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PubMed2003

Avoidable hospitalisation rates in Singapore, 1991-1998: assessing trends and inequities of quality in primary care.

STUDY OBJECTIVES: To assess avoidable hospitalisation as an indicator of quality of primary care by examining trends and gender and ethnic variations. DESIGN AND SETTING: Aggregated nationwide data in Singapore from 1991 to1998 were analysed for hospitalisations for chronic diseases that are avoidable by timely, appropriate, and effective primary care: asthma, congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, and hypertension (avoidable hospitalisations). MAIN RESULTS: Of a total of 1 479 494 hospitalisations, 6.7% were for ambulatory care sensitive conditions (ACSC). The annual rate of avoidable hospitalisation was 29.4 per 10 000 population. Women had lower rates of avoidable hospitalisations than men (22.4 versus 29.5 per 10 000), as well as for total hospitalisations (496.2 versus 515.5 per 10 000). Adjusted for total hospitalisation, men were 1.3 times more likely than women to be hospitalised for ACSC. With similar adjustments for baseline utilisation, Indian and Malays had 1.7 and 1.8 times higher rates of avoidable hospitalisations than Chinese. Avoidable hospitalisation decline was -9.1% overall; greater in men (-11.8%) than in women (-5.3%); greater for Chinese (-15.8%), than Malays (-1.1%) and Indians (increase of +4.3%). CONCLUSION: Gender and ethnic differences and declining trends in avoidable hospitalisation demonstrated in this study suggest that avoidable hospitalisation rates are a sensitive indicator for assessing quality of primary ambulatory care.

Adolescent↗

PubMed1996

Utilization of radiologic services in different payment systems and patient populations.

PURPOSE: To report population-based utilization rates and their variability across and within populations, geographic areas, and different payment systems for diagnostic radiology and radiation oncology procedures. MATERIALS AND METHODS: Aggregated claims data were obtained from four sources for up to nine radiologic modalities. The data cover Medicare, health maintenance organizations (HMOs), and conventional insurance. For some sources, the data were separated into four age groups. All radiologic services, including those provided by nonradiologists, were included. RESULTS: Average annual ambulatory diagnostic radiology utilization rates ranged from 570 procedures per 1,000 nonelderly persons in an HMO setting to 1,970 per 1,000 for Medicare enrollees. Radiation oncology utilization rate added 11 procedures per 1,000 to the HMO population rate and 260 per 1,000 to the Medicare population rate. In the Medicare data, the diagnostic radiology utilization rate in the 25th percentile state was 78% of the rate in the 75th percentile state. In a small sample of HMOs, the 25th percentile HMO rate was 45% of the 75th percentile HMO rate. CONCLUSION: Much variability exists in utilization rates. National or regional averages are not a good guide to the utilization rates in a specific patient population and should not be taken as norms. Only actual data from a patient population are likely to provide radiologists with fairly accurate predictions of their future utilization rates.

Adolescent↗

PubMed2000

Proliferative activity and tumorigenic conversion: impact on cellular metabolism in 3-D culture.

Oxygen consumption, glucose, lactate, and ATP concentrations, as well as glucose and lactate turnover rates, have been studied in a three-dimensional carcinogenesis model of differently transformed rat embryo fibroblasts (spontaneously immortalized Rat1 and myc-transfected M1, and the ras-transfected, tumorigenic descendants Rat1-T1 and MR1) to determine metabolic alterations that accompany tumorigenic conversion. Various bioluminescence techniques, thymidine labeling, measurement of PO(2) distributions with microelectrodes, and determination of cellular oxygen uptake rates (Qc(O(2))) have been applied. In the ras-transfected, tumorigenic spheroid types, the size dependencies of some of the measured parameters exhibited sharp breaks at diameters of approximately 830 microm for Rat1-T1 and approximately 970 microm for MR1 spheroids, respectively, suggesting that some fundamental change in cell metabolism occurred at these characteristic diameters (denoted as "metabolic switch"). Qc(O(2)) decreased and lactate concentration increased as functions of size below the characteristic diameters. Concomitantly, glucose and lactate turnover rates decreased in MR1 spheroids and increased in Rat1-T1. Spheroids larger than the characteristic diameters (exhibiting cell quiescence and lactate accumulation) showed an enhancement of Qc(O(2)) with size. Systematic variations in the ATP and glucose levels in the viable cell rim were observed for Rat1-T1 spheroids only. Proliferative activity, Qc(O(2)), and ATP levels in small, nontumorigenic Rat1 and M1 aggregates did not differ systematically from those recorded in the largest spheroids of the corresponding ras transfectants. Unexpectedly, respiratory activity was present not only in viable but also in the morphologically disintegrated core regions of M1 aggregates. Our data suggest that myc but not ras transfection exerts major impacts on cell metabolism. Moreover, some kind of switch has been detected that triggers profound readjustment of tumor cell metabolism when proliferative activity begins to stagnate, and that is likely to initiate some other, yet unidentified energy-consuming process.

