Grading bloodstream infection risk using citrulline as a biomarker of intestinal mucositis in patients receiving intensive therapy.

Earlier studies have suggested that severe intestinal mucositis (IM; citrulline < 10 µmol/L) is an independent risk factor for bloodstream infections (BSI) after cytotoxic therapy. Our aim was to grade IM in patients receiving commonly used chemotherapy and conditioning regimens, and characterize its relationship with BSI incidence. In a retrospective analysis of remission induction (RI) chemotherapy, or conditioning for autologous and allogeneic hematopoietic stem cell transplantation (HSCT; myeloablative conditioning [MAC] and non-myeloablative and reduced-intensity conditioning [NMA/RIC]), data were collected on central venous catheter (CVC) characteristics and BSI. The relationship between BSI occurrence and the degree of IM (determined by citrulline levels) and neutropenia was analyzed. In 626 CVC episodes, 268 (42.8%) laboratory-confirmed BSIs (LCBIs) occurred, classified as mucosal barrier injury (MBI)-LCBIs in 179 (28.6%) episodes, central line-associated BSIs in 113 (18.1%) episodes, and catheter-related BSIs in 55 (8.8%) episodes. In NMA/RIC, the mean duration of hypocitrullinemia was 0.77 days, with LCBI and MBI-LCBI occurring in 11.1% and 4.8% of episodes. In autologous HSCT, RI, and MAC allogeneic HSCT, LCBI and MBI-LCBI occurred frequently (40.0-63.8% and 22.8-53.2% of episodes, respectively) and the mean duration of hypocitrullinemia was significantly higher (9.2-13.8 days). There was a strong correlation between LCBI and the duration of hypocitrullinemia (Pearson's correlation coefficient R = 0.96), as opposed to the relationship between LCBI and the duration of neutropenia (R = 0.42). We conclude that citrulline can be used to grade BSI risk for commonly used intensive treatment regimens.

The Mortality After Release from Incarceration Consortium (MARIC): Protocol for a multi-national, individual participant data meta-analysis.

INTRODUCTION: More than 30 million adults are released from incarceration globally each year. Many experience complex physical and mental health problems, and are at markedly increased risk of preventable mortality. Despite this, evidence regarding the global epidemiology of mortality following release from incarceration is insufficient to inform the development of targeted, evidence-based responses. Many previous studies have suffered from inadequate power and poor precision, and even large studies have limited capacity to disaggregate data by specific causes of death, sub-populations or time since release to answer questions of clinical and public health relevance. OBJECTIVES: To comprehensively document the incidence, timing, causes and risk factors for mortality in adults released from prison. METHODS: We created the Mortality After Release from Incarceration Consortium (MARIC), a multi-disciplinary collaboration representing 29 cohorts of adults who have experienced incarceration from 11 countries. Findings across cohorts will be analysed using a two-step, individual participant data meta-analysis methodology. RESULTS: The combined sample includes 1,337,993 individuals (89% male), with 75,795 deaths recorded over 9,191,393 person-years of follow-up. CONCLUSIONS: The consortium represents an important advancement in the field, bringing international attention to this problem. It will provide internationally relevant evidence to guide policymakers and clinicians in reducing preventable deaths in this marginalized population. KEY WORDS: Mortality; incarceration; prison; release; individual participant data meta-analysis; consortium; cohort.

Inhibition of bromodomain and extraterminal domain reduces growth and invasive characteristics of chemoresistant ovarian carcinoma cells.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy worldwide. Development of chemoresistance and peritoneal dissemination are the major reasons for low survival rate in the patients. The bromodomain and extraterminal domain (BET) proteins are known as epigenetic 'readers,' and their inhibitors are novel epigenetic strategies for cancer treatment. Accumulating body of evidence indicates that epigenetic modifications have critical roles in development of EOC, and overexpression of the BET family is a key step in the induction of important oncogenes. Here, we examined the mechanistic activity of I-BET151, a pan-inhibitor of the BET family, in therapy-resistant EOC cells. Our findings showed that I-BET151 diminished cell growth, clonogenic potential, and induced apoptosis. I-BET151 inhibited cell proliferation through down-modulation of FOXM1 and its targets aurora kinase B and cyclin B1. I-BET151 attenuated migration and invasion of the EOC cells by down-regulation of epithelial-mesenchymal transition markers fibronectin, ZEB2, and N-cadherin. I-BET151 synergistically enhanced cisplatin chemosensitivity by down-regulation of survivin and Bcl-2. Our data provide insights into the mechanistic activity of I-BET151 and suggest that BET inhibition has potential as a therapeutic strategy in therapy-resistant EOC. Further in vivo investigations on the therapeutic potential of I-BET151 in EOC are warranted.

