Assessing the Prevalence Of Non-Medical Prescription Opioid Use In The Canadian General Adult Population: Evidence Of Large Variation Depending On Survey Questions Used

Background Morbidity and mortality related to Prescription Opioid Analgesics (POAs) have been rising sharply in North America. Non-Medical Prescription Opioid Use (NMPOU) in the general population is a key indicator of POA-related harm, yet the role of question item design for best NMPOU prevalence estimates in general population surveys is unclear, and existing NMPOU survey data for Canada are limited. Methods We tested the impact of different NMPOU question items by comparing an item in the 2008 and 2009 (N = 2,017) samples of the CAMH Monitor surveys – an Ontario adult general population survey – with a newly developed item used in the 2010 (N = 2,015) samples of the Centre for Addiction and Mental Health (CAMH) Monitor surveys. To control for a potential difference in the population demographics between surveys, we adjusted for gender, age, region, income, prescription opioid use, cigarette smoking, weekly binge drinking, cannabis use in the past three months, and psychological distress in our analyses. Results The prevalence of NMPOU as measured by the 2008 and 2009 CAMH monitor (2.0% [95% CI: 1.2% to 2.8%]) was significantly different when compared to the prevalence of NMPOU as measured by the 2010 CAMH monitor (7.7% [95% CI: 6.3% to 9.2%]) (p < 0.001). This difference was also found when stratifying our analysis by sex (p < 0.001) and when adjusting for all potential confounding covariates. Conclusion It is highly unlikely that the extensive NMPOU prevalence differences observed from the different survey items reflect an actual increase of NMPOU or changes in NMPOU determinants, but rather point to measurement effects. It appears that we currently do not have accurate estimates of NMPOU in the Canadian general population, even though these estimates are needed to guide and implement targeted interventions. Given the current substantial morbidity and mortality impact of NMPOU, there is an urgent need to systematically develop, validate and standardize NMPOU items for future general population surveys in Canada

Harms of Prescription Opioid Use in the United States

Background Consumption levels of prescription opioids (POs) have increased substantially worldwide, particularly the United States. An emerging perspective implicates increasing consumption levels of POs as the primary system level driving factor behind the observed PO-related harms. As such, the present study aimed to assess the correlations between consumption levels of POs and PO-related harms, including non-medical prescription opioid use (NMPOU), PO-related morbidity and PO-related mortality. Findings Pearson’s product-moment correlations were computed using published data from the United States (2001 – 2010). Consumption levels of POs were extracted from the technical reports published by the International Narcotics Control Board, while data for NMPOU was utilized from the National Survey on Drug Use and Health. Additionally, data for PO-related morbidity (substance abuse treatment admissions per 10,000 people) and PO-related mortality (PO overdose deaths per 100,000 people) were obtained from published studies. Consumption levels of POs were significantly correlated with prevalence of NMPOU in the past month (r =0.741, 95% CI =0.208–0.935), past year (r =0.638, 95% CI =0.014–0.904) and lifetime (r =0.753, 95% CI =0.235-0.938), as well as average number of days per person per year of NMPOU among the general population (r =0.900, 95% CI =0.625-0.976) and NMPOU users (r =0.720, 95% CI =0.165–0.929). Similar results were also obtained for PO-related morbidity and PO-related mortality measures. Conclusion These findings suggest that reducing consumption levels of POs at the population level may be an effective strategy to limit PO-related harms

Temporal Changes in Alcohol-Related Morbidity and Mortality in Germany

Aims: Trends in morbidity and mortality, fully or partially attributable to alcohol, for adults aged 18–64 were assessed for Germany. Methods: The underestimation of population exposure was corrected by triangulating survey data with per capita consumption. Alcohol-attributable fractions by sex and two age groups were estimated for major disease categories causally linked to alcohol. Absolute numbers, population rates and proportions relative to all hospitalizations and deaths were calculated. Results: Trends of 100% alcohol-attributable morbidity and mortality over thirteen and eighteen years, respectively, show an increase in rates of hospitalizations and a decrease in mortality rates. Comparisons of alcohol-attributable morbidity including diseases partially caused by alcohol revealed an increase in hospitalization rates between 2006 and 2012. The proportion of alcohol-attributable hospitalizations remained constant. Rates of alcohol-attributable mortality and the proportion among all deaths decreased. Conclusions: The increasing trend in mortality due to alcohol until the mid-1990s has reversed. The constant proportion of all hospitalizations that were attributable to alcohol indicates that factors such as improved treatment and easier health care access may have influenced the general increase in all-cause morbidity. To further reduce alcohol-related mortality, efforts in reducing consumption and increasing treatment utilization are needed

