Genome-Wide DNA Methylation Profiling as a Prognostic Marker in Pituitary Adenomas-A Pilot Study.

BACKGROUND: The prediction of the regrowth potential of pituitary adenomas after surgery is challenging. The genome-wide DNA methylation profiling of pituitary adenomas may separate adenomas into distinct methylation classes corresponding to histology-based subtypes. Specific genes and differentially methylated probes involving regrowth have been proposed, but no study has linked this epigenetic variance with regrowth potential and the clinical heterogeneity of nonfunctioning pituitary adenomas. This study aimed to investigate whether DNA methylation profiling can be useful as a clinical prognostic marker. METHODS: A DNA methylation analysis by Illumina's MethylationEPIC array was performed on 54 pituitary macroadenomas from patients who underwent transsphenoidal surgery during 2007-2017. Twelve patients were excluded due to an incomplete postoperative follow-up, degenerated biobank-stored tissue, or low DNA methylation quality. For the quantitative measurement of the tumor regrowth rate, we conducted a 3D volumetric analysis of tumor remnant volume via annual magnetic resonance imaging. A linear mixed effects model was used to examine whether different DNA methylation clusters had different regrowth patterns. RESULTS: The DNA methylation profiling of 42 tissue samples showed robust DNA methylation clusters, comparable with previous findings. The subgroup of 33 nonfunctioning pituitary adenomas of an SF1-lineage showed five subclusters with an approximately unbiased score of 86%. There were no overall statistically significant differences when comparing hazard ratios for regrowth of 100%, 50%, or 0%. Despite this, plots of correlated survival estimates suggested higher regrowth rates for some clusters. The mixed effects model of accumulated regrowth similarly showed tendencies toward an association between specific DNA methylation clusters and regrowth potential. CONCLUSION: The DNA methylation profiling of nonfunctioning pituitary adenomas may potentially identify adenomas with increased growth and recurrence potential. Larger validation studies are needed to confirm the findings from this explorative pilot study.

Education and Age in Return to Work After Ischemic Stroke: A Danish Nationwide Registry-based Cohort Study.

OBJECTIVES: To investigate return to work and workforce detachment in ischemic stroke, including the association with age and level of education. METHODS: Patients in the workforce aged 18 to 60 with first-time ischemic stroke between 1997 and 2017 were identified in Danish registers and followed for 5 years. The cumulative incidence of return to work and subsequent workforce detachment was computed overall and stratified according to age group and education level. Cox regression analysis was used for multivariate analysis. RESULTS: A total of 28,325 patients were included (median age 52.3 (interquartile range (IQR) 46.1 to 56.6) and 64.3% male). After 1 year, 62.0% were in the workforce, highest in age group 18 to 30 (80.0%) and lowest in patients aged 51 to 60 (58.5%). One-year cumulative incidence of return to work overall was 73.4% (20,475), highest in the young age group (87.0%, 76.7%, 74.5%, and 71.3% for age group 18 to 30, 31 to 40, 41 to 50, and 51 to 60, respectively) and high education (80.3%, 72.1%, and 71.3% for long higher, basic or vocational education, respectively). One-year cumulative incidence of subsequent workforce detachment was 25.6% (5248), lowest in young age (22.4%, 23.1%, 24.1%, and 27.2% for age groups 18 to 30, 31 to 40, 41 to 50, and 51 to 60, respectively) and high level of education (13.0%, 28.4%, and 27.2% for long higher, basic, and vocational education, respectively). During the full follow-up, 10,855 (53.0%) left the workforce again. CONCLUSIONS: A high proportion of patients returned to work within 1 year, but more than half left the workforce again. Young age and long education were associated with a higher incidence of return to work and lower subsequent workforce detachment.

Influence of remote carbamate protective groups on the ß-selectivity in rhamnosylations.

