Selecting patient-reported outcome measures: "what" and "for whom".

Patient-reported outcomes (PROMs) are becoming more widely implemented across health care for important reasons. However, with thousands of PROMs available and the science of psychometrics becoming more widely applied in health measurement, choosing the right ones to implement can be puzzling. This article provides a framework of the different types of PROMs by organizing them into 4 categories based upon "what" is being measured and "from whom" the questions are asked: (1) condition-specific and domain-specific, (2) condition-specific and global, (3) universal and global, and (4) universal and domain-specific. We delve deeper into each category with clinical examples. This framework can empower health care leaders and policymakers to make more informed decisions when selecting the best PROMs to implement, ensuring PROMs deliver on their potential to promote high quality, patient-centered care.

Restoration of Epicardial Blood Flow After Left Ventricular Unloading With the Impella CP Heart Pump in a Patient With STEMI Treated With Surgical Revascularization.

Left main occlusion presenting as ST-segment elevation myocardial infarction is an exceedingly morbid condition. This article reports a case of cardiac arrest in a patient after a treadmill stress test. Coronary angiography revealed 100% occlusion of the left main coronary artery. Left ventricular unloading with the Impella CP heart pump (ABIOMED/Johnson & Johnson MedTech) was used, after which epicardial blood flow was restored without angioplasty. The patient underwent surgical revascularization. Despite a prolonged revascularization time, there was no evidence of severe myocardial injury postoperatively.

Single-cell genomics and regulatory networks for 388 human brains.

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.8 million nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550,000 cell type-specific regulatory elements and >1.4 million single-cell expression quantitative trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.

Patterns of Social Needs Predict Quality-of-Life and Healthcare Utilization Outcomes in Patients from a Large Hospital System.

BACKGROUND: Unmet social needs (SNs) often coexist in distinct patterns within specific population subgroups, yet these patterns are understudied. OBJECTIVE: To identify patterns of social needs (PSNs) and characterize their associations with health-related quality-of-life (HRQoL) and healthcare utilization (HCU). DESIGN: Observational study using data on SNs screening, HRQoL (i.e., low mental and physical health), and 90-day HCU (i.e., emergency visits and hospital admission). Among patients with any SNs, latent class analysis was conducted to identify unique PSNs. For all patients and by race and age subgroups, compared with no SNs, we calculated the risks of poor HRQoL and time to first HCU following SNs screening for each PSN. PATIENTS: Adult patients undergoing SNs screening at the Mass General Brigham healthcare system in Massachusetts, United States, between March 2018 and January 2023. MAIN MEASURES: SNs included: education, employment, family care, food, housing, medication, transportation, and ability to pay for household utilities. HRQoL was assessed using the Patient-Reported Outcomes Measurement Information System Global-10. KEY RESULTS: Six unique PSNs were identified: "high number of social needs," "food and utility access," "employment needs," "interested in education," "housing instability," and "transportation barriers." In 14,230 patients with HRQoL data, PSNs increased the risks of poor mental health, with risk ratios ranging from 1.07(95%CI:1.01-1.13) to 1.80(95%CI:1.74-1.86). Analysis of poor physical health yielded similar findings, except that the "interested in education" showed a mild protective effect (0.97[95%CI:0.94-1.00]). In 105,110 patients, PSNs increased the risk of 90-day HCU, with hazard ratios ranging from 1.09(95%CI:0.99-1.21) to 1.70(95%CI:1.52-1.90). Findings were generally consistent in subgroup analyses by race and age. CONCLUSIONS: Certain SNs coexist in distinct patterns and result in poorer HRQoL and more HCU. Understanding PSNs allows policymakers, public health practitioners, and social workers to identify at-risk patients and implement integrated, system-wide, and community-based interventions.

Validation of Enhancer Regions in Primary Human Neural Progenitor Cells using Capture STARR-seq.

Genome-wide association studies (GWAS) and expression analyses implicate noncoding regulatory regions as harboring risk factors for psychiatric disease, but functional characterization of these regions remains limited. We performed capture STARR-sequencing of over 78,000 candidate regions to identify active enhancers in primary human neural progenitor cells (phNPCs). We selected candidate regions by integrating data from NPCs, prefrontal cortex, developmental timepoints, and GWAS. Over 8,000 regions demonstrated enhancer activity in the phNPCs, and we linked these regions to over 2,200 predicted target genes. These genes are involved in neuronal and psychiatric disease-associated pathways, including dopaminergic synapse, axon guidance, and schizophrenia. We functionally validated a subset of these enhancers using mutation STARR-sequencing and CRISPR deletions, demonstrating the effects of genetic variation on enhancer activity and enhancer deletion on gene expression. Overall, we identified thousands of highly active enhancers and functionally validated a subset of these enhancers, improving our understanding of regulatory networks underlying brain function and disease.

