Nusinersen therapy changed the natural course of spinal muscular atrophy type 1: What about spine and hip?

Purpose: Spinal muscular atrophy type 1 has a devastating natural course and presents a severe course marked by scoliosis and hip subluxation in nonambulatory patients. Nusinersen, Food and Drug Administration-approved spinal muscular atrophy therapy, extends survival and enhances motor function. However, its influence on spinal and hip deformities remains unclear. Methods: In a retrospective study, 29 spinal muscular atrophy type 1 patients born between 2017 and 2021, confirmed by genetic testing, treated with intrathecal nusinersen, and had registered to the national electronic health database were included. Demographics, age at the first nusinersen dose, total administrations, and Children's of Philadelphia Infant Test of Neuromuscular Disorders scores were collected. Radiological assessments included parasol rib deformity, scoliosis, pelvic obliquity, and hip subluxation. Results: Mean age was 3.7 ± 1.1 (range, 2-6), and average number of intrathecal nusinersen administration was 8.9 ± 2.9 (range, 4-19). There was a significant correlation between Children's of Philadelphia Infant Test of Neuromuscular Disorders score and the number of nusinersen administration (r = 0.539, p = 0.05). The correlation between Children's of Philadelphia Infant Test of Neuromuscular Disorders score and patient age (r = 0.361) or the time of first nusinersen dose (r = 0.39) was not significant (p = 0.076 and p = 0.054, respectively). While 93.1% had scoliosis, 69% had pelvic obliquity, and 60.7% had hip subluxation, these conditions showed no significant association with patient age, total nusinersen administrations, age at the first dose, or Children's of Philadelphia Infant Test of Neuromuscular Disorders scores. Conclusion: Disease-modifying therapy provides significant improvements in overall survival and motor function in spinal muscular atrophy type 1. However, progressive spine deformity and hip subluxation still remain significant problems in the majority of cases which would potentially need to be addressed.

Survival in systemic sclerosis associated pulmonary arterial hypertension in the current treatment era-results from a nationwide study.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a leading cause of mortality in systemic sclerosis (SSc). This nationwide study aims to describe real world treatment characteristics and assess survival rates of patients with SSc-PAH. METHODS: In this retrospective cohort study, patients with SSc-PAH were identified from Turkish Ministry of Health National Electronic Database (from January 2016 to September 2022), using ICD-10 codes. Data on demographics, treatment characteristics, and death was collected. Kaplan-Meier curves were used to calculate cumulative probabilities of survival at 1, 3, and 5 years. RESULTS: Five hundred forty-seven patients (90.7% female) with SSc-PAH were identified. Median age at PAH diagnosis was 59.9 (50.0-67.4) years. During a median follow-up duration of 3.2 (1.5-4.8) years, 199 (36.4%) deaths occurred. Estimated survival rates at 1, 3, and 5 years were 90.2%, 73.2%, and 56.6%, respectively. Survival was similar among patients with and without interstitial lung disease (p = 0.20). Patients who used immunosuppressives had better survival than those who did not (p < 0.001). No difference was observed in survival rates according to initial PAH-specific treatment regimen (monotherapy or combination) (p = 0.49). CONCLUSION: Compared to most of historical cohorts, higher survival rates for SSc-PAH were observed in this study. Early diagnosis of PAH may have contributed to these findings. The impact of immunosuppressive therapy on prognosis of SSc-PAH needs to be further investigated in prospective studies. Key Points • Early diagnosis is pivotal for better outcomes in SSc-PAH. • Implementation of PAH treatment guidelines in routine clinical practice is still poor and should be improved. • Effect of immunosuppressive therapies on disease course has to be defined in SSc-PAH.

Navigating Heart Failure: Unveiling Sex Disparities in Guideline-Directed Medical Therapy Combinations.

