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AbstractObjectivesMethodsResultsConclusionsWe investigated the relationship between occupational lead exposure and amyotrophic lateral sclerosis (ALS) survival in Denmark.We identified 2,161 ALS cases diagnosed from 1982 to 2013 with at least 5 years of employment history before ALS diagnosis, via the Danish National Patient Registry. Cases were followed until March 2017. We defined lead exposure as never employed in a lead job, ever employed in a lead job, and ever employed in a lead job by exposure probability (<50% vs. ≥50%), excluding jobs held in the 5 years before diagnosis in main analyses. Survival was evaluated using Cox proportional hazards models and stratified by sex and age of diagnosis.Median age of diagnosis was 63.5 years, and individuals in lead-exposed jobs were diagnosed at a younger age. Adjusted hazard ratios (aHR) were slightly decreased for men ever lead-exposed (aHR:0.92, 95%CI: 0.80, 1.05) and more so among those diagnosed at age 60–69 (lead ≥ 50% aHR: 0.66, 95%CI: 0.45, 0.98), but reversed for men diagnosed at age 70 and later (aHR: 2.03, 95%CI: 1.13, 3.64). No apparent pattern was observed among women.Occupational lead exposure contributed to shorter survival among men diagnosed at older ages. The inverse associations observed for men diagnosed earlier could relate to possible healthy worker hire effect or health advantages of working in lead-exposed jobs. Our results are consistent with an adverse impact of lead exposure on ALS survival at older ages, with the age at which lead’s effects on survival worsen later on among those in lead-exposed jobs. [ABSTRACT FROM AUTHOR]

Background: South Carolina has arguably the most robust Alzheimer's Registry in the United States. For enhanced planning in both clinical practice and research and better utilization of the Registry data, it is important to understand survival after Registry entry. To this end, we conducted exploratory analyses to examine the patterns of longevity/survival in the South Carolina Alzheimer's Disease Registry. Methods: The sample included 42,028 individuals in the South Carolina Alzheimer's Disease Registry (SCADR). Participants were grouped into four cohorts based on their year of diagnosis. Longevity in the Registry (LIR), or the length of survival in the registry, was calculated based on the years of reported diagnosis and death. Results: The median LIR varied between 24 to 36 months depending on the cohort, with 75% of individuals in the three recent cohorts surviving for at least 12 months. Across all cohorts, 25% of the participants survived at least 60 months. The median LIR of females was longer than that of males. Individuals whose race was classified as Asian, American Indian, and other than listed had longer LIR compared to White, African American, and Hispanic individuals. Median LIR was shorter for Registry cases diagnosed at an earlier age (less than 65 years). Conclusion: Our data indicate that significant longevity is to be expected in the SCADR but that there is interesting variability which needs to be explored in subsequent studies. The SCADR is a rich data source prime for use in research studies and analyses. [ABSTRACT FROM AUTHOR]

Coronary functional testing to formally diagnose coronary microvascular dysfunction (CMD) reduces cardiovascular events and alleviates angina. This study aims to investigate the extensive and complex journey that patients with CMD undergo, from the onset of chest pain to eventual diagnosis. Data from the Coronary Microvascular Disease Registry (CMDR) were analyzed, including information on the date of first documentation of chest pain, number of non-invasive and invasive tests the patient underwent, emergency department visits, and hospitalizations. In addition, we estimated the total cost per patient. A total of 61 patients with CMD diagnosis were included in this analysis. Most patients in our cohort were older than 50 years of age. The median time from initial chest pain symptoms to diagnosis was 0.62 (interquartile range [IQR]: 0.06–2.96) years. During this period, patients visited the emergency department a median of 1.0 (IQR: 0.0–2.0) times. Diagnostic tests included 3.0 (IQR: 2.0–6.0) electrocardiograms, 3.0 (IQR: 0.0–6.0) high-sensitivity troponin tests, and 1.0 (IQR: 1.0–2.0) echocardiograms. Prior to diagnosis of CMD, 13 (21.3 %) patients had left heart catheterization without coronary functional testing. Non-invasive testing for ischemia was conducted in 43 (70.5 %) patients. Alternative non-cardiac diagnoses were given to 11 (18.0 %) patients during the diagnostic process, with referrals made to gastroenterology for 16 (26.2 %) and pulmonology for 10 (16.4 %) patients. The cost was almost $2000/patient. Timely identification of CMD offers promising opportunities for prompt symptom alleviation, accompanied by reduced visits to the emergency department, cardiovascular testing, invasive medical procedures, and consequently reduced healthcare expenses. • Angina pectoris impacting millions of individuals around the world • Coronary microvascular dysfunction (CMD) is a known etiology to cause angina. • This study reveals the journey of CMD patients from chest pain to diagnosis. • Healthcare providers must improve CMD awareness and understanding. • Further research is crucial to optimize CMD management. [ABSTRACT FROM AUTHOR]

Coronary microvascular dysfunction (CMD) is a prevalent condition among patients with cardiovascular risk factors, leading to a reduced quality of life and an increased risk of major adverse cardiovascular events. Novel invasive techniques have emerged to more accurately diagnose CMD. However, CMD's natural history remains poorly understood due to limited data. To address this knowledge gap, the Coronary Microvascular Disease Registry (CMDR) was established with the primary aim of standardizing comprehensive coronary functional testing and understanding of CMD. CMDR is a prospective, multicenter registry enrolling an unlimited number of consecutive subjects who undergo comprehensive invasive hemodynamic assessment of the entire coronary arterial vasculature. Patients undergoing acetylcholine provocation test for coronary vasospasm will also be included. Follow-up assessments will be conducted at 30 days and annually for up to 5 years. The primary endpoint is Canadian Cardiovascular Society angina grade over time. Secondary endpoints, including all-cause mortality, cardiovascular death, acute myocardial infarction, stroke, hospitalizations, medication changes, and subsequent coronary interventions, will be analyzed to establish long-term safety and clinical outcomes in patients undergoing invasive CMD assessment. CMDR aims to characterize the clinical and physiologic profile of patients undergoing comprehensive invasive coronary functional testing, simultaneously providing crucial longitudinal information on the natural history and outcomes of these patients. This will shed light on CMD's course and clinical implications, which, in turn, holds the potential to significantly improve diagnostic and treatment strategies for CMD patients, ultimately leading to the enhancement of their overall prognosis and quality of life. clinicaltrials.gov , NCT05960474 • CMD leads to reduced quality of life and increased risk of MACE. • CMD's natural history remains poorly understood due to limited data. • Coronary Microvascular Disease Registry aims to standardize CMD understanding. • CMDR will characterize CMD patients' clinical and physiologic profiles. • This holds the potential to improve diagnosis and treatment of CMD patients. [ABSTRACT FROM AUTHOR]

Background: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure and various motor symptoms. While MSA‐C (cerebellar type) predominates in East Asia, MSA‐P (parkinsonian type) predominates in Europe and North America. This nationwide patient registry aimed to (1) conduct a prospective natural history study of MSA in Japan, (2) facilitate patient recruitment for clinical trials, and (3) deposit bioresources and clinical information in a biobank. Methods: Thirteen institutions participated in this study. Clinical information was obtained by neurologists from the patients visiting the hospital every 12 months to assess the UMSARS Part 2 scores and by telephone interviews by nurses every 6 months to assess UMSARS Part 1 scores and to determine whether clinical events had occurred. Results: Demographic data from 329 MSA patients (216 MSA‐C and 113 MSA‐P) were analyzed. The mean age at symptom onset was 58.2 years (standard deviation, 8.9); the mean duration of symptoms at enrollment was 3.5 years (standard deviation, 2.2). The mean 12‐month changes in the UMSARS Part 1 and Part 2 scores were 7.9 (standard deviation, 5.6) and 6.4 (standard deviation, 5.9), respectively. The patient registry proved useful in recruiting participants for clinical trials, including those with gene variants. Clinical information and biospecimens were deposited in a biobank. Discussion: The study highlighted the importance of telephone interviews in minimizing drop‐out rates in natural history studies and demonstrated similar MSA progression rates across populations. The deposited bioresources are available to researchers upon request, aiming to contribute to future MSA researches. [ABSTRACT FROM AUTHOR]

