¿Qué puede esconder el retraso global del desarrollo? A propósito de un caso de causa genética / What can Global Developmental Delay Conceal? Apropos of a Case with a Genetic Cause

Se presenta un niño de 6 años con antecedente de retraso del lenguaje que llevó a sus padres a realizar múltiples consultas. En un primer momento, su cuadro fue interpretado como parte de un retraso global del desarrollo. Posteriormente, el paciente presentó convulsiones y episodios de descompensación metabólica, comenzando desde entonces su seguimiento por los Servicios de neurología, genética y metabolismo. Finalmente, tras varios estudios complementarios, por medio de un exoma trío se arribó al diagnóstico de síndrome de microduplicación del cromosoma 7q11.23, lo que justifica tanto el retraso global de desarrollo del paciente como su clínica neurológica. (AU)

A six-year-old boy presents with a history of language delay that led his parents to make multiple consultations. At first, we interpreted his condition as part of a global developmental delay. Subsequently, the patient presented seizures and episodes of metabolic decompensation, and since then, he had to be followed up by neurology, genetics, and metabolism services. Finally, after several complementary studies, following a trio exome analysis, we diagnosed chromosome 7q11.23 microduplication syndrome, which explains his global developmental delay and neurological symptoms. (AU)

Determinants of patients’ delay with disability in the diagnosed leprosy cases in the three major states of India: A case-control study

Background: Skin lesions are the most common early symptoms of leprosy, often ignored by patients at an early stage and misdiagnosed as other dermatological diseases by healthcare personnel, leading to delay in diagnosis and treatment of leprosy precipitating permanent neurological deficit, deformities and serious disabilities. Aims: The objective is to evaluate the duration of delay and factors responsible for the delay in reporting of patients, among the newly detected leprosy cases (Grade 1 and Grade 2 disability patients). Methods: A case-control study was conducted during 2014–2016 in three major states of India (Delhi, Gujarat and West Bengal) in 140 randomly recruited newly registered adult leprosy patients (aged 18 years and above) with Grade 2/1 disabilities (cases) and 140 Grade 0 disability patients (controls) in each of these Indian states. Results: It is established that the major contributors for the delay in the early diagnosis of leprosy have been patient-related factors. The median patient delay in the three states of Delhi, Gujarat and West Bengal were five months (0.7–1.8), 2.8 months (2–14) and 12 months (2–24), respectively. Limitations: The study design is case-control and has an inbuilt reporting bias due to the retrospective nature of data collection but the data collection was carried with caution to reduce the recall bias. As the study is carried out in three states, generalisation of interpretation was cautiously executed. The matching ratio of cases and controls was 1:1 in this study, but we could not increase the controls due to operational feasibility during the conduct of the study. Conclusion: Patient delay is a crucial factor responsible for the disability among new leprosy cases. A higher patient delay in these three states reflects that the community is not aware about the signs and symptoms of leprosy. Reducing patient delay is very important for reducing disabilities in the newly diagnosed cases.

A-case-report-of-zellweger-syndrome-with-global-deveopmental-delay

Peroxisome biogenesis disorder are related to spectrum of genetic diseases that range from severe Zellweger syndrome to milder infantile Refsum disease. Zellweger syndrome is characterized by dysmorphic features, severe hypotonia, seizures, failure to thrive, liver dysfunction and skeletal defects. We report a case of Zellweger syndrome, confirmed by clinical, biochemical and molecular findings, diagnosed in context of dysmorphism, and seizures.

Renal-limited systemic lupus erythematosus: Avoiding delay in diagnosis

Nephrotic syndrome (NS) and glomerulonephritis (GN) are disorders of varied etiologies. Systemic lupus erythematosus (SLE) is one of the multisystemic diseases causing NS and GN. SLE is often suspected whenever NS/GN is associated with extrarenal manifestations. However, it presents solely as NS or GN without extrarenal features in a handful of cases. This affects the prognosis adversely as negligent delay in diagnosis of SLE and initiation of immunosuppressive therapy is associated with poorer response. We present a series of five women who presented solely with renal manifestations. The diagnosis of SLE was delayed, as the women did not have any extrarenal features. We started immunosuppressive therapy after a diagnosis of lupus nephritis was made in retrospect after a kidney biopsy. This case series highlights the importance of performing serology tests for SLE in all young female patients who present with NS/GN to avoid delay in diagnosis.

