Long-Term Follow-up of a Randomized Controlled Trial Evaluating a Mobile Health Intervention for Self-Management in Lung Transplant Recipients.

Mobile health interventions may help transplant recipients follow their complex medical regimens. Pocket Personal Assistant for Tracking Health (Pocket PATH) is one such intervention tailored for lung transplant recipients. A randomized controlled trial showed Pocket PATH's superiority to usual care for promoting the self-management behaviors of adherence, self-monitoring and communication with clinicians during posttransplant year 1. Its long-term impact was unknown. In this study, we examined associations between Pocket PATH exposure during year 1 and longer term clinical outcomes-mortality and bronchiolitis obliterans syndrome (BOS)-among 182 recipients who survived the original trial. Cox regression assessed whether (a) original group assignment and (b) performance of self-management behaviors during year 1 predicted time to outcomes. Median follow-up was 5.7 years after transplant (range 4.2-7.2 years). Pocket PATH exposure had no direct effect on outcomes (p-values >0.05). Self-monitoring was associated with reduced mortality risk (hazard ratio [HR] 0.45; 95% confidence interval [CI] 0.22-0.91; p = 0.027), and reporting abnormal health indicators to clinicians was associated with reduced risks of mortality (HR 0.15; 95% CI 0.04-0.65; p = 0.011) and BOS (HR 0.27; 95% CI 0.08-0.86; p = 0.026), regardless of intervention group assignment. Although Pocket PATH did not have a direct impact on long-term outcomes, early improvements in self-management facilitated by Pocket PATH may be associated with long-term clinical benefit.

Banff Histopathological Consensus Criteria for Preimplantation Kidney Biopsies.

The Banff working group on preimplantation biopsy was established to develop consensus criteria (best practice guidelines) for the interpretation of preimplantation kidney biopsies. Digitally scanned slides were used (i) to evaluate interobserver variability of histopathologic findings, comparing frozen sections with formalin-fixed, paraffin-embedded tissue of wedge and needle core biopsies, and (ii) to correlate consensus histopathologic findings with graft outcome in a cohort of biopsies from international medical centers. Intraclass correlations (ICCs) and univariable and multivariable statistical analyses were performed. Good to fair reproducibility was observed in semiquantitative scores for percentage of glomerulosclerosis, arterial intimal fibrosis and interstitial fibrosis on frozen wedge biopsies. Evaluation of frozen wedge and core biopsies was comparable for number of glomeruli, but needle biopsies showed worse ICCs for glomerulosclerosis, interstitial fibrosis and tubular atrophy. A consensus evaluation form is provided to help standardize the reporting of histopathologic lesions in donor biopsies. It should be recognized that histologic parameters may not correlate with graft outcome in studies based on organs deemed to be acceptable after careful clinical assessment. Significant limitations remain in the assessment of implantation biopsies.

Elevated ST2 Distinguishes Incidences of Pediatric Heart and Small Bowel Transplant Rejection.

Elevated serum soluble (s) suppressor of tumorigenicity-2 is observed during cardiovascular and inflammatory bowel diseases. To ascertain whether modulated ST2 levels signify heart (HTx) or small bowel transplant (SBTx) rejection, we quantified sST2 in serially obtained pediatric HTx (n = 41) and SBTx recipient (n = 18) sera. At times of biopsy-diagnosed HTx rejection (cellular and/or antibody-mediated), serum sST2 was elevated compared to rejection-free time points (1714 ± 329 vs. 546.5 ± 141.6 pg/mL; p = 0.0002). SBTx recipients also displayed increased serum sST2 during incidences of rejection (7536 ± 1561 vs. 2662 ± 543.8 pg/mL; p = 0.0347). Receiver operator characteristic (ROC) analysis showed that serum sST2 > 600 pg/mL could discriminate time points of HTx rejection and nonrejection (area under the curve [AUC] = 0.724 ± 0.053; p = 0.0003). ROC analysis of SBTx measures revealed a similar discriminative capacity (AUC = 0.6921 ± 0.0820; p = 0.0349). Quantitative evaluation of both HTx and SBTx biopsies revealed that rejection significantly increased allograft ST2 expression. Pathway and Network Analysis of biopsy data pinpointed ST2 in the dominant pathway modulated by rejection and predicted tumor necrosis factor-α and IL-1ß as upstream activators. In total, our data indicate that alloimmune-associated pro-inflammatory cytokines increase ST2 during rejection. They also demonstrate that routine serum sST2 quantification, potentially combined with other biomarkers, should be investigated further to aid in the noninvasive diagnosis of rejection.

