Seasonal temperatures in West Antarctica during the Holocene.

The recovery of long-term climate proxy records with seasonal resolution is rare because of natural smoothing processes, discontinuities and limitations in measurement resolution. Yet insolation forcing, a primary driver of multimillennial-scale climate change, acts through seasonal variations with direct impacts on seasonal climate1. Whether the sensitivity of seasonal climate to insolation matches theoretical predictions has not been assessed over long timescales. Here, we analyse a continuous record of water-isotope ratios from the West Antarctic Ice Sheet Divide ice core to reveal summer and winter temperature changes through the last 11,000 years. Summer temperatures in West Antarctica increased through the early-to-mid-Holocene, reached a peak 4,100 years ago and then decreased to the present. Climate model simulations show that these variations primarily reflect changes in maximum summer insolation, confirming the general connection between seasonal insolation and warming and demonstrating the importance of insolation intensity rather than seasonally integrated insolation or season duration2,3. Winter temperatures varied less overall, consistent with predictions from insolation forcing, but also fluctuated in the early Holocene, probably owing to changes in meridional heat transport. The magnitudes of summer and winter temperature changes constrain the lowering of the West Antarctic Ice Sheet surface since the early Holocene to less than 162 m and probably less than 58 m, consistent with geological constraints elsewhere in West Antarctica4-7.

Prosocial motives underlie scientific censorship by scientists: A perspective and research agenda.

Science is among humanity's greatest achievements, yet scientific censorship is rarely studied empirically. We explore the social, psychological, and institutional causes and consequences of scientific censorship (defined as actions aimed at obstructing particular scientific ideas from reaching an audience for reasons other than low scientific quality). Popular narratives suggest that scientific censorship is driven by authoritarian officials with dark motives, such as dogmatism and intolerance. Our analysis suggests that scientific censorship is often driven by scientists, who are primarily motivated by self-protection, benevolence toward peer scholars, and prosocial concerns for the well-being of human social groups. This perspective helps explain both recent findings on scientific censorship and recent changes to scientific institutions, such as the use of harm-based criteria to evaluate research. We discuss unknowns surrounding the consequences of censorship and provide recommendations for improving transparency and accountability in scientific decision-making to enable the exploration of these unknowns. The benefits of censorship may sometimes outweigh costs. However, until costs and benefits are examined empirically, scholars on opposing sides of ongoing debates are left to quarrel based on competing values, assumptions, and intuitions.

Progressive Resistance Training or Neuromuscular Exercise for Hip Osteoarthritis : A Multicenter Cluster Randomized Controlled Trial.

BACKGROUND: Exercise is recommended as first-line treatment for patients with hip osteoarthritis (OA). However, randomized controlled trials providing evidence for the optimal exercise type are lacking. OBJECTIVE: To investigate whether progressive resistance training (PRT) is superior to neuromuscular exercise (NEMEX) for improving functional performance in patients with hip OA. DESIGN: Multicenter, cluster-randomized, controlled, parallel-group, assessor-blinded, superiority trial. (ClinicalTrials.gov: NCT04714047). SETTING: Hospitals and physiotherapy clinics. PARTICIPANTS: 160 participants with clinically diagnosed hip OA were enrolled from 18 January 2021 to 28 April 2023 and randomly assigned to PRT (n = 82) or NEMEX (n = 78). INTERVENTION: Twelve weeks of PRT or NEMEX with 2 supervised 60-minute group sessions each week. The PRT intervention consisted of 5 high-intensity resistance training exercises targeting muscles at the hip and knee joints. The NEMEX intervention included 10 exercises and emphasized sensorimotor control and functional stability. MEASUREMENTS: The primary outcome was change in the 30-second chair stand test (30s-CST). Key secondary outcomes were changes in scores on the pain and hip-related quality of life (QoL) subscales of the Hip Disability and Osteoarthritis Outcome Score (HOOS). RESULTS: The mean changes from baseline to 12-week follow-up in the 30s-CST were 1.5 (95% CI, 0.9 to 2.1) chair stands with PRT and 1.5 (CI, 0.9 to 2.1) chair stands with NEMEX (difference, 0.0 [CI, -0.8 to 0.8] chair stands). For the HOOS pain subscale, mean changes were 8.6 (CI, 5.3 to 11.8) points with PRT and 9.3 (CI, 5.9 to 12.6) points with NEMEX (difference, -0.7 [CI, -5.3 to 4.0] points). For the HOOS QoL subscale, mean changes were 8.0 (CI, 4.3 to 11.7) points with PRT and 5.7 (CI, 1.9 to 9.5) points with NEMEX (difference, 2.3 [CI, -3.0 to 7.6] points). LIMITATION: Participants and physiotherapists were not blinded. CONCLUSION: In patients with hip OA, PRT is not superior to NEMEX for improving functional performance, hip pain, or hip-related QoL. PRIMARY FUNDING SOURCE: Independent Research Fund Denmark.