Evolução do atraso diagnóstico na doença inflamatória intestinal em idade pediátrica e o impacto da pandemia COVID-19 / Evolution of diagnostic delay in pediatric inflammatory bowel disease and the impact of the covid-19 pandemic

ABSTRACT Background: Pediatric inflammatory bowel disease (IBD) is increasingly prevalent, but diagnosis can still be challenging. Diagnostic delay is particularly deleterious in this age group. Objective This study explores the evolution of diagnostic delay in pediatric IBD and the influence of the COVID-19 pandemic. Methods Retrospective study including all pediatric IBD patients diagnosed during 2014, 2019 and 2020 in a tertiary hospital. Diagnostic delay, time to first medical visit, time to pediatric gastroenterologist (PG) visit and time to diagnosis were calculated and compared within a gap of five years (2019 and 2014) and with the year of onset of the pandemic (2020 and 2019). Results A total of 93 participants were included (2014: 32, 2019: 30, 2020: 31). No significant differences were observed in diagnostic delay, time to first medical visit in Crohn's disease (CD), time to PG visit and time to diagnosis when comparing 2019-2014 and 2020-2019. Time to first visit in ulcerative colitis (UC) and Undetermined-IBD increased in 2019 (P=0.03), with new decrease in 2020 (P=0.04). Diagnostic delay was longer in DC compared to UC plus Undetermined-IBD. Conclusion Diagnostic delay is still an important matter in pediatric IBD, with no significant change over the last years. The time to the first PG visit and the time for diagnosis seem to have the greatest impact on diagnostic delay. Thus, strategies to enhance recognition of IBD symptoms among first-line physicians and to improve communication, facilitating referral, are of utmost importance. Despite the restraints in the health care system caused by the pandemic, time to diagnosis in pediatric IBD was not impaired during 2020 in our center.

RESUMO Contexto Apesar da prevalência crescente da doença inflamatória intestinal (DII) em idade pediátrica, o seu diagnóstico pode ser desafiante. Um atraso no diagnóstico é particularmente deletério nesta faixa etária. Objetivo Este estudo investiga a evolução do atraso diagnóstico na DII pediátrica e o impacto da pandemia COVID-19 no mesmo. Métodos Estudo retrospetivo que incluiu todos os doentes em idade pediátrica diagnosticados com DII durante 2014, 2019 e 2020 num hospital terciário. O atraso diagnóstico, o tempo para a primeira visita médica, o tempo para a primeira visita ao gastroenterologista pediátrico (GP) e o tempo para o diagnóstico foram calculados e comparados num intervalo de cinco anos (2019 e 2014) e com o ano marcado pelo surgimento da pandemia COVID-19 (2020 e 2019). Resultados Foram incluídos 93 participantes (2014: 32, 2019: 30, 2020: 31). Não se observou diferença significativa no atraso diagnóstico, no tempo para a primeira visita médica na doença de Crohn (DC), no tempo para a primeira visita ao GP e no tempo para o diagnóstico após comparação entre 2019-2014 e 2020-2019. Na colite ulcerosa e colite indeterminada, o tempo para a primeira visita médica aumentou em 2019 (P=0,03), com nova diminuição em 2020 (P=0,04). O atraso diagnóstico foi superior na DC comparativamente com a colite ulcerosa e colite indeterminada. Conclusão O atraso diagnóstico na DII pediátrica continua a ser um tema importante, que não sofreu alteração significativa ao longo dos últimos anos. O tempo para a primeira visita ao GP e o tempo para o diagnóstico parecem ter maior impacto no atraso diagnóstico, pelo que são necessárias estratégias para aumentar o reconhecimento dos sintomas da DII entre os médicos de primeira linha, bem como melhorar a comunicação e a referenciação. Apesar das restrições causadas pela pandemia no sistema de saúde, o tempo para o diagnóstico na DII pediátrica não foi comprometido no nosso centro em 2020.

