Estimated Annual Healthcare Costs After Acute Pulmonary Embolism: Results From a Prospective Multicentre Cohort Study.

OBJECTIVE: Patients surviving acute pulmonary embolism (PE) necessitate long-term treatment and follow-up. However, the chronic economic impact of PE on European healthcare systems remains to be determined. METHODS AND RESULTS: We calculated the direct cost of illness during the first year after discharge for the index PE, analyzing data from a multicentre prospective cohort study in Germany. Main and accompanying readmission diagnoses were used to calculate DRG-based hospital reimbursements; anticoagulation costs were estimated from the exact treatment duration and each drug's unique national identifier; and outpatient post-PE care costs from guidelines-recommended algorithms and national reimbursement catalogues. Of 1017 patients enrolled at 17 centres, 958 (94%) completed ≥ 3-month follow-up; of those, 24% were rehospitalized (0.34 [95% CI 0.30-0.39] readmissions per PE survivor). Age, coronary artery, pulmonary and kidney disease, diabetes, and (in the sensitivity analysis of 837 patients with complete 12-month follow-up) cancer, but not recurrent PE, were independent cost predictors by hurdle gamma regression accounting for zero readmissions. Estimated rehospitalization cost was €1138 (95% CI 896-1420) per patient. Anticoagulation duration was 329 (IQR 142-365) days, with estimated average per-patient costs of €1050 (median 972; IQR 458-1197); costs of scheduled ambulatory follow-up visits amounted to €181. Total estimated direct per-patient costs during the first year after PE ranged from €2369 (primary analysis) to €2542 (sensitivity analysis). CONCLUSIONS: By estimating per-patient costs and identifying cost drivers of post-PE care, our study may inform decisions concerning implementation and reimbursement of follow-up programmes aiming at improved cardiovascular prevention. (Trial registration number: DRKS00005939).

Does an instructional video as a stand-alone tool promote the acquisition of practical clinical skills? A randomised simulation research trial of skills acquisition and short-term retention.

BACKGROUND: The effectiveness of instructional videos as a stand-alone tool for the acquisition of practical skills is yet unknown because instructional videos are usually didactically embedded. Therefore, we evaluated the acquisition of the skill of a humeral intraosseous access via video in comparison to that of a self-study with an additional retention test. METHODS: After ethical approval, we conducted two consecutive studies. Both were designed as randomised controlled two-armed trials with last-year medical students as independent samples at our institutional simulation centre of a tertiary university hospital centre. In Study 1, we randomly assigned 78 participants to two groups: Vid-Self participants watched an instructional video as an intervention, followed by a test, and after seven days did a self-study as a control, followed by a test. Self-Vid ran through the trial in reverse order. In Study 2, we investigated the influence of the sequence of the two teaching methods on learning success in a new sample of 60 participants: Vid-Self watched an instructional video and directly afterward did the self-study followed by a test, whereas Self-Vid ran through that trial in reverse order. In Studies 1 and 2, the primary outcome was the score (worst score = 0, best score = 20) of the test after intervention and control. The secondary outcome in Study 1 was the change in score after seven days. RESULTS: Study 1: The Vid-Self (Participants n = 42) was superior to the Self-Vid (n = 36) (mean score 14.8 vs. 7.7, p < 0.001). After seven days, Self-vid outperformed Vid-Self (mean score 15.9 vs. 12.5, p < 0.001). Study 2: The Vid-Self (n = 30) and Self-Vid (n = 30) scores did not significantly differ (mean 16.5 vs. mean 16.5, p = 0.97). CONCLUSION: An instructional video as a stand-alone tool effectively promotes the acquisition of practical skills. The best results are yielded by a combination of an instructional video and self-study right after each other, irrespective of sequence. TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT05066204 (13/04/2021) (Study 1) and NCT04842357 (04/10/2021) (Study 2).

Sparse Group Penalties for bi-level variable selection.

Many data sets exhibit a natural group structure due to contextual similarities or high correlations of variables, such as lipid markers that are interrelated based on biochemical principles. Knowledge of such groupings can be used through bi-level selection methods to identify relevant feature groups and highlight their predictive members. One of the best known approaches of this kind combines the classical Least Absolute Shrinkage and Selection Operator (LASSO) with the Group LASSO, resulting in the Sparse Group LASSO. We propose the Sparse Group Penalty (SGP) framework, which allows for a flexible combination of different SGL-style shrinkage conditions. Analogous to SGL, we investigated the combination of the Smoothly Clipped Absolute Deviation (SCAD), the Minimax Concave Penalty (MCP) and the Exponential Penalty (EP) with their group versions, resulting in the Sparse Group SCAD, the Sparse Group MCP, and the novel Sparse Group EP (SGE). Those shrinkage operators provide refined control of the effect of group formation on the selection process through a tuning parameter. In simulation studies, SGPs were compared with other bi-level selection methods (Group Bridge, composite MCP, and Group Exponential LASSO) for variable and group selection evaluated with the Matthews correlation coefficient. We demonstrated the advantages of the new SGE in identifying parsimonious models, but also identified scenarios that highlight the limitations of the approach. The performance of the techniques was further investigated in a real-world use case for the selection of regulated lipids in a randomized clinical trial.

