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Biomedical subjects

R E Johnson

Publications and source records attributed to R E Johnson.

At least 109 records · Page 6Linked to original sources

Enrollment duration, service use, and costs of care for severely mentally ill members of a health maintenance organization.

BACKGROUND: The rapid growth of prepaid health care and the increasing enrollment of Medicaid clients in health maintenance organizations (HMOs) raise concerns about the adequacy of services for persons with severe mental illness in capitated health plans. Uncontrolled studies have suggested that enrollment of HMO members with mental illness may be prematurely terminated. METHODS: We identified 250 adult Kaiser Permanente Northwest Region (Portland, Ore) members who were enrolled during 1986 or 1987 and had chart diagnoses of schizophrenia or bipolar disorder. Severely mentally ill subjects were matched by age and sex with control HMO members with and without diabetes mellitus. Records of the HMO and the state mental health agency were reviewed to determine HMO enrollment duration, private and public service utilization, and HMO costs of care during the 4-year follow-up period. RESULTS: The severely mentally ill subjects had 42 months of HMO enrollment during the follow-up period compared with 37 months for the controls without diabetes mellitus and 47 months for the patients with diabetes mellitus (P < .001). When HMO enrollment prior to the study was taken into account, the severely mentally ill subjects and those with diabetes mellitus had similar membership duration. Among the severely mentally ill subjects, community mental health service use was related to longer duration of HMO enrollment (P < .05) but HMO costs of care per member per month were not related to retention. The severely mentally ill subjects were high users of mental health services but their use of general medical care was similar to that of the controls without diabetes mellitus. CONCLUSIONS: This controlled study found no evidence for early termination of HMO members with costly mental illness. Use of community mental health care was associated with longer duration of HMO enrollment.

Adolescent↗

Laryngoceles and saccular cysts.

Laryngoceles and saccular cysts are related, benign abnormalities of the larynx. The pathophysiology of both lesions can involve congenital as well as acquired factors, and the appearance of both may range from incidental findings on laryngoscopy to symptoms such as hoarseness, dysphagia, dyspnea, and laryngeal discomfort. The surgical techniques used for treatment of laryngoceles and saccular cysts are controversial. We present two cases for comparison and discuss the history, diagnosis, and surgical treatment of laryngoceles and saccular cysts. Emphasis is on the surgical approach, which in both cases transected the thyrohyoid membrane externally and provided excellent visualization and exposure without significant morbidity.

Adult↗

Lithium use and discontinuation in a health maintenance organization.

OBJECTIVE: For decades, lithium has been prescribed to treat bipolar disorder. Its efficacy has been documented by clinical trials and by data from specialized clinics. An issue of considerable interest is the use of lithium in managed care systems. This project examined the use of lithium and its continuity of use by enrollees of a health maintenance organization (HMO). METHOD: In a 6-year longitudinal cohort study, 1,594 lithium users aged 15 years and older who were enrolled in an HMO were followed from 1986-1991. Data were obtained from automated databases and from medical record review of a random 5% subsample of the group (N = 74). RESULTS: Bipolar disorder was the most frequent morbidity treated. Eighty-four percent (N = 62 or 74) received services from a psychiatrist. Annual prevalence of lithium use increased over the 6-year period from 1.4 to 2.3 persons per thousand HMO members. Duration of use varied widely with some long-term but many short-term users. Discontinuation of treatment was associated with evaluated rates of psychiatric hospitalization and use of psychiatric emergency services. Lithium users were much more likely to receive a variety of other psychotropic drugs than nonusers of the same sex and age. CONCLUSIONS: Lithium use in this population was more often sporadic than continuous. Discontinuation of lithium was associated with psychiatric hospitalization. If lithium is to be a cost-effective treatment for bipolar disorder, managed care systems will need to improve adherence to drug treatment regimens.

Adolescent↗

OTC drug use in an HMO: comparing the elderly and younger adults.

The study described the self-reported use of over-the-counter (OTC) drugs among older adult and younger adult HMO members, and identified the factors associated with their use. The study population was 1,642 HMO members aged 65 and over, and 3,417 members 18 through 64 years of age. Sources of data were a mail questionnaire, and automated outpatient pharmacy, and visit data. The findings showed the elderly were less likely to use most kinds of common OTC drugs. They also used them less intensely, and were less likely to use OTC drugs in conjunction with prescription drugs, than young adults. For both age groups, OTC drug use did not appear to be a substitute for formal medical services. The major factors associated with the use of OTCs in both age groups were female gender and increased bodily pain.

Adolescent↗

Buprenorphine's physical dependence potential: antagonist-precipitated withdrawal in humans.