Single-cell genomics and regulatory networks for 388 human brains.

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet, little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multi-omics datasets into a resource comprising >2.8M nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550K cell-type-specific regulatory elements and >1.4M single-cell expression-quantitative-trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.

Patient-reported outcome measures for primary hyperparathyroidism: a systematic review of measurement properties.

BACKGROUND: The quality of patient-reported outcome measures (PROMs) used to assess the outcomes of primary hyperparathyroidism (PHPT), a common endocrine disorder that can negatively affect patients' health-related quality of life due to chronic symptoms, has not been rigorously examined. This systematic review aimed to summarize and evaluate evidence on the measurement properties of PROMs used in adult patients with PHPT, and to provide recommendations for appropriate measure selection. METHODS: After PROSPERO registration (CRD42023438287), Medline, EMBASE, CINAHL Complete, Web of Science, PsycINFO, and Cochrane Trials were searched for full-text articles in English investigating PROM development, pilot studies, or evaluation of at least one PROM measurement property in adult patients with any clinical form of PHPT. Two reviewers independently identified studies for inclusion and conducted the review following the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) Methodology to assess risk of bias, evaluate the quality of measurement properties, and grade the certainty of evidence. RESULTS: From 4989 records, nine PROM development or validation studies were identified for three PROMs: the SF-36, PAS, and PHPQoL. Though the PAS demonstrated sufficient test-retest reliability and convergent validity, and the PHPQoL sufficient test-retest reliability, convergent validity, and responsiveness, the certainty of evidence was low-to-very low due to risk of bias. All three PROMs lacked sufficient evidence for content validity in patients with PHPT. CONCLUSIONS: Based upon the available evidence, the SF-36, PAS, and PHPQoL cannot currently be recommended for use in research or clinical care, raising important questions about the conclusions of studies using these PROMs. Further validation studies or the development of more relevant PROMs with strong measurement properties for this patient population are needed.

Five-year survival prognosis of young, middle-aged, and elderly adult female invasive breast cancer patients by clinical and lifestyle characteristics.

PURPOSE: Early-onset breast cancer incidence has been increasing globally and in Taiwan. However, previous studies have not comprehensively examined how clinical and lifestyle characteristics influence the 5-year survival of breast cancer diagnosed at different stages of adulthood. METHODS: We analyzed the Taiwan National Cancer Registry and Cause of Death datasets to understand how clinical factors (including tumor and treatment characteristics) and lifestyle factors (including body mass index, cigarette smoking, and alcohol consumption) were associated with the 5-year survival of 8471 young, 57,695 middle-aged, and 14,074 elderly female adult invasive breast cancer patients respectively diagnosed at age 20-39, 40-64, and ≥ 65 years between 2002 and 2015, with mortality follow-up to 2020. Poisson regression was used for obtaining the crude and adjusted 5-year survival risk ratios. RESULTS: Clinical and lifestyle characteristics were distributed differently but had mostly similar direction of association with 5-year survival for the three age groups. Receiving any treatment was associated with better survival, especially for elderly patients. Being underweight at initial cancer treatment was associated with worse survival than having normal weight, especially for elderly patients. Current smokers had worse survival than never smokers for middle-aged and elderly patients. The 5-year breast cancer-specific survival was not significantly higher for those of age 45-49 years than 40-44 years, despite the recommended starting screening age is 45 years in Taiwan. CONCLUSION: Our findings contribute to the understanding of early-onset and later-onset female breast cancer characteristics and prognosis, which may inform surveillance and treatment strategies to achieve better breast cancer prognosis.

Current Status and Future Directions of Image-Guided Adaptive Brachytherapy for Locally Advanced Cervical Cancer.

