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PubMed2005

How evolutionary pressure against protein aggregation shaped chaperone specificity.

As protein aggregation is potentially lethal, control of protein conformation by molecular chaperones is essential for cellular organisms. This is especially important during protein expression and translocation, since proteins are then unfolded and therefore most susceptible to form non-native interactions. Using TANGO, a statistical mechanics algorithm to predict protein aggregation, we here analyse the aggregation propensities of 28 complete proteomes. Our results show that between 10% and 20% of the residues in these proteomes are within aggregating protein segments and that this represents a lower limit for the aggregation tendency of globular proteins. Further, we show that not only evolution strongly pressurizes aggregation downwards by minimizing the amount of strongly aggregating sequences but also by selectively capping strongly aggregating hydrophobic protein sequences with arginine, lysine and proline. These residues are strongly favoured at these positions as they function as gatekeepers that are most efficient at opposing aggregation. Finally, we demonstrate that the substrate specificity of different unrelated chaperone families is geared by these gatekeepers. Chaperones face the difficulty of having to combine substrate affinity for a broad range of hydrophobic sequences and selectivity for those hydrophobic sequences that aggregate most strongly. We show that chaperones achieve these requirements by preferentially binding hydrophobic sequences that are capped by positively charged gatekeeper residues. In other words, targeting evolutionarily selected gatekeepers allows chaperones to prioritize substrate recognition according to aggregation propensity.

Algorithms↗
PubMed1989

Access to emergency departments: a survey of HMO policies.

An unresolved question related to the practice of health maintenance organizations' (HMOs) controlling access to medical care is whether such screening of patients seeking emergency department treatment impairs efficient patient care or endangers patients. A preliminary study was undertaken to determine whether so-called gatekeeping of access to EDs was common practice. Medical directors of HMOs in 39 states and the District of Columbia were surveyed by a mail questionnaire to assess policies regarding ED access. There were 98 (80.3%) respondents to 122 questionnaires, representing 26% of all federally qualified HMOs in the United States. Of the 98 respondents, 90 (92%) used the distinctions "life-threatening" and "nonlife-threatening" in defining their ED access policies. In life-threatening situations, members were permitted to go to any hospital without calling the gatekeeper first. In nonlife-threatening situations 78 of 98 (80%) required that permission be obtained prior to an ED visit. Most required a telephone call; nonphysicians could act as gatekeepers in 46 of 78 (59%). Thirty-nine percent of the 98 respondents limited their members to using the EDs of certain hospitals only. Ninety-four of 98 (96%) reviewed all ED visits prior to making any payment. We discuss here the implications of these gatekeeping policies.

Emergencies↗
PubMed2004

Effect of salt bridges on the energy landscape of a model protein.

The effect of introducing salt bridges (gatekeepers) into an off-lattice three-color, 46-bead model protein is investigated in terms of the effect on global optimization statistics. The global minima for all the gatekeepers that exhibited faster folding in previous molecular dynamics studies are located more rapidly than for the original potential, although the global minimum itself may change. Visualization of the underlying potential energy surface using disconnectivity graphs reveals that the gatekeepers exhibit structure intermediate between the original potential and a Go model. Competition between low-lying minima and the global minimum is reduced in the gatekeepers compared to the original potential, and interconversion barriers are generally smaller.

Journal Article↗
PubMed1991

Integrating the community into geriatric case management: public health interventions.

Gatekeepers, or nontraditional referral sources, have proven to be an effective means of case finding and outreach for the mental health needs of isolated senior citizens. A two-year project administered by the Public Health Division of the Health Services Department in a San Francisco Bay Area county found the gatekeeper concept to be an effective means of case finding in the public health setting. Program statistics showed similar profiles of individuals referred by gatekeepers and other referral sources except that gatekeepers referred more individuals living alone.

Aged↗
PubMed2004

Determining gaps in a county-wide community nutrition education program for older adults.

