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Biomedical subjects

G A Nichols

Publications and source records attributed to G A Nichols.

At least 19 recordsLinked to original sources

Weight changes following the initiation of new anti-hyperglycaemic therapies.

OBJECTIVE: The objective of this study was to quantify 1-year weight gain associated with the initiation of sulphonylurea (SU), metformin, insulin and thiazolidinedione (TZD) therapy in a representative real world population of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: The study population was 9546 members of Kaiser Permanente North-west (KPNW) who initiated an anti-hyperglycaemic drug between 1996 and 2002 and continued use of that drug for at least 12 months without adding other therapies. Change in weight was calculated as the annualized difference between baseline and follow-up weight and was adjusted for demographic and clinical characteristics. We then compared the weight changes observed in patients newly initiating SU, metformin, insulin and TZD therapies. RESULTS: After adjustment for demographic and clinical characteristics that might affect weight change, metformin initiators lost an average of 2.4 kg while all other groups gained weight. SU initiators gained the least (1.8 kg), followed by insulin initiators (3.3 kg) and TZD subjects (5.0 kg). All comparisons were highly statistically significant. CONCLUSIONS: In an observational study of 1-year weight changes following the initiation of SUs, metformin, insulin or TZDs, we found similar but somewhat smaller weight changes than those previously reported in clinical trials. Our observed weight changes could not be explained by the many other factors we tested and seemed to apply across the full spectrum of diabetes patients. Our report provides valuable information that will allow the patient and clinician to anticipate, and perhaps address, expected weight changes that accompany the initiation of anti-hyperglycaemic drugs.

Adult↗

Effects of weight gain on medical care costs.

OBJECTIVE: To examine in middle-aged adults the effect of medical care costs of large, rapid weight gain compared to weight maintenance. DESIGN: : Retrospective cohort study for a 3-y time period. SETTING AND PARTICIPANTS: Population-based sample (N=15174) of men and women members of a large managed care organization, aged 35-65 y, with a body mass index (BMI) >25 kg/m(2) at baseline. Health-care utilization and costs were measured at baseline and over the 3-y follow-up period. RESULTS: Mean age at baseline was 49.7 y and mean BMI was 31.5 kg/m(2). During the 3-y follow-up period, 40.8% were classified as weight maintainers (+/-4 pounds), 45.3% gained 5-19 pounds, and 13.9% gained >/=20 pounds. A weight gain of >/=20 pounds was significantly associated with increased total medical care costs in all subgroups evaluated. Among all subjects, for those who gained >/=20 pounds compared to those who maintained weight, the adjusted 3-y increase in costs was 561 dollars. Among the subgroup with baseline comorbidities, the adjusted 3-y change in total medical care costs was 711 dollars. Multivariate analyses showed no significant differences between those who gained 5-19 pounds and those who maintained weight. Baseline BMI and comorbidities were also significant predictors of change in medical care costs, independent of weight gain. CONCLUSION: A large 3-y weight gain (>/=20 lb) in middle-aged overweight and obese adults is associated with a correspondingly larger increase in total medical care costs compared to weight maintainers. The prevention of large weight gains holds promise for significantly reducing future medical care costs. Future studies should examine the causes of rapid weight gain and evaluate approaches to prevent and reverse such weight gain.

Adult↗

Functional status before and after diagnosis of Type 2 diabetes.

