Median Delay In Diagnosis Research Articles

Clinical profile and management of pediatric hereditary angioedema in resource-constrained settings: our experience from a single centre in North India.

Hereditary angioedema (HAE) is a rare genetic disorder. The pattern of HAE is different in children as compared to adults. There is limited literature from developing countries where all first-line treatments are either unavailable or not easily accessible.Data of children with HAE were retrieved from medical records of patients registered in the Pediatric Immunodeficiency Clinic at our institute.Of the 206 patients with HAE, 61 were diagnosed before the age of 18years. Male: female ratio was 1.1:1. Median age at onset of symptoms and diagnosis were 6.2years (range 1-17years) and 10.7years (range 1.5-18years) respectively. Median delay in diagnosis was 4.9years (range 0-16years). The commonest presentation was facial swelling (51/61) followed by swelling of extremities (47/61). Laryngeal edema and abdominal symptoms were reported in 28/61 and 31/61 patients respectively. Abdominal attacks were found to be less common in children as compared to adults. Most patients in our cohort received fresh-frozen plasma (n = 5/61) as on-demand therapy. Long-term prophylaxis included attenuated androgens (n = 25/61) and tranexamic acid (n = 23/61). Median duration of follow-up was 2242 patient months. One patient died on follow-up in this cohort.This is the largest single-centre cohort of pediatric HAE from resource-constrained settings. Facial attacks were more common, and there were significant delays in diagnosis when the age of onset of symptoms was younger. Gastrointestinal symptoms were less common in children than adults. HIGHLIGHTS: One of the largest single-centre cohorts of pediatric HAE and the only one from resource-constrained settings. There were significant delays in diagnosis when the age of onset of symptoms was younger. Abdominal attacks were found to be less common in children as compared to adults.

Insulinoma in Patients with Diabetes- A Systematic Review of Previously Reported Cases

Abstract Introduction: Paradoxical co-existence of insulinoma and diabetes is extremely rare. Although a few case reports addressed this association, a comprehensive study elucidating this relationship has been lacking. We performed a systematic review of published cases of insulinoma in diabetes. Methods: We conducted a literature search using PubMed and Google Scholar, employing various combinations of the following terms: ‘insulinoma’, ‘diabetes’, ‘nesidioblastosis’, ‘endogenous hyperinsulinism’, ‘hypoglycaemia’, and ‘hyperglycaemia’ (from January 1900 to January 30, 2024). Exclusion criteria included non-English publications, duplicate articles, reports lacking sufficient data, cases of endogenous hyperinsulinemic hypoglycaemia other than insulinoma, and inaccessible articles. Statistical analysis was performed using appropriate methods. Results: Sixty patients were considered for the final analysis. Mean age was 61 ± 15 years (range: 17–96 years) with a slight female preponderance; 88.3% had type-2 diabetes with a median duration of 8 years. The median delay in diagnosis of insulinoma was 6 months. Median blood glucose varied from 30.5 mg/dL to 235 mg/dL, with a mean HbA1c of 5.6 ± 1.3% (range: 2.9%–8.2%). Critical sampling data were available in 75% of cases. The median size of the insulinoma was 2 cm. Furthermore, 5.2% of insulinomas were extra-pancreatic. Among pancreatic insulinomas, 14.5% were multi-focal. One-third of cases were malignant. Surgical resection was done in 70.9% of cases, while 40% received drug therapy and 12.7% received both, with 20.7% overall mortality. Malignant insulinoma (P = 0.007), micro-angiopathic (P = 0.018) and macro-angiopathic complications (P = 0.039), and other co-morbidities (P = 0.009) were associated with unfavourable prognosis, while being overweight and obese (P = 0.020) at presentation was associated with favourable prognosis. Conclusion: This first systematic review provides insights into the uniqueness of insulinoma in diabetes.

