Search

David A Brott,1 Michael J Goodman,1 Richard P Hermann,1 Isobel Anderson,2 Alexandre Kiazand1 1Patient Safety Center of Excellence, Chief Medical Office Organization, AstraZeneca Pharmaceuticals, Gaithersburg, MD, USA; 2Patient Safety Center of Excellence, Chief Medical Office Organization, AstraZeneca Pharmaceuticals, Macclesfield, UKCorrespondence: David A BrottTakeda Pharmaceuticals, 300 Massachusetts Avenue, Cambridge, MA, USATel +1 3042408302Email David.Brott@Takeda.comBackground: Identification of laboratory parameter clinical safety signals depends on the terminology and scoring criteria. Grade 1 scoring criteria in the Common Terminology Criteria for Adverse Events (CTCAE) is typically based on the healthy volunteer reference range (HVRR). The objectives of this study were to determine 1) what laboratory parameters in individuals with diabetes are potentially different from the HVRR and 2) what fold change from baseline should be expected in this population.Materials and Methods: Baseline data from the individuals with diabetes clinical trial data (TransCelerate dataset) were compared to the HVRR using a 10% threshold above HVRR to classify laboratory parameters as potentially different from the HVRR. These parameters were then evaluated longitudinally to determine the expected x-baseline values for individuals with diabetes for potential use in identifying drug-induced changes.Results: The baseline data determined that 28% of the laboratory parameters evaluated were potentially different from the HVRR. Longitudinal data analysis determined 1) thresholds for 13 of these laboratory parameters with the subjects above the threshold having greater variability than those below the threshold, and 2) the expected upper limits (x-baseline) were calculated for the laboratory parameters. For example, a 1.8– 2.6 x-baseline value for alanine aminotransferase, depending on how the baseline is calculated, is expected in individuals with diabetes.Conclusion: It is not uncommon for laboratory parameters in individuals with diabetes clinical trials to be potentially different from the HVRR, and the x-baseline criteria for 13 of these laboratory biomarkers was determined for this population. This suggests consideration in modifying the current CTCAE grade 1 criteria of > 1.5– 3.0 x-baseline should be further investigated as to if the current criteria detects too many false-positive signals in this population.Keywords: diabetes, biomarkers, reference range, laboratory parameter, pharmacovigilance

David A Brott,1 Michael J Goodman,1 Richard P Hermann,1 Michael Merz,2 Roser Calvo,1 Nadereh Poorkhalkali,3 Alexandre Kiazand1 1Patient Safety, Safety Science, AstraZeneca Pharmaceuticals, Gaithersburg, MD, USA; 2Patient Safety, Safety Science, AstraZeneca Pharmaceuticals, Webel, Germany; 3Patient Safety, Safety Science, AstraZeneca Pharmaceuticals, Gothenburg, Sweden Background: Liver biomarkers alanine aminotransferase (ALT) and bilirubin in patients with hepatitis are above the healthy volunteer reference range (HVRR) at baseline (prior to receiving the clinical trial medication). Discussions continue as how to best distinguish drug-induced liver injury in patients with abnormal baseline values participating in clinical trials. This study investigated if other baseline routine clinical safety biomarkers (lab parameters) are different from the HVRR. Materials and methods: Clinical trial data (TransCelerate dataset) from placebo and standard of care treated patients were compared to the HVRR using a 10% threshold above or below the HVRR to classify a lab parameter in a patient population as potentially different from the HVRR at baseline. The TransCelerate dataset, batch 4, contained data from patients with Alzheimer’s, asthma, COPD, cardiovascular disease, diabetes, hidradenitis, hypercholesterolemia, rheumatoid arthritis, schizophrenia, stroke, and ulcerative colitis. A subset of the 200 biomarkers in TransCelerate were evaluated in this pilot: glucose, platelet count, neutrophil count, ALT, aspartate aminotransferase (AST), and bilirubin. Results: Glucose was potentially higher than the HVRR in patients with diabetes, COPD, cardiovascular disease, hypercholesterolemia, and schizophrenia. At least one or more of the hematology and hepatic biomarkers were different from the HVRR in at least one patient population, except bilirubin. All the patient populations, except Alzheimer’s and asthma, had at least one biomarker that was higher than the HVRR. Summary: The routine biomarkers evaluated in this pilot study demonstrated that not all lab parameters in patient populations are similar to the HVRR. Further efforts are needed to determine which biomarkers are different from the HVRR and how to evaluate the biomarkers in patient populations for detecting drug-induced altered lab values in clinical trials. Keywords: patient populations, reference range, healthy volunteer, biomarkers

Junji Lin,1 Yunfeng Li,2 Haijun Tian,2 Michael J Goodman,1 Susan Gabriel,2 Tara Nazareth,2 Stuart J Turner,2,3 Stephen Arcona,2 Kristijan H Kahler21Department of Pharmacotherapy, University of Utah, Salt Lake City, UT, USA; 2Health Economics and Outcomes Research, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 3Ernest Mario School of Pharmacy, Rutgers University, New Brunswick, NJ, USA Background: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for lung infections and other pathologies (eg, pneumonia); however, few studies have evaluated the impact of pneumonia on health care resource utilization and costs in this population. The purpose of this study was to estimate health care resource utilization and costs among COPD patients with newly acquired pneumonia compared to those without pneumonia. Methods: A retrospective claims analysis using Truven MarketScan® Commercial and Medicare databases was conducted. COPD patients with and without newly acquired pneumonia diagnosed between January 1, 2004 and September 30, 2011 were identified. Propensity score matching was used to create a 1:1 matched cohort. Patient demographics, comorbidities (measured by Charlson Comorbidity Index), and medication use were evaluated before and after matching. Health care resource utilization (ie, hospitalizations, emergency room [ER] and outpatient visits), and associated health care costs were assessed during the 12-month follow-up. Logistic regression was conducted to evaluate the risk of hospitalization and ER visits, and gamma regression models and two-part models compared health care costs between groups after matching. Results: In the baseline cohort (N=467,578), patients with newly acquired pneumonia were older (mean age: 70 versus [vs] 63 years) and had higher Charlson Comorbidity Index scores (3.3 vs 2.6) than patients without pneumonia. After propensity score matching, the pneumonia cohort was nine times more likely to have a hospitalization (odds ratio; 95% confidence intervals [CI] =9.2; 8.9, 9.4) and four times more likely to have an ER visit (odds ratio; 95% CI =4.4; 4.3, 4.5) over the 12-month follow-up period compared to the control cohort. The estimated 12-month mean hospitalization costs ($14,353 [95% CI: $14,037–$14,690]), outpatient costs ($6,891 [95% CI: $6,706–$7,070]), and prescription drug costs ($1,104 [95% CI: $1,054–$1,142]) were higher in the pneumonia cohort than in the control cohort. Conclusion: This study demonstrated elevated health care resource use and costs in patients with COPD after acquiring pneumonia compared to those without pneumonia. Keywords: COPD, health care costs, cost effectiveness/economics, outcomes research

