Pharmacokinetic Modeling of the Effect of Tariquidar on Ondansetron Disposition into the Central Nervous System.

PURPOSE: Serotonin (5-HT3) receptor antagonists are promising agents for treatment of neuropathic pain. However, insufficient drug exposure at the central nervous system (CNS) might result in lack of efficacy. The goal of this study was to evaluate the impact of administration of a Pgp inhibitor (tariquidar) on ondansetron exposure in the brain, spinal cord, and cerebrospinal fluid in a wild-type rat model. METHODS: Ondansetron (10 mg/kg) and tariquidar (7.5 mg/kg) were administered intravenously, plasma and tissue samples were collected and analyzed by HPLC. A mathematical model with brain, spinal cord, cerebrospinal fluid and two systemic disposition compartments was developed to describe the data. RESULTS: The results demonstrate that tariquidar at 7.5 mg/kg resulted in a complete inhibition of Pgp efflux of ondansetron in the brain and spinal cord. The compartmental model successfully captured pharmacokinetics of ondansetron in wild type and Pgp knockout (KO) animals receiving the drug alone or in wild type animals receiving the ondansetron and tariquidar combination. CONCLUSIONS: The study provided important quantitative information on enhancement of CNS exposure to ondansetron using co-administration of Pgp Inhibitor in a rat model, which will be further utilized in conducting a clinical study. Tariquidar co-administration resulted in ondansetron CNS exposure comparable to observed in Pgp KO rats. Results also highlighted the effect of tariquidar on plasma disposition of ondansetron, which may not be dependent on Pgp inhibition, and should be evaluated in future studies.

Commissioning and validation of a single photon beam model in RayStation for multiple matched Elekta Linacs.

PURPOSE: A single treatment planning system (TPS) model for matched linacs provides flexible clinical workflows from patient treatment to intensity-modulated radiation therapy (IMRT) quality assurance (QA) measurement. Since general guidelines for building a single TPS model and its validation for matched linacs are not well established, we present our RayStation photon TPS modeling strategy for matched Elekta VersaHD linacs. METHOD: The four linacs installed from 2013 to 2020 were matched in terms of Percent Depth Dose (PDD), profile, output factor and wedge factors for 6-MV, 10-MV, 15-MV, and 6-MV-FFF, and maintained following TG-142 recommendations until RayStation commissioning. The RayStation single model was built to represent all four linacs within the tolerance limits recommended by MPPG-5.a. The comprehensive validation tests were performed for one linac following MPPG-5.a and TG-119 guidelines, and spot checks for the other three. Our TPS modeling/validation method was evaluated by re-analyzing the previous 103 patient-specific IMRT/volumetric modulated arc therapy (VMAT) QA measurements with the calculated planar doses by the single model in comparison with the analysis results using four individual Pinnacle TPS models. RESULTS: For all energies, our single model PDDs were within 1% agreement of the four-linac commissioning measurements. The MPPG-5.a validation tests from 5.1 through 7.5 and all TG-119 measurements passed within the recommended tolerance limits. The IMRT QA results (mean ± standard deviation) for RayStation single model versus Pinnacle individual models were 98.9% ± 1.3% and 98.0% ± 1.4% for 6-MV, 99.9% ± 0.1% and 99.1% ± 1.9% for 10-MV, and 98.2% ± 1.3% and 97.9% ± 1.8% for 6-MV-FFF, respectively. CONCLUSION: We successfully built and validated a single photon beam model in RayStation for four Elekta Linacs. The proposed new validation methods were proven to be both efficient and effective.

Predicting Fetal Alcohol Spectrum Disorders Using Machine Learning Techniques: Multisite Retrospective Cohort Study.

