Identification of a novel TP53 germline mutation E285V in a rare case of paediatric adrenocortical carcinoma and choroid plexus carcinoma.

Paediatric choroid plexus carcinomas (CPC) and adrenocortical carcinomas (ACC) are exceedingly rare tumours, each occurring at an annual rate of 0.3 cases per million children or less. Although both tumour types are associated with Li-Fraumeni syndrome (LFS), the penetrance of germline TP53 mutations in CPC remains to be established. We report here a young boy without a family history of cancer who presented with CPC and subsequently ACC. Genetic testing revealed a novel de novo germline TP53 mutation (E285V). Neither tumour underwent loss of heterozygosity. Consistent with this observation, functional analyses demonstrated that E285V acts as a dominant negative mutant that is defective in regulating target gene expression, growth suppression and apoptosis. These results further strengthen the association between germline TP53 mutations and childhood CPC, even when occurring in the absence of familial tumour susceptibility.

Comparing measures of patient safety for inpatient care provided to veterans within and outside the VA system in New York.

CONTEXT: Previous studies have compared measures of patient safety for veterans using the VA system to the general population. Discrepancies in the results of those studies suggest that the choice of an appropriate comparison group is critical for accurate interpretation of results and for determining whether to take actions to address findings. We explored another method of providing consumer information by comparing the experiences of VA enrolled patients who received care in the VA to those who received care outside the VA system. OBJECTIVE: For male veterans living in New York State and enrolled in the VA healthcare system, to determine (a) whether those who obtain care outside the VA system experience different measures of patient safety than those treated within the VA system, and (b) whether cross-system comparisons of measures of patient safety among older veterans reflect those of the full age spectrum. DESIGN: Retrospective cohort analysis. SETTING: All VA and non-VA hospitals in New York State. PATIENTS: 353,570 male New York State residents who were enrolled in the VA system in 1998, 1999 or 2000. MAIN OUTCOME MEASURES: The Agency for Healthcare Research and Quality (AHRQ) has developed Patient Safety Indicators (PSIs) from hospital discharge data. To standardise these indicators across settings, AHRQ has provided software for risk-adjustment purposes so that the indicators can be compared across settings of care. We used the PSI software to calculate risk-adjusted PSI rates with 95% confidence intervals to compare veterans' inpatient care provided within and outside the VA system. RESULTS: Risk-adjusted rates for nine of 15 PSIs did not differ between care provided within and outside the VA system. However, compared with care provided outside the VA system, risk-adjusted rates of decubitus ulcer, postoperative sepsis, infection due to medical care, postoperative respiratory failure and postoperative metabolic derangement occurred at lower rates within the VA system, while death in low mortality DRGs occurred at a higher rate in the VA system. Findings for patients aged 65 and older were similar to those of the entire age spectrum. CONCLUSIONS: Using AHRQ's PSI software, male veterans in New York who obtain their inpatient care within the VA received care that was comparable with or somewhat better than those who obtained their inpatient care outside the VA. The experiences of older patients reflected those of younger patients. Given that our findings are much more similar to reported comparisons between the VA and Medicare than to comparisons between the VA and the general population, we conclude that, should system comparisons be made, choice of comparison groups will be critical to accurate interpretation of findings; however, prior to such interpretation, the validity of the PSIs must be determined within VA.

Rats with lesions of the hippocampus are impaired on the delayed nonmatching-to-sample task.

Rats with ibotenic acid lesions of the hippocampus (H-IBO) were trained on the trial-unique delayed nonmatching-to-sample task (DNMS) using a short delay of 4 s. The H-IBO group learned the nonmatching rule as quickly as control animals. However, performance was impaired on the DNMS task when the delay between the sample and choice phase was increased to 1 or 2 min. The use of 4-s delay (probe) trials indicated that the H-IBO animals retained the nonmatching-to-sample rule throughout testing. In a second experiment, using the same groups of rats, extended training at the 1-min delay did not ameliorate the deficit produced by H-IBO lesions. The finding of impaired recognition memory in rats after hippocampal lesions is consistent with findings from humans and monkeys. Several methodological issues are considered that have complicated the interpretation of earlier studies of recognition memory in rats following hippocampal lesions. The capacity for recognition memory in humans, monkeys, and rodents is discussed as a straightforward example of hippocampus-dependent (declarative) memory.

