Systematic review: Lost-time injuries in the US mining industry.

BACKGROUND: The mining industry is associated with high levels of accidents, injuries and illnesses. Lost-time injuries are useful measures of health and safety in mines, and the effectiveness of its safety programmes. AIMS: To identify the type of lost-time injuries in the US mining workforce and to examine predictors of these occupational injuries. METHODS: Primary papers on lost-time injuries in the US mining sector were identified through a literature search in eight health, geology and mining databases, using a systematic review protocol tailored to each database. The Critical Appraisal Skills Programme (CASP), Framework of Quality Assurance for Administrative Data Source and the Cochrane Collaboration 'Risk of bias' assessment tools were used to assess study quality. RESULTS: A total of 1736 articles were retrieved before duplicates were removed. Fifteen articles were ultimately included with a CASP mean score of 6.33 (SD 0.62) out of 10. Predictors of lost-time injuries included slips and falls, electric injuries, use of mining equipment, working in underground mining, worker's age and occupational experience. CONCLUSIONS: This is the first systematic review of lost-time injuries in the US mining sector. The results support the need for further research on factors that contribute to workplace lost-time injuries as there is limited literature on the topic. Safety analytics should also be applied to uncover new trends and predict the likelihood of future incidents before they occur. New insights will allow employers to prevent injuries and foster a safer workplace environment by implementing successful occupational health and safety programmes.

p16INK4a , a Senescence Marker, Influences Tenofovir/Emtricitabine Metabolite Disposition in HIV-Infected Subjects.

The goal of this study was to explore the relationships between tenofovir (TFV) and emtricitabine (FTC) disposition and markers of biologic aging, such as the frailty phenotype and p16INK4a gene expression. Chronologic age is often explored in population pharmacokinetic (PK) analyses, and can be uninformative in capturing the impact of aging on physiology, particularly in human immunodeficiency virus (HIV)-infected patients. Ninety-one HIV-infected participants provided samples to quantify plasma concentrations of TFV/FTC, as well as peripheral blood mononuclear cell (PBMC) samples for intracellular metabolite concentrations; 12 participants provided 11 samples, and 79 participants provided 4 samples, over a dosing interval. Nonlinear mixed effects modeling of TFV/FTC and their metabolites suggests a relationship between TFV/FTC metabolite clearance (CL) from PBMCs and the expression of p16INK4a , a marker of cellular senescence. This novel approach to quantifying the influence of aging on PKs provides rationale for further work investigating the relationships between senescence and nucleoside phosphorylation and transport.

Population Pharmacokinetics Modeling of Unbound Efavirenz, Atazanavir, and Ritonavir in HIV-Infected Subjects With Aging Biomarkers.

Unbound drug is the pharmacodynamically relevant concentration. This study aimed to determine if chronologic age or markers of biologic aging, such as the frailty phenotype and p16INK4a gene expression, altered unbound pharmacokinetics (PKs) of efavirenz (EFV) and atazanavir/ritonavir (ATV/RTV). Sixty human immunodeficiency virus (HIV)-infected participants receiving EFV and 31 receiving ATV/RTV provided 1 to 11 samples to quantify total and unbound plasma concentrations. Population PK models with total and unbound concentrations simultaneously described are developed for each drug. The unbound fractions for EFV, ATV, and RTV are 0.65%, 5.67%, and 0.63%, respectively. Covariate analysis suggests RTV unbound PK is sensitive to body size; unbound fraction of RTV is 34% lower with body mass index (BMI) above 30 kg/m2 . No alterations in drug clearance or unbound fraction with age, frailty, or p16INK4a expression were observed. Assessing functional and physiologic aging markers to inform potential PK changes is necessary to determine if drug/dosing changes are warranted in the aging population.

Design and validation of a questionnaire to assess organizational culture in French hospital wards.

