Traditional risk factors and nodal yield-still relevant with high-quality risk-adapted adjuvant treatment for locally advanced head and neck cancer?

OBJECTIVE: Patients with locally advanced head and neck cancer (LAHNC) often undergo multimodal therapy including radical resection of the primary tumor and neck dissection (ND) followed by risk-adapted adjuvant radio(chemo)therapy (R(C)T). Quality parameters influencing local control and survival of these patients have been postulated: resection status (R status), extranodal extension (ENE), interval to adjuvant treatment ≤6 weeks, R(C)T given when indicated, and nodal yield (NY) ≥18 lymph nodes per neck. For other solid tumors the trend is towards less extensive lymph node surgery to avoid toxicity such as lymphedema, damage to peripheral nerves, dysesthesia, or paresthesia. The present study aims to investigate whether the number of nodes removed during neck dissection for LAHNC is still predictive for outcome when patients receive risk-adapted adjuvant treatment according to current guidelines. METHODS: Between 2008 and 2015, 468 patients with LAHNC undergoing R(C)T with curative intent were prospectively registered in a database (UICC III/IV). Among them, 359 patients received adjuvant treatment and 295 underwent neck dissection. There were 119 (40%) patients with an oropharyngeal primary, 49 (17%) with cancer of the larynx/hypopharynx, 88 (30%) of the oral cavity, and 39 (13%) of the nasal/paranasal sinuses and cancer of unknown primary (CUP). Median follow-up was 45.6 months. Histopathology revealed an R1 status in 65 (22%) cases and ENE in 93 (31%) cases. 150 (51%) patients received RCT; the median time to adjuvant treatment from the day of tumor resection was 44 days (35-54) and overall treatment time (OTT; time from surgery to the last day of R(C)T) was 90 days (82-101). Factors influencing disease-free survival (DFS) were adjusted and analyzed using CART analysis (removed nodes, number of positive nodes, body mass index (BMI), ENE, T and N classification, R status, and primary site). Local control (LC), distant metastases-free survival (DMFS), and overall survival (OS) were analyzed using Kaplan-Meier statistics and multivariate analysis (MVA) for factors predictive for DFS and OS. RESULTS: CART analysis (Classification and Regression Trees) showed that T classification (T3/4) is the most important predictor for DFS, followed by age (> 61 years) and BMI (< 17.4). Primary site (OPC vs. other) and number of removed nodes (< 17) were shown to be less important for DFS, while ECE, N classification, and R status seem to be of little relevance. MVA revealed number of positive nodes, non-OPC, and T3/4 to be negative predictive factors for DFS. For OS, the number of positive nodes and non-OPC primary were predictive. Five-year rates were 86.1% for LC, 87.9% DMFS, 76.5% DFS, and 67.2% for OS. CONCLUSION: In this patient cohort, the number of removed nodes is not relevant for DFS and OS, while the number of positive nodes and T classification have a negative impact on these endpoints. The high-risk factors positive resection margin and ECE seem to lose their negative impact on DFS and OS. High-quality care in head and oncology is only possible within a close multidisciplinary team and network.

Validation of the automated neuropsychological assessment metrics for assessing cognitive impairment in systemic lupus erythematosus.

OBJECTIVE: We previously demonstrated the utility of the Automated Neuropsychological Assessment Metrics (ANAM) for screening cognitive impairment (CI) in patients with systemic lupus erythematosus (SLE) and developed composite indices for interpreting ANAM results. Our objectives here were to provide further support for the ANAM's concurrent criterion validity against the American College of Rheumatology neuropsychological battery (ACR-NB), identify the most discriminatory subtests and scores of the ANAM for predicting CI, and provide a new approach to interpret ANAM results using Classification and Regression Tree (CART) analysis. METHODS: 300 adult SLE patients completed an adapted ACR-NB and ANAM on the same day. As per objectives, six models were built using combinations of ANAM subtests and scores and submitted to CART analysis. Area under the curve (AUC) was calculated to evaluate the ANAM's criterion validity compared to the adapted ACR-NB; the most discriminatory ANAM subtests and scores in each model were selected, and performance of models with the highest AUCs were compared to our previous composite indices; decision trees were generated for models with the highest AUCs. RESULTS: Two models had excellent AUCs of 86 and 89%. Eight most discriminatory ANAM subtests and scores were identified. Both models demonstrated higher AUCs against our previous composite indices. An adapted decision tree was created to simplify the interpretation of ANAM results. CONCLUSION: We provide further validity evidence for the ANAM as a valid CI screening tool in SLE. The decision tree improves interpretation of ANAM results, enhancing clinical utility.