Qualitative study on delayed experience of seeking medical treatment in patients with advanced lung cancer / 中国实用护理杂志

Objective:To explore the causes and feelings of delayed experience of seeking medical treatment in patients with advanced lung cancer, and to provide new insights for more targeted health education and medical care services.Methods:A semi-structured in depth interview based on the theory of planned behavior was conducted among 30 patients with advanced lung cancer who experienced medical delay from November to December in 2021 admitted to First Affiliated Hospital of Guangxi Medical University. The interview content was analyzed and abstracted by using Colaizzi phenomenological analysis method and Nvivo11.0 software.Results:The delay duration of 30 patients with advanced lung cancer ranged from 90 to 213 days. Four subject groups were extracted by generic analysis: the cause of delay, the cause to seek medical help, the worry about the disease, and solutions.Conclusions:The delay behavior of patients with advanced lung cancer is affected by external situational factors such as symptom severity, family economic capacity, social support, accessibility of health services, prevalence of novel coronavirus, and subjective psychological factors such as sense of stigma and burden of disease, it is necessary to reduce the occurrence of medical delay in patients with advanced lung cancer through the comprehensive management strategy of multiple channels.

Effects of Delay in Tumor-Immune System on Stability / 医用生物力学

Objective To study stability of the deterministic tumor-immune system with time delay by means of linear stability analysis method. Methods In tumor-immune system, since it took some time for immune cells to recognize tumor cells and respond appropriately, time delay was considered in this process, then the model was simplified by using Taylor expansion of small delay, and the equilibrium points were solved out. By linear stability analysis method, the stability of these equilibrium points was studied. Finally, the trajectory of the system and that around each equilibrium point were simulated by numerical calculation method, so as to verify the result of theoretical analysis. Results The system had four meaningful equilibrium points with small delay, including a stable focus, a stable node, and two saddles. Moreover, the type and stability of these equilibrium points were not affected by the delay. Numerical simulation demonstrated the conclusion from theoretical analysis. Conclusions Under the condition of small delay, the type and stability of equilibrium points in the system are notaffected by the delay. The results are helpful to further understand dynamic mechanisms of tumor immune response, and provide references for tumor growth and treatment

Diagnostic Methods of Global Developmental Delay Caused by 10q24.3 Heterozygous Loss： A Case Discussion / 中山大学学报(医学科学版)

ObjectiveTo discuss the diagnostic methods of global developmental delay caused by 10q24.3 heterozygous loss. MethodsA retrospective analysis was conducted on the clinical data of one child with global developmental delay， and the results of low depth whole-genome copy number variation sequencing （CNVseq） and family whole exome sequencing （WES） of the child and his parents. ResultsThe patient was a 10-month-old male with developmental retardation in four areas， with some special features （ocular hypertelorism， strabismus， flat nose bridge， protruding forehead， cleft palate， high palatal arch， etc.） and hypotonia of limbs. The CNVseq and WES test showed that the patient had new 10q24.3 heterozygosis loss. Because this region contains the gene SUFU associated with basal cell nevus syndrome and the gene CNNM2 associated with hypomagnesemia， seizures， and mental retardation， and the gene TRIM8 associated of Focal segmental glomerulosclerosis with neurodevelopmental syndrome， we speculated that the cause of the disease in the child was highly related to the heterozygosity deletion of SUFU gene and CNNM2 gene and TRIM8 gene. ConclusionGenetic testing should be improved as soon as possible for children with global developmental delay and special facial manifestations， so as to make clear diagnosis and to judge prognosis.

Current Situation and Influencing Factors of Delay in Seeking Medical Treatment Among Residents in Rural Areas of Sichuan Province / 中国医学科学院学报

Objective To understand the current situation and explore the influencing factors of delay in seeking medical treatment for common symptoms of residents in the rural areas of Sichuan province. Methods In July 2019,multi-stage random sampling was carried out in Zigong city,Sichuan province,and the data were collected by face-to-face questionnaire interview.The residents who had lived at hometown for more than half a year in the past year and had seen a doctor in the most recent month were surveyed.Logistic regression was adopted to predict the influencing factors of delay in seeking medical treatment. Results A total of 342 subjects were enrolled,and the incidence of delay in seeking medical treatment was 13.45%(46/342).Compared with the young and middle-aged(<65 years)people,the elderly(≥65 years)people were more likely to have delay in seeking medical treatment (OR=2.187,95%CI=1.074-4.457,P=0.031).The rural residents who gave higher score of the overall quality of township health centers were less likely to have delay in seeking medical treatment (OR=0.854,95%CI=0.735-0.992,P=0.039). Conclusions The occurrence of delay in seeking medical treatment for common symptoms of rural residents in Sichuan province is low.Age and the overall quality evaluation of township health centers affect the occurrence of delay in medical treatment among the rural residents in Sichuan province.Efforts should be made to improve the awareness of disease prevention among the elderly in rural areas.The investment in health resources in township health centers should be increased to strengthen the introduction and training of talents.These measures can improve the health services in township health centers,guide residents to make timely use of health resources,and reduce the occurrence of delay in seeking medical treatment.

