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Hospitalization of children for surgery: the parents' view.

A qualitative study based on interviews with nine families was implemented to explore the parental experience when a child is hospitalized for surgery. Participant observation during the stress points identified in the literature and interviews with parents both in the hospital and in the home after the child was discharged were the major sources of data. Sources of parental stress, parental roles during the child's hospitalization, coping strategies used by parents, and parents' suggestions for health care professionals, particularly nursing staff, were explored. The need for health care professionals to make themselves available to parents and to negotiate roles with parents were key findings.

Alberta↗

Reteplase: a new thrombolytic for the treatment of acute myocardial infarction.

OBJECTIVE: To summarize the published data on reteplase, the most recent thrombolytic agent approved by the Food and Drug Administration for use in the management of acute myocardial infarction in adults. DATA SOURCES: Published data on reteplase identified by MEDLINE searches (January 1985-June 1997), as well as other pertinent literature. DATA SYNTHESIS: Reteplase is a new thrombolytic agent derived from human tissue plasminogen activator. Its mechanism of action is similar to that of alteplase, but it differs in pharmacokinetic and pharmacodynamic properties. Certain structural changes contribute to differences in pharmacokinetic properties such as a prolonged half-life (15 min), which allows it to be administered as two 10-MU bolus injections. Reteplase has been shown to have fibrin specificity similar to that of alteplase, but with a lower binding affinity for fibrin. This enables reteplase to bind to the thrombus repeatedly and increases its fibrinolytic potential. In clinical trials, reteplase demonstrated more rapid and complete coronary patency compared with alteplase, without a significant increase in clinical adverse events. However, the improvement in coronary artery patency with reteplase versus alteplase did not result in a reduction in mortality in the GUSTO III trial. CONCLUSIONS: Despite evidence that use of reteplase results in an improved coronary artery patency rate versus accelerated infusion alteplase, an improvement in mortality rate with reteplase was not shown. Reteplase may have an advantage over alteplase due to a more rapid and simpler dosing regimen, but the significance of this difference is yet to be determined.

Clinical Trials as Topic↗

Cholinesterase inhibitors: a therapeutic strategy for Alzheimer disease.

OBJECTIVE: To provide a review of acetylcholinesterase inhibitors (AChEIs) tested as therapeutic agents for Alzheimer disease (AD). DATA SOURCES: MEDLINE searches (January 1986-July 1998) identified pertinent literature. Selected references from these articles, as well as abstracts from recent meetings and package insert literature from approved compounds, were also used as source material. DATA EXTRACTION: AChEIs were reviewed with regard to chemical structure, mechanism of inhibition, substrate specificity, pharmacokinetics/pharmacodynamics, safety/tolerability, and efficacy. DATA SYNTHESIS: Cholinergic deficits, leading to cognitive impairment, are a significant aspect of neurodegeneration in AD. AChEIs reduce the degradation of acetylcholine, thus enhancing cholinergic transmission. In addition to the two agents approved by the Food and Drug Administration, tacrine and donepezil, six other compounds of diverse chemical structure and mechanism of inhibition including physostigmine, metrifonate, rivastigmine, and galantamine are under investigation as potential therapy for AD. These compounds are structurally diverse, possess unique patterns of specificities for the various forms of cholinesterase enzymes, use distinct mechanisms of enzyme inhibition, present unique adverse event profiles, and offer relatively similar mean gains in cognitive abilities to patients with AD in controlled clinical trials. CONCLUSIONS: Relative to placebo, new AChEIs in development provide modest improvements in cognition for patients with mild to moderate AD, with improved tolerability profiles and more convenient dosing relative to tacrine. The availability of a wide array of AChEIs soon to be accessible to patients with AD will provide additional options to those who cannot tolerate or do not respond to drugs currently used for AD.

Alzheimer Disease↗

Flavopiridol, a novel cyclin-dependent kinase inhibitor, in clinical development.

