Clinical application of the mean babbling level and syllable structure level.

PURPOSE: This clinical exchange reviews two independent phonological assessment measures: mean babbling level (MBL) and syllable structure level (SSL). Both measures summarize phonetic inventory and syllable shape in a calculated average and have been used in research to describe the phonological abilities of children ages 9 to 36 months. An example of the measures' clinical use is presented. METHOD: Six studies reporting MBL and SSL were reviewed. Combined, the studies included 207 participants. One hundred twenty-eight of those were developing language as expected, and 79 were identified as having speech-language impairment. CONCLUSION: Overall, the studies indicate that SSL is a reliable measure that increases as children develop. Children with language impairment exhibit lower SSL scores than children with typical language skills. Further, a lower than expected MBL is predictive of a lack of meaningful speech at 24 months of age. IMPLICATION: MBL and SSL have clinical application in terms of initial evaluation as well as progress monitoring. Recommendations for standardized corpus inclusion procedures are presented.

Test-retest reliability of independent measures of phonology in the assessment of toddlers' speech.

PURPOSE: The purpose of this study was to assess the temporal stability of 5 independent measures of phonological skill: phonetic inventory (initial, final), word shape, syllable structure level, and the index of phonetic complexity. METHOD: Ten toddlers with typical development participated in two 20-min play sessions within a 1-week period. Test-retest reliability for each measure was determined. RESULTS: Syllable structure level and index of phonetic complexity achieved high test-retest reliability. Word-final phonetic inventory and word shape analyses had moderate but not significant reliability. Word-initial phonetic inventory was not reliable. DISCUSSION: Twenty-minute conversational speech samples were insufficient to obtain reliable results for all measures. Practitioners may want to obtain more extensive sampling when using a phonetic inventory for diagnosis or progress monitoring purposes. Reliable measures within the constraint of a 20-min session, syllable structure level and index of phonetic complexity provide summarized information concerning the phonetic and syllabic characteristics of a child's speech. Syllable structure level places less emphasis on accurate phonetic transcription, making it a good option for speech that is difficult to transcribe.

Evaluation of a Culturally Tailored Skills Intervention for Latinos with Persistent Psychotic Disorders.

Fifty-nine Latino participants diagnosed with persistent psychotic disorders were assigned to either a culturally tailored skills-training intervention (n = 21), an equivalent non-tailored intervention (n = 15), or a community-based support group (n = 23). Participants completed a number of skills-based performance assessments (e.g., UCSD performance-based skills assessment; UPSA) and a well-being measure prior to and immediately post-treatment. Compared to those in the non-tailored intervention, participants receiving the tailored intervention showed significant improvement in several outcomes. These results indicate that Latino individuals with persistent psychotic disorders benefit from interventions which consider cultural values and mores.

Usefulness of the UCSD performance-based skills assessment (UPSA) for predicting residential independence in patients with chronic schizophrenia.

The objective of this study was to examine the sensitivity and specificity of a performance-based measure of functional capacity, the UCSD Performance-based Skills Assessment (UPSA), for the prediction of independent living status in patients with chronic schizophrenia-related conditions. A sample of 434 adults with schizophrenia or schizoaffective disorder was administered the UPSA and assessed for independent living status. Participants were classified as "independent" if they were living alone in an apartment, house, or single-resident occupancy (e.g., hotel room) and non-independent if they resided in a care facility (e.g., Board-and-Care home, Skilled Nursing Facility). Receiver Operator Characteristic (ROC) curves were calculated with the UPSA and Mattis' Dementia Rating Scale (DRS) scores as predictor variables and residential independence as the state variable. Of the 434 participants, 99 (23%) were living independently at the time of assessment. The discriminant validity of the UPSA was adequate (ROC area under the curve=0.74; 95% CI: 0.68-0.79), with greatest dichotomization for the UPSA at a cutoff score of 75 (68% accuracy, 69% sensitivity, 66% specificity), or 80 (68% accuracy, 59% sensitivity, 76% specificity). The UPSA was also a significantly better predictor of living status than was the DRS, based on ROC (z=2.43, p=.015). The UPSA is a brief measure of functional capacity that predicts the ability of patients with schizophrenia to reside independently in the community.

