Effect of a Nurse-Led Preventive Psychological Intervention on Symptoms of Posttraumatic Stress Disorder Among Critically Ill Patients: A Randomized Clinical Trial.

Importance: A meta-analysis of outcomes during the 6 months after intensive care unit (ICU) discharge indicate a prevalence for clinically important posttraumatic stress disorder (PTSD) symptoms of 25%. Objective: To determine whether a nurse-led preventive, complex psychological intervention, initiated in the ICU, reduces patient-reported PTSD symptom severity at 6 months. Design, Setting, and Participants: A multicenter, parallel-group, cluster-randomized clinical trial with integrated economic and process evaluations conducted in 24 ICUs in the United Kingdom. Participants were critically ill patients who regained mental capacity following receipt of level 3 (intensive) care. A total of 2961 eligible patients were identified from September 2015 to January 2017. A total of 2048 were approached for participation in the ICU, of which 1458 provided informed consent. Follow-up was completed December 2017. Interventions: Twenty four ICUs were randomized 1:1 to the intervention or control group. Intervention ICUs (n = 12; 669 participants) delivered usual care during a baseline period followed by an intervention period. The preventive, complex psychological intervention comprised promotion of a therapeutic ICU environment plus 3 stress support sessions and a relaxation and recovery program delivered by trained ICU nurses to high-risk (acutely stressed) patients. Control ICUs (n = 12; 789 participants) delivered usual care in both baseline and intervention periods. Main Outcomes and Measures: The primary clinical outcome was PTSD symptom severity among survivors at 6 months measured using the PTSD Symptom Scale-Self-Report questionnaire (score range, 0-51, with higher scores indicating greater symptom severity; the minimal clinically important difference was considered to be 4.2 points). Results: Among 1458 enrolled patients (mean [SD] age, 58 [16] years; 599 women [41%]), 1353 (93%) completed the study and were included in the final analysis. At 6 months, the mean PTSD Symptom Scale-Self-Report questionnaire score in intervention ICUs was 11.8 (baseline period) compared with 11.5 (intervention period) (difference, -0.40 [95% CI, -2.46 to 1.67]) and in control ICUs, 10.1 (baseline period) compared with 10.2 (intervention period) (difference, 0.06 [95% CI, -1.74 to 1.85]) between periods. There was no significant difference in PTSD symptom severity at 6 months (treatment effect estimate [difference in differences] of -0.03 [95% CI, -2.58 to 2.52]; P = .98). Conclusions and Relevance: Among critically ill patients in the ICU, a nurse-led preventive, complex psychological intervention did not significantly reduce patient-reported PTSD symptom severity at 6 months. These findings do not support the use of this psychological intervention. Trial Registration: ISRCTN53448131.

Models of Peer Support to Remediate Post-Intensive Care Syndrome: A Report Developed by the Society of Critical Care Medicine Thrive International Peer Support Collaborative.

OBJECTIVES: Patients and caregivers can experience a range of physical, psychologic, and cognitive problems following critical care discharge. The use of peer support has been proposed as an innovative support mechanism. DESIGN: We sought to identify technical, safety, and procedural aspects of existing operational models of peer support, among the Society of Critical Care Medicine Thrive Peer Support Collaborative. We also sought to categorize key distinctions between these models and elucidate barriers and facilitators to implementation. SUBJECTS AND SETTING: Seventeen Thrive sites from the United States, United Kingdom, and Australia were represented by a range of healthcare professionals. MEASUREMENTS AND MAIN RESULTS: Via an iterative process of in-person and email/conference calls, members of the Collaborative defined the key areas on which peer support models could be defined and compared, collected detailed self-reports from all sites, reviewed the information, and identified clusters of models. Barriers and challenges to implementation of peer support models were also documented. Within the Thrive Collaborative, six general models of peer support were identified: community based, psychologist-led outpatient, models-based within ICU follow-up clinics, online, groups based within ICU, and peer mentor models. The most common barriers to implementation were recruitment to groups, personnel input and training, sustainability and funding, risk management, and measuring success. CONCLUSIONS: A number of different models of peer support are currently being developed to help patients and families recover and grow in the postcritical care setting.

Intrusive memories of hallucinations and delusions in traumatized intensive care patients: An interview study.