OBJECTIVE: To review preclinical and clinical information on flavopiridol, an inhibitor of cyclin-dependent kinases (CDKs), tested as an antitumor agent. DATA SOURCES: Primary and review articles were identified by MEDLINE search (1990-June 2001). Abstracts from recent meetings were also used as source materials. DATA EXTRACTION: Flavopiridol was reviewed with regard to its mechanisms, preclinical and clinical results, pharmacokinetics, and metabolism. DATA SYNTHESIS: Flavopiridol is an inhibitor of several CDKs and displays unique anticancer properties. In addition to direct CDK inhibition, flavopiridol also exhibited other features such as inducing apoptosis in many cancer cell lines, decreasing cyclin D1 concentration, and inhibiting angiogenesis. Preclinical xenograft models showed significant antitumor activity for flavopiridol. The regimen using 72-hour continuous infusion every 2 weeks has been most extensively applied in clinical trials, with a 1-hour infusion currently being explored to achieve higher peak concentrations. Several Phase I and II trials have been reported, with some evidence of antitumor activity noted. Further Phase I and II trials using flavopiridol as a single agent and in combination with standard chemotherapeutic regimens and various tumor types are ongoing. CONCLUSIONS: Flavopiridol is the first CDK inhibitor to enter clinical trials. Several Phase I and Phase II clinical trials with different regimens (72-h or 1-h infusion) have been completed. Initial clinical trials have been intriguing, but many questions remain: What is the best regimen (< or =72-h infusion)? Does optimal future development of this drug depend on the combination with other chemotherapy? What is the best combination of flavopiridol with other chemotherapy?

Antineoplastic Agents↗

Pramlintide for the treatment of diabetes mellitus.

OBJECTIVE: To provide an overview of the role of amylin, as well as that of pramlintide, a synthetic analog of amylin, in maintaining glucose homeostasis; and discuss the pharmacology, pharmacokinetics, efficacy, adverse effects, and role of pramlintide in the control of postprandial hyperglycemia. DATA SOURCES: The data presented in this review were obtained from published literature, abstracts presented at scientific meetings, and information on file with the manufacturer. MEDLINE searches (1986-March 2003) using the search terms pramlintide and amylin were conducted to identify clinical trials and review articles. Additionally, the bibliographies of the identified articles were reviewed. DATA SYNTHESIS: Clinical trials have demonstrated that amylin in combination with insulin controls postprandial glucose levels by decreasing food intake, slowing gastric emptying, and suppressing glucagon secretion. Clinical trials also showed significant decreases in mean plasma glucose levels and glycosylated hemoglobin, as well as the added benefits of weight loss and reduction in insulin doses. The most commonly reported adverse effects associated with pramlintide in clinical trials were gastrointestinal complaints and hypoglycemia, which occurred most frequently during initiation of therapy. CONCLUSIONS: The administration of insulin alone often does not result in optimal metabolic control. The treatment of amylin deficiency, in addition to insulin deficiency, may be warranted in order to obtain glucose homeostasis. The role of pramlintide, an amylin analog, will become clearer as more clinical data become available.

Amino Acid Sequence↗

Sitagliptin: a dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.

OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of sitagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor in the management of type 2 diabetes mellitus. DATA SOURCES: A MEDLINE search (1966-February 2006) was conducted for English-language articles using the terms dipeptidyl peptidase IV inhibitor, incretin, MK-0431, and sitagliptin. Abstracts from the American Diabetes Association annual meetings in 2004 and 2005 were included as sources of data. STUDY SELECTION AND DATA EXTRACTION: Articles pertaining to the pharmacology of sitagliptin, its pharmacokinetics, safety and efficacy were reviewed. DATA SYNTHESIS: Sitagliptin is a potent, competitive, reversible inhibitor of the DPP-IV enzyme. It is eliminated renally, with a terminal half-life of 11.8-14.4 hours. In Phase II clinical trials, sitagliptin was found to be superior to placebo for the treatment of type 2 diabetes mellitus. Results of a small trial comparing sitagliptin with glipizide indicate that both treatments are comparable. The efficacy of sitagliptin has also been demonstrated when used as adjunctive therapy with metformin. Few adverse effects have been reported. Weight gain and hypoglycemia have not been seen with sitagliptin therapy. CONCLUSIONS: Based on its unique mechanism of action, sitagliptin will provide practitioners with an additional tool in the treatment of diabetes. Review of the literature to date implies sitagliptin may be effective as monotherapy in type 2 diabetes. In addition, existing evidence supports the use of sitagliptin as adjunct therapy to sulfonylureas and metformin. Another advantage of sitagliptin use is that it appears to be free from the adverse effects of weight gain and hypoglycemia that are associated with currently available treatments.

