Degree of anxiety in food allergic children in a tertiary care center.

BACKGROUND: The link between internalizing psychiatric disorders, such as anxiety and depression, and allergic diseases has attracted a high level of interest from psychiatrists and immunologists. Recent studies have found increased anxiety in children with asthma, but findings in children with food allergy (FA) have been inconsistent. OBJECTIVE: It was hypothesized that children with FA would score significantly higher on a standardized anxiety screen than general pediatric (GP) patients but not as high as patients with diagnosed anxiety disorders. METHODS: A total of 114 patients aged 8 to 16 years (37 with confirmed anxiety disorder from a pediatric psychiatry clinic, 40 with confirmed FA from a pediatric allergy clinic, and 43 well-care patients from a GP clinic) and their mothers completed the Screen for Child Anxiety Related Emotional Disorders (SCARED). RESULTS: Children and mothers in the allergy group did not report increased levels of anxiety in children on total SCARED scores or subscales compared with children and mothers from the GP group. There was a trend toward increased panic disorder symptoms reported in children by mothers of children in the allergy group, but this finding did not reach statistical significance. CONCLUSION: Children with FA did not have increased anxiety; however, there was a trend for mothers of children with allergies to report more symptoms of panic disorder in their children. It remains important to screen families for anxiety-related symptoms and refer them to mental health services when indicated.

Effects of injectable extended-release naltrexone (XR-NTX) for opioid dependence on residential rehabilitation outcomes and early follow-up.

BACKGROUND AND OBJECTIVES: Little is known about the use of extended-release naltrexone (XR-NTX) during residential rehabilitation, and its effects on early outcomes and rates of follow-up treatment. This study examined patient characteristics and rates of treatment completion and engagement in post-residential care of opioid dependent patients who received XR-NTX during residential rehabilitation, compared with patients who did not receive this medication. METHODS: Electronic records for opioid dependent patients from three Pennsylvania residential detoxification and treatment facilities (N = 7,687) were retrospectively analyzed. We determined the proportion of patients who received XR-NTX (INJ), and compared rates of treatment completion and engagement in follow-up care relative to a naturalistic control group of patients recommended for, but not administered, XR-NTX (Non-INJ). Data on whether the patient initiated follow-up care were available from one site (N = 3,724). RESULTS: Overall, 598 (7.8%) patients were recommended for XR-NTX and of these, 168 (28.1%) received injections. Compared to non-INJ patients, INJ patients were less likely to leave against medical advice (4.8% vs. 30.2%, p < .001) and more likely to initiate follow-up care (37.7% vs. 19.7%, p < .001). These differences remained significant after controlling for demographic covariates using regression analysis. CONCLUSIONS: XR-NTX was associated with higher rates of residential and early post-residential care engagement in patients with opioid dependence. SCIENTIFIC SIGNIFICANCE: XR-NTX may be an effective adjunct in the residential treatment and aftercare of patients with opioid dependence.

Affect Modulated Startle Response in Anorexia Nervosa, Restricting Type: Implications for Theory and Practice.

OBJECTIVE: Individuals with anorexia nervosa (AN), restricting type demonstrate unique emotional responses to hedonically positive stimuli beyond eating disorder (ED)-related stimuli. The goal of this study was to evaluate differences in responses to five types of emotionally positive stimuli among acutely ill anorexia nervosa (IAN), restricting type patients, weight-recovered anorexia patients (WRAN), and healthy controls (HCs) using affect modulated startle response (AMSR) as an objective measure. METHOD: A total of 28 participants were recruited (n=28). Fourteen participants were recruited as IAN using the Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) criteria, seven were WRAN, and seven were HC females. All participants were female and aged between 8 and 18 years. The participants viewed images depicting negative, neutral, standardized, and non-eating disorder (ED)-related positive stimuli. Additionally, four categories of ED-related stimuli (high-calorie food, body image, success, and parent-child relationships) were presented to all participants during a standard AMSR paradigm. RESULTS:  No significant between-group differences were found for any of the four ED stimulus categories; all groups showed an inhibited startle response to the four ED-related categories. In contrast, IAN and WRAN showed reduced hedonic responses to standardized positive stimuli relative to HC-replicating previous results. Reduced hedonic response to the standardized (non-ED) positive stimuli was highly correlated with self-reported social anxiety, low self-esteem, body dissatisfaction, asceticism, interpersonal problems, and ineffectiveness. CONCLUSION: AN patients had a reduced hedonic response to some non-ED-related positive stimuli, which correlated with several anxiety-related traits. In contrast, their early automatic responses to high-calorie food, normal weight models, images of success, and positive parent-child relationships did not differ from HC, suggesting these stimuli are either being evaluated as highly interesting or hedonically positive.