Adenosine Triphosphate↗

PubMed2006

Melanin-concentrating hormone stimulates human growth hormone secretion: a novel effect of MCH on the hypothalamic-pituitary axis.

Melanin-concentrating hormone (MCH), a 19-amino acid orexigenic (appetite-stimulating) hypothalamic peptide, is an important regulator of energy homeostasis. It is cleaved from its precursor prepro-MCH (ppMCH) along with several other neuropeptides whose roles are not fully defined. Because pituitary hormones such as growth hormone (GH), ACTH, and thyroid-stimulating hormone affect body weight and composition, appetite, insulin sensitivity, and lipoprotein metabolism, we investigated whether MCH exerts direct effects on the human pituitary to regulate energy balance using dispersed human fetal pituitaries (21-22 wk gestation) and cultured GH-secreting adenomas. We found that MCH receptor-1 (MCH-R1), but not MCH receptor-2, is expressed in both normal (fetal and adult) human pituitary tissues and in GH cell adenomas. MCH (10 nM) stimulated GH release from human fetal pituitary cultures by up to 62% during a 4-h incubation (P < 0.05). Interestingly, neuropeptide EI (10 nM), which is also cleaved from ppMCH, increased human GH secretion by up to 124% in fetal pituitaries. A milder, albeit significant, induction of GH secretion by MCH (20%) was seen in cultured GH-secreting pituitary adenomas. A comparable stimulation of GH secretion was seen when cultured mouse pituitary cells were treated with MCH. Treatment of cultured GH adenoma cells with MCH (100 nM) induced extracellular signal-regulated kinases 1 and 2 phosphorylation, suggesting activation of MCH-R1. In aggregate, these data suggest that MCH may regulate pituitary GH secretion and imply a potential cross-talk mechanism between appetite-regulating neuropeptides and pituitary hormones.

Animals↗

PubMed2006

WNK kinases influence TRPV4 channel function and localization.

TRPV4, a renally expressed nonselective cation channel of the transient receptor potential (TRP) family, is gated by hypotonicity. Kinases of the WNK family influence expression and function of the thiazide-sensitive Na+-Cl- cotransporter, and monogenic human hypertension has been linked to mutations in the gene coding for WNK4. Along with TRPV4, WNK isoforms are highly expressed in the distal nephron. We show here that coexpression of WNK4 downregulates TRPV4 function in human embryonic kidney (HEK-293) cells and that this effect is mediated via decreased cell surface expression of TRPV4; total abundance of TRPV4 in whole cell lysates is unaffected. The effect of the related kinase WNK1 on TRPV4 function and surface expression was similar to that of WNK4. Disease-causing point mutations in WNK4 abrogate, but do not eliminate, the inhibitory effect on TRPV4 function. In contrast to wild-type WNK4, a kinase-dead WNK4 point mutant failed to influence TRPV4 trafficking; however, deletion of the entire WNK4 kinase domain did not blunt the effect of WNK4 on localization of TRPV4. Deletion of the extreme COOH-terminal putative coiled-coil domain of WNK4 abolished its effect. In immunoprecipitation experiments, we were unable to detect direct interaction between TRPV4 and either WNK kinase. In aggregate, these data indicate that TRPV4 is functionally regulated by WNK family kinases at the level of cell surface expression. Because TRPV4 and WNK kinases are coexpressed in the distal nephron in vivo and because there is a tendency toward hypercalcemia in TRPV4-/- mice, we speculate that this pathway may impact systemic Ca2+ balance. In addition, because WNK kinases and TRPV4 are activated by anisotonicity, they may comprise elements of an osmosensing or osmotically responsive signal transduction cascade in the distal nephron.