BACKGROUND: Fetal alcohol syndrome (FAS) is a lifelong developmental disability that occurs among individuals with prenatal alcohol exposure (PAE). With improved prediction models, FAS can be diagnosed or treated early, if not completely prevented. OBJECTIVE: In this study, we sought to compare different machine learning algorithms and their FAS predictive performance among women who consumed alcohol during pregnancy. We also aimed to identify which variables (eg, timing of exposure to alcohol during pregnancy and type of alcohol consumed) were most influential in generating an accurate model. METHODS: Data from the collaborative initiative on fetal alcohol spectrum disorders from 2007 to 2017 were used to gather information about 595 women who consumed alcohol during pregnancy at 5 hospital sites around the United States. To obtain information about PAE, questionnaires or in-person interviews, as well as reviews of medical, legal, or social service records were used to gather information about alcohol consumption. Four different machine learning algorithms (logistic regression, XGBoost, light gradient-boosting machine, and CatBoost) were trained to predict the prevalence of FAS at birth, and model performance was measured by analyzing the area under the receiver operating characteristics curve (AUROC). Of the total cases, 80% were randomly selected for training, while 20% remained as test data sets for predicting FAS. Feature importance was also analyzed using Shapley values for the best-performing algorithm. RESULTS: Overall, there were 20 cases of FAS within a total population of 595 individuals with PAE. Most of the drinking occurred in the first trimester only (n=491) or throughout all 3 trimesters (n=95); however, there were also reports of drinking in the first and second trimesters only (n=8), and 1 case of drinking in the third trimester only (n=1). The CatBoost method delivered the best performance in terms of AUROC (0.92) and area under the precision-recall curve (AUPRC 0.51), followed by the logistic regression method (AUROC 0.90; AUPRC 0.59), the light gradient-boosting machine (AUROC 0.89; AUPRC 0.52), and XGBoost (AUROC 0.86; AURPC 0.45). Shapley values in the CatBoost model revealed that 12 variables were considered important in FAS prediction, with drinking throughout all 3 trimesters of pregnancy, maternal age, race, and type of alcoholic beverage consumed (eg, beer, wine, or liquor) scoring highly in overall feature importance. For most predictive measures, the best performance was obtained by the CatBoost algorithm, with an AUROC of 0.92, precision of 0.50, specificity of 0.29, F1 score of 0.29, and accuracy of 0.96. CONCLUSIONS: Machine learning algorithms were able to identify FAS risk with a prediction performance higher than that of previous models among pregnant drinkers. For small training sets, which are common with FAS, boosting mechanisms like CatBoost may help alleviate certain problems associated with data imbalances and difficulties in optimization or generalization.

Selective de-implementation of routine in vivo dosimetry.

As cone-beam computed tomography (CBCT) has become the localization method for a majority of cases, the indications for diode-based confirmation of accurate patient set-up and treatment are now limited and must be balanced between proper resource allocation and optimizing efficiency without compromising safety. We undertook a de-implementation quality improvement project to discontinue routine diode use in non-intensity modulated radiotherapy (IMRT) cases in favor of tailored selection of scenarios where diodes may be useful. After analysis of safety reports from the last 5 years, literature review, and stakeholder discussions, our safety and quality (SAQ) committee introduced a recommendation to limit diode use to specific scenarios in which in vivo verification may add value to standard quality assurance (QA) processes. To assess changes in patterns of use, we reviewed diode use by clinical indication 4 months prior and after the implementation of the revised policy, which includes use of diodes for: 3D conformal photon fields set up without CBCT; total body irradiation (TBI); electron beams; cardiac devices within 10 cm of the treatment field; and unique scenarios on a case-by-case basis. We identified 4459 prescriptions and 1038 unique instances of diode use across five clinical sites from 5/2021 to 1/2022. After implementation of the revised policy, we observed an overall decrease in diode use from 32% to 13.2%, with a precipitous drop in 3D cases utilizing CBCT (from 23.2% to 4%), while maintaining diode utilization in the 5 selected scenarios including 100% of TBI and electron cases. By identifying specific indications for diode use and creating a user-friendly platform for case selection, we have successfully de-implemented routine diode use in favor of a selective process that identifies cases where the diode is important for patient safety. In doing so, we have streamlined patient care and decreased cost without compromising patient safety.

Effectiveness of Digital Interventions for Preventing Alcohol Consumption in Pregnancy: Systematic Review and Meta-analysis.