COMPANION: development of a patient-centred complexity and casemix classification for adult palliative care patients based on needs and resource use - a protocol for a cross-sectional multi-centre study.

BACKGROUND: A casemix classification based on patients' needs can serve to better describe the patient group in palliative care and thus help to develop adequate future care structures and enable national benchmarking and quality control. However, in Germany, there is no such an evidence-based system to differentiate the complexity of patients' needs in palliative care. Therefore, the study aims to develop a patient-oriented, nationally applicable complexity and casemix classification for adult palliative care patients in Germany. METHODS: COMPANION is a mixed-methods study with data derived from three subprojects. Subproject 1: Prospective, cross-sectional multi-centre study collecting data on patients' needs which reflect the complexity of the respective patient situation, as well as data on resources that are required to meet these needs in specialist palliative care units, palliative care advisory teams, and specialist palliative home care. Subproject 2: Qualitative study including the development of a literature-based preliminary list of characteristics, expert interviews, and a focus group to develop a taxonomy for specialist palliative care models. Subproject 3: Multi-centre costing study based on resource data from subproject 1 and data of study centres. Data and results from the three subprojects will inform each other and form the basis for the development of the casemix classification. Ultimately, the casemix classification will be developed by applying Classification and Regression Tree (CART) analyses using patient and complexity data from subproject 1 and patient-related cost data from subproject 3. DISCUSSION: This is the first multi-centre costing study that integrates the structure and process characteristics of different palliative care settings in Germany with individual patient care. The mixed methods design and variety of included data allow for the development of a casemix classification that reflect on the complexity of the research subject. The consecutive inclusion of all patients cared for in participating study centres within the time of data collection allows for a comprehensive description of palliative care patients and their needs. A limiting factor is that data will be collected at least partly during the COVID-19 pandemic and potential impact of the pandemic on health care and the research topic cannot be excluded. TRIAL REGISTRATION: German Register for Clinical Studies trial registration number: DRKS00020517 .

Accuracy of Transient Elastography Data Combined With APRI in Detection and Staging of Liver Disease in Pediatric Patients With Cystic Fibrosis.

BACKGROUND & AIMS: Liver disease develops in 15%-72% of patients with cystic fibrosis, and 5%-10% develop cirrhosis or portal hypertension, usually during childhood. Transient elastography (TE) is a noninvasive method to measure liver stiffness. We aimed to validate its accuracy in detection of liver disease and assessment of fibrosis in children with cystic fibrosis. METHODS: We performed a cross-sectional study to evaluate the accuracy of TE in analysis of liver disease in 160 consecutive children who presented with cystic fibrosis (9.0 ± 0.4 years old, 53% male) at a tertiary referral pediatric center in Australia, from 2011 through 2016. Patients were classified as having cystic fibrosis-associated liver disease (CFLD) or cystic fibrosis without liver disease (CFnoLD) based on clinical, biochemical, and imaging features. Fibrosis severity was determined from histologic analysis of dual-pass liver biopsies from children with CFLD, as the reference standard. Data from healthy children without cystic fibrosis (n = 64, controls) were obtained from a separate study. Liver stiffness measurements (LSMs) were made by Fibroscan analysis, using the inter-quartile range/median ≤30% of 10 valid measurements. Children with macronodularity or portal hypertension with heterogeneous changes on ultrasound without available biopsy were assigned to the category of stage F3-F4 fibrosis. RESULTS: LSM was made reliably in 86% of children; accuracy increased with age. LSMs were significantly higher in children with CFLD (10.7 ± 2.4 kPa, n = 33) than with CFnoLD (4.6 ± 0.1 kPa, n = 105) (P < .0001) or controls (4.1 ± 0.1kPa) (P < .0001); LSMs were higher in children with CFnoLD than controls (P < .05). At a cut-off value of 5.55kPa, LSM identified children with CFLD with an area under the receiver operating characteristic (AUROC) curve of 0.82, 70% sensitivity, and 82% specificity (P < .0001). Classification and regression tree models that combined LSM and aspartate aminotransferase to platelet ratio index (APRI) identified children with CFLD with an AUROC curve of 0.89, 87% sensitivity, and 74% specificity (odds ratio, 18.6). LSMs correlated with fibrosis stage in patients with CFLD (r = 0.67, P = .0001). A cut-off value of 8.7kPa differentiated patients with stage F3-F4 fibrosis from patients with stage F1-F2 fibrosis (AUROC, 0.87; 75% sensitivity; 100% specificity, P=.0002). The combination of LSMs and APRI improved the differentiation of patients with F3-F4 fibrosis vs F1-F2 fibrosis (AUROC, 0.92; 83% sensitivity; and 100% specificity (P < .01). CONCLUSIONS: LSMs made by TE accurately detect liver disease in children with cystic fibrosis; diagnostic accuracy increases when LSMs are combined with APRI. LSMs also differentiate between children with cystic fibrosis with mild-moderate fibrosis vs advanced fibrosis.

