Collaborative workflow between pathologists and deep learning for evaluation of tumor cellularity in lung adenocarcinoma

Owing to the high demand for molecular testing, the reporting of tumor cellularity in cancer samples has become a mandatory task for pathologists. However, the pathological estimation of tumor cellularity is often inaccurate. We developed a collaborative workflow between pathologists and artificial intelligence (AI) models to evaluate tumor cellularity in lung cancer samples and prospectively applied it to routine practice. We also developed a quantitative model that we validated and tested on retrospectively analyzed cases and ran the model prospectively in a collaborative workflow where pathologists could access the AI results and apply adjustments (Adjusted-Score). The Adjusted-Scores were validated by comparing them with the ground truth established by manual annotation of hematoxylin-eosin slides with reference to immunostains with thyroid transcription factor-1 and napsin A. For training, validation, retrospective testing, and prospective application of the model, we used 40, 10, 50, and 151 whole slide images, respectively. The sensitivity and specificity of tumor segmentation were 97% and 87%, and the accuracy of nuclei recognition was 99%. Pathologists altered the initial scores in 87% of the cases after referring to the AI results and found that the scores became more precise after collaborating with AI. For validation of Adjusted-Score, we found the Adjusted-Score was significantly closer to the ground truth than non-AI-aided estimates (p<0.05). Thus, an AI-based model was successfully implemented into the routine practice of pathological investigations. The proposed model for tumor cell counting efficiently supported the pathologists to improve the prediction of tumor cellularity for genetic tests.

Socially Relevant Approaches to the Detection of Dementia in Minority Older Adults

Substantial gaps remain in the scientific literature regarding low-income minority older adult populations with Alzheimer’s disease and related dementias (ADRDs). Access to care and early cognitive screening are often barriers to advancing ADRD detection in low socioeconomic status (SES) minority older adults. Additionally, there is the need for demographically (age, education, sex, race, ethnicity, and income) corrected normative scores in cognitive measures. Our cross-sectional study evaluated the psychometrics of the Mini-Mental State Exam-2 (MMSE-2) and the NIH Toolbox Cognition Battery (NIHTB-CB). The sample consisted of n=80 community-based older adults without a diagnosis of dementia living in low-income high-rise housing units. Acceptability is assessed with a brief 6-item acceptability survey, multiple linear regression is used to get predicted cognitive scores adjusted for age, education, income, ethnicity, race, and sex, and t-test comparison of the adjusted scores found in this study to established norms. Results found a mean age of 73, 70% black, 48% with &lt; 12th-grade education, 51% have a monthly income of &lt; $1,000, and 49% with undiagnosed cognitive impairment (CI) by both measures. When applying demographic adjustments in the NIHTB-CB 1) standard scores; 2) age-corrected scores, and 3) demographically correct scores all remained significant (p &gt; 0.0001). Participants reported high (80-95%) acceptability for the community-based cognitive screening, 18% reported concerns with cultural appropriateness of the questions in the NIHTB-CB as compared to 5% with the MMSE-2. This research lays the foundation for a community-based cognitive screening and care coordination program for the low SES minority older adult population.

Translation and cultural validation of the University of Washington Caregiver Stress and Benefit Scales