OBJECTIVE: Psychological morbidity, including post-traumatic stress disorder (PTSD), is common in survivors of intensive care. Intrusive memories of trauma are important symptoms of PTSD. Research has not established which aspects of intensive care are most traumatizing; invasive medical procedures, fear of dying from life-threatening illness or injury, or effects of psychoactive drugs, including hallucinations and delusions. Our study aimed to investigate the roots of post-intensive care trauma by interviewing survivors with symptoms of PTSD. Were their intrusive memories primarily of real events or hallucinations and delusions from intensive care? DESIGN: Interview study as part of a mixed-methods investigation of psychological outcomes post-intensive care. METHODS: We used purposive sampling to identify patients with intrusive memories of intensive care unit. Detailed interviews were conducted to investigate the nature and content of post-intensive care memories. Intrusive memories were categorized as factual, hallucinatory/delusional, or uncertain. RESULTS: Thematic saturation was achieved after 17 interviews. Approximately 70% (12/17) of patients had hallucinatory/delusional intrusive memories of intensive care, while 12% (2/17) had factual but no hallucinatory/delusional memories; 18% (3) were uncertain whether memories were factual or hallucinatory/delusional. Further analysis suggested that 88% of all patients had hallucinatory/delusional intrusive memories. The content of intrusive memories commonly merged realistic events (involving intensive care staff, environment, medical procedures and unpleasant physical experiences) with delusions and frightening hallucinations. CONCLUSIONS: We found that patients in this in-depth study were more traumatized by frightening hallucinations/delusions than real events, suggesting they may have post-psychosis PTSD, rather than classic PTSD. Interventions are needed to diagnose and treat intensive care hallucinations/delusions, or minimize effects, to prevent PTSD.

Detecting acute distress and risk of future psychological morbidity in critically ill patients: validation of the intensive care psychological assessment tool.

INTRODUCTION: The psychological impact of critical illness on a patient can be severe, and frequently results in acute distress as well as psychological morbidity after leaving hospital. A UK guideline states that patients should be assessed in critical care units, both for acute distress and risk of future psychological morbidity; but no suitable method for carrying out this assessment exists. The Intensive care psychological assessment tool (IPAT) was developed as a simple, quick screening tool to be used routinely to detect acute distress, and the risk of future psychological morbidity, in critical care units. METHODS: A validation study of IPAT was conducted in the critical care unit of a London hospital. Once un-sedated, orientated and alert, critical care patients were assessed with the IPAT and validated tools for distress, to determine the IPAT's concurrent validity. Fifty six patients took IPAT again to establish test-retest reliability. Finally, patients completed posttraumatic stress disorder (PTSD), depression and anxiety questionnaires at three months, to determine predictive validity of the IPAT. RESULTS: One hundred and sixty six patients completed the IPAT, and 106 completed follow-up questionnaires at 3 months. Scale analysis showed IPAT was a reliable 10-item measure of critical care-related psychological distress. Test-retest reliability was good (r =0.8). There was good concurrent validity with measures of anxiety and depression (r =0.7, P <0.01; r =0.6, P <0.01). With a cut-point of ≥7, the IPAT had 82% sensitivity and 65% specificity to detect concurrent anxiety; and 80% sensitivity and 66% specificity to detect concurrent low mood (area under the curve (AUC) =0.8 for both). Predictive validity for psychological morbidity was good (r =0.4, P <0.01; r =0.64, P <0.01 for PTSD with days 1 and 2 data). The IPAT had 69% specificity and 57% sensitivity to predict future psychological morbidity (AUC =0.7). CONCLUSIONS: The IPAT was found to have good reliability and validity. Sensitivity and specificity analysis suggest the IPAT could provide a way of allowing staff to assess psychological distress among critical care patients after further replication and validation. Further work is also needed to determine its utility in predicting future psychological morbidity.

The effect of intravenous interferon-beta-1a (FP-1201) on lung CD73 expression and on acute respiratory distress syndrome mortality: an open-label study.