Development of the paediatric society of the African league against rheumatism (PAFLAR) JIA registry and clinical profile of JIA in Africa from the PAFLAR JIA registry

BackgroundThe spectrum of Juvenile Idiopathic Arthritis (JIA) in Africa is still largely unknown. We thus set out to illustrate how we set up the PAFLAR JIA registry and describe the clinical profile of Juvenile Idiopathic Arthritis across various regions in Africa.MethodsWe carried out a retrospective observational cohort study where collaborators were trained on use of the existing PAFLAR REDCAP database to enter data for the JIA patients currently under their care capturing their epidemiological data, clinical features, laboratory investigations, diagnosis and therapy at initial diagnosis. Descriptive statistics including means, standard deviations, medians, interquartile ranges (IQR) for continuous variables and proportions for categorical variables were calculated as appropriate. Tests for difference between groups were performed between categorical variables using Pearson’s chi-square or Fisher’s exact tests. All analyses were performed using SPSS version 22 software.ResultsWe enrolled 302 patients, 58.6% (177 of 302) of whom were female. The median age of disease onset was 7 years (range 3–11 years) and the median age at diagnosis was 8.5 years (range 5–12 years). The median duration delay in diagnosis was 6 months (range 1-20.8 months). The JIA categories included Systemic JIA 18.9% (57), Oligoarticular JIA 19.2% (83), Polyarticular RF + ve 5% (15), Polyarticular RF-ve 17.9% (54), Enthesitis Related Arthritis (ERA) 18.2% (55), Psoriatic Arthritis 7% (21) and undifferentiated JIA 5.6% (17). As regards treatment the commonest therapies were NSAID therapy at 31.1%, synthetic DMARDs at 18.1%, synthetic DMARDs combined with NSAIDs at 17.5% and steroid therapy at 9.6%. Biological DMARDs accounted for 2.3% of therapies offered to our patients at diagnosis. The average JADAS score was 10.3 (range 4.8–18.2) and the average CHAQ score was 1.3 (range 0.7-2.0).ConclusionOur study highlights strategies involved in setting up a Pan-African paediatric rheumatology registry that embraces our broad diversity and the vast spectrum of JIA in Africa while comparing the various therapies available to our patients. The PAFLAR JIA registry strives to ensure a comprehensive representation of the diverse healthcare landscapes within the continent. Further longitudinal observation studies are required to ascertain the long-term outcomes of our patients and ultimately help inform policy to create a more favorable health ecosystem to support the healthcare needs of JIA patients in Africa.

Characteristics of large granular lymphocyte leukemia associated with variable common immunodeficiency disorders: A study of 12 cases.

Common Variable Immunodeficiency Disorders (CVID) and Large Granular Lymphocytes leukemia (LGLL) exhibit diverse clinical manifestations including infections, dysimmunity, and lymphoproliferation. Recent decades have seen the discovery of new genes in the lymphopoiesis pathway, such as JAK-STAT. This case series supplemented by a literature review aims to describe clinical and biological characteristics of patients with both CIVD and LGLL. Patients were included through a call for comments to French and Belgian centers and through a literature review via PubMed. Clinical characteristics were compared to two large French cohort involving CVID and LGLL patients. Twelve patients were included. In all cases, CVID precedes LLGL (median diagnosis delay for LLGL was 7 years). Most cases presented with splenomegaly and autoimmune cytopenia. Ten out of 12 patients underwent splenectomy during follow up. Patients with LGLL and CVID differ from patients without immune deficiency in term of clinical presentation and prognosis. We suggest CVID may act as a trigger of LGL lymphocytosis, due to endogenous and exogenous antigenic pressure leading to the selection of a dominant LGL clone and stimulation of the JAK-STAT pathway. The role of splenomegaly and splenectomy in LGLL onset warrant further investigation in future studies.

Delays in accessing childhood cancer care in western Kenya: A single-center, retrospective study

IntroductionApproximately 80 % of children with cancer live in resource-limited settings where prompt access to diagnosis and treatment is challenging. Data regarding delays in diagnosis and treatment and outcomes of children with cancer in Kenya are lacking. This study aims to 1) compare the reported and expected number of children with cancer; 2) explore diagnosis, treatment, and total delays; 3) determine patient characteristics that influence delays; and 4) investigate treatment outcomes. MethodsThis study combined a retrospective medical records review with a case report. Data on delays and treatment outcomes of children from Bungoma County (Kenya) who were diagnosed with cancer at a large academic hospital between 2010 and 2016 were collected. ResultsBetween 2010 and 2016, 92 children, an average of 13 per year, were referred from Bungoma. These 13 children constitute only 9 % of the expected 140 children developing cancer in this region. The most common diagnoses were non-Hodgkin lymphoma (17 %) and acute lymphoblastic leukemia (16 %). The median total delay was 108 (7–1731) days. The median diagnosis delay was 97 days, longer than the median treatment delay (3 days; P < 0.001). A longer total delay was associated with referral from another facility (P = 0.008), longer symptom duration (P < 0.001), solid tumors (P = 0.013), stage (P = 0.012), and tribe (P = 0.044). The event-free survival was 21 %. The reasons for treatment failure were abandonment (41 %), progressive/relapsed disease (25 %), or death (13 %). The case study highlights that health beliefs and fear of conventional medicine can delay healthcare seeking. ConclusionUnderdiagnosis and delays in accessing childhood cancer care are considerable in Bungoma. Increasing awareness among the general public and personnel of primary-care facilities is essential to reducing delays in this county.