Background English versions of the University of Washington Caregiver Stress (UW-CSS) and Benefit (UW-CBS) Scales were developed in the United States (US) to measure impact on caregivers of caring for a child/children. Caregiving stress and benefit are important constructs to study worldwide. The purpose of this study was to translate and validate the UW-CSS and UW-CBS into French, German, Italian, and Spanish languages. Method UW-CSS and UW-CBS were translated using forward and backward translation with reconciliation. Cognitive interviews (CIs) were completed with caregivers of children < 18 years with severe epilepsy. Translated versions were also administered to at least 100 caregivers in each of the four countries: France, Germany, Italy, and Spain. Differential item functioning (DIF) analyses were used to assess linguistic and cultural bias by country. The US development sample of 722 caregivers was used as a comparison sample for DIF analyses. DIF adjusted scores were calculated to determine impact of DIF on the item response theory (IRT)-based T-score. Benefit and stress scores were also calculated and compared across countries and health condition subgroups. Finally, short forms were modified to minimize the impact of DIF on the UW-CSS and UW-CBS T-scores and to reflect feedback from CIs. Results Interviews were completed with 47 caregivers (German n = 14; Spanish n = 10; French n = 13; Italian n = 10). UW-CSS and UW-CBS were administered to 456 (German n = 117, Spanish n = 114, French n = 115, Italian n = 110) caregivers of children with and without health conditions. All stress items functioned well in CIs, though results indicated statistically significant DIF for three items in multiple countries and in the overall sample. Four of the 13 benefit items were problematic based on CI feedback, and six items showed DIF in one or more countries or in the combined sample. However, average differences between DIF adjusted and non-adjusted scores were minimal for both scales and all comparisons, indicating the impact of DIF on the total score was negligible. Conclusion Modified short forms functioned well in all four of the translated versions. All language versions are freely publicly available.

Parenteral artemisinins are associated with reduced mortality and neurologic deficits and improved long-term behavioral outcomes in children with severe malaria

Background In 2011, the World Health Organization recommended injectable artesunate as the first-line therapy for severe malaria (SM) due to its superiority in reducing mortality compared to quinine. There are limited data on long-term clinical and neurobehavioral outcomes after artemisinin use for treatment of SM. Methods From 2008 to 2013, 502 Ugandan children with two common forms of SM, cerebral malaria and severe malarial anemia, were enrolled in a prospective observational study assessing long-term neurobehavioral and cognitive outcomes following SM. Children were evaluated a week after hospital discharge, and 6, 12, and 24 months of follow-up, and returned to hospital for any illness. In this study, we evaluated the impact of artemisinin derivatives on survival, post-discharge hospital readmission or death, and neurocognitive and behavioral outcomes over 2 years of follow-up. Results 346 children received quinine and 156 received parenteral artemisinin therapy (artemether or artesunate). After adjustment for disease severity, artemisinin derivatives were associated with a 78% reduction in in-hospital mortality (adjusted odds ratio, 0.22; 95% CI, 0.07–0.67). Among cerebral malaria survivors, children treated with artemisinin derivatives also had reduced neurologic deficits at discharge (quinine, 41.7%; artemisinin derivatives, 23.7%, p=0.007). Over a 2-year follow-up, artemisinin derivatives as compared to quinine were associated with better adjusted scores (negative scores better) in internalizing behavior and executive function in children irrespective of the age at severe malaria episode. After adjusting for multiple comparisons, artemisinin derivatives were associated with better adjusted scores in behavior and executive function in children <6 years of age at severe malaria exposure following adjustment for child age, sex, socioeconomic status, enrichment in the home environment, and the incidence of hospitalizations over follow-up. Children receiving artesunate had the greatest reduction in mortality and benefit in behavioral outcomes and had reduced inflammation at 1-month follow-up compared to children treated with quinine. Conclusions Treatment of severe malaria with artemisinin derivatives, particularly artesunate, results in reduced in-hospital mortality and neurologic deficits in children of all ages, reduced inflammation following recovery, and better long-term behavioral outcomes. These findings suggest artesunate has long-term beneficial effects in children surviving severe malaria.

