Cyclooxygenase 2 selective agents and upper gastrointestinal disease.
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Biomedical subjects
Publications and source records attributed to R H Palmer.
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OBJECTIVE: The purpose of this study was to compare the tolerability and efficacy of nabumetone and naproxen in the treatment of patients with rheumatoid arthritis (RA). The occurrence of gastrointestinal (GI) adverse events was compared. BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have similar efficacy at equipotent doses, but the therapeutic response to various NSAIDs often differs in individual patients. METHODS: This was a 3-month, randomized, double-blind, multicenter, parallel-group study conducted in adult patients with RA. The study had 2 phases: a 3- to 14-day washout period and a 12-week treatment period. During the treatment phase, the tolerability and efficacy of nabumetone 2000 mg/d were compared with those of naproxen 1000 mg/d. The change from baseline in efficacy variables, including global assessments, number of tender or swollen joints, and pain, was evaluated. The study was sized to provide an 80% power to detect a 15% difference in the percentage improvement on the physician's global assessment (alpha = 0.05). GI safety was assessed by monitoring the occurrence of clinically important adverse GI events. RESULTS: A total of 346 RA patients at 31 US rheumatology centers were randomly assigned to treatment (173 patients per group). The study population was predominantly white (87.0%) and female (70.5%), with a mean age of 54 years. Both treatments improved the signs and symptoms of RA, with no statistically significant differences between groups for any efficacy variables. No serious GI adverse events occurred with either NSAID. The most frequent treatment-related adverse events in both groups were predominantly GI in origin, as were those that resulted in withdrawal from the study. Diarrhea with lower abdominal pain was the most common adverse event in the nabumetone group; upper abdominal pain was the most common adverse event in the naproxen group. The only significant difference between the 2 groups was a higher incidence of diarrhea (P < 0.01) in patients receiving nabumetone. CONCLUSIONS: Nabumetone 2000 mg/d was as effective as naproxen 1000 mg/d in relieving the signs and symptoms of RA. In this study, no serious GI adverse events were observed with either NSAID, but nabumetone was associated with a higher incidence of diarrhea.
AIM: To compare the efficacy and gastrointestinal (GI) safety of nabumetone with two comparator non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac SR and piroxicam. METHODS: Two randomized, double-blind, multicentre, parallel group trials were carried out in patients with moderate to severe osteoarthritis of the hip or knee. During the 6 month treatment phase, the safety and efficacy of nabumetone (1500-2000 mg/day) was compared to diclofenac SR (100 mg/day) or piroxicam (20-30 mg/day). GI safety was evaluated by reviewing all adverse events reported during the trials and presenting all cases of ulcers (complicated and uncomplicated), as well as other bleeding events that may have been associated with NSAID administration. RESULTS: Most of the efficacy parameters showed no significant differences between the NSAIDs, although diclofenac SR was significantly better than nabumetone in one of 18 efficacy parameters. Nabumetone-treated patients experienced significantly fewer ulcer and bleeding events compared to patients treated with the comparator NSAIDs [1.1% (4/348) vs. 4.3% (15/346), P = 0.01]. Bleeding events, including outright upper or lower GI bleeding or a significant decline in haemoglobin, occurred in significantly fewer patients treated with nabumetone than with the comparator NSAIDs [1.1% (4/348) vs. 3.5% (12/346), P < 0.05]. More importantly, complications associated with either ulcers (perforation) or bleeding (leading to hospitalization or withdrawal) occurred in significantly fewer patients receiving nabumetone [0% (0/348)] than with comparator NSAIDs [1.4% (5/346), (P < 0.05)]. CONCLUSION: The results suggest that nabumetone was similar in efficacy by most criteria to diclofenac SR and piroxicam in relieving the symptoms of osteoarthritis; however, nabumetone's GI safety profile was generally superior to that of both comparator NSAIDs. In the pooled analysis, nabumetone was associated with a significantly lower total incidence of ulcers and bleeding events, and a significantly lower incidence of complications associated with these events.
