Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19: The HOT-COVID Randomized Clinical Trial.

Importance: Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial. Objective: To assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023. Interventions: Patients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days. Results: Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital. Conclusion and Relevance: In adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg. Trial Registration: ClinicalTrials.gov Identifier: NCT04425031.

Heart rate responses, agreement and accuracy among persons with severe disabilities participating in the indirect movement program: Team Twin-an observational study.

Introduction: Heart rate (HR) monitors are rarely used by people living with disabilities (PLWD), and their accuracy is undocumented. Thus, this study aims to describe the HR response during the Team Twin co-running program and, secondly, to assess the agreement and accuracy of using HR monitors among PLWD. Methods: This 16-week single-arm observational study included 18 people with various disabilities. During the study, the subjects wore a Garmin Vivosmart 4 watch (wrist). To evaluate the agreement and accuracy we applied Garmin's HRM-DUAL™ chest-worn HR monitors for comparison with the Vivosmart 4. The HR response analysis was performed descriptively and with a mixed regression model. The HR agreement and accuracy procedure was conducted on a subsample of five subjects and analyzed using Lin's concordance analysis, Bland and Altman's limits of agreement, and Cohen's kappa analysis of intensity zone agreement. This study was prospectively registered at Clinical Trials.gov (NCT04536779). Results: The subjects had a mean age of 35 (±12.6), 61% were male, 72% had cerebral palsy were 85% had GMFCS V-IV. HR was monitored for 202:10:33 (HH:MM:SS), with a mean HR of 90 ± 17 bpm during training and race. A total of 19% of the time was spent in intensity zones between light and moderate (30%-59% HR reserve) and 1% in vigorous (60%-84% HR reserve). The remaining 80% were in the very light intensity zone (<29% HR reserve). HR was highest at the start of race and training and steadily decreased. Inter-rater agreement was high (k = 0.75), limits of agreement were between -16 and 13 bpm, and accuracy was acceptable (Rc = 0.86). Conclusion: Disability type, individual, and contextual factors will likely affect HR responses and the agreement and accuracy for PLWD. The Vivosmart 4, while overall accurate, had low precision due to high variability in the estimation. These findings implicate the methodical and practical difficulties of utilizing HR monitors to measure HR and thus physical activity in adapted sports activities for severely disabled individuals.

Device-based physical activity measures for population surveillance-issues of selection bias and reactivity.

Background: Device-based measurement in physical activity surveillance is increasing, but research design choices could increase the risk of self-selection bias and reactive behaviour. The aim of this study is to compare the self-reported physical activity profiles of four different samples: participants in a large national survey, participants in a telephone-based survey of non-responders, participants in the large national survey who accepted the invitation to device-based measuring, and the same sample during the week of monitoring. Methods: In October 2020, 163,133 Danish adults participated in a national survey and of those 39,480 signed up for device-based measurements. A balanced random sample (n = 3,750) was invited to wear an accelerometer of whom 1,525 accepted the invitation. Additionally, a short telephone-based survey on 829 non-responders to the national survey was conducted. Sociodemographic characteristics and self-reported weekly frequencies of physical activity across four domains are compared. Results: The participants in the national survey were older, more often female, and more often not working. Participants in the telephone-based survey were younger, more often doing unskilled work, and were more often active at home and at work. The participants in the device-based sample were more often active during transport and leisure in the national survey, and participants categorized in the most active category increased during the week of monitoring from 29.0% to 60.7% and from 58.5% to 81.7% for active transport and leisure activities, respectively. Conclusion: Recruiting a population representative sample for device-based measurement of physical activity is challenging, and there is a substantial risk of sample selection bias and measurement reactivity. Further research in this area is needed if device-based measures should be considered for population physical activity surveillance.

Left ventricular outflow tract velocity-time integral improves outcome prediction in patients with secondary mitral regurgitation.