Nutritional status and its influencing factors in children with newly diagnosed inflammatory bowel disease / 中国当代儿科杂志

OBJECTIVES@#To investigate the nutritional status and its influencing factors in children with newly diagnosed inflammatory bowel disease (IBD).@*METHODS@#A retrospective analysis was conducted on the clinical data of children who were diagnosed with IBD for the first time in Hunan Children's Hospital from January 2015 to December 2021. Diagnostic delay was defined as the time from the symptom onset to IBD diagnosis being in the upper quartile (P76-P100) of all IBD children in the study. Multivariate logistic regression analysis was used to explore the risk factors for emaciation and growth retardation.@*RESULTS@#A total of 125 children with newly diagnosed IBD were included, with Crohn's disease being the main type (91.2%). The rates of emaciation and growth retardation were 42.4% (53 cases) and 7.2% (9 cases), respectively, and the rate of anemia was 77.6% (97 cases). Diagnostic delay was noted in 31 children (24.8%), with the time from the symptom onset to IBD diagnosis of 366 to 7 211 days. Multivariate logistic regression analysis showed that diagnostic delay was a risk factor for emaciation and growth retardation (OR=2.73 and OR=4.42, respectively; P<0.05) and that age was positively associated with emaciation (OR=1.30, P<0.05).@*CONCLUSIONS@#Children with newly diagnosed IBD have poor nutritional status, and the rates of anemia, emaciation, and growth retardation are high. Diagnostic delay is associated with malnutrition in children with IBD.

Börjeson -Forssman -Lehmann syndrome: A case report / 中南大学学报(医学版)

Börjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked intellectual disability. The main features of the patients include intellectual disability/global developmental delay, characteristic face, anomalies of fingers and toes, hypogonadism, linear skin hyperpigmentation, and tooth abnormalities in female patients, and obesity in male patients. A case of BFLS caused by a novel mutation of PHF6 gene who was treated in the Department of Pediatrics, Xiangya Hospital, Central South University was reported. The 11 months old girl presented the following symptons: Global developmental delay, characteristic face, sparse hair, ocular hypertelorism, flat nasal bridge, hairy anterior to the tragus, thin upper lip, dental anomalies, ankyloglossia, simian line, tapering fingers, camptodactylia, and linear skin hyperpigmentation. The gene results of the second-generation sequencing technology showed that there was a novel heterozygous mutation site c.346C>T (p.Arg116*) of the PHF6 (NM032458.3), variation rating as pathogenic variation. During the follow-up, the patient developed astigmatism, strabismus, awake bruxism, and stereotyped behavior, and the linear skin hyperpigmentation became gradually more evident. The disease is lack of effective therapy so far.

Heterogeneidad clínica y molecular en los trastornos asociados con CDKL5 / Clinical and molecular heterogeneity in CDLK5 disorders

Resumen Introducción: El síndrome por deficiencia de CDKL5 es originado por variantes patogénicas en el gen CDKL5, con un espectro clínico variable que va desde pacientes con características del trastorno del espectro autista hasta epilepsia de inicio temprano y refractaria al tratamiento. Inicialmente fue considerado como una forma atípica de síndrome de Rett. Casos clínicos: Presentamos tres pacientes no relacionadas, evaluadas por retraso global del desarrollo y epilepsia refractaria. Los tres casos eran hemicigotos a una variante patógena de CDKL5. En una paciente se realizó panel de 306 genes asociados con epilepsia; en las otras dos se realizó microarreglo genómico comparativo. Las características clínicas y los hallazgos en el electroencefalograma y la resonancia magnética cerebral se han descrito clásicamente en el espectro de manifestaciones de este síndrome. Conclusiones: El síndrome por deficiencia de CDKL5 representa un reto para los médicos, ya que en muchos casos las manifestaciones clínicas y los estudios electroencefalográficos y de neuroimagen pueden ser inespecíficos. Debe sospecharse este síndrome ante la presencia de retraso global del desarrollo, fenotipo conductual autista y epilepsia, asociado o no con dismorfias. Dada la similitud entre diversas encefalopatías epilépticas, se deben solicitar paneles multigénicos que incluyan la secuenciación y el análisis de duplicación/deleción en los que se contemple este gen y sus posibles diagnósticos diferenciales, aunque sin olvidar la utilidad de las técnicas genómicas en casos poco claros.

