Tag: statistics

Diabetologia. 2022 Oct 11. doi: 10.1007/s00125-022-05806-2. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: We examined the contribution of rare HNF1A variants to type 2 diabetes risk and age of diagnosis, and the extent to which their impact is affected by overall genetic susceptibility, across three ancestry groups.

METHODS: Using exome sequencing data of 160,615 individuals of the UK Biobank and 18,797 individuals of the BioMe Biobank, we identified 746 carriers of rare functional HNF1A variants (minor allele frequency ≤1%), of which 507 carry variants in the functional domains. We calculated polygenic risk scores (PRSs) based on genome-wide association study summary statistics for type 2 diabetes, and examined the association of HNF1A variants and PRS with risk of type 2 diabetes and age of diagnosis. We also tested whether the PRS affects the association between HNF1A variants and type 2 diabetes risk by including an interaction term.

RESULTS: Rare HNF1A variants that are predicted to impair protein function are associated with increased risk of type 2 diabetes in individuals of European ancestry (OR 1.46, p=0.049), particularly when the variants are located in the functional domains (OR 1.89, p=0.002). No association was observed for individuals of African ancestry (OR 1.10, p=0.60) or Hispanic-Latino ancestry (OR 1.00, p=1.00). Rare functional HNF1A variants were associated with an earlier age at diagnosis in the Hispanic-Latino population (β=-5.0 years, p=0.03), and this association was marginally more pronounced for variants in the functional domains (β=-5.59 years, p=0.03). No associations were observed for other ancestries (African ancestry β=-2.7 years, p=0.13; European ancestry β=-3.5 years, p=0.20). A higher PRS was associated with increased odds of type 2 diabetes in all ancestries (OR 1.61-2.11, p<10^-5) and an earlier age at diagnosis in individuals of African ancestry (β=-1.4 years, p=3.7 × 10^-6) and Hispanic-Latino ancestry (β=-2.4 years, p<2 × 10^-16). Furthermore, a higher PRS exacerbated the effect of the functional HNF1A variants on type 2 diabetes in the European ancestry population (p_interaction=0.037).

CONCLUSIONS/INTERPRETATION: We show that rare functional HNF1A variants, in particular those located in the functional domains, increase the risk of type 2 diabetes, at least among individuals of European ancestry. Their effect is even more pronounced in individuals with a high polygenic susceptibility. Our analyses highlight the importance of the location of functional variants within a gene and an individual’s overall polygenic susceptibility, and emphasise the need for more genetic data in non-European populations.

PMID:36216889 | DOI:10.1007/s00125-022-05806-2

Ann Intern Med. 2022 Oct 11. doi: 10.7326/M22-0835. Online ahead of print.

ABSTRACT

BACKGROUND: The effectiveness of screening for colorectal cancer (CRC) by sex and age in randomized trials is uncertain.

OBJECTIVE: To evaluate the 15-year effect of sigmoidoscopy screening on CRC incidence and mortality.

DESIGN: Pooled analysis of 4 large-scale randomized trials of sigmoidoscopy screening.

SETTING: Norway, the United States, the United Kingdom, and Italy.

PARTICIPANTS: Women and men aged 55 to 64 years at enrollment.

INTERVENTION: Sigmoidoscopy screening.

MEASUREMENTS: Primary end points were cumulative incidence rate ratio (IRR) and mortality rate ratio (MRR) and rate differences after 15 years of follow-up comparing screening versus usual care in intention-to-treat analyses. Stratified analyses were done by sex, cancer site, and age at screening.

RESULTS: Analyses comprised 274 952 persons (50.7% women), 137 493 in the screening and 137 459 in the usual care group. Screening attendance was 58% to 84%. After 15 years, the rate difference for CRC incidence was 0.51 cases (95% CI, 0.40 to 0.63 cases) per 100 persons and the IRR was 0.79 (CI, 0.75 to 0.83). The rate difference for CRC mortality was 0.13 deaths (CI, 0.07 to 0.19 deaths) per 100 persons, and the MRR was 0.80 (CI, 0.72 to 0.88). Women had less benefit from screening than men for CRC incidence (IRR for women, 0.84 [CI, 0.77 to 0.91]; IRR for men, 0.75 [CI, 0.70 to 0.81]; P = 0.032 for difference) and mortality (MRR for women, 0.91 [CI, 0.77 to 1.17]; MRR for men, 0.73 [CI, 0.64 to 0.83]; P = 0.025 for difference). There was no statistically significant difference in screening effect between persons aged 55 to 59 years and those aged 60 to 64 years.

LIMITATION: Data from the U.K. trial were less granular because of privacy regulations.

