The National Cancer Database Conforms to the Standardized Framework for Registry and Data Quality.

BACKGROUND: Standardization of procedures for data abstraction by cancer registries is fundamental for cancer surveillance, clinical and policy decision-making, hospital benchmarking, and research efforts. The objective of the current study was to evaluate adherence to the four components (completeness, comparability, timeliness, and validity) defined by Bray and Parkin that determine registries' ability to carry out these activities to the hospital-based National Cancer Database (NCDB). METHODS: Tbis study used data from U.S. Cancer Statistics, the official federal cancer statistics and joint effort between the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute (NCI), which includes data from National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results (SEER) to evaluate NCDB completeness between 2016 and 2020. The study evaluated comparability of case identification and coding procedures. It used Commission on Cancer (CoC) standards from 2022 to assess timeliness and validity. RESULTS: Completeness was demonstrated with a total of 6,828,507 cases identified within the NCDB, representing 73.7% of all cancer cases nationwide. Comparability was followed using standardized and international guidelines on coding and classification procedures. For timeliness, hospital compliance with timely data submission was 92.7%. Validity criteria for re-abstracting, recording, and reliability procedures across hospitals demonstrated 94.2% compliance. Additionally, data validity was shown by a 99.1% compliance with histologic verification standards, a 93.6% assessment of pathologic synoptic reporting, and a 99.1% internal consistency of staff credentials. CONCLUSION: The NCDB is characterized by a high level of case completeness and comparability with uniform standards for data collection, and by hospitals with high compliance, timely data submission, and high rates of compliance with validity standards for registry and data quality evaluation.

Survival Among Patients With High-Risk Gastrointestinal Cancers During the COVID-19 Pandemic.

Importance: Prior reports demonstrated that patients with cancer experienced worse outcomes from pandemic-related stressors and COVID-19 infection. Patients with certain malignant neoplasms, such as high-risk gastrointestinal (HRGI) cancers, may have been particularly affected. Objective: To evaluate disruptions in care and outcomes among patients with HRGI cancers during the COVID-19 pandemic, assessing for signs of long-term changes in populations and survival. Design, Setting, and Participants: This retrospective cohort study used data from the National Cancer Database to identify patients with HRGI cancer (esophageal, gastric, primary liver, or pancreatic) diagnosed between January 1, 2018, and December 31, 2020. Data were analyzed between August 23 and September 4, 2023. Main Outcome and Measures: Trends in monthly new cases and proportions by stage in 2020 were compared with the prior 2 years. Kaplan-Meier curves and Cox regression were used to assess 1-year mortality in 2020 compared with 2018 to 2019. Proportional monthly trends and multivariable logistic regression were used to evaluate 30-day and 90-day mortality in 2020 compared with prior years. Results: Of the 156 937 patients included in this study, 54 994 (35.0%) were aged 60 to 69 years and 100 050 (63.8%) were men. There was a substantial decrease in newly diagnosed HRGI cancers in March to May 2020, which returned to prepandemic levels by July 2020. For stage, there was a proportional decrease in the diagnosis of stage I (-3.9%) and stage II (-2.3%) disease, with an increase in stage IV disease (7.1%) during the early months of the pandemic. Despite a slight decrease in 1-year survival rates in 2020 (50.7% in 2018 and 2019 vs 47.4% in 2020), survival curves remained unchanged between years (all P > .05). After adjusting for confounders, diagnosis in 2020 was not associated with increased 1-year mortality compared with 2018 to 2019 (hazard ratio, 0.99; 95% CI, 0.97-1.01). The rates of 30-day (2.1% in 2018, 2.0% in 2019, and 2.1% in 2020) and 90-day (4.3% in 2018, 4.4% in 2019, and 4.6% in 2020) operative mortality also remained similar. Conclusions and Relevance: In this retrospective cohort study, a period of underdiagnosis and increase in stage IV disease was observed for HRGI cancers during the pandemic; however, there was no change in 1-year survival or operative mortality. These results demonstrate the risks associated with gaps in care and the tremendous efforts of the cancer community to ensure quality care delivery during the pandemic. Future research should investigate long-term survival changes among all cancer types as additional follow-up data are accrued.

