Late Diagnosis Group Research Articles

The Impact of Age of Diagnosis in Children with Primary Ciliary Dyskinesia.

The typical symptoms for primary ciliary dyskinesia (PCD) manifest after birth and in early infancy, however diagnosis is often not confirmed during infancy. There is currently a lack of evidence in PCD regarding the impact of the age of diagnosis on clinical outcomes. To determine whether early diagnosis is related to improved long-term outcomes. This was a retrospective study of patients diagnosed with PCD between 2000 to 2022. We divided our cohort to three groups according to the age of diagnosis. 1) early diagnosis (<1 year); typical diagnosis (1-7 years) and late diagnosis (8-14 years). We compared various clinical long-term outcomes between the groups. Over the study period, 110 patients were included in the analysis, with 41 patients in the early diagnosis group, 35 in the typical diagnosis group and 34 patients in the late diagnosis group. The presence of unexplained neonatal respiratory distress (NRDS) and organ laterality defect were higher in the early diagnosis group with rates between the early, typical, and late diagnosis groups for NRDS (80% vs 53% vs 61%, p=0.045) and laterality defect (64% vs 50% vs 18%, p<0.001). At the end of the first decade of life, patients in the early diagnosis and the typical age of diagnosis had better forced expiratory volume in 1 second (FEV1), compared to the late diagnosis group (93.5% and 93.1% vs 80.2%, P=0.002), respectively, but there was no significant change in the annual rate of decline between the groups once diagnosis was confirmed. Patient diagnosed late had significantly higher rates of pulmonary exacerbations (Pex) compared to typical age (1.95 vs 0.75 Pex/year, p<0.01) Conclusion: Late diagnosis (>8 years) was associated with lower FEV1 throughout childhood, although once diagnosed, the annual rate of decline was not different. These findings demonstrate the negative effect of delayed diagnosis in pediatric PCD.

AB023. Early diagnosis and treatment lead to improve survival of glioblastoma patients.

Glioblastoma (GBM) is one of the worst prognostic cancers and one of the reasons is that GBM patients rapidly deteriorated and half of them had a Karnofsky performance status (KPS) with 70 or less at the initial presentation. We discuss the significance of early diagnosis and treatment to the clinical outcomes of GBM patients. Data of IDH-wildtype GBM patients treated at our institution between 2010 and 2019 were retrospectively reviewed. Patients were classified into early or late diagnosis groups with a threshold of 14 days from initial symptoms. Also, patients were divided into early, intermediate, and late surgery groups with thresholds of 21 and 35 days. Patients were also divided into two groups: neurosurgeon and non-neurosurgeon groups, based on the primary doctor whom patients sought for an initial evaluation. Representative symptoms and patient prognosis were examined. Of 153 patients, 72 and 81 were classified into the early and late diagnosis groups. The proportion of patients with preoperative KPS scores ≥90 was 48.6% and 29.6% in the early and late diagnosis groups (P=0.01). Median overall survival was significantly longer in the early surgery group (n=43) than in the late surgery group (n=86) (28.4 vs. 18.7 months, P=0.006). The neurosurgeon group exhibited a significantly shorter duration from the first hospital visit to the first surgery than the non-neurosurgeon group (18 vs. 29 days, P<0.001). Furthermore, the overall survival of the neurosurgeon group was significantly more prolonged than that of the non-neurosurgeon group (22.9 vs. 14.0 months, P=0.04). Early diagnosis and surgery within 3 weeks from the initial symptoms are associated with improved patient survival. Early GBM treatment will be beneficial for patients with GBM. A short duration from the first hospital visit to the first surgery is essential in enhancing GBM patient prognosis.

Insights into Central Congenital Hypothyroidism: A Multicenter Retrospective Analysis.