BackgroundInhibitors of hydroxymethylglutaryl-coenzyme A reductase (statins) increase new bone formation in rodents and in human cells in vitro. Statin use is associated with increased bone mineral density of the femoral neck. We undertook a population-based case-control study at six health-maintenance organisations in the USA to investigate further the relation between statin use and fracture risk among older women.MethodsWe investigated women aged 60 years or older. Exposure, outcome, and confounder information was obtained from automated claims and pharmacy data from October, 1994, to September, 1997. Cases had an incident diagnosis of non-pathological fracture of the hip, humerus, distal tibia, wrist, or vertebrae between October, 1996, and September, 1997. Controls had no fracture during this period. We excluded women with records of dispensing of drugs to treat osteoporosis.FindingsThere were 928 cases and 2747 controls. Compared with women who had no record of statin dispensing during the previous 2 years, women with 13 or more statin dispensings during this period had a decreased risk of non-pathological fracture (odds ratio 0.48 [95% CI 0.27-0.83]) after adjustment for age, number of hospital admissions during the previous year, chronic disease score, and use of non-statin lipid-lowering drugs. No association was found between fracture risk and fewer than 13 dispensings of statins or between fracture risk and use of non-statin lipid-lowering drugs.InterpretationStatins seem to be protective against non-pathological fracture among older women. These findings are compatible with the hypothesis that statins increase bone mineral density in human beings and thereby decrease the risk of osteoporotic fractures.

Background: Allergic rhinitis causes significant economic losses and substantial reductions in quality of life. Improving a patient's symptoms can therefore enhance the patient's quality of life. Objective: To measure the relative cost-effectiveness of prescription second-generation antihistamines (levocetirizine, desloratadine, and fexofenadine) and montelukast based on their impact on quality of life in patients with uncomplicated allergic rhinitis. Methods: A retrospective, cost-effectiveness model was constructed using 1-year costs to managed care payers and using the Rhinoconjunctivitis Quality of Life Questionnaire to measure the quality of life in patients taking prescription second-generation antihistamines or montelukast for the treatment of allergic rhinitis. Clinical trial results for levocetirizine, desloratadine, fexofenadine (brand and generic), or montelukast were combined as standardized mean differences to create a pooled effectiveness measure. The costs of prescription drugs and physician office visits for allergic rhinitis were used as direct costs measures. Sensitivity was assessed by a Monte Carlo simulation run 1000 times. Results: All the drugs in the study showed significant improvement in quality of life, with levocetirizine showing the greatest improvement. The incremental cost-effectiveness of levocetirizine dominated montelukast (incremental cost-effective ratio, -1317; 95% confidence interval, -7471, -212). The incremental cost-effectiveness favored levocetirizine compared with desloratadine and branded fexofenadine. Conclusion: There are significant differences in the cost-effectiveness of various oral prescription agents with regard to improving quality of life of patients with allergic rhinitis. [ABSTRACT FROM AUTHOR]

Objective: Allergic rhinitis imposes a significant health and economic burden both on individualsand the healthcare system. Second-generation prescription antihistamines, levocetirizine,fexofenadine, and desloratadine, and the leukotriene receptor antagonist, montelukast,differ in their ability to relieve common rhinitis symptoms. The purpose of this studywas to compare the cost-effectiveness of prescription agents based on their effectiveness inrelieving nasal symptoms.Methods: Effectiveness was measured as the composite of nasal symptoms, including congestion,rhinorrhea, and sneezing, from clinical studies that compared each of the 4 comparatorsto placebo. Direct costs included prescription therapy and rhinitis-related physicianoffice visits. Physician office visit costs were collected from an analysis of the PharMetricsinsurance claims database. Sensitivity analyses were conducted using a Monte Carlo simulation to assess therobustness of the average and incremental cost-effectiveness ratios.Results: The cost per clinically significant improvement of nasal symptoms for levocetirizine was less than for theother model comparator agents. The incremental cost-effectiveness ratio for levocetirizine dominated montelukastand desloratadine and was lower than either branded or generic fexofenadine.Conclusion: Levocetirizine is a cost-effective therapy for the relief of nasal symptoms of allergic rhinitis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To test the substitution hypothesis, that community-based care reduces the probability of institutional placement for at-risk elderly. RESEARCH DESIGN: The closure of the Social Health Maintenance Organization (Social HMO) at HealthPartners (HP) in Minnesota in 1994 and the continuation of the Social HMO at Kaiser Permanente Northwest (KPNW) in Oregon/Washington comprised a 'natural experiment.' Using multinomial logistic regression analyses, we followed cohorts of Social HMO enrollees for up to 5 years, 1995 to 1999. To adjust for site effects and secular trends, we also followed age- and gender-matched Medicare-Tax Equity and Fiscal Responsibility Act (TEFRA) cohorts, enrolled in the same HMOs but not in the Social HMOs. SUBJECTS: All enrollees in the Social HMO for at least 4 months in 1993 and an age-gender matched sample of Medicare-TEFRA enrollees. To be included, individuals had to be alive and have a period out of an institution after January 1, 1995 (total n = 18,143). MEASURES: The primary data sources were the electronic databases at HP and KPNW. The main outcomes were long-term nursing home placement (90+ days) or mortality. Covariates were age, gender, a comorbidity index, and geographic site effect. RESULTS: Adjusting for variations in the 2 sites, we found no difference in probability of mortality between the 2 cohorts, but approximately a 40% increase in long-term institutional placement associated with the termination of the Social HMO at HealthPartners (odds ratio, 1.43; 95% confidence interval, 1.15-1.79). CONCLUSIONS: The Social HMO appears to help at-risk elderly postpone long-term nursing home placement. [ABSTRACT FROM AUTHOR]