Predictors of everyday functioning among older Mexican Americans vs. Anglo-Americans with schizophrenia.

OBJECTIVE: We assessed clinical, demographic, and cognitive predictors of everyday functioning in Mexican American and Anglo-American outpatients with schizophrenia. METHOD: Three groups of participants aged 40 years and over with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder were compared: 79 Anglo-Americans, 24 Mexican American patients who chose to be tested in English, and 33 Mexican American patients who preferred Spanish. The study was conducted from October 2001 to July 2004. RESULTS: On demographic, clinical, cognitive, and functional measures, Anglo-American participants were generally similar to Mexican American participants who opted for being tested in English. Mexican American participants who preferred Spanish were significantly different from the other 2 groups on several measures, including everyday functioning performance. To determine the predictors of everyday functioning, separate regression analyses were conducted for each of the 3 groups. Cognitive ability consistently accounted for the greatest proportion of variance in performance regardless of ethnicity, language preference, or education. Among the Mexican American participants, level of acculturation was the second strongest predictor of everyday functioning when the group was examined as a whole; however, acculturation was not a significant predictor when controlling for language preference. CONCLUSION: Cognitive performance and language preference (a proxy for acculturation) may play a particularly important role in predicting ability to perform everyday tasks. Further studies to better understand the potential impact of ethnicity, culture, education, and language on everyday functioning may help develop more specific and culture-sensitive intervention strategies for different ethnic groups.

Development and pilot testing of a new psychosocial intervention for older Latinos with chronic psychosis.

Latinos constitute the largest minority in the United States, and there is an increasing number of Latino patients with schizophrenia and other psychoses living into old age. However, few specific behavioral interventions have been developed aimed at improving the functioning of this group. We evaluated a psychosocial intervention designed to improve the everyday living skills of middle-aged and older outpatients with very chronic psychotic disorders. Three psychiatric clinics, specializing in care of Latinos, were randomly assigned to (1) a 24-session intervention entitled Programa de Entrenamiento para el Desarrollo de Aptitudes para Latinos (PEDAL) group therapy (n = 21) targeting areas identified in our previous work as being problematic for this population (e.g., using public transportation) or (2) a time-equivalent friendly support group (SG; n = 8). Compared to the patients randomized to SG, PEDAL-treated patients' performance on everyday living skills improved significantly postintervention and was still significantly better at a 6-month maintenance follow-up period and at a 12-month no-treatment follow-up period. There was no significant change in psychopathology. Limitations of this pilot study are discussed. Results suggest that participation in this skills training program, designed specifically for older Latino patients with long-standing psychotic disorders, has the potential to significantly increase the patients' independence and improve functional skills.

Approaches to learning of student nurses.

This paper presents findings from a study of student nurses' learning styles in an Institution of Higher Education in South Wales, United Kingdom (UK). The aim of the research was to evaluate students' approaches to learning as measured by a study process questionnaire (SPQ). The questionnaire is viewed as a reliable and valid measure of students' learning, and has been used extensively with students in higher education in Australia. The SPQ is a 42-item questionnaire measuring surface, deep and achieving approaches to learning. It was distributed to 300 student nurses attending the common foundation program of a preregistration-nursing course. Data were entered into SPSS Windows Release 10. The results indicated that many of the students were taking a surface approach or surface-achieving approach to their studies. There was little difference in results between undergraduates and diploma students or between students majoring in different nursing specialties. The deep and achieving approaches to learning scores correlated positively and significantly with overall mean assessment scores of students, the deep approach with Sociology scores and negatively and significantly with Psychology scores. The implications of these results are discussed in relation to curriculum design and the demands of higher education.

Alabama coronary artery bypass grafting project: results of a statewide quality improvement initiative.