Central congenital hypothyroidism (CCH) is a thyroid hormone deficiency at birth caused by inadequate pituitary stimulation of the thyroid gland. Although primary CH has been studied extensively, studies on CCH are sparse. To assess the prevalence of CCH in Israel and describe its clinical features, neonatal screening results, and outcomes. Multicenter cross-sectional retrospective chart review. Nine pediatric endocrine units throughout Israel. Patients diagnosed with CCH in 1987-2021 were categorized into early (within 14 days of life) and late (after 14 days) diagnosis groups. Newborn screening (NBS) results were retrospectively retrieved from the national NBS program dataset. CCH prevalence in Israel was about 1:42,800 live births. Subjects were 94 patients (54 males), of these, 84% had multiple pituitary hormone deficiencies and 16% had isolated CCH. The median age at diagnosis was 50 days (range, 1-8760), with 66% having moderate to severe hypothyroidism. NBS detected only three infants. Early diagnosis occurred in 34% due to hypopituitarism, while 66% were diagnosed later due to growth and developmental delays. Neurodevelopmental sequelae included mental retardation (12%), learning difficulties (18%), delayed speech (27%), and motor clumsiness (19%), with no significant differences in outcomes between early and late diagnosis. Despite high rates of neurodevelopmental sequelae, no differences were found between early and late diagnosis groups. Further research is needed to assess the impact of delayed diagnosis on neurological outcomes in newborns with CCH. Improved strategies for detecting CHH in newborns are also necessary.

The Role of Early Diagnosis and Intervention in Improving Outcomes for Lung Cancer

Introduction : For lung cancer patients, early diagnosis and treatments are essential to battering outcomes. The objective of this world is to compare early diagnosis vs late diagnosis in terms of overall survival ,progression _free survival, quality of life and adverse events associated to treatment. Methodology: A Prospective cohort trial of seventy_ eight lung cancer patients was Conducted at Hayatabad Medical Complex in Peshawar from December 2021 to March 2024. 39 patients had early diagnosis (n=39) while 39 received late diagnosis(n=39) . Low_ dose Computed Tomography (DCT) screening and prompt symptom presentation lead to early diagnosis; incidental or symptomatic results were the basis for late diagnosis. Overall Survival(OS) , progression_ free survival (PFS), quality of life(QoL) , and frequency of serious adverse events associated to therapy were the outcomes. Results: At a median 'OS of 38 months compared to 14 months in the late diagnosis group (p&lt;0.001) and median PFS of 34 months compared to 10 months(p&lt;0.001), the early diagnosis group showed noticeably superior results. At 12 months, 'the early diagnosis group had a better QoL scores' a mean global health status of 75 compared to 55(p&lt;0.01). Early diagnosis group (18%) had a lower frequency of serious adverse effects than did the late diagnosis group(45%). Conclusion: In patients with lung cancer, early detection and intervention greatly increases survival rates, prolong intervals without progression, improves quality of life, and lower serious side effects associated to therapy. The results emphasized the need of early diagnosis techniques and efficient screening programs in the treatment of lung cancer. Keywords: lung Cancer, early diagnosis, low dose computed tomography, overall survival, progression free survival, quality of life, treatment related adverse events

SCREENING PRACTICES AND LATE DIAGNOSIS OF HYDROXYCHLOROQUINE RETINOPATHY IN ASIAN PATIENTS.

To investigate the associations between screening practices and late diagnosis in Asian patients with hydroxychloroquine retinopathy. In total, 92 Korean patients with hydroxychloroquine retinopathy were included and separated into late diagnosis and earlier diagnosis groups according to the retinopathy stage at the time of diagnosis. Details of screening practices regarding timing and modalities for baseline and annual monitoring examinations were compared between the two groups. Adherence to the current American Academy of Ophthalmology guidelines was compared between the two groups. Timing of baseline and initial monitoring examinations was appropriate as per the Academy of Ophthalmology guidelines in only 5.3% of patients with late diagnosis. There were significant differences in the proportions of patients receiving initial monitoring at 5 years of use and those receiving annual monitoring between the late and earlier diagnosis groups ( P = 0.003 and <0.001, respectively). The duration from the start date of hydroxychloroquine therapy to the first monitoring examination was significantly prolonged in the late diagnosis group ( P < 0.001). Multivariate logistic regression revealed significant association of the time duration with the first monitoring examination ( P = 0.042) and age ( P = 0.028) with late diagnosis. Results of this study suggest that poor adherence to the Academy of Ophthalmology guideline, particularly delayed initial monitoring, may be associated with late diagnosis of hydroxychloroquine retinopathy.