BACKGROUND: We describe here a case of Henoch-Schönlein purpura (HSP) that occurred 10 days after administration of the meningococcal polysaccharide vaccine and came to the attention of a Vaccine Safety Datalink (VSD) investigator (but did not occur in the VSD cohort). Periodic case reports have linked vaccines to HSP. OBJECTIVE: To better understand the potential risk for HSP after immunization with the meningococcal polysaccharide vaccine. PATIENTS AND METHODS: We studied the VSD cohort to estimate the 42-day postvaccination incidence rate of HSP in the VSD population 16 to 20 years of age. Electronic data from all 8 VSD sites were gathered. All subjects aged 16 to 20 years who received a meningococcal polysaccharide vaccine were followed for 42 days after that vaccination for evidence of HSP. Background rates were determined by examining all the nonexposed time of the same cohort. RESULTS: No cases of HSP were seen in the 42 days after 49027 doses of meningococcal polysaccharide vaccine among the entire VSD adolescent and young adult population. The background incidence rate was 4.2 per 100000 person-years. CONCLUSION: These data provide the strongest evidence so far that HSP is not associated with receipt of meningococcal polysaccharide vaccine in the 16- to 20-year age group. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of this study was to assess the safety of routine trivalent influenza vaccine (TIV) administration among healthy children 6 through 23 months of age, after the Advisory Committee on Immunization Practices recommendation. METHODS: The study was a retrospective case-control study of children receiving TIV in the first 2 seasons after the Advisory Committee on Immunization Practices recommendation. We assessed outcomes in the 42 days after vaccination in a population of 13,383 children. Each case subject was matched, according to age and gender, with 3 control subjects. Hazard ratios were calculated with conditional logistic regression analysis. RESULTS: We found no statistically significantly elevated hazard ratios for the first TIV dose. An elevated risk of pharyngitis was found for children receiving a second TIV dose. No elevated risk of seizure was found. CONCLUSION: These results, for a population of healthy children, showed no medically significant adverse events related to TIV among children 6 to 23 months of age. [ABSTRACT FROM AUTHOR]

Empirical studies of health care cost, productivity, and output have focused primarily on intermediate goods and services. Consumers are ultimately interested in final goods such as improved health or health-related quality of life, but health services research continues to address whether health services financing and delivery are structured in ways to maximize production of intermediate goods, regardless of the link between these services and final outcomes. Increasing rates of growth of health care cost and dissatisfaction with the quality of U.S. health care force us to reexamine how productivity and cost are analyzed so that research properly informs policy and practice. The authors examine recent changes in the U.S. health care sector that suggest the need to revise how health services research approaches analyses of cost, production, and output; consider alternative notions of final goods; and review the availability and quality of data necessary to conduct this research. [ABSTRACT FROM AUTHOR]

Background: Physicians may soon be able to diagnose Alzheimer's disease (AD) in its early stages using fluid biomarkers like amyloid. However, it is acknowledged that additional biomarkers need to be characterized which would facilitate earlier monitoring of AD pathogenesis., Objective: To determine if a potential novel inflammation biomarker for AD, symmetric dimethylarginine, has utility as a baseline serum biomarker for discriminating prodromal AD from cognitively unimpaired controls in comparison to cerebrospinal fluid amyloid-β42 (Aβ 42 )., Methods: Data including demographics, magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography scans, Mini-Mental State Examination and Functional Activities Questionnaire scores, and biomarker concentrations were obtained from the Alzheimer's Disease Neuroimaging Initiative for a total of 146 prodromal AD participants and 108 cognitively unimpaired controls., Results: Aβ 42 ( p  = 0.65) and symmetric dimethylarginine ( p  = 0.45) were unable to predict age-matched cognitively unimpaired controls and prodromal AD participants. Aβ 42 was negatively associated with regional brain atrophy and hypometabolism as well as cognitive and functional decline in cognitively unimpaired control participants ( p  < 0.05) that generally decreased in time. There were no significant associations between Aβ 42 and symmetric dimethylarginine with imaging or neurocognitive biomarkers in prodromal AD patients., Conclusions: Correlations were smaller between Aβ 42 and neuropathological biomarkers over time and were absent in prodromal AD participants, suggesting a plateau effect dependent on age and disease stage. Evidence supporting symmetric dimethylarginine as a novel biomarker for AD as a single measurement was not found., Competing Interests: The authors have no conflicts of interest to report., (© 2023 – The authors. Published by IOS Press.)