Background: Transcatheter aortic valve implantation (TAVI) is increasingly being used in younger patients and those with lower peri‐procedural risk, meaning more patients will live long enough to experience structural valve deterioration (SVD) of the bioprosthesis, indicating repeated TAVI. Experience of repeated TAVI—transcatheter heart valve (THV) implantation into an index THV is limited. This registry aims to assess the peri‐procedural and short‐term safety, efficacy and durability of repeated TAVI. Methods: The ReTAVI Prospective observational registry is an investigator‐initiated, multicentre, international, prospective registry of patients undergoing repeated TAVI using balloon‐expandable SAPIEN prosthesis to evaluate procedural and short‐term safety, efficacy and durability as well as anatomical and procedural factors associated with optimal results. The registry will enrol at least 150 patients across 60 high‐volume centres. Patients must be ≥18 years old, have had procedural success with their first TAVI, have index THV device failure, intend to undergo repeated TAVI and be considered suitable candidates by their local Heart Team. All patients will undergo a 30‐day and 12‐month follow‐up. The estimated study completion is 2025. Conclusions: The registry will collect pre‐, peri‐, postoperative and 12‐months data on patients undergoing repeated TAVI procedures with THVs for failure of the index THV and determine VARC‐3‐defined efficacy and safety at 30 days and functional outcome at 12 months. The registry will expand existing data sets and identify patient characteristics/indicators related to complications and clinical benefits for patients with symptomatic severe calcific degenerative aortic stenosis. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) is a group of rare hereditary collagen disorders. Hearing loss (HL) is a known complication linked to changes in the bones of the middle ear seen in OI. We aimed to determine the prevalence, age at debut, incidence, and risk of HL, surgery on bones of the middle ear, and use of hearing aids. A Danish nationwide, register-based cohort study. Data were extracted from the Danish National Patient register. Anyone with an OI diagnosis between January 1st 1977 and December 31st 2018, matched 1:5 with a reference population (Ref.Pop) on birthyear and sex, were included. 864 persons (487 women) with OI were included in the study and 4276 (2330 women) in the Ref.Pop. The sub-hazard ratio (SHR) for any HL was 4.56 [95% CI 3.64–5.71], with a prevalence of 17.0% and 4.0% in the OI cohort and Ref.Pop. Median age at debut was 42 and 58 years, respectively. The risk of otosclerosis and/or surgery was higher in the OI cohort (SHR 22.51 [95% CI 12.62–40.14]), with a median age at debut of 43 and 32 years in the OI cohort and Ref.Pop, respectively. Hearing aid use was more frequent in the OI cohort (SHR 4.16 [95% CI 3.21–5.40]) than in the Ref.Pop. The median age at debut was 45 and 60 years in the OI cohort and Ref.Pop, respectively. Persons with OI have a higher risk and prevalence of HL, hearing aids, and surgery, debuting younger, and prevalence increases with age. [ABSTRACT FROM AUTHOR]

The advancement of medical toxicology knowledge has traditionally relied on case reports and case series because of the ethical challenges involved in studying poisoned patients. The growing availability of several large databases and registries now allows researchers to describe and analyze patterns in poisoned patients who share a particular exposure, outcome, or condition. A large database or registry can be useful in generating hypotheses, supporting extramural funding applications, and planning more rigorous studies. Knowing how to access and interpret data in registries such as NPDS, NHAMCS, and HCUP is essential for all stakeholders engaged in medical toxicology research. This review describes the strengths and limitations of different toxicology-relevant registries and databases and how to leverage these powerful tools to advance the science in the field of medical toxicology. [ABSTRACT FROM AUTHOR]

The Toxicology Investigators Consortium (ToxIC) was launched as a prospective multi-center registry of cases who receive medical toxicology consultations. Now, with over 100,000 cases, the Core Registry continues to address many medical toxicology research questions and has served as the foundation for multiple sub-registries, including the North American Snakebite Registry and the Medications for Opioid Use Disorder sub-registry. ToxIC also has evolved a portfolio of non-registry-based projects utilizing medical toxicology physician site principal investigators who enroll patients through emergency departments, irrespective of whether they received a medical toxicology consultation. These studies include the FDA-ACMT COVID-19 ToxIC Pharmacovigilance Project, which identifies adverse drug reactions related to the treatment of COVID-19, the Fentalog Study a toxico-surveillance study of suspected opioid overdose cases, the Drug Overdose Toxico-Surveillance Reporting Program which enrolls either suspected stimulant or opioid overdose cases, and the just being launched Real-World Examination of Naloxone for Drug Overdose Reversal project. Given ToxIC's experience in multi-center studies and its well-developed infrastructure, it is well-positioned to provide a nimble response on the part of the medical toxicology community to addressing evolving toxicological threats, drug and chemical toxicosurveillance, and other important medical toxicology priorities. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria (NTM) are emerging as notable causative agents of opportunistic infections. To examine clinical significance, species distribution, and temporal trends of NTM in Denmark, we performed a nationwide register-based study of all unique persons with NTM isolated in the country during 1991–2022. We categorized patients as having definite disease, possible disease, or isolation by using a previously validated method. The incidence of pulmonary NTM increased throughout the study period, in contrast to earlier findings. Mycobacterium malmoense, M. kansasii, M. szulgai, and M. avium complex were the most clinically significant species based on microbiologic findings; M. avium dominated in incidence. This study shows the need for surveillance for an emerging infection that is not notifiable in most countries, provides evidence to support clinical decision-making, and highlights the importance of not considering NTM as a single entity. [ABSTRACT FROM AUTHOR]

Background and Objectives Methods Results Discussion and Conclusions Scientific Significance More knowledge is needed to identify and reach those at overdose risk with preventive measures. We examined past 12‐month health service utilization, identified the most frequently utilized service, explored this utilization in more detail, and examined correlates of overdose death.A population‐based nested case–control registry study including all drug overdose deaths (1 January 2010 to 31 December 2018) in Norway through the Cause of Death Registry (n = 2388). The year‐, age‐ and gender‐matched controls included through a population registry (n = 21,465). Data cross‐linked with population and patient registries. Multivariable conditional logistic regression analyses estimated the likelihood of overdose death.The cases (vs. controls) attended a higher median number of services (3 vs. 1). The General Practitioner (GP) was the most utilized service. The majority (55.7%) of cases had 11–50 encounters, while the majority (60.7%) of the controls had 1–5 encounters. No high school diploma, no employment, urban living, social welfare benefits/disability pension, single‐person household, recent incarceration, multiple health service utilization and frequent GP encounters, as well psychological and certain physical diagnoses were correlates of overdose death among the GP attenders.The cases had utilized more services than the controls and the GP was the most frequently utilized service. In addition to low socioeconomic status, psychological and certain physical diagnoses were correlates of overdose death.This is the first national case–control registry study to document the high utilization of multiple primary and secondary health care services before drug overdose death, as well as reasons for attendance and correlates of overdose death. [ABSTRACT FROM AUTHOR]

Survival analysis (also referred to as time-to-event analysis) is the study of the time elapsed from a starting date to some event of interest. In practice, these analyses can be challenging and, if methodological errors are to be avoided, require the application of appropriate techniques. By using simulations and real-life data based on the French national registry of patients with primary immunodeficiencies (CEREDIH), we sought to highlight the basic elements that need to be handled correctly when performing the initial steps in a survival analysis. We focused on non-parametric methods to deal with right censoring, left truncation, competing risks, and recurrent events. Our simulations show that ignoring these aspects induces a bias in the results; we then explain how to analyze the data correctly in these situations using non-parametric methods. Rare disease registries are extremely valuable in medical research. We discuss the application of appropriate methods for the analysis of time-to-event from the CEREDIH registry. The objective of this tutorial article is to provide clinicians and healthcare professionals with better knowledge of the issues facing them when analyzing time-to-event data. [ABSTRACT FROM AUTHOR]

Introduction/Aims Methods Results Discussion In Guillain–Barré syndrome (GBS), patients with dysautonomia demonstrate sympathetic overactivity (SO). This study assessed the role of prazosin (α1‐blocker) in the management of SO.This cohort study was conducted from January 2022 to September 2023. Thirty‐two GBS patients with SO received prazosin (2.5–10 mg three times a day) (prazosin group). For comparison, we included historical controls that included 33 GBS patients having SO with similar baseline characteristics, including median age and disability, who did not receive prazosin, from a GBS registry of patients admitted during February 2018–December 2021. The primary endpoint was days to resolution of SO. Secondary endpoints were daily fluctuations in the systolic (SBP) and diastolic blood pressure (DBP), duration of hospital stay, in‐hospital mortality, and disability at 3 months.The median ages of both the treatment and the control groups were 36 (IQR 25–49) years and 43 (66.2%) were males. The demographic and clinical parameters were comparable. Prazosin resulted in significantly earlier normalization of SO compared to the control group (median 15 vs. 20 days; p = .01). The mean fluctuations in the SBP and DBP at 15 days were significantly lower in the prazosin group. However, the duration of hospital stay and good recovery at 3 months were comparable. Three patients developed hypotension, while two patients died (ventilator‐associated pneumonia) in the prazosin group.This study provides new evidence supporting the role of prazosin in SO, and needs randomized trials to confirm our findings. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionTo identify prevalence of and risk factors for loss to follow up (LTFU) among a national cohort of patients with primary open-angle glaucoma (POAG).This retrospective cohort study analyzed data from the IRIS® Registry (Intelligent Research in Sight) database from 2014 through 2019 to assess LTFU among adult patients with POAG. POAG patients with at least one clinical encounter in 2014 were included. LTFU was defined as exceeding one year without a clinical encounter during the study period.Among 553,663 glaucoma patients, 277,019 (50%) became LTFU, of whom 184,548 (67%) never returned to care and 92,471 (33%) re-established follow-up after a lapse. Risk of LTFU was greatest among those younger than 60 years (RR = 1.38; 95% CI: 1.36–1.39) or older than 80 years (RR = 1.39; 95% CI: 1.38–1.40) compared to those in their 60s. Compared to White race, risk for LTFU was highest among Native Hawaiian/Pacific Islander (RR = 1.24; 95% CI: 1.17–1.31), Hispanic ethnicity (RR = 1.19; 95% CI: 1.18–1.20), and Black race (RR = 1.10; 95% CI: 1.09–1.11). Medicare insurance was associated with lower risk of LTFU (RR = 0.79; 95% CI: 0.78–0.79), whereas unknown/missing/no insurance was associated with greater risk (RR = 1.33; 95% CI: 1.32–1.34), compared to private insurance. Compared to mild-stage POAG, risk of LTFU was higher for moderate-stage (RR = 1.10; 95% CI: 1.08–1.13) and severe-stage disease (RR = 1.35; 95% CI: 1.32–1.38).We found a 50% prevalence of LTFU among POAG patients in the IRIS Registry over a 6-year study period, with greater risk among minority groups and those with more advanced disease. [ABSTRACT FROM AUTHOR]