In this work, we present the synthesis of a series of L-thiorhamnosyl donors containing O-carbamate protective groups and the study of their influence on the selectivity in rhamnosylations. It is found that a carbamate on the C-4 position increased the ß selectivity compared with carbamates on the C2 or C3 positions, respectively, and when no carbamate group was installed. In addition it is found that the observed ß selectivity was greater when the 4-O carbamate had less electron withdrawing groups on the nitrogen. The influence of using triflic acid catalysis was studied as well and it was found to lower the ß-selectivity. In addition a new efficient one step synthesis of selectively 2,4-O-benzylated rhamnosides was established using phase transfer catalysis.

Poor socioeconomic outcomes: Completion of the final examination after lower secondary education mitigates risks associated with gestational age.

AIM: To investigate the influence of gestational age (GA) on the association between completion of the final examination after 10-11 years of basic education and education, financial independence and income in early adulthood. METHODS: A nationwide register-based study including individuals born in Denmark between 1990 and 1992. Completion of the examination was evaluated at age 18 and education, financial independence and income at age 28. RESULTS: Of 165 683 individuals included, 15.7%, 10.8% and 5.5% had low educational level, were not financially independent and had low income. For those who completed the examination odds ratio (OR) ranged from 1.03 at GA = 32-36 weeks to 1.25 at ≤27 weeks for low education, from 1.10 to 0.91 for not being financial independent and from 1.06 to 1.48 for low income. For those who did not complete the examination, OR increased from 7.55 at ≥37 weeks to 15.03 at ≤27 weeks for low education and from 4.68 to 15.31 for not being financial independent. For low income, OR was 2.57 and independent of GA. CONCLUSION: For individuals who completed the examination, the odds of poor socioeconomic outcomes were independent of GA. Individuals who did not complete the examination had increased odds of poor socioeconomic outcomes, particularly as GA decreased.

The Influence of Size on the Intracranial Distribution of Biomedical Nanoparticles Administered by Convection-enhanced Delivery in Minipigs.

Because of the blood-brain barrier (BBB), successful drug delivery to the brain has long been a key objective for the medical community, calling for pioneering technologies to overcome this challenge. Convection-enhanced delivery (CED), a form of direct intraparenchymal microinfusion, shows promise but requires optimal infusate design and real-time distribution monitoring. The size of the infused substances appears to be especially critical, with current knowledge being limited. Herein, we examined the intracranial administration of polyethylene glycol (PEG)-coated nanoparticles (NPs) of various sizes using CED in groups of healthy minipigs (n = 3). We employed stealth liposomes (LIPs, 130 nm) and two gold nanoparticle designs (AuNPs) of different diameters (8 and 40 nm). All were labeled with copper-64 for quantitative and real-time monitoring of the infusion via positron emission tomography (PET). NPs were infused via two catheters inserted bilaterally in the putaminal regions of the animals. Our results suggest CED with NPs holds promise for precise brain drug delivery, with larger LIPs exhibiting superior distribution volumes and intracranial retention over smaller AuNPs. PET imaging alongside CED enabled dynamic visualization of the process, target coverage, timely detection of suboptimal infusion, and quantification of distribution volumes and concentration gradients. These findings may augment the therapeutic efficacy of the delivery procedure while mitigating unwarranted side effects associated with nonvisually monitored delivery approaches. This is of vital importance, especially for chronic intermittent infusions through implanted catheters, as this information enables informed decisions for modulating targeted infusion volumes on a catheter-by-catheter, patient-by-patient basis.

Efficient Training of Probabilistic Neural Networks for Survival Analysis.

Variational Inference (VI) is a commonly used technique for approximate Bayesian inference and uncertainty estimation in deep learning models, yet it comes at a computational cost, as it doubles the number of trainable parameters to represent uncertainty. This rapidly becomes challenging in high-dimensional settings and motivates the use of alternative techniques for inference, such as Monte Carlo Dropout (MCD) or Spectral-normalized Neural Gaussian Process (SNGP). However, such methods have seen little adoption in survival analysis, and VI remains the prevalent approach for training probabilistic neural networks. In this paper, we investigate how to train deep probabilistic survival models in large datasets without introducing additional overhead in model complexity. To achieve this, we adopt three probabilistic approaches, namely VI, MCD, and SNGP, and evaluate them in terms of their prediction performance, calibration performance, and model complexity. In the context of probabilistic survival analysis, we investigate whether non-VI techniques can offer comparable or possibly improved prediction performance and uncertainty calibration compared to VI. In the MIMIC-IV dataset, we find that MCD aligns with VI in terms of the concordance index (0.748 vs. 0.743) and mean absolute error (254.9 vs. 254.7) using hinge loss, while providing C-calibrated uncertainty estimates. Moreover, our SNGP implementation provides D-calibrated survival functions in all datasets compared to VI (4/4 vs. 2/4, respectively). Our work encourages the use of techniques alternative to VI for survival analysis in high-dimensional datasets, where computational efficiency and overhead are of concern.