Abstract Background: CDKL5 deficiency syndrome is caused by pathogenic variants in the CDKL5 gene, with a variable clinical spectrum ranging from patients with characteristics of autism spectrum disorder to early-onset epilepsy refractory to treatment. Initially, until the gene was discovered, it was considered an atypical form of Rett syndrome. This study aimed to describe the clinical and molecular heterogeneity in CDLK5 disorders among three female patients with CDKL5 pathogenic variants. Case reports: We reported three unrelated Mexican female patients evaluated for global developmental delay and epilepsy. All three cases were hemizygotes to a CDKL5 pathogenic variant. In one patient, we performed a 306 gene panel associated with epilepsy. In the other two cases, a human genomic microarray was performed. We describe their clinical features electroencephalogram and brain magnetic resonance evaluations. Conclusions: CDKL5 deficiency syndrome represents a challenge for clinicians since the clinical manifestations, electroencephalographic and neuroimaging studies can be non-specific. This syndrome should be suspected in the presence of global developmental delay, autistic behavioral phenotype and epilepsy, associated or not with dysmorphia. Given the similarity between various epileptic encephalopathies, multigene panels including sequencing and duplication/deletion analysis should be requested in which this gene and its possible differential diagnoses are considered, without forgetting the usefulness of genomic techniques in unclear cases.

Characterization of the SRD5A3-CDG Clinical Spectrum

Abstract We aimed to characterize the clinical spectrum of patients diagnosed with SRD5A3-CDG, a subtype of congenital disorders of glycosylation (CDG) due to variants in the steroid 5a-reductase type 3 (SRD5A3) gene. It presents with multi-systemic involvement including neurological disability, dermatologic abnormalities, and ophthalmological defects. We conducted a cross-sectional study of children (n=6, ages 4-16 years) with a confirmed diagnosis of SRD5A3-CDG (c.57G>A, p.W19X). Families completed a detailed medical history questionnaire, two quality of life measures, and an adaptive behavior scale. Prevalent clinical features in our cohort included visual impairment (6/6), developmental delay (6/6), nystagmus (5/6), retinal dystrophy (4/6), and hypotonia (3/6). The Vineland Adaptive Behavior Scales demonstrated deficits across all functional domains (Composite Mean 36.17 ± 26.88), although one child did not show significant deficits. The QI-Disability Form demonstrated a mean total score of 64.8 (±12.7), and the PedsQL-Family Impact Module demonstrated a mean total score of 56.5 (±31.5). Vineland composite scores did not correlate with levels of disability captured by the QI-Disability Form (Pearson Correlation range -0.63 to +0.69, p>0.05 on all subscales). Ultimately, despite genotypic homogeneity, there is notable variability in adaptive functioning and quality of life among affected children that does not correlate with age.

Risk predictive models of healthcare-seeking delay among imported malaria patients in Jiangsu Province based on the machine learning / 中国血吸虫病防治杂志

