Malignancy Rate, Number Needed to Treat, and Positive Predictive Value for Breast MRI.

Breast MRI is being used more frequently for advanced screening for breast cancer. Patients may be at increased risk, or are symptomatic, with nonsuspicious mammograms. There is little data regarding the likelihood of a recommendation for biopsy, or for detecting a malignancy, in this population. We intended to determine the malignancy rate, number needed to treat, and positive predictive value for patients receiving adjunctive MRI at our institution. A retrospective review of all breast MRIs from 2008 to 2010 was done. Patients with any prior diagnosis of breast cancer, or BRCA+ were excluded. There were 324 patients. Most common reasons for ordering the breast MRI included: abnormal test result 130 (44%), palpable mass 74 (23%), family history 58 (18%), breast pain 47 (15%), and nipple discharge 45 (14%). Breast Imaging-Reporting and Data System score (BIRADS) was 1 or 2 in 36 per cent, 4 or 5 in 18 per cent, 3 in 26 per cent, 0 in 10 per cent, and not given in 9 per cent. Biopsy was recommended in 77 (24%), with biopsy actually performed in 57 (18%). Of the eight cancers identified, four (1.2%) were ductal carcinoma in situ (DCIS) and four (1.2%) were invasive cancer, yielding a true-positive rate of 2.5 per cent. Number needed to treat was 40. Positive predictive value was 14 per cent with a false-positive rate of 86 per cent. In this group of generally higher risk women, typically prescreened with mammography, 1.2 per cent had an invasive cancer, and another 1.2 per cent had DCIS. Those who undergo biopsy are 6.1 times more likely to have benign pathology. The efficacy of adjunctive breast MRI could be improved through refinements in indication, test interpretation, or alternative screening strategies.

Laparoscopic Hysterectomy and Urinary Tract Injury: Experience in a Health Maintenance Organization.

STUDY OBJECTIVES: To evaluate the incidence, detection, characteristics, and management of urinary tract injury in a cohort undergoing laparoscopic hysterectomy, and to identify potential risk factors for urinary tract injury with laparoscopic hysterectomy. DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: Kaiser Permanente San Diego Medical Center, 2001 to 2012. PATIENTS: Women who underwent attempted laparoscopic hysterectomy for benign indications. INTERVENTIONS: Total laparoscopic hysterectomy, laparoscopic-assisted vaginal hysterectomy, and laparoscopic supracervical hysterectomy. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical characteristics, surgical techniques, and perioperative complications were abstracted from the medical record. Multivariable logistic regression analysis assessed independent risk factors for ureteral or bladder injury. RESULTS: A total of 3523 patients (mean age, 45.9 ± 8.0 years; median parity, 2; range, 0-10), with a median body mass index (BMI) of 29 kg/m(2) (range, 16-72 kg/m(2)), underwent laparoscopic hysterectomy; 20% had intraoperative cystoscopy. The incidence of urinary tract injury was 1.3% (46 of 3523); of the 46 patients with injuries, 19 (0.54%) had ureteral injuries, 25 (0.71%) had bladder injuries, and 2 (0.06%) had both types. Of the 21 ureteral injuries, 6 (29%) were diagnosed intraoperatively and 15 (71%) were diagnosed postoperatively, including 4 with normal intraoperative cystoscopy. Of the 27 bladder injuries, 23 (85%) were identified intraoperatively. In multivariable logistic analysis, a BMI of 26 to 30 kg/m(2) (compared with >30 kg/m(2)) was associated with an increased risk of ureteral injury, and a BMI ≤25 kg/m(2) (compared with >30 kg/m(2)) and the presence of endometriosis were associated with an increased risk of bladder injury. CONCLUSION: Urinary tract injury occurred in 1.3% of laparoscopic hysterectomies, with ureteral injuries almost as common as bladder injuries. Normal intraoperative cystoscopy findings did not exclude the presence of ureteral injury.

Uterine sarcomas and parasitic myomas after laparoscopic hysterectomy with power morcellation.