Infant Ustekinumab Clearance, Risk of Infection, and Development After Exposure During Pregnancy.

BACKGROUND: Evidence on ustekinumab safety in pregnancy is gradually expanding, but its clearance in the postnatal period is unknown. The aim of this study was to investigate ustekinumab concentrations in umbilical cord blood and rates of clearance after birth, as well as how these correlate with maternal drug concentrations, risk of infection, and developmental milestones during the first year of life. METHODS: Pregnant women with inflammatory bowel disease were prospectively recruited from 19 hospitals in Denmark and the Netherlands between 2018 and 2022. Infant infections leading to hospitalization/antibiotics and developmental milestones were assessed. Serum ustekinumab concentrations were measured at delivery and specific time points. Nonlinear regression analysis was applied to estimate clearance. RESULTS: In 78 live-born infants from 76 pregnancies, we observed a low risk of adverse pregnancy outcomes and normal developmental milestones. At birth, the median infant-mother ustekinumab ratio was 2.18 (95% confidence interval, 1.69-2.81). Mean time to infant clearance was 6.7 months (95% confidence interval, 6.1-7.3 months). One in 4 infants at 6 months had an extremely low median concentration of 0.015 µg/mL (range 0.005-0.12 µg/mL). No variation in median ustekinumab concentration was noted between infants with (2.8 [range 0.4-6.9] µg/mL) and without (3.1 [range 0.7-11.0] µg/mL) infections during the first year of life (P = .41). CONCLUSIONS: No adverse signals after intrauterine exposure to ustekinumab were observed with respect to pregnancy outcome, infections, or developmental milestones during the first year of life. Infant ustekinumab concentration was not associated with risk of infections. With the ustekinumab clearance profile, live attenuated vaccination from 6 months of age seems of low risk.

Time intervals between pumping did not affect breastmilk protein produced by mothers of preterm infants.

AIM: Few studies investigate factors that might influence the content of expressed breastmilk. This study aims to investigate the influence of the intervals between breastmilk pumping and the time of the day on protein and fat concentration in breastmilk. METHODS: Mothers of very preterm infants in a neonatal ward who expressed more than 400 mL per day were included. Expressed breastmilk was obtained from each mother over 30 h who were pumping at strictly planned and varying intervals: 2, 3, 4 and 6 h. All samples were analysed using infrared transmission spectroscopy. RESULTS: Ten mothers participated at a median of 22 days postpartum. A total of 176 milk samples were analysed, and the average protein and fat concentrations in g/100 mL were 1.1 ± 0.23 and 4.2 ± 1.3, respectively. The time intervals between breast pumping sessions did not impact protein content, but fat content decreased by longer intervals (p < 0.01). The time of the day for milk pumping did not influence the protein or fat content. CONCLUSION: A single milk sample collected after any 2-6 h interval, at any time during the day, represents the protein content in the breastmilk, but not the fat content which decreased with longer intervals.

Preterm children born below 33-35 weeks of gestation have an increased risk of mathematical difficulties.