AIMS: We examined functional health status prior to the diagnosis of Type 2 diabetes, and measured the effect on functional health status of receiving the diagnosis. METHODS: After the ADA reduced its fasting plasma glucose level for diagnosing diabetes from > 7.8 to > 7.0 mmol/l, we identified 1014 members of a large HMO who met the new criteria, and an age- and gender-matched comparison group who did not. We mailed questionnaires to these subjects in 1998, and again in 1999 to 623 who met the new criteria, after some had been notified of their diabetes, while others had not. We used the SF-12(R) Health Survey to measure physical and mental subjective health status. RESULTS: Mean age of respondents meeting new diagnostic criteria (n = 498) was 67.3 + 10.4 years, 43.6% were women. Comparison group respondents (n = 589) were 66.7 + 10.6 years, 45.2% women. The groups were not statistically different on either characteristic. Prior to the diagnosis of Type 2 diabetes, physical functioning was already lower in subjects who met the new criteria than in the comparison group (39.5 vs. 42.1, P < 0.001), mental functioning was similar (51.4 vs. 51.9, P = 0.406). Among those who newly met diagnostic criteria for diabetes, there was no difference in the change in health status (mental or physical) in those who reported receiving a diagnosis (n = 105) compared with those who did not (n = 168). CONCLUSIONS: Physical health status is already reduced prior to diabetes diagnosis, perhaps because of obesity or other aspects of the insulin resistance syndrome. Receiving a diabetes diagnosis after adjusting the diagnostic criteria does not adversely affect either mental or physical health status.

Aged↗

Health care costs associated with escalation of drug treatment in type 2 diabetes mellitus.

The cost of different intensities of therapy in HMO patients with type 2 diabetes mellitus was studied. Health care utilization data from 1995 were obtained for 12,200 registrants from the Kaiser Permanente Northwest Diabetes Registry who had type 2 diabetes mellitus. The data were used to determine costs associated with the escalation of antidiabetic therapies in persons with type 2 diabetes mellitus. The total annual costs (in 1993 dollars) associated with no drug therapy, a sulfonylurea only, metformin, a sulfonylurea plus insulin, and insulin alone were $4400, $4187, $4838, $8856, and $7365, respectively. Per patient total costs were higher for patients who had received antidiabetic therapy in 1995 or previously than for those who had not ($5303 versus $4365) and for patients who had received insulin therapy than for those who had not ($7379 versus $4117). Macrovascular complications accounted for 62-89% of the cost associated with inpatient treatment of diabetes-related complications. The total cost of treating patients with type 2 diabetes mellitus at an HMO increased as antidiabetic therapies escalated.

Aged↗

Treated prevalence, incidence, and pharmacotherapy of child and adolescent mood disorders in an HMO.

This study examined the "treated" prevalence, incidence, and pharmacotherapy of child and adolescent mood disorders in a managed care setting. General prevalence patterns across age and sex were similar to those reported in community epidemiology studies, although, not unexpectedly, the overall rates were somewhat lower. Primary care providers identified a substantial proportion of the youth with a mood disorder. Antidepressant medication was used more often by youth identified with a mood disorder in medical care settings than by those youth identified in specialty mental health care settings. These results are valuable in determining if youth with mood disorders receiving medication prescriptions across settings are treated according to current best practice guidelines (such as the adult depression guidelines [U.S. Department of Health and Human Services, 1993]), that is, primarily with SSRI medications.

Adolescent↗

Body mass index and future healthcare costs: a retrospective cohort study.