Data-driven optimization of version 9 American Joint Committee on Cancer staging system for anal cancer.

INTRODUCTION: The American Joint Committee on Cancer (AJCC) staging system undergoes periodic revisions to maintain contemporary survival outcomes related to stage. Recently, the AJCC has developed a novel, systematic approach incorporating survival data to refine stage groupings. The objective of this study was to demonstrate data-driven optimization of the version 9 AJCC staging system for anal cancer assessed through a defined validation approach. METHODS: The National Cancer Database was queried for patients diagnosed with anal cancer in 2012 through 2017. Kaplan-Meier methods analyzed 5-year survival by individual clinical T category, N category, M category, and overall stage. Cox proportional hazards models validated overall survival of the revised TNM stage groupings. RESULTS: Overall, 24,328 cases of anal cancer were included. Evaluation of the 8th edition AJCC stage groups demonstrated a lack of hierarchical prognostic order. Survival at 5 years for stage I was 84.4%, 77.4% for stage IIA, and 63.7% for stage IIB; however, stage IIIA disease demonstrated a 73.0% survival, followed by 58.4% for stage IIIB, 59.9% for stage IIIC, and 22.5% for stage IV (p <.001). Thus, stage IIB was redefined as T1-2N1M0, whereas Stage IIIA was redefined as T3N0-1M0. Reevaluation of 5-year survival based on data-informed stage groupings now demonstrates hierarchical prognostic order and validated via Cox proportional hazards models. CONCLUSION: The 8th edition AJCC survival data demonstrated a lack of hierarchical prognostic order and informed revised stage groupings in the version 9 AJCC staging system for anal cancer. Thus, a validated data-driven optimization approach can be implemented for staging revisions across all disease sites moving forward.

Alterations in Cancer Treatment During the First Year of the COVID-19 Pandemic in the US.

Importance: The COVID-19 pandemic created challenges to the evaluation and treatment of cancer, and abrupt resource diversion toward patients with COVID-19 put cancer treatment on hold for many patients. Previous reports have shown substantial declines in cancer screening and diagnoses in 2020; however, the extent to which the delivery of cancer care was altered remains unclear. Objective: To assess alterations in cancer treatment in the US during the first year of the COVID-19 pandemic. Design, Setting, and Participants: This retrospective cohort study used data from the National Cancer Database (NCDB) on patients older than 18 years with newly diagnosed cancer from January 1, 2018, to December 31, 2020. Main Outcomes and Measures: The main outcomes were accessibility (time to treatment, travel distance, and multi-institutional care), availability (proportional changes in cancer treatment between years), and utilization (reductions by treatment modality, hospital type) of cancer treatment in 2020 compared with 2018 to 2019. Autoregressive models forecasted expected findings for 2020 based on observations from prior years. Results: Of 1 229 654 patients identified in the NCDB in 2020, 1 074 225 were treated for cancer, representing a 16.8% reduction from what was expected. Patients were predominately female (53.8%), with a median age of 66 years (IQR, 57-74 years), similar to demographics in 2018 and 2019. Median time between diagnosis and treatment was 26 days (IQR, 0-36 days) in 2020, and median travel distance for care was 11.1 miles (IQR, 5.0-25.3 miles), similar to 2018 and 2019. In 2020, fewer patients traveled longer distances (20.2% reduction of patients traveling >35 miles). The proportions of patients treated with chemotherapy (32.0%), radiation (29.5%), and surgery (57.1%) were similar to those in 2018 and 2019. Overall, 146 805 fewer patients than expected underwent surgery, 80 480 fewer received radiation, and 68 014 fewer received chemotherapy. Academic hospitals experienced the greatest reduction in cancer surgery and treatment, with a decrease of approximately 484 patients (-19.0%) per hospital compared with 99 patients (-12.6%) at community hospitals and 110 patients (-12.8%) at integrated networks. Conclusions and Relevance: This study found that among patients diagnosed with cancer in 2020, access and availability of treatment remained intact; however, reductions in treated patients varied across treatment modalities and were greater at academic hospitals than at community hospitals and integrated networks compared with expected values. These results suggest the resilience of cancer service lines and frame the economic losses from reductions in cancer treatment during the pandemic.

