Smoking, nicotine and pregnancy 2 (SNAP2) trial: protocol for a randomised controlled trial of an intervention to improve adherence to nicotine replacement therapy during pregnancy.

INTRODUCTION: Smoking during pregnancy is harmful to unborn babies, infants and women. Nicotine replacement therapy (NRT) is offered as the usual stop-smoking support in the UK. However, this is often used in insufficient doses, intermittently or for too short a time to be effective. This randomised controlled trial (RCT) explores whether a bespoke intervention, delivered in pregnancy, improves adherence to NRT and is effective and cost-effective for promoting smoking cessation. METHODS AND ANALYSIS: A two-arm parallel-group RCT was conducted for pregnant women aged ≥16 years and who smoke ≥1 daily cigarette (pre-pregnancy smoked ≥5) and who agree to use NRT in an attempt to quit. Recruitment is from antenatal care settings and via social media adverts. Participants are randomised using blocked randomisation with varying block sizes, stratified by gestational age (<14 or ≥14 weeks) to receive: (1) usual care (UC) for stop smoking support or (2) UC plus an intervention to increase adherence to NRT, called 'Baby, Me and NRT' (BMN), comprising adherence counselling, automated tailored text messages, a leaflet and website. The primary outcome is biochemically validated smoking abstinence at or around childbirth, measured from 36 weeks gestation. Secondary outcomes include NRT adherence, other smoking measures and birth outcomes. Questionnaires collect follow-up data augmented by medical record information. We anticipate quit rates of 10% and 16% in the control and intervention groups, respectively (risk ratio=1.6). By recruiting 1320 participants, the trial should have 90% power (alpha=5%) to detect this intervention effect. An economic analysis will use the Economics of Smoking in Pregnancy model to determine cost-effectiveness. ETHICS AND DISSEMINATION: Ethics approval was granted by Bloomsbury National Health Service's Research Ethics Committee (21/LO/0123). Written informed consent will be obtained from all participants. Findings will be disseminated to the public, funders, relevant practice/policy representatives, researchers and participants. TRIAL REGISTRATION NUMBER: ISRCTN16830506. PROTOCOL VERSION: 5.0, 10 Oct 2023.

Social Risk Determinants for Successful Same Calendar Day Discharge in Total Joint Arthroplasty.

Background: While many studies have examined the impact of comorbidities on the success of same calendar day discharge (SCDD) in total joint arthroplasty (TJA), literature surrounding the impact of social determinants is lacking. Purpose: We sought to investigate the relationship between various social determinants and success of SCDD after primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). Methods: We conducted a retrospective review of 1160 THA and 1813 TKA performed at a single academic institution between November 2020 and August 2022. Social factors including substance use, occupation, marital status, income, and participation in physical exercise were included. In addition, aspects of discharge planning were reviewed such as living situation and transportation details. Results: Overall, 952 (32%) patients had successful SCDD, whereas 2021 (68%) patients were discharged on postoperative day 1 (POD1) or greater. Successful SCDD patients were more likely to have health care (4.8% vs 2.5%) and active (5.4% vs 4.6%) rather than sedentary occupations, be married (79.6% vs 67.4%), have access to transportation (95.6% vs 92.9%), live in a higher median income area ($64,044 [16,183] vs $61,572 [14,594]), and exercise weekly (62.6% vs 23.9%). Interestingly, the successful patients had more stories in their homes (1.62 [0.56] vs 1.43 [0.53]), more stairs to enter their homes (5.19 [5.22] vs 4.60 [5.24]), lived farther from the hospital (43.3 [138.0] vs 32.0 [75.9] miles), and a higher prevalence of alcohol use (60.7% vs 44.7%) and tobacco use (19.3% vs 17.3%). Conclusion: These findings may help arthroplasty surgeons to better understand the social factors that contribute to successful SCDD in TJA patients, ultimately aiding in patient selection and preoperative counseling.

Racial Disparities in COVID-19 Severity Are Partially Mediated by Chronic Stress-Evidence from a Large Integrated Healthcare System.