AbstractBackground and aimsMethodsResultsConclusionThis study explored the associations between symptoms of the Suicide Crisis Syndrome (SCS) at admission and self-harm and death by suicide post-discharge. The association between clinicians’ emotional responses toward inpatients at admission and post-discharge self-harm and suicide death was also explored.Within the first 24-h of admission, patients completed a self-report measure of symptoms of SCS, and clinicians reported their emotional responses toward the patients. Follow-up data were obtained from the Norwegian Patient Registry and the Norwegian Cause of Death Registry.Within 18 months post-discharge, 44 (12.7%) out of 347 patients had self-harmed, and five patients (1.4%) had died by suicide. At admission, patients who later self-harmed reported higher symptoms of SCS compared to the other patients. Clinicians reported more negative emotional responses toward the self-harm group. In a regression analysis, previous suicidal behavior and a diagnosis of “emotionally unstable personality disorder” (EUPD; F60.3) were associated with increased risk of self-harm post-discharge.The results indicated that patients with post-discharge episodes of self-harm are significantly different from patients who do not self-harm in terms of more intense symptoms of SCS during admission. Clinicians’ negative emotional responses may be relevant in the assessment of the risk of post-discharge self-harm. [ABSTRACT FROM AUTHOR]

Background: Satisfaction with prosthesis plays a key role in regaining mobility and is important for optimizing prosthetic usage, mobility, and increasing compliance with medical regimen. Despite unchangeable factors like age and comorbidities, other factors, like pain, received rehabilitation, satisfaction with assistive devices, service, and information, can be changed and might contribute to a better usage and acceptance of the prosthesis and amputees' mobility. Objectives: The aim of the study was to analyze mobility, pain, supply of assistive devices, and additional therapies received after major limb amputations. Furthermore, a correlation of those parameters was evaluated. Methods: Retrospective identification of patients with major limb amputation (operation and procedures classification system (OPS)) and relevant related demographics within the clinical documentation system during a four-year observation time. In addition, we undertook prospective assessment of mobility (K-level), pain qualities, additional therapies, self-rated overall quality of life (QoL) and degree of adaptation to the life after amputation, dependency from caregivers, and satisfaction with the provided assistive devices (QUEST). Results: A total of 164 patients (mean age 68, age range: 19 to 97 years) underwent major limb amputation. A total of 27 questionnaires were returned and analyzed. All those traumatic and nontraumatic amputees received assistive devices. Although mobility and QoL decreased significantly after amputation, a high satisfaction with provided prosthetic and assistive devices and care was found. Conclusions: Amputation registries are becoming elementary to allow for nationwide comparisons of clinics, to identify the requirements of amputees, and to design an interdisciplinary care model for a successful comprehensive approach. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Late onset Pompe disease (LOPD) is a rare neuromuscular disorder caused by a deficit in acid alpha‐glucosidase. Macroglossia and swallowing disorders have already been reported, but no study has focused yet on its frequency and functional impact on patients' daily life.We reviewed 100 adult LOPD patients followed in 17 hospitals in France included in the French national Pompe disease registry. The Swallowing Quality of Life Questionnaire and the Sydney Swallow Questionnaire were completed by patients, and a specialist carried out a medical examination focused on swallowing and assigned a Salassa score to each patient. Respiratory and motor functions were also recorded. Subgroup analysis compared patients with and without swallowing difficulties based on Salassa score.Thirty‐two percent of patients presented with swallowing difficulties, often mild but sometimes severe enough to require percutaneous endoscopic gastrostomy (1%). Daily dysphagia was reported for 20% of our patients and aspirations for 18%; 9.5% were unable to eat away from home. Macroglossia was described in 18% of our patients, and 11% had lingual atrophy. Only 15% of patients presenting with swallowing disorders were followed by a speech therapist. Swallowing difficulties were significantly associated with macroglossia (p = 0.015), longer duration of illness (p = 0.032), and a lower body mass index (p = 0.047).Swallowing difficulties in LOPD are common and have significant functional impact. Increased awareness by physicians of these symptoms with systematic examination of the tongue and questions about swallowing can lead to appropriate multidisciplinary care with a speech therapist and dietitian if needed. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions The prevalence of Down syndrome (DS) is approximately 1 per 1000 births and is influenced by increasing maternal age over the last few decades. DS is strongly associated with congenital heart defects (CHDs), especially atrioventricular septal defect (AVSD). Our objectives were to investigate the prevalence of live‐born infants with DS having a severe CHD in the Norwegian population over the last 20 years and compare outcomes in infants with AVSD with and without DS.Information on all births from January 1, 2000 to December 31, 2019 was obtained from the Medical Birth Registry of Norway. We also obtained data on all infants with severe CHDs in Norway registered in Oslo University Hospital's Clinical Registry for Congenital Heart Defects during 2000–2019 and accessed individual‐level patient data from the electronic hospital records of selected cases. Infants with AVSD and DS were compared to infants with AVSD without chromosomal defects. Crude and adjusted odds ratios (ORs) of infant mortality and need for surgery during the first year of life, with associated 95% confidence intervals (CIs), were estimated by logistic regression.A total of 1 177 926 infants were live‐born in Norway during the study period. Among these, 1456 (0.1%) had DS. The prevalence of infants with DS having a severe CHDs was relatively stable, with a mean of 17 cases per year. The most common CHD associated with DS was AVSD (44.4%). Infants with AVSD and DS were more likely to have cardiac intervention during their first year of life compared to infants with AVSD without chromosomal defects (adjusted OR [aOR]: 2.52; 95% CI 1.27, 4.98). However, we observed no difference in infant mortality during first year of life between the two groups (aOR: 1.08; 95% CI 0.43, 2.70).The prevalence of live‐born infants with severe CHDs and DS has been stable in Norway across 20 years. Infants with AVSD and DS did not have higher risk of mortality during their first year of life compared to infants with AVSD without chromosomal defects, despite a higher risk of operative intervention. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is an incurable, progressive neurodegenerative disease with a significant health burden and poorly understood etiology. This analysis assessed the narrative responses from 3,061 participants in the Centers for Disease Control and Prevention's National ALS Registry who answered the question, "What do you think caused your ALS?" Data analysis used qualitative methods and artificial intelligence (AI) using natural language processing (NLP), specifically, Bidirectional Encoder Representations from Transformers (BERT) to explore responses regarding participants' perceptions of the cause of their disease. Both qualitative and AI analysis methods revealed several, often aligned themes, which pointed to perceived causes including genetic, environmental, and military exposures. However, the qualitative analysis revealed detailed themes and subthemes, providing a more comprehensive understanding of participants' perceptions. Although there were areas of alignment between AI and qualitative analysis, AI's broader categories did not capture the nuances discovered using the more traditional, qualitative approach. The qualitative analysis also revealed that the potential causes of ALS were described within narratives that sometimes indicate self-blame and other maladaptive coping mechanisms. This analysis highlights the diverse range of factors that individuals with ALS consider as perceived causes for their disease. Understanding these perceptions can help clinicians to better support people living with ALS (PLWALS). The analysis highlights the benefits of using traditional qualitative methods to supplement or improve upon AI-based approaches. This rapidly evolving area of data science has the potential to remove barriers to accessing the rich narratives of people with lived experience. [ABSTRACT FROM AUTHOR]

Objective: Twin studies have demonstrated that posttraumatic stress disorder (PTSD) is moderately heritable, and the pattern of findings across studies suggests higher heritability in females compared with males. Formal testing of sex differences has yet to be done in twin studies of PTSD. The authors sought to estimate the genetic and environmental contributions to PTSD, and to formally test for sex differences, in the largest sample to date of both sexes, among twins and siblings. Methods: Using the Swedish National Registries, the authors performed structural equation modeling to decompose genetic and environmental variance for PTSD and to formally test for quantitative and qualitative sex differences in twins (16,242 pairs) and in full siblings within 2 years of age of each other (376,093 pairs), using diagnostic codes from medical registries. Results: The best-fit model suggested that additive genetic and unique environmental effects contributed to PTSD. Evidence for a quantitative sex effect was found, such that heritability was significantly greater in females (35.4%) than males (28.6%). Evidence of a qualitative sex effect was found, such that the genetic correlation was high but less than complete (rg=0.81, 95% CI=0.73–0.89). No evidence of shared environment or special twin environment was found. Conclusions: This is the first demonstration of quantitative and qualitative sex effects for PTSD. The results suggest that unique environmental effects, but not the shared environment, contributed to PTSD and that genetic influences for the disorder are stronger in females compared with males. Although the heritability is highly correlated, it is not at unity between the sexes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness and safety of nusinersen for the treatment of 5q-spinal muscular atrophy (SMA) among Chinese pediatric patients. Methods: Using a longitudinal, multi-center registry, both prospective and retrospective data were collected from pediatric patients with 5q-SMA receiving nusinersen treatment across 18 centers in China. All patients fulfilling the eligibility criteria were included consecutively. Motor function outcomes were assessed post-treatment by SMA type. Safety profile was evaluated among patients starting nusinersen treatment post-enrollment. Descriptive analyses were used to report baseline characteristics, effectiveness, and safety results. Results: As of March 2nd, 2023, 385 patients were included. Most patients demonstrated improvements or stability in motor function across all SMA types. Type II patients demonstrated mean changes [95% confidence interval (CI)] of 4.4 (3.4–5.4) and 4.1 (2.8–5.4) in Hammersmith Functional Motor Scale-Expanded (HFMSE), and 2.4 (1.7–3.1) and 2.3 (1.2–3.4) in Revised Upper Limb Module (RULM) scores at months 6 and 10. Type III patients exhibited mean changes (95% CI) of 3.9 (2.5–5.3) and 4.3 (2.6–6.0) in HFMSE, and 2.1 (1.2–3.0) and 1.5 (0.0–3.0) in RULM scores at months 6 and 10. Of the 132 patients, 62.9% experienced adverse events (AEs). Two patients experienced mild AEs (aseptic meningitis and myalgia) considered to be related to nusinersen by the investigator, with no sequelae. Conclusions: These data underscore the significance of nusinersen in Chinese pediatric patients with SMA regarding motor function improvement or stability, and support recommendations on nusinersen treatment by Chinese SMA guidelines and continuous coverage of nusinersen by basic medical insurance. [ABSTRACT FROM AUTHOR]