Rationale and Objectives: Diagnostic radiology residents may participate in an annual diagnostic imaging tournament that enables residents to engage in friendly competition, network with peers, and practice for board examinations. Medical students would likely enjoy a similar activity, which could increase their interest and knowledge in radiology. Given the lack of initiatives designed to promote competition and learning in medical school radiology education, we designed and implemented the RadiOlympics, the first known national medical student radiology competition in the United States., Material and Methods: A draft version of the competition was emailed to many medical schools in the United States. Medical students interested in assisting with implementation of the competition were invited to a meeting to refine the layout. Ultimately, the format of seven rounds of five questions each and a final round of ten questions all over four months was decided. Questions were written by students and approved by faculty. At the conclusion of the competition, surveys were sent out to gather feedback and gauge how this competition has influenced their interest in radiology., Results: Out of 89 schools that were successfully contacted, 16 schools' radiology clubs agreed to participate, which made up 187 medical students on average per round. At the conclusion of the competition, feedback from students was very positive. Students' confidence in interpreting imaging studies increased after the competition (p < 0.001), although there was not an increased interest in radiology as a career (p = 0.77)., Conclusion: The RadiOlympics is a national competition that can be successfully organized by medical students for medical students and is an engaging opportunity for medical students to be exposed to radiology., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Introduction: Hemodialysis (HD) patients have significant burden of cerebral ischemic pathology noted on brain imaging. These ischemic type lesions maybe due to cerebral hypoperfusion that may be occurring during blood pressure (BP) fluctuations commonly noted during HD sessions. We evaluated changes in cerebral perfusion and measured an index of cerebral autoregulation (CA index) during HD to identify potential risk factors for intradialytic decline in cerebral perfusion and impaired cerebral autoregulation., Methods: In this cross-sectional study, we included HD patients age 50 years or older receiving conventional in-center HD. We measured cerebral perfusion during HD, using cerebral oximetry, and calculated the correlation between cerebral perfusion and BP during HD as an index of CA. We measured the association between potential risk factors for intradialytic decline in cerebral perfusion and CA index., Findings: We included 32 participants and 118 HD sessions in our analysis. The mean ± SD decline in cerebral oxygen saturation during HD was 6.5% ± 2.9% with a relative decline from baseline values of 9.2% ± 4.4%. Greater drop in systolic BP (SBP) during HD was associated with decline in cerebral oxygen saturation, p = 0.02. Impaired CA index was noted in 37.3% of HD sessions. Having diabetes and >20 mmHg drop in SBP during HD were associated with increased (worse) CA index with an increase of 0.24 95%CI [0.06, 0.41] for diabetes and increase of 0.43 95%CI [0.27, 0.56] for a >20 mmHg drop in SBP during HD., Discussion: Cerebral perfusion can decline during HD and is associated with changes in systemic BP. This may be due to impaired cerebral autoregulation in HD patients. Risk factors for worse CA index include diabetes and >20 mmHg drop in SBP during HD. This study highlights the risk of intradialytic decline in cerebral perfusion and impaired cerebral autoregulation in HD patients., (© 2021 International Society for Hemodialysis.)

Ranavirus is the second most common infectious cause of amphibian mortality. These viruses affect caudates, an order in which information regarding Ranavirus pathogenesis is scarce. In the Netherlands, two strains (CMTV-NL I and III) were suspected to possess distinct pathogenicity based on field data. To investigate susceptibility and disease progression in urodeles and determine differences in pathogenicity between strains, 45 adult smooth newts (Lissotriton vulgaris) were challenged via bath exposure with these ranaviruses and their detection in organs and feces followed over time by PCR, immunohistochemistry and in situ hybridization. Ranavirus was first detected at 3 days post infection (p.i.) in the oral cavity and upper respiratory mucosa. At 6 days p.i, virus was found in connective tissues and vasculature of the gastrointestinal tract. Finally, from 9 days p.i onwards there was widespread Ranavirus disease in various organs including skin, kidneys and gonads. Higher pathogenicity of the CMTV-NL I strain was confirmed by higher correlation coefficient of experimental group and mortality of challenged animals. Ranavirus-exposed smooth newts shed virus in feces intermittently and infection was seen in the absence of lesions or clinical signs, indicating that this species can harbor subclinical infections and potentially serve as disease reservoirs.

This article summarizes the current literature regarding patient satisfaction after total knee arthroplasty. In 10% to 15% of cases, the operation has not met the patients' expectations. The causes of this dissatisfaction are multifactorial, and include patient-related factors, details related to the surgical procedure and prosthesis chosen, perioperative factors, and factors associated with nursing and general medical care. However, surgeons must bear the brunt of patients' dissatisfaction. This dissatisfaction erodes the doctor-patient relationship, and may have implications in an emerging health care economy in which doctors and hospitals are reimbursed based on both clinical outcome and patient satisfaction., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The theoretical underpinnings for flight, including animal flight with flapping wings, predict a curvilinear U-shaped or J-shaped relationship between flight speed and the power required to maintain that speed. Experimental data have confirmed this relationship for a variety of bird and bat species but not insects, possibly due to differences in aerodynamics and physiology or experimental difficulties. Here we quantify modulation of the main flight motor muscles (the dorsolongitudinal and dorsoventral) via electromyography in hawkmoths (Manduca sexta) flying freely over a range of speeds in a wind tunnel and show that these insects exhibit a U-shaped speed-power relationship, with a minimum power speed of 2ms -1 , indicating that at least large flying insects achieve sufficiently high flight speeds that drag and power become limiting factors., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Food branded with a Natural label can be found in any grocery store across the United States. Consumers consider this label to be an important attribute when making a purchasing decision and billions of dollars are spent annually on these products. While many consumers believe Natural foods are healthier, heavy reliance on that assumption is misguided as “Natural” has no formal legal definition—it’s merely defined pursuant to an FDA approved informal policy. Another important health attribute in a consumer’s purchasing decision is the presence of natural flavors in food. However, unlike the term Natural, FDA has promulgated legally binding regulations for natural flavors. These flavors are currently the fourth most common food ingredient listed on food labels. In reality, “natural flavors” are a far cry from what consumers might expect, as they can contain both artificial and synthetic chemicals (often used as processing aids). Nonetheless, without a legally binding Natural regulation, there has been little opportunity to contest the naturalness of natural flavors in the past. Recently, FDA has initiated a notification of request for comments on use of the term Natural, so an attempt to promulgate regulations may be underway. Thus, it is appropriate to consider where natural flavors will fall if binding regulations are set forth. This article looks at the Natural debate, its history, and model regulatory standards worth considering. Within that context, it also provides a critical discussion concerning a misunderstood, yet federally regulated, ingredient that our society so heavily consumes: natural flavors.

To investigate the mechanism(s) of action of mindfulness based stress reduction (MBSR(BC)) including reductions in fear of recurrence and other potential mediators. Eighty-two post-treatment breast cancer survivors (stages 0-III) were randomly assigned to a 6-week MBSR(BC) program (n = 40) or to usual care group (UC) (n = 42). Psychological and physical variables were assessed as potential mediators at baseline and at 6 weeks. MBSR(BC) compared to UC experienced favorable changes for five potential mediators: (1) change in fear of recurrence problems mediated the effect of MBSR(BC) on 6-week change in perceived stress (z = 2.12, p = 0.03) and state anxiety (z = 2.03, p = 0.04); and (2) change in physical functioning mediated the effect of MBSR(BC) on 6-week change in perceived stress (z = 2.27, p = 0.02) and trait anxiety (z = 1.98, p = 0.05). MBSR(BC) reduces fear of recurrence and improves physical functioning which reduces perceived stress and anxiety. Findings support the beneficial effects of MBSR(BC) and provide insight into the possible cognitive mechanism of action.