Association between multimorbidity patterns and chronic pain in elderly primary care patients: a cross-sectional observational study.

BACKGROUND: Multimorbidity is a highly prevalent health problem, which may reduce adherence, produce conflicts in treatment, and is not yet supported by evidence-based clinical recommendations. Many older people suffer from more than one chronic disease as well as from chronic pain. There is some evidence that disease management can become more complex if multimorbid patients suffer from chronic pain. In order to better consider the patients' comorbidity spectrum in clinical pain treatment recommendations, evidence is needed regarding which disease combinations are frequently related with the presence of chronic pain. Therefore, our aim is to identify diseases and disease combinations in a multimorbid population, which are associated with the patient-reported presence of chronic pain. METHODS: Analyses are based on cross-sectional data of the MultiCare Cohort Study, an observational cohort study based on interviews with 3189 multimorbid patients aged 65+, randomly selected from 158 practices, and their GPs. The response rate was 46.2 %. Data were collected in GP interviews and comprehensive patient interviews. Diseases and disease combinations associated with chronic pain were identified by CART (classification and regression tree) analyses performed separately for both genders. 46 chronic conditions were used as predictor variables and a dichotomized score from the Graded Chronic Pain Scale was used as outcome variable. RESULTS: About 60 % of the study participants were female. Women more often reported chronic pain than men. The most important predictor of a higher pain level in the female population was chronic low back problems, especially if combined with chronic gastritis, hyperuricemia/gout, cardiac insufficiency, neuropathies or depression. Regarding the pain level the male population was also divided best by chronic low back problems, especially if combined with intestinal diverticulosis, neuropathies or chronic ischemic heart disease. CONCLUSIONS: Our analyses are a first step in identifying diseases and disease combinations that are related to chronic pain. The most important condition seems to be low back problems. Back pain and pain in other body regions seems to be interrelated with cardiometabolic conditions. In women, psychosocial issues like depression also seem to be relevant. TRIAL REGISTRATION: ISRCTN89818205 .

Age-appropriate BMI cut-offs for malnutrition among older adults in India.

With the increasing prevalence of obesity in India, body mass index (BMI) has garnered importance as a disease predictor. The current World Health Organization (WHO) body mass index (BMI) cut-offs may not accurately portray these health risks in older adults aged 60 years and above. This study aims to define age-appropriate cut-offs for older adults (60-74 years and 75 years and above) and compare the performance of these cut-offs with the WHO BMI cut-offs using cardio-metabolic conditions as outcomes. Using baseline data from the Longitudinal Ageing Study in India (LASI), classification and regression tree (CART) cross-sectional analysis was conducted to obtain age-appropriate BMI cut-offs based on cardio-metabolic conditions as outcomes. Logistic regression models were estimated to compare the association of the two sets of cut-offs with cardio-metabolic outcomes. The area under the receiver operating characteristic curve (AUC), sensitivity and specificity were estimated. Agreement with waist circumference, an alternate measure of adiposity, was conducted. For older adults aged 60-74 years and 75 years and above, the cut-off for underweight reduced from < 18.5 to < 17.4 and < 13.3 respectively. The thresholds for overweight and obese increased for older adults aged 60-74 years old from > = 25 to > 28.8 and > = 30 to > 33.7 respectively. For older adults aged 75 years and above, the thresholds decreased for both categories. The largest improvement in AUC was observed in older adults aged 75 years and above. The newly derived cut-offs also demonstrated higher sensitivity and specificity among all age-sex stratifications. There is a need to adopt greater rigidity in defining overweight/obesity among older adults aged 75 years and above, as opposed to older adults aged 60-74 years old among whom the thresholds need to be less conservative. Further stratification in the low risk category could also improve BMI classification among older adults. These age-specific thresholds may act as improved alternatives of the current WHO BMI thresholds and improve classification among older adults in India.

