Importance of hospital and clinical factors for early mortality in Takotsubo syndrome: Insights from the Swedish Coronary Angiography and Angioplasty Registry.

BACKGROUND: Takotsubo syndrome (TTS) is an acute heart failure syndrome with symptoms similar to acute myocardial infarction. TTS is often triggered by acute emotional or physical stress and is a significant cause of morbidity and mortality. Predictors of mortality in patients with TS are not well understood, and there is a need to identify high-risk patients and tailor treatment accordingly. This study aimed to assess the importance of various clinical factors in predicting 30-day mortality in TTS patients using a machine learning algorithm. METHODS: We analyzed data from the nationwide Swedish Coronary Angiography and Angioplasty Registry (SCAAR) for all patients with TTS in Sweden between 2015 and 2022. Gradient boosting was used to assess the relative importance of variables in predicting 30-day mortality in TTS patients. RESULTS: Of 3,180 patients hospitalized with TTS, 76.0% were women. The median age was 71.0 years (interquartile range 62-77). The crude all-cause mortality rate was 3.2% at 30 days. Machine learning algorithms by gradient boosting identified treating hospitals as the most important predictor of 30-day mortality. This factor was followed in significance by the clinical indication for angiography, creatinine level, Killip class, and age. Other less important factors included weight, height, and certain medical conditions such as hyperlipidemia and smoking status. CONCLUSIONS: Using machine learning with gradient boosting, we analyzed all Swedish patients diagnosed with TTS over seven years and found that the treating hospital was the most significant predictor of 30-day mortality.

Highlights of the 2023 American Joint Replacement Registry Annual Report.

The 2023 report represents a full decade of published annual reports of the American Joint Replacement Registry (AJRR). The number of cases being captured continues to rapidly grow, as are over 3.2 million patients included in AJRR. Matched-pair primary and revision data is more robust with 10-year survivorship being available. Similarly, implant-specific survivorship has been included for common implants being used in the United States. The data mined from the AJRR have led to numerous publications and presentations. Numerous trends have emerged, and others have been reinforced with the most recent data. The authors encourage readers to more thoroughly review the full report at the following link: https://www.aaos.org/registries/publications/ajrr-annual-report/.

Population based study on the progress in survival of primarily metastatic lung cancer patients in Germany.

Lung cancer is known for its high mortality; many patients already present with metastases at the time of diagnosis. The aim of this study is to assess the impact of new treatment strategies on the survival of primarily metastatic lung cancer patients and to analyze the differences in outcomes between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients. Population-based data, provided by the Robert-Koch Institute in Germany, was used and patients diagnosed between 2007 and 2018 were included in the study. We differentiated between NSCLC and SCLC patients and analyzed the survival over time for both sexes separately, using the Kaplan-Meier method. To evaluate survival advantages, we calculated multivariable hazard ratios. In total, 127,723 patients were considered for the study. We observed a moderate increase in survival over time. All patients showed an increased survival rate when undergoing chemotherapy. Minimal to no increase in survival was shown in NSCLC patients when receiving radiotherapy, whereas SCLC patients' survival time did benefit from it. NSCLC patients receiving immunotherapy showed an increase in survival as well. It can be concluded that advancements in radiotherapy, the application of chemotherapy, and the introduction of immunotherapies lead to an increased survival time of both NSCLC and SCLC primarily metastatic lung cancer patients.

Stability and change in maternal wellbeing and illbeing from pregnancy to three years postpartum.

