Mapping general anesthesia states based on electro-encephalogram transition phases.

Cortical electro-encephalography (EEG) served as the clinical reference for monitoring unconsciousness during general anesthesia. The existing EEG-based monitors classified general anesthesia states as underdosed, adequate, or overdosed, lacking predictive power due to the absence of transition phases among these states. In response to this limitation, we undertook an analysis of the EEG signal during isoflurane-induced general anesthesia in mice. Adopting a data-driven approach, we applied signal processing techniques to track θ- and δ-band dynamics, along with iso-electric suppressions. Combining this approach with machine learning, we successfully developed an automated algorithm. The findings of our study revealed that the dampening of the δ-band occurred several minutes before the onset of significant iso-electric suppression episodes. Furthermore, a distinct γ-frequency oscillation was observed, persisting for several minutes during the recovery phase subsequent to isoflurane-induced overdose. As a result of our research, we generated a map summarizing multiple brain states and their transitions, offering a tool for predicting and preventing overdose during general anesthesia. The transition phases identified, along with the developed algorithm, have the potential to be generalized, enabling clinicians to prevent inadequate anesthesia and, consequently, tailor anesthetic regimens to individual patients.

Development of specific growth charts for children with Fanconi anemia.

Patients with Fanconi anemia (FA) are often perceived to have poor growth when general population growth curves are utilized. We hypothesize that FA patients have unique growth and aimed to create FA-specific growth charts. Height and weight data from ages 0 to 20 years were extracted from medical records of patients treated at the Fanconi Anemia Comprehensive Care Clinic at the University of Minnesota. Height, weight, and BMI growth curves were generated and fitted to reference percentiles using the Lambda-Mu-Sigma method. FA-specific percentiles were compared to WHO standards for ages 0-2 and CDC references for ages 2-20. In FA males, the 50th height- and weight-for-age percentiles overlap with the 3rd reference percentile. In FA females, only the 50th height-for-age percentile overlaps with the 3rd reference percentile. For weight, FA females show progressive growth failure between 6 and 24 months followed by stabilization around the 50th percentile. The FA BMI-for-age percentiles show similar patterns to the weight-for-age percentiles but have different timing of onset of adiposity rebound and broader variability in females. Growth in FA patients follows a different trajectory than available normative curves. FA-specific growth charts may be useful to better guide accurate growth expectations, evaluations, and treatment.

Unraveling a history of overlap: A phenotypic comparison of RBCK1-related disease and glycogen storage disease type IV.

RBCK1-related disease is a rare, multisystemic disorder for which our current understanding of the natural history is limited. A number of individuals initially carried clinical diagnoses of glycogen storage disease IV (GSD IV), but were later found to harbor RBCK1 pathogenic variants, demonstrating challenges of correctly diagnosing RBCK1-related disease. This study carried out a phenotypic comparison between RBCK1-related disease and GSD IV to identify features that clinically differentiate these diagnoses. Literature review and retrospective chart review identified 25 individuals with RBCK1-related disease and 36 with the neuromuscular subtype of GSD IV. Clinical features were evaluated to assess for statistically significant differences between the conditions. At a system level, any cardiac, autoinflammation, immunodeficiency, growth, or dermatologic involvement were suggestive of RBCK1, whereas any respiratory involvement suggested GSD IV. Several features warrant further exploration as predictors of RBCK1, such as generalized weakness, heart transplant, and recurrent infections, among others. Distinguishing RBCK1-related disease will facilitate correct diagnoses and pave the way for accurately identifying affected individuals, as well as for developing management recommendations, treatment, and an enhanced understanding of the natural history. This knowledge may also inform which individuals thought to have GSD IV should undergo reevaluation for RBCK1.

Retrospective chart review of GI bleeding in people with von Willebrand disease.

INTRODUCTION: Gastrointestinal (GI) bleeding events (BEs) in von Willebrand disease (VWD) are difficult to diagnose and often recurrent. Limited data from clinical trials has led to lack of consensus on treatment options. AIM: Describe current treatments and outcomes for GI BEs in people with VWD. METHODS: This retrospective, observational, multicentre chart review study was conducted from January 2018 through December 2019 and included patients with inherited VWD with ≥1 GI BE in the preceding 5 years. Baseline characteristics, number and aetiology of BEs, associated GI-specific morbidities/lesions, treatment and outcomes were analysed descriptively. RESULTS: Sixty bleeds were reported in 20 patients with type 1 (20%), type 2 (50%) and type 3 (30%) VWD. During the 5-year study period, 31 (52%) BEs had one identified or suspected cause; multiple causes were reported in 11 (18%). Most GI BEs (72%) were treated with a combination of von Willebrand factor (VWF), antifibrinolytics and/or other haemostatic or non-haemostatic treatments. Time to resolution did not differ by VWF treatment use; however, BEs treated with non-VWF treatments tended to resolve later. In patients with GI-specific morbidities/lesions, 84% resolved with first-line treatment; time to resolution tended to be longer than in patients without such morbidities/lesions. Thirteen BEs occurred in patients receiving prophylaxis and 47 in patients receiving on-demand treatment; 18 BEs resulted in a switch to prophylaxis after bleed resolution. CONCLUSIONS: This study confirms the unmet need for the management of recurrent GI BEs in people with VWD and the need for prospective data, especially on prophylaxis.

