Background:
Involuntary weight loss may occur during systemic anti-cancer therapy (SACT), causing treatment disruption and poorer prognoses. There remain gaps in clinical awareness as to which ...patients may benefit from nutritional interventions that aim to prevent unintended weight loss during SACT.
We utilised England’s population-level cancer registry data, conducting a pan-cancer assessment of patient weight loss during SACT. We aimed to identify cancers with weight loss-associated treatment modifications, potential beneficiaries of nutritional intervention.
Methods:
This cross-sectional study used England’s Cancer Analysis System database, including SACT-treated adults with one tumour and ⩾2 weight recordings between 2014 and 2018. Binary weight loss (threshold: 2.5%) was derived from patients’ most negative weight change from first SACT weight recording. The Martin et al. body mass index-adjusted weight loss grading system (BMI-WLG) was assigned. We describe binary weight loss, BMI-WLG and treatment modification status by cancer. Multivariate logistic regression models of weight loss (binary and BMI-WLG) and a composite outcome of patient treatment-modification status by cancer were produced.
Results:
Our study population contained 200,536 patients across 18 cancers; 28% experienced binary weight loss during SACT. Weight loss patients were more likely to have multiple types of treatment modifications recorded across all cancers. Regression analyses included 86,991 patients. Binary weight loss was associated (p < 0.05) with higher likelihood of treatment modification in; colon Odds Ratio (OR) = 1.72, 95% confidence interval (CI): 1.42, 2.07; gynaecologic (excl. ovarian) (OR = 1.48, 95% CI: 1.08, 2.01); stomach (OR = 1.46, 95% CI: 1.04, 2.06); lung (OR = 1.38, 95% CI: 1.21, 1.58); leukaemia (OR = 1.30, 95% CI: 1.09, 1.55); head and neck (OR = 1.30, 95% CI: 1.02, 1.65) and oesophageal (OR = 1.29, 95% CI: 1.01, 1.64) cancers. In lung, colon, and grouped gastro-intestinal cancers, association between BMI-WLG and treatment modification increased by WLG.
Discussion:
Our study is a wide assessment of weight loss during SACT using England’s cancer registry data. Across different cancers we found patients have weight loss-associated treatment modifications during SACT, a precursor to poorer prognoses. Our findings highlight cancers that may benefit from improved nutritional intervention during SACT.
BACKGROUND:Early life exposure to air pollution has been linked with cognitive impairment in children, but the results have not been conclusive. We analyzed the association between traffic-related ...air pollution and cognitive function in a prospective birth cohort in Rome.
METHODS:A cohort of 719 newborns was enrolled in 2003–2004 as part of the GASPII project. At age 7 years, 474 children took the Wechsler Intelligence Scale for Children-III to assess their cognitive development in terms of IQ composite scores. Exposure to air pollutants (NO2, PMcoarse, PM2.5, PM2.5 absorbance) at birth was assessed using land use regression models. We also considered variables indicating traffic intensity. The effect of environmental pollution on IQ was evaluated performing a linear regression model for each outcome, adjusting for gender, child age at cognitive test, maternal age at delivery, parental educational level, siblings, socio-economic status, maternal smoking during pregnancy, and tester. To account for selection bias at enrollment and during follow-up, the regression models were weighted for the inverse probabilities of participation and follow-up.
RESULTS:A 10 μg/m higher NO2 exposure during pregnancy was associated with 1.4 fewer points (95% confidence interval = −2.6, −0.20) of verbal IQ, and 1.4 fewer points (95% confidence interval = −2.7, −0.20) of verbal comprehension IQ. Similar associations were found for traffic intensity in a 100 m buffer around home. Other pollutants showed negative associations with larger confidence intervals.
CONCLUSIONS:Consistent with previous evidence, this study suggests an association of exposure to NO2 and traffic intensity with the verbal area of cognitive development.See Video Abstract at http://links.lww.com/EDE/B12.
Creatine Kinase Is Decreased in Childhood Asthma Guerra, Stefano; Ledford, Julie G; Melén, Erik ...
American journal of respiratory and critical care medicine,
03/2023, Volume:
207, Issue:
5
Journal Article
Peer reviewed
Open access
The identification of novel molecules associated with asthma may provide insights into the mechanisms of disease and their potential clinical implications.
To conduct a screening of circulating ...proteins in childhood asthma and to study proteins that emerged from human studies in a mouse model of asthma.
We included 2,264 children from eight birth cohorts from the Mechanisms of the Development of ALLergy project and the Tucson Children's Respiratory Study. In cross-sectional analyses, we tested 46 circulating proteins for association with asthma in the selection stage and carried significant signals forward to a validation and replication stage. As CK (creatine kinase) was the only protein consistently associated with asthma, we also compared whole blood CK gene expression between subjects with and without asthma (
= 249) and used a house dust mite (HDM)-challenged mouse model to gain insights into CK lung expression and its role in the resolution of asthma phenotypes.
