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PubMed1997

Geography of AIDS-associated Kaposi's sarcoma in Europe.

BACKGROUND: Classical Kaposi's sarcoma (KS) is about four times more common in southern Europeans than in northern Europeans. OBJECTIVE: To describe the epidemiology of AIDS-associated KS (AIDS-KS) in Europe and to determine whether it occurs with increased frequency in southern Europe. METHODS: Analysis of the 'European non-aggregate AIDS data set', as of September 1995. Countries with a cumulative total of > or = 50 KS cases as the presenting manifestation of AIDS were included. Homosexual men were excluded from south versus non-south comparisons because of possible confounding effects due to their route of HIV transmission. RESULTS: KS was the presenting manifestation of AIDS for 13.3% (16,367 out of 122,679) of men and 2% (491 out of 24,826) of women. In all countries, the risk for KS was higher in individuals who acquired HIV infection via sexual rather than parenteral transmission. Among AIDS patients, there is little difference by sex in the risk of KS in injecting drug users (IDU) or transfusion recipients. The percentage with KS increased with age among homosexual and bisexual men, from 10% in the age group 15-19 years to 23% in the age group 30-39 years. In all countries, the percentage with KS declined over time. The risk of KS was not significantly higher in southern Europe. The percentage with KS in southern Europe was slightly lower than in northern Europe (P > 0.1) in male IDU (1.8% versus 2.1%), and only slightly higher (P > 0.1) in female IDU (1.5% versus 1.1%), in male transfusion recipients (3.5% versus 3.0%), in female transfusion recipients (2.4% versus 2.3%), and in both heterosexual men (7.5% versus 6.2%) and women (2.0% versus 1.6%) excluding those originating from countries where heterosexual HIV transmission is frequent. CONCLUSIONS: The strong geographic predilection described for classical KS in southern Europe was not seen for AIDS-KS. If KS is caused by a viral infection in an immunodeficient host, our findings suggest the geographical variations in classical KS are not due to variation in prevalence of the causative virus but may be due to geographical variations in the prevalence of a form of mild immunodeficiency.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Quality of life (QoL) in dementia: a comparison of the perceptions of people with dementia and care staff in residential homes.

Evaluating quality of life (QoL) in people with dementia has become increasingly valued, for example in assessing the effectiveness of interventions or making treatment decisions. This study compared the QoL of people with dementia as assessed by the individuals and their care staff, and possible factors associated with the discrepancy between ratings. Seventy-six dyads of people with dementia and care staff in 9 residential homes were recruited. People with dementia were interviewed, using the "quality of life-Alzheimer disease" (QoL-AD) and assessed for severity of cognitive impairment. Staff completed the QoL-AD with respect to the person with dementia, and measures assessing their job satisfaction, level of hope, and person-centeredness. Results showed that people with dementia and care staff rated QoL differently. Some items on the QoL-AD ("physical health," "family," and "friends") were rated similarly between the 2 groups and others differently ("ability to do chores," "marriage/closest relationship," "memory," and "life as a whole"). Neither staff factors (hope, person-centeredness, or job satisfaction) nor the severity of cognitive impairment in the people with dementia explained the discrepancy between ratings. However, when data were aggregated within residential settings, a correlation between increased hope in staff and better resident assessed QoL emerged. Care homes should be aware that low staff hope may be linked to lower resident QoL. Effective training and support for care staff may impact on residents' QoL.

Adolescent↗

PubMed2002

Familial head and neck cancer: molecular analysis of a new clinical entity.

