Diagnostic delays in familial Mediterranean fever: a Juvenile Inflammatory Rheumatism (JIR) cohort study.

Several studies reported that Familial Mediterranean Fever (FMF) diagnosis may be missed or delayed even in countries with a high FMF prevalence. Our aim was to study on a large cohort of European FMF patients the frequency and associated factors of diagnosis delay. Clinical data were extracted from the Juvenile Inflammatory Rheumatism (JIR)-cohort. All FMF patients fulfilled Livneh Criteria and had been sequenced for MEFV exon 10. FMF-diagnostic delay (d-FMF) was defined as the duration between the onset of the symptoms and the diagnosis of more than 10 years. 960 FMF patients were enrolled: delayed diagnosis (d-FMF) was noted in 200 patients (20%). d-FMF patients were significantly older compared to non d-FMF with a median age of 46.4 years old vs. 15.5 (p < 0.0001). Women displayed more d-FMF compared to men (56 vs. 47%, p = 0.03). Clinical presentation during attacks was not statistically significant except for erysipelas-like erythema, which was higher among d-FMF patients (33 vs. 22%, p = 0.0003). The presence of one or two pathogenic MEFV mutation was not different between patients. Compared to other FMF, d-FMF patients displayed significantly more AA amyloidosis (10 vs. 2.6%, p < 0.0001) and received more biotherapy (18 vs. 3.8%, p < 0.0001). Twenty percent of FMF patients had a diagnostic delay >10 years, including more women. The differential diagnosis of abdominal attacks with menstrual pain may be an explanation, and erysipelas-like erythema may not be recognized as FMF by all practitioners.

Diagnostic delay in patients from the international map of axial spondyloarthritis: geographic, socio-demographic and disease-related factors.

OBJECTIVES: To assess diagnostic delay and its associated factors globally, in a large sample of patients included in the International Map of Axial Spondyloarthritis (IMAS). METHODS: IMAS is a cross-sectional online survey (2017-2022) of 5,557 axSpA patients from 27 countries. Diagnostic delay was calculated as the difference between age at diagnosis and age at first symptom onset reported by patients. Associations between diagnostic delay and regions, sociodemographic characteristics, as well as disease-related factors were explored through univariable and multivariable linear regression analysis. RESULTS: Data from 5,327 patients who reported data on diagnostic delay in IMAS survey were analysed: 3,294 were from Europe, 752 from North America, 590 from Asia, 545 from Latin America, and 146 from Africa. Overall, patients reported a mean diagnostic delay of 7.4 years (median: 4.0) since symptom onset, with substantial variation across regions; being the highest delay in South Africa and the lowest in Asia. The variables associated with longer diagnostic delay in the final multivariable regression model were: younger age at symptom onset (b=-0.100), female gender (b = 2.274), being diagnosed by rheumatologist (b = 1.163), greater number of HCPs seen before diagnosis (b = 1.033), and history of uveitis (b = 1.286). CONCLUSION: In this global sample of axSpA patients, the mean diagnostic delay was 7.4 years, and showed significant differences across regions. Younger age at symptom onset, female gender, diagnosis made by a rheumatologist, greater number of HCPs seen before diagnosis, and the history of uveitis were the parameters associated with a longer diagnostic delay in axSpA patients.

Oral Squamous Cell Carcinoma: Features and Medico-Legal Implications of Diagnostic Omission.

Early diagnosis of oncologic pathologies has a crucial role to determine patient's prognosis and therapeutic path. Nonetheless, clinical errors and omissions that can occur during diagnostic, as well as detection of preneoplastic or neoplastic condition, may result in devasting consequences both for patients in terms of health and for professionals in terms of medico-legal responsibility. This study is aimed at examining in depth, through the presentation of a specific clinical case, the medico-legal aspects inherent to the diagnosis of oral cancer, analyzing the preventive, interceptive, and diagnostic strategies, the legal implications of clinical evaluation errors and diagnostic omission, and the type of medical damage produced and professional liability. The medico-legal landscape surrounding oral squamous cell carcinoma is multifaceted and characterized by diagnostic challenges, treatment complexities, and legal considerations. Health-care providers must remain vigilant in navigating these complexities to ensure optimal patient care while mitigating legal risks. By prioritizing high-quality medical records, fostering transparent communication with patients, and implementing preventive strategies, health-care institutions can strive to minimize the incidence of litigation and uphold standards of ethical practice in oral carcinoma cases. Additionally, continued research and education in forensic and legal medicine are essential in informing evidence-based practices and promoting patient safety in this evolving field.

