Procedure for the identification of population characteristics for targeting intervention services on the basis of outcome-goal priorities: Case management services for the chronic mentally ill

Although the processes involved in rational patient targeting may be obvious for certain services, for others, both the appropriate sub-populations to receive services and the procedures to be used for their identification may be unclear. This project was designed to address several research questions which arise in the attempt to deliver appropriate services to specific populations. The related difficulties are particularly evident for those interventions about which findings regarding effectiveness are conflicting. When an intervention clearly is not beneficial (or is dangerous) to a large, diverse population, consensus regarding withholding the intervention from dissemination can easily be reached. When findings are ambiguous, however, conclusions may be impossible.^ When characteristics of patients likely to benefit from an intervention are not obvious, and when the intervention is not significantly invasive or dangerous, the strategy proposed herein may be used to identify specific characteristics of sub-populations which may benefit from the intervention. The identification of these populations may be used both in further informing decisions regarding distribution of the intervention and for purposes of planning implementation of the intervention by identifying specific target populations for service delivery.^ This project explores a method for identifying such sub-populations through the use of related datasets generated from clinical trials conducted to test the effectiveness of an intervention. The method is specified in detail and tested using the example intervention of case management for outpatient treatment of populations with chronic mental illness. These analyses were applied in order to identify any characteristics which distinguish specific sub-populations who are more likely to benefit from case management service, despite conflicting findings regarding its effectiveness for the aggregate population, as reported in the body of related research. However, in addition to a limited set of characteristics associated with benefit, the findings generated, a larger set of characteristics of patients likely to experience greater improvement without intervention. ^

Rapid effects of 1alpha,25-dihydroxyvitamin D3 on osteoblasts: Studies of membrane transducers that affect calcium signals

1,25-dihydroxyvitamin D3 [1,25(OH)2D 3] exerts pleiotropic effects on osteoblasts via both long-term nuclear receptor-mediated and rapid membrane-initiated pathways during bone remodeling and mineral homeostasis. This study explored the membrane transducers that mediate rapid effects of 1,25(OH)2D3 on osteoblasts, including sphingomyelinase (SMase) and L-type voltage sensitive calcium channels (VSCCs). ^ It was previously demonstrated that 1,25(OH)2D3 stimulates transmembrane influx of Ca2+ through VSCCs in ROS 17/2.8 osteoblasts, however the molecular identity of 1,25(OH)2D 3-regulated VSCC has not been known. In this study, on the basis of in vitro tests of three unique ribozymes specifically cleaving a1C mRNA, I transfected ROS 17/2.8 cells with vectors coding recombinant ribozyme modified with U1 snRNA structure, and successfully selected stable clonal cells in which the expression of a1C was strikingly reduced. Ca2+ influx studies in these cells compared to control transfectants showed selective attenuation of depolarization- and 1,25(OH)2D3-regulated Ca2+ responses. These results allow us to conclude that the cardiac ( a1C ) subtype of the L-type VSCC is the major membrane transducer of Ca 2+ influx in osteoblasts. ^ I also demonstrated that 1,25(OH)2D3 induces a rapid hydrolysis of membrane sphingomyelin (SM) in ROS 17/2.8 cells, with the concomitant generation of ceramide, detectable at 15 minute, and maximal at 1 hour after addition. Sphingosine, sphingosine-1-phosphate (SPP) and sphingosylphosphorylcholine (SPC), downstream products of SM hydrolysis, but not ceramide, elicit Ca 2+ release from intracellular stores. Considering ceramide, sphingosine, and SPP as second messengers modulating intracellular kinases or phosphatases, these findings implicate sphingolipid-signaling pathways in transducing rapid effects of 1,25(OH)2D3 on osteoblasts. In structure/function analyses of sphingolipid signaling, it was observed that psychosine elicits Ca2+ release from intracellular stores. This challenges the dogma that sphingosine phosphorylation permits mobilization of Ca2+ , because psychosine is a sphingosine analog galactosylated at 1-carbon, preventing phosphorylation at that site. Psychosine is the pathological metabolite found in patients with Krabbe's disease, suggesting that psychosine disrupts the physiological sphingolipid signaling by chronic release of Ca2+ from intracellular stores. ^ Slower SM turnover than Ca2+ influx through VSCCs in response to 1,25(OH)2D3 demonstrates ceramide does not mediate the 1,25(OH)2D3-induced Ca2+ signaling, a conclusion endorsed further by the failure of ceramide to induce Ca 2+ signaling. ^

THE ISOLATION AND IDENTIFICATION OF O-ACETYLATED SIALIC ACIDS ON HUMAN CELLS (NEURAMINIC ACIDS, PAPER CHROMATOGRAPHY, HUMAN MALIGNANCY, BIOSYNTHETIC LABELING)