Major heart failure (HF) trials remain insufficient in terms of assessing the differences in clinical characteristics, biomarkers, treatment efficacy, and safety because of the under-representation of women. The study aimed to present sex-related disparities in HF management, including differences in demographics, co-morbidities, cardiac biomarkers, prescribed medications, and treatment outcomes. The study utilized anonymized data from the Turkish Ministry of Health's National Electronic Database between January 1, 2016, and December 31, 2022. The cohort analysis included 2,501,231 adult patients with HF. Specific therapeutic combinations were analyzed using a Cox regression model to obtain relative risk reduction for all-cause death. The primary end point was all-cause mortality. In the cohort, 48.7% (n = 1,218,911) were male, whereas 51.3% (n = 1,282,320) were female. Female patients exhibited a higher median age (71 vs 68 years) and manifested higher prevalence of diabetes mellitus, anemia, atrial fibrillation, anxiety, and ischemic stroke. Male patients demonstrated higher rates of previous myocardial infarction, dyslipidemia, chronic obstructive pulmonary disease, and chronic kidney disease. Higher concentrations of natriuretic peptides were observed in female patients. Renin-angiotensin aldosterone inhibitor, ß blockers, mineralocorticoid receptor antagonists, sodium/glucose cotransporter 2 inhibitor (SGLT2i), and ivabradine were more commonly prescribed in male patients, whereas loop diuretics, digoxin, and ferric carboxymaltose were more frequent in female patients. Male patients had higher rates of cardiac resynchronization therapy and implantable cardioverter defibrillator implantation rates. All-cause mortality and hospitalization rates were higher in male patients. Compared with monotherapy, all combinations, including SGLT2i, showed a beneficial effect on all-cause mortality in both female and male patients with HF. In hospitalized patients with HF, the addition of digoxin to renin-angiotensin aldosterone inhibitor, mineralocorticoid receptor antagonists, and ß blockers was superior to monotherapy regarding all-cause mortality in female patients with HF compared with male patients with HF. In conclusion, this study highlights that sex-specific responses to HF medication combinations compared with monotherapy and differences in co-morbidities underscore the importance of tailored management strategies. Digoxin showed a contrasting effect on all-cause mortality between both sexes after hospitalization, whereas SGLT2i exhibited a consistent beneficial effect in both sexes when added to all combinations.

Exploring Regional Disparities in Heart Failure Epidemiology and Outcomes: A Comprehensive Study Across Geographical Regions in Türkiye.

Background: Heart failure (HF) is a common condition that affects 1-3% of the general population. Its prevalence exhibits notable international and intranational disparities, partly explained by socioeconomic status, religion, ethnic diversity, and geographic factors. A comprehensive understanding of the epidemiological symptoms of HF in different regions of Türkiye has yet to be revealed. Aims: To examine epidemiological data from 2016 to 2022, focusing on crucial patient characteristics and geographical regions, to determine the incidence and prevalence of HF in Türkiye across seven diverse geographical regions. Study Design: A nationwide population-based retrospective cohort study. Methods: The comprehensive National Electronic Database of the Turkish Ministry of Health was used in this study to obtain data that covers the whole Turkish population from January 1, 2016, to December 31, 2022. The International Classification of Diseases-10 (ICD-10) codes were used to identify adults with HF (n = 2,701,099) and associated comorbidities. Türkiye is divided into seven geographically distinct regions. Epidemiological characteristics and survival data of these regions were analyzed separately. All-cause mortality was set as the primary outcome. Results: In , the total estimated prevalence of adult patients with HF is 2.939%, ranging from 2.442% in Southeastern Anatolia to 4.382% in the Black Sea Region. Except for the Eastern Anatolia Region, the three most often reported comorbidities were hypertension, dyslipidemia, and anxiety disorders. The rates of prescribing guideline-directed medical therapy (GDMT) for HF and other medications varied significantly. GDMT prescription rates were lowest in the Eastern Anatolia Region (82.6% for beta-blockers, 48.7% for RASi, 31.8% for mineralocorticoid receptor antagonists, and 9.4% for SGLT2i). The Mediterranean and Aegean regions had the highest median N-terminal brain natriuretic peptide (NT-proBNP) levels of 1,990,0 pg/ml (518.0-6,636,0) and 1,441,0 pg/ml (363.0-5,000,0), respectively. From 2016 to 2022, 915,897 (33.9%) of 2,701,099 patients died. The Eastern Anatolia Region had the lowest all-cause mortality rate of 26.5%, whereas the Black Sea Region had the highest all-cause mortality rate of 35.3%. Conclusion: Our real-world analysis revealed geographic disparities in HF characteristics, such as decreased mortality in socioeconomically challenged regions. Higher stress susceptibility in developed regions may increase the likelihood of adverse outcomes.

Association between hyponatremia, inflammation, and mortality in patients undergoing peritoneal dialysis: A nationwide observations.