BACKGROUND: Although many organizational culture questionnaires have been developed, there is a lack of any validated multidimensional questionnaire assessing organizational culture at hospital ward level and adapted to health care context. Facing the lack of an appropriate tool, a multidisciplinary team designed and validated a dimensional organizational culture questionnaire for healthcare settings to be administered at ward level. METHODS: A database of organizational culture items and themes was created after extensive literature review. Items were regrouped into dimensions and subdimensions (classification validated by experts). Pre-test and face validation was conducted with 15 health care professionals. In a stratified cluster random sample of hospitals, the psychometric validation was conducted in three phases on a sample of 859 healthcare professionals from 36 multidisciplinary medicine services: 1) the exploratory phase included a description of responses' saturation levels, factor and correlations analyses and an internal consistency analysis (Cronbach's alpha coefficient); 2) confirmatory phase used the Structural Equation Modeling (SEM); 3) reproducibility was studied by a test-retest. RESULTS: The overall response rate was 80 %; the completion average was 97 %. The metrological results were: a global Cronbach's alpha coefficient of 0.93, higher than 0.70 for 12 sub-dimensions; all Dillon-Goldstein's rho coefficients higher than 0.70; an excellent quality of external model with a Goodness of Fitness (GoF) criterion of 0.99. Seventy percent of the items had a reproducibility ranging from moderate (Intra-Class Coefficient between 50 and 70 % for 25 items) to good (ICC higher than 70 % for 33 items). CONCLUSIONS: COMEt (Contexte Organisationnel et Managérial en Etablissement de Santé) questionnaire is a validated multidimensional organizational culture questionnaire made of 6 dimensions, 21 sub-dimensions and 83 items. It is the first dimensional organizational culture questionnaire, specific to healthcare context, for a unit level assessment showing robust psychometric properties (validity and reliability). This tool is suited for research purposes, especially for assessing organizational context in research analysing the effectiveness of hospital quality improvement strategies. Our tool is also suited for an overall assessment of ward culture and could be a powerful trigger to improve management and clinical performance. Its psychometric properties in other health systems need to be tested.

Model-Based Analysis of Unbound Lopinavir Pharmacokinetics in HIV-Infected Pregnant Women Supports Standard Dosing in the Third Trimester.

Physiological changes during pregnancy can affect drug pharmacokinetics. Here we present a population pharmacokinetic model to describe the longitudinal change of unbound lopinavir/ritonavir (LPV/RTV) PK parameters with gestational age, and to predict unbound LPV concentrations under different dosing regimens. The changes in apparent intrinsic clearances of LPV and RTV during pregnancy are described using an exponential function of gestational age. The unbound fractions of LPV/RTV are not significantly different between pregnancy and postpartum. Simulation reveals that despite increases in LPV intrinsic clearance, effective LPV inhibitory quotient (IQ) values are predicted with the standard dosing (400/100 mg b.i.d.) in >90% of simulations, with ≤4-fold increase in viral IC50. As viral susceptibility decreases, higher doses increase the likelihood of efficacy. With ≥40-fold increases in IC50, IQs suggest alternate regimens be considered. This approach refines previous LPV PK reports, and supports that standard dosing is effective with susceptible virus.

Traumatic brain injury rehabilitation, the programs applied in French UEROS units, and the specificity of the Limoges experience.

First created in 1996, the French evaluation, retraining, social and vocational orientation units (UEROS) now play a fundamental role in the social and vocational rehabilitation of patients with brain injury. As of today, there exist 30 UEROS centers in France. While their care and treatment objectives are shared, their means of assessment and retraining differ according to the experience of each one. The objective of this article is to describe the specific programs and the different tools put to work in the UEROS of Limoges. The UEROS of Limoges would appear to offer a form of holistic rehabilitation management characterized by the importance of psycho-education and its type of approach towards vocational reintegration.

Pharmacokinetics of two common antiretroviral regimens in older HIV-infected patients: a pilot study.

