Polycyclic aromatic compounds (PAHs and oxygenated PAHs) and trace metals in fish species from Ghana (West Africa): Bioaccumulation and health risk assessment

We report the concentrations of 28 PAHs, 15 oxygenated PAHs (OPAHs) and 11 trace metals/metalloids (As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Se, and Zn) in muscle and gut + gill tissues of demersal fishes (Drapane africana, Cynoglossus senegalensis and Pomadasys peroteti) from three locations along the coast of the Gulf of Guinea (Ghana). The concentrations of ∑ 28PAHs in muscle tissues averaged 192 ng g− 1 dw (range: 71–481 ng g− 1 dw) and were not statistically different between locations. The concentrations of ∑ 28 PAHs were higher in guts + gills than in muscles. The PAH composition pattern was dominated by low molecular weight compounds (naphthalene, alkyl-naphthalenes and phenanthrene). All fish tissues had benzo[a]pyrene concentrations lower than the EU limit for food safety. Excess cancer risk from consumption of some fish was higher than the guideline value of 1 × 10− 6. The concentrations of ∑ 15 OPAHs in fish muscles averaged 422 ng g− 1 dw (range: 28–1715 ng g− 1dw). The ∑ 15 OPAHs/∑ 16 US-EPA PAHs concentration ratio was > 1 in 68% of the fish muscles and 100% of guts + gills. The log-transformed concentrations of PAHs and OPAHs in muscles, guts + gills were significantly (p < 0.05) correlated with their octanol–water partitioning coefficients, strongly suggesting that equilibrium partitioning from water/sediment into fish tissue was the main mechanism of bioaccumulation. The trace metal concentrations in the fish tissues were in the medium range when compared to fish from other parts of the world. The concentrations of some trace metals (Cd, Cu, Fe, Mn, Zn) were higher in guts + gills than in muscle tissues. The target hazard quotients for metals were < 1 and did not indicate a danger to the local population. We conclude that the health risk arising from the consumption of the studied fish (due to their PAHs and trace metals content) is minimal.

Effect of Health Risk Assessment and Counselling on Health Behaviour and Survival in Older People: A Pragmatic Randomised Trial.

BACKGROUND Potentially avoidable risk factors continue to cause unnecessary disability and premature death in older people. Health risk assessment (HRA), a method successfully used in working-age populations, is a promising method for cost-effective health promotion and preventive care in older individuals, but the long-term effects of this approach are unknown. The objective of this study was to evaluate the effects of an innovative approach to HRA and counselling in older individuals for health behaviours, preventive care, and long-term survival. METHODS AND FINDINGS This study was a pragmatic, single-centre randomised controlled clinical trial in community-dwelling individuals aged 65 y or older registered with one of 19 primary care physician (PCP) practices in a mixed rural and urban area in Switzerland. From November 2000 to January 2002, 874 participants were randomly allocated to the intervention and 1,410 to usual care. The intervention consisted of HRA based on self-administered questionnaires and individualised computer-generated feedback reports, combined with nurse and PCP counselling over a 2-y period. Primary outcomes were health behaviours and preventive care use at 2 y and all-cause mortality at 8 y. At baseline, participants in the intervention group had a mean ± standard deviation of 6.9 ± 3.7 risk factors (including unfavourable health behaviours, health and functional impairments, and social risk factors) and 4.3 ± 1.8 deficits in recommended preventive care. At 2 y, favourable health behaviours and use of preventive care were more frequent in the intervention than in the control group (based on z-statistics from generalised estimating equation models). For example, 70% compared to 62% were physically active (odds ratio 1.43, 95% CI 1.16-1.77, p = 0.001), and 66% compared to 59% had influenza vaccinations in the past year (odds ratio 1.35, 95% CI 1.09-1.66, p = 0.005). At 8 y, based on an intention-to-treat analysis, the estimated proportion alive was 77.9% in the intervention and 72.8% in the control group, for an absolute mortality difference of 4.9% (95% CI 1.3%-8.5%, p = 0.009; based on z-test for risk difference). The hazard ratio of death comparing intervention with control was 0.79 (95% CI 0.66-0.94, p = 0.009; based on Wald test from Cox regression model), and the number needed to receive the intervention to prevent one death was 21 (95% CI 12-79). The main limitations of the study include the single-site study design, the use of a brief self-administered questionnaire for 2-y outcome data collection, the unavailability of other long-term outcome data (e.g., functional status, nursing home admissions), and the availability of long-term follow-up data on mortality for analysis only in 2014. CONCLUSIONS This is the first trial to our knowledge demonstrating that a collaborative care model of HRA in community-dwelling older people not only results in better health behaviours and increased use of recommended preventive care interventions, but also improves survival. The intervention tested in our study may serve as a model of how to implement a relatively low-cost but effective programme of disease prevention and health promotion in older individuals. TRIAL REGISTRATION International Standard Randomized Controlled Trial Number: ISRCTN 28458424.