Treatment of Meningiomas Involving the Optic Canal with Endoscopic Transnasal Decompression of the Optic Nerve.

BACKGROUND: Management of patients with optic nerve sheath meningiomas (ONSMs) is controversial and the treatment strategy in this patient group is still up for discussion. Transnasal endoscopic orbital and optic nerve decompression aims to reduce the pressure in the orbit and on the optic nerve and thereby prevent vision loss. This article presents material from 7 cases of transnasal endoscopic orbital decompression. METHODS: The study design is a retrospective cohort study. The aim was to include all patients with a meningioma residing along the nerve sheath and who were operated using endoscopic transnasal decompression of the orbit and if needed the optic canal at Odense University Hospital. Data from the medical records were collected and pre- and postoperative eye examinations were compared. In addition, it was recorded whether there were complications to the procedure and whether additional treatments were given. RESULTS: In total, 4 women and 3 men were included in the study. Four out of 7 patients experienced improvement in vision after the operation. One patient experienced unchanged vision and 2 patients experienced deterioration of vision after surgery. CONCLUSIONS: The current report of 7 patients with ONSM shows promising results for this surgical procedure as 4 out of 7 patients experienced improvement in their vision at follow-up examinations. The 2 patients who experienced deterioration of vision already had severely reduced vision preoperatively, which indicates that surgery should be considered before the vision becomes significantly reduced.

Risk of pharmacological treatment of anxiety and depression after admission for acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Anxiety and depression are very common in patients with COPD and may lead to lower quality of life and higher risk of exacerbations and mortality. This study aimed to examine the incidence of anxiety and depression within one year after admission with acute exacerbation in COPD (AECOPD). The secondary aim was to examine the characteristics of the patients who develop anxiety and depression. METHODS: This retrospective cohort study used the Danish National Patient Registry. Patients aged 40-90 years admitted for COPD between 01.01.99 and 31.12.18 were included. Patients with mental disorders within 10 years before admission were excluded. Age, sex, educational level, inhaled medication, and comorbidities were evaluated. Anxiety or depression were defined by redemption of anxiolytics or antidepressants within one year after admission. RESULTS: We included 97,929 patients. Anxiolytics and antidepressants were redeemed by 4 and 5 % of patients respectively. Higher age, male sex, treatment with short acting ß2-agonists and short acting muscarinic antagonists, cancer and heart failure were positively associated to risk of anxiety or depression, while diabetes and treatment with triple inhalation therapy showed an inverse association. CONCLUSION: Respectively four and five per cent of patients redeemed anxiolytics and antidepressants within the first year after their first severe AECOPD. Several patient characteristics were significantly associated to risk of anxiety or depression. The results from this study support that there is a risk of anxiety and depression after AECOPD in addition to the known risk of preexisting anxiety and depression.

Proarrhythmic drugs, drug levels, and polypharmacy in victims of sudden arrhythmic death syndrome: An autopsy-based study from Denmark.