PURPOSE: Motherhood affects women's mental health, encompassing aspects of both wellbeing and illbeing. This study investigated stability and change in wellbeing (i.e., relationship satisfaction and positive affect) and illbeing (i.e., depressive and anxiety symptoms) from pregnancy to three years postpartum. We further investigated the mutual and dynamic relations between these constructs over time and the role of genetic propensities in their time-invariant stability. DATA AND METHODS: This four-wave longitudinal study included 83,124 women from the Norwegian Mother, Father, and Child Cohort Study (MoBa) linked to the Medical Birth Registry of Norway. Data were collected during pregnancy (30 weeks) and at 6, 18 and 36 months postpartum. Wellbeing and illbeing were based on the Relationship Satisfaction Scale, the Differential Emotions Scale and Hopkins Symptoms Checklist-8. Genetics were measured by the wellbeing spectrum polygenic index. Analyses were based on random intercept cross-lagged panel models using R. RESULTS: All four outcomes showed high stability and were mutually interconnected over time, with abundant cross-lagged predictions. The period of greatest instability was from pregnancy to 6 months postpartum, followed by increasing stability. Prenatal relationship satisfaction played a crucial role in maternal mental health postpartum. Women's genetic propensity to wellbeing contributed to time-invariant stability of all four constructs. CONCLUSION: Understanding the mutual relationship between different aspects of wellbeing and illbeing allows for identifying potential targets for health promotion interventions. Time-invariant stability was partially explained by genetics. Maternal wellbeing and illbeing develop in an interdependent way from pregnancy to 36 months postpartum.

Healthcare-seeking behavior preceding diagnosis of Lyme neuroborreliosis: population-based nationwide matched nested case-control study.

OBJECTIVES: To identify diagnostic opportunities, we investigated healthcare-seeking behavior among patients with Lyme neuroborreliosis (LNB) within 28 weeks before diagnosis. METHODS: We conducted a population-based, nationwide matched nested case-control study (Denmark, 2009-2021). As cases, we included all Danish residents with LNB (positive Borrelia burgdorferi intrathecal antibody index test and cerebrospinal fluid pleocytosis). We randomly selected controls from the general population, matched 10:1 on date of birth and sex. Exposures were assignment of diagnostic codes for symptoms, contact to medical specialties, medical wandering, and undergoing diagnostic procedures. We calculated the weekly and 3-months proportion of individuals with exposures and calculated absolute risk differences with corresponding 95% confidence intervals (95%CI). RESULTS: We included 1,056 cases with LNB and 10,560 controls. Within 3 months before diagnosis, the most frequent assigned symptoms were pain (difference: 13.0%, 95%CI: 10.9-15.1). Cases with LNB exhibited increased contact to most specialties, particularly general practitioners (difference: 48.7%, 95%CI: 46.0-51.4), neurology (difference: 14.3%, 95%CI: 11.7-16.8), and internal medicine (difference: 11.1%, 95%CI: 8.7-13.5), and medical wandering (difference: 17.1%, 95%CI: 14.3-20.0). Common diagnostic procedures included imaging of the brain (difference: 10.2, 95%CI: 8.3-12.1), the spine (difference: 8.8%, 85%CI: 7.0-10.6), and the abdomen (difference: 7.2%, 95%CI: 5.4-9.1). The increase in healthcare-seeking behavior was observed up to 12 weeks preceding diagnosis. CONCLUSIONS: Pain appears to be an ambiguous symptom of LNB, potentially contributing to delays in establishing the correct diagnosis. It would be difficult to identify patients with LNB more effectively as the increased healthcare-seeking behavior preceding diagnosis is distributed across many medical specialties.

Survival of advanced/recurrent gastrointestinal stromal tumors treated with tyrosine kinase inhibitors in Taiwan: a nationwide registry study.

BACKGROUND: Most gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan. METHODS: Patients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan-Meier method. Cox regression analysis was used to analyze the prognostic factors of survival. RESULTS: A total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01-14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39-10.89). CONCLUSIONS: We present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival.

Use of Period Analysis to Timely Assess Five-Year Relative Survival for the Patients With Bone Cancer.