Making an equal system equitable: Proposing a sex-adjusted MELDNa score for liver transplantation allocation

Background & Aims: Liver allocation is determined by the model for end-stage liver disease (MELD), a scoring system based on four laboratory measurements. During the MELD era, sex disparities in liver transplant have increased and there are no modifications to MELD based on sex. We use data from electronic health records (EHRs) to describe sex differences in MELD labs and propose a sex adjustment. Methods: We extracted lab values for creatinine, International Normalized Ratio of prothrombin rate, bilirubin, and sodium from EHRs at Vanderbilt University Medical Center (VUMC) and the All of Us Research Project to determine sex differences in lab traits. We calculated MELDNa scores within liver transplant recipients, non-transplanted liver disease cases, and non-liver disease controls separately. To account for sex differences in lab traits in MELDNa scoring, we created a sex-adjusted MELDNa map which outputs adjusted female scores mapped to male scores of equal liver disease severity. Using waitlist data from the Liver Simulated Allocation Modeling, we conducted simulations to determine if the sex-adjusted scores reduced sex disparities. Results: All component MELDNa lab values and calculated MELDNa scores yielded significant sex differences within VUMC (n=623,931) and All of Us (n=56,715) resulting in MELDNa scoring that disadvantaged females who, despite greater decompensation traits, had lower MELDNa scores. In simulations, the sex-adjusted MELDNa score modestly increased female transplantation rate and decreased overall death. Conclusions: Our results demonstrate pervasive sex differences in all labs used in MELDNa scoring and highlight the need and utility of a sex-adjustment to the MELDNa protocol.

Association of Patient-Reported Physician Awareness of Complementary Medicine, Medical Care Experience and Care Quality

The aim was to examine the association of patient-reported physician awareness of biological CAM use and patient perceptions of care experience and quality with a population-based study of patients with incident lung and colorectal cancer. This was a secondary data analysis using regression models. Outcomes of interest were patient reports of medical care experience and quality ratings. Among 716 patients who reported biological CAM use, 69% reported their physicians were aware of this. Patients who reported physician awareness of biological CAM use had higher adjusted scores for medical care experience ( + 5.4, 95%CI:2.3,8.6) and care quality ( + 3.6, 95%CI:−0.3, + 7.5). These associations suggest that physicians should be encouraged to inquire about biological CAM use.

Maze Test Score Adjustments When Using Non-Dominant Hand in Fitness-To-Drive Assessments

Older drivers with health impairments may be required to undertake fitness-to-drive assessments. Scores on the Occupational Therapy-Drive Home Maze Test (OT-DHMT) can contribute to fitness-to-drive recommendations. The OT-DHMT is a short, timed maze test that has been shown to be valid and reliable, and norms are available for completion with a driver’s dominant hand. However, the validity of a person’s score when using their non-dominant hand to complete the test, for example following stroke, is unknown. This study aimed to determine if a person’s OT-DHMT score time (in seconds) requires adjustment when completed with a non-dominant hand. The OT-DHMT was administered with a normative sample of 150 participants, aged 21-81 years (mean=48.6,SD=19.38). Overall, OT-DHMT score times were significantly faster when using a dominant (M=15.73) compared with non-dominant (M=17.64) hand, d=1.91 (CI 1.13, 2.69), t= 4.84,p&lt; .01. Employing a generalised weighted least squares regression model indicated that multiplying a driver’s non-dominant hand time by .833 seconds for drivers aged ≤60, and by .929 seconds for drivers aged 61+ can approximate dominant hand completion times. Adjusted scores can then be compared against normed scores to aid fitness-to-drive recommendations. The adjustment required for people aged ≤60 is larger than for older people, reinforcing previous findings that younger people have faster OT-DHMT completion times. These findings support the clinical utility and vaildity of using the OT-DHMT with older people undergoing fitness-to-drive assessment who may be required to use their non-dominant hand due to conditions such as stroke, arthritis or amputation.