OBJECTIVE: The tumor suppressor gene p16 encodes a cyclin-dependent kinase inhibitor that normally inhibits cell proliferation by causing a G1 cell cycle arrest. The p16 gene is frequently mutated in a variety of somatic tumors, as well as in familial melanoma and familial pancreatic carcinoma. We identified a family with a high incidence of head and neck squamous cell carcinoma (HNSCC) and melanoma. Molecular analyses of the p16 gene locus in blood and tumor DNA from this family was performed to determine whether an association between germline p16 gene mutation and HNSCC exists. STUDY DESIGN: Molecular pedigree analyses. METHODS: Exon 2 of p16 was polymerase chain reaction amplified from blood, tumor, or nontumor DNA isolated from affected and unaffected members, then directly sequenced and compared with consensus p16 sequence. Cell cycle position of cells expressing wild-type or mutant p16 was determined by flow cytometry. RESULTS: Molecular analyses revealed a nonfunctional germline point mutation within exon 2 of the p16 gene that encodes a mutant p16 protein substituting proline at amino acid position 87 for the wild-type arginine (p16R87P). Relative to wild-type p16, p16R87P lost ability to cause a growth arrest following ectopic expression. The mutant (p16R87P) allele segregated with cancer predisposition in tested family members, and analyses of HNSCC tumor tissues demonstrated universal loss of wild-type allele. CONCLUSIONS: Significance of the mutant p16 (p16R87P) in HNSCC tumorigenesis is strongly suggested by its loss of cell cycle arrest activity and its retention in tumor tissue with simultaneous loss of the wild-type allele. Further, the germline p16 mutation segregated with cancer predisposition within the family. In aggregate, these data suggest that there is a direct causal relationship between the germline p16 mutation in this family and HNSCC tumorigenesis. Based on our observations, the spectrum of familial cancers associated with p16 mutations should include a new clinical entity, familial HNSCC.

Alleles↗

PubMed1989

Health services research and quality of care. Assignments for the 1990s.

The unabated rise in health care costs is bringing health services research into center stage as an applied science to help guide health care managers, purchasers, and regulators. To be equal to the task, health services research must pursue at least four intellectual agendas: the study of efficacy (knowing what works), the study of appropriateness (using what works), the study of the execution of care (doing well what works), and the study of the purposes of care (the values that underlie action). The responsibility for the financing and conduct of the research agendas varies with the level of aggregation of data and effort needed for each topic. All four topics must be pursued effectively if health care quality is to be successfully defined, measured, and protected.

Economics, Hospital↗

PubMed1991

Organizational assessment in intensive care units (ICUs): construct development, reliability, and validity of the ICU nurse-physician questionnaire.

Health Services Research has a growing need for reliable and valid measures of managerial practices and organizational processes. A national study of 42 intensive care units involving over 1,700 respondents provides evidence for the reliability and validity of a comprehensive set of measures related to leadership, organizational culture, communication, coordination, problem solving-conflict management and team cohesiveness. The data also support the appropriateness of aggregating individual respondent data to the unit level. Implications for further research are discussed.

Analysis of Variance↗

PubMed1992

Explaining area variation in the use of Medicare home health services.

This study examines the determinants of area-level variation in Medicare home health use in 1985 for the entire United States, using data from Medicare Home Health Bills, the Medicare/Medicaid Automated Certification System, the Medicare Provider Analysis and Review Files, and other sources. Weighted two-stage least squares regression was used to analyze variation in the number of home health users per 1,000 enrollees and the average number of visits received per user. The data were aggregated to the Metropolitan Statistical Area and the rural part of the state, resulting in 343 units of analysis. According to the study's results, higher proportions of Medicare enrollees use home health services in areas with fewer nursing home beds per enrollee, higher hospital discharge rates, and shorter mean lengths of stay, higher Medicare reimbursement ceilings for skilled nursing home health visits, and more home health agencies per enrollee. Other things being equal, beneficiaries in New England are 40% more likely to use home health services than their counterparts in other regions with similar climates. The average number of visits received by home health users appears to be higher in areas where there are more agencies per enrollee and a higher share of agencies that are proprietary. There also appear to be large regional differences in the number of visits received per user. Our results imply that constrained access to nursing home beds is leading to higher levels of Medicare home health use and that there may be further savings from the substitution of home health services for hospital days. The study shows that Medicare reimbursement ceilings may constrain use and that access may be a problem for beneficiaries in areas with fewer agencies per enrollee. This study also points to significant regional variation in the proportion of beneficiaries who use home health services, even with controls for many different explanatory variables. Overall, our results suggest the possibility of serious limitations in access to Medicare home health services.

Certificate of Need↗

PubMed1998

Variations in standardized hospital mortality rates for six common medical diagnoses: implications for profiling hospital quality.

