Time Of Delayed Diagnosis Research Articles

Clinical characteristics and therapeutic outcomes of acromegalic patients with giant growth hormone-secreting pituitary adenomas: a single-center study of 67 cases.

Acromegalic patients with giant growth hormone-secreting pituitary adenomas (GHPAs) (≥ 40mm) are relatively rare, and their clinical characteristics and treatment outcome data are limited. This study aims to analyze the clinical practice experience of giant GHPAs. Sixty-seven acromegalic patients with giant GHPAs and 67 patients with macro GHPAs (10-39mm), matched for age and gender from the same hospital during the same period, were retrospectively recruited. The clinical characteristics, treatment, and outcomes were analyzed. Enlargement of the extremities and facial features were the most common symptoms in most patients (92.5%). Compared with the macroadenoma group, more frequent visual impairment (86.6% vs. 25.4%, P < 0.001) and gonadal axis dysfunction (49.3% vs. 34.3%, P = 0.008), higher preoperative fasting GH, nadir GH after OGTT and IGF-1 levels, and a higher proportion of extrasellar tumor invasion were seen in the giant adenoma group. As the adenoma size increases, the total resection rate decreases, and postoperative complications and multimodal treatment strategies increase significantly. Fasting and nadir GH levels remained higher at 1week postoperatively, and there were more surgical complications and cases of anterior hypopituitarism in the giant group. After a median follow-up of 36months, 12 patients (36.4%) in the giant GHPA group and 17 (36.2%) in the macro GHPA group achieved biochemical remission. Other factors such as age of onset, age of diagnosis, delayed diagnosis time, metabolic complications, p53 positive rate, and Ki-67 index showed no significant difference between the two groups. With aggressive multimodal therapy, the biochemical remission rate of acromegalic patients with giant GHPAs is comparable to that of patients with macro adenoma. However, postoperative complications and hypopituitarism need to be closely monitored.

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.

Clinical and Genetic Analysis in Neurological Wilson's Disease Patients With Neurological Worsening Following Chelator Therapy.

Objectives: None of the previous studies have focused on the genetic effect on neurological worsening in neurological Wilson’s disease (WD) patients following chelator therapy. We aimed to evaluate the clinical and genetic role in the occurrence of neurological worsening. Methods: We retrospectively reviewed the medical records of neurological WD patients who received initial chelator therapy and genetic test. Clinical, laboratory, and genetic data were collected. The genotype was classified into two types: 1) severe mutation genotype: patients who carried at least one of the following three types of mutations: frameshift mutation, splicing mutation, or nonsense mutation; 2) non-severe mutation genotype: patients who only carried missense mutations. Then, the clinical features and genotype of the patients with and without neurological worsening were investigated. Results: Forty-seven neurological WD patients were identified with a median age at onset of 16.17 years (range 7.75–47 years) and 35 (74.5%) males. The mean interval from onset to diagnosis was 0.6 years (range: 0.5 months-6.25 years). Neurological deterioration was observed in 29 patients (61.7%) and the other 18 patients (38.3%) were stable or improved during anti-copper treatment. The neurological worsening was completely irreversible in 6 cases (20.7%) and partially irreversible in 16 cases (55.2%). The common deteriorated symptoms were as follows: rigidity in 20 cases (69%), speech difficulties in 20 cases (69%)), walking difficulties in 13 cases (44.8%), dysphagia in 9 cases (31%), and salivation in 9 cases (31%). The patients with neurological worsening had significantly younger age (p = 0.028), shorter delayed diagnosis time (p = 0.011), higher rate of dystonia (p = 0.003), and severe mutation genotype (p = 0.036), compared to those without neurological worsening. Conclusion: We found that younger age of onset, the presence of dystonia, and genotype with severe mutations may be predictive of neurological worsening in the neurological WD patients that received chelator therapy. For those patients, chelator therapy should be given with caution and needs closer observation during follow-up.

Analysis of the Phenotypic Variability as Well as Impact of Early Diagnosis and Treatment in Six Affected Families With ALDH7A1 Deficiency.