OBJECTIVES: This study examined the validity of the Complications Screening Program (CSP) by testing whether (1) ICD-9-CM codes used to identify a complication are coded completely and accurately and (2) the CSP algorithm successfully separates conditions present on admission from those occurring in the hospital. METHODS: We compared diagnosis and procedure codes contained in the Medicare claim with codes abstracted from an independent re-review of more than 1,200 medical records from Connecticut and California. RESULTS: Eighty-nine percent of the surgical cases and 84% of the medical cases had their CSP trigger codes corroborated by re-review of the medical record. For 13% of the surgical cases and 58% of the medical cases, the condition represented by the code was judged to be present on admission rather than occurring in-hospital. The positive predictive value of the claim was greater than 80% for the surgical risk pool, suggesting the value of the CSP as a screening tool. CONCLUSIONS: The CSP has validity as a screen for most surgical complications but only for 1 medical complication. The CSP does not have validity as a "stand-alone" tool to identify more than a few in-hospital surgery-related events. The addition of an indicator to the Medicare claim to capture the timing of secondary diagnoses would improve the validity of the CSP for identifying both surgical and medical in-hospital events.
OBJECTIVE: The use of administrative data to identify inpatient complications is technically feasible and inexpensive but unproven as a quality measure. Our objective was to validate whether a screening method that uses data from standard hospital discharge abstracts identifies complications of care and potential quality problems. DESIGN: This was a case-control study with structured implicit physician reviews. SETTING: Acute-care hospitals in California and Connecticut in 1994. PATIENTS: The study included 1,025 Medicare beneficiaries greater than 265 years of age. METHODS: Using administrative data, we stratified acute-care hospitals by observed-to-expected complication rates and randomly selected hospitals within each state. We randomly selected cases flagged with 1 of 17 surgical complications and 6 medical complications. We randomly selected controls from unflagged cases. MAIN OUTCOME MEASURE: Peer-review organization physicians' judgments about the presence of the flagged complication and potential quality-of-care problems. RESULTS: Physicians confirmed flagged complications in 68.4% of surgical and 27.2% of medical cases. They identified potential quality problems in 29.5% of flagged surgical and 15.7% of medical cases but in only 2.1% of surgical and medical controls. The rate of physician-identified potential quality problems among flagged cases exceeded 25% in 9 surgical screens and 1 medical screen. Reviewers noted several potentially mitigating circumstances that affected their judgments about quality, including factors related to the patients' illness, the complexity of the case, and technical difficulties that clinicians encountered. CONCLUSIONS: For some types of complications, screening administrative data may offer an efficient approach for identifying potentially problematic cases for physician review. Understanding the basis for physicians' judgments about quality requires more investigation.
BACKGROUND: Hospital discharge diagnoses, coded by use of the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), increasingly determine reimbursement and support quality monitoring. Prior studies of coding validity have investigated whether coding guidelines were met, not whether the clinical condition was actually present. OBJECTIVE: To determine whether clinical evidence in medical records confirms selected ICD-9-CM discharge diagnoses coded by hospitals. RESEARCH DESIGN AND SUBJECTS: Retrospective record review of 485 randomly sampled 1994 hospitalizations of elderly Medicare beneficiaries in Califomia and Connecticut. MAIN OUTCOME MEASURE: Proportion of patients with specified ICD-9-CM codes representing potential complications who had clinical evidence confirming the coded condition. RESULTS: Clinical evidence supported most postoperative acute myocardial infarction diagnoses, but fewer than 60% of other diagnoses had confirmatory clinical evidence by explicit clinical criteria; 30% of medical and 19% of surgical patients lacked objective confirmatory evidence in the medical record. Across 11 surgical and 2 medical complications, objective clinical criteria or physicians' notes supported the coded diagnosis in >90% of patients for 2 complications, 80% to 90% of patients for 4 complications, 70% to <80% of patients for 5 complications, and <70% for 2 complications. For some complications (postoperative pneumonia, aspiration pneumonia, and hemorrhage or hematoma), a large fraction of patients had only a physician's note reporting the complication. CONCLUSIONS: Our findings raise questions about whether the clinical conditions represented by ICD-9-CM codes used by the Complications Screening Program were in fact always present. These findings highlight concerns about the clinical validity of using ICD-9-CM codes for quality monitoring.