Background: While timely assessment of long-term survival for patients with bone cancer is essential for evaluation on early detection and prognosis level of treatment of bone cancer, those data are extremely scarce in China. We aimed to timely and accurately assess long-term survival for patients with bone cancer in Eastern China. Methods: Patients diagnosed with bone cancer during 2004 - 2018 from four cancer registries with high-quality data from Taizhou, Eastern China were included. Five-year relative survival (RS) of bone cancer patients was calculated by period analysis for overall and the stratification. We further predicted 5-year RS during upcoming 2019 - 2023 using a model-based period analysis and survival data during 2004 - 2018. Results: Overall, 5-year RS for patients with bone cancer during 2014 - 2018 reached 46.6%, being 40.8% for male and 51.0% for female. Five-year RS declined along with aging, decreasing from 58.9% for age < 45 years to 41.5% for age > 60 years, while 5-year RS for urban area was higher compared to rural area (59.1% vs. 44.3%). The 5-year RS during upcoming 2019 - 2023 reached 48.3%. We found a clear upward trend in 5-year RS during 2004 - 2023 for overall and the stratification by sex, age at diagnosis, and region. Conclusions: We found that, for first time in China using period analysis, most up-to-date 5-year RS for patients with bone cancer reached 46.6% during 2014 - 2018, and is projected to reach 48.3% for the period 2019 - 2023, which has important implications for timely evaluation on early detection and prognosis level of treatment for patients with bone cancer in Eastern China.

The CARMEN-France registry of adult patients with immune thrombocytopenia and autoimmune hemolytic anemia in France.

The CARMEN-France registry is a prospective, multicenter registry in France including adult patients with a new diagnosis of immune thrombocytopenia or of autoimmune immune hemolytic anemia (2402 patients included in December 31, 2023). The recording of clinical, biological and treatment data allows detailed epidemiological and pharmacoepidemiological real-world studies. This review summarizes the CARMEN-France registry protocol, gives examples of studies conducted in the registry, and indicates future directions such as inclusion of patient reported outcomes, linkage with the French national health insurance database and linkage with other registries in Europe.

Primary outcomes and characteristics of clinical trial registries (up to October 2021) on COVID-19 vaccines.

OBJECTIVES: To analyse the general and primary outcome-related characteristics of clinical trials protocols on COVID-19 vaccines. STUDY DESIGN AND SETTING: A meta-research study. A search for clinical trial protocols on COVID-19 vaccines was conducted on the ClinicalTrials.gov platform. We considered all protocols of comparative trials registered up to October 26, 2021. RESULTS: Two hundred and eighty-two trials were analysed. The median expected trial duration was 445 days (interquartile range [IQR] = 225), and the median target sample size was 420 participants (IQR = 1638). A retrospective registry (after the start date) was observed for 42.55% of the trials. Randomization procedures were planned by 84.75% and full-blinding procedures by 34.75% of the 282 trials. Most trials were labelled as active or still recruiting, and 14 trials (5%) were completed. None of the 14 trials labelled as completed on our search date had results available. Industry funding was reported by 198 trials (70.2%). Most studies declared more than one primary outcome, usually a safety or immunogenicity outcome, and 59 studies (20.9%) had at least one primary efficacy outcome. The description of the primary efficacy outcomes was limited in most cases, referred to as a non-specified 'efficacy' outcome (18.6%) or described as 'COVID-19 cases' (32.2%). CONCLUSION: the primary outcomes of clinical trials on COVID-19 vaccines are poorly described, and the registers provide insufficient information about them. The registry was retrospectively fulfilled for many trials, which may lead to bias and research waste. Outcomes were generically described and did not provide transparent information for replication in practice, further trials or meta-analyses.

Validation of the Geriatrics at Risk Score (GeRi-Score) on 120-day follow-up, the influence of preoperative geriatric visits, and the time to surgery on the outcome of hip fracture patients: an analysis from the Registry for Geriatric Trauma (ATR-DGU).

