Validating inborn error of immunity prevalence and risk with nationally representative electronic health record data.

BACKGROUND: The 10 Warning Signs of Primary Immunodeficiency were created 30 years ago to advance recognition of inborn errors of immunity (IEI). However, no population-level assessment of their utility applied to electronic health record (EHR) data has been conducted. OBJECTIVE: We sought to quantify the value of having ≥2 warning signs (WS) toward diagnosing IEI using a highly representative real-world US cohort. A secondary goal was estimating the US prevalence of IEI. METHODS: In this cohort study, we accessed normalized and de-identified EHR data on 152 million US patients. An IEI cohort (n = 41,080), in which patients were defined by having at least 1 verifiable IEI diagnosis placed ≥2 times in their record, was compared with a matched set of controls (n = 250,262). WS were encoded along with relevant diagnoses, relative weights were calculated, and the proportion of IEI cases versus controls with ≥2 WS was compared. RESULTS: The proportion of IEI cases with ≥2 WS significantly differed from controls (0.33 vs 0.031; P < .0005, χ2 test). We also estimated a US IEI prevalence of 6 per 10,000 individuals (41,080/73,165,655; 0.056%). WS 9 (≥2 deep-seated infections), 7 (fungal infections), 5 (failure to thrive) and 4 (≥2 pneumonias in 1 year) were the most heavily weighted among the IEI cohort. CONCLUSIONS: This nationally representative US-based cohort study demonstrates that presence of WS and associated clinical diagnoses can facilitate identification of patients with IEI from EHR data. In addition, we estimate that 6 in 10,000, or approximately 150,000 to 200,000 individuals are affected by IEI across the United States.

Tuberculosis Diagnostic Delays and Treatment Outcomes among Patients with COVID-19, California, USA, 2020.

We assessed tuberculosis (TB) diagnostic delays among patients with TB and COVID-19 in California, USA. Among 58 persons, 43% experienced TB diagnostic delays, and a high proportion (83%) required hospitalization for TB. Even when viral respiratory pathogens circulate widely, timely TB diagnostic workup for at-risk persons remains critical for reducing TB-related illness.

Travel Time to Treating Center is Associated With Diagnostic Delay in Pediatric Inflammatory Bowel Disease.

BACKGROUND & AIMS: Delayed diagnosis of inflammatory bowel disease (IBD) leads to prolonged symptoms and worse long-term outcomes. We sought to evaluate whether race, ethnicity, disease type, and social factors are associated with delayed diagnosis of pediatric IBD. METHODS: We performed a cross-sectional study of newly diagnosed pediatric patients with IBD at 22 United States sites from 2019 to 2022. Parents/guardians reported race, ethnicity, time between symptom onset and diagnosis, and other social determinants of health. Through bivariate and multivariable analyses using generalized estimating equations, we evaluated associations between these factors and diagnosis time defined as ≤60 days, 61 to 180 days, 181 to 365 days, and >365 days. RESULTS: We enrolled 869 participants (mean age at diagnosis, 13.1 years; 52% male; 57% Crohn's disease [CD]; 34% ulcerative colitis [UC]; 8% Hispanic; 30% non-White). Overall, the mean time to diagnosis was 265.9 days. After adjustment, factors associated with longer diagnosis time included CD vs UC (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.9-3.5), 2 or more other health conditions (OR, 1.7; 95% CI, 1.1-2.7), and longer travel time to clinic (>1 hour [OR, 1.7; 95% CI, 1.2-2.4], >2 hours (OR, 1.8; 95% CI, 1.2-2.9] each vs <30 minutes). There was no association with race, ethnicity, birth country, gender, parent education, household income, insurance type, health literacy, and health system distrust. CONCLUSIONS: Consistent with prior literature, diagnostic delay is longer for CD than UC. Reassuringly, time to diagnosis is equitable across racioethnic groups. New models of diagnostic care are needed for communities affected by longer travel times.

Diagnostic delay in monogenic disease: A scoping review.