Peripheral hypertrophic subepithelial corneal opacification - Role of tear secretion, medication and systemic diseases.

BACKGROUND: Peripheral hypertrophic subepithelial corneal opacification (PHSCO) is a corneal disease that may severely affect vision. The major goal of this study was to test the hypothesis that tear secretion, medication and systemic diseases are associated with PHSCO. METHODS: This is a retrospective, case-control study conducted at the Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz. We analysed medical records of patients diagnosed with PHSCO. Sex, age, Schirmer's test II, general medication and medical history were assessed and compared to an age- and sex-matched control group from the Gutenberg Health Study (GHS). RESULTS: One hundred ninety-five eyes of 112 patients with PHSCO were included. Eighty-eight patients were female with a mean age of 55.3 ± 14.7 years (23-89 years) and 24 patients were male with a mean age of 59.3 ± 12.6 years (38-84 years). In 83 patients (74.1%) both eyes were involved. The Schirmer's test II was significantly reduced in patients with PHSCO compared to the GHS control group (p < 0.001). Patients with PHSCO were more frequently administered artificial tears and steroid eye drops (p < 0.001) and were more hyperopic than healthy controls (p = 0.01). Systemic diseases or medication did not differ markedly between PHSCO and healthy controls. CONCLUSION: Reduced tear secretion and more frequent use of artificial tears in patients with PHSCO suggest a link between PHSCO and dry eye disease. The results of the study do not support our hypothesis that PHSCO is associated with systemic diseases. Interestingly, patients with PHSCO were less frequently on ß-blockers than control subjects.

Clinical parameters and inflammatory biomarkers among patients with multibracket appliances: a prospective clinical trial.

BACKGROUND: Aim of the presented study was to investigate changes in clinical parameters and active matrix metalloproteinase-8 (aMMP-8) levels in gingival crevicular fluid of patients before and during treatment with multibrackets appliances. METHODS: Fifty-five adolescents scheduled for the treatment were included. Clinical parameters and subgingival samples were obtained at six time points: 1 week before appliance insertion (T0), 3 (T1), 6 (T2) weeks, 3 (T3), 6 (T4) months, and 1 year (T5) after that. Gingival index and plaque index were assessed to evaluated changes on the clinical status. Subgingival samples were collected to analyze changes in aMMP-8. RESULTS: Scores for gingival and plaque index increased after bracket insertion. The gingival index increased from T2 (p < 0.05) until T5 (p < 0.0001). Plaque index also increased, reaching its maximum peak at T3 (p < 0.05). Moreover, an increase of aMMP-8 levels (p < 0.05) was noted. There was no significant between upper and lower jaws. CONCLUSIONS: Treatment with multibracket appliances in adolescents favors dental plaque accumulation and may transitionally increase gingival and plaque index and aMMP-8 levels leading to gingival inflammation, even 1 year after therapy began. TRIAL REGISTRATION: This study was approved by the Ethics Committee of the dental medical association Rheiland-Pfalz, Germany (process no. 837.340.12 (8441-F)), and followed the guidelines of Good Clinical Practices.

Awake tracheal intubation in routine airway management: A retrospective analysis in a tertiary centre.