Abstract 050: Leveraging Electronic Health Records To Assess Delay In Hypertension Diagnosis: Insights From A Large Regional Health System

Introduction: Timely hypertension diagnosis is vital for effective management and prevention of complications. This study assessed hypertension diagnosis delays in a large regional health system using electronic health records (EHRs). Methods: Retrospective analysis of EHR data (2010-2021) in Sentara Healthcare System was conducted. Hypertension diagnosis was defined as two outpatient blood pressure (BP) readings &gt;=140/90 mmHg within two years, with at least 30 days separation. The delay in diagnosis was determined as the time elapsed from the computable diagnosis to the structured diagnosis documented in the EHR. Results: Among 302,774 patients with computable hypertension diagnosis, 23.6% lacked a structured diagnosis. Furthermore, 23.8% received early structured diagnosis (after first BP elevation), and 18.6% received eventual structured diagnosis (after second BP elevation). Among those who received an eventual structured diagnosis, the median delay in hypertension diagnosis was 21.7 months (interquartile range: 7.5-45.5 months). Prescription rate for antihypertensive medication was significantly lower for patients with no structured diagnosis (44.2%) and eventual structured diagnosis (38.1%) than for those with early structured diagnosis (82.3%). Longer delays were associated with older age, male gender, and Black patients. Conclusions: The study highlights concerning delays in hypertension diagnosis, impacting timely intervention and complication prevention. By leveraging EHR data, health systems can identify areas for improvement and enhance the efficiency of hypertension diagnosis, leading to improved patient outcomes.

Epidemiology, outcomes, and disproportionate burden of food-dependent exercise-induced anaphylaxis from the Hong Kong Multidisciplinary Anaphylaxis Management Initiative (HK-MAMI).

Anaphylaxis is a life-threatening allergic reaction that poses a considerable burden on populations across all ethnicities and age groups. The Hong Kong Multidisciplinary Anaphylaxis Management Initiative (HK-MAMI) was established to streamline the assessment of patients with anaphylaxis via a multidisciplinary and protocol-driven approach. This prospective study aims to define the etiology, clinical manifestations, and treatment of patients with anaphylaxis in Hong Kong. Prospective clinical data from allergologic investigations from patients who completed evaluation by the HK-MAMI pathway between January 2017 and August 2022 were analyzed. Of the 161 patients referred via the HK-MAMI, 131 (81.4%) met the diagnostic criteria for anaphylaxis. The median delay in diagnosis was 2 years (range 0-30 years). The majority of anaphylaxis cases were attributed to food-dependent exercise-induced anaphylaxis (FDEIA), especially wheat-dependent exercise-induced anaphylaxis. In acute management settings, paired tryptase samples were taken in only around one-third of anaphylaxis cases, with 82.5% of the samples demonstrating significant elevation. There was a general underprescription of adrenaline autoinjectors, especially for food-related anaphylaxis. Patients with FDEIA had later ages of onset and diagnosis, and they presented with more cardiovascular manifestations. Skin prick tests and specific IgE level tests were able to diagnose 95% of FDEIA cases. Our study highlights the significant burden of FDEIA, and especially WDEIA, in Hong Kong, its association with severe presentations, and difficulties encountered in emergency or primary care settings. We advocate appropriate adrenaline use during acute-care management and discharge plans, as well as taking serum mast cell tryptase samples during acute episodes. Interdisciplinary collaboration remains crucial to upholding proper and optimized care for patients with anaphylaxis in Hong Kong.

Neurologic involvement in seronegative primary Sjögren's syndrome with positive minor salivary gland biopsy: a single-center experience.