Determining sample size and a passing criterion for respirator fit-test panels.

Few studies have proposed methods for sample size determination and specification of passing criterion (e.g., number needed to pass from a given size panel) for respirator fit-tests. One approach is to account for between- and within- subject variability, and thus take full advantage of the multiple donning measurements within subject, using a random effects model. The corresponding sample size calculation, however, may be difficult to implement in practice, as it depends on the model-specific and test panel-specific variance estimates, and thus does not yield a single sample size or specific cutoff for number needed to pass. A simple binomial approach is therefore proposed to simultaneously determine both the required sample size and the optimal cutoff for the number of subjects needed to achieve a passing result. The method essentially conducts a global search of the type I and type II errors under different null and alternative hypotheses, across the range of possible sample sizes, to find the lowest sample size which yields at least one cutoff satisfying, or approximately satisfying all pre-determined limits for the different error rates. Benchmark testing of 98 respirators (conducted by the National Institute for Occupational Safety and Health) is used to illustrate the binomial approach and show how sample size estimates from the random effects model can vary substantially depending on estimated variance components. For the binomial approach, probability calculations show that a sample size of 35 to 40 yields acceptable error rates under different null and alternative hypotheses. For the random effects model, the required sample sizes are generally smaller, but can vary substantially based on the estimate variance components. Overall, despite some limitations, the binomial approach represents a highly practical approach with reasonable statistical properties.

Regional brain injury on conventional and diffusion weighted MRI is associated with outcome after pediatric cardiac arrest.

BACKGROUND: To assess regional brain injury on magnetic resonance imaging (MRI) after pediatric cardiac arrest (CA) and to associate regional injury with patient outcome and effects of hypothermia therapy for neuroprotection. METHODS: We performed a retrospective chart review with prospective imaging analysis. Children between 1 week and 17 years of age who had a brain MRI in the first 2 weeks after CA without other acute brain injury between 2002 and 2008 were included. Brain MRI (1.5 T General Electric, Milwaukee, WI, USA) images were analyzed by 2 blinded neuroradiologists with adjudication; images were visually graded. Brain lobes, basal ganglia, thalamus, brain stem, and cerebellum were analyzed using T1, T2, and diffusion-weighted images (DWI). RESULTS: We examined 28 subjects with median age 1.9 years (IQR 0.4-13.0) and 19 (68 %) males. Increased intensity on T2 in the basal ganglia and restricted diffusion in the brain lobes were associated with unfavorable outcome (all P < 0.05). Therapeutic hypothermia had no effect on regional brain injury. Repeat brain MRI was infrequently performed but demonstrated evolution of lesions. CONCLUSION: Children with lesions in the basal ganglia on conventional MRI and brain lobes on DWI within the first 2 weeks after CA represent a group with increased risk of poor outcome. These findings may be important for developing neuroprotective strategies based on regional brain injury and for evaluating response to therapy in interventional clinical trials.

Lifestyle predicts falls independent of physical risk factors.

SUMMARY: Many falls occur among older adults with no traditional risk factors. We examined potential independent effects of lifestyle on fall risk. Not smoking and going outdoors frequently or infrequently were independently associated with more falls, indicating lifestyle-related behavioral and environmental risk factors are important causes of falls in older women. INTRODUCTION: Physical and lifestyle risk factors for falls and population attributable risks (PAR) were examined. METHODS: We conducted a 4-year prospective study of 8,378 community-dwelling women (mean age = 71 years, SD = 3) enrolled in the Study of Osteoporotic Fractures. Data on number of falls were self-reported every 4 months. Fall rates were calculated (# falls/woman-years). Poisson regression was used to estimate relative risks (RR). RESULTS: Physical risk factors (p < or = 0.05 for all) included tall height (RR = 0.89 per 5 in.), dizziness (RR = 1.16), fear of falling (RR = 1.20), self-reported health decline (RR = 1.19), difficulty with Instrumental Activities of Daily Living (IADLs) (RR = 1.12, per item), fast usual-paced walking speed (RR = 1.18, per 2 SD), and use of antidepressants (RR = 1.20), benzodiazepines (RR = 1.11), or anticonvulsants (RR = 1.62). Protective physical factors (p < or = 0.05 for all) included good visual acuity (RR = 0.87, per 2 SD) and good balance (RR = 0.85 vs. poor). Lifestyle predicted fewer falls including current smoking (RR = 0.76), going outdoors at least twice weekly but not more than once a day (RR = 0.89 and vs. twice daily). High physical activity was associated with more falls but only among IADL impaired women. Five potentially modifiable physical risk factors had PAR > or = 5%. CONCLUSIONS: Fall interventions addressing modifiable physical risk factors with PAR > or = 5% while considering environmental/behavioral risk factors are indicated.

