Results of a global, patient-based survey assessing the impact of psoriatic arthritis discussed in the context of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory musculoskeletal disease, manifesting as peripheral arthritis, enthesitis, dactylitis, spondylitis, and skin and nail psoriasis. A core set of domains for measuring the impact of PsA has been developed, including pain, patient global assessment, physical function, health-related quality of life (HRQoL), and fatigue. To understand the impact of PsA on health domains from a patient's perspective, a global survey was developed and results reported in the context of the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire. METHODS: An online patient-based global survey was conducted by The Harris Poll in Australia, Brazil, Canada, France, Spain, Taiwan, the UK, and the US between November 2, 2017 and March 12, 2018. Eligible patients were ≥ 18 years old with a diagnosis of PsA for > 1 year, had visited a rheumatologist/dermatologist in the past 12 months and reported using ≥ 1 synthetic/biologic disease-modifying antirheumatic drug for PsA. Patients reported on PsA severity and symptoms, and the impact of PsA on HRQoL. After survey completion, responses were aligned with PsAID health domains. Descriptive statistics and chi-square tests were conducted. RESULTS: This analysis included 1286 patients from eight countries. Most patients (97%) reported musculoskeletal symptoms relating to PsA in the past year. Common moderate/major impacts of PsA were on physical activity (78%), ability to perform certain activities (76%), work productivity (62%), and career path (57%). Skin/nail symptoms occurred in 80% of patients. Overall, 69% of patients reported that PsA had a moderate/major impact on emotional/mental wellbeing, 56% on romantic relationships/intimacy, and 44% on relationships with family and friends. Social impacts included emotional distress (58%), social shame or disapproval (32%), and ceased participation in social activities (45%). Over half of all patients experienced unusual fatigue over the past 12 months (52%). The health domains that patients reported as being impacted by PsA aligned with life impact domains of the patient-derived PsAID health domains. CONCLUSION: These results highlight the impact of PsA on multiple health domains from a patient perspective that should be considered during shared decision-making processes between healthcare providers and patients.

Measuring the cost of care in benign prostatic hyperplasia using time-driven activity-based costing (TDABC).

BACKGROUND: Determining '"value'" in health care, defined as outcomes per unit cost, depends on accurately measuring cost. We used time-driven activity-based costing (TDABC) to determine the cost of care in men with benign prostatic hyperplasia (BPH) - a common urologic condition. METHODS: We implemented TDABC across the entire care pathway for BPH including primary and specialist care in both inpatient and outpatient settings. A team of expert stakeholders created detailed process maps, determined space and product costs, and calculated personnel capacity cost rates. A model pathway was derived from practice guidelines and calculated costs were applied. RESULTS: Although listed as 'optional' in practice guidelines, invasive diagnostic testing can increase costs by 150% compared with the standalone urology clinic visit. Of five different surgical options, a 400% cost discrepancy exists between the most and least expensive treatments. CONCLUSIONS: TDABC can be used to measure cost across an entire care pathway in a large academic medical center. Sizable cost variation exists between diagnostic and surgical modalities for men with BPH. IMPLICATIONS: As financial risk is shifted toward providers, understanding the cost of care will be vital. Future work is needed to determine outcome discrepancy between the diagnostic and surgical modalities in BPH.

Use of patient ethnography to support quality improvement in benign prostatic hyperplasia.

BACKGROUND: Patient-centeredness is a primary aim of quality improvement (QI) but optimal strategies to achieve that goal remain elusive. Benign prostatic hyperplasia (BPH) is one of the commonest urologic diagnoses and significantly affects quality of life. Patient ethnography is an emerging qualitative method of observation and dynamic interviews to understand the context through which the patient experiences care. We implemented patient ethnography to support our QI infrastructure and improve patient-centeredness in BPH. PROBLEM: Little is known about how to measure whether processes of care are patient-centered. We did not know whether the care processes our patients experienced provided value from their perspective. GOALS: We sought to discover previously unrecognized components of care that patients perceived to be of low value. Our primary goal was to develop QI initiatives that targeted low-value themes identified in the ethnography. Our secondary goal was a rapid rollout of three targeted initiatives. STRATEGY: We used a 4-step patient ethnography: (1) created detailed process maps to define phases of care, (2) interviewed patients, (3) synthesized transcript data in focus groups using the Crawford Slip method, and (4) targeted undesirable components of care for QI. Semi-structured interviews with seven representative patients identified low-value themes. Focus groups, comprised of primary care physicians, case coordinators, nurses, and urologists, evaluated the interview transcripts and generated improvement opportunities prioritized based on feasibility, patient value, scalability, and innovation. We used affinity mapping and priority matrix techniques to prioritize QI opportunities. RESULTS: We identified five low-value themes from the patient interviews and developed corresponding QI opportunities. These included issues surrounding the referral and consultation process as well as postoperative care, especially home urinary catheter maintenance. Six months after completing the ethnography three of five targeted improvement opportunities had been implemented.