Regional contributions of six preventable risk factors to achieving the 25 × 25 non-communicable disease mortality reduction target: a modelling study

Background Countries have agreed to reduce premature mortality from the four main non-communicable diseases (NCDs) by 25% from 2010 levels by 2025 (referred to as the 25 × 25 target). Countries also agreed on a set of global voluntary targets for selected NCD risk factors. Previous analyses have shown that achieving the risk factor targets can contribute substantially towards meeting the 25 × 25 mortality target at the global level. We estimated the contribution of achieving six of the globally agreed risk factor targets towards meeting the 25 × 25 mortality target by region. Methods We estimated the eff ect of achieving the targets for six risk factors (tobacco and alcohol use, salt intake, obesity, and raised blood pressure and glucose) on NCD mortality between 2010 and 2025. Our methods accounted for multicausality of NCDs and for the fact that, when risk factor exposure increases or decreases, the harmful or benefi cial eff ects on NCDs accumulate gradually. We used data for risk factor and mortality trends from systematic analyses of available country data. Relative risks for the eff ects of individual and multiple risks, and for change in risk after decreases or increases in exposure, were from reanalyses and meta-analyses of epidemiological studies. Findings The probability of dying between the ages 30 years and 70 years from the four main NCDs in 2010 ranged from 19% in the region of the Americas to 29% in southeast Asia for men, and from 13% in Europe to 21% in southeast Asia for women. If current trends continue, the probability of dying prematurely from the four main NCDs is projected to increase in the African region but decrease in the other fi ve regions. If the risk factor targets are achieved, the 25 × 25 target will be surpassed in Europe in both men and women, and will be achieved in women (and almost achieved in men) in the western Pacifi c; the regions of the Americas, the eastern Mediterranean, and southeast Asia will approach the target; and the rising trend in Africa will be reversed. In most regions, a more ambitious approach to tobacco control (50% reduction relative to 2010 instead of the agreed 30%) will contribute the most to reducing premature NCD mortality among men, followed by addressing raised blood pressure and the agreed tobacco target. For women, the highest contributing risk factor towards the premature NCD mortality target will be raised blood pressure in every region except Europe and the Americas, where the ambitious (but not agreed) tobacco reduction would have the largest benefi t. Interpretation No WHO region will meet the 25 × 25 premature mortality target if current mortality trends continue. Achieving the agreed targets for the six risk factors will allow some regions to meet the 25 × 25 target and others to approach it. Meeting the 25 × 25 target in Africa needs other interventions, including those addressing infectionrelated cancers and cardiovascular disease

Use of Accelerometers in a Large Field-Based Study of Children: Protocols, Design Issues, and Effects on Precision

Background: Objective methods can improve accuracy of physical activity measurement in field studies but uncertainties remain about their use. Methods: Children age 11 years from the Avon Longitudinal Study of Parents and Children (ALSPAC), were asked to wear a uni-axial accelerometer (MTI Actigraph) for 7 days. Results: Of 7159 children who attended for assessment, 5595 (78%) provided valid measures. The reliability coefficient for 3 days of recording was .7 and the power to detect a difference of 0.07 SDs (P ≤ .05) was \u3e 90%. Measures tended to be higher on the first day of recording (17 counts/min; 95% CI, 10-24) and if children wore the monitor for fewer days, but these differences were small. The children who provided valid measures of activity were different from those who did not, but the differences were modest. Conclusion: Objective measures of physical activity can be incorporated into large longitudinal studies of children

Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations

Estimating uncertainty of alcohol-attributable fractions for infectious and chronic diseases

