Understanding Barriers to Diagnosis in a Rare, Genetic Disease: Delays and Errors Diagnosing Schwannomatosis

Diagnosis of rare, genetic diseases is challenging, but conceptual frameworks of the diagnostic process can be used to guide benchmarking and process improvement initiatives. Using the National Academy of Medicine diagnostic framework, we assessed the extent of, and reasons for, diagnostic delays and errors in schwannomatosis, a neurogenetic syndrome characterized by nerve sheath tumors and chronic pain. We reviewed the medical records of 97 patients with confirmed or probable schwannomatosis seen in two U.S. tertiary care clinics from 2005-2016. Survival analysis revealed a median time from first symptom to diagnosis of 16.7 years (95% CI, 7.5-26.0 years) and median time from first medical consultation to diagnosis of 9.8 years (95% CI, 3.5-16.2 years). Factors associated with longer times to diagnosis included initial signs/symptoms that were intermittent, non-specific, or occurred at younger ages (p<0.05). Thirty-six percent of patients experienced a misdiagnosis of underlying genetic condition (18.6%), pain etiology (16.5%) and/or tumor imaging/pathology (11.3%). One-fifth (19.6%) of patients had a clear missed opportunity for appropriate workup that could have led to an earlier schwannomatosis diagnosis. These results suggest that interventions in clinician education, genetic testing availability, expert review of pathology findings, and automatic triggers for genetics referrals may improve diagnosis in schwannomatosis.

Overdiagnosis of urinary tract infection linked to overdiagnosis of pneumonia: a multihospital cohort study

Urinary tract infection (UTI) and community-acquired pneumonia (CAP) are the most common infections treated in hospitals. UTI and CAP are also commonly overdiagnosed, resulting in unnecessary antibiotic use and diagnostic delays. While much is known individually about overdiagnosis of UTI and CAP, it is not known whether hospitals with higher overdiagnosis of one also have higher overdiagnosis of the other. Correlation of overdiagnosis of these two conditions may indicate underlying hospital-level contributors, which in turn may represent targets for intervention. To evaluate the association of overdiagnosis of UTI and CAP, we first determined the proportion of hospitalised patients treated for CAP or UTI at 46 hospitals in Michigan who were overdiagnosed according to national guideline definitions. Then, we used Pearson’s correlation coefficient to compare hospital proportions of overdiagnosis of CAP and UTI. Finally, we assessed for ‘diagnostic momentum’ (ie, accepting a previous diagnosis without sufficient scepticism) by determining how often overdiagnosed patients remained on antibiotics on day 3 of hospitalisation. We included 14 085 patients treated for CAP (11.4% were overdiagnosed) and 10 398 patients treated for UTI (27.8% were overdiagnosed) across 46 hospitals. Within hospitals, the proportion of patients overdiagnosed with UTI was moderately correlated with the proportion of patients overdiagnosed with CAP (r=0.53, p<0.001). Over 80% (81.8% (n=952/1164) of UTI; 89.9% (n=796/885) of CAP) of overdiagnosed patients started on antibiotics by an emergency medicine clinician remained on antibiotics on day 3 of hospitalisation. In conclusion, we found overdiagnosis of UTI and CAP to be correlated at the hospital level. Reducing overdiagnosis of these two common infections may benefit from systematic interventions.

The circuits of healthcare: Understanding healthcare seeking behaviour—A qualitative study with tuberculosis patients in Lisbon, Portugal

Background Understanding health delivery service from a patient´s perspective, including factors influencing healthcare seeking behaviour, is crucial when treating diseases, particularly infectious ones, like tuberculosis. This study aims to trace and contextualise the trajectories patients pursued towards diagnosis and treatment, while discussing key factors associated with treatment delays. Tuberculosis patients’ pathways may serve as indicator of the difficulties the more vulnerable sections of society experience in obtaining adequate care. Methods We conducted 27 semi-structured interviews with tuberculosis patients attending a treatment centre in a suburban area of Lisbon. We invited nationals and migrant patients in active treatment to participate by sharing their illness experiences since the onset of symptoms until the present. The Health Belief Model was used as a reference framework to consolidate the qualitative findings. Results By inductive analysis of all interviews, we categorised participants’ healthcare seeking behaviour into 4 main types, related to the time participants took to actively search for healthcare (patient delay) and time the health system spent to diagnose and initiate treatment (health system delay). Each type of healthcare seeking behaviour identified (inhibited, timely, prolonged, and absent) expressed a mindset influencing the way participants sought healthcare. The emergency room was the main entry point where diagnostic care cascade was initiated. Primary Health Care was underused by participants. Conclusions The findings support that healthcare seeking behaviour is not homogeneous and influences diagnostic delays. If diagnostic delays are to be reduced, the identification of behavioural patterns should be considered when designing measures to improve health services’ delivery. Healthcare professionals should be sensitised and perform continuous capacity development training to deal with patients´ needs. Inhibited and prolonged healthcare seeking behaviour contributes significantly to diagnostic delays. These behaviours should be detected and reverted. Timely responses, from patients and the healthcare system, should be promoted.

