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PubMed2000

Abdominal pain and appendicitis: is there a difference in referrals between HMO pediatricians and private pediatricians?

BACKGROUND: In the last few years, there have been many reports of the rising incidence of late appendicitis and perforated appendicitis. The rise of managed care medicine has been blamed for this, because the health maintenance organizations (HMO) and gatekeepers allegedly want to keep the child away from the surgeon and hospital to save costs. METHODS: The authors were in a unique position a number of years ago because they had only a single HMO in their area of practice (New Brunswick, NJ) employing 14 pediatricians, and 86 pediatricians were in private practice or on the medical school staff. The HMO had a yearly contract with the pediatric surgeons, and all visits and surgeries were covered by a yearly agreement (capitated agreement). The authors compared the number of children with appendicitis, perforated appendicitis, or just abdominal pain (not requiring surgery), between both groups over a 5-year period (1991 to 1996). RESULTS: A total of 492 patients were referred with abdominal pain over a 5-year period. Two hundred eight (42%) had appendicitis, and 284 (58%) had just abdominal pain and eventually were sent home. The HMO pediatricians diagnosed appendicitis accurately in 46% of their patients (55 of 118), and 54% were abdominal pain that was not appendicitis (63 of 118). For the private pediatricians, the percentages were: 40% of their patients had appendicitis (153 of 374), and 60% had abdominal pain without appendicitis (221 of 374). The incidence of perforated appendicitis was similar (28% HMO v 30% private), and the incidence of negative explorations were similar (8% HMO v 9% private). CONCLUSIONS: The results are very similar in both groups, with a similar percentage of abdominal pain not being appendicitis (60% v 54%). HMO patients did not pay for consultations, and the HMO was not charged for any consultations. However, it does not appear that they overused the consultations for abdominal pain that were not appendicitis. Their accuracy for correct diagnosis of appendicitis was similar to the private group (46% v 40%), and the incidence of perforated appendicitis for both groups was 28% to 30%. The authors cannot draw any conclusions from their experience that HMOs in general do refer patients to surgeons in a timely fashion, and do not delay the referrals to avoid the cost of consultation, because the authors had a capitated agreement with their HMO, and consultations were free. Both groups of pediatricians, the HMO and the private pediatricians, did not realize financial gain or loss by sending children to the pediatric surgeon and were not penalized by sending patients with abdominal pain to the surgeon. On the contrary, their referral habits and judgments were similar and did not appear to change by being part of an HMO.

Abdominal Pain↗
PubMedDate not supplied

Better decisions through science: exercise testing scores.

Statistical tools can be used to create scores for assisting in the diagnosis of coronary artery disease and assessing prognosis. General practitioners and internists frequently function as gatekeepers, deciding which patients must be referred to the cardiologist. Therefore, they need to use the basic tools they have available (ie, history, physical examination and the exercise test) in an optimal fashion. Scores derived from multivariable statistical techniques considering clinical and exercise data have demonstrated superior discriminating power compared with diagnosis only using the ST segment response. In addition, by stratifying patients as to probability of disease and prognosis, they provide a more practical management strategy than a response of normal or abnormal. Although computers, as part of information management systems, can calculate complicated equations and derive these scores, physicians are reluctant to trust them. However, when represented as nomograms or simple additive discrete pieces of information, scores are more readily accepted. The scores have been compared with physician judgment and have been found to estimate the presence of coronary disease and prognosis as well as expert cardiologists and often better than nonspecialists. However, the discriminating power of specific variables from the medical history and exercise test remains unclear because of inadequate study design and differences in study populations. Should expired gases be substituted for estimated METs? Should ST/heart rate index be used instead of putting ST depression and heart rate separately into the models? Should right-sided chest leads and heart rate in recovery be considered? There is a need for further evaluation of these easily obtained variables to improve the accuracy of prediction algorithms, especially in women. The portability and reliability of scores must be ensured because access to specialized care must be safeguarded. Assessment of the clinical and exercise test data and application of the newer scores can empower the clinician to assure the cardiac patient access to appropriate and cost-effective cardiologic care.

Age Factors↗
PubMed2002

Comment--the REMATCH trial: Long-term use of a left ventricular assist device for end-stage heart failure.