OBJECTIVES: The authors determined whether standardized hospital mortality rates varied for six common medical diagnoses. METHODS: The retrospective cohort study included 89,851 patients aged 18 years and older discharged from 30 hospitals in a large metropolitan area in 1991 to 1993 with a principal diagnosis of acute myocardial infarction, congestive heart failure, pneumonia, stroke, obstructive lung disease, or gastrointestinal hemorrhage. For each hospital, standardized mortality ratios (observed/predicted mortality) were determined using validated risk-adjustment models that were based on clinical data elements abstracted from patients' hospital records. Hospitals also were categorized into quintiles on the basis of standardized mortality ratios. Correlations between standardized mortality ratios and agreement between quintile rankings were determined for each pair of diagnoses. RESULTS: Correlations between hospital-standardized mortality ratios for individual diagnoses were generally weak. For the 15 possible pairs of diagnoses, Pearson coefficients ranged from -0.10 to 0.43; only six were 0.30 or greater. Agreement between hospital quintile rankings was also generally low, with weighted kappa values ranging from -0.12 to 0.42. Three of 15 kappa values were less than 0 (ie, agreement lower than chance), and only four exceeded 0.20, the threshold for "fair" agreement. Although simulated analyses found that random variation and relatively low hospital volumes accounted for some of the difference in standardized mortality ratios for diagnoses, a large proportion of the difference remained unexplained. CONCLUSIONS: Standardized hospital mortality rates varied for six diagnoses that likely are managed by similar practitioners. Although variability may be decreased by restricting analyses to hospitals with large volumes, the findings indicate that for many hospitals, diagnosis-specific mortality rates may be an inconsistent measure of hospital quality, even when data are aggregated for multiple years.

Adolescent↗

PubMed1989

HIV and HTLV-I infections in the Americas: a regional perspective.

With over 143,000 cases of AIDS reported to the World Health Organization from 145 countries and with an estimated 5 to 10 million people worldwide infected with HIV, AIDS has become firmly established as a global pandemic. In the region of the Americas over 100,862 cases of AIDS have been reported with indigenous transmission documented in 45 to 46 countries. While North America has the highest annual number of AIDS cases per population, with 72 cases/million, the Caribbean subregion has a disproportionately high number of cases, with annual rates as high as 200 to 300 cases/million population for some countries. Despite differences in absolute number of cases, there has been a remarkable similarity in the temporal rate of increase of AIDS in the countries of the Americas, reflecting delayed introduction of the virus to some areas with an early exponential increase similar to that observed initially in the United States. Although the modes of transmission of HIV are the same throughout the region, evidence of increasing bisexual and heterosexual transmission, particularly in the Caribbean subregion, has resulted in a lower male-to-female ratio of AIDS cases and increased perinatal transmission. Clinically, a resurgence of diarrheal diseases, respiratory infections, and tuberculosis has been documented in association with HIV infection in many tropical countries of the Americas. With relatively high rates of HTLV-I infection already established in the Caribbean subregion, the overall public health problems of the Americas will be markedly potentiated by further spread of these 2 human retroviruses. If HIV infection continues to penetrate the poor and less advantaged populations in Latin America and the Caribbean, the potential exists for a massive epidemic in the Americas that may rapidly parallel the situation in Africa.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

The impact of nurses' empathic responses on patients' pain management in acute care.

BACKGROUND: Although nurses have the major responsibility for pain management, little is known about nurses' responses to patients in the process of managing acute pain. OBJECTIVE: To examine the relationship between nurses' empathic responses and their patients' pain intensity and analgesic administration after surgery. METHODS: Two hundred twenty-five patients from four cardiovascular units in three university-affiliated hospitals were interviewed on the third day after their initial, uncomplicated coronary artery bypass graft (CABG) surgery about their pain and current pain management. Concurrently, their nurses' (n = 94) empathy and pain knowledge and beliefs were assessed. Patient data were aggregated and linked with the assigned nurse to form 80 nurse-patient pairs. RESULTS: Nurses were moderately empathic, and their responses did not significantly influence their patients' pain intensity or analgesia administered. Patients reported moderate to severe pain but received only 47% of their prescribed analgesia. Patients' perceptions of their nurse's attention to their pain were not positive, and empathy explained only 3% of variance in patients' pain intensity. Deficits in knowledge and misbeliefs about pain management were evident for nurses independent of empathy, and knowledge explained 7% of variance in analgesia administered. Hospital sites varied significantly in analgesic practices and pain inservice education for nurses. CONCLUSIONS: Empathy was not associated with patients' pain intensity or analgesic administration.