Background: Due to an increasing occupational usage of isothiazolinone (IT)‐containing preservatives, and their potential to cause skin sensitization and allergic contact dermatitis, that is, chronic disease, there is a need for more knowledge on how highly exposed workers are affected. Objectives: The overall objective was to explore dermatological symptoms of potentially long‐lasting or chronic character in Swedish painters. Methods: Building painters from western and southern Sweden were initially invited to perform a questionnaire on occurrence of skin symptoms. Participants with affirmative responses, and the right inclusion criteria, were further invited to patch testing with four different ITs: benzisothiazolinone (BIT), methylisothiazolinone, methylchloroisothiazolinone and octylisothiazolinone. Results: There was a tendency towards higher occurrence of positive patch test reactions among the painters compared with occupationally unexposed registry patients; however, not statistically significant differences. BIT was the substance most frequently causing positive test results in both groups. The occurrence of adult‐onset eczema was higher in painters than in the control group of electricians, and just shy of statistical significance concerning any of several skin locations (face/legs/arms/hands). Conclusion: Building painters present with positive patch test reactions to common paint preservatives (ITs), and they report adult‐onset eczema more often than do less occupationally exposed groups. [ABSTRACT FROM AUTHOR]

Background: Chronic pain remains prevalent after open inguinal hernia repair and nerve-handling strategies are debated. Some guidelines suggest sparing nerves that are encountered; however, the nerve identification rates are unclear. This study aimed to investigate the nerve identification rates in a register-based nationwide cohort. Methods: This study was reported according to the RECORD guideline and used prospective, routinely collected data from the Danish Hernia Database, which was linked with the National Patient Registry. We included patients ≥ 18 years old, undergoing Lichtenstein hernia repair with information on nerve handling of the iliohypogastric and ilioinguinal nerves. Results: We included 30,911 open hernia repairs performed between 2012 and 2022. The ilioinguinal nerve was identified in 73% of the repairs and the iliohypogastric nerve in 66% of repairs. Both nerves were spared in more than 94% of cases where they were identified. Female patient sex, emergency and recurrence surgery, general anesthesia, medial and saddle hernias, and large defect size all result in lower nerve identification rates for both nerves. Conclusion: The Ilioinguinal nerve was recognized in 73% of cases, while the iliohypogastric nerve was recognized in 66% with almost all identified nerves being spared during surgery. Several pre- and intraoperative factors influenced identification rates of the ilioinguinal and iliohypogastric nerve. [ABSTRACT FROM AUTHOR]

Aims: Increasing numbers of patients with advanced heart failure and significant comorbidity and social barriers are considered for left ventricular assist devices (LVADs). We sought to examine health care utilization post‐LVAD implantation, including the influence of individual‐level socio‐economic position and multimorbidity. Methods and results: We conducted a Danish nationwide cohort study linking individual‐level data from clinical LVAD databases, the Scandiatransplant Database, and Danish national medical and administrative registries. Socio‐economic position included cohabitation status, educational level, and employment status. Multimorbidity was defined as two or more chronic conditions from at least two chronic disease groups. Health care utilization (hospital activity, general practice activity, and redeemed medical prescriptions) within 2 years post‐discharge after LVAD implantation was evaluated using descriptive statistics at 0.5 year intervals. We identified 119 patients discharged alive with first‐time LVAD implanted between 2006 and 2018. The median age of the patients was 56.1 years, and 88.2% were male. Patients were followed until heart transplantation, LVAD explantation, death, 31 December 2018, or for 2 years. The median follow‐up was 0.8 years. The highest median use of health care services was observed 0–0.5 years post‐LVAD discharge compared with the subsequent follow‐up intervals: 0.5–1, 1–1.5, and 1.5–2 years, respectively. The median (interquartile range) number of hospitalizations was 10 (7–14), bed days 14 (9–28), outpatient visits 8 (5–12), telephone contacts with a general practitioner 4 (2–8), and total redeemed medical prescriptions 26 (19–37) within 0–0.5 years post‐LVAD discharge compared with the median utilization within the consecutive follow‐up periods [e.g. within 0.5–1 year: hospitalizations 5 (3–8), bed days 8 (4–14), outpatient visits 5 (3–8), telephone contacts 2 (0–5), and redeemed medical prescriptions 24 (18–30)]. The median use of health care services was stable from 0.5 years onwards. The median number of hospitalizations and bed days was slightly higher in patients living alone with a low educational level or low employment status within 0–0.5 years post‐LVAD implantation. Finally, the median number of in‐hospital days and redeemed prescriptions was higher among patients with pre‐existing multimorbidity. Conclusions: Among patients who underwent LVAD implantation, health care utilization was high in the early post‐LVAD discharge phase and was influenced by socio‐economic position. Multimorbidity influenced the number of in‐hospital days and redeemed prescriptions during the 2 year follow‐up. [ABSTRACT FROM AUTHOR]

Despite improvements over recent years, morbidity and mortality associated with heart failure (HF) are higher in countries in the Central and Eastern Europe and Baltic region than in Western Europe. With the goal of improving the standard of HF care and patient outcomes in the Central and Eastern Europe and Baltic region, this review aimed to identify the main barriers to optimal HF care and potential areas for improvement. This information was used to suggest methods to improve HF management and decrease the burden of HF in the region that can be implemented at the national and regional levels. We performed a literature search to collect information about HF epidemiology in 11 countries in the region (Bulgaria, Croatia, Czechia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Serbia, and Slovenia). The prevalence of HF in the region was 1.6–4.7%, and incidence was 3.1–6.0 per 1000 person‐years. Owing to the scarcity of published data on HF management in these countries, we also collected insights on local HF care and management practices via two surveys of 11 HF experts representing the 11 countries. Based on the combined results of the literature review and surveys, we created national HF care and management profiles for each country and developed a common patient pathway for HF for the region. We identified five main barriers to optimal HF care: (i) lack of epidemiological data, (ii) low awareness of HF, (iii) lack of national HF strategies, (iv) infrastructure and system gaps, and (v) poor access to novel HF treatments. To overcome these barriers, we propose the following routes to improvement: (i) establish regional and national prospective HF registries for the systematic collection of epidemiological data; (ii) establish education campaigns for the public, patients, caregivers, and healthcare professionals; (iii) establish formal HF strategies to set clear and measurable policy goals and support budget planning; (iv) improve access to quality‐of‐care centres, multidisciplinary care teams, diagnostic tests, and telemedicine/telemonitoring; and (v) establish national treatment monitoring programmes to develop policies that ensure that adequate proportions of healthcare budgets are reserved for novel therapies. These routes to improvement represent a first step towards improving outcomes in patients with HF in the Central and Eastern Europe and Baltic region by decreasing disparities in HF care within the region and between the region and Western Europe. [ABSTRACT FROM AUTHOR]