Background: Skeletal muscle mass declines after the age of 50. Loss of skeletal muscle mass is associated with increased morbidity and mortality., Objective: This study aims to identify predictors of low skeletal muscle mass in older adults toward development of a practical clinical assessment tool for use by clinicians to identify patients requiring dual-energy X-ray absorptiometry (DXA) screening for muscle mass., Methods: Data were drawn from the National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2004. Appendicular skeletal mass (ASM) was calculated based on DXA scans. Skeletal muscle mass index (SMI) was defined as the ratio of ASM divided by height in square centimeters. Elderly participants were classified as having low muscle mass if the SMI was 1 standard deviation (SD) below the mean SMI of young adults (20-40 years old). Logistic regression was conducted separately in males and females age ≥65 years of age to examine the relationship between patients identified as having low muscle mass and health behavior characteristics, adjusting for comorbid conditions. The model was validated on a separate sample of 200 patients., Results: Among the NHANES study population, 551 (39.7 %) males and 374 (27.5 %) females had a SMI below the 1 SD cutoff point. NHANES study subjects with a low SMI were older (mean age, 76.2 vs. 72.7 for male; 76.0 vs. 73.7 for female; and both p < 0.0001) and had a lower body mass index (mean BMI, 24.1 vs. 29.4 for male; 22.9 vs. 29.7 for female; p < 0.0001). In adjusted logistic regression analyses, age (for males) and BMI (for both males and females) remained statistically significant. A parsimonious logistic regression model adjusting for age and BMI only had a C statistic of 0.89 for both males and females. The discriminatory power of the parsimonious model increased to 0.93 for males and 0.95 for females when the cutoff defining low SMI was set to 2 SD below the SMI of young adults. In the validation sample, the sensitivity was 81.6 % for males and 90.6 % for females. The specificity was 66.2 % for males and females., Conclusions: BMI was strongly associated with a low SMI and may be an informative predictor in the primary care setting. The predictive model worked well in a validation sample.

Objective: To examine the relationship of three alternative measures of adherence with seven negative outcomes associated with epilepsy for development of a quality measure in epilepsy., Design: Retrospective cohort analysis., Setting: PharMetrics national claims database., Participants: Patients in the PharMetrics database for the years 2004-08 taking antiepileptic drugs., Intervention: None., Main Outcome Measures: For each definition of adherence, the odds ratios (ORs) comparing non-adherent with adherent groups were assessed for consistency and direction for the number of hospital admissions, emergency room (ER) visits, head injuries including traumatic brain injuries, falls, motor vehicle accidents (MVAs), fractures and a 'seizure' outcome defined as hospital admissions or ER visits with a primary diagnosis of epilepsy or convulsions., Results: The inclusion criteria were met by 31 635 individuals. In the multivariate analysis, the adherent group had lower odds of hospital admissions with ORs for the eight specifications ranging from 0.729 to 0.872 and ER visits where ORs for the eight specifications ranged from 0.750 to 0.893. The eight ORs for head injuries ranged from 0.647 to 0.888. For fractures, the ORs ranged from 0.407 to 0.841. Our proxy for seizure was inconsistently associated with adherence status., Conclusions: All the adherence measures defined non-adherent groups that were associated with negative outcomes in epilepsy.

Objective: Healthcare providers are under increasing stress and work-related burnout has become common. Mindfulness-based interventions have a potential role in decreasing stress and burnout. The purpose of this study was to determine if a continuing education course based on mindfulness-based stress reduction could decrease burnout and improve mental well-being among healthcare providers, from different professions., Design: This was a pre-post observational study conducted in a university medical center. A total of 93 healthcare providers, including physicians from multiple specialties, nurses, psychologists, and social workers who practiced in both university and community settings, participated. The intervention was a continuing education course based on mindfulness-based stress reduction that met 2.5 hours a week for 8 weeks plus a 7-hour retreat. The classes included training in four types of formal mindfulness practices, including the body scan, mindful movement, walking meditation and sitting meditation, as well as discussion focusing on the application of mindfulness at work. The course was offered 11 times over 6 years. The main outcome measures were work-related burnout as measured by the Maslach Burnout Inventory and self-perceived mental and physical well-being as measured by the SF-12v2., Results: Maslach Burnout Inventory scores improved significantly from before to after the course for both physicians and other healthcare providers for the Emotional Exhaustion (p < 0.03), Depersonalization (p < 0.04), and Personal Accomplishment (p < 0.001) scales. Mental well-being measured by the SF12v2 also improved significantly (p < 0.001). There were no significant changes in the SF12v2 physical health scores., Conclusion: A continuing education course based on mindfulness-based stress reduction was associated with significant improvements in burnout scores and mental well-being for a broad range of healthcare providers.

Many advances in hand surgery have been supported and enabled by the integral relationship that exists between the profession of hand surgery and industry. This relationship takes many forms, including medical education, development of new technology and methodology, research, and opportunities for patient education. As with all of these endeavors, the primary focus of both the physician and industry must be the care of the patient. When a collaborative relationship exists between physicians and industry, a conflict of interest is present and must be recognized as such and managed to avoid any detriment to patient care. Although the hand surgeon, the patient, and industry share the common interest of advancement of patient care, there does exist real and potential conflicts of interest, which are unavoidable, but not necessarily undesirable. Multiple guidelines exist to govern relationships between industry and physicians. The cooperative relationship between the physician and industry is not only helpful, but it can be critical to the advancement of and innovations in patient care. When properly managed, collaboration between the physician and industry can effectively achieve the common goal of serving the best interest of the patient., (Copyright © 2012 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

This paper reviews the economic evaluation literature on pharmacotherapy for migraine and identifies important trends and gaps in the literature. Given the tremendous economic burden of migraine and the availability of various therapies for migraine treatment, economic evaluation of alternative therapies plays a critical role in identifying the most cost-effective therapy to optimize health care resource allocation and clinical decisions. Particularly, physicians and clinical administrators are expected to take an active role in resource allocation decisions at the clinical level. Thus, it is important for them to be familiar with the economic evaluation in migraine pain management, and most importantly, methodologies of economic analyses and the associated shortcomings of published estimates. In this paper, the methodological characteristics of these studies are examined and their results are compared and interpreted. Alternative treatment and health outcome measures are defined and data sources described while methods for assessing the direct and indirect costs are explored. Directions for future research are identified and discussed.