AIM: To investigate the association between gestational age (GA) and grade point averages by domains of language and mathematics at the end of lower secondary education. METHODS: A nationwide register-based study including all Danish children born in 1992-1997 who completed lower secondary education. Grades were evaluated by GA. Domain-specific differences in grades were investigated, and academic profiles were made. RESULTS: The study population comprised 319 796 children. For language, only minor differences in grades were observed. The grades in mathematics ranged from 7.02 (95% confidence interval [CI]: 7.00-7.04) at GA = 40 weeks to 5.86 (95% CI: 5.61-6.11) at GA <28 weeks. Grade differences showed lower grades in mathematics, compared to language, below GA 33-35 weeks. The academic profile of mathematical difficulties was more prevalent among GA <32 weeks. Average/high grades within both domains represented the predominant academic profile, constituting 68.8% at GA 39-41 weeks and 56.6% at GA <28 weeks. CONCLUSION: Only in mathematics decreasing GA was associated with lower grades. Increased mathematical difficulties were found below GA 33-35 weeks. The academic profile of mathematical difficulties was more prevalent among GA <32 weeks. However, the absolute differences in grades were small, and the predominant academic profile was average/high grades within both domains across all GA.

Enantioselective Single and Dual α-C-H Bond Functionalization of Cyclic Amines via Enzymatic Carbene Transfer.

Cyclic amines are ubiquitous structural motifs found in pharmaceuticals and biologically active natural products, making methods for their elaboration via direct C-H functionalization of considerable synthetic value. Herein, we report the development of an iron-based biocatalytic strategy for enantioselective α-C-H functionalization of pyrrolidines and other saturated N-heterocycles via a carbene transfer reaction with diazoacetone. Currently unreported for organometallic catalysts, this transformation can be accomplished in high yields, high catalytic activity, and high stereoselectivity (up to 99:1 e.r. and 20,350 TON) using engineered variants of cytochrome P450 CYP119 from Sulfolobus solfataricus. This methodology was further extended to enable enantioselective α-C-H functionalization in the presence of ethyl diazoacetate as carbene donor (up to 96:4 e.r. and 18,270 TON), and the two strategies were combined to achieve a one-pot as well as a tandem dual C-H functionalization of a cyclic amine substrate with enzyme-controlled diastereo- and enantiodivergent selectivity. This biocatalytic approach is amenable to gram-scale synthesis and can be applied to drug scaffolds for late-stage C-H functionalization. This work provides an efficient and tunable method for direct asymmetric α-C-H functionalization of saturated N-heterocycles, which should offer new opportunities for the synthesis, discovery, and optimization of bioactive molecules.

Children in Denmark with cerebral palsy rarely complete elementary school.

AIM: To investigate how children with cerebral palsy (CP) perform in the Danish school system and which factors are associated with school performance. METHOD: This was a population-based cohort study including 463 126 children born from 1997 to 2003. Data were extracted from seven national registries. The study encompassed 818 children with CP (483 [59.0%] males, 335 [41.0%] females) and 417 731 without CP (214 535 [51.4%] males, 203 196 [48.6%] females). We evaluated two primary outcomes: not completing 10 years of elementary school, defined as attending fewer than eight final mandatory exams; and grade point averages (GPAs). Mann-Whitney U tests were used to analyse differences in GPAs and logistic regressions were used to calculate odds ratios (ORs). RESULTS: Among children with and without CP, 62.6% and 12.4% did not complete elementary school respectively (OR = 11.85 [10.28-13.66]). Additionally, children with CP who attended all final exams achieved lower overall GPAs than children without CP (6.6 vs 7.3, p = 0.001). In children with CP, comorbidities, maternal education, severity of motor impairments, and intellectual deficits were associated with increased odds of not completing elementary school. Notably, one-third of children with CP with apparent normal intelligence did not complete school, despite special educational measures. INTERPRETATION: Danish children with CP rarely complete elementary school despite initiatives for a more supportive educational system. The complexity of individual needs in children with CP may be challenging for an inclusive school environment. WHAT THIS PAPER ADDS: Children with cerebral palsy (CP) have a high risk of not completing elementary school. Children with CP achieve lower overall grades than children without CP. Motor impairment, comorbidities, and maternal education are associated with poor school performance. Intellectual impairment is the most important predictor of poor school performance.

Rapid reductions and millennial-scale variability in Nordic Seas sea ice cover during abrupt glacial climate changes.