Survival outcomes used to validate version 9 of the American Joint Committee on Cancer staging system for appendiceal cancer.

The standard for cancer staging in the United States for all cancer sites, including primary carcinomas of the appendix, is the American Joint Committee on Cancer (AJCC) staging system. AJCC staging criteria undergo periodic revisions, led by a panel of site-specific experts, to maintain contemporary staging definitions through the evaluation of new evidence. Since its last revision, the AJCC has restructured its processes to include prospectively collected data because large data sets have become increasingly robust and available over time. Thus survival analyses using AJCC eighth edition staging criteria were used to inform stage group revisions in the version 9 AJCC staging system, including appendiceal cancer. Although the current AJCC staging definitions were maintained for appendiceal cancer, incorporating survival analysis into the version 9 staging system provided unique insight into the clinical challenges in staging rare malignancies. This article highlights the critical clinical components of the now published version 9 AJCC staging system for appendix cancer, which (1) justified the separation of three different histologies (non-mucinous, mucinous, signet-ring cell) in terms of prognostic variance, (2) demonstrated the clinical implications and challenges in staging heterogeneous and rare tumors, and (3) emphasized the influence of data limitations on survival analysis for low-grade appendiceal mucinous neoplasms.

Orthostatic intolerance and neurocognitive impairment in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Objectives: The Institute of Medicine (IOM 2015. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington: The National Academies Press) suggested new criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), which requires an endorsement of either neurocognitive impairment or orthostatic intolerance (OI) in addition to other core symptoms. While some research supports the inclusion of OI as a core symptom, others argue that overlap with neurocognitive impairment does not justify the either/or option. The current study assessed methods of operationalizing OI using items from the DePaul Symptom Questionnaire (DSQ-1 and -2) as a part of the IOM criteria. Evaluating the relationship between OI and neurocognitive symptoms may lead to a better understanding of diagnostic criteria for ME/CFS. Methods: Two-hundred and forty-two participants completed the DSQ. We examined how many participants met the IOM criteria while endorsing different frequencies and severities of various OI symptoms. Results: Neurocognitive impairment was reported by 93.4% of respondents. OI without concurrent neurocognitive symptoms only allowed for an additional 1.7-4.5% of participants to meet IOM criteria. Conclusions: Neurocognitive symptoms and OI overlap in ME/CFS, and our results do not support the IOM's inclusion of neurocognitive impairment and OI as interchangeable symptoms. Furthermore, our findings highlight the need for a uniform method of defining and measuring OI via self-report in order to accurately study OI as a symptom of ME/CFS.

Evaluating information loss in the National Cancer Database from cases lost to follow-up.

BACKGROUND AND OBJECTIVES: Cancer registries must focus on data capture which returns value while reducing resource burden with minimal loss of data. Identifying the optimum length of follow-up data collection for patients with cancer achieves this goal. METHODS: A two-step analysis using entropy calculations to assess information gain for each follow-up year, and second-order differences to compare survival outcomes between the defined follow-up periods and lifetime follow-up. A total of 391 567 adult cases, deidentified in the National Cancer Database and diagnosed in 1989. Comparisons examined a subset of 61 908 lung cancer cases, 48 387 colon and rectal cancer cases, and 64 134 breast cancer cases in adults. A total of 4133 pediatric cases were diagnosed in 1989 examining 1065 leukemia cases and 494 lymphoma cases. RESULTS: Annual increases in information gain fell below 1% after 16 years of follow-up for adult cases and 9 years for pediatric cases. Comparison of second-order differences showed 62% of the comparisons were similar between 15 years and lifetime follow-up when examining restricted mean survival time. In addition, 90% of the comparisons were statistically similar when comparing hazard ratios. CONCLUSIONS: Survival analysis using 15 years postdiagnosis follow-up showed minimal differences in information gain compared to lifetime follow-up.

