BACKGROUND: People with a rare disease commonly experience long delays from the onset of symptoms to diagnosis. Rare diseases are challenging to diagnose because they are clinically heterogeneous, and many present with non-specific symptoms common to many diseases. We aimed to explore the experiences of people with myositis, primary immunodeficiency (PID), and sarcoidosis from symptom onset to diagnosis to identify factors that might impact receipt of a timely diagnosis.
METHODS: This was a qualitative study using semi-structured interviews. Our approach was informed by Interpretive Phenomenological Analysis (IPA). We applied the lens of uncertainty management theory to tease out how patients experience, assess, manage and cope with puzzling and complex health-related issues while seeking a diagnosis in the cases of rare diseases.
RESULTS: We conducted interviews with 26 people with a rare disease. Ten participants had been diagnosed with a form of myositis, 8 with a primary immunodeficiency, and 8 with sarcoidosis. Time to diagnosis ranged from 6 months to 12 years (myositis), immediate to over 20 years (PID), and 6 months to 15 years (sarcoidosis). We identified four themes that described the experiences of participants with a rare disease as they sought a diagnosis for their condition: (1) normalising and/or misattributing symptoms; (2) particularising by clinicians; (3) asserting patients\' self-knowledge; and (4) working together through the diagnosable moment.
CONCLUSIONS: Managing medical uncertainty in the time before diagnosis of a rare disease can be complicated by patients discounting their own symptoms and/or clinicians discounting the scale and impact of those symptoms. Persistence on the part of both clinician and patient is necessary to reach a diagnosis of a rare disease. Strategies such as recognising pattern failure and accommodating self-labelling are key to diagnosis.

This study investigated the association between serum albumin concentration and 12-weeks mortality of HIV/AIDS with late diagnosis in China. This retrospective cohort study included, 1079 inpatients diagnosis with late HIV/AIDS between January 2018 and December 2021. Disease progression was estimated based on the 12-weeks mortality rate. Cox proportional hazards regression models were used to evaluate the relationship between serum albumin levels and disease progression. The effects of serum albumin levels on mortality was estimated via Kaplan-Meier curves. The mortality risk decreased by 7% with every 1 g/L increase in serum albumin after adjustment ([HR] = 0.93, 95% CI: 0.88-0.97). Compared with that of the low (< 28 g/L) serum albumin group, the middle (28-34 g/L) group\'s mortality risk decreased by 70% (HR = 0.30, 95% CI: 0.15-0.59), and that of the high (≥ 34 g/L) group decreased by 40% (HR = 0.6, 95% CI: 0.29-1.23) after adjustment. Our findings suggest a positive correlation between the increase in serum albumin levels upon admission and a decrease in mortality at 12 weeks post-discharge among patients with late AIDS/HIV diagnosis. Further research is needed to characterize the role of serum albumin in 12-weeks mortality prevention in patients with a late diagnosis.

BACKGROUND: Tuberculosis (TB) infectiousness decreases significantly with only a few days of treatment, but delayed diagnosis often leads to late treatment initiation. We conducted a sequential explanatory mixed methods study to understand the barriers and facilitators to prompt diagnosis among people with TB.
METHODS: We enrolled 100 adults who started TB treatment in the Carabayllo district of Lima, Peru, between November 2020 and February 2022 and administered a survey about their symptoms and healthcare encounters. We calculated total diagnostic delay as time from symptom onset to diagnosis. We conducted semi-structured interviews of 26 participants who had a range of delays investigating their experience navigating the health system. Interview transcripts were inductively coded for concepts related to diagnostic barriers and facilitators.
RESULTS: Overall, 38% of participants sought care first from public facilities and 42% from the private sector. Only 14% reported being diagnosed with TB on their first visit, and participants visited a median of 3 (interquartile range [IQR] health facilities before diagnosis. The median total diagnostic delay was 9 weeks (interquartile range [IQR] 4-22), with a median of 4 weeks (IQR 0-9) before contact with the health system and of 3 weeks (IQR 0-9) after. Barriers to prompt diagnosis included participants attributing their symptoms to an alternative cause or having misconceptions about TB, and leading them to postpone seeking care. Once connected to care, variations in clinical management, health facility resource limitations, and lack of formal referral processes contributed to the need for multiple healthcare visits before obtaining a diagnosis. Facilitators to prompt diagnosis included knowing someone with TB, supportive friends and family, referral documents, and seeing a pulmonologist.
CONCLUSIONS: Misinformation about TB among people with TB and providers, poor accessibility of health services, and the need for multiple encounters to obtain diagnostic tests were major factors leading to delays. Extending the hours of operation of public health facilities, improving community awareness and provider training, and creating a formal referral process between the public and private sectors should be priorities in the efforts to combat TB.

