The Epidemiological Transition of Surgically Treated Proximal Hip Fractures in Austria over the Course of the Pandemic-Back to Normal or a New Normal?

BACKGROUND: The COVID-19 pandemic has had a significant impact on the treatment protocols of orthopedic and trauma departments, but its specific effect on the mortality of hip fracture patients due to possible delays in surgery remains uncertain. This study aimed to investigate whether the COVID-19 pandemic worsened the mortality of patients with hip fractures. MATERIALS AND METHODS: This study included 246 prospectively enrolled patients who suffered from hip fractures during the Austrian State of Emergency period between 1 March and 30 June 2020 and 2021 and were admitted to a tertiary care trauma center. This cohort was compared with a retrospective control group of 494 patients admitted for hip fractures during the same timeframe in 2017, 2018, and 2019. These groups were compared to a prospective recruited "post-COVID-19 collective consisting of the years 2022 and 2023 including 313 patients. RESULTS: This study found a 22% reduction in admissions during the COVID-19 period compared to the pre-COVID period (p = 0.018), as well as significant changes in gender (p = 0.013) and place of accident (p = 0.049). No other changes in demographic variables were observed. The 30-day mortality rate was 14.67% in the pre-COVID period, compared to 15.18% during the COVID-19 period (p = 0.381). No differences were observed in surgical complication rates or in the relationship between comorbidity burden and survival. CONCLUSION: This study did not show a higher perioperative mortality rate due to COVID-19. However, under current circumstances, with potentially reduced surgical and hospital bed capacities, it is expected that this condition might require a high degree of resources in times when resources are potentially scarce, such as during an ongoing pandemic. LEVEL OF EVIDENCE: Level III.

Predictive Validity of Mortality after Surgically Treated Proximal Femur Fractures Based on Four Nutrition Scores-A Retrospective Data Analysis.

BACKGROUND: Hip fractures are becoming a growing concern due to an aging population. The high costs to the healthcare system and far-reaching consequences for those affected, including a loss of independence and increased mortality rates, make this issue important. Poor nutritional status is a common problem among geriatric patients and is associated with a worse prognosis. Nutritional screening tools can help identify high-risk patients and enable individualized care to improve survival rates. MATERIAL AND METHODS: This retrospective study investigates four nutritional scores and laboratory parameters' predictive significance concerning postoperative mortality after surgical treatment of proximal femur fractures at 1, 3, 6, and 12 month/s for patients over 60 years using the chi-square test, Cox regression analysis, and receiver operating characteristics (ROC). The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines were used as part of the screening of the respective nutritional status of the patients, in particular to filter out malnutrition. RESULTS: A total of 1080 patients were included in this study, whereas 8.05% suffered from malnutrition, defined as a body mass index (BMI) below 18.5 kg/m2. The Mini Nutritional Assessment (MNA) screening tool identified the highest proportion of malnourished patients at 14.54%. A total of 36.39% of patients were at risk of malnutrition according to three nutrition scores, with MNA providing the most significant proportion at 41.20%. Patients identified as malnourished had a higher mortality rate, and MNA screening was the only tool to show a significant correlation with postoperative mortality in all survey intervals. The MNA presented the best predictive significance among the screening tools, with a maximum area under the curve (AUC) of 0.7 at 12 month postoperatively. CONCLUSIONS: MNA screening has a solid correlation and predictive significance regarding postoperative mortality-therefore routine implementation of this screening in orthopedic/traumatology wards is recommended. Moreover, nutritional substitution therapy can offer a relatively inexpensive and easy-to-implement measure. The Graz malnutrition screening (GMS) shows moderate predictive power and could be considered as an alternative for patients under 60 years of age. A higher albumin level is associated with improved survival probability, but cannot be indicative of nutritional status.

Comprehensive genetic screening of early-onset dementia patients in an Austrian cohort-suggesting new disease-contributing genes.

Early-onset dementia (EOD), with symptom onset before age 65, has a strong genetic burden. Due to genetic and clinical overlaps between different types of dementia, whole-exome sequencing (WES) has emerged as an appropriate screening method for diagnostic testing and novel gene-finding approaches. We performed WES and C9orf72 repeat testing in 60 well-defined Austrian EOD patients. Seven patients (12%) carried likely disease-causing variants in monogenic genes, PSEN1, MAPT, APP, and GRN. Five patients (8%) were APOE4 homozygote carriers. Definite and possible risk variants were detected in the genes TREM2, SORL1, ABCA7 and TBK1. In an explorative approach, we cross-checked rare gene variants in our cohort with a curated neurodegeneration candidate gene list and identified DCTN1, MAPK8IP3, LRRK2, VPS13C and BACE1 as promising candidate genes. Conclusively, 12 cases (20%) carried variants relevant to patient counseling, comparable to previously reported studies, and can thus be considered genetically resolved. Reduced penetrance, oligogenic inheritance and not yet identified high-risk genes might explain the high number of unresolved cases. To address this issue, we provide complete genetic and phenotypic information (uploaded to the European Genome-phenome Archive), enabling other researchers to cross-check variants. Thereby, we hope to increase the chance of independently finding the same gene/variant-hit in other well-defined EOD patient cohorts, thus confirming new genetic risk variants or variant combinations.