Financing academic departments of psychiatry.

OBJECTIVE: The authors describe the many financial challenges facing academic departments of psychiatry and the resulting opportunities that may arise. METHOD: The authors review the history of financial challenges, the current economic situation, and what may lie ahead for academic departments of psychiatry. RESULTS: The current environment has many risks and opportunities for departments of psychiatry. Successful departments will be those that assess their particular strengths and limitations and explore their options for funding. CONCLUSION: Departments of psychiatry should have multiple funding streams and take advantage of opportunities in their local or regional service area.

Reregulation of cortisol levels and sleep in patients with prescription opioid use disorder during long-term residential treatment.

OBJECTIVE: Research has demonstrated that hypothalamic-pituitary-adrenal (HPA) axis function and sleep patterns are dysregulated in patients diagnosed with opioid use disorder (OUD). It is unclear whether and/or when cortisol and sleep might re-regulate over time, and, whether re-regulation is associated with abstinence following discharge from residential treatment. The current study evaluated changes in sleep and basal cortisol levels in prescription OUD patients in residential treatment, and the association between these measures and treatment outcome following discharge. METHOD: As part of a larger study, 55 participants with prescription OUD provided two days of salivary cortisol samples and 12 consecutive nights of sleep actigraphy between days 19-30 of residential treatment (Time Point 1; TP1). Thirteen of the original 55 participants remained in residence and repeated the measures between days 60-72 (Time Point 2; TP2). Thirty-seven healthy controls (HC) provided baseline measures (TP1) of salivary cortisol and sleep. Treatment outcome data, abstinence vs relapse, were established at 120 days following discharge. RESULTS: Prescription OUD patients had higher cortisol levels and lower total sleep time (TST) than HC at TP1. At TP2, TST and cortisol levels no longer differed from HCs in the subgroup of patients who remained abstinent following discharge after TP2. Individuals whose cortisol and TST did not change from TP1 to TP2 were more likely to relapse following discharge from residential treatment. CONCLUSION: Re-regulation of TST and cortisol levels while in residential treatment was associated with better treatment outcome following discharge for prescription OUD patients.

Consensus report on impulsive aggression as a symptom across diagnostic categories in child psychiatry: implications for medication studies.

OBJECTIVE: To determine whether impulsive aggression (IA) is a meaningful clinical construct and to ascertain whether it is sufficiently similar across diagnostic categories, such that parallel studies across disorders might constitute appropriate evidence for pursuing indications. If so, how should IA be assessed, pharmacological studies designed, and ethical issues addressed? METHOD: Experts from key stakeholder communities, including academic clinicians, researchers, practicing clinicians, U.S. Food and Drug Administration, National Institute of Mental Health, industry sponsors, and patient and family advocates, met for a 2-day consensus conference on November 4 and 5, 2004. After evaluating summary presentations on current research evidence, participants were assigned to three workgroups, examined core issues, and generated consensus guidelines in their areas. Workgroup recommendations were discussed by the whole group to reach consensus, and then further iterated and condensed into this report postconference by the authors. RESULTS: Conference participants agreed that IA is a substantial public health and clinical concern, constitutes a key therapeutic target across multiple disorders, and can be measured with sufficient precision that pharmacological studies are warranted. Additional areas of consensus concerned types of measures, optimal study designs, and ethical imperatives. CONCLUSION: Derived from scientific evidence and clinical experience, these consensus-driven recommendations can guide the design of future studies.

Daily sleep quality affects drug craving, partially through indirect associations with positive affect, in patients in treatment for nonmedical use of prescription drugs.

OBJECTIVE: Sleep disturbance has been identified as a risk factor for relapse in addiction to a range of substances. The relationship between sleep quality and treatment outcome has received relatively little attention in research on nonmedical use of prescription drugs (NMUPD). This study examined the within-person association between sleep quality and craving in medically detoxified patients in residence for the treatment of NMUPD. METHOD: Participants (n=68) provided daily reports of their sleep quality, negative affect (NA), positive affect (PA), and craving for an average of 9.36 (SD=2.99) days. Within-person associations of sleep quality and craving were examined using multilevel modeling. Within-person mediation analyses were used to evaluate the mediating roles of NA and PA in the relationship between sleep quality and craving. RESULTS: Greater cravings were observed on days of lower than usual sleep quality (γ10=-0.10, p=0.003). Thirty-one percent of the overall association between sleep quality and craving was explained by PA, such that poorer sleep quality was associated with lower PA and, in turn, lower PA was associated with greater craving. No evidence emerged for an indirect association between sleep quality and craving through NA. CONCLUSIONS: Daily fluctuations in sleep quality were associated with fluctuations in craving, an association partially explained by the association between sleep quality and daily PA. These data encourage further research on the relationship between sleep, affect, and craving in NMUPD patients, as well as in patients with other substance use disorders.