Risk assessment and preventive measures

A prerequisite for preventive measures is to diagnose erosive tooth wear and to evaluate the different etiological factors in order to identify persons at risk. No diagnostic device is available for the assessment of erosive defects. Thus, they can only be detected clinically. Consequently, erosion not diagnosed in the early stage may render timely preventive measures difficult. In order to assess the risk factors, patient should record their dietary intake for a distinct period of time. Then a dentist can determine the erosive potential of the diet. Particularly, patients with more than four dietary acid intakes have a higher risk for erosion when other risk factors (such as holding the drink in the mouth) are present. Regurgitation of gastric acids (reflux, vomiting, alcohol abuse, etc.) is a further important risk factor for the development of erosion which has to be taken into account. Based on these analyses, an individually tailored preventive program may be suggested to the patients. It may comprise dietary advice, optimization of fluoride regimes, stimulation of salivary flow rate, use of buffering medicaments and particular motivation for nondestructive toothbrushing habits with a low abrasive toothpaste. The frequent use of fluoride gel and fluoride solution in addition to fluoride toothpaste offers the opportunity to reduce somewhat abrasion of tooth substance. It is also advisable to avoid abrasive tooth cleaning and whitening products, since they may remove the pellicle and may render teeth more susceptible to erosion. Since erosion, attrition and abrasion often occur simultaneously all causative components must be taken into consideration when planning preventive strategies.

Risk assessment and causal preventive measures.

A prerequisite for preventive measures is to diagnose erosive tooth wear and to evaluate the different etiological factors in order to identify persons at risk. No diagnostic device is available for the assessment of erosive defects. Thus, they can only be detected clinically. Consequently, erosion not diagnosed at an early stage may render timely preventive measures difficult. In order to assess the risk factors, patients should record their dietary intake for a distinct period of time. Then a dentist can determine the erosive potential of the diet. A table with common beverages and foodstuffs is presented for judging the erosive potential. Particularly, patients with more than 4 dietary acid intakes have a higher risk for erosion when other risk factors are present. Regurgitation of gastric acids is a further important risk factor for the development of erosion which has to be taken into account. Based on these analyses, an individually tailored preventive program may be suggested to the patients. It may comprise dietary advice, use of calcium-enriched beverages, optimization of prophylactic regimes, stimulation of salivary flow rate, use of buffering medicaments and particular motivation for nondestructive toothbrushing habits with an erosive-protecting toothpaste as well as rinsing solutions. Since erosion and abrasion often occur simultaneously, all of the causative components must be taken into consideration when planning preventive strategies but only those important and feasible for an individual should be communicated to the patient.

Proposal on How To Conduct a Biopharmaceutical Process Failure Mode and Effect Analysis (FMEA) as a Risk Assessment Tool