Animals↗

Underuse of controller medications among children with persistent asthma in the Ohio medicaid population: evolving differences with new medications.

BACKGROUND: Despite innovations in asthma care, morbidity and mortality have increased significantly. Underuse of controller medications is a major contributor to increased morbidity and mortality. OBJECTIVE: To determine the extent of underuse of asthma controller medications among Ohio Medicaid children and to determine if there are racial differences in controller medication claims. METHODS: We conducted a retrospective analysis of Ohio Medicaid claims data. The source data included all institutional, medical service, and pharmacy claims for fee-for-service patients between January 1, 1997, and December 31, 2001. We identified children with persistent asthma using Health Employer Data Information System criteria. The primary outcome was a controller medication claim. We used multivariable logistic regression to identify risk factors for underutilizing asthma controller medications and applied generalized estimating equations to account for repeated measures. RESULTS: The proportion of children with claims for a controller medication increased from 53% in 1997 to 67% in 2001. Although there were no racial differences in medication claims in 1997, a smaller proportion of African American children had a claim for a controller medication in 2001 (64.8% vs 67.8%, P < .001). Leukotriene antagonists (LTAs) were driving this difference. Individuals residing in urban areas were significantly less likely to have claims for LTAs when compared with those who resided in nonurban areas. CONCLUSIONS: Overall use of asthma controller medications among Ohio Medicaid children was poor. There was a widening racial difference in controller medication claims over the 5-year study. Regional differences in LTA claims were driving this racial difference.

Adolescent↗

Evaluation of staging, cytoreduction and second-look operation of 119 ovarian cancer patients.

OBJECTIVE: This study was conducted on patients with ovarian cancer in order to evaluate survival. DESIGN: A retrospective study of 119 cases of ovarian cancer from January 1977 to December 1992 with observation until 1993. LOCATION: Department of Gynecology and Obstetrics, Ribeirão Preto School of Medicine, São Paulo University. PARTICIPANTS: Of the 119 cases, 70 (58.8%) presented epithelial carcinomas and 21 (17.6%) tumors of the sexual girdle/stroma. DATA SOURCE: The data were obtained from the medical records of the patients. MEASUREMENT: Statistical analysis of survival time was based on the nonparametric Mann-Whitney test with the level of significance set at P < 0.05. RESULTS: The patients with a negative second look had a mean survival of 79.4 +/- 48.5 months versus 24.2 +/- 15.1 months for patients with a positive second look (P < 0.02). CONCLUSIONS: It is concluded that patients with a negative second look present a better prognosis compared to those with residual disease.

Female↗

Cost-effectiveness analysis of antithrombotic therapy in nonurgent percutaneous coronary intervention.