BACKGROUND: Implantable left ventricular assist devices (LVADs) have been used primarily as bridges to cardiac transplantation, although some patients have been maintained long term on these devices and a few have recovered enough to be weaned. This trial was designed to evaluate their suitability as long-term myocardial replacement therapy in patients who are ineligible for cardiac transplantation. METHODS AND RESULTS: One hundred twenty-nine patients with end-stage heart failure who were ineligible for cardiac transplantation were randomly assigned to receive an LVAD (Thoratec HeartMate; Thoratec, Pleasanton, CA) or optimal medical therapy, with a primary end point of all-cause mortality. To be eligible, patients had to have New York Heart Association (NYHA) class IV heart failure for at least 90 days despite attempted therapy with an angiotensin-converting enzyme inhibitor, diuretics, and digoxin; an ejection fraction </=25%; and an exercise peak O(2) uptake </=12 mL. kg(-1). min(-1) (later increased to 14 mL. kg(-1). min(-1)). Patient eligibility was approved by a gatekeeper at the coordinating center. RESULTS: Survival was significantly improved from 25% at 1 year in the medical therapy group to 52% in the LVAD group (relative risk, 0.52; 95% confidence interval, 0.34-0.78; P = 0.001). However, at 2 years only 23% in the LVAD group were alive (compared with 8% in the medical group). Fifty of 54 deaths in the medical group were caused by left ventricular dysfunction; in the LVAD group, of the 41 total deaths, 17 were caused by sepsis, 7 by LVAD failure, 4 by cerebrovascular disease, 2 by pulmonary embolus, and only 1 by left ventricular dysfunction. Serious adverse events were 2.35 times as frequent in the LVAD group, predominately caused by infection, bleeding, neurologic dysfunction, and device malfunction. NYHA class improved in all LVAD survivors at 1 year. Quality of life was significantly improved more compared with the medical therapy group by some indices, but not by the Minnesota Living With Heart Failure Questionnaire. CONCLUSIONS: The use of an LVAD resulted in improved survival and quality of life in patients with extremely severe heart failure (75% 1-year mortality in the medical control group). However, only 23% of LVAD patients survived to 2 years and complications were frequent.

Comment↗
PubMed2002

[Risks, chances and perspectives of restricting the free choice of doctors by patients].

Population surveys regarding free access to primary care physicians and medical specialists focus on selected aspects of public opinion. They are helpful but not sufficient in answering the relevant question: 'What are appropriate and efficient ways of access to the health care system?'. More important than survey results would be options for practical decisions by the patients themselves, based on a system offering different possibilities of choice. Competent piloting by 'gatekeepers' would need a problem- oriented and patient-centred medical education for primary-care physicians, starting during medical education and training and continuing throughout the professional medical careers. It should focus on three additional issues: New, alternative and unbiased ways of access to medical care should be developed, tried and evaluated to ensure beneficial use of the full potential of our health care system.

Forecasting↗
PubMed2005

[Efficiency of general practice in Switzerland].

BACKGROUND: In their capacity as gatekeepers, affect the entire cost of treatment of patients including cost for medication and inpatient care. Thus, it is of special interest to examine the production process of general practitioners. AIM: To study efficiency differences between general medical practices, taking into account a possible Managed Care participation by the physician. METHODS: A stochastic frontier analysis based on billing data of 1,500 Swiss physicians from 1997 - 1999 is applied to measure the relative efficiency of general practitioners. The number of consultations serves as output and the charged services as inputs of production. RESULTS: Most productive physicians are members of primary physicians' networks, in which the gate-keeping function of general practitioners is of central importance. For the "production" of one consultation they use 15 percent less resources than an average physician in a conventional medical practice. DISCUSSION AND CONCLUSION: In principle, assessment of efficiency of primary care physicians is possible. Differences in efficiency between physicians can be explained by characteristics of the individual medical practice. Disadvantages of the approach exist in the neglect of the patients' severity of illness and in having indirect measures of quality of medical care available.

Algorithms↗
PubMed1999

Changes in the scope of care provided by primary care physicians.

