Self-management including exercise, education and activity modification compared to usual care for adolescents with Osgood-Schlatter (the SOGOOD trial): protocol of a randomized controlled superiority trial.

BACKGROUND: Osgood-Schlatter is the most frequent growth-related injury affecting about 10% of physically active adolescents. It can cause long-term pain and limitations in sports and physical activity, with potential sequela well into adulthood. The management of Osgood-Schlatter is very heterogeneous. Recent systematic reviews have found low level evidence for surgical intervention and injection therapies, and an absence of studies on conservative management. Recently, a novel self-management approach with exercise, education, and activity modification, demonstrated favorable outcomes for adolescents with patellofemoral pain and Osgood-Schlatter in prospective cohort studies. AIM: The aim of this trial is to assess the effectiveness of the novel self-management approach compared to usual care in improving self-reported knee-related function in sport (measured using the KOOS-child 'Sport/play' subscale) after a 5-month period. METHODS: This trial is a pragmatic, assessor-blinded, randomized controlled trial with a two-group parallel arm design, including participants aged 10-16 years diagnosed with Osgood-Schlatter. Participants will receive 3 months of treatment, consisting of either usual care or the self-management approach including exercise, education, and activity modification, followed by 2 months of self-management. Primary endpoint is the KOOS-child 'Sport/play' score at 5 months. This protocol details the planned methods and procedures. DISCUSSION: The novel approach has already shown promise in previous cohort studies. This trial will potentially provide much-needed level 1 evidence for the effectiveness of the self-management approach, representing a crucial step towards addressing the long-term pain and limitations associated with Osgood-Schlatter. TRIAL REGISTRATION: Clinicaltrials.gov: NCT05174182. Prospectively registered December 30th 2021. Date of first recruitment: January 3rd 2022. Target sample size: 130 participants.

Factors Associated With Time to Decannulation in Patients With Tracheostomy Following Severe Traumatic Brain Injury.

BACKGROUND: Prolonged tracheal tube placement following severe traumatic brain injury (TBI) can cause serious complications. Safe removal requires sufficient ability for independent breathing and airway protection. Thus, identifying important factors for time to removal of the tracheal tube (decannulation) is essential for safe and efficient weaning. This study aimed to identify significant factors for time to decannulation in a Danish population of subjects with tracheostomy after TBI. METHODS: This was a retrospective register-based cohort study. Subjects with moderate and severe TBI and a tracheal tube were selected from the Danish Head Trauma Database between 2011-2021. Time to decannulation was calculated as time from injury to decannulation. Associations between selected explanatory variables representing demographic and clinical characteristics and time to decannulation were analyzed using linear regression models. RESULTS: A total 324 subjects were included with a median of 44 d to decannulation. Primary analysis found that an improvement in swallowing ability during the initial 4 weeks of rehabilitation was associated with an 8.2 d reduction in time to decannulation (95% CI -12.3 to -4.2, P < .001). Change in overall sensorimotor ability reduced time to decannulation by 0.94 (95% CI -0.78 to -0.10, P = .03) d. Change in cognitive abilities from rehab admission to 4-week follow-up did not significantly affect the number of days to decannulation (P = .66). Secondary analysis showed pneumonia was associated with the largest estimated increase of 24.4 (95% CI 15.9-32.9, P < .001) d and that increased cognitive functioning at rehabilitation admission was associated with a significant reduction in time to decannulation. CONCLUSIONS: This study found that a change in swallowing ability is a potentially significant factor for reducing time to decannulation. Identifying factors that could explain differences in time to decannulation is essential for patient outcomes, especially if these factors are modifiable and could be targeted in rehabilitation and treatment.

Development and validation of prognostic machine learning models for short- and long-term mortality among acutely admitted patients based on blood tests.

Several scores predicting mortality at the emergency department have been developed. However, all with shortcomings either simple and applicable in a clinical setting, with poor performance, or advanced, with high performance, but clinically difficult to implement. This study aimed to explore if machine learning algorithms could predict all-cause short- and long-term mortality based on the routine blood test collected at admission. METHODS: We analyzed data from a retrospective cohort study, including patients > 18 years admitted to the Emergency Department (ED) of Copenhagen University Hospital Hvidovre, Denmark between November 2013 and March 2017. The primary outcomes were 3-, 10-, 30-, and 365-day mortality after admission. PyCaret, an automated machine learning library, was used to evaluate the predictive performance of fifteen machine learning algorithms using the area under the receiver operating characteristic curve (AUC). RESULTS: Data from 48,841 admissions were analyzed, of these 34,190 (70%) were randomly divided into training data, and 14,651 (30%) were in test data. Eight machine learning algorithms achieved very good to excellent results of AUC on test data in a of range 0.85-0.93. In prediction of short-term mortality, lactate dehydrogenase (LDH), leukocyte counts and differentials, Blood urea nitrogen (BUN) and mean corpuscular hemoglobin concentration (MCHC) were the best predictors, whereas prediction of long-term mortality was favored by age, LDH, soluble urokinase plasminogen activator receptor (suPAR), albumin, and blood urea nitrogen (BUN). CONCLUSION: The findings suggest that measures of biomarkers taken from one blood sample during admission to the ED can identify patients at high risk of short-and long-term mortality following emergency admissions.