Diagnosis delay in Egyptian rheumatoid-arthritis patients: underlying factors and outcomes – retrospective observational study

Background. Early initiation of rheumatoid arthritis (RA) treatment leads to better outcomes and low disease activity. In spite of these, there is a significant delay between symptom onset and the initiation of therapy. Objective. This study aimed to investigate this diagnostic delay and to analyze its associated factors and outcomes. Patients and method. This cross-sectional study included 167 RA patients fulfilling the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) classification criteria. All patients were subjected to full clinical, laboratory and radiological assessment and treatment was also received; Disease Activity Score (DAS-28) functional disability evaluation using Modified Health Assessment Questionnaire (MHAQ) MHAQ were reported. Diagnostic delay was assessed regarding duration, associated factors and outcomes. Furthermore, RA patients were divided into early and late diagnosis group with a cutoff of one year and were compared regarding different disease parameters. Results. The median (IQR) lag in diagnosis of RA patients was 12 months (4 24), MHAQ score was significantly positively correlated with delay in diagnosis (p = 0.02). Early diagnosis group patients were statistically significant urban residents (p = 0.01), employed (p = 0.02), with higher educational level (p = 0.02), lower functional index MHAQ (p = 0.02), and were significantly visiting rheumatology specialists early in the disease compared to the late diagnosis group (p =&lt;0.0001). Conclusion. Early diagnosis is still suboptimal. Unemployment, specialist visits other than rheumatology, female gender, rural residence, and lower educational level were associated with the delay in diagnosis in RA patients. Patients with delayed diagnosis showed worse functional disability index.

Physical growth and intellectual function of children with congenital hypothyroidism: An observational study

Introduction: Congenital hypothyroidism (CH) is an important preventable cause of mental retardation. Objectives: To assess growth parameters and the developmental outcome of children with permanent CH on follow up. Method: This was a hospital-based observational study done in the paediatric endocrinology clinic of a tertiary care hospital in South India. The study population included all children with permanent CH aged 5-18 years attending the clinic from March 2017 to March 2018. Weight, height and head circumference of children were measured and the body mass index (BMI) was calculated. Ultrasonography (USG) of the thyroid was done for all patients and structural abnormalities of the thyroid (aplasia, hypoplasia or ectopic gland) were taken as dysgenesis. If USG had normal thyroid it was taken as dyshormonogenesis. Intelligence quotient (IQ) assessment was done by a clinical psychologist. Results: There were 35 children with CH enrolled in the study. Of this, 17 (49%) were diagnosed on or before 6 months of age and 18 (51%) after 6 months of age; 24 (69%) had thyroid dysgenesis and 11 (31%) had dyshormonogenesis; 4 had severe stunting and 5 were obese. Among the 17 children diagnosed on or before 6 months of age, 12 (70.6%) had normal intelligence and 5 (29.4%) had IQ &lt;85 whereas among the 18 children diagnosed after 6 months of age 6 (33%) had normal intelligence and 12 (66%) had IQ &lt;85, which was statistically significant (p=0.028). There were no significant differences between early and late diagnosis groups in other parameters like developmental delay, stunting and BMI. Among 24 children with dysgenesis of thyroid gland, 14 (58%) had IQ &lt;85 whereas among 11 children with dyshormonogenesis, 3 (37.5%) had IQ &lt;85. This was not statistically significant (p=0.08). Conclusions: In this study, a statistically significantly larger proportion of children diagnosed on or before 6 months of age had normal intelligence compared to children diagnosed after 6 months of age. There were no significant differences between early and late diagnosis groups in other parameters like developmental delay, stunting and BMI. Sri Lanka Journal of Child Health, 2023: 52(2): 148-154

The Effect of Timing and Methods for the Diagnosis of Gestational Diabetes Mellitus on Obstetric Complications.