Buprenorphine is a partial mu opioid agonist with demonstrated efficacy in the treatment of opioid dependence. One potential advantage of buprenorphine over full mu opioid agonists is its reported low physical dependence profile. This study systematically examined physical dependence produced by maintenance with a clinically relevant dose of buprenorphine using antagonist challenge procedures. In this residential laboratory study, eight opioid-dependent volunteers maintained on 8 mg/day of sublingual buprenorphine were each challenged on independent occasions with placebo, i.m. naloxone (0.3, 1.0, 3.0 and 10.0 mg/70 kg) and p.o. naltrexone (0.3, 1.0 and 3.0 mg/70 kg) 14 hr after their daily buprenorphine dose using a repeated measures, cross-over design. Both naloxone and naltrexone precipitated time- and dose-dependent withdrawal, as evidenced by changes in subject-rated, observer-rated and physiological measures. Significant precipitated withdrawal occurred at 3.0 and 10 mg/70 kg i.m. of naloxone and 3.0 mg/70 kg p.o. of naltrexone. These results indicate that buprenorphine maintenance produces physical dependence and that i.m. naloxone and p.o. naltrexone produce equivalent effects in withdrawal precipitation under these conditions. Findings have implications for selection of antagonist doses for use in formulating combination agonist/antagonist medications and for use in transition of drug abusers from buprenorphine to antagonist maintenance therapies.

Adult↗

Incidence of clinically identified sarcoidosis in a northwest United States population.

The purpose of this study was to estimate the incidence of clinically identified (i.e., ascertained either because of symptoms or an incidental chest radiograph) sarcoidosis in a geographically and ethnically defined United States population. We employed a research-quality database of a large health maintenance organization (HMO), Kaiser Permanente, Northwest Region (KPNW), which collects morbidity and utilization data for a random sample of members sociodemographically representative of the service area of the HMO, to identify persons with suspected or confirmed sarcoidosis. Nine clinically identified incident cases of sarcoidosis were verified within the 1.87*10(5) person-year sample over a 21-year span, 1967-1987, an estimated annual all-ethnicity incidence rate of 4.8/10(5) (95 percent confidence interval ((CI)): 1.7, 7.9). Among persons of Caucasian ancestry, the estimated annual incidence was 2.8/10(5) (95 percent CI: 0.4, 5.2). If the incidence among Caucasians and the relative risk of developing sarcoidosis among African-Americans in the KPNW population is representative of the U.S. population, we estimate the incidence of clinically identified sarcoidosis in the latter to be 7.3. If, in addition, clinically identified cases constitute 42 percent of those that are clinically ascertainable (i.e., identified by mass population screening in addition to cases detected because of symptoms or incidental chest radiographs), as observed in the Swedish population, our estimate of the U.S. incidence of clinically ascertainable sarcoidosis would be 17.4.

Adolescent↗

Requirement of the yeast RTH1 5' to 3' exonuclease for the stability of simple repetitive DNA.

Simple repetitive DNA sequences are unstable in human colorectal cancers and a variety of other cancers. Mutations in the DNA mismatch repair genes MSH2, MLH1, and PMS1 result in elevated rates of spontaneous mutation and cause a marked increase in the instability of simple repeats. Compared with the wild type, a null mutation in the yeast RTH1 gene, which encodes a 5' to 3' exonuclease, was shown to increase the rate of instability of simple repetitive DNA by as much as 280 times and to increase the spontaneous mutation rate by 30 times. Epistasis analyses were consistent with the hypothesis that this RTH1-encoded nuclease has a role in the MSH2-MLH-1-PMS1 mismatch repair pathway.

Adaptor Proteins, Signal Transducing↗

4,5-Dihydro-3-(methanesulfonamidophenyl)-1-phenyl-1H-2,4-benzodiazepines: a novel class III antiarrhythmic agents.

A series of 4,5-dihydro-3-[2-(methanesulfonamidophenyl)ethyl]-1-phenyl- 1H-2,4-benzodiazepines has been identified as potential antiarrhythmic agents that interact at the delayed rectifier myocardial potassium channels (IKr) and prolong the ventricular effective refractory period (ERP) in rabbit isolated Langendorff heart preparations. Structure-activity relationship (SAR) studies based upon prolongation of ERP indicate that placement of the sulfonamido group is important for potent activity in this model. Furthermore, methanesulfonamido has enhanced activity over its ethyl or trifluoromethyl analogs. Slightly greater activity was observed in compounds that had a heteroatom in the ethyl bridge that connects the methanesulfonamidophenyl to the benzodiazepine. Further incremental improvements in activity were noted when the 1-phenyl ring was substituted with a variety of substituents. Chirality of the compounds of interest in this series does not appear to influence activity in this model. Several of these compounds were chosen for advanced evaluation, and all possess high selectivity for blockade of potassium current in hearts relative to other ion channels. In addition, these compounds prolong cardiac refractoriness in dogs following oral dosing. Thus, these agents may represent potential new class III agents, but with the potential liability of myocardial IKr blockers.

