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Biomedical subjects

A Gafni

Publications and source records attributed to A Gafni.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comparison of human papillomavirus DNA testing and repeat Papanicolaou test in women with low-grade cervical cytologic abnormalities: a randomized trial. HPV Effectiveness in Lowgrade Paps (HELP) Study No. 1 Group.

BACKGROUND: Results of cervical cytology screening showing atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL) indicate risk for high-grade cervical intraepithelial neoplasia (CIN 2 or 3). In a community-based randomized trial we compared the test performance of human papillomavirus (HPV) DNA testing with that of 6-month repeat Papanicolaou (Pap) test in detecting histologically confirmed CIN 2 or 3. METHODS: We randomly assigned 212 women aged 16-50 years with ASCUS or LSIL on cervical cytology screening to undergo either immediate HPV DNA testing or a repeat Pap test in 6 months. Cervical swabs for the HPV DNA testing and the Pap smears were obtained by their family physicians. We tested the swabs for oncogenic HPV using the Hybrid Capture II assay (Digene Corp., Beltsville, Md.). Community-based pathologists examined the Pap smears. All women were referred for colposcopy by their family physicians. Two gynecological pathologists assessed the histology findings. We calculated test performance in women who completed the trial using CIN 2 or 3 as the reference standard. RESULTS: A total of 159 women completed the study. Compared with HPV DNA testing, which detected 87.5% (7/8) of the cases of CIN 2 or 3, repeat Pap smear showing high-grade intraepithelial neoplasia (HSIL) detected 11.1% (1/9) of cases (p = 0.004), and repeat Pap smear showing ASCUS, LSIL or HSIL detected 55.6% (5/9) (p = 0.16). Corresponding specificities were 50.6%, 95.2% (p = 0.002) and 55.6% (p = 0.61). Loss to follow-up was 17.1% in the HPV test group and 32.7% in the repeat Pap group (p = 0.009). Given the 7 cases of CIN 2 or 3 detected by HPV testing and the 5 cases detected by the repeat Pap smear, the incremental cost of HPV testing was calculated to be $3003 per additional case of CIN identified. INTERPRETATION: HPV DNA testing was more costly but was associated with significantly less loss to follow-up. It may detect more cases of CIN 2 or 3 in women with low-grade cytologic abnormalities.

Adolescent↗
PubMed2000

Hydrogen exchange at the core of Escherichia coli alkaline phosphatase studied by room-temperature tryptophan phosphorescence.

The room-temperature tryptophan (Trp) phosphorescence lifetime is sensitive to details of the local environment and has been shown to increase significantly in some proteins following H-D exchange. Careful analysis of the phosphorescence lifetime distribution of Trp 109 in Escherichia coli alkaline phosphatase (AP) in solution as a function of time during the H-D exchange shows that this process corresponds to a two-state reaction resulting from the deuteration of a single, specific hydrogen in the core of the protein. The absence of a pH dependence of the exchange rate suggests that the exchange is not an EX2 process, and therefore, a certain degree of unfolding is required for exchange to occur. This discovery opens up the use of phosphorescence-detected hydrogen exchange as a sensitive tool for monitoring the local susceptibility and activation energy for exchange in proteins having a phosphorescent Trp and, for example, for studying the effects of local mutations upon that susceptibility.

Alkaline Phosphatase↗
PubMed2000

Aggregation of an amyloidogenic fragment of human islet amyloid polypeptide.

Native human islet amyloid polypeptide (hIAPP) has been identified as the major component of amyloid plaques found in the pancreatic islets of Langerhans of persons affected by type 2 diabetes mellitus. Early studies of hIAPP determined that a segment of the molecule, amino acids 20-29, is responsible for its aggregation into amyloid fibrils. The present study demonstrates that the aggregation of hIAPP 20-29-Trp is a nucleation-dependent process, displaying a distinct lag time before the onset of rapid aggregation. Moreover, the lag time can be eliminated by seeding the sample of unaggregated peptide with preformed fibrils. In contrast to the expectation from the conventional model of nucleation-dependent aggregation, however, the lag time of hIAPP aggregation does not depend on peptide concentration. To explain this observation, a modified version of the standard model of nucleation-dependent aggregation is presented in which the monomeric peptide concentration is buffered by an off-aggregation-pathway formation of peptide micelles.

Amyloid↗
PubMed2000

A cross-cultural consumer-based decision aid for screening mammography.