Aim. To compare the impact of the time and method of diagnosis on gestational diabetes mellitus (GDM) in women who gave birth at the Hospital of the Lithuanian University of Health Sciences (LUHS) Kauno klinikos. Methods. A retrospective study was performed using data from the Department of Obstetrics and Gynecology of the LUHS Birth Registry to analyze the data of women who gave birth and had GDM in 2020-2021. The subjects were divided based on the type of diagnosis: GDM was diagnosed either at the first antenatal visit when fasting plasma glycemia (FPG) was ≥5.1 mmol/L (early diagnosis group) or after OGTT at 24 + 0 - 28 + 6 weeks of gestation when at least one pathological glycemic index was observed: fasting glycemia 5.1-6.9 mmol/L or 1-h glycemia ≥10.0 mmol/L or 2 h glycemia 8.5-11.0 mmol/L (late diagnosis group). The results were processed using IBM SPSS. Results. The early diagnosis group had 1254 (65.7%) women, the late diagnosis group had 654 (34.3%). More primigravida women were in the late diagnosis group (p = 0.017) while more multigravida were in the early diagnosis group (p = 0.033). The early diagnosis group had more obese women (p = 0.001), including those with a BMI > 40 (p = 0.001). In the early diagnosis group, GDM was more frequently diagnosed in women who gained <11 kg (p = 0.005), while in the late diagnosis group->16 kg (p = 0.001). FPG was higher in the early diagnosis group (p = 0.001). Glycemia was more commonly corrected with lifestyle changes in the late diagnosis group (p = 0.001), and with additional insulin therapy in the early diagnosis group (p = 0.001). Polyhydramnios and preeclampsia were more common in the late diagnosis group (p = 0.027 and p = 0.009). There were more large-for-gestational-age neonates in the late diagnosis group (p = 0.005). Macrosomia was more common in the late diagnosis group (p = 0.008). Conclusions. GDM is more commonly diagnosed with OGTT in primigravida women. Higher pregestational weight and BMI has an impact on the early diagnosis of GDM and need for insulin therapy with lifestyle changes. Late diagnosis of GDM is connected with obstetric complications.

Early Diagnosis and Surgical Intervention Within 3 Weeks From Symptom Onset Are Associated With Prolonged Survival of Patients With Glioblastoma.

BACKGROUND:Glioblastoma (GBM) is a rapidly growing and most life-threatening malignant brain tumor. The significance of early treatment to the clinical outcomes of patients with GBM is unclear.OBJECTIVE:To determine whether early diagnosis and surgery improve the preoperative and postoperative Karnofsky performance status (KPS) and prognosis of patients with GBM.METHODS:Data of isocitrate dehydrogenase-wildtype patients with GBM treated at our institution between January 2010 and December 2019 were reviewed. Patients were classified into early or late diagnosis groups with a threshold of 14 days from initial symptoms. In addition, patients were divided into early, intermediate, and late surgery groups with thresholds of 21 and 35 days. Representative symptoms and patient prognoses were examined.RESULTS:Of 153 patients, 72 and 81 were classified into the early and late diagnosis groups. The median tumor volume was significantly smaller in the former group. The proportion of patients with preoperative KPS scores 90 was 48.6% and 29.6% in the early and late diagnosis groups (P = .016). The early, intermediate, and late surgery groups included 43, 24, and 86 patients. The median overall survival was significantly longer in the early surgery group than in the late surgery group (28.4 vs 18.7 months, P = .006). Multivariate analysis demonstrated that significant predictors of shorter survival included extent of tumor resection (partial or biopsy), preoperative and postoperative KPS 60, and O6-methylguanine-DNA-methyltransferase promoter status (unmethylated).CONCLUSION:Early diagnosis within 2 weeks and surgical interventions within 3 weeks from the symptom onset are associated with prolonged patient survival. Early GBM treatment will benefit patients with GBM.