As compared with the lowest CK tertile, children in the highest tertile had significantly lower odds for asthma in selection (adjusted odds ratio, 95% confidence interval: 0.31; 0.15-0.65;
= 0.002), validation (0.63; 0.42-0.95;
= 0.03), and replication (0.40; 0.16-0.97;
= 0.04) stages. Both cytosolic CK forms (
and
) were underexpressed in blood from asthmatics compared with control subjects (
= 0.01 and 0.006, respectively). In the lungs of HDM-challenged mice,
expression was reduced, and after the HDM challenge, a CKB inhibitor blocked the resolution of airway hyperresponsiveness and reduction of airway mucin.
Circulating concentrations and gene expression of CK are inversely associated with childhood asthma. Mouse models support a possible direct involvement of CK in asthma protection via inhibition of airway hyperresponsiveness and reduction of airway mucin.
Background
The European post‐authorisation study (EU PAS) register is a repository launched in 2010 by the European Medicines Agency (EMA). All EMA‐requested PAS, commonly observational studies, must ...be recorded in this register. Multi‐database studies (MDS) leveraging secondary data have become an important strategy to conduct PAS in recent years, as reflected by the type of studies registered in the EU PAS register.
Objectives
To analyse and describe PAS in the EU PAS register, with focus on MDS.
Methods
Studies in the EU PAS register from inception to 31st December 2018 were described concerning transparency, regulatory obligations, scope, study type (e.g., observational study, clinical trial, survey, systematic review/meta‐analysis), study design, type of data collection and target population. MDS were defined as studies conducted through secondary use of >1 data source not linked at patient‐level. Data extraction was carried out independently by 14 centres with expertise in pharmacoepidemiology, using publicly available information in the EU PAS register including study protocol, whenever available, using a standardised data collection form. For validation purposes, a second revision of key fields for a 15% random sample of studies was carried out by a different centre. The inter‐rater reliability (IRR) was then calculated. Finally, to identify predictors of primary data collection‐based studies/versus those based on secondary use of healthcare databases) or MDS (vs. non‐MDS), odds ratios (OR) and 95% confidence intervals (CI) were calculated fitting univariate logistic regression models.
Results
Overall, 1426 studies were identified. Clinical trials (N = 30; 2%), systematic reviews/meta‐analyses (N = 16; 1%) and miscellaneous study designs (N = 46; 3%) were much less common than observational studies (N = 1227; 86%). The protocol was available for 63% (N = 360) of 572 observational studies requested by a competent authority. Overall, 36% (N = 446) of observational studies were based fully or partially on primary data collection. Of 757 observational studies based on secondary use of data alone, 282 (37%) were MDS. Drug utilisation was significantly more common as a study scope in MDS compared to non‐MDS studies. The overall percentage agreement among collaborating centres that collected the data concerning study variables was highest for study type (93.5%) and lowest for type of secondary data (67.8%).
Conclusions
Observational studies were the most common type of studies in the EU PAS register, but 30% used primary data, which is more resource‐intensive. Almost half of observational studies using secondary data were MDS. Data recording in the EU PAS register may be improved further, including more widespread availability of study protocols to improve transparency.
the Inverse probability weighting (IPW) is a methodology developed to account for missingness and selection bias caused by non-randomselection of observations, or non-random lack of some information ...in a subgroup of the population.
to provide an overview of IPW methodology and an application in a cohort study of the association between exposure to traffic air pollution (nitrogen dioxide, NO₂) and 7-year children IQ.
this methodology allows to correct the analysis by weighting the observations with the probability of being selected. The IPW is based on the assumption that individual information that can predict the probability of inclusion (non-missingness) are available for the entire study population, so that, after taking account of them, we can make inferences about the entire target population starting from the nonmissing observations alone.The procedure for the calculation is the following: firstly, we consider the entire population at study and calculate the probability of non-missing information using a logistic regression model, where the response is the nonmissingness and the covariates are its possible predictors.The weight of each subject is given by the inverse of the predicted probability. Then the analysis is performed only on the non-missing observations using a weighted model.
IPW is a technique that allows to embed the selection process in the analysis of the estimates, but its effectiveness in "correcting" the selection bias depends on the availability of enough information, for the entire population, to predict the non-missingness probability. In the example proposed, the IPW application showed that the effect of exposure to NO2 on the area of verbal intelligence quotient of children is stronger than the effect showed from the analysis performed without regard to the selection processes.