Prediction of violent crime on discharge from secure psychiatric hospitals: A clinical prediction rule (FoVOx).

BACKGROUND: Current approaches to assess violence risk in secure hospitals are resource intensive, limited by accuracy and authorship bias and may have reached a performance ceiling. This study seeks to develop scalable predictive models for violent offending following discharge from secure psychiatric hospitals. METHODS: We identified all patients discharged from secure hospitals in Sweden between January 1, 1992 and December 31, 2013. Using multiple Cox regression, pre-specified criminal, sociodemographic, and clinical risk factors were included in a model that was tested for discrimination and calibration in the prediction of violent crime at 12 and 24 months post-discharge. Risk cut-offs were pre-specified at 5% (low vs. medium) and 20% (medium vs. high). RESULTS: We identified 2248 patients with 2933 discharges into community settings. We developed a 12-item model with good measures of calibration and discrimination (area under the curve=0.77 at 12 and 24 months). At 24 months post-discharge, using the 5% cut-off, sensitivity was 96% and specificity was 21%. Positive and negative predictive values were 19% and 97%, respectively. Using the 20% cut-off, sensitivity was 55%, specificity 83% and the positive and negative predictive values were 37% and 91%, respectively. The model was used to develop a free online tool (FoVOx). INTERPRETATION: We have developed a prediction score in a Swedish cohort of patients discharged from secure hospitals that can assist in clinical decision-making. Scalable predictive models for violence risk are possible in specific patient groups and can free up clinical time for treatment and management. Further evaluation in other countries is needed. FUNDING: Wellcome Trust (202836/Z/16/Z) and the Swedish Research Council. The funding sources had no involvement in writing of the manuscript or decision to submit or in data collection, analysis or interpretation or any aspect pertinent to the study.

Risk assessment tools in criminal justice and forensic psychiatry: The need for better data.

Violence risk assessment tools are increasingly used within criminal justice and forensic psychiatry, however there is little relevant, reliable and unbiased data regarding their predictive accuracy. We argue that such data are needed to (i) prevent excessive reliance on risk assessment scores, (ii) allow matching of different risk assessment tools to different contexts of application, (iii) protect against problematic forms of discrimination and stigmatisation, and (iv) ensure that contentious demographic variables are not prematurely removed from risk assessment tools.

Parental and perinatal risk factors for sexual offending in men: a nationwide case-control study.

BACKGROUND: Prior studies suggest parental and perinatal risk factors are associated with later offending. It remains uncertain, however, if such risk factors are similarly related to sexual offending. METHOD: We linked socio-demographic, family relations, and perinatal (obtained at birth) data from the nationwide Swedish registers from 1973 to 2009 with information on criminal convictions of cases and control subjects. Male sex offenders (n = 13 773) were matched 1:5 on birth year and county of birth in Sweden to male controls without sexual or non-sexual violent convictions. To examine risk-factor specificity for sexual offending, we also compared male violent, non-sexual offenders (n = 135 953) to controls without sexual or non-sexual violent convictions. Predictors included parental (young maternal or paternal age at son's birth, educational attainment, violent crime, psychiatric disorder, substance misuse, suicide attempt) and perinatal (number of older brothers, low Apgar score, low birth weight, being small for gestational age, congenital malformations, small head size) variables. RESULTS: Conditional logistic regression models found consistent patterns of statistically significant, small to moderate independent associations of parental risk factors with sons' sexual offending and non-sexual violent offending. For perinatal risk factors, patterns varied more; small for gestational age and small head size exhibited similar risk effects for both offence types whereas a higher number of older biological brothers and any congenital malformation were small, independent risk factors only for non-sexual violence. CONCLUSIONS: This nationwide study suggests substantial commonalities in parental and perinatal risk factors for the onset of sexual and non-sexual violent offending.

Adherence to antipsychotic medication among homeless adults in Vancouver, Canada: a 15-year retrospective cohort study.

