Role of the laboratory in monitoring patients receiving dual antiplatelet therapy.

INTRODUCTION: The increasing demand for therapeutic monitoring in patients receiving antiplatelet therapy has been paralleled by the development of instruments and tests whose clinical usefulness is still under debate. We devised a laboratory approach to detect patients with antiplatelet resistance at risk to develop thrombotic events. METHODS: One hundred and eighty patients, under aspirin and clopidogrel after angioplasty and stent implantation, were studied by PFA100(®) with collagen/epinephrine (CoEPI, cutoff 165s) cartridge and by Multiplate(®) using arachidonic acid (ASPItest, pos < 862AUC), ADP (ADPtest, pos < 417AUC), and collagen (COLtest, pos < 607AUC). RESULTS: Only 67 of 173 patients with ASPI < 862 displayed a prolonged CoEPI and up to 65 patients had normal CoEPI despite ASPI < 300. Patients with ASPI < 300 had significantly lower COL than patients with ASPI > 300. One hundred and thirty-eight patients displaying ADP < 417 had significantly lower COL than those with ADP > 417. Association between COL and ADP remained after ASPI stratification: in patients with suboptimal (ASPI 300-892) or maximal (ASPI < 300) response to aspirin, having ADP < 417 (clopidogrel responsive) increased COL positivity, respectively, from 9.5 to 58.8% and from 47.6 to 82.7%. CONCLUSION: A combination of specific tests may be useful in identifying higher-risk patients with poor compliance or drug resistance who potentially may benefit from therapy change.

[Extended high frequency audiometry in the prevention of noise-induced hearing loss]. / Uso delle alte frequenze nella prevenzione precoce della ipoacusia da rumore.

An early detection of noise induced hearing loss (NIHL) may allow more effective protection measures. Our aim was to investigate the usefulness of high-frequency audiometry to evaluate the possibility of a future use of the high frequencies audiometry as an early indicator for noise induced hearing loss. A cross-sectional study was performed involving 204 industrial noise exposed and 100 non-industrial noise-exposed workers. Each subject was tested with both conventional-frequency (0.25-8 kHz) and high-frequency (9-18 kHz) audiometry during the annually health surveillance campaign conducted in two Italian cement factories. As expected, noise exposed workers were found to have significantly higher hearing thresholds (P < 0.05) at both conventional and extended high frequencies. Marked differences were found for EHFA. Moreover, significant differences at EHFA were detected also in the subgroup of noise-exposed workers with normal findings at conventional audiometry. Our finding indicate that the use of the extended high frequency test may represent a useful tool for detecting early changes of hearing impairment and that it could be used in addition to the conventional test to better prevent the progression of noise hearing loss.

A comprehensive analysis of verbal fluency deficit in geriatric schizophrenia.

Deficits in verbal fluency are common in schizophrenia and may provide keys to some of the abnormalities in the semantic system in schizophrenia. While a number of studies have outlined the severity and implications of verbal fluency deficits in younger schizophrenia patients, these findings have not yet been extended to older patients with schizophrenia. In this study, 392 older (age >/= 50) patients with schizophrenia were administered phonological and semantic (i.e., category) fluency examinations, as well as tests of learning, memory, language, and praxic skills, and rated for clinical symptoms and functional status. When compared to normative standards, 82% of the patients were impaired in semantic fluency and 83% were impaired in phonological fluency. Both semantic and phonological fluency impairment were significantly correlated with other cognitive variables, total scores on the functional status measure, and with the social and self-care subscales. Scores were uncorrelated with the severity of psychosis, but were correlated with the severity of negative symptoms. Furthermore, the severity of poverty of speech (a clinical measure of verbal underproductivity) was moderate in magnitude and failed to enter as a predictor of verbal fluency, indicating that impaired fluency scores are not simply an artifact of general underproductivity or mutism. The findings support conclusions from studies with younger schizophrenia patients that suggest that verbal fluency impairment is a consequence of a disorganized semantic system. Verbal fluency impairment remains common and functionally relevant in schizophrenia patients in late life.

Six-year follow-up study of cognitive and functional status across the lifespan in schizophrenia: a comparison with Alzheimer's disease and normal aging.

