic repair of isolated TFCC injury and reported objective or patient-reported outcome measures were included. Fifteen studies representing 478 patients fulfilled the inclusion criteria. An average of 84% of patients were able to fully return to their previous work or sport activities. Most studies reported that range of motion (ROM) and grip strength (GS) both returned to >90% of the contralateral side, and every study that evaluated pain levels found a significant reduction in pain postoperatively. Mayo Modified Wrist Score was reported as excellent or good in 83% of patients, and the average Disabilities of the Arm, Shoulder, and Hand score was 13.8 postoperatively. CONCLUSION: Patients were able to return to their previous work or sport activities at a high rate after TFCC repair, even those participating in more strenuous activities. Measurable functional outcomes of ROM and GS were also reliably restored to near preinjury levels. Patient-reported outcomes of pain and disability were similarly improved after TFCC repair. Current literature has established the long-term success of TFCC repair but is lacking in evaluation of the time points at which patients can expect functional status to be restored.

A Critical Assessment of the Transgender Health Care Workforce in the United States and the Capacity to Deliver Gender-Affirming Bottom Surgery.

BACKGROUND: Gender-affirming surgery is a critical component of transgender health care, but access information is limited. The study aim was to assess workforce capacity to perform gender affirming bottom surgeries (GABSs) in the United States. METHODS: A questionnaire was administered via email, phone call, or fax from February to May 2020 to 86 practices identified as performing GABS by searching 10 Web-based databases with standardized keywords. Questions assessed training capacity, surgical capacity, and surgeon experience. RESULTS: Thirty-two of 86 practices responded, 20 met the inclusion criteria. Practices were identified in 15 states, with an average 2.4 (SD, 1.3) surgeons performing GABS per year. States with the greatest number of total providers offering GABS were Illinois (n = 21), Texas (n = 10), and Massachusetts (n = 13). No significant correlation between number of GABS types offered and geographic population density (r = -0.40, P = 0.08), or between number of providers and geographic population density (r = 0.19, P = 0.44). Vaginoplasty was most frequently performed, with the longest waitlists and highest number of waitlist additions per month. Phalloplasty was the second most common procedure, and waitlist additions per month exceeded provider capacity to perform the procedure. Most surgeons performing GABS were plastic surgeons and urologists, whereas obstetricians/gynecologists performed the majority of hysterectomies. CONCLUSIONS: This study demonstrated a shortage of providers with requisite training and experience to provide GABS. Although more robust studies are needed to better characterize the relationship between the number of patients seeking GABS and available providers, these findings indicate a need for improved training.

Dynamic relationships between emotional distress, persecutory ideation, and metacognition in schizophrenia.

OBJECTIVE: Determine whether metacognitive capacity (i.e., a range of abilities that involve recognition, reflection, and integration of mental states) influences the relationships between emotional distress and persecutory ideation (PI). METHODS: The present study examined emotional distress, metacognition and PI in a sample (n = 337) of individuals with schizophrenia or schizoaffective disorder and clinician-rated PI. Pearson and partial correlations were used to examine relationships between variables, as well as between-subjects analysis of variances to compare groups characterized based on emotional distress and persecutory ideation scores. RESULTS: While emotional distress and PI are associated with one another, metacognition is negatively associated with PI and positively associated with emotional distress. Subgroup comparisons demonstrated that individuals with high emotional distress and low PI had significantly higher metacognitive capacity than those elevated in PI or reduced in both emotional distress and PI. CONCLUSIONS: Findings suggest metacognitive capacity may relate to improved awareness of distress and reduced PI.

Quantitative assessment of carotid plaque morphology (geometry and tissue composition) using computed tomography angiography.