CONCLUSION: This pooled analysis of all large randomized trials of sigmoidoscopy screening demonstrates a significant and sustained effect of sigmoidoscopy on CRC incidence and mortality for 15 years.

PRIMARY FUNDING SOURCE: Health Fund of South-East Norway.

PMID:36215714 | DOI:10.7326/M22-0835

Ann Intern Med. 2022 Oct 11. doi: 10.7326/M22-0760. Online ahead of print.

ABSTRACT

BACKGROUND: It is important to document the performance of rapid antigen tests (Ag-RDTs) in detecting SARS-CoV-2 variants.

OBJECTIVE: To compare the performance of Ag-RDTs in detecting the Delta (B.1.617.2) and Omicron (B.1.1.529) variants of SARS-CoV-2.

DESIGN: Secondary analysis of a prospective cohort study that enrolled participants between 18 October 2021 and 24 January 2022. Participants did Ag-RDTs and collected samples for reverse transcriptase polymerase chain reaction (RT-PCR) testing every 48 hours for 15 days.

SETTING: The parent study enrolled participants throughout the mainland United States through a digital platform. All participants self-collected anterior nasal swabs for rapid antigen testing and RT-PCR testing. All Ag-RDTs were completed at home, whereas nasal swabs for RT-PCR were shipped to a central laboratory.

PARTICIPANTS: Of 7349 participants enrolled in the parent study, 5779 asymptomatic persons who tested negative for SARS-CoV-2 on day 1 of the study were eligible for this substudy.

MEASUREMENTS: Sensitivity of Ag-RDTs on the same day as the first positive (index) RT-PCR result and 48 hours after the first positive RT-PCR result.

RESULTS: A total of 207 participants were positive on RT-PCR (58 Delta, 149 Omicron). Differences in sensitivity between variants were not statistically significant (same day: Delta, 15.5% [95% CI, 6.2% to 24.8%] vs. Omicron, 22.1% [CI, 15.5% to 28.8%]; at 48 hours: Delta, 44.8% [CI, 32.0% to 57.6%] vs. Omicron, 49.7% [CI, 41.6% to 57.6%]). Among 109 participants who had RT-PCR-positive results for 48 hours, rapid antigen sensitivity did not differ significantly between Delta- and Omicron-infected participants (48-hour sensitivity: Delta, 81.5% [CI, 66.8% to 96.1%] vs. Omicron, 78.0% [CI, 69.1% to 87.0%]). Only 7.2% of the 69 participants with RT-PCR-positive results for shorter than 48 hours tested positive by Ag-RDT within 1 week; those with Delta infections remained consistently negative on Ag-RDTs.

LIMITATION: A testing frequency of 48 hours does not allow a finer temporal resolution of the analysis of test performance, and the results of Ag-RDTs are based on self-report.

CONCLUSION: The performance of Ag-RDTs in persons infected with the SARS-CoV-2 Omicron variant is not inferior to that in persons with Delta infections. Serial testing improved the sensitivity of Ag-RDTs for both variants. The performance of rapid antigen testing varies on the basis of duration of RT-PCR positivity.

PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute of the National Institutes of Health.

PMID:36215709 | DOI:10.7326/M22-0760

Am J Audiol. 2022 Oct 10:1-11. doi: 10.1044/2022_AJA-21-00270. Online ahead of print.

ABSTRACT

PURPOSE: Internet-based cognitive behavioral therapy (ICBT) has been found to be effective for tinnitus management, although there is limited understanding about who will benefit the most from ICBT. Traditional statistical models have largely failed to identify the nonlinear associations and hence find strong predictors of success with ICBT. This study aimed at examining the use of an artificial neural network (ANN) and support vector machine (SVM) to identify variables associated with treatment success in ICBT for tinnitus.

METHOD: The study involved a secondary analysis of data from 228 individuals who had completed ICBT in previous intervention studies. A 13-point reduction in Tinnitus Functional Index (TFI) was defined as a successful outcome. There were 33 predictor variables, including demographic, tinnitus, hearing-related and treatment-related variables, and clinical factors (anxiety, depression, insomnia, hyperacusis, hearing disability, cognitive function, and life satisfaction). Predictive models using ANN and SVM were developed and evaluated for classification accuracy. SHapley Additive exPlanations (SHAP) analysis was used to identify the relative predictor variable importance using the best predictive model for a successful treatment outcome.

RESULTS: The best predictive model was achieved with the ANN with an average area under the receiver operating characteristic value of 0.73 ± 0.03. The SHAP analysis revealed that having a higher education level and a greater baseline tinnitus severity were the most critical factors that influence treatment outcome positively.

CONCLUSIONS: Predictive models such as ANN and SVM help predict ICBT treatment outcomes and identify predictors of outcome. However, further work is needed to examine predictors that were not considered in this study as well as to improve the predictive power of these models.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21266487.