CONTEXT: Efforts to improve quality of care in the cardiac surgery field have focused on reducing the risk-adjusted mortality associated with common surgical procedures, such as coronary artery bypass grafting (CABG). However, the best methodological approach to improvement is under debate. OBJECTIVE: To test an intervention to improve performance of CABG surgery. DESIGN AND SETTING: Quality improvement project based on baseline (July 1, 1995-June 30, 1996) and follow-up (July 1-December 31, 1998) performance measurements from medical record review for all 20 Alabama hospitals that provided CABG surgery. PATIENTS: Medicare patients discharged after CABG surgery in Alabama (n = 5784), a comparison state (n = 3214), and a national sample (n = 3758). INTERVENTION: Confidential hospital-specific performance feedback and assistance with multimodal improvement interventions, including the option to share relevant experience with peers. MAIN OUTCOME MEASURES: Duration of intubation, reintubation rate, aspirin therapy at discharge, use of the internal mammary artery (IMA), hospital readmission rate, and risk-adjusted in-hospital mortality. RESULTS: Proportion of extubation within 6 hours increased from 9% to 41% in Alabama, decreased from 40% to 39% in the comparison state, and increased from 12% to 25% in the national sample. Use of IMA increased from 73% to 84%, 48% to 55%, and 74% to 81%, respectively, in the 3 samples, but aspirin use increased only in Alabama (from 88% to 92%). The amount of improvement in all 3 of these process measures was greater in Alabama than in the other samples (IMA use for Alabama vs comparison state was P =.001 and for Alabama vs national sample, P =.02; and P<.001 for all other comparisons). Risk-adjusted mortality decreased in Alabama (4.9% to 2.9%), but this decrease was not statistically significantly different from mortality changes in the other groups (odds ratio, 0.76; 95% confidence interval, 0.54-1.07 vs national sample). CONCLUSION: Confidential peer-based regional performance feedback and process-oriented analysis of shared experience are associated with some improvement in quality of care for patients who underwent CABG surgery.

1,4-Benzodiazepine peripheral cholecystokinin (CCK-A) receptor agonists.

A series of 1,4-benzodiazepines, N-1-substituted with an N-isopropyl-N-phenylacetamide moiety, was synthesized and screened for CCK-A agonist activity. In vitro agonist activity on isolated guinea pig gallbladder along with in vivo induction of satiety following intraperitoneal administration in a rat feeding assay was demonstrated.

Alabama coronary artery bypass grafting Cooperative Project: baseline data. Alabama CABG Cooperative Project Study Group.

BACKGROUND: The Alabama Cooperative CABG Project is a statewide process-oriented analysis of coronary artery bypass grafting (CABG). The purpose of this report is to present the first information generated by this analysis, which will serve as a baseline for subsequent quality improvement projects. METHODS: Medical records of Medicare beneficiaries from Alabama, a comparison state, and a national random sample who had isolated CABG between July 1, 1995, and June 30, 1996, were examined. Fifty-six demographic, procedural, and outcome variables were abstracted. Quality indicators identified by the Alabama Quality Assurance Foundation Study Group included: internal mammary artery use, prescription of aspirin at discharge, duration of postoperative intubation, use of intraaortic balloon pump, readmission to intensive care unit, hospital readmission within 30 days, return to the operating room for bleeding, and in-patient mortality. Benchmark performance rates for quality indicators reflecting care processes were calculated. RESULTS: Alabama, the comparison state, and the national sample consisted of 4,092, 2,290, and 1,119 patients, respectively. The processes of care and outcome, including risk-adjusted mortality, for CABG across the state of Alabama are generally similar to other states and nationwide samples. However, there was considerable variation at the local hospital level in Alabama for each quality indicator. CONCLUSIONS: The data provide a "snapshot" of practice patterns for CABG in Alabama. A specific quality indicator (duration of intubation) was identified as a focus for statewide improvement. Hospital-specific variations in quality indicators suggested opportunities for improvement in other indicators at a number of hospitals.

Intraregional decline in case-fatality and hospital use after occlusive stroke in the Southeastern United States.