To assess the demographics, neurologic manifestations, comorbidities, and treatment of patients with seronegative primary Sjögren's syndrome (pSS). We conducted a retrospective chart review on patients with seronegative pSS evaluated by a neurologist at the University of Utah Health between January 2010 and October 2018. The diagnosis was based on characteristic symptoms, positive minor salivary gland biopsy according to the American-European Consensus Group 2002 criteria, and seronegative antibody status. Of 45 patients who met the study criteria, 42 (93.3%) were Caucasian, and 38 (84.4%) were female. The patients' mean age at diagnosis was 47.8 ± 12.6 (range 13-71) years. Paresthesia, numbness and dizziness, and headache were noted in 40 (88.9%), 39 (86.7%), and 36 patients (80.0%), respectively. Thirty-four patients underwent brain magnetic resonance imaging. Of these, 18 (52.9%) showed scattered nonspecific periventricular and subcortical cerebral white matter T2/fluid-attenuated inversion recovery hyperintense foci. Twenty-nine patients (64.4%) presented to the neurology clinic prior to pSS diagnosis, and the median delay in diagnosis from the first neurology clinic visit was 5 (interquartile ranges 2.0-20.5) months. Migraine and depression were the most common comorbidities in 31 patients (68.9%). Thirty-six patients received at least one immunotherapy, and 39 were on at least one medication for neuropathic pain. Patients often display various nonspecific neurological symptoms. Clinicians should express a high degree of skepticism regarding seronegative pSS and consider minor salivary gland biopsy to avoid delaying diagnosis, as undertreatment can affect patients' quality of life.

A Study of Factors Influencing Delayed Diagnosis in Pediatric Cancers: A Step Towards Better Outcomes-A Cross-sectional Study.

Annually, India contributes to one-fifth of newly diagnosed pediatric cancers worldwide. Poor outcome in India as compared with developed nations is mainly attributed to delayed diagnosis and study of factors influencing delay in diagnosis holds paramount importance in formulating strategies and counter-measures to improve survival. It was a cross-sectional study conducted on children diagnosed with malignancy at a tertiary care hospital. Diagnosis delay was defined and further divided into patient delay and physician delay. Various patient-related factors and socioeconomic factors that could affect diagnosis were studied. Statistical analysis included descriptive analysis, Mann-Whitney U test, Kruskal-Wallis test, and multivariate linear regression. Of 185 patients enrolled, median diagnosis delay, patient delay, and physician delays were 59, 30, and 7 days respectively. Median diagnosis delay was significantly higher in younger children, children of illiterate parents, and low income. Median diagnosis delay in children presenting to a general practitioner (9 [4 to 29] days) was higher than those presenting to a pediatrician (5.5 [2 to 18] days). Sex, occupation of parents, and distance from oncology center did not affect time for diagnosis. We concluded that augmentation of the parent's attitudes, increased awareness, and decentralization of specialized pediatric care to rural areas can significantly reduce mortality from, otherwise, curable malignancies.

Delay in Diagnosis and Treatment of Primary Bone Tumors

Background. Delay in the diagnosis and treatment of bone tumors continues to be a common problem. Prolonged diagnosis can significantly reduce the chances of successful treatment of the disease. Accordingly, the aim of this study was to assess the delay in the diagnosis of primary bone tumors, identify the most common symptoms and analyze the course of the diagnostic and therapeutic path.Material and methods. Thirty-two (K=18; M=14) patients treated surgically for primary bone tumors were included in the retrospective study. Patient records were analyzed. Delay in diagnosis was defined as the time from the onset of symptoms to the initial diagnosis and referral to an orthopedic oncology center.Results. The median delay in diagnosis was 7 (3-12) months. For tumors located in the pelvis, the delay was 10 months, compared to 5 months for the upper limb and 7 months for the lower limb (p=0.2312). The delay was 6 months In patients with osteosarcoma, and 8 months in chondrosarcoma patients (p=0.1786). At the first office visit, an x-ray was ordered in 19 cases (59.4%), of whom 9 patients (47.4%) were referred on to the oncology center. The most common symptoms were pain in the affected area (90.6%), limited mobility (28.1%) and pathological fracture (25%). After admission to an orthopedic department, a biopsy was performed after 5.5 (3-8.2) days. The histology results were ready after another 14 (8-18) days, and surgical treatment was performed after 95 (76-100) days.Conclusions. 1. Although patients show typical symptoms of bone tumors, only a small proportion are referred directly to an oncology center. After a primary bone tumor is suspected, further diagnostic and therapeutic activities proceed efficiently, in accordance with the current guidelines.