Diagnostic Journey of Korean Patients with Spinal Muscular Atrophy.

PURPOSE: Spinal muscular atrophy (SMA) is an autosomal recessive genetic disease characterized by the loss of motor neurons in the spinal cord and brainstem, leading to muscle atrophy and weakness. To understand the diagnostic process of Korean patients with SMA, we analyzed their clinical characteristics and challenges. MATERIALS AND METHODS: We conducted a retrospective study of 38 patients with SMA (9 type II and 29 type III) between January 2000 and September 2023. Clinical, laboratory, and genetic data were reviewed. RESULTS: The median ages at symptom onset and diagnosis were 3.0 years [interquartile range (IQR): 1.0-7.3 years] and 25.0 years (IQR: 10.5-37.3 years), respectively. The median diagnostic delay was 19.6 years (IQR: 6.4-31.0 years). A significantly longer delay was observed in SMA type III patients (median: 21.0 years, IQR: 11.0-31.0 years) compared to SMA type II patients (median: 3.0 years, IQR: 0.9-21.0 years) (p=0.021). No significant difference was observed in the number of clinic visits before diagnosis between patients with SMA type II (median: 2.0, IQR: 1.0-4.5) and those with type III (median: 2.0, IQR: 2.0-6.0, p=0.282). The number of clinic visits before diagnosis showed no significant association with the age at symptom onset and diagnosis (p=0.998 and 0.291, respectively). CONCLUSION: Our investigation is the first examination of the diagnostic journey of Korean patients with SMA. As treatments for SMA progress, the significance of an accurate diagnosis has increased, highlighting the importance of reviewing the diagnostic advancements made thus far.

Patient journey, disease burden, and functional disability in patients with axial spondyloarthritis in South Africa: results of International Map of Axial Spondyloarthritis (IMAS).

OBJECTIVE: To assess the unmet needs of South Africans with axial spondyloarthritis (axSpA) focusing on the patient journey, functional disability, and health-related quality of life. METHODS: One hundred forty-six South African axSpA patients completed the International Map of Axial Spondyloarthritis (IMAS) online survey. Patient journey, functional disability, activities of daily living, and psychological stress were analyzed in relation to socio-demographic characteristics, disease activity, diagnostic delay, extra-musculoskeletal manifestations, and drug therapy. RESULTS: Majority were female (82.2%) and Caucasian (89.7%) and the mean age of participants, age at onset of initial symptoms, and diagnostic delay were 44.7, 26.7, and 10.8 years, respectively. Participants reported a mean of 3.4 visits to healthcare professionals prior to a definitive diagnosis of axSpA, mostly made by rheumatologists (77.9%). Active disease (BASDAI ≥ 4) was reported by 87%, 69.9% suffered from psychological distress (general health questionnaire-12 score ≥ 3), and more than two-thirds suffered functional limitations in daily, personal, and social activities. Multivariable logistic analysis showed that active disease was more common in females [OR (95% CI) = 4.3 (1.2-15.2)] and was associated with greater functional limitation [OR (95% CI) = 1.1 (1.0-1.2)]. CONCLUSION: Of all the regions assessed in the IMAS (n = 5557 participants, 27 countries), South Africans reported the longest delay in diagnosis. The South African patient journey depicts a process burdened with diagnostic challenges and delays, coupled with patients experiencing significant personal and social limitations. These results emphasize the urgent need to establish local diagnostic and treatment guidelines for axSpA in South Africa, to reduce diagnostic delay, and to control disease activity associated with functional limitation in axSpA. Key Points • Axial spondyloarthritis (axSpA) in South Africans is associated with significant limitations in physical, mental, and social functioning. • First study to describe the unmet needs of South African patients with axSpA.

MASTering systemic mastocytosis: Lessons learned from a large patient cohort.