OBJECTIVE: Quantification of carotid plaque morphology (geometry and tissue composition) may help stratify risk for future stroke and assess plaque progression or regression in response to medical risk factor modification. We assessed the feasibility and reliability of morphologic measurements of carotid plaques using computed tomography angiography (CTA) and determined the minimum detectable change in plaque features by this approach. METHODS: CTA images of both carotid arteries in 50 patients were analyzed by two observers using a semiautomatic image analysis program, yielding 93 observations per user (seven arteries were excluded because of prior stenting). One observer repeated the analyses 4 weeks later. Measurements included total plaque volume; percentage stenosis (by diameter and area); and tissue composition for calcium, lipid-rich necrotic core (LRNC), and intraplaque hemorrhage (IPH). Reliability of measurements was assessed by intraclass and interclass correlation and Bland-Altman plots. Dice similarity coefficient (DSC) and modified Hausdorff distance (MHD) assessed reliability of geometric shape measurements. We additionally computed the minimum amount of change in these features detectable by our approach. RESULTS: The cohort was 51% male (mean age, 70.1 years), and 56% had a prior stroke. The mean (± standard deviation) plaque volume was 837.3 ± 431.3 mm3, stenosis diameter was 44.5% ± 25.6%, and stenosis area was 58.1% ± 29.0%. These measurements showed high reliability. Intraclass correlation coefficients for plaque volume, percentage stenosis by diameter, and percentage stenosis by area were 0.96, 0.87, and 0.83, respectively; interclass correlation coefficients were 0.88, 0.84, and 0.78. Intraclass correlations for tissue composition were 0.99, 0.96, and 0.86 (calcium, LRNC, and IPH, respectively), and interclass correlations were 0.99, 0.92, and 0.92. Shape measurements showed high intraobserver (DSC, 0.95 ± 0.04; MHD, 0.16 ± 0.10 mm) and interobserver (DSC, 0.94 ± 0.05; MHD, 0.19 ± 0.12 mm) luminal agreement. This approach can detect a change of at least 3.9% in total plaque volume, 1.2 mm3 in calcium, 4.3 mm3 in LRNC, and 8.6 mm3 in IPH with the same observer repeating measurements and 9.9% in plaque volume, 1.9 mm3 in calcium, 7.9 mm3 in LRNC, and 6.8 mm3 in IPH for two different observers. CONCLUSIONS: Carotid plaque geometry (total volume, diameter stenosis, and area stenosis) and tissue composition (calcium, LRNC, and IPH) are measured reliably from clinical CTA images using a semiautomatic image analysis program. The minimum change in plaque volume detectable is ∼4% if the same observer makes both measurements and ∼10% for different observers. Small changes in plaque composition can also be detected reliably. This approach can facilitate longitudinal studies for identifying high-risk plaque features and for quantifying plaque progression or regression after treatment.

A Comparative Effectiveness Trial to Reduce Burnout and Improve Quality of Care.

Clinician burnout is presumed to negatively impact healthcare quality; yet scant research has rigorously addressed this hypothesis. Using a mixed-methods, randomized, comparative effectiveness design, we tested two competing approaches to improve care-one addressing clinician burnout and the other addressing how clinicians interact with consumers-with 192 clinicians and 469 consumers at two community mental health centers. Although qualitative reports were promising, we found no comparative effectiveness for either intervention on burnout, patient-centered processes, or other outcomes. Discussion includes identifying ways to strengthen approaches to clinician burnout.

The Relationship Between Professional Burnout and Quality and Safety in Healthcare: A Meta-Analysis.

BACKGROUND: Healthcare provider burnout is considered a factor in quality of care, yet little is known about the consistency and magnitude of this relationship. This meta-analysis examined relationships between provider burnout (emotional exhaustion, depersonalization, and reduced personal accomplishment) and the quality (perceived quality, patient satisfaction) and safety of healthcare. METHODS: Publications were identified through targeted literature searches in Ovid MEDLINE, PsycINFO, Web of Science, CINAHL, and ProQuest Dissertations & Theses through March of 2015. Two coders extracted data to calculate effect sizes and potential moderators. We calculated Pearson's r for all independent relationships between burnout and quality measures, using a random effects model. Data were assessed for potential impact of study rigor, outliers, and publication bias. RESULTS: Eighty-two studies including 210,669 healthcare providers were included. Statistically significant negative relationships emerged between burnout and quality (r = -0.26, 95 % CI [-0.29, -0.23]) and safety (r = -0.23, 95 % CI [-0.28, -0.17]). In both cases, the negative relationship implied that greater burnout among healthcare providers was associated with poorer-quality healthcare and reduced safety for patients. Moderators for the quality relationship included dimension of burnout, unit of analysis, and quality data source. Moderators for the relationship between burnout and safety were safety indicator type, population, and country. Rigor of the study was not a significant moderator. DISCUSSION: This is the first study to systematically, quantitatively analyze the links between healthcare provider burnout and healthcare quality and safety across disciplines. Provider burnout shows consistent negative relationships with perceived quality (including patient satisfaction), quality indicators, and perceptions of safety. Though the effects are small to medium, the findings highlight the importance of effective burnout interventions for healthcare providers. Moderator analyses suggest contextual factors to consider for future study.