Adult↗

PubMedDate not supplied

Treating uncomplicated Neisseria gonorrhoeae infections: is the anatomic site of infection important?

BACKGROUND: The efficacy of new antimicrobial regimens against Neisseria gonorrhoeae infection of sites other than the urethra and cervix is rarely adequately assessed. GOAL OF THIS STUDY: To learn whether modern antigonococcal agents eradicate infections at some mucosal sites less reliably than at others. STUDY DESIGN: This was a systematic review of published therapeutic trials of various antimicrobial regimens for the biological cure of uncomplicated mucosal Neisseria gonorrhoeae infections. Data were aggregated by treatment regimen and the cure rates were calculated by site of infection. RESULTS: Of 16,737 infections, 96.4% were cured--female urethra, 98.4%; male urethra, 96.4%; cervix, 98.0%; female pharynx, 83.7%; male pharynx, 79.2%; female rectum, 97.9%; and male rectum, 95.3%. The differences between the cure rates at the pharynx and at all other sites were statistically significant in the crude analysis and after stratifying by treatment regimen. CONCLUSION: Modern antigonococcal regimens highly effective against infection of the urethra are highly effective at the cervix and rectum as well, but pharyngeal infections are more difficult to cure.

Anti-Bacterial Agents↗

PubMed1995

Comparison of substrate metabolism by wild type CYP2D6 protein and a variant containing methionine, not valine, at position 374.

We have analysed kinetic parameters of cDNA-derived CYP2D6 proteins derived from the original CYP2D6 cDNA isolate (Gonzalez FJ et al. Nature 1988: 331, 442-446) which contains methionine at position 374 (CYP2D6-Met) and a modified cDNA which contains valine at position 374 (CYP2D6-Val). This latter protein is predicted from the CYP2D6 genomic sequence. Several quantitative differences, but no qualitative differences in metabolism were observed. CYP2D6-Met was found to have a two-fold lower Km and a three-fold lower turnover rate for (R)(+)-bufuralol 1'-hydroxylation as compared to CYP2D6-Val. In contrast, CYP2D6-Met and CYP2D6-Val had a similar Km for debrisoquine 4-hydroxylation while CYP2D6-Val had an 18-fold higher turnover rate. CYP2D6-Val and CYP2D6-Met had similar Kms for metoprolol but CYP2D6-Val showed a three-fold higher capacity for the O-demethylation reaction compared to alpha-hydroxylation which is more similar to that seen in human liver. In the case of sparteine, CYP2D6-Val and CYP2D6-Met showed similar capacities for formation of the 2-dehydrosparteine metabolite but the Km value for CYP2D6-Met was six-fold higher than that for CYP2D6-Val. Kinetic differences between CYP2D6-Met and CYP2D6-Val were further probed by examination of apparent Ki for inhibition of (R,S)(+/-)-bufuralol 1'-hydroxylation. Similar Ki values (within a factor of three) were observed for perhexiline and (R,S)-propranolol while quinidine and dextromethorphan were 8.5-fold and 21-fold more effective inhibitors of CYP2D6-Val relative to CYP2D6-Met. An allele specific polymerase chain reaction assay was developed for the CYP2D6-Met allele. The CYP2D6-Met allele was not found among 83 individuals. In the aggregate, these data indicated that the CYP2D6-Val allele is the more common allele in human populations. The quantitative kinetic differences between these two enzymes appears most pronounced for substrates/inhibitors with rigid structures. CYP2D6-Val more often has a substantially lower Km and/or a substantially higher capacity to metabolize those substrates.

B-Lymphocytes↗

PubMed2000

Designing an ambulatory clinical practice for outcomes improvement: from vision to reality--the Spine Center at Dartmouth-Hitchcock, year one.