BACKGROUND: The association between volume of patients treated and quality of care has important implications for patient referral policies and approaches to quality improvement. Most studies have focused on hospital volume alone and health outcomes. OBJECTIVES: The objective of this work was to examine the association of hospital and physician volume with use of aspirin and reperfusion therapy in the management of acute myocardial infarction (AMI) in eligible patients. METHODS: We reviewed charts of 2,215 patients treated at 35 Minnesota hospitals for AMI between October 1, 1992, and July 31, 1993, comparing use of aspirin and reperfusion therapy in eligible patients across different physician and hospital volume categories through multiple logistic regression. RESULTS: Aspirin use did not vary significantly with physician volume. Use of reperfusion therapy was reduced among the lowest-volume physicians only (adjusted OR, 0.38; 95% CI, 0.15-0.94). Compared with the highest volume hospitals (treating >200 patients), aspirin use among lower-volume hospitals was lower. This was statistically significant only in the hospitals treating <30 patients (adjusted OR, 0.54; 95% CI, 0.30-0.97). These same hospitals had increased odds of using thrombolytics (adjusted OR, 3.02; 95% CI, 1.40-6.53). CONCLUSIONS: Differences in use of aspirin and reperfusion therapy occur at the extremes of hospital and physician volume. These observed differences are in the anticipated direction, except for the increased use of thrombolytics at very-low-volume hospitals. This may be a "desperation reaction" with a perceived lack of other alternatives, such as cardiac catheterization labs and cardiologists.
The National Inventory of Mental Health Quality Measures was funded by the Agency for Healthcare Research and Quality to (1) inventory process measures for assessing the quality of mental health care; (2) identify clinical, administrative, and quality domains where measures have been developed; and (3) identify areas where further research and development is needed. Among the 86 measures identified, most evaluated treatment of major mental disorders, for example, schizophrenia (24 percent) and major depression (21 percent). A small proportion focused on children (8 percent) or the elderly (9 percent). Domains of quality included treatment appropriateness (65 percent), continuity (26 percent), access (26 percent), coordination (13 percent), detection (12 percent), and prevention (6 percent). Few measures were evaluated for reliability (12 percent) or validity (3 percent). Measures imposing a lower burden were more likely to be in use (chi 2 = 4.41, p = .036). Further measures are needed to assess care for several priority clinical and demographic groups. Research should focus on measure validity, reliability, and implementation costs. In order to foster quality improvement activities and use of common measures and specifications for mental health care, the inventory of quality measures will be made available at www.challiance.org/cqaimh.
The mammalian focal adhesion kinase (FAK) family of nonreceptor protein-tyrosine kinases have been implicated in controlling a multitude of cellular responses to the engagement of cell surface integrins and G protein-coupled receptors. We describe here a Drosophila melanogaster FAK homologue, DFak56, which maps to band 56D on the right arm of the second chromosome. Full-length DFak56 cDNA encodes a phosphoprotein of 140 kDa, which shares strong sequence similarity not only with mammalian p125(FAK) but also with the more recently described mammalian Pyk2 (also known as CAKbeta, RAFTK, FAK2, and CADTK) FAK family member. DFak56 has intrinsic tyrosine kinase activity and is phosphorylated on tyrosine in vivo. As is the case for FAK, tyrosine phosphorylation of DFak56 is increased upon plating Drosophila embryo cells on extracellular matrix proteins. In situ hybridization and immunofluorescence staining analysis showed that DFak56 is ubiquitously expressed with particularly high levels within the developing central nervous system. We utilized the UAS-GAL4 expression system to express DFak56 and analyze its function in vivo. Overexpression of DFak56 in the wing imaginal disc results in wing blistering in adults, a phenotype also observed with both position-specific integrin loss of function and position-specific integrin overexpression. Our results imply a role for DFak56 in adhesion-dependent signaling pathways in vivo during D. melanogaster development.