Background: Systemic mastocytosis (SM), a rare condition affecting about 32,000 individuals in the United States, is often misdiagnosed or underdiagnosed owing to its nonspecific symptoms and the need for invasive biopsies. Objective: Our aim was to identify, classify, and characterize the natural history of patients with SM. Methods: In a retrospective cohort study, administrative data from a large managed care organization was used to identify patients with confirmed SM, based on World Health Organization criteria. Demographic data, delay to diagnosis, disease progression, and health care resource utilization were examined. Results: Of 116 patients with confirmed SM, 77% had indolent SM, 2% had smoldering SM, 12% had SM with associated hematologic neoplasm, 9% had aggressive SM, and none had mast cell leukemia. In all, 5 patients were misclassified as having a less advanced SM subtype initially and 3 were completely undiagnosed (missed diagnosis). The average delay to diagnosis of SM was 58.3 plus or minus 73.1 months. In all, 18% of patients progressed from a nonadvanced form of SM (indolent or smoldering SM) to an advanced form of SM (aggressive SM, SM with associated hematologic neoplasm, or mast cell leukemia) over an average of 88.3 plus or minus 82.7 months. Patients with SM had increased health care utilization, including increases in their numbers of hospital admissions, emergency room visits, urgent care visits, and specialty provider visits, after diagnosis versus before. Conclusions: Rare diseases such as SM would benefit from increased understanding and awareness to improve diagnostic accuracy. Prospective studies are needed to better characterize this patient population and determine the type of follow-up needed to recognize advanced forms of SM so that appropriate treatment can be implemented.

'It was hell on earth': perspectives of people living with celiac disease on diagnostic delay.

BACKGROUND: Celiac disease (CD) is underdiagnosed and associated with diagnostic delays. This has long-term consequences for the health and well-being of people living with the condition. Little is known about the qualitative configurations of the assessment processes of people living with CD. METHODS: Using a thematic network analysis of 24 in-depth interviews, this study explored the experiences of people living with CD related to their assessment processes leading to being diagnosed. RESULTS: A significant diagnostic delay (up to 26 years) was evident in many interviews. Factors contributing to diagnostic delay included limited knowledge about CD among general practitioners (GP) and in the general population, categorisations of symptoms as 'typical' or 'atypical' and psychosomatic explanations of symptoms. Diagnostic delay resulted in (1) decreased psychological well-being due to severe symptoms, changes in self-perception and self-blame; (2) decreased physiological well-being due to comorbidities; and (3) mistrust in the healthcare system, leading to an increase in informants' responsibility for expediting their assessment processes. This suggested the presence of a neoliberal tendency because informants felt they were primarily responsible for their assessment processes. CONCLUSIONS: We encourage the implementation of initiatives to increase awareness of CD among GPs as well as more consistent and frequent use of the screening guideline due to variations in its clinical presentation. Increased awareness and consistency could reduce variations in assessment processes given GPs' varying knowledge about the condition.

Misdiagnosis and underdiagnosis of multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Diagnostic errors in multiple sclerosis (MS) impact patients and healthcare systems. OBJECTIVES: This study aimed to determine the prevalence of MS misdiagnosis and underdiagnosis, time delay in reaching a correct diagnosis and potential impact of sex. METHODS: Systematic review and meta-analysis on MS diagnostic errors. RESULTS: Out of 3910 studies, we included 62 for a qualitative synthesis and 24 for meta-analyses. Frequency of misdiagnosis (incorrect assignment of an MS diagnosis) ranged from 5% to 41%, with a pooled proportion based on six studies of 15% (95% CI: 9%-26%, n = 1621). The delay to rectify a misdiagnosis ranged from 0.3 to 15.9 years. Conversely, underdiagnosis (unrecognized diagnosis of MS) ranged from 3% to 58%, with a pooled proportion in four studies of 36% (95% CI: 20%-55%, n = 728). Pooling seven studies comprising 2851 individuals suggested a diagnostic delay to establish a correct MS diagnosis of 17.3 months (95% CI: 11.9-22.7) in patients underdiagnosed. In a meta-analysis of five studies, women were 2.1 times more likely to be misdiagnosed with MS compared to men (odds ratio, 95% CI: 1.53-2.86). CONCLUSION: This study provides summary-level evidence for the high prevalence of MS misdiagnosis and underdiagnosis. Future studies are needed to understand the causes of these diagnostic challenges in MS care.

Exploring the User Acceptability and Feasibility of a Clinical Decision Support Tool Designed to Facilitate Timely Diagnosis of New-Onset Type 1 Diabetes in Children: Qualitative Interview Study Among General Practitioners.