Double-blind, placebo-controlled trial of methylphenidate in older, depressed, medically ill patients.

OBJECTIVE: The authors examined the efficacy of methylphenidate in the treatment of depression in a group of older, medically ill patients. METHOD: Sixteen patients underwent an 8-day double-blind, randomized, placebo-controlled crossover trial; 13 completed the trial. RESULTS: Statistically and clinically significant treatment responses were found. CONCLUSIONS: These results support the use of methylphenidate in older, medically ill patients in whom rapid resolution of depressive symptoms is crucial.

Resolution of depressive symptoms in medical inpatients after discharge.

OBJECTIVE: Most studies to date demonstrate a high prevalence of depressive symptoms and depressive disorders in general medical inpatients. In order to determine whether these symptoms represent a self limited epiphenomenon of medical illness or evidence of psychiatric comorbidity, assessment of the natural history of such symptoms in this population is necessary. In this study we focused on resolution versus persistence of depressive symptoms in hospitalized medical patients following medical, but not psychiatric, treatment. METHOD: Every second admission to the acute care medical ward of a VA teaching hospital was assessed for inclusion in the study. Fifty-seven were screened, fifty participated initially, forty-two remained in the study for the one-week post-discharge follow-up, and thirty-three remained at the one-month follow-up. Depressive symptomatology was measured with the Beck Depression Inventory at each time point. Subjects whose scores at follow-ups were above threshold were considered to have persistent symptoms and those whose scores fell below threshold were considered to have resolved. No patients were treated with antidepressants prior to or during the study. RESULTS: With a conventionally accepted threshold score (14) on the BDI as representing clinically significant depression, roughly half of those patients identified as depressed at the time of admission were nondepressed at both follow-ups. The BDI predicted persistence of depression with a sensitivity of .64 and specificity of .74 at one week and .71 and .73 at one month. Raising the threshold score to 20 raised the sensitivity to 1.00 and the specificity to .95 at one week and 1.00 and .93 at one month. CONCLUSIONS: Depressive symptoms seen in acutely-ill medical patients can be expected to resolve without potentially-hazardous antidepressant treatment in a significant number of patients. Persistence of depressive symptoms may be better predicted by raising the threshold on commonly used self-report scales.

Multiple timing and the allocation of attention.

Two experiments were designed to examine the effects of multiple timing tasks on prospective time judgment performance. In experiment 1, subjects were required to monitor the durations of one, two, three, or four concurrent target stimuli which began and ended at different times, and then reproduce one of those durations subsequently chosen at random. Time judgment accuracy deteriorated as the number of target stimuli increased. In experiment 2, subjects used the production method to generate specified durations for one, two, three, or four partially overlapping stimuli. Timing was less accurate in conditions involving more target stimuli. In the multiple-target conditions, time judgments were less accurate for the later- rather than earlier-onset targets. The results support an attentional model of timing, and suggest that timing is an effortful process which draws from limited attentional resources.

Relationship between utilization of mental health and medical services in a VA hospital.

Previous research has demonstrated a reduction in utilization of medical services following the initiation of psychiatric services for certain patients. The phenomenon has been called the offset effect. The authors investigated the offset effect in a Veterans Administration medical center setting. They found that the offset effect emerged only for patients who had high rates of use of medical services who received mental health services for 1 year or less. They discuss factors related to higher rates of medical care utilization as well as important differences between the present and previous research that require further study.

Women physicians and their mentors.