PMID:36215687 | DOI:10.1044/2022_AJA-21-00270

JCO Oncol Pract. 2022 Oct 10:OP2200300. doi: 10.1200/OP.22.00300. Online ahead of print.

ABSTRACT

PURPOSE: Individuals diagnosed with cancer age between 15 and 39 years (adolescents and young adults [AYAs]) have not seen improvement in survival compared with children or older adults; clinical trial accrual correlates with survival. Unique unmet needs among AYAs related to psychosocial support and fertility preservation (FP) are associated with health-related quality of life.

METHODS: We enhanced existing structures and leveraged faculty/staff across pediatric/adult oncology to create novel teams focused on AYA (age 15-39 years) care at a single center, with minimal dedicated staff and no change to revenue streams. We aimed to influence domains shown to drive survival and health-related quality of life: clinical trial enrollment, physician/staff collaboration, psychosocial support, and FP. We captured metrics 3 months after patients presented to the institution and compared them before/after Program implementation using descriptive statistics.

RESULTS: Among 139 AYAs (age 15-39 years) from the pre-Program era (January 2016-February 2019: adult, n = 79; pediatric, n = 60), and 279 from the post-Program era (February 2019-March 2022: adult, n = 215; pediatric, n = 64), there was no change in clinical trial enrollment(P ≥ .3), whereas there was an increase in the proportion of AYAs referred for supportive care and psychology (pediatric: P ≤ .02; adult: P ≤ .001); whose oncologists discussed FP (pediatric: 15% v 52%, P < .0001; adult: 37% v 50%, P = .0004); and undergoing FP consults (pediatric: 8% v39%, P < .0001; adult 23% v 38%, P = .02).

CONCLUSION: This team-based framework has effected change in most targeted domains. To affect all domains and design optimal interventions, it is crucial to understand patient-level and facility-level barriers/facilitators to FP and clinical trial enrollment.

PMID:36215685 | DOI:10.1200/OP.22.00300

Eur J Public Health. 2022 Oct 10:ckac115. doi: 10.1093/eurpub/ckac115. Online ahead of print.

ABSTRACT

BACKGROUND: Effectiveness of tobacco taxation can be undermined through smokers applying price-minimizing behaviours rather than quitting or reducing consumption. Common price-minimizing strategies are buying cheaper tobacco [discount brands or roll-your-own (RYO) tobacco], bulk buying and cross-border purchasing. This study analyses trends in and factors associated with such behaviours in four European countries from 2006 to 2020.

METHODS: Data came from adult smokers participating in the International Tobacco Control (ITC) Surveys conducted between 2006 and 2020 in England (9 waves, n = 768-4149), France (4 waves, n = 1415-1735), Germany (5 waves, n = 513-1515) and the Netherlands (10 waves, n = 1191-2177). Country-specific generalized estimating equation regression models were fit to assess trends in smoking RYO tobacco, discount brands, bulk buying and cross-border purchasing within the European Union.

RESULTS: Buying discount brands or RYO tobacco was the most common strategy in all countries, except France. Except for buying discount brands, estimates of price-minimizing behaviours were highest in France (2019: RYO = 27.2%, discount brands = 17.3%, bulk buying = 34.1%, cross-border purchasing = 34.2%), and lowest in Germany (2018: RYO = 18.6%, discount brands = 43.7%, bulk buying = 8.0%, cross-border purchasing = 9.8%). Direction and magnitude of trends differed by country, and behaviour. Young smokers were less likely to buy in bulk. Low-income and low-education smokers were more likely to purchase RYO tobacco or discount brands. The association with discount brands was not found for French low-income smokers.

CONCLUSIONS: Smoking cheaper tobacco is the most prevalent price-minimizing strategy in three countries (England, Germany and Netherlands), and more prevalent among low-income individuals. Harmonizing prices across products and countries would reduce switching to cheaper tobacco.

PMID:36215655 | DOI:10.1093/eurpub/ckac115

J Opt Soc Am A Opt Image Sci Vis. 2022 Aug 1;39(8):1360-1370. doi: 10.1364/JOSAA.461542.

ABSTRACT

Metrics of color-difference formula improvement (i.e., standardized residual sum of squares and Pearson product moment correlation) are shown to convey the same information. Furthermore, each metric has two computational forms that assume different linear data models, specifically, with or without an ordinate intercept. It is essential to choose a computational form that matches the data model. We recommend explicitly declaring whether or not the data have been centered, i.e., by subtracting the mean value from each datum, to match the intercept-free data model. Statistical testing of the metrics assumes independent, normally distributed randomness of residuals from the data model, and homogeneous variance. Procedures consistent with these assumptions include robust statistical tests, homogenizing data transformations, and meta-analysis.