BACKGROUND: Racial and ethnic minorities have experienced a disproportionate burden of severe COVID-19. Whether chronic stress, also disproportionately experienced by racial and ethnic minorities, explains this excess risk is unknown. METHODS: We identified 9577 adults (≥ 18 years) diagnosed with COVID-19 from January 1, 2020, through September 30, 2021, enrolled in Kaiser Permanente Georgia (KPGA) with complete biomarker data. Self-reported race (Black or White) was defined from electronic medical records. Chronic stress, defined as allostatic load (AL), a composite score (scale 0-7) based on seven cardio-metabolic biomarkers, was categorized as below (low AL) or above (high AL) the median. Severe COVID-19 was defined as hospitalization or mortality within 30 days of COVID-19 diagnosis. The association between race, AL, and severe COVID-19 was assessed using multivariable Poisson regression. The mediating effect of AL was assessed using the Valeri and VanderWeele method. All results were expressed as risk ratios (RRs) with 95% confidence intervals. RESULTS: Overall, Black (vs. White) KPGA members had an 18% excess risk of AL (RR: 1.18, 95%CI: 1.14-1.23) and a 24% excess risk of severe COVID-19 (RR: 1.24, 95%CI: 1.12, 1.37). AL explained 23% of the Black-White disparities in severe COVID-19. CONCLUSIONS: In our study, chronic stress, characterized by AL, partially mediated Black-White disparities in severe COVID-19 outcomes.

Toxicity Weighting for Human Biomonitoring Mixture Risk Assessment: A Proof of Concept.

Chemical mixture risk assessment has, in the past, primarily focused on exposures quantified in the external environment. Assessing health risks using human biomonitoring (HBM) data provides information on the internal concentration, from which a dose can be derived, of chemicals to which human populations are exposed. This study describes a proof of concept for conducting mixture risk assessment with HBM data, using the population-representative German Environmental Survey (GerES) V as a case study. We first attempted to identify groups of correlated biomarkers (also known as 'communities', reflecting co-occurrence patterns of chemicals) using a network analysis approach (n = 515 individuals) on 51 chemical substances in urine. The underlying question is whether the combined body burden of multiple chemicals is of potential health concern. If so, subsequent questions are which chemicals and which co-occurrence patterns are driving the potential health risks. To address this, a biomonitoring hazard index was developed by summing over hazard quotients, where each biomarker concentration was weighted (divided) by the associated HBM health-based guidance value (HBM-HBGV, HBM value or equivalent). Altogether, for 17 out of the 51 substances, health-based guidance values were available. If the hazard index was higher than 1, then the community was considered of potential health concern and should be evaluated further. Overall, seven communities were identified in the GerES V data. Of the five mixture communities where a hazard index was calculated, the highest hazard community contained N-Acetyl-S-(2-carbamoyl-ethyl)cysteine (AAMA), but this was the only biomarker for which a guidance value was available. Of the other four communities, one included the phthalate metabolites mono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) with high hazard quotients, which led to hazard indices that exceed the value of one in 5.8% of the participants included in the GerES V study. This biological index method can put forward communities of co-occurrence patterns of chemicals on a population level that need further assessment in toxicology or health effects studies. Future mixture risk assessment using HBM data will benefit from additional HBM health-based guidance values based on population studies. Additionally, accounting for different biomonitoring matrices would provide a wider range of exposures. Future hazard index analyses could also take a common mode of action approach, rather than the more agnostic and non-specific approach we have taken in this proof of concept.

Machine Learning on Medicare Claims Poorly Predicts the Individual Risk of 30-Day Unplanned Readmission After Total Joint Arthroplasty, Yet Uncovers Interesting Population-level Associations With Annual Procedure Volumes.