PURPOSE: The standard of care for patients with locally advanced cervical cancer is definitive chemoradiation followed by a brachytherapy boost. This review describes the current status and future directions of image-guided adaptive brachytherapy for locally advanced cervical cancer. METHODS: A systematic search of the PubMed and Clinicaltrials.gov databases was performed, focusing on studies published within the last 10 years. The search queried "cervical cancer [AND] image-guided brachytherapy [OR] magnetic resonance imaging (MRI) [OR] adaptive brachytherapy". DISCUSSION: The retroEMBRACE and EMBRACE-I trials have established the use of MRI as the standard imaging modality for brachytherapy application and planning. Quantitative imaging and radiomics have the potential to improve outcomes, with three ongoing prospective studies examining the use of radiomics to further risk-stratify patients and personalize brachytherapy. Another active area of investigation includes utilizing the superior soft tissue contrast provided by MRI to increase the dose per fraction and decrease the number of fractions needed for brachytherapy, with several retrospective studies demonstrating the safety and feasibility of three-fraction courses. For developing countries with limited access to MRI, trans-rectal ultrasound (TRUS) appears to be an effective alternative, with several retrospective studies demonstrating improved target delineation with the use of TRUS in conjunction with CT guidance. CONCLUSIONS: Further investigation is needed to continue improving outcomes for patients with locally advanced cervical cancer treated with image-guided brachytherapy.

Non-Operative, Active Surveillance of Larger Malignant and Suspicious Thyroid Nodules.

CONTEXT: Active surveillance for papillary thyroid cancer (PTC) meeting criteria for surgical resection is uncommon. Which patients may prove reasonable candidates for this approach is not well defined. OBJECTIVE: To examine the feasibility and safety of active surveillance for patients with known or suspected intrathyroidal PTC up to 4cm in diameter. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of all consecutive patients who underwent non-operative active surveillance of suspicious or malignant thyroid nodules over a 20-year period from 2001-2021. We included patients with an initial US-FNA confirming either: a) Bethesda 5 or 6 cytology or, b) a "suspicious" AFIRMA molecular test. The primary outcomes and measures included the rate of adverse oncologic outcomes (mortality and recurrence), as well as the cumulative incidence of size/volume growth. RESULTS: Sixty-nine patients were followed with active surveillance for 1 year or longer (average 55 months), with 26 patients (38%) having nodules ≥ 2 cm. No patients were found to develop new incident occurrence of lymph node or distant metastasis. One patient however, demonstrated concern for progression to a dedifferentiated cancer on repeat core biopsy 17 years after initial start non-operative selection. 21% of patients had an increase in maximum diameter more than 3 mm, and volume increase ≥50% was noted in 25% of patients. Thirteen patients ultimately underwent delayed (rescue) surgery, and no disease recurrence was noted after such treatment. Age and initial nodule size were not predictors of nodule growth. CONCLUSIONS: These data expand consideration of active surveillance of papillary thyroid carcinoma in select patients with intrathyroidal suspected malignancy >1cm in diameter. Rescue surgery, if required at a later timepoint, appears effective.

3D Convolutional Deep Learning for Nonlinear Estimation of Body Composition from Whole-Body Morphology.

Total and regional body composition are strongly correlated with metabolic syndrome and have been estimated non-invasively from 3D optical scans using linear parameterizations of body shape and linear regression models. Prior works produced accurate and precise predictions on many, but not all, body composition targets relative to the reference dual X-Ray absorptiometry (DXA) measurement. Here, we report the effects of replacing linear models with nonlinear parameterization and regression models on the precision and accuracy of body composition estimation in a novel application of deep 3D convolutional graph networks to human body composition modeling. We assembled an ensemble dataset of 4286 topologically standardized 3D optical scans from four different human body shape databases, DFAUST, CAESAR, Shape Up! Adults, and Shape Up! Kids and trained a parameterized shape model using a graph convolutional 3D autoencoder (3DAE) in lieu of linear PCA. We trained a nonlinear Gaussian process regression (GPR) on the 3DAE parameter space to predict body composition via correlations to paired DXA reference measurements from the Shape Up! scan subset. We tested our model on a set of 424 randomly withheld test meshes and compared the effects of nonlinear computation against prior linear models. Nonlinear GPR produced up to 20% reduction in prediction error and up to 30% increase in precision over linear regression for both sexes in 10 tested body composition variables. Deep shape features produced 6-8% reduction in prediction error over linear PCA features for males only and a 4-14% reduction in precision error for both sexes. Our best performing nonlinear model predicting body composition from deep features outperformed prior work using linear methods on all tested body composition prediction metrics in both precision and accuracy. All coefficients of determination (R2) for all predicted variables were above 0.86. We show that GPR is a more precise and accurate method for modeling body composition mappings from body shape features than linear regression. Deep 3D features learned by a graph convolutional autoencoder only improved male body composition accuracy but improved precision in both sexes. Our work achieved lower estimation RMSEs than all previous work on 10 metrics of body composition.