The use of bubble charts in analyzing second stage cesarean delivery rates.

BACKGROUND: The incidence of second stage cesarean delivery has been rising globally because of the failure or the anticipated difficulty of performing instrumental delivery. Yet, the best way to interpret the figure and its optimal rate remain to be determined. This is because it is strongly influenced by the practice of other 2 modes of birth, namely cesarean delivery performed before reaching the second stage and assisted vaginal birth during the second stage. In this regard, a bubble chart that can display 3-dimensional data through its x-axis, y-axis, and the size of each plot (presented as a bubble) may be a suitable method to evaluate the relationship between the rates of these 3 modes of births. OBJECTIVE: This study aimed to conduct an epidemiologic study on the incidence of second stage cesarean deliveries rates among >300,000 singleton term births in 10 years from 8 obstetrical units and to compare their second stage cesarean delivery rates in relation to their pre-second stage cesarean delivery rates and assisted vaginal birth rates using a bubble chart. STUDY DESIGN: The territory-wide birth data collected between 2009 and 2018 from all 8 public obstetrical units (labelled as A to H) were reviewed. The inclusion criteria were all singleton pregnancies with cephalic presentation that were delivered at term (≥37 weeks' gestation). Pre-second stage cesarean delivery rate was defined as all elective cesarean deliveries and those emergency cesarean deliveries that occurred before full cervical dilatation was achieved as a proportion of the total number of births. The second stage cesarean delivery rate and assisted vaginal birth rate were calculated according to the respective mode of delivery as a proportion of the number of cases that reached full cervical dilatation. The rates of these 3 modes of births were compared among the parity groups and among the 8 units. Using a bubble chart, each unit's second stage cesarean delivery rate (y-axis) was plotted against its pre-second stage cesarean delivery rate (x-axis) as a bubble. Each unit's second stage cesarean delivery to assisted vaginal birth ratio was represented by the size of the bubble. RESULTS: During the study period, a total of 353,434 singleton cephalic presenting term pregnancies were delivered in the 8 units, and 180,496 (51.1%) were from nulliparous mothers. When compared with the multiparous group, the nulliparous group had a significantly lower pre-second stage cesarean delivery rate (18.58% vs 21.26%; P<.001) but a higher second stage cesarean delivery rate (0.79% vs 0.22%; P<.001) and a higher assisted vaginal birth rate (17.61% vs 3.58%; P<.001). Using the bubble of their averages as a reference point in the bubble chart, the 8 units' bubbles were clustered into 5 regions indicating their differences in practice: unit B and unit H were close to the average in the center. Unit A and unit F were at the upper right corner with a higher pre-second stage cesarean delivery rate and second stage cesarean delivery rate. Unit D and unit E were at the opposite end. Unit C was at the upper left corner with a low pre-second stage cesarean delivery rate but a high second stage cesarean delivery rate, whereas unit G was at the opposite end. Unit C and unit G were also in the extremes in terms of pre-second stage cesarean delivery to assisted vaginal birth ratio (0.09 and 0.01, respectively). Although some units seemed to have very similar second stage cesarean delivery rates, their obstetrical practices were differentiated by the bubble chart. CONCLUSION: The second stage cesarean delivery rate must be evaluated in the context of the rates of pre-second stage cesarean delivery and assisted vaginal birth. A bubble chart is a useful method for analyzing the relationship among these 3 variables to differentiate the obstetrical practice between different units.

Using the traditional microscope for mineral grain orientation determination: A prototype image analysis pipeline for optic-axis mapping (POAM).

This paper reports on the development of an open-source image analysis software 'pipeline' dedicated to petrographic microscopy. Using conventional rock thin sections and images from a standard polarising microscope, the pipeline can classify minerals and subgrains into objects and obtain information about optic-axis orientation. Five metamorphic rocks were chosen to test and illustrate the method. Thin sections were imaged using reflected and cross- and plane-polarised transmitted light. Images were taken at different angles of the polariser and analyser (360° with 10° steps), both with and without the full-lambda plate. The resulting image stacks were analysed with a modular pipeline for optic-axis mapping (POAM). POAM consists of external and internal software packages that register, segment, classify, and interpret the visible light spectra using object-based image analysis (OBIAS). The mapped fields-of-view and grain orientation stereonets of interest are presented in the context of whole-slide images. Two innovations are reported. First, we used hierarchical tree region merging on blended multimodal images to classify individual grains of rock-forming minerals into objects. Second, we assembled a new optical mineralogy algorithm chain that identifies the mineral slow axis orientation. The c-axis orientation results were verified with scanning electron microscopy electron backscattered diffraction (SEM-EBSD) data. For quartz (uniaxial) in a granite mylonite the test yielded excellent correspondence of c-axis azimuth and good agreement for inclination. For orthorhombic orthopyroxene in a deformed garnet harzburgite, POAM produced acceptable results for slow axis azimuth. In addition, the method identified slight anisotropy in garnet that would not be appreciated by traditional microscopy. We propose that our method is ideally suited for two commonly performed tasks in mineralogy. First, for mineral grain classification of entire thin sections scans on blended images to provide automated modal abundance estimates and grain size distribution. Second, for prospective fields of view of interest, POAM can rapidly generate slow axis crystal orientation maps from multiangle image stacks on conventionally prepared thin sections for targeting detailed SEM-EBSD studies.