BACKGROUND: Strategies to control medical costs and improve the quality of care often translate into decisions affecting the range of services primary care physicians provide to patients, which patients are referred for specialty care, and the points in disease processes at which referrals are made. This study focused on physicians' assessments of changes in the scope of care provided by primary care physicians and their assessments of the appropriateness of the scope of the care that primary care physicians are expected to provide. METHODS: We analyzed data from the 1996-1997 Community Tracking Study Physician Survey. Telephone interviews were conducted with 12,385 physicians (reflecting a response rate of 65 percent) who were drawn from a representative random sample of physicians providing direct patient care in the continental United States and not employed by the federal government. The analysis was based on responses from the 7015 primary care physicians and 5092 specialists who had been in practice for at least two years. RESULTS: Thirty percent of the primary care physicians and 50 percent of the specialists reported that the scope of care provided by primary care physicians had increased during the previous two years. Twenty-four percent of the primary care physicians and 38 percent of the specialists reported that the scope of care expected to be provided by primary care physicians was greater than it should be. According to multivariate analysis, primary care physicians other than general or family practitioners (i.e., pediatricians and general internists), those who were in one- or two-physician practices, those who received revenues from capitation, and those who served as gatekeepers for their patients' care were significantly more likely to report that the scope of care they were expected to provide was greater than it should be. CONCLUSIONS: The finding that nearly one in four primary care physicians reported that the scope of care they were expected to provide was greater than it should be arouses concern about the potential impact of changes in the delivery of health care. The associations we found between financial and administrative aspects of managed care and physicians' concern about the scope of care they provide to their patients deserve careful consideration.

Data Collection↗
PubMed2006

Pay for performance in commercial HMOs.

BACKGROUND: Pay for performance has increasingly become the subject of intense interest and debate, both of which have been heightened as the Centers for Medicare and Medicaid Services moves closer to adopting this approach for Medicare. Although many claims have been made for the effectiveness of this approach, the extent of its national penetration remains unknown. METHODS: We surveyed a sample of 252 health maintenance organizations (HMOs) (response rate, 96%) drawn from 41 metropolitan areas across the nation about use of pay for performance. We determined the prevalence of pay-for-performance programs, detailed the features of such programs, and examined the adoption of pay for performance as a function of the characteristics of both the health plans and markets. RESULTS: More than half the HMOs, representing more than 80% of persons enrolled, use pay for performance in their provider contracts. Of the 126 health plans with pay-for-performance programs, nearly 90% had programs for physicians and 38% had programs for hospitals. Use of pay for performance was statistically associated with geographic region, use of primary care providers (PCPs) as gatekeepers, use of capitation to pay PCPs, and whether the plans themselves received bonuses or penalties according to performance. CONCLUSIONS: Pay for performance is now commonly used by HMOs, especially those that are situated to assign responsibility for a particular patient to a PCP or medical group. As the design of Medicare with pay for performance moves forward, it will be important to leverage the early experience of pay for performance in the commercial market.

Contracts↗
PubMed2000

Regulation of immunologic homeostasis in peripheral tissues by dendritic cells: the respiratory tract as a paradigm.

Dendritic cells are now recognized as the gatekeepers of the immune response, possessing a unique potential for acquisition of antigens at extremely low exposure levels and for efficient presentation of these in an immunogenic form to the naive T-cell system. Dendritic cell populations throughout the body exhibit a wide range of features in common that are associated with their primary functions, and these are considered in the initial section of this review. In addition, it is becoming evident that the properties and functions of these cells are refined by microenvironmental factors unique to their tissues of residence, a prime example being mucosal microenvironments such as those in respiratory tract tissues, and the latter represents the focus of the second section of this review.

Antibody Formation↗
PubMedDate not supplied

Accessibility and distribution of the Norwegian National Air Emergency Service: 1988-1998.