PURPOSE: Diagnostic delay in monogenic disease is reportedly common. We conducted a scoping review investigating variability in study design, results, and conclusions. METHODS: We searched the academic literature on January 17, 2023, for original peer reviewed journals and conference articles that quantified diagnostic delay in monogenic disease. We abstracted the reported diagnostic delay, relevant study design features, and definitions. RESULTS: Our search identified 259 articles quantifying diagnostic delay in 111 distinct monogenetic diseases. Median reported diagnostic delay for all studies collectively in monogenetic diseases was 5.0 years (IQR 2-10). There was major variation in the reported delay within individual monogenetic diseases. Shorter delay was associated with disorders of childhood metabolism, immunity, and development. The majority (67.6%) of articles that studied delay reported an improvement with calendar time. Study design and definitions of delay were highly heterogenous. Three gaps were identified: (1) no studies were conducted in the least developed countries, (2) delay has not been studied for the majority of known, or (3) most prevalent genetic diseases. CONCLUSION: Heterogenous study design and definitions of diagnostic delay inhibit comparison across studies. Future efforts should focus on standardizing delay measurements, while expanding the research to low-income countries.

Clinical, biochemical, and molecular insights into Cerebrotendinous Xanthomatosis: A nationwide study of 100 Turkish individuals.

OBJECTIVE: Cerebrotendinous xanthomatosis (CTX) is an inherited metabolic disorder characterized by progressive neurologic and extraneurologic findings. The aim of this retrospective, descriptive study was to explore the time of presentation and diagnosis, and to expand the phenotype and genotype of CTX, based on a nationwide and comprehensive series of patients in Turkey. METHODS: The demographic, clinical, biochemical and genotypic characteristics of the CTX patients were reviewed. Data on molecular analysis, age of onset and diagnosis, diagnostic delay, neurologic and extraneurologic symptomatology, results of plasma cholestanol levels, brain magnetic resonance imaging and electromyography at the time of diagnosis were reviewed. RESULTS: 100 confirmed CTX patients from 72 families were included. The mean age at diagnosis was 28.16 ± 14.28 years, and diagnostic delay was 18.39 ± 13.71 years. 36 patients were diagnosed in childhood. Frequency of intention tremor (p = 0.069), peripheral neuropathy (p = 0.234) and psychiatric manifestations (p = 0.396) did not differ between two groups, demonstrating the high rate in pediatric patients. Three adult patients showed a milder phenotype without neurologic involvement. Seven patients had normal plasma cholestanol levels despite neurological impairment. Sequencing of the CYP27A1 gene revealed 25 different variants, with a novel c.671_672del variant not previously described in literature. CONCLUSION: Based on the observations of this Turkish CTX cohort, it is emphasized that the true prevalence of CTX is probably underestimated and that it has a wide spectrum of clinical phenotypes even without neurological impairment. In children, abnormal cerebellar findings, peripheral neuropathy and psychiatric findings associated with intellectual disability have been suggested as warning signs to avoid diagnostic delay. In cases of clinical suspicion, molecular analysis is recommended despite normal plasma cholestanol levels, as severe neurologic involvement may occur in CTX patients without elevated cholestanol levels.

Diagnostic delay is associated with uveitis and inflammatory bowel disease in AS: a study of extra-musculoskeletal manifestations in SpA.