The threat of bioterrorism in the wake of the September 11, 2001, terrorist attacks cannot be ignored. Syndromic surveillance, the practice of electronically monitoring and reporting real-time medical data to proactively identify unusual disease patterns, highlights the conflict between safeguarding public health while protecting individual privacy. Both the Health Insurance Portability and Accountability Act and the Common Rule (which promulgates protections for individuals in federally sponsored medical research programs) safeguard individuals. Public health law protects the entire populace; uneven state-level implementation lacks adequate privacy protections. We propose 3 models for a nationwide bioterrorism surveillance review process: a nationally coordinated systems approach to using protected health information, creating public health information privacy boards, expanding institutional review boards, or some combination of these.

Objective: To examine patient and provider barriers and facilitators of colorectal cancer (CRC) screening among mid-Atlantic Latinos seeking care at urban primary care clinics and describe implications for the design of interventions in primary care., Design and Method: Nine focus groups were conducted with 70 Latino patients and 27 primary care providers. Content analysis of focus group transcripts was performed using established qualitative techniques., Results: Comments on CRC screening fell into 10 content areas: primary care site or provider characteristics (25% patient/21% provider comments); knowledge (18% patient/12% provider comments); cost/insurance coverage (10%/25%); attitudes (14%/7%); ordering of priorities (10%/11%); language (12%/7%); procedural issues regarding screenings (8%/10%); discrimination (2%/1%); and issues related to being a new immigrant (.2%/6%). Patient lack of understanding of the screening test procedures, inadequate knowledge about colorectal cancer, inadequate numbers of Spanish-speaking providers, and the cost of screening were most often cited as barriers by patients. Both providers and patients repeatedly mentioned the lack of funding and referral sources for colonoscopy as a key barrier to performing screening, even with lower-cost fecal occult blood tests, as colonoscopy follow-up would not be available. Patients favored receiving CRC screening recommendations from their usual continuity physician, but were open to receiving information on test procedures and indications from a Spanish-speaking health educator., Conclusions: Efforts to improve funding and availability of colonoscopy for low-income persons could proceed in tandem with linguistically and culturally appropriate clinic-based efforts to improve CRC screening among Latinos.

Background: Studies indicate that success of radiofrequency (RF) ablation of atrial fibrillation (AF) may be in part due to vagal denervation. RFAof supraventricular tachycardia (SVT) has been associated with vagal denervation. The effects of slow pathway (SP) ablation on AF inducibility have not been studied., Objective: To test the hypothesis that SP ablation renders AF less inducible., Methods: Consecutive patients referred for SVT were studied. After atrioventricular nodal reentrant tachycardia (AVNRT) was confirmed they underwent induction of AF. After SP ablation AF induction was reattempted. Vulnerability to AF was reassessed., Results: Twenty-four patients were enrolled; eight were not inducible for AF in the preablative state. Mean CLof the AVNRT was 340 +/- 16 ms. The average RF ablation time was 131 +/- 42 seconds. Presence of junctional rhythm was required. Of the 16 with inducible AF two patients had AF induced during routine invasive electrophysiology study. None of these had inducible AF after SP ablation. Fourteen of 16 patients required specific AF induction. Ten of these were noninducible after SP ablation; two were inducible after SP ablation but with a more aggressive pacing protocol (P < 0.03 compared to preablation) and two had no change in AF vulnerability. Seven of the eight noninducible patients remained noninducible for AF post SP ablation. In the 12 patients who were inducible prior but noninducible after ablation the mean atrial effective refractory period (AERP) increased for both BCL at 400 and 600 ms (400/216 +/- 8 ms preablation vs 400/248 +/- 12 ms postablation, P < 0.03; 600/228 +/- 8 ms preablation vs 600/259 +/- 6 ms postablation, P < 0.04). There were no significant changes in AERP of patients who remained inducible or who were noninducible before ablation. The average ablation time for patients who became noninducible after ablation was significantly higher than those who had no change in inducibility or remained inducible but at a more aggressive pacing threshold (157 +/- 24 seconds vs 35 +/- 5 seconds; P < 0.005)., Conclusion: SP ablation acutely decreases vulnerability to pacing-induced AF in patients with AVNRT. This may reflect the effect of ablation on atrial vagal tone.

Background: This report updates 2001 estimates of disease burden prevented and cost effectiveness of tobacco-use screening and brief intervention relative to that of other clinical preventive services. It also addresses repeated counseling because the literature has focused on single episodes of treatment, while in reality that is neither desirable nor likely., Methods: Literature searches led to four models for calculating the clinically preventable burden of deaths and morbidity from smoking as well as the cost effectiveness of providing the service annually over time. The same methods were used in similar calculations for other preventive services to facilitate comparison., Results: Using methods consistent with existing literature for this service, an estimated 190,000 undiscounted quality-adjusted life years (QALYs) are saved at a cost of $1100 per QALY saved (discounted). These estimates exclude financial savings from smoking-attributable disease prevented and use the average 12-month quit rate in clinical practice for tobacco screening and brief cessation counseling with cessation medications (5.0%) and without (2.4%). Including the savings of prevented smoking-attributable disease and using the effectiveness of repeated interventions over the lifetime of smokers (23.1%), 2.47 million QALYs are saved at a cost savings of $500 per smoker who receives the service., Conclusions: This analysis makes repeated clinical tobacco-cessation counseling one of the three most important and cost-effective preventive services that can be provided in medical practice. Greater efforts are needed to achieve more of this potential value by increasing current low levels of performance.

Decision makers want to know which healthcare services matter the most, but there are no well-established, practical methods for providing evidence-based answers to such questions. Led by the National Commission on Prevention Priorities, the authors update the methods for determining the relative health impact and economic value of clinical preventive services. Using new studies, new preventive service recommendations, and improved methods, the authors present a new ranking of clinical preventive services in the companion article. The original ranking and methods were published in this journal in 2001. The current methods report focuses on evidence collection for a priority setting exercise, guidance for which is effectively lacking in the literature. The authors describe their own standards for searching, tracking, and abstracting literature for priority setting. The authors also summarize their methods for making valid comparisons across different services. This report should be useful to those who want to understand additional detail about how the ranking was developed or who want to adapt the methods for their own purposes.