OBJECTIVE: To evaluate the accessibility and distribution of the Norwegian National Air Emergency Service in the 10-year period from 1988 to 1998. MATERIAL AND METHODS: The primary material was annual standardized activity data that included all helicopter missions. A multivariate model of determinants for use of the helicopter service was computed by linear regression. Accessibility was measured as the percentage of the population reached in different flying times, and we evaluated the service using a simulation of alternative locations for the helicopter bases. RESULTS: The helicopter service (HEMS) has short access times, with a mean reaction time of 8 minutes and a mean response time of 26 minutes for acute missions. Nearly all patients (98%) are reached within 1 hour. A simulation that tested alternative locations of the helicopter bases compared with current locations showed no increase in accessibility. The use of the service shows large regional differences. Multivariate analyses showed that the distances of the patients from the nearest helicopter base and the nearest hospital are significant determinants for the use of HEMS. CONCLUSION: Establishment of a national service has given the Norwegian population better access to highly qualified prehospital emergency services. Furthermore, the HEMS has a compensating effect in adjusting for differences in traveling distances to a hospital. Safety, cost-containment, and gatekeeper functions remain challenges.

Air Ambulances↗
PubMedDate not supplied

The internet as a catalyst for shifting power in provider-patient relationships.

Traditional provider-patient relationships can be characterized with a gatekeeper model in which the provider role is keeper of medical knowledge and major decision-maker. Internet access by many persons makes possible a shift that expands power and control of health information, which is no longer just accessible to a privileged few. Although congruent with emerging social norms, patient participation in health care remains controversial. Some provider or physician groups historically relied on dominant societal ideologies to promote resolution of this challenge while maintaining their own power. Through use of a critical social theory analysis, we examine provider-patient relationships by reviewing the political, economic, and social perspectives within a historical context and identify ideologies, assumptions, and supporting structures that contribute to the existing situation. In addition, we analyze constraints on Internet use that affect oppressed groups and offer ideas to eliminate oppressive ideology and foster social change. Future initiatives that support change are discussed.

Health Personnel↗
PubMed2002

Entry one: striving for best practice in professional assessment.

The aim of this study was to develop a best practice model of professional assessment to ensure efficient and effective delivery of home-based services to frail and disabled elders. In 2000, an innovative model of professional assessment was introduced by one of Australia's largest providers of home-based care in order to reduce multiple assessments and to reduce the utilisation of assessment as a gatekeeping tool for limiting access to services. Data was analysed from a random sample of 1500 clients drawn from a population of 5000 as well as through the use of a survey tool administered to the Organisation's assessment staff and other key stakeholders. Results revealed that, contrary to popular belief, carer advocacy plays a significant role in the professional assessment process to the point that clients with carers received significantly more services and service time that clients without such support. However, if not monitored, assessment can also be used as a gate-keeping tool as opposed to one that can provide significant benefits to the consumers through comprehensive need articulation. We argue that the "professional" approach does not preclude empowerment and that assessment should not be used as a gate-keeping tool.

Aged↗
PubMed2004

Evolutionary dynamics of tumor suppressor gene inactivation.

Tumor suppressor genes (TSGs) are important gatekeepers that protect against somatic evolution of cancer. Losing both alleles of a TSG in a single cell represents a step toward cancer. We study how the kinetics of TSG inactivation depends on the population size of cells and the mutation rates for the first and second hit. We calculate the probability as function of time that at least one cell has been generated with two inactivated alleles of a TSG. We find three different kinetic laws: in small, intermediate, and large populations, it takes, respectively, two, one, and zero rate-limiting steps to inactivate a TSG. We also study the effect of chromosomal and other genetic instabilities. Small lesions without genetic instability can take a very long time to inactivate the next TSG, whereas the same lesions with genetic instability pose a much greater risk for cancer progression.

Alleles↗
PubMed2004

Intestinal villous M cells: an antigen entry site in the mucosal epithelium.

M cells located in the follicle-associated epithelium of Peyer's patches (PP) are shown to be the principal sites for the sampling of gut luminal antigens. Thus, PP have long been considered the gatekeepers of the mucosal immune system. Here, we report a distinct gateway for the uptake of gut bacteria: clusters of non-follicle-associated epithelium-associated Ulex europaeus agglutinin (UEA)-1(+) cells, which we have designated intestinal villous M cells. Interestingly, villous M cells are developed in various PP [or gut-associated lymphoid tissue (GALT)]-null mice, such as in utero lymphotoxin beta receptor (LTbetaR)-Ig-treated, lymphotoxin alpha (LTalpha)(-/-), tumor necrosis factor/LTalpha(-/-), and inhibition of differentiation 2 (Id2)(-/-) mice. Intestinal villous M cells have been observed to take up GFP-expressing Salmonella, Yersinia, and Escherichia coli-expressing invasin, as well as gut bacterial antigen for subsequent induction of antigen-specific immune responses. Thus, the identified villous M cells could be an alternative and PP-independent gateway for the induction of antigen-specific immune responses by means of the mucosal compartment.