Constraining the past sea ice variability in the Nordic Seas is critical for a comprehensive understanding of the abrupt Dansgaard-Oeschger (D-O) climate changes during the last glacial. Here we present unprecedentedly detailed sea ice proxy evidence from two Norwegian Sea sediment cores and an East Greenland ice core to resolve and constrain sea ice variations during four D-O events between 32 and 41 ka. Our independent sea ice records consistently reveal a millennial-scale variability and threshold response between an extensive seasonal sea ice cover in the Nordic Seas during cold stadials and reduced seasonal sea ice conditions during warmer interstadials. They document substantial and rapid sea ice reductions that may have happened within 250 y or less, concomitant with reinvigoration of deep convection in the Nordic Seas and the abrupt warming transitions in Greenland. Our empirical evidence thus underpins the cardinal role of rapid sea ice decline and related feedbacks to trigger abrupt and large-amplitude climate change of the glacial D-O events.

The effect of gestational age on major neurodevelopmental disorders in preterm infants.

BACKGROUND: Preterm infants have an increased risk of neurodevelopmental disorders. We established a direct quantitative comparison of the association between the degree of prematurity and three different neurodevelopmental disorders. METHODS: In this cohort study, we combined data from 995,498 children in the Danish Medical Birth Register, from birth years 1997-2013, with information on cerebral palsy, epilepsy, and special educational needs. We estimated the gestational week-specific prevalence and risk for each of the disorders. RESULTS: The risk ratio of cerebral palsy at gestational weeks 21-24, compared to term birth, was more than ten times higher than for the two other disorders. The prevalence of epilepsy and special educational needs declined almost parallel, with 9.2% (4.6%-13.5%) and 12.5% (11.2%-13.7%), respectively, per week of gestation toward term birth. Cerebral palsy did not decline similarly: from gestational weeks 21-24 until week 29 the prevalence declined insignificantly by 0.6% (-11.1%-11.0%) per week; whereas from week 29 until term, the prevalence declined markedly by 36.7% (25.9%-45.9%) per week. CONCLUSIONS: The prevalence and risk of cerebral palsy are affected differently by the degree of prematurity compared with epilepsy and special educational needs, possibly reflecting important differences in cerebral pathophysiology. IMPACT: For each week of gestation toward term birth, there was a clear log-linear decline in the prevalence of early childhood epilepsy and special educational needs. In contrast, the risk of cerebral palsy was high at the earliest gestational age, and the prevalence did not decline significantly until gestational week 29, from where it declined notably by nearly 40% for each week of gestation until term birth. Our results indicate important differences in the pathophysiological processes that associate preterm birth with these three neurodevelopmental disorders.

The association between low skeletal muscle mass and delirium: results from the nationwide multi-centre Italian Delirium Day 2017.

INTRODUCTION: Delirium and sarcopenia are common, although underdiagnosed, geriatric syndromes. Several pathological mechanisms can link delirium and low skeletal muscle mass, but few studies have investigated their association. We aimed to investigate (1) the association between delirium and low skeletal muscle mass and (2) the possible role of calf circumference mass in finding cases with delirium. METHODS: The analyses were conducted employing the cross-sectional "Delirium Day" initiative, on patient 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes and hospices in Italy in 2017. Delirium was diagnosed as a 4 + score at the 4-AT scale. Low skeletal muscle mass was operationally defined as calf circumference ≤ 34 cm in males and ≤ 33 cm in females. Logistic regression models were used to investigate the association between low skeletal muscle mass and delirium. The discriminative ability of calf circumference was evaluated using non-parametric ROC analyses. RESULTS: A sample of 1675 patients was analyzed. In total, 73.6% of participants had low skeletal muscle mass and 24.1% exhibited delirium. Low skeletal muscle mass and delirium showed an independent association (OR: 1.50; 95% CI 1.09-2.08). In the subsample of patients without a diagnosis of dementia, the inclusion of calf circumference in a model based on age and sex significantly improved its discriminative accuracy [area under the curve (AUC) 0.69 vs 0.57, p < 0.001]. DISCUSSION AND CONCLUSION: Low muscle mass is independently associated with delirium. In patients without a previous diagnosis of dementia, calf circumference may help to better identify those who develop delirium.

Prediction of ABO hemolytic disease of the newborn using pre- and perinatal quantification of maternal anti-A/anti-B IgG titer.