Public health implications of smokeless tobacco use as a harm reduction strategy.

Harm reduction strategies involve promoting a product that has adverse health consequences as a substitute for one that has more severe adverse health consequences. Smokeless tobacco low in nitrosamine content offers potential benefits in reducing smoking prevalence rates. Possible harm arises from the potential for such products to serve as a gateway to more harmful tobacco products, public misinterpretation of "less harmful" as "safe," distraction from the public health goal of tobacco elimination, and ethical issues involved in advising those marketing these harmful products. We offer a research agenda to provide a stronger basis for evaluating the risks and benefits of smokeless tobacco as a means of reducing the adverse health effects of tobacco.

Possible evidence for re-regulation of HPA axis and brain reward systems over time in treatment in prescription opioid-dependent patients.

OBJECTIVES: There is growing evidence for a neuroadaptive model underlying vulnerability to relapse in opioid dependence. The purpose of this study was to evaluate clinical measures hypothesized to mirror elements of allostatic dysregulation in patients dependent on prescription opioids at 2 time points after withdrawal, compared with healthy control participants. METHODS: Recently withdrawn (n = 7) prescription opioid-dependent patients were compared with the patients in supervised residential care for 2 to 3 months (extended care; n = 7) and healthy controls (n = 7) using drug cue reactivity, affect-modulated startle response tasks, salivary cortisol, and 8 days of sleep actigraphy. Prefrontal cortex was monitored with functional near-infrared spectroscopy during the cue reactivity task. RESULTS: Startle response results indicated reduced hedonic response to natural rewards among patients recently withdrawn from opioids relative to extended care patients. The recently withdrawn patients showed increased activation to pill stimuli in right dorsolateral prefrontal cortex relative to extended care patients. Cortisol levels were elevated among recently withdrawn patients and intermediate for extended care relative to healthy controls. Actigraphy indicated disturbed sleep between recently withdrawn patients and extended care patients; extended care patients were similar to controls. Dorsolateral prefrontal cortex activation to drug and natural reward cues, startle responses to natural reward cues, day-time cortisol levels, time in bed, and total time spent sleeping were all correlated with the number of days since last drug use (ie, time in supervised residential treatment). CONCLUSIONS: These results suggest possible re-regulation of dysregulated hypothalamic-pituitary-adrenal axis and brain reward systems in prescription opioid-dependent patients over the drug-free period in residential treatment.

Direct comparison of the psychometric properties of multiple interview and patient-rated assessments of suicidal ideation and behavior in an adult psychiatric inpatient sample.

OBJECTIVE: Compare the accuracy, agreement, internal consistency, and interrater reliability of 3 interviews to assess suicidal ideation and behavior in accordance with US Food and Drug Administration guidance about reporting categories. METHOD: Adults admitted to a psychiatric inpatient unit (N = 199) completed 3 assessments of past month and lifetime suicidal ideation and behavior-the Columbia Suicide Severity Rating Scale (C-SSRS), the Suicide Tracking Scale (STS), and the Sheehan Suicidality Tracking Scale (S-STS)-in randomized, counterbalanced order. "Missing gold standard" latent class analyses defined categories for ideation and behavior. Analyses also evaluated the S-STS mapping to C-SSRS categories. Three trained judges re-rated 89 randomly selected interview videotapes. Cohen κ, the primary outcome measure, quantified agreement above chance. Data were collected between November 2011 and June 2013. RESULTS: All 3 assessments showed excellent accuracy for suicidal ideation (κ = 0.72 to 1.00) and attempts (κ = 0.82 to 0.95) calibrated against latent classes. Interrater agreement ranged from κ = 0.52 to 1.00. Interrater agreement about more granular C-SSRS categories varied more widely (κ = 0.48 to 1.00), and the C-SSRS and S-STS assigned significantly different numbers of cases to many categories. Cronbach α was < 0.55 for the C-SSRS ideation and between 0.78 and 0.92 for the other scales. CONCLUSIONS: All 3 assessments showed good accuracy for broad categories of suicidal ideation and behavior. More granular, specific categories usually were rated reliably, but the C-SSRS and S-STS differed significantly in regard to which patients were assigned to these subcategories. Using any of these interviews would improve reliability over unstructured assessment in evaluating suicidal ideation and behavior. Clinical predictive validity of these interviews, and particularly the more granular categories, remains to be shown.