OBJECTIVE: The purpose of this study was to describe the incidence and risk factors for uterine sarcomas and parasitic myomas at the time of power morcellation. STUDY DESIGN: We performed a retrospective review of 3523 women who underwent laparoscopic hysterectomy from 2001-2012. Univariate analyses were used for the morcellation cases to identify potential risk factors. Multivariable logistic regression was performed. RESULTS: Nine hundred forty-one patients underwent power morcellation at the time of hysterectomy; 10 of 941 patients (1.1%) were diagnosed subsequently with uterine sarcomas or parasitic myomas. The overall incidence of uterine sarcoma was 6 of 941 (0.6%), with a median age of 47 years (range, 41-52 years). There was no association among any of the factors analyzed and uterine sarcoma. Three of 6 patients had sarcoma diagnosed on initial pathologic evaluation of the morcellated specimen; 3 patients had delayed diagnosis of sarcoma with benign disease at the time of the initial procedure (median time to second evaluation, 6 years). For parasitic myomas (n=4), the median age was 35 years (range, 32-40 years), and the median time to second evaluation was 5 years. On multivariate analysis, age<40 years (odds ratio, 26; 95% confidence interval, 2.7015-261.9; P≤.01) was associated with higher risk of the development of parasitic myomas. CONCLUSION: Uterine sarcoma was found in 0.6% of patients who underwent power morcellation but was not found to be associated significantly with any preoperative factors. All 6 cases were noted to have apparent fibroid tumors as an indication for their hysterectomy. Age<40 years was a risk factor for parasitic myomas after power morcellation. Patients should be counseled about these complications before power morcellation.

Breast cancer care in the community: challenges, opportunities, and outcomes.

In the USA, 80% of patients with breast cancer are treated by community breast surgeons. NCDB data indicate that there are only small differences in outcomes between lower volume cancer programs and higher volume programs. There is some evidence that breast cancer patients of high-volume breast focused surgeons may have improved outcomes. This article discusses the challenges community breast surgeons face and some ways that the quality of care could be monitored and improved. Quality reporting programs of the Commission on Cancer and Mastery of Breast Surgery Program of the American Society of Breast Surgeons are recommended as tools to track and improve outcomes in breast cancer care.

Factor structure and concurrent validity of the Satisfaction with Life Domains Scale for Cancer (SLDS-C).

The Satisfaction with Life Domains Scale for Cancer (SLDS-C) is a brief self-report measure of quality of life that uses a familiar and easily understood graphic response format of smiling and frowning faces. This article explores the factor structure and further examines the validity of the SLDS-C compared with another cancer specific quality-of-life measure, the Functional Assessment of Cancer Therapy Scale-General (FACT-G), in a sample of patients with a variety of cancer diagnoses. A self-administered questionnaire containing the SLDS-C and the FACT-G was completed by 352 adult cancer survivors who were at various points post diagnosis. Three SLDS-C factor subscales were derived from analyses of these data: "Life as a Whole," "Daily Activities," and "Social Relationships." Evidence for the concurrent validity of the SLDS-C is presented, including its correlation with the total score of the FACT-G (r = .76) and its correlation with subscale scores of this widely used cancer quality-of-life measure. The SLDS-C has a high level of internal consistency (alpha = .94), and differences in SLDS-C total scores were found for time since diagnosis, number of diagnoses, spread of disease, type of cancer, and treatment status.

Treatment enhances ultradian rhythms of CSF monoamine metabolites in patients with major depressive episodes.

Unipolar and bipolar depressions show abnormal behavioral manifestations of ultradian (less than 24 h) rhythms, but abnormal rhythms of the central neurotransmitters thought to be important for depression pathophysiology (eg dopamine (DA) and serotonin (5-HT)) have not been shown in this time frame. Since antidepressant treatments normalize disrupted rhythms in depression (eg rapid-eye-movement sleep and hormonal rhythms), we hypothesized that depression-related changes in ultradian oscillations of DA and 5-HT might be revealed during antidepressant treatment. Cerebrospinal fluid (CSF) samples collected q10 min for 24 h in 13 patients experiencing major depressive episodes (MDE) before and after treatment for 5 weeks with sertraline or bupropion were assayed for levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), and their ratio was calculated. Data were analyzed in the frequency domain using Fourier transforms and multivariate permutation testing. Antidepressant treatments were associated with decreased variance for 5-HIAA, increased variance for HVA, and markedly increased variance for the HVA : 5-HIAA ratio (p<0.05, p<0.02, and p<0.003, respectively). With treatment, the correlations between 5-HIAA and HVA weakened (p=0.06). Power spectral density (PSD-the Fourier magnitude squared) of the 5-HIAA signals at periods of 1.75 and 3.7 h (both p<0.05) decreased, while circadian cycling of HVA levels (p<0.05) and of the ratio (p<0.005) increased after treatment. The PSD of the full-length HVA : 5-HIAA ratio series after treatment increased in rapid variability (20-103 min periods, p<0.05). Spectrographic windowing demonstrated a focal span of enhanced HVA : 5-HIAA ratio variability following antidepressant treatment, in an approximately 84-min period through the evening (p<0.05). Periodic neurotransmitter relationships in depressed patients were altered by treatment in this analysis of a small data set. This may represent a baseline abnormality in the regulation of periodic functions involved in the depression pathophysiology, but it could also be due to an unrelated antidepressant effect. Further studies including comparisons with healthy subject data are in progress.