BACKGROUND: Unplanned hospital readmissions after total joint arthroplasty (TJA) represent potentially serious adverse events and remain a critical measure of hospital quality. Predicting the risk of readmission after TJA may provide patients and clinicians with valuable information for preoperative decision-making. QUESTIONS/PURPOSES: (1) Can nonlinear machine-learning models integrating preoperatively available patient, surgeon, hospital, and county-level information predict 30-day unplanned hospital readmissions in a large cohort of nationwide Medicare beneficiaries undergoing TJA? (2) Which predictors are the most important in predicting 30-day unplanned hospital readmissions? (3) What specific information regarding population-level associations can we obtain from interpreting partial dependency plots (plots describing, given our modeling choice, the potentially nonlinear shape of associations between predictors and readmissions) of the most important predictors of 30-day readmission? METHODS: National Medicare claims data (chosen because this database represents a large proportion of patients undergoing TJA annually) were analyzed for patients undergoing inpatient TJA between October 2016 and September 2018. A total of 679,041 TJAs (239,391 THAs [61.3% women, 91.9% White, 52.6% between 70 and 79 years old] and 439,650 TKAs [63.3% women, 90% White, 55.2% between 70 and 79 years old]) were included. Model features included demographics, county-level social determinants of health, prior-year (365-day) hospital and surgeon TJA procedure volumes, and clinical classification software-refined diagnosis and procedure categories summarizing each patient's Medicare claims 365 days before TJA. Machine-learning models, namely generalized additive models with pairwise interactions (prediction models consisting of both univariate predictions and pairwise interaction terms that allow for nonlinear effects), were trained and evaluated for predictive performance using area under the receiver operating characteristic (AUROC; 1.0 = perfect discrimination, 0.5 = no better than random chance) and precision-recall curves (AUPRC; equivalent to the average positive predictive value, which does not give credit for guessing "no readmission" when this is true most of the time, interpretable relative to the base rate of readmissions) on two holdout samples. All admissions (except the last 2 months' worth) were collected and split randomly 80%/20%. The training cohort was formed with the random 80% sample, which was downsampled (so it included all readmissions and a random, equal number of nonreadmissions). The random 20% sample served as the first test cohort ("random holdout"). The last 2 months of admissions (originally held aside) served as the second test cohort ("2-month holdout"). Finally, feature importances (the degree to which each variable contributed to the predictions) and partial dependency plots were investigated to answer the second and third research questions. RESULTS: For the random holdout sample, model performance values in terms of AUROC and AUPRC were 0.65 and 0.087, respectively, for THA and 0.66 and 0.077, respectively, for TKA. For the 2-month holdout sample, these numbers were 0.66 and 0.087 and 0.65 and 0.075. Thus, our nonlinear models incorporating a wide variety of preoperative features from Medicare claims data could not well-predict the individual likelihood of readmissions (that is, the models performed poorly and are not appropriate for clinical use). The most predictive features (in terms of mean absolute scores) and their partial dependency graphs still confer information about population-level associations with increased risk of readmission, namely with older patient age, low prior 365-day surgeon and hospital TJA procedure volumes, being a man, patient history of cardiac diagnoses and lack of oncologic diagnoses, and higher county-level rates of hospitalizations for ambulatory-care sensitive conditions. Further inspection of partial dependency plots revealed nonlinear population-level associations specifically for surgeon and hospital procedure volumes. The readmission risk for THA and TKA decreased as surgeons performed more procedures in the prior 365 days, up to approximately 75 TJAs (odds ratio [OR] = 1.2 for TKA and 1.3 for THA), but no further risk reduction was observed for higher annual surgeon procedure volumes. For THA, the readmission risk decreased as hospitals performed more procedures, up to approximately 600 TJAs (OR = 1.2), but no further risk reduction was observed for higher annual hospital procedure volumes. CONCLUSION: A large dataset of Medicare claims and machine learning were inadequate to provide a clinically useful individual prediction model for 30-day unplanned readmissions after TKA or THA, suggesting that other factors that are not routinely collected in claims databases are needed for predicting readmissions. Nonlinear population-level associations between low surgeon and hospital procedure volumes and increased readmission risk were identified, including specific volume thresholds above which the readmission risk no longer decreases, which may still be indirectly clinically useful in guiding policy as well as patient decision-making when selecting a hospital or surgeon for treatment. LEVEL OF EVIDENCE: Level III, therapeutic study.

Emfit Bed Sensor Activity Shows Strong Agreement with Wrist Actigraphy for the Assessment of Sleep in the Home Setting.