This study assessed gaps in nutrition education between what was offered by organizations and what was wanted by older adults. In Phase I, 258 gatekeepers were interviewed. In Phase II, 37 non-institutionalized older adults were assigned to five focus groups. Study results indicated a consistency between gatekeepers and participants for services, topics, methods/information sources, and communication routes. However, a gap was found because participants wanted education on more topics and were interested in more specific information, whereas gatekeepers provided more general information. This study concluded that gatekeepers need to provide more topics and in greater specificity when planning for nutrition education programs for older adults.

Aged↗
PubMed2001

Group practice strategies to manage pharmaceutical cost in an HMO network.

OBJECTIVE: To evaluate the prevalence of various pharmaceutical cost management strategies used by group practices within a managed care network and their relationship to drug costs among enrollees. STRATEGIES STUDIED: Care management (gatekeeping, practice profiling, practice guidelines, case management), techniques for maintaining clinic medication records, and policies regulating physician interaction with pharmaceutical sales representatives (PSRs). STUDY DESIGN: Cross-sectional survey of primary care group practice organizations (n = 103) affiliated with Blue Cross Blue Shield of Minnesota in early 1996. METHODS: Multivariate linear regression analysis was performed on corresponding claims data for members continuously enrolled in these practices from January 1 to December 31, 1995 (n = 76,387), using the patient as the unit of analysis. RESULTS: Substantial variation in strategy prevalence was observed; this variation was thought to influence pharmaceutical costs. Seventy-six percent of practices had medication lists in outpatient medical records, 53% had policies limiting pharmaceutical detailing, and 44% had patients assigned to primary care gatekeepers; however, only 10% used outpatient nurse case managers. Use of outpatient nurse case managers (P < .010), primary care physician gatekeeping (P < .002), policies to control pharmaceutical detailing (P < .001), and medication lists and outpatient charts (P < .001) was found to be independently associated with lower pharmaceutical expenditures. Significant colinearity was found between group size and the strategies studied. CONCLUSIONS: Significantly lower pharmaceutical costs per member per year were observed in the groups reporting primary care gatekeeping, outpatient medication records, outpatient case managers, and policies regarding physician interactions with PSRs.

Adolescent↗
PubMed2004

Does patient cost sharing matter? Its impact on recommended versus controversial cancer screening services.

OBJECTIVES: To examine whether there are differential impacts of patient cost sharing and health plan organizational characteristics on the use of a recommended cancer screening service (mammography) versus a controversial cancer screening service (prostate cancer screening [PCS]). STUDY DESIGN: Observational cohort using the 1996 Medical Expenditure Panel Survey. PATIENTS AND METHODS: A nationally representative sample of privately insured individuals was examined. Outcome measures were the receipt of mammography and PCS. Logistic regression was used to assess the impact of patient cost sharing and health plan organizational characteristics on the receipt of mammography and PCS, controlling for other covariates. RESULTS: Patient cost sharing and gatekeeper requirements were strong predictors of PCS but were statistically insignificant predictors of mammography. Men in health plans with a copayment over dollar 10 (odds ratio [OR] = 0.38, 95% confidence interval [CI] = 0.19-0.78) or with deductibles over dollar 250 (OR = 0.38, 95% CI = 0.23-0.62) were significantly less likely to receive PCS than men in plans with no or lower copayments and deductibles. Men in gatekeeper plans were less likely to receive PCS than those without gatekeepers (OR = 0.48, 95% CI = 0.29-0.81). CONCLUSIONS: We found the impact of cost sharing on utilization is different between mammography and PCS. Prostate cancer screening utilization appears to respond to financial incentives while mammography utilization does not. The use of copayments, deductibles, and gatekeepers may discourage controversial services but may not have an adverse effect on more recommended services. These findings have implications for the design of insurance benefits and plan organizational structure.