P326 PREFAB-study: PRediction tool for Early identification of patients at risk of Crohn's disease in perianal Fistulas and ABscesses: interim analysis of a prospective pilot study at a non-academic, IBD-expert centre in the Netherlands

Abstract Background Perianal abscesses (PAA) and perianal fistulas (PAF) are life impairing conditions associated with Crohn’s disease (CD). A retrospective study at Flevohospital showed a reduced median delay in diagnosis of CD from 33 months (IQR 23-64) in the period 2007-2016 to 3 months (IQR 0-5) in the period 2017-2021, with &amp;lt;20% of patients diagnosed &amp;lt;1 year after the first perianal surgical procedure in 2007-2016 versus 79% in 2017-2021. This study also showed CD in up to 10% of patients with PAA/PAF, which was reason to continue data collection in a larger prospective pilot study to identify risk factors for CD in patients presenting with PAA/PAF. Methods All consecutive patients ≥16 years presenting with PAA/PAF were included. Patients were prospectively screened for risk factors/red flags from a ‘perianal Red Flag Index Questionnaire’ (pRFI) (identified from previous literature searches/expert opinion) and fecal calprotectin (FC-)samples were taken in all patients. Colonoscopy was performed in case of ≥5 positive answers in the pRFI and/or FC-values ≥150mcg/g. Results Sixty-nine patients were included (72,5% male) with median age of 41 years (IQR 30,5-54,6). Thirty-five patients (50,7%) presented with PAA, whereas 34 patients presented with PAF (49,3%). Thirty-one patients (44,9%) had recurrent PAA/PAF. Additional colonoscopy was performed in 11 patients, in whom 5 patients (7,2%) eventually were diagnosed with CD with a median delay of 44 months (IQR 7,5-87,5, still 5 patients in diagnostic work-up). Median FC-values were 552mcg/g (IQR 198,5-4585) in patients with confirmed CD and 31,5mcg/g (IQR 10-102,75) in patients without CD (p=0,002). Risk factors associated with CD were a younger age, presence of PAF (compared to PAA only), higher number of previous perianal interventions, multiple internal fistula openings, fissures and proctitis (p&amp;lt;0,05 in all). Conclusion This pilot study reveals several risk factors associated with CD in patients presenting with PAA/PAF and forms the basis for development of a clinical decision tool that incorporates both the pRFI questionnaire and selected FC-measurement to early identify patients at risk of CD when presenting with perianal disease. This clinical decision tool will be subject of a larger prospective multicentre study to reduce diagnostic/treatment delay, thereby improving outcomes in patients with Crohn’s fistulas.

P255 Diagnostic delay and economic burden in Inflammatory Bowel Disease: a single-centre experience in patients treated with biologics

Abstract Background Inflammatory Bowel Disease (IBD), Crohn's Disease (CD) and Ulcerative Colitis (UC), are chronic and immune-mediated diseases with a relapsing-remitting trend. The overall incidence of these diseases is increasing. However, it is estimated that more than one third of patients experienced symptoms for more than one year before diagnosis. Delay in IBD diagnosis has several clinical, therapeutic and economic implications. Early diagnosis and proper treatment are the cornerstones for improving the standard of care for these patients.This study aims to evaluate the diagnostic delay in patients with IBD and to analyze the clinical and economic burden of the delay in IBD diagnosis in patients treated with biological drugs. Methods An observational and retrospective study was performed in IBD patients, regularly followed in our IBD Unit. Data regarding delay in IBD diagnosis were assessed through a questionnaire evaluating the disease course. Moreover, data about biologics dispensation were obtained from the medical records in the period 2014-2020. Results 606 IBD patients were enrolled. The median delay in IBD diagnosis was 5.0 months (IQR:1.0 11.0); it was statistically lower in UC patients (4 months (IQR: 1.0 12.0)) compared to CD (6 months (IQR: 2.0 12.0)) ( p =0.041). Of these 606, 229 patients were treated with biological therapy; in this subgroup 58.9% showed a diagnostic delay. The statistical analysis showed that the diagnostic delay was statistically significant associated with biological drugs (p=0.041). Conversely, there was no association with surgical treatment. Moreover, it has appeared that the diagnostic delay is associated, with a trend of statistical significance, with need to switch or swap to other biologics (p=0.058). Regarding economic burden, patients with delayed diagnosis have significantly higher median annual cost of biological therapy than patients without diagnostic delay (€7179.26 vs € 5131.51 p= 0.009). Conclusion The diagnostic delay in IBD represents a challenge with clinical, therapeutic and economic impact. It’s crucial to cooperate with general practitioner and gastroenterologists not dedicated to IBD in order to reduce the diagnostic delay and guarantee an effective, appropriate and early treatment that will improve the patients’ quality of life and meanwhile reduce the health care system costs.