BACKGROUND: Tuberculosis(TB) and Diabetes comorbidity is an emerging public health problem in India. Delays in diagnosing TB or Diabetes would lead to adverse outcomes among comorbid patients, and attempts must be made to reduce these delays. Against this background, the study has been undertaken to clarify the role of sociocultural factors in determining diagnostic delays for TB and Diabetes among comorbid patients.
METHODS: A cross-sectional cultural epidemiological survey of the randomly selected 180 TB-Diabetes comorbid patients was carried out. The study examined sociocultural factors of delayed diagnosis of TB and Diabetes among urban and rural TB-Diabetes comorbid patients registered under TB-Diabetes collaborative activities under the National TB Elimination Programme (NTEP) in the Satara district of Maharashtra by using a semi-structured interview schedule. The patterns of distress (PDs) and perceived causes(PCs) of TB and Diabetes were compared with patients\' and providers\' diagnostic delays of TB and Diabetes based on prominence categories. In addition, the relationship between PDs and PCs as explanatory variables and TB and Diabetes diagnostic delays as outcome variables were assessed using stepwise multiple logistic regression.
RESULTS: Of the 180 TB-Diabetes comorbid patients, the proportion of men was higher, and they were 4.7 times more likely to get a delayed Diabetes diagnosis. Those who reported side effects of drugs and stigma reduced social status as the PDs were 2-3 times more likely to delay reaching TB facilities/providers (patients\' diagnostic delay). Those who perceived inadequate diet and mental-emotional stress as the causes of TB were about three times more likely to reach the TB providers/facilities after two weeks. Also, those who perceived TB as a cause of punishment for prior deeds were two times more likely to reach TB facilities/providers after two weeks. Patients who reported fever and chest pain as the symptoms of TB were two times more likely to delay the diagnosis of TB. Patients who reported tobacco consumption, unhealthy lifestyles, thoughts, worries, tension, and germs or infection as perceived causes of TB were about two times more likely to be diagnosed after two weeks. Patients who reported excessive thirst as a diabetes symptom were about two times more likely to get delayed >2 weeks to reach diabetes facilities/providers. Patients who perceived environmental/occupational exposure as the cause of Diabetes were two times more likely to reach the diabetes facilities/providers after two weeks. Patients who reported excessive thirst and stroke as the physical problems of Diabetes were 3.2 and 9.6 times more likely to get delayed in the diagnosis of Diabetes (providers\' diagnostic delay). Patients who perceived violation of taboo or misbehaviour as the perceived cause of Diabetes were 6.7 times more likely to get a delayed diagnosis of Diabetes.
CONCLUSIONS: The sociocultural factors associated with TB and Diabetes diagnostic delays among comorbid patients are essential considerations in the evolving context of implementing TB-Diabetes collaborative activities. Therefore, acknowledging sociocultural factors concerning delayed diagnosis and minimising delays would strengthen joint TB-Diabetes collaborative activities under the National framework locally and nationally.