Animals↗

Photodesorption from low-temperature water ice in interstellar and circumsolar grains.

Dust grains in the interstellar medium and the outer Solar System commonly have a coating of water ice, which affects their optical properties and surface chemistry. The thickness of these icy mantles may be determined in part by the extent of photodesorption (photosputtering) by background ultraviolet radiation. But this process is poorly understood, with theoretical estimates of the photodesorption rate spanning several orders of magnitude. Here we report measurements of the absolute ultraviolet photodesorption yield of low-temperature water ice. Our results indicate that the rate of photodesorption is appreciable. In particular, it can account for the absence of icy mantles on grains in diffuse interstellar clouds, it exceeds solar-wind ion erosion and sublimation in the outer Solar System, and it is important in determining the lifetimes of icy mantles in dense molecular clouds.

Extraterrestrial Environment↗

Use of prostate-specific antigen for prostate cancer screening in primary care practice.

OBJECTIVE: To examine prostate-specific antigen (PSA) as a screening test in randomly selected primary care practices. DESIGN: Chart abstractions of a random selection of 552 men (age, > or = 50 years) and physician and practice-level surveys. SETTING: Fifty-eight randomly selected, nonteaching, non-governmental, primary care practices in a 43-county area in Virginia. MAIN OUTCOME MEASURES: Documented evidence of PSA screening for asymptomatic male patients and physician self-report on regular (annual or biannual) use of PSA screening. RESULTS: Of 496 asymptomatic men, 123 (25%) seen in a 1-year period had documentation of PSA screening. Sixty (50%) of 120 asymptomatic men with documentation of a health maintenance examination had a PSA screening, whereas only 63 (17%) of 376 men without health maintenance examination had a PSA screening (chi 2, P < .001), after adjusting for race, insurance status, and age. Comparison of PSA screening use before and after the November 1992 publication of the American Cancer Society guidelines on PSA screening revealed that PSA screening after the publication date was 26%, compared with 19% before the data (P = .045), adjusting for health maintenance examination and the length of time for which the patient was eligible for screening. Logistic regression on physician self-report of regular vs not regular PSA use found an odds ratio of 6.12 (95% confidence interval, 1.28 to 29.30) for influence of the guidelines and 0.96 (95% confidence interval, 0.93 to 0.99) for the proportion receiving Medicaid or uninsured in the practice. CONCLUSIONS: Despite controversy over PSA as a screening test, PSA screening has now spread substantially in primary care practice.

Aged↗

Assessment of nalmefene glucuronide as a selective gut opioid antagonist.

Opioid use often causes troublesome constipation as a side-effect. Selective antagonism of the intestinal actions of opioids might be useful in the treatment of opioid-induced constipation. We tested the inactive metabolite of nalmefene, nalmefene glucuronide, which showed promise of gut selectivity in rodent models, by administering ascending doses in single-blind, placebo-controlled fashion to five methadone-maintained, opioid-dependent male volunteers. Assessment of whether systemic or gut-selective opioid antagonist effects occurred was measured by vital signs, pupillary diameter, opioid withdrawal symptom scales, and bowel function. Oral nalmefene glucuronide precipitated symptoms and signs consistent with the opioid abstinence syndrome in all five subjects a mean of 9.0 h after dosing. We conclude that nalmefene glucuronide does not appear to exert sufficient gut selectivity to be useful in antagonizing constipation due to exogenous opioid administration without antagonizing systemic opioid effects.

Adult↗

A placebo controlled clinical trial of buprenorphine as a treatment for opioid dependence.

Large-scale placebo controlled clinical trials assessing the efficacy of medications for the treatment of drug dependence have generally been limited to alcohol, cocaine and nicotine dependent populations. The purpose of the present study was to assess the early (1-2 week) clinical effectiveness of buprenorphine versus placebo in an opioid dependent population. The study used a parallel-group design with a behavioral choice component to compare buprenorphine (a mu-opioid partial agonist) to placebo for the treatment of opioid dependence. Opioid dependent volunteer patients participated in a 14-day study to assess the effectiveness and patient acceptance of this new pharmacotherapy for the treatment of opioid dependence. Patients were randomly assigned to placebo (n = 60) or 2 mg (n = 60) or 8 mg (n = 30) daily sublingual buprenorphine. All doses were administered double-blind. On days 6-13 all patients could request a dose change, knowing that their new dose would be randomly chosen from the remaining 2 alternatives. Compared to placebo, patients given buprenorphine (independent of dose) showed greater time on initial dose, requested fewer dose changes, used less illicit opioids (assessed by urinalysis), and rated dose adequacy higher. These results demonstrate that a placebo controlled study with a behavioral choice component is an effective means of assessing the potential efficacy and acceptability of new pharmacotherapies for opioid dependence.