OBJECTIVE: To assess the relationship between body mass index (BMI) and future healthcare costs. RESEARCH METHODS AND PROCEDURES: We undertook a retrospective cohort study of the relationship between obesity and future healthcare costs at Kaiser Permanente Northwest Division, a large health maintenance organization in Portland, Oregon. Study subjects (n = 1286) consisted of persons who responded to a 1990 health survey that was mailed to a random sample of adult Kaiser Permanente Northwest Division members who were 35 to 64 years of age; had a BMI > or = 20 kg/m(2) (based on self-reported height and weight); did not smoke cigarettes; and did not have a history of coronary heart disease, stroke, human immunodeficiency virus, or cancer. Subjects were stratified according to their BMI in 1990 (20 to 24.9, 25 to 29.9, and > or = 30 kg/m(2); n = 545, 474, and 367, respectively). We then tallied their costs (in 1998 US dollars) for all inpatient care, outpatient services, and prescription drugs over a 9-year period (1990 through 1998). RESULTS: For persons with BMIs of 20 to 24.9 kg/m(2), mean (+/-SE) annual costs of prescription drugs, outpatient services, inpatient care, and all medical care averaged $261 (+/-18), $848 (+/-59), $532 (+/-85), and $1631 (+/-120), respectively, over the study period. Cost ratios (95% confidence intervals) for persons with BMIs of 25 to 29.9 kg/m(2) and > or = 30 kg/m(2), respectively, were 1.37 (1.12 to 1.66) and 2.05 (1.62 to 2.55) for prescription drugs, 0.96 (0.83 to 1.13) and 1.14 (0.97 to 1.37) for outpatient services, 1.20 (0.81 to 1.86) and 1.38 (0.91 to 2.14) for inpatient care, and 1.10 (0.91 to 1.35) and 1.36 (1.11 to 1.68) for all medical care. DISCUSSION: Future healthcare costs are higher for persons who are overweight, especially those with BMIs > or = 30 kg/m(2).

Adult↗

Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors.

OBJECTIVE: To estimate the prevalence and incidence of congestive heart failure (CHF) in populations with and without type 2 diabetes and to identify risk factors for diabetes-associated CHF. RESEARCH DESIGN AND METHODS: We searched the inpatient and outpatient electronic medical records of 9,591 individuals diagnosed with type 2 diabetes before 1 January 1997 and those of an age- and sex-matched control group without diabetes for a diagnosis of CHF. Among those without a baseline diagnosis of CHF, we searched forward for 30 months for incident cases of CHF. We constructed multiple logistic regression models to identify risk factors for both prevalent and incident CHF. RESULTS: CHF was prevalent in 11.8% (n = 1,131) of diabetic subjects and 4.5% (n = 435) of control subjects at baseline. We observed incident cases of CHF in 7.7% of diabetic subjects free of CHF at baseline (650 of 8,460) and in 3.4% of control subjects (314 of 9,156). In diabetic subjects, age, diabetes duration, insulin use, ischemic heart disease, and elevated serum creatinine were independent risk factors for both prevalent and incident CHF. Better glycemic control at baseline, and improved glycemic and blood pressure control at follow-up predicted the development of CHF. CONCLUSIONS: Despite controlling for age, duration of diabetes, presence of ischemic heart disease, and presence of hypertension, insulin use was associated with both prevalent and incident CHF. Why insulin use and better glycemic control both at baseline and follow-up independently predicted CHF deserves further study.

Age Distribution↗

Following depression in primary care: do family practice physicians ask about depression at different rates than internal medicine physicians?

OBJECTIVE: To determine whether the chronically or recurrently depressed patients of family practice and internal medicine physicians differed in the proportion reporting that their primary care physician asked them about depression symptoms. DESIGN: A cross-sectional observational study of chronically or recurrently depressed survey respondents who identified a family practice or internal medicine physician as their primary care provider. SETTING: A large not-for-profit group-model health maintenance organization in the northwestern United States, with a population representative of its service area. PATIENTS: Health maintenance organization members (n= 1161) with ongoing or recurring depression or dysthymia who responded to a 1993 survey and who identified either a family practice or internal medicine physician as their primary care provider. MAIN OUTCOME MEASURE: Patients' self-report of their primary care physician asking them: (1) whether they had been feeling sad, blue, or depressed; (2) to fill out a questionnaire about their mood or feelings; and (3) whether they had been thinking about death or suicide. RESULTS: Chronically or recurrently depressed patients of family practice physicians were more likely to report that their physician asked them about depressive symptoms than were patients of internal medicine physicians (34.0% vs 27.3%) (P=.02). This finding persisted in a multivariate analysis. CONCLUSION: Family practice physicians may be more attentive to depressive disorders than internal medicine physicians.

Cross-Sectional Studies↗

Controlled trials of CQI and academic detailing to implement a clinical practice guideline for depression.