ObjectiveTo describe the clinical characteristics of 12 patients from six families with pyridoxine-dependent epilepsy (PDE) carrying ALDH7A1 mutations, and analyze the impact of early diagnosis and treatment, as well as possible genotype–phenotype relationship.MethodsClinical and genetics data of 12 patients were collected.ResultsFamily 1–3 presented with symptoms in the neonatal period, while family 4-6 presented during early infancy. In the same family, the age of onset was similar. The focal motor seizure appeared in all patients. The affected identical twins from family 4 were diagnosed with infantile spasms. Mutation analysis identified nine different ALDH7A1 mutations among six families. The neurodevelopment of siblings in family 1 was mild delay and normal separately due to the minor difference of delayed diagnosis time. Siblings in family 2 showed severely delayed and normal development respectively due to the significant difference of a delayed diagnosis for 4 years. In family 5, although the difference of the delayed diagnosis time is up to 7 years, the nearly normal psychomotor development in both patients might be due to infrequent seizures before the delayed diagnosis. A severe phenotype exhibited in family 3, 4, and 6. The survived affected patients presented with severe developmental delay or refractory seizures and their twins or older sisters presented a similar clinical history and died in the early days of life. Mutation analysis showed D511N and IVS11 + 1G > A in family 3, V188A and exon1 deletion in family 4, and Y354C and exon 8–13 deletion in family 6.ConclusionPatients from the same family often have the same phenotype, including onset age and seizure type. Early treatment with pyridoxine and infrequent seizures showed positive relationship with prognosis. The deletion of exon 1 and exon 8–13 might be associated with the severe phenotype.

Recovery of hypothalamus-pituitary-gonadal dysfunction after the treatment of suprasellar germ cell tumors.

To investigate the incidence of hypothalamus-pituitary-gonadal (HPG) axis initiation/recovery after treatment and to identify predictive risk factors for noninitiation/recovery. A total of 127 consecutive suprasellar germ cell tumor (GCT) patients managed at Peking Union Medical College Hospital (2006-2019) were retrospectively analyzed. Prepubertal patients (followed up until 13 years of age for girls and 14 years of age for boys) and patients with HPG dysfunction (followed up for 2 years) were divided into the initiation/recovery and noninitiation/recovery groups. Of the 127 suprasellar GCT patients, 75 met the follow-up criteria, 28 (37.3%) of whom experienced HPG axis initiation/recovery. Compared to the noninitiation/recovery group, the initiation/recovery group included more males and had shorter delayed diagnosis times, smaller tumor sizes, lower panhypopituitarism rates, thinner pituitary stalk widths, lower visual deficit rates, and higher serum testosterone and estradiol levels. The cutoff values of pituitary stalk width, tumor size, and delayed diagnosis time used to predict noninitiation/recovery were 6.9 mm, 6.9 mm and 1.7 years, respectively. Tumor size ≥6.9 mm (odds ratio (OR) = 7.5, 95% CI: 2.2-25.8, P = 0.001), panhypopituitarism (OR = 5.0, 95% CI: 1.4-17.6, P = 0.013), and delayed diagnosis time ≥1.7 years (OR = 5.7, 95% CI: 1.5-20.7, P = 0.009) were risk factors for noninitiation/recovery. Among suprasellar GCT patients, nearly one-third of prepubertal patients and patients with HPG dysfunction experience HPG axis initiation/recovery after treatment. Tumor size ≥6.9 mm, panhypopituitarism, and delayed diagnosis time ≥1.7 years were identified as predictive risk factors for noninitiation/recovery.

Six Gynecological Cancer Patients Infected With SARS-CoV-2 After Surgery or Radio-/Chemo-Therapy Treatment: Case Series

ObjectiveRecently, the number of gynecological cancer patients infected with SARS-CoV-2 has been increasing. This article was committed to studying the influence of gynecological tumor treatment history compared to the Coronavirus Disease 2019 (COVID-19), which was of great significance for the treatment of gynecological cancer patients during the outbreak of COVID-19.MethodsWe retrospectively analyzed the diagnosis and treatment of six gynecological cancer patients infected with SARS-CoV-2 in Tongji Hospital in Wuhan from January 30 to March 25, 2020. To better explain the treatment of gynecological cancer patients during the epidemic of COVID-19, we summarized the case characteristics, auxiliary examination, treatment plan, and outcome of these six patients.ResultsWe observed a high rate of nosocomial SARS-CoV-2 infection among these six gynecological cancer patients, who were in a low immune state. Also, due to the influence of cancer treatment history, COVID-19-related atypical symptoms became the first symptom of COVID-19 in some cases, which increased the difficulty of diagnosis. Furthermore, in terms of treatment for these cases, immune boosters and reagents that raised white blood cells were applied, except for in symptomatic antiviral treatment. At present, all patients in this study were discharged from the hospital with a good prognosis.ConclusionAfter cancer-related treatment, the gynecological cancer patients became more susceptible to COVID-19. Besides, the history of cancer treatment made the diagnosis of COVID-19 difficult, which also affected the treatment of COVID-19. Therefore, we put forward the corresponding therapy suggestions for gynecological cancer patients during the outbreak of COVID-19.