INTRODUCTION: While awake tracheal intubation (ATI) is regarded as the gold standard for difficult airway management according to current guidelines, there seems to be a reluctance in its application. This retrospective cohort study, conducted at a German tertiary hospital over a 2-year period, aimed to demonstrate that integrating awake tracheal intubation using flexible bronchoscopy (ATI:FB) into routine airway management makes it a successful and safe approach. MATERIALS AND METHODS: In 2019 and 2020, records from the data acquisition system (DAQ) and archived anesthesia records were screened to evaluate the specifics of ATI:FB procedures, focusing on overall success and safety. Analysis included complications, time required for ATI:FB, and potential influencing factors such as patient characteristics, indication, medical/operative specialty, sedation technique, route and experience of anesthesiologist. Logistic regression assessed the impact of various variables on occurrence of complications and linear regression, with log(time) as the dependent variable, evaluated median time required to perform ATI:FB. RESULTS: ATI:FB constituted 4.3 % (n = 1,911) of all airway management procedures, predominantly observed in dental, oral, and maxillofacial surgery (46.5 %) and otorhinolaryngology (38.4 %). The success rate for ATI:FB was notably high at 99.6 %, with only 5.4 % of cases experiencing complications, including technical issues, agitation, and visibility obstruction due to mucous secretion. Complication risk was influenced by the medical specialty and the experience of the anesthesiologist. A strong effect was observed in otorhinolaryngology (OR = 4.54, 95 % CI [1.64; 14.06]). The median time required for ATI:FB was 16 minutes (IQR: 11 to 23), with factors such as indication (p < 0.0001), experience of anesthesiologist (p < 0.0001), sedation technique (p = 0.0408), priority of the procedure (p = 0.0134), and medical/operative specialty (p < 0.0001) affecting the duration. The median time required for ATI:FB differed significantly based on the experience of the anesthesiologist (p < 0.0001). CONCLUSION: ATI:FB proves successful and safe, with low complications and manageable procedural time. Experience of the anesthesiologist is a modifiable factor enhancing safety, emphasizing the need for ATI:FB integration into routine airway management.

Interpretability of bi-level variable selection methods.

Variable selection is usually performed to increase interpretability, as sparser models are easier to understand than full models. However, a focus on sparsity is not always suitable, for example, when features are related due to contextual similarities or high correlations. Here, it may be more appropriate to identify groups and their predictive members, a task that can be accomplished with bi-level selection procedures. To investigate whether such techniques lead to increased interpretability, group exponential LASSO (GEL), sparse group LASSO (SGL), composite minimax concave penalty (cMCP), and least absolute shrinkage, and selection operator (LASSO) as reference methods were used to select predictors in time-to-event, regression, and classification tasks in bootstrap samples from a cohort of 1001 patients. Different groupings based on prior knowledge, correlation structure, and random assignment were compared in terms of selection relevance, group consistency, and collinearity tolerance. The results show that bi-level selection methods are superior to LASSO in all criteria. The cMCP demonstrated superiority in selection relevance, while SGL was convincing in group consistency. An all-round capacity was achieved by GEL: the approach jointly selected correlated and content-related predictors while maintaining high selection relevance. This method seems recommendable when variables are grouped, and interpretation is of primary interest.

Ultrafast Brain MRI with Deep Learning Reconstruction for Suspected Acute Ischemic Stroke.

Background Deep learning (DL)-accelerated MRI can substantially reduce examination times. However, studies prospectively evaluating the diagnostic performance of DL-accelerated MRI reconstructions in acute suspected stroke are lacking. Purpose To investigate the interchangeability of DL-accelerated MRI with conventional MRI in patients with suspected acute ischemic stroke at 1.5 T. Materials and Methods In this prospective study, 211 participants with suspected acute stroke underwent clinically indicated MRI at 1.5 T between June 2022 and March 2023. For each participant, conventional MRI (including T1-weighted, T2-weighted, T2*-weighted, T2 fluid-attenuated inversion-recovery, and diffusion-weighted imaging; 14 minutes 18 seconds) and DL-accelerated MRI (same sequences; 3 minutes 4 seconds) were performed. The primary end point was the interchangeability between conventional and DL-accelerated MRI for acute ischemic infarction detection. Secondary end points were interchangeability regarding the affected vascular territory and clinically relevant secondary findings (eg, microbleeds, neoplasm). Three readers evaluated the overall occurrence of acute ischemic stroke, affected vascular territory, clinically relevant secondary findings, overall image quality, and diagnostic confidence. For acute ischemic lesions, size and signal intensities were assessed. The margin for interchangeability was chosen as 5%. For interrater agreement analysis and interrater reliability analysis, multirater Fleiss κ and the intraclass correlation coefficient, respectively, was determined. Results The study sample consisted of 211 participants (mean age, 65 years ± 16 [SD]); 123 male and 88 female). Acute ischemic stroke was confirmed in 79 participants. Interchangeability was demonstrated for all primary and secondary end points. No individual equivalence indexes (IEIs) exceeded the interchangeability margin of 5% (IEI, -0.002 [90% CI: -0.007, 0.004]). Almost perfect interrater agreement was observed (P > .91). DL-accelerated MRI provided higher overall image quality (P < .001) and diagnostic confidence (P < .001). The signal properties of acute ischemic infarctions were similar in both techniques and demonstrated good to excellent interrater reliability (intraclass correlation coefficient, ≥0.8). Conclusion Despite being four times faster, DL-accelerated brain MRI was interchangeable with conventional MRI for acute ischemic lesion detection. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Haller in this issue.