BACKGROUND: Alcohol consumption in pregnancy has been associated with serious fetal health risks and maternal complications. While previous systematic reviews of digital interventions during pregnancy have targeted smoking cessation and flu vaccine uptake, few studies have sought to evaluate their effectiveness in preventing alcohol consumption during pregnancy. OBJECTIVE: This systematic review aims to assess (1) whether digital interventions are effective in preventing alcohol consumption during the pregnancy/pregnancy-planning period, and (2) the differential effectiveness of alternative digital intervention platforms (ie, computers, mobiles, and text messaging services). METHODS: PubMed, Embase, CINAHL, and Web of Science were searched for studies with digital interventions aiming to prevent alcohol consumption among pregnant women or women planning to become pregnant. A random effects primary meta-analysis was conducted to estimate the combined effect size and extent to which different digital platforms were successful in preventing alcohol consumption in pregnancy. RESULTS: Six studies were identified and included in the final review. The primary meta-analysis produced a sample-weighted odds ratio (OR) of 0.62 (95% CI 0.42-0.91; P=.02) in favor of digital interventions decreasing the risk of alcohol consumption during pregnancy when compared to controls. Computer/internet-based interventions (OR 0.59, 95% CI 0.38-0.93) were an effective platform for preventing alcohol consumption. Too few studies of text messaging (OR 0.29, 95% CI 0.29-2.52) were available to draw a conclusion. CONCLUSIONS: Overall, our review highlights the potential for digital interventions to prevent alcohol consumption among pregnant women and women planning to become pregnant. Considering the advantages of digital interventions in promoting healthy behavioral changes, future research is necessary to understand how certain platforms may increase user engagement and intervention effectiveness to prevent women from consuming alcohol during their pregnancies.

Correction: Measurement of Digital Literacy Among Older Adults: Systematic Review.

[This corrects the article DOI: 10.2196/26145.].

Measurement of Digital Literacy Among Older Adults: Systematic Review.

BACKGROUND: Numerous instruments are designed to measure digital literacy among the general population. However, few studies have assessed the use and appropriateness of these measurements for older populations. OBJECTIVE: This systematic review aims to identify and critically appraise studies assessing digital literacy among older adults and to evaluate how digital literacy instruments used in existing studies address the elements of age-appropriate digital literacy using the European Commission's Digital Competence (DigComp) Framework. METHODS: Electronic databases were searched for studies using validated instruments to assess digital literacy among older adults. The quality of all included studies was evaluated using the Crowe Critical Appraisal Tool (CCAT). Instruments were assessed according to their ability to incorporate the competence areas of digital literacy as defined by the DigComp Framework: (1) information and data literacy, (2) communication and collaboration, (3) digital content creation, (4) safety, and (5) problem-solving ability, or attitudes toward information and communication technology use. RESULTS: Searches yielded 1561 studies, of which 27 studies (17 cross-sectional, 2 before and after, 2 randomized controlled trials, 1 longitudinal, and 1 mixed methods) were included in the final analysis. Studies were conducted in the United States (18/27), Germany (3/27), China (1/27), Italy (1/27), Sweden (1/27), Canada (1/27), Iran (1/27), and Bangladesh (1/27). Studies mostly defined older adults as aged ≥50 years (10/27) or ≥60 years (8/27). Overall, the eHealth Literacy Scale (eHEALS) was the most frequently used instrument measuring digital literacy among older adults (16/27, 59%). Scores on the CCAT ranged from 34 (34/40, 85%) to 40 (40/40, 100%). Most instruments measured 1 or 2 of the DigComp Framework's elements, but the Mobile Device Proficiency Questionnaire (MDPQ) measured all 5 elements, including "digital content creation" and "safety." CONCLUSIONS: The current digital literacy assessment instruments targeting older adults have both strengths and weaknesses, relative to their study design, administration method, and ease of use. Certain instrument modalities like the MDPQ are more generalizable and inclusive and thus, favorable for measuring the digital literacy of older adults. More studies focusing on the suitability of such instruments for older populations are warranted, especially for areas like "digital content creation" and "safety" that currently lack assessment. Evidence-based discussions regarding the implications of digitalization for the treatment of older adults and how health care professionals may benefit from this phenomenon are encouraged.

Correction: Measurement of Digital Literacy Among Older Adults: Systematic Review.

[This corrects the article DOI: 10.2196/26145.].

Pharmacokinetic Modeling of the Impact of P-glycoprotein on Ondansetron Disposition in the Central Nervous System.