Old age and multiple comorbidity are associated with delayed diagnosis of Guillain–Barre syndrome

To assess whether older age and presence of comorbidities were associated with a delayed diagnosis of Guillain–Barré syndrome (GBS). The medical records of 140 patients diagnosed with GBS at Severance Hospital from March 2011 to December 2020 were retrospectively reviewed. Comorbidity profiles were assessed using the Charlson comorbidity index (CCI). The age-adjusted CCI (ACCI) score was calculated, which further incorporated the effect of age. Patients were classified into the early diagnosis group (diagnosis duration ≤ 14 days) and late diagnosis group (diagnosis duration > 14 days). Clinical features and comorbidity profiles were compared between the two groups. The cumulative incidence of diagnosis was compared between the low and high ACCI groups. Age was significantly higher in the late diagnosis group (61.8 ± 15.0 years) than in the early diagnosis group (49.1 ± 18.4, p = 0.001). The CCI score was higher in the late diagnosis group (≥ 3 in 26.1%) than in the early diagnosis group (≥ 3 in 5.1%, p = 0.01). The ACCI score demonstrated a positive correlation with the diagnosis duration (β = 1.636, p < 0.001), indicating that the diagnosis was delayed in patients with a higher ACCI score. The duration from onset to diagnosis was longer in the high ACCI group than in the low ACCI group (log-rank test, p < 0.001). The diagnosis duration was significantly longer, especially in patients with malignancy and cardiovascular diseases. Delayed diagnosis of GBS is associated with older age and multiple comorbidities. Diagnostic delay was significant in patients with malignancies and cardiovascular diseases. Early suspicion of GBS is required in these patients.

Treatment of Posttransplant Hepatocellular Carcinoma Recurrence.

In patients who receive liver transplant to treat hepatocellular carcinoma, 10% to 15% posttransplant recurrence is observed. In the present study, we evaluated the long-term outcomes of patients who had received liver transplant for treatment of hepatocellular carcinoma. Of the 683 livertransplants that we performed, 72 were in response to hepatocellular carcinoma. The physical examination and laboratory and imaging results of the patients were retrospectively analyzed and recorded. The recipients were evaluated according to the Başkent criteria and divided into 2 groups: early diagnosis and late diagnosis. Among 72 total patients in our study, 19 (26.3%) were pediatric recipients. Hepatocellular carcinoma recurred in 7 patients (9.7%; 5 adult, 2 pediatric). Except for one patient, all were in the late diagnosis group.The mean survivaltime of all patients was 137.45 ± 10 months.The mean survival in the early diagnosis group was longer than in the late diagnosis group. During follow-up, 11 patients died from recurrence and distant metastasis. In patients with hepatocellular carcinoma who received liver transplant, we found that postoperative recurrence of hepatocellular carcinoma and distant metastasis can be treated with surgery and/or with interventional radiology methods, which may improve patient survival after liver transplant.

Analysis of autoantibody spectrum and human herpesvirus 6 in adult patients with ‘early’ versus ‘late’ diagnosis of ‘possible limbic encephalitis’

New onset temporal seizures are increasingly encountered in adult patients. Many of those fulfill diagnostic criteria for possible or definite limbic encephalitis (LE). LE is associated with autoantibodies (autoABs) against neuronal surface structures (‘neuronal’ autoABs), ‘onconeuronal’ or GAD65. AutoABs can emerge in a paraneoplastic setting. However, by far not all patients with possible/definite LE have an oncological history. AutoABs have also found to arise in the context of viral encephalitis. Rare associations between autoAB-positive LE and human herpes virus 6 (HHV-6) infection have been as well reported. Our present analysis was dedicated to learn about potentially different autoAB spectra and HHV-6 detection rates in adult-onset temporal seizure patients with possible LE and largely different time spans between first seizure events and referral to a tertiary epileptological center due to pharmacoresistent seizures. We scrutinized serum/CSF samples obtained from adults with ‘early diagnosis’ of possible LE (≤ 30 months after first seizure event; n = 94) versus a patient group with ‘late diagnosis’ of possible LE (≥ 97 months; n = 45) for the presence of autoABs and HHV-6 DNA. AutoABs were detected in CSF and/or serum samples (n = 20) in 21.3 % of the early diagnosis patients with the highest abundance of anti-LGI1 (n = 8), significantly more frequent than in the late diagnosis group (autoAB positive: n = 4 (8.9 %); *p < 0.05, Fisher’s Exact Test). Quantitative PCR revealed viral HHV-6 DNA in only one serum sample of the early diagnosis cohort but no evidence in corresponding CSF samples or in any sample of the late diagnosis group. The present data demonstrate a higher incidence of distinct autoABs in adults with early diagnosis of possible LE. The distinct spectra of autoABs have to be taken into account in the differential diagnosis of possible LE patients with short versus more sustained duration of temporal seizure activity.