Background: Alcohol is a major risk factor for burden of disease and injuries globally. This paper presents a systematic method to compute the 95% confidence intervals of alcohol-attributable fractions (AAFs) with exposure and risk relations stemming from different sources.Methods: The computation was based on previous work done on modelling drinking prevalence using the gamma distribution and the inherent properties of this distribution. The Monte Carlo approach was applied to derive the variance for each AAF by generating random sets of all the parameters. A large number of random samples were thus created for each AAF to estimate variances. The derivation of the distributions of the different parameters is presented as well as sensitivity analyses which give an estimation of the number of samples required to determine the variance with predetermined precision, and to determine which parameter had the most impact on the variance of the AAFs.Results: The analysis of the five Asian regions showed that 150 000 samples gave a sufficiently accurate estimation of the 95% confidence intervals for each disease. The relative risk functions accounted for most of the variance in the majority of cases.Conclusions: Within reasonable computation time, the method yielded very accurate values for variances of AAFs

Birds of a feather eat plastic together: high levels of plastic ingestion in Great Shearwater adults and juveniles across their annual migratory cycle

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Robuck, A. R., Hudak, C. A., Agvent, L., Emery, G., Ryan, P. G., Perold, V., Powers, K. D., Pedersen, J., Thompson, M. A., Suca, J. J., Moore, M. J., Harms, C. A., Bugoni, L., Shield, G., Glass, T., Wiley, D. N., & Lohmann, R. Birds of a feather eat plastic together: high levels of plastic ingestion in Great Shearwater adults and juveniles across their annual migratory cycle. Frontiers in Marine Science, 8, (2022): 719721, https://doi.org/10.3389/fmars.2021.719721.Limited work to date has examined plastic ingestion in highly migratory seabirds like Great Shearwaters (Ardenna gravis) across their entire migratory range. We examined 217 Great Shearwaters obtained from 2008–2019 at multiple locations spanning their yearly migration cycle across the Northwest and South Atlantic to assess accumulation of ingested plastic as well as trends over time and between locations. A total of 2328 plastic fragments were documented in the ventriculus portion of the gastrointestinal tract, with an average of 9 plastic fragments per bird. The mass, count, and frequency of plastic occurrence (FO) varied by location, with higher plastic burdens but lower FO in South Atlantic adults and chicks from the breeding colonies. No fragments of the same size or morphology were found in the primary forage fish prey, the Sand Lance (Ammodytes spp., n = 202) that supports Great Shearwaters in Massachusetts Bay, United States, suggesting the birds directly ingest the bulk of their plastic loads rather than accumulating via trophic transfer. Fourier-transform infrared spectroscopy indicated that low- and high-density polyethylene were the most common polymers ingested, within all years and locations. Individuals from the South Atlantic contained a higher proportion of larger plastic items and fragments compared to analogous life stages in the NW Atlantic, possibly due to increased use of remote, pelagic areas subject to reduced inputs of smaller, more diverse, and potentially less buoyant plastics found adjacent to coastal margins. Different signatures of polymer type, size, and category between similar life stages at different locations suggests rapid turnover of ingested plastics commensurate with migratory stage and location, though more empirical evidence is needed to ground-truth this hypothesis. This work is the first to comprehensively measure the accumulation of ingested plastics by Great Shearwaters over the last decade and across multiple locations spanning their yearly trans-equatorial migration cycle and underscores their utility as sentinels of plastic pollution in Atlantic ecosystems.This project was supported by the NOAA Fisheries National Seabird Program and the Volgenau Foundation. AR acknowledges support from the National Oceanic and Atmospheric Administration Dr. Nancy Foster Scholarship Program (NOAA Award Number NA17NOS4290028), the Robert and Patricia Switzer Foundation, the STEEP Superfund Research Program (NIEHS Award Number P42ES027706), and the Oak Ridge Institute for Science and Education (ORISE) program. LB was funded by INCT-Mar COI and PQ Grant No. 311409/2018-0, both by the Brazilian National Research Council (CNPq). JS was funded by the National Science Foundation Graduate Research Fellowship program