Background: Influenza causes approximately 36,000 deaths per year in the United States despite the presence of an effective vaccine. This assessment of the value of influenza vaccination to the U.S. population is part of an update to the 2001 ranking of clinical preventive services recommended by the U.S. Preventive Services Task Force. The forthcoming ranking will include the new recommendation of the Advisory Committee on Immunization Practices to extend influenza vaccination to adults aged 50 to 64 years., Methods: This service is evaluated on the two most important dimensions: burden of disease prevented and cost effectiveness. Study methods, described in a companion article, are designed to ensure consistency across many services., Results: Over the lifetime of a birth cohort of 4 million, it is estimated that about 275,000 quality-adjusted life years (QALYs) would be saved if influenza vaccination were offered annually to all people after age 50. Eighty percent of the QALYs saved (220,000) would be achieved by offering the vaccine only to persons aged 65 and older. In year 2000 dollars, the cost effectiveness of influenza vaccination is $980 per QALY saved in persons aged 65 and older, and $28,000 per QALY saved in persons aged 50 to 64. When the costs of patient time and travel are excluded, the cost effectiveness ratio of vaccinating 50- to 64-year-olds decreases to $7200 per QALY saved, and vaccinating those aged 65 and older saves $17 per person vaccinated., Conclusions: Influenza vaccination is a high-impact, cost-effective service for persons aged 65 and older. Vaccinations are also cost effective for persons aged 50 to 64.

Background: Colorectal cancer is the second leading cause of cancer-related death in the United States, yet recommended screenings are not delivered to most people. This assessment of colorectal cancer screening's value to the U.S. population is part of the update to a 2001 ranking of recommended clinical preventive services found in the accompanying article. This article describes the burden of disease prevented and cost-effectiveness as a result of offering patients a choice of colorectal cancer screening tools., Methods: Methods used were designed to ensure consistent estimates across many services and are described in more detail in the companion articles. In a secondary analysis, the authors also estimated the impact of increasing offers for colorectal cancer screening above current levels among the current cross-section of adults aged 50 and older., Results: If a birth cohort of 4 million were offered screening at recommended intervals, 31,500 deaths would be prevented and 338,000 years of life would be gained over the lifetime of the birth cohort. In the current cross-section of people aged 50 and older, 18,800 deaths could be prevented each year by offering all people in this group screening at recommended intervals. Only 58% of these deaths are currently being prevented. In year 2000 dollars, the cost effectiveness of offering patients aged 50 and older a choice of colorectal cancer screening options is $11,900 per year of life gained., Conclusions: Colorectal cancer screening is a high-impact, cost-effective service used by less than half of persons aged 50 and older.

Background: Decision makers at multiple levels need information about which clinical preventive services matter the most so that they can prioritize their actions. This study was designed to produce comparable estimates of relative health impact and cost effectiveness for services considered effective by the U.S. Preventive Services Task Force and Advisory Committee on Immunization Practices., Methods: The National Commission on Prevention Priorities (NCPP) guided this update to a 2001 ranking of clinical preventive services. The NCPP used new preventive service recommendations up to December 2004, improved methods, and more complete and recent data and evidence. Each service received 1 to 5 points on each of two measures--clinically preventable burden and cost effectiveness--for a total score ranging from 2 to 10. Priorities for improving delivery rates were established by comparing the ranking with what is known of current delivery rates nationally., Results: The three highest-ranking services each with a total score of 10 are discussing aspirin use with high-risk adults, immunizing children, and tobacco-use screening and brief intervention. High-ranking services (scores of 6 and above) with data indicating low current utilization rates (around 50% or lower) include: tobacco-use screening and brief intervention, screening adults aged 50 and older for colorectal cancer, immunizing adults aged 65 and older against pneumococcal disease, and screening young women for Chlamydia., Conclusion: This study identifies the most valuable clinical preventive services that can be offered in medical practice and should help decision-makers select which services to emphasize.

Objective: The US Vaccine Adverse Event Reporting System (VAERS) is a passive reporting system to which anyone can report an event. Publicity related to potential adverse events may change reporting patterns. The objective of this paper is to show how litigation-related reports have influenced the trends in possible adverse event reports to VAERS., Methods: The VAERS public-use data files were downloaded in July 2004 and translated into identical SAS data sets for analysis. Cases that were related to litigation were identified using a word search algorithm. All cases for the most frequently reported symptoms in litigation (overdose, neuropathy, autism, "mental retardation," arthralgia, and "speech disorder") were reviewed., Results: In recent years, most case reports to VAERS that were related to overdose, neuropathy, and thimerosal were related to litigation. Many cases that were related to autism and mental retardation were as well., Conclusions: This review shows a previously undisclosed rise in the number of reports to the VAERS related to pending litigation for vaccine injury. The implications of this for understanding longitudinal reporting patterns are discussed.

Background: For patients with a chronic disease, increased cost-sharing for medications may lead to unintended consequences, including reduced use of medications essential for control of their disease., Objective: The objective of this study was to estimate the effects of small ($1-6 per 30-day supply), moderate ($7-10), and large (>$10) increases in medication cost-sharing on 12-month trends in oral hypoglycemic (OH) use among adults with type 2 diabetes., Methods: We conducted a quasiexperimental study using a time series with comparison group design. Data were obtained from computerized membership, benefit, and pharmacy dispensing data of 5 managed care organizations (MCOs). A total of 13,110 12-month episodes of OH use and a medication cost-sharing increase ("intervention") were matched with 13,110 that had no increase. The dependent variable was OH average daily dose (ADD) standardized to each episode's mean OH ADD in the 6-month preintervention period. The principal independent variable was change in cost per 30-day OH supply between the 6-month pre- and postintervention periods. Effects of changes in cost-sharing on OH ADD were estimated using segmented time series regression., Results: Episodes with >$10 increase in cost-sharing had significantly (alpha=0.05) decreased OH ADD in the postintervention period. At 6 months after this increase, OH ADD had decreased by 18.5% from that predicted from the preintervention trend. Episodes with a $1 to $10 increase in cost-sharing and those with no increase in cost-sharing had significant linear increases in OH use over the 12-month period., Conclusions: Large increases in medication cost-sharing were associated with immediate and persistent reductions in OH use. Small and moderate increases had little effect on OH use in the 6-month period after the increase.