273 The Consequences of a Failed Screening Programme

Abstract Introduction Controversy exists surrounding the efficacy of the UK screening programme for developmental dysplasia of the hip (DDH). Method Clinical records were reviewed in children who were treated surgically for DDH. Demographic data, age and mode of presentation, and surgical treatments were analysed, as well as outcomes, re-operation rate and AVN incidence. Late diagnosis was defined as greater than 4 months. Results 106 children (16 male, 90 female) underwent surgery from 1997 to 2018. 95 hips were operated for dislocation and 22 were operated for dysplasia. 13 patients had bilateral dislocations. Of the dislocated hips, the median age at diagnosis was 9 months (IQR 2-19). 56% were diagnosed late. In the late diagnosis group the median age for diagnosis was 19 months (IQR 15-21). We have identified an increasing trend in late presentation in recent years. This has been matched with an increasing trend in operation rates for dislocation per 1000 births. Conclusions This study demonstrates that DDH is being diagnosed increasingly late, which correlates with an increased need for surgical management. This suggests that the current UK screening programme is failing to identify children with DDH in a timely fashion, which necessitates more aggressive surgical treatment and less favourable outcomes.

The symptom experience of early and late treatment seekers before an atrial fibrillation diagnosis.

Atrial fibrillation is a complex condition associated with a broad spectrum of symptoms, coupled with variability in the frequency, duration and severity of symptoms. Early treatment seeking is important to reduce the risk of stroke, heart failure and dementia. Despite the increasing prevalence, there remains a limited understanding of the symptom experience prior to an atrial fibrillation diagnosis, and how these experiences influence treatment-related decisions and time frames. This qualitative study aimed to explore the symptom experiences of patients receiving an early diagnosis of less than 48 hours and a late diagnosis of 48 hours or more after symptom awareness. Twenty-six adults were interviewed guided by the symptom experience model. The symptom checklist was used to probe patient's symptoms further. Data were analysed using a two-step approach to thematic analysis utilising concepts from the symptom experience model. The two groups differed in their perception, evaluation and response to symptoms. The early diagnosis group (n = 6) experienced traumatic, severe and persistent symptoms, evoking concern and urgent treatment seeking. Conversely, the late diagnosis group (n = 20) reported more vague, paroxysmal symptoms that were readily ignored, self-theorised as non-illness related, and engaged in non-treatment strategies. Healthy self-perceptions, past experiences, atrial fibrillation knowledge and healthcare provider interactions influenced early or late treatment seeking. For many, the atrial fibrillation pre-diagnosis was a tumultuous period, requiring prolonged periods to recognise symptoms and formulate treatment-seeking responses. This study may promote future research and strategies aimed at facilitating the early identification and response to symptoms among atrial fibrillation patients.

Importance of early diagnosis for developmental dysplasia of the hip: A 5-year radiological outcome study comparing the effect of early and late diagnosis.