Duloxetine for the treatment of major depressive disorder in older patients.

OBJECTIVE: The efficacy and safety of duloxetine, a dual reuptake inhibitor of serotonin (5-HT) and norepinephrine (NE), were evaluated in the treatment of major depressive disorder (MDD) and associated pain symptoms in patients age 55 and older. METHODS: Efficacy data were obtained from patients age > or =55 who participated in two identical, multicenter, double-blind studies in which patients with MDD were randomized to receive placebo (N=43) or duloxetine (60 mg/day; N=47) for 9 weeks. The primary efficacy measure was the mean change in Ham-D-17 total score. Pain symptoms were assessed with visual-analog scales. Safety data for patients age > or =55 were pooled from six randomized, 8- or 9-week, double-blind studies of duloxetine in which patients with MDD were randomized to receive placebo (N=90) or duloxetine (40 mg/day-120 mg/day; N=119). RESULTS: The combined results of these two investigations found that duloxetine was significantly superior to placebo for mean change in Ham-D-17 total score. The estimated probability of remission for duloxetine-treated patients (44.1%) was also significantly higher than that for placebo (16.1%). Reductions in overall pain, back pain, and pain while awake were also significantly greater for duloxetine than placebo. The rate of discontinuation due to adverse events was significantly higher for duloxetine-treated patients (21.0%) than placebo (6.7%). Abnormal elevations in vital signs at endpoint were not significantly different from placebo. CONCLUSIONS: In these two investigations, duloxetine 60 mg/day was an efficacious treatment for MDD and also alleviated pain symptoms in depression patients age 55 and older.

Treatment of glossodynia with olanzapine.

A 73-year-old white male with a 6-month history of glossodynia, unresponsive to clotrimazole troches, cevimeline, triamcinolone dental paste, paroxetine, and lorazepam presented to the dermatology clinic for consultation. Work-up revealed no oral abnormalities and no underlying systemic disorder. He denied symptoms consistent with a psychiatric disorder. A detailed free amnestic assessment by a board certified Geriatric Psychiatrist (John S. Kennedy, MD) found that the patient was oppressed by the pain. He did not meet the criteria for major depression nor did he have any anxiety disorder or delusions. Because of the presence of dysphoria and anticipatory anxiety secondary to glossodynia, the patient was started on olanzapine. Improvement of pain symptoms were noted within 3 days with full resolution of symptoms at 1- and 3-month follow-ups. Dysphoria and anticipatory anxiety remitted fully upon pain relief.

The rate, pattern, and cost of use of antiparkinsonian agents among patients treated for schizophrenia in a managed care setting.

OBJECTIVE: To examine the use and economic cost of antiparkinsonian agents during the medication management of patients diagnosed with schizophrenic disorders in a naturalistic healthcare setting. DESIGN: Cross-sectional retrospective analysis of 1-year (1999) administrative data from a large managed care organization. PATIENTS AND METHODS: Patients were 1938 adults who were treated for a schizophrenic disorder. Monthly per patient utilization rate and cost of antiparkinsonian agents, and the proportion of the total psychiatric medication costs attributed to the antiparkinsonian agents, were compared across antipsychotic medications (typical, atypical, olanzapine, risperidone), age, sex, and diagnostic subtype. RESULTS: About one third (39%) of the patients were treated with typical antipsychotics only, and half of them (51%) received antiparkinsonian agents. Those treated with atypical antipsychotics only (41%) were considerably less likely to receive antiparkinsonian agents (25%), and the rate of use differed by atypical type such that risperidone-treated patients were more likely to receive antiparkinsonian agents than those treated with olanzapine. Lower utilization rates of antiparkinsonian agents were also found among patients age 75 years or older, and among those diagnosed with a schizoaffective disorder. Average monthly per patient cost of antiparkinsonian agents was 3.0 dollars, constituting 2.6% of the monthly expenditure on all psychiatric medications. CONCLUSIONS: Adjunctive use of antiparkinsonian agents differs widely among patients who are treated with typical or atypical antipsychotic drugs, and differs between types of atypical antipsychotics. The choice of atypical antipsychotics that have a lower liability for extrapyramidal symptoms may assist in optimizing the long-term functional outcomes of schizophrenia patients.