Skin cancer survivorship and sun protection behaviors in the United States.

BACKGROUND: Skin cancer survivors are more vulnerable to subsequent skin cancers and other malignancies, but previous studies have not examined in detail their sun protection behavior prevalence by sociodemographic factors. We aimed to understand the sociodemographic disparities in the prevalence of three important types of sun protection behaviors: using sunscreen, seeking shade, and wearing protective clothing, among skin cancer survivors and those without skin cancer history. METHODS: We used the 2015 U.S. National Health Interview Survey to analyze 29,523 participants, of which 772 were skin cancer survivors and 28,751 were those without skin cancer history. We assessed overall and specific sun protection behavior prevalence based on using sunscreen, seeking shade, and wearing protective clothing. Weighted Poisson regression was used to estimate prevalence ratios. RESULTS: Melanoma and nonmelanoma skin cancer survivors had similar overall sun protection behavior (p > .05). Among all skin cancer survivors, 36.0% infrequently used sunscreen, 50.2% infrequently wore protective clothing, 47.8% infrequently sought shade, and 30.0% lacked frequent overall sun protection, which significantly differed from those without skin cancer history (p < .0001). The prevalence of frequent overall sun protection behavior was lower for those who were younger at survey, males, less educated, single or never married, or lived in poverty, regardless of their skin cancer history (p < .01). CONCLUSIONS: By identifying subpopulations with higher prevalence of infrequent sun protection among those with or without skin cancer history, our findings may encourage efforts to reduce sociodemographic disparities in sun protection behaviors and promote primary and tertiary skin cancer prevention.

Prevalence of Current Cigarette Smoking by Sociodemographic Characteristics in U.S. Cancer Survivors.

BACKGROUND: Cancer survivors are especially vulnerable to the carcinogenic effects of tobacco smoking, but there lacks a study comprehensively examining the sociodemographic disparities in current smoking prevalence in this population. In this study, we quantified the current cigarette smoking prevalence in cancer survivors and those without cancer history by sociodemographic factors, to identify subpopulations with high current smoking burden. METHODS: We conducted a cross-sectional study of 3,679 cancer survivors and 27,350 participants without cancer history who were 18 years of age or above in the 2019 National Health Interview Survey. Data for the study variables were obtained from computer-assisted personal or telephone interviews. Weighted Poisson regression was used to estimate prevalence ratios and 95% confidence intervals. RESULTS: Although the current smoking prevalence for cancer survivors was slightly lower than for those without cancer history, the prevalence exceeded 30% in cancer survivors in poverty or without health insurance. Individuals with significantly higher current smoking prevalence had lower education levels, were unmarried, did not have health insurance, or lived in poverty. The associations of age, sex, race, health insurance status, and poverty status with current smoking significantly differed between cancer survivors and those without cancer history. Sociodemographic disparities in current smoking prevalence were found in survivors of either smoking-related or nonsmoking-related cancers. CONCLUSION: High current smoking prevalence still exists in subpopulations of cancer survivors and those without cancer history. Our findings may strengthen efforts to reduce sociodemographic disparities in current smoking prevalence and to lower the overall smoking prevalence.

Sex differences in patients with primary hyperparathyroidism.