Relationships Between Speech, Spatial and Qualities of Hearing Short Form SSQ12 Item Scores and their Use in Guiding Rehabilitation for Cochlear Implant Recipients.

Cochlear implantation successfully improves hearing in most adult recipients. However, in rare cases, post-implant rehabilitation is required to maximize benefit. The primary aim of this investigation was to test if self-reports by cochlear implant users indicate the need for post-implant rehabilitation. Listening performance was assessed with the Speech, Spatial and Qualities short-form SSQ12, which was self-administered via a web-based survey. Subjects included over 2000 adult bilateral or unilateral cochlear implant users with at least one year of experience. A novel application of regression tree analysis identified core SSQ12 items that serve as first steps in establishing a plan for further rehabilitation: items 1, 8, and 11 dealing with single-talker situations, loudness perception, and clarity, respectively. Further regression and classification tree analyses revealed that SSQ12 item scores were weakly related to age, degree of tinnitus, and use of bilateral versus unilateral implants. Conversely, SSQ12 scores were strongly associated with self-rated satisfaction and confidence in using their cochlear implant. The SSQ12 total scores did not vary significantly over 1-9 or more years' experience. These findings suggest that the SSQ12 may be a useful tool to guide rehabilitation at any time after cochlear implantation. Identification of poor performance may have implications for timely management to improve the outcomes, through various techniques such as device fitting adjustments, counseling, active sound exposure, and training spatial hearing.

Impact of compensatory growth on survival in newborn kittens.

In the feline species, the mortality of live-born kittens over the first 2 months of life is around 10%. Although some losses are inevitable, progress in veterinary medicine and improved knowledge of feline neonatalogy should make it possible to reduce them to a lower level. The objectives of this study were: (i) to describe early growth in kittens, and (ii) to assess whether low birth weight kittens develop compensatory growth during the first week of life and if so, whether compensatory growth is associated with increased chances of survival. Using data collected from 5,504 kittens born in 193 different French catteries, five growth rates were calculated to reflect the growth of kittens during the first week after birth. Low birth weight kittens had higher growth rates than normal birth weight kittens. In addition, low birth weight kittens whose early growth was in the lowest 25% had a significantly higher 0-2 months mortality rate than all the other groups. Weight loss (or lack of weight gain) between birth and Day 2 was identified as a risk factor for 0-2 months mortality whatever the birth weight category. Finally, critical early growth thresholds were determined separately for low and normal birth weight kittens. These figures could help caregivers to validate the adequacy or inadequacy of kitten early growth. They will be able to quickly identify and provide appropriate care for the kittens whose growth is deemed insufficient in order to improve their chances of survival.

Further Clarification of Pain Management Complexity in Radiotherapy: Insights from Modern Statistical Approaches.

BACKGROUND: The primary objective of this study was to assess the adequacy of analgesic care in radiotherapy (RT) patients, with a secondary objective to identify predictive variables associated with pain management adequacy using a modern statistical approach, integrating the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and the Classification and Regression Tree (CART) analysis. METHODS: This observational, multicenter cohort study involved 1387 patients reporting pain or taking analgesic drugs from 13 RT departments in Italy. The Pain Management Index (PMI) served as the measure for pain control adequacy, with a PMI score < 0 indicating suboptimal management. Patient demographics, clinical status, and treatment-related factors were examined to discern the predictors of pain management adequacy. RESULTS: Among the analyzed cohort, 46.1% reported inadequately managed pain. Non-cancer pain origin, breast cancer diagnosis, higher ECOG Performance Status scores, younger patient age, early assessment phase, and curative treatment intent emerged as significant determinants of negative PMI from the LASSO analysis. Notably, pain management was observed to improve as RT progressed, with a greater discrepancy between cancer (33.2% with PMI < 0) and non-cancer pain (73.1% with PMI < 0). Breast cancer patients under 70 years of age with non-cancer pain had the highest rate of negative PMI at 86.5%, highlighting a potential deficiency in managing benign pain in younger patients. CONCLUSIONS: The study underscores the dynamic nature of pain management during RT, suggesting improvements over the treatment course yet revealing specific challenges in non-cancer pain management, particularly among younger breast cancer patients. The use of advanced statistical techniques for analysis stresses the importance of a multifaceted approach to pain management, one that incorporates both cancer and non-cancer pain considerations to ensure a holistic and improved quality of oncological care.

Classification and regression tree (CART) analysis of endometrial carcinoma: Seeing the forest for the trees.