Non-adherence, medication beliefs and symptom burden among patients receiving hemodialysis -a cross-sectional study.

BACKGROUND: Non-adherence to medication is a common and complex issue faced by individuals undergoing hemodialysis (HD). However, more knowledge is needed about modifiable factors influence on non-adherence. This study investigated the prevalence of non-adherence, medication beliefs and symptom burden and severity among patients receiving HD in Denmark. Associations between non-adherence, medications beliefs and symptom burden and severity were also explored. METHOD: A cross-sectional questionnaire-based multisite study, including 385 participants. We involved patient research consultants in the study design process and the following instruments were included: Medication Adherence Report Scale, Beliefs about Medication Questionnaire and Dialysis Symptom Index. Logistic regression analysis was performed. RESULTS: The prevalence of non-adherence was 32% (95% CI 27-37%) using a 23-point-cut-off. Just over one third reported being concerned about medication One third also believed physicians to overprescribe medication, which was associated with 18% increased odds of non-adherence. Symptom burden and severity were high, with the most common symptoms being tiredness/ lack of energy, itching, dry mouth, trouble sleeping and difficulties concentrating. A high symptom burden and/or symptom severity score was associated with an increased odd of non-adherence. CONCLUSION: The study found significant associations between non-adherence and, beliefs about overuse, symptom burden and symptom severity. Our results suggest health care professionals (HCP) should prioritize discussion about medication adherence with patients with focus on addressing patient-HCP relationship, and patients' symptom experience. Future research is recommended to explore the effects of systematically using validated adherence measures in clinical practice on medication adherence, patient-HCP communication and trust. Additionally, studies are warranted to further investigate the relationship between symptom experience and adherence in this population. TRIAL REGISTRATION: NCT03897231.

Acceptability of restrictions in the COVID-19 pandemic: a population-based survey in Denmark and Sweden.

Introduction: Denmark and Sweden initially adopted different responses to the COVID-19 pandemic although the two countries share many characteristics. Denmark responded swiftly with many mandatory restrictions. In contrast, Sweden relied on voluntary restrictions and a more "relaxed" response during the first wave of the pandemic. However, increased rates of COVID-19 cases led to a new approach that involved many more mandatory restrictions, thus making Sweden's response similar to Denmark's in the second wave of the pandemic. Aim: The aim was to investigate and compare the extent to which the populations in Denmark and Sweden considered the COVID-19 restrictions to be acceptable during the first two waves of the pandemic. The study also aimed to identify the characteristics of those who were least accepting of the restrictions in the two countries. Materials and methods: Cross-sectional surveys were conducted in Denmark and Sweden in 2021. The study population was sampled from nationally representative web panels in the two countries, consisting of 2,619 individuals from Denmark and 2,633 from Sweden. The questionnaire captured key socio-demographic characteristics. Acceptability was operationalized based on a theoretical framework consisting of seven constructs and one overarching construct. Results: The respondents' age and gender patterns were similar in the two countries. The proportion of respondents in Denmark who agreed with the statements ("agree" alternative) that captured various acceptability constructs was generally higher for the first wave than the second wave of the pandemic. The opposite pattern was seen for Sweden. In Denmark, 66% in the first wave and 50% in the second wave were accepting of the restrictions. The corresponding figures for Sweden was 42% (first wave) and 47% (second wave). Low acceptance of the restrictions, defined as the 25% with the lowest total score on the seven acceptability statements, was associated with younger age, male gender and lower education levels. Conclusion: Respondents in Sweden were more accepting of the restrictions in the second wave, when the country used many mandatory restrictions. In contrast, respondents in Denmark were more accepting of the restrictions in the first wave than in the second wave, implying an increased weariness to comply with the restrictions over time. There were considerable socio-demographic differences between those who expressed low acceptance of the restrictions and the others in both countries, suggesting the importance of tailoring communication about the pandemic to different segments of the population.