Objective To create risk predictive models of healthcare-seeking delay among imported malaria patients in Jiangsu Province based on machine learning algorithms, so as to provide insights into early identification of imported malaria cases in Jiangsu Province. Methods Case investigation, first symptoms and time of initial diagnosis of imported malaria patients in Jiangsu Province in 2019 were captured from Infectious Disease Report Information Management System and Parasitic Disease Prevention and Control Information Management System of Chinese Center for Disease Control and Prevention. The risk predictive models of healthcare-seeking delay among imported malaria patients were created with the back propagation (BP) neural network model, logistic regression model, random forest model and Bayesian model using thirteen factors as independent variables, including occupation, species of malaria parasite, main clinical manifestations, presence of complications, severity of disease, age, duration of residing abroad, frequency of malaria parasite infections abroad, incubation period, level of institution at initial diagnosis, country of origin, number of individuals travelling with patients and way to go abroad, and time of healthcare-seeking delay as a dependent variable. Logistic regression model was visualized using a nomogram, and the nomogram was evaluated using calibration curves. In addition, the efficiency of the four models for prediction of risk of healthcare-seeking delay among imported malaria patients was evaluated using the area under curve (AUC) of receiver operating characteristic curve (ROC). The importance of each characteristic was quantified and attributed by using SHAP to examine the positive and negative effects of the value of each characteristic on the predictive efficiency. Results A total of 244 imported malaria patients were enrolled, including 100 cases (40.98%) with the duration from onset of first symptoms to time of initial diagnosis that exceeded 24 hours. Logistic regression analysis identified a history of malaria parasite infection [odds ratio (OR) = 3.075, 95% confidential interval (CI): (1.597, 5.923)], long incubation period [OR = 1.010, 95% CI: (1.001, 1.018)] and seeking healthcare in provincial or municipal medical facilities [OR = 12.550, 95% CI: (1.158, 135.963)] as risk factors for delay in seeking healthcare among imported malaria cases. BP neural network modeling showed that duration of residing abroad, incubation period and age posed great impacts on delay in healthcare-seek among imported malaria patients. Random forest modeling showed that the top five factors with the greatest impact on healthcare-seeking delay included main clinical manifestations, the way to go abroad, incubation period, duration of residing abroad and age among imported malaria patients, and Bayesian modeling revealed that the top five factors affecting healthcare-seeking delay among imported malaria patients included level of institutions at initial diagnosis, age, country of origin, history of malaria parasite infection and individuals travelling with imported malaria patients. ROC curve analysis showed higher overall performance of the BP neural network model and the logistic regression model for prediction of the risk of healthcare-seeking delay among imported malaria patients (Z = 2.700 to 4.641, all P values < 0.01), with no statistically significant difference in the AUC among four models (Z = 1.209, P > 0.05). The sensitivity (71.00%) and Youden index (43.92%) of the logistic regression model was higher than those of the BP neural network (63.00% and 36.61%, respectively), and the specificity of the BP neural network model (73.61%) was higher than that of the logistic regression model (72.92%). Conclusions Imported malaria cases with long duration of residing abroad, a history of malaria parasite infection, long incubation period, advanced age and seeking healthcare in provincial or municipal medical institutions have a high likelihood of delay in healthcare-seeking in Jiangsu Province. The models created based on the logistic regression and BP neural network show a high efficiency for prediction of the risk of healthcare-seeking among imported malaria patients in Jiangsu Province, which may provide insights into health management of imported malaria patients.

Status and trend analysis of neuropsychological development of children aged 0‒2 in Tongzhou， Beijing， 2017‒2021 / 上海预防医学

ObjectiveTo describe the neuropsychological development screening of 0‒2 years in Tongzhou from 2017 to 2021 so as to understand the status and trend of developmental delay （DD）. MethodsAnnual report data of 21 community health service centers in Tongzhou District from 2017 to 2021 were clustered， Chi square test was used to analyze the differences in positive rate and DD rate of children aged 0‒2 years with different ages and household registration， and Chi square trend test was used to analyze the linear trend of each age group and household registration. The Gesell test results in 762 children with developmental delay were analyzed， and Chi square test was used to compare the age distribution differences in gross motor， fine motor， language and personal-social behaviors. ResultsThe DD rate of children aged 0‒2 years in 2017‒2021 was 0.43％. A decreasing trend of DD rate in the 0‒ age group was observed （χ2=14.135， P<0.001）， while an increasing trend of DD rate in the 1‒ and <3 age groups was observed （χ2=5.375， P=0.020； χ2=5.558， P=0.018）. The DD rate of children aged 0‒2 years with Beijing household registration was higher （χ2=12.504， P<0.001）. The DD rate of gross motor was the highest in the 0‒ age group （64.60%）， the DD rate of language was the highest in the <3 age group （85.97%）， and a statistically significant difference of gross motor and language was separately found in the three age groups （χ2=183.061， P<0.001； χ2=78.450， P<0.001）. ConclusionAge and Beijing household registration are the influencing factors of DD for children aged 0‒2， and 0‒ years and <3 years are the critical periods for guidance and intervention to promote the development of gross motor and language abilities.