BACKGROUND: Pulmonary vascular leakage occurs early in acute respiratory distress syndrome (ARDS). Mortality is high (35-45%), but no effective pharmacotherapy exists. Production of anti-inflammatory adenosine by ecto-5'-nucleotidase (CD73) helps maintain endothelial barrier function. We tested whether interferon-beta-1a (IFN-beta-1a), which increases CD73 synthesis, can reduce vascular leakage and mortality in patients with ARDS. METHODS: In ex-vivo studies, we first established that IFN-beta-1a induced CD73 up-regulation in cultured human lung tissue samples. We then tested the safety, tolerability, and efficacy of intravenous human recombinant IFN-beta-1a (FP-1201) in patients with ARDS in an open-label study (comprising dose-escalation and expansion phases). We recruited patients from eight intensive care units in the UK. Eligible patients were aged 18 years or older, had ARDS, and were being treated with assisted ventilation. We established an optimal tolerated dose (OTD) in the first, dose-escalation phase. Once established, we gave all subsequently enrolled patients the OTD of intravenous FP-1201 for 6 days. We assessed 28-day mortality (our primary endpoint) in all patients receiving the OTD versus 28-day mortality in a group of patients who did not receive treatment (this control group comprised patients in the study but who did not receive treatment because they were screened during the safety windows after dose escalation). This trial is registered with ClinicalTrials.gov, number NCT00789685, and the EU Clinical Trials Register EudraCT, number 2008-000140-13. FINDINGS: IFN-beta-1a increased the number of CD73-positive vessels in lung culture by four times on day 1 (p=0·04) and by 14·3 times by day 4 (p=0·004). For the clinical trial, between Feb 23, 2009, and April 7, 2011, we identified 150 patients, of whom 37 were enrolled into the trial and given treatment. The control group consisted of 59 patients who were recruited to take part in the study, but who did not receive treatment. Demographic characteristics and severity of illness did not differ between treatment and control groups. The optimal tolerated FP-1201 dose was 10 µg per day for 6 days. By day 28, 3 (8%) of 37 patients in the treatment cohort and 19 (32%) of 59 patients in the control cohort had died-thus, treatment with FP-1201 was associated with an 81% reduction in odds of 28-day mortality (odds ratio 0·19 [95% CI 0·03-0·72]; p=0·01). INTERPRETATION: FP-1201 up-regulates human lung CD73 expression, and is associated with a reduction in 28-day mortality in patients with ARDS. Our findings need to be substantiated in large, prospective randomised trials, but suggest that FP-1201 could be the first effective, mechanistically targeted, disease-specific pharmacotherapy for patients with ARDS.

Improved intensive care unit survival for critically ill allogeneic haematopoietic stem cell transplant recipients following reduced intensity conditioning.

The use of allogeneic haematopoietic stem cell transplantation (Allo-HSCT) is a standard treatment option for many patients with haematological malignancies. Historically, patients requiring intensive care unit (ICU) admission for transplant-related toxicities have fared extremely poorly, with high ICU mortality rates. Little is known about the impact of reduced intensity Allo-HSCT conditioning regimens in older patients on the ICU and subsequent long-term outcomes. A retrospective analysis of data collected from 164 consecutive Allo-HSCT recipients admitted to ICU for a total of 213 admissions, at a single centre over an 11·5-year study period was performed. Follow-up was recorded until 31 March 2011. Autologous HSCT recipients were excluded. In this study we report favourable ICU survival following Allo-HSCT and, for the first time, demonstrate significantly better survival for patients who underwent Allo-HSCT with reduced intensity conditioning compared to those treated with myeloablative conditioning regimens. In addition, we identified the need for ventilation (invasive or non-invasive) as an independently significant adverse factor affecting short-term ICU outcome. For patients surviving ICU admission, subsequent long-term overall survival was excellent; 61% and 51% at 1 and 5 years, respectively. Reduced intensity Allo-HSCT patients admitted to ICU with critical illness have improved survival compared to myeloablative Allo-HSCT recipients.

Medication issues experienced by patients and carers after discharge from the intensive care unit.

PURPOSE: Medication-related problems (MRPs) frequently occur at the interfaces of care settings. We examined this further because little has been published about MRPs experienced by patients/carers after discharge from the intensive care unit (ICU). METHODS AND MATERIALS: Medication history data were collected before, during, and after ICU admission and by face-to-face semistructured interviews with 21 patients and 13 carers attending the ICU Follow-up Clinic (FC) of our 35-bed adult ICU. RESULTS: A total of 122 drugs were prescribed regularly before ICU admission, 168 on ICU discharge, 132 at hospital discharge, and 128 at the FC. Medication-related problems were identified with hypnotics/anxiolytics, antidepressants, proton pump inhibitors, and analgesics. Good follow-up was observed in all 4 cases where the antidysrhythmic agent amiodarone was initiated on ICU. Patients/carers described 20 cases of difficulty in obtaining appropriate and timely supplies and 19 of insufficient information. CONCLUSIONS: These results show that our incidence of MRPs after ICU discharge was encouragingly infrequent, in which we attribute it to targeted medicine reconciliation and the availability of our FC. However, MRPs were perceived to stem from inadequate communication at the interfaces of care and the lack of opportunity for patients/carers to obtain relevant information. We recommend that FC should focus on MRPs during their consultation and that further research in this area should be performed to examine our observations further.