Dermoscopy as a diagnostic tool to differentiate between tinea pedis and plantar psoriasis

<p><strong>Background</strong>: Clinical differentiation between tinea pedis and plantar psoriasis may sometimes be challenging, with consequent diagnostic delays and unnecessary therapies; in such cases histopathological analysis helps to differentiate the 2 conditions. In this study we used a dermoscope as a non-invasive tool to investigate the significance of specific dermoscopic features and to improve their non-invasive differentiation.</p><p><strong>Methods:</strong> A clinical diagnosis of plantar psoriasis/tinea pedis was made on basis of accepted literature and proved by histopathology. Image capturing was performed using a dermoscope. Based on combination of history, clinical, and dermoscopic examination conclusive diagnosis with specific dermoscopic features for each disease was achieved.</p><p><strong>Results:</strong> The 15 patients of biopsy proven tinea pedis and 17 patients of biopsy proven plantar psoriasis were selected. We found that the presence of whitish powdery scales located in the furrows with apparently uninvolved skin in between was significant in tinea pedis whereas the presence of silvery white scales on a pinkish red erythematous background with regularly distributed red dots was significant in plantar psoriasis.</p><p><strong>Conclusions:</strong> Dermoscopy showed significant patterns in tinea pedis and plantar psoriasis due to their well-known different histological and physio pathological background, with white diffuse scales reflecting the dry and hyperkeratotic nature of plantar psoriasis and the red dots signifying the pin point blood vessels seen clinically as Auspitz sign. The peculiar scaling in tinea pedis might result from the predilection of dermatophytes to proliferate in moist environment, such as the furrows.</p>

Redefining the Use of Digital Communities: AD Knowledge in an Online Educated Cohort of Midlife and Older Blacks

The normalization of memory loss continues to contribute to diagnostic delays among older adult African Americans with dementia. We utilized an innovative recruitment method to establish a solely online study to examine perceptions and knowledge levels of Alzheimer’s Disease in a highly educated geographically diverse cohort of 223 African Americans aged 50-84. Participants were recruited through largely electronic communications. Sample participants were primarily female (n=196), with 51.1% having completed a master’s degree, and 58.2% of participants with household incomes of $90,000 or higher. Study findings revealed that although highly educated, 42% of sample participants believed significant memory loss was a normal part of aging and 59.6% felt that God’s Will was a possible cause of AD. A sizable majority of participants, 86.5%, felt most family physicians were not trained to diagnose AD. Findings underscore the need for physician and community education within diverse populations, regardless of education and SES status.

Patient perspectives on health care provider practices leading to an axial spondyloarthritis diagnosis: an exploratory qualitative research study

Background The average time to a diagnosis for people with axial spondyloarthritis (axSpA) is 7-10 years. Delayed diagnosis may result in increased structural damage, worse physical function, and worse quality of life relative to patients with a timely axSpA diagnosis. Understanding patient experiences may provide insights for how to reduce diagnostic delays. Objective To provide foundational knowledge about patient experiences with healthcare providers leading to an axSpA diagnosis. Methods We conducted an exploratory qualitative research study with six focus groups interviews with participants recruited from three rheumatology clinics within the United States (MA (n = 3); CO (n = 2); PA (n = 1)) that included a total of 26 adults (10 females, 16 males) with rheumatologist confirmed diagnosis of axSpA in 2019. Focus groups were ~ 2 h, audio recorded, transcribed, and subject to dual coding. The codes reviewed were in relation to the patients’ diagnostic experiences. Results Patients described frustrating and lengthy diagnostic journeys. They recognized that the causes of diagnostic delays in axSpA are multifactorial (e.g., no definitive diagnostic test, disease characteristics, lack of primary care provider’s awareness about axSpA, trust). Patients described how doctors minimized or dismissed complaints about symptoms or told them that their issues were psychosomatic. Patients believed the healthcare system contributed to diagnostic delays (e.g., lack of time in clinical visits, difficulty accessing rheumatologists, health insurance challenges). Advice to physicians to reduce the diagnostic delay included allowing time for patients to give a complete picture of their illness experience, listening to, and believing patients, earlier referral to rheumatology, provision of HLA-B27 gene testing, and that physicians need to partner with their patients. Conclusions Patients desire a definitive test that could be administered earlier in the course of axSpA. Until such a test is available, patients want clinicians who listen to, believe, and partner with them, and who will follow them until a diagnosis is reached. Educating primary care clinicians about guidelines and referral for diagnosis of axSpA could reduce diagnostic delay.

P.089 A report of a patient presenting with orbital apex syndrome secondary to NK cell lymphoma (nasal type)

Background: Orbital apex syndrome (OAS) can be caused by a broad range of disorders. There are several challenges present in the evaluation of these patients and in reaching a final diagnosis. We report the case of a 69-year-old male who presented with OAS that was determined to be secondary to a rare malignancy (NK cell lymphoma, nasal type). Methods: We analyze the pitfalls and diagnostic delays in this patient’s evaluation. Furthermore we propose a work up for undifferentiated cases of OAS. Results: To accurately diagnose the underlying cause of OAS, a direct biopsy should be obtained whenever possible. The appropriate imaging sequences should be arranged as lesions in this region can be easily missed. Adjunct tests include assessment in the serum and CSF for granulomatous and infectious diseases, along with chest imaging. As many causes are PET enhancing, PET CT is a useful modality for identifying sites for biopsy. Conclusions: OAS can provide a diagnostic challenge for clinicians, however a systematic approach can help determine the underlying etiology.