We measured sensitivity and timeliness of a syndromic surveillance system to detect bioterrorism events. A hypothetical anthrax release was modeled by using zip code population data, mall customer surveys, and membership information from HealthPartners Medical Group, which covers 9% of a metropolitan area population in Minnesota. For each infection level, 1,000 releases were simulated. Timing of increases in use of medical care was based on data from the Sverdlovsk, Russia, anthrax release. Cases from the simulated outbreak were added to actual respiratory visits recorded for those dates in HealthPartners Medical Group data. Analysis was done by using the space-time scan statistic. We evaluated the proportion of attacks detected at different attack rates and timeliness to detection. Timeliness and completeness of detection of events varied by rate of infection. First detection of events ranged from days 3 to 6. Similar modeling may be possible with other surveillance systems and should be a part of their evaluation.

Objective: We evaluated the positive predictive values (PPVs) of specific criteria based upon International Classification of Diseases, 9th revision (ICD-9-CM) codes documented in health plan administrative databases for identification of cases of serious myopathy and rhabdomyolysis., Study Design and Setting: We conducted a retrospective study among patients enrolled in 11 geographically dispersed managed care organizations. Cohorts of new users of specific statins and fibrates were identified by selecting patients with an initial dispensing of the drug during the period 1 January 1998 to 30 June 2001. Potential cases of serious myopathy or rhabdomyolysis were identified using specific criteria based upon ICD-9-CM codes suggesting a muscle disorder or acute renal failure., Results: A total of 194 hospitalizations meeting the criteria for chart review selection were identified among 206,732 new users of statins and 15,485 new users of fibrates. Overall, 31 cases of serious, clinically important myopathy or rhabdomyolysis (18%) were confirmed through chart review. Of these, 26 (84%) had a claim including codes for myoglobinuria (ICD-9-CM 791.3) or other disorders of muscle, ligament, and fascia (ICD-9-CM 728.89). A PPV of 74% (26 of 35 patients meeting criteria) was found for a composite definition that included (1) a primary or secondary discharge code for myoglobinuria, (2) a primary code for "other disorders of muscle," or (3) a secondary code for "other disorders of muscle" accompanied by a claim for a CK test within 7 days of hospitalization or a discharge code for acute renal failure., Conclusion: For rare adverse events such as serious myopathy or rhabdomyolysis, large population-based databases that include diagnosis and laboratory test claims data can facilitate epidemiologic research.

Our objective was to describe the historical pattern of the decline in weekend births. Data on 906,100 health maintenance organization enrollees' birthdates were analyzed to show patterns of birth by day of week from 1910 to 1999. The decline in Sunday births dates to the 1930s, and the decline in Saturday births dates to the 1950s, far earlier than previously demonstrated in the literature. The expected natural birth process has been significantly modified. By examining a much longer time series than in other literature, it is also possible to see that the trend is not abating and may be increasing.

Ankle equinus is the most commonly identified impairment of individuals with spastic hemiplegia (SH). However, it is not clear how equinus at the ankle may contribute to gait deviations at other joints. The purpose of this study was to determine what compensatory gait deviations may occur as a result of an imposed, unilateral equinus constraint. Gait data were collected on 12 adult subjects with and without one ankle constrained in equinus using a unique taping method. Knee extension at initial contact, knee extension in mid stance, and hip extension at terminal stance were all found to be significantly reduced on the ipsilateral side as a result of the ankle constraint. On the unconstrained or contralateral side, subjects tended to adopt a foot-flat or toe-first initial contact pattern. This study suggests that stance phase limitations in both hip and knee extension in the gait of persons with hemiplegia are not necessarily caused by limited length of the involved side hamstrings and/or hip flexors, but rather that they can occur as the result of an ankle plantarflexor contracture alone. Deviations in the contralateral foot contact pattern can also occur secondary to unilateral equinus and should not be assumed to represent bilateral involvement.

Context: Lipid-lowering agents are widely prescribed in the United States. Reliable estimates of rhabdomyolysis risk with various lipid-lowering agents are not available., Objective: To estimate the incidence of rhabdomyolysis in patients treated with different statins and fibrates, alone and in combination, in the ambulatory setting., Design, Setting, and Patients: Drug-specific inception cohorts of statin and fibrate users were established using claims data from 11 managed care health plans across the United States. Patients with at least 180 days of prior health plan enrollment were entered into the cohorts between January 1, 1998, and June 30, 2001. Person-time was classified as monotherapy or combined statin-fibrate therapy., Main Outcome Measure: Incidence rates of rhabdomyolysis per 10,000 person-years of treatment, number needed to treat, and relative risk of rhabdomyolysis., Results: In 252,460 patients treated with lipid-lowering agents, 24 cases of hospitalized rhabdomyolysis occurred during treatment. Average incidence per 10,000 person-years for monotherapy with atorvastatin, pravastatin, or simvastatin was 0.44 (95% confidence interval [CI], 0.20-0.84); for cerivastatin, 5.34 (95% CI, 1.46-13.68); and for fibrate, 2.82 (95% CI, 0.58-8.24). By comparison, the incidence during unexposed person-time was 0 (95% CI, 0-0.48; P = .056). The incidence increased to 5.98 (95% CI, 0.72-216.0) for combined therapy of atorvastatin, pravastatin, or simvastatin with a fibrate, and to 1035 (95% CI, 389-2117) for combined cerivastatin-fibrate use. Per year of therapy, the number needed to treat to observe 1 case of rhabdomyolysis was 22,727 for statin monotherapy, 484 for older patients with diabetes mellitus who were treated with both a statin and fibrate, and ranged from 9.7 to 12.7 for patients who were treated with cerivastatin plus fibrate., Conclusions: Rhabdomyolysis risk was similar and low for monotherapy with atorvastatin, pravastatin, and simvastatin; combined statin-fibrate use increased risk, especially in older patients with diabetes mellitus. Cerivastatin combined with fibrate conferred a risk of approximately 1 in 10 treated patients per year.