OBJECTIVE: The objectives of the study are to evaluate which clinicopathologic factors influenced overall survival (OS) in endometrial carcinoma and to determine if the surgical effort to assess para-aortic (PA) lymph nodes (LNs) at initial staging surgery impacts OS. METHODS: All patients diagnosed with endometrial cancer from 1/1993-12/2011 who had LNs excised were included. PALN assessment was defined by the identification of one or more PALNs on final pathology. A multivariate analysis was performed to assess the effect of PALNs on OS. A form of recursive partitioning called classification and regression tree (CART) analysis was implemented. Variables included: age, stage, tumor subtype, grade, myometrial invasion, total LNs removed, evaluation of PALNs, and adjuvant chemotherapy. RESULTS: The cohort included 1920 patients, with a median age of 62 years. The median number of LNs removed was 16 (range, 1-99). The removal of PALNs was not associated with OS (P=0.450). Using the CART hierarchically, stage I vs. stages II-IV and grades 1-2 vs. grade 3 emerged as predictors of OS. If the tree was allowed to grow, further branching was based on age and myometrial invasion. Total number of LNs removed and assessment of PALNs as defined in this study were not predictive of OS. CONCLUSION: This innovative CART analysis emphasized the importance of proper stage assignment and a binary grading system in impacting OS. Notably, the total number of LNs removed and specific evaluation of PALNs as defined in this study were not important predictors of OS.

Predicting risk of 2-year incident dementia using the CAMCOG total and subscale scores.

BACKGROUND: being able to identify individuals at high risk of dementia is important for diagnostics and intervention. Currently, there is no standard approach to assessing cognitive function in older aged individuals to best predict incident dementia. OBJECTIVE: to identify cognitive changes associated with an increased risk of 2-year incident dementia using the Cambridge Cognitive Examination (CAMCOG). DESIGN: longitudinal population representative sample aged 65+ years. METHODS: individuals were from the Medical Research Council Cognitive Function and Ageing Study. Classification and Regression Tree analysis was used to detect the optimal cut-off value for the CAMCOG total, subscales and composite memory and non-memory scores, for predicting dementia. Sensitivity and specificity of each cut-off score were assessed. RESULTS: from the 2,053 individuals without dementia at the first assessment, 137 developed dementia at the 2-year follow-up. The results indicate similar discriminative accuracy for incident dementia based on the CAMCOG total, memory subscale and composite scores. However, sensitivity and specificity of cut-off values were generally moderate. Scores on the non-memory subscales generally had high sensitivity but low specificity. Compared with the CAMCOG total score they had significantly lower discriminative accuracy. CONCLUSION: in a population setting, cut-off scores from the CAMCOG memory subscales predicted dementia with reasonable accuracy. Scores on the non-memory scales have lower accuracy and are not recommend for predicting high-risk cases unless all non-memory subdomain scores are combined. The added value of cognition when assessed using the CAMCOG to other risk factors (e.g. health and genetics) should be tested within a risk prediction framework.

Low level of BRCA2 in peripheral blood lymphocytes is associated with an increased risk for head and neck squamous cell carcinoma (HNSCC) in a population of North-East India: a case-control study.

Background: We investigated the role of DNA repair proteins breast cancer susceptibility 2 (BRCA2), xeroderma pigmentosum group D (XPD) and apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) in determining the risk for head and neck squamous cell cancer (HNSCC) in a case-control study from North-East India. Methods: Expression of BRCA2, XPD and APE1 genes in the matched tumour, normal adjacent tissue (NAT) and blood of 12 HNSCC patients and blood of 8 age- and gender-matched controls was determined by quantitative real-time PCR. Results were validated by expression analysis of the corresponding proteins in the peripheral blood lymphocytes (PBLs) of 228 subjects (106 patients and 122 controls) by a slot-blot immunoassay. Findings: Expression of the BRCA2 and XPD genes in tumour tissue of HNSCC patients declined progressively as the cancer stage advanced, was reverse that of the NAT, but was mirrored by the expression in the blood. BRCA2 and XPD proteins were significantly (p < 0.0001) downregulated in the PBL of HNSCC patients to 71% and 77% the levels in controls, showing significant negative correlation with HNSCC stage (Spearman correlation coefficient (r s) of -0.9060, p < 0.0001 for BRCA2; r s of -0.8008, p < 0.01 for XPD). On the contrary, APE1 was significantly upregulated in PBL of HNSCC patients to 1.47 fold the level in controls, showing significant positive correlation with HNSCC stage (r s of 0.7023, p < 0.01). Classification and regression tree analyses predicted low levels of BRCA2 protein in PBL as the single most important risk factor for HNSCC, independent of gender. Smokers above 36 years of age with low level of BRCA2 appeared to exhibit a 1.78-fold increased risk for HNSCC (with a 1.78-fold increased risk for HNSCC (OR = 1.78, 95% confidence interval (CI) = 0.33-9.52) though this risk was not significant statistically. Similarly, low levels of BRCA2 appeared to indicate a moderate, but non-significant risk for HNSCC in non-smokers aged between 36 and 56 years (OR = 1.15, 95% CI = 0.21-6.37). Conclusions: Low level of BRCA2 protein in the peripheral blood indicates increased risk for HNSCC.