Change of Intraocular Pressure Over 5 Years and its Relationship to Cardiovascular Parameters: Results From the Gutenberg Health Study.

Purpose: To investigate the longitudinal change in intraocular pressure (IOP) over 5 years and its relationship with cardiovascular parameters in a population-based sample in Germany. Methods: The Gutenberg Health Study is a prospective, observational, single-center cohort study. The sample was equally stratified for sex, residence, and age decade. IOP was measured with noncontact tonometry at baseline and at 5-year follow-up. Cardiovascular parameters, including body mass index (BMI), systolic blood pressure, and diabetes status, were assessed. Participants without IOP measurement at one time point, who were taking IOP-lowering medications, or who had ophthalmic surgery during the 5-year follow-up interval were excluded, as well as those with glaucoma diagnosis. Univariable and multivariable linear regression analyses were conducted. Results: This analysis included 9633 participants (48.9% female). The mean IOP increased from 14.04 ± 2.78 mmHg at baseline to 14.77 ± 2.92 mmHg at 5-year follow-up (P < 0.001). In multivariable linear regression analyses, an increase in BMI was associated with an increase in IOP over time (P < 0.001), whereas a higher baseline BMI was associated with a lower IOP change (P < 0.001). Higher age and male sex were associated with higher IOP change (P < 0.001). A change in systolic blood pressure was associated with IOP change, whereas baseline systolic blood pressure and diabetes status were not associated. Conclusions: This population-based study found a relationship between IOP change over 5 years and BMI and systolic blood pressure change, respectively. These findings suggest the importance of monitoring cardiovascular risk factors in IOP management.

Comparison of Ultra-High-Resolution and Normal-Resolution CT-Angiography for Intracranial Aneurysm Detection in Patients with Subarachnoid Hemorrhage.

RATIONALE AND OBJECTIVES: Ruptured intracranial aneurysms (IAs) are the leading cause for atraumatic subarachnoid hemorrhage. In case of aneurysm rupture, patients may face life-threatening complications and require aneurysm occlusion. Detection of the aneurysm in computed tomography (CT) imaging is therefore essential for patient outcome. This study provides an evaluation of the diagnostic accuracy of Ultra-High-Resolution Computed Tomography Angiography (UHR-CTA) and Normal-Resolution Computed Tomography Angiography (NR-CTA) concerning IA detection and characterization. MATERIALS AND METHODS: Consecutive patients with atraumatic subarachnoid hemorrhage who received Digital Subtraction Angiography (DSA) and either UHR-CTA or NR-CTA were retrospectively included. Three readers evaluated CT-Angiography regarding image quality, diagnostic confidence and presence of IAs. Sensitivity and specificity were calculated on patient-level and segment-level with reference standard DSA-imaging. CTA patient radiation exposure (effective dose) was compared. RESULTS: One hundred and eight patients were identified (mean age = 57.8 ±â€¯14.1 years, 65 women). UHR-CTA revealed significantly higher image quality and diagnostic confidence (P < 0.001) for all readers and significantly lower effective dose (P < 0.001). Readers correctly classified ≥55/56 patients on UHR-CTA and ≥44/52 patients on NR-CTA. We noted significantly higher patient-level sensitivity for UHR-CTA compared to NR-CTA for all three readers (reader 1: 41/41 [100%] vs. 28/34 [82%], reader 2: 41/41 [100%] vs. 30/34 [88%], reader 3: 41/41 [100%] vs. 30/34 [88%], P ≤ 0.04). Segment-level analysis also revealed significantly higher sensitivity for UHR-CTA compared to NR-CTA for all three readers (reader 1: 47/49 [96%] vs. 34/45 [76%], reader 2: 47/49 [96%] vs. 37/45 [82%], reader 3: 48/49 [98%] vs. 37/45 [82%], P ≤ 0.04). Specificity was comparable for both techniques. CONCLUSION: We found Ultra-High-Resolution CT-Angiography to provide higher sensitivity than Normal-Resolution CT-Angiography for the detection of intracranial aneurysms in patients with aneurysmal subarachnoid hemorrhage while improving image quality and reducing patient radiation exposure.

Orthodontists' instructions for oral hygiene in patients with removable and fixed orthodontic appliances.