The treatment of chronic insomnia: drug indications, chronic use and abuse liability. Summary of a 2001 New Clinical Drug Evaluation Unit meeting symposium.

This paper summarizes a group of presentations and panel discussions on chronic insomnia at the 2001 NCDEU meeting. The presentations and discussions focused on the twin issues of efficacy and concerns of abuse liability with long-term hypnotic therapy. The panel concluded that insomnia may be an epidemiological marker for a variety of difficulties including accidents, increased health care utilization and subsequent development of major depression. Whether or not treatment of insomnia will prevent these long-term problems has not yet been determined. Since the mid-1980s there has been a rapid rise in the off-label use of antidepressants, particularly trazodone, for treating insomnia. Some participants expressed concern at the lack of data for this practice, particularly the absence of dose-response and tolerance information, and noted that the small amount of efficacy data available is not encouraging. Similarly, there are minimal data to support the use of antihistamines as sleep aids; moreover, their side effect profile and interactions with other drugs may be under appreciated. The limited data available on nightly long-term usage of the newer non-benzodiazepine hypnotics, primarily of six-months' duration, suggest an absence of tolerance, but more data for both nightly and non-nightly administration are needed. Insomniacs tend to show therapy-seeking, rather than drug-seeking behavior, and patients without histories of drug abuse are unlikely to self-escalate dosage of currently available hypnotics. There is fairly good agreement on the characteristics of an ideal hypnotic. All currently available agents, while effective and safe, do not achieve this ideal. The next few years are likely to see the appearance of a variety of agents with new and promising mechanisms of action.

A postmarketing study of relative abuse liability of hypnotic sedative drugs.

AIMS: To demonstrate the utility of postmarketing studies using in-treatment drug and alcohol abusers as informants for assessing the relative abuse liability of sedative-hypnotic drugs. DESIGN: A survey was conducted that ascertained exposure to a variety of drugs with hypnotic/sedative properties and elicited subjective evaluations indicative of abuse liability. METHODS: Complete data were obtained from 297 admissions (78% male) to three addiction treatment sites in the United Kingdom. Subjects were asked 15 questions about 12 different drugs, including five benzodiazepines, three antidepressants, two non-benzodiazepine hypnotics and two antihistamines (plus one fictitious drug). Three of the benzodiazepines (diazepam, nitrazipam, temazepam) emerged as having substantially more abuse liability than any of the other drugs tested, as revealed by higher scores on abuse liability items (purchased on street, taken to get high, like drug, potential for addiction to drug). The antihistamines (chlorpheniramine, diphenhydramine) had lowest abuse liability profiles, while the antidepressants (amitriptyline, fluoxetine, trazadone) and non-benzodiazepine hypnotics (zolpidem, zopiclone) had similar profiles. CONCLUSION: This pilot study suggests that postmarketing information on hypnotic drug use obtained from drug addicts entering treatment produces data consistent with other measures of abuse liability. The data suggest that the risk of misuse of newer non-benzodiazepine hypnotics may be less than that of benzodiazepine drugs, and similar to that of sedating antidepressants. The new methodology may serve to clarify or validate premarketing abuse liability data, and may help to inform the regulatory process and physician practice.

Effect of two Howard Hughes Medical Institute research training programs for medical students on the likelihood of pursuing research careers.

PURPOSE: To assess the effect of Howard Hughes Medical Institute's (HHMI) two one-year research training programs for medical students on the awardees' research careers. METHOD: Awardees of the HHMI Cloister Program who graduated between 1987 and 1995 and awardees of the HHMI Medical Fellows Program who graduated between 1991 and 1995 were compared with unsuccessful applicants to the programs and MD-PhD students who graduated during the same periods. Logistic regression analyses were conducted to assess research career outcomes while controlling for academic and demographic variables that could affect selection to the programs. RESULTS: Participation in both HHMI programs increased the likelihood of receiving National Institutes of Health postdoctoral support. Participation in the Cloister Program also increased the likelihood of receiving a faculty appointment with research responsibility at a medical school. In addition, awardees of the Medical Fellows Program were not significantly less likely than Medical Scientist Training Program (MSTP) and non-MSTP MD-PhD program participants to receive a National Institutes of Health postdoctoral award, and awardees of the Cloister Program were not significantly less likely than non-MSTP MD-PhD students to receive a faculty appointment with research responsibility. Women and underrepresented minority students were proportionally represented among awardees of the two HHMI programs whereas they were relatively underrepresented in MD-PhD programs. CONCLUSIONS: The one-year intensive research training supported by the HHMI training programs appears to provide an effective imprinting experience on medical students' research careers and to be an attractive strategy for training physician-scientists.