Predictors for Developing Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Following Infectious Mononucleosis.

Background: About 10% of individuals who contract infectious mononucleosis (IM) have symptoms 6 months later that meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Our study for the first time examined whether it is possible to predict who will develop ME/CFS following IM. Methods: We have reported on a prospectively recruited cohort of 4,501 college students, of which 238 (5.3%) developed IM. Those who developed IM were followed-up at six months to determine whether they recovered or met criteria for ME/CFS. The present study focuses on 48 students who after six months had a diagnosis of ME/CFS, and a matched control group of 58 students who had no further symptoms after their IM. All of these 106 students had data at baseline (at least 6 weeks prior to the development of IM), when experiencing IM, and 6 months following IM. Of those who did not recover from IM, there were two groups: 30 were classified as ME/CFS and 18 were classified as severe ME/CFS. We measured the results of 7 questionnaires, physical examination findings, the severity of mononucleosis and cytokine analyses at baseline (pre-illness) and at the time of IM. We examined predictors (e.g., pre-illness variables as well as variables at onset of IM) of those who developed ME/CFS and severe ME/CFS following IM. Results: From analyses using receiver operating characteristic statistics, the students who had had severe gastrointestinal symptoms of stomach pain, bloating, and an irritable bowel at baseline and who also had abnormally low levels of the immune markers IL-13 and/or IL-5 at baseline, as well as severe gastrointestinal symptoms when then contracted IM, were found to have a nearly 80% chance of having severe ME/CFS persisting six months following IM. Conclusions: Our findings are consistent with emerging literature that gastrointestinal distress and autonomic symptoms, along with several immune markers, may be implicated in the development of severe ME/CFS.

Causal attributions and perceived stigma for myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic disease with the hallmark symptom of post-exertional malaise. Evidence for physiological causes is converging, however, currently no diagnostic test or biomarker is available. People with ME/CFS experience stigmatization, including the perception that the disease is psychosomatic. In a sample of 499 participants with self-diagnosed ME/CFS, we investigated perceived stigma as a pathway through which perceived others' causal attributions relate to lower satisfaction with social roles and activities and functional status. Higher perceived attributions by others to controllable and unstable causes predicted lower health-related and social outcomes via higher perceived stigma.

Risk factors for suicide in chronic fatigue syndrome.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) includes symptoms such as post-exertional malaise, unrefreshing sleep, and cognitive impairments. Several studies suggest these patients have an increased risk of suicidal ideation and early mortality, although few have published in this area. This study explores risk factors for suicide among 64 individuals with ME/CFS using archival data, 17 of which died from suicide. Results indicated an increased risk of suicide for those for those utilizing the label CFS, for those with limited overall functioning, and for those without comorbid illnesses. Findings suggest that stigma and functional impairments limit access to care and social supports.

College student symptoms as assessed by a student health survey.

ObjectiveWe sought to identify the general health of college students.ParticipantsA total of 4402 university freshmen and sophomores were recruited to report their general health through an online questionnaire.MethodsResponses from the DePaul Symptom Questionnaire were analyzed. We then conducted latent class analyses to evaluate 54 different symptoms among participants.ResultsA four class solution was identified, consisting of a group of asymptomatic students (35.65%), a second group of students reporting mild fatigue and sleep symptoms (38.87%), a third group reporting moderate sleep and fatigue symptoms (20.36%), and a group reporting moderate and severe complaints on the majority of symptoms (5.11%). Female students had 2.07 times the relative risk of the severe symptom class of men. Indigenous students have 2.88 times the relative risk of occupying the severe symptom class than non-indigenous students.ConclusionsThe results suggest that about 5% of college students have varied symptoms of a moderate to severe degree. Future research is needed to better assess whether there are biological associations with these self-report findings, as well as to determine longer-term implications of these symptoms.

FIGO staging for carcinoma of the vulva: 2021 revision.