BACKGROUND: Hemolysis in fetus/newborns is often caused by maternal antibodies. There are currently no established screening procedures for maternal ABO antibodies harmful to fetus/newborn. We investigated the clinical significance, and predictive value of maternal anti-A/B titer for hyperbilirubinemia in ABO-incompatible newborns. METHODS: We conducted a case-control study of blood group O mothers and their ABO-compatible (O) vs. -incompatible (A/B) newborns receiving phototherapy, and of ABO-incompatible newborns receiving phototherapy vs. no phototherapy. Newborn data and treatment modalities were recorded, and total serum bilirubin and hemoglobin were measured. Maternal anti-A/B immunoglobulin-γ (IgG) titers were measured prenatally and perinatally, and negative and positive predictive values (NPV, PPV) were calculated to assess the risk of developing hyperbilirubinemia requiring phototherapy. RESULTS: We found a significantly higher maternal IgG antibody titer in the case group (p < 0.001). Maternal anti-A/B titers at first trimester had modest predictive values: NPV = 0.82 and PPV = 0.65 for neonatal hyperbilirubinemia; titers at birth improved the predictive values: NPV = 0.93 and PPV = 0.73. Newborn hemoglobin was significantly lower in incompatibles compared to compatibles (p = 0.034). Furthermore, increased anti-A/B IgG production during pregnancy was associated with hyperbilirubinemia and hemolysis in incompatible newborns. CONCLUSIONS: There was a significant association between maternal anti-A/B IgG titer and hyperbilirubinemia requiring treatment. IMPACT: Maternal anti-A/B IgG titer in the first trimester and at birth is predictive of hemolytic disease of the ABO-incompatible newborn. Increased IgG anti-A/B production throughout pregnancy in mothers to ABO-incompatible newborns developing hyperbilirubinemia contrasts a constant or reduced production in mothers to newborns not developing hyperbilirubinemia. Screening tools available in most immunohematology laboratories can identify clinically important IgG anti-A/B. Use of maternal samples taken at birth yielded NPV = 0.93 and PPV = 0.73.

Multicentre study found that adherence to national antibiotic recommendations for neonatal early-onset sepsis was low.

AIM: Our aim was to evaluate adherence to the Dutch neonatal early-onset sepsis (EOS) guidelines, adapted from UK guidance. We also looked at the effect on antibiotic recommendations and duration. METHOD: This was a multicentre, prospective observational cross-sectional study carried out in seven hospitals in the Netherlands between 1 September 2018 and 1 November 2019. We enrolled 1024 neonates born at 32 weeks of gestation or later if they demonstrated at least one EOS risk factor or clinical signs of infection. RESULTS: The Dutch guidelines recommended antibiotic treatment for 438/1024 (42.8%) of the neonates designated at risk, but only 186/438 (42.5%) received antibiotics. The guidelines advised withholding antibiotics for 586/1024 (57.2%) of neonates and in 570/586 (97.3%) cases the clinicians adhered to this recommendation. Blood cultures were obtained for 182/186 (97.8%) infants who started antibiotics and only four were positive, for group B streptococci. Antibiotic treatment was continued for more than 3 days in 56/178 (31.5%) neonates, despite a negative blood culture. CONCLUSION: Low adherence to the Dutch guidelines meant that the majority of neonates did not receive the antibiotic treatment that was recommended, while some antibiotic use was prolonged despite negative blood cultures. The guidelines need to be revised.

upd(20)mat is a rare cause of the Silver-Russell-syndrome-like phenotype: Two unrelated cases and screening of large cohorts.

Silver-Russell syndrome (SRS) is an imprinting disorder characterized by prenatal and postnatal growth retardation, relative macrocephaly, feeding difficulties and body asymmetry. Recently, upd(20)mat has been identified in few patients with SRS-like features, suggestive of a new imprinting disorder characterized by prenatal and postnatal growth failure. Here, we describe two male patients with upd(20) and feeding difficulties, prenatal and postnatal growth retardation and normal cognitive development. During pregnancy, confined placental mosaicism for trisomy 20 was detected in one of the patients but was not investigated further until identification of upd(20)mat in the neonatal period. To evaluate whether upd(20)mat should be part of the first trier genetic diagnostic in patients with growth retardation, we screened a large cohort of patients (n = 673) referred to our laboratories for SRS-testing without detecting any upd(20). Our results, along with the existing evidence, indicate that upd(20)mat is a very rare cause of growth retardation, but should be followed up when confined placental mosaicism for trisomy 20 mosaicism is observed during pregnancy.