PMID:36215579 | DOI:10.1364/JOSAA.461542

J Nucl Med. 2022 Sep 2:jnumed.122.264424. doi: 10.2967/jnumed.122.264424. Online ahead of print.

ABSTRACT

Objective: To determine the negative predictive value (NPV) of a 12-14 week post-treatment PET/CT for 2-year progression-free survival (PFS) and locoregional control (LRC) in patients with p16-positive locoregionally advanced oropharyngeal cancer (LA-OPC). Study was a secondary endpoint in NRG-HN002, a non-comparative phase II trial in p16-positive LA-OPC, stage T1-T2, N1-N2b or T3, N0-N2b (AJCC, 7th ed.) and ≤ 10 pack-year smoking. Patients were randomized in a 1:1 ratio to reduced-dose IMRT with or without cisplatin. Methods: PET/CT scans were reviewed centrally. Tumor response evaluations for the primary site, right neck, and left neck were carried out using a 5-point ordinal scale (Hopkins Criteria). Overall scores were then assigned as ‘Negative,’ Positive,’ or ‘Indeterminate’. Patients with a ‘Negative’ score for all three evaluation sites were given an overall score of ‘Negative.’ The hypotheses were NPV for PFS and LRC at two years post-treatment ≤ 90% vs >90% (1-sided alpha 0.10). Results: There were 316 patients enrolled, of whom 306 were randomized and eligible. Of these, 131 (42.8%) patients consented to a post-therapy PET/CT, and 117 (89.3%) patients were eligible for PET/CT analysis. The median time from the end of treatment to PET/CT scan was 94 days (range 52-139). Estimated 2-year PFS and LRC rates in the analysis subgroup were 91.3% (95% confidence interval CI [84.6, 95.8%]) and 93.8% (95% CI [87.6, 97.5%]), respectively. Post-treatment scans were negative for residual tumor for 115 patients (98.3%) and positive for two patients (1.7%). NPV for 2-year PFS was 92.0% (90% lower confidence bound [LCB] 87.7%; P = 0.30) and for LRC was 94.5% (90% LCB 90.6%; P = 0.07). Conclusion: In the context of deintensification with reduced-dose radiation, the NPV of a 12-14 week post-therapy PET/CT for 2-year LRC is estimated to be > 90%, similar to that reported for patients receiving standard chemoradiation. However, there is insufficient evidence to conclude that the NPV is > 90% for PFS.

PMID:36215572 | DOI:10.2967/jnumed.122.264424

J Opt Soc Am A Opt Image Sci Vis. 2022 Oct 1;39(10):1857-1865. doi: 10.1364/JOSAA.470040.

ABSTRACT

A narrow beam propagating through the disordered optical fiber first undergoes diffusive broadening, until its width becomes comparable to the localization length. The study of numerical algorithms and statistical methods in the simulation analysis process of disordered optical fibers demonstrates that the influence of polarization characteristics and transverse grids on calculation errors is critical for statistical numerical simulation in disordered systems. We performed a detailed numerical analysis of the effect of different design parameters in disordered fibers on the localization effect-that is, the localization length, including the refractive index contrast, feature size, and fill-fraction. The results show that the optimal fill-fraction is 50%, and that higher refractive index contrast and larger feature size relative to the wavelength both result in a smaller effective beam width. Finally, numerical evidence is also provided that optical images can be transported via transverse Anderson localization.

PMID:36215558 | DOI:10.1364/JOSAA.470040

J Opt Soc Am A Opt Image Sci Vis. 2022 Jun 1;39(6):B65-B77. doi: 10.1364/JOSAA.450595.

ABSTRACT

Predicting the quality of natural images without using a reference image has always been a challenging task. Numerous approaches have been proposed in the past, but they mainly focused on spatial and frequency domain degradations like blur, noise, and compression. Image quality metrics (IQMs) in literature perform with quite a high accuracy for such types of degraded images. However, their performances are not good on the images modified in the color domain. In this study, psychophysical experiments were conducted to assess the quality of the color domain images. A new dataset was developed for this purpose. Additionally, a second dataset consisting of color domain modified images from the three previously published datasets were used in the psychophysical experiments. The newly developed dataset was then used to develop three IQMs based on absolute values, relative values, and statistical analysis of image color appearance attributes. Their performances were then evaluated together with five spatial domain IQMs from the literature using cross-database evaluation methodology. The results showed that the color-domain IQMs outperformed the other models. The absolute and relative attributes-based models, when combined, achieved the best performance. The present results suggest that more effort is needed to improve the performance of color domain IQMs for image quality estimation.

PMID:36215544 | DOI:10.1364/JOSAA.450595