PURPOSE: Wrist-worn actigraphy via research-grade devices, a well-established approach to the assessment of rest-activity, is limited by poor compliance, battery life, and lack of direct evidence for time spent physically in the bed. A non-invasive bed sensor (Emfit) may provide advantages over actigraphy for long-term sleep assessment in the home. This study compared sleep-wake measurements between this sensor and a validated actigraph. PATIENTS AND METHODS: Thirty healthy subjects (6 to 54 years) underwent simultaneous monitoring with both devices for 14 days and filled out a daily sleep diary. Parameters included bed entry time, sleep start, sleep end, bed exit time, rest interval duration, and wake after sleep onset (WASO). The agreement between the two devices was measured using Bland-Altman plots and inter-class correlation coefficients (ICC). In addition, sensitivity, specificity, and accuracy were obtained from epoch-by-epoch comparisons of Emfit and actigraphy. RESULTS: Fifteen percent of the subjects reported that wearing the actigraph was a burden. None reported that using the bed sensor was a burden. The minimal detectable change between Emfit and actigraphy was 11 minutes for bed entry time, 14 minutes for sleep start, 14 minutes for sleep end, 10 minutes for bed exit time, 20 minutes for rest interval duration, and 110 minutes for WASO. Inter-class correlation coefficients revealed an excellent agreement for all sleep parameters (ICC=0.99, 95% CI 98-99) except for WASO (ICC=0.46, 95% CI 0.33-0.56). Sensitivity, specificity, and accuracy were 0.62, 0.93, and 0.88, respectively. Kappa correlation analysis revealed a moderate correlation between the two devices (κ=0.55, p<0.0001). CONCLUSION: Emfit is an acceptable alternative to actigraphy for the estimation of bed entry time, sleep start, sleep end, bed exit time, and rest interval duration. However, WASO estimates are poorly correlated between the two devices. Emfit may offer methodological advantages in situations where actigraphy is challenging to implement.

The in vitro assessment of the toxicity of volatile, oxidisable, redox-cycling compounds: phenols as an example.

Phenols are regarded as highly toxic chemicals. Their effects are difficult to study in in vitro systems because of their ambiguous fate (degradation, auto-oxidation and volatility). In the course of in vitro studies of a series of redox-cycling phenols, we found evidences of cross-contamination in several in vitro high-throughput test systems, in particular by trimethylbenzene-1, 4-diol/trimethylhydroquinone (TMHQ) and 2,6-di-tertbutyl-4-ethylphenol (DTBEP), and investigated in detail the physicochemical basis for such phenomenon and how to prevent it. TMHQ has fast degradation kinetics followed by significant diffusion rates of the resulting quinone to adjacent wells, other degradation products being able to air-diffuse as well. DTBEP showed lower degradation kinetics, but a higher diffusion rate. In both cases the in vitro toxicity was underestimated because of a decrease in concentration, in addition to cross-contamination to neighbouring wells. We identified four degradation products for TMHQ and five for DTBEP indicating that the current effects measured on cells are not only attributable to the parent phenolic compound. To overcome these drawbacks, we investigated in detail the physicochemical changes occurring in the course of the incubation and made use of gas-permeable and non-permeable plastic seals to prevent it. Diffusion was greatly prevented by the use of both plastic seals, as revealed by GC-MS analysis. Gas non-permeable plastic seals, reduced to a minimum compounds diffusion as well oxidation and did not affect the biological performance of cultured cells. Hence, no toxicological cross-contamination was observed in neighbouring wells, thus allowing a more reliable in vitro assessment of phenol-induced toxicity.

Sedimentation assessment and effects in Venda Nova dam reservoir (Portugal).

Sediment quantity and quality in dam reservoirs is often neglected and usually only water quality is monitored in many countries, such as in Portugal. Nevertheless, there are risks associated to sedimentation in dam reservoirs, particularly considering that many dams in the world are ageing into an overextended lifetime. The present study was conducted with the goal to understand how sedimentation monitoring in Portuguese dam reservoirs could be attained, as that information is essential to tackle any sedimentation effects that may have occurred. A dam reservoir in the north of Portugal, the Venda Nova reservoir, was selected for the study. First, historical relevant data was compiled and then new data for sediment and water quality analysis was collected. The results show that since the reservoir was filled, after the dam construction conclusion in 1951, the reservoir morphology has been affected by the sedimentation at different rates and underwent multiple transformations from 1946 (before the dam construction) to 2004 (last topobathymetric survey). An expressive morphology transformation detected in 1984 led to an intervention to remove some of the accumulated material. It was verified, as well, that the asymmetrical contamination of the sediments and water is still strongly influenced by a nearby mine even if now inactive. The methodology applied, if periodically used, will be helpful to understand the sedimentation phenomena in Portuguese and other European dam reservoirs where reservoir sedimentation has been overlooked, and can play a key role to improve river continuity and to comply with the Environmental Quality Standards under the EU Water Framework Directive (2000/60/EC).