No effect of multi-strain probiotic supplementation on metabolic and inflammatory markers and newborn body composition in pregnant women with obesity: Results from a randomized, double-blind placebo-controlled study.

BACKGROUND AND AIMS: Modulation of the gut microbiome composition with probiotics may have beneficial metabolic effects in pregnant women with obesity. The aim was to investigate the effect of probiotic supplementation during pregnancy on metabolic and inflammatory markers and the body composition of the offspring. METHODS AND RESULTS: A randomized double-blind trial in 50 pregnant women (pre-pregnancy BMI ≥30 and < 35 kg/m2) comparing multi-strain probiotics (Vivomixx®; 450 billion CFU/d) versus placebo from 14 to 20 weeks of gestation until delivery was carried out. Participants were followed with two predelivery visits at gestational week 27-30 and 36-37 and with one postdelivery visit. All visits included fasting blood samples (C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin, C-peptide, glucose, glucagon, and glucagon-like peptide-1 (GLP-1)). At delivery, umbilical cord blood samples were collected (GLP-1 and glucagon). At the postdelivery visit, a dual-energy X-ray absorptiometry (DXA) scan of the newborn was performed. Forty-nine of 50 participants completed the study until delivery, and 36 mother-offspring dyads underwent postdelivery examinations including a DXA scan. There were no significant differences in changes in measured biomarkers between the probiotic versus the placebo group. No differences were found in newborn body composition or GLP-1 and glucagon. GLP-1 measured in umbilical blood samples was positively correlated to fat percent in offspring from the probiotic group. CONCLUSION: In this study of pregnant women with obesity and their newborns, there was no effect of probiotic supplementation in mothers or babies on metabolic or inflammatory biomarkers or on body composition of offspring. This study was registered at clinicaltrials.gov as NCT02508844.

Pulmonary telerehabilitation vs. conventional pulmonary rehabilitation - a secondary responder analysis.

Home-based pulmonary telerehabilitation (PTR) has been proposed to be equivalent to supervised outpatient pulmonary rehabilitation (PR) but available randomised trials have failed to reach the minimal important changes (MIC). The purpose of this study was to analyse the proportion of MIC responders and non-responders on short-term (10 weeks from baseline) and long-term (62 weeks from baseline) in total and between groups in 134 patients with COPD randomised (1:1) to either home-based PTR or traditional hospital-based outpatient PR. Difference between PTR and PR on 6MWD response proportion could not be shown at 10 (OR=0.72, CI=0.34 to 1.51, p=0.381) or 62 weeks (OR=1.12, CI=0.40 to 3.14, p=0.834). While the evidence and knowledge of PTR accumulate, outpatient supervised PR for now remains the standard of care, with home-based PTR as a strong secondary option for those unable to attend out-patient programmes.

Performance of Panel-Estimated GFR Among Hospitalized Older Adults.

RATIONALE & OBJECTIVE: Older adults represent nearly half of all hospitalized patients and are vulnerable to inappropriate dosing of medications eliminated through the kidneys. However, few studies in this population have evaluated the performance of equations for estimating the glomerular filtration rate (GFR)-particularly those that incorporate multiple filtration markers. STUDY DESIGN: Cross-sectional diagnostic test substudy of a randomized clinical trial. SETTING & PARTICIPANTS: Adults≥65 years of age presenting to the emergency department of Copenhagen University Hospital Amager and Hvidovre in Hvidovre, Denmark, between October 2018 and April 2021. TESTS COMPARED: Measured GFR (mGFR) determined using 99mTc-DTPA plasma clearance compared with estimated GFR (eGFR) calculated using 6 different equations based on creatinine; 3 based on creatinine and cystatin C combined; and 2 based on panels of markers including creatinine, cystatin C, ß-trace protein (BTP) and/or ß2-microglobulin (B2M). OUTCOME: The performance of each eGFR equation compared with mGFR with respect to bias, relative bias, inaccuracy (1-P30), and root mean squared error (RMSE). RESULTS: We assessed eGFR performance for 106 patients (58% female, median age 78.3 years, median mGFR 62.9mL/min/1.73m2). Among the creatinine-based equations, the 2009 CKD-EPIcr equation yielded the smallest relative bias (+4.2%). Among the creatinine-cystatin C combination equations, the 2021 CKD-EPIcomb equation yielded the smallest relative bias (-3.4%), inaccuracy (3.8%), and RMSE (0.139). Compared with the 2021 CKD-EPIcomb, the CKD-EPIpanel equation yielded a smaller RMSE (0.136) but larger relative bias (-4.0%) and inaccuracy (5.7%). LIMITATIONS: Only White patients were included; only a subset of patients from the original clinical trial underwent GFR measurement; and filtration marker concentration can be affected by subclinical changes in volume status. CONCLUSIONS: The 2009 CKD-EPIcr, 2021 CKD-EPIcomb, and CKD-EPIpanel equations performed best and notably outperformed their respective full-age spectrum equations. The addition of cystatin C to creatinine-based equations improved performance, while the addition of BTP and/or B2M yielded minimal improvement. FUNDING: Grants from public sector industry (Amgros I/S) and government (Capital Region of Denmark). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with registration number NCT03741283. PLAIN-LANGUAGE SUMMARY: Inaccurate kidney function assessment can lead to medication errors, a common cause of hospitalization and early readmission among older adults. Several novel methods have been developed to estimate kidney function based on a panel of kidney function markers that can be measured from a single blood sample. We evaluated the accuracy of these new methods (relative to a gold standard method) among 106 hospitalized older adults. We found that kidney function estimates combining 2 markers (creatinine and cystatin C) were highly accurate and noticeably more accurate than estimates based on creatinine alone. Estimates incorporating additional markers such as ß-trace protein and ß2-microglobulin did not further improve accuracy.