Deep learning-based segmentation of whole-body fetal MRI and fetal weight estimation: assessing performance, repeatability, and reproducibility.

OBJECTIVES: To develop a deep-learning method for whole-body fetal segmentation based on MRI; to assess the method's repeatability, reproducibility, and accuracy; to create an MRI-based normal fetal weight growth chart; and to assess the sensitivity to detect fetuses with growth restriction (FGR). METHODS: Retrospective data of 348 fetuses with gestational age (GA) of 19-39 weeks were included: 249 normal appropriate for GA (AGA), 19 FGR, and 80 Other (having various imaging abnormalities). A fetal whole-body segmentation model with a quality estimation module was developed and evaluated in 169 cases. The method was evaluated for its repeatability (repeated scans within the same scanner, n = 22), reproducibility (different scanners, n = 6), and accuracy (compared with birth weight, n = 7). A normal MRI-based growth chart was derived. RESULTS: The method achieved a Dice = 0.973, absolute volume difference ratio (VDR) = 1.8% and VDR mean difference = 0.75% ([Formula: see text]: - 3.95%, 5.46), and high agreement with the gold standard. The method achieved a repeatability coefficient = 4.01%, ICC = 0.99, high reproducibility with a mean difference = 2.21% ([Formula: see text]: - 1.92%, 6.35%), and high accuracy with a mean difference between estimated fetal weight (EFW) and birth weight of - 0.39% ([Formula: see text]: - 8.23%, 7.45%). A normal growth chart (n = 246) was consistent with four ultrasound charts. EFW based on MRI correctly predicted birth-weight percentiles for all 18 fetuses ≤ 10thpercentile and for 14 out of 17 FGR fetuses below the 3rd percentile. Six fetuses referred to MRI as AGA were found to be < 3rd percentile. CONCLUSIONS: The proposed method for automatic MRI-based EFW demonstrated high performance and sensitivity to identify FGR fetuses. CLINICAL RELEVANCE STATEMENT: Results from this study support the use of the automatic fetal weight estimation method based on MRI for the assessment of fetal development and to detect fetuses at risk for growth restriction. KEY POINTS: • An AI-based segmentation method with a quality assessment module for fetal weight estimation based on MRI was developed, achieving high repeatability, reproducibility, and accuracy. • An MRI-based fetal weight growth chart constructed from a large cohort of normal and appropriate gestational-age fetuses is proposed. • The method showed a high sensitivity for the diagnosis of small fetuses suspected of growth restriction.

Patterns of use of advanced wound matrices in the Veterans Administration clinics.

Chronic wounds are a common and costly health issue affecting millions of individuals in the United States, particularly those with underlying conditions such as diabetes, venous insufficiency, and peripheral artery disease. When standard treatments fail, advanced wound care therapies, such as skin substitutes, are often applied. However, the clinical effectiveness, indications, and comparative benefits of these therapies have not been well established. In this study, we report on the usage of both acellular and cellular, single and bilayer, natural and synthetic, dermal, and epidermal skin substitutes in a VA hospital system. We performed a retrospective chart review to understand the ordering and usage patterns of advanced wound therapies for patients with chronic wounds at the VA Northern California Health Care System. We examined types of products being recommended, categories of users recommending the products, indications for orders, and rate of repeated orders. Neuropathic, venous, or pressure ulcers were the main indications for using advanced wound matrices. Only 15.6% of patients for whom the matrices were ordered had supporting laboratory tests. Exactly 34.3% of the ordered matrices were not applied. And the use of wound matrices resulted in increased costs per patient visit of $1018-$3450. Our study sheds light on the usage patterns of these therapies in a VA healthcare facility and highlights the need for more robust evidence-based studies to determine the true benefits, efficacy, and cost-effectiveness of these innovative treatment options.

Effectiveness of romosozumab in patients with osteoporosis at high fracture risk: a Japanese real-world study.