Delay in Diagnosis and Treatment of Primary Bone Tumors during COVID-19 Pandemic in Poland.

The COVID-19 pandemic has affected all of the medical specialties, including orthopedic oncology. Therefore, the aim of the study was to assess how it influenced the diagnostic and therapeutic processes for patients with bone neoplasms. We evaluated 87 patients treated due for bone neoplasms before (Group I, n = 36) and during the COVID-19 pandemic (Group II, n = 51). A delay in diagnosis was defined as the period between the initial clinical symptoms and the date of referral to an oncology center. The patients from Group II were asked to complete a short questionnaire regarding the COVID-19 pandemic. The median general delay in diagnosis before the pandemic was 7 months, while during the pandemic, it was 10 months (p = 0.728). The biopsy delay was lower in the pre-pandemic group: median-6.5 vs. 12 days (p = 0.025). The patients from Group II were diagnosed with larger tumors compared to those in Group I: the median values were 75 vs. 56 mm (p = 0.025), respectively. After an X-ray examination, the bone neoplasms were suspected more frequently in the Group II: 63% vs. 44% cases (p = 0.024), respectively. In Group II, 20 (60.8%) cases of SARS-CoV-2 infection were reported, however, no respiratory failure cases were noticed. The pandemic affected the diagnostic process of primary bone tumors, resulting in delays in performing biopsies. During the pandemic, the patients reported larger diameters of their bone lesions.

Pediatric Behçet's disease: Experience of a single tertiary center.

The aim of this study was to examine the clinical and phenotypic features of pediatric Behçet's disease (PEDBD) in our clinic and present the rates of fulfilling the diagnostic criteria. Thirty-four patients (20 males, 14 females; mean age: 16.0±2.1 years; range, 10 to 18 years) diagnosed with PEDBD between January 2010 and December 2019 were retrospectively evaluated. Patients were reclassified according to 1990 International Study Group (ISG) criteria, 2014 International Criteria for Behçet's Disease (ICBD), and PEDBD criteria. The mean age at diagnosis was 12.6±3.1 years, the median diagnosis delay time was 12.0 (range, 4.5 to 27.0) months, and the mean age at symptom onset was 10.8±2.9 years. The mean follow-up period was 31.9±20.9 months. Oral aphthous ulcer was observed in 33 (97.1%), genital ulcer in 16 (47.0%), ocular involvement in 15 (44.1%), skin lesion in 11 (32.3%), joint involvement in nine (26.4%), both vascular and neurological involvement in six (17.6%) patients. The pathergy test was positive in 11 (37.8%) patients, and human leukocyte antigen (HLA)-B51 was positive in 11 (78.5%) of 14 patients. The rates of patients meeting the criteria for ISG, ICBD, and PEDBD were 52.9%, 82.4%, and 50.0%, respectively. Pathergy and HLA-B51 can be used as supportive findings in patients who do not meet the diagnostic criteria. However, expert opinion is still the gold standard in diagnosis.