Retrospective cohort study of diabetes mellitus and antipsychotic treatment in a geriatric population in the United States.

OBJECTIVES: The objective of this study was to investigate risk of diabetes among elderly patients during treatment with antipsychotic medications. DESIGN: We conducted a longitudinal, retrospective study assessing the incidence of new prescription claims for antihyperglycemic agents during antipsychotic therapy. SETTING: Prescription claims from the AdvancePCS claim database were followed for 6 to 9 months. PARTICIPANTS: Study participants consisted of patients in the United States aged 60+ and receiving antipsychotic monotherapy. The following cohorts were studied: an elderly reference population (no antipsychotics: n = 1,836,799), those receiving haloperidol (n = 6481) or thioridazine (n = 1658); all patients receiving any conventional antipsychotic monotherapy (n = 11,546), clozapine (n = 117), olanzapine (n = 5382), quetiapine (n = 1664), and risperidone (n = 12,244), and all patients receiving any atypical antipsychotic monotherapy (n = 19,407). MEASUREMENTS: We used Cox proportional hazards regression to determine the risk ratio of diabetes for antipsychotic cohorts relative to the reference population. Covariates included sex and exposure duration. RESULTS: New antihyperglycemic prescription rates were higher in each antipsychotic cohort than in the reference population. Overall rates were no different between atypical and conventional antipsychotic cohorts. Among individual antipsychotic cohorts, rates were highest among patients treated with thioridazine (95% confidence interval [CI], 3.1- 5.7), lowest with quetiapine (95% CI, 1.3-2.9), and intermediate with haloperidol, olanzapine, and risperidone. Among atypical cohorts, only risperidone users had a significantly higher risk (95% CI, 1.05-1.60; P = 0.016) than for haloperidol. Conclusions about clozapine were hampered by the low number of patients. CONCLUSION: These data suggest that diabetes risk is elevated among elderly patients receiving antipsychotic treatment. However, causality remains to be demonstrated. As a group, the risk for atypical antipsychotic users was not significantly different than for users of conventional antipsychotics.

Comparison of risperidone and olanzapine in the control of negative symptoms of chronic schizophrenia and related psychotic disorders in patients aged 50 to 65 years.

BACKGROUND: This analysis compares the efficacy of risperidone and olanzapine in controlling negative and positive symptoms of chronic psychosis in older patients. METHOD: Post hoc assessments were made in a subset of risperidone-treated (N = 19) and olanzapine-treated (N = 20) older patients (aged 50 to 65 years) from a large international, multicenter, parallel, double-blind, 28-week study of patients aged 18 to 65 years (N = 339) randomly assigned to receive risperidone (4-12 mg/day) or olanzapine (10-20 mg/day). Assessments were made using repeated-measures analysis. RESULTS: At both 8 weeks and 28 weeks, the magnitude of changes in Positive and Negative Syndrome Scale (PANSS) positive symptom subscale scores did not differ between treatment groups (8 weeks: risperidone, -6.5; olanzapine, -6.8, p = .866; 28 weeks: risperidone, -6.5; olanzapine, -7.0; p = .804). However, by the 8-week timepoint, olanzapine had reduced PANSS negative subscale scores significantly more than risperidone (-8.8 vs. -4.9, p = .032). By the 28-week endpoint, olanzapine had continued to maintain significantly greater reduction in baseline-to-endpoint PANSS negative scores (-8.1 vs. -3.5, p = .032) and led to significantly greater reduction in scores on the Scale for the Assessment of Negative Symptoms (SANS) dimensions of affective flattening (-5.2 vs. -0.6, p = .033) and alogia (-3.8 vs. -0.3, p = .007). Patients in the olanzapine treatment group also demonstrated numerically greater reduction of both SANS summary (-3.7 vs. -1.0, p = .078) and SANS composite scores (-14.1 vs. -4.1, p = .075). CONCLUSION: These data demonstrate that, in older patients with schizophrenia and related psychotic disorders, risperidone and olanzapine have approximately equal efficacy in controlling positive symptoms. However, olanzapine appears to be more efficacious in maintaining control over negative symptoms.