INTRODUCTION: To describe the real-world use of romosozumab in Japan, we conducted a chart review of > 1000 Japanese patients with osteoporosis (OP) at high risk of fracture, across multiple medical institutions. MATERIALS AND METHODS: Treatment-naïve and prior OP-treatment patients who received romosozumab for 12 months followed by ≥ 6 months of sequential OP treatment were included. The primary objective described the baseline demographics and clinical characteristics; secondary objectives evaluated changes in bone mineral density (BMD) and bone turnover markers in all patients and effectiveness of romosozumab in a sub-group of treatment-naïve patients using the fracture risk assessment tool (FRAX®). RESULTS: Of the 1027 patients (92.4% female), 45.0% were treatment-naïve. The mean ± SD age of treatment-naïve versus prior OP-treatment patients was 76.8 ± 8.5 and 77.1 ± 8.5 years. The most frequent prior OP treatment was bisphosphonates (45.0%). Romosozumab treatment for 12 months increased BMD at the lumbar spine in all groups; the median percent change from baseline in lumbar spine BMD was higher in the treatment-naïve (13.4%) versus prior OP-treatment group (bisphosphonates [9.2%], teriparatide [11.3%], denosumab [DMAb, 4.5%]). DMAb, bisphosphonates, or teriparatide after romosozumab maintained the BMD gains at all skeletal sites at month 18 in treatment-naïve patients. Most treatment-naïve patients were at high risk of fracture, BMD increased consistently with romosozumab regardless of the baseline fracture risk assessed by FRAX. CONCLUSION: This large-scale, multicenter chart review provides clinically relevant insights into the profiles of patients initiating romosozumab, effectiveness of real-world romosozumab use, and sequential therapy in Japanese patients at high risk of fracture.

Prenatal prediction of adverse outcome using different charts and definitions of fetal growth restriction.

OBJECTIVE: Antenatal growth assessment using ultrasound aims to identify small fetuses that are at higher risk of perinatal morbidity and mortality. This study explored whether the association between suboptimal fetal growth and adverse perinatal outcome varies with different definitions of fetal growth restriction (FGR) and different weight charts/standards. METHODS: This was a retrospective cohort study of 17 261 singleton non-anomalous pregnancies at ≥ 24 + 0 weeks' gestation that underwent routine ultrasound at a tertiary referral hospital. Estimated fetal weight (EFW) and Doppler indices were converted into percentiles using a reference standard (INTERGROWTH-21st (IG-21)) and various reference charts (Hadlock, Fetal Medicine Foundation (FMF) and Swedish). Test characteristics were assessed using the consensus definition, Society for Maternal-Fetal Medicine (SMFM) definition and Swedish criteria for FGR. Adverse perinatal outcome was defined as perinatal death, admission to the neonatal intensive care unit at term, 5-min Apgar score < 7 and therapeutic cooling for neonatal encephalopathy. The association between FGR according to each definition and adverse perinatal outcome was compared. Multivariate logistic regression analysis was used to test the strength of association between ultrasound parameters and adverse perinatal outcome. Ultrasound parameters were also tested for correlation. RESULTS: IG-21, Hadlock and FMF fetal size references classified as growth-restricted 1.5%, 3.6% and 4.6% of fetuses, respectively, using the consensus definition and 2.9%, 8.8% and 10.6% of fetuses, respectively, using the SMFM definition. The sensitivity of the definition/chart combinations for adverse perinatal outcome varied from 4.4% (consensus definition with IG-21 charts) to 13.2% (SMFM definition with FMF charts). Specificity varied from 89.4% (SMFM definition with FMF charts) to 98.6% (consensus definition with IG-21 charts). The consensus definition and Swedish criteria showed the highest specificity, positive predictive value and positive likelihood ratio in detecting adverse outcome, irrespective of the reference chart/standard used. Conversely, the SMFM definition had the highest sensitivity across all investigated growth charts. Low EFW, abnormal mean uterine artery pulsatility index (UtA-PI) and abnormal cerebroplacental ratio were significantly associated with adverse perinatal outcome and there was a positive correlation between the covariates. Multivariate logistic regression showed that UtA-PI > 95th percentile and EFW < 5th percentile were the only parameters consistently associated with adverse outcome, irrespective of the definitions or fetal growth chart/standard used. CONCLUSIONS: The apparent prevalence of FGR varies according to the definition and fetal size reference chart/standard used. Irrespective of the method of classification, the sensitivity for the identification of adverse perinatal outcome remains low. EFW, UtA-PI and fetal Doppler parameters are significant predictors of adverse perinatal outcome. As these indices are correlated with one other, a prediction algorithm is advocated to overcome the limitations of using these parameters in isolation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Association between fetal growth restriction and stillbirth in twin compared with singleton pregnancies.