INTRODUCTION: Hyponatremia is the most common electrolyte disorder often present in peritoneal dialysis (PD) patients. The aim of this retrospective study was to investigate the effect of hyponatremia on mortality in patients undergoing PD. METHODS: The health records of adult individuals with an inserted PD catheter identified via the centralized national e-health database were used. RESULTS: The mean age of the 846 patients included in the study was 52.48 years (±14.6). The mean sodium level was 136.51 mEq/L. Sodium levels <137 mEq/L were associated with higher death risk independent of comorbidities. There was a 0.821 times less reduction in mortality for each mEq /L increase in serum sodium. CONCLUSION: Our study provides evidence that monitoring and adjusting serum sodium levels is crucial in managing PD patients with hyponatremia, as low serum sodium level was found to be a significant and independent predictor of mortality.

Fracture Patterns and Mortality in Osteopetrosis: A 7-year Retrospective Analysis from Türkiye's National Registry.

BACKGROUND: The aim of this study is to determine the demographic data, fracture treatment methods, and medical treatments of patients diagnosed with osteopetrosis in the national registry. METHODS: Patients with International Classification of Diseases (ICD)-10 code Q78.2 for osteopetrosis between January 1, 2016 and April 11, 2023 were retrospectively reviewed. Data on sex, age at time of diagnosis, fracture history, mortality, and use of medications were evaluated for all patients. In addition, open reduction and internal fixation, closed reduction and internal fixation, closed reduction and casting, and conservative treatment methods were noted. The number of patients requiring deformity surgery was determined. The incidence and prevalence of osteopetrosis were also calculated in this cross-sectional study. RESULTS: A total of 476 patients diagnosed with osteopetrosis were identified. The mean age at time of diagnosis of these patients was 5.79 ± 5.43 years. A total of 101 patients died. As the age at diagnosis decreased, the mortality rate of the patients increased with statistical significance ( P <0.001). A total of 192 fractures were seen in 121 osteopetrosis patients in this study. Femur fractures were most common among these patients with osteopetrosis. A history of fracture was statistically significantly less common in patients using a combination of vitamin D + calcium compared with patients not using such medication ( P <0.001). In this 7-year cross-sectional study, the incidence was found to be 1 in 416,000 and the prevalence was 0.00199% in the population under 18 years of age. CONCLUSION: Younger age at diagnosis is associated with higher mortality in patients with osteopetrosis. In addition, the combination of vitamin D and calcium were associated with lower fracture incidence. LEVEL OF EVIDENCE: Prognostic Level II.

Trends in heart failure between 2016 and 2022 in Türkiye (TRends-HF): a nationwide retrospective cohort study of 85 million individuals across entire population of all ages.

Background: Data on the burden of heart failure (HF) outside western countries are limited, but available data suggest it may present differently in other countries. The aim of this study was to examine the incidence, prevalence, and survival rates of HF in Türkiye, with a specific focus on how these rates vary according to age, sex, comorbidities, and socioeconomic status (SES). Methods: We harnessed the extensive National Electronic Database of the Turkish Ministry of Health, covering Turkey's entire population from January 1, 2016, to December 31, 2022, to identify 2,722,151 cases of HF and their associated comorbidities using ICD-10 codes. Analyzing the primary endpoint of all-cause mortality, our study utilized anonymized data to examine patient demographics, comorbidities, socioeconomic status, and survival patterns, employing statistical techniques to delve into relationships and trends. The data were segmented by gender, socioeconomic status, and age, involving cross-tabulations and statistical metrics to explore connections, odds ratios, and survival rates. Findings: The estimated prevalence of HF was 2.114% in Türkiye at the end of 2022, with an annual incidence ranging between 3.00 and 6.06 per 1000 person years. Females were older than males (69.8 ± 13.9 years vs. 66.8 ± 13.9 years, respectively). The most common comorbidities were congenital heart diseases and anemia under the age of 20, and hypertension and atherosclerotic cardiovascular disease in the adult population. Only 23.6% (643,159/2,722,151) of patients were treated with any triple guideline-directed medical therapy (GDMT) and 3.6% (96,751/2,722,151) of patients were on quadruple GDMT. The survival rates for patients with HF at 1, 5, and 7 years were 83.3% (95% CI: 83.2-83.3), 61.5% (95% CI: 61.4-61.6), and 57.7% (95% CI: 57.6-57.8) among females, and 82.1% (95% CI: 82.0-82.2), 58.2% (95% CI: 58.1-58.3), and 54.2% (95% CI: 54.0-54.3) among males. Despite a tendency for an increase from the highest to the lowest SES, the prevalence of HF and mortality were paradoxically lowest in the lowest SES region. Interpretation: The prevalence, incidence, and survival rates of HF in Türkiye were comparable to western countries, despite the notable difference of HF onset occurring 8-10 years earlier in the Turkish population. Drug usage statistics indicate there is a need for effective strategies to improve treatment with GDMT. Funding: None.