Is absolute amount or change in exercise more associated with quality of life in adult cancer survivors?

BACKGROUND: The present study examined the association between quality of life (QOL) in adult cancer survivors and the (a) absolute current amount of exercise and (b) change in exercise since cancer diagnosis. METHODS: Three hundred fifty-two (mean age = 59.6) adult cancer survivors recruited from outpatient clinics in four states (Iowa, Wisconsin, Minnesota, and Georgia) and a minority support groups completed a survey including demographic, medical, exercise behavior, and QOL questions. RESULTS: Hierarchical multiple regression analyses controlling for important demographic and medical variables showed that adult cancer survivors who currently exercised three times per week had significantly higher QOL than those who did not (beta = 0.13, P < 0.05). Furthermore, compared to adult cancer survivors who exercised less since their cancer diagnosis, those who maintained (beta = 0.28, P < 0.08) or increased (beta = 0.24, P < 0.01) the amount of exercise they performed since their cancer diagnosis had significantly higher QOL. Finally, examination of the DeltaR(2)(adjusted) between the two exercise models showed that the absolute current amount of exercise explained an additional 1% (DeltaR(2)(adjusted) = 0.01 P < 0.05) of the variance in QOL whereas the change in exercise explained an additional 7% (DeltaR(2)(adjusted) = 0.07, P < 0.01). CONCLUSION: Change in exercise since cancer diagnosis may be a more important correlate of QOL in adult cancer survivors than the absolute current amount of exercise.

The effects of antipsychotic drug treatment on prolactin concentrations in elderly patients.

OBJECTIVE: To describe the change in serum prolactin concentrations in elderly agitated nursing home patients with dementia who were newly initiated on olanzapine or switched to olanzapine treatment from either conventional antipsychotics or risperidone. METHODS: During an 8-week open-label olanzapine efficacy trial in elderly nursing home patients demonstrating clinically significant behavioral and psychological symptoms of dementia, serum prolactin concentrations were drawn on four occasions: at time of consent, following a washout period from previous therapy, midway through the study, and at endpoint. To assess post-hoc the effects of prolactin concentrations upon switching to olanzapine treatment, patients were divided into three different groups, based upon status at time of consent: those not taking antipsychotic medication, those taking any conventional antipsychotic, and those taking risperidone. Prolactin concentrations were assessed using a mixed-effect repeated-measures model. Symptom severity was measured using the Brief Psychiatric Rating Scale (BPRS), the Cohen-Mansfield Agitation Inventory (CMAI), the Clinical Global Impression (CGI)-Severity scale, and the Mini-Mental State Examination (MMSE), and the same repeated measures analysis was performed on these scales. RESULTS: Patients not on antipsychotic medication at study entry (29 females, 7 males) experienced a significant increase in prolactin concentration baseline to endpoint (P < 0.05) but remained below upper limit of normal for prolactin for both males and females. There was a nonsignificant increase in prolactin concentrations when patients were switched from conventional antipsychotic medications (mean dose 152.41 +/- 192.48 mg/day chlorpromazine equivalents) to olanzapine (2.5 to 10 mg/day) (22 females, 9 males). Patients who entered the study on risperidone (mean dose 1.31 +/- 0.91 mg/day) (13 females, 4 males) experienced a significant decrease in prolactin concentration (P < 0.001). While 62.5% of risperidone-treated patients had above-normal prolactin concentrations at baseline, only 21.4% had above-normal concentrations at endpoint (P = 0.033). Clear correlations between prolactin concentrations and clinical outcomes could not be determined. CONCLUSION: Consistent with previous findings in younger patients, olanzapine appeared to be a prolactin-sparing antipsychotic medication in the elderly with only modest prolactin increases observed. In addition, patients who were receiving risperidone and then switched to olanzapine experienced a significant reduction in prolactin concentrations that was sustained over the 8-week treatment course with olanzapine. One possible explanation for olanzapine's relatively modest increase in prolactin is that, unlike conventionals or risperidone, olanzapine binds less tightly with the dopamine D(2) receptor.