BACKGROUND: "Women should have mammograms" is the usual perspective of educational interventions about screening. The perspective that "women should be informed" about potential risks and benefits so they can make value- and evidence-integrated personal decisions has recently been advocated. However, this perspective has not previously been operationalized. We developed an evidence-based cross-cultural mammography decision aid (MDA), for European American and Mexican American women who are 50-70 years old, at average risk of breast cancer, of varying educational levels, and English- or Spanish-speaking. METHODS: MDA development included: (1) content development by a multidisciplinary team and lay women and (2) testing for validity and reliability. Four parts include: (1) introduction; (2) information about logistics (cost, time, discomfort) and risks (sequelae of false-positive or negative results; (3) probability of developing breast cancer; and (4) benefit of mammography regarding breast cancer outcomes (e.g., death and recurrence). We assessed reliability (stability of decisions with the same information) after 1-2 weeks. We assessed validity (comprehension of information) quantitatively (probabilities were changed to see whether preferences changed predictably) and qualitatively (focus groups, standardized probes for comprehension). Subjects were a convenience sample of 49 European American (50-81 years old) and 54 Mexican American (49-89 years old) women from administrative staff at a medical school, the waiting room of an indigent primary care clinic, and a community center. RESULTS: Reliability was 100%. In quantitative validity testing, 22 of 28 women (89%) changed preference as predicted with changed probabilities. Comprehension was confirmed qualitatively in all phases of testing with both Spanish and English versions. CONCLUSION: The decision aid is valid and reliable in English and Spanish for southwestern Mexican American and European American women at average risk of breast cancer, including those of low educational levels.

Aged↗
PubMed2000

Developing a model of collaborative research: the complexities and challenges of implementation.

While the benefits of collaborative research have been well documented, fewer publications exist regarding the complex, problematic issues involved in these undertakings. This paper offers an integrated collaborative research model to depict the complexities and challenges of initiation and implementation of a 2 1/2 year joint research project between a community hospital and a university school of nursing in Southern Ontario, Canada. A sampling of the experiences of the researchers are analyzed to clarify the dynamic and often competing issues and interactions involved in encouraging hospital-wide research involvement during periods of organizational growth and change. The model reflects the simultaneous interaction of organizational, change and collaborative processes while maintaining the rigor of the research (RCT), and ensuring minimal disruption to the service agency. Quantitative outcomes of this collaboration are presented through an analysis of participant involvement on multiple organizational levels. Recommendations for future collaborative research, including design and methodological issues and collaborative and change strategies are offered. The complexity of balancing the necessary trade-offs required of successful collaborative research are highlighted and will be useful to those considering and planning future collaborations.

Clinical Nursing Research↗
PubMed2000

Do potential patients prefer tissue plasminogen activator (TPA) over streptokinase (SK)? An evaluation of the risks and benefits of TPA from the patient's perspective.

BACKGROUND: In patients with acute myocardial infarction, TPA (compared to SK), has been shown to reduce the 30-day mortality rate at the expense of an increased rate of stroke. The assumption in the literature is that were it not for cost issues, all patients presenting with a myocardial infarction would choose TPA. Our hypothesis is that, for many informed individuals, regardless of cost, the increased risk of stroke may deter them from selecting TPA over SK. OBJECTIVE: To assess which thrombolytic drug informed patients would prefer and to explore the clinical and economic implications of such preferences. DESIGN: Prospective survey. SETTING: Tertiary care hospital. PATIENTS: 120 hospitalized patients with cardiac disease who would be "at risk" for a myocardial infarction. INTERVENTIONS: Face-to-face interviews utilizing a decision instrument. MEASUREMENTS: To minimize bias in soliciting patients' preferences and to standardize the presentation of information we developed a decision instrument which portrays a case scenario of a myocardial infarction, describes treatment outcomes (survival and stroke rate), and displays the likelihood of these outcomes with SK and TPA using three scenarios: a base stroke risk (all patients data), a lower stroke risk (<75 years old data), a higher stroke risk (>75 years old data). Outcome data were derived from the published literature (GUSTO study). RESULTS: When presented the overall results of the GUSTO study, 60/120 (50%) expressed a preference for SK. When presented the outcome data for the subgroups of patients <75 years old (lower stroke rate), 37/120 (31%) preferred SK. When presented the subgroup data for patients >75 years old (higher stroke risk), 67/120 (56%) preferred SK. CONCLUSIONS: Regardless of the scenario that individuals were presented with, a substantial proportion of individuals (31-56%) who could potentially require thrombolytic therapy chose SK over TPA. This study should be repeated in other settings to establish the generalizability of our results. Assuming that these results will be consistent, considering the patient's perspective has significant implications on clinical decision making as well as from an economic perspective.