Cognitive Practice Effects Delay Diagnosis; Implications for Clinical Trials

ObjectivePractice effects on cognitive tests obscure decline, thereby delaying detection of mild cognitive impairment (MCI). This reduces opportunities for slowing Alzheimer’s disease progression and can hinder clinical trials. Using a novel method, we assessed the ability of practice-effect-adjusted diagnoses to detect MCI earlier, and tested the validity of these diagnoses based on AD biomarkers.MethodsOf 889 Alzheimer’s Disease Neuroimaging Initiative participants who were cognitively normal (CN) at baseline, 722 returned at 1-year-follow-up (mean age=74.9±6.8). Practice effects were calculated by comparing returnee scores at follow-up to demographically-matched individuals who had only taken the tests once, with an additional adjustment for attrition effects. Practice effects for each test were subtracted from follow-up scores. The lower scores put additional individuals below the impairment threshold for MCI. CSF amyloid-beta, phosphorylated tau, and total tau were measured at baseline and used for criterion validation.ResultsPractice-effect-adjusted scores increased MCI incidence by 26% (p<.001). Adjustment increased proportions of amyloid-positive MCI cases (+20%) and reduced proportions of amyloid-positive CNs (−6%) (ps<.007). With the increased MCI base rate, adjustment for practice effects would reduce the sample size needed for detecting significant drug treatment effects by an average of 21%, which we demonstrate would result in multi-million-dollar savings in a clinical trial.InterpretationAdjusting for practice effects on cognitive testing leads to earlier detection of MCI. When MCI is an outcome, this reduces recruitment needed for clinical trials, study duration, staff and participant burden, and can dramatically lower costs. Importantly, biomarker evidence also indicates improved diagnostic accuracy.

Assessment of the Fairness of Privacy Policies of Mobile Health Apps: Scale Development and Evaluation in Cancer Apps

Background Cancer patients are increasingly using mobile health (mHealth) apps to take control of their health. Many studies have explored their efficiency, content, usability, and adherence; however, these apps have created a new set of privacy challenges, as they store personal and sensitive data. Objective The purpose of this study was to refine and evaluate a scale based on the General Data Protection Regulation and assess the fairness of privacy policies of mHealth apps. Methods Based on the experience gained from our previous work, we redefined some of the items and scores of our privacy scale. Using the new version of our scale, we conducted a case study in which we analyzed the privacy policies of cancer Android apps. A systematic search of cancer mobile apps was performed in the Spanish version of the Google Play website. Results The redefinition of certain items reduced discrepancies between reviewers. Thus, use of the scale was made easier, not only for the reviewers but also for any other potential users of our scale. Assessment of the privacy policies revealed that 29% (9/31) of the apps included in the study did not have a privacy policy, 32% (10/31) had a score over 50 out of a maximum of 100 points, and 39% (12/31) scored fewer than 50 points. Conclusions In this paper, we present a scale for the assessment of mHealth apps that is an improved version of our previous scale with adjusted scores. The results showed a lack of fairness in the mHealth app privacy policies that we examined, and the scale provides developers with a tool to evaluate their privacy policies.

Thermodynamic model and Raman spectra of MgO–P2O5 glasses

The structure of binary glasses xMgO·(1−x)P2O5 (x = 0.30, 0.35, 0.40, 0.45, 0.50, and 0.55) was studied by thermodynamic model (TDM) of Shakhmatkin and Vedishcheva (SV) and Raman spectroscopy. In the TDM, six following system components were considered: MgO (M), P2O5 (P), MgO·2P2O5 (MP2), MgO·P2O5 (MP), 2MgO·P2O5 (M2P), 3MgO·P2O5 (M3P). The principal component analysis (PCA) of experimental Raman spectra resulted in three independent components. The baseline subtracted and thermally corrected Raman spectra were analyzed by the multivariate curve analysis (MCR) for three components. The MCR resulted in the Raman spectra and relative abundance of each component. The experimental spectra were reproduced by the MCR on the level of 99.9%. Correlation analysis attributed the MCR components to M2P, MP, and MP2. Then the Malfait’s decomposition was performed based on the TDM-SV equilibrium molar amounts of system components (MP2, MP, and M2P) resulting in partial Raman spectra (PRS). Normalized MCR loadings coincide with normalized PRS. Adjusted scores were reproduced with good accuracy equilibrium molar amounts of system components.