Animals↗

PubMed2000

Urea protects from the proapoptotic effect of NaCl in renal medullary cells.

Hypertonic NaCl upregulated two sensitive and specific biochemical indices of apoptosis, caspase-3 activation and annexin V binding, in a time- and dose-dependent fashion in renal medullary mIMCD3 cells. Pretreatment with urea (200 mM for 30 min) protected from the proapoptotic effect of hypertonic stress (200 mosmol/kgH(2)O) in this model. The protective effect of urea was dose dependent and was effective even when applied a short time (< or =1 h) following NaCl exposure; this protective effect was not observed in the nonrenal 3T3 cell line. In both mIMCD3 and 3T3 cells, urea failed to protect from the proapoptotic stressor, ultraviolet (UV)-B irradiation. The ability of urea to protect from hypertonic stress was approximately comparable to the protective effect of peptide mitogens epidermal growth factor and insulin-like growth factor (IGF), but it potentiated the IGF effect. Interestingly, the tyrosine kinase inhibitor, genistein, potentiated the proapoptotic effect of urea yet abrogated the proapoptotic effect of hypertonic stress. In aggregate, these data indicate that urea protects from the proapoptotic effect of hypertonic stress in a potentially cell type-specific and stimulus-specific fashion.

3T3 Cells↗

PubMed2006

Fluorescence correlation spectroscopy and fluorescence lifetime imaging microscopy.

With few and commercially available add-ons, both confocal and full-field fluorescence microscopes can be adapted to provide more information on the biological sample of interest. In this review we discuss the possibilities offered by two additional functionalities to fluorescence microscopes, fluorescence correlation spectroscopy (FCS) and fluorescence lifetime imaging mi croscopy (FLIM). FCS measurements at a single point in a sample allow kinetic and diffusion properties of fluorescently labeled molecules to be determined, as well as their concentration and aggregation state. Data from multiple points of the sample can be acquired using scanning-FCS, image correlation spectroscopy, and raster image correlation spectroscopy. These techniques cover phenomena with characteristic durations from sub-microsecond to second time scales. The power of FLIM lies in the fact that the measured fluorescent lifetime of a fluorophore is sensitive to the molecular environment of that fluorophore. FLIM is a robust means to quantify Forster resonance energy transfer and thus determine protein-protein interactions or protein conformational changes. In addition, FLIM is very valuable for functional imaging of ion concentrations in cells and tissues as it can be applied in heterogeneously labeled samples. In summary, FCS and FLIM allow information to be gathered beyond localization, including diffusional mobility, protein clustering and interactions, and molecular environment.

Animals↗

PubMed1998

Recurrent carotid stenosis : results of the asymptomatic carotid atherosclerosis study.

BACKGROUND AND PURPOSE: We sought to determine the incidence of recurrent carotid stenosis in patients in the Asymptomatic Carotid Atherosclerosis Study (ACAS) who had undergone carotid endarterectomy and were prospectively followed with Doppler ultrasound for up to 5 years. METHODS: The ACAS database was interrogated to determine the rate of recurrent carotid stenosis (>/=60%) based up angiogram-validated Doppler data, with a 90% and a 95% positive predictive value, as well as information concerning the technologists' interpretation of percent stenosis. These 3 parameters are reported for each of 3 time intervals: within 3 months of operation (residual disease), between 3 and 18 months (early restenoses), and between 18 and 60 months (late restenosis). RESULTS: Of the 825 patients randomized to the surgical arm of the study, 720 actually underwent carotid endarterectomy, and 645 had complete ultrasound data. The aggregate incidence of residual and recurrent carotid stenosis for all time intervals ranged from 12.7% to 20.4%, depending on the positive predictive value confidence level desired. Residual disease occurred in 4.1% to 6.5%; true, early restenosis was found in 7.6% to 11.4%; and late restenosis occurred in 1.9% to 4.9%. None of the traditional risk factors showed a statistically significant effect on recurrent stenosis. The use of patch angioplasty closure reduced overall risk of restenosis from 21.2% to 7.1%, from 16.7% to 4.6%, and from 27.4% to 8.2%, depending on the PPV confidence level desired (P<0.001). Of the 136 patients judged to have recurrent stenosis, only 8 (5.9%) underwent reoperation (only 1 for symptoms). There was no correlation between late stroke and recurrent stenosis. CONCLUSIONS: Carotid endarterectomy is a durable procedure with a low rate of true restenosis, particularly when patch angioplasty is used to close the arteriotomy.