OBJECTIVE: To identify changes in mortality and hospital use among patients admitted for ischemic stroke in Alabama. BACKGROUND: The decline in stroke mortality in the Southeast is greater than in other US regions. Whether this decline in a result of decreased incidence or improved case-fatality rates is unknown. METHODS: We examined Medicare hospitalization data from approximately 625,000 beneficiaries and identified patients admitted for ischemic stroke between January 1992 and December 1994. The search was carried out using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes pertinent to all diagnoses related to ischemic stroke. Data relevant to mortality and length of stay (LOS) were collected, and comparisons were made of the average case-fatality rate and LOS in each of the 3 years. RESULTS: No significant difference was found in the incidence of ischemic stroke during the 3 years. The number of admissions was 4438 for 1992, 4124 for 1993, and 4762 for 1994. Conversely, the average LOS showed a significant decline, with values of 10.05, 9,36, and 8.72 days, respectively (P<.0003). A significant decline in mortality, with average case-fatality rates of 11.72%, 11.56%, and 9.71%, respectively (P<.003), was also found. CONCLUSION: These data suggest that the decline in stroke mortality in the Southeast is because of improved patient survival after stroke, rather than decreased incidence. Although several factors may be contributing to the decreased case-fatality rates, improved care of hospitalized stroke patients is likely of primary importance. Additionally, decreased mortality associated with decreased LOS suggests more efficient hospital use.

A congestive heart failure project with measured improvements in care.

This project was designed to improve the in-hospital management of Medicare beneficiaries with congestive heart failure (CHF). Eleven hospitals were studied using two indicators: (a) assessment of left ventricular (LV) function, and (b) use of angiotensin converting enzyme (ACE) inhibitors in patients with systolic dysfunction. Baseline performance rates were obtained for 990 cases with the Diagnosis Related Group (DRG) 127 for CHF discharged January 1994 to December 1994. Baseline data feedback presentations in 1995 spurred quality improvement plans with interventions such as physician education, critical care maps, and standing orders. Follow-up abstractions were performed on 612 discharges October 1995 through April 1997. The study demonstrated 12% improvement (53% to 65%, p < .01) in assessing LV function and 20% improvement (54% to 74%, p < .01) in appropriate ACE inhibitor use. Projects emphasizing Health Care Quality Improvement Program (HCQIP) principles can successfully affect health care management for the Medicare population.

Optimization of 3-(1H-indazol-3-ylmethyl)-1,5-benzodiazepines as potent, orally active CCK-A agonists.

We previously described a series of 3-(1H-indazol-3-ylmethyl)-1,5-benzodiazepine CCK-A agonists exemplified by compound 1 (GW 5823), which is the first reported binding selective CCK-A full agonist demonstrating oral efficacy in a rat feeding model. In this report we describe analogs of compound 1 designed to explore changes to the C3 and N1 pharmacophores and their effect on agonist activity and receptor selectivity. Agonist efficacy in this series was affected by stereoelectronic factors within the C3 moiety. Binding affinity for the CCK-A vs CCK-B receptor showed little dependence on the structure of the C3 moiety but was affected by the nature of the second substituent at C3. Structure-activity relationships at the N1-anilidoacetamide "trigger" moiety within the C3 indazole series were also investigated. Both agonist efficacy and binding affinity within this series were modulated by variation of substituents on the N1-anilidoacetamide moiety. Evaluation of several analogs in an vivo mouse gallbladder emptying assay revealed compound 1 to be the most potent and efficacious of all the analogs tested. The pharmacokinetic and pharmacodynamic profile of 1 in rats is also discussed.

Discovery of 1,5-benzodiazepines with peripheral cholecystokinin (CCK-A) receptor agonist activity (II): Optimization of the C3 amino substituent.

Analogs of the previously reported 1,5-benzodiazepine peripheral cholecystokinin (CCK-A) receptor agonist 1 were prepared which explore substitution and/or replacement of the C-3 phenyl urea moiety. Agonist efficacy on the isolated guinea pig gallbladder (GPGB) was retained with a variety of substituted ureas and amide analogs. Three compounds were identified which were orally active in the mouse gallbladder emptying assay (MGBE). The 2-indolamide (52) and N-(carboxymethyl)-2-indolamide (54) derivatives had improved affinity for the human CCK-A receptor but reduced agonist efficacy on the GPGB. Neither indolamide was orally active in a rat feeding assay. In contrast, the (3-carboxyphenyl)urea derivative (29, GW7854) had moderately increased affinity for the human CCK-B receptor but was a potent full agonist on the GPGB and was orally active in both the MGBE and rat feeding assays. GW7854 was a full agonist (EC50 = 60 nM) for calcium mobilization on CHO K1 cells expressing hCCK-A receptors and a potent antagonist of CCK-8 (pA2 = 9.1) on CHO K1 cells expressing hCCK-B receptors. GW7854 is a potent mixed CCK-A agonist/CCK-B antagonist which is orally active in two in vivo models of CCK-A-mediated agonist activity.