Declines in Religiosity Predict Increases in Violent Crime-but Not Among Countries With Relatively High Average IQ.

Many scholars have argued that religion reduces violent behavior within human social groups. Here, we tested whether intelligence moderates this relationship. We hypothesized that religion would have greater utility for regulating violent behavior among societies with relatively lower average IQs than among societies with relatively more cognitively gifted citizens. Two studies supported this hypothesis. Study 1, a longitudinal analysis from 1945 to 2010 (with up to 176 countries and 1,046 observations), demonstrated that declines in religiosity were associated with increases in homicide rates-but only in countries with relatively low average IQs. Study 2, a multiverse analysis (171 models) using modern data (97-195 countries) and various controls, consistently confirmed that lower rates of religiosity were more strongly associated with higher homicide rates in countries with lower average IQ. These findings raise questions about how secularization might differentially affect groups of different mean cognitive ability.

Sensitive NMR method for detecting carbohydrate influx into competing chemocatalytic pathways.

Reaction pathways are often tracked with stable isotopes in order to determine the provenance of products in the pathway and to deduce mechanistic information. NMR spectroscopy can provide direct insight into the specific labelling position of the stable isotope. We suggest a simple assay that allows rapid quantitative measurements of isotope distributions in biomass-derived products using commercially available carbohydrate substrates and routine instrumentation. In the assay, biomass-derived products in post reaction material are quantitatively reduced with NaBH4 to install hydrogens at each carbon site in the product. In this manner, the detection of 13C and 12C sites becomes possible in multiplets of the sensitive 2D 1H-1H TOCSY experiment. The approach detects the usage of competing upstream reactions from isotope patterns in chemically identical reaction products. Changing influx into Sn-Beta-catalysed carbohydrate conversion reactions in the absence and in the presence of K+ was quantitatively assessed, showing how the presence of K+ alters the intial reactions towards methyl lactate.

High-sensitivity Troponin T in hemodialysis patients: a randomized placebo-controlled sub-study investigating angiotensin-II-blockade, variation over time and associations with clinical outcome.

BACKGROUND: Troponin T (TnT) is a well-known risk factor for negative outcome in hemodialysis (HD) patients, but little is known about variation over time, and the impact of clinical and dialysis specific factors. This study investigated the effect of angiotensin II receptor blockade (ARB), short and long-term variation in TnT and associations with clinical parameters. METHODS: In this analysis based on the SAFIR-cohort (Clinical Trials ID: NCT00791830) 81 HD patients were randomized double-blind for placebo (n = 40) or angiotensin II receptor blocker (ARB) treatment (n = 41) with irbesartan (150-300 mg) and followed for 12 months with six serial measurements of TnT using a high-sensitivity assay. RESULTS: Fifty-four patients (67%) completed follow-up. Baseline TnT-medians (min-max) were (placebo/ARB): 45(14-295)/46(10-343) ng/L. ARB-treatment did not significantly affect mean TnT-levels over the 12-month study period. Median week-to-week and one-year TnT-variation (5th-95th-percentile range) using all samples regardless of intervention were: 0(- 14-10) ng/L (week-to-week) and 3(- 40-71) ng/L (12 months). Median TnT-amplitude, capturing the change from the lowest to the highest TnT-value observed during the one-year study period was 38% or 20.5 ng/L. Median ratios with 95% limits of agreement were: 1.00(0.73-1.37); P = 0.92 (1 week/baseline; n = 77) and 1.07(0.52-2.25); P = 0.19 (12 months/baseline; n = 54). Baseline TnT was positively correlated with diabetes, ultrafiltration volume, arterial stiffness, change in intradialytic total peripheral resistance and N-terminal pro b-type natriuretic peptide (NT-proBNP) and negatively correlated with hematocrit, residual renal function and change in intradialytic cardiac output. High baseline TnT was associated with a higher risk of admission and cardiovascular (CV) events during follow-up. Increase in TnT over time (ΔTnT = 12-months-baseline) was significantly associated with increase in left ventricular (LV) mass and NT-proBNP and decrease in LV ejection fraction and late intradialytic stroke volume. ΔTnT was not significantly associated with admissions, CV or intradialytic hypotensive events during follow-up. Admissions were significantly more likely with a high (TnT-amplitude> 20.5 ng/L) than a low TnT-amplitude. Peaks in TnT were less frequent in aspirin-treated patients. CONCLUSION: ARB-treatment had no significant effect on TnT-levels. Week-to-week variation was generally low, yet over 12 months individual patients had considerable TnT fluctuations. Rise in TnT over time was significantly correlated with markers of cardiac deterioration. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00791830 . Date of registration: November 17, 2008. EudraCT no: 2008-001267-11.