OBJECTIVE: Follow-up studies of cognitive functions of poor-outcome (long-term institutionalized) elderly patients with schizophrenia have demonstrated deterioration over time, while stable cognitive functions over time have been reported for younger, better-outcome schizophrenic patients. This study examined whether cognitive changes in elderly schizophrenic patients with a history of long-term institutional stay extended to institutionalized younger patients. The rate of decline was compared to changes associated with Alzheimer's disease. METHOD: Patients with schizophrenia (N=107) age 20-80 years were followed over 6 years and assessed with the Clinical Dementia Rating and the Mini-Mental State Examination. The schizophrenic subjects age 50 and older were compared to 136 healthy comparison subjects and 118 Alzheimer's disease patients age 50 and older who were assessed over a similar follow-up period. RESULTS: There was a significant age group effect on the magnitude of cognitive decline for the schizophrenic subjects, with older subjects experiencing greater levels of decline over the follow-up. Neither the healthy individuals nor the Alzheimer's disease patients demonstrated similar age-related differences in the magnitude of cognitive change over the follow-up, with healthy comparison subjects showing no change and Alzheimer's disease patients manifesting decline regardless of age at the initiation of the follow-up. CONCLUSIONS: Institutionalized schizophrenic patients demonstrated an age-related pattern of cognitive change different from that observed for Alzheimer's disease patients and healthy individuals. The cognitive and functional status of these schizophrenic patients was fairly stable until late life, suggesting that cognitive change may not be occurring in younger patients over an interval as long as 6 years.

Aggression in elderly schizophrenia patients: a comparison of nursing home and state hospital residents.

This study examined the role of cognitive functioning, adaptive functioning, and symptomatology in predicting aggression in institutionalized geriatric schizophrenic patients residing in either a state institution (n=56) or a nursing home (n=113). Patients were assessed with a neuropsychological battery and rated for positive and negative symptoms, social functioning, and aggressiveness. Nursing home residents were older and more cognitively and functionally impaired than institutional residents. The prevalence of verbal, but not physical, aggression was similar to findings in younger, acutely hospitalized patients in previous studies. In the hospitalized group, severity of negative symptoms was predictive of physical aggression. In the nursing home group, severity of positive symptoms was predictive of verbal aggression and self-care deficit was predictive of physical aggression. Results indicate that verbal aggression, like positive symptoms, decreases little with aging in institutionalized schizophrenic patients, and that predictors of aggressive behavior are as difficult to identify in elderly patients as in younger ones.

Guanfacine treatment of cognitive impairment in schizophrenia.

Norepinephrine plays a significant role in the working memory functions of the prefrontal cortex by its actions at alpha-2a noradrenergic receptors. Guanfacine has demonstrated efficacy in reversing working memory deficits in non-human primate. In the present study the effect of guanfacine adjunctive treatment to neuroleptics on the cognitive performance of schizophrenic patients was investigated in a four week, placebo-controlled, double-blind, parallel design trial. The primary analyses revealed no significant differences between guanfacine and placebo treatment; however, exploratory non-parametric statistics revealed some significant and some trend differences between guanfacine and placebo on spatial working memory test performance and CPT reaction time in those subjects treated with atypical neuroleptics.

The convergence of neuropsychological testing and clinical ratings of cognitive impairment in patients with schizophrenia.

This study examined the relationship between clinical rating of cognitive symptoms and performance on neuropsychological tests in acute and chronic samples of patients with schizophrenia. Two separate studies examined patients who varied widely in their lifetime functional outcome, including 263 elderly poor-outcome inpatients and 20 acutely admitted patients. In the first study, six cognitive performance measures were collected, and in the second study, five different measures were collected. Correlations with different symptom models of cognitive and negative symptoms were examined. In both samples, cognitive symptoms were never more highly correlated with cognitive test performance than with negative symptoms. When cognitive and negative symptom ratings were combined, they never accounted for as much as half of the variance in performance on the cognitive tests in both samples. These data suggest that clinical assessment of symptoms is not a viable alternative to neuropsychological testing to obtain information about cognitive functioning in schizophrenia. These results may also be specific to the clinical rating scale used, the Positive and Negative Syndrome Scale (PANSS).