A classification and regression tree analysis identifies subgroups of childhood type 1 diabetes.

BACKGROUND: Diabetes in childhood and adolescence includes autoimmune and non-autoimmune forms with heterogeneity in clinical and biochemical presentations. An unresolved question is whether there are subtypes, endotypes, or theratypes within these forms of diabetes. METHODS: The multivariable classification and regression tree (CART) analysis method was used to identify subgroups of diabetes with differing residual C-peptide levels in patients with newly diagnosed diabetes before 20 years of age (n=1192). The robustness of the model was assessed in a confirmation and prognosis cohort (n=2722). FINDINGS: The analysis selected age, haemoglobin A1c (HbA1c), and body mass index (BMI) as split parameters that classified patients into seven islet autoantibody-positive and three autoantibody-negative groups. There were substantial differences in genetics, inflammatory markers, diabetes family history, lipids, 25-OH-Vitamin D3, insulin treatment, insulin sensitivity and insulin autoimmunity among the groups, and the method stratified patients with potentially different pathogeneses and prognoses. Interferon-É£ and/or tumour necrosis factor inflammatory signatures were enriched in the youngest islet autoantibody-positive groups and in patients with the lowest C-peptide values, while higher BMI and type 2 diabetes characteristics were found in older patients. The prognostic relevance was demonstrated by persistent differences in HbA1c at 7 years median follow-up. INTERPRETATION: This multivariable analysis revealed subgroups of young patients with diabetes that have potential pathogenetic and therapeutic relevance. FUNDING: The work was supported by funds from the German Federal Ministry of Education and Research (01KX1818; FKZ 01GI0805; DZD e.V.), the Innovative Medicine Initiative 2 Joint Undertaking INNODIA (grant agreement No. 115797), the German Robert Koch Institute, and the German Diabetes Association.

Prediction Tool to Identify Children at Highest Risk of Tuberculosis Disease Progression Among Those Exposed at Home.

BACKGROUND: There is a dearth of research to understand which children, among those who are exposed at home to tuberculosis (TB), are at the highest risk of TB disease, to tailor care. We sought to identify predictors of TB progression in children. METHODS: We conducted a prospective cohort study of children living with adults with pulmonary TB in Lima, Peru (2009-2012). We applied classification and regression tree analysis to examine potential predictors of incident TB disease during 12 months in 3 age groups (0-4, 5-9, and 10-14 years). We calculated the relative risk (RR) for top predictors in each age group. RESULTS: Among 4545 children 0-14 years old, 156 (3.4%) were diagnosed with TB within 1 year of household exposure to TB (3.4%, 2.3%, and 4.7% in children 0-4, 5-9, and 10-14 years old, respectively). The most important predictor of TB was having a positive tuberculin skin test (TST) result, with RRs of 6.6 (95% CI, 4.0-10.7), 6.6 (95% CI, 3.2-13.6), and 5.2 (95% CI, 3.0-9.0) in the age groups 0-4, 5-9, and 10-14 years, respectively. In young children with a positive TST, not using isoniazid preventive treatment further increased risk of disease (RR, 12.2 [95% CI, 3.8-39.2]). CONCLUSIONS: We present a tool that identifies child household contacts at high risk of TB disease progression based on data collected during contact tracing. In addition to the use of TB preventive therapy for all children exposed at home to TB, those children at highest risk of progressing to TB disease may benefit from more frequent follow-up.

Integrated Clinical and Magnetic Resonance Imaging Assessments Late After Fontan Operation.