AIMS: Left ventricular outflow velocity-time integral (LVOT-VTI) has been shown to improve outcome prediction in different patients' subsets, with or without heart failure (HF). Nevertheless, the prognostic value of LVOT-VTI in patients with HF and secondary mitral regurgitation (MR) has never been investigated so far. Therefore, in the present study, we aimed to assess the prognostic value different metrics of LV forward output, including LVOT-VTI, in HF patients with secondary MR. METHODS AND RESULTS: Consecutive patients with HF and moderate-to-severe/severe secondary MR and systolic dysfunction (i.e., left ventricular ejection fraction [LVEF] <50%) were retrospectively selected and followed-up for the primary endpoint of cardiac death. Out of the 287 patients analyzed (aged 74 ± 11 years, 70% men, 46% ischemic etiology, mean LVEF 30 ± 9%, mean LVOT-VTI 20 ± 5 cm), 71 met the primary endpoint over a 33-month median follow-up (16-47 months). Patients with an LVOT-VTI ≤17 cm (n = 96, 32%) showed the greatest risk of cardiac death (Log Rank 44.3, p < 0.001) and all-cause mortality (Log rank 8.6, p = 0.003). At multivariable regression analysis, all the measures of LV forward volume (namely LVOT-VTI, stroke volume index, cardiac output, and cardiac index) were predictors of poor outcomes. Among these, LVOT-VTI was the most accurate in risk prediction (univariable C-statistics 0.70 [95%CI 0.64-0.77]). CONCLUSION: Left ventricular forward output, noninvasively estimated through LVOT-VTI, improves outcome prediction in HF patients with low LVEF and secondary MR.

Trends in social inequality in mortality in Denmark 1995-2019: the contribution of smoking- and alcohol-related deaths.

BACKGROUND: During the past decades, social inequality in mortality has increased in several countries, including Denmark. Modifiable risk factors, such as smoking and harmful alcohol consumption, have been suggested to moderate the association between socioeconomic position and health-related outcomes. The present study aims to investigate the contribution of smoking- and alcohol-related deaths to the trends in educational inequality in mortality in Denmark 1995-2019 among individuals aged 30-74 years. METHODS: Nationwide data on mortality and highest attained educational level divided into quartiles were derived from administrative registers. Alcohol-related mortality was directly estimated using information on alcohol-related deaths from death certificates. Smoking-related mortality was indirectly estimated using the Peto-Lopez method. The contribution of smoking- and alcohol-related deaths to the social inequality gap in mortality 1995-2019 was calculated. RESULTS: Alongside a decrease in all-cause mortality in Denmark 1995-2019, absolute differences in the mortality rate (per 100 000 person-year) between the lowest and the highest educational quartile increased from 494 to 607 among men and from 268 to 376 among women. Among both men and women, smoking- and alcohol-related deaths explained around 60% of the social inequality in mortality and around 50% of the increase in mortality inequality. CONCLUSION: Smoking and harmful alcohol consumption continue to be important risk factors and causes of social inequality in mortality, with around half of the increase in Denmark 1995-2019 being attributable to smoking- and alcohol-related deaths. Future healthcare planning and policy development should aim at reducing social inequality in modifiable health risk behaviours and their negative consequences.

Valve disease in cardiac amyloidosis: an echocardiographic score.

Cardiac amyloidosis (CA) may affect all cardiac structures, including the valves. From 423 patients undergoing a diagnostic workup for CA we selected 2 samples of 20 patients with amyloid transthyretin (ATTR-) or light-chain (AL-) CA, and age- and sex-matched controls. We chose 31 echocardiographic items related to the mitral, aortic and tricuspid valves, giving a value of 1 to each abnormal item. Patients with ATTR-CA displayed more often a shortened/hidden and restricted posterior mitral valve leaflet (PMVL), thickened mitral chordae tendineae and aortic stenosis than those with AL-CA, and less frequent PMVL calcification than matched controls. Score values were 15.8 (13.6-17.4) in ATTR-CA, 11.0 (9.3-14.9) in AL-CA, 12.8 (11.1-14.4) in ATTR-CA controls, and 11.0 (9.1-13.0) in AL-CA controls (p = 0.004 for ATTR- vs. AL-CA, 0.009 for ATTR-CA vs. their controls, and 0.461 for AL-CA vs. controls). Area under the curve values to diagnose ATTR-CA were 0.782 in patients with ATTR-CA or matched controls, and 0.773 in patients with LV hypertrophy. Patients with ATTR-CA have a prominent impairment of mitral valve structure and function, and higher score values. The valve score may help identify patients with ATTR-CA among patients with CA or unexplained hypertrophy.

Are changes in physical activity during COVID-19 associated with mental health among Danish university students?

