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.

Sex steroids and bone density in premenopausal and perimenopausal women.

Bone density begins to decline in women before menopause, and the degree of bone loss is variable. We performed a cross-sectional analysis on the entry data of a 5-yr prospective study of risk factors for osteoporosis to determine the correlation of bone density with serum sex steroid concentrations and body weight. We studied 292 healthy white women, aged 35-50 yr, who were menstruating regularly or had had menses in the past 12 months. Blood samples were drawn in the early follicular phase for estradiol (E2), testosterone (T), dehydroepiandrosterone sulfate, and sex hormone-binding globulin (SHBG). Free levels of E2 (FE2) and T (FT) were calculated based on total T and E2, SHBG, and albumin levels. Women were classified as premenopausal (FSH, less than 12 U/L) and perimenopausal (FSH greater than or equal to 12 U/L; n = 46; 16%). Bone density was measured by dual photon absorptiometry of the lumbar spine (L2-L4) and hip and by single photon absorptiometry of the wrist. Perimenopausal women were older than premenopausal women (45.5 +/- 3.5 and 41.0 +/- 3.9 yr, respectively), but did not differ in height or weight. While bone density did not correlate with age in each group, perimenopausal women had significantly lower bone density at the L2-L4 and femoral neck (L2-L4, 1.18 +/- 0.14 in perimenopausal and 1.24 +/- 0.12 g/cm2 in premenopausal women; femur, 0.84 +/- 0.11 in perimenopausal and 0.90 +/- 0.11 g/cm2 in premenopausal women; P less than 0.005). Body weight showed the strongest positive correlation with bone density. Log FT, percent FT, and FE2 percent correlated positively with bone density, even after controlling for weight. Log SHBG was negatively correlated with bone density in premenopausal women at the hip and wrist after controlling for weight. FSH was inversely correlated with bone density, and E2 and T were lower in perimenopausal than premenopausal women. These data suggest that women who are still menstruating may have relative deficiencies in both E2 and T, with reduced bone densities as a consequence.

Evaluation of potential health effects associated with serum polychlorinated biphenyl levels.

In late 1983, we conducted a cross-sectional epidemiologic study to evaluate persons at risk of exposure to three chemical waste sites by comparing clinical disease end points and clinical chemistry parameters with serum polychlorinated biphenyls (PCB) levels. A total of 106 individuals participated in the study. The only statistically significant finding in regard to self-reported, physician-diagnosed health problems was a dose-response relationship between serum PCB levels and the occurrence of high blood pressure; however, this association failed to achieve statistical significance (p = 0.08) when we controlled for possible confounding effects of both age and smoking. Serum triglyceride and cholesterol levels were also higher in the group with elevated serum PCBs; additionally, there were isolated statistically significant correlations of serum aspartate aminotransferase (SGOT) with serum lipid fraction-adjusted PCB level (r = -0.21) and serum albumin (r = -0.24) and total bilirubin (r = 0.30) with serum PCB level. Although the ranges of serum levels reported herein from exposures to PCBs in the general environment are lower than those that have been associated with acute symptoms or illness in other studies, whether these levels are associated with long-term health risks is not known. Associations of such chronic, low-dose exposures with observable health effects as suggested by this study must be evaluated further before any final conclusions can be drawn.

BRCA1 and BRCA2 gene mutations and risk of breast cancer. Public health perspectives.