Methods of fracture treatment must strike a balance between fracture stability and soft tissue integrity. With highly comminuted diaphyseal fractures, exhaustive attempts at anatomical reconstruction often fail to achieve a load-sharing fixation and concurrently traumatize the vascular supply of the already damaged tissue. The lack of balance in this scenario makes failure likely. The strategies of biological osteosynthesis are used when the surgeon determines before surgery that anatomical reconstruction of the multiple cortical fragments is unlikely to result in load sharing. In these highly comminuted fractures, better results can be achieved by applying a set of biological osteosynthesis strategies in which preservation of vascular supply to the damaged bone is balanced with rigid fracture fixation.
BACKGROUND: The Complications Screening Program (CSP) aims to identify 28 potentially preventable complications of hospital care using computerized discharge abstracts, including demographic information, diagnosis and procedure codes. OBJECTIVE: To validate the CSP as a quality indicator by using explicit process of care criteria to determine whether hospital discharges flagged by the CSP experienced more process problems than unflagged discharges. METHODS: The (CSP was applied to computerized hospital discharge abstracts from Mledicare beneficiaries > 65 years old admitted in 1994 to hospitals in California and Connecticut for major surgery or medical treatment. ()f 28 CSP complications, 17 occurred sufficient frequently to study. Discharges flagged (cases) and unflagged (controls) by the (CSP were sampled and photocopied medical records were obtained. Physicians specified detailed, objective, explicit criteria, itemizing 'key steps' in processes of care that could potentially have prevented or caused complications. Trained nurses abstracted medical records using these explicit criteria. Process problem rates between cases and controls were compared. RESULTS: The final sample included 740 surgical and 416 medical discharges. Rates of process problems were high, ranging from 24.4 to 82.5% across CSP screens for surgical cases. Problems were lower for medical cases, ranging from 2.0 to 69.1% across CSP screens. Problem rates were 45.7% for surgical and 5.0% for medical controls. Rates of problems did not differ significantly across flagged and unflagged discharges. CONCLUSIONS: The CSP did not flag discharges with significantly higher rates of explicit process problems than unflagged discharges. Various initiatives throughout the USA use techniques similar to the CSP to identify complications of care. Based on these CSP findings, such approaches should be evaluated cautiously.
BACKGROUND: Physicians' agreement with quality evaluation criteria, and estimates of their own and their colleagues' compliance with these criteria were compared with actual compliance. METHODS: Physicians practicing in 10 health centers in Spain defined 13 quality evaluation criteria for two patient conditions (upper respiratory infections and high serum cholesterol). Compliance with criteria was measured by an external team, using random samples of medical records stratified by condition in each health center (n= 1,000). Concurrently, physicians were surveyed regarding agreement with the criteria, and were asked to estimate their own and their health center's rate of compliance with these criteria. RESULTS: Agreement ratings varied from 5.9 to 9.1 on a 10-point scale. Actual compliance rates ranged from 1.8 to 91.7% of records. Agreement correlated significantly with self-reported compliance but not with actual compliance. Estimates of one's own and one's health center compliance were positive and significantly correlated for all criteria, but were significantly higher for oneself than for one's health center for six of 13 criteria. CONCLUSIONS: Wide variation in physicians' agreement on quality criteria and in actual performance reveal a lack of clear guidelines. Agreement on criteria did not always translate into compliance with criteria. Physicians tended to rate their own performance as better than the average of their peers, suggesting that aggregate data may not influence physicians to change. Self-estimate of one's own or one's colleagues performance is not a good proxy for actual performance so that peer ratings are of dubious value for performance appraisal.