With the publication of the quality guideline ICH Q9 "Quality Risk Management" by the International Conference on Harmonization, risk management has already become a standard requirement during the life cycle of a pharmaceutical product. Failure mode and effect analysis (FMEA) is a powerful risk analysis tool that has been used for decades in mechanical and electrical industries. However, the adaptation of the FMEA methodology to biopharmaceutical processes brings about some difficulties. The proposal presented here is intended to serve as a brief but nevertheless comprehensive and detailed guideline on how to conduct a biopharmaceutical process FMEA. It includes a detailed 1-to-10-scale FMEA rating table for occurrence, severity, and detectability of failures that has been especially designed for typical biopharmaceutical processes. The application for such a biopharmaceutical process FMEA is widespread. It can be useful whenever a biopharmaceutical manufacturing process is developed or scaled-up, or when it is transferred to a different manufacturing site. It may also be conducted during substantial optimization of an existing process or the development of a second-generation process. According to their resulting risk ratings, process parameters can be ranked for importance and important variables for process development, characterization, or validation can be identified. LAY ABSTRACT: Health authorities around the world ask pharmaceutical companies to manage risk during development and manufacturing of pharmaceuticals. The so-called failure mode and effect analysis (FMEA) is an established risk analysis tool that has been used for decades in mechanical and electrical industries. However, the adaptation of the FMEA methodology to pharmaceutical processes that use modern biotechnology (biopharmaceutical processes) brings about some difficulties, because those biopharmaceutical processes differ from processes in mechanical and electrical industries. The proposal presented here explains how a biopharmaceutical process FMEA can be conducted. It includes a detailed 1-to-10-scale FMEA rating table for occurrence, severity, and detectability of failures that has been especially designed for typical biopharmaceutical processes. With the help of this guideline, different details of the manufacturing process can be ranked according to their potential risks, and this can help pharmaceutical companies to identify aspects with high potential risks and to react accordingly to improve the safety of medicines.

A qualitative risk assessment approach for Swiss dairy products: opportunities and limitations

Switzerland implemented a risk-based monitoring of Swiss dairy products in 2002 based on a risk assessment (RA) that considered the probability of exceeding a microbiological limit value set by law. A new RA was launched in 2007 to review and further develop the previous assessment, and to make recommendations for future risk-based monitoring according to current risks. The resulting qualitative RA was designed to ascertain the risk to human health from the consumption of Swiss dairy products. The products and microbial hazards to be considered in the RA were determined based on a risk profile. The hazards included Campylobacter spp., Listeria monocytogenes, Salmonella spp., Shiga toxin-producing Escherichia coli, coagulase-positive staphylococci and Staphylococcus aureus enterotoxin. The release assessment considered the prevalence of the hazards in bulk milk samples, the influence of the process parameters on the microorganisms, and the influence of the type of dairy. The exposure assessment was linked to the production volume. An overall probability was estimated combining the probabilities of release and exposure for each combination of hazard, dairy product and type of dairy. This overall probability represents the likelihood of a product from a certain type of dairy exceeding the microbiological limit value and being passed on to the consumer. The consequences could not be fully assessed due to lack of detailed information on the number of disease cases caused by the consumption of dairy products. The results were expressed as a ranking of overall probabilities. Finally, recommendations for the design of the risk-based monitoring programme and for filling the identified data gaps were given. The aims of this work were (i) to present the qualitative RA approach for Swiss dairy products, which could be adapted to other settings and (ii) to discuss the opportunities and limitations of the qualitative method.

Screening and testing for endocrine disruption in fish-biomarkers as "signposts," not "traffic lights," in risk assessment