BACKGROUND: Differences in presenting symptoms of primary hyperparathyroidism and outcomes of parathyroidectomy between sexes have been described, but whether these can be assessed by perioperative use of a validated tool, such as the Pasieka Parathyroidectomy Assessment Score, is unknown. METHOD: All patients with primary hyperparathyroidism were asked to complete symptom assessment at the preoperative and postoperative visits. The assessment included a query for 13 Pasieka Parathyroidectomy Assessment Score parameters evaluated using a visual analog scale as described by Pasieka (summative score 0-1,300), and general quality of life and wellness. A review of a prospectively maintained database of primary hyperparathyroidism patients (January 2016-December 2019) was performed, and those who had a 6-month cure after initial parathyroidectomy were included. RESULTS: The study cohort was mostly women (77%, 541/701). The median preoperative Pasieka Parathyroidectomy Assessment Score was higher in women (155, 0-1,190) than in men (80.5, 0-855, P < .001), although there were similar rates of asymptomatic primary hyperparathyroidism (Pasieka Parathyroidectomy Assessment Score = 0, 12.5% vs 7%, P = .042). After curative parathyroidectomy, women reported a substantial reduction in symptomatology, with Pasieka Parathyroidectomy Assessment Score declining by 35% at initial postoperative visit (median, 155 vs 100, P < .001), further decreasing to 48% by 6 months (155 vs 80, P < .001). The Pasieka Parathyroidectomy Assessment Score in men did change but to a much smaller degree at both the initial postoperative visit (80.5 vs 70; P = .036) and at 6 months (80.5 vs 57.5; P = .048). CONCLUSION: When assessed with the Pasieka Parathyroidectomy Assessment Score, improvement in symptoms was clearly demonstrated for women after curative parathyroidectomy. Whether symptom improvement also occurs in men is less apparent but may be due to disparities in the development and validation of outcomes tools in general.

A gravity-driven droplet fluidic point-of-care test.

We report a simple droplet fluidic point-of-care test (POCT) that uses gravity to manipulate the sequence, timing, and motion of droplets on a surface. To fabricate this POCT, we first developed a surface coating toolbox of nine different coatings with three levels of wettability and three levels of slipperiness that can be independently tailored. We then fabricated a device that has interconnected fluidic elements-pumps, flow resistors and flow guides-on a highly slippery solid surface to precisely control the timing and sequence of motion of multiple droplets and their interactions on the surface. We then used this device to carry out a multi-step enzymatic assay of a clinically relevant analyte-lactate dehydrogenase (LDH)-to demonstrate the application of this technology for point-of-care diagnosis.

Anisotropic material depletion in epitaxial polymer crystallization.

The physical properties of a semicrystalline polymer thin film are intimately related to the morphology of its crystalline domains. While the mechanisms underlying crystallization of flat-on oriented polymer crystals are well known, similar mechanisms remain elusive for edge-on oriented thin films due to the propensity of substantially thin films to adopt flat-on orientations. Here, we employ an epitaxial polymer-substrate relationship to enforce edge-on crystallization in thin films. Using matrix-assisted pulsed laser evaporation (MAPLE), we deposit films in which crystal nucleation is spatially separated from subsequent epitaxial crystallization. These experiments, together with phase-field simulations, demonstrate a highly anisotropic and localized material depletion during edge-on crystallization. These results provide deeper insight into the physics of polymer crystallization under confinement and introduce a processing motif in the crystallization of ultrathin structured films.

Targeted Therapies in Early-Stage Resectable Non-Small-Cell Lung Cancer: New Kids on the Block.

PURPOSE: With increased adoption of next-generation sequencing, tailored therapy on the basis of molecular status is being delivered for patients with early-stage resectable non-small-cell lung cancer (NSCLC). The purpose of this narrative review was to focus on recent developments of targeted therapies in the adjuvant and neoadjuvant/adjuvant setting for early-stage disease. METHODS: A systematic search of the MEDLINE/PubMed database was performed, focusing on studies published within the past 10 years. Our search queried "early-stage NSCLC (AND) tyrosine kinase inhibitor (TKI; OR) epidermal growth factor receptor (EGFR; OR) anaplastic lymphoma kinase (ALK)" and was limited only to prospective and ongoing studies. RESULTS: Most studies examining the benefit of targeted therapies in early-stage resectable NSCLC have been for EGFR-TKIs in the adjuvant setting. Currently, only one study, the ADAURA trial of adjuvant osimertinib, has demonstrated an overall survival benefit with the use of an EGFR-TKI in the adjuvant setting. Future work to build on the success of the ADAURA trial is focused on determining the optimal duration of targeted therapies and using biomarkers, such as circulating tumor DNA, to risk-stratify patients and guide maintenance targeted therapy duration. CONCLUSION: The results of several ongoing studies are eagerly awaited regarding the use of targeted therapies in the neoadjuvant/adjuvant setting and for more uncommon or rare mutations such as ALK, ROS proto-oncogene 1, rearranged during transfection, mesenchymal-epithelial transition factor, and B-Raf proto-oncogene V600E. The treatment landscape for early-stage NSCLC harboring actionable mutations is likely to shift dramatically in the upcoming decade.