Systematic endoscopic assessment of bleeding sites in severe epistaxis: the role of the S-point and the superior epistaxis.

BACKGROUND: Systematic endoscopic assessment (SEA) of bleeding sites is critical for topodiagnosis and treatment of severe epistaxis, which is not limited to the posterior region. A bleeding site originating from the ethmoidal vasculature, the S-point, has recently been described. The aim of this study is to ascertain the prevalence of each bleeding site in severe epistaxis using a SEA protocol that includes the S-point. METHODOLOGY: Prospective longitudinal study of 51 severe epistaxis patients who underwent 53 SEA under general anesthesia from April 2018 through March 2019. SEA consisted of use of a rigid nasal endoscope; no reduction in blood pressure; no use of topical vasoconstrictor; systematic search of all regions of the nose. Bleeding sites were assigned to either superior or posterior epistaxis. RESULTS: At least one bleeding site was identified in 37 evaluations (69.8%). The S-point was the most common bleeding site (28.3%), followed by the lateral middle turbinate (9.4%), non-S-point upper septum (7.5%), nasal roof (7.5%), and upper lateral wall (7.5%). Superior epistaxis was identified in the most of cases (27 SEA, 50.9%), whereas only 14 SEA (26.4%) identified posterior epistaxis â€" fewer than the 16 SEA that did not identify any bleeding sites (30.2%). There were two recurrences (3.8%). CONCLUSIONS: Systematic endoscopic assessment effectively identified bleeding sites in 69.8% of severe epistaxis. The S-point was the most common bleeding site identified (28.3%). Finally, superior epistaxis corresponded to more than half of the identified bleeding sites, demonstrating the importance of examining this region judiciously in patients with severe epistaxis.

Investigation of Machine Learning Approaches for Traumatic Brain Injury Classification via EEG Assessment in Mice.

Due to the difficulties and complications in the quantitative assessment of traumatic brain injury (TBI) and its increasing relevance in today's world, robust detection of TBI has become more significant than ever. In this work, we investigate several machine learning approaches to assess their performance in classifying electroencephalogram (EEG) data of TBI in a mouse model. Algorithms such as decision trees (DT), random forest (RF), neural network (NN), support vector machine (SVM), K-nearest neighbors (KNN) and convolutional neural network (CNN) were analyzed based on their performance to classify mild TBI (mTBI) data from those of the control group in wake stages for different epoch lengths. Average power in different frequency sub-bands and alpha:theta power ratio in EEG were used as input features for machine learning approaches. Results in this mouse model were promising, suggesting similar approaches may be applicable to detect TBI in humans in practical scenarios.

Malnutrition in all its forms and socioeconomic status in Bolivia.

OBJECTIVE: To estimate the prevalence of malnutrition (undernutrition and excess BMI) among children under the age of 5 years and women of reproductive age in Bolivia considering three socioeconomic indicators: wealth, education and ethnicity. DESIGN: We used the 2008 nationally representative Bolivian Demographic and Health Survey (DHS). Malnutrition's prevalence was estimated by wealth, ethnicity and educational level. Wealth index was measured based on the DHS methodology and nutritional status by using WHO standards and indicators. Education level (EL) was categorized by years of formal education. SETTING: Bolivia. PARTICIPANTS: In total, 5·903 children <5 years, 3·345 adolescent women (15-19 years) and 12·297 women (20-49 years) with available information on anthropometric measurements·. RESULTS: A disproportionate prevalence of malnutrition was observed among different wealth groups: lower wealth tertiles show the higher prevalence of stunting (>30 %) and anaemia (>40 %) in all ages· The prevalence of overweight and obesity tends to rise with age from childhood (10·02-11·60) to adolescence (27·9-31·03), reaching highest levels in women of reproductive age (56·02-57·76). According to wealth tertiles, higher prevalence of overweight and obesity was found in children of high tertile (12·23), adolescent women of low (32·56) and adult women of medium tertile (63·08). CONCLUSIONS: The present study shows that currently Bolivia is in a transitional stage, faces not only the problem of undernutrition but also those of overnutrition, showing strong inequalities according to socioeconomic and education status. This study calls for state-specific policies keeping in view of the nature of inequality in malnutrition in the country and its differential characteristics across wealth status.