OBJECTIVES: Twin pregnancies are at higher risk of stillbirth compared to singletons. Fetal growth restriction (FGR) is a major cause of perinatal mortality, but its impact on twins vs singletons remains unclear. The primary objective of this study was to investigate the association of FGR and small-for-gestational age (SGA) with stillbirth in twin compared with singleton pregnancies. A secondary objective was to assess these associations stratified by gestational age at delivery. Furthermore, we aimed to compare the associations of FGR and SGA with stillbirth in twin pregnancies using twin-specific vs singleton birth-weight charts, stratified by chorionicity. METHODS: This was a retrospective cross-sectional study of pregnancies receiving obstetric care and giving birth between 1999 and 2022 at St George's Hospital, London, UK. The exclusion criteria included triplet and higher-order pregnancies, those resulting in miscarriage or live birth at ≤ 23 + 6 weeks, termination of pregnancy and missing data regarding birth weight or gestational age at birth. Birth-weight data were collected and FGR and SGA were defined as birth weight <5th and <10th centiles, respectively. While standard logistic regression was used for singleton pregnancies, the association of FGR and SGA with stillbirth in twin pregnancies was investigated using mixed-effects logistic regression models. For twin pregnancies, intercepts were allowed to vary for twin pairs to account for intertwin dependency. Analyses were stratified by gestational age at delivery and chorionicity. Statistical significance was set at P ≤ 0.001. RESULTS: The study included 95 342 singleton and 3576 twin pregnancies. There were 494 (0.52%) stillbirths in singleton and 41 (1.15%) stillbirths in twin pregnancies (17 dichorionic and 24 monochorionic). SGA and FGR were associated significantly with stillbirth in singleton pregnancies across all gestational ages at delivery: the odds ratios (ORs) for SGA and FGR were 2.36 ((95% CI, 1.78-3.13), P < 0.001) and 2.67 ((95% CI, 2.02-3.55), P < 0.001), respectively, for delivery before 32 weeks; 2.70 ((95% CI, 1.71-4.31), P < 0.001) and 2.82 ((95% CI, 1.78-4.47), P < 0.001), respectively, for delivery between 32 and 36 weeks; and 3.85 ((95% CI, 2.83-5.21), P < 0.001) and 4.43 ((95% CI, 3.16-6.12), P < 0.001), respectively, for delivery after 36 weeks. In twin pregnancies, when stratified by gestational age at delivery, both SGA and FGR determined by twin-specific birth-weight charts were associated with increased odds of stillbirth for those delivered before 32 weeks (SGA: OR, 3.87 (95% CI, 1.56-9.50), P = 0.003 and FGR: OR, 5.26 (95% CI, 2.11-13.01), P = 0.001), those delivered between 32 and 36 weeks (SGA: OR, 6.67 (95% CI, 2.11-20.41), P = 0.001 and FGR: OR, 9.54 (95% CI, 3.01-29.40), P < 0.001) and those delivered beyond 36 weeks (SGA: OR, 12.68 (95% CI, 2.47-58.15), P = 0.001 and FGR: OR, 23.84 (95% CI, 4.62-110.25), P < 0.001). However, the association of stillbirth with SGA and FGR in twin pregnancies was non-significant when diagnosis was based on singleton charts (before 32 weeks: SGA, P = 0.014 and FGR, P = 0.005; 32-36 weeks: SGA, P = 0.036 and FGR, P = 0.008; after 36 weeks: SGA, P = 0.080 and FGR, P = 0.063). CONCLUSION: Our study demonstrates that SGA and, especially, FGR are associated significantly with an increased risk of stillbirth across all gestational ages in singleton pregnancies, and in twin pregnancies when twin-specific birth-weight charts are used. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Balancing the efforts of chart review and gains in PRS prediction accuracy: An empirical study.

OBJECTIVE: Phenotypic misclassification in genetic association analyses can impact the accuracy of PRS-based prediction models. The bias reduction method proposed by Tong et al. (2019) has demonstrated its efficacy in reducing the effects of bias on the estimation of association parameters between genotype and phenotype while minimizing variance by employing chart reviews on a subset of the data for validating phenotypes, however its improvement of subsequent PRS prediction accuracy remains unclear. Our study aims to fill this gap by assessing the performance of simulated PRS models and estimating the optimal number of chart reviews needed for validation. METHODS: To comprehensively assess the efficacy of the bias reduction method proposed by Tong et al. in enhancing the accuracy of PRS-based prediction models, we simulated each phenotype under different correlation structures (an independent model, a weakly correlated model, a strongly correlated model) and introduced error-prone phenotypes using two distinct error mechanisms (differential and non-differential phenotyping errors). To facilitate this, we used genotype and phenotype data from 12 case-control datasets in the Alzheimer's Disease Genetics Consortium (ADGC) to produce simulated phenotypes. The evaluation included analyses across various misclassification rates of original phenotypes as well as quantities of validation set. Additionally, we determined the median threshold, identifying the minimal validation size required for a meaningful improvement in the accuracy of PRS-based predictions across a broad spectrum. RESULTS: This simulation study demonstrated that incorporating chart review does not universally guarantee enhanced performance of PRS-based prediction models. Specifically, in scenarios with minimal misclassification rates and limited validation sizes, PRS models utilizing debiased regression coefficients demonstrated inferior predictive capabilities compared to models using error-prone phenotypes. Put differently, the effectiveness of the bias reduction method is contingent upon the misclassification rates of phenotypes and the size of the validation set employed during chart reviews. Notably, when dealing with datasets featuring higher misclassification rates, the advantages of utilizing this bias reduction method become more evident, requiring a smaller validation set to achieve better performance. CONCLUSION: This study highlights the importance of choosing an appropriate validation set size to balance between the efforts of chart review and the gain in PRS prediction accuracy. Consequently, our study establishes a valuable guidance for validation planning, across a diverse array of sensitivity and specificity combinations.

Effectiveness of standard treatments in non-small-cell lung cancer with METexon14 skipping mutation: a real-world study.