Angioplasty↗

PubMed1994

Identification and induction of human keratinocyte-derived IL-12.

Interleukin 12 is a heterodimeric molecule that serves as a potent co-stimulator enhancing the development of Th1 cells. As one of the classical Th1 cell-mediated responses is contact sensitivity in skin, we wondered whether IL-12 might be produced by epidermal cells and serve as a mediator of this immune response. Using a sensitive, quantitative PCR technique we demonstrate that p35 chain mRNA of IL-12 is produced constitutively by human epidermal cells, whereas p40 chain mRNA can only be detected in epidermis treated with contact allergen, but not epidermis exposed to irritants or tolerogens. Time course studies showed a dramatic induction of IL-12 p40 mRNA 4 h after in vivo allergen treatment reaching peak strength after 6 h. In cell depletion assays we show that epidermal keratinocytes are the major source of this cytokine in the epidermis. This was further supported by analysis of mRNA derived from the human keratinocyte cell line HaCat expressing IL-12 p35 and p40 mRNA upon stimulation. The presence of bioactive IL-12 in supernatants derived from allergen-stimulated epidermal cells was demonstrated by IL-12-specific bioassay. Additional evidence for the functional importance of IL-12 in primary immune reactions in skin was obtained in allogeneic proliferation assays using human haptenated epidermal cells containing Langerhans cells as APC and allogeneic CD4+ T cells as responders. Anti-IL-12 mAb inhibited the proliferation of T cells by approximately 50%. In aggregate our data demonstrate that nonlymphoid keratinocytes are capable of producing functional IL-12 and provide evidence for the functional significance of IL-12 in primary immune responses in skin.

Antibodies, Monoclonal↗

PubMed1999

Revising and assessing axis II, Part I: developing a clinically and empirically valid assessment method.

OBJECTIVE: Personality pathology is difficult to measure. Current instruments have problems with validity and rely on a direct-question format that may be inappropriate for the assessment of personality. In addition, they are designed specifically to address current DSM-IV categories and criteria, which limits their utility in making meaningful revisions of those criteria. These problems suggest the need for consideration of alternative approaches to assessing and revising axis II. METHOD: This article describes the development and validation of an assessment tool designed to allow clinicians to provide detailed, clinically rich personality descriptions in a systematic and quantifiable form (the Shedler-Westen Assessment Procedure, or SWAP-200). A total of 797 randomly selected psychiatrists and psychologists used the SWAP-200 to describe either an actual patient or a hypothetical, prototypical patient with one of 14 personality disorders (one of the 10 DSM-IV axis II disorders or one of four disorders included in the appendix or in DSM-III-R) or a healthy, high-functioning patient. RESULTS: The data yielded aggregated descriptions of actual patients in each diagnostic category (N = 530) as well as aggregated descriptions of hypothetical, prototypical patients (N = 267). SWAP-200 descriptions of patients with personality disorders showed high convergent and discriminant validity on a variety of criteria. The diagnostic procedure lends itself to both categorical and dimensional personality disorder diagnoses. Descriptions of individual patients resemble MMPI profiles, based on the degree of match between the patient's profile and a criterion group, except that they are based on clinician observation rather than self-report. CONCLUSIONS: The SWAP-200 represents an approach to the measurement and classification of personality disorders that has potential for refining axis II categories and criteria empirically in ways that are both psychometrically and clinically sound.

Adult↗

PubMed1984

Methodological observations on applied behavioral science.