Cytokine balance in the lungs of patients with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) involves an intense inflammatory response in the lungs, with accumulation of both pro- and antiinflammatory cytokines in bronchoalveolar lavage fluid (BALF). Our goal was to determine how the balance between pro- and antiinflammatory mediators in the lungs changes before and after the onset of ARDS. We identified 23 patients at risk for ARDS and 46 with established ARDS and performed serial bronchoalveolar lavage (BAL). We used immunoassays to measure tumor necrosis factor alpha (TNF-alpha) and soluble TNF-alpha receptors I and II; interleukin 1 beta (IL-1 beta), IL-1 beta receptor antagonist, and soluble IL-1 receptor II; IL-6 and soluble IL-6 receptor; and IL-10. We used sensitive bioassays to measure net TNF-alpha, IL-1 beta, and IL-6 activity. Although individual cytokines increased before and after onset of ARDS, greater increases occurred in cognate receptors and/or antagonists, so that molar ratios of agonists/antagonists declined dramatically at the onset of ARDS. The molar ratios remained low for 7 d or longer, limiting the activity of soluble IL-1 beta and TNF-alpha in the lungs at the onset of ARDS. This significant antiinflammatory response early in ARDS may provide a key mechanism for limiting the net inflammatory response in the lungs.

Ethical challenges at the beginning of the millennium.

In the mid-1980s, the Centers for Disease Control and Prevention (CDC) recognized the need to study genetic risk factors for common diseases such as diabetes and heart disease. To take advantage of a rare opportunity to obtain a nationally representative, population-based sample to study genetic risk factors, the CDC collected and stored DNA as part of the Third National Health and Nutrition Examination Survey (NHANES III). At the time, the methods for studying these risk factors in large epidemiologic studies were not available. However, in the midst of planning for NHANES III, a revolution was occurring in the field of genetics. The resulting changes would provide a means to realize the goal of explaining why some people are more susceptible than others to risks such as elevated cholesterol or exposure to carcinogens. During this period, ethicists were increasingly asking questions about the safety and risks for participants in genetic research. Was genetic research different from other research? Were new rules for obtaining informed consent for genetic research needed, or should our methods of obtaining informed consent be equally rigorous for all research? When collection of the NHANES III DNA bank was complete in 1994, the CDC and the National Institutes of Health (NIH) held a workshop to address these questions. The published recommendations of this workshop stimulated a national debate that resulted in a significant change in the way genetic epidemiologic research is done in the United States including not only stored biologic specimens but data collected for one purpose but used for another. In 1999, the National Bioethics Advisory Commission (NBAC) published recommendations for the ethical use of human biological materials. The recommendations of the NBAC and policies and practices of the CDC about informed consent for research on stored tissue samples will serve as models for future epidemiologic research. The problems that were recognized in the national debate that ensued and the solutions that followed will affect the way we gain access to biological specimens and data in the 21st century. Published in 2001 by John Wiley & Sons, Ltd.

Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States.