Aims: The benefits associated with being physical active on mental health is well-established, but little is known on how rapid changes in physical activity are associated with mental health. This study investigated the association between changes in physical activity and mental health among Danish university students during the first COVID-19 lockdown. Methods: Online survey data were collected among 2,280 university students at the University of Southern Denmark and University of Copenhagen in May-June 2020 as part the "COVID-19 International Student Well-being Study." Multiple linear regressions were used to analyze associations between changes in physical activity and mental health (depression and stress scores) adjusted for potential socio-economic confounders. Results: During the first COVID-19 lockdown, 40% decreased their moderate and 44% their vigorous physical activity, while 16% increased their moderate and 13% their vigorous physical activity. Overall, students with a stable physical activity level had the lowest mean depressive and stress scores. Adjusted analyses showed that a decrease in vigorous and moderate physical activity level was significantly associated with a higher depression score (mean difference (vigorous): 1.36, p < 0.001 and mean difference (moderate): 1.55, p < 0.001). A decrease in vigorous physical activity and an increase in moderate physical activity was associated with a 1-point increase in the PSS-4 stress score (p < 0.001). Conclusion: A substantial proportion of students changed their physical activity level during lockdown. Our findings emphasize the importance of staying physically active during COVID-19 lockdown. This knowledge might be important for relevant health authorities to bridle post-pandemic mental health challenges.

The development of a health-promoting employment intervention with physical activity for young people Not in Education, Employment or Training (NEET): NEXT STEP-on the path to education and job.

BACKGROUND: In the EU, approx. 16.5% of the 20-34-year-olds are Not in Education, Employment or Training (NEET). Research shows that good health is an important progression factor towards employment, and daily physical activity as well as participation in sports has a positive effect on physical and mental health as well as in the development of life skill. However, there is an absence of studies investigating what role physical activity can play in the employment efforts. The aim of this study is to investigate experiences with physical activity in employment interventions and to describe the development of a health-promoting employment intervention with physical activity for young people aged 18-30 years who are NEET. METHODS: The study combined an evidence-based approach with practice-based experiences. It included a Mapping of Danish employment interventions with physical activity for young people NEET, an overview of national reports and international literature, a workshop with leaders and employees from Danish municipalities, and fieldwork in four municipalities. Key findings were grouped thematically and were transformed into intervention content in a close dialog with relevant researchers and practitioners. RESULTS: In general, physical activity was assessed as a meaningful method when working with young people NEET. A range of positive experiences was highlighted, including successful experiences, surplus of mental resources, new ways of meeting, and new social relations. Based on these findings, a 16-week health-promoting employment intervention, NEXT STEP, was developed with the following intervention components: (1) fixed boundaries, (2) body and physical activity, (3) social relations and network, and (4) life skills and future. NEXT STEP is designed to be implemented in Danish job centers. CONCLUSION: The study found the great potential of including physical activity in employment interventions for young people NEET. The planning and development of the intervention have reinforced a comprehensive evaluation; however, the first intervention in its entirety is ready for testing in a randomized feasibility trial.

[Lichen sclerosus in women].

This review investigates women suffering from chronic vulval pruritus who may suffer from lichen sclerosus (LS). LS is a chronic inflammatory skin condition involving the vulva and anogenital regions. Treatment may be initiated upon suspicion, although the diagnosis is predominantly clinical and at times a skin biopsy is needed to confirm the diagnosis. LS is treated with potent to very potent topical steroids initially for three months. Prophylactic lifelong treatment is recommended to avoid long term scarring, sexual dysfunction, improve quality of life and to prevent cancer. Mild cases can be managed in general practice.

Investigation of an Enterobacter hormaechei OXA-436 carbapenemase outbreak: when everything goes down the drain.

Over a time period of 18 months an Enterobacter hormaechei sequence type (ST) 90, harboring a bla OXA-436 carbapenemase gene, was isolated from seven patients at Odense University Hospital, Denmark. The patients were all from the same department, but there was no apparent direct epidemiological link. Whole genome sequencing (WGS) was performed on all clinical isolates as well as on a number of environmental samples including two E. hormaechei ST90 isolates carrying the bla OXA-436 gene, which were isolated in samples from two shower drains at the department. These drains were suspected to be the source of the outbreak.

Non-Invasive Estimation of Right Atrial Pressure Using a Semi-Automated Echocardiographic Tool for Inferior Vena Cava Edge-Tracking.