Aporte de los inmigrantes a la tuberculosis en un Servicio de Salud de Chile / Contribution of immigrants to tuberculosis in a Health Service in Chile

La evaluación del Programa de Control de la Tuberculosis de Chile muestra un creciente aumento de casos de tuberculosis en pacientes extranjeros en las comunas de Santiago de mayor incidencia de esta enfermedad. Mediante la evaluación de los casos diagnosticados durante una década se comprobó un creciente aporte de casos de tuberculosis en el grupo de inmigrantes, desde cerca de 10% el año 2005 hasta cerca de 30% en 2014. La mayor proporción de casos de extranjeros ocurre en la comuna de mayor incidencia (Santiago), con cifras iniciales de 17% el año 2005, llegando a 29% en 2015. La eficacia del tratamiento en los inmigrantes (87,6%) está cerca de la meta nacional (90%) y es mejor que la de los chilenos (81,5%). Encontramos una proporción mayor de casos extranjeros que abandonan la terapia (11%) en relación a los chilenos (7,7%), pero la letalidad en extranjeros es menor (1,5%) que la de los chilenos (10,6%). Se deberán reforzar las estrategias de control de tuberculosis, focalizadas en la población extranjera.

The assessment of Chilean Tuberculosis Control Program shows a growing increase of tuberculosis cases in foreign patients in communes of the city of Santiago with higher incidence of this disease. Through the evaluation of the cases diagnosed in a decade we found an increasing contribution of foreigners, ranging from about 10% in 2005 to 30% in 2014. The greatest proportion of tuberculosis cases in foreigners was detected in Santiago, the commune with the highest incidence. In this area, tuberculosis incidence ranged from 17% in 2005, to 29% in 2015. Treatment efficiency in foreigners (87.6%) is close to our national goal (90%) and better than in Chilean patients (81.5%). We found a higher proportion of foreign cases defaulting therapy (11%) in relation to Chilean (7.7%), but the death rate in foreigners was less than in Chileans (1.5 versus 10.6%). We must strengthen tuberculosis control strategies focused on foreigner populations.

On the path to rabies elimination: The need for risk assessments to improve administration of post-exposure prophylaxis.

BACKGROUND: Costs of rabies post-exposure prophylaxis (PEP) often remain high in regions where rabies has been controlled in dogs, presenting a challenge for sustaining rabies elimination programmes. We investigated the potential for bite patient risk assessments to improve PEP provision and surveillance in settings approaching elimination of dog-mediated rabies. METHODS: We conducted a longitudinal study of patients presenting to animal bite treatment centres (ABTCs) on the island province of Bohol in the Philippines to investigate the health status of biting dogs and to quantify current expenditure on PEP. RESULTS: Incidence of bite patients presenting to ABTCs was high (>300/100,000 persons/year) and increasing, resulting in substantial health provider costs. Over $142,000 was spent on PEP in 2013 for a population of 1.3 million. From follow up of 3820 bite patients we found that  >92% were bitten by healthy dogs (alive 14 days after the bite) and just 1.4% were bitten by probable or confirmed rabid dogs. The status of dogs that bit 6% of patients could not be determined. During the course of investigations of bites by suspect dogs, we were able to obtain samples for case confirmation, identify exposed persons who had not sought PEP as well as in-contact dogs at risk of developing rabies. We calculate that expenditure on PEP could at least be halved through more judicious approaches to provision of PEP, based on the histories of biting animals determined through risk assessments with bite patients. CONCLUSIONS: We conclude that a One Health approach to surveillance based on Integrated Bite Case Management could improve the sustainability and effectiveness of rabies elimination programmes while also improving patient care by identifying those genuinely in need of lifesaving PEP.