BACKGROUND: Several clinical and cardiac magnetic resonance (CMR)-derived parameters have been shown to be associated with death or heart transplant late after the Fontan operation. OBJECTIVES: The objective of this study was to identify the relative importance and interactions of clinical and CMR-based parameters for risk stratification after the Fontan operation. METHODS: Fontan patients were retrospectively reviewed. Clinical and CMR parameters were analyzed using univariable Cox regression. The primary endpoint was time to death or (listing for) heart transplant. To identify the patients at highest risk for the endpoint, classification and regression tree survival analysis was performed, including all significant variables from Cox regression. RESULTS: The cohort consisted of 416 patients (62% male) with a median age of 16 years (25th, 75th percentiles: 11, 23 years). Over a median follow-up of 5.4 years (25th, 75th percentiles: 2.4, 10.0 years) after CMR, 57 patients (14%) reached the endpoint (46 deaths, 7 heart transplants, 4 heart transplant listings). Lower total indexed end-diastolic volume (EDVi) was the strongest predictor of transplant-free survival. Among patients with dilated ventricles (EDVi ≥156 ml/BSA1.3), worse global circumferential strain (GCS) was the next most important predictor (73% vs. 44%). In patients with smaller ventricles (EDVi <156 ml/BSA1.3), New York Heart Association functional class ≥II was the next most important predictor (30% vs. 4%). CONCLUSIONS: In this cohort of patients late after Fontan operation, increased ventricular dilation was the strongest independent predictor of death or transplant (listing). Patients with both ventricular dilation and worse GCS were at highest risk. These data highlight the value of integrating CMR and clinical parameters for risk stratification in this population.

Prognostic Value of the Three-Dimensional Right Ventricular Ejection Fraction in Patients With Asymptomatic Aortic Stenosis.

Background: The right ventricular (RV) function is an important prognostic marker of asymptomatic aortic stenosis (AS). However, previous publications have not addressed the additive value of conventional RV parameters over left heart parameters. Whether three-dimensional echocardiography (3DE)-derived RV ejection fraction (RVEF) has prognostic utility independent of 3DE derived left heart parameters is also unknown. We investigated the prognostic utility of 3DE RVEF in patients with asymptomatic AS. Methods: We retrospectively selected 392 asymptomatic AS patients. RVEF, left ventricular ejection fraction (LVEF) and left atrial volumes (LAVs) were measured using 3DE datasets. We determined the association of those parameters, as well as of aortic valve replacement (AVR), and Charlson's comorbidity index with cardiac events. We also analyzed whether RVEF has incremental value over two-dimensional echocardiography (2DE) RV parameters. Results: During a median follow-up of 27 months, 57 patients developed cardiac events, and 68 patients received AVR. Univariate Cox proportional hazard analysis revealed that RVEF was associated with cardiac events (p < 0.001). Multivariate analysis revealed that RVEF was significantly associated with cardiac events (p < 0.001) even after adjusting for AVR, Charlson's comorbidity index, LVEF, LAV, E/e', and indexed aortic valve area (iAVA). An incremental value of RVEF over left heart parameters was also demonstrated using a nested regression model. Classification and regression-tree analysis selected RVEF first with a cut-off value of 41%. RVEF had incremental value over iAVA, LVEF, and 2DE conventional RV parameters for its association with future outcomes. Conclusions: 3DE RVEF had significant prognostic value even after adjusting for comorbidities, left heart parameters, and conventional 2DE RV parameters in asymptomatic aortic stenosis.

Sleeping patterns and childhood obesity: an epidemiological study in 1,728 children in Greece.

STUDY OBJECTIVES: Sleep is an essential normal function for children's growth and development, but over the years, lifestyle changes have resulted in insufficient sleep, a factor that may be associated with increased childhood obesity. The aim of this study was to evaluate the association between sleep duration and sleep patterns separately on weekdays and weekends regarding children's weight status. METHODS: This study was conducted among Greek students (55.1% girls) in 2014-2016. Children's weight status was classified according to the International Obesity Task Force tables and guidelines. Sleep duration was determined based on the sleep and wake time that children reported, separately for weekdays and weekends. Classification and regression tree analysis was used to derive sleep patterns and evaluate their relation to children's weight status. RESULTS: Multiadjusted analysis revealed an inverse association between average duration of sleep on weekdays and weekends with the likelihood of being overweight/obese (odds ratio per 1 hour 0.82; 95% confidence interval, 0.73-0.92). This was more prominent on weekends than on weekdays. Children who had lower duration on weekdays, but catch-up sleep duration on weekends, were 2% (95% confidence interval, 0.97-0.99) less likely to be overweight/obese compared to those children having both less or increased sleep duration on weekdays and weekends. CONCLUSIONS: Sleep duration and sleep patterns seem to be associated with childhood weight status. Interventions should be developed to educate parents on the importance of an adequate sleep duration and healthy sleep patterns for their children's healthy development.