Evaluation of four laboratory-based high-throughput SARS-CoV-2 automated antigen tests compared to RT-PCR on nasal and oropharyngeal samples.

BACKGROUND: The demand for RT-PCR testing has been unprecedented during the SARS-CoV-2 pandemic. Fully automated antigen tests (AAT) are less cumbersome than RT-PCR, but data on performance compared to RT-PCR are scarce. METHODS: The study consists of two parts. A retrospective analytical part, comparing the performance of four different AAT on 100 negative and 204 RT-PCR positive deep oropharyngeal samples divided into four groups based on RT-PCR cycle of quantification levels. In the prospective clinical part, 206 individuals positive for and 199 individuals negative for SARS-CoV-2 were sampled from either the anterior nasal cavity (mid-turbinate) or by deep oropharyngeal swabs or both. The performance of AATs was compared to RT-PCR. RESULTS: The overall analytical sensitivity of the AATs differed significantly from 42% (95% CI 35-49) to 60% (95% CI 53-67) with 100% analytical specificity. Clinical sensitivity of the AATs differed significantly from 26% (95% CI 20-32) to 88% (95% CI 84-93) with significant higher sensitivity for mid-turbinate nasal swabs compared to deep oropharyngeal swabs. Clinical specificity varied from 97% to 100%. CONCLUSION: All AATs were highly specific for detection of SARS-CoV-2. Three of the four AATs were significantly more sensitive than the fourth AAT both in terms of analytical and clinical sensitivity. Anatomical test location significantly influenced the clinical sensitivity of AATs.

Automated Oxygen Administration Alleviates Dyspnea in Patients Admitted with Acute Exacerbation of COPD: A Randomized Controlled Trial.

Objective: Devices for Automated Oxygen Administration (AOA) have been developed to optimize the therapeutic benefit of oxygen supplementation. We aimed to investigate the effect of AOA on multidimensional aspects of dyspnea and as-needed consumption of opioids and benzodiazepines, as opposed to conventional oxygen therapy, in hospitalized patients with Acute Exacerbation of COPD (AECOPD). Method and Patients: A multicenter randomized controlled trial across five respiratory wards in the Capital Region of Denmark. Patients admitted with AECOPD (n=157) were allocated 1:1 to either AOA (O2matic Ltd), a closed loop device automatically delivering oxygen according to the patient's peripheral oxygen saturation (SpO2), or conventional nurse-administered oxygen therapy. Oxygen flows and SpO2 levels were measured by the O2matic device in both groups, while dyspnea, anxiety, depression, and COPD symptoms were accessed by Patient Reported Outcomes. Results: Of the 157 randomized patients, 127 had complete data for the intervention. The AOA reduced patients' perception of overall unpleasantness significantly on the Multidimensional Dyspnea Profile (MDP) with a difference in medians of -3 (p=0.003) between the intervention group (n=64) and the control group (n=63). The AOA also provided a significant between group difference in all single items within the sensory domain of the MDP (all p-values≤0.05) as well as in the Visual Analogue Scale - Dyspnea (VAS-D) within the past three days (p=0.013). All between group differences exceeded the Minimal Clinical Important Difference of the MDP and VAS-D, respectively. AOA did not seem to have an impact on the emotional response domain of the MDP, the COPD Assessment Test, the Hospital Anxiety and Depression Scale, or use of as-needed opioids and/or benzodiazepines (all p-values>0.05). Conclusion: AOA reduces both breathing discomfort and physical perception of dyspnea in patients admitted with AECOPD but did not seem to impact the emotional status or other COPD symptoms.