Changing geographical patterns and trends in cancer incidence in children and adolescents in Europe, 1991-2010 (Automated Childhood Cancer Information System): a population-based study.

BACKGROUND: A deceleration in the increase in cancer incidence in children and adolescents has been reported in several national and regional studies in Europe. Based on a large database representing 1·3 billion person-years over the period 1991-2010, we provide a consolidated report on cancer incidence trends at ages 0-19 years. METHODS: We invited all population-based cancer registries operating in European countries to participate in this population-based registry study. We requested a listing of individual records of cancer cases, including sex, age, date of birth, date of cancer diagnosis, tumour sequence number, primary site, morphology, behaviour, and the most valid basis of diagnosis. We also requested population counts in each calendar year by sex and age for the registration area, from official national sources, and specific information about the covered area and registration practices. An eligible registry could become a contributor if it provided quality data for all complete calendar years in the period 1991-2010. Incidence rates and the average annual percentage change with 95% CIs were reported for all cancers and major diagnostic groups, by region and overall, separately for children (age 0-14 years) and adolescents (age 15-19 years). We examined and quantified the stability of the trends with joinpoint analyses. FINDINGS: For the years 1991-2010, 53 registries in 19 countries contributed a total of 180 335 unique cases. We excluded 15 162 (8·4%) of 180 335 cases due to differing practices of registration, and considered the quality indicators for the 165 173 cases included to be satisfactory. The average annual age-standardised incidence was 137·5 (95% CI 136·7-138·3) per million person-years and incidence increased significantly by 0·54% (0·44-0·65) per year in children (age 0-14 years) with no change in trend. In adolescents, the combined European incidence was 176·2 (174·4-178·0) per million person-years based on all 35 138 eligible cases and increased significantly by 0·96% (0·73-1·19) per year, although recent changes in rates among adolescents suggest a deceleration in this increasing trend. We observed temporal variations in trends by age group, geographical region, and diagnostic group. The combined age-standardised incidence of leukaemia based on 48 458 cases in children was 46·9 (46·5-47·3) per million person-years and increased significantly by 0·66% (0·48-0·84) per year. The average overall incidence of leukaemia in adolescents was 23·6 (22·9-24·3) per million person-years, based on 4702 cases, and the average annual change was 0·93% (0·49-1·37). We also observed increasing incidence of lymphoma in adolescents (average annual change 1·04% [0·65-1·44], malignant CNS tumours in children (average annual change 0·49% [0·20-0·77]), and other tumours in both children (average annual change 0·56 [0·40-0·72]) and adolescents (average annual change 1·17 [0·82-1·53]). INTERPRETATION: Improvements in the diagnosis and registration of cancers over time could partly explain the observed increase in incidence, although some changes in underlying putative risk factors cannot be excluded. Cancer incidence trends in this young population require continued monitoring at an international level. FUNDING: Federal Ministry of Health of the Federal German Government, the European Union's Seventh Framework Programme, and International Agency for Research on Cancer.

Global Cancer Inequalities.

Social inequalities in cancer are increasingly relevant to research, implementation science, and policy. In this brief perspective we provide an overview of global cancer inequalities by assessing different outcomes according to the Human Development Index (HDI); the HDI is a United Nations Development Programme composite indicator including the following measures: (i) access to education (based on mean and expected years of schooling), (ii) a long and healthy life (based on life expectancy), and (iii) a decent standard of living (based on gross national income per capita). We additionally touch upon the importance of prevention, access to oncological services, and the need to monitor progress in reducing and avoiding inequalities at subnational, national, world region, and global levels.

Is there association between human development index and tuberculosis mortality risk? Evidence from a spatial analysis study in the south of Brazil.