PURPOSE: The purpose of this study was to investigate the level of adherence to antipsychotic prescription medication in a well-defined homeless cohort over a 15-year period. We hypothesized that adherence would be well below the recommended threshold for clinical effectiveness (80 %), and that it would be strongly associated with modifiable risk factors in the social environment in which homeless people live. METHOD: Linked baseline data (including comprehensive population-level administrative prescription records) were examined in a subpopulation of participants from two pragmatic-randomized trials that investigated Housing First for homeless and mentally ill adults. Adherence to antipsychotic medication was operationalized using the medication possession ratio. Multivariable logistic regression was used to estimate effect sizes between socio-demographic, homelessness-related and illness factors, and medication possession ratio. RESULTS: Among the 290 participants who met inclusion criteria for the current analysis, adherence to antipsychotic prescription was significantly associated with: history of psychiatric hospitalization; receipt of primary medical services; long-acting injectable antipsychotic formulations; and duration of homelessness. Mean medication possession ratio in the pre-randomization period was 0.41. Socio-demographic characteristics previously correlated with antipsychotic non-adherence were not significantly related to medication possession ratio. CONCLUSIONS: This is the first study to quantify the very low level of adherence to antipsychotic medication among homeless people over an extended observation period of 15 years. Each of the four factors found to be significantly associated with adherence presents opportunities for intervention. Strategies to end homelessness for this population may represent the greatest opportunity to improve adherence to antipsychotic medication.

Coercion, competence, and consent in offenders with personality disorder.

Competence to consent to treatment has not previously been examined in a personality disorder cohort without comorbid mental disorder. We examined competence and coercion in 174 individuals diagnosed with severe personality disorder using two validated tools (the MacArthur Competence Assessment Tool for Treatment and the MacArthur Coercion Assessment Scale - Short Form). Competence was not categorically impaired, but there were variations within the sample on dimensional competence measures. Further, there were significant negative correlations between experienced coercion and competence. Higher coercion scores were associated with two components of competence: lower understanding and reasoning. Patients who consented to treatment had higher scores on competence measures and experienced less coercion. These findings suggest that therapeutic approaches that decrease experienced coercion and increase competence may increase the engagement of individuals diagnosed with severe personality disorders in treatment.

Schizophrenia and subsequent neighborhood deprivation: revisiting the social drift hypothesis using population, twin and molecular genetic data.

Neighborhood influences in the etiology of schizophrenia have been emphasized in a number of systematic reviews, but causality remains uncertain. To test the social drift hypothesis, we used three complementary genetically informed Swedish cohorts. First, we used nationwide Swedish data on approximately 760 000 full- and half-sibling pairs born between 1951 and 1974 and quantitative genetic models to study genetic and environmental influences on the overlap between schizophrenia in young adulthood and subsequent residence in socioeconomically deprived neighborhoods. Schizophrenia diagnoses were ascertained using the National Patient Registry. Second, we tested the overlap between childhood psychotic experiences and neighborhood deprivation in early adulthood in the longitudinal Twin Study of Child and Adolescent Development (TCHAD; n=2960). Third, we investigated to what extent polygenic risk scores for schizophrenia predicted residence in deprived neighborhoods during late adulthood using the TwinGene sample (n=6796). Sibling data suggested that living in deprived neighborhoods was substantially heritable; 65% (95% confidence interval (95% CI): 60-71%) of the variance was attributed to genetic influences. Although the correlation between schizophrenia and neighborhood deprivation was moderate in magnitude (r=0.22; 95% CI: 0.20-0.24), it was entirely explained by genetic influences. We replicated these findings in the TCHAD sample. Moreover, the association between polygenic risk for schizophrenia and neighborhood deprivation was statistically significant (R(2)=0.15%, P=0.002). Our findings are primarily consistent with a genetic selection interpretation where genetic liability for schizophrenia also predicts subsequent residence in socioeconomically deprived neighborhoods. Previous studies may have overemphasized the relative importance of environmental influences in the social drift of schizophrenia patients. Clinical and policy interventions will therefore benefit from the future identification of potentially causal pathways between different dimensions of cognitive functions and socioeconomic trajectories derived from studies adopting family-based research designs.

Evidence-based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology.

The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.