Development of a new program for diagnosis and treatment of spine-related problems provided a unique opportunity to design and implement a new model for delivery of health care incorporating outcomes measurement and improvement. Key features include: application of microsystem thinking and interdisciplinary practice; integration of a uniform outcomes measurement tool, the Dartmouth Clinical Value Compass; and touch pad technology for data collection. This, for the first time, provided clinically meaningful point-of-service data and aggregated information for improvement. A further advantage was the ability to integrate a clinical research program within this microsystem. A multisite clinical research trial, the Spine Patient Outcomes Research Trial (SPORT), modeled on the Spine Center microsystem and funded by The National Institute of Arthritis, Musculoskeletal and Skin Diseases and the Office of Research on Woman's Health, the National Institutes of Health, and the National Institute of Occupational Safety and Health, the Centers for Disease Control and Prevention, is currently underway. The significant problems we face today cannot be solved by the same level of thinking that created them.

Ambulatory Care↗

PubMed2002

Current controversies in deep vein thrombosis prophylaxis after orthopaedic surgery.

As a result of easy measurable perioperative bleeding and a high number of subclinical deep vein thromboses after surgery, total hip replacement has become a benchmark for antithrombotic drug development. Today, a nonscientific evidence-based transatlantic view on thromboprophylaxis in orthopaedic surgery exists. Efforts should be taken to bridge these divergent opinions. We need to standardize study designs that allow unbiased comparison and aggregation of data to get insight in rare complications like the cauda equina syndrome associated with spinal analgesic techniques and anticoagulation and to optimize thromboprophylaxis in homogeneous groups of patients. Dosage, timing of initiation in relation to surgery, and duration of prophylaxis seems a crucial and open question for all homogeneous groups of orthopaedic patients. A definition on surgical bleeding, which allows practical measurement procedures and quantification, is lacking. Clinical studies on vascular endpoints are warranted to achieve relevant basic data for health economic analyses, which also lack scientific standardized procedures. An intercontinental close cooperation is needed to solve these issues.

Anticoagulants↗

PubMed2002

Usefulness of the BASIS-32 in evaluating program level outcomes.

The Behavior and Symptom Identification Scale (BASIS-32) is a survey used to collect clients' reported perceptions of their symptoms and functioning. This article assesses the usefulness of the BASIS-32 for evaluating program outcomes in California's statewide performance outcome system for adults with serious mental illnesses. The authors found that, while the instrument could be useful at the clinical level, it did not work well when data were aggregated at the program or system level. Not only did clients drastically under-report their symptoms, but improvements over time, although statistically significant, were negligible and of little practical use for assessing system-level outcomes. In addition, the costs and logistical complexities associated with site licensing became increasingly difficult to justify when compared to obtaining similar information from other sources.

Journal Article↗

PubMedDate not supplied

Monitoring reproductive aging in a 5-year prospective study: aggregate and individual changes in luteinizing hormone and follicle-stimulating hormone with age.

OBJECTIVE: This study describes age-related changes in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in a 5-year prospective study of reproductive aging. DESIGN: Participants (n = 156 college-educated, white, US women; 25 to 58 y) were recruited from the TREMIN Research Program on Women's Health. They collected daily urine specimens for 6 months in each of 5 consecutive years. Specimens were assayed for LH and FSH. Aggregate changes were calculated in LH and FSH with age, and multilevel models were used to estimate individual hormone trajectories and within-woman and between-woman variances by age. RESULTS: Aggregate LH levels increased beginning after age 45; FSH increased at all ages, accelerating after age 45. Individual-level patterns with age included the following: reproductive-age LH and FSH levels, with increasing FSH and increasing or decreasing LH (ages 20 to 49); rapidly increasing LH and FSH (ages 40 to 59); and increasing or steady postmenopausal LH and FSH (ages 46 to 62). FSH levels were consistently high in the latter category, but LH levels overlapped with levels found in younger women (<45 y). Individual LH patterns showed more variability (5% to 35% of total variance) than FSH (3% to 22% of total variance). Both hormones had relatively low variation within individuals compared with between-woman differences (65% to 97% of total variance). CONCLUSIONS: Aggregate-level data do not reflect differences across women and oversimplify the age-related increases and variability in LH and FSH. Individual FSH levels are not distinguishable from reproductive-age levels until after rapid perimenopausal increases in FSH occur; individuals vary in whether their postmenopausal LH levels are distinguishable from reproductive-age levels.