Analysis of co-medication in people with dementia.

BACKGROUND AND PURPOSE: Dementia prevalence is increasing, with numbers projected to double by 2050. Risk factors for its development include age and cardiovascular comorbidities, which are found more often in patients with dementia and should be treated properly to improve outcomes. In this case-control study, we analysed a large population-based prescription database to explore the patterns of co-medication in patients with dementia. METHODS: Prescription claims covering >99% of the Austrian population from 2005 to 2016 were obtained. Patients who were treated with an approved antidementia drug (ADD) were included and co-medication exposure was recorded. A group of people not taking ADDs was matched for age, sex and follow-up duration as a control. RESULTS: We included 70,799 patients on ADDs who were exposed to a mean of 5.3 co-medications while control patients were treated with a total of 5.2 co-medications (p < 0.001). We found that patients on ADDs received less somatic (4.1 vs. 4.5) but more psychiatric medication (1.1 vs. 0.6; p < 0.001 for both). Patients on ADDs were less likely to be treated for pain, cardiovascular conditions or hyperlipidemia. More than 50% of patients on ADDs were treated with antidepressants or antipsychotics. Greater number of co-medications was associated with markers of more intensive antidementia treatment. CONCLUSION: Patients on ADDs received more medications overall but were less frequently treated for somatic conditions known to be more prevalent in this group. Together, our data suggest that management of comorbidities in dementia could be improved to optimize outcome and quality of life.

C9orf72 repeat length might influence clinical sub-phenotypes in dementia patients.

BACKGROUND: C9orf72 repeat expansions have been observed in a wide variety of neurodegenerative disorders. The cut-off between normal and pathogenic alleles is not well established as repeat sizing methods are often semi-quantitative. However, intermediate alleles might influence disease prevalence and phenotype, as seen for other repeat expansion disorders. We aimed to further delineate the prevalence of small, intermediate and expanded C9orf72 alleles and elucidate their potential influence on the disease phenotype. METHODS: DNA derived from patients (n = 1804) and healthy individuals (n = 643) was obtained from multiple collectives in Austria. Genotyping was performed using a two-step PCR assay followed by Southern blotting. RESULTS: 3.4% of clinically diagnosed frontotemporal dementia (FTD; n = 5/147) cases and 0.8% of clinically diagnosed Alzheimer's disease (AD; n = 5/602) cases were carriers of a pathological C9orf72 repeat expansion. A significantly earlier disease onset was detected in expansion carriers compared to non-carriers in the FTD and AD cohorts (median 50 years, range 39-64 vs. median 64 years, range 36-92, p = 0.018 and median 63 years, range 54-71 vs. median 74 years, range 45-92, p = 0.006, respectively). C9orf72 intermediate alleles were significantly associated with cerebellar symptoms (p = 0.0004) and sensory deficits in the dementia cohort (p = 0.01). CONCLUSIONS: C9orf72 repeat expansion carriers showed earlier disease onset compared to non-carriers with clinical diagnosis of FTD and AD. Furthermore, C9orf72 intermediate repeats might modify the phenotypic expression in dementia.

A case of primary optic pathway demyelination caused by oncocytic oligodendrogliopathy of unknown origin.

We report the case of a 22-year-old woman presenting with an acute onset of dizziness, gait dysbalance and blurred vision. Magnetic resonance imaging included 3 Tesla and 7 Tesla imaging and revealed a T2-hyperintense, T1-hypointense, non-contrast-enhancing lesion strictly confined to the white matter affecting the right optic radiation. An extensive ophthalmologic examination yielded mild quadrantanopia but no signs of optic neuropathy. The lesion was biopsied. The neuropathological evaluation revealed a demyelinating lesion with marked tissue vacuolization and granular myelin disintegration accompanied by mild T cell infiltration and a notable absence of myelin uptake by macrophages. Oligodendrocytes were strikingly enlarged, displaying oncocytic characteristics and showed cytoplasmic accumulation of mitochondria, which had mildly abnormal morphology on electron microscopy. The diagnosis of multiple sclerosis was excluded. Harding's disease, a variant of Leber's hereditary optic neuropathy, was then suspected. However, neither PCR for relevant mutations nor whole exome sequencing yielded known pathogenetic mutations in the patient's genome. We present a pattern of demyelinating tissue injury of unknown etiology with an oncocytic change of oligodendrocytes and a lack of adequate phagocytic response by macrophages, which to the best of our knowledge, has not been described before.