Unlike most carbohydrates, sialic acids have a restricted distribution in nature, being present in higher animals and in certain bacteriae. Unfortunately, most studies have not taken into account the fact that the parent sialic acid molecules, N-acetyl(or N-glycolyl)-neuraminic acid can be O-substituted at the 4, 7, 8 and 9 positions, generating many compounds and isomers. The approach and results of this research study demonstrates that proportions of non-, mono-, di-, and tri-O-acetylated sialic acids can be identified and quantitated on normal and malignant human cells. This was accomplished using a paper chromatographic technique to isolate and resolve individual species of non and O-substituted sialic acids. The chemical nature of these O-substituents, as an acetyl ester, was determined on the basis of chemical degradation, enzymatic and fast atom bombardment-mass spectrometry analysis.^ The working hypothesis of this study, that O-acetylated sialic acids are expressed in a restricted manner on normal and malignant cells, was confirmed using the above experimental approach; which identified mono-, di-, and tri-O-acetylated sialic acids on a variety of normal and malignant human cells. These O-acetylated sialic acids were expressed in restricted manner on subpopulations and subcellular fractions of PHL melanoma cells. Aberrant expression of O-acetylated sialic acids was associated with adenocarcinoma of the colon, leading to a nearly complete loss of di- and tri-O-acetylated sialic acids.^ Thus, the ability to isolate and identify biosynthetically radiolabeled O-acetylated sialic acids offers an efficient method of monitoring the expression of O-acetylated sialic acids in biochemical and cellular interactions. Furthermore, the ability to identify abnormal ratios of O-acetylated sialic acids in the human colon, represents a possible diagnostic tool to evaluate and identify patients who may be genetically or culturally predisposed to the development of adenocarcinoma of the colon. ^

THE POTENTIAL EFFECTS OF A COMMUNITY DEVELOPMENT PROGRAM ON DEMOGRAPHIC VARIABLES IN HIMALAYAN INDIAN VILLAGES

A community development program operating in the mountains of North India was studied to assess its potential effects on mortality, fertility and migration patterns in the community which it served. The development program operated in Jaunpur Block, Tehri-Garhwal District, Uttar Pradesh State. Two comparable villages in the district were studied. The development program had been working in one for two years, and the other was completely untouched by the program.^ Since not enough time had elapsed since the beginning of the development program's work for any effects on demographic patterns to be visable in Jaunpur Block, this study looked to attitudes of village residents as indicators of future demographic trends. Existing demographic patterns and their interrelationship with socio-religious customs were examined in the test village. A questionnaire was then administered to ascertain attitudinal differences between the residents of the test village and the control village.^ The primary work of the community development program was to train women as village health workers. The results of the attitudinal comparison of the residents of the two villages showed a marked difference in attitudes relating to the position of women in society. The data showed a higher esteem for women in the test village than in the control village, and it is argued that this difference may be attributable to the work of the development program.^ Predicting future demographic trends in Jaunpur Block on the basis of the observed difference in villagers' attitudes toward the status of women is speculatory. Jaunpur Block appears to be in the demographic stage of pre-transition, maintaining relatively high rates of both mortality and fertility. Based on demographic transition theory the next significant change in demographic patterns in Jaunpur is predicted to be a decline in mortality, and an increase in the status of women is unrelated to this prediction.^ The community development program which was studied terminated unexpectedly during the time of this study. A case study of the program's final months is presented, and speculation on the future course of demographic trends in Jaunpur Block is related to the possible alternatives for future development in the area. ^

MEASURING THE EFFECT OF ILLNESS ON THE EXPECTED REMAINING SERVICE TIME FOR THE ACTIVE DUTY ARMY: A LIFE TABLE APPROACH

A life table methodology was developed which estimates the expected remaining Army service time and the expected remaining Army sick time by years of service for the United States Army population. A measure of illness impact was defined as the ratio of expected remaining Army sick time to the expected remaining Army service time. The variances of the resulting estimators were developed on the basis of current data. The theory of partial and complete competing risks was considered for each type of decrement (death, administrative separation, and medical separation) and for the causes of sick time.^ The methodology was applied to world-wide U.S. Army data for calendar year 1978. A total of 669,493 enlisted personnel and 97,704 officers were reported on active duty as of 30 September 1978. During calendar year 1978, the Army Medical Department reported 114,647 inpatient discharges and 1,767,146 sick days. Although the methodology is completely general with respect to the definition of sick time, only sick time associated with an inpatient episode was considered in this study.^ Since the temporal measure was years of Army service, an age-adjusting process was applied to the life tables for comparative purposes. Analyses were conducted by rank (enlisted and officer), race and sex, and were based on the ratio of expected remaining Army sick time to expected remaining Army service time. Seventeen major diagnostic groups, classified by the Eighth Revision, International Classification of Diseases, Adapted for Use In The United States, were ranked according to their cumulative (across years of service) contribution to expected remaining sick time.^ The study results indicated that enlisted personnel tend to have more expected hospital-associated sick time relative to their expected Army service time than officers. Non-white officers generally have more expected sick time relative to their expected Army service time than white officers. This racial differential was not supported within the enlisted population. Females tend to have more expected sick time relative to their expected Army service time than males. This tendency remained after diagnostic groups 580-629 (Genitourinary System) and 630-678 (Pregnancy and Childbirth) were removed. Problems associated with the circulatory system, digestive system and musculoskeletal system were among the three leading causes of cumulative sick time across years of service. ^