OBJECTIVES: To examine the prevalence of extra-musculoskeletal manifestations (EMM) and the association between diagnostic delay and their incidence in AS and PsA. METHODS: This was a retrospective, cohort study comprising two single centre cohorts in Europe and one multicentre cohort in Latin America (RESPONDIA). Crude prevalence of EMMs (uveitis, IBD and psoriasis) was calculated across geographic area and adjusted by direct standardization. Cox proportional hazard analysis was performed to assess the association between diagnostic delay and EMM incidence. RESULTS: Of 3553 patients, 2097 had AS and 1456 had PsA. The overall prevalence of uveitis was 22.9% (95% CI: 21.1, 24.8) in AS and 3.8% (95% CI: 2.9, 5.0) in PsA; 8.1% (95% CI: 7.0, 9.4) and 2.1% (1.3, 2.9), respectively, for IBD; and 11.0% (95% CI: 9.7, 12.4) and 94.6% (93.0, 95.9), respectively, for psoriasis. The EMM often presented before the arthritis (uveitis 45.1% and 33.3%, and IBD 37.4% and 70%, in AS and PsA, respectively). In the multivariable model, longer diagnostic delay (≥5 years) associated with more uveitis (hazard ratio [HR] 4.01; 95% CI: 3.23, 4.07) and IBD events (HR 1.85; 95% CI: 1.28, 2.67) in AS. Diagnostic delay was not significantly associated with uveitis (HR 1.57; 95% CI: 0.69, 3.59) or IBD events (HR 1.59; 95% CI: 0.39, 6.37) in PsA. CONCLUSION: EMMs are more prevalent in AS than PsA and often present before the onset of the articular disease. A longer diagnostic delay is associated with the 'de novo' appearance of uveitis and IBD in AS, highlighting the need to enhance diagnostic strategies to shorten the time from first symptom to diagnosis in SpA.

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.

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.

Timing the clinical onset of epileptic spasms in infantile epileptic spasms syndrome: A tertiary health center's experience.

OBJECTIVE: Lead time to treatment (clinical onset of epileptic spasms [ES] to initiation of appropriate treatment) is known to predict outcomes in infantile epileptic spasms syndrome (IESS). Timing the clinical onset of ES is crucial to establish lead time. We investigated how often ES onset could be established to the nearest week. We aimed to (1) ascertain the exact date or estimate the nearest week of ES onset and (2) compare clinical/demographic factors between patients where date of ES onset was determined or estimated to the nearest week and patients whose date of ES onset could not be estimated to the nearest week. Reasons for difficulties in estimating date of ES onset were explored. METHODS: Retrospective chart review of new onset IESS patients (January 2019-May 2022) extracted the date or week of the clinical onset of ES. Predictors of difficulty in date of ES onset estimation to the nearest week were examined by regression analysis. Sources contributing to difficulties determining date of ES onset were assessed after grouping into categories (provider-, caregiver-, disease-related). RESULTS: Among 100 patients, date of ES onset was estimated to the nearest week in 47%. On univariable analysis, age at diagnosis (p = .021), development delay (p = .007), developmental regression/stagnation (p = .021), ES intermixed with other seizures (p = .011), and nonclustered ES at onset (p = .005) were associated with difficulties estimating date of ES onset. On multivariable analysis, failure to establish date of ES onset was related to ES intermixed with other seizures (p = .004) and nonclustered ES at onset (p = .003). Sources contributing to difficulties determining date of ES onset included disease-related factors (ES characteristics, challenges interpreting electroencephalograms) and provider/caregiver-related factors (delayed diagnosis). SIGNIFICANCE: Difficulties with estimation of lead time (due to difficulties timing ES onset) can impact clinical care (prognostication), as even small increments in lead time duration can have adverse developmental consequences.

A systematic literature review on the global epidemiology of Dravet syndrome and Lennox-Gastaut syndrome: Prevalence, incidence, diagnosis, and mortality.

Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) are rare developmental and epileptic encephalopathies associated with seizure and nonseizure symptoms. A comprehensive understanding of how many individuals are affected globally, the diagnostic journey they face, and the extent of mortality associated with these conditions is lacking. Here, we summarize and evaluate published data on the epidemiology of DS and LGS in terms of prevalence, incidence, diagnosis, genetic mutations, and mortality and sudden unexpected death in epilepsy (SUDEP) rates. The full study protocol is registered on PROSPERO (CRD42022316930). After screening 2172 deduplicated records, 91 unique records were included; 67 provided data on DS only, 17 provided data on LGS only, and seven provided data on both. Case definitions varied considerably across studies, particularly for LGS. Incidence and prevalence estimates per 100 000 individuals were generally higher for LGS than for DS (LGS: incidence proportion = 14.5-28, prevalence = 5.8-60.8; DS: incidence proportion = 2.2-6.5, prevalence = 1.2-6.5). Diagnostic delay was frequently reported for LGS, with a wider age range at diagnosis reported than for DS (DS, 1.6-9.2 years; LGS, 2-15 years). Genetic screening data were reported by 63 studies; all screened for SCN1A variants, and only one study specifically focused on individuals with LGS. Individuals with DS had a higher mortality estimate per 1000 person-years than individuals with LGS (DS, 15.84; LGS, 6.12) and a lower median age at death. SUDEP was the most frequently reported cause of death for individuals with DS. Only four studies reported mortality information for LGS, none of which included SUDEP. This systematic review highlights the paucity of epidemiological data available for DS and especially LGS, demonstrating the need for further research and adoption of standardized diagnostic criteria.