CONTENT: Breast cancer is the most common cancer and the second most common cause of cancer death among U.S. women. In 1998, about 178,700 new cases will be diagnosed and 43,500 women will die from the disease. Mutations in the BRCA1 gene, which was cloned in 1994 and is located on chromosome 17q, have been identified as causes of predisposition to breast, ovarian, and other cancers. A second breast cancer gene, BRCA2, has been localized to chromosome 13q. Using inferential procedures, the overall carrier frequency of BRCA1 gene mutations has been estimated at 1 in 500 in the general U.S. population. Recent studies have indicated that the carrier frequency of a specific BRCA1 allele, the 185delAG mutation, may be as high as 0.8% to 1% among women of Ashkenazi Jewish descent. CONCLUSIONS: Due to the proliferation of laboratories offering genetic tests for breast cancer susceptibility, their appropriate use in public health needs careful scrutiny. Several issues are raised when such genetic tests are considered for population-based prevention programs for breast cancer. Public health agencies, such as the Centers for Disease Control and Prevention, are important to monitoring and evaluating genetic testing done outside of research protocols. If genetic tests for breast cancer are to be incorporated into future prevention programs, evaluation is needed of whether the testing can have the intended effect.

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.

Current activities at the Centers for Disease Control and Prevention's National Diabetes Laboratory.

In 1997, the Centers for Disease Control and Prevention established the National Diabetes Laboratory in order to help prevent and treat type 1 diabetes. This state-of-the-art laboratory collaborates with research scientists and key national and international organizations throughout the world to identify and study risk factors for type 1 diabetes by developing measurements for glycosylated proteins, developing and evaluating technology for measuring genetic risk factors for the disease, and working to standardize autoantibody measurements. Developing improved technologies for diagnosing and managing diabetes and developing reference materials for properly calibrating and standardizing blood glucose meters are also critical aspects of the laboratory's work. In addition, the laboratory provides quality storage for valuable collections of biologics and other materials and facilitates sharing of specimens, associated epidemiologic data, and test results. Working with our partners in diabetes research, we are improving the diagnosis, treatment, and prevention of type 1 diabetes.

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.

Assessment of reproductive disorders and birth defects in communities near hazardous chemical sites. I. Birth defects and developmental disorders.

Members of the workgroup on birth defects and developmental disorders discussed methods to assess structural anomalies, genetic changes and mutations, fetal and infant mortality, functional deficits, and impaired fetal and neonatal growth. Tier 1 assessments for all five adverse reproductive outcomes consist of questionnaires and reviews of medical records rather than laboratory testing of biologic specimens. The work-group members noted a role for neurodevelopmental testing and for limited genetic studies, such as karyotyping in Tier 2 assessments. Emerging methodologies to identify chromosomal aberrations, DNA adducts, and repair inhibition were reserved for Tier 3.

Evaluation of in vivo interactions in mice between flurazepam and two neuroactive steroids.

The development of neuroactive steroids as anticonvulsant medications may be useful both as a primary treatment and as an adjuvant to other anticonvulsants. They may be limited, however, by sedative and ataxic side effects. In the current study, 3 alpha-hydroxy-5 beta-pregnan-20-one and alfaxalone, two prototypic neuroactive steroids, were shown to potentiate the ability of flurazepam to antagonize electrically precipitated tonic hindlimb extension in mice at doses that by themselves had little antiseizure efficacy. While alfaxalone alone lacked motor incoordinating effects at a dose (18.0 mg/kg) that potentiated the antiseizure efficacy of flurazepam, the same dose of 3 alpha-hydroxy-5 beta-pregnan-20-one possessed both the ability to potentiate flurazepam's anticonvulsant effect and disrupt mouse rotorod performance. The data suggest that allosteric interactions that have been described in vitro between neuroactive steroids and other modulators of the GABAA receptor complex may have relevance for the intact animal. Finally, the data also suggest that neuroactive steroids could be developed as short-lived adjuvant antiseizure medications in certain critical situations (e.g., medication-refractory status epilepticus). However, the motor incoordinating effects resulting from the combination of neuroactive steroids and flurazepam suggest that their usefulness as adjuvant medications in the chronic therapy of seizure disorders may be limited.

Alkaline phosphatase isoenzymes and osteocalcin in serum of normal subjects.