The non-invasive estimation of right atrial pressure (RAP) would be a key advancement in several clinical scenarios, in which the knowledge of central venous filling pressure is vital for patients' management. The echocardiographic estimation of RAP proposed by Guidelines, based on inferior vena cava (IVC) size and respirophasic collapsibility, is exposed to operator and patient dependent variability. We propose novel methods, based on semi-automated edge-tracking of IVC size and cardiac collapsibility (cardiac caval index­CCI), tested in a monocentric retrospective cohort of patients undergoing echocardiography and right heart catheterization (RHC) within 24 h in condition of clinical and therapeutic stability (170 patients, age 64 ± 14, male 45%, with pulmonary arterial hypertension, heart failure, valvular heart disease, dyspnea, or other pathologies). IVC size and CCI were integrated with other standard echocardiographic features, selected by backward feature selection and included in a linear model (LM) and a support vector machine (SVM), which were cross-validated. Three RAP classes (low < 5 mmHg, intermediate 5−10 mmHg and high > 10 mmHg) were generated and RHC values used as comparator. LM and SVM showed a higher accuracy than Guidelines (63%, 71%, and 61% for LM, SVM, and Guidelines, respectively), promoting the integration of IVC and echocardiographic features for an improved non-invasive estimation of RAP.

Multi-chamber speckle tracking imaging and diagnostic value of left atrial strain in cardiac amyloidosis.

AIMS: Cardiac amyloidosis (CA) affects the four heart chambers, which can all be evaluated through speckle-tracking echocardiography (STE). METHODS AND RESULTS: We evaluated 423 consecutive patients screened for CA over 5 years at two referral centres. CA was diagnosed in 261 patients (62%) with either amyloid transthyretin (ATTR; n = 144, 34%) or amyloid light-chain (AL; n = 117, 28%) CA. Strain parameters of all chambers were altered in CA patients, particularly those with ATTR-CA. Nonetheless, only peak left atrial longitudinal strain (LA-PALS) displayed an independent association with the diagnosis of CA or ATTR-CA beyond standard echocardiographic variables and cardiac biomarkers (Model 1), or with the diagnosis of ATTR-CA beyond the validated IWT score in patients with unexplained left ventricular (LV) hypertrophy. Patients with the most severe impairment of LA strain were those most likely to have CA or ATTR-CA. Specifically, LA-PALS and/or LA-peak atrial contraction strain (PACS) in the first quartile (i.e. LA-PALS <6.65% and/or LA-PACS <3.62%) had a 3.60-fold higher risk of CA, and a 3.68-fold higher risk of ATTR-CA beyond Model 1. Among patients with unexplained LV hypertrophy, those with LA-PALS or LA-PACS in the first quartile had an 8.76-fold higher risk for CA beyond Model 1, and a 2.04-fold higher risk of ATTR-CA beyond the IWT score. CONCLUSIONS: Among STE measures of the four chambers, PALS and PACS are the most informative ones to diagnose CA and ATTR-CA. Patients screened for CA and having LA-PALS and/or LA-PACS in the first quartile have a high likelihood of CA and ATTR-CA.

Echocardiographic Biventricular Coupling Index to Predict Precapillary Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a frequent and detrimental condition. Right heart catheterization (RHC) is the gold standard to identify PH subtype (precapillary from postcapillary PH) and is key for treatment allocation. In this study, the novel echocardiographic biventricular coupling index (BCI), based on the ratio between right ventricular stroke work index and left ventricular E/E' ratio, was tested for the discrimination of PH subtype using RHC as the comparator. METHODS: BCI was derived in 334 consecutive patients who underwent transthoracic echocardiography and RHC for all indications. BCI was then tested in a validation cohort of 1,349 patients. RESULTS: The accuracy of BCI to identify precapillary PH was high in the derivation cohort (area under the curve, 0.82; 95% CI, 0.78-0.88; P < .001; optimal cut point, 1.9). BCI identified patients with precapillary PH with high accuracy also in the validation cohort (area under the curve, 0.87 [95% CI, 0.85-0.89; P < .001]; subgroup with PH: area under the curve, 0.91 [95% CI, 0.89-0.93; P < .001]; cut point, 1.9; sensitivity, 82%; specificity, 89%; positive predictive value, 77%; negative predictive value, 92%). BCI outperformed both the D'Alto score (Z = 3.56; difference between areas = 0.05; 95% CI, 0.02-0.07; P < .001) and the echocardiographic pulmonary-to-left atrial ratio index (Z = 2.88; difference between areas = 0.02; 95% CI, 0.01-0.04; P = .004). CONCLUSIONS: BCI is a novel, noninvasive index based on routinely available echocardiographic parameters that identifies with high accuracy patients with precapillary PH. BCI may be of value in the screening workup of patients with PH.

[Multidisciplinary examination and treatment of vulvodynia].