Background: Sub-Saharan Africa bears the highest burden of sickle cell disease (SCD) globally with Nigeria, Democratic Republic of Congo, Tanzania, Uganda being the most affected countries. Uganda reports approximately 20,000 SCD births annually, constituting 6.67% of reported global SCD births. Despite this, there is a paucity of comprehensive data on SCD from the African continent. SCD registries offer a promising avenue for conducting prospective studies, elucidating disease severity patterns, and evaluating the intricate interplay of social, environmental, and genetic factors. This paper describes the establishment of the Sickle Pan Africa Research Consortium (SPARCo) Uganda registry, encompassing its design, development, data collection, and key insights learned, aligning with collaborative efforts in Nigeria, Tanzania, and Ghana SPARCo registries. Methods: The registry was created using pre-existing case report forms harmonized from the SPARCo data dictionary and ontology to fit Uganda clinical needs. The case report forms were developed with SCD data elements of interest including demographics, consent, baseline, clinical, laboratory and others. That data was then parsed into a customized REDCap database, configured to suit the optimized ontologies and support retrieval aggregations and analyses. Patients were enrolled from one national referral and three regional referral hospitals in Uganda. Results: A nationwide electronic patient-consented registry for SCD was established from four regional hospitals. A total of 5,655 patients were enrolled from Mulago National Referral Hospital (58%), Jinja Regional Referral (14.4%), Mbale Regional Referral (16.9%), and Lira Regional Referral (10.7%) hospitals between June 2022 and October 2023. Conclusion: Uganda has been able to develop a SCD registry consistent with data from Tanzania, Nigeria and Ghana. Our findings demonstrate that it's feasible to develop longitudinal SCD registries in sub-Saharan Africa. These registries will be crucial for facilitating a range of studies, including the analysis of SCD clinical phenotypes and patient outcomes, newborn screening, and evaluation of hydroxyurea use, among others. This initiative underscores the potential for developing comprehensive disease registries in resource-limited settings, fostering collaborative, data-driven research efforts aimed at addressing the multifaceted challenges of SCD in Africa. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion Determine long‐term trends in population‐based incidence and outcomes of rib fracture hospitalisations.This was a data linkage study of rib fracture cases identified between 2015 and 2022 in New South Wales, Australia. Routinely collected health data were linked between ED, admitted patient and death registry data collection. The primary outcomes were age‐specific incidence of rib fracture hospitalisation cases and risk‐adjusted 30 days mortality. Other outcomes of interest were hospital length of stay (LOS), admission rate and ICU admissions.A total of 70 609 cases were analysed. Overall, the number of rib fracture hospitalisations increased by 25% between 2015 and 2022. The highest proportion of cases was in the 45–65 years (28%) and 65–85 years (31%) age groups. On a per population basis, the incidence rate increased by 2% per annum. After adjusting for age, comorbidity and injury severity, there was no significant trend in 30 days mortality observed between 2015 and 2022. The median inpatient LOS was 4 days with 38% of patients staying 1–2 days. Regional and rural areas were associated with more severe chest injuries.Rib fracture hospitalisations have increased with older patients driving this trend. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is characterized by a sudden decline in the kidneys' abilities to remove waste products and maintain water and electrolyte homeostasis. This study aims to determine the incidence and predictors of acute kidney injury among neonates with perinatal asphyxia admitted at the neonatal intensive care unit of West Amhara Comprehensive Specialized Hospital, Northwest Ethiopia, 2023. Multicentred institution-based retrospective follow-up study was conducted from October 1, 2021, to September 30, 2023, among 421 perinatal asphyxia neonates. A simple random sampling technique was used. The data were collected using a data extraction checklist from the medical registry of neonates. The collected data were entered into EPI-DATA V.4.6.0.0. and analyzed using STATA V.14. The Kaplan–Meier failure curve and log-rank test were employed. Bivariable and multivariable Cox regression was carried out to identify predictors of Acute kidney injury. Statistical significance was declared at a p ≤ 0.05. The overall incidence of AKI was 54 (95% CI 47.07–62.51) per 100 neonate days. C/S delivery (AHR = 0.64; (95% CI 0.43–0.94), prolonged labor (AHR = 1.43; 95% CI 1.03–1.99) low-birth weight times (AHR = 1.49; (95% CI 1.01–2.20), stage three HIE(AHR: 1.68; (95% CI (1.02–2.77), No ANC follow up (AHR = 1.43; 95% CI 1.9 (1.07–3.43) and Hyperkalemia (AHR = 1.56; 95% CI 1.56 (1.05–2.29); 95% CI) were significant predictors. The incidence rate of acute kidney injury was higher than in other studies conducted on other groups of neonates. Cesarean section delivery, prolonged low birthweight, no Anc follow-up, stage 3 HIE, and neonatal hyperkalemia were predictors of acute kidney injury. However, it needs further prospective study. Therefore, the concerned stakeholders should give due attention and appropriate intervention to these predictors. [ABSTRACT FROM AUTHOR]

Background: Globally, researchers are working on projects aiming to enhance the availability of data for rare disease research. While data sharing remains critical, developing suitable methods is challenging due to the specific sensitivity and uniqueness of rare disease data. This creates a dilemma, as there is a lack of both methods and necessary data to create appropriate approaches initially. This work contributes to bridging this gap by providing synthetic datasets that can form the foundation for such developments. Methods: Using a hierarchical data generation approach parameterised with publicly available statistics, we generated datasets reflecting a random sample of rare disease patients from the United States (US) population. General demographics were obtained from the US Census Bureau, while information on disease prevalence, initial diagnosis, survival rates as well as race and sex ratios were obtained from the information provided by the US Centers for Disease Control and Prevention as well as the scientific literature. The software, which we have named SynthMD, was implemented in Python as open source using libraries such as Faker for generating individual data points. Results: We generated three datasets focusing on three specific rare diseases with broad impact on US citizens, as well as differences in affected genders and racial groups: Sickle Cell Disease, Cystic Fibrosis, and Duchenne Muscular Dystrophy. We present the statistics used to generate the datasets and study the statistical properties of output data. The datasets, as well as the code used to generate them, are available as Open Data and Open Source Software. Conclusion: The results of our work can serve as a starting point for researchers and developers working on methods and platforms that aim to improve the availability of rare disease data. Potential applications include using the datasets for testing purposes during the implementation of information systems or tailored privacy-enhancing technologies. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions There has been a global rise in cases of dermatophytosis and, in particular, recalcitrant and recurrent cases on tinea of the glabrous skin. This phenomenon, particularly prevalent in India, has been linked to the concerning rise of antifungal resistance. The challenge is amplified by a dearth of comprehensive, international data to understand the global scope and characteristics of such cases.This study aims to collate international insights, focusing on areas outside Europe (as this was previously published), to map the extent and characteristics of clinical and, where possible, laboratory confirmed tinea of the glabrous skin through an online survey administered to dermatologists globally.An online survey was distributed from February 2022 to July 2023 and captured data on respondents' experience of recalcitrant and recurrent tinea of the glabrous skin over the preceding 3 years.A total of 260 responses were received spreads across 36 countries, excluding Europe. In total, 91.7% reported seeing cases of recalcitrant or recurrent tinea of the glabrous skin over the preceding 3 years. Common anatomical sites affected were the trunk and groin. T. mentagrophytes and T. rubrum were the predominant species implicated, and there were low rates of laboratory confirmed dermatophyte resistance.The high rates of reported recalcitrant and recurrent tinea of the glabrous skin underscore an urgent need for global collaborative efforts and enhanced diagnostic measures. The findings advocate for the establishment of a standardized global disease registry, regulation of over‐the‐counter antifungal and steroid combinations, correlation of clinical suspicion with laboratory confirmed drug resistance and exploration of alternative therapeutic strategies to mitigate the burgeoning challenge of dermatophyte resistance. [ABSTRACT FROM AUTHOR]

Background: Idiopathic Normal Pressure Hydrocephalus (iNPH) is a chronic condition affecting the elderly. It is characterized by a triad of symptoms and radiological findings. Glaucoma is the leading cause of irreversible blindness worldwide. Earlier studies have proposed that the rate of glaucoma is higher in iNPH patients, and of a possible link between ventriculoperitoneal shunt (VP) treatment and the development of glaucoma. Objectives: This study aimed to determine the prevalence of glaucoma among iNPH patients and assess the impact of VPs on glaucoma prevalence. Methods: A cohort study was conducted at Kuopio University Hospital (KUH), including 262 patients with a ventriculoperitoneal shunt. Clinical data were obtained from the Kuopio NPH Registry and medical records. Patients were grouped by iNPH status: iNPH (+) – probable/possible iNPH (n = 192), and iNPH (-) – other causes of hydrocephalus (congenital, secondary, obstructive) (n = 70). We conducted statistical analysis using the Independent Samples T-test, Fisher's exact test, and Pearson Chi-Square. We compared demographics, glaucoma prevalence, brain biopsies positive for Amyloid-β (Aβ) and hyperphosphorylated tau (HPτ) as well as comorbidities for hypertension and diabetes medication. Age stratification assessed glaucoma prevalence in the full cohort. Results: Both iNPH (+) and iNPH (-) groups had comparable demographic and comorbidity profiles. The prevalence of glaucoma in the iNPH (+) group was 11.5% (n = 22) and 11.4% (n = 8) in the iNPH (-) group without a statistically significant difference (p = 1.000). Brain biopsies positive for Amyloid-β (Aβ) and hyperphosphorylated tau (HPτ) were similar. Conclusions: Neither shunted iNPH patients nor those with a comorbid condition other than iNPH showed a markedly higher prevalence of glaucoma. Instead, both groups exhibited age-related increases in glaucoma prevalence, similar to the trends observed in population-based studies. Our data does not suggest a correlation between VP shunts and an elevated rate of glaucoma. [ABSTRACT FROM AUTHOR]

Summary A decade after International Myeloma Working Group (IMWG) biomarkers (SLiM criteria) were introduced, this real‐world study examined their impact on diagnosis, therapy and outcomes in myeloma. Using the ANZ MRDR, 3489 newly diagnosed patients from 2013 to 2023, comprising 3232 diagnosed by CRAB (‘CRAB patients’, including 1758 who also satisfied ≥1 SLiM criteria) and 257 by SLiM (‘SLiM patients’) criteria were analysed. CRAB patients had higher R‐ISS and lower performance status, with no difference in cytogenetic risk. SLiM patients had improved progression‐free survival (PFS, 37.5 vs. 32.2 months, hazard ratio [HR] 1.31 [1.08–1.59], p = 0.003), overall survival (80.9 vs. 73.2 months, HR 1.64 [1.26–2.13], p < 0.001) and PFS2 (54.6 vs. 40.3 months, HR 1.51 [1.22–1.86], p < 0.001) compared with CRAB patients, partially explained by earlier diagnosis, with no differential impact between the plasma cell and light‐chain criteria on PFS. However, 34% of CRAB patients did not manifest SLiM characteristics, raising the possibility that SLiM features are associated with different biological behaviours contributing to a better prognosis, for example, improved PFS2 in SLiM patients suggested less disease resistance at first relapse. These data support earlier initiation of therapy by SLiM. The superior survival outcomes of SLiM versus CRAB patients highlight the importance of defining these subgroups when interpreting therapeutic outcomes at induction and first relapse. [ABSTRACT FROM AUTHOR]