BACKGROUND: TAFRO syndrome is a systemic inflammatory disorder, manifesting as thrombocytopenia (t), anasarca (a), fever (f), reticulin myelofibrosis/renal insufficiency (r), and organomegaly (o), and considered as a unique clinical subtype of idiopathic multicentric Castleman disease (iMCD). Such syndrome gave rise to a clinical picture similar to that of either a connective tissue disease or an autoimmune disease.
METHODS: A Chinese young female initially presenting with arthralgia, Raynaud phenomenon, generalized edema, and a positive anti-small nuclear ribonucleoprotein particle antibody was diagnosed as mixed connective tissue disease. The kidney biopsy showed thrombotic microangiopathy. Bone marrow smear showed bone marrow hyperplasia and biopsy revealed suspected light chain restricted expression, megakaryocyte proliferation, and moderate to severe bone marrow fibrosis. A lymph node biopsy was conducted and the histopathological findings were consistent with the subtype of mixed Castleman disease. The clinical symptoms were relieved after regular chemotherapy.
METHODS: After above examination results and clinical manifestations, the final diagnoses was TAFRO syndrome.
METHODS: The she was started on chemotherapy with bortezomib, cyclophosphamide, and dexamethasone.
RESULTS: After chemotherapy, symptoms such as thrombocytopenia, hematuria and proteinuria disappeared, lymphadenopathy and VEGF level decreased, and bone marrow fibrosis relieved.
CONCLUSIONS: Our case illustrated the first cases of shared characteristics of mixed connective tissue disease and iMCD-TAFRO syndrome. Cytokines may play a role in the shared pathogenicity of the iMCD-TAFRO syndrome and systemic autoimmune diseases. Therapy directly against inflammatory factors such as corticosteroids or chemotherapy have an important therapeutic implication.

BACKGROUND: Late presentation with advanced HIV disease (LP-AHD) remains a significant challenge to Human Immunodeficiency Virus (HIV) care, contributing to increased morbidity, mortality, and healthcare costs. Despite global efforts to enhance early diagnosis, a considerable proportion of individuals with HIV infection are unaware of being infected and therefore present late for HIV care. For the first time in Ghana, this study assessed the prevalence of LP-AHD and associated factors among people diagnosed with HIV (PDWH).
METHODS: This bi-center retrospective cross-sectional study included 315 PDWH at the Aniniwah Medical Centre and Komfo Anokye Teaching Hospital, both in Kumasi, Ghana. A well-structured questionnaire was used to collect data on sociodemographic, clinical, lifestyle and psychosocial factors from the study participants. Statistical analyses were done in SPSS version 26.0 and GraphPad Prism version 8.0 at significant p-value of < 0.05 and 95% confidence interval. Predictors of LP-AHD were assessed using binary logistic regression models.
RESULTS: This study observed that, 90 out of the 315 study PDWH (28.6%) reported late with advanced HIV disease (AHD). Participants within the age group of 36-45 years (adjusted Odds Ratio [aOR]: 0.32, 95% CI: 0.14-0.69; p = 0.004) showed a significantly decreased likelihood of LP-AHD. However, participants who perceived cost of HIV care to be high (aOR: 7.04, 95% CI: 1.31-37.91; p = 0.023), who were diagnosed based on clinical suspicion (aOR: 13.86, 95 CI: 1.83-104.80; p = 0.011), and missed opportunities for early diagnosis by clinicians (aOR: 2.47, 95% CI: 1.30-4.74; p = 0.006) were significantly associated with increased likelihood of LP-AHD.
CONCLUSIONS: The prevalence of LP-AHD among PDWH in Ghana is high. Efforts to improve early initiation of HIV/AIDS care should focus on factors such as the high perceived costs of HIV care, diagnosis based on clinical suspicion, and missed opportunities for early diagnosis by physicians.