Gender differences in poor outcome patients with lifelong schizophrenia.

Gender effects have been reported quite consistently in schizophrenia, with male patients having an earlier age of onset, poorer functional outcome, greater negative symptoms and cognitive impairment, and less severe positive symptoms. Because age of onset, cognitive impairments, and negative symptoms are all correlated with poorer functional status, it is not clear if previously reported gender differences in symptoms are just recapturing gender differences in functional outcome. In this study, 205 geriatric patients with lifelong poor-outcome schizophrenia (43% male) were examined for the severity of schizophrenic symptoms, cognitive impairments, and specific deficits in adaptive skills, as well as for demographic differences such as age at first psychiatric admission, premorbid education, and current treatment status. Previously reported gender differences were replicated in these patients with a uniformly poor functional outcome, with male patients having more severe negative symptoms and an earlier age of first psychiatric admission. No differences in cognitive functioning or specific functional deficits were found, however. These findings suggest that negative symptom severity is greater in male patients regardless of functional outcome and that the association of cognitive deficits with gender may be found only in patients with better functional outcome. The study of gender-related differences in brain structure or function and their interaction with overall course of illness might help understand these differences in symptom presentation.

Relationship of cognitive functioning, adaptive life skills, and negative symptom severity in poor-outcome geriatric schizophrenia patients.

The authors assessed whether cognitive functioning and negative symptoms are related to functional outcome across severity of negative symptoms and examined relationships between symptom domains in patients with high versus low negative symptom severity. The interrelationships between cognitive functioning and functional skills in poor-outcome geriatric schizophrenic patients were compared between those who were in the first (n = 81) and the fourth quartiles (n = 127) of negative symptom severity based on the normative data in the Positive and Negative Syndrome Scale. It was found that negative symptoms and cognitive functioning were the strongest correlates of functional status in geriatric poor-outcome schizophrenic patients--regardless of negative symptom severity. Interestingly, the greater the severity of negative symptoms, the less strongly negative symptoms were related to functional outcome. The present findings demonstrate that the relationship of cognitive functioning to social and adaptive functioning remains significant despite differing levels of negative symptom severity.

Clinical, cognitive and functional characteristics of long-stay patients with schizophrenia: a comparison of VA and state hospital patients.

Long-stay patients constitute a small proportion of all patients with schizophrenia, but in both VA and state psychiatric systems these patients account for a majority of the costs associated with treatment of the illness. VA and state patients would be expected to differ in several respects, including age at onset and premorbid educational status. Little additional information is available about the differences between these samples. Seventy-four long-stay male patients at a chronic state psychiatric center were compared with 50 male veterans from long-stay psychiatric facilities on positive and negative symptoms, cognitive deficits and functional status. The two samples did not differ on positive symptom severity, but the state patients had more severe negative and cognitive symptoms as well as functional deficits. Of all of the variables measured, deficit in self care was the only variable that entered a stepwise discriminant analysis. The correlation between functional and symptomatic variables was the same in both groups, and the group differences and correlations were not influenced by differences in educational status. These data indicate that VA patients may have reduced severity of functional and cognitive impairments relative to state hospital patients, but that the relationship between the different illness variables was similar in the two groups.

Differential preservation of cognitive functions in geriatric patients with lifelong chronic schizophrenia: less impairment in reading compared with other skill areas.

BACKGROUND: Our study examined the differential performance of cognitive skills in geriatric, cognitively impaired schizophrenic patients (n = 165) with a lengthy course of institutional stay and a poor overall functional outcome. Their relative deficits were compared with a sample of healthy elderly individuals. METHODS: Schizophrenic patients were matched one-to-one with healthy individuals of the same age and education and compared on a number of measures of cognitive functioning. The schizophrenic patients' old-learning performance was also compared with their educational level only. RESULTS: Mini-Mental State Examination (Folstein et al 1975) scores of the patients were in the moderately demented range (M = 20.36), and these patients underperformed healthy control subjects by more than 1 to slightly less than 3 standard deviations on measures of memory, praxis, and verbal skills. Wide Range Achievement Test-Revised word-recognition reading scores were found to be at the 10th-grade level, although the patients on average had completed 11 years of formal education. CONCLUSIONS: These results suggest that even in schizophrenic patients with significant cognitive impairment, reading scores are relatively consistent with educational attainment. These data indicate that poor performance on measures of cognitive functioning in this population does not necessarily occur on measures of old learning.