Objectives: To address improvements in quality of life, we analysed the relative contributions of factors to EuroQol 5 Dimensions (EQ-5D) in abatacept-treated rheumatoid arthritis patients in the Orencia® Registry in Geographically Assembled Multicenter Investigation (ORIGAMI) study. Methods: Patients who were evaluable for disease activity through to  Week 52 in the ORIGAMI study were divided into those achieving Simplified Disease Activity Index-remission/low disease activity (remission/LDA; n = 178) and patients with moderate disease activity/high disease activity (MDA/HDA; n = 99). We compared the changes in EQ-5D and other outcomes through to Week 52. Focusing on the remission/LDA group, the contribution of each factor to the variance of EQ-5D at baseline and Week 52 was examined using analysis of variance. Results: The remission/LDA group showed greater improvements than the MDA/HDA group in EQ-5D, Japanese Health Assessment Questionnaire, visual analogue scale for pain (Pain VAS), and patient's global assessment (PtGA). In the remission/LDA group, factors significantly contributing to EQ-5D were sex, C-reactive protein, and Pain VAS at baseline, and PtGA and age at Week 52. Conclusions: In rheumatoid arthritis patients who achieved remission/LDA during abatacept treatment, PtGA and age at Week 52 contribute to the variance of EQ-5D, suggesting that the identification of factors associated with PtGA may be important to address improvements in quality of life. [ABSTRACT FROM AUTHOR]

• Using data from the CHEC-SC study of modulator-induced sweat chloride (SC) concentrations, we describe the proportion of individuals with post-modulator SC above the diagnostic threshold for CF (≥60 mmol/L). • Across all FDA-approved modulators, elexacaftor/tezacaftor/ivacaftor (ETI) was associated with lower SC, with SC <60 mmol/L in approximately 80 % of individuals on ETI. • Among individuals with F508/minimal function variants or F508del/F508del, 31 % and 18 % had post-modulator SC ≥60 mmol/L respectively. • Higher post-modulator SC concentrations in a substantial number of individuals suggest that additional CFTR modulation may be achievable. Sweat chloride (SC) concentrations in people with cystic fibrosis (PwCF) reflect relative CF transmembrane conductance regulator (CFTR) protein function, the primary CF defect. Populations with greater SC concentrations tend to have lesser CFTR function and more severe disease courses. CFTR modulator treatment can improve CFTR function within specific CF genotypes and is commonly associated with reduced SC concentration. However, SC concentrations do not necessarily fall to concentrations seen in the unaffected population, suggesting potential for better CFTR treatment outcomes. We characterized post-modulator SC concentration variability among CHEC-SC study participants by genotype and modulator. PwCF receiving commercially approved modulators for ≥90 days were enrolled for a single SC measurement. Clinical data were obtained from chart review and the CF Foundation Patient Registry (CFFPR). Variability of post-modulator SC concentrations was assessed by cumulative SC concentration frequencies. Post-modulator SC concentrations (n = 3787) were collected from 3131 PwCF; most (n = 1769, 47 %) were collected after elexacaftor/tezacaftor/ivacaftor (ETI) treatment. Modulator use was associated with lower SC distributions, with post-ETI concentrations the lowest on average. Most post-ETI SC concentrations were <60 mmol/L (79 %); 26 % were <30 mmol/L. Post-ETI distributions varied by genotype. All genotypes containing at least one F508del allele had individuals with post-ETI SC ≥60 mmol/L, with the largest proportion being F508del/minimal function (31 %). Post-modulator SC concentration heterogeneity was observed among all genotypes and modulators, including ETI. The presence of PwCF with post-modulator SC concentrations within the CF diagnostic range suggests room for additional treatment-associated CFTR restoration in this population. [ABSTRACT FROM AUTHOR]

Purpose: Spinal muscular atrophy (SMA) is a rare, autosomal-recessive disease characterized by progressive muscular atrophy and weakness resulting in substantial disability and short life expectancy. The objective of this cross-sectional study was to assess health-related quality of life (HRQoL) of adults with SMA in Germany in the era of disease-modifying therapy. Methods: Adults with SMA were recruited via the German national TREAT-NMD SMA patient registry. HRQoL was measured using the EQ-5D-5L, the Health Utilities Index Mark III (HUI), and the Short Form (36) Health Survey (SF-36). Estimates were stratified by current best motor function of the lower limb and trunk (i.e., non-sitter, sitter, and walker) and SMA type (i.e., type I, II, and III). Results: A total of 82 adults with SMA (mean age: 42 years, 51% female) self-completed the study questionnaire. The mean EQ-5D-5L utility was estimated at 0.5135 (range across subgroups: 0.31–0.99), mean EQ-VAS at 69.71 (64.67–90.00), mean HUI-derived utility at 0.3171 (– 0.02–0.96), mean SF-6D utility at 0.6308 (0.58–0.65), and mean SF-36 Physical Component Summary and Mental Health Component Summary scores at 33.78 (9.92–53.10) and 53.49 (21.02–72.25), respectively. Conclusions: We show that adults with SMA experience considerable impairment across a wide range of health dimensions, including mobility, dexterity, pain, and emotional well-being. However, our results exhibit non-trivial variability across clinical subgroups and HRQoL measures. These data contribute to our understanding of the subjective impact of living with a severely debilitating neuromuscular disease, such as SMA. [ABSTRACT FROM AUTHOR]

Objective: Obstetric anal sphincter injuries (OASIS) are severe complications to vaginal births with potential long‐term consequences. Maternal origin has been proposed to affect the overall risk, but the association and underlying explanation are uncertain. The objective was to assess the association between maternal country of birth and OASIS. Methods: A Swedish nationwide cohort study including singleton term vaginal births during 2005–2016. Data were extracted from the Swedish Medical Birth Registry and Statistics Sweden. Modified Poisson regression analyses were performed to obtain crude and adjusted risk ratios (RRs). Adjustments were made in four cumulative steps. Sub‐analyses were performed to investigate the risk of OASIS associated with female genital circumcision (FGC). Results: In all, 988 804 births were included. The rate of OASIS in Swedish‐born women was 3.5%. Women from East/Southeast Asia had an increased risk of OASIS (adjusted RR [aRR] 1.71, 95% confidence interval [CI] 1.60–1.83), as did women born in Sub‐Saharan Africa (aRR 1.60, 95% CI 1.49–1.72). The risk remained significantly increased also after adjustment for maternal height. By contrast, women from South/Central America had a decreased risk of OASIS (aRR 0.65, 95% CI 0.56–0.76). FGC was associated with an increased risk of OASIS (aRR 3.05, 95% CI 2.60–3.58). Episiotomy appeared to have an overall protective effect (aRR 0.95, 95% CI 0.92–0.98), but not significantly more protective among women with female genital mutilation. Conclusions: Country of birth plays an important role in the risk of OASIS. Women from East/Southeast Asia and Sub‐Saharan Africa are at significantly increased risk as compared with Swedish‐born women, whereas women from South/Central America are at lower risk. FGC is also a significant risk factor for OASIS. Synopsis: Maternal country of birth plays an important role in the risk of sphincter injuries. Female genital circumcision is associated with increased risk of sphincter injuries. [ABSTRACT FROM AUTHOR]

Introduction: Maternal and infant mortality rates in Finland are among the lowest in the world, yet preventable obstetric injuries occur every year. The aim of this study was to describe obstetric claims, their compensation rates, and temporal trends of claims reported to the Patient Insurance center. Material and Methods: A nationwide, register‐based study was conducted. Data consisted of obstetric claims reported to the Patient Insurance Center between 2012 and 2022. Data analyzed included the year of injury, compensation criteria, maternal age, birth hospital, delivery method, reported causes of injury, and maternal or neonatal injury. The data were analyzed with descriptive statistics and logistic regression models. Results: A total of n = 849 obstetric claims were filed during the study period, of which n = 224 (26.4%) received compensation. The rate of claims was 0.15%, and the rate of compensation was 0.04% in relation to the total volume of births during the period. Substandard care was the most common (97.3%) criterion for compensation. There was a curvilinear increase in the claims rate and a linear increase in compensation rates from 2013 to 2019. More claims were filed and compensated for cesarean and vacuum‐assisted deliveries than for unassisted vaginal deliveries. Delayed delivery (18.7%) and surgical technique failure (10.9%) were the most reported causes of injuries. Retained surgical bodies were the induced cause of injury with the highest rate of compensated claims (86.7%). The most common maternal injury was infection (17.9%) and pain (11.7%). Among neonatal injuries, severe (19.2%) and mild asphyxia (16.6%) were the most frequent. Burn injuries (93.3%) and fetal or neonatal death (60.5%) had the highest rate of compensated claims. Conclusions: The study provided new information on substandard care and injuries in obstetric care in Finland. An increasing trend in claims and compensation rates was found. Identifying contributors to substandard care that lead to fetal asphyxia is important for improving obstetric safety. Further analysis of the association of claims and compensation rates with operative deliveries is needed to determine their causality. Frequent review of obstetric claims would be useful in providing more recent data on substandard care and preventable injuries. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prevalence and natural history of POLG disease in the Norwegian population. Methods: A national, population‐based, retrospective study using demographic, clinical, and genetic data of patients with genetically confirmed POLG disease. The patients were diagnosed between 2002 and 2022, and were included into the Norwegian POLG Patient Registry. Patients were stratified according to age at disease onset (early <12 years, juvenile to adult 12–40 years, late ≥40 years) and resident region. Results: Ninety‐one patients were included. The point prevalence of POLG disease was 1:149,253. Birth prevalence was 1:48,780. Median age at clinical onset was 16 years (range: 2 months to 70 years). Onset occurred early in 35% (32 out of 91), juvenile‐adult in 55% (50 out of 91) and late in 10% (9 out of 91). A distinct seasonal pattern in disease onset was observed, with 57% (52 out of 91) presenting between May and August. Forty‐five patients (49%) had acute exacerbations that required intensive care, and this affected 72% of those in the early‐onset group. The mortality rate was 54% (49 out of 91), with a median time from disease onset to death of 3 years (range: 1 month to 36 years). Interpretation: We provide the point prevalence and birth prevalence of POLG disease in the first nationwide study in which epidemiological and clinical data were integrated. Seasonal variations in clinical onset may offer valuable insights into disease mechanisms and modifying factors. The findings from this study are crucial for quantifying the disease burden, and contribute to evidence‐based healthcare planning. [ABSTRACT FROM AUTHOR]