A comprehensive framework to estimate the frequency, duration and risk factors for diagnostic delays using simulation-based methods

The incidence of diagnostic delays is unknown for many diseases and particular healthcare settings. Many existing methods to identify diagnostic delays are resource intensive or inapplicable to various diseases or settings. In this paper we propose a comprehensive framework to estimate the frequency of missed diagnostic opportunities for a given disease using real-world longitudinal data sources. We start by providing a conceptual model of the disease-diagnostic, data-generating process. We then propose a simulation-based method to estimate measures of the frequency of missed diagnostic opportunities and duration of delays. This approach is specifically designed to identify missed diagnostic opportunities based on signs and symptoms that occur prior to an initial diagnosis, while accounting for expected patterns of healthcare that may appear as coincidental symptoms. Three different simulation algorithms are described for implementing this approach. We summarize estimation procedures that may be used to parameterize the simulation. Finally, we apply our approach to the diseases of tuberculosis, acute myocardial infarction, and stroke and evaluate the estimated frequency and duration of diagnostic delays for these diseases. Our approach can be customized to fit a range of disease and we summarize how the choice of simulation algorithm may impact the resulting estimates.

Case Report: Atypical Cutaneous Presentation of Human T-cell Lymphotropic Virus Type 1-Related Adult T-cell Lymphoma

Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus endemic in many parts of the world. Because of migration, cases of HTLV-1 in non-HTLV-1 endemic countries have been increasingly reported. Clinical presentation of HTLV-1 infection is highly variable, with a significant risk of diagnostic delays. Skin can be the first site affected by HTLV-1-related manifestations such as cutaneous involvement of adult T-cell leukemia/lymphoma (ATLL) and infective dermatitis associated with HTLV-1. A 32-year-old Nigerian man was admitted to the infectious disease department for high fever, asthenia, lymphocytosis, and vesicular bullous lesions on both hand palms and lower limbs. After clinical work-up was performed, bacterial superinfected herpes simplex viurs-2 ulcers were the presenting sign of HTLV-1-related chronic type ATLL. Standard treatment based on interferon-α plus zidovudine was started, but it was poorly tolerated; therefore, switching to an off-label dual antiretroviral regimen was attempted. The increasing prevalence of HTLV-1 in nonendemic areas may enhance the development of alternative treatments with better efficacy and tolerability profiles.

Factors Associated With Diagnostic Delays in Human Brucellosis in Tongliao City, Inner Mongolia Autonomous Region, China

The diagnostic delays pose a huge challenge to human brucellosis (HB), which increases the risk of chronicity and complications with a heavy disease burden. This study aimed to quantify and identify the associated factors in the diagnostic delays to its prevention, reduction, and elimination. This study analyzed risk factors associated with the diagnostic delays in a cross-sectional study with data collected from Tongliao City, Inner Mongolia Autonomous Region of China. Diagnostic delays were defined with a cutoff of 30, 60, and 90 days. In different delay groups, risk factors of diagnostic delays were analyzed by univariate analysis and modeled by multivariate logistic regression analysis. A total of 14,506 cases were collected between January 1, 2005, and December 31, 2017, of which the median diagnostic delays was 29 days [interquartile range (IQR): 14–54 days]. Logistic regression analysis indicated that the older age category was associated with longer diagnostic delays across all groups. Longer diagnostic delays increase with age among three delay groups (p for trend &lt;0.001). Occupation as herdsman was associated with shorter diagnostic delays in group 1 with 30 days [adjusted odds ratio (aOR), 0.890 (95% CI 0.804–0.986)]. Diagnostic delays was shorter in patients with brucellosis who were reported in CDC in all delay groups [aOR 0.738 (95% CI 0.690–0.790), 0.539 (95% CI 0.497–0.586), and 0.559 (95% CI 0.504–0.621)]. Pastoral/agricultural area was associated with shorter diagnostic delays in group 1 with 30 days [aOR, 0.889 (95%CI 0.831–0.951)] and group 3 with 90 days [aOR, 0.806 (95%CI 0.727–0.893)]. Stratified analysis showed that the older age category was associated with an increased risk of a long delay in both genders (p &lt; 0.05). The older age group-to-youth group OR increased along with increased delay time (p for trend &lt;0.001). Furthermore, the pastoral/agricultural area was associated with a shorter delay in males (p &lt; 0.05). Delays exist in the diagnosis of HB. We should pay great attention to the risk factors of diagnostic delays, such as older population, non-herdsman, non-pastoral/agricultural area, non-disease prevention, and control agencies. Effective measures should shorten the diagnostic delays, achieve early detection, diagnosis, and treatment, and reduce the risk of HB's chronicity, complications, and economic burden.