Adult↗

PubMed2003

Microtubule-associated protein-2 and class III beta-tubulin are expressed in extraskeletal myxoid chondrosarcoma.

Extraskeletal myxoid chondrosarcoma is a rare soft tissue sarcoma of uncertain histogenetic origin. Because recent reports have indicated neural-neuroendocrine differentiation in some extraskeletal myxoid chondrosarcomas, we investigated 25 tumors for expressions of microtubule-associated protein-2 and Class III beta-tubulin, which are major components of microtubules and specifically localized in neurons and their derivatives. Immunohistochemical expression of microtubule-associated protein-2 and Class III beta-tubulin was studied in extraskeletal myxoid chondrosarcomas using formalin-fixed, paraffin-embedded tissues. Cytoplasmic expressions of microtubule-associated protein-2 and Class III beta-tubulin were detected in 21 (84%) and 13 (52%) of the 25 extraskeletal myxoid chondrosarcomas, respectively, although the number of positively stained tumor cells varied. Expression of the Class III beta-tubulin gene was also assessed in two immunohistochemically positive cases by in situ hybridization using an oligonucleotide probe specific for its transcript, and both cases showed expression of Class III beta-tubulin transcript. Another case was examined with immunoelectron microscopy, and immunogold particles for Class III beta-tubulin were localized to microtubular aggregates. Our data indicate that microtubules in extraskeletal myxoid chondrosarcoma are similar to those found in neurons, further supporting the concept that neural-neuroendocrine differentiation occurs in a significant number of extraskeletal myxoid chondrosarcoma.

Chondrosarcoma↗

PubMed2007

Effects of partner notification on reducing gonorrhea incidence rate.

OBJECTIVE: The objective of this study was to estimate the effectiveness of partner notification (PN) by linking measures of PN with the gonorrhea incidence rate in New York State exclusive of New York City. STUDY DESIGN: Gonorrhea cases were identified from the Communicable Disease Confidential Case Reports system. Case interview data were obtained from the case management database. Gonorrhea incidence data and interview data were aggregated from individual records and then linked at the county level. RESULTS: From 1992 to 2002, 100,756 gonorrhea cases were reported and 37% were interviewed. A total of 34,807 partners were elicited from 37,393 index cases: 18,291 (52.5%) partners sought medical evaluation, 10,159 (29.2%) received preventive treatment, and 7,474 (21.5%) were infected and treated. The gonorrhea incidence rate was inversely correlated with the percent of partners given preventive treatment and positively related to the percent of infected partners. CONCLUSIONS: Our study adds new evidence that PN is an effective mechanism to detect new cases and interrupt disease transmission within communities.

Contact Tracing↗

PubMed2007

In-vitro efficacy of different platelet glycoprotein IIb/IIIa antagonists and thrombolytics on platelet/fibrin-mediated clot dynamics in human whole blood using thrombelastography.

Suppressing platelet activation improves efficacy of thrombolytic therapy for stroke and acute myocardial infarction. Combination treatment with recombinant tissue plasminogen activator (r-tPA) and glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor that binds with high affinity to platelets may therefore improve the efficacy of thrombolytic therapy. The effect of platelet GPIIb/IIIa antagonists and/or r-tPA on the dynamics of platelet/fibrin clot formation, strength, and lysis was determined using thrombelastography in human blood under thrombin or tissue factor stimulation. The study utilized platelet GPIIb/IIIa antagonists with high affinity and slow off-rate (Class I) from resting and activated platelets in comparison with Class II antagonists (lower affinity and fast off-rate from platelet GPIIb/IIIa receptors). The combination of the active form of roxifiban (XV459; Class I) or the active form of orbofiban (Class II) with a subeffective concentration of r-tPA resulted in a synergistic effect in clot lysis with roxifiban active form XV459 but not with that of orbofiban at therapeutically achievable concentrations that inhibit human platelet aggregation. These data indicate differential enhanced thrombolysis of low levels of r-tPA with high-affinity Class I but not with low-affinity Class II GPIIb/IIIa antagonists in the absence of anticoagulants.

Anticoagulants↗