BACKGROUND: Sudden arrhythmic death syndrome (SADS), characterized by an unknown or inconclusive cause of death at autopsy together with a negative or nonlethal toxicology screening result, is the most common cause of sudden cardiac death in victims younger than 35 years. The complete causality of SADS remains unclear, with drugs being a potential risk factor. OBJECTIVE: This study aimed to describe the toxicologic profiles of SADS victims, focusing on proarrhythmic drugs, drug levels, and polypharmacy. METHODS: All deaths in Denmark of those aged 1-35 years in 2000-2019 and 36-49 years in 2007-2019 were examined through death certificates, national registries, and autopsy reports with toxicology screenings. We investigated all sudden unexpected death victims with an autopsy performed, including negative or nonlethal drug findings, where cause of death was unknown or inconclusive (SADS). RESULTS: We identified 477 SADS victims; 313 (66%) had a positive toxicology screening result (adjudicated nonlethal), with an average of 2.8 drugs per case. More than half of the SADS victims with a positive toxicology screening result had QT-prolonging or brugadogenic drugs present. Polypharmacy was present in 66%, psychotropic polypharmacy in 37%, and QT-prolonging polypharmacy in 22%, with the most frequent overall and QT-prolonging drug combination being an antipsychotic and a psychoanaleptic drug. QT-prolonging drugs were more often present at suprapharmacologic levels than non-QT-prolonging drugs. CONCLUSION: The majority of the SADS population had a positive toxicology screening result, with a notably large proportion having proarrhythmic drugs and polypharmacy. This highlights the need for future focus on drugs as a risk factor for SADS.

Prediction model for future OHCAs based on geospatial and demographic data: An observational study.

This study used demographic data in a novel prediction model to identify areas with high risk of out-of-hospital cardiac arrest (OHCA) in order to target prehospital preparedness. We combined data from the nationwide Danish Cardiac Arrest Registry with geographical- and demographic data on a hectare level. Hectares were classified in a hierarchy according to characteristics and pooled to square kilometers (km2). Historical OHCA incidence of each hectare group was supplemented with a predicted annual risk of at least 1 OHCA to ensure future applicability. We recorded 19,090 valid OHCAs during 2016 to 2019. The mean annual OHCA rate was highest in residential areas with no point of public interest and 100 to 1000 residents per hectare (9.7/year/km2) followed by pedestrian streets with multiple shops (5.8/year/km2), areas with no point of public interest and 50 to 100 residents (5.5/year/km2), and malls with a mean annual incidence per km2 of 4.6. Other high incidence areas were public transport stations, schools and areas without a point of public interest and 10 to 50 residents. These areas combined constitute 1496 km2 annually corresponding to 3.4% of the total area of Denmark and account for 65% of the OHCA incidence. Our prediction model confirms these areas to be of high risk and outperforms simple previous incidence in identifying future risk-sites. Two thirds of out-of-hospital cardiac arrests were identified in only 3.4% of the area of Denmark. This area was easily identified as having multiple residents or having airports, malls, pedestrian shopping streets or schools. This result has important implications for targeted intervention such as automatic defibrillators available to the public. Further, demographic information should be considered when implementing such interventions.

Incidence and Survival of Out-of-Hospital Cardiac Arrest in Public Housing Areas in 3 European Capitals.

BACKGROUND: Strategies to reach out-of-hospital cardiac arrests (called cardiac arrest) in residential areas and reduce disparities in care and outcomes are warranted. This study investigated incidences of cardiac arrests in public housing areas. METHODS: This register-based cohort study included cardiac arrest patients from Amsterdam (the Netherlands) from 2016 to 2021, Copenhagen (Denmark) from 2016 to 2021, and Vienna (Austria) from 2018 to 2021. Using Poisson regression adjusted for spatial correlation and city, we compared cardiac arrest incidence rates (number per square kilometer per year and number per 100 000 inhabitants per year) in public housing and other residential areas and examined the proportion of cardiac arrests within public housing and adjacent areas (100-m radius). RESULTS: Overall, 9152 patients were included of which 3038 (33.2%) cardiac arrests occurred in public housing areas and 2685 (29.3%) in adjacent areas. In Amsterdam, 635/1801 (35.3%) cardiac arrests occurred in public housing areas; in Copenhagen, 1036/3077 (33.7%); and in Vienna, 1367/4274 (32.0%). Public housing areas covered 42.4 (12.6%) of 336.7 km2 and 1 024 470 (24.6%) of 4 164 700 inhabitants. Across the capitals, we observed a lower probability of 30-day survival in public housing versus other residential areas (244/2803 [8.7%] versus 783/5532 [14.2%]). The incidence rates and rate ratio of cardiac arrest in public housing versus other residential areas were incidence rate, 16.5 versus 4.1 n/km2 per year; rate ratio, 3.46 (95% CI, 3.31-3.62) and incidence rate, 56.1 versus 36.8 n/100 000 inhabitants per year; rate ratio, 1.48 (95% CI, 1.42-1.55). The incidence rates and rate ratios in public housing versus other residential areas were consistent across the 3 capitals. CONCLUSIONS: Across 3 European capitals, one-third of cardiac arrests occurred in public housing areas, with an additional third in adjacent areas. Public housing areas exhibited consistently higher cardiac arrest incidences per square kilometer and 100 000 inhabitants and lower survival than other residential areas. Public housing areas could be a key target to improve cardiac arrest survival in countries with a public housing sector.