Diurnal variation of cerebrospinal fluid hypocretin-1 (Orexin-A) levels in control and depressed subjects.

BACKGROUND: Hypocretins, excitatory neuropeptides at monoaminergic synapses, appear to regulate human sleep-wake cycles. Undetectable cerebrospinal fluid hypocretin-1 levels are seen in narcolepsy, which is frequently associated with secondary depression. Shortened rapid eye movement latency is observed in both narcolepsy and depression. Cerebrospinal fluid hypocretin-1 levels have not been reported in mood disorders. METHODS: We examined hypocretin-1 levels in 14 control and 15 depressed subjects. Cerebrospinal fluid was drawn continuously in supine subjects for 24 hours with an indwelling intrathecal catheter under entrained light-dark conditions. Depressed subjects were studied before and after 5 weeks of sertraline (n=10, three nonresponders) or bupropion (n=5, two nonresponders). RESULTS: Hypocretin-1 levels varied slightly (amplitude 10%) but significantly across the diurnal cycle in control subjects, with amplitude significantly reduced in depression (3%). Levels were lowest at midday, surprising for a hypothetically wake-promoting peptide. Mean hypocretin levels trended higher in depressive than in control subjects. Hypocretin-1 levels decreased modestly but significantly after sertraline (-14%) but not bupropion. CONCLUSIONS: Our results are consistent with previous physiologic findings in depression indicating dampened diurnal variations in hypocretin-1. The finding that sertraline but not bupropion slightly decreased cerebrospinal fluid hypocretin-1 indicates a serotoninergic influence on hypocretin tone.

Do adults change their lifestyle behaviors after a cancer diagnosis?

OBJECTIVE: To examine changes in lifestyle behaviors after a cancer diagnosis and medical and demographic influences on such changes. METHODS: Adult cancer survivors (n = 352) completed a survey including demographic, medical, and lifestyle behavior change questions. RESULTS: Results showed that since cancer diagnosis, 46% of smokers quit smoking, 47% improved their dietary habits, and 30.1% exercised less. Adult cancer survivors who changed their lifestyle behaviors varied, depending on various demographic and medical variables and physician recommendation. CONCLUSION: It appears from our data that cancer diagnosis in adults may have a positive influence on smoking and diet and a negative influence on exercise.

Association of a critical CSF tryptophan threshold level with depressive relapse.

This work studies association between relapse during acute tryptophan depletion (ATD) and CSF level of tryptophan (TRP) in remitted depressives treated with sertraline or bupropion. Eight medication-responding depressives ingested an ATD amino acid mixture during 48-h continuous CSF sampling before and after treatment. Mood rating scores were compared with nadir levels of TRP in CSF. CSF TRP nadirs averaged 8.7% of am baselines in remitted patients. Mood relapsed whenever the CSF nadir was below 40 nmol/l TRP in remitted patients, and never when above (Fisher's exact test, P=0.029). Relapsing medication responders also showed very low preantidepressant ATD-induced nadirs. ATD-induced relapses were associated with low CSF TRP levels. Individual susceptibility to depletion may be independent of antidepressant treatment, mood state, or treatment status. Resistance to relapse may invoke an undefined, protective CNS mechanism against extremely low CSF levels of TRP during ATD.

Pharmacotherapy of behavioral and psychological symptoms of dementia: a review of atypical antipsychotics.

OBJECTIVE: To review the literature on use of antipsychotics to treat behavioral and psychological symptoms of dementia (BPSD). DATA SOURCES: Information was selected from a MEDLINE search of English-language medical literature using the search terms "antipsychotics" and "elderly." Manual searches of pertinent journal article references, and review of poster presentations at recent professional meetings were also performed. STUDY SELECTION: Meta-analyses published in 1990 and 1998 were used as a starting point for information about conventional antipsychotics. Articles reporting the results of controlled trials of conventional antipsychotics published since the second meta-analysis (October 1998) were included. Also included were articles reporting the results of controlled clinical trials of atypical antipsychotics (i.e., clozapine, risperidone, olanzapine, quetiapine, ziprasidone) for the treatment of dementia in the elderly. Studies and post hoc analyses of special patient populations (Parkinson's disease, schizophrenia, treatment-refractory BPSD) were excluded. One open-label extension and one post hoc analysis were included because they provide valuable information about the long-term use of atypical antipsychotics. One poster was included, as it contained the only data available from a controlled trial of quetiapine. DATA EXTRACTION: Data were extracted from the literature, as well as a recent scientific poster presentation. Two meta-analyses and six controlled studies were identified for inclusion. DATA SYNTHESIS: There are few controlled clinical trials of the use of antipsychotics in elderly patients with dementia. Currently available information indicates these medications are useful in the treatment of behavioral and psychological symptoms of dementia, but the clinician must exercise caution because of the drugs' potential side effects. CONCLUSION: While widely prescribed on an "off-label" basis, there is a dearth of placebo-controlled clinical trials necessary to evaluate safety, and head-to-head comparative studies necessary to contrast efficacy and safety of atypical antipsychotics in treating BPSD.