The longitudinal relationship of clinical symptoms, cognitive functioning, and adaptive life in geriatric schizophrenia.

Cognitive dysfunction is increasingly being recognized as a major contributor to the adaptive impairment seen in most patients with schizophrenia. Reported here is a prospective longitudinal evaluation of the relationship between cognitive and adaptive functioning in elderly patients with schizophrenia. It was hypothesized that baseline cognitive and negative, but not positive symptoms, would be predictive of cross-sectional impairment and longitudinal outcome. Subjects were 168 elderly patients with schizophrenia, free of major neurological disorders, who were residents of a long-term psychiatric facility. Subjects were assessed at baseline and again an average of 15months later. The PANSS was used to assess the severity of symptoms of schizophrenia. Cognitive symptoms were assessed using the components of the CERAD cognitive battery. Social and adaptive functioning was assessed using the SAFE scale. Spearman correlations were determined among clinical variables, and the rank ordering of prediction of SAFE scale scores at follow-up was determined using a stepwise regression procedure. At follow-up, adaptive life skills correlated with cognitive performance and negative symptoms (Spearman rho values 0. 41-0.57, all p values <0.0001), but not positive symptoms (r=0.09, n. s.). Among cognitive tasks, verbal learning and memory were most highly correlated with adaptive skills at follow-up. These results confirm and extend previous studies that indicate that cognitive impairments are predictive, both cross-sectionally and longitudinally, of adaptive life skills in persons with schizophrenia. Negative symptoms, but not positive symptoms, were correlated with impaired adaptive skills. Taken together, these results underscore the need to develop more effective treatments for cognitive and negative symptoms in schizophrenia.

Prevalence and correlates of parkinsonism in an institutionalized population of geriatric patients with chronic schizophrenia.

BACKGROUND: Geriatric patients with chronic schizophrenia are at increased risk for parkinsonism and cognitive impairment, but the relationship between the two has been insufficiently studied. OBJECTIVES: (1) To determine the prevalence of parkinsonism in a cohort of institutionalized geriatric patients with chronic schizophrenia (N=79). (2) To examine the relationship of parkinsonism to potentially relevant variables including cognitive functioning, positive and negative symptoms, sex, age, age at first hospitalization, psychopharmacological regimen and tardive dyskinesia (TD). METHOD: Tremor, rigidity and bradykinesia were rated on a five-point severity scale. Clinically significant parkinsonism was defined by the unambiguous presence of at least two of those signs. TD was assessed with the Modified Simpson Dyskinesia Scale. Schizophrenic symptoms were rated with the Positive and Negative Syndrome Scale, and cognitive functioning with the Mini-Mental State Examination and the Consortium to Establish a Registry for Alzheimer's Disease battery. RESULTS: The prevalence of parkinsonism was 19% and was significantly higher in women than in men. Age was a significant predictor of parkinsonism. Independent of age, bradykinesia was significantly correlated with MMSE, fluency and naming. Tremor, rigidity and medication status did not correlate with any cognitive variable assessed. Cognitive measures did not differ between subjects meeting and not meeting criteria for clinically significant parkinsonism. Rigidity and bradykinesia were significantly correlated with negative symptoms but no parkinsonism sign correlated with positive symptoms. Twelve subjects received ratings consistent with both TD and parkinsonism; however, no parkinsonian variable predicted the co-occurrence of TD. CONCLUSIONS: The present correlations suggest potential overlap among the neural substrates for bradykinesia, cognitive impairment and negative symptoms; however, further research is required to clarify that issue.

Convergence of cognitive and adaptive decline in late-life schizophrenia.