INTRODUCTION: The aim of this questionnaire-based survey was to evaluate information on frequencies, instructions and products relating to oral hygiene (OH) in orthodontic practices. METHODS: Using a computer-generated randomization list, 1000 orthodontists were selected and sent a questionnaire. The size and number of inhabitants of the federal states of Germany were considered. The federal states with the highest return rate (Baden-Wuerttemberg [BW], Bavaria [B], Hesse [H], Lower Saxony [LS], Nordrhein-Westphalia [NRW]) were considered and differences between the 16 federal states were divided into North, South, East and Central Germany. RESULTS: The response rate of the questionnaires was 52.4%. The majority (53.8%) worked in one practice alone. Most (59.1%) have been orthodontists for 5-25 years. For vestibular multibracket appliances (MBA) in BW, B, H and LS over 90% recommended interdental brushes (IDB). In NRW 91.4% recommend fluoride gel. In B and H more than 80% chose electric toothbrush (ETB), in BW, LS and NRW more than 80% manual toothbrush (MTB). For lingual MBA (LMBA) in BW, H, LS and NRW with approximately 50% each fluoride gel, IDB and MTB were chosen. In B fluoride gel, IDB and ETB. For removable apparatus (RA), five federal states recommended MTB (>80%) and ETB (BW, B, H > 80%; NRW > 70%; LS > 60%). CONCLUSION: Electric toothbrushes are recommended for the use with all appliances, only with removable appliances manual toothbrushes are favoured. For vestibular MBA it is strongly advised to use IDB additionally.

Prevalence of Overweight and Obesity, Its Complications, and Progression in a 10-Year Follow-Up in the Gutenberg Health Study (GHS).

INTRODUCTION: Overweight and obesity lead to numerous complications and their treatment. The associated costs represent a health and sociopolitical burden. Therefore, the development of overweight and obesity is of great importance for health policy. METHODS: The Gutenberg Health Study (GHS), a population-based observational study of individuals aged 35-74 years in the city of Mainz and the district of Mainz-Bingen, examined current data on the prevalence and development of overweight and obesity and their association with concomitant diseases and medication use. RESULTS: Among men, 48.1% were overweight and 26.3% had obesity. Among women, these proportions were 32.1% and 24.1%, respectively. Elevated body mass index (BMI) was associated with numerous complications, particularly insulin resistance and type 2 diabetes, arterial hypertension, elevated triglycerides and low HDL cholesterol, and cardiovascular disease. Accordingly, medications to treat these conditions were used significantly more often in individuals with elevated BMI. During the 10-year observation period, mean weight increased in the population. Both men and women had a moderate but significant increase in BMI compared to men and women of the same age at baseline. Individual weight changes over the 10-year observation period, on the other hand, were age-dependent. In the two younger age decades, weight gain was observed, while in the oldest age decade, mean body weight decreased. CONCLUSION: These current data confirm that overweight and obesity are associated with relevant complications and that these complications lead to significant use of appropriate medications. The study also suggests that there is a significant trend toward increased prevalence of obesity (BMI ≥30) over the 10-year period.

Age standardization and time-of-day performance for the Oldenburg Sentence Test (OLSA): results from the population-based Gutenberg Health Study.

PURPOSE: The Oldenburg Sentence Test (OLSA) is a German matrix test designed to determine speech recognition thresholds (SRT). It is widely used for hearing-aids and cochlear implant fitting, but an age-adjusted standard is still lacking. In addition, knowing that the ability to concentrate is an important factor in OLSA performance, we hypothesized that OLSA performance would depend on the time of day it was administered. The aim of this study was to propose an age standardization for the OLSA and to determine its diurnal performance. METHODS: The Gutenberg Health Study is an ongoing population-based study and designed as a single-centre observational, prospective cohort study. Participants were interviewed about common otologic symptoms and tested with pure-tone audiometry and OLSA. Two groups-subjects with and without hearing loss-were established. The OLSA was performed in two runs. The SRT was evaluated for each participant. Results were characterized by age in 5-year cohorts, gender and speech recognition threshold (SRT). A time stamp with an hourly interval was also implemented. RESULTS: The mean OLSA SRT was - 6.9 ± 1.0 dB (group 1 male) and - 7.1 ± 0.8 dB (group 1 female) showing an inverse relationship with age in the whole cohort, whereas a linear increase was observed in those without hearing loss. OLSA-SRT values increased more in males than in females with increasing age. No statistical significance was found for the diurnal performance. CONCLUSIONS: A study with 2900 evaluable Oldenburg Sentence Tests is a novelty and representative for the population of Mainz and its surroundings. We postulate an age- and gender-standardized scale for the evaluation of the OLSA. In fact, with an intergroup standard deviation (of about 1.5 dB) compared to the age dependence of 0.7 dB/10 years, this age normalization should be considered as clinically relevant.

