Living with non-cardiac chest pain - An inductive qualitative interview study of spouses' perspectives.

AIM: To explore spouses' experiences of living with a partner suffering from non-cardiac chest pain (NCPP). DESIGN: An inductive qualitative study. METHODS: Individual interviews (n = 10) were performed with spouses of partners having NCCP and cardiac anxiety. The analysis was performed according to Patton's guide for content analysis of qualitative data. RESULTS: Three categories and seven subcategories were identified. First, 'a feeling of being neglected', where spouses felt ignored by healthcare professionals and excluded by their partners. Secondly, 'a tension between hope and despair' encompassed feelings of faith, support, unpreparedness for chest pain and situational frustration. Lastly, in 'a threat to ordinary life', spouses noted chest pain-induced changes impacting daily life, finances, leisure and relationships. To conclude, NCCP in partners significantly affects their spouses emotionally and practically. Spouses felt neglected and isolated, oscillating between hope and despair and experiencing faith, powerlessness and frustration. They also faced challenges in daily life and relationships.

Translation, cross-cultural adaptation, and preliminary validation of a patient-reported outcome measure for genetic counseling outcomes in Sweden.

Genetic counseling is key for understanding the consequences of hereditary and genetic diseases and, therefore, crucial for patients, their families, and healthcare providers. Genetic counseling facilitates individuals' comprehension, decision-making, and adaptation to hereditary diseases. This study focuses on the Swedish adaptation of the Genetic Counseling Outcome Scale-24 (GCOS-24), an internationally validated, patient-reported outcome measure (PROM) for quantifying patient empowerment in genetic counseling. This study aimed to translate and cross-culturally adapt the GCOS-24 to measure patient-reported outcome from genetic counseling in Sweden. The adaptation process was meticulously conducted, adhering to international guidelines, with cross-cultural adaptation, translation, and back translation, to ensure semantic, conceptual, and idiomatic equivalence with the original English version. Face validity and understandability was assured using qualitative cognitive interviews conducted with patient representatives, and by a committee of experts in the field. The psychometric properties of the Swedish version of GCOS-24 (GCOS-24swe) were evaluated using a robust sample of 374 patients. These individuals received genetic counseling by telephone or video, necessitated by the constraints of the COVID-19 pandemic. Participants responded to GCOS-24swe both before and after genetic counseling. The GCOS-24swe demonstrated face validity, good internal consistency (Cronbach's alpha = 0.86), significant responsiveness (Cohen's d = 0.65, p < 0.001), and good construct validity. The study's findings underscore the GCOS-24swe's potential as an effective instrument in both clinical practice and research within Sweden. It offers a valuable means for assessing patient empowerment, a key goal of genetic counseling. Additional psychometric assessment of test-retest reliability and interpretability would further enhance the utility of GCOS-24swe.

Synchronization of optically self-assembled nanorotors.

Self-assembly of nanoparticles by means of interparticle optical forces provides a compelling approach toward contact-free organization and manipulation of nanoscale entities. However, exploration of the rotational degrees of freedom in this process has remained limited, primarily because of the predominant focus on spherical nanoparticles, for which individual particle orientation cannot be determined. Here, we show that gold nanorods, which self-assemble in water under the influence of circularly polarized light, exhibit synchronized rotational motion at kilohertz frequencies. The synchronization is caused by strong optical interactions and occurs despite the presence of thermal diffusion. Our findings elucidate the intricate dynamics arising from the transfer of photon spin angular momentum to optically bound matter and hold promise for advancing the emerging field of light-driven nanomachinery.

Relationship of device measured physical activity type and posture with cardiometabolic health markers: pooled dose-response associations from the Prospective Physical Activity, Sitting and Sleep Consortium.

AIMS/HYPOTHESIS: The aim of this study was to examine the dose-response associations of device-measured physical activity types and postures (sitting and standing time) with cardiometabolic health. METHODS: We conducted an individual participant harmonised meta-analysis of 12,095 adults (mean ± SD age 54.5±9.6 years; female participants 54.8%) from six cohorts with thigh-worn accelerometry data from the Prospective Physical Activity, Sitting and Sleep (ProPASS) Consortium. Associations of daily walking, stair climbing, running, standing and sitting time with a composite cardiometabolic health score (based on standardised z scores) and individual cardiometabolic markers (BMI, waist circumference, triglycerides, HDL-cholesterol, HbA1c and total cholesterol) were examined cross-sectionally using generalised linear modelling and cubic splines. RESULTS: We observed more favourable composite cardiometabolic health (i.e. z score <0) with approximately 64 min/day walking (z score [95% CI] -0.14 [-0.25, -0.02]) and 5 min/day stair climbing (-0.14 [-0.24, -0.03]). We observed an equivalent magnitude of association at 2.6 h/day standing. Any amount of running was associated with better composite cardiometabolic health. We did not observe an upper limit to the magnitude of the dose-response associations for any activity type or standing. There was an inverse dose-response association between sitting time and composite cardiometabolic health that became markedly less favourable when daily durations exceeded 12.1 h/day. Associations for sitting time were no longer significant after excluding participants with prevalent CVD or medication use. The dose-response pattern was generally consistent between activity and posture types and individual cardiometabolic health markers. CONCLUSIONS/INTERPRETATION: In this first activity type-specific analysis of device-based physical activity, ~64 min/day of walking and ~5.0 min/day of stair climbing were associated with a favourable cardiometabolic risk profile. The deleterious associations of sitting time were fully attenuated after exclusion of participants with prevalent CVD and medication use. Our findings on cardiometabolic health and durations of different activities of daily living and posture may guide future interventions involving lifestyle modification.