Policy makers and administrators have become frustrated with single-subject designs because these designs appear unable, at first blush, to provide them with essential information that they can use in planning or change at the organizational or institutional level of management. Practitioners have become frustrated with prior exclusive reliance on traditional group experimental designs because they fail to provide useful information for conducting therapy or delivering services. The following article by Professor Gingerich makes a large and important contribution toward mitigating these two apparently divergent needs. Gingerich describes how meta-analysis can provide useful information for managers through aggregations of data obtained from single-subject, time-series designs. The article also discusses the use of meta-analysis of time-series data as a basis for improving the quality of scientific investigations.

Evaluation Studies as Topic↗

PubMed1996

The inhibiting effect of aqueous Azadirachta indica (Neem) extract upon bacterial properties influencing in vitro plaque formation.

The purpose of this investigation was to examine the inhibitory effects of aqueous extracts derived from the bark-containing sticks (Neem stick) of Azadirachta indica upon bacterial aggregation, growth, adhesion to hydroxyapatite, and production of insoluble glucan, which may affect in vitro plaque formation. Neem stick extracts were screened for minimal bacterial growth inhibition (MIC) against a panel of streptococci by means of a broth dilution assay. Initial bacterial attachment was quantified by the measurement of the adhesion of 3H-labeled Streptococcus sanguis to saliva-conditioned synthetic hydroxyapatite. The effect of the Neem stick extract upon insoluble glucan synthesis was measured by the uptake of radiolabeled glucose from 14C-sucrose. Aggregating activity of the Neem stick extracts upon a panel of streptococci was also examined. No inhibition of bacterial growth was observed among the streptococcal strains tested in the presence of < or = 320 micrograms/mL of the Neem stick extract. The pre-treatment of S. sanguis with the Neem stick extract or the gallotannin-enriched extract from Melaphis chinensis at 250 micrograms/mL resulted in a significant inhibition of the bacterial adhesion to saliva-conditioned hydroxyapatite. Pre-treatment of saliva-conditioned hydroxyapatite with the Neem stick or gallotannin-rich extract prior to exposure to bacteria yielded significant reductions in bacterial adhesion. The Neem stick extract and the gallotannin-enriched extract from Melaphis chinensis inhibited insoluble glucan synthesis. Incubation of oral streptococci with the Neem stick extract resulted in a microscopically observable bacteria aggregation. These data suggest that Neem stick extract can reduce the ability of some streptococci to colonize tooth surfaces.

Alkaloids↗

PubMed1997

Children of parents with bipolar disorder: a metaanalysis of risk for mental disorders.

OBJECTIVE: To compare the prevalence rates of mental disorders among children of parents with bipolar disorder and of parents with no mental disorders. METHOD: Seventeen studies, meeting specific selection criteria, were included in the metaanalyses. Risks for mental disorders among children were estimated by aggregating raw data from the selected studies. RESULTS: Results indicate that in comparison with children of parents with no mental disorders, children of parents with bipolar disorder are 2.7 times more likely to develop any mental disorder and 4.0 times more likely to develop an affective disorder. The metaanalyses indicate that during childhood and adolescence, the risks for any mental disorder and for affective disorders in children are consistently but moderately related to having a parent who suffers from bipolar disorder. CONCLUSIONS: Risk factors that could account for the psychopathology observed in children of bipolar parents are explored.

Adolescent↗

PubMed2002

Trauma scoring.

Severity scales to characterize the nature and extent of injury are important adjuncts to trauma care systems, trauma research and many of the elements of a complete public health approach to injury. This article provides a brief overview of severity scale development over the past 30 years during which the science to support such initiatives has matured substantially. Anatomical, physiological, intensive care, composite and complex scales and models now abound and are being applied to a variety of tasks with increasing precision. Trauma registries enable the meaningful aggregation of data for the development and testing of models. Future challenges are identified as are potentially fruitful avenues of research.

Disability Evaluation↗

PubMed1993

Perinatal mortality in a northern Nigerian rural community.