The goal of this study was to analyse the spatial pattern of tuberculosis (TB) mortality using different approaches, namely: mortality rates (MR), spatial relative risks (RR) and Bayesian rates (Global and Local) and their association with human development index (HDI), Global and its three dimensions: education, longevity and income. An ecological study was developed in Curitiba, Brazil based on data from Mortality Information System (2008-2014). Spatial scan statistics were used to compute RR and identify high-risk clusters. Bivariate Local Indicator of Spatial Associations was used to assess associations. MR ranged between 0 and 25.24/100.000 with a mean (standard deviation) of 1.07 (2.66). Corresponding values for spatial RR were 0-27.46, 1.2 (2.99) and for Bayesian rates (Global and Local) were 0.49-1.66, 0.90 (0.19) and 0-6.59, 0.98 (0.80). High-risk clusters were identified for all variables, except for HDI-income and Global Bayesian rate. Significant negative spatial relations were found between MR and income; between RR and HDI global, longevity and income; and Bayesian rates with all variables. Some areas presented different patterns: low social development/low risk and high risk/high development. These results demonstrate that social development variables should be considered, in mortality due TB.

What do nursing home residents with mental-physical multimorbidity need and who actually knows this? A cross-sectional cohort study.

OBJECTIVE: Aging societies will bring an increase in the number of long-term care residents with mental-physical multimorbidity. To optimize care for these residents, it is important to study their care needs, since unmet needs lower quality of life. To date, knowledge about care needs of residents with mental-physical multimorbidity is limited. The aim of this study was to explore (un)met care needs of residents with mental-physical multimorbidity and determinants of unmet needs. METHODS: Cross-sectional cohort study among 141 residents with mental-physical multimorbidity without dementia living in 17 geronto-psychiatric nursing home units across the Netherlands. Data collection consisted of chart review, semi-structured interviews, (brief) neuropsychological testing, and self-report questionnaires. The Camberwell Assessment of Need for the Elderly (CANE) was used to rate (un)met care needs from residents' and nursing staff's perceptions. Descriptive and multivariate regression analyses were conducted. RESULTS: Residents reported a mean number of 11.89 needs (SD 2.88) of which 24.2% (n = 2.88, SD 2.48) were unmet. Nursing staff indicated a mean number of 14.73 needs (SD 2.32) of which 10.8% (n = 1.59, SD 1.61) were unmet. According to the residents, most unmet needs were found in the social domain as opposed to the psychological domain as reported by the nursing staff. Different opinions between resident and nursing staff about unmet needs was most common in the areas accommodation, company, and daytime activities. Further, nearly half of the residents indicated 'no need' regarding behavior while the nursing staff supposed that the resident did require some kind of support. Depression, anxiety and less care dependency were the most important determinants of unmet needs. CONCLUSIONS: Systematic assessment of care needs showed differences between the perspectives of resident and nursing staff. These should be the starting point of a dialogue between them about needs, wishes and expectations regarding care. This dialogue can subsequently lead to the most optimal individually tailored care plan. To achieve this, nurses with effective communication and negotiation skills, are indispensable.

The global cancer burden and human development: A review.

AIMS: This review examines the links between human development and cancer overall and for specific types of cancer, as well as cancer-related risk-factors and outcomes, such as disability and life expectancy. METHODS: To assess human development, the Human Development Index was utilized continuously and according to four levels (low, medium, high, very high), where the low and very high categories include the least and most developed countries, respectively. All studies that assessed aspects of the global cancer burden using this measure were reviewed. RESULTS: Although the present cancer incidence burden is greater in higher Human Development Index countries, a greater proportion of the global mortality burden is observed in less developed countries, with a higher mean fatality rate in the latter countries. Further, the future cancer burden is expected to disproportionally affect less developed regions; in particular, it has been estimated that low and medium Human Development Index countries will experience a 100% and 81% increase in cancer incidence from 2008 to 2030, respectively. Disparities were also observed in risk factors and average health outcomes, such as a greater number of years of life lost prematurely and fewer cancer-related gains in life expectancy observed in lower versus higher Human Development Index settings. CONCLUSIONS: From a global perspective, there remain clear disparities in the cancer burden according to national Human Development Index scores. International efforts are needed to aid countries in social and economic transition in order to efficiently plan, implement and evaluate cancer control initiatives as a means to reduce the widening gap in cancer occurrence and survival worldwide.