PURPOSE: Modulation of 5-HT3 receptor in the central nervous system (CNS) is a promising approach for treatment of neuropathic pain. The goal was to evaluate the role of P-glycoprotein (Pgp) in limiting exposure of different parts of the CNS to ondansetron (5-HT3 receptor antagonist) using wild-type and genetic knockout rat model. METHODS: Plasma pharmacokinetics and CNS (brain, spinal cord, and cerebrospinal fluid) disposition was studied after single 10 mg/kg intravenous dose. RESULTS: Pgp knockout resulted in significantly higher concentrations of ondansetron in all tested regions of the CNS at most of the time points. The mean ratio of the concentrations between KO and WT animals was 2.39-5.48, depending on the region of the CNS. Male and female animals demonstrated some difference in ondansetron plasma pharmacokinetics and CNS disposition. Mechanistic pharmacokinetic model that included two systemic disposition and three CNS compartments (with intercompartmental exchange) was developed. Pgp transport was incorporated as an efflux from the brain and spinal cord to the central compartment. The model provided good simultaneous description of all data sets, and all parameters were estimated with sufficient precision. CONCLUSIONS: The study provides important quantitative information on the role of Pgp in limiting ondansetron exposure in various regions of the CNS using data from wild-type and Pgp knockout rats. CSF drug concentrations, as a surrogate to CNS exposure, are likely to underestimate the effect of Pgp on drug penetration to the brain and the spinal cord.

Lymphatic Distribution of Etanercept Following Intravenous and Subcutaneous Delivery to Rats.

PURPOSE: The purpose of this work was to investigate the role of the lymphatic system in the pharmacokinetics of etanercept, a fusion protein. METHODS: Etanercept 1 mg/kg was administered intravenously (IV) and subcutaneously (SC) to thoracic lymph duct-cannulated and sham-operated control rats. Blood and lymph samples were obtained for up to 6 days. RESULTS: Model-based SC bioavailability of etanercept was 65.2% in the control group. In lymph-cannulated rats, etanercept concentration in the lymph was consistently lower than in serum following IV dosing; and the concentration in the lymph was significantly higher than in serum after SC injection. The absorption occurred predominantly through the lymphatic pathway (82.7%), and only 17.3% by direct uptake into the central compartment (blood pathway). Lymphatic cannulation reduced the area under the serum concentration-time curve by 28% in IV group and by 91% in SC group. A mechanistic pharmacokinetic model that combined dual absorption pathways with redistribution of the systemically available protein drug into lymph was developed. The model successfully captured serum and lymph data in all groups simultaneously, and all parameters were estimated with sufficient precision. CONCLUSIONS: Lymphatic system was shown to play an essential role in systemic disposition and SC absorption of etanercept.

Association between changes in economic activity and catastrophic health expenditure: findings from the Korea Health Panel Survey, 2014-2016.

BACKGROUND: The rate of catastrophic health expenditure (CHE) continues to rise in South Korea. This study examined the association between changes in economic activity and CHE experiences in South Korea. METHODS: This study analyzed the Korea Health Panel Survey data using a logistic regression analysis to study the association between changes in economic activity in 2014-2015 and the participants' CHE experiences in 2015. The study included a total of 12,454 individuals over the age of 19. The subgroup analyses were organized by sex, age, health-related variables, and household level variables, and the reasons for leaving economic activity. RESULTS: Those who quit economic activities were more likely to experience CHE than those who continued to engage in economic activities (OR [odds ratio] = 2.10; 95% CI [confidence interval]: 1.31-3.36). The subgroup analysis results, according to health-related variables, showed that there is a tendency to a higher Charlson comorbidity index, a higher OR, and, in groups that quit their economic activities, people with disabilities were more likely to experience CHE than people without disabilities (OR = 5.63; 95% CI 1.71-18.59, OR = 1.82; 95% CI 1.08-3.08, respectively). Another subgroup analysis found that if the reason for not participating in economic activity was a health-related issue, the participant was more likely to experience CHE (active → inactive: OR = 2.40; 95% CI 0.61-9.43, inactive → inactive OR = 1.65; 95% CI 1.01-2.68). CONCLUSIONS: Those individuals who became unemployed were more likely to experience CHE, especially if health problems precipitated the job loss. Therefore, efforts are needed to expand coverage for those people who suffer from high medical expenses.

Statin adherence and risk of all-cause, cancer, and cardiovascular mortality among dyslipidemia patients: A time-dependent analysis.