Clinical outcomes of a short-term family-focused intervention for patients with atrial fibrillation-A randomised clinical trial.

AIMS: To evaluate a family-focused intervention for patients with atrial fibrillation (AF) in addition to conventional care and to establish its effect on health-related quality of life (HRQoL), anxiety, depression, AF symptoms, and family support. BACKGROUND: AF is a widespread heart disease affecting the well-being of patients and their family members physically and psychologically. Supporting patients and their family members could potentially facilitate regaining family strength and improve HRQoL. METHODS: Patients with newly diagnosed AF were randomised to standard care or additional family-focused intervention with change in global score of the Atrial Fibrillation Quality of Life Questionnaire (AFEQT) as primary outcome after six months' follow-up. Secondary outcomes included the Hospital Anxiety and Depression Score, the European Heart Rhythm Association score, the Ice Expressive Family Functioning Questionnaire, and the Ice Family-Perceived Support Questionnaire (ICE-FPSQ). RESULTS: Sixty-eight patients received standard care (n = 35) or family focused intervention (n = 33). The median change at the six-month follow-up on the global AFEQT score was 4.17 (-1.46-9.17) in the control group and 5.83 (-2.5-30) in the intervention group, yielding a median difference of -1.67 (p = 0.500). Change in ICE-FPSQ showed significant positive scores in favour of intervention (p < 0.001); other secondary outcome changes were non-significant. CONCLUSION: The family-focused intervention had a small positive but non-significant effect on HRQoL compared to standard care. To address the impact of AF on the patients and family members seems to improve anxiety and depression scores and perceived family support.

Stratified care in hip arthroscopy: can we predict successful and unsuccessful outcomes? Development and external temporal validation of multivariable prediction models.

OBJECTIVE: Although hip arthroscopy is a widely adopted treatment option for hip-related pain, it is unknown whether preoperative clinical information can be used to assist surgical decision-making to avoid offering surgery to patients with limited potential for a successful outcome. We aimed to develop and validate clinical prediction models to identify patients more likely to have an unsuccessful or successful outcome 1 year post hip arthroscopy based on the patient acceptable symptom state. METHODS: Patient records were extracted from the Danish Hip Arthroscopy Registry (DHAR). A priori, 26 common clinical variables from DHAR were selected as prognostic factors, including demographics, radiographic parameters of hip morphology and self-reported measures. We used 1082 hip arthroscopy patients (surgery performed 25 April 2012 to 4 October 2017) to develop the clinical prediction models based on logistic regression analyses. The development models were internally validated using bootstrapping and shrinkage before temporal external validation was performed using 464 hip arthroscopy patients (surgery performed 5 October 2017 to 13 May 2019). RESULTS: The prediction model for unsuccessful outcomes showed best and acceptable predictive performance on the external validation dataset for all multiple imputations (Nagelkerke R2 range: 0.25-0.26) and calibration (intercept range: -0.10 to -0.11; slope range: 1.06-1.09), and acceptable discrimination (area under the curve range: 0.76-0.77). The prediction model for successful outcomes did not calibrate well, while also showing poor discrimination. CONCLUSION: Common clinical variables including demographics, radiographic parameters of hip morphology and self-reported measures were able to predict the probability of having an unsuccessful outcome 1 year after hip arthroscopy, while the model for successful outcome showed unacceptable accuracy. The externally validated prediction model can be used to support clinical evaluation and shared decision making by informing the orthopaedic surgeon and patient about the risk of an unsuccessful outcome, and thus when surgery may not be appropriate.

How well do nurses know their patients? Agreement between patients' degree-of-worry and nurses' estimation of patients' degree-of-worry-An observational study.