Biomarkers are currently best used as mechanistic "signposts" rather than as "traffic lights" in the environmental risk assessment of endocrine-disrupting chemicals (EDCs). In field studies, biomarkers of exposure [e.g., vitellogenin (VTG) induction in male fish] are powerful tools for tracking single substances and mixtures of concern. Biomarkers also provide linkage between field and laboratory data, thereby playing an important role in directing the need for and design of fish chronic tests for EDCs. It is the adverse effect end points (e.g., altered development, growth, and/or reproduction) from such tests that are most valuable for calculating adverseNOEC (no observed effect concentration) or adverseEC10 (effective concentration for a 10% response) and subsequently deriving predicted no effect concentrations (PNECs). With current uncertainties, biomarkerNOEC or biomarkerEC10 data should not be used in isolation to derive PNECs. In the future, however, there may be scope to increasingly use biomarker data in environmental decision making, if plausible linkages can be made across levels of organization such that adverse outcomes might be envisaged relative to biomarker responses. For biomarkers to fulfil their potential, they should be mechanistically relevant and reproducible (as measured by interlaboratory comparisons of the same protocol). VTG is a good example of such a biomarker in that it provides an insight to the mode of action (estrogenicity) that is vital to fish reproductive health. Interlaboratory reproducibility data for VTG are also encouraging; recent comparisons (using the same immunoassay protocol) have provided coefficients of variation (CVs) of 38-55% (comparable to published CVs of 19-58% for fish survival and growth end points used in regulatory test guidelines). While concern over environmental xenoestrogens has led to the evaluation of reproductive biomarkers in fish, it must be remembered that many substances act via diverse mechanisms of action such that the environmental risk assessment for EDCs is a broad and complex issue. Also, biomarkers such as secondary sexual characteristics, gonadosomatic indices, plasma steroids, and gonadal histology have significant potential for guiding interspecies assessments of EDCs and designing fish chronic tests. To strengthen the utility of EDC biomarkers in fish, we need to establish a historical control database (also considering natural variability) to help differentiate between statistically detectable versus biologically significant responses. In conclusion, as research continues to develop a range of useful EDC biomarkers, environmental decision-making needs to move forward, and it is proposed that the "biomarkers as signposts" approach is a pragmatic way forward in the current risk assessment of EDCs.

The PRO-AGE study: an international randomised controlled study of health risk appraisal for older persons based in general practice

BACKGROUND: This paper describes the study protocol, the recruitment, and base-line data for evaluating the success of randomisation of the PRO-AGE (PRevention in Older people-Assessment in GEneralists' practices) project. METHODS/DESIGN: A group of general practitioners (GPs) in London (U.K.), Hamburg (Germany) and Solothurn (Switzerland) were trained in risk identification, health promotion, and prevention in older people. Their non-disabled older patients were invited to participate in a randomised controlled study. Participants allocated to the intervention group were offered the Health Risk Appraisal for Older Persons (HRA-O) instrument with a site-specific method for reinforcement (London: physician reminders in electronic medical record; Hamburg: one group session or two preventive home visits; Solothurn: six-monthly preventive home visits over a two-year period). Participants allocated to the control group received usual care. At each site, an additional group of GPs did not receive the training, and their eligible patients were invited to participate in a concurrent comparison group. Primary outcomes are self-reported health behaviour and preventative care use at one-year follow-up. In Solothurn, an additional follow-up was conducted at two years. The number of older persons agreeing to participate (% of eligible persons) in the randomised controlled study was 2503 (66.0%) in London, 2580 (53.6%) in Hamburg, and 2284 (67.5%) in Solothurn. Base-line findings confirm that randomisation of participants was successful, with comparable characteristics between intervention and control groups. The number of persons (% of eligible) enrolled in the concurrent comparison group was 636 (48.8%) in London, 746 (35.7%) in Hamburg, and 1171 (63.0%) in Solothurn. DISCUSSION: PRO-AGE is the first large-scale randomised controlled trial of health risk appraisal for older people in Europe. Its results will inform about the effects of implementing HRA-O with different methods of reinforcement.

Health risk appraisal in older people 2: the implications for clinicians and commissioners of social isolation risk in older people

BACKGROUND: Social isolation is associated with poorer health, and is seen by the World Health Organisation (WHO) as one of the major issues facing the industrialised world. AIM: To explore the significance of social isolation in the older population for GPs and for service commissioners. DESIGN OF STUDY: Secondary analysis of baseline data from a randomised controlled trial of health risk appraisal. SETTING: A total of 2641 community-dwelling, non-disabled people aged 65 years and over in suburban London. METHOD: Demographic details, social network and risk for social isolation based on the 6-item Lubben Social Network Scale, measures of depressed mood, memory problems, numbers of chronic conditions, medication use, functional ability, self-reported use of medical services. RESULTS: More than 15% of the older age group were at risk of social isolation, and this risk increased with advancing age. In bivariate analyses risk of social isolation was associated with older age, education up to 16 years only, depressed mood and impaired memory, perceived fair or poor health, perceived difficulty with both basic and instrumental activities of daily living, diminishing functional ability, and fear of falling. Despite poorer health status, those at risk of social isolation did not appear to make greater use of medical services, nor were they at greater risk of hospital admission. Half of those who scored as at risk of social isolation lived with others. Multivariate analysis showed significant independent associations between risk of social isolation and depressed mood and living alone, and weak associations with male sex, impaired memory and perceived poor health. CONCLUSION: The risk of social isolation is elevated in older men, older persons who live alone, persons with mood or cognitive problems, but is not associated with greater use of services. These findings would not support population screening for individuals at risk of social isolation with a view to averting service use by timely intervention. Awareness of social isolation should trigger further assessment, and consideration of interventions to alleviate social isolation, treat depression or ameliorate cognitive impairment.