BACKGROUND: The release of the Agency for Health Care Policy and Research (AHCPR)'s Guideline for the Detection and Treatment of Depression in Primary Care created an opportunity to evaluate under naturalistic conditions the effectiveness of two clinical practice guideline implementation methods: continuous quality improvement (CQI) and academic detailing. A study conducted in 1993-1994 at Kaiser Permanente Northwest Division, a large, not-for-profit prepaid group practice (group-model) HMO, tested the hypotheses that each method would increase the number of members receiving depression treatment and would relieve depressive symptoms. METHODS: Two trials were conducted simultaneously among adult primary care physicians, physician assistants, and nurse practitioners, using the same guideline document, measurement methods, and one-year follow-up period. The academic detailing trial was randomized at the clinician level. CQI was assigned to one of the setting's two geographic areas. To account for intraclinician correlation, both trials were evaluated using generalized equations analysis. RESULTS: Most of the CQI team's recommendations were not implemented. Academic detailing increased treatment rates, but--in a cohort of patients with probable chronic depressive disorder--it failed to improve symptoms and reduced measures of overall functional status. CONCLUSIONS: New organizational structures may be necessary before CQI teams and academic detailing can substantially change complex processes such as the primary care of depression. New research and treatment guidelines are needed to improve the management of persons with chronic or recurring major depressive disorder.

Adult↗

Case-control study of 10 years of comprehensive diabetes care.

OBJECTIVE: To describe the long-term clinical impact of a comprehensive management program instituted throughout a health system for members with diabetes mellitus. DESIGN: 10 year case-control evaluation. SETTING: Kaiser Permanente Northwest, Portland, OR. PARTICIPANTS: Members of the health maintenance organization between 1987 and 1996; members with diabetes were compared with equal numbers of members without diabetes. The number of participants with diabetes ranged from 5331 in 1987 to 13,099 in 1996. MAIN OUTCOME MEASURES: Number in diabetes register, mortality, change in comorbidity, rates of uptake of preventive health measures, use of pharmaceuticals, levels of risk factors, hospital days per thousand per year, emergency room visits per thousand per year. RESULTS: The prevalence of diabetes identified in this population rose from 2.54% (7,895/310,819) in 1987 to 3.66% (14,741/402,754) in 1996, and the mean (SEM) age of members at the time of diagnosis fell slightly from 62.9 (+/- 0.21) years to 62.0 (+/- 0.13) years (P < 0.05). By 1996, 10,885 of the 13,099 (83% +/- 0.3%) of members with diabetes had an annual laboratory test to assess glycemic control, the annual screening rate for retinopathy was 67.6% (+/- 0.4%), the rate of uptake of influenza immunizations was 60.2% (7,886/13,099) and the screening rate for nephropathy was 43% (5,698/13,099) (+/- 0.49%). The use of home glucose testing increased from 32.4% (1721/5331) of members with diabetes to 53.0% (6,942/12,099); the use of lipid lowering drugs increased from 3.5% (187/55,331) to 19.8% (2,594/13,099). The use of angiotensin converting enzyme inhibitors increased from 8.5% to 34.8% of members with diabetes. Mean blood pressure decreased from 144/82 mm Hg (+/- 0.8/0.4) to 138/79 mm Hg (+/- 0.3/0.15), and mean total cholesterol concentrations dropped from 243 mg/dL (+/- 4.2) to 215 mg/dL (+/- 0.6). By 1996, 56.4% (7,388/1,3099) (+/- 0.5%) of members on the diabetes register had good to excellent glycemic control (HbA1c < 8%). Mortality decreased from 4.8% (256/5331) (+/- 0.3%) to 3.6% (472/13,099) (+/- 0.2%) among members with diabetes, this was a more rapid decrease than was observed among those without diabetes (P < 0.01). The annual ratio of visits to the emergency room by members with diabetes to members without fell from 2.5 to 1.8, and the ratio for the number of days spent in acute care in the hospital dropped from 3.6 to 2.5. CONCLUSIONS: This centrally organized program based in a primary care setting and utilizing a register of patients with diabetes was associated with substantial improvements in the process and outcomes of care in a large population of health maintenance organization members with diabetes.