Association Between Vegetation Size and Outcome in the Partial Oral Antibiotic Endocarditis Treatment Trial.

Step-down oral antibiotic therapy is associated with a non-inferior long-term outcome compared with continued intravenous antibiotic therapy in the treatment of left-sided infective endocarditis. We aimed to analyze whether step-down oral therapy compared with continued intravenous antibiotic therapy is also associated with a non-inferior outcome in patients with large vegetations (vegetation length ≥ 10 mm) or among patients who underwent surgery before step-down oral therapy. We included patients without presence of aortic root abscess at diagnosis from the POET (Partial Oral Antibiotic Endocarditis Treatment) study. Multivariable Cox regression analyses were used to find associations between large vegetation, cardiac surgery, step-down oral therapy, and the primary end point (composite of all-cause mortality, unplanned cardiac surgery, embolic event, or relapse of positive blood cultures during follow-up). A total of 368 patients (age 68 ± 12, 77% men) were included. Patients with large vegetations (n = 124) were more likely to undergo surgery compared with patients with small vegetations (n = 244) (65% vs 20%, p <0.001). During a median 1,406 days of follow-up, 146 patients reached the primary end point. Large vegetations were not associated with the primary end point (hazard ratio 0.74, 95% confidence interval 0.47 to 1.18, p = 0.21). Step-down oral therapy was non-inferior to continued intravenous antibiotic in all subgroups when stratified by the presence of a large vegetation at baseline and early cardiac surgery. Step-down oral therapy is safe in the presence of a large vegetation at diagnosis and among patients who underwent early cardiac surgery.

Cardiomyopathy in First-Degree Relatives of Patients Presenting With Acute Myocarditis: Prevalence and Prognostic Significance.

BACKGROUND: Acute myocarditis has been genetically linked to dilated cardiomyopathy (DCM), but the clinical significance remains uncertain. We investigated the prevalence and long-term prognosis of DCM and heart failure (HF) among unselected patients hospitalized with acute myocarditis and their first-degree relatives compared with an age- and sex-matched cohort. METHODS: This was an observational study utilizing the Danish nationwide registries, where all patients with a first-time myocarditis diagnosis from 1995 to 2018 were identified and matched (on birth year and sex) with 10 controls from the general population. RESULTS: Totally 3176 patients with acute myocarditis and 31 760 controls were included (median age, 49.8 [Q1-Q3, 32.5-70.2] years; 35.6% female). At baseline, patients with myocarditis had a higher prevalence of DCM (7 [0.2%] versus 8 [0.0%]) and HF (336 [10.6%] versus 695 [2.2%]) than controls; P<0.0001 for both. Patients with myocarditis more often had siblings with DCM (12 [0.4%] versus 17 [0.05%]) or HF (36 [1.1%] versus 89 [0.3%]); P<0.0001, odds ratios 7.09 (3.38-14.85) and 2.92 (1.25-6.80), respectively, whereas parental DCM and HF did not differ among patients with myocarditis and controls. Patients with myocarditis had greater 20-year incidence of DCM, HF, and all-cause mortality (0.5% [0.3%-0.9%], 15% [13%-17%], and 47% [44%-50%]) compared with controls (0.06% [0.03%-0.11%], 6.8% [6.4%-7.3%], and 34% [33%-35%]; P<0.0001). Having a first-degree relative with DCM or HF was associated with increased long-term mortality among the patients with myocarditis (hazard ratio, 1.40 [1.11-1.77]) but not among the controls (hazard ratio, 0.90 [0.81-1.01]; Pdifference=0.0008). CONCLUSIONS: Acute myocarditis aggregates with DCM within families, where it carries a worsened prognosis. A differential association between parents and siblings (with sibling preponderance) could suggest that additional environmental factors are important for myocarditis development even in predisposed individuals.