Genetic and environmental determinants of violence risk in psychotic disorders: a multivariate quantitative genetic study of 1.8 million Swedish twins and siblings.

Patients diagnosed with psychotic disorders (for example, schizophrenia and bipolar disorder) have elevated risks of committing violent acts, particularly if they are comorbid with substance misuse. Despite recent insights from quantitative and molecular genetic studies demonstrating considerable pleiotropy in the genetic architecture of these phenotypes, there is currently a lack of large-scale studies that have specifically examined the aetiological links between psychotic disorders and violence. Using a sample of all Swedish individuals born between 1958 and 1989 (n=3 332 101), we identified a total of 923 259 twin-sibling pairs. Patients were identified using the National Patient Register using validated algorithms based on International Classification of Diseases (ICD) 8-10. Univariate quantitative genetic models revealed that all phenotypes (schizophrenia, bipolar disorder, substance misuse, and violent crime) were highly heritable (h(2)=53-71%). Multivariate models further revealed that schizophrenia was a stronger predictor of violence (r=0.32; 95% confidence interval: 0.30-0.33) than bipolar disorder (r=0.23; 0.21-0.25), and large proportions (51-67%) of these phenotypic correlations were explained by genetic factors shared between each disorder, substance misuse, and violence. Importantly, we found that genetic influences that were unrelated to substance misuse explained approximately a fifth (21%; 20-22%) of the correlation with violent criminality in bipolar disorder but none of the same correlation in schizophrenia (Pbipolar disorder<0.001; Pschizophrenia=0.55). These findings highlight the problems of not disentangling common and unique sources of covariance across genetically similar phenotypes as the latter sources may include aetiologically important clues. Clinically, these findings underline the importance of assessing risk of different phenotypes together and integrating interventions for psychiatric disorders, substance misuse, and violence.

Silibinin affects tumor cell growth because of reduction of stemness properties and induction of apoptosis in 2D and 3D models of MDA-MB-468.

Silibinin, with a strong antioxidant activity and a weak cytotoxic property, is considered a candidate for cancer prevention. As there is no information on its effect on breast cancer tumor-initiating cells [cancer stem cells (CSCs)] in a 3D culture model, which more closely mimic natural tissues, we carried out this study to determine whether silibinin can target breast CSCs in MDA-MB-468 cells cultured under 3D and 2D conditions. Silibinin was added to culture medium of MDA-MB-468 at a half maximal inhibitory concentration (IC50) dose in 2D and 3D models. Then, stemness properties were assessed using colony and sphere-formation tests. Flow cytometry and real-time PCR were used to determine the different expression levels of stem cell-related marker at protein and mRNA levels under both culture conditions. Our results showed that silibinin inhibits cell growth in a dose-dependent manner by induction of apoptosis, alteration of the cell cycle, reduction of stemness properties and function, and induction of tumoral differentiation. The mechanism of silibinin action and also the response of tumor cells differed when cells were cultured in a 3D model compared with a 2D model. Silibinin may potentially target breast CSCs. Moreover, tumor-initiating cells are more sensitive to silibinin in a 3D culture than in a 2D culture.

Systematic meta-analyses and field synopsis of genetic association studies of violence and aggression.

A large number of candidate gene studies for aggression and violence have been conducted. Successful identification of associations between genetic markers and aggression would contribute to understanding the neurobiology of antisocial behavior and potentially provide useful tools for risk prediction and therapeutic targets for high-risk groups of patients and offenders. We systematically reviewed the literature and assessed the evidence on genetic association studies of aggression and related outcomes in order to provide a field synopsis. We searched PubMed and Huge Navigator databases and sought additional data through reviewing reference lists and correspondence with investigators. Genetic association studies were included if outcome data on aggression or violent behavior either as a binary outcome or as a quantitative trait were provided. From 1331 potentially relevant investigations, 185 studies constituting 277 independent associations on 31 genes fulfilled the predetermined selection criteria. Data from variants investigated in three or more samples were combined in meta-analyses and potential sources of heterogeneity were investigated using subgroup analyses. In the primary analyses, which used relaxed inclusion criteria, we found no association between any polymorphism analyzed and aggression at the 5% level of significance. Subgroup analyses, including by severity of outcome, age group, characteristics of the sample and ethnicity, did not demonstrate any consistent findings. Current evidence does not support the use of such genes to predict dangerousness or as markers for therapeutic interventions.