Patient- and parent-reported diagnostic delay in children with central nervous system tumors in Denmark.

BACKGROUND: Diagnostic delays in childhood tumors of the central nervous system (CNS) pose a significant challenge. The aim of this study was to map diagnostic delay and presenting symptoms in Denmark. METHODS: The study was a retrospective questionnaire study, mapping delay and symptoms in pediatric patients (0-17 years), diagnosed with a CNS tumor from 2015 to 2019. Descriptive analysis was performed to measure delay in days, reported as total diagnostic interval (TDI), patient interval (PI), and diagnostic interval (DI). Analysis of symptoms, contacts to healthcare professionals, and socioeconomic status was also performed. RESULTS: We included 89 patients (median age 7.0 years, 54% male). The TDI was median of 106 days (range: 0-2694 days). Low-grade tumors had longer TDI than high-grade tumors (125 vs. 43 days; p ≤ .02). Patients aged 15-17 displayed the longest TDI (median 665 days). Number of symptoms at onset were inversely associated with longer TDI in patients presenting one symptom (247 days) and patients presenting two to three (110 days) or greater than three complaints (66 days). PI was not associated with sex (p = .14), tumor grade (p = .63), location (p = .32), or socioeconomic status (p = .82). Most frequent single complaint at onset was headache (19%), most frequent combination of symptoms was headache and vomiting (60%). CONCLUSION: We found TDIs longer than reported in contemporary publications. TDI was longer in patients with low-grade tumors and only few symptoms at the time of onset. The findings support the crucial need of awareness and improved diagnostic tools to recognize and interpret symptoms to promote timely diagnosis.

Time to Diagnose Endometriosis: Current Status, Challenges and Regional Characteristics-A Systematic Literature Review.

BACKGROUND: Endometriosis diagnosis reportedly faces delays of up to 10 years. Despite growing awareness and improved guidelines, information on the current status is limited. OBJECTIVES: To systematically assess the published evidence on the status of time to diagnosis in individuals with endometriosis, with respect to the definition of time to diagnosis, geographical location and patient characteristics. SEARCH STRATEGY: MEDLINE (via PubMed) and Embase were searched for publications reporting time to diagnosing endometriosis since 2018. No restrictions to population or comparators were applied. All publications were screened by two independent reviewers. SELECTION CRITERIA: Search results were limited to primary publications of randomised controlled trials, non-randomised trials and observational studies. Case reports, secondary publications and grey literature were excluded. No restrictions were made regarding language, provided that an English title and abstract were available. DATA COLLECTION AND ANALYSIS: Publications were assessed with respect to time to diagnosis, diagnostic methods, study type, study country and potential bias. MAIN RESULTS: The 17 publications eligible for inclusion in this literature review were all observational studies. The publications reported diagnosis times between 0.3 and 12 years, with variations depending on the definition of time to diagnosis (overall, primary, or clinical), geographical location and characteristics of the included study population. Evidence was of poor to good quality overall. CONCLUSIONS: Diagnostic delay is still present, primarily driven by physicians, and this review underscores the need for standardised definitions, increased awareness and targeted diagnostic interventions.

Body map stories from Colombia: experiences of people affected by leprosy and the influence of peers during diagnosis and treatment.