OBJECTIVE: Transthyretin cardiac amyloidosis (ATTR-CA) is a rare and progressive cardiomyopathy caused by amyloid fibril deposition in myocardial tissue. Diagnostic challenges have historically hampered timely detection. Recent advances in noninvasive diagnostic techniques have facilitated ATTR-CA diagnosis. We aimed to examine the development of a regional network for the diagnosis and management of ATTR-CA and describe a cohort of patients with ATTR-CA, investigate diagnostic pathways and assess clinical outcomes according to diagnosis periods.
METHODS: We performed a survey study analyzing answers from 11 cardiology centers and we conducted a retrospective study including patients with ATTR-CA attending a referral center between 1 January 2012 and 31 December 2022, and categorized by the period of diagnosis (2012-2016 and 2017-2022).
RESULTS: Over the years, a growing number of patients reached a diagnosis and were treated in the surveyed nonreferral centers of the region. The retrospective study showed a more significant diagnostic delay in the earlier period rather than the later one [13.4 (5-30.2) vs. 10.6 (5.0-17.9) months, P = 0.04]. Patients diagnosed after 2017 showed a greater survival rate than those diagnosed earlier ( P = 0.02). In the multivariate analysis, the year of diagnosis from 2017 remained independently associated with mortality [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.28-0.79; P = 0.005].
CONCLUSIONS: This study emphasized the shift toward noninvasive diagnostic criteria. It revealed a positive impact on patient survival and disease management with the use of disease-modifying therapies and diagnostic developments in more recent years. The findings underscore the importance of disease awareness and networking to reduce diagnostic delays and enhance patient journeys for ATTR-CA.

This is a case of a woman in her 50s with HIV and uncontrolled diabetes who presented to the emergency department with urinary retention and a painful gluteal cleft lesion, admitted for cellulitis. Since initial CT and soft tissue ultrasound (US) were negative for fluid collection, the care team was surprised to find her symptoms continued to progress despite intravenous antibiotics. Finally, MRI 9 days into her admission demonstrated a 12-cm perirectal horseshoe abscess. The patient was ultimately treated with incision and drainage with Penrose drain placement. This case demonstrates the importance of maintaining a high suspicion for horseshoe abscess, a complex form of ischiorectal fossa abscess which can be missed on CT and US imaging, and which may expand rapidly in immunosuppressed patients.

UNASSIGNED: A prehospital delay from symptom onset to hospital arrival resulted in stroke-related complications or in-hospital deaths in acute stroke patients. We aimed to investigate trends in prehospital visits as a cause of prehospital delay using data from the Korean Health Insurance Service.
UNASSIGNED: This nationwide, population-based, retrospective cohort study included 524,524 newly-diagnosed stroke patients admitted via the emergency departments of secondary and tertiary hospitals. We obtained the prehospital visits rate from 2010 to 2019 and identified the related characteristics.
UNASSIGNED: Prehospital visits were observed in 111,465 patients (21.3%). The prehospital visits rate decreased from 25.1% in 2010 to 17.8% in 2019, but the number of patients increased from 11,255 cases in 2010 to 11,747 cases in 2019. Fortunately, the rate of delayed admission for more than one day decreased from 26.7% to 21.3%. However, 10.4% of patients were diagnosed more than two days later. Young, females, or patients with higher income status and living in low urbanization areas exhibited a higher rate of prehospital visits.
UNASSIGNED: Prehospital visits in Korean stroke patients decreased from 25.1% in 2010 to 17.8% in 2019. However, more than 10,000 patients still visited other medical institutions before admission to treatment.

We present an adult patient with schizophrenia who was later found to have hyperhomocysteinemia, a condition that increases the risk of several diseases, due to a deficiency in folic acid. Although folic acid supplementation quickly normalized the hyperhomocysteinemia and folic acid levels, it did not significantly improve the overall mental and cognitive health. Genotype analysis was performed and the patient was found to have two pathogenic variants in the MTRR gene, 66GG and 524TT, which encodes for methionine synthase reductase (MSR), an enzyme crucial for homocysteine metabolism. The results can shed light on the reasons behind the patient\'s hyperhomocysteinemia and folic acid deficiency. Hyperhomocysteinemia confers an increased risk of several diseases. Indeed, the patient has neurodevelopment and cardiovascular health problems for decades. Given the rarity of the condition and the nonspecific nature of the symptoms, the detection of hyperhomocysteinemia or MSR deficiency can often be delayed or overlooked. Considering the potential irreversible and detrimental consequences of prolonged hyperhomocysteinemia and folic acid deficiency that our patient is likely experiencing, we suggest that clinicians be vigilant for associated signs when they encounter adolescents exhibiting psychotic symptoms, especially those with additional physical symptoms and a history of resistance to treatment.