To revise the FIGO staging for carcinoma of the vulva using a new approach that involves analyses of prospectively collected data. The FIGO Committee for Gynecologic Oncology reviewed the recent literature to gain an insight into the impact of the 2009 vulvar cancer staging revision. The Committee resolved to revise the staging with a goal of simplification and actively collaborated with the United States National Cancer Database to analyze prospectively collected data on carcinoma of the vulva. Many tumor characteristics were collected for all stages of vulvar cancer treated between 2010 and 2017. Statistical analysis was performed with SAS software. Overall survival was estimated based on tumor characteristics. Log-rank and Wilcoxon tests were used to analyze overall survival similarities between and within groups of tumor characteristics. Characteristics with similar survivals were then grouped into the same stages and substages. Kaplan-Meier overall survival curves were generated for the resulting stages and substages. There were 12 063 cases with available data. The resulting new staging for carcinoma of the vulva has two substages in Stage I, no substage in Stage II, three substages in Stage III, and two substages in Stage IV. The Kaplan-Meier overall survival curves showed clear separation between stages and substages. The 2021 vulvar cancer staging is the first from the FIGO Committee for Gynecologic Oncology to be derived from data analyses. This revision has a new definition for depth of invasion, uses the same definition for lymph node metastases utilized in cervical cancer, and allows findings from cross-sectional imaging to be incorporated into vulvar cancer staging. The 2021 FIGO staging for carcinoma of the vulva is data-derived, validated, and much simpler than earlier revisions.

COVID-19 Symptoms Over Time: Comparing Long-Haulers to ME/CFS.

INTRODUCTION: Our objective was to determine which symptoms among long-hauler COVID-19 patients change over time, and how their symptoms compare to another chronic illness group. 278 long-haulers completed two symptom questionnaires at one time point, with one recounting experiences from an average of 21.7 weeks prior. METHODS: We used a comparison group of 502 patients diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Participants completed a standardized symptom questionnaire and a list of additional CDC COVID-19 symptoms. RESULTS: Over time, the long-haulers reported an overall reduction of most symptoms including unrefreshing sleep and post-exertional malaise, but an intensification of neurocognitive symptoms. When compared to ME/CFS, the COVID-19 sample was initially more symptomatic for the immune and orthostatic domains but over time, the long-haulers evidenced significantly less severe symptoms than those with ME/CFS, except in the orthostatic domain. Among the COVID-19 long haulers, several neurocognitive symptoms got worse over time, whereas improvements occurred in most other areas. CONCLUSIONS: These types of differential patterns of symptoms over time might contribute to helping better understand the pathophysiology of those reporting prolonged illness following COVID-19.

Risks for Developing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in College Students Following Infectious Mononucleosis: A Prospective Cohort Study.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) involves severe fatigue, unrefreshing sleep, and cognitive impairment, leading to functional difficulties; prior studies have not evaluated risk factors with behavioral and immune data collected before developing ME/CFS. Up to 5% of university students develop infectious mononucleosis (IM) annually, and 9-12% meet criteria for ME/CFS 6 months later. We sought to determine predictors of ME/CFS. METHODS: We enrolled college students at the start of the school year (time 1), identified those who developed IM (time 2), and followed them for 6 months (time 3), identifying 3 groups: those who developed ME/CFS, severe ME/CFS (meeting >1 set of criteria), and who were asymptomatic. We conducted 8 behavioral and psychological surveys and analyzed cytokines at 3 time points. RESULTS: 238 of the 4501 students (5.3%) developed IM; 6 months later, 55 of the 238 (23%) met criteria for ME/CFS and 157 (66%) were asymptomatic. 67 of the 157 asymptomatic students served as controls. Students with severe ME/CFS were compared with students who were asymptomatic at 3 time points. The former group was not different from the latter group at time 1 (prior to developing IM) in stress, coping, anxiety, or depression but were different in several behavioral measures and had significantly lower levels of IL-6 and IL-13. At time 2 (when they developed IM), the 2 ME/CFS groups tended to have more autonomic complaints and behavioral symptoms while the severe-ME/CFS group had higher levels of IL-12 and lower levels of IL-13 than the recovered group. CONCLUSIONS: At baseline, those who developed ME/CFS had more physical symptoms and immune irregularities, but not more psychological symptoms, than those who recovered.