BACKGROUND AND AIM: Results have been mixed and uncertainty still remains regarding the impact of statin adherence on premature deaths. Thus, we investigated the association between statin adherence and risks of all-cause, cancer, and cardiovascular mortality among dyslipidemia patients in South Korea. METHODS AND RESULTS: We used data from the National Health Insurance Service (NHIS) National Sample Cohort for the years 2003-2013, which included data on 107,954 middle-aged and elderly dyslipidemia patients. Among these patients, a time-dependent Cox proportional hazards model was used to estimate the hazard ratios (HRs) of all-cause, cancer, and cardiovascular mortality depending on proportion of days covered (PDC) by statin medication. A total of 3073 (2.85%) individuals died within the study period. Of these individuals, 1143 (1.06%) died from cancer, and 687 (0.64%) died from cardiovascular diseases. Relative to good medication adherence (>80%), moderate (50-80%) (hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 1.14-1.43) and poor (<50%) (HR: 1.58, 95% CI: 1.41-1.78) adherence were associated with increased risk of all-cause mortality. Poor adherence was also associated with increased risk of cancer (HR: 1.33, 95% CI: 1.16-1.52) and cardiovascular (HR: 1.27, 95% CI: 1.06-1.51) mortality. CONCLUSION: Such findings reveal that relative to good statin adherence, moderate and/poor adherence is associated with increased risks of all-cause, cancer, and cardiovascular mortality. Clinicians should assess for dyslipidemia, link statin adherence problems to potential mortality risk, and monitor outcomes in both medication adherence and disease complications.

Association between commensality with depression and suicidal ideation of Korean adults: the sixth and seventh Korean National Health and Nutrition Examination Survey, 2013, 2015, 2017.

OBJECTIVES: This study investigated whether commensality (eating a meal with others) is associated with mental health (depression, suicidal ideation) in Korean adults over 19 years old. METHODS: Our study employed data from the sixth and seventh Korea National Health and Nutritional Examination Surveys (KNHANES) for 2013, 2015, and 2017. The study population consisted of 14,125 Korean adults (5854 men and 8271 women). In this cross-sectional study, data were analyzed with the Rao-Scott chi-square test and multiple logistic regression to evaluate the association between commensality(0[includes skipping meals] to 3 times eating meals together) and both depression and suicidal ideation using select questions from the Mental Health Survey. By setting socioeconomic factors, health conditions, and behavioral factors as confounders, we conducted a subgroup analysis to reveal the effect on depression and suicidal ideation commensality. RESULTS: Commensality was significantly associated with depression and suicidal ideation (p < 0.05). In both sexes, people who ate fewer meals together had poorer mental health. In a subgroup analysis, we revealed greater odds of developing depression in men when living in rural areas and belonging to low-income groups. In contrast, greater odds of suicidal ideation in men who ate alone when living in the city and belonging to high-income groups. On the other hand, Women in every region had greater odds of being depressed if they ate alone. And greater odds of suicidal ideation in women who ate alone when living in the city and belonging to medium-high income groups. CONCLUSIONS: Our analysis confirmed that Korean adults with lower chance of commensality had greater risk of developing depression and suicidal ideation. And it could be affected by individuals' various backgrounds including socioeconomic status. As a result, to help people with depression and prevent a suicidal attempt, this study will be baseline research for social workers, educators and also policy developers to be aware of the importance of eating together.

Beyond ultrasound: CT and MRI of ectopic pregnancy.

OBJECTIVE: Although ultrasound is the primary modality used in the diagnosis of ectopic pregnancy, various forms of this condition and their complications may occasionally be further evaluated with MRI or may be incidentally detected on CT or MRI when an alternative diagnosis is suspected. CONCLUSION: Various types of ectopic pregnancy have characteristic imaging features. Radiologists should be familiar with these features and should always consider the possibility of ectopic pregnancy in the setting of hemoperitoneum or a pelvic mass in a woman of child-bearing age. Familiarity with the typical CT and MRI appearances of various forms of ectopic pregnancy facilitates prompt and accurate diagnosis and treatment.

Characteristics and Barriers of Emergency Department Patients Overdue for Cancer Screening.