Glucagon-like-peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors and cardiovascular outcomes in diabetes in relation to achieved glycemic control. A Danish nationwide study.

AIM: To compare the cardiovascular preventive effect associated with glucagon-like-peptide-1 receptor agonists (GLP-1 RA) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) according to the achieved target level of glycated hemoglobin (HbA1c). METHODS: We used retrospective Danish registries to include type 2 diabetes patients already in metformin treatment initiating GLP-1 RA or DPP-4i between 2007 and 2021. Patients were included 6 months after GLP-1 RA or DPP-4i initiation. The last available HbA1c measurement before inclusion was collected. The achieved HbA1c level was categorized according to a target level below or above 53 mmol/mol (7%). The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause death. We used a multivariable Cox proportional hazard model to estimate the effect of HbA1c levels on the outcome among GLP-1 RA users compared to DPP-4i users. RESULTS: The study included 13 634 GLP-1 RA users (median age 56.9, interquartile range [IQR]: 48.5-65.5; 53% males) and 39 839 DPP-4i users (median age 63.4, IQR: 54.6-71.8; 61% males). The number of GLP-1 RA and DPP-4i users according to achieved HbA1c levels were as follows: HbA1c ≤ 53 mmol/mol (≤7.0%): 3026 (22%) versus 4824 (12%); HbA1c > 53 mmol/mol (>7.0%): 6577 (48%) versus 17 508 (44%); missing HbA1c: 4031 (30%) versus 17 507 (44%). During a median follow-up of 5 years (IQR: 2.6-5.0), 954 GLP-1 RA users experienced the primary outcome compared to 7093 DPP-4i users. The 5-year risk (95% confidence interval [CI]) of the outcome associated with GLP1-RA versus DPP-4i according to HbA1c categories was as follows: HbA1c ≤ 53 mmol/mol: 10.3% (8.2-12.3) versus 24.3% (22.7-25.8); HbA1c > 53 mmol/mol: 16.0% (14.3-17.6) versus 21.1% (20.3-21.9); missing HbA1c: 17.1% (15.7-18.5) versus 25.6% (24.9-26.3). The preventive effect associated with GLP-1 RA versus DPP-4i was significantly enhanced when achieving lower HbA1c levels: HbA1c ≤ 53 mmol/mol: 0.65 (0.52-0.80); HbA1c > 53 mmol/mol: 0.92 (0.83-1.03); missing HbA1c: 0.92 (0.84-1.02) (p value for interaction <.001). CONCLUSION: GLP-1 RA use was associated with a lower rate of major adverse cardiovascular outcomes. The association was stronger in patients achieving the target glycemic level and weaker in patients not achieving the target glycemic level, suggestive of an interaction between achieved HbA1c level and GLP-1 RA.

Long-Term Cardiovascular Risk Associated With Treatment of Attention-Deficit/Hyperactivity Disorder in Adults.