Investigating risk factors for psychological morbidity three months after intensive care: a prospective cohort study.

INTRODUCTION: There is growing evidence of poor mental health and quality of life among survivors of intensive care. However, it is not yet clear to what extent the trauma of life-threatening illness, associated drugs and treatments, or patients' psychological reactions during intensive care contribute to poor psychosocial outcomes. Our aim was to investigate the relative contributions of a broader set of risk factors and outcomes than had previously been considered in a single study. METHODS: A prospective cohort study of 157 mixed-diagnosis highest acuity patients was conducted in a large general intensive care unit (ICU). Data on four groups of risk factors (clinical, acute psychological, socio-demographic and chronic health) were collected during ICU admissions. Post-traumatic stress disorder (PTSD), depression, anxiety and quality of life were assessed using validated questionnaires at three months (n = 100). Multivariable analysis was used. RESULTS: At follow-up, 55% of patients had psychological morbidity: 27.1% (95% CI: 18.3%, 35.9%) had probable PTSD; 46.3% (95% CI: 36.5%, 56.1%) probable depression, and 44.4% (95% CI: 34.6%, 54.2%) anxiety. The strongest clinical risk factor for PTSD was longer duration of sedation (regression coefficient = 0.69 points (95% CI: 0.12, 1.27) per day, scale = 0 to 51). There was a strong association between depression at three months and receiving benzodiazepines in the ICU (mean difference between groups = 6.73 points (95% CI: 1.42, 12.06), scale = 0 to 60). Use of inotropes or vasopressors was correlated with anxiety, and corticosteroids with better physical quality of life. CONCLUSIONS: Strikingly high rates of psychological morbidity were found in this cohort of intensive care survivors. The study's key finding was that acute psychological reactions in the ICU were the strongest modifiable risk factors for developing mental illness in the future. The observation that use of different ICU drugs correlated with different psychological outcomes merits further investigation. These findings suggest that psychological interventions, along with pharmacological modifications, could help reduce poor outcomes, including PTSD, after intensive care.

A multidisciplinary team approach to weaning from prolonged mechanical ventilation.

OBJECTIVE: To establish whether multidisciplinary team-led strategies to maintain continuity across the weaning process result in an increase in the proportion of patients surviving prolonged mechanical ventilation and reduce the length of time patients are ventilated. DESIGN: A quality improvement programme was conceived and implemented for patients receiving mechanical ventilation for >21 days. SETTING: University teaching hospital general intensive care unit. INTERVENTIONS: The introduction of long-term weaning plans. MEASUREMENTS AND MAIN RESULTS: Intensive care unit survival odds ratio and 95% confidence interval. 0.181 (0.06-0.49) P<0.01 and hospital survival odds ratio and 95% confidence interval 0.2 (0.08-0.61) P<0.01, Duration of mechanical ventilation (median 95@ confidence interval ) 53 days (32-37) vs 43 days (39-44) P=0.03. CONCLUSION: Long-term weaning plans led by a multidisciplinary, team were associated with a reduction in intensive care unit and hospital mortality, and duration of mechanical ventilation in patients ventilated for ≥ 21 days. Strategies to maintain continuity in this patient parent group are likely fundamental to improving outcome.

On comparing a single case with a control sample: an alternative perspective.

Corballis [Corballis, M. C. (2009). Comparing a single case with a control sample: Refinements and extensions. Neuropsychologia] offers an interesting position paper on statistical inference in single-case studies. The following points arise: (1) Testing whether we can reject the null hypothesis that a patient's score is an observation from the population of control scores can be a legitimate aim for single-case researchers, not just clinicians. (2) Counter to the claim made by Corballis [Corballis, M. C. (2009). Comparing a single case with a control sample: Refinements and extensions. Neuropsychologia], Crawford and Howell's [Crawford, J. R., & Howell, D. C. (1998). Comparing an individual's test score against norms derived from small samples. The Clinical Neuropsychologist, 12, 482-486] method does test whether we can reject the above null hypothesis. (3) In all but the most unusual of circumstances Crawford and Howell's method can also safely be used to test whether the mean of a notional patient population is lower than that of a control population, should neuropsychologists wish to construe the test in this way. (4) In contrast, the method proposed by Corballis is not legitimate for either of these purposes because it fails to allow for uncertainty over the control mean (as a result Type I errors will not be under control). (5) The use of a mixed ANOVA design to compare a case to controls (with or without the adjustment proposed by Corballis) is beset with problems but these can be overcome using alternative methods.