A validation of the GeRi-Score on 120-day mortality, the impact of a pre-operative visit by a geriatrician, and timing of surgery on the outcome was conducted. The score has predictive value for 120-day mortality. No advantage was found for surgery within 24 h or a preoperative geriatric visit. PURPOSE: Numerous tools predict mortality among patients with hip fractures, but they include many variables, require time-consuming assessment, and are difficult to calculate. The GeRi-Score provides a quick method of pre-operative assessment. The aim of this study is to validate the score in the 120-day follow-up and determine the impact of a pre-operative visit by a geriatrician and timing of surgery on the patient outcome. METHODS: A retrospective analysis of the AltersTraumaRegister DGU® from 2017 to 2021 was conducted, including all proximal femur fractures. The patients were divided into low-, moderate-, and high-risk groups based on the GeRi-Score. Mortality was analyzed using logistic regression. To determine the influence of the time to surgery and the preoperative visit by a geriatrician, matching was performed using the exact GeRi-Score, preoperative walking ability, type of fracture, and the time to surgery. RESULTS: The study included 38,570 patients, divided into 12,673 low-risk, 18,338 moderate-risk, and 7,559 high-risk patients. The moderate-risk group had three times the mortality risk of the low-risk group (OR 3.19 (95% CI 2.68-3.79; p<0.001)), while the high-risk group had almost eight times the mortality risk than the low-risk group (OR 7.82 (95% CI 6.51-9.93; p<0.001)). No advantage was found for surgery within the first 24 h across all groups. There was a correlation of a preoperative geriatric visit and mortality showing an increase in the moderate and high-risk group on in-house mortality. CONCLUSIONS: The GeRi-Score has predictive value for 120-day mortality. No advantage was found for surgery within 24 h. The analysis did not demonstrate a benefit of the preoperative geriatric visit, but more data are needed.

Eligibility of Asian and European registry patients for phase III trials in heart failure with reduced ejection fraction.

AIMS: Traditional approaches to designing clinical trials for heart failure (HF) have historically relied on expertise and past practices. However, the evolving landscape of healthcare, marked by the advent of novel data science applications and increased data availability, offers a compelling opportunity to transition towards a data-driven paradigm in trial design. This research aims to evaluate the scope and determinants of disparities between clinical trials and registries by leveraging natural language processing for the analysis of trial eligibility criteria. The findings contribute to the establishment of a robust design framework for guiding future HF trials. METHODS AND RESULTS: Interventional phase III trials registered for HF on ClinicalTrials.gov as of the end of 2021 were identified. Natural language processing was used to extract and structure the eligibility criteria for quantitative analysis. The most common criteria for HF with reduced ejection fraction (HFrEF) were applied to estimate patient eligibility as a proportion of registry patients in the ASIAN-HF (N = 4868) and BIOSTAT-CHF registries (N = 2545). Of the 375 phase III trials for HF, 163 HFrEF trials were identified. In these trials, the most frequently encountered inclusion criteria were New York Heart Association (NYHA) functional class (69%), worsening HF (23%), and natriuretic peptides (18%), whereas the most frequent comorbidity-based exclusion criteria were acute coronary syndrome (64%), renal disease (55%), and valvular heart disease (47%). On average, 20% of registry patients were eligible for HFrEF trials. Eligibility distributions did not differ (P = 0.18) between Asian [median eligibility 0.20, interquartile range (IQR) 0.08-0.43] and European registry populations (median 0.17, IQR 0.06-0.39). With time, HFrEF trials became more restrictive, where patient eligibility declined from 0.40 in 1985-2005 to 0.19 in 2016-2022 (P = 0.03). When frequency among trials is taken into consideration, the eligibility criteria that were most restrictive were prior myocardial infarction, NYHA class, age, and prior HF hospitalization. CONCLUSIONS: Based on 14 trial criteria, only one-fifth of registry patients were eligible for phase III HFrEF trials. Overall eligibility rates did not differ between the Asian and European patient cohorts.

Can Machine Learning Assist in Diagnosis of Primary Immune Thrombocytopenia? A Feasibility Study.