Background Home dialysis therapies such as peritoneal dialysis (PD) and home hemodialysis (HHD) are beneficial for quality of life and patient empowerment. The short technique survival time partly explains their low prevalence. We aimed to assess the risk of transfer to facility-based hemodialysis in patients treated with autonomous PD, assisted PD and HHD. Methods This was a retrospective study using data from the REIN registry of patients starting home dialysis in France from 2002 to 2019. The risks of transfer to facility-based hemodialysis (HD) were compared between three modalities of home dialysis (HHD, nurse-assisted PD, autonomous PD) using survival models with a propensity score (PS)-matched and unmatched cohort of patients. Results The study included 17 909 patients: 628 in the HHD group, 10 214 in the autonomous PD group, and 7067 in the assisted PD group. During the follow-up period, there were 5347 transfers to facility-based HD. The observed number of transfers was 2458 (13.7%) at 1 year and 5069 (28.3) at 5 years after the start of home dialysis, including 3272 (32%) on autonomous PD, 1648 (23.3%) on assisted PD, and 149 (23.7) on HHD. Owing to clinical characteristics differences, only 38% of HHD patients could be matched to patients from the others group. In the PS-matched cohort, the adjusted Cox model showed no difference in the risk of transfer for assisted PD (cs-HR 1.04, 95% CI 0.75–1.44) or HHD (cs-HR 1.07, 95% CI 0.77–1.48) compared with autonomous PD. Conclusions Unlike results from other countries, where nurse assistance is not fully available for PD-associated care, there was no difference in technique survival between autonomous PD, nurse-assisted PD, and HHD in France. This discrepancy may be attributed to our inclusion of a broader spectrum of patients who derive significant benefits from assisted PD. [ABSTRACT FROM AUTHOR]

Background: Suxamethonium is hydrolysed by butyrylcholinesterase (BChE) and a low BChE activity can result in a prolonged duration of action of suxamethonium. The BChE activity is reduced during pregnancy and postpartum period by up to 33%. However, it can also be reduced by mutations in the BChE gene. In this study, we assessed BChE activity and mutations in the BChE gene in pregnant and postpartum patients with prolonged duration of action of suxamethonium. It was hypothesised that at least 30% of patients with a low BChE activity did not have a mutation in the BChE gene. Methods: In this registry study we focused on pregnant and postpartum patients with a history of prolonged duration of action of suxamethonium referred to the Danish Cholinesterase Research Unit (DCRU) between March 2007 and January 2023. Primary outcome was the proportion of patients without a mutation among patients with a low BChE activity. Secondary outcomes were the proportion of patients with a low BChE activity and the proportion of patients with a mutation out of the total number of patients. Results: A total of 40 patients were included and among patients with a low BChE activity, 6% (95% CI: 1%–21%) did not have a mutation. Out of the total number of included patients referred to the DCRU, 90% (95% CI: 76%–97%) had a mutation and 94% (95% CI: 80%–99%) had a low BChE activity. Conclusion: Among pregnant and postpartum patients with a history of prolonged duration of action of suxamethonium and a low BChE activity, 6% did not have a mutation in the BChE gene. Our findings suggest that during pregnancy and postpartum clinically relevant prolonged duration of action of suxamethonium rarely occurs in genotypically normal patients. [ABSTRACT FROM AUTHOR]

Background and aims: Although minimally invasive hysterectomy offers advantages, abdominal hysterectomy remains the predominant surgical method. Creating a standardized dataset and establishing a hysterectomy registry system present opportunities for early interventions in reducing volume and selecting benign hysterectomy methods. This research aims to develop a dataset for designing benign hysterectomy registration system. Methods: Between April and September 2020, a qualitative study was carried out to create a data set for enrolling patients who were candidate for hysterectomy. At this stage, the research team conducted an information needs assessment, relevant data element identification, registry software development, and field testing; Subsequently, a web-based application was designed. In June 2023the registry software was evaluated using data extracted from medical records of patients admitted at Al-Zahra Hospital in Tabriz, Iran. Results: During two months, 40 patients with benign hysterectomy were successfully registered. The final dataset for the hysterectomy patient registry comprise 11 main groups, 27 subclasses, and a total of 91 Data elements. Mandatory data and essential reports were defined. Furthermore, a web-based registry system designed and evaluated based on data set and various scenarios. Conclusion: Creating a hysterectomy registration system is the initial stride toward identifying and registering hysterectomy candidate patients. this system capture information about the procedure techniques, and associated complications. In Iran, this registry can serve as a valuable resource for assessing the quality of care delivered and the distribution of clinical measures. [ABSTRACT FROM AUTHOR]

In the rapidly evolving field of digital asset management, centralized and decentralized global registries have become essential tools for organizing, tracking, and distributing digital assets. However, existing systems often face challenges regarding security, censorship resistance, interoperability, customizability, and scalability. This research paper aims to address these gaps by proposing a novel decentralized global registry system based on blockchain technology and non-fungible tokens (NFTs). The research paper makes several key contributions to the field of digital asset management. First, it provides a detailed system design for the proposed decentralized global registry, outlining its architectural components, functional modules, and integration with blockchain and NFT technologies. Second, it offers a thorough comparative analysis of the advantages and limitations of the proposed system in relation to existing centralized and decentralized registries. Finally, the paper presents potential use cases and practical applications of the proposed system in various industries, demonstrating its versatility and adaptability to different contexts and requirements. In conclusion, this research paper contributes significantly to the ongoing efforts to improve digital asset management by presenting a novel, decentralized global registry system based on blockchain technology and NFTs. The proposed system addresses the key limitations of existing solutions and offers a promising direction for future research and development in this critical field. [ABSTRACT FROM AUTHOR]

Purpose: The long-term outcomes of patients with staple line leaks (SLL) after SG are under-reported. The purpose of this study is to evaluate the long-term outcomes of patients with SLL after SG. Materials and Methods: A retrospective analysis of a maintained patient registry of patients undergoing SG between January 2012 and December 2020 in a single bariatric center was analyzed and included patients with SLL. Outcomes were compared to a group without SLL. Results: During this period, 1985 patients underwent SG of which 61 patients (3.1%) developed leak. 26 patients (1.3%) had overt SLL and the rest had organ space infection around the staple line. The mean age and body mass index (BMI) were 39.8 ± 11.3 and 41.5 ± 4.7, respectively. 7 patients (11.4%) underwent concomitant surgery and 12 patients (19.7%) had intraoperative complications. Leak was complicated by Clavien-Dindo ≥ 3 in 31 patients (50.8%). Reoperation rate was 27.8% (n = 17). ≥ 2 interventions were required in 26% of patients (n = 16). Two patients died during hospitalization due to septic complications. Long-term follow-up of median 121 months was available in 78% of the cohort (n = 48). The median total weight loss and BMI were 27% and 30.1 kg/m2, respectively. Weight loss outcomes were higher in comparison to patients without SLL. Seven patients (14.6%) underwent SG revision. All associated medical problems improved during follow-up except for gastroesophageal reflux which was found in 50% of cohort. Conclusion: Long-term outcomes of SG patients with SLL are satisfactory in terms of weight loss, resolution of comorbidities, and requirement for surgical revision. [ABSTRACT FROM AUTHOR]

Rationale: Nontuberculous mycobacteria (NTM) are prevalent among patients with bronchiectasis. However, the long-term natural history of patients with NTM and bronchiectasis is not well described. Objectives: To assess the impact of NTM on 5-year clinical outcomes and mortality in patients with bronchiectasis. Methods: Patients in the Bronchiectasis and NTM Research Registry with ⩾5 years of follow-up were eligible. Data were collected for all-cause mortality, lung function, exacerbations, hospitalizations, and disease severity. Outcomes were compared between patients with and without NTM at baseline. Mortality was assessed using Cox proportional hazards models and the log-rank test. Measurements and Main Results: In total, 2,634 patients were included: 1,549 (58.8%) with and 1,085 (41.2%) without NTM at baseline. All-cause mortality (95% confidence interval) at Year 5 was 12.1% (10.5%, 13.7%) overall, 12.6% (10.5%, 14.8%) in patients with NTM, and 11.5% (9.0%, 13.9%) in patients without NTM. Independent predictors of 5-year mortality were baseline FEV1 percent predicted, age, hospitalization within 2 years before baseline, body mass index, and sex (all P < 0.01). The probabilities of acquiring NTM or Pseudomonas aeruginosa were approximately 4% and 3% per year, respectively. Spirometry, exacerbations, and hospitalizations were similar, regardless of NTM status, except that annual exacerbations were lower in patients with NTM (P < 0.05). Conclusions: Outcomes, including exacerbations, hospitalizations, rate of loss of lung function, and mortality rate, were similar across 5 years in patients with bronchiectasis with or without NTM. [ABSTRACT FROM AUTHOR]