Clinical laboratory tests are increasingly being used to evaluate individuals for osteoporosis and other metabolic bone diseases. Serum bone alkaline phosphatase (AP) [EC 3.1.3.1, orthophosphoric-monoester phosphohydrolase (alkaline optimum)] and osteocalcin are used to assess osteoblastic activity. Although methods for assessing relative amounts of AP isoenzymes continuously appear in the literature, no single method is satisfactory for quantification. Polyacrylamide gel electrophoresis with densitometric scanning combined with two-point heat inactivation was used to obtain quantitative values for AP isoenzymes. Serum bone AP concentrations correlated positively and significantly with serum osteocalcin concentrations obtained by radioimmunoassay for women. Men had significantly higher total alkaline phosphatase and bone AP than women, whereas liver AP concentrations did not differ between the two groups. Bone AP correlated negatively and significantly with age in men, but not women. Osteocalcin concentrations tended to be higher in men, but not significantly.

Osteocalcin and bone alkaline phosphatase in the serum of women with liver disease.

To identify the types of liver disease in which osteopenia is a prominent feature and to understand the mechanisms of bone loss, bone mineral density was measured in the lumbar spine and hip, bone alkaline phosphatase, osteocalcin, and biochemical markers of calcium homeostasis were measured in 42 women, aged 33 to 52, with chronic liver disease and in 299 healthy women of similar age. In control women, bone alkaline phosphatase and osteocalcin correlated negatively with bone density at all sites (p less than 0.05). In women with liver disease, osteocalcin correlated negatively with bone density in the lumbar spine (p less than 0.007), whereas bone alkaline phosphatase did not correlate with bone density at any site. Bone alkaline phosphatase correlated positively with osteocalcin in control women (p = 0.001) and negatively with osteocalcin in women with liver disease (p = 0.03). Serum bone alkaline phosphatase in women with liver disease was increased significantly over serum bone alkaline phosphatase of control women, probably because of decreased clearance owing to defective function or decreased numbers of hepatic asialoglycoprotein receptors. Bone density was lower in the lumbar spines and hips of women with primary sclerosing cholangitis, primary biliary cirrhosis, and chronic active hepatitis or fibrosis without cirrhosis than in the lumbar spine and hips of control women. However, the differences were not significant, possibly because of the small sample size. It is concluded that, in liver disease, osteocalcin is a more reliable marker of osteoblastic function than bone alkaline phosphatase. Although our results show that bone density may decrease in women with cholestatic liver disease, larger studies are needed to determine the degree of osteopenia.

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.

A comparison of two methods for quantifying D-glucaric acid.

The relative usefulness of two spectrophotometric methods for quantifying urinary D-glucaric acid was evaluated. The enzyme inhibition method measures the inhibition of beta-D-glucuronidase by the 1,4-glucarolactone produced from D-glucaric acid in urine by boiling at acidic pH. The glyoxylic acid method measures glyoxylic acid produced from the oxidation of D-glucaric acid which has first been separated from other urinary compounds by ion exchange chromatography. For a group of 61 healthy adults, the enzyme inhibition method gave a range similar to that of previously reported values: 0 to 6.44 mmol D-glucaric acid/mol creatinine (99% confidence limits). Similar values were obtained from standard solutions by the two methods. Recovery was approximately 105% by both methods. Urinary concentrations, however, were often from 3 to 10 times higher by the glyoxylic acid method. The higher values were probably due to interference from ascorbic acid and other glyoxylic acid-producing compounds, because the reduction of interfering compounds with sodium borohydride before chromatography resulted in concentrations of less than half of those originally observed. It is concluded that the modification of the enzyme inhibition method is preferable because it is less subject to interference and less labor intensive than the glyoxylic acid method.

N-acetyl-beta-D-glucosaminidase assay in urine: urea inhibition.