INTRODUCTION: Almost one third of people affected by leprosy in Colombia suffer from disability, which often results from delayed diagnosis and treatment. We aimed to explore the experience of people affected by leprosy during the process of diagnosis and treatment and if and how this experience was influenced by peers. METHODS: A qualitative study using body map stories was conducted from October 2019 to February 2020 in Colombia. Adult people affected by leprosy were recruited through patient associations in different cities. We conducted three sessions with an average duration of 2-3 h per participant, during which the participants created a painted map of their body and chose symbols to represent their experience, while being engaged in an informal interview. The sessions were audio recorded, transcribed verbatim and analyzed thematically by an interdisciplinary team, consisting of physicians, social workers and a person affected by leprosy. RESULTS: The 17 study participants (11 female) were aged 20 to 70 years. Leprosy-related manifestations ranged from no to advanced disability. Some participants were active members of associations for people affected by leprosy. Three main themes were identified during analysis: (1) A long pathway to diagnosis, (2) Therapy as a double-edged sword and (3) The influence of other people affected by leprosy. The participants described an often years-long process until being diagnosed, which was marked by insecurities, repeated misdiagnosis, and worsening mental and physical health. Delayed diagnosis was related to late health care seeking, but also to inadequate health communication, lack of leprosy-related knowledge and negligence among health care workers. A high desire to cure motivated the participants to take their medication rigorously, despite the high treatment burden. Support from peers, either within the own social environment or provided from associations, contributed to a faster diagnosis and increased therapy adherence. Peers helped to recognize the symptoms, urged patients to seek care, recommended physicians with leprosy-related knowledge and provided a realistic example of both disease severity and curability. CONCLUSION: People affected by leprosy experience a significant burden during the process of diagnosis and treatment. Involving well-trained peers could foster early diagnosis, treatment compliance and prevention of disability.

Delay in diagnosis is associated with decreased treatment effectiveness in children with rumination syndrome.

OBJECTIVES: Rumination syndrome (RS) is challenging to diagnose, which can lead to diagnostic delays. Our objective was to evaluate the length of time from RS symptom onset to diagnosis in patients referred to our institution and to examine whether this duration predicts treatment outcomes. METHODS: We conducted a review of patients with RS evaluated at our institution. Data were collected from chart review and patient/family reported questionnaires. We evaluated the time from symptom onset to diagnosis over time and whether it was associated with symptom resolution. RESULTS: We included 247 patients with RS (60% female, median age of 14 years, interquartile range [IQR]: 9-16 years). The median age at symptom onset was 11 years (IQR: 5-14 years) and median age at diagnosis was 13 years (IQR: 9-15 years) for a median duration of 1 year (IQR: 0-3 years) between symptom onset and diagnosis. Length of time between symptom onset and diagnosis did not change significantly at our institution from 2016 to 2022. Among the 164 children with outcome data, 47 (29%) met criteria for symptom resolution after treatment. A longer time to diagnosis was associated with a lower likelihood of symptom resolution after treatment (p = 0.01). CONCLUSION: In our experience, the time to RS diagnosis after symptom onset is shorter than previously described. A longer delay in diagnosis is associated with lower likelihood of symptom resolution after treatment, emphasizing the importance of a prompt recognition of rumination symptoms and a timely diagnosis.

NT-proBNP course during MIS-C post-COVID-19: an observational study.