STUDY OBJECTIVE: To perform a cost-effectiveness analysis comparing three treatment approaches during nonurgent percutaneous coronary intervention (PCI): bivalirudin with provisional glycoprotein (GP) IIb-IIIa inhibitor therapy, unfractionated heparin (UFH) with eptifibatide, and UFH with abciximab. DESIGN: Literature-based decision model from an institutional perspective. DATA SOURCE: Patient data from the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 study and three other randomized controlled trials that included UFH and routine GP IIb-IIIa inhibitor (eptifibatide or abciximab) therapy. All included studies were comparable based on patient population, procedural techniques, and general treatment approaches. MEASUREMENTS AND MAIN RESULTS: We included patient populations undergoing contemporary nonurgent PCI to identify probabilities of success or complications (myocardial infarction, urgent revascularization, thrombocytopenia, and major or minor bleeding at 30 days). Costs were assigned to each outcome by incorporating diagnosis-related group-- and/or Current Procedural Terminology--associated costs, institutional drug acquisition costs, and unit replacement costs of platelets and red blood cells. In the base-case analysis, the use of bivalirudin with provisional GP IIb-IIIa inhibitor therapy dominated the UFH and planned GP IIb-IIIa inhibitor approach: UFH with eptifibatide was 74 US dollars more expensive and 1.2% less effective, and UFH with abciximab was 777 US dollars more expensive and 2.3% less effective. Sensitivity analyses indicated that the model results were robust, but also revealed that bivalirudin lost its cost-effectiveness, resulting in UFH with eptifibatide becoming more cost-effective, when two or more vials of bivalirudin were necessary in greater than 27% of cases or when the use of provisional GP IIb-IIIa inhibitor therapy exceeded 20%. CONCLUSION: This analysis indicates that bivalirudin with provisional GP IIb-IIIa inhibitor therapy is the most cost-effective antithrombotic treatment strategy in nonurgent PCI when its use and dosing are consistent with the REPLACE-2 trial.

Abciximab↗

Prenatal care in Finland: from primary to tertiary health care?

Traditionally, the Finnish prenatal care system has been based on special maternity centers outside hospitals. In recent years, however, the use of hospital outpatient clinics has increased. The purpose of this study was to describe the use of the clinics and to see whether clinics serve as an addition or as an alternative to maternity centers. We used several different data sources (statistics, documents, interviews, questionnaires). The main source was data on visits for all women who gave birth in Helsinki in a five-week period in 1987. The content of care and means of care delivery differ between clinics and maternity centers. Clinics are technologically and provider-oriented without continuity of care. Clinics are not just referral centers for high-risk mothers; at least half of pregnant women visit them. Ultrasound screening is an important reason for use of the clinic. Background characteristics as well as the outcome of pregnancy were similar among women visiting a hospital clinic a maximum of one time (low users), two to three times, or four times or more (high users). Standardizing for the length of gestation, high users made fewer visits to maternity centers than did low users. Hospital clinic care now seems to replace care in maternity centers, and we found a weak trend toward a pluralistic prenatal care.

Adult↗

[Management of the acute respiratory distress syndrome].

OBJECTIVE: To review the current support and treatment strategies of the acute respiratory distress syndrome. DATA SOURCES: Original data from our research laboratory and from representative scientific articles on acute respiratory distress syndrome and acute lung Injury searched through Medline. SUMMARY OF THE FINDINGS: Despite advances in the understanding of the pathogenesis of acute respiratory distress syndrome, this syndrome still results in significant morbidity and mortality. Mechanical ventilation, the main therapeutic modality for acute respiratory distress syndrome, is no longer considered simply a support modality, but a therapy capable of influencing the course of the disease. New ventilation strategies, such as high-frequency oscillatory ventilation appear to be promising. This text reviews the current knowledge of acute respiratory distress syndrome management, including conventional and non-conventional ventilation, the use of surfactant, nitric oxide, modulators of inflammation, extracorporeal membrane oxygenation and prone position. CONCLUSIONS: The last decade was marked by significant advances, such as the concept of protective ventilation for acute respiratory distress syndrome. The benefit of alternative strategies, such as high-frequency oscillatory ventilation, the use of surfactant and immunomodulators continue to be the target of study.

Adrenal Cortex Hormones↗

Optimal dosing with risperidone: updated recommendations.