87 perinatal deaths which occurred out of 1484 births in a rural area of Northern Nigeria over a 9 month period were reviewed. The perinatal mortality rate was 58.6 per 1000 births. Babies born to very young adolescent mothers aged between 10-14 years had the highest perinatal mortality of 375 per 1000 births. Statistically significant relationships were also established between perinatal mortality and parity, educational status of the mother and birth weight. The leading cause of perinatal death was birth trauma which accounted for 48% of all perinatal deaths. Strategies for the reduction of perinatal mortality in the rural community are highlighted.

Adolescent↗

PubMed2006

Sample-size requirements for developing strategies, based on the pupal/demographic survey, for the targeted control of dengue.

Several methods to determine the sample size required for a reliable and practical assessment of the number of Aedes aegypti pupae in a community in Puerto Rico have been explored. Because the pupae were highly aggregated, the data were fitted to a negative binomial distribution. Classical statistical-inference methods for sample-size determination demanded the sampling of >3,000 premises for a reliable estimation of the mean number of pupae/person (with a 15% error). This number was reduced to 1,000-1,200 premises after applying a finite-population correction. Database sub-sampling simulations, with increasing sample sizes, showed that the variability in the mean relative abundance of container types and in the mean number of pupae/container substantially decreased after sampling 186 and 310 premises, respectively. Sequential sampling was applied to test the hypotheses that the number of female pupae/person was at least 0.19 (considered the dengue epidemic threshold) or no greater than 0.10 (arbitrarily set as the safe level). After sampling only 25 premises in the first survey and 125 in the second, it was determined that the densities of female pupae were above the epidemic threshold. Thus, sequential sampling provided substantial reductions in the sample size required to determine if vector control was needed. Validation of the Ae. aegypti thresholds required for dengue transmission could confer viability and efficiency to dengue-vector surveillance and control programmes.

Aedes↗

PubMed2006

cPath: open source software for collecting, storing, and querying biological pathways.

BACKGROUND: Biological pathways, including metabolic pathways, protein interaction networks, signal transduction pathways, and gene regulatory networks, are currently represented in over 220 diverse databases. These data are crucial for the study of specific biological processes, including human diseases. Standard exchange formats for pathway information, such as BioPAX, CellML, SBML and PSI-MI, enable convenient collection of this data for biological research, but mechanisms for common storage and communication are required. RESULTS: We have developed cPath, an open source database and web application for collecting, storing, and querying biological pathway data. cPath makes it easy to aggregate custom pathway data sets available in standard exchange formats from multiple databases, present pathway data to biologists via a customizable web interface, and export pathway data via a web service to third-party software, such as Cytoscape, for visualization and analysis. cPath is software only, and does not include new pathway information. Key features include: a built-in identifier mapping service for linking identical interactors and linking to external resources; built-in support for PSI-MI and BioPAX standard pathway exchange formats; a web service interface for searching and retrieving pathway data sets; and thorough documentation. The cPath software is freely available under the LGPL open source license for academic and commercial use. CONCLUSION: cPath is a robust, scalable, modular, professional-grade software platform for collecting, storing, and querying biological pathways. It can serve as the core data handling component in information systems for pathway visualization, analysis and modeling.

Computational Biology↗

PubMedDate not supplied

Design and implementation of an application and associated services to support interdisciplinary medication reconciliation efforts at an integrated healthcare delivery network.

Confusion about patients' medication regimens during the hospital admission and discharge process accounts for many preventable and serious medication errors. Many organizations have begun to redesign their clinical processes to address this patient safety concern. Partners HealthCare, an integrated delivery network in Boston, Massachusetts, has answered this interdisciplinary challenge by leveraging its multiple outpatient electronic medical records (EMR) and inpatient computerized provider order entry (CPOE) systems to facilitate the process of medication reconciliation. This manuscript describes the design of a novel application and the associated services that aggregate medication data from EMR and CPOE systems so that clinicians can efficiently generate an accurate pre-admission medication list. Information collected with the use of this application subsequently supports the writing of admission and discharge orders by physicians, performance of admission assessment by nurses, and reconciliation of inpatient orders by pharmacists. Results from early pilot testing suggest that this new medication reconciliation process is well accepted by clinicians and has significant potential to prevent medication errors during transitions of care.

Clinical Pharmacy Information Systems↗