The dissatisfaction (dsf) gene is necessary for appropriate sexual behavior and sex-specific neural development in both sexes. dsf males are bisexual and mate poorly, while mutant females resist male courtship and fail to lay eggs. Males and females have sex-specific neural abnormalities. We have cloned dsf and rescued both behavioral and neural phenotypes. dsf encodes a nuclear receptor closely related to the vertebrate Tailless proteins and is expressed in both sexes in an extremely limited set of neurons in regions of the brain potentially involved in sexual behavior. Expression of a female transformer cDNA under the control of a dsf enhancer in males leads to dsf-like bisexual behavior.
Combining opinion from expert panels is becoming a more common method of selecting criteria to define quality of health care. The Rand Corporation pioneered this method is the 1950s and 1960s in the context of forecasting technological events. Since then, numerous organizations have adopted the methodology to develop local and national policy. In the context of quality of care, opinion is typically elicited from a sample of experts regarding the appropriateness or importance of a medical treatment for several well-defined clinical cohorts. The information from the experts is then combined in order to create a standard or performance measure of care. This article describes how to use the panel process to elicit information from diverse panels of experts. Methods are demonstrated using the data from five distinct panels convened as part of the Harvard Q-SPAN-CD study, a nationally-funded project whose goal is to identify a set of cardiovascular-related performance measures.
PURPOSE: To analyze the challenge of using health outcomes data to compare plans, networks and providers. ANALYSIS: Different questions require different designs for collecting and interpreting health outcomes data. When evaluating effectiveness of treatments, tests or other technologies, the question is what processes improve health outcomes? For this purpose, the strongest evidence comes from a double-blind randomized controlled trial. In program evaluations, the question is 'what is the impact of this policy and related programs on health outcomes?' For this purpose, we may be able to randomize subjects, but are more likely to have a quasi-experimental or an epidemiological design. When we compare plans, networks and providers for quality improvement purposes the question is 'do these specific plans perform differently from one another?', or, 'are these specific plans improving their performance over time?' We want to isolate for study the effects attributable to specific plans. Designs that yield strong evidence cannot be applied because we lack experimental control. CONCLUSIONS: When we already have strong evidence linking specific processes of care with specific outcomes, comparing process data may reveal more about performance of plans, networks and providers than comparing outcomes data. Comparisons of process data are easier to interpret and more sensitive to small differences than comparisons of outcomes data. Outcomes data are most useful for tracking care given by high volume providers over long periods of time, targeting areas for quality improvement and for detecting problems in implementation of processes of care.
The Institute of Medicine defines health care quality as increasing "the likelihood of desired health outcomes" using "services ... consistent with current professional knowledge." This definition implies that quality measures can be based on either achieving health care outcomes or completing processes that experts agree have been shown by scientific evidence to improve outcomes. Process-based measures are especially suitable when the user needs to know how to improve quality, when provider comparisons show equivalent outcomes but all providers should improve processes, when measures are needed to evaluate health care that is intended to improve long-term outcomes, or when the contribution of individual providers (especially providers who have a small number of cases) needs to be defined. However, many different process-based measures are needed to comprehensively assess quality, and many process-based measures require detailed clinical data currently found only in medical records. Therefore, the expense of abstracting records is a barrier to process-based measurement. Fortunately, large-scale process-based measures are becoming more feasible because the required clinical data are being included in large databases. The merging of existing inpatient and outpatient databases with pharmacy and laboratory databases is an important step toward obtaining data that link all patient admissions, appointments, diagnostic procedures, and prescriptions with diagnoses and test results. Other data that are valuable for process-based measures must still be obtained by abstracting data from records, including clinical findings, patient preferences, and medical and family history. In the future, such data may be added to large databases to create computerized medical records.