Multisystem inflammatory syndrome in children (MIS-C or PIMS-TS) is a severe disease. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is used for positive and differential diagnosis, diagnosis of complications and severity, and cardiogenic shock prediction. However, contrasting cut-offs have been suggested. The aims of the present study were to compare NT-proBNP values depending on the time of measurement and to describe the NT-proBNP course during the MIS-C episode. The data from a single-centre cohort observational study on the impact of time to diagnosis, defined as the time from first symptom to diagnosis of MIS-C, were used for the purpose of this study, with an extended period of inclusion from May 2020 to April 2023. The timing and level of all NT-proBNP samples available for each patient were retrospectively collected. Thirty-seven children (18 (49%) females, median age 8.8 years, 14 (38%) with shock) were included. Until diagnosis, NT-proBNP increased with time and was significantly higher at 6 days from first symptoms than at 3 days (median (interquartile range) 32,933 (7773-61,592) versus 1994 (1291-4190) pg/mL, respectively, p = 0.031). From diagnosis, NT-proBNP decreased by at least 50% after 3.0 (2.1-5.3) days (n = 12) when NT-proBNP at diagnosis was low ≤ 11,000 pg/mL versus 1.8 (0.7-3.4) days (n = 16) when NT-proBNP at diagnosis was high (p = 0.040), and after 3.6 (2.4-5.9) days (n = 7) when fever persisted after 48 h versus 1.8 (0.8-3.0) days (n = 21) when fever resolved before 48 h (p = 0.004).  Conclusions: During the MIS-C episode, NT-proBNP increased over time until diagnosis and treatment. It dropped faster thereafter in children with high NT-proBNP at diagnosis > 11,000 pg/mL and slower in case of persistent fever. What is Known: • NT-proBNP is useful in MIS-C for positive and differential diagnosis, diagnosis of complications and severity, and cardiogenic shock prediction. • Contrasting cut-offs for differential diagnosis and severity assessment have been suggested. What is New: • Before diagnosis, NT-proBNP increases with time and is significantly higher at 6 days from first symptoms than at 3 days suggesting different cut-offs depending on the timing of measurement. • From diagnosis and treatment initiation, the 50% NT-proBNP drop occurs earlier in children with high NT-proBNP at diagnosis > 11,000 pg/mL and later in children with persistent fever.

Diagnostic delay in patients with sporadic hereditary transthyretin-mediated amyloidosis.

BACKGROUND: Hereditary transthyretin-mediated amyloidosis (ATTRv amyloidosis) is a rare progressively incapacitating condition with a wide range of genotype/phenotype presentations. It is frequently diagnosed late in its course, particularly in sporadic cases. OBJECTIVES: Analysing predictors of diagnostic delay in this subpopulation should be, therefore, a priority. METHODS: 109 apparently sporadic ATTRv amyloidosis patients followed in a reference centre in Hospital de Santa Maria (ULS Santa Maria-CAML), in Lisbon, were studied. Time from symptom onset to diagnosis, age, sex, municipality of origin and initial symptoms were obtained. Diagnostic delay was compared between different decades with a Kruskal-Wallis test, and its predictors were evaluated in a univariate model followed by a binary logistic regression analysis to calculate the adjusted odds ratio. RESULTS: The median diagnostic delay was 1262 days. There was a non-significant difference in diagnostic delay between the 80 s, 90 s, 2000s and 2010s decades. There was a non-significant trend for a longer diagnostic delay in woman and in patients having no neurologic symptoms at onset. CONCLUSION: There is an important diagnostic delay in sporadic cases of ATTRv amyloidosis. Awareness should be spread among clinicians regarding the various manifestations of this disease, stressing the importance of family history and epidemiological data.

Changes in the diagnostic trajectory of transthyretin cardiac amyloidosis over six years.

Awareness of transthyretin amyloid cardiomyopathy (ATTR-CM) has increased over the years due to diagnostic and therapeutic developments. Timely initiation of novel disease-modifying treatments improves both morbidity and mortality, which underlines the necessity for a prompt diagnosis. Nevertheless, early diagnosis of ATTR-CM remains challenging. This is a retrospective observational cohort study of patients diagnosed with ATTR-CM. Between 2016 and 2023, 87 patients were diagnosed with cardiac amyloidosis of which 65 (75%) patients with ATTR-CM and 22 (25%) patients with light chain amyloidosis. This study included 65 ATTR-CM patients (mean age 77 ± 7 years; 86% male) of whom 59 (91%) with wild-type ATTR-CM (ATTRwt) and six (9%) with variant ATTR-CM. We observed a surge in ATTR-CM diagnoses from 3 patients/year (2016-2020) to 16 patients/year (2021-2023), driven by ATTRwt. Nevertheless, the interval between the onset of heart failure symptoms and ATTR-CM diagnosis has not changed significantly (2016-2020 27.3 months [18.6-62.4]; 2021-2023 30.0 months [8.6-57.2]; p = 0.546), driven by time to referral. Red flags for ATTR-CM preceded diagnosis by several years: left ventricular hypertrophy (79%, 5.8 years [3.3-7.0]) and carpal tunnel syndrome (49%, 6.8 years [2.3-12.1]). Despite the presence of typical red flags, symptom-to-diagnosis duration has remained similar driven by time to referral. Improved recognition of red flags for ATTR-CM could reduce the time to diagnosis and improve overall recognition.