Real-world analysis of haemophilia patients in China: A single centre's experience.

The management of haemophilia is critical to minimize the risk of disability and reduce the burden on China's healthcare system. This study was based on a single centre in China and was conducted to understand the evolution of real-world haemophilia care over the past 15years. We retrospectively analysed clinical characteristics, diagnosis, treatment and medical expenditures of 428 patients with haemophilia from January 2004 to December 2018 from the Institute of Hematology & Blood Diseases Hospital in Tianjin, China. The delayed diagnosis time significantly decreased from 13.3±5.1years before 2004 to 0.4±0.4year in 2014-2018 (P<.05). Among children and adults receiving prophylactic treatment, the annual factor consumption increased from 2004-2008 (168.8IU/kg in children and 120.7IU/kg in adults) to 2009-2013 (389.2IU/kg in children and 316.2IU/kg in adults) and 2014-2018 (1328.0IU/kg in children and 878.8IU/kg in adults, P<.001). The annual medical insurance expenditure for haemophilia had increased steadily over the past 10years. The number of patients tested regularly for inhibitors increased from 2004 (1.9% [2/105]) to 2018 (21.5% [59/275]). The seroprevalence of hepatitis C virus (HCV) was 33.8% during the years examined, while the incidence rates of HCV among patients significantly decreased (7.3% in 2008 to 0.4% in 2018). Significant improvements in the management of haemophilia were observed from 2004 to 2018. These results highlight the joint effort of the reimbursement policy and drug regulatory management paving the way for a better future for patients with haemophilia in China.

A risk analysis based on a two-stage delayed diagnosis regression model with application to chronic disease progression

This paper presents a two-stage regression model for quantifying different stages of a disease progression with delayed diagnosis time and for identifying the risk factors associated with each stage. Conventional chronic disease progression studies reported replied on the assumption that the time of the confirmation of a disease state by diagnosis is the start time of this disease state. Clearly this will lead to biased estimates of progression since the disease state should have already occurred before the diagnosis, but the true occurrence time is unknown. This later confirmation is called the delayed diagnosis in this paper and a delay-time modelling procedure is developed for the identification of the unknown stages of progression. A hazard-based regression model is also proposed for a further risk analysis. We apply the developed methods to hepatitis C data and the analysis shows that considering the delayed diagnosis significantly improved the model fit in comparison with the conventional model. We also find that the risk factors associated with each stage are more significant, particularly in the second stage of progression, than those based on the conventional model. We conclude that such delayed phenomena in diagnosis should be taken into account when modelling the chronic disease progression process and conducting related risk analysis.

Impact of delayed diagnosis time in estimating progression rates to hepatitis C virus-related cirrhosis and death

Delay of the diagnosis of hepatitis C virus (HCV), and its treatment to avert cirrhosis, is often present sincethe early stage of HCV progression is latent. Current methods to determine the incubation time to HCV-related cirrhosis and the duration time from cirrhosis to subsequent events (e.g. complications or death) used to be based on the time of liver biopsy diagnosis and ignore this delay which led to an interval censoring for the first event time and a double censoring for the subsequent event time. To investigate the impact of this delay in estimating HCV progression rates and relevant estimating bias, we present a correlated two-stage progression model for delayed diagnosis time and fit the developed model to the previously studied hepatitis C cohort data from Edinburgh. Our analysis shows that taking the delayed diagnosis into account gives a mildly different estimate of progression rate to cirrhosis and significantly lower estimated progression rate to HCV-related death in comparison with conventional modelling. We also find that when the delay increases, the bias in estimating progression increases significantly.