Effects of lipodystrophy on quality of life and depression in HIV-infected men on HAART.

The aim of the study was a prospective assessment of the possible consequences of a diagnosis of lipodystrophy on health-related quality of life (HRQL) and depressive symptomatology in HIV-seropositive men who have sex with men. A standardized physical assessment for lipodystrophy was introduced within a prospective study in April 1999. Over a 2-year follow- up, 37 HIV-seropositive men who met the criteria for lipodystrophy were longitudinally compared to 92 HIV-seropositive men without lipodystrophy and 88 HIV-seronegative men on measures of HRQL and depression. A series of questionnaires, which included the Medical Outcomes Study Short-Form 36 (SF-36) and the Center for Epidemiological Studies-Depression (CES-D), were administered to assess HRQL and depression, respectively. SF-36 scores were summarized using the mental and physical components; CES-D results were reported as both dichotomous (with or with clinical depression) and continuous scores. Neither the mental nor physical components of the SF-36 showed any significant differences between patients with lipodystrophy versus HIV-seropositive patients without lipodystrophy. Similarly, lipodystrophy status was not significantly associated with either continuous depression scores or presence of clinical depression. However, consistent with previous results, HIV-seropositive men without lipodystrophy (compared to HIV-seronegative men) reported higher scores on both components of the SF-36 scales and both categorizations of the CES-D. The results of this study suggest that lipodystrophy does not negatively affect HRQL or depression, above and beyond, the diagnosis of HIV infection, although the impact of the severity of lipodystrophy on these conditions will require further study.

Comparative pulmonary toxicity of 6 abrasive blasting agents.

Inhalation of silica dust is associated with pulmonary fibrosis. Therefore, substitute abrasive materials have been suggested for use in abrasive blasting operations. To date, toxicological evaluation of most substitute abrasives has been incomplete. Therefore, the objective of this study was to compare the pulmonary toxicity of a set of substitute abrasives (garnet, staurolite, coal slag, specular hematite, and treated sand) to that of blasting sand. Rats were exposed to blasting sand or an abrasive substitute by intratracheal instillation and pulmonary responses to exposure were monitored 4 weeks postexposure. Pulmonary damage was monitored as lactate dehydrogenase (LDH) in the acellular lavage fluid. Pulmonary inflammation was evaluated from the yield of polymorphonuclear leukocytes (PMN) obtained by bronchoalveolar lavage. The activity of alveolar macrophages was determined by measuring zymosan-stimulated chemiluminescence. Blasting sand caused lung damage and showed histologic evidence for inflammation and fibrosis. Garnet, staurolite, and treated sand exhibited toxicity and inflammation that were similar to blasting sand, while coal slag caused greater pulmonary damage and inflammation than blasting sand. In contrast, specular hematite did not significantly elevate LDH or PMN levels and did not stimulate macrophage activity 4 weeks postexposure.

An in vitro comparison of the susceptibilities of bacterial isolates from patients with conjunctivitis and blepharitis to newer and established topical antibiotics.