Aim: To assess real-world clinical outcomes with standard therapies for advanced non-small-cell lung cancer (aNSCLC) with METexon14 skipping mutation (METex14).Methods: In an oncologists-led retrospective review of medical records, data were abstracted and analyzed for patients initiating first-line (1L) systemic therapy after 1 January 2017.Results: In total 287 aNSCLC patients with METex14, the real-world best overall response rate was 73.4% for capmatinib (n = 146), 68.8% for immunotherapy (IO) monotherapy (n = 48), 52.0% for chemotherapy (CT, n = 30), and 54.8% for IO + CT (n = 63). As compared with capmatinib, patients receiving IO (hazard ratio [HR]: 1.57; 95% CI: 0.77-3.20; p = 0.220), CT (HR: 2.41; 95% CI: 1.19-4.85; p = 0.014) and IO + CT (HR: 2.33; 95% CI: 1.35-4.04; p = 0.003) had higher rates of progression. Further, patients receiving CT (HR: 4.43; 95% CI: 1.54-12.75; p = 0.006) and IO + CT (HR: 3.53, 95% CI: 1.41-8.85; p = 0.007) had higher rates of mortality than patients receiving capmatinib.Conclusion: The study showed better clinical outcomes with capmatinib than other standard therapies in 1L setting for aNSCLC harboring METex14.

Real-world study that investigated the outcomes of different therapies used to treat non-small-cell lung cancer patients with mesenchymal-epithelial transition exon 14 skipping mutationWhat is this article about? A real-world study that investigated clinical outcomes in patients with diagnosis of advanced non-small-cell lung cancer (aNSCLC) with mesenchymal-epithelial transition exon 14 (METex14) skipping­a rare form of genetic mutation­who received treatment with one of the commonly used therapies for this disease: immunotherapy, chemotherapy, immunotherapy + chemotherapy combination and capmatinib, which is a highly selective inhibitor of MET tyrosine kinase protein involved in the growth of cancer cells.What were the results? The study showed that, in general, patients treated with capmatinib as the frontline therapy more frequently achieved a clinical response in the form of complete tumor resolution or tumor shrinkage, had a lower risk of disease worsening and lived longer than patients who were treated with immunotherapy, chemotherapy or immunotherapy + chemotherapy combination.What do the results of the study mean? This study suggests that capmatinib is effective in treating patients with aNSCLC with METex14 skipping who have not been treated with another anticancer therapy previously. It provides evidence to support the use of capmatinib in the frontline setting and may inform clinical decision-making in routine practice.

Disease landscape of advanced HER2-breast cancer patients by treatment line in three EU countries and USA.

Aim: To report treatment patterns and quality of life (QoL) in HER2-negative advanced breast cancer patients.Methods: Data were drawn from a cross-sectional survey in Europe and USA.Results: Hormone plus targeted therapy was the most frequent first-line (1L, 62%) and second-line (2L, 45%) treatment for HR+/HER2-patients. Chemotherapy was most frequent at third-line or greater (3L+, 39%) for HR+/HER2- patients, 2L (51%) and 3L+ (48%) for triple negative breast cancer (TNBC) patients. Time to progression was 13.8 (2L) and 11.0 (3L+) months for HR+/HER2- patients. No comparisons were observed for TNBC patients. EQ-5D-5L scores were highest in patients at 1L and lowest at 3L+.Conclusion: Reduced QoL and treatment response were reported in patients at later lines of therapy.

Breast cancer is the most common cancer in women. Differences in survival are seen depending on how widespread or advanced the cancer is, how many different treatments the patient has been given, as well as whether certain receptors on the tumor are present or absent. Many new treatments are available which can target these receptors. These treatments have improved survival in patients with advanced breast cancer, but other benefits for the patient are not always clear. In addition, differences between countries are possible as official guidance can vary. This study aimed to understand these issues, by asking physicians and their patients across Europe and USA for their views on quality of life and satisfaction with their treatments. We found that, in general, physicians prescribed treatments as recommended in the treatment guidelines. As breast cancer progressed and treatment stopped working, patients were switched on to different treatments. Survival, quality of life and treatment satisfaction were all worse in patients who had switched treatments. It appears that the patients lose confidence that their new treatment will work to improve their quality of life. We also saw differences in some of these outcomes between Europe and USA, which were likely due to differences in the treatment guidelines between countries. Both quality of life and treatment satisfaction are important for the well-being of patients with advanced breast cancer as they now live longer with these new treatments. This should be considered by physicians and taken into account for future work.

Identifying Patients With Primary Biliary Cholangitis and Cirrhosis Using Administrative Data in a National Cohort.