CONTEXT: Population-based estimates of the prevalence of disease-associated mutations, such as hemochromatosis (HFE) gene mutations, are needed to determine the usefulness of genetic screening. OBJECTIVE: To estimate the prevalence of the HFE mutations C282Y and H63D in the US population. DESIGN: Cross-sectional population-based study of samples in the DNA bank from phase 2 of the Third National Health and Nutrition Examination Survey conducted from 1992 to 1994. SETTING AND PARTICIPANTS: Genotyped samples of cells from a total of 5171 participants, cross-classified by sex, age, and race/ethnicity in the analysis. MAIN OUTCOME MEASURES: Estimates of the prevalence of C282Y and H63D mutations. RESULTS: The prevalence of C282Y homozygosity is estimated to be 0.26% (95% confidence interval [CI], 0.12%-0.49%); 1.89% (95% CI, 1.48%-2.43%) for H63D homozygosity; and 1.97% (95% CI, 1.54%-2.49%) for compound heterozygosity. The prevalence estimates for C282Y heterozygosity (C282Y/wild type) are 9.54% among non-Hispanic whites, 2.33% among non-Hispanic blacks, and 2.75% among Mexican-Americans. The prevalence estimates of the C282Y mutation in the US population are 5.4% (95% CI, 4.7%-6.2%) and 13.5% (95% CI, 12.5%-14.8%) for the H63D mutation. CONCLUSIONS: Estimates of prevalence of HFE mutations are within the expected range for non-Hispanic whites and blacks but the estimated prevalence of the C282Y mutation among Mexican-Americans is less than expected. Mutation data now need to be linked to clinically relevant indices, such as transferrin saturation level.

Anti-interleukin 8 autoantibody: interleukin 8 complexes in the acute respiratory distress syndrome. Relationship between the complexes and clinical disease activity.

Increased levels of interleukin 8 (IL-8) are found in bronchoalveolar lavage (BAL) fluids from patients with the acute respiratory distress syndrome (ARDS). However, IL-8 is not an efficient predictor of the course of ARDS. Our prior studies demonstrated that IL-8 present in lung fluids from patients with ARDS is associated with anti-IL-8 autoantibodies (anti-IL-8:IL-8 complexes). These data led us to hypothesize that the complexes might better predict the development of acute lung injury. Accordingly, we measured concentrations of free and complexed IL-8 in BAL fluids from 19 patients at risk and 45 with established ARDS on Days 1, 3, 7, 14, and 21 after the onset of ARDS. The concentrations of anti-IL-8:IL-8 complexes in patients with ARDS on Day 1 were significantly higher than in patients at risk (p < 0.05). There was a significant association between anti-IL-8:IL-8 complex concentrations and the onset of ARDS (p = 0.03). Similarly, anti-IL-8:IL-8 complex concentrations were significantly higher in patients on Day 1 of ARDS who later died (p < 0.05), and the association between high anti-IL-8: IL-8 complex concentrations and the probability of dying was significant (p = 0.03). The presence of anti-IL-8:IL-8 complexes in BAL fluids of patients with ARDS is an important prognostic indicator for the development and outcome of ARDS.

Nitric oxide and nitrotyrosine in the lungs of patients with acute respiratory distress syndrome.

Nitric oxide (NO) end-products (nitrate and nitrite) are present in bronchoalveolar lavage (BAL) fluid of patients with inflammatory lung diseases. Reactive oxygen-nitrogen intermediates damage macromolecules by oxidation or nitration of critical residues in proteins. The goal of this study was to measure NO end-products (nitrate+ nitrite), in BAL fluid before and after the onset of acute respiratory distress syndrome (ARDS) and to determine if these products are associated with expression of inducible nitric oxide synthase enzyme (iNOS) in BAL cells and nitration of BAL proteins. We performed bronchoalveolar lavage (BAL) in patients at risk for ARDS (n = 19), or with ARDS (n = 41) on Days 1, 3, 7, 14, and 21 after onset, and measured total nitrite (after reducing nitrate to nitrite) and protein-associated nitrotyrosine concentration in each BAL fluid sample. Cytospin preparations of BAL cells were analyzed by immunocytochemistry for iNOS and nitrotyrosine. Nitrate+nitrite were detected in BAL fluid from patients at risk for ARDS, and for as long as 21 d after the onset of ARDS. Nitrotyrosine was detectable in all BAL fluid samples for as long as 14 d after the onset of ARDS (range, 38.8 to 278.5 pmol/mg of protein), but not in BAL of normal volunteers. Alveolar macrophages of patients with ARDS were positive for iNOS and nitrotyrosine, and remained positive for as long as 14 d after onset of ARDS. The BAL nitrate+nitrite did not predict the onset of ARDS, but the concentration was significantly higher on Days 3 and 7 of ARDS in patients who died. Thus, NO end products accumulate in the lungs before and after onset of ARDS; iNOS is expressed at high levels in AM during ARDS; and nitration of intracellular and extracellular proteins occurs in the lungs in ARDS. The data support the concept that NO-dependent pathways are important in the lungs of patients before and after the onset of ARDS.