Breast Neoplasms↗
PubMed2002

Managed care, primary care, and the patient-practitioner relationship.

OBJECTIVES: This study examines how specific attributes of managed health plans influence patients' relationships with their primary care practitioners (PCPs) and determines whether these effects are mediated by access to, continuity with, or perceived choice of PCPs. DESIGN, SETTING, PATIENTS: The data source was the nationally representative 1996/97 Community Tracking Study Household Survey (cumulative response rate 65%). The study population (N = 19,415) was composed of 18- to 64-year-old adults whose most recent visit in the past 12 months was made to their primary care delivery site. MAIN OUTCOME MEASURE: Patients' ratings of their interpersonal relationships with their PCPs as measured by a 7-item scale. RESULTS: Gatekeeping arrangements that require patients to select a primary care physician or obtain authorization for specialty referrals were associated with lower ratings of the patient-PCP relationship. Health plan use of a provider network had no effect on the patient-PCP scale score. Although there were no significant differences across any insurance payer categories, uninsured adults rated their relationships with PCPs as significantly poorer than did their insured counterparts. Shorter office waits, having a specific clinician at the primary care site, better perceived choice of PCPs, and a longer duration of relationship with the primary care practitioner were associated with higher ratings of the patient-PCP relationship. Perceived choice of primary care practitioners, but not access to or continuity with PCPs, attenuated some of the negative effects of gatekeeping arrangements on patients' relationships with their primary care practitioners. CONCLUSIONS: Managed health plans that loosen restrictions on provider choice, relax gatekeeping arrangements, or promote access to and continuity with PCPs, are likely to experience higher patient satisfaction with their primary care practitioner relationships. Lack of health insurance impedes the development of patients' relationships with their primary care practitioners.

Adolescent↗
PubMed2001

Evaluation of knee consultations to a referral-only orthopedic clinic in a managed care system.

One hundred sixty-five knee consultations to a referral-only orthopedic service over a 2-year period were reviewed to document the gatekeeper diagnosis and initial treatment plan. These data were compared to the orthopedic evaluation. The majority of gatekeeper referral diagnoses were nonspecific or inaccurate. Several misdiagnoses resulted in prolonged patient recovery (delayed quadriceps tendon repair) and reinjury (recurrent instability of unrecognized anterior cruciate ligament-deficient knees). These findings suggest the gatekeeper model may be inadequate to appropriately manage knee disorders.

Adolescent↗
PubMedDate not supplied

Effect of managed care and financing on practice constraints and career satisfaction in primary care.

BACKGROUND: The shift away from third party insurers to risk-sharing arrangements affecting care management and clinicians could be the most fundamental change in the health care system. Analysis was undertaken to study how managed care, practice setting, and financial arrangements affect physicians' perceived impact on their practice. METHODS: Data were taken from the Community Tracking Study (CTS) physician survey, a national survey of active physicians in the United States fielded between August 1996 and August 1997. Survey instruments were completed by 7,146 primary care physicians in internal medicine (2,355), family practice (3,168), and pediatrics (1,623). The dependent variables are career satisfaction and perceived limitations and pressures on time spent with patients, clinical freedom, income, and continuity. To study the unique effect of financing and gatekeeping arrangements and practice setting, the dependent variables were regressed on gatekeeping, practice revenue, individual physician compensation, practice setting, specialty, age-group, sex, international medical graduate, board certification, and recent change in practice ownership. RESULTS: Total managed care revenue, or individual physician incentives, have no effect on career satisfaction and relatively limited effects on time pressure, income pressure, or patient continuity. In contrast, primary care gatekeeping has a highly significant adverse effect on the same outcome measures. After controlling for financial factors, demographic characteristics, and training differences, physicians in solo and 2-physician practices are significantly more likely to be dissatisfied with their medical career, more likely to report no clinical freedom, and more likely to feel income pressure than physicians in group practices, staff model HMOs, medical schools, or other settings. CONCLUSION: Physicians in solo and 2-physician practices were least satisfied with their careers and reported more constraints on their clinical freedom and income than physicians in other settings. Physicians in group practices or staff model HMOs are more likely to report time pressure than physicians in solo or 2-physician practices. Family practice falls between internal medicine (less satisfied, more practice constraints) and pediatrics (more satisfied, fewer practice constraints).