Metacognition Is Necessary for the Emergence of Motivation in People With Schizophrenia Spectrum Disorders: A Necessary Condition Analysis.

Metacognition deficits are a putative cause of reduced motivation in people with schizophrenia spectrum disorders. However, it is unclear whether certain levels of metacognition are necessary for motivation to emerge. This study used a Necessary Condition Analysis to test whether metacognition was necessary for the presence of motivation and to identify the minimum level of metacognition necessary for high motivation to be possible in people with schizophrenia spectrum disorders (N = 175). Participants completed clinician-rated measures of metacognition and motivation. Necessary Condition Analysis revealed that metacognition is a necessary condition for motivation and that high levels of motivation were only possible, although not guaranteed, when at least a basic level of metacognition was present. The findings suggest that metacognition is a necessary building block for the development of motivation. Results suggest that targeting metacognition may be essential for improving motivation among people with schizophrenia spectrum disorders who do not meet this metacognition threshold.

Additional support for the cognitive model of schizophrenia: evidence of elevated defeatist beliefs in schizotypy.

OBJECTIVES: The cognitive model of poor functioning in schizophrenia posits that defeatist performance beliefs-overgeneralized negative beliefs about one's ability to perform tasks-develop prior to the onset of psychosis and contribute to the development and maintenance of negative symptoms and poor functioning. Although several studies with schizophrenia samples have provided support for the model, there is a paucity of research investigating these beliefs in individuals with schizotypy-those exhibiting traits reflecting a putative genetic liability for schizophrenia. This study had two aims: to examine whether defeatist performance beliefs (1) are elevated in schizotypy compared to controls and (2) are associated with decreased quality of life and working memory and increased negative but not positive schizotypy traits in the schizotypy group. METHODS: Schizotypy (n=48) and control (n=53) groups completed measures of schizotypy traits, defeatist performance beliefs, quality of life, and working memory. RESULTS: Analyses revealed that the schizotypy group reported significantly more defeatist performance beliefs than the control group. Within the schizotypy group, increased defeatist performance beliefs were significantly associated with greater negative schizotypy traits and lower quality of life. No significant associations were observed between defeatist performance beliefs and positive schizotypy traits and working memory. CONCLUSIONS: Results generally support the theoretical validity of the cognitive model of poor functioning in schizophrenia and suggest that elevated defeatist performance beliefs may contribute to the manifestation of subclinical negative symptom traits and reduced quality of life among those with a latent vulnerability for schizophrenia.

The Role of Metacognitive Self-Reflectivity in Emotional Awareness and Subjective Indices of Recovery in Schizophrenia.

Emotional awareness deficits in people with schizophrenia have been linked to poorer objective outcomes, but no work has investigated the relationship between emotional awareness and subjective recovery indices or metacognitive self-reflectivity. The authors hypothesized that increased emotional awareness would be associated with greater self-esteem, hope, and self-reflectivity and that self-reflectivity would moderate links between emotional awareness and self-esteem and hope-such that significant relationships would only be observed at lower levels of self-reflectivity. Participants were 56 people with schizophrenia spectrum disorders. Correlations revealed that better emotional awareness was significantly associated with increased self-esteem and hope but not self-reflectivity. Self-reflectivity moderated the relationship between emotional awareness and self-esteem but not hope. Overall, findings suggest that emotional awareness may affect self-esteem for those low in self-reflectivity, but other factors may be important for those with greater self-reflectivity. Results emphasize the importance of interventions tailored to enhance self-reflective capacity in clients with schizophrenia.

Theory of Mind in Schizophrenia: Associations With Clinical and Cognitive Insight Controlling for Levels of Psychopathology.