Introduction: People without reliable access to healthcare are more likely to be diagnosed with late-stage cancer that could have been treated more effectively if diagnosed earlier. Emergency departments (ED) may be a novel place for cancer screening education for underserved patients. In this study we sought to determine patient characteristics and barriers to cancer screening for those patients who presented to a large, academic safety-net ED and were overdue for breast, cervical, and colorectal cancer screening since the coronavirus 2019 (COVID-19) pandemic. Methods: Adult ED patients eligible for at least one cancer screening based on US Preventive Serivces Task Force guidelines completed a web-based survey. We examined the association of demographic characteristics and having a personal physician with being overdue on screening using chi-square or the Fisher exact test for categorical variables and t-tests for continuous variables. Results: Of 221 participants, 144 were eligible for colorectal, 96 for cervical, and 55 for breast cancer screening. Of eligible patients, 46% (25/55) were overdue for breast cancer screening, 43% (62/144) for colorectal, and 40% (38/96) for cervical cancer screening. There were no significant characteristics associated with breast cancer screening. Being overdue for cervical cancer screening was significantly more likely for patients who were of Asian race (P = 0.02), had less than a high school diploma (P = 0.01), and were without a routine checkup within the prior five years (P = 0.01). Overdue for colorectal cancer screening was associated with patients not having insurance (P = 0.04), being in their 40s (P = 0.03), being Hispanic (P = 0.01), and not having a primary care physician (P=0.01). Of 97 patients overdue for at least one screening, the most common barriers were cost (37%), lack of time (37%), and lack of knowledge of screening recommendations (34%). Only 8.3% reported that the COVID-19 pandemic delayed their screening. Conclusion: The ED may be a novel setting to target patients for cancer screening education. Future work that refers patients to free screening programs and primary care physicians may help improve disparities in cancer screening and cancer mortality rates for underserved populations.

Behavioral marker-based predictive modeling of functional status for older adults with subjective cognitive decline and mild cognitive impairment: Study protocol.

Objective: This study describes a research protocol for a behavioral marker-based predictive model that examines the functional status of older adults with subjective cognitive decline and mild cognitive impairment. Methods: A total of 130 older adults aged ≥65 years with subjective cognitive decline or mild cognitive impairment will be recruited from the Dementia Relief Centers or the Community Service Centers. Data on behavioral and psychosocial markers (e.g. physical activity, mobility, sleep/wake patterns, social interaction, and mild behavioral impairment) will be collected using passive wearable actigraphy, in-person questionnaires, and smartphone-based ecological momentary assessments. Two follow-up assessments will be performed at 12 and 24 months after baseline. Mixed-effect machine learning models: MErf, MEgbm, MEmod, and MEctree, and standard machine learning models without random effects [random forest, gradient boosting machine] will be employed in our analyses to predict functional status over time. Results: The results of this study will be fundamental for developing tailored digital interventions that apply deep learning techniques to behavioral data to predict, identify, and aid in the management of functional decline in older adults with subjective cognitive decline and mild cognitive impairment. These older adults are considered the optimal target population for preventive interventions and will benefit from such tailored strategies. Conclusions: Our study will contribute to the development of self-care interventions that utilize behavioral data and machine learning techniques to provide automated analyses of the functional decline of older adults who are at risk for dementia.

Punitive state policies targeting alcohol use during pregnancy and alcohol consumption among pregnant women.

This study aimed to determine whether punitive state alcohol policies targeting pregnant women who drink alcohol are associated with decreased alcohol consumption among pregnant women over time. This study used data from the Pregnancy Risk Assessment Monitoring System (15 states) between 1990 and 2015. A difference-in-difference (DiD) approach was employed to determine whether passage of state laws changed alcohol consumption rates among pregnant women, while controlling for state and time fixed effects. The study specifically examined punitive state alcohol policies that clarify the admissibility of evidence in child welfare proceedings related to prenatal alcohol exposure, focusing on allegations of child abuse, child neglect, child deprivation, or child dependence, as well as proceedings seeking termination of parental rights. Punitive state alcohol policies were not significantly associated with decreased rates of alcohol consumption among pregnant women (+ 1.54%, 95% CI, -1.47-4.55), within 3 years of implementation. State alcohol policies that adopted a punitive stance toward pregnant women who drink alcohol did not result in the reduction of drinking during pregnancy. Given that punitive policies may not effectively reduce alcohol consumption during pregnancy, our findings highlight the need for reevaluation and potential reform to better address maternal/child health outcomes.

Subjective Cognitive Decline in Community-Dwelling Older Adults With Objectively Normal Cognition: Mediation by Depression and Instrumental Activities of Daily Living.