This retrospective study compared new and established topical antibiotics with regard to the in vitro susceptibility of bacterial isolates recovered from patients with conjunctivitis (n = 385) and blepharitis (n = 173) using the National Committee for Clinical Laboratory Standards-approved disk diffusion method. The percent susceptibility of recovered isolates to single antibiotic agents or combinations were ranked from greatest to least: chloramphenicol, bacitracin/polymyxin B, ofloxacin, sulfa, ciprofloxacin, trimethoprim/polymyxin B, norfloxacin, gentamicin, bacitracin, trimethoprim, tobramycin, neomycin, erythromycin, and polymyxin B. We determined that none of the available topical antibiotics provided 100% broad spectrum coverage in vitro. Established antibiotics often provided coverage comparable to the newer drugs. Due to the unproven value of in vitro testing as a predictor of clinical outcome in bacterial blepharitis and conjunctivitis, the ophthalmologist should choose therapy based on clinical experience, ongoing critical evaluation of available antibiotics, and cost-effectiveness.

A matched case-control study of convenience store robbery risk factors.

Convenience store clerks have been shown to be at high risk for assault and homicide, mostly owing to robbery or robbery attempts. Although the literature consistently indicates that at least some environmental designs are effective deterrents of robbery, the significance of individual interventions and policies has differed across past studies. To address these issues, a matched case-control study of 400 convenience store robberies in three metropolitan areas of Virginia was conducted. Conditional logistic regression was implemented to evaluate the significance of various environmental designs and other factors possibly related to convenience store robbery. Findings indicate that numerous characteristics of the surrounding environment and population were significantly associated with convenience store robbery. Results also showed that, on a univariate level, most crime prevention factors were significantly associated with a lower risk for robbery. Using a forward selection process, a multivariate model, which included cash handling policy, bullet-resistant shielding, and numerous characteristics of the surrounding area and population, was identified. This study addressed numerous limitations of the previous literature by prospectively collecting extensive data on a large sample of diverse convenience stores and directly addressing the current theory on the robbers' selection of a target store through a matched case-control design.

Time course of pulmonary response of rats to inhalation of crystalline silica: histological results and biochemical indices of damage, lipidosis, and fibrosis.

Previous studies have determined that alpha-quartz (crystalline silica) can cause pulmonary inflammation, damage, and fibrosis. However, the temporal relationship between silica inhalation and pulmonary inflammation, damage, and fibrosis has not been fully examined. To address this gap in our knowledge of silica-induced pulmonary fibrosis, a chronic inhalation study using rats was designed. Specifically, rats were exposed to a silica aerosol (15 mg/m3 silica, 6 h/d, 5 d/wk, 116 d), and measurements of pulmonary inflammation, damage, and fibrosis were monitored throughout the study. We report (1) data demonstrating that the silica aerosol generation and exposure system produced a consistent silica aerosol of respirable size particles; (2) the time course of silica deposition in the lung; (3) calculations that demonstrate that the rats were not in pulmonary overload; (4) histopathological data demonstrating time-dependent enhancement of silica-induced alveolitis, epithelial hypertrophy and hyperplasia, alveolar lipoproteinosis, and pulmonary fibrosis in the absence of overload; and (5) biochemical data documenting the development of lipidosis, lung damage, and fibrosis.

Random sampling or 'random' model in skin flux measurements? [Commentary on "Investigation of the mechanism of flux across human skin in vitro by quantitative structure-permeability relationships"].

Transdermal therapy receives increasing attention as an attractive alternative to traditional drug delivery. Unfortunately the exact algorithm of transdermal permeation that could guide medicinal chemists towards delivery optimization at an early stage of the drug design process still remains to be decoded. This paper discusses some major hurdles on the way to full understanding of Quantitative Structure-Activity Relationships (QSAR) of skin permeation. From the statistical perspective, a recently published combined data set is found to be inappropriate with respect to the distribution of major molecular descriptors, and therefore should be approached cautiously as a source for QSAR model training and in modelling of occupational and environmental skin exposures.

Misclassification of physical work exposures as a design issue for musculoskeletal intervention studies.

OBJECTIVES: This study determined the impact of misclassification due to using job titles as surrogate variables for physical work exposures to assess confounding in a study of the preventive effect of back belts on back injury. The authors present retail merchandise data that quantify misclassification from residual confounding by physical work exposures on injury rate ratios when available administrative job titles are used. METHODS: Job title and direct observation data on 134 workers were used to calculate the percentage to which the job-title-adjusted rate ratio for back injury accounts for confounding by the true physical work exposures, awkward postures, and heavy weight handling. Workers' compensation data, an estimate of the effect of back belts from the literature, and the percentage of adjustment of the rate ratio due to the job title variable were used to calculate the magnitude of bias from the rate ratio adjusted for job title. RESULTS: The job title variable was found to have sensitivities of 97% and 85% and specificities of 68% and 58% for awkward postures and heavy weight handling, respectively. The magnitude of confounding bias remaining for the back-injury rate ratio when the job title surrogate was used was 24% for postures and 45% for heavy weight handling. CONCLUSIONS: The administrative job title performed poorly in this setting; residual confounding was sufficient to bias the rate ratio from 2.0 to 1.3. The effect of additional sources of misclassification and the need for better exposure measures than job title are discussed.