Serial cerebrospinal fluid tryptophan and 5-hydroxy indoleacetic acid concentrations in healthy human subjects.

The role of the serotonergic system in the pathogenesis of behavioral disorders such as depression, alcoholism, obsessive-compulsive disorder, and violence is not completely understood. Measurement of the concentration of neurotransmitters and their metabolites in cerebrospinal fluid (CSF) is considered among the most valid, albeit indirect, methods of assessing central nervous system function in man. However, most studies in humans have measured lumbar CSF concentrations only at single time points, thus not taking into account rhythmic or episodic variations in levels of neurotransmitters, precursors, or metabolites. We have continuously sampled lumbar CSF via subarachnoid catheter in 12 healthy volunteers, aged 20-65 years. One ml (every 10 min) CSF samples were collected at a rate of 0.1ml/min for 24-hour (h), and the levels of tryptophan (TRP) and 5-hydroxy indoleacetic acid (5-HIAA) were measured. Variability across all 12 subjects was significantly greater (P < 0.0001) than the variability seen in repeated analysis of a reference CSF sample for both 5-HIAA (32.0% vs 7.9%) and TRP (25.4% vs 7.0%), confirming the presence of significant biological variability during the 24-hr period examined. This variability could not be explained solely by meal related effects. Cosinor analysis of the 24-hr TRP concentrations from all subjects revealed a significant diurnal pattern in CSF TRP levels, whereas the 5-HIAA data were less consistent. These studies indicate that long-term serial CSF sampling reveals diurnal and biological variability not evident in studies based on single CSF samples.

Characterizing behavioral and psychological symptoms of dementia (BPSD) among geropsychiatric inpatients.

OBJECTIVE: The purpose of this database analysis was to determine if, upon hospital admission, particular behavioral and psychological symptoms of dementia (BPSD) could be linked to patient characteristics, levels of cognitive or clinical functioning, and/or type of residence before hospitalization. METHODS: Sampled were geropsychiatric inpatients with a primary DSM-IV discharge diagnosis of dementia, who participated in the Mental Health Outcomes, Inc. CQI+(SM) measurement program between January 1, 1996 and December 31, 1999 and who had admission data on all study variables and dementia subtype diagnosis at discharge (N = 2256). BPSD clusters were derived from the 16 behavioral items of the Psychogeriatric Dependency Rating Scale (PGDRS). Subgroups were formed on (1) level of cognitive impairment, (2) depressive symptoms, (3) independence of prior residence, (4) age, (5) gender, (6) race, (7) dementia subtype, and (8) prior psychiatric hospitalization. The relationship of these variables to presence of each PGDRS item was explored with Chi-Square Automatic Interaction Detection (CHAID). A random sample (75% of the patient sample) was used to create the model, with the remaining 25% used for cross-validation. Binary multiple logistic regression was employed to obtain odds ratios for variables significantly related (at < or = 0.01) to PGDRS items. RESULTS: The sample was 66% female, with an average age of 81. The regression analysis revealed that cognitive functioning was significantly associated with 12 of 16 PGDRS items. Odds ratios indicated a 7% to 36% increase in odds of observing the target BPSD for a 3-point difference in MMSE. Also, living in a "dependent" environment (eg, nursing home) before hospitalization was significantly associated with 10 behaviors. Odds of displaying four (active aggression, disruptive behavior, noisy behavior, and verbal aggression) more than doubled for those admitted from a dependent living environment versus an independent one. Finally, age was related to only 1 PGDRS item (socially objectionable behavior). CONCLUSIONS: Findings help identify particular behaviors of dementia associated with being admitted to acute care from a restricted environment such as a nursing home. Treatments effectively targeting these BPSD may impact the intensity and costs of services required.