Effect of diagnosis delay on pulmonary function in children with asthma

BackgroundThe effects of a delayed diagnosis of asthma on lung function in children have not been well investigated. Therefore, a retrospective cohort study was conducted in a children’s hospital to analyse the effect of delayed diagnosis time on lung function in children with asthma.MethodsWe conducted a retrospective cohort study in Jinan Children's Hospital from January 1, 2010, to December 31, 2020. All children were divided into different groups according to the presence or absence of rhinitis, age at first onset (first coughing and wheezing attack) and delayed diagnosis duration (≤ 3 months, 3–12 months, 1–3 years, 3–5 years and > 5 years).ResultsA total of 1,014 children with asthma were included in this study. The median (quartile) delay in asthma diagnosis among all participants was 11 (2, 26) months. The shortest delay in diagnosis time was on the same day of onset, and the longest delay in diagnosis time was 10 years. The median (quartile) duration of delayed diagnosis was 10 (2, 26) months in 307 asthmatic children without rhinitis and 11 (2, 26) months in 707 children with asthma and rhinitis (P < 0.05). The delayed diagnosis time was shorter among female children than among male children (P < 0.05), and the first %predicted forced volume capacity (FVC%pred) results for females were higher than those for males (P = 0.036). The children whose age at first asthma onset was ≤ 3 years had a longer delayed diagnosis duration than those whose age at first onset was > 3 years (P < 0.05). The FVC%pred and %predicted forced expiratory volume in 1 s (FEV1%pred) in the first and second pulmonary function tests were significantly lower in the five delayed diagnosis groups (all P < 0.05). After standardised treatment for 3–6 months, FVC%pred showed a significant difference in the third test among the 5 groups (P < 0.05), but the other pulmonary function indices showed no significant difference. Logistic regression analysis showed that longer delay and young age of onset were associated with lower lung function (P < 0.05), whereas sex, rhinitis and eczema had no significant effects (all P > 0.05) on FVC%pred and FEV1%pred.ConclusionAlthough delayed asthma diagnosis can lead to lung function impairment in children with asthma, lung function can be improved quickly after standardised treatment. Therefore, early asthma diagnosis and standardised treatment are very important.

A systematic review and meta-analysis of delayed help-seeking, delayed diagnosis and duration of untreated illness in bipolar disorders.

To examine the time delay between the age at onset of symptoms or episodes of bipolar disorders (BD) and the age at diagnosis of and/or receipt of clinical practice guideline recommended interventions for BD. Systematic search of five databases to identify publications from January 2000 to July 2022 that reported one or more of the following reliable and valid estimates of latency: delay in help seeking (DHS), delay in diagnosis (DD) and duration of untreated BD (DUB). Eligible studies were included in random effects meta-analyses and multivariate meta-regression was used to assess factors associated with each latency construct. Screening of 1074 publications identified 59 eligible studies (reported in 66 publications) of >40,000 individuals that estimated DHS (8 studies), DD (20 studies) and/or DUB (45 studies). The median DHS, DD and DUB were 3.5 (IQR: 2.8, 8.48), 6.7 (IQR: 5.6, 8.9) and 5.9 years (IQR: 1.1, 8.2), respectively. Key factors associated with shorter DD included older age and residing outside North America; shorter DUB was associated with psychotic or manic onset and access to early intervention services. Greater consensus on definitions of latency constructs and better-quality targeted research is required regarding DHS, DD and DUB. This review suggests that, while the peak age at onset of BD is 15-25, diagnosis and guideline recommended interventions (e.g., mood stabilizers) are likely to be delayed until age 25-35 years except for a minority of individuals with access to early intervention services.

Clinical and laboratory characteristics of a group of patients with ataxia-telangiectasia syndrome

This study presents the clinical and laboratory data of 50 patients with ataxia-telangioectasia syndrome (AT) (Louis-Bar syndrome) treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (Moscow, Russia) between 2012 and 2021. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. We found that the patients experienced a significant diagnostic delay (the median delay in diagnosis was 4.5 years), although the first typical symptoms of AT were present at an earlier age (the median age was 1.5 years). The majority of patients showed laboratory signs of immunodeficiency, yet only 24% of the children developed severe infections. However, lung infections resulted in bronchiectasis in 16% of the patients and were the cause of death in 4/10 cases. Fifty-two percent of the patients had autoimmune complications, including interstitial lung disease and skin granulomas, and 24% of the patients developed malignant neoplasms. Of patients who underwent testing, 85% had KREC and/or TREC levels below the cutoff values used for neonatal screening of primary immunodeficiency disorders in Russia, which suggests that the majority of AT cases could be diagnosed by neonatal screening. Early diagnosis, multidisciplinary approach and high clinical suspicion for neoplastic manifestations are crucial for the successful management of AT.

PFAPA Syndrome: Clinical, Laboratory and Therapeutic Features in a Single-Centre Cohort.