Ergonomic exposure assessment: an application of the PATH systematic observation method to retail workers. Postures, Activities, Tools and Handling.

This study examined biomechanical stressor variables (physical work exposures) in relation to job title, gender, and back-belt status in 134 retail store workers. The principal concerns were to quantitatively describe physical work exposures and to determine the degrees to which these quantitative variables correlated with job title and with the use of back belts. An additional objective was to assess the inter-rater reliability of the observation method. The systematic observation method employed was based on a modification of the PATH (Postures, Activities, Tools, and Handling) measurement method. Chi-square analysis indicated that the frequencies of bent or twisted postures followed the pattern of unloaders > stockers > department managers. For weight handled per lift, lower, or carry, the pattern was unloaders > department managers > stockers. The mean lifting frequencies per hour were 35.9 for department managers, 48.8 for stockers, and 137.4 for unloaders. Back-belt-wearing percentages were higher for unloaders (63%) compared with stockers (48%) and department managers (25%). Back-belt-wearing workers had higher levels of biomechanical stressor variables, including arm position, twisting, weight handled, and number of lifts per hour. Kappa statistics ranged from 0.5 to 0.63, a level of adequate or good reliability beyond chance. The method employed in this study is applicable in studies that require only fairly crude distinctions among biomechanical stressor variables. Nevertheless, this level of distinction may be sufficient when implementing intervention studies and control strategies for many material-handling-intensive jobs.

Higher 1,25-dihydroxyvitamin D3 concentrations associated with lower fall rates in older community-dwelling women.

INTRODUCTION: The purpose of this study was to examine the relationships of vitamin D supplementation and serum concentrations of vitamin D metabolites and parathyroid hormone (PTH) with neuromuscular function and falls in older community-dwelling women. METHODS: We examined these relationships using a 4-year prospective multi-center study among 9,526 community-dwelling women enrolled in the Study of Osteoporotic Fractures (median age: 70 years; interquartile range: 67-75) and a subset of 389 women (97%) out of 400 who were randomly selected from the entire cohort for serum measures. Measurements included: vitamin D supplementation, serum 25-hydroxyvitamin D(3) [25(OH)D(3)], serum 1,25-dihydroxyvitamin D(3) [1,25(OH) (2)D(3)], and serum intact parathyroid hormone (iPTH); grip and quadriceps strength, chair-stand time, walking speed, reaction time, and balance-walk time (including changes in grip strength, chair-stand time, walking speed and balance-walk time over approximately 3.7 years); and incident fall rates (number of falls/woman-years). RESULTS: In 9,526 women, vitamin D supplementation was not associated with any measures of neuromuscular function, change in neuromuscular function, or fall rates (p>0.01 for all). In a subgroup of 389 women, there was a trend of higher 25(OH)D(3) concentration with slightly weaker grip strength (p=0.007), and women in the fourth quartile of 1,25(OH)(2)D(3) had a faster chair-stand time (p=0.017) than women in the first quartile; still, in general, concentrations of 25(OH)D(3), 1,25(OH)(2)D(3), and iPTH were not associated with either neuromuscular function or changes in neuromuscular function (p>0.05 for all). However, higher 1,25(OH)(2)D(3) concentration was associated with lower fall rates (p=0.039). CONCLUSIONS: Higher 1,25(OH)(2)D(3) concentration is associated with a lower fall risk in older community-dwelling women, but vitamin D supplementation, and 25(OH)D(3) and iPTH concentrations are not associated with either neuromuscular function or falls.

Multianalyte profiling of serum cytokines for detection of pancreatic cancer.