Attitude of Health Personnel↗
PubMed2000

Doctor-patient communication in different European health care systems: relevance and performance from the patients' perspective.

Our aim is to investigate differences between European health care systems in the importance attached by patients to different aspects of doctor-patient communication and the GPs' performance of these aspects, both being from the patients' perspective. 3658 patients of 190 GPs in six European countries (Netherlands, Spain, United Kingdom, Belgium, Germany, Switzerland) completed pre- and post-visit questionnaires about relevance and performance of doctor-patient communication. Data were analyzed by variance analysis and by multilevel analysis. In the non-gatekeeping countries, patients considered both biomedical and psychosocial communication aspects to be more important than the patients in the gatekeeping countries. Similarly, in the patients' perception, the non-gatekeeping GPs dealt with these aspects more often. Patient characteristics (gender, age, education, psychosocial problems, bad health, depressive feelings, GPs' assessment of psychosocial background) showed many relationships. Of the GP characteristics, only the GPs' psychosocial diagnosis was associated with patient-reported psychosocial relevance and performance. Talking about biomedical issues was more important for the patients than talking about psychosocial issues, unless the patients presented psychosocial problems to the GP. Discrepancies between relevance and performance were apparent, especially with respect to biomedical aspects. The implications for health policy and for general practitioners are discussed.

Adolescent↗
PubMed2001

A review of inherited cancer syndromes and their relevance to oral squamous cell carcinoma.

This paper examines the genetic defects associated with inherited cancer syndromes and their relevance to oral cancer. Tumour suppressor genes are now thought of as either gatekeepers or caretakers according to whether they control cell growth directly by inhibiting cell proliferation and/or promoting cell death (gatekeepers) or whether they maintain the integrity of the genome by DNA repair mechanisms (caretakers). In disorders such as xeroderma pigmentosum, ataxia telangiectasia, Bloom syndrome and Fanconi's anaemia, where there are defective caretaker genes, there is an increased incidence of second primary malignancies, including oral cancer. By contrast, with the exception of Li Fraumeni syndrome, abnormalities of gatekeeper genes do not predispose to oral cancer. Not only do Li Fraumeni patients develop second primary malignancies, but defects of the p53 pathway (p53 mutation, MDM2 over-expression, CDKN2A deletion) appear to be a ubiquitous feature of sporadic oral cancer as it occurs in the West. The findings suggest that genetic instability is of fundamental importance in the pathogenesis of oral cancer.

Carcinoma, Squamous Cell↗
PubMed2000

DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation.

Cancer susceptibility genes have been classified into two groups: gatekeepers and caretakers. Gatekeepers are genes that control cell proliferation and death, whereas caretakers are DNA repair genes whose inactivation leads to genetic instability. Abrogation of both caretaker and gatekeeper function markedly increases cancer susceptibility. Although the importance of Ku80 in DNA double-strand break repair is well established, neither Ku80 nor other components of the non-homologous end-joining pathway are known to have a caretaker role in maintaining genomic stability. Here we show that mouse cells deficient for Ku80 display a marked increase in chromosomal aberrations, including breakage, translocations and aneuploidy. Despite the observed chromosome instabilities, Ku80-/- mice have only a slightly earlier onset of cancer. Loss of p53 synergizes with Ku80 to promote tumorigenesis such that all Ku80-/- p53-/- mice succumb to disseminated pro-B-cell lymphoma before three months of age. Tumours result from a specific set of chromosomal translocations and gene amplifications involving IgH and c-Myc, reminiscent of Burkitt's lymphoma. We conclude that Ku80 is a caretaker gene that maintains the integrity of the genome by a mechanism involving the suppression of chromosomal rearrangements.