Abstract
The numbers of international collaborations among birth cohort studies designed to better understand asthma and allergies have increased in the last several years. However, differences in ...definitions and methods preclude direct pooling of original data on individual participants. As part of the Mechanisms of the Development of Allergy (MeDALL) Project, we harmonized data from 14 birth cohort studies (each with 3–20 follow-up periods) carried out in 9 European countries during 1990–1998 or 2003–2009. The harmonization process followed 6 steps: 1) organization of the harmonization panel; 2) identification of variables relevant to MeDALL objectives (candidate variables); 3) proposal of a definition for each candidate variable (reference definition); 4) assessment of the compatibility of each cohort variable with its reference definition (inferential equivalence) and classification of this inferential equivalence as complete, partial, or impossible; 5) convocation of a workshop to agree on the reference definitions and classifications of inferential equivalence; and 6) preparation and delivery of data through a knowledge management portal. We agreed on 137 reference definitions. The inferential equivalence of 3,551 cohort variables to their corresponding reference definitions was classified as complete, partial, and impossible for 70%, 15%, and 15% of the variables, respectively. A harmonized database was delivered to MeDALL investigators. In asthma and allergy birth cohorts, the harmonization of data for pooled analyses is feasible, and high inferential comparability may be achieved. The MeDALL harmonization approach can be used in other collaborative projects.
BACKGROUND: The European post-authorisation study (EU PAS) register is a repository launched in 2010 by the European Medicines Agency (EMA). All EMA-requested PAS, commonly observational studies, ...must be recorded in this register. Multi-database studies (MDS) leveraging secondary data have become an important strategy to conduct PAS in recent years, as reflected by the type of studies registered in the EU PAS register. OBJECTIVES: To analyse and describe PAS in the EU PAS register, with focus on MDS. METHODS: Studies in the EU PAS register from inception to 31(st) December 2018 were described concerning transparency, regulatory obligations, scope, study type (e.g. observational study, clinical trial, survey, systematic review/meta-analysis), study design, type of data collection and target population. MDS were defined as studies conducted through secondary use of >1 data source not linked at patient-level. Data extraction was carried out independently by 14 centres with expertise in pharmacoepidemiology, using publicly available information in the EU PAS register including study protocol, whenever available, using a standardised data collection form. For validation purposes, a second revision of key fields for a 15% random sample of studies was carried out by a different centre. The inter-rater reliability (IRR) was then calculated. Finally, to identify predictors of primary data collection-based studies /vs those based on secondary use of healthcare databases) or MDS (vs. non-MDS), odds ratios (OR) and 95% confidence intervals (CI) were calculated fitting univariate logistic regression models. RESULTS: Overall, 1,426 studies were identified. Clinical trials (N=30; 2%), systematic reviews/meta-analyses (N=16; 1%) and miscellaneous study designs (N=46; 3%) were much less common than observational studies (N=1,227; 86%). The protocol was available for 63% (N=360) of 572 observational studies requested by a competent authority. Overall, 36% (N=446) of observational studies were based fully or partially on primary data collection. Of 757 observational studies based on secondary use of data alone, 282 (37%) were MDS. Drug utilisation was significantly more common as a study scope in MDS compared to non-MDS studies. The overall percentage agreement among collaborating centres that collected the data concerning study variables was highest for study type (93.5%) and lowest for type of secondary data (67.8%). CONCLUSIONS: Observational studies were the most common type of studies in the EU PAS register, but 30% used primary data, which is more resource-intensive. Almost half of observational studies using secondary data were MDS. Data recording in the EU PAS register may be improved further, including more widespread availability of study protocols to improve transparency.
to test the validity of algorithms to identify diabetes, chronic obstructive pulmonary disease (COPD), hypertension, and hypothyroidism from routinely collected health data using information from ...self-reported diagnosis and laboratory or functional test.
clinical or self-reported diagnosis from three surveys conducted in Lazio Region (Central Italy) between year 2010 and 2014 were assumed as gold standard and compared to the results of the algorithms application to administrative data.
prevalence resulted from administrative data and from information available in the surveys were compared. Sensitivity, specificity, positive predictive value, and positive likelihood ratio of algorithms with respect to self-reported diagnosis, laboratory or functional test, assumed as gold standards, were calculated.
we analyzed data of 7,318 subjects (1,545 for diabetes, 1,783 for COPD, 2,448 for hypertension, and 1,542 for hypothyroidism). For hypertension and hypothyroidism, we observed a higher prevalence from laboratory or functional test compared to self-reported diagnosis (54.5% vs. 44.9% and 7.5% vs. 1.5%). Sensitivity of administrative data with respect to self-reported diagnosis resulted 90.9%, 38.5%, 88.3%, and 47.8%, respectively, for diabetes, COPD, hypertension, and hypothyroidism. Respectively, specificity was 97.4%, 91.7%, 84.8% and 91.8%; positive predictive value was 70,9%, 38.1%, 82.6% and 8.1%. All values of positive likelihood ratio resulted moderate (about 5), with exception of the diabetes algorithm and the disease-specific payment exemptions register for hypertension (respectively 35.5 and 17.4).
hypertension and hypothyroidism resulted markedly underdiagnosed from self-reported data. Case identification algorithms are highly specific, allowing their utilization for selection of cohort of subject affected by chronic diseases. The sub-optimal sensitivity observed for COPD and hypothyroidism could limit the utilization of the algorithms for prevalence estimation.
PDF