AIM: To assess the agreement between patients' self-reported degree-of-worry (DOW) and nurses' evaluation of patients' DOW. DESIGN: An observational cohort study with patients and their primary nurses. METHODS: Between 22 February and 27 March 2021, data collection among patients and their nurses in an emergency department was carried out. Patients ≥18 years, cognitively intact and Danish or English speaking were eligible to participate. Nurses regardless of seniority and gender were eligible for participation. The single-item degree-of-worry measure, 'how worried are you about the condition you are here today on a scale from 1 to 10, where 1 is minimally worried and 10 is maximum worried' as well as information on gender, age, co-morbidity, triage level and medical reason for encounter was collected from patients. The corresponding nurses were asked; 'how worried do you think your patient is about the condition he/she is there today on a scale from 1 to 10, where 1 is minimally worried and 10 is maximum worried?' Nurses also supplied data on gender, age, seniority as a Registered Nurse and in the ED. Agreement between patients' self-reported degree-of-worry and nurses' evaluation of patients' degree-of-worry was assessed with weighted Cohen's Kappa. RESULTS: A total of 194 patient-nurse pairs were included for analysis. The agreement between patients' DOW and nurses' evaluation of patients' DOW categorised as DOWlow , DOWmiddle and DOWhigh was in total agreement in n = 85 pairs (43.8%) of the ratings, which corresponds to a weighted Cohen's Kappa of 0.19 (0.08-0.30; p < 0.001). CONCLUSION: Nurses estimate of their patients' DOW was in very poor agreement. This indicates that nurses are not able to assess the patient's DOW to a satisfactory level. This result is troubling as it may have serious consequences for patient care as it indicates that the nurses do not know their patients' perspectives.

Achilles tendon gait dynamics after rupture: A three-armed randomized controlled trial comparing an individualized treatment algorithm vs. operative or non-operative treatment.

BACKGROUND: Individual treatment selection has been proposed as the key to optimized treatment. The purpose was to investigate if treatment selection using the individualized treatment algorithm Copenhagen Achilles Rupture Treatment Algorithm (CARTA) differs between patients treated as usual regarding gait dynamics and tendon elongation. METHODS: The patients were randomized to one of three parallel groups: 1) intervention group: participants treated according to CARTA, 2) control group: participants treated non-operatively, 3) control group: participants treated operatively. The primary outcome was ankle peak power during push off during walking at 12 months. RESULTS: 156 patients were assessed for eligibility. 21 were allocated to the intervention group, and 20 and 19 to the control groups. The results indicated no statistically significant differences between the intervention group and the control groups. CONCLUSIONS: Individualized treatment selection based on CARTA did not demonstrate less affected gait dynamics or less tendon elongation than patients treated as usual.

Estimated glomerular filtration rate based on creatinine, cystatin C, ß-trace protein and ß2 microglobulin in patients undergoing nontraumatic lower extremity amputation.

AIMS: The study's aim is to compare current and new equations for estimating glomerular filtration rate (GFR) based on creatinine, cystatin C, ß-trace protein (BTP) and ß2 microglobulin (B2M) among patients undergoing major amputation. METHODS: This is a secondary analysis of data from a prospective cohort study investigating patients undergoing nontraumatic lower extremity amputation. Estimated GFR (eGFR) was calculated using equations based on creatinine (eGFRcre[2009] and eGFRcre[2021]), cystatin C (eGFRcys), the combination of creatinine and cystatin C (eGFRcomb[2012] and eGFRcomb[2021]) or a panel of all 4 filtration markers (eGFRpanel). Primary outcome was changed in eGFR across amputation according to each equation. Two case studies of prior amputation with GFR measured by 99mTc-DTPA clearance are described to illustrate the relative accuracies of each eGFR equation. RESULTS: Analysis of the primary outcome included 29 patients (median age 75 years, 31% female). Amputation was associated with a significant decrease in creatinine concentration (-0.09 mg/dL, P = 0.004), corresponding to a significant increase in eGFRcre[2009] (+6.1 mL/min, P = 0.006) and eGFRcre[2021] (+6.3 mL/min, P = 0.006). Change across amputation was not significant for cystatin C, BTP, B2M or equations incorporating these markers (all P > 0.05). In both case studies, eGFRcre[2021] yielded the largest positive bias, eGFRcys yielded the largest negative bias and eGFRcomb[2012] and eGFRcomb[2021] yielded the smallest absolute bias. CONCLUSION: Creatinine-based estimates were substantially higher than cystatin C-based estimates before amputation and significantly increased across amputation. Estimates combining creatinine and cystatin were stable across amputation, while the addition of BTP and B2M is unlikely to be clinically relevant.

Evaluation of Multi-Frequency Bioelectrical Impedance Analysis against Dual-Energy X-ray Absorptiometry for Estimation of Low Muscle Mass in Older Hospitalized Patients.