Australia utilises a selective ultrasound screening programme. The rate of late diagnosis of developmental dysplasia of the hip (DDH) in Australia is increasing. The aim of this study is to quantify the treatment required and compare the 5-year radiological outcomes between early and late diagnosis in children with DDH with frank dislocation. We performed a case-matched control study of children with frank DDH dislocations from 2000 to 2010 comparing three groups: children with an early diagnosis successfully treated in a Pavlik harness (SP), children with an early diagnosis who failed Pavlik harness treatment (FP) and children with a late diagnosis (LD). Minimum follow-up was 4 years. A total of 115 hips were included. Patients in the LD group required significantly more open reductions (P < 0.001), acetabular osteotomies (P < 0.001) and femoral osteotomies (P < 0.001). LD was also associated with significantly higher rates of growth disturbance at 46.3%, compared to 20.6% in the FP group and 5% in the SP group (P < 0.001). Overall, there were excellent radiological outcomes in 58.5% of the LD group compared to 79.4% in the FP group and 100% in the SP group. In Australia, high rates of LD in DDH persist in the context of selective ultrasound screening. While good radiological outcomes are achievable, a significantly greater level of surgical intervention is required and this is associated with significantly higher rates of growth disturbance. Optimisation of screening in Australia is vital.

Pulse Oximetry Screening Has Not Changed Timing of Diagnosis or Mortality of Critical Congenital Heart Disease.

This study evaluates the effectiveness of mandatory pulse oximetry screening. The objective is to evaluate whether mandatory pulse oximetry testing had decreased the late critical congenital heart disease (CCHD) diagnosis rate and reduced mortality in neonatal subjects. This was a single center, retrospective cohort study comparing the timing of diagnosis of CCHD between neonates undergoing cardiac surgery in 2009-2010, prior to mandatory pulse oximetry screening, and neonates in 2015-2016, after mandatory pulse oximetry screening was instituted. Follow-up was for 1year. We defined CCHD as lesions requiring surgical correction within 30days of life. Exclusions included: pacemaker insertions, vascular ring divisions, closure of patent ductus arteriosus, arterial cutdown, or extracorporeal membrane oxygenation cannulation without structural heart disease as the sole procedure, or if subjects were born at home. Infants diagnosed prior to discharge from birth hospital were defined as early postnatal; late postnatal subjects were diagnosed after birth hospital discharge. In-hospital mortality and 1-year mortality were measured. A total of 527 neonates were included; 251 (47.6%) comprised the pre-mandatory pulse oximetry screening cohort (2009-2010). Only 3.6% of the 2009-2010 cohort and 4.3% of the 2015-2016 cohort were diagnosed late (p = 0.66). One-year mortality decreased during the study period (17.2% in 2009-2010 vs 10.5% in 2015-2016, p = 0.03). There were no deaths in the late CCHD diagnosis groups. Mandatory pulse oximetry screening legislation has not changed the late postnatal diagnosis rate at our institution. Mortality for neonatal CCHD has declined, but this decline is not attributable to mandatory pulse oximetry screening.

Natural history, with clinical, biochemical, and molecular characterization of classical homocystinuria in the Qatari population.

Classical homocystinuria (HCU) is the most common inborn error of metabolism in Qatar, with an incidence of 1:1800, and is caused by the Qatari founder p.R336C mutation in the CBS gene. This study describes the natural history and clinical manifestations of HCU in the Qatari population. A single center study was performed between 2016 and 2017 in 126 Qatari patients, from 82 families. Detailed clinical and biochemical data were collected, and Stanford-Binet intelligence, quality of life and adherence to treatment assessments were conducted prospectively. Patients were assigned to one of three groups, according to the mode of diagnosis: (a) late diagnosis group (LDG), (b) family screening group (FSG), and (c) newborn screening group (NSG). Of the 126 patients, 69 (55%) were in the LDG, 44 (35%) in the NSG, and 13 (10%) in the FSG. The leading factors for diagnosis in the LDG were ocular manifestations (49%), neurological manifestations (45%), thromboembolic events (4%), and hyperactivity and behavioral changes (1%). Both FSG and NSG groups were asymptomatic at time of diagnosis. NSG had significantly higher intelligence quotient, quality of life, and adherence values compared with the LDG. The LDG and FSG had significantly higher methionine levels than the NSG. The LDG also had significantly higher total homocysteine levels than the NSG and FSG. Regression analysis confirmed these results even when adjusting for age at diagnosis, current age, or adherence. These findings increase the understanding of the natural history of HCU and highlight the importance of early diagnosis and treatment. SYNOPSIS: A study in 126 Qatari patients with HCU, including biochemical, clinical, and other key assessments, reveals that patients with a late clinical diagnosis have a poorer outcome, hereby highlighting the importance of early diagnosis and treatment.