A reinvestigation of the D-homoannular rearrangement and subsequent degradation pathways of (11 beta,16 alpha)-9-fluoro-11,16,17,21- tetrahydroxypregna-1,4-diene-3,20-dione (triamcinolone).

The commercial anti-inflammatory drug triamcinolone has been shown to rearrange by similar, but distinct pathways when exposed to certain trace metal ions or to dilute aqueous base. In the presence of aqueous base, the 16-hydroxy-20-keto system undergoes reverse aldol cleavage of the 16,17-bond, followed by aldol cyclization linking C-16 to C-20. This base-catalyzed rearrangement gives a 16 beta,17 alpha-dihydroxy product and a corresponding 16 alpha,17 alpha-dihydroxy product in roughly 4 to 1 ratio. Metal-catalyzed rearrangement provides the 16 alpha,17 alpha-dihydroxy product with extremely high stereoselectivity. Mechanistic models are proposed that help explain the ratio of products isolated from each route. The studies presented suggest that similar forms of rearrangement could be of preparative value in syntheses requiring specific stereochemistry of appropriately substituted bicyclic alpha,beta-dihydroxyketones. Under more vigorous conditions of aqueous base treatment these rearrangement products undergo further decomposition with loss of formaldehyde from the hydroxymethyl group, followed by beta-elimination of water. Reaction of the beta-elimination product with formaldehyde results in the formation of a dimeric species linked by a methylene group.

Bridged gamma-carbolines and derivatives possessing selective and combined affinity for 5-HT2 and D2 receptors.

A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles and 6,7,8,9,10,11-hexahydro-7,11-imino-5H-cyclooct[b]indoles was prepared. Structural modifications of the lead compound, 11-[4-(4-fluorobenzoyl)propyl]-5,6,7,8,9,10-hexahydro-7,10- iminocyclohept[b]indole (5, Ki = 0.82 nM vs [3H]ketanserin) enabled the identification of the functionality necessary for high affinity at serotonin 5-HT2 and dopamine D2 receptors in ligand binding studies. The indole ring, as well as the benzoyl or isosteric benzisoxazole moiety, were essential for high affinity. Variations of the length of the side chains resulted in ligands having either selective affinity for the 5-HT2 receptor or a combination of 5-HT2 and D2 affinity. In vivo binding studies were performed on selected members in this series. The most potent member, 2-fluoro-11-[4-(4-fluorobenzoyl)butyl]-5,6,7,8,9,10-hexahydro-7,10- iminocyclohept[b]indole (36) had an ED50 of < 1 mg/kg at the 5-HT2 and D2 receptors following oral administration.

Synthesis and in vitro evaluation of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles: high-affinity ligands for the N,N'-di-o-tolylguanidine-labeled sigma binding site.

A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclo[b]indoles substituted at the 5 and/or 11 positions was synthesized from tropinone. Affinity for sigma binding sites was determined using [3H]-N,N'-di-o-tolylguanidine ([3H]DTG) and [3H]-(+)-3-(3-hydroxyphenyl)-N-1-propylpiperidine ([3H]-(+)-3-PPP) and for the dopamine D2 receptor labeled with [3H]sulpiride. Nearly all compounds studied in this series possessed a higher affinity for [3H]DTG than [3H]-(+)-PPP-labeled sigma sites, suggesting that [3H]DTG and [3H]-(+)-3-PPP radioligands label pharmacologically distinct sigma binding sites, as reported previously. Substitution at the 11 position with side chains containing a four-carbon tether resulted in compounds having the highest affinity for the [3H]DTG-labeled sigma site. The most potent and selective member of this series was 11-[4-(2-furanyl)butyl]-5,6,7,8,9,10-hexahydro-7,10-iminocyclohept [b] indole (40). Enantioselectivity was investigated by preparing the (+)- and (-)-isomers of 40. These studies revealed that (+)-40 was more potent at the [3H]-DTG-labeled sigma site whereas (-)-40 had a higher affinity at sigma sites labeled with [3H]-(+)-PPP. Racemic 40 was observed to possess a higher affinity than either of its respective enantiomers at both the [3H]DTG- and [3H]-(+)-3-PPP-labeled sites, suggesting an allosteric interaction.