Case-Control Studies↗

Achieving further glycemic control in type 2 diabetes mellitus.

OBJECTIVES: To identify patients with type 2 diabetes mellitus who were in poor glycemic control and therapeutic adjustments that might improve control. DESIGN: Using electronic pharmacy data, we assigned subjects to 1 of 4 therapeutic categories. We then identified patients within each category who did not meet the recommended standard of glycemic control (glycosylated hemoglobin [Hb A(1c)] <0. 08 [<8.0%]) and studied their therapetic regimens for possible improvements. SUBJECTS: The subjects were 5,061 members of a large group-model health maintenance organization who had type 2 diabetes and 12 months of 1997 health plan eligibility. Main outcome measures The dosage of antihyperglycemic agents (sulfonylureas, metformin, and insulin) in relation to glycemic control as measured by the Hb A(1c). RESULTS: A significant number (n = 1,570 [31.0%]) of persons with type 2 diabetes might improve their glycemic control with simple adjustments to their pharmacologic therapy. CONCLUSION: Busy clinicians with heavy workloads can improve their management of diabetes by identifying patients whose glycemic control could be improved through a change in medication or simple adjustment in dosage.

Aged↗

Type 2 diabetes: incremental medical care costs during the 8 years preceding diagnosis.

OBJECTIVE: To describe and analyze medical care costs for the 8 years preceding a diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS: From electronic records of a large group-model health maintenance organization (HMO), we ascertained the medical care costs preceding diagnosis for all members with type 2 diabetes who were newly diagnosed between 1988 and 1995. To isolate incremental costs (costs caused by the future diagnosis of diabetes), we subtracted the costs of individually age- and sex-matched HMO members without impending diabetes from the costs of members who were destined to receive this diagnosis. We also compared these prediagnosis costs with the first 3 years of postdiagnosis costs. RESULTS: An economic burden from impending diabetes is apparent for at least 8 years before diagnosis, beginning with costs for outpatient and pharmacy services. Diabetes-associated incremental costs (costs of type 2 diabetic patients minus matched costs of nondiabetic patients) averaged $1,205 per type 2 diabetic patient per year during the first eight prediagnostic years, including $1,913 each year for the 3 years preceding diagnosis. In the year immediately preceding diagnosis, incremental costs were equivalent to those observed in the second and third years after diagnosis. CONCLUSIONS: Incremental costs of diabetes begin at least 8 years before diagnosis and grow at an accelerating rate as diagnosis approaches and immediately after diagnosis. These incremental costs span the full range of medical services. Furthermore, the majority of these costs are for conditions not normally associated with diabetes or its complications.

Age Factors↗

Predictors of glycemic control in insulin-using adults with type 2 diabetes.

OBJECTIVE: To determine the characteristics that influence glycemic control among insulin-using adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied all 1,333 eligible members of a large not-for-profit health maintenance organization who responded to a 1997 survey. We tested associations among demographic, treatment, and psychometric variables with mean 1997 HbA1c values. The Problem Areas in Diabetes (PAID) instrument was used to assess the emotional effect of living with diabetes, and the Short Form 12 Physical Function Scale was used to assess the effect of physical limitations on daily activities. Based on differences between and within treatment groups, we built models to predict glycemic control for subgroups of subjects who were using insulin alone and those who were using insulin in combination with an oral hypoglycemic agent. RESULTS: Younger age, lower BMI, and increased emotional distress about diabetes (according to the PAID scale) were all significant predictors (P < 0.05) of worse glycemic control. However, except among individuals with an HbA1c level of >8.0 who were receiving combination therapy, only approximately 10% of the variance in glycemic control could be predicted by demographic, treatment, or psychometric characteristics. CONCLUSIONS: Personal characteristics explain little of the variation in glycemic control in insulin-using adults with type 2 diabetes. Possible explanations are that the reduced complexity of control in type 2 diabetes makes the disease less sensitive to personal factors than control in type 1 diabetes, that health-related behavior is less driven by personal and environmental characteristics among older individuals, or that, in populations exposed to aggressive glycemic control with oral hypoglycemic agents and nurse care managers, personal differences become largely irrelevant.