Primary Immune Thrombocytopenia (ITP) is a rare autoimmune disease characterised by the immune-mediated destruction of peripheral blood platelets in patients leading to low platelet counts and bleeding. The diagnosis and effective management of ITP are challenging because there is no established test to confirm the disease and no biomarker with which one can predict the response to treatment and outcome. In this work, we conduct a feasibility study to check if machine learning can be applied effectively for the diagnosis of ITP using routine blood tests and demographic data in a non-acute outpatient setting. Various ML models, including Logistic Regression, Support Vector Machine, k-Nearest Neighbor, Decision Tree and Random Forest, were applied to data from the UK Adult ITP Registry and a general haematology clinic. Two different approaches were investigated: a demographic-unaware and a demographic-aware one. We conduct extensive experiments to evaluate the predictive performance of these models and approaches, as well as their bias. The results revealed that Decision Tree and Random Forest models were both superior and fair, achieving nearly perfect predictive and fairness scores, with platelet count identified as the most significant variable. Models not provided with demographic information performed better in terms of predictive accuracy but showed lower fairness scores, illustrating a trade-off between predictive performance and fairness.

Establishing the Saudi pediatric and youth diabetes registry: initial data and challenges.

The Saudi National Diabetes Registry focuses mainly on adult patients. In 2020, the National Guard Health Authority (NGHA) launched the Saudi Pediatric and Youth Diabetes Registry (SPYDR), for children and adolescents with diabetes. This report is about the first data and the challenges we faced during SPYDR initiation. Patients were identified from the electronic medical records of the Saudi NGHA hospitals using the International Classification of Disease (ICD-10). A trained coordinator verified the diagnosis and entered patients' details into the registry and a random sample was validated by experienced endocrinologists. The data were analyzed according to patients' demography, diabetes subtypes, duration, control, and complications. The challenges faced by the team were identified and addressed. At the time of manuscript submission, 2,344 individuals were enrolled. Their mean age at diagnosis was 9.08 (±4.27) years and 1,136 (48.46%) were females. Of these, 91.3% have type 1 (T1D), and 6.4% have type 2 diabetes (T2D). The mean HbA1c was 10.45% (±2.36) and duration of diabetes was 5.31 (±3.05) years. The main challenges included the COVID-19 pandemic, data validation, and centers' participation. However, within 12 months of initiation enrolled subjects matched the expected number. Despite the challenges, the first step of SPYDR was achieved. The initial data confirmed that T1D is the most common form of childhood diabetes, and the frequency of T2D is comparable to regional and international data. SPYDR provides the infrastructure for data sharing and collaborative research with the enrollment of patients from other Saudi healthcare institutes.

Nusinersen effectiveness and safety in pediatric patients with 5q-spinal muscular atrophy: a multi-center disease registry in China.

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.

Challenges in collecting information on sexual orientation and gender identity for cancer patients: perspectives of hospital and central cancer registry abstractors.

PURPOSE: Sexual and gender minority (SGM) populations experience cancer treatment and survival disparities; however, inconsistent sexual orientation and gender identity (SOGI) data collection within clinical settings and the cancer surveillance system precludes population-based research toward health equity for this population. This qualitative study examined how hospital and central registry abstractors receive and interact with SOGI information and the challenges that they face in doing so. METHODS: We conducted semi-structured interviews with 18 abstractors at five Surveillance, Epidemiology, and End Results (SEER) registries, as well as seven abstractors from commission on cancer (CoC)-accredited hospital programs in Iowa. Interviews were transcribed, cleaned, and coded using a combination of a priori and emergent codes. These codes were then used to conduct a descriptive analysis and to identify domains across the interviews. RESULTS: Interviews revealed that abstractors had difficulty locating SOGI information in the medical record: this information was largely never recorded, and when included, was inconsistently/not uniformly located in the medical record. On occasion, abstractors reported situational recording of SOGI information when relevant to the patient's cancer diagnosis. Abstractors further noticed that, where reported, the source of SOGI information (i.e., patient, physician) is largely unknown. CONCLUSION: Efforts are needed to ensure standardized implementation of the collection of SOGI variables within the clinical setting, such that this information can be collected by the central cancer registry system to support population-based equity research addressing LGBTQ + disparities.

Is the increase in the number of total hip arthroplasties in Japan due to an aging society?