Primary causes of medical instability of Medicare patients at discharge 1990-1991.

BACKGROUND: HCFA-sponsored Peer Review Organizations nationwide have been criticized by organized medicine, Medicare beneficiaries and interested Congressional parties for being punitive without exploiting educational opportunities garnered through their massive data collection capabilities. Until now this data has been poorly analyzed and has not been adequately utilized as a positive motivational tool. METHODS: HCFA has developed, with the cooperation of the medical community, six generic screens for Peer Review Organizations to utilize when evaluating quality care provided Medicare beneficiaries in an acute care setting. Through the sheer volume of cases seen, significant inpatient information can be obtained that cannot be duplicated in any other epidemiological endeavor. Line item discrepancies can be further studied through small-area-analysis to determine "who" as well as "what" may be the problem. RESULTS: By compiling and reviewing data in a systematic manner over two years (1990-1991), the Alabama Quality Assurance Foundation (AQAF) has singled out problems with patient medical stability at discharge as the predominant concern for care providers and reviewers alike. CONCLUSIONS: Having determined the primary problem in rendering quality care in a Prospective Payment System to Medicare beneficiaries lies in premature discharges, subsequent small-area-analysis further narrows the focus of concerned individuals. Hopefully, practitioners and providers alike will act on their own initiative in correcting this problem. Follow-up review will be utilized to assure this self-corrective action.

(Aminoalkoxy)chromones. Selective sigma receptor ligands.

A series of (aminoalkoxy)chromones has been prepared, members of which bind potently (16-100 nM) at the sigma binding site and bind weakly (greater than 1000 nM) at the dopamine D2 receptor and 33 other receptors, second messenger systems, and ion channels. At the sigma receptor, the preferred position of attachment for the aminoalkoxy side chain to the chromone ring followed the rank order: 7-position greater than 5-position greater than 6-position. Chromones that contained a 2-substituent that was not coplanar with the chromone ring system showed improved binding over compounds with coplanar substituents. The most potent compound at the sigma site, 7-[[7-(4-hydroxypiperidyl)heptyl]oxy]-2-phenylchromone (74), had receptor affinities (IC50) of 16 nM at the [3H]DTG site, 19 nM at the [3H]-(+)-3-PPP site, and 4000 nM (Ki) at the dopamine D2 receptor. The most selective compound examined, 6-[[6-(4-hydroxypiperidyl)hexyl]-oxy]-2-cyclopentylchromone (58), exhibited IC50s of 51 nM at the [3H]DTG site, 55 nM at the [3H]-(+)-3-PPP site, and 21,000 nM (Ki) at the dopamine D2 receptor. Compound 44 (6-[[6-(4-hydroxypiperidyl)hexyl]oxy]-3-methylflavone, NPC 16377) was systemically effective (ip and po) in two behavioral models predictive of antipsychotic compounds and systemically active in animal models of ischemia.

Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-on e (TIBO) derivatives. 2.

In the first paper of this series a new structure with anti-HIV-1 activity was disclosed and analogues were synthesized to explore the structure-activity relationship of changes in the substituent (R) attached at the N-6 position of 9. This study describes the syntheses and anti-HIV-1 testing of analogues with variations of the five-membered urea ring of the 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk] [1,4]benzodiazepin-2(1H)-one (TIBO) structures. Although many different rings were synthesized to replace the cyclic urea of TIBO, most were found to be inactive in inhibiting the replication of the HIV-1 virus in MT-4 cells. The exceptions were replacement of the urea oxygen with sulfur or selenium to give the corresponding thio- or selenoureas. These were found to be more active than the oxygen counterparts. A small series of analogues was synthesized and tested which allowed direct comparison of urea and thiourea derivatives. Without exception, the latter were always more active than the former. The most active compound of this series (8d) was found to inhibit the HIV-1 virus with an IC50 of 0.012 microM which is comparable to that of AZT.