Thyroid surgery in children and adolescents: results from a multi-institutional German and Austrian database.

BACKGROUND: Outcomes of paediatric thyroid surgery have only been reported in smaller series or over long intervals. The aim of this multicentre study was to describe the recent outcomes of paediatric thyroid surgery in Germany and Austria. METHODS: Patients aged less than or equal to 18 years who underwent thyroid surgery and were prospectively documented in the StuDoQ|Thyroid registry between March 2017 and August 2022 were studied. RESULTS: In total, 604 patients from 90 institutions were included. The mean age was 15.4 years and 75 per cent of patients were female. The most frequent benign pathologies were nodular goitre (35.6 per cent), follicular adenoma (30.1 per cent), and Graves' disease (28.5 per cent). Among 126 thyroid malignancies, papillary thyroid carcinoma was diagnosed in 77.8 per cent of patients, follicular thyroid carcinoma was diagnosed in 10.3 per cent of patients, and medullary thyroid carcinoma was diagnosed in 8.7 per cent of patients. Lymph node metastases were found in 45.9 per cent of patients with papillary thyroid carcinoma and in 36.4 per cent of patients with medullary thyroid carcinoma. Vascular invasion was found in 62.9 per cent of patients with follicular thyroid carcinoma. The mean tumour diameters were 18, 42, and 13 mm in patients with papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary thyroid carcinoma respectively. Early postoperative recurrent laryngeal nerve injury was seen in 27 of 556 patients (4.9 per cent) (22 of 617 (3.6 per cent) nerves at risk with intermittent intraoperative nerve monitoring and 5 of 237 (2.1 per cent) nerves at risk with continuous intraoperative nerve monitoring). Persistent recurrent laryngeal nerve injury was documented in 4 of 556 patients (0.7 per cent). Early postoperative hypoparathyroidism correlated with Graves' disease, thyroid carcinoma, and lymph node dissection. CONCLUSION: Papillary thyroid carcinoma and follicular thyroid carcinoma in children were often advanced at presentation. Persistent or recurrent lymph node metastases were mainly seen in papillary thyroid carcinoma. Overall survival was excellent, but longer follow-up is needed.

Long-term mortality in patients with pulmonary embolism: results in a single-center registry.

Background: While numerous studies have investigated short-term outcomes after pulmonary embolism (PE), long-term mortality remains insufficiently studied. Objectives: To investigate long-term outcomes in an unselected cohort of patients with PE. Methods: A total of 896 consecutive patients with PE enrolled in a single-center registry between May 2005 and December 2017 were followed up for up to 14 years. The observed mortality rate was compared with the expected rate in the general population. Results: The total follow-up time was 3908 patient-years (median, 3.1 years). The 1- and 5-year mortality rates were 19.7% (95% CI, 17.2%-22.4%) and 37.1% (95% CI, 33.6%-40.5%), respectively. The most frequent causes of death were cancer (28.5%), PE (19.4%), infections (13.9%), and cardiovascular events (11.6%). Late mortality (after >30 days) was more frequent than expected in the general population, a finding that was consistent in patients without cancer (the 5-year standardized mortality ratios were 2.77 [95% CI, 2.41-3.16] and 1.80 [95% CI, 1.50-2.14], respectively). Active cancer was the strongest risk factor for death between 30 days and 3 years (hazard ratio [HR], 6.51; 95% CI, 4.67-9.08) but was not associated with later mortality. Death after >3 years was predicted by age (HR, 1.86; 95% CI, 1.51-2.29 per decade), chronic heart failure (HR, 1.66; 95% CI, 1.02-2.70), and anemia (HR, 1.62; 95% CI, 1.09-2.41). Conclusion: The risk of mortality in patients with PE remained elevated compared with that in the general population throughout the follow-up period. The main driver of long-term mortality during the first 3 years was cancer. After that, mortality was predicted by age, chronic heart failure, and anemia.

Early warning for SpO2 decrease by the oxygen reserve index in neonates and small infants.