Animals↗
PubMed2005

Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54.

We have recently described a molecular gatekeeper of the hypothalamic-pituitary-gonadal axis with the observation that G protein-coupled receptor 54 (GPR54) is required in mice and men for the pubertal onset of pulsatile luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion to occur. In the present study, we investigate the possible central mode of action of GPR54 and kisspeptin ligand. First, we show that GPR54 transcripts are colocalized with gonadotropin-releasing hormone (GnRH) neurons in the mouse hypothalamus, suggesting that kisspeptin, the GPR54 ligand, may act directly on these neurons. Next, we show that GnRH neurons seem anatomically normal in gpr54-/- mice, and that they show projections to the median eminence, which demonstrates that the hypogonadism in gpr54-/- mice is not due to an abnormal migration of GnRH neurons (as occurs with KAL1 mutations), but that it is more likely due to a lack of GnRH release or absence of GnRH neuron stimulation. We also show that levels of kisspeptin injected i.p., which stimulate robust LH and FSH release in wild-type mice, have no effect in gpr54-/- mice, and therefore that kisspeptin acts directly and uniquely by means of GPR54 signaling for this function. Finally, we demonstrate by direct measurement, that the central administration of kisspeptin intracerebroventricularly in sheep produces a dramatic release of GnRH into the cerebrospinal fluid, with a parallel rise in serum LH, demonstrating that a key action of kisspeptin on the hypothalamo-pituitary-gonadal axis occurs directly at the level of GnRH release. The localization and GnRH release effects of kisspeptin thus define GPR54 as a major control point in the reproductive axis and suggest kisspeptin to be a neurohormonal effector.

Animals↗
PubMed2005

Disulfide trapping to localize small-molecule agonists and antagonists for a G protein-coupled receptor.

A key question regarding the signaling mechanism for G protein-coupled receptors (GPCRs) is what triggers agonism versus antagonism. Peptide analogs derived from the chemokine, complement fragment 5 anaphylatoxin (C5a), can act as agonists or antagonists to the C5a receptor, a member of the GPCR family [Gerber, B. O., Meng, E. C., Dotsch, V., Baranski, T. J. & Bourne, H. R. (2001) J. Biol. Chem. 276, 3394-4000]. Recently, we showed that two Cys residues engineered near a proposed binding site in the C5a receptor on transmembrane helices III and VI can selectively and reversibly trap short Cys-containing 3-mer peptides derived from C5a by disulfide bond formation [Buck, E. A., Bourne, H. & Wells, J. A. (November 18, 2004) J. Biol. Chem., 10.1074/jbc.C400500200]. Here, a library of 10,000 compounds, each containing an exchangeable thiol, was screened to identify specific small-molecule mimics that block binding of C5a. Some of the selected compounds acted as agonists and were as potent as the natural C5a ligand, and some acted as antagonists. A residue near these compounds, Ile-116 in helix III, functions as a "gatekeeper" to modulate these effects. A small substitution, Ile-116-Ala, enhanced affinity for some compounds and allowed antagonists to function as agonists; a larger substitution, Ile-116-Trp, decreased affinity and agonism. Thus, subtle changes in either the structure of the ligand or the receptor at the site between helix III, VI, and VII can switch the receptor on or off. This ligand binding and activation site may be similarly positioned in other members of the chemokine receptor family. Selective ligand trapping by reversible disulfide formation may serve to nucleate the development of small-molecule mimics.

Binding Sites↗
PubMed2005

Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases.