Aged↗
PubMed2000

Noninvasive positive pressure ventilation in the setting of severe, acute exacerbations of chronic obstructive pulmonary disease: more effective and less expensive.

OBJECTIVE: The use of noninvasive ventilation for patients with acute respiratory failure has become increasingly popular over the last decade. Although the literature provides good evidence for the effectiveness of noninvasive ventilation in addition to standard therapy compared with standard therapy alone in patients with chronic obstructive pulmonary disease (avoiding intubation and improving hospital mortality), the associated costs have not been rigorously measured. Adding noninvasive positive pressure ventilation (NPPV) to standard therapy in the setting of a severe, acute exacerbation of chronic obstructive pulmonary disease (COPD) in patients with respiratory acidosis who are at high risk of requiring endotracheal intubation is both more effective and less expensive. DESIGN: Economic evaluation based on theoretical model. SETTING: This analysis base case was modeled for a tertiary care, teaching hospital. PATIENTS OR OTHER PARTICIPANTS: Carefully selected patients with severe exacerbations of COPD. INTERVENTION: The two alternative therapies compared were standard therapy (oxygen, bronchodilators, steroids, and antibiotics) and standard therapy plus NPPV. MEASUREMENTS AND MAIN RESULTS: As the hypothesis was dominance, the main outcomes modeled and calculated were costs, mortality rate, and rates of intubation between the two interventions. To determine clinical effectiveness, we used a meta-analysis of randomized trials evaluating the impact of NPPV on hospital survival. A decision tree was constructed and probabilities were applied at each chance node using research evidence and a comprehensive regional database. To provide data for this economic evaluation, MEDLINE literature searches were conducted. Bibliographies of relevant articles were reviewed, as were personal files. To estimate the costs of the alternative therapeutic approaches, eight types of hospitalization days were costed using the London Health Sciences Center costing data. Sensitivity analyses were performed, varying all assumptions made. The meta-analysis yielded an odds ratio for hospital mortality in the NPPV arm, compared with standard therapy, of 0.22 (95% confidence interval, 0.10-0.66). By using baseline case assumptions, we found a cost savings of $3,244 (1996, Canadian), per patient admission, if NPPV were adopted in favor of standard therapy. These findings present a scenario of clear dominance for treatment with NPPV. Sensitivity analyses did not alter the results appreciably. CONCLUSIONS: We conclude that from a hospital's perspective, NPPV and standard therapy for carefully selected patients with acute, severe exacerbations of COPD are more effective and less expensive than standard therapy alone.

Acute Disease↗
PubMed1999

Cost effectiveness of highly active antiretroviral therapy in HIV-infected patients. Swiss HIV Cohort Study.

BACKGROUND: Highly active antiretroviral therapy (HAART) has become the most important strategy for treating HIV infection in developed countries; however, access to HAART might vary under different funding policies. The Swiss health care system provides unrestricted access to HAART for all patients who need these newer combination therapies. This study investigated the impact of this funding policy on the society and health care system. METHODS: A cost-effectiveness analysis with natural history data and productivity estimates was based on the Swiss HIV Cohort Study. A random sample of patient charts was used to estimate health care costs. In addition to a base-case scenario, a pessimistic and an optimistic scenario of natural disease history was developed. Costs were expressed in 1997 Swiss francs (100 CHF correspond to about US$67) and effects as projected years of life gained. RESULTS: In the analysis limited to health care costs, on the basis of projected survival in each scenario, the cost-effectiveness ratio was 33,000 CHF (base case), 14,000 CHF (optimistic), and 45,000 CHF (pessimistic) per year of life gained. When changes in productivity were included, cost savings occurred in the base-case and optimistic scenarios. The cost-effectiveness ratio was 11,000 CHF per year of life gained in the pessimistic scenario. CONCLUSIONS: HAART increases expected survival and health care costs. However, when productivity gains are included, society will probably save costs or pay a low price for substantial health benefits. The study provides strong arguments, from a societal perspective, to continue the current policy of providing unrestricted access to HAART in Switzerland. The presented results also suggest that this policy could be of interest for other developed countries. Decision makers in developed countries where access to HAART is limited should re-evaluate their policy for the benefit of the society at large.

Anti-HIV Agents↗
PubMed1999

Proline isomerization is unlikely to be the cause of slow annealing and reactivation during the folding of alkaline phosphatase.