The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome.

Post-exertional malaise, or a variation of this term, is a key symptom of myalgic encephalomyelitis and chronic fatigue syndrome, as this symptom is mentioned in almost all myalgic encephalomyelitis and chronic fatigue syndrome case definitions. Until now there has not been a comprehensive questionnaire to assess post-exertional malaise. To rectify this situation, in this article we describe the development of a new questionnaire, called the DePaul Post-Exertional Malaise Questionnaire, which was based on input from hundreds of patients. Preliminary validation was provided by the findings of significant and predictable relationships between different domains of this post-exertional malaise questionnaire and physical functioning.

A Comparison of Patients with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis from the United States and Japan.

Chronic fatigue syndrome (CFS) and Myalgic Encephalomyelitis (ME) are debilitating conditions found globally. Yet, most studies on these illnesses include patients from the United States (U.S) and the United Kingdom (U.K.). The current study compares impairment levels of 124 patients living in Japan with 210 patients from the U.S. All patients are from tertiary-care settings that specialize in ME/CFS. The DePaul Symptom Questionnaire and Medical Outcomes Short-Form 36 were completed and used to assess the participants' symptoms and functional abilities. The U.S. sample showed more impairment in neurocognitive, gastrointestinal and post-exertional malaise symptoms when compared to the Japanese sample. Japanese women demonstrated significantly worse impairment in physical, role-physical, and mental health functioning than Japanese men. Interestingly, Japanese women reported similar functional impairment levels to both men and women in the U.S., despite being less likely to receive disability benefits. These findings may be due to national differences in disability status and gender parity.

A hierarchical logistic regression predicting rapid respiratory rates from post-exertional malaise.

Background: Past research has found high rates of hyperventilation in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), but hyperventilation can be influenced by psychological factors. Clinical respiratory rates have been less frequently assessed. Aim: This study aimed to identify the predictors of rapid respiratory rates in patients referred to an outpatient clinic specializing in ME/CFS. Methods: Adults (n = 216) referred to an outpatient clinic specializing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) participated in a two-day cardiopulmonary exercise test. As part of that evaluation, subjects had resting respiratory rates measured on two consecutive days. The current study used questionnaires to assess the relationship between tachypnea (rapid respiratory rates) and a variety of domains including post-exertional malaise (PEM), a common complaint in patients with ME/CFS, and psychiatric/somatic symptoms, using hierarchical logistic regression analysis. Results: PEM was a significant predictor of tachypnea, while psychological/somatic assessments and sedentary behaviors were not significantly predictive of tachypnea. Conclusions: These findings suggest that respiratory rate may be useful as an objective clinical metric of PEM, and potentially ME/CFS.

The Prevalence of Pediatric Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in a Community­Based Sample.

BACKGROUND: Most pediatric prevalence studies of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have been based upon data from tertiary care centers, a process known for systematic biases such as excluding youth of lower socioeconomic status and those less likely to have access to health care. In addition, most pediatric ME/CFS epidemiologic studies have not included a thorough medical and psychiatric examination. The purpose of this study was to determine the prevalence of pediatric ME/CFS from an ethnically and sociodemographically diverse community-based random sample. METHOD: A sample of 10,119 youth aged 5-17 from 5622 households in the Chicagoland area were screened. Following evaluations, a team of physicians made final diagnoses. Youth were given a diagnosis of ME/CFS if they met criteria for three selected case definitions. A probabilistic, multi-stage formula was used for final prevalence calculations. RESULTS: The prevalence of pediatric ME/CFS was 0.75%, with a higher percentage being African American and Latinx than Caucasian. Of the youth diagnosed with ME/CFS, less than 5% had been previously diagnosed with the illness. CONCLUSIONS: Many youth with the illness have not been previously diagnosed with ME/CFS. These findings point to the need for better ways to identify and diagnose youth with this illness.