Cognitive impairment has proven to be a major predictor of overall functional deficit in schizophrenia. Despite the significant impairments seen on the part of many patients with schizophrenia that implicate decline at some point in time, there have been no longitudinal studies of adaptive decline in patients with schizophrenia. In this study, 57 geriatric patients with chronic schizophrenia were examined with measures of clinical symptoms, cognitive impairments, and adaptive functioning while living in a chronic psychiatric hospital and followed up an average of two and a half years after their referral to nursing home care. Cognitive functioning and adaptive functioning both declined over the follow-up period, whereas there was no change in schizophrenic symptoms. Changes in cognitive functioning accounted for 25% of the variance in adaptive decline, whereas the baseline severity of cognitive impairment and schizophrenia symptoms were uncorrelated with adaptive decline. These data indicate that cognitive decline may predict deterioration in overall functional status and imply that treatment of cognitive impairment might have a beneficial effect on global functional status.

Cognitive decline in late-life schizophrenia: a longitudinal study of geriatric chronically hospitalized patients.

BACKGROUND: Geriatric schizophrenic patients with a chronic course of institutionalization manifest cognitive and functional impairments that implicate decline at some time point after the onset of illness. The rate of change in cognitive and functional status in these patients has not yet been identified with a longitudinal study. METHODS: Three hundred and twenty-six schizophrenic patients entered a 30-month follow-up study with two separate assessments of the patients. Overall functional and cognitive status was indexed with the Clinical Dementia Rating (CDR). Survival analysis was used to examine changes in cognitive and functional status, including worsening for the less impaired patients and improvements on the part of more impaired patients. RESULTS: Approximately 30% of the patients who had baseline scores in the less impaired range manifested a worsening of their CDR ratings to a score of 2.0 (moderate) or more severe, whereas only 7% of the sample with lower scores at baseline appeared to improve in their functioning. Several characteristics of the patients at baseline assessment predicted increased risk for cognitive and functional decline, including lower levels of education, older age, and more severe positive symptoms. CONCLUSIONS: Cognitive and functional decline can be detected in a short-term follow-up in a subset of geriatric long-stay patients with schizophrenia. This decline appears distributed across patients and not due to the presence of progressive degenerative dementing conditions. Later research will have to identify the causes of this decline, possibly on the basis of the risk factors identified in this study.

Symptoms, cognitive functioning, and adaptive skills in geriatric patients with lifelong schizophrenia: a comparison across treatment sites.

OBJECTIVE: Although many geriatric patients with schizophrenia have been referred to nursing home care, little is known about their characteristics. Across nursing home and chronic hospital settings, the authors directly assessed poor outcome geriatric patients with schizophrenia and contrasted their cognitive, symptomatic, and adaptive functioning to that of acutely admitted patients with a better outcome over the lifetime course of the illness. METHOD: The subjects were 97 chronically hospitalized patients with schizophrenia, 37 patients with chronic schizophrenia who lived in nursing homes, and 31 acutely admitted geriatric patients with schizophrenia. These patients were rated with the Positive and Negative Syndrome Scale, tested with a neuropsychological battery, evaluated with the Mini-Mental State examination, and rated on a scale of social and adaptive deficits, the Social Adaptive Functioning Evaluation scale. RESULTS: Each group of patients proved discriminable from the other two: nursing home patients displayed the most severe adaptive deficits, and acutely admitted patients were the least cognitively impaired. Cognitive impairment was the strongest predictor of adaptive deficits for all three groups, and negative symptom differences among the groups were smaller than differences in cognitive impairment. Nursing home patients had the least severe positive symptoms, and the acutely ill and chronic hospital patients did not differ on positive symptoms. CONCLUSIONS: Cognitive impairment is a predictor of both overall outcome and specific adaptive deficits. These data suggest that interventions aimed at cognitive impairment may have an impact on overall functional status. In comparison, positive symptom severity is less strongly correlated with overall adaptive outcome and is uncorrelated with specific deficits in adaptive skills.

Characteristics of elderly psychiatric patients retained in a state hospital during downsizing: a prospective study with replication.