A systematic review of outcome measures used in forensic mental health research with consensus panel opinion.

OBJECTIVE: To describe and assess outcome measures in forensic mental health research, through a structured review and a consensus panel. DATA SOURCES: A search of eight electronic databases, including CINAHL, EMBASE and MEDLINE, was conducted for the period 1990-2006. REVIEW METHODS: In the structured review, search and medical subject heading terms focused upon two factors: the use of a forensic participant sample and the experimental designs likely to be used for outcome measurement. Data extraction included general information about the identity of the reference, specific information regarding the study and information pertaining to the outcome measures used. The consensus exercise was implemented in two stages. At the first stage, participants were asked to complete ratings about the importance of various potential areas of outcome measurement in a written consultation. At the second stage, they were asked to attend a consensus meeting to review and agree results relating to the domains, to consider and rate specific outcome instruments identified as commonly used from the structured review and to discuss strengths, weaknesses and future priorities for outcome measurement in forensic mental health research. RESULTS: The final sample of eligible studies for inclusion in the review consisted of 308 separate studies obtained from 302 references. The consensus group agreed on 11 domains of forensic mental health outcome measurement, all of which were considered important. Nine different outcome measure instruments were used in more than four different studies. The most frequently used outcome measure was used in 15 studies. According to the consensus group, many domains beyond recidivism and mental health were important but under-represented in the review of outcomes. Current instruments that may show future promise in outcome measurement included risk assessment tools. The outcome measure of repeat offending behaviour was by far the most frequently used, occurring in 72% of the studies included in the review. Its measurement varied with position in the criminal justice system, offence specification and method of measurement. The consensus group believed that recidivism is only an indication of the amount of antisocial acts that are committed. CONCLUSIONS: A wide range of domains are relevant to assessing outcomes of interventions in forensic mental health services. Evaluations need to take account of public safety, but also clinical, rehabilitation and humanitarian outcomes. Recidivism is a very high priority; the public expects interventions that will reduce future criminal behaviour. Greater attention needs to be given to validity of measurement, given the enormous variety of approaches to measurement. More research is needed on methods to take account of the heterogeneity of seriousness of forms of recidivism in outcome measurement. Validity of self-report instruments regarding recidivism also needs examination by further research. Mental health is clearly also an important dimension of outcome. The review provides clear support for the view that domains such as quality of life, social function and psychosocial adjustment have not been extensively employed in forensic mental health research, but are relevant and important issues. The role of such instruments needs more consideration.

Dementia in prison: ethical and legal implications.

As the number of elderly prisoners increases in the UK and other Western countries, there will be individuals who develop dementia whilst in custody. We present two case vignettes of men with dementia in English prisons, and explore some of the ethical implications that their continuing detention raises. We find little to support their detention in the various purposes of prison put forward by legal philosophers and penologists, and conclude by raising some of the possible implications of The Human Rights Act 1998.

Psychiatric, demographic and personality characteristics of elderly sex offenders.

BACKGROUND: Psychiatric disorders are purported to play a role in the aetiology of violent crime, but evidence for their role in sexual offending is less clear. The authors investigated the prevalence of psychiatric morbidity and personality disorders in elderly incarcerated sex offenders compared with elderly non-sex offenders. METHOD: One hundred and one sex offenders and 102 non-sex offenders aged over 59 years wereinterviewed using standardized semi-structured interviews for psychiatric illness (the Geriatric Mental State) and the personality disorder (Structured Clinical Interview for DSM-IV personality disorders). Data on demographic, offence and victim characteristics were collected. RESULTS: Six per cent of the elderly sex offenders had a psychotic illness, 7% a DSM-IV major depressive episode and 33% a personality disorder; and 1% had dementia. These prevalence figures were not different from the elderly non-sex offenders interviewed in this study. Differences emerged at the level of personality traits with sex offenders having more schizoid, obsessive-compulsive, and avoidant traits, and fewer antisocial traits compared with non-sex offenders. CONCLUSIONS: Elderly sex offenders and non-sex-offenders have similar prevalence rates of mental illness. However, elderly sex offenders have increased schizoid, obsessive-compulsive, and avoidant personality traits, supporting the view that sex offending in the elderly is associated more with personality factors than mental illness or organic brain disease.

