A Systematic Review and Meta-analysis of Iowa Oral Performance Instrument Measures in Persons with Parkinson's Disease Compared to Healthy Adults.

Measures of tongue strength and endurance using the Iowa Oral Performance Instrument (IOPI) may have diagnostic utility during clinical swallowing evaluations for persons with Parkinson's disease (PwPD). Thus, the objective was to systematically analyze the existing literature comparing IOPI values of tongue strength and endurance between age- and sex-match pairs of PwPD and healthy adults as well as across disease stages. A systematic review of 12 databases and Google Scholar identified five peer-reviewed articles published in English (1990-2019) that compared tongue strength and/or endurance between PwPD and controls. Individual-level data were published in two studies and provided by authors for three studies. Study appraisal included the NIH Quality Assessment Tool and STROBE checklists. Limited data for posterior tongue pressures restricted meta-analyses to anterior pressures. Meta-analyses of group means indicated reduced tongue strength across 106 matched pairs (p < .001, I2 = 0%) and a trend for reduced endurance across 41 matched pairs (p = .07, I2 = 54%). Participant-level analyses found reduced strength (96 pairs, p < .001) and endurance (41 pairs, p = .011) secondary to PD. Tongue strength (n = 68), but not endurance (n = 41), inversely correlated with disease stage when controlling for age (p ≤ .018). Overall, clinicians should be aware that reduced anterior tongue strength and endurance are as follows : expected in approximately one-third and one-fourth of PwPD, respectively, and reduced anterior tongue strength may manifest as early as Hoehn and Yahr stage 2 with continual decline as disease progresses. Further investigation is warranted regarding the relation among tongue strength, tongue endurance, and swallowing physiology as well as applications of tongue pressure training within dysphagia rehabilitation for PwPD.

Impact of individual level uncertainty of lung cancer polygenic risk score (PRS) on risk stratification.

BACKGROUND: Although polygenic risk score (PRS) has emerged as a promising tool for predicting cancer risk from genome-wide association studies (GWAS), the individual-level accuracy of lung cancer PRS and the extent to which its impact on subsequent clinical applications remains largely unexplored. METHODS: Lung cancer PRSs and confidence/credible interval (CI) were constructed using two statistical approaches for each individual: (1) the weighted sum of 16 GWAS-derived significant SNP loci and the CI through the bootstrapping method (PRS-16-CV) and (2) LDpred2 and the CI through posteriors sampling (PRS-Bayes), among 17,166 lung cancer cases and 12,894 controls with European ancestry from the International Lung Cancer Consortium. Individuals were classified into different genetic risk subgroups based on the relationship between their own PRS mean/PRS CI and the population level threshold. RESULTS: Considerable variances in PRS point estimates at the individual level were observed for both methods, with an average standard deviation (s.d.) of 0.12 for PRS-16-CV and a much larger s.d. of 0.88 for PRS-Bayes. Using PRS-16-CV, only 25.0% of individuals with PRS point estimates in the lowest decile of PRS and 16.8% in the highest decile have their entire 95% CI fully contained in the lowest and highest decile, respectively, while PRS-Bayes was unable to find any eligible individuals. Only 19% of the individuals were concordantly identified as having high genetic risk (> 90th percentile) using the two PRS estimators. An increased relative risk of lung cancer comparing the highest PRS percentile to the lowest was observed when taking the CI into account (OR = 2.73, 95% CI: 2.12-3.50, P-value = 4.13 × 10-15) compared to using PRS-16-CV mean (OR = 2.23, 95% CI: 1.99-2.49, P-value = 5.70 × 10-46). Improved risk prediction performance with higher AUC was consistently observed in individuals identified by PRS-16-CV CI, and the best performance was achieved by incorporating age, gender, and detailed smoking pack-years (AUC: 0.73, 95% CI = 0.72-0.74). CONCLUSIONS: Lung cancer PRS estimates using different methods have modest correlations at the individual level, highlighting the importance of considering individual-level uncertainty when evaluating the practical utility of PRS.

Multiple newly identified loci associated with prostate cancer susceptibility.

Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at