Epidemiology and demographics of pediatric proximal femur fractures in Türkiye: results from a government-based health registry.

We evaluate the epidemiology and incidence of pediatric proximal femur fractures, treatment trends among different hospital levels, and complication rates among different treatment modalities by examining a national health registry in Türkiye. The health records of individuals aged ≤16 years admitted to public, private, and university hospitals were collected via the e-health database of the Turkish Ministry of Health. A total of 2388 children treated for proximal femur fractures from 2016 to 2021 with at least 2 years of follow-up were included in the study. While 2033 (85.1%) patients were treated with closed reduction and spica casts, 355 (14.8%) were operated on. Mean age was 8.603 ±â€…5.11 years. Male incidence was 2-fold greater compared to female patients (36.4% female and 63.6% male patients; P < 0.001). The frequency of cases was significantly increased in the age groups of 3-4 and 13-16 years. Comorbidities causing limited ambulation were detected in 6.5% of all cases, and 163 (8.0%) patients in the conservative group and 98 (27.6%) patients in the surgery group had at least one complication. The incidence was 0.45 per 100 000 children aged ≤16 years. This study reports the largest patient cohort to date, providing evidence on the epidemiology and incidence of pediatric proximal femur fractures using health registry data. We have found that the most common treatment modality for proximal femur fractures is closed reduction with spica casts. The rate of avascular necrosis is similar among patients treated surgically and those treated conservatively.

Prevalence, Incidence, and Surgical Treatment Trends of Cerebral Palsy across Türkiye: A Nationwide Cohort Study.

BACKGROUND: Cerebral Palsy (CP) is the most prevalent neurodevelopmental disorder in childhood. Our aim is to identify the demographics of CP in Turkish children in addition to clinical associations and surgical preferences. METHODS: Based on national health system data and the International Classification of Diseases (ICD)-10 code for CP, data were evaluated from a total of 53,027 children with CP born between 2016 and 2022, and 9658 of them underwent orthopedic surgery in those years. The incidence and frequency of CP were assessed for the parameters of age and gender. Age at the time of surgery; codes pertaining to surgical interventions; and regions, cities, and hospitals where diagnoses and surgical procedures were performed were also evaluated. RESULTS: There were 29,606 male (55.8%) and 23,421 (44.2%) female patients. The diagnoses of the patients were mostly (76.1%) performed in secondary and tertiary hospitals. The prevalence of CP among children in 2016-2022 was estimated to be 7.74/1000 children. The minimum and maximum incidence rates of cerebral palsy among children between 2016 and 2022 were calculated to be 0.45 and 1.05 per 1000, respectively. Tenoplasty-myoplasty tendon transfer operations were the most common surgeries (47.1%). CONCLUSION: CP remains a significant health challenge, underpinning a considerable proportion of childhood motor dysfunction. A dedicated national registry system for CP focused on classifying the condition, streamlining treatment, and tracking outcomes would be a valuable tool in our collective efforts to address this critical issue more effectively.