BACKGROUND: Up to half of the children with new-onset type 1 diabetes present to the hospital with diabetic ketoacidosis, a life-threatening condition that can develop because of diagnostic delay. Three-quarters of Australian children visit their general practitioner (GP) the week before presenting to the hospital with diabetic ketoacidosis. Our prototype, DIRECT-T1DM (Decision-Support for Integrated, Real-Time Evaluation and Clinical Treatment of Type 1 Diabetes Mellitus), is an electronic clinical decision support tool that promotes immediate point-of-care testing in general practice to confirm the suspicion of diabetes. This avoids laboratory testing, which has been documented internationally as a cause of diagnostic delay. OBJECTIVE: In this investigation, we aimed to pilot and assess the feasibility and acceptability of our prototype to GP end users. We also explored the challenges of diagnosing type 1 diabetes in the Australian general practice context. METHODS: In total, 4 GPs, a pediatric endocrinologist, and a PhD candidate were involved in conceptualizing the DIRECT-T1DM prototype, which was developed at the Department of General Practice and Primary Care at the University of Melbourne. Furthermore, 6 GPs were recruited via convenience sampling to evaluate the tool. The study involved 3 phases: a presimulation interview, simulated clinical scenarios, and a postsimulation interview. The interview guide was developed using the Consolidated Framework for Implementation Research (CFIR) as a guide. All phases of the study were video, audio, and screen recorded. Audio recordings were transcribed by the investigating team. Analysis was carried out using CFIR as the underlying framework. RESULTS: Major themes were identified among three domains and 7 constructs of the CFIR: (1) outer setting-time pressure, difficulty in diagnosing pediatric type 1 diabetes, and secondary care considerations influenced GPs' needs regarding DIRECT-T1DM; (2) inner setting-DIRECT-T1DM fits within existing workflows, it has a high relative priority due to its importance in patient safety, and GPs exhibited high tension for change; and (3) innovation-design recommendations included altering coloring to reflect urgency, font style and bolding, specific language, information and guidelines, and inclusion of patient information sheets. CONCLUSIONS: End-user acceptability of DIRECT-T1DM was high. This was largely due to its implications for patient safety and its "real-time" nature. DIRECT-T1DM may assist in appropriate management of children with new-onset diabetes, which is an uncommon event in general practice, through safety netting.

Spatiotemporal distribution and risk factors for patient and diagnostic delays among groups with tuberculous pleurisy: an analysis of 5-year surveillance data in eastern China.

Objective: To understand and analyze the factors relating to patient and diagnostic delays among groups with tuberculous pleurisy (TP), and its spatiotemporal distribution in Zhejiang Province. Methods: Data of all tuberculous pleurisy patients were collected from the existing Tuberculosis Information Management System. A time interval of > 2 weeks between first symptom onset and visit to the designated hospital was considered a patient delay, and a time interval of > 2 weeks between the first visit and a confirmed TP diagnosis was considered a diagnostic delay. Univariate and multivariate logistic regression analyses were used to explore factors influencing patient and diagnostic delays in patients with TP. Spatial autocorrelation and spatiotemporal scan analyses were used to identify hot spots and risk clusters, respectively. Results: In total, 10,044 patients with TP were included. The median time and interquartile range for patients seeking medical care and diagnosis were 15 (7-30) and 1 (0-8) days, respectively. The results showed that people aged > 65 years, retirees, and residents of Jinhua, Lishui, and Quzhou were positively correlated with patient delay, whereas retreatment patients, houseworkers, unemployed people, and residents of Zhoushan or Ningbo were positively correlated with diagnostic delay. Additionally, high-risk clusters of patient delays were observed in the midwestern Zhejiang Province. The most likely clusters of TP diagnostic delays were found in southeast Zhejiang Province. Conclusion: In summary, patient delay of TP in Zhejiang province was shorter than for pulmonary tuberculosis in China, while the diagnostic delay had no difference. Age, city, occupation, and treatment history were related to both patient and diagnostic delays in TP. Interventions in central and western regions of Zhejiang Province should be initiated to improve the early detection of TP. Additionally, the allocation of health resources and accessibility of health services should be improved in the central and eastern regions of Zhejiang Province.