Animals↗
PubMed2000

Effects of primary care coordination on public hospital patients.

OBJECTIVE: To evaluate the effect of primary care coordination on utilization rates and satisfaction with care among public hospital patients. DESIGN: Prospective randomized gatekeeper intervention, with 1-year follow-up. SETTING: The Adult General Medical Clinic at San Francisco General Hospital, a university-affiliated public hospital. PATIENTS: We studied 2,293 established patients of 28 primary care physicians. INTERVENTION: Patients were randomized based on their primary care physician's main clinic day. The 1,121 patients in the intervention group (Ambulatory Patient-Physician Relationship Organized to Achieve Coordinated Healthcare [APPROACH] group) required primary care physician approval to receive specialty and emergency department (ED) services; 1,172 patients in the control group did not. MEASUREMENTS AND MAIN RESULTS: Changes in outpatient, ED, and inpatient utilization were measured for APPROACH and control groups over the 1-year observation period, and the differences in the changes between groups were calculated to estimate the effect of the intervention. Acceptability of the gatekeeping model was determined via patient satisfaction surveys. RESULTS: Over the 1-year observation period, APPROACH patients decreased their specialty use by 0.57 visits per year more than control patients did ( P =.04; 95% confidence interval [CI] -1.05 to -0.01). While APPROACH patients increased their primary care use by 0.27 visits per year more than control patients, this difference was not statistically significant (P =.14; 95% CI, -0.11 to 0.66). Changes in low-acuity ED care were similar between the two groups (0. 06 visits per year more in APPROACH group than control group, P =. 42; 95% CI, -0.09 to 0.22). APPROACH patients decreased yearly hospitalizations by 0.14 visits per year more than control patients (P =.02; 95% CI, -0.26 to -0.03). Changes in patient satisfaction with care, perceived access to specialists, and use of out-of-network services between the 2 groups were similar. CONCLUSIONS: A primary care model of health delivery in a public hospital that utilized a gatekeeping strategy decreased outpatient specialty and hospitalization rates and was acceptable to patients.

Demography↗
PubMed2004

Demand and supply for psychological help in general practice in different European countries: access to primary mental health care in six European countries.

BACKGROUND: The general practitioner is usually the first health care contact for mental problems. The position of a general practitioner may vary between health care systems, depending on the referral system (gatekeepers versus directly accessible specialists), presence of fixed lists and the payment system. This may influence patients' expectations and requests for help and GPs' performance. In this paper the effects of working in different health care systems on demand and supply for psychological help were examined. METHODS: Data were collected in six European countries with different health care system characteristics (Belgium, Germany, The Netherlands, Spain, Switzerland and the UK). For 15 consecutive contacts with 190 GPs in the six countries, each patient completed questionnaires concerning reason for visit and expectations (before) and evaluation (after consultation). General practitioners completed registration forms on each consultation, indicating familiarity with the patient and diagnosis. General practitioners completed a general questionnaire about their personal and professional characteristics as well. RESULTS: Practices in different countries differed considerably in the proportion of psychological reasons for the visit by the patient and psychological diagnoses by the GP. Agreement between patients' self-rated problems and GPs' diagnoses also varied. Patients in different countries evaluated their GPs' psychological performance differently as well, but evaluation was not correlated with agreement between request for help and diagosis. In gatekeeping countries, patients had more psycho-social requests, GPs made more psychological diagnoses and agreement between both was relatively high. Evaluation, however, was more positive in non-gatekeeping countries. Individual characteristics of doctors and patients explained only a relatively small part of variance. CONCLUSIONS: Health care system characteristics do affect GPs' performance in psycho-social care.

Europe↗
PubMed1996

Primary health care physicians' treatment of psychosocial problems: implications for social work.