BACKGROUND: The number of total hip arthroplasty (THA) is increasing globally, including Japan. The Japanese Orthopaedic Association has been conducting a registry of joint replacement surgery, but there may be a gap between the reported numbers of THA in the registry and the actual number. This study aimed to investigate the exact number of THA and assess the trends in Japan using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). METHODS: We downloaded data from 2014 to 2019 from the NDB Open Data. Data on primary THA were extracted, and we calculated the annual number and number for each 10-year age group and sex. We also compared the number and trends between elderly and non-elderly groups. RESULTS: During the study period, number of THAs increased by approximately 20,000, showing a continuous upward trend. The highest number of THAs were performed on patients in their 60s, except for the years 2014 and 2019. Comparison of the numbers in 2014 and 2019 by age group showed an increase in the number in patients in their 90s (by 2.05 times). There were significantly a greater number of elderly patients (P < 0.001). The number of THAs performed was higher in women than in men (P < 0.001). CONCLUSION: The number of THAs in Japan increased substantially from 2014 to 2019, despite a decrease in population. Significantly higher number of THAs were performed on elderly patients in Japan, which might be due to an aging society. The NDB data is highly valuable for epidemiological research in Japan, as it might enable the early detection of issues occurring during THA, facilitating their prompt integration into daily clinical practice.

Detecting familial hypercholesterolemia: An observational study leveraging mandatory universal pediatric total cholesterol screening in Slovakia.

BACKGROUND: In Slovakia, a mandatory national universal pediatric total cholesterol (TC) screening program is in place to identify cases of familial hypercholesterolemia (FH). However, the program's effectiveness has not been systematically assessed. OBJECTIVE: This study aimed to estimate the prevalence of FH among parents of children that had elevated TC levels identified during screening. METHODS: This prospective, non-interventional, observational study enrolled parents of 11-year-old children who underwent TC screening in 23 selected pediatric outpatient clinics between 2017 and 2018. FH was diagnosed using the Dutch Lipid Clinic Network (DLCN) criteria and targeted next-generation sequencing. The primary objective was to estimate the proportion of children with a TC level of >188 mg/dL (>4.85 mmol/L) who had a parent with a confirmed diagnosis of FH. RESULTS: A total of 112 parents of 56 children with an elevated TC level were enrolled. Five children (8.9%) had a parent in whom FH was genetically confirmed. Without genetic analysis, all five parents would only be diagnosed with "possible FH" by DLCN criteria. Of parents, 83.9% (n = 94/112) had an LDL-C level of >116 mg/dL (>3 mmol/L), but only 5.3% (n = 5/94) received lipid-lowering therapy. Among the five parents with genetically confirmed FH, all had an LDL-C level >116 mg/dL (>3 mmol/L), with a mean (±SD) of 191 (±24) mg/dL (4.94 [±0.61] mmol/L). Only two of these parents received lipid-lowering therapy. CONCLUSIONS: The present study demonstrates the significance of mandatory universal pediatric TC screening in identifying families with FH and other at-risk families in need of lipid-lowering therapy.

Genetic and environmental determinants of bone quality: a cross-sectional analysis of the Hungarian Twin Registry.

There is abundant evidence that bone mineral content is highly heritable, while the heritability of bone quality (i.e. trabecular bone score [TBS] and quantitative ultrasound index [QUI]) is rarely investigated. We aimed to disentangle the role of genetic, shared and unique environmental factors on TBS and QUI among Hungarian twins. Our study includes 82 twin (48 monozygotic, 33 same-sex dizygotic) pairs from the Hungarian Twin Registry. TBS was determined by DXA, QUI by calcaneal bone ultrasound. To estimate the genetic and environmental effects, we utilized ACE-variance decomposition. For the unadjusted model of TBS, an AE model provided the best fit with > 80% additive genetic heritability. Adjustment for age, sex, BMI and smoking status improved model fit with 48.0% of total variance explained by independent variables. Furthermore, there was a strong dominant genetic effect (73.7%). In contrast, unadjusted and adjusted models for QUI showed an AE structure. Adjustments improved model fit and 25.7% of the total variance was explained by independent variables. Altogether 70-90% of the variance in QUI was related to additive genetic influences. We found a strong genetic heritability of bone quality in unadjusted models. Half of the variance of TBS was explained by age, sex and BMI. Furthermore, the adjusted model suggested that the genetic component of TBS could be dominant or an epistasis could be present. In contrast, independent variables explained only a quarter of the variance of QUI and the additive heritability explained more than half of all the variance.