The accuracy of multi-frequency (MF) bioelectrical impedance analysis (BIA) to estimate low muscle mass in older hospitalized patients remains unclear. This study aimed to describe the ability of MF-BIA to identify low muscle mass as proposed by The Global Leadership Initiative on Malnutrition (GLIM) and The European Working Group on Sarcopenia in Older People (EWGSOP-2) and examine the association between muscle mass, dehydration, malnutrition, and poor appetite in older hospitalized patients. In this prospective exploratory cohort study, low muscle mass was estimated with MF-BIA against dual-energy X-ray absorptiometry (DXA) in 42 older hospitalized adults (≥65 years). The primary variable for muscle mass was appendicular skeletal muscle mass (ASM), and secondary variables were appendicular skeletal muscle mass index (ASMI) and fat-free mass index (FFMI). Cut-off values for low muscle mass were based on recommendations by GLIM and EWGSOP-2. MF-BIA was evaluated against DXA on the ability to estimate absolute values of muscle mass by mean bias, limits of agreement (LOA), and accuracy (5% and 10% levels). Agreement between MF-BIA and DXA to identify low muscle mass was evaluated with sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). The association between muscle mass, dehydration, malnutrition, and poor appetite was visually examined with boxplots. MF-BIA overestimated absolute values of ASM with a mean bias of 0.63 kg (CI: -0.20:1.46, LOA: -4.61:5.87). Agreement between MF-BIA and DXA measures of ASM showed a sensitivity of 86%, specificity of 94%, PPV of 75% and NPV of 97%. Boxplots indicate that ASM is lower in patients with malnutrition. This was not observed in patients with poor appetite. We observed a tendency toward higher ASM in patients with dehydration. Estimation of absolute ASM values with MF-BIA should be interpreted with caution, but MF-BIA might identify low muscle mass in older hospitalized patients.

Binucleated embryos at the two-cell stage show higher blastocyst formation rates and higher pregnancy and live birth rates compared to non-multinucleated embryos.

STUDY QUESTION: How does nucleus status at the two-cell stage predict blastocysts formation and clinical outcome after single blastocyst transfer? SUMMARY ANSWER: Binucleated embryos at the two-cell stage (2BI) show higher rates of good quality blastocyst formation, pregnancy and live birth compared to those with one nucleus in each blastomere (2MONO), whereas true multinucleated embryos at the two-cell stage (2MULTI) show lower rates of good quality blastocyst formation and pregnancy compared to 2MONO embryos. WHAT IS KNOWN ALREADY: The introduction of time-lapse culture has made it possible to study nucleus status at the two-cell stage more consistently and it shows that multinucleation at the two-cell stage (2MN) is a common event. The effect of 2MN is still unclear. High numbers of 2MN with the potential to develop to blastocysts that become clinical pregnancies and result in birth of healthy babies with no impaired perinatal outcome have been reported. However, some studies have found 2MN to be associated with impaired implantation and live birth. Furthermore, knowledge on how the different subgroups of multinucleation affects the IVF outcome is limited. STUDY DESIGN SIZE DURATION: A non-interventional retrospective study was performed in a public fertility clinic. Blastocyst formation data from 223 women attending their first IVF cycle between May 2016 and December 2018, and clinical outcome data from 1314 single blastocyst transfers between May 2014 and December 2018 were used for the study. Fresh and frozen-thawed embryo transfers were included. PARTICIPANTS/MATERIALS SETTING METHODS: Embryos were cultured until the blastocyst stage in a time-lapse incubator and nucleus status at the two-cell stage, the Gardner score and other morphokinetic parameters were annotated. We compared blastocyst development and clinical outcome, including positive hCG, ongoing pregnancy and live birth, of embryos with 2BI and/or 2MULTI blastomeres to 2MONO embryos. MAIN RESULTS AND THE ROLE OF CHANCE: Embryos with 2BI in one blastomere (2BI1) were twice as likely to develop to good quality blastocysts (odds ratio (OR) 2.54, 95% CI 1.30-4.95, P = 0.006) compared to 2MONO embryos. Embryos with 2MULTI in both blastomeres (2MULTI2) were significantly less able to develop to good quality blastocysts (OR 0.38, 95% CI 0.23-0.63, P < 0.001) compared to 2MONO embryos. Embryos with 2BI in both blastomeres (2BI2) had a significantly better chance of resulting in a positive hCG (OR 2.40, 95% CI 1.11-5.20, P = 0.027), ongoing pregnancy (OR 2.79, 95% CI 1.29-6.04, P = 0.009) and live birth (OR 3.16, 95% CI 1.43-6.95, P = 0.004) compared to 2MONO blastocysts after single blastocyst transfer. In contrast, 2MULTI2 embryos were significantly less likely to result in a positive hCG (OR 0.58, 95% CI 0.35-0.97, P = 0.036) and ongoing pregnancy (OR 0.51, 95% CI 0.28-0.94, P = 0.030) compared to 2MONO blastocysts. LIMITATIONS REASONS FOR CAUTION: Discrepancies among the existing studies regarding the definition of multinucleation may lead to different conclusions. Even though the distinction between binucleation and true multinucleation was a strength in our study design, a further distinction between true multinucleated and micronucleated embryos could be interesting to investigate in future studies. Also, we included any anucleated embryos in the 2MONO group. For the study of clinical outcomes, the patients were allowed to be included with more than one transfer cycle. Both fresh and thawed transfers were included. WIDER IMPLICATIONS OF THE FINDINGS: We find it important to discriminate between binucleation and true multinucleation when evaluating embryo nucleus status at the two-cell stage. Embryos displaying 2BI1 and 2BI2 have significantly better good quality blastocyst formation rates and clinical outcome after single blastocyst transfers, respectively. 2MULTI2 embryos have impaired blastocyst development potential and poorer clinical outcomes. STUDY FUNDING/COMPETING INTERESTS: H.S.N. received an unrestricted grant from Merck for 3 months' normal salary for a medical Doctor (A.L.T.) to write the manuscript. Merck was not involved in the study design, analysis, interpretation of data, writing the paper or the decision to submit the manuscript for publication. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S, Astra Zeneca, Cook Medical and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). The other authors did not report any potential conflicts of interest. All authors declared no conflicts of interest regarding this work. TRIAL REGISTRATION NUMBER: N/A.