Implementing interventions to reduce work-related stress among health-care workers: an investment appraisal from the employer's perspective.

PURPOSE: The Stress-Prevention@Work implementation strategy has been demonstrated to be successful in reducing stress in employees. Now, we assess the economic return-on-investment to see if it would make for a favourable business case for employers. METHODS: Data were collected from 303 health-care workers assigned to either a waitlisted control condition (142 employees in 15 teams) or to Stress-Prevention@Work (161 employees in 15 teams). Main outcome was productivity losses measured using the Trimbos and iMTA Cost questionnaire in Psychiatry. Measurements were taken at baseline, 6, and 12 months post-baseline. RESULTS: The per-employee costs of the strategy were €50. Net monetary benefits were the benefits (i.e., improved productivity) minus the costs (i.e., intervention costs) and were the main outcome of this investment appraisal. Per-employee net benefits amounted to €2981 on average, which was an almost 60-fold payout of the initial investment of €50. There was a 96.7% likelihood for the modest investment of €50 to be offset by cost savings within 1 year. Moreover, a net benefit of at least €1000 still has a likelihood of 88.2%. CONCLUSIONS: In general, there was a high likelihood that Stress-Prevention@Work offers an appealing business case from the perspective of employers, but the employer should factor in the additional per-employee costs of the stress-reducing interventions. Still, if these additional costs were as high as €2981, then costs and benefits would break even. This study was registered in the Netherlands National Trial Register, trial code: NTR5527.

Role of comprehensive geriatric assessment in low surgical risk older patients with aortic stenosis.

BACKGROUND: Among elderly with severe aortic stenosis (AS), Comprehensive Geriatric Assessment (CGA) originally contributed to address to transcatheter aortic valve implantation (TAVI) patients not suitable to surgical aortic valve replacement(SAVR). Nevertheless, TAVI has recently been proposed also in lower surgical risk patients. AIMS: To evaluate predictors of TAVI procedure and clinical outcomes among these patients. METHODS: For each patient ≥ 65 years with severe AS referring to our Cardiac Surgery Division, CGA was performed, including functional and cognitive status, comorbidity burden, frailty, nutritional status, gait speed, hand-grip strength and number of medications. Surgical risk was evaluated according to the Society of Thoracic Surgeons (STS) score (low-risk < 4%). Post-procedural outcomes (30-day survival and post-procedural complications) were obtained by medical records and a one-year follow-up assessed survival, and functional and cognitive performance. RESULTS: Among 154 subjects (mean age 82.9 years), 52 were at low-risk according to STS score. 32 patients were addressed to TAVI, 20 to SAVR. Variables significantly associated with TAVI-approach were lower gait speed (p 0.030) and higher number of medications (p 0.015). Short and long-term outcomes did not differ between groups. DISCUSSION: Among CGA variables, gait speed and number of medications were associated with the decision to perform TAVI instead of SAVR, even in patients at low surgical risk. 30-day and one-year survival and one-year functional and cognitive decline were similar between groups, despite a relevant prevalence of frailty in the TAVI group. CONCLUSIONS: We suggest that gait speed and number of medications should be considered in selecting appropriate candidates to TAVI among low surgical risk patients.