BACKGROUND: Incrementing numbers of patients treated for attention-deficit/hyperactivity disorder (ADHD) call for scrutiny concerning long-term drug-safety. OBJECTIVES: This study aims to investigate associations between long-term use of ADHD treatment and cardiovascular outcomes. METHODS: Using nationwide registers, adult patients first-time initiated on ADHD treatment between 1998 and 2020 were identified. Exposure groups were prior users, <1 defined daily dose (DDD) per day, ≥1 DDD per day determined at start of follow-up, and 1 year after patients' first claimed prescription. Outcomes were acute coronary syndromes, stroke, heart failure, and a composite of the above. RESULTS: At start of follow-up, 26,357, 31,211, and 15,696 individuals were correspondingly categorized as prior users (42% female, median age: 30 years [Q1-Q3: 23-41 years]), <1 DDD per day (47% female, median age: 31 years [Q1-Q3: 24-41 years]), and ≥1 DDD per day (47% female, median age: 33 years [Q1-Q3: 25-41 years]), respectively. Comparing ≥1 DDD per day with prior users, elevated standardized 10-year absolute risk of stroke (2.1% [95% CI: 1.8%-2.4%] vs 1.7% [95% CI: 1.5%-1.9%]), heart failure (1.2% [95% CI: 0.9%-1.4%] vs 0.7% [95% CI: 0.6%-0.8%]), and the composite outcome (3.9% [95% CI: 3.4%-4.3%] vs 3.0% [95% CI: 2.8 %-3.2%]) was found-with corresponding risk ratios of 1.2 (95% CI: 1.0-1.5), 1.7 (95% CI: 1.3-2.2), and 1.3 (95% CI: 1.1-1.5). No apparent associations were found for acute coronary syndrome (1.0% [95% CI: 0.8%-1.2%] vs 0.9% [95% CI: 0.8%-1.0%]). CONCLUSIONS: Possible associations between elevated long-term cardiovascular risk and increasing dosage of ADHD treatment use in a young patient group should warrant further investigation.

Broadband long-wavelength upconversion in ultra-short nonlinear crystals.

Since the inception of the second-order nonlinear frequency conversion in 1961, enhancing the inherent low conversion efficiency has been a primary objective. This goal has been successfully accomplished through the utilization of cm-long nonlinear crystals characterized by high quality and nonlinearity, coupled with versatile phase-matching strategies and high-power mixing lasers. However, the reliance on lengthy nonlinear crystals and the necessity for precise phase-matching introduce stringent tolerances on acceptance angles and spectral bandwidths for the interacting fields, thereby constraining its widespread applicability in scientific and industrial domains. This challenge is addressed by combining a broadly tunable ∼5 mW quantum cascade laser operating in the 9.5-12.5 µm range with upconversion detection in ∼100 µm long AGS crystals. Using a tightly focused continuous wave Nd:YVO4 laser with 20 mW output power and spatial filtering of the upconverted beam lead to a SNR of 55 for 50 µs averaging time sufficient for many applications.

Idiopathic normal pressure hydrocephalus: Validation of the DESH score as a prognostic tool for shunt surgery response.

OBJECTIVE: Several radiological markers have been linked to clinical improvement after shunt surgery for idiopathic normal pressure hydrocephalus (iNPH). However, iNPH has no pathognomonic feature, and patients are still diagnosed as probable, possible, or unlikely cases based on clinical symptoms, imaging findings, and invasive supplementary tests. The predictive value of the disproportionately enlarged subarachnoid space hydrocephalus (DESH) score is not yet conclusively determined, but it might offer a more accurate diagnostic method. The aim of the present retrospective cohort study was to validate the predictive power of the DESH score for clinical improvement after shunt surgery in iNPH patients. METHODS: We retrospectively obtained presurgical MRI and/or CT scans from 71 patients with iNPH who underwent ventriculoperitoneal shunt surgery. Radiological images were evaluated for Evans index (EI), corpus callosal angle (CA), tight high convexity (THC), Sylvian fissure dilation, and focal sulci dilation. These markers were aggregated to determine the DESH score. Patient journal entries were used to subjectively determine the extent of improvement in gait function, urinary incontinence, and/or cognition as a measure of shunt surgery response. RESULTS: Multiple logistic regression analysis, controlling for age and sex (α = 0.05), showed that DESH score was significantly correlated (OR 1.77) with subjective shunt-surgery response at a minimum of 1-month follow-up. Patients with higher DESH scores were more likely to have a favorable response to shunt surgery. CONCLUSION: Aggregating radiological markers into the DESH score is useful for predicting shunt responders among iNPH patients and can aid the selection of patients for surgery. These findings provide further support for the DESH score as a diagnostic tool for iNPH.

Is General Anesthesia for Peripheral Vascular Surgery Correlated with Impaired Outcome in Patients with Cardiac Comorbidity? A Closer Look into the Nationwide Danish Cohort.