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease, characterized by painful and recurrent lesions in apocrine gland-bearing skin areas. It is a heterogeneous disease, which makes assessment and data collection difficult. Questionnaires with detailed items, such as the Belgian European Registry for Hidradenitis Suppurativa (ERHS-Be), are useful to study HS and its associated comorbidities. The aim of this registry was to uncover new factors associated with HS and understand HS patients' clinical profiles and efficacy of treatments. Material and Methods: The ERHS-Be registry is based on questionnaires, with sections for sociodemographic data, medical and HS history, clinical examination, and treatment plan. It allows identification of different clinical phenotypes and automatic calculation of severity scores. Results: At present, 606 patients are included in the ERHS-Be (67% women, 33% men). The mean age at the first visit is 38.5 years. Tobacco use is present in 72.6% of patients. A family history of HS is noted in 42% of patients. Comorbidities are documented in this cohort: depression is present in 43.8% of patients, arthritis in 27.8%, obesity in 31.5%, hypertension in 10.6%, diabetes mellitus in 6.4%, and dyslipidemia in 12.4%. Moreover, 7.7% of patients suffer from IBD and 27.4% have a pilonidal sinus. History of severe acne is found in 32.1% of patients and psoriasis in 9.3%. Thirteen percent of women in our cohort suffer from polycystic ovarian syndrome. Severity of disease is quantified in 533 patients: for instance, Hurley I, II, and III scores proportions are, respectively, 32.3%, 52.7%, and 15%, while the mean IHS4 score is 5.2. This registry also enables determination of relative phenotype proportions in our cohort, according to different classifications. Conclusion: The ERHS-Be questionnaires allow systematic and larger data collection, including detailed comorbidities, phenotypes, and severity of disease. Analysis of this large database will contribute to a better understanding and management of HS, at a time where new therapeutic options are becoming available. [ABSTRACT FROM AUTHOR]

DSP‐cardiomyopathy has recently been recognised as a specific type of cardiomyopathy. Using an in‐house Mendelian disease registry, we aimed to identify probands with likely pathogenic or pathogenic DSP variants. We detected these variants in 4.8% and 77.8% of genotype‐positive probands referred for dilated and non‐dilated left ventricular cardiomyopathy (NDLVC), respectively. We identified six Slovenian probands with the DSP:c.3793G>T and characterised them along with further eight of their relatives at the molecular and phenotypic level. Medical records revealed NDLVC with arrhythmia in six individuals (five probands, one relative; 33 ± 14 years; three males, three females). All had subepicardial late gadolinium enhancement on cardiac MRI (CMRI), and five received an ICD. Four individuals (one proband, three relatives; 48 ± 14 years; all female) had no ECG and/or cardiac abnormalities on CMRI detected. Our analysis presents a Slovenian‐specific molecular pathology of DSP cardiomyopathy, delineates the clinical manifestation of DSP:c.3793C>T, and thereby improves the understanding of the clinical outcomes associated with truncating DSP variants. [ABSTRACT FROM AUTHOR]

Background: Nowadays, different therapeutic options are available for the first-line treatment of metastatic renal cell carcinoma (mRCC). Immuno-combinations are the standard first-line therapy in all mRCC patients regardless of the International Metastatic RCC Database Consortium (IMDC) risk category, even though TKI monotherapy is still a therapeutic option in selected patients. However, comparisons between the different first-line treatment strategies are lacking and few real-world data are available in this setting. For this reason, the regimen choice represents an important issue in clinical practice and the optimal treatment sequence remains unclear. Methods: The REGAL study is a multicentric prospective observational study enrolling mRCC patients treated with first-line systemic therapy according to clinical practice in a real-world setting. A retrospective cohort of mRCC patients who received first-line systemic therapy from the 1st of January 2021 will also be included. The primary objective is to identify potential prognostic and predictive factors that could help guide the treatment choice; secondary objectives included the assessment of the prognostic performance of the novel prognostic Meet-URO score (IMDC score + neutrophil-to-lymphocyte ratio + bone metastases) compared with the IMDC score and the comparison between treatment strategies according to response and survival outcomes and toxicity profile. Discussion: Considering the high number of therapeutic first-line strategies available for mRCC, the identification of clinical prognostic and predictive factors to candidate patients to a preferable systemic therapy is still an unmet clinical need. The Meet-URO 33 study aims to provide a large-scale real-world database on mRCC patients, to identify the clinical predictive and prognostic factors and the different performances between the ICI-based combinations according to response, survival and toxicity. Trial Registration: CESC IOV 2023-78. [ABSTRACT FROM AUTHOR]

Background: Long-term patient registries are important for evaluating treatment outcomes in patients with rare diseases, and can provide insights into natural disease history and progression in real-world clinical practice. Initiated in 2010, the Gaucher Outcome Survey (GOS) is an ongoing, international, multicenter, observational registry (ClinicalTrials.gov Identifier: NCT03291223) for patients with a diagnosis of Gaucher disease (GD), irrespective of treatment type or status, with a primary objective to monitor safety and long-term effectiveness of velaglucerase alfa. Methods: Here, we evaluated the GOS population 12 years after the registry initiation. Results: As of 25 February 2023, 2084 patients enrolled in the GOS and 1643 received GD-specific treatment. Patients exhibited broad heterogeneity at baseline: age of diagnosis (0 to 85.3 years), hemoglobin concentrations (<80.0 g/L to >150 g/L), platelet counts (<50 × 109/L to >450 × 109/L), and liver and spleen volumes. Most patients treated with enzyme replacement therapy or substrate reduction therapy reported improvements in clinical parameters within 1 year of treatment initiation, maintained over the course of treatment up to 12 years, whereas untreated patients had baseline values closer to standard reference thresholds and showed stability over time. Conclusion: The 12-year data from the GOS confirm the impact of long-term treatment with GD-specific agents and offer insights into disease progression and outcomes in a real-world setting. [ABSTRACT FROM AUTHOR]

Background: The Angelman Syndrome Registry (RISA) was developed as a retrospective study with the following objectives: to evaluate the clinical history of individuals with Angelman Syndrome (AS) in Italy and compare it with the existing literature; to investigate the feasibility of gathering data by directly involving participants in the data collection process; and to explore the relationship between different symptoms and genotypes. Methods: Established in 2018, RISA enrolled a total of 82 participants, with 62 (75.6%) providing complete data. Demographic, clinical, and genetic information was collected using electronic case report forms. Descriptive statistics characterized the sample, while associations between genotype and clinical characteristics were examined. Results: Descriptive analysis revealed a median participant age of 8.0 years, with males comprising 48.8% of the sample. Deletion (58.1%) was the most common genotype. The majority (82.2%) experienced epilepsy, with seizures typically onset before 3 years of age. Most patients (86.2%) required multiple anti-epileptic drugs for control, with generalized tonic–clonic seizures and atypical absence seizures being most prevalent. The deletion group exhibited more severe developmental delays and a trend towards higher seizure severity. Sleep problems affected 69.4% of participants, characterized by difficulties in sleep onset and maintenance. Conclusions: This study offers valuable insights into the clinical history and genetic characteristics of AS in Italy, consistent with the prior literature. Additionally, it underscores the efficacy of patient registries in capturing comprehensive data on rare diseases such as AS, highlighting their potential to advance research and enhance patient care. [ABSTRACT FROM AUTHOR]

Background: The low prevalence of rare diseases poses a significant challenge in advancing their understanding. This study aims to delineate the clinical and genetic characteristics of patients with rare eye diseases (RED) enrolled in the Spanish Rare Diseases Patient Registry. Methods: A total of 864 patients from the registry database were included. Diseases were categorized into inherited retinal dystrophies (n=688); anterior segment diseases (n=48); congenital malformations (n=27); and syndromic diseases with ocular involvement including muscular (n=46), neurological (n=34), or metabolic (n=13); inflammatory diseases (n=4); and tumors (n=4). Data on visual acuity (VA) and/or visual field (VF), symptoms and signs, concurrent diseases in syndromic cases, age of onset and at diagnosis, affected genes, disability rating, inability to work and dependency grade recognition were collected. Results: A mean diagnostic delay of 7 years from symptom onset was observed. Commonly reported symptoms included photophobia, night blindness, and progressive vision loss (≥57% of patients). Cataract was the most prevalent secondary disease (46%), with pseudophakia being the most common ocular surgery (26%). Hearing loss and cardiovascular diseases were the most prevalent concurrent systemic diseases (≥13%). Certificates of disability, incapacity for work, and dependency were held by 87%, 42%, and 19% of patients, respectively. Among the 719 patients with available VA data, 193 (27%) were blind, and 188 (26%) had moderate to severe visual impairment. Over half of the patients (54%) exhibited VF defects, and 216 (25%) had concentric contraction ≤5° or abolished VF. Most had genetic diseases with autosomal recessive (55%), autosomal dominant (30%), X-linked (9%), and mitochondrial (6%) patterns. One patient had mutations in both recessive USH2A and dominant RHO genes simultaneously. Of the 656 patients (75.7%) who underwent genetic testing, only 461 (70.3%) received a positive result (pathogenic or likely pathogenic mutations explaining the phenotype). We found 62 new gene variants related to RED not previously reported in databases of genetic variants related to specific phenotypes. Conclusions: This study delineates the clinical and genotypic profiles of RED in Spain. Genetic diseases, particularly retinal disorders, predominate, but a significant proportion of affected patients remain genetically undiagnosed, hindering potential gene therapy endeavors. Despite notable improvements in reducing diagnosis delays, it is still remarkable. RED frequently lead to disability and blindness among young populations. [ABSTRACT FROM AUTHOR]