This study surveyed 189 women physicians in order to compare the experiences of those who had male mentors with those who had female mentors. Respondents with high-ranking male mentors reported more career sponsorship. However, those with lower ranking female mentors reported more personal advice. In addition, those with female mentors reported fewer problems retaining their autonomy in the relationship. The mentor's administrative or academic rank, rather than gender, was the chief determinant of sponsoring effectiveness. These results suggest that women physicians face a dilemma in their choice of mentors, and underscore the importance of promoting women physicians to positions of authority in medical schools and training hospitals.

Primary process content in paranoid schizophrenic speech.

Free speech samples given by paranoid schizophrenics, nonschizophrenic paranoids, and nonpsychotic psychiatric patients were submitted to computerized content analysis. Speech samples were searched for words belonging to the Regressive Imagery Dictionary (Martindale, 1975), which yields a well-validated measure of primary process content. Three word-concreteness dictionaries were also employed. Compared to the other groups, paranoid schizophrenics produced speech higher in primary process content as well as in transitive verb concreteness. Results are consistent with psychoanalytic theory.

Integration of VA and CMHC care: utilization and long-term outcome. Community Mental Health Center.

An innovative treatment program was established through which VA outpatient mental health care was decentralized via integration with the CMHC system in northern Vermont. A long-term follow-up study evaluated the success of Veterans' Integrated Community Care (VICC) in meeting its goal of enhanced access to care and better treatment outcomes. Three groups were compared: veterans who were transferred from VA hospital care to VICC care, veterans who were treated at the VA hospital only, and veterans who were newly reached through the VICC program. Follow-ups were conducted 18 months after intake and at least two years thereafter. Results indicate that all groups were improved symptomatically at the first follow-up, but only VICC patients maintained this improvement subsequently. By the last follow-up, VICC patients had reduced their utilization of VA psychiatric care, whereas veterans who had received only hospital-based care had not. VICC treatment represents a viable alternative to centralized VA mental health care.

Current need versus treatment history as predictors of use of outpatient psychiatric care.

The authors conducted a study of treatment utilization and outcome on a sample of 116 psychiatric outpatients at a Veterans Administration (VA) hospital. Utilization and outcome measures were obtained at a follow-up interview 18 months after a baseline assessment. Comparisons between patients with high and low rates of utilization revealed negligible relationships between use of services and severity of illness, clinical change, or demographics. However, previous use of VA outpatient and inpatient psychiatric services and VA psychiatric disability rating predicted utilization of psychiatric care during the study. The authors conclude that use of VA outpatient psychiatric care may reflect patients' help-seeking history more than their current clinical need.

Measurement of combat exposure, posttraumatic stress disorder, and life stress among Vietnam combat veterans.

Two scales developed to assess combat exposure and posttraumatic stress disorder symptomatology in Vietnam veterans displayed very high reliability. High levels of posttraumatic stress disorder were associated with more current life stresses and other standardized indices of dysphoria.

Developmental functions in a chronic psychiatric population: diagnosis.

The research in psychopathology has revealed little interest in distinguishing between types of chronic mental patients. Chronics have usually been treated as a homogeneous group, and other possible subtypes have remained undefined because of the "melting-pot" effects of extensive hospitalization. Recently, there has been a renewed interest in the chronic patient, as well as in a differentiation of the largest group of such patients, the chronic schizophrenic. Ss were 129 inpatients at a state mental hospital in Maine. The present report begins the specification of a diagnostic system for chronic patients with the use of tasks that reflect developmental functions. Factor analysis of a set of developmental tasks, ranging from early reflex tests to later cognitive operations, resulted in a test battery which clearly defines specific developmental functions. Of most importance, the clusters of patients derived from these factors exhibited differential profiles indicating strengths and weaknesses on the developmental functions. The assumption of a developmental task sequence was not supported by the results, but the diagnosis of the chronic patient in terms of developmental functions appears promising.