BACKGROUND: Drug dosages utilized during controlled clinical trials are not always optimal for patients encountered in day-to-day practice. The original trials of risperidone, a novel antipsychotic, suggested that an initial target dose of 6 mg/day was appropriate, but these trials were necessarily conducted among patients who were chronically impaired, hospitalized, and often partly drug resistant. DATA SOURCES: Relevant data relating to the dosage of risperidone identified through an online (MEDLINE) search using the keywords risperidone, schizophrenia, schizoaffective disorder dementia, bipolar disorder, and dose were supplemented by a review of international and U.S. Congress abstracts in which the dose of risperidone was specifically described. CONCLUSION: On the basis of naturalistic studies, clinical audit, phase 4 trials, positron emission tomography data, and 5 years of clinical experience, the currently recommended target dose of risperidone is 4 mg/day for most patients, with less-rapid titration than previously recommended. Moreover, a lower dose than this and slower titration may be appropriate for elderly patients, young patients, and first-episode patients.

Adolescent↗

A systematic review of modafinil: Potential clinical uses and mechanisms of action.

BACKGROUND: Modafinil is a novel wake-promoting agent that has U.S. Food and Drug Administration approval for narcolepsy and shift work sleep disorder and as adjunctive treatment of obstructive sleep apnea/hypopnea syndrome. Modafinil has a novel mechanism and is theorized to work in a localized manner, utilizing hypocretin, histamine, epinephrine, gamma-aminobutyric acid, and glutamate. It is a well-tolerated medication with low propensity for abuse and is frequently used for off-label indications. The objective of this study was to systematically review the available evidence supporting the clinical use of modafinil. DATA SOURCES: The search term modafinil OR Provigil was searched on PubMed. Selected articles were mined for further potential sources of data. Abstracts from major scientific conferences were reviewed. Lastly, the manufacturer of modafinil in the United States was asked to provide all publications, abstracts, and unpublished data regarding studies of modafinil. DATA SYNTHESIS: There have been 33 double-blind, placebo-controlled trials of modafinil. Additionally, numerous smaller studies have been performed, and case reports of modafinil's use abound in the literature. CONCLUSIONS: Modafinil is a promising drug with a large potential for many uses in psychiatry and general medicine. Treating daytime sleepiness is complex, and determining the precise nature of the sleep disorder is vital. Modafinil may be an effective agent in many sleep conditions. To date, the strongest evidence among off-label uses exists for the use of modafinil in attention-deficit disorder, postanesthetic sedation, and cocaine dependence and withdrawal and as an adjunct to antidepressants for depression.

Animals↗

Do NHS walk-in centres in England provide a model of integrated care?

PURPOSE: To undertake a comprehensive evaluation of NHS walk-in centres against criteria of improved access, quality, user satisfaction and efficiency. CONTEXT: Forty NHS walk-in centres have been opened in England, as part of the UK governments agenda to modernise the NHS. They are intended to improve access to primary care, provide high quality treatment at convenient times, and reduce inappropriate demand on other NHS providers. Care is provided by nurses rather than doctors, using computerised algorithms, and nurses use protocols to supply treatments previously only available from doctors. DATA SOURCES: Several linked studies were conducted using different sources of data and methodologies. These included routinely collected data, site visits, patient interviews, a survey of users of walk-in centres, a study using simulated patients to assess quality of care, analysis of consultation rates in NHS services near to walk-in centres, and audit of compliance with protocols. CONCLUSION & DISCUSSION: The findings illustrate many of the issues described in a recent WHO reflective paper on Integrated Care, including tensions between professional judgement and use of protocols, problems with incompatible IT systems, balancing users' demands and needs, the importance of understanding health professionals' roles and issues of technical versus allocative efficiency.

Journal Article↗

Eosinophilia-myalgia syndrome: lessons for public health researchers.