The cost of insuring the uninsured in the U.S.

Objectives: This study included two overarching objectives. Through a systematic review of the literature published between 1990 and 2012, the first objective aimed to assess whether insuring the uninsured would result in higher costs compared to insuring the currently insured. Studies that quantified the actual costs associated with insuring the uninsured in the U.S. were included. Based upon 2009 data from the Medical Expenditure Panel Survey (MEPS), the second objective aimed to assess and compare the self-reported health of populations with four different insurance statuses. The second part of this study involved a secondary data analysis of both currently insured and currently uninsured individuals who participated in the MEPS in 2009. The null hypothesis was that there were no differences across the four categories of health insurance status for self-reported health status and healthcare service use. The alternative hypothesis was that were differences across the four categories of health insurance status for self-reported health status and healthcare service use. Methods: For the systematic review, three databases were searched using search terms to identify studies that actually quantified the cost of insuring the uninsured. Thirteen studies were selected, discussed, and summarized in tables. For the secondary data analysis of MEPS data, this study compared four categories of health insurance status: (1) currently uninsured persons who will become eligible for Medicaid under the Patient Protection and Affordable Care Act (PPACA) healthcare reforms in 2014; (2) currently uninsured persons who will be required to buy private insurance through the PPACA health insurance exchanges in 2014; (3) persons currently insured under Medicaid or SCHIP; and (4) persons currently insured with private insurance. The four categories were compared on the basis of demographic information, health status information, and health conditions with relatively high prevalence. Chi-square tests were run to determine if there were differences between the four groups in regard to health insurance status and health status. With some exceptions, the two currently insured groups had worse self-reported health status compared to the two currently uninsured groups. Results: The thirteen studies that met the inclusion criteria for the systematic review included: (1) three cost studies from 1993, 1995, and 1997; (2) four cost studies from 2001, 2003, and 2004; (3) one study of disabilities and one study of immigrants; (4) two state specific studies of uninsured status; and (5) two current studies of healthcare reform. Of the thirteen studies reviewed, four directly addressed the study question about whether insuring the uninsured was more or less expensive than insuring the currently insured. All four of the studies provided support for the study finding that the cost of insuring the uninsured would generally not be higher than insuring those already insured. One study indicated that the cost of insuring the uninsured would be less expensive than insuring the population currently covered by Medicaid, but more expensive to insure than the populations of those covered by employer-sponsored insurance and non-group private insurance. While the nine other studies included in the systematic review discussed the costs associated with insuring the uninsured population, they did not directly compare the costs of insuring the uninsured population with the costs associated with insuring the currently insured population. For the MEPS secondary data analysis, the results of the chi-square tests indicated that there were differences in the distribution of disease status by health insurance status. As anticipated, with some exceptions, the uninsured reported lower rates of disease and healthcare service use. However, for the variable attention deficit disorder, the uninsured reported higher disease rates than the two insured groups. Additionally, for the variables high blood pressure, high cholesterol, and joint pain, the currently insured under Medicaid or SCHIP group reported a lower rate of disease than the two currently insured groups. This result may be due to the lower mean age of the currently insured under Medicaid or SCHIP group. Conclusion: Based on this study, with some exceptions, the costs for insuring the uninsured should not exceed healthcare-related costs for insuring the currently uninsured. The results of the systematic review indicated that the U.S. is already paying some of the costs associated with insuring the uninsured. PPACA will expand health insurance coverage to millions of Americans who are currently uninsured, as the individual mandate and insurance market reforms will require. Because many of the currently uninsured are relatively healthy young persons, the costs associated with expanding insurance coverage to the uninsured are anticipated to be relatively modest. However, for the purposes of construing these results, it is important to note that once individuals obtain insurance, it is anticipated that they will use more healthcare services, which will increase costs. (Abstract shortened by UMI.)^