Activities of Daily Living↗

Ten-year follow-up of antidiabetic drug use, nonadherence, and mortality in a defined population with type 2 diabetes mellitus.

Studies performed for drug registration provide little insight into the long-term use and effectiveness of drugs in "real world" populations and settings. To obtain such insight, we used 10 years of electronic medical-record data from Kaiser Permanente Northwest Division, a large, group-model health maintenance organization in the United States, to study drug transitions, lapses in drug therapy, and mortality among 693 persons with newly diagnosed type 2 diabetes mellitus in 1988. We also studied an equivalently defined cohort of 1071 persons with new diagnoses in 1994, for whom the availability of laboratory results via electronic data permitted additional analyses. Cumulative mortality in the 1988 cohort increased steadily to 207 of 571 patients (36%) by 1997 (year 10). In 1988, 548 of 693 patients (79%) received initial monotherapy with a sulfonylurea. Insulin use rose as the use of sulfonylureas declined. Over this period, 504 of 693 patients (73%) discontinued or added drug therapy. Eight percent to 10% of both sulfonylurea users and insulin users discontinued drug use during the study period. In the 1994 cohort, two thirds of the subjects who discontinued therapy and were tested for glycosylated hemoglobin (Hb A1c) (n = 86) maintained good-to-excellent glycemic control. However, 78 discontinuers (38%) were not tested for Hb A1c, and, among this subset, 32% failed to visit a primary care clinician. The results of this study suggest that 5% to 10% of persons with type 2 diabetes mellitus avoid contact with the medical care system. Avoidance persists for at least the first 10 years after diagnosis but is more common in the first year after diagnosis. In addition, secondary failure of sulfonylureas begins within 1 year of diagnosis and continues at a steady pace. Almost 80% of patients initially treated with sulfonylureas added or switched to metformin or insulin within 10 years of diagnosis.

Cohort Studies↗

Type 2 diabetes: incremental medical care costs during the first 8 years after diagnosis.

OBJECTIVE: To describe and analyze the time course of medical care costs caused by type 2 diabetes, from the time of diagnosis through the first 8 postdiagnostic years. RESEARCH DESIGN AND METHODS: From electronic health maintenance organization (HMO) records, we ascertained the ongoing medical care costs for all members with type 2 diabetes who were newly diagnosed between 1988 and 1995. To isolate incremental costs (costs caused by the diagnosis of diabetes), we subtracted the costs of individually matched HMO members without diabetes from costs of members with diabetes. RESULTS: The economic burden of diabetes is immediately apparent from the time of diagnosis. In year 1, total medical costs were 2.1 times higher for patients with diabetes compared with those without diabetes. Diabetes-associated incremental costs (type 2 diabetic costs minus matched costs for people without diabetes) averaged $2,257 per type 2 diabetic patient per year during the first 8 postdiagnostic years. Annual incremental costs varied relatively little over the period but were higher during years 1, 7, and 8 because of higher-cost hospitalizations for causes other than diabetes or its complications. CONCLUSIONS: For the first 8 years after diabetes diagnosis, patients with type 2 diabetes incurred substantially higher costs than matched nondiabetic patients, but those high costs remained largely flat. Once the growth in costs due to general aging is controlled for, it appears that diabetic complications do not increase incremental costs as early as is commonly believed. Additional research is needed to better understand how diabetes and its diagnosis affect medical care costs over longer periods of time.