OBJECTIVES: The pharmacokinetics (PK) of antiretrovirals (ARVs) in older HIV-infected patients are poorly described. Here, the steady-state PK of two common ARV regimens [tenofovir (TFV)/emtricitabine (FTC)/efavirenz (EFV) and TFV/FTC/atazanavir (ATV)/ritonavir (RTV)] in older nonfrail HIV-infected patients are presented. METHODS: HIV-infected subjects ≥ 55 years old not demonstrating the frailty phenotype were enrolled in an unblinded, intensive-sampling PK study. Blood plasma (for TFV, FTC, EFV, ATV and RTV concentrations) and peripheral blood mononuclear cells [PBMCs; for tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) concentrations] were collected at 11 time-points over a 24-hour dosing interval. Drug concentrations were analysed using validated liquid chromatography-ultraviolet detection (LC-UV) or liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. Noncompartmental pharmacokinetic analysis was used to estimate PK parameters [area under the concentration-time curve over 24 h (AUC0-24h ) and maximal concentration (Cmax )]. These parameters were compared with historical values from the general HIV-infected population. RESULTS: Six subjects on each regimen completed the study. Compared with the general population, these elderly subjects had 8-13% decreased TFV AUC0-24h and Cmax , and 19-78% increased FTC and RTV AUC0-24h and Cmax . Decreased ATV AUC0-24h (12%) and increased Cmax (9%) were noted, while EFV exposure was unchanged (5%) with a 16% decrease in Cmax . Intracellular nucleoside/tide metabolite concentrations and AUC are also reported for these subjects. CONCLUSIONS: This study demonstrates that the PK of these ARVs are altered by 5-78% in an older HIV-infected population. Implications of PK differences for clinical outcomes, particularly with the active nucleoside metabolites, remain to be explored. This study forms the basis for further study of ARV PK, efficacy, and toxicity in older HIV-infected patients.

A phenotype-genotype approach to predicting CYP450 and P-glycoprotein drug interactions with the mixed inhibitor/inducer tipranavir/ritonavir.

The effects of tipranavir/ritonavir (TPV/r) on hepatic and intestinal P-glycoprotein (P-gp) and cytochrome P450 (CYP) enzyme activity were evaluated in 23 volunteers. The subjects received oral (p.o.) caffeine, warfarin + vitamin K, omeprazole, dextromethorphan, and midazolam and digoxin (p.o. and intravenous (i.v.)) at baseline, during the first three doses of TPV/r (500 mg/200 mg b.i.d.), and at steady state. Plasma area under the curve (AUC)(0-infinity) and urinary metabolite ratios were used for quantification of protein activities. A single dose of TPV/r had no effect on the activity of CYP1A2 and CYP2C9; it weakly inhibited CYP2C19 and P-gp; and it potently inhibited CYP2D6 and CYP3A. Multiple dosing produced weak induction of CYP1A2, moderate induction of CYP2C19, potent induction of intestinal P-gp, and potent inhibition of CYP2D6 and CYP3A, with no significant effects on CYP2C9 and hepatic P-gp. Several P450/transporter single-nucleotide polymorphisms correlated with the baseline phenotype but not with the extent of inhibition or induction. Although mixed induction and inhibition are present, this approach offers an understanding of drug interaction mechanisms and ultimately assists in optimizing the clinical use of TPV/r.

Preliminary questions before studying mild traumatic brain injury outcome.

OBJECTIVES: To point out from the literature the issues in mild traumatic brain injury outcome. METHODOLOGY-RESULTS: The literature review allows to point out several different factors involved in the difficulty to study mild traumatic brain injury: mild traumatic brain injury definition, postconcussional syndrome definition, diagnosis threshold, severity and functional symptoms outcome, neuropsychological tests, unspecific syndrome feature, individual factors, confounding factors and treatment interventions. DISCUSSION-CONCLUSION: The mild traumatic brain injury outcome study is complicated by the definitions issues and especially their practical use and by the multiplicity and the intricate interrelationships among involved factors. The individual outcome and social cost weight is widely emphasized for an event still considered as medically trivial. The well-ordered preventive interventions necessity and the targeted treatment programs need for the persisting postconcussive symptoms complete our critical review.

[French version of structured interviews for the Glasgow Outcome Scale: guidelines and first studies of validation]. / Version française de l'entretien structuré pour l'échelle de devenir de Glasgow (GOS): recommandations et premières études de validation.

OBJECTIVES: The Glasgow Outcome Scale (GOS) is the most widely used outcome measure after traumatic brain injury. The GOS's reliability is improved by a structured interview. The two aims of this paper were to present a French version of the structured interview for the five-point Glasgow Outcome Scale and the extended eight-point GOS (GOSE) and to study their validity. METHODS: The French version was developed using back-translation. Concurrent validity was studied by comparison with GOS/GOSE without structured interview. Inter-rater reliability was studied by comparison between assignments made by untrained head injury observers and trained head injury observers. Strength of agreement between ratings was assessed using the Kappa statistic. RESULTS: The French version and the guidelines for their use are given in the Appendix. Ratings were made for 25 brain injured patients and 25 relatives. Concurrent validity was good and inter-rater reliability was excellent. CONCLUSION: Using the structured interview for the GOS will give a more reliable assessment of the outcome of brain injured patients by French-speaking rehabilitation teams and a more precise assessment with the extended GOS.