Metabolomics of neonatal blood spots reveal distinct phenotypes of pediatric acute lymphoblastic leukemia and potential effects of early-life nutrition.

Early-life exposures are believed to influence the incidence of pediatric acute lymphoblastic leukemia (ALL). Archived neonatal blood spots (NBS), collected within the first days of life, offer a means to investigate small molecules that reflect early-life exposures. Using untargeted metabolomics, we compared abundances of small-molecule features in extracts of NBS punches from 332 children that later developed ALL and 324 healthy controls. Subjects were stratified by early (1-5 y) and late (6-14 y) diagnosis. Mutually-exclusive sets of metabolic features - representing putative lipids and fatty acids - were associated with ALL, including 9 and 19 metabolites in the early- and late-diagnosis groups, respectively. In the late-diagnosis group, a prominent cluster of features with apparent 18:2 fatty-acid chains suggested that newborn exposure to the essential nutrient, linoleic acid, increased ALL risk. Interestingly, abundances of these putative 18:2 lipids were greater in infants who were fed formula rather than breast milk (colostrum) and increased with the mother's pre-pregnancy body mass index. These results suggest possible etiologic roles of newborn nutrition in late-diagnosis ALL.

Untargeted Metabolomics of Archived Dried Blood Spots Reveals Lipid Modulation at Birth Associated with Pediatric Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is the most common form of childhood leukemia. Metabolomics analysis of archived dried blood spots (DBS) collected at birth provides a snapshot of early life exposures that can provide insights into the causes and underlying prenatal biology of ALL.We received single 4.7-mm DBS punches (equivalent to ~8 µL whole blood) collected between 1985 and 2005 for over 300 ALL cases and their matched controls as part of the California Childhood Leukemia Study. Matching was performed on date of birth and gender and roughly matched on ethnicity. DBS were extracted with acetonitrile and analyzed with an Agilent 1290 UHPLC system connected to a 6550 QTOF HRMS (Santa Clara, US) in ESI (-) mode. Analysis was performed on subjects stratified by age at diagnosis as a means of distinguishing between potentially different ALL phenotypes (early: 1-5 years; late: 6-14 years). In order to minimize the number of false positives, associations between metabolite features and ALL were determined with an ensemble of statistical methods, namely, linear regression p-values, bootstrapped regularized logistic regression (LASSO), and random forest.There was no overlap in features selected for associations with early diagnosis (9 features) and late diagnosis (24 features) of ALL. Annotated metabolites were primarily fatty acid and glycerophospholipids. Several of the selected metabolites were associated with the time to ALL diagnosis, suggesting that they reflect effects of disease progression rather than causal exposures. Interestingly, several metabolites selected in the late diagnosis group were highly associated with breastfeeding practice, a known risk factor of ALL. Since DBS are collected within 48 hours of birth, they include nutrients from one or more infant feedings. These results suggest that lipids associated with neonatal nutrition may be involved with initiation of ALL in early life and should be a focus of future targeted research.

Is early HIV infection diagnosis at a reference center a reality in the state of Ceara?

Early diagnosis of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) can decrease transmission and significantly affect morbidity and mortality; however, Brazil still confronts the reality of late HIV diagnosis. Medical records of 284 HIV-positive patients were reviewed in this cross-sectional study. Of all patients, 28% were diagnosed in the context of health assessments, whereas 27% were symptomatic at diagnosis. Early HIV infection (Group 1) was diagnosed in 60.2% of participants. They were younger than those with late diagnosis (Group 2) (p = 0.002). These findings highlight the need for strategies to increase HIV testing in asymptomatic individuals and older patients.