OBJECTIVE: General anesthesia (GA) may impair outcome after vascular surgery. The use of anticoagulant medication is often used in patients with cardiac comorbidity. Regional anesthesia (RA) requires planning of discontinuation before neuraxial blockade(s) in this subgroup. This study aimed to describe the effect of anesthesia choice on outcome after vascular surgery in patients with known cardiac comorbidity. DESIGN: Retrospective cohort study. SETTING: Danish hospitals. PARTICIPANTS: 6302 patients with known cardiac comorbidity, defined as ischemic heart disease, valve disease, pulmonary vascular disease, heart failure, and cardiac arrhythmias, undergoing lower extremity vascular surgery between 2005 and 2017. INTERVENTIONS: GA versus RA. MEASUREMENTS AND MAIN RESULTS: Data were extracted from national registries. GA was defined as anesthesia with mechanical ventilation. Multivariable regression models were used to describe the incidence of postoperative complications as well as 30-day mortality, hypothesizing that better outcomes would be seen after RA. The rate of RA decreased from 48% in 2005 to 20% in 2017. The number of patients with 1 or more complications was 9.7% vs 6.2% (p < 0.001), and 30-day mortality was 6.0% vs 3.4% (p < 0.001) after GA. After adjusting for baseline differences, the odds ratio (OR) was significantly lower for medical complications (cardiac, pulmonary, renal, new dialysis, intensive care unit and other medical complications; OR, 0.97; 95% confidence interval [CI], 0.95-0.98) and 30-day mortality (OR 0.98; 95% CI, 0.97-0.99) after RA. CONCLUSIONS: RA may be associated with a better outcome than GA after lower extremity vascular surgery in patients with a cardiac comorbidity. Prioritizing RA, despite the inconvenience of discontinuing anticoagulants, may be recommended.

Effect of Implantable Cardioverter-defibrillators in Nonischemic Heart Failure According to Background Medical Therapy: Extended Follow-up of the DANISH Trial.

BACKGROUND: The Heart Failure Collaboratory (HFC) score integrates types and dosages of guideline-directed pharmacotherapies for heart failure (HF) with reduced ejection fraction (HFrEF). We examined the effects of cardioverter-defibrillator (ICD) implantation according to the modified HFC (mHFC) score in 1116 patients with nonischemic HFrEF from the Danish Study to Assess the Efficacy of ICDs in Patients with Nonischemic Systolic HF on Mortality (DANISH). METHODS AND RESULTS: Patients were assigned scores for renin-angiotensin-system inhibitors, beta-blockers and mineralocorticoid receptor antagonists (0, no use; 1, < 50% of maximum dosage; 2, ≥ 50% of maximum dosage). The maximum score was 6, corresponding to ≥ 50% of maximum dosage for all therapies. The median baseline mHFC score was 4, and the median follow-up was 9.5 years. Compared with an mHFC score of 3-4, an mHFC score of 1-2 was associated with a higher rate of all-cause death (mHFC = 1-2: adjusted HR 1.67 [95% CI, 1.23-2.28]; mHFC = 3-4, reference; mHFC = 5-6: adjusted HR 1.07 [95% CI, 0.87-1.31]). ICD implantation did not reduce all-cause death compared with control (reference) (HR 0.89 [95% CI, 0.74-1.08]), regardless of mHFC score (mHFC = 1-2: HR 0.98 [95% CI, 0.56-1.71]; mHFC = 3-4: HR 0.89 [95% CI,0.66-1.20]; mHFC = 5-6: HR 0.85 [95% CI, 0.64-1.12]; Pinteraction, 0.65). Similarly, ICD implantation did not reduce cardiovascular death (HR 0.87 [95% CI, 0.70-1.09]), regardless of mHFC score (Pinteraction, 0.59). The ICD group had a lower rate of sudden cardiovascular death (HR, 0.60 [95% CI,0.40-0.92]); this association was not modified by mHFC score (Pinteraction, 0.35). CONCLUSIONS: Lower mHFC scores were associated with higher rates of all-cause death. ICD implantation did not result in an overall survival benefit in patients with nonischemic HFrEF, regardless of mHFC score.