Real-world applicability of glial fibrillary acidic protein and neurofilament light chain in Alzheimer's disease.

Background: Blood-based biomarkers may add a great benefit in detecting the earliest neuropathological changes in patients with Alzheimer's disease (AD). We examined the utility of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) regarding clinical diagnosis and differentiation between amyloid positive and negative patients. To evaluate the practical application of these biomarkers in a routine clinical setting, we conducted this study in a heterogeneous memory-clinic population. Methods: We included 167 patients in this retrospective cross-sectional study, 123 patients with an objective cognitive decline [mild cognitive impairment (MCI) due to AD, n = 63, and AD-dementia, n = 60] and 44 age-matched healthy controls (HC). Cerebrospinal fluid (CSF) and plasma concentrations of NfL and GFAP were measured with single molecule array (SIMOA®) technology using the Neurology 2-Plex B kit from Quanterix. To assess the discriminatory potential of different biomarkers, age- and sex-adjusted receiver operating characteristic (ROC) curves were calculated and the area under the curve (AUC) of each model was compared. Results: We constructed a panel combining plasma NfL and GFAP with known AD risk factors (Combination panel: age+sex+APOE4+GFAP+NfL). With an AUC of 91.6% (95%CI = 0.85-0.98) for HC vs. AD and 81.7% (95%CI = 0.73-0.90) for HC vs. MCI as well as an AUC of 87.5% (95%CI = 0.73-0.96) in terms of predicting amyloid positivity, this panel showed a promising discriminatory power to differentiate these populations. Conclusion: The combination of plasma GFAP and NfL with well-established risk factors discerns amyloid positive from negative patients and could potentially be applied to identify patients who would benefit from a more invasive assessment of amyloid pathology. In the future, improved prediction of amyloid positivity with a noninvasive test may decrease the number and costs of a more invasive or expensive diagnostic approach.

Mortality and Epidemiological Changes in Proximal Hip Fractures in the Course of a Pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had an immense impact on the treatment protocols of orthopedic and trauma departments, yet its specific effect on mortality in patients with hip fractures due to possible surgical delays is still unclear. The purpose of this paper was to investigate whether the COVID-19 pandemic worsened the mortality rate of hip fracture patients. PATIENTS AND METHODS: This study comprised 175 prospectively included patients who (1) suffered from hip fractures, (2) presented during the Austrian state of emergency period from 15 March 2020 to 30 May 2021, and (3) were admitted to a level I trauma center. This cohort was compared with a retrospective control group of 339 patients admitted for hip fractures during the same timeframe in 2017, 2018, and 2019. RESULTS: An admission reduction of 22% in the COVID period compared with the pre-COVID period was evident (p = 0.018). The 30-day mortality rate was 14.67% (pre-COVID) compared with 15.18% (p = 0.381). No differences in surgical complication rates or relationships between comorbidity burden and survival were observed. There were no significant changes in demographic variables, except for admission rate, gender (p = 0.013), and place of accident (p = 0.049). CONCLUSION: Surgeons should be reassured to take COVID-19 precautions, as this study did not show higher perioperative mortality due to COVID-19 measures. Under the current circumstances, with possibly reduced surgical and hospital bed capacities, it is expected that hip fractures may continue to require a high degree of resources.

Prescription patterns of antidementives in a high income country: A pharmacoepidemiologic study.

INTRODUCTION: Dementia is a leading and growing cause of morbidity and mortality. The aim of this study was to investigate real-world prescription patterns of antidementive medication in one of the largest cohorts published thus far to optimize use in this growing population. METHODS: Prescription claims from 2005 to 2016 were provided by Austrian sickness funds, covering 98% of the population of Austria. Patients treated with at least one of the four approved antidementive drugs (ADDs) were included. Prescription prevalence was calculated for 2014 and 2015, and prescription patterns were traced on an individual level during the entire study period. RESULTS: A total of 127,896 patients were treated with an ADD between 2005 and 2016. The prevalence was 0.93% in 2014 and 1% in 2015. The median age at initiation of treatment was 82.3 years, and 65% were female. Initial therapy was a cholinesterase inhibitor (ChEI) in 80% and memantine in 20%. The median duration of therapy was 13.3 months. Eighteen percent of patients switched medication: two thirds to receive memantine, and one third to a different cholinesterase inhibitor. More than 26% discontinued treatment early. CONCLUSION: We find that discontinuation of ADDs is more frequent than switching; memantine is a common starting drug and age at the start of treatment is rather high in this population. Interpretation should be cautious, but the data may suggest that treatment guidelines are followed inconsistently. Appropriate provision of the available options should be emphasized to optimize cognitive survival, comorbidity, quality of life, and health care expenditures.