The in vitro folding of Escherichia coli alkaline phosphatase (AP) from the guanidine hydrochloride (GdnHCl) denatured state is characterized by a significant slow phase in the post activational recovery of native protein lability (probed by the susceptibility to GdnHCl denaturation and occurring on the time scale of days) as well as a slow phase in the recovery of activity (on the time scale of minutes). Slow folding events have often been attributed to cis-trans isomerizations of X-Pro peptide bonds, a plausible explanation for AP, which contains 21 prolines per subunit. To investigate the role of proline isomerization in the two measures of refolding mentioned above, we have performed "double-jump" GdnHCl denaturation/renaturation experiments, with a third jump, where the rate of unfolding of refolded protein upon exposure to denaturant was added to assess the rate of change of lability. Our measurements of the time evolution of both the lability and the reactivation of refolded AP as a function of denaturation time show that proline isomerization is unlikely to be the cause of either of these slow events in the refolding of AP. The conclusions are further confirmed by the absence of proline isomerization effects when AP is refolded in the presence of human and periplasmic E. coli peptidyl-prolyl isomerase.

Alkaline Phosphatase↗
PubMed1999

Prevalence of dysthymic disorder in primary care.

BACKGROUND: Dysthymic disorder is characterised as a chronic state of depressed mood which is not otherwise attributable to physical, psychological or social events. While it can occur alone, there is increasing evidence that the majority of individuals who meet criteria for dysthymic disorder also experience more severe episodic mood disorders throughout their lifetime, and there is also an aggregation of mood disorders within their family members. Patients with dysthymic disorder are most often seen in primary care. Some researchers suggest that the majority of these individuals are never diagnosed or are not diagnosed until a more severe episodic mood disorder develops. The objective of this study was to determine the 12-month prevalence of Axis I psychiatric disorders, and in particular dysthymic disorder, in a primary care Health Service Organization in Ontario, Canada. METHODS: Eligible and consenting adults registered with a primary care Health Service Organization were screened using the modified form of the University of Michigan Composite International Diagnostic Interview. RESULTS: Of the 6280 eligible subjects, 4327 (69%) consented to screening. Two hundred and twenty-two (5.1%) subjects screened positive for dysthymic disorder. In addition, 90% of those who screened positive for dysthymic disorder also screened positive for other Axis I disorders including major depressive disorder, panic, simple phobia, and generalized anxiety disorder. CONCLUSIONS: There is much potential for the primary care physician to play a pivotal role in the recognition and treatment of dysthymic disorder and associated Axis I disorders. A focus on the family as a unit for care may be especially important given the reported aggregation of dysthymic disorder within families.

Adolescent↗
PubMed1999

Decision-making in the physician-patient encounter: revisiting the shared treatment decision-making model.

In this paper we revisit and add elements to our earlier conceptual framework on shared treatment decision-making within the context of different decision-making approaches in the medical encounter (Charles, C., Gafni, A., Whelan, T., 1997. Shared decision-making in the medical encounter: what does it mean? (or, it takes at least two to tango). Social Science & Medicine 44, 681 692.). This revised framework (1) explicitly identifies different analytic steps in the treatment decision-making process; (2) provides a dynamic view of treatment decision-making by recognizing that the approach adopted at the outset of a medical encounter may change as the interaction evolves; (3) identifies decision-making approaches which lie between the three predominant models (paternalistic, shared and informed) and (4) has practical applications for clinical practice, research and medical education. Rather than advocating a particular approach, we emphasize the importance of flexibility in the way that physicians structure the decision-making process so that individual differences in patient preferences can be respected.

Canada↗
PubMed1999

Economic evaluations in the hip arthroplasty literature: lessons to be learned.

Readers are increasingly encountering articles dealing with health economic evaluations that compare various surgical strategies, leaving orthopaedists with the challenge of determining which program is cost-efficient and truly pertains to their setting. This study carries out a systematic review of the literature to appraise the quality, quantity, and type of economic evaluation as it pertains to the hip arthroplasty literature. To identify all relevant articles, we conducted a comprehensive computerized bibliographic search of Medline from 1966 to 1996. This search produced 1,611 abstracts that were screened. Studies that were incorporated met the following inclusion criteria: i) formal economic analysis, ii) an intervention specific to hip arthroplasty, and iii) the perspective of the study was evident (ie, patient, provider, society). These studies were appraised with regards to methodologic soundness based on 8 established economic principles. Only 68 articles from the 138 retrieved met the study criteria. Only 2 of the 68 articles met all 8 criteria of a comprehensive economic evaluation. The hip arthroplasty literature is deficient in methodologically sound economic evaluations. Several guidelines are introduced to aid orthopaedists in appraising the various economic studies, and recommendations are made to improve the quality of these studies in the orthopaedic literature. We suggest that the generation of such information should rank high on the priority list of the orthopaedic profession, granting agencies, and governments.

Arthroplasty, Replacement, Hip↗