Antihypertensive Agents↗

Changing patterns of antidepressant use and costs in a health maintenance organisation.

This study examined changes in the utilisation and costs of different antidepressants, particularly the selective serotonin reuptake inhibitors (SSRIs), and changes in the use of mental health services in a US health maintenance organisation (HMO) over the 8-year period following the introduction of SSRIs. It was hypothesised that SSRIs would be used increasingly in this setting, and that SSRI users would show a pattern of mental health service utilisation that was indicative of more severe psychiatric illnesses or prior treatment failures. Both hypotheses were accepted. The use of antidepressants nearly tripled over the 8-year period, with SSRIs showing the largest increase; per capita antidepressant costs increased more than 10-fold, largely because of the high cost per unit of SSRIs. Estimated daily doses of SSRIs were largely within the recommended ranges, although the duration of use was short if their primary purpose was the treatment of depression. Incident (first-time) users of SSRIs, and patients who switched to SSRIs from other antidepressants, used more inpatient and outpatient mental health services than users of other antidepressants. Use of the psychiatric hospital among antidepressant users increased, then decreased back to its first year level, psychiatric hospital days appeared to decrease over time, and outpatient mental health visits increased. The inverse relationship between use of SSRIs and use of inpatient mental health services suggests the need for a cost-effectiveness analysis in this setting.

Antidepressive Agents↗

Replicating the chronic disease score (CDS) from automated pharmacy data.

Michael Von Korff and colleagues at the Center for Health Studies, Group Health Cooperative (GHC) of Puget Sound created a measure of chronic disease status (CDS) using automated outpatient pharmacy data. They reported the measure appeared to provide a stable and valid measure of health status. The availability of such a measure could become a new tool for a variety of applications, including screening, resource allocation, and quality assurance. The measure was replicated for its reliability and construct and predictive validity in the KPNW membership using automated pharmacy data. Reliability and validity were tested using correlation and regression techniques. The CDS showed test-retest reliability over time. It showed construct validity with the RAND-36 instrument and the BSI-8 depression screener. It showed predictive validity with health care visits and hospitalizations. The results were similar to those at GHC. The findings indicated that the CDS can serve, with certain precautions, as a readily accessible low cost measure of health status.

Chronic Disease↗

Age-related changes in gallbladder contractility and cytoplasmic Ca2+ concentration in the guinea pig.

Gallbladder (GB) motility diminishes with aging. This study was performed to characterize mechanisms that are involved in changes in GB contractility that occur during aging. Cytoplasmic Ca2+ concentrations ([Ca2+]i) and the contractile force of guinea pig GB muscle strips were simultaneously measured using fura-2 and force-displacement transducers. The binding ability of the Ca2+ channel antagonist and GB muscle compliance were also examined. The COOH-terminal octapeptide of cholecystokinin (CCK-8) evoked a dose-dependent increase in force and [Ca2+]i. Changes of [Ca2+]i and contractile force of muscle strips in response to CCK-8 were significantly greater in young (2 mo old) compared with mature and aged (12 and 24 mo old) guinea pigs (changes in [Ca2+]i, ED50: 46.1 nM at 2 mo, 6.1 microM at 12 mo, and 2.8 mM at 24 mo; changes of contractile force, ED50: 24.8 microM at 2 mo, 2.1 mM at 12 mo, and 357 mM at 24 mo). However, the magnitude of the contraction at each percent change in [Ca2+]i was actually similar in young and aged guinea pigs. In a Ca(2+)-free buffer, the responses of [Ca2+]i and force to CCK-8 in both young and aged GB muscles decreased, but those were still dose and age dependent. Binding ability of the Ca2+ channel antagonist did not differ in the young and aged groups, but the compliance of the GB muscle strip decreased with aging. These results suggest that both a reduced mobilization of intracellular Ca2+ and a decreased muscle compliance are responsible, at least in part, for age-related reduced contraction of guinea pig GB in response to CCK.

Aging↗