Pulmonary epithelium is a prominent source of proteinase-activated receptor-1-inducible CCL2 in pulmonary fibrosis.

RATIONALE: Studies in patients and experimental animals provide compelling evidence of the involvement of the major thrombin receptor, proteinase-activated receptor-1 (PAR(1)), and the potent chemokine, chemokine (CC motif) ligand-2 (CCL2)/monocyte chemotactic protein-1, in the pathogenesis of idiopathic pulmonary fibrosis (IPF). PAR(1) knockout mice are protected from bleomycin-induced lung inflammation and fibrosis and this protection is associated with marked attenuation in CCL2 induction. OBJECTIVES: The aim of this study was to determine which cell types represent the major source of PAR(1)-inducible CCL2 in the fibrotic lung. METHODS: Using immunohistochemistry and dual immunofluorescence, we examined PAR(1) and CCL2 expression in the bleomycin model and human IPF lung. PAR(1) and CCL2 gene expression was also assessed in laser-captured alveolar septae from patients with IPF. The ability of PAR(1) to induce CCL2 production by lung epithelial cells was also examined in vitro. MEASUREMENTS AND MAIN RESULTS: We report for the first time that PAR(1) and CCL2 are coexpressed and co-up-regulated on the activated epithelium in fibrotic areas in IPF. Similar observations were found in bleomycin-induced lung injury. Furthermore, we show that thrombin is a potent inducer of CCL2 gene expression and protein release by cultured lung epithelial cells via a PAR(1)-dependent mechanism. CONCLUSIONS: These data support the notion that PAR(1) activation on lung epithelial cells may represent an important mechanism leading to increased local CCL2 release in pulmonary fibrosis. Targeting PAR(1) on the pulmonary epithelium may offer a unique opportunity for therapeutic intervention in pulmonary fibrosis and other inflammatory and fibroproliferative conditions associated with excessive local generation of thrombin and CCL2 release.

Testing for a deficit in single-case studies: effects of departures from normality.

In neuropsychological single-case research inferences concerning a patient's cognitive status are often based on referring the patient's test score to those obtained from a modestly sized control sample. Two methods of testing for a deficit (z and a method proposed by Crawford and Howell [Crawford, J. R. & Howell, D. C. (1998). Comparing an individual's test score against norms derived from small samples. The Clinical Neuropsychologist, 12, 482-486]) both assume the control distribution is normal but this assumption will often be violated in practice. Monte Carlo simulation was employed to study the effects of leptokurtosis and the combination of skew and leptokurtosis on the Type I error rates for these two methods. For Crawford and Howell's method, leptokurtosis produced only a modest inflation of the Type I error rate when the control sample N was small-to-modest in size and error rates were lower than the specified rates at larger N. In contrast, the combination of leptokurtosis and skew produced marked inflation of error rates for small Ns. With a specified error rate of 5%, actual error rates as high as 14.31% and 9.96% were observed for z and Crawford and Howell's method respectively. Potential solutions to the problem of non-normal data are evaluated.

Absence of proteinase-activated receptor-1 signaling affords protection from bleomycin-induced lung inflammation and fibrosis.