Hidden psychiatric morbidity in elderly prisoners.

BACKGROUND: The number of elderly prisoners has increased significantly in Western countries over the past decade. Little is known about the psychiatric morbidity of this population. AIMS: To determine the prevalence of psychiatric morbidity in elderly sentenced prisoners. METHOD: A stratified sample of 203 male sentenced prisoners aged over 59 years, from 15 prisons in England and Wales, representing one in five men in this age group, was interviewed using semistructured standardised instruments for psychiatric illness and personality disorder. RESULTS: More than half of the elderly prisoners had a psychiatric diagnosis. The most common diagnoses were personality disorder and depressive illness. CONCLUSIONS: The prevalence of depressive illness was five times greater than that found in other studies of younger adult prisoners and elderly people in the community. Underdetected, undertreated depressive illness in elderly prisoners is an increasing public health problem.

Health of elderly male prisoners: worse than the general population, worse than younger prisoners.

BACKGROUND: Assessment of the health of men aged 60 and over in English and Welsh prisons. METHODS: 203 men were interviewed from 15 prisons, comprising one-fifth of all sentenced men in this age group in England and Wales. Assessment included semi-structured interviews covering chronic and acute health problems, and recording of major illnesses from the medical notes and prison reception health screen. RESULTS: 85% of the elderly prisoners had one or more major illnesses reported in their medical records, and 83% reported at least one chronic illness on interview. The most common illnesses were psychiatric, cardiovascular, musculoskeletal and respiratory. CONCLUSION: The rates of illness in elderly prisoners are higher than those reported in other studies of younger prisoners and surveys of the general population of a similar age. The increasing number of elderly people in prison poses specific health challenges for prison health-care services.

Predictors of general surgical complications after heart transplantation.

BACKGROUND: Several studies have reported the incidence, morbidity, and mortality of general surgical conditions (GSCs) in orthotopic heart transplant (OHT) patients. The following is the largest reported series of such patients and the first study with sufficient patient numbers to formally evaluate peritransplant variables as risk factors for GSC development. STUDY DESIGN: A GSC was defined as a condition for which a general surgeon had been consulted or as a general surgical condition recognized at the time of autopsy. The records of 453 consecutive patients who underwent OHT between 1981 and 1999 were reviewed to identify patients who developed a GSC. Kaplan-Meier actuarial analysis on this cohort, and univariate and multivariate logistic regression models applied to a subpopulation of 324 consecutive OHT patients between 1987 and 1997 were used to determine factors associated with and predictive of GSC after OHT. RESULTS: Of 453 OHT patients, 371 (81.9%) were men, and the average age was 44.5 +/- 15 (standard deviation) years. Median followup was 2,086 days (range 1 to 6,642 days). Ninety-three patients (20.5%) developed 111 GSCs. Of these, 78 were men, and the average age was 49.9+/-10.2 years. There were 83 general surgical interventions. Actuarial analyses revealed that age greater than 50 years, pretransplant diagnosis of ischemic (PTDxI) versus nonischemic heart disease, and previous general surgical history were factors associated (p < 0.05) with a higher GSC incidence. Gender, more urgent transplant priority status, cardiopulmonary bypass time, total graft ischemic time, and intensive care unit length of stay were not associated with GSC. Factors associated with GSC on univariate analysis, with odds ratios (ORs) and 95% confidence intervals (CIs) included: age analyzed as a continuous variable (OR 1.04 per year; CI 1.01, 1.06 per year; p = 0.0021), PTDxI (OR 2.40; CI 1.39, 4.15; p = 0.0016), and pretransplant general surgical history (OR 3.35; CI 1.65, 6.82; p = 0.0008). Multivariate analysis revealed that only pretransplant general surgical history (OR 3.27; CI 1.58, 6.76; p = 0.0004) and PTDxI (OR 2.37; CI 1.35, 4.16; p = 0.0023) were associated with subsequent development of GSC. CONCLUSIONS: A pretransplant diagnosis of ischemic heart disease and previous history of a general surgical procedure are two independent risk factors that predispose OHT patients to development of GSC. Because GSC may arise insidiously in immunosuppressed patients, identification of OHT patients at higher risk for GSC will permit timely intervention decisions, decreasing morbidity and mortality in this challenging group of patients.