Administration, Sublingual↗

Buprenorphine treatment of opioid dependence: clinical trial of daily versus alternate-day dosing.

Buprenorphine, a mu-opioid partial agonist, has demonstrated efficacy for the treatment of opioid dependence comparable to that of methadone. The clinical utility of buprenorphine would be enhanced if it could be dosed on a less than daily basis. The current study is a parallel-group outpatient clinical trial of daily versus alternate-day dosing with 8 mg sublingual (s.l.) buprenorphine. Participants were randomly assigned to daily (n = 51) or alternate-day (n = 48) schedules of active medication administration for an 11-week double-blind trial. Patients assigned to alternate-day buprenorphine received placebo every other day. Primary outcome measures were retention in treatment and urine specimens positive for opiates. Clinic attendance, dose adequacy ratings, withdrawal symptomatology, and urine specimens positive for cocaine were secondary outcome measures. Neither endpoint analysis with the intent-to-treat sample nor time course analysis with treatment completers revealed any statistically significant differences between the dosing schedules on any outcome measure. Examination of 95% confidence intervals suggested a non-significant trend for the daily dosing schedule to have superior clinical efficacy at the dose tested. Nevertheless, these results are generally consistent with previous studies of less than daily dosing with buprenorphine and support the conclusion that an alternate-day dosing schedule can be effective in and acceptable to a substantial portion of patients.

Adult↗

Patient use of a computer for prevention in primary care practice.

A computerized health information system for prevention can provide an efficient way to enhance the doctor-patient interaction and provide patient-specific education materials. A computer system called HealthTouch was developed by family physicians and placed in 29 randomly selected primary care practices in Virginia for 1 year. Data were collected from three sources: randomly selected patients' charts, the HealthTouch data base, and patient telephone interviews. Data from these sources were combined, and frequency distributions and comparisons of responses by demographic attributes were analyzed using the chi-square statistic. During the study year, 9799 adult patients used the HealthTouch system. HealthTouch users were younger, on average, than the overall patient population, and the majority (89%) were either very satisfied or satisfied with the system. Computers are effective tools to collect, organize, and store patient information about prevention.

Adult↗

Use of an automated prescription database to identify individuals with asthma.

We used medication-dispensing information for 4 years (1/1/87 through 12/31/90) to examine the utilization of anti-asthma medications among 175,562 members of a large health maintenance organization. A total of 297,863 anti-asthma medications was dispensed during the study period, over one-half of which (55%) were beta-agonists, followed by aminophylline preparations (23%) and inhaled corticosteroids (13%). Next, we compared the predictive value of three algorithms for identifying individuals with asthma: (1) two or more beta-agonist dispensings, (2) both a beta-agonist and an inhaled corticosteroid dispensing, and (3) five or more total anti-asthma dispensings. We performed chart reviews for 40 subjects aged 5-45 years in each of these three groups and made a clinical judgment, based on all available information in the chart, as to whether each patient had asthma. Two levels of certainty were used: "any asthma" and "definite asthma." All 120 charts reviewed presented a clinical picture consistent with asthma. However, patients identified by the algorithm that included both a beta-agonist and an inhaled corticosteroid were more likely to meet our criteria for "definite" asthma and more likely to have moderate to severe asthma. These results demonstrate the feasibility of using an automated outpatient pharmacy database to identify patients with asthma.

Adolescent↗

New treatments for Chlamydia trachomatis genital infection.

To provide information for the formulation of treatment guidelines, we review recently published articles and abstracts on advances in the treatment of Chlamydia trachomatis genital infection. We ask specific questions about new treatments that are answered on the basis of the results of clinical trials and efficacy studies. New, potentially effective treatments for C. trachomatis genital infection include azithromycin and ofloxacin. Clinical studies indicate that the efficacy of these agents is equivalent to that of the current recommended agent doxycycline. Both azithromycin and ofloxacin are substantially more expensive than doxycycline. Azithromycin has the advantage of being given as a single dose, while doxycycline and ofloxacin are administered for 1 week. Issues of compliance, cost, and toxicity for specific patients should be considered when deciding whether to treat C. trachomatis genital infections with these agents.

Azithromycin↗