Activation of the coagulation cascade is commonly observed in the lungs of patients with both acute and chronic inflammatory and fibrotic lung disorders, as well as in animal models of these disorders. The aim of this study was to examine the contribution of the major thrombin receptor, proteinase-activated receptor-1 (PAR-1), during the acute inflammatory and chronic fibrotic phases of lung injury induced by intratracheal instillation of bleomycin in mice. Inflammatory cell recruitment and increases in bronchoalveolar lavage fluid (BALF) protein were attenuated by 56 +/- 10% (P < 0.05) and 53 +/- 12% (P < 0.05), respectively, in PAR-1-deficient (PAR-1-/-) mice compared with wild-type (WT) mice. PAR-1-/- mice were also protected from bleomycin-induced pulmonary fibrosis with total lung collagen accumulation reduced by 59 +/- 5% (P < 0.05). The protection afforded by PAR-1 deficiency was accompanied by significant reductions in pulmonary levels of the potent PAR-1-inducible proinflammatory and profibrotic mediators, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-beta-1 (TGF-beta1), and connective tissue growth factor/fibroblast-inducible secreted protein-12 (CTGF/FISP12). In addition, PAR-1 was highly expressed in inflammatory and fibroproliferative lesions in lung sections obtained from patients with fibrotic lung disease. These data show for the first time that PAR-1 signaling plays a key role in experimentally induced lung injury, and they further identify PAR-1 as one of the critical receptors involved in orchestrating the interplay between coagulation, inflammation, and remodeling in response to tissue injury.

Inferential methods for comparing a single case with a control sample: modified t-tests versus mycroft et al.'s (2002) modified anova.

Mycroft, Mitchell, and Kay (2002) have criticised existing inferential methods (e.g., Crawford & Howell, 1998) for comparing a single case with a control sample and propose that such comparisons be made using a modified ANOVA. It is argued that the assumptions made by Mycroft et al. are questionable and, even if they held, would not invalidate Crawford and Howell's method. Crawford and Howell's null hypothesis is that the patient is an observation from the control population whereas Mycroft et al.'s null hypothesis is that the control population and a notional population of patients have a common mean. Even if one accepts Mycroft et al.'s conceptualisation, their arguments only have force if (1) the variance of a notional population of patients was larger than that of the control population, and (2) patients with impaired performance were balanced exactly by patients whose performance had been enhanced relative to controls. Furthermore, the modified ANOVA would have the undesirable consequence of reducing statistical power unnecessarily and it requires users to provide some estimate of the variance of a hypothetical population.

Angiotensin II and the fibroproliferative response to acute lung injury.

Angiotensin II (ANG II), generated by activation of local renin-angiotensin systems, is believed to play an important role in tissue repair and remodeling, in part via transforming growth factor-beta (TGF-beta). Angiotensin-converting enzyme (ACE) inhibitors have been shown to abrogate experimental lung injury via a number of potential mechanisms; however, the potentially fibroproliferative role for ANG II in the lung has not been characterized. We hypothesized that, after lung injury, ANG II would stimulate fibroblast procollagen synthesis and promote lung collagen deposition in rats. In vitro, ANG II was a potent inducer of procollagen production in human lung fibroblasts via activation of the type 1 receptor and, at least in part, via the autocrine action of TGF-beta. After bleomycin-induced lung injury, an increase in lung ANG II concentration was observed by day 3 that preceded increases in lung collagen and was maintained until death at day 21. Administration of an ACE inhibitor (ramipril) reduced ACE activity, ANG II concentration, TGF-beta expression, and collagen deposition. Losartan (an ANG II type 1 receptor antagonist) also attenuated the increase in TGF-beta expression and lung collagen deposition. These observations suggest that ANG II, possibly generated locally within the lung, may play an important role in the fibrotic response to acute lung injury, at least in part via the action of TGF-beta. ACE inhibitors and receptor antagonists, already widely used clinically, should be assessed as potential new therapies for fibrotic lung disease.

Intra-individual measures of association in neuropsychology: inferential methods for comparing a single case with a control or normative sample.

Performance on some neuropsychological tests is best expressed as an intra-individual measure of association (such as a parametric or non-parametric correlation coefficient or the slope of a regression line). Examples of the use of intra-individual measures of association (IIMAs) include the quantification of performance on tests designed to assess temporal order memory or the accuracy of time estimation. The present paper presents methods for comparing a patient's performance with a control or normative sample when performance is expressed as an IIMA. The methods test if there is a significant difference between a patient's IIMA and those obtained from controls, yield an estimate of the abnormality of the patient's IIMA, and provide confidence limits on the level of abnormality. The methods can be used with normative or control samples of any size and will therefore be of particular relevance to single-case researchers. A method for comparing the difference between a patient's scores on two measures with the differences observed in controls is also described (one or both measures can be IIMAs). All the methods require only summary statistics (rather than the raw data from the normative or control sample); it is hoped that this feature will encourage the development of norms for tasks that use IIMAs to quantify performance. Worked examples of the statistical methods are provided using data from a clinical case and controls. A computer program (for PCs) that implements the methods is described and made available.