Treatment delay and influencing factors of tuberculosis patients in Xianning from 2008 to 2021 / 公共卫生与预防医学

Objective To analyze the current situation, change trend and influencing factors of the delay in the treatment of tuberculosis patients in Xianning from 2008 to 2021, and to provide a scientific basis for controlling the tuberculosis epidemic. Methods The current situation and trend of the delay in the treatment of tuberculosis patients in Xianning City from 2008 to 2021 were described, and the multivariate Logistic regression analysis model was used to explore the influencing factors of the treatment delay in tuberculosis patients. Results The delay rate of seeking medical care for tuberculosis patients in Xianning from 2008 to 2021 was 58.53%, and the delay rate in the first six years tended to be stable. From 2014 to 2016, it increased slightly and then decreased year by year to 44.76% in 2021. Different gender and age groups showed the same trends as overall patients. The analysis results of the multivariate Logistic regression analysis model showed that females, household registration address in Jiayu County, occupations including service industries, workers, farmers and herdsmen, retirees, and others, the diagnosis result being positive for etiology, and the direct treatment in the patient source were high-risk factors for patients with delayed treatment. The risk of delay in treatment in ≥ 65-year-old patients was lower than that of < 25-year-old patients. Conclusion From 2008 to 2021, the phenomenon of delay in the treatment of patients with pulmonary tuberculosis in Xianning City is relatively common, and the high-risk factors of the delay in treatment need to be paid more attention to.

Epidemiological characteristics of pulmonary tuberculosis among the elderly population at ages of 65 years and older in Yangzhou City / 预防医学

Objective@#To investigate the epidemiological characteristics of pulmonary tuberculosis (PTB) among the elderly at ages of 65 years and older in Yangzhou City, Jiangsu Province from 2017 to 2021, so as to provide the evidence for the development of PTB prevention and control measures in the elderly. @*Methods@#Data of PTB cases at ages of 65 years and older in Yangzhou City from 2017 to 2021 were collected from the Tuberculosis Management Information System of the Chinese Disease Control and Prevention Information System, including age, gender, current address, population classification and diagnosis classification. Descriptive epidemiological methods were used to analyze the temporal distribution, regional distribution, population distribution and delay in healthcare-seeking of PTB cases.@*Results@#A total of 3 283 PTB patients at ages of 65 years and older were registered in Yangzhou City from 2017 to 2021, accounting for 41.12% of the total number of PTB cases. The incidence decreased from 112.10/105 to 66.03/105 (P<0.05), with an average annual incidence of 80.43/105. There were 1 236 cases of PTB cases from April to July, accounting for 37.65%. Guangling District had the highest annual incidence of 96.45/105, followed by Hanjiang District (89.29/105) and Jiangdu district (87.05/105). The average annual incidence of PTB in males was 134.07/105, which was higher than that in females (30.55/105, P<0.05). There were 1 070 cases of PTB cases at ages of 65-69 years, accounting for 32.59%. The highest incidence was seen in men at ages of 85 years and older (200.39/105) and in women at ages of 80-84 years (38.34/105). Farmers were the predominant occupation of PTB cases (2 488 cases, 75.78%). There were 2 365 cases of PTB with delay in healthcare-seeking, accounting for 72.04%.@* Conclusions @#The incidence of PTB in the elderly at ages of 65 years and older in Yangzhou City showed an overall downward trend from 2017 to 2021, peaked from April to July, and was higher in Guangling District, Hanjiang District and Jiangdu District. Males and farmers had higher risks of PTB.