BACKGROUND: The accuracy of administrative codes to capture patients with both primary biliary cholangitis (PBC) and cirrhosis could be challenging because of the potential for incorrect coding due to the old nomenclature "Primary Biliary Cirrhosis." Therefore, the aim of this study was to examine the positive predictive value (PPV) of International Classification of Diseases (ICD) codes for PBC and cirrhosis. METHODS: This was a retrospective cohort study using data from the VA Corporate Data Warehouse. Eligibility criteria included adult patients diagnosed to have PBC and cirrhosis based on one inpatient or two outpatient ICD 9 or 10 codes, and were validated against chart review of each participant. RESULTS: We identified 1408 patients who were found to have ICD codes for both cirrhosis and PBC. The ICD 9/10 codes for PBC and cirrhosis had a PPV of 0.75 (95% CI 0.73-0.75) for cirrhosis, 0.75 for PBC (95% CI 0.73-0.78), and 0.52 (0.50-0.55) for PBC and cirrhosis. When portal hypertension was combined with ICD 9/10 codes, the PPV of cirrhosis improved to 0.92 (0.90-0.94), and that of PBC cirrhosis improved to 0.64 (0.60-0.67). By combining ICD 9/10 codes for portal hypertension and receipt of ursodeoxycholic acid (UDCA), the PPV for cirrhosis improved to 0.91 (0.88-0.94), PBC increased to 0.78 (0.74-0.82), and that for PBC cirrhosis to 0.69 (0.65-0.74). CONCLUSIONS: In a large national cohort, the use of ICD 9/10 codes had modest reliability for identifying participants with PBC and cirrhosis. The PPV for cirrhosis can be improved by incorporating ICD 9/10 codes for portal hypertension with receipt of UDCA.

Performance of the non-laboratory based 2019 WHO cardiovascular disease risk prediction chart in Eastern Sub-Saharan Africa.

BACKGROUND AND AIMS: The World Health Organization (WHO) updated its cardiovascular disease (CVD) risk prediction charts in 2019 to cover 21 global regions. We aimed to assess the performance of an updated non-lab-based risk chart for people with normoglycaemia, impaired fasting glucose (IFG), and diabetes in Eastern Sub-Saharan Africa. METHODS AND RESULTS: We used data from six WHO STEPS surveys conducted in Eastern Sub-Saharan Africa between 2012 and 2017. We included 9857 participants aged 40-69 years with no CVD history. The agreement between lab- and non-lab-based charts was assessed using Bland-Altman plots and Cohen's kappa. The median age of the participants was 50 years (25-75th percentile: 44-57). The pooled median 10-year CVD risk was 3 % (25-75th percentile: 2-5) using either chart. According to the estimation, 7.5 % and 8.4 % of the participants showed an estimated CVD risk ≥10 % using the non-lab-based chart or the lab-based chart, respectively. The concordance between the two charts was 91.3 %. The non-lab-based chart underestimated the CVD risk in 57.6 % of people with diabetes. In the Bland-Altman plots, the limits of agreement between the two charts were widest among people with diabetes (-0.57-7.54) compared to IFG (-1.75-1.22) and normoglycaemia (-1.74-1.06). Kappa values of 0.79 (substantial agreement), 0.78 (substantial agreement), and 0.43 (moderate agreement) were obtained among people with normoglycaemia, IFG, and diabetes, respectively. CONCLUSIONS: Given limited healthcare resources, the updated non-lab-based chart is suitable for CVD risk estimation in the general population without diabetes. Lab-based risk estimation is suitable for individuals with diabetes to avoid risk underestimation.

Menstrual blood loss is an independent determinant of hemoglobin and ferritin levels in premenopausal blood donors.

INTRODUCTION: To prevent blood donors from developing iron deficiency (ferritin <15 µg/L) and subsequent anemia (hemoglobin <120 g/L), blood services rely on information about known risk factors, including the donor's sex and age. For example, while Finnish women are able to donate whole blood with a minimum donation interval of 91 days, women in the 18 to 25-year-old age group are recommended to donate no more than once per year. Menstrual blood loss is not accounted for in blood donation interval recommendations, despite being a known risk factor of iron deficiency. We aim to investigate to what extent menstrual bleeding is associated with ferritin and hemoglobin levels in female blood donors, and quantify the association of other menstruation-related variables not currently accounted for by blood services (i.e., use of hormonal contraception, heavy menstrual bleeding) with iron deficiency or anemia. MATERIAL AND METHODS: The study population consisted of 473 premenopausal and 491 postmenopausal Dutch whole blood donors. Exclusion criteria were current pregnancy, BMI ≥50, ferritin ≥200, pictorial blood assessment chart (PBAC) ≥400, and age <18 or ≥70 years. Menstrual blood loss was quantified using a PBAC, a semiquantitative method to evaluate the number of used menstrual products and the degree of staining. We identified predictors of log(ferritin)/hemoglobin and iron deficiency/anemia using Bayesian linear and logistic regression models and quantified the average percentage of variance in log(ferritin) and hemoglobin explained by the covariates. RESULTS: Menstrual blood loss accounted for most of the explained variance in hemoglobin (8%) and second only to the number of days since last donation for ferritin (8%). Heavy menstrual bleeding (PBAC ≥150, OR = 3.56 [1.45-8.85], prevalence 13%) was associated with anemia, and use of levonorgestrel-releasing intrauterine device was negatively associated with iron deficiency (OR = 0.06 [0.01-0.44]). After statistical control for menstrual blood loss, age was not associated with iron status. CONCLUSIONS: Menstrual blood loss and blood donation were the most important determinants of iron status in premenopausal women. Thus, results suggest that accounting for menstrual blood loss in donation interval guidelines may benefit blood donors.

Verification of a nationwide population-based myopia growth chart in a large longitudinal cohort of 1155 Korean children.