ObjectiveThe aim of this study is to describe a group of Romanian children with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome.MaterialsThis consisted of 39 children diagnosed with PFAPA syndrome according to Thomas’ criteria (eight patients with an age at diagnosis <1 year and 31 patients with an age at diagnosis >1 year).MethodsRetrospective analysis of the patients with PFAPA syndrome was focused on clinical features, laboratory findings and therapeutic methods. Comparison between the two groups divided by age at onset was also investigated.ResultsMedian age at onset was 1.58 years, and median age at diagnosis was 2.97 years. The mean interval between episodes was 35.5 days and the mean duration per febrile episode was 4.1 days. The median diagnosis delay was 2.42 years. The patients presented pharyngitis (100%), adenitis (94.8%) and aphthous lesions (66.7%). The frequency of febrile attacks was higher in children with an age at diagnosis under 1 year (p = 0.0287). Younger age was associated with the presence of aphthae. The mean value of C-reactive protein (CRP) was 7.9mg/dl and the mean value of leucocytes was 14,839/mm3. In 95% of patients given oral corticosteroids, remission of symptoms was reported within 24 h. In three patients, tonsillectomy was performed with complete remission of the disease.ConclusionWe present a cohort of children with PFAPA syndrome, with clinical and laboratory features similar to those described in the literature. Febrile attacks had a higher incidence in children with younger age at the onset of the disease. The patients had a favorable response to corticosteroids.

In Urticarial Vasculitis, Long Disease Duration, High Symptom Burden, and High Need for Therapy Are Linked to Low Patient-Reported Quality of Life

Urticarial vasculitis (UV) is a rare and difficult-to-treat chronic skin disease defined by long-lasting urticarial lesions and the histopathologic finding of leukocytoclastic vasculitis. As of yet, little is known about UV patients' perspective on the disease. To assess UV patients' perspective on the clinical course, treatment response, greatest challenges, and quality-of-life (QOL) impairment. A web-based questionnaire was disseminated in a Facebook group of patients with UV. Patients with UV confirmed by skin biopsy were included. Patients with UV had a mean age of 47.3 ± 12.3 years and were mostly female (94.3%; n= 82 of 87). The median delay in diagnosis was 8.1 months (interquartile range, 2.0-46.3). Normocomplementemia and hypocomplementemia were present in 54.0% (n= 27) and 46.0% (n= 23) of 50 patients, respectively. Most patients with UV (51.8%; n= 43 of 83) reported severely decreased QOL due to their disease. Low QOL was also the most frequently reported greatest challenge for patients with UV (40.7%), followed by the long-standing course of UV with frequent relapses (14.8%). Low QOL correlated with long disease duration (r= 0.298; P= .02) and high numbers of clinical symptoms (r= 0.294; P= .007). Patients with UV with allergies, lung diseases, and chronic infections reported lower QOL. Patients with UV with low QOL were treated with analgesics, dapsone, montelukast, omalizumab, and colchicine more often than patients with UV with higher QOL (P < .05 for all). Our results show a considerable impairment in QOL in patients with UV associated with long disease duration, high symptom burden, and a high need for therapy. Improvement of the management of UV by further research is necessary.

Identification of novel pathogenic variants in the GCDH gene and assessment of neurodevelopmental outcomes in 24 children with glutaric aciduria type 1.

To evaluate the pathogenic variants in GCDH gene and to assess the neurodevelopmental outcomes in children with Glutaric aciduria type 1 (GA-1). Cross-sectional observational study between January 2019 and June 2020 in consecutive North Indian children with a clinical and biochemical suspicion of GA-1. Variants in the coding regions of GCDH gene were identified through Sanger sequencing. Neurodevelopmental and quality of life assessment was done using standardized scales. 24 children with GA-1 were identified. The median age at diagnosis was 12 months and the median delay in diagnosis was 3 months. Genetic analysis was done in 14 cases. It revealed 12 variants (11 missense and one nonsense) from 13 patients. Most of the pathogenic variants were in exon 9 and exon 5. Three novel variants were identified in three patients: two missense variants c.169G>A (p.Glu57Lys), c.1048T > C (p.Cys350Arg) and one nonsense variant c.331C > T (p.Lys111Ter). On neurodevelopmental assessment, majority of children with GA-1 were non ambulatory (62.5%), had limited hand skills (58.3%) and impaired communication (58.3%). Overall, poor global development was noted in 43.7%. A pre-existing developmental delay was significantly associated with impaired communication skills (p=0.03), and the number of episodes of encephalopathy were significantly associated with impaired gross motor skill (p=0.02). Presence of encephalopathy was significantly associated with poor performance in social emotional (p=0.01) and cognitive (p=0.03) domains of Developmental Profile-III scale and development of severe dystonia (p=0.01). Our findings highlight the clinical, biochemical, radiological and genetic spectrum of GA-1 in children in North India and report the presence of novel pathogenic variations.