Women suffering from chronic vulvar pain seek help in the healthcare system on numerous occasions. The most common type is provoked localized vulvodynia (PVD) in which the pain has been persistent for more than three months without identifiable cause. The aetiology of PVD is multifactorial and the diagnosis is based upon medical history and gynaecological assessment including a bio-psycho-social evaluation. Danish and international guidelines point to the advantages of a multidisciplinary approach, where physical, psycho-sexual assessment is integrated in a multidisciplinary treatment programme as summarized in this review.

CMR predictors of secondary moderate to severe mitral regurgitation and its additive prognostic role in previous myocardial infarction.

BACKGROUND: We aimed to determine predictors and the additive prognostic role of moderate to severe (MS) ischemic mitral regurgitation (MR) in myocardial infarction (MI). METHODS: Four hundred twenty-two patients with previous MI underwent cardiac magnetic resonance (CMR) imaging for the assessment of left ventricular (LV) ejection fraction (EF), end-diastolic (EDV) and end-systolic volume (ESV), sphericity index, wall motion score index (WMSI), and late gadolinium enhancement (LGE). Echocardiography was performed to assess MR. RESULTS: Thirty-eight had from moderate to severe MR (MS-MR group) and 384 did not (No MS-MR group). The S-MR group had higher LV volumes, sphericity index, WMSI, and LGE extent, and lower LVEF. At univariate logistic regression analysis, dilated volumes, SI >0.43, dyskinesia of inferolateral wall, papillary muscle (PM)-LGE, and LGE extent >16% were associated with MS-MR. At multivariate analysis, only SI (OR=5.7) and PM-LGE (OR=3) were independently associated with MS-MR. Considering only patients without LV dilatation, only dyskinesia in the inferolateral wall was a predictor of MS-MR (OR 34.8). Thirty cardiac events (cardiac death, appropriate implantable cardioverter-defibrillator firing, and resuscitated cardiac arrest) occurred during a median follow-up of 1,276 days. After adjusting the prognostic variables at univariate analysis by age (>65 years) and selecting those that were significant (EDV > 95 ml/m2, ESV >53 ml/m2, EF <30%, WMSI >1.65, LGE >12%, S-MR), only WMSI >1.65 and MS-MR remained an independent predictor of cardiac events. CONCLUSIONS: Increased WMSI and PM-LGE in the overall population and inferolateral dyskinesia in patients without ESV dilatation are predictors of MS-MR; MS-MR and elevated WMSI have independent negative prognostic value.

Structure-Activity Studies of 3,9-Diazaspiro[5.5]undecane-Based γ-Aminobutyric Acid Type A Receptor Antagonists with Immunomodulatory Effect.

The 3,9-diazaspiro[5.5]undecane-based compounds 2027 and 018 have previously been reported to be potent competitive γ-aminobutyric acid type A receptor (GABAAR) antagonists showing low cellular membrane permeability. Given the emerging peripheral application of GABAAR ligands, we hypothesize 2027 analogs as promising lead structures for peripheral GABAAR inhibition. We herein report a study on the structural determinants of 2027 in order to suggest a potential binding mode as a basis for rational design. The study identified the importance of the spirocyclic benzamide, compensating for the conventional acidic moiety, for GABAAR ligands. The structurally simplified m-methylphenyl analog 1e displayed binding affinity in the high-nanomolar range (Ki = 180 nM) and was superior to 2027 and 018 regarding selectivity for the extrasynaptic α4ßδ subtype versus the α1- and α2- containing subtypes. Importantly, 1e was shown to efficiently rescue inhibition of T cell proliferation, providing a platform to explore the immunomodulatory potential for this class of compounds.

Molecular Determinants and Pharmacological Analysis for a Class of Competitive Non-transported Bicyclic Inhibitors of the Betaine/GABA Transporter BGT1.