This study explores the extent to which primary care physicians serve as gatekeepers for the treatment of psychosocial problems and the extent to which they have contact with social workers. We also attempted to identify physician variables related to gatekeeping and amount of contact with social workers. Data from a national study of the role of primary care physicians in Israel were used. About one-third of the physicians had regular contact with social workers, one-quarter had contact less often, and about one-third almost never had contact. Variables associated with gatekeeping for psychosocial problems included having a large caseload, specializing in family medicine, practicing in a rural location, and being under age 55. Variables associated with social work contact were affiliation with the largest health maintenance organization and specialization in family medicine.

Adolescent↗
PubMed1998

Quality indicators for general practice: which ones can general practitioners and health authority managers agree are important and how useful are they?

BACKGROUND: The aim of the study was to assess the face validity of quality indicators being proposed for use in general practice by health authorities. METHOD: A national survey of health authorities was carried out to identify quality indicators being proposed for use in general practice. A two-stage Delphi process was used to establish general practitioners' (GPs') and health authority managers' views on the face validity of identified indicators. A total of 240 separate indicators identified by health authorities and the NHS Executive as potential markers of the quality of general practice care were assessed. Indicators related to access, organizational performance, preventive care, care for a small number of chronic diseases, prescribing and gatekeeping. The subjects were a purposive sample of 47 health authority managers and 57 general practice course organizers. RESULTS: Thirty-six indicators received median validity scores of 8 or 9 out of a maximum possible score of 9. Of this set, 83 per cent was rated identically by both groups of respondents. Prescribing and gatekeeping indicators generally received low validity scores. CONCLUSION: Acceptable face valid indicators were identified for all domains except gatekeeping. However, the indicators rated by the sample do not cover all aspects of care. No indicators were proposed for use by health authorities relating to effective communication, care of acute illness, health outcomes or patient evaluation. Although it is possible to develop indicators of general practice care which have face validity in the view of both GPs and managers, these will be very partial measures of quality. In the indicators used in this study, no explicit distinction was made between indicators designed to assess minimum standards with which all practices should comply, and indicators which could be used to reward higher levels of performance. Failure to separate these will result in antagonism from practitioners to quality improvement initiatives in the NHS, and a failure to engage the profession in improving quality of care.

Attitude of Health Personnel↗
PubMed2004

Moving beyond the typologies of managed care: the example of health plan predictors of screening mammography.

OBJECTIVES: To develop a framework of factors to characterize health plans, to identify how plan characteristics were measured in a national survey, and to apply our findings to an analysis of the predictors of screening mammography. DATA SOURCE: The primary data were from the 1996 Medical Expenditure Panel Survey. STUDY DESIGN: Women ages 40+, with private insurance, and no history of breast cancer were included in the study (N = 2,909). We used multivariate logistic regression to estimate mammography utilization in the past two years relative to health plan and demographic factors. Health plan measures included whether there is a defined provider network, whether coverage is restricted to a network, use of gatekeepers, level of cost containment, copayment and deductible amounts, coinsurance rate, and breadth of benefit coverage. PRINCIPAL FINDINGS: We found no significant difference in reported mammography utilization using a dichotomous comparison of individuals enrolled in managed care versus indemnity plans. However, women in health plans with a defined provider network were more likely to report having received a mammogram in the past two years than those without networks (adjusted OR= 1.21, 95 percent CI = 1.07-1.36), and women in gatekeeper plans were more likely to report receiving mammography than those without gatekeepers (adjusted OR = 1.18, 95 percent CI = 1.03-1.36). Restricted out-of-network coverage, use of cost containment, enrollee cost sharing, and breadth of benefit coverage did not appear to affect mammography use. CONCLUSIONS: It is important to examine the effect of individual health plan components on the utilization of health care, rather than use the traditional broader categorizations of managed versus nonmanaged care or simple health plan typologies.

Adult↗