Promotion of health in older people: a randomised controlled trial of health risk appraisal in British general practice

BACKGROUND: there is inadequate evidence to support currently formulated NHS strategies to achieve health promotion and preventative care in older people through broad-based screening and assessment in primary care. The most extensively evaluated delivery instrument for this purpose is Health Risk Appraisal (HRA). This article describes a trial using HRA to evaluate the effect on health behaviour and preventative-care uptake in older people in NHS primary care. METHODS: a randomised controlled trial was undertaken in three London primary care group practices. Functionally independent community-dwelling patients older than 65 years (n = 2,503) received a self-administered Health Risk Appraisal for Older Persons (HRA-O) questionnaire leading to computer-generated individualised written feedback to participants and general practitioners (GPs), integrated into practice information-technology (IT) systems. All primary care staff received training in preventative health in older people. The main outcome measures were self-reported health behaviour and preventative care uptake at 1-year follow-up. RESULTS: of 2,503 individuals randomised, 2,006 respondents (80.1%) (intervention, n = 940, control n = 1,066) were available for analysis. Intervention group respondents reported slightly higher pneumococcal vaccination uptake and equivocal improvement in physical activity levels compared with controls. No significant differences were observed for any other categories of health behaviour or preventative care measures at 1-year follow-up. CONCLUSIONS: HRA-O implemented in this way resulted in minimal improvement of health behaviour or uptake of preventative care measures in older people. Supplementary reinforcement involving contact by health professionals with patients over and above routine clinical encounters may be a prerequisite to the effectiveness of IT-based delivery systems for health promotion in older people.

Whole-body vibration exposure study in U.S. railroad locomotives--an ergonomic risk assessment

Whole-body vibration exposure of locomotive engineers and the vibration attenuation of seats in 22 U.S. locomotives (built between 1959 and 2000) was studied during normal revenue service and following international measurement guidelines. Triaxial vibration measurements (duration mean 155 min, range 84-383 min) on the seat and on the floor were compared. In addition to the basic vibration evaluation (aw rms), the vector sum (av), the maximum transient vibration value (MTVV/aw), the vibration dose value (VDV/(aw T1/4)), and the vibration seat effective transmissibility factor (SEAT) were calculated. The power spectral densities are also reported. The mean basic vibration level (aw rms) was for the fore-aft axis x = 0.18 m/sec2, the lateral axis y = 0.28 m/sec2, and the vertical axis z = 0.32 m/sec2. The mean vector sum was 0.59 m/sec2 (range 0.27 to 1.44). The crest factors were generally at or above 9 in the horizontal and vertical axis. The mean MTVV/aw was 5.3 (x), 5.1 (y), and 4.8 (z), and the VDV/(aw T1/4) values ranged from 1.32 to 2.3 (x-axis), 1.33 to 1.7 (y-axis), and 1.38 to 1.86 (z-axis), generally indicating high levels of shocks. The mean seat transmissibility factor (SEAT) was 1.4 (x) and 1.2 (y) and 1 (z), demonstrating a general ineffectiveness of any of the seat suspension systems. In conclusion, these data indicate that locomotive rides are characterized by relatively high shock content (acceleration peaks) of the vibration signal in all directions. Locomotive vertical and lateral vibrations are similar, which appears to be characteristic for rail vehicles compared with many road/off-road vehicles. Tested locomotive cab seats currently in use (new or old) appear inadequate to reduce potentially harmful vibration and shocks transmitted to the seated operator, and older seats particularly lack basic ergonomic features regarding adjustability and postural support.