To realize the full potential of targeted protein kinase inhibitors for the treatment of cancer, it is important to address the emergence of drug resistance in treated patients. Mutant forms of BCR-ABL, KIT, and the EGF receptor (EGFR) have been found that confer resistance to the drugs imatinib, gefitinib, and erlotinib. The mutations weaken or prevent drug binding, and interestingly, one of the most common sites of mutation in all three kinases is a highly conserved "gatekeeper" threonine residue near the kinase active site. We have identified existing clinical compounds that bind and inhibit drug-resistant mutant variants of ABL, KIT, and EGFR. We found that the Aurora kinase inhibitor VX-680 and the p38 inhibitor BIRB-796 inhibit the imatinib- and BMS-354825-resistant ABL(T315I) kinase. The KIT/FLT3 inhibitor SU-11248 potently inhibits the imatinib-resistant KIT(V559D/T670I) kinase, consistent with the clinical efficacy of SU-11248 against imatinib-resistant gastrointestinal tumors, and the EGFR inhibitors EKB-569 and CI-1033, but not GW-572016 and ZD-6474, potently inhibit the gefitinib- and erlotinib-resistant EGFR(L858R/T790M) kinase. EKB-569 and CI-1033 are already in clinical trials, and our results suggest that they should be considered for testing in the treatment of gefitinib/erlotinib-resistant non-small cell lung cancer. The results highlight the strategy of screening existing clinical compounds against newly identified drug-resistant mutant variants to find compounds that may serve as starting points for the development of next-generation drugs, or that could be used directly to treat patients that have acquired resistance to first-generation targeted therapy.

Aminoquinolines↗
PubMed2005

Perforin-dependent elimination of dendritic cells regulates the expansion of antigen-specific CD8+ T cells in vivo.

The lifespan and survival of dendritic cells (DC) in vivo are potentially critical to the expansion of T cell immune responses. We have previously reported that DC loaded with specific antigen are rapidly eliminated by cytotoxic T lymphocytes (CTL) in vivo, but the site, mechanism, and consequences of DC elimination were not defined. In this article we show that DC elimination in vivo occurs in a perforin-dependent manner and does not require IFN-gamma or the presence of CD4(+)CD25(+) regulatory T cells. Most importantly, failure to eliminate DC had profound consequences on the CTL immune response. Perforin-deficient mice showed a progressive increase in the numbers of antigen-specific CD8(+) T cells after repeated immunizations with DC. In contrast, in control mice the number of antigen-specific CD8(+) T cells did not notably increase with repeated immunizations. Lastly, we also show that CTL-mediated elimination of DC occurs in peripheral tissues but not in the lymph node. Our data suggest that CTL act as "gatekeepers" that control access of antigen-loaded DC into the lymph node, thereby preventing continued expansion of antigen-specific T cells.

Adoptive Transfer↗
PubMed2006

Phosphorylation of the ATP-binding loop directs oncogenicity of drug-resistant BCR-ABL mutants.

The success of targeting kinases in cancer with small molecule inhibitors has been tempered by the emergence of drug-resistant kinase domain mutations. In patients with chronic myeloid leukemia treated with ABL inhibitors, BCR-ABL kinase domain mutations are the principal mechanism of relapse. Certain mutations are occasionally detected before treatment, suggesting increased fitness relative to wild-type p210 BCR-ABL. We evaluated the oncogenicity of eight kinase inhibitor-resistant BCR-ABL mutants and found a spectrum of potencies greater or less than p210. Although most fitness alterations correlate with changes in kinase activity, this is not the case with the T315I BCR-ABL mutation that confers clinical resistance to all currently approved ABL kinase inhibitors. Through global phosphoproteome analysis, we identified a unique phosphosubstrate signature associated with each drug-resistant allele, including a shift in phosphorylation of two tyrosines (Tyr253 and Tyr257) in the ATP binding loop (P-loop) of BCR-ABL when Thr315 is Ile or Ala. Mutational analysis of these tyrosines in the context of Thr315 mutations demonstrates that the identity of the gatekeeper residue impacts oncogenicity by altered P-loop phosphorylation. Therefore, mutations that confer clinical resistance to kinase inhibitors can substantially alter kinase function and confer novel biological properties that may impact disease progression.

Adenosine Triphosphate↗