OBJECTIVE: Subjective cognitive decline (SCD) refers to self-reported memory loss despite normal cognitive function and is considered a preclinical stage of Alzheimer's disease. This study aimed to examine the mediating effects of depression and Instrumental Activities of Daily Living (IADL) on the association between the scoring of Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) and Subjective Cognitive Decline Questionnaire (SCD-Q). METHODS: A sample of 139 community-dwelling older adults aged 65-79 with normal cognitive function completed the SCD-Q, a comprehensive neuropsychological battery, and functional/psychiatric scales. We conducted 1) a correlation analysis between SCD-Q scores and other variables and 2) a path analysis to examine the mediating effects of depression and IADL on the relationship between CDR-SB and SCD-Q. RESULTS: CDR-SB was found to be indirectly associated with SCD-Q, with depressive symptoms mediating this relationship. However, no direct association was observed between SCD-Q and CDR-SB. Additionally, IADL was not associated with SCD-Q and did not mediate the relationship between CDR-SB and SCD-Q. The model fit was acceptable (minimum discrepancy function by degrees of freedom divided [CMIN/DF]=1.585, root mean square error of approximation [RMSEA]=0.065, comparative fit index [CFI]=0.955, Tucker-Lewis index [TLI]=0.939). CONCLUSION: Our results suggest that SCD-Q is influenced by depressive symptoms, but not by IADL. The role of depressive symptoms as a mediator between CDR-SB and SCD-Q indicates that psychological factors may contribute to the perception of SCD. Therefore, interventions targeting depression may mitigate the concerns associated with SCD and reduce feelings of worse performance compared to others of the same age group.

Association of conduit dimensions with perioperative outcomes and long-term quality of life after esophagectomy for malignancy.

Objective: The impact of conduit dimensions and location of esophagogastric anastomosis on long-term quality of life after esophagectomy remains unexplored. We investigated the association of these parameters with surgical outcomes and patient-reported quality of life at least 18 months after esophagectomy. Methods: We identified all patients who underwent esophagectomy for cancer from 2018 to 2020 in our institution. We reviewed each patient's initial postoperative computed tomography scan measuring the gastric conduit's greatest width (centimeters), linear staple line length (centimeters), and relative location of esophagogastric anastomosis (vertebra). Quality of life was ascertained using patient-reported outcome measures. Perioperative complications, length of stay, and mortality were collected. Multivariate regressions were performed. Results: Our study revealed that a more proximal anastomosis was linked to an increased risk of pulmonary complications, a lower recurrence rate, and greater long-term insomnia. Increased maximum intrathoracic conduit width was significantly associated with trouble enjoying meals and reflux long term after esophagectomy. A longer conduit stapled line correlated with fewer issues related to insomnia, improved appetite, less dysphagia, and significantly enhanced "social," "role," and "physical'" aspects of the patient's long-term quality of life. Conclusions: The dimensions of the gastric conduit and the height of the anastomosis may be independently associated with outcomes and long-term quality of life after esophagectomy for cancer.

Fundus-to-Antrum Ratio Measured with Fluoroscopy within One Week after Endoscopic Sleeve Gastroplasty Predicts Total Body Weight Loss over Time.

Background and Aims: Endoscopic sleeve gastroplasty (ESG) is a minimally invasive bariatric procedure to induce weight loss through restrictive physiology. This study was designed to evaluate the fluoroscopic measurement of gastric dimensions after ESG as a predictor of Total Body Weight Loss (TBWL) over time. Methods: Post-ESG patients were enrolled prospectively between August 2013 and August 2019. An upper gastrointestinal (GI) fluoroscopy was obtained within 7 days after the procedure. Two blinded, independent radiologists reviewed fluoroscopic images and measured the gastric lumen transverse diameter in three separate areas of the fundus, body, and antrum. The primary outcome was achieving a TBWL of ten percent or more after ESG. Results: In total, 162 patients were included in the analysis (65% female) and had a mean body mass index (BMI) of 39 ± 6 at baseline. Patients had a mean maximum TBWL of 16.5 ± 8.3%. Respectively, 92%, 75%, and 50% of patients achieved a TBWL of 5%, 10%, or 15% or more. The mean post-procedural UGI gastric fundus/antrum transverse measurement ratio was 1.2 ± 0.6. A higher fundus-to-antrum ratio was significantly associated with a TBWL of 10% or more during follow-up in the multivariable model (OR 2.49, 95% CI 1.31-4.71; p-value 0.005). The prediction score based on the fundus-to-antrum ratio hd an area under the ROC curve of 0.79 (95% CI 0.75-0.83) for predicting a TBWL of 10% or more during follow-up. Conclusions: Measuring gastric the fundus/antrum ratio within one week of endoscopic sleeve gastroplasty (ESG) is a consistent and independent predictive measure of sustained TBWL during long-term follow-up.