[The psychopathology of the unawareness of cognitive impairments and behavioral limitations in traumatic brain-injured patients]. / Psychopathologie de la méconnaissance des troubles cognitifs et comportementaux des traumatisés crâniens sévères.

OBJECTIVE: To explore the unawareness of cognitive impairments and behavioral limitations using a psychopathological approach. PATIENTS AND SETTING: Fifteen patients with chronic severe TBI. Outpatient TBI rehabilitation programs in three different centers. MAIN OUTCOME MEASURES: Case reports. The data from semi-structured interviews with the patients and their families, at least six months after the accident, were compared with data supplied by the Patient Competency Rating Scale (PCRS) and the Neurobehavioral Rating Scale-Revised (NRS-R). RESULTS: Nine patients demonstrated unawareness of their limitations according to the PCRS (Group I), whereas six did not (Group II). Psychic phenomena specific to patients of group I were found. Some of these were specific to brain injury, such as the lack of representation of cognitive impairments and behavioral limitations or the difficulty to integrate the brain-injury into one's psychic space. Others were not specific to brain injury such as mourning process difficulties, personality characteristics, defense mechanisms. Several psychic phenomena coexisted in the same patient. CONCLUSION: This study shows the complexity of unawareness of cognitive impairments and behavioral limitations and makes future clinical and theoretical definition indispensable.

The inhibition of DNA repair capacity by stilbene estrogen in Leydig cells: its implications in the induction of instability in the testicular genome.

In this study, we examined the effect of stilbene estrogen, diethylstilbestrol (DES), on the DNA repair capacity of mouse Leydig cells using the host cell reactivation assay. Cells transfected with UV-damaged plasmids, undamaged plasmids, or no plasmids (sham treatment) were grown in serum, serum-free, or DES plus serum-free medium. The serum-grown cells which have a shorter cell cycle time (16h) showed a 40% decrease in DNA repair capacity when compared to serum-free cells with a longer cell cycle time (25h). A significant decrease in the DNA repair capacity of the Leydig cells exposed to DES was observed compared to untreated cells grown in a serum-free environment (P<0.05). The effect of DES on DNA repair in Leydig cells was dose dependent. We have recently shown that DES stimulates the growth of Leydig cells. Stimulatory growth of Leydig cells coupled with a decrease in DNA repair capacity by DES may allow the accumulation of mutagenic lesions in DNA. The mutagenic lesions may result from the attack of redox cycling products of DES and/or errors of replication. This, in turn, may produce alterations in the genome of Leydig cells resulting in genetically unstable cells that may serve as precursor cells for testicular carcinogenesis.

Regulation of the growth of mouse Leydig cells by the inactive stereoisomer, 17alpha-estradiol: Lack of correlation between the elevated expression of ERalpha and difference in sensitivity to estradiol isomers.

We examined the effects of 17alpha-estradiol, the biologically inactive stereoisomer of 17beta-estradiol, on cell growth and cell cycle kinetics using the normalized mouse TM3 Leydig cells. A significant biphasic stimulatory growth response was observed by 17alpha-estradiol exposure with peaks at 1 pg/ml (157.13%) and 100 ng/ml (120.04%) (p<0.05). The growth stimulatory effects of 17alpha-estradiol were inhibited by tamoxifen. A significant decrease in cell cycle time of Leydig cells exposed to 17alpha-estradiol was observed in treated cells (p<0.05). RT-PCR analysis indicated that exposure to Leydig cells to 1 pg/ml and 100 ng/ml 17alpha-estradiol resulted in a 10- and 5-fold increases in the expression of ERalpha, respectively. Similar effects were observed with exposure to equivalent concentrations of 17beta-estradiol. Difference in sensitivity to stereoisomers of estradiol to growth response of Leydig cells did not correlate with the elevated expression of ERalpha. We conclude that the TM3 Leydig cells are sensitive to the non-typical estrogen, 17alpha-estradiol, presumably through the activation of ER-independent signaling transduction pathways.

An effective protection factor study of respirators used by primary lead smelter workers.