The German cochlear implant registry: one year experience and first results on demographic data.

PURPOSE: Clinical registries have great potential for quality control of medical procedures regarding the indications, therapeutic processes and results, including their possible complications. This is particularly true when providing patients with severe hearing loss or deafness with a cochlear implant (CI). This treatment represents a lifelong care process that requires continuous quality control over time. On the initiative of the Executive Committee of the German Society of Otorhinolaryngology (Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V., DGHNO-KHC), a national German CI registry (Deutsches Cochlear Implant Register, DCIR) was established in January 2022. This article focuses on the first demographic and baseline data of the DCIR. METHODS: The DCIR covers the complete therapeutic process from indication, surgery, fitting and lifelong aftercare in CI therapy. By the end of 2022, 75 hospitals in Germany had agreed to contribute to the DCIR. RESULTS: During the year 2022, 63 hospitals actively contributed data to the DCIR. Pseudonymized data from 2,292 CI implantations (2,176 primary implantations, 99 explantations with immediate re-implantations and 17 re-implantations following an earlier explantation) in 2,108 patients were documented. Cochlear implantation was accomplished in 1,807 adults (≥ 18 years) and 301 children (< 18 years). Fourty patients (1,9%) were children < 1 year of age and 55 (2,6%) were patients > 85 years. From the total of 2,292 implantations, 226 (9.9%) were performed as simultaneous bilateral implantations (CI implantation in both ears of 113 patients on the same day of surgery) and 412 implantations (19.1% of 2,162 implantations with data provided on the contralateral ear's hearing status) were in patients with single sided deafness (normal hearing in the contralateral ear). In addition, the reported complications in 2022 were also evaluated. Seven reports (0.4%) of mild to moderate severe facial nerve dysfunctions were documented. No reports of severe or total facial nerve dysfunction (House-Brackmann grade V/VI), meningitis or death related to CI therapy were documented. CONCLUSION: Although still in the start-up phase, these initial DCIR data already provide an interesting first insight into the demographic structure and baseline data of CI therapy in Germany. The successful implementation of the DCIR represents an important step towards continuous quality control of CI care.

Comparison of Demographics: National Amyotrophic Lateral Sclerosis Registry and Clinical Trials Data.

OBJECTIVE: To characterize the participant demographics in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database compared with the web-portal National Amyotrophic Lateral Sclerosis (ALS) Registry (the Registry). METHODS: Demographics and ALS symptom information were compared between the self-reported registrant data in the Registry web portal (2010-2021) and the latest available PRO-ACT data (updated August 2022), which is a collection of clinical trials data. RESULTS: Greater percentages of younger (≤ 59 years old) but smaller percentages of older (60 + years old) participants were represented in PRO-ACT compared to Registry. Enrollment for minority race groups was greater in the Registry portal data, but race information was largely missing/unknown in PRO-ACT database. Median age at the time of diagnosis and age at the time of symptom onset were significantly higher for Registry enrollees compared to the participants of PRO-ACT. Symptom onset sites were similarly reported, but duration between self-noted symptom onset and diagnosis was slight, but significantly longer for the Registry enrollees (11 vs. 9 months). Hispanic were as likely as non-Hispanic to participate in research studies, based on the Registry data. CONCLUSION: There was a notable difference in the age distribution and minority representation of enrollees between the PRO-ACT and Registry study populations. Age distribution in the PRO-ACT database skewed to a younger and less diverse cohort. Despite the clinical heterogeneity and complex disease mechanism of ALS, identifying the underrepresented demographic niche in the PRO-ACT and Registry study populations can help improve patient participation and criteria for patient selection to enhance generalizability.