INTRODUCTION: Continuously assessing the oxygenation levels of patients to detect and prevent hypoxemia can be advantageous for safe anesthesia, especially in neonates and small infants. The oxygen reserve index (ORI) is a new parameter that can assess oxygenation through a relationship with arterial oxygen partial pressure (PaO2 ). The aim of this study was to examine whether the ORI provides a clinically relevant warning time for an impending SpO2 (pulse oximetry hemoglobin saturation) reduction in neonates and small infants. METHODS: ORI and SpO2 were measured continuously in infants aged <2 years during general anesthesia. The warning time and sensitivity of different ORI alarms for detecting impending SpO2 decrease were calculated. Subsequently, the agreement of the ORI and PaO2 with blood gas analyses was assessed. RESULTS: The ORI of 100 small infants and neonates with a median age of 9 months (min-max, 0-21 months) and weight of 8.35 kg (min-max, 2-13 kg) were measured. For the ORI/PaO2 correlation, 54 blood gas analyses were performed. The warning time and sensitivity of the preset ORI alarm during the entire duration of anesthesia were 84 s (25th-75th percentile, 56-102 s) and 55% (95% CI 52%-58%), and those during anesthesia induction were 63 s (40-82 s) and 56% (44%-68%), respectively. The positive predictive value of the preset ORI alarm were 18% (95% CI 17%-20%; entire duration of anesthesia) and 27% (95% CI 21%-35%; during anesthesia induction). The agreement of PaO2 intervals with the ORI intervals was poor, with a kappa of 0.00 (95% CI = [-0.18; 0.18]). The weight (p = .0129) and height (p = .0376) of the infants and neonates were correlated to the correct classification of the PaO2 interval with the ORI interval. CONCLUSIONS: The ORI provided an early warning time for detecting an impending SpO2 decrease in small infants and neonates in the defined interval in this study. However, the sensitivity of ORI to forewarn a SpO2 decrease and the agreement of the ORI with PaO2 intervals in this real-life scenario were too poor to recommend the ORI as a useful early warning indicator for this age group.

Randomized multicenter study on the plaque removal efficacy of 2 interdental brushes around the base of orthodontic brackets.

INTRODUCTION: The objective of this multicenter study was to analyze the efficacy of cleaning 2 interdental brushes (IDBs) around brackets in patients with fixed orthodontic appliances. METHODS: The study design was a multicenter, randomized, examiner-blinded crossover study with 3 interventions, the first of which was a baseline intervention. This study included 20 patients (12 females, 8 males) aged 12-18 years with fixed orthodontic devices examined at the Department of Orthodontics, University Medical Center of the Johannes Gutenberg University Mainz, and the Children's Dental Clinic St. Gallen. The outcome was a conventional, cylindrically shaped IDB (IDBG-S [IB]; Top Caredent GmbH, Schönau, Germany) was examined in comparison with an innovative waist-shaped IDB (Circum, CDB-8 [CB]; Top Caredent GmbH). The participants did not use the IDB themselves. The brushing procedure was performed professionally by 1 operator (C.E.). Each buccal tooth surface with a bracket was split into 8 areas, the main areas being 1 and 8. These main areas, which were difficult for toothbrushes to reach, were mesial (area 1) and distal (area 8) of the bracket edges in the gingival direction. Plaque index (PI) scores were assessed at 2 examinations before and after the cleaning procedure on 8 tooth surfaces in the area with orthodontic brackets. A computer-generated program randomly allocated the IDB sequence to the participants. Examiners (L.Z.-G. and Y.W.) assessing the outcomes were blinded to the intervention and the randomized allocation of participants to the different IDBs. RESULTS: Both IDBs showed a plaque removal effect (CB, 0.68 [interquartile range, 0.63-0.77]; IB, 0.43 [interquartile range, 0.33-0.55]). The difference between the 2 IDB was statistically significant (P = 0.002). In particular, the CB yielded a higher plaque removal efficacy (CB effect, 0.68; IB effect, 0.21) at the main areas 1 and 8, which were difficult to reach. Ten participants were randomized to each sequence, and all 20 completed the study. No side effects or adverse events were reported or observed. CONCLUSION: The waist-shaped brush head of the CB significantly enhanced plaque reduction in total and particularly in problem areas. REGISTRATION: This trial was registered at the German Clinical Trials Registry (no. DRKS00014088; https://www.drks.de/drks_web/navigate.xxdo?navigationId=trial.HTML&TRIAL_ID=DRKS00014088) PROTOCOL: The protocol was not published before trial commencement. FUNDING: This study was supported by the manufacturer Top Caredent GmbH, Schönau, Germany, which provided all interdental brushes used in this study.

Validation of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in an academic tertiary care centre.