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.

Pre-assessment of patients with suspected axial spondyloarthritis combining student-led clinics and telemedicine: a qualitative study.

OBJECTIVE: Patients referred to rheumatologists are currently facing months of inefficient waiting time due to the increasing demand and rising workforce shortage. We piloted a pre-assessment of patients with suspected axial spondyloarthritis (axSpA) combining student-led clinics and telemedicine (symptom assessment, symptom monitoring and at-home capillary self-sampling) to improve access to rheumatology care. The aim of this study was to explore (1) current challenges accessing axSpA care and (2) patients' first-hand experiences. METHODS: Embedded within a clinical trial, this study was based on qualitative interviews with patients with suspected axSpA (n = 20). Data was analysed via qualitative content analysis. RESULTS: Student-led clinics were perceived as high-quality care, comparable to conventional rheumatologist-led visits. Patients expressed that their interactions with the students instilled a sense of trust. History-taking and examinations were perceived as comprehensive and meticulous. Telehealth tools were seen as empowering, offering immediate and continuous access to symptom assessment at home. Patients reported a lack of specificity of the electronic questionnaires, impeding accurate responses. Patients requested a comments area to supplement questionnaire responses. Some patients reported receiving help to complete the blood collection. CONCLUSION: Patients' access to rheumatology care is becoming increasingly burdensome. Pre-assessment including student-led clinics and telemedicine was highly accepted by patients. Patient interviews provided valuable in-depth feedback to improve the piloted patient pathway.

Age at diagnosis and diagnostic delay across attention-deficit hyperactivity and autism spectrums.

BACKGROUND: Despite the known benefits of accurate and timely diagnosis for children with attention-deficit hyperactivity disorder and autism spectrum disorders (autism), for some children this goal is not always achieved. Existing research has explored diagnostic delay for autism and attention-deficit hyperactivity disorder only, and when attention-deficit hyperactivity disorder and autism co-occur, autism has been the focus. No study has directly compared age at diagnosis and diagnostic delay for males and females across attention-deficit hyperactivity disorder, autism and specifically, attention-deficit hyperactivity disorder + autism. METHODS: Australian caregivers (N = 677) of children with attention-deficit hyperactivity disorder, autism or attention-deficit hyperactivity disorder + autism were recruited via social media (n = 594) and the Monash Autism and ADHD Genetics and Neurodevelopment Project (n = 83). Caregivers reported on their child's diagnostic process. Diagnostic delay was the mean difference between general initial developmental concerns and the child's attention-deficit hyperactivity disorder and autism diagnosis. RESULTS: Children with autism were significantly younger at autism diagnosis than the attention-deficit hyperactivity disorder + autism group (ηp2 = 0.06), whereas children with attention-deficit hyperactivity disorder were significantly older at attention-deficit hyperactivity disorder diagnosis than the attention-deficit hyperactivity disorder + autism group (ηp2 = 0.01). Delay to attention-deficit hyperactivity disorder and autism diagnosis was significantly longer in the attention-deficit hyperactivity disorder + autism group compared to attention-deficit hyperactivity disorder (ηp2 = 0.02) and autism (η2 = 0.04) only. Delay to autism diagnosis for females with autism (η2 = 0.06) and attention-deficit hyperactivity disorder + autism (η2 = 0.04) was longer compared to males. CONCLUSIONS: Having attention-deficit hyperactivity disorder + autism and being female were associated with longer delays to diagnosis. The reasons for these delays and possible adverse effects on outcomes require further study.