Blood flow restriction added to usual care exercise in patients with early weight bearing restrictions after cartilage or meniscus repair in the knee joint: a feasibility study.

PURPOSE: Blood flow restriction - low load strength training (BFR-LLST) is theoretically superior to traditional heavy strength training when rehabilitating patients who cannot heavily load tissues following surgery. The main purpose of this study was to examine the feasibility of BFR-LLST added to usual care exercise early after cartilage or meniscus repair in the knee joint. METHODS: We included 42 patients with cartilage (n = 21) or meniscus repair (n = 21) of the knee joint. They attended 9 weeks of BFR-LLST added to a usual care exercise program at an outpatient rehabilitation center. Outcome measures were assessed at different time points from four (baseline) to 26 weeks postoperatively and included adherence, harms, knee joint and thigh pain, perceived exertion, thigh circumference (muscle size proxy), isometric knee-extension strength, self-reported disability and quality of life. RESULTS: On average, patients with cartilage or meniscus repair completed > 84% of the total BFR-LLST supervised sessions. Thirty-eight patients reported 146 adverse events of which none were considered serious. No decrease in thigh circumference or exacerbation of knee joint or quadriceps muscle pain of the operated leg was found in either group during the intervention period. CONCLUSIONS: BFR-LLST added to usual care exercise initiated early after cartilage or meniscus repair seems feasible and may prevent disuse thigh muscle atrophy during a period of weight bearing restrictions. Harms were reported, but no serious adverse events were found. Our findings are promising but need replication using a RCT-design. TRIAL REGISTRATION: NCT03371901 , preprint (open access):  https://www.medrxiv.org/content/10.1101/2022.03.31.22272398v1.

Mild Cognitive Impairment Is Associated with Poorer Nutritional Status on Hospital Admission and after Discharge in Acutely Hospitalized Older Patients.

In acutely hospitalized older patients (≥65 years), the association between mild cognitive impairment (MCI) and malnutrition is poorly described. We hypothesized that (1) MCI is associated with nutritional status on admission and after discharge; (2) MCI is associated with a change in nutritional status; and (3) a potential association is partly explained by frailty, comorbidity, medication use, and age. We combined data from a randomized controlled trial (control group data) and a prospective cohort study (ClinicalTrials.gov: NCT01964482 and NCT03052192). Nutritional status was assessed on admission and follow-up using the Mini Nutritional Assessment-Short Form. MCI or intact cognition (noMCI) was classified by three cognitive performance tests at follow-up. Data on frailty, comorbidity, medication use, and age were drawn from patient journals. MCI (n = 42) compared to noMCI (n = 47) was associated with poorer nutritional status with an average difference of -1.29 points (CI: -2.30; -0.28) on admission and -1.64 points (CI: -2.57; -0.70) at 4-week follow-up. Only age influenced the estimates of -0.85 (CI: -1.86; 0.17) and -1.29 (CI: -2.25; -0.34), respectively. In acutely hospitalized older patients, there is an association between MCI and poorer nutritional status upon admission and four weeks after discharge. The association is partly explained by higher age.