Acute lung injury and acute respiratory distress syndrome. The clinical syndrome.

Acute lung injury (ALI) is a syndrome of severe acute respiratory failure defined by a constellation of clinical criteria. The exact incidence of ALI is not known, but it generally occurs in the setting of acute severe illness. The course of ALI after onset is quite variable, but outcome is associated with risk factor, age, and comorbidity. Survival from this syndrome has improved over time. Survivors often are impaired after hospital discharge but tend to improve over time; however, ALI does confer a significant additional burden on survivors with regard to pulmonary function and health-related quality of life.

Diabetic patients have a decreased incidence of acute respiratory distress syndrome.

OBJECTIVE: Our ability to predict which critically ill patients will develop acute respiratory distress syndrome (ARDS) is imprecise. Based on the effects of diabetes mellitus on the inflammatory cascade, we hypothesized that a history of diabetes might alter the incidence of ARDS. DESIGN: A prospective multicenter study. SETTING: Intensive care units at four university medical centers. PATIENTS: One hundred thirteen consecutive patients with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients were prospectively followed during their intensive care course for the development of ARDS. A history of diabetes was identified in 28% (32/113) of the patients. In this study, nondiabetics were more likely to develop septic shock from a pulmonary source (48%, 39/81) compared with diabetics (25%, 8/32) (p = .02). Forty-one percent (46/113) of the patients with septic shock developed ARDS. Forty-seven percent of the nondiabetic patients developed ARDS compared with only 25% of those with diabetes (p = .03, relative risk = 0.53, 95% confidence interval = 0.28-0.98). In a multivariate logistic regression analysis, when we adjusted for several variables including source of infection, the effect of diabetes on the incidence of ARDS remained significant (p = .03, odds ratio = 0.33, 95% confidence interval = 0.12-0.90). CONCLUSIONS: In patients with septic shock, a history of diabetes is associated with a lower risk of developing ARDS compared with nondiabetics.

Risks associated with genetic testing: health insurance discrimination or simply business as usual?

Doctors can test patients for mutations that put them at high risk for hereditary forms of such diseases as breast and ovarian cancer. Even though the opportunities for disease prevention using genetic testing will increase with time, the risks of testing, which include insurance loss and employment discrimination, currently make testing problematic. Some have proposed making use of genetic information in health insurance underwriting illegal. But in the current system of risk-based underwriting, it is hard to imagine that insurance companies will willingly forego access to a growing body of information on risk. If the American public chooses to limit the use of genetic information, a reassessment of current laws or methods of paying for health care will be needed.

Diclofenac sodium (Voltaren) reduced exercise-induced injury in human skeletal muscle.

PURPOSE: To examine the effects of prolonged systemic administration of diclofenac sodium (Voltaren), a nonsteroidal anti-inflammatory drug, on objective indices of exercise-induced muscle damage in humans. METHODS: Fifty-four volunteers (mean age, 26.4 yr; range, 18-35) participated in this randomized double-blind, placebo-controlled trial. To achieve steady-state tissue levels, either placebo or diclofenac was orally administered two times a day for 27 consecutive days. A strenuous 20-min stepping exercise program, about which the subjects were unfamiliar, was conducted on day 15. Creatine kinase (CK) activities were measured immediately before the exercise session and on days 16, 18, and 27. Vastus lateralis muscle samples were obtained immediately before exercise and on day 27 for subsequent histological characterization of muscle inflammation. RESULTS: The preexercise muscle samples revealed no difference in muscle damage between the two groups. However, the postexercise muscle samples showed that the diclofenac-treated group demonstrated less muscle tissue damage than placebo-treated subjects (P = 0.002). The administration of diclofenac also resulted in a significant lowering of post-/pre-exercise CK ratios on days 18 (P = 0.03) and 27 (P = 0.02) compared with the placebo group, an indirect finding that supports the possibility of diclofenac reducing exercise-induced muscle damage. CONCLUSION: These findings demonstrate preadministration of diclofenac (in accordance with tissue half-life pharmacokinetics) significantly reduces quantitative indices of exercise-induced skeletal muscle damage in human muscle.