OBJECTIVE: This study examined the clinical characteristics of elderly inpatients associated with retention in a large state hospital during a period of rapid reduction in the inpatient census. DESIGN: During the first year of the study all inpatients age 65 or greater were individually evaluated. Patients remaining in the hospital during the second year were reevaluated and followed for an additional year. Separate statistical analysis of the data allowed for replication of findings. SETTING: The study was conducted at Pilgrim Psychiatric Center, the largest state hospital in New York State. PARTICIPANTS: The entire inpatient population over the age of 65 were included in the study (N = 806). The average age of the sample was 76 years and 70% were assigned a lifetime research diagnosis of schizophrenia. The majority of patients were hospitalized for long periods (mean = 33.9 years) and had significant cognitive impairment. MAIN OUTCOME MEASURES: Cognitive functioning was assessed on the Clinical Dementia Rating Scale. Severity of psychiatric symptoms was evaluated on the PANSS. Occurrence of dangerous behavior and medical and psychiatric treatment were obtained from the patients' medical histories. MAIN RESULTS: The findings, replicated across assessments, were that patients retained had more severe symptoms of excitement, hostility and impulsive behavior than those discharged, while uncooperativeness, delusions, grandiosity and suspiciousness were also more severe in those retained than those discharged. CONCLUSIONS: Elderly patients who are very difficult to place are so characterized because of behavior disorders that are difficult to manage rather than psychotic symptoms, cognitive impairment or medical disorders.

Symptom severity and cognitive impairment in chronically hospitalised geriatric patients with affective disorders.

BACKGROUND: Affective disorders typically have a better outcome than schizophrenia, although recent evidence suggests that some patients with affective disorder have a relatively poor outcome, with cognitive impairments and persistent symptomatology. METHOD: Fifty chronically hospitalised geriatric patients with mood disorders (major depression or bipolar disorder) were compared on the clinical symptoms and aspects of cognitive impairment with 308 geriatric schizophrenic patients who were hospitalised at the same institution. The two samples did not differ in current age or in premorbid education level, but the affective patients had a later age of onset and more females in the sample. RESULTS: There were no overall differences in cognitive functioning between the groups, although the clinical symptom profiles resembled those seen in better outcome patients. CONCLUSIONS: Cognitive impairment is present in poor-outcome patients with affective disorders as well as schizophrenia, suggesting that cognitive impairments predict poor outcome across psychiatric disorders and not just in schizophrenia.

Age-related differences in formal thought disorder in chronically hospitalized schizophrenic patients: a cross-sectional study across nine decades.

OBJECTIVE: This study used a cross-sectional design to examine the frequency of occurrence and severity of 10 different signs of thought disorder in schizophrenic patients across the lifespan. METHOD: Schizophrenic patients, who ranged in age from 19 to 96 years (N = 392), were examined with the Scale for Assessment of Thought, Language, and Communication. The cognitive functioning of the geriatric patients (patients over the age of 64, N = 120) was also assessed. RESULTS: Poverty of speech was more common and more severe in geriatric patients, while four different signs of thought disorder that reflect disconnected speech were less common and less severe in geriatric patients. Analysis of covariance found that the lower severity of disconnection thought disorders in the older patients was not attributable to differences in the amount of speech produced. CONCLUSIONS: Aspects of disconnected speech were less severe in older patients, while the severity and frequency of poverty of speech were greater. These findings suggest that the two previously identified separate dimensions of communication disorder in schizophrenia vary differently with age and possibly in their cognitive and biological underpinnings.

Social-Adaptive Functioning Evaluation (SAFE): a rating scale for geriatric psychiatric patients.

Geriatric chronic psychiatric inpatients often remain in a chronic psychiatric hospital because of serious deficits in adaptive life functions. Because the additional complications and adaptive changes associated with aging have not been considered in previous scales, the Social-Adaptive Functioning Evaluation (SAFE) was developed. The items in the scale measure social-interpersonal, instrumental, and life skills functioning and are designed to be rated by observation, caregiver contact, and interaction with the subject if possible. Interrater and test-retest reliability were examined (n = 60) and convergent and discriminant validity were rated against other relevant measures (n = 50) in separate studies, with all being found adequate. The factor structure of the scale was examined with exploratory factor analysis, revealing a three-factor structure. Finally, predictive validity was examined in a preliminary study of 140 patients, 45 of whom were discharged after the assessment. The results indicate that patients who remained hospitalized could be discriminated from those who were sent to nursing homes or community care on the basis of certain SAFE items and subscales. These results support the use of this instrument in later studies of geriatric psychiatric patients.