OBJECTIVES: To assess the sensitivity and specificity of the 2019 EULAR/American College of Rheumatology (ACR) classification criteria for systemic lupus erythematosus (SLE) in outpatients at an academic tertiary care centre and to compare them to the 1997 ACR and the 2012 Systemic Lupus International Collaborating Clinics criteria. METHODS: Prospective and retrospective observational cohort study. RESULTS: 3377 patients were included: 606 with SLE, 1015 with non-SLE autoimmune-mediated rheumatic diseases (ARD) and 1756 with non-ARD diseases (hepatocellular carcinoma, primary biliary cirrhosis, autoimmune hepatitis). The 2019 criteria were more sensitive than the 1997 criteria (87.0% vs 81.8%), but less specific (98.1% vs 99.5% in the entire cohort and 96.5% vs 98.8% in patients with non-SLE ARD), resulting in Youden Indexes for patients with SLE/non-SLE ARD of 0.835 and 0.806, respectively. The most sensitive items were history of antinuclear antibody (ANA) positivity and detection of anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies. These were also the least specific items. The most specific items were class III/IV lupus nephritis and the combination of low C3 and low C4 complement levels, followed by class II/V lupus nephritis, either low C3 or low C4 complement levels, delirium and psychosis, when these were not attributable to non-SLE causes. CONCLUSIONS: In this cohort from an independent academic medical centre, the sensitivity and specificity of the 2019 lupus classification criteria were confirmed. Overall agreement of the 1997 and the 2019 criteria was very good.

Much higher prevalence of keratoconus than announced results of the Gutenberg Health Study (GHS).

Keratoconus appears to be a rare corneal disease with a prevalence previously estimated at 1:2000. The aim of our study was to investigate the prevalence of keratoconus in a large German cohort and to evaluate possible associated factors. METHOD: In the population-based, prospective, monocentric cohort study, Gutenberg Health Study, 12,423 subjects aged 40-80 years were examined at the 5-year follow-up. Subjects underwent a detailed medical history and a general and ophthalmologic examination including Scheimpflug imaging. Keratoconus diagnosis was performed in two steps: all subjects with conspicuous TKC analysis of corneal tomography were included in further grading. Prevalence and 95% confidence intervals were calculated. Logistic regression analysis was carried out to investigate association with age, sex, BMI, thyroid hormone, smoking, diabetes, arterial hypertension, atopy, allergy, steroid use, sleep apnea, asthma, and depression. RESULTS: Of 10,419 subjects, 75 eyes of 51 subjects were classified as having keratoconus. The prevalence for keratoconus in the German cohort was 0.49% (1:204; 95% CI: 0.36-0.64%) and was approximately equally distributed across the age decades. No gender predisposition could be demonstrated. Logistic regression showed no association between keratoconus and age, sex, BMI, thyroid hormone, smoking, diabetes, arterial hypertension, atopy, allergy, steroid use, sleep apnea, asthma, and depression in our sample. CONCLUSION: The prevalence of keratoconus disease in a mainly Caucasian population is approximately tenfold higher than previously reported in the literature using latest technologies (Scheimpflug imaging). Contrary to previous assumptions, we did not find associations with sex, existing atopy, thyroid dysfunction, diabetes, smoking, and depression.

Intraocular Pressure and Its Relation to Climate Parameters-Results From the Gutenberg Health Study.

Purpose: To investigate the association between intraocular pressure (IOP) and climate parameters. Methods: The Gutenberg Health Study (GHS) is a population-based cohort study in Mainz, Germany. Participants underwent two comprehensive ophthalmologic examinations (baseline visit and five-year follow up) including non-contact tonometry, objective refraction, pachymetry, perimetry, and fundus imaging in the time frame of 2007 to 2017. The respective climate parameters were assessed at the University Mainz including temperature, air humidity, and air pressure. Associations of IOP and climatic parameters were computed using component models and cross-correlation plots. Multivariable regression analysis was performed to adjust for age, sex, body mass index, diabetes, central corneal thickness, and systolic blood pressure. To further explore the link between systolic blood pressure, temperature, and IOP, an effect mediation analysis was conducted. Results: A total of 14,632 participants (age 55 ± 11 years at baseline, 49.1% female) were included in this analysis. Mean IOP was 14.24 ± 2.8 mm Hg at baseline. There was a similar periodic change in IOP and in temperature, as shown in the component models. IOP was not associated with air humidity. In univariable and multivariable regression analyses we found a significant association between lower IOP during the summer months with higher air temperature (B = -0.011, P < 0.001). This could be partially explained in mediation analysis by lower systolic blood pressure at higher air temperature. Furthermore, IOP was associated with air pressure in univariable (B = 0.005, P = 0.04.) and multivariable models (B = 0.006, P = 0.03). Conclusions: There is a periodic annual change of IOP with higher values in winter and lower values in summer supporting the hypothesis of an impact of environmental temperature on IOP, which is partly mediated by lower systolic blood pressure in summer.