Urea inhibition of urinary N-acetyl-beta-D-glucosaminidase (NAG) was examined with human isoenzymes and total enzyme in urine. The fluorometric substrate 4-methylumbelliferyl-N-acetyl-beta-D-glucosaminide (MUNAG) and the colorimetric substrate m-cresolsulfonphthaleinyl-N-acetyl-beta-D-glucosaminide (MCPNAG) were used to determine substrate kinetics and apparent urea inhibition kinetics. Apparent KmS of 0.47 (MUNAG) and 0.35 mmol/L (MCPNAG) for human NAG isoenzyme A and 0.46 (MUNAG) and 0.30 mmol/L (MCPNAG) for human NAG isoenzyme B were determined. Apparent Kis of approximately 100 mmol/L for urea inhibition of both isoenzymes in either substrate and apparent Kis of 79 (MUNAG) and 91 mmol/L (MCPNAG) for NAG in dilute urine samples were found. The potential for urea inhibition at physiological concentrations of urea and at normal assay dilutions therefore exists. Inhibition at these dilutions was minimal when substrate concentrations of 2 x Km or greater were used, but the substrate MUNAG at 1/2 x Km gave the highest sensitivity and lower blanks and allowed better quantitation of low activity samples. Within-run CVs of 3.2% with MUNAG and 10% with MCPNAG were found for low activity samples.

A semiautomated procedure for urinary D-glucaric acid using a centrifugal analyzer.

The most commonly used method for quantifying D-glucaric acid, the enzyme inhibition method, is a two-step procedure. In the first step of the present study, urine was boiled at acidic pH to convert glucaric acid to 1,4-glucarolactone, which inhibits beta-glucuronidase activity. In the second step, inhibition of beta-glucuronidase by the prepared urine was measured. This is an indirect measure of the D-glucaric acid concentration. The second step was adapted to a Cobas-Bio centrifugal analyzer. Values on a reference population obtained by the manual method were highly correlated with values obtained by the semiautomated method described here (r = 0.976, p = 0.25), and precision was comparable by the two methods. The throughput increased from 8 to 20 samples per day when the automated method was used.

Effects of legally mandated child-abuse reports on the therapeutic relationship: a survey of psychotherapists.

In a national survey of 907 licensed psychologists regarding mandated reporting of child maltreatment, predictors of outcome included: therapeutic alliance; role strain; therapist explicitness; family vs. individual treatment; and whether or not the client was the perpetrator. Therapists were asked to describe a case involving reporting, its impact on treatment, informed consent procedures, as well as their own attitudes and beliefs. Implications for research are discussed, and recommendations for clinical training and practice are offered.

Effect of low-level body burdens of lead on the mental development of children: limitations of meta-analysis in a review of longitudinal data.

The effect of low-level body burdens of lead on the intelligence of children, as measured by intelligence quotient (IQ), was assessed. We reviewed 35 reports from five longitudinal studies conducted in the United States and Australia. In each of these studies, infants were followed for 58 mo or less. The study populations consisted of low- and middle-socioeconomic-class infants who had low-level exposure to environmental lead. Blood-lead levels were measured in a standard fashion at various times, beginning in the prenatal period, and intelligence was first measured at 6 mo of age and was followed by subsequent assessments. Studies were assessed for quality by a review panel blinded to the identity of the investigators and their affiliations. Efforts were made to pool the data with meta-analytic techniques, but efforts were unsuccessful because the methods used to analyze and report data were inconsistent. Inconsistencies were as follows: (a) there were few instances in which IQ and blood-lead levels were measured at comparable times in different studies; (b) incompatibilities existed among the studies, including differences in independent variables, data transformations, and statistical parameters reported; (c) results conflicted when measurement intervals were comparable (i.e., heterogeneity); (d) patterns of regression and correlation coefficients were inconsistent; and (e) data were insufficient to interconvert the parameters reported. Consequently, definitive conclusions regarding the effect of low-level body burdens of lead on IQ could not be determined from the longitudinal data. Examination of the weight of the evidence from this and other studies, however, suggests an adverse relationship of lead on the intelligence of children.

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.