CART-analysis embedded in social theory: A case study comparing quantitative data analysis strategies for intersectionality-based public health monitoring within and beyond the binaries.

Implementation of an intersectionality perspective into quantitative health research might support the process of unravelling complex socio-cultural and economic power relations which underly and shape patterns of health and disease within populations. Intersectionality-informed health monitoring and health reporting integrating a sex/gender-sensitive perspective could serve as a fertile ground to strengthen the essential function of health reporting to support political decision-making. We aimed at the integration of social theory into quantitative data analysis by taking into consideration 4 distinct central sex/gender theoretical concepts in health research. We developed and tested an intersectionality-based, sex/gender-sensitive strategy comparing 5 distinct models based on different combinations of the binary sex/gender variable, socio-cultural and economic variables (defined from an intersectionality perspective) as well as solution-linked sex/gender variables. We used CART-analysis as a quantitative, non-parametric, exploratory method to detect subgroups with high prevalence of frequent mental distress (FMD). Analyses were based on data from a National Health Telephone Interview Survey conducted in Germany. Depending on model and detected subgroup of our comparative approach, prevalence of FMD ranged between approximately 5 %-25%. Within the model including the binary sex/gender variable, socio-cultural and economic variables, sex/gender turned out to be the most important attribute. Comparing the models which included solution-linked sex/gender variables to the model not including these variables illustrated that the CART-algorithm was able to detect subgroups with the same prevalence of FMD, but with approximately 14% as opposed to 4.5% of the study population being affected. For these models, social support served as the primary splitting variable and not the binary sex/gender variable. Including or not including the binary sex/gender variable in the models with the solution-linked variables did not make a substantial difference. Embedding CART-analysis in social theory might have the potential to further sex/gender sensitivity in health reporting and might support decision-making when considering the allocation of health-related interventions.

An Algorithm for the Diagnosis of Behçet Disease Uveitis in Adults.

Purpose: To develop an algorithm for the diagnosis of Behçet's disease (BD) uveitis based on ocular findings.Methods: Following an initial survey among uveitis experts, we collected multi-center retrospective data on 211 patients with BD uveitis and 207 patients with other uveitides, and identified ocular findings with a high diagnostic odds ratio (DOR). Subsequently, we collected multi-center prospective data on 127 patients with BD uveitis and 322 controls and developed a diagnostic algorithm using Classification and Regression Tree (CART) analysis and expert opinion.Results: We identified 10 items with DOR >5. The items that provided the highest accuracy in CART analysis included superficial retinal infiltrate, signs of occlusive retinal vasculitis, and diffuse retinal capillary leakage as well as the absence of granulomatous anterior uveitis or choroiditis in patients with vitritis.Conclusion: This study provides a diagnostic tree for BD uveitis that needs to be validated in future studies.

Behavioral and Psychological Symptoms of Dementia (BPSD): Clinical Characterization and Genetic Correlates in an Italian Alzheimer's Disease Cohort.

BACKGROUND: The occurrence of Behavioral and Psychological Symptoms of Dementia (BPSD) in Alzheimer's Disease (AD) patients hampers the clinical management and exacerbates the burden for caregivers. The definition of the clinical distribution of BPSD symptoms, and the extent to which symptoms are genetically determined, are still open to debate. Moreover, genetic factors that underline BPSD symptoms still need to be identified. PURPOSE: To characterize our Italian AD cohort according to specific BPSD symptoms as well as to endophenotypes. To evaluate the associations between the considered BPSD traits and COMT, MTHFR, and APOE genetic variants. METHODS: AD patients (n = 362) underwent neuropsychological examination and genotyping. BPSD were assessed with the Neuropsychiatric Inventory scale. RESULTS: APOE and MTHFR variants were significantly associated with specific single BPSD symptoms. Furthermore, "Psychosis" and "Hyperactivity" resulted in the most severe endophenotypes, with APOE and MTHFR implicated as both single risk factors and "genexgene" interactions. CONCLUSIONS: We strongly suggest the combined use of both BPSD single symptoms/endophenotypes and the "genexgene" interactions as valid strategies for expanding the knowledge about the BPSD aetiopathogenetic mechanisms.