An industrial hygiene study was conducted at a primary lead smelter to determine the effective protection factors for negative pressure and powered air purifying half-mask respirators. The study involved 99 paired personal samples taken in six different work areas, in which randomly chosen subjects from the workforce wore dual sampling pumps connected to closed-face 37-mm cassettes. The cassettes were attached either to the workers' lapels for exposure measurements outside the respirator or to a ported respirator for exposure measurements inside the respirator. Samples were collected throughout the work shift and analyzed for lead according to National Institute of Occupational Safety and Health (NIOSH) Method 7082. Using particle size distribution data obtained for the same workplaces, the within-mask samples were corrected for sampling bias. The negative pressure half-mask respirators showed a mean effective protection factor of 6.5 and a mean corrected effective protection factor of 4.56, with a 5th percentile less than 0.5. Approximately 80 percent and 90 percent of the effective protection factors and the corrected effective protection factors, respectively, were equal to or less than the assigned protection factor of 10. For the powered air purifying half-mask respirators, the means for effective protection factor and corrected effective protection factor were 18.20 and 11.92, respectively, with a 5th percentile of 1.0 or less. Approximately 90 percent and 95 percent of the effective protection factors and the corrected effective protection factors, respectively, were equal to or less than the assigned protection factor of 50. The uncorrected and corrected within-mask lead concentrations for both types of respirators exceeded the Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) for lead by 19 percent to 58 percent. These results indicate that the straight application of assigned protection factors to actual workplace situations may not always be appropriate.

[Psychological aspects of awakening from severe brain injuries: a theoretical approach]. / Aspects psychiques de l'éveil des traumatisés craniens sévères: une approche théorique.

As they take care of brain injured patients from coma to socioprofessional return, the authors suggest a psychopathological pattern of coma and awareness. Psychoanalytics concepts of need, request, wish, object a, fantasy and "Jouissance" allows reflexion on psychic events of awareness and suggest the way of taking care of these patients. Recovery from brain injury combines neurological recovering with nursing people's wish and questions again about the peculiar structure of the human being.

[Prospective study of the analgesic action of clomipramine versus placebo in refractory lumbosciatica (68 cases)]. / Etude prospective de l'action antalgique de la clomipramine versus placebo dans les lombosciatalgies rebelles (68 cas).

The authors sought to determine the analgesic activity of clomipramine (CMP) versus placebo, efficacy and side-effects according to the time of administration, long term clinical results and the relationship between plasma levels and analgesic effect. This double-blind randomised trial involved the infusion of 250 ml of glucose solution morning and evening versus placebo. CMP was administered at progressive doses for 8 days (maximum dosage 75 mg), either in the morning at 8 a.m. or in the evening at 6 p.m. Sixty eight patients accepted to be treated, all suffering from low back pain with or without sciatica. Maintenance treatment at the dose of 75 mg/day was then administered. CMP had a statistically significant analgesic action independent (rapidity of action) of its antidepressant activity. CMP was more effective and better tolerated (sedative and tranquilizer effect) in the evening. Long term results were poor (75% of cases). There was no link between plasma levels and clinical response. The authors noted that the analgesic activity of CMP was rapid, but for a duration limited to the short term and that this efficacy compared with the quite good results obtained with the placebo could be explained by a possible methodological bias (patients hospitalised and treated by intravenous infusions). The finding that CMP was better tolerated in the evening, without any loss of efficacy, is a positive feature (chronotherapeutic trial). Poor long term results could be partially explained by side-effects (66%). There was no relationship between analgesic effect and plasma levels.

[Psychologic and human implications of intensive care and rehabilitation of severe head injuries patients]. / Les enjeux psychiques et humains de la réanimation et de la réhabilitation des traumatisés crâniens sévères.

Consequences which are involved in intensive care and rehabilitation of severely head injuries patients seem to be numerous, variable in different times and different situations. However, the authors, for more than ten years, have taken care of severely injured patients from coma to socio-professional reinsertion, and so, it allowed them to concentrate their interest to that main point: it is necessary to make a place to the patient as a desiring patient, and not only as brain injured patient who needs medical care, medical knowledge and who needs be repaired. So the Psycho-Rehabilitation Unit works this way, to allow a new intra and intersubjective homeostasis, in spite of injury and sequellae.