PhD faculty in clinical departments of U.S. medical schools, 1981-1999: their widening presence and roles in research.

PURPOSE: To analyze the growth, research activities, and academic status of PhD faculty in U. S. medical school clinical departments between 1981 and 1999. METHOD: Full-time U.S. medical school faculty who had PhDs and appointments in clinical departments in 1981 and 1999 and junior PhD faculty who became assistant professors between 1981 and 1990 were selected from the Faculty Roster System of the Association of American Medical Colleges. Their research activities and academic statuses were compared with those of MD or MD/PhD faculty in clinical departments or PhD faculty in basic science departments in the same years. RESULTS: The number of PhD faculty in clinical departments now exceeds the number of PhD faculty in basic science departments. PhD faculty in clinical departments come from diverse research backgrounds, contribute substantially to the research intensity of their institutions, and are more likely than their counterparts in basic science departments to become involved in research involving human participants or human tissues. PhD faculty in clinical departments are less likely than their counterparts in basic science departments, but are as likely as physicians in clinical departments, to be rewarded with academic promotion. They are less likely than their physician colleagues to be promoted in research-intensive departments such as departments of medicine and at top 20 research-intensive schools. CONCLUSIONS: The burgeoning career opportunities for PhD faculty in clinical departments should be reflected in the course work, mentorship, and potential thesis topics of PhD training programs. In lieu of tenure, research-intensive medical schools should develop alternative career tracks providing somewhat greater job stability for these faculty.

Medical schools' attitudes and perceptions regarding the use of central institutional review boards.

PURPOSE: To investigate the current practices, attitudes, perceptions, and future plans of U.S. medical schools regarding the use of central institutional review boards (IRBs) to review research involving human participants. METHOD: In 2003, a survey instrument was distributed via fax and e-mail to the deans of research at the 125 accredited U.S. medical schools. Each dean was asked to have the instrument completed by the official at that school who decided on the use of a central versus local IRB. The survey instrument consisted primarily of a variety of closed-ended questions. RESULTS: Eighty-eight medical schools (69.8%) completed the instrument; 76% of these indicated that they had never used a central IRB and 24% had used a central IRB. Most of the respondents expressed no interest in using a central IRB in the future because they believed that their local IRB was working efficiently, and they were concerned about issues of institutional liability and the loss of local representation in the review process. Of the medical schools that had used a central IRB, most were pleased with the performance of the central IRB and would continue to use a central IRB in the future. Of interest, most of these respondents did not agree that a central IRB had helped them to attract industry-sponsored research. CONCLUSIONS: In spite of much discussion about the advantages of central IRBs in expediting overview of human subjects research, especially in multicenter trials, the majority of medical schools surveyed had never used a central IRB and expressed no interest in doing so.

Methodological issues and controversies in clinical trials with child and adolescent patients with bipolar disorder: report of a consensus conference.

OBJECTIVE: To achieve consensus among researchers, pharmaceutical industry representatives, federal regulatory agency staff, and family advocates on a template for clinical trials of acute mania/bipolar disorder in children and adolescents. METHOD: The American Academy of Child and Adolescent Psychiatry, in collaboration with Best Practice, convened a group of experts from the key stakeholder communities (including adult psychiatrists with expertise in bipolar disorder) and assigned them to workgroups to examine core methodological issues surrounding the design of clinical trials and, ultimately, to generate a consensus statement encompassing: (1) inclusion/exclusion criteria, (2) investigator training needs and site selection, (3) assessment and outcome measures, (4) protocol design and ethical issues unique to trials involving children/adolescents, and (5) regulatory agency perspectives on these deliberations. RESULTS: Conference participants reached agreement on 18 broad methodological questions. Key points of consensus were to assign priority to placebo-controlled studies of acute manic episodes in children and adolescents aged 10-17 years, who may or may not be hospitalized, and who may or may not suffer from common comorbid psychiatric disorders; to require that specialist diagnostic "gatekeepers" screen youths' eligibility to participate in trials; to monitor interviewer and rater competency over the course of the trial using agreed upon standards; and to develop new tools for assessment, including scales to measure aggression/rage and cognitive function, while using the best available instruments (e.g., Young Mania Rating Scale) in the interim. CONCLUSIONS: Methodologically rigorous, large-scale clinical trials of treatment of acute mania are urgently needed to provide information regarding the safety and efficacy, in youth, of diverse agents with potential mood-stabilizing properties.