Modulation of neutrophil apoptosis by granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor during the course of acute respiratory distress syndrome.

OBJECTIVE: To determine whether bronchoalveolar lavage fluid (BALF) from patients either at risk for the acute respiratory distress syndrome (ARDS) or with sustained ARDS modulates neutrophil apoptosis; to measure the BALF concentrations of the apoptosis inhibitors granulocyte colony-stimulating factor (G-CSF) and granulocyte/macrophage colony-stimulating factor (GM-CSF) before and after the onset of ARDS; and to determine whether the BALF concentrations of G-CSF and/or GM-CSF are associated with clinical outcome. DESIGN: Prospective cohort study. SETTING: Tertiary university hospital. PATIENTS: Twenty patients at risk for ARDS and 45 patients with established ARDS. INTERVENTIONS: Patients at risk for ARDS underwent bronchoalveolar lavage within 24 hrs of being identified, then again 72 hrs later. Patients with ARDS underwent bronchoalveolar lavage within 24 hrs of meeting ARDS criteria, then again on days 3, 7, and 14 of the disease. MEASUREMENTS AND MAIN RESULTS: Normal peripheral blood neutrophil were incubated overnight in BALF from normal volunteers, from patients at risk for ARDS, or from patients with ARDS. neutrophil apoptosis was determined by flow cytometric analysis of annexin V binding. G-CSF and GM-CSF were measured in BALF by immunoassays. Compared with normal BALF, BALF from patients on days 1 and 3 of ARDS inhibited neutrophil apoptosis, but BALF from patients at later stages of ARDS, or from patients at risk for ARDS, did not. The BALF concentrations of both G-CSF and GM-CSF were elevated early in ARDS and decreased toward later stages. Patients who lived had significantly higher concentrations of GM-CSF in the BALF than those who died. CONCLUSIONS: We conclude that the antiapoptotic effect of ARDS BALF on normal neutrophil is highest during early ARDS, and decreases during late ARDS. G-CSF and GM-CSF are present in BALF from patients with ARDS, and their concentrations parallel the antiapoptotic effect of ARDS BALF. These data support the concept that the life-span of neutrophil in the air spaces is modulated during acute inflammation. GM-CSF in the air spaces is associated with improved survival in patients with ARDS.

Talk is cheap: measuring drinking outcomes in clinical trials.

OBJECTIVE: To evaluate the correspondence among measures of self-reported drinking, standard biological indicators and the reports of collateral informants, and to identify patient characteristics associated with observed discrepancies among these three sources of research data. METHOD: Using data collected from a large-scale clinical trial of treatment matching with alcoholics (N = 1,726), these three alternative outcome measures were compared at the time of admission to treatment and at 12 months after the end of treatment. RESULTS: Patient self-reports and collateral reports agreed most (97.1%) at treatment admission when heavy drinking was unlikely to be denied. In contrast, liver function tests were relatively insensitive, with positive serum gamma-glutamyl transpeptidase (GGTP) values obtained from only 39.7% of those who admitted to heavy drinking. At 15-month follow-up the correspondence between client self-report and collateral report decreased to 84.7%, but agreement with blood chemistry values increased to 51.6%. When discrepancies occurred, they still indicated that the client' s self-report is more sensitive to the amount of drinking than the biochemical measures. Patients who presented discrepant results tended to have more severe drinking problems, more previous treatments, higher levels of pretreatment drinking and significantly greater levels of cognitive impairment, all of which could potentially interfere with accurate recall. CONCLUSIONS: In clinical trials using self-selected research volunteers, biochemical tests and collateral informant reports do not add sufficiently to self-report measurement accuracy to warrant their routine use. Resources devoted to collecting these alternative sources of outcome data might be better invested in interview procedures designed to increase the validity of self-report information.