Early detection of pancreatic cancer might improve clinical outcome. Significant alterations in the levels of individual serum cytokines have been reported in pancreatic cancer. We hypothesized that a multicytokine panel could serve as biomarkers for pancreatic cancer. To evaluate the diagnostic utility of such a panel, we have utilized a novel multianalyte LabMAP profiling technology that allows simultaneous measurement of multiple markers. In this study, a panel of 31 serological markers including cytokines, chemokines, growth and angiogenic factors in combination with CA 19-9 was analyzed in sera of pancreatic cancer patients, patients with chronic pancreatitis, and matched control healthy subjects. Statistical analysis identified a multicytokine panel that was able to distinguish pancreatic cancer from healthy controls with a sensitivity of 85.7% and specificity of 92.3%, which was superior to performance of CA 19-9 alone. Importantly, a multicytokine panel allowed the discrimination of pancreatic cancer from chronic pancreatitis with high sensitivity of 98% and specificity of 96.4%. In conclusion, we demonstrated that analysis of multiple serum cytokines using a novel LabMAP technology is a promising approach for development of a diagnostic assay for pancreatic cancer.

Risk factors for back injury in 31,076 retail merchandise store workers.

Risk factors for work-associated strain or sprain back injuries were investigated in a cohort of 31,076 material handlers from 260 retail merchandise stores in the United States. The workers studied were those with significant material-handling responsibilities--daily lifting and movement of merchandise. Workers in jobs with the greatest physical work requirements had an injury rate of 3.64 per 100 person-years versus 1.82 in workers with lesser work requirements. The unadjusted injury rate for males was 3.67 per 100 person-years compared with 2.34 per 100 person-years for females, but the excess for males was confounded by higher physical work requirements for men in the stocker/receiver job category. The injury rate ratio for short versus long duration of employment was 3.53 (95% confidence interval: 2.90, 4.30); for medium versus long duration of employment, it was 1.38 (95% confidence interval: 1.18, 1.62). The elevated rate ratios were maintained when the data were stratified by subsets with different rates of turnover. The results suggest that workers with the greatest physical work requirements and those with the shortest duration of employment are at the highest risk of back injuries. However, selection forces causing worker turnover within this cohort of active workers are not well characterized and have the potential to bias the measures for time-related factors such as duration of employment.

Robbery characteristics and employee injuries in convenience stores.

BACKGROUND: Each year approximately 30,000 convenience store employees are at risk for injuries related to robberies and many are fatal. METHODS: A prospective cohort study of 460 convenience store robberies from 1 February 1995 to 30 September 1996 was conducted to uncover possible associations between injury and pertinent robbery circumstances and work environments. Data collection sources included police reports, employee interviews, store evaluations, and relevant Census data. Rate ratios and correlation statistics were calculated to identify associations with injury and relationships between variables. RESULTS: Injury risk was strongly associated with the following characteristics: employee resistance, robberies without firearms or money taken, daytime and merchandise robberies, stores with limited escape routes and no cash policy or drop safe, older clerks, and surrounding areas with lower valued buildings, less expensive rent, more vacant structures, and younger residents. Numerous intercorrelations between these characteristics were identified. DISCUSSION: Training opportunities, store procedures, and environmental designs are important factors to consider in reducing robbery-related injuries.

Slip and fall-related injuries in relation to environmental cold and work location in above-ground coal mining operations.

BACKGROUND: The association between slip and fall-related injuries and environmental temperature was examined for mostly enclosed (inside vehicles, machinery, or buildings), outdoor (outside, not enclosed), and enclosed/outdoor jobs in the coal mining industry to see if differences existed among the three work locations that had varying exposure to cold temperatures. METHODS: Temperature data from the National Climatic Data Center and injury data from the Mine Safety and Health Administration were evaluated from 1985-1990 for seven states. Proportionate methods were used to examine the relationship between slips and falls and temperature. RESULTS: Proportionate injury ratios of slips and fall-related injuries increased as temperature declined for all three work locations. Proportion of slips and fall-related injuries that occurred while running/walking increased with declining temperature, with the ground outside as the most common source of these injuries. CONCLUSIONS: Outside movement becomes a greater hazard at freezing temperatures for workers in all locations, not just outdoor workers. Any intervention methods geared toward reducing injury incidents facilitated by cold weather must also be directed toward workers who spend time in more enclosed locations.