OBJECTIVE: To evaluate predictive value of the myopia growth chart based on population-based health survey data using longitudinal cohorts. METHODS: Patients aged from 5 to 18 years and underwent two or more cycloplegic refraction (CR) exams with at least one year of interval were included. Percentile deviation was calculated by subtracting percentile at final exam from the percentile at initial exam based on the chart. Spherical equivalent (SE) deviation was calculated by SE at final CR subtracted from predicted SE based on initial CR using the chart. RESULTS: 2310 eyes from 1155 subjects were included. There were 1344 eyes (58.2%) categorized as inliers, where both initial and final CR were within the 2nd to 99th percentile. Mean percentile and SE deviations were + 11.0 ± 22.9 percentiles and -0.60 ± 1.33 diopters, each. Outliers, those except the inliers, were 966 eyes (41.8%). Most outliers (709 eyes, 73.4%) were outside the chart for both initial and final exam. The rest of the outliers (257 eyes, 26.2%) were within the 2 to 99 percentile range on the chart at least once, either at initial or final exams; most of those (202 eyes, 78.6%) progressed toward myopia more than predicted. CONCLUSIONS: In our large cohorts, both inliers and outliers tended to progress toward more myopia than predicted from the chart. This suggests the chart predicts childhood myopia rather conservatively. The myopia growth chart may be useful as a screening tool in detecting children at high risk of developing high myopia.

Title - Long term outcomes of vitrectomy and ERM peel: Can pre-operative metamorphopsia measured using the D-Chart help improve surgical candidate selection?

PURPOSE: To assess the predictive value of pre-operative metamorphopsia, measured using the D-Chart, in patients undergoing epiretinal membrane (ERM) surgery and how this relates to improvement in quality of life after surgery. METHODS: 17 patients from vitreo-retinal surgery clinics at a tertiary ophthalmology centre were recruited when listed for pars plana vitrectomy (PPV) with ERM peel between September 2019 - February 2020. Pre-operatively patients underwent visual acuity (VA), Visual-Function Index 14 (VF-14) and metamorphopsia (D-Chart-Thomson Software Solutions) assessment and answered a questionnaire regarding cardinal ERM symptoms. Post-operatively patients were re-assessed in the same domains. RESULTS: 13 patients completed the protocol (inclusion rate 76%) with a mean follow-up of 32.1 (± 3.1) months. Mean pre-operative VA of the affected eye was 0.42 logMAR (± 0.25). Mean pre-operative VF-14 score was 81.51 (± 12.8) and mean M-Score of the affected eye was 14.6 (± 12.7). Post-operatively, mean VA of the operated eye was 0.11 logMAR (± 0.11), mean VF-14 score was 97.4 (± 3.8) and mean M-Score was 1.31 (± 2.8). Mean improvement in VA was 0.31 logMAR (p < 0.001), in VF-14 15.9 (p = 0.002), and M-Score -13.3 (p = 0.003). There was a significant association between pre-operative D-Chart score and improvement in VA (r = -0.570, p = 0.042), visual functioning (r = 0.606 p = 0.028) and metamorphopsia (r = 0.916 p < 0.001), with those demonstrating poorer D-Chart scores showing greater improvements. CONCLUSION: Pre- and post-operative visual distortion measured using the D-Chart, correlates with vision related quality of life in patients undergoing epiretinal membrane surgery. Patients with worse pre-operative distortion scores noticed the greatest improvements in distortion and vision related quality of life following surgery. With a mean follow-up time of 32.1 months, this long-term follow-up data further reinforces the efficacy of vitrectomy and ERM peel by demonstrating significant and sustained improvement in visual acuity, metamorphopsia and visual functioning. The authors suggest there is a role for D-Chart assessment pre-operatively to improve selection of patients in ERM surgery.

Ten-year risk assessment for cardiovascular disease & associated factors among adult Indians (aged 40-69 yr): Insights from the National Noncommunicable Disease Monitoring Survey (NNMS).

Background & objectives Cardiovascular diseases (CVDs) are extremely prevalent in India, making early detection of people at high risk for CVDs and prevention crucial. This study aimed to estimate CVD risk distribution in older adults (40-69 yr) in India using WHO's non-laboratory risk chart and identify factors associated with elevated CVD risk (10%). Methods The current study used a nationally representative sample of 40-69 yr adults in India. The population's 10-yr CVD risk was defined as very low-to-low (10%), moderate (10-20%) and high to very high (>20%). We attempted univariable and multivariable logistic regressions to identify factors related to higher CVD risk (≥10%). Results Out of 4480 participants, 50 per cent were younger participants (40-49 years). The proportions of the population with very low to low, moderate and high to very high CVD risk were 84.9, 14.4 and 0.7 per cent, respectively. The estimated 10-year CVD risk was higher for people with unemployed [Adjusted Odds Ratio (AOR): 5.12; 95% Confidence Interval (CI): 3.63, 7.24], followed by raised blood glucose (AOR: 1.81; 95%CI: 1.39, 2.34). Interpretation & conclusions The non-laboratory-based chart proves valuable in low-resource settings, especially at the primary healthcare level, facilitating efficient CVD risk assessment and resource allocation. Further research is needed to explore the association of second-hand smoke with CVD risk in the Indian population.