Clinical characteristics of adult and paediatric patients with familial hypercholesterolemia: A real-life cross-sectional study from the Turkish National Database.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is the most common cause of premature atherosclerotic cardiovascular disease (ASCVD). Türkiye is among the countries with the highest rate of ASCVD. However, no population-based study has been published so far on the prevalence of FH, demographic and clinical characteristics, burden of ASCVD, treatment compliance, and attainment of low-density lipoprotein cholesterol (LDL-C) targets. METHODS: We performed a study using the Turkish Ministry of Health's national electronic health records involving 83,063,515 citizens as of December 2021 dating back 2016. Adults fulfilling the diagnostic criteria of definite or probable FH according to the Dutch Lipid Network Criteria (DLNC), and children and adolescents fulfilling the criteria of probable FH according to the European Atherosclerosis Society (EAS) Consensus Panel report formed the study population (n = 157,790). The primary endpoint was the prevalence of FH. RESULTS: Probable or definite FH was detected in 0.63% (1 in 158) of the adults and 0.61% (1 in 164) of the total population. The proportion of adults with LDL-C levels >4.9 mmol/L (190 mg/dL) was 4.56% (1 in 22). The prevalence of FH among children and adolescents was 0.37% (1 in 270). Less than one-third of the children and adolescents, and two-thirds of young adults (aged 18-29) with FH were already diagnosed with dyslipidaemia. The proportion of adults and children and adolescents on lipid-lowering treatment (LLT) was 32.1% and 1.5%, respectively. The overall discontinuation rate of LLT was 65.8% among adults and 77.9% among children and adolescents. Almost no subjects on LLT were found to attain the target LDL-C levels. CONCLUSIONS: This nationwide study showed a very high prevalence of FH in Türkiye. Patients with FH are diagnosed late and treated sub-optimally. Whether these findings may explain the high rates of premature ASCVD in Türkiye needs further investigation. These results denote the urgent need for country-wide initiatives for early diagnosis and effective management of FH patients.

Characteristics of diabetes mellitus patients in Turkey: An analysis of national electronic health records.

BACKGROUND: It was estimated that there were 537 million people with diabetes mellitus in 2021, representing 10.5% of the global adult population. Diabetes prevalence in Turkey is 13.5%, according to a meta-analysis and 17.3% according to a recent study. Although the primary purpose of Electronic Health Records (EHRs) is clinical, researchers can use them to conduct epidemiologic investigations. This study aims to document the prevalence of diabetes and to evaluate the healthcare utilization of people with diabetes compared to the people without diabetes, based on national EHR. METHODS: Only people over 14 years old were included in the analysis. Our criteria for being diabetic were 1) having an HbA1c over 6.5% (48 mmol/mol), 2) having a prescription with DM diagnosis, ICD-10 codes E10-E14, or 3) having at least two fasting blood glucose measurements over 126 mg/dl. RESULTS: At the end of 2020, there were 7,178,674 individuals with diabetes, with 11.12% prevalence, 13.10% in women while 9.12% in men. Age-adjusted healthcare facility admission per capita was 15.5 for people with diabetes, 9.5 for people without diabetes, while the number of prescriptions was 7.9 for people with diabetes while 4.5 for people without diabetes in 2019. The mean number of prescriptions containing antidiabetics was 2.88 per person with diabetes in 2019. DISCUSSION: Approximately 11% of Turkish people have diagnosed with diabetes. We estimate that about one-third of people with diabetes are undiagnosed and the majority of these people are men. The results show that such large databases have the capability of supplying a vast amount of information to the scientific community.

Outcome of COVID-19 in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors.

INTRODUCTION: In this study, we aim to report the outcome of COVID-19 in chronic myeloid leukemia (CML) patients receiving tyrosine kinase inhibitor (TKI). METHOD: The data of 16 laboratory-confirmed COVID-19 patients with CML receiving TKI and age, gender, and comorbid disease matched COVID-19 patients without cancer at a 3/1 ratio (n = 48), diagnosed between March 11, 2020 and May 22, 2020 and included in the Republic of Turkey, Ministry of Health database, were analyzed retrospectively. RESULTS: The rates of intensive care unit (ICU) admission, and mechanical ventilation (MV) support were lower in CML patients compared to the control group, however, these differences did not achieve statistical significance (p = 0.1, and p = 0.2, respectively). The length of hospital stay was shorter in CML patients compared with the control group; however, it was not statistically significant (p = 0.8). The case fatality rate (CFR) in COVID-19 patients with CML was 6.3%, and it was 12.8% in the control group. Although the CFR in CML patients with COVID-19 was lower compared to the control group, this difference did not achieve statistical significance (p = 0.5). When CML patients were divided into 3 groups according to the TKI, no significant difference was observed regarding the rate of ICU admission, MV support, CFR, the length of stay in both hospital and ICU (all p > 0.05). CONCLUSION: This study highlights that large scale prospective and randomized studies should be conducted in order to investigate the role of TKIs in the treatment of COVID-19.