The betaine/GABA transporter 1 (BGT1) is a member of the GABA transporter (GAT) family with still elusive function, largely due to a lack of potent and selective tool compounds. Based on modeling, we here present the design, synthesis and pharmacological evaluation of five novel conformationally restricted cyclic GABA analogs related to the previously reported highly potent and selective BGT1 inhibitor (1S,2S,5R)-5-aminobicyclo[3.1.0]hexane-2-carboxylic acid (bicyclo-GABA). Using [3H]GABA radioligand uptake assays at the four human GATs recombinantly expressed in mammalian cell lines, we identified bicyclo-GABA and its N-methylated analog (2) as the most potent and selective BGT1 inhibitors. Additional pharmacological characterization in a fluorescence-based membrane potential assay showed that bicyclo-GABA and 2 are competitive inhibitors, not substrates, at BGT1, which was validated by a Schild analysis for bicyclo-GABA (pK B value of 6.4). To further elaborate on the selectivity profile both compounds were tested at recombinant α1ß2γ2 GABAA receptors. Whereas bicyclo-GABA showed low micromolar agonistic activity, the N-methylated 2 was completely devoid of activity at GABAA receptors. To further reveal the binding mode of bicyclo-GABA and 2 binding hypotheses of the compounds were obtained from in silico-guided mutagenesis studies followed by pharmacological evaluation at selected BGT1 mutants. This identified the non-conserved BGT1 residues Q299 and E52 as the molecular determinants driving BGT1 activity and selectivity. The binding mode of bicyclo-GABA was further validated by the introduction of activity into the corresponding GAT3 mutant L314Q (38 times potency increase cf. wildtype). Altogether, our data reveal the molecular determinants for the activity of bicyclic GABA analogs, that despite their small size act as competitive inhibitors of BGT1. These compounds may serve as valuable tools to selectively and potently target BGT1 in order to decipher its elusive pharmacological role in the brain and periphery such as the liver and kidneys.

When Movement Moves: Study Protocol for a Multi-Method Pre/Post Evaluation Study of Two Programmes; the Danish Team Twin and Cycling Without Age.

Physical activity (PA) can improve physical, mental, and social health, leading to quality of life (QoL). However, some are unable to participate independently due to age-related impairments or disabilities. This study protocol presents the design, methods, outcomes, strengths and limitations of the study "When Movement Moves" (WMM). WMM investigates whether indirect PA in a social context, where persons are unable to participate independently, can result in outcomes similar to those of independent PA, by evaluating the effects of disabled's, elderly, volunteers', relatives' and nursing staff's participation in either the running programme (Team Twin) or cycling programme (Cycling Without Age). Both programmes seek to enhance QoL through indirect PA in a social context, making PA possible for elderly and disabled persons through PA conducted by abled-bodied volunteers. WMM is a multi-method 12-16-week pre/post evaluation with quality of life, physical, mental and social health as main outcomes. Pre/post measurements consist of questionnaires, clinical examinations, and physical and cognitive appraisal. Throughout, interviews and participant observations will be conducted. Combined results will provide essential knowledge on the effects and experiences of indirect PA. Explorative data will pave the way for further research. Findings may inform policies, guidelines and health promotion among the elderly and disabled.

Being and doing in the outdoors brings something extra! Evaluating the Danish Healthy in Nature Project.

PURPOSE: Little is known of the potential of using nature and outdoor activities in relation to community-based health promotion programmes. This study seeks a better understanding of how people with mental or chronic physical health problems experience a local outdoor health promotion or rehabilitation programmes and a better understanding of how these programs contribute to the participant's health and well-being. METHODS: The study is based on data from the Healthy in Nature project targeting adults with chronic physical health problems and adults with mental health problems. Data was collected using a qualitative multiple case study design involving five selected cases with both qualitative interviews and observation. Data was analysed using Braun et al.'s 6-phase guide to qualitative reflexive thematic analysis, employing Self-Determination Theory as a theoretical framework. Results: Overall, the participants in the two groups experienced increased competence, autonomy, and relatedness, and the participants expressed the importance of both being in a natural environment and doing outdoor activities (friluftsliv). CONCLUSIONS: The study makes a valuable contribution to the field of health promotion and rehabilitation pointing to nature and friluftsliv as important elements that offer great potential to community-based health promotion.

HOXA9-methylated DNA as a diagnostic biomarker of ovarian malignancy.

Aim: In ovarian cancer, methylated HOXA9 (meth-HOXA9) has been proposed as a relevant biomarker, however, its role in the carcinogenic development remains unknown. This study aimed at evaluating meth-HOXA9 as a diagnostic biomarker in ovarian cancer. Materials & methods: The meth-HOXA9 status was examined in 138 tissue specimens encompassing normal ovaries, benign- and borderline tumors, and ovarian cancer using droplet digital PCR. Results: Meth-HOXA9 was detected in 93% (82/88) and 88% (14/16) of ovarian cancer and borderline tumors, respectively. In patients with benign ovarian tumors meth-HOXA9 was detected in 17% (3/18). Using receiver operating characteristic (ROC) analysis meth-HOXA9 had a diagnostic accuracy of 98%. Conclusion: Meth-HOXA9 is highly cancer specific and could serve as a general diagnostic marker of ovarian malignancy.