PM2.5-bound oxygenated PAHs, nitro-PAHs and parent-PAHs from the atmosphere of a Chinese megacity: seasonal variation, sources and cancer risk assessment

Polycyclic aromatic compounds (PACs) in air particulate matter contribute considerably to the health risk of air pollution. The objectives of this study were to assess the occurrence and variation in concentrations and sources of PM2.5-bound PACs [Oxygenated PAHs (OPAHs), nitro-PAHs and parent-PAHs] sampled from the atmosphere of a typical Chinese megacity (Xi'an), to study the influence of meteorological conditions on PACs and to estimate the lifetime excess cancer risk to the residents of Xi'an (from inhalation of PM2.5-bound PACs). To achieve these objectives, we sampled 24-h PM2.5 aerosols (once in every 6 days, from 5 July 2008 to 8 August 2009) from the atmosphere of Xi'an and measured the concentrations of PACs in them. The PM2.5-bound concentrations of Σcarbonyl-OPAHs, ∑ hydroxyl + carboxyl-OPAHs, Σnitro-PAHs and Σalkyl + parent-PAHs ranged between 5–22, 0.2–13, 0.3–7, and 7–387 ng m− 3, respectively, being markedly higher than in most western cities. This represented a range of 0.01–0.4% and 0.002–0.06% of the mass of organic C in PM2.5 and the total mass of PM2.5, respectively. The sums of the concentrations of each compound group had winter-to-summer ratios ranging from 3 to 8 and most individual OPAHs and nitro-PAHs had higher concentrations in winter than in summer, suggesting a dominant influence of emissions from household heating and winter meteorological conditions. Ambient temperature, air pressure, and wind speed explained a large part of the temporal variation in PACs concentrations. The lifetime excess cancer risk from inhalation (attributable to selected PAHs and nitro-PAHs) was six fold higher in winter (averaging 1450 persons per million residents of Xi'an) than in summer. Our results call for the development of emission control measures.

Human and ecological risk assessment of a crop protection chemical: a case study with the azole fungicide epoxiconazole.

Conventional risk assessments for crop protection chemicals compare the potential for causing toxicity (hazard identification) to anticipated exposure. New regulatory approaches have been proposed that would exclude exposure assessment and just focus on hazard identification based on endocrine disruption. This review comprises a critical analysis of hazard, focusing on the relative sensitivity of endocrine and non-endocrine endpoints, using a class of crop protection chemicals, the azole fungicides. These were selected because they are widely used on important crops (e.g. grains) and thereby can contact target and non-target plants and enter the food chain of humans and wildlife. Inhibition of lanosterol 14α-demethylase (CYP51) mediates the antifungal effect. Inhibition of other CYPs, such as aromatase (CYP19), can lead to numerous toxicological effects, which are also evident from high dose human exposures to therapeutic azoles. Because of its widespread use and substantial database, epoxiconazole was selected as a representative azole fungicide. Our critical analysis concluded that anticipated human exposure to epoxiconazole would yield a margin of safety of at least three orders of magnitude for reproductive effects observed in laboratory rodent studies that are postulated to be endocrine-driven (i.e. fetal resorptions). The most sensitive ecological species is the aquatic plant Lemna (duckweed), for which the margin of safety is less protective than for human health. For humans and wildlife, endocrine disruption is not the most sensitive endpoint. It is concluded that conventional risk assessment, considering anticipated exposure levels, will be protective of both human and ecological health. Although the toxic mechanisms of other azole compounds may be similar, large differences in potency will require a case-by-case risk assessment.

SWISSspine—a nationwide health technology assessment registry for balloon kyphoplasty: methodology and first results

The Swiss Federal Office of Public Health demanded a nationwide health technology assessment registry for cervical and lumbar total disc arthroplasty and for balloon kyphoplasty (BKP) to make a decision about reimbursement of these interventions.

Molecular risk assessment of BIG 1-98 participants by expression profiling using RNA from archival tissue

The purpose of the work reported here is to test reliable molecular profiles using routinely processed formalin-fixed paraffin-embedded (FFPE) tissues from participants of the clinical trial BIG 1-98 with a median follow-up of 60 months.