Poor insight in schizophrenia is a risk factor for both poor outcomes and treatment adherence. Accordingly, interest in identifying causes of poor insight has increased. This study explored whether theory of mind (ToM) impairments are linked to poor clinical and cognitive insight independent of psychopathology. Participants with schizophrenia (n = 37) and control subjects (n = 40) completed assessments of ToM with the Hinting Task and the Brüne Picture Sequencing Task, clinical insight and psychopathology with the Positive and Negative Syndrome Scale, and cognitive insight with the Beck Cognitive Insight Scale. Results indicated that the schizophrenia group had greater impairments in ToM relative to control subjects. In the schizophrenia group, the Hinting Task performance was related to both cognitive and clinical insight, with only the relationship with cognitive insight persisting after controlling for psychopathology. Picture Sequencing Task performance was related to cognitive insight only. Future research directions and clinical implications are discussed.

Intrinsic motivation as a mediator between metacognition deficits and impaired functioning in psychosis.

OBJECTIVE: Poor functioning has long been observed in individuals with psychosis. Recent studies have identified metacognition - one's ability to form complex ideas about oneself and others and to use that information to respond to psychological and social challenges-as being an important determinant of functioning. However, the exact process by which deficits in metacognition lead to impaired functioning remains unclear. This study first examined whether low intrinsic motivation, or the tendency to pursue novel experiences and to engage in self-improvement, mediates the relationship between deficits in metacognition and impaired functioning. We then examined whether intrinsic motivation significantly mediated the relationship when controlling for age, education, symptoms, executive functioning, and social cognition. DESIGN: Mediation models were examined in a cross-sectional data set. METHODS: One hundred and seventy-five individuals with a psychotic disorder completed interview-based measures of metacognition, intrinsic motivation, symptoms, and functioning and performance-based measures of executive functioning and social cognition. RESULTS: Analyses revealed that intrinsic motivation mediated the relationship between metacognition deficits and impaired functioning (95% CI of indirect effect [0.12-0.43]), even after controlling for the aforesaid variables (95% CI of indirect effect [0.04-0.29]). CONCLUSIONS: Results suggest that intrinsic motivation may be a mechanism that underlies the link between deficits in metacognition and impaired functioning and indicate that metacognition and intrinsic motivation may be important treatment targets to improve functioning in individuals with psychosis. PRACTITIONER POINTS: The findings of this study suggest that deficits in metacognition may indirectly lead to impaired functioning through their effect on intrinsic motivation in individuals with psychosis. Psychological treatments that target deficits in both metacognition and intrinsic motivation may help to alleviate impaired functioning in individuals with psychosis. LIMITATIONS: The cross-sectional design of this study is a limitation, and additional longitudinal studies are needed to confirm the direction of the findings and rule out rival hypotheses. Generalization of the findings may be limited by the sample composition. It may be that different relationships exist between metacognition, intrinsic motivation, and functioning in those with early psychosis or among those in an acute phase or who decline treatment.

The "Critical" Elements of Illness Management and Recovery: Comparing Methodological Approaches.

This study examined three methodological approaches to defining the critical elements of Illness Management and Recovery (IMR), a curriculum-based approach to recovery. Sixty-seven IMR experts rated the criticality of 16 IMR elements on three dimensions: defining, essential, and impactful. Three elements (Recovery Orientation, Goal Setting and Follow-up, and IMR Curriculum) met all criteria for essential and defining and all but the most stringent criteria for impactful. Practitioners should consider competence in these areas as preeminent. The remaining 13 elements met varying criteria for essential and impactful. Findings suggest that criticality is a multifaceted construct, necessitating judgments about model elements across different criticality dimensions.

Metacognitive Deficits in Schizophrenia: Presence and Associations With Psychosocial Outcomes.

Early formulations of schizophrenia suggested that the disorder involves a loss of ability to form integrated ideas about oneself, others, and the world, resulting in reductions in complex goal-directed behaviors. Exploring this position, the current review describes evidence that persons with schizophrenia experience decrements in their ability to form complex ideas about themselves and to ultimately use that knowledge to respond to psychological and social challenges. Studies are detailed that find greater levels of these impairments, defined as metacognitive deficits, in persons with schizophrenia in both early and later phases of illness as compared with other clinical and community groups. Furthermore, studies linking metacognitive deficits with poorer psychosocial functioning and other variables closely linked to outcomes are summarized. Clinical implications are also discussed.