Delayed medical visit among tuberculosis patients and risk factors in Huaibei City， Anhui Province from 2017 to 2021 / 上海预防医学

ObjectiveTo understand the situation about time interval between the onset and medical visit among tuberculosis patients in Huaibei City， Anhui Province from 2017 to 2021， and to determine the delayed medical visit and its risk factors， as to provide evidence for tuberculosis prevention and control. MethodsCase information of confirmed tuberculosis patients in Huaibei City in 2017‒2021 was collected from the tuberculosis management information system. Factors associated with time interval between the onset and medical visit were analyzed using rank sum test and multivariate linear regression. Furthermore， factors associated with the delayed medical visit were determined by Chi-square test， Chi-square Cocharan⁃Mantel⁃Haensze test and logistic regression. ResultsThe median time interval between the onset of tuberculosis and medical visit were 22 days among the tuberculosis patients in Huaibei City from 2017‒2021， and the proportion of delayed medical visit was 68.57%. There was an overall decreasing trend in the proportion of delayed medical visit over years （χtrend2=17.342， P=0.002）. Using the multivariate linear regression， positive for Mycobacterium Tuberculosis in the pathogenic diagnosis， and presence of comorbidities were determined to be the risk factors associated with increased time interval between the onset and medical visit. Furthermore， logistic regression analysis showed that patients aged ≤24 years （OR=0.596， 95%CI：0.503‒0.706， P<0.05）， 25‒ years （OR=0.667， 95%CI：0.559‒0.796， P<0.05）， 35‒ years （OR=0.762， 95%CI：0.613‒0.947， P<0.05）， and 45‒54 years （OR=0.838， 95%CI：0.711‒0.987， P<0.05） had significantly lower risk of delayed medical visit than those aged ≥ 55 years old group. Regarding the household registration status， non-local residents had lower risk of delayed medical visit than local residents （OR=0.838， 95%CI：0.732‒0.960， P<0.05）. ConclusionPositive for Mycobacterium tuberculosis in the pathogenic diagnosis， and presence of comorbidities were risk factors associated with increased time interval between the onset and medical visit. The proportion of delayed medical visit among tuberculosis patients in Huaibei City from 2017 to 2021 showed a decreasing trend over 5 years， and age ≥55 years old and local residents were risk factors associated with delayed medical visit.

Clinical phenotype and genetic characteristics of patients with typical 16p11.2 microdeletion syndrome / 中华神经科杂志

Objective:To analyze the clinical phenotype, copy number variation, treatment and follow-up characteristics of children with typical 16p11.2 deletion syndrome.Methods:The clinical data of 10 children with typical 16p11.2 deletion syndrome who were treated in the Department of Neurology, Children′s Hospital of Fudan University from August 2011 to December 2021 were retrospectively collected, and their clinical phenotype, copy number variation, treatment and follow-up were summarized.Results:Among the 10 children, 4 are female and 6 are male, all with epilepsy. Nine patients had epilepsy in infancy, and the age of onset was 6.0 (4.0, 8.5) months. Four cases had focal seizures (1 with fever), 4 had generalized tonic-clonic seizures, and 2 had focal seizures with generalized tonic-clonic seizures. Eight cases had cluster seizures (more than 2 to 10 seizures within 24 hours), and 1 case had 1 status epilepticus. Nine children did not show obvious developmental delay at the onset of epilepsy, and 1 child had developmental delay at the onset of epilepsy at 14 months of age. One child had parallel toes at left foot, and 1 had macrocephaly and low limb muscle tone. Genetic testing found that 10 children carried typical 16p11.2 heterozygous deletion, the starting position of the deletion fragment was Chr16:29478119-29675016, the ending position was Chr16:30125670-30206112, and the deletion length was 525-712 kb, all of which were considered pathogenic variants. In the antiepileptic drug treatment, 4 children were treated with oxcarbazepine, 2 with sodium valproate, 2 was switched to oxcarbazepine after levetiracetam was ineffective, 1 with levetiracetam combined with sodium valproate, and 1 with levetiracetam in combination with sodium valproate and ketogenic diet, and all 10 children had no seizures. One patient developed episodic exercise-induced dyskinesia at school age, and the seizures decreased after treatment with oxcarbazepine. Follow-up of 10 children found that 9 children had different degrees of developmental delay (language was significantly affected), 3 cases were combined with autism-like manifestations, and 1 case had poor comprehension, learning difficulties, and repeated grades after entering regular primary schools.Conclusion:The typical 16p11.2 microdeletion syndrome has the deletion of gene fragments in the proximal region of 16p11.2, characterized by drug-responsive cluster seizures with onset in infancy, which may be accompanied by language delay, autism spectrum disorder and nonspecific malformations.