OBJECTIVE: To review epidemiological investigations into the epidemic of eosinophilia-myalgia syndrome which occurred predominantly in the United States of America in mid to late 1989, and examine the implications for similar urgent public health research in Australia. DATA SOURCES: Published data from epidemiological research, and relevant regulatory statements. OUTCOME: Intensive epidemiological investigations established that eosinophilia-myalgia syndrome was strongly associated with ingestion of L-tryptophan produced by a single manufacturer. It is likely that an identified contaminant has a role in pathogenesis, although the mechanism of action remains unclear. CONCLUSIONS: Rapid epidemiological investigation led to early containment measures and prevention of further public exposure to the causative agent. The episode highlighted the importance of preparedness amongst public health organisations to promptly initiate investigations of disease outbreaks, and demonstrated the benefits of a nation-wide ability to coordinate these studies. There may be encumbrances to urgent public health research in the form of inadequate mechanisms of data linkage. It is recommended that attention be given to such barriers now rather than in a time of crisis.

Australia↗

Magnetic resonance angiography.

OBJECTIVE: To outline the physical principles of magnetic resonance angiography (MRA), major current MRA techniques, clinical indications and some of the limitations of MRA. The rapidly changing nature of MRA techniques is stressed. DATA SOURCES AND DATA EXTRACTION: The MRA literature for the last eight years is reviewed with particular attention to the changing clinical role of MRA. Details of specific MRA techniques are omitted for simplicity and because of their lack of direct relevance to the clinicians requesting MRA examinations. Data concerning the clinical role of MRA techniques are extracted from the literature and combined with our own clinical experience. DATA SYNTHESIS: While stressing the rapidly changing nature of this new investigational technique, we find that MRA has a number of current roles in patient management. CONCLUSIONS: MRA is currently a useful investigation and will in all likelihood become more useful in the future as the technique improves further and becomes more available.

Angiography↗

Is there gender bias in research fellowships awarded by the NHMRC?

OBJECTIVE: To assess whether there is gender bias in the allocation of research fellowships granted by the Research Fellowships Committee of the National Health and Medical Research Council. DATA SOURCES: Anonymous data from applications for a research fellowship from 1994 to 1997. RESULTS: More men than women apply for research fellowships (sex ratio, 2.5:1), but there is no difference in the proportion of male or female applicants who succeed in their application. Among new applicants, men tend to apply for a higher level of fellowship than women. CONCLUSIONS: Lack of data about the numbers of eligible men and women means that we cannot draw conclusions about self-selection biases among potential applicants. However, the selection procedures of the Committee appear to be unbiased. The gender of applicants does not influence the outcome of their application.

Databases, Factual↗

Cost-utility of three approaches to the diagnosis of sleep apnea: polysomnography, home testing, and empirical therapy.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is usually diagnosed with overnight polysomnography in a sleep laboratory. Home sleep studies can be performed at lower cost, but results are somewhat less reliable. Bedside diagnosis of OSAS without any testing has also been discussed. OBJECTIVE: To model the costs and utility of laboratory polysomnography, home study, and no testing during the 5 years after initial evaluation for OSAS. DESIGN: Cost-utility analysis. DATA SOURCES: Published data. TARGET POPULATION: Hypothetical cohort of persons suspected of having OSAS. TIME HORIZON: The 5 years after initial evaluation for OSAS. PERSPECTIVE: Societal. INTERVENTION: Nasal continuous positive airway pressure when OSAS was diagnosed. MEASUREMENTS: Quality of life, survival and charges (as proxies for costs) for each diagnostic method. RESULTS OF BASE-CASE ANALYSIS: Under almost all modeled conditions, polysomnography provided maximal quality-adjusted life-years in the 5 years after the initial diagnostic evaluation. The incremental charges for polysomnography over home study or no testing were about $13,400 and $9200, respectively, per quality-adjusted life-year gained during this period. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to the utility of treatment in the absence of OSAS. CONCLUSIONS: The cost-utility of polysomnography instead of home study or no testing in the diagnosis of OSAS compares favorably with that of other procedures for which society judges the added utility per dollar spent to be worthwhile. More precise determination of certain key variables in this model should be a goal of future research.

Cost-Benefit Analysis↗