Long-term effects and predictors of change of internet-delivered cognitive behavioural therapy on cardiac anxiety in patients with non-cardiac chest pain: a randomized controlled trial.

BACKGROUND: Approximately half of patients who seek care at Emergency Departments due to chest pain are diagnosed with Non-Cardiac Chest Pain (NCCP). Concerns for heart disease and misinterpretation of the symptoms increase cardiac anxiety and have a negative impact on patients' lives. Psychological interventions such as internet-delivered cognitive behavioral therapy (iCBT) are effective in treating psychological conditions such as anxiety, by helping patients to learn how to manage chest pain. AIMS: To evaluate the effects of a nurse-led iCBT program on cardiac anxiety and secondary outcomes, as bodily sensations, depressive symptoms, health-related quality of life and chest pain frequency in patients with NCCP at 6- and 12-month follow-up, and to explore predictors that can have impact on the effects of the iCBT program on psychological distress. METHODS: A longitudinal study of a Randomized Controlled Trial (RCT) evaluating the long-term effects of an iCBT program (n = 54) in patients with NCCP, compared to psychoeducation (n = 55). The primary outcome, cardiac anxiety was measured using the Cardiac Anxiety Questionnaire (CAQ), and the secondary outcomes were measured with The Body Sensations Questionnaire (BSQ), Patient Health Questionnaire-9 (PHQ-9), The EuroQol Visual Analog Scale (EQ-VAS) and a self-developed question to measure chest pain frequency. All measurements were performed before and after the intervention, and 3, 6 and 12 months after the intervention. Linear mixed model was used to test between-group differences in primary and secondary outcomes and multiple regression analysis was used to explore factors that may have an impact on the treatment effect of iCBT on cardiac anxiety. RESULTS: A total of 85% (n = 93/109) participants completed the 12-month follow-up. Mixed model analysis showed no statistically significant interaction effect of time and group between the iCBT and psychoeducation groups regarding cardiac anxiety over the 12-month follow-up. However, there was a statistically significant interaction effect of time and group (p = .009) regarding chest pain frequency favouring the iCBT group. In addition, we found a group effect in health-related quality of life (p = .03) favouring the iCBT group. The regression analysis showed that higher avoidance scores at baseline were associated with improvement in cardiac anxiety at 12-month follow-up. CONCLUSIONS: Cardiac anxiety was reduced in patients with NCCP, but iCBT was not more effective than psychoeducation. Patients with a high tendency to avoid activities or situations that they believe could trigger cardiac symptoms may benefit more from psychological interventions targeting cardiac anxiety. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov NCT03336112 on 08/11/2017.

The ATM Ser49Cys Variant Effects ATM Function as a Regulator of Oncogene-Induced Senescence.

An apical component of the cell cycle checkpoint and DNA damage repair response is the ataxia-telangiectasia mutated (ATM) Ser/Thr protein kinase. A variant of ATM, Ser49Cys (rs1800054; minor allele frequency = 0.011), has been associated with an elevated risk of melanoma development; however, the functional consequence of this variant is not defined. ATM-dependent signalling in response to DNA damage has been assessed in a panel of patient-derived lymphoblastoid lines and primary human melanocytic cell strains heterozygous for the ATM Ser49Cys variant allele. The ATM Ser49Cys allele appears functional for acute p53-dependent signalling in response to DNA damage. Expression of the variant allele did reduce the efficacy of oncogene expression in inducing senescence. These findings demonstrate that the ATM 146C>G Ser49Cys allele has little discernible effect on the acute response to DNA damage but has reduced function observed in the chronic response to oncogene over-expression. Analysis of melanoma, naevus and skin colour genomics and GWAS analyses have demonstrated no association of this variant with any of these outcomes. The modest loss of function detected suggest that the variant may act as a modifier of other variants of ATM/p53-dependent signalling.

Longitudinal Associations between 24-H Movement Behaviors and Cardiometabolic Biomarkers: A Natural Experiment over Retirement.

INTRODUCTION: Physical activity, sedentary behavior and sleep, that is, 24-h movement behaviors, often change in the transition from work to retirement, which may affect cardiometabolic health. This study investigates the longitudinal associations between changes in 24-h movement behaviors and cardiometabolic biomarkers during the retirement transition. METHODS: Retiring public sector workers (n = 212, mean age 63.5 years, SD 1.1) from the Finnish Retirement and Aging study used a thigh-worn Axivity accelerometer and filled out a diary to obtain data on daily time spent in sedentary behavior (SED), light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) and sleep before and after retirement (one year in-between). Cardiometabolic biomarkers, including LDL-cholesterol, HDL-cholesterol, total:HDL-cholesterol ratio, triglycerides, C-reactive protein (CRP), fasting glucose and insulin, were measured. Associations between changes in 24-h movement behaviors and cardiometabolic biomarkers were analyzed using compositional robust regression and isotemporal substitution analysis. RESULTS: Increasing LPA in relation to remaining behaviors was associated with an increase in HDL-cholesterol and decrease in total:HDL-cholesterol ratio (p < 0.05 for both). For instance, reallocation of 30 min from sleep/SED to LPA was associated with an increase in HDL-cholesterol by 0.02 mmol/l. Moreover, increasing MVPA in relation to remaining behaviors was associated with a decrease in triglycerides (p = 0.02). Reallocation of 30 min from SED/sleep to MVPA was associated with 0.07 - 0.08 mmol/l decrease in triglycerides. Findings related to LDL-cholesterol, CRP, fasting glucose and insulin were less conclusive. CONCLUSIONS: During the transition from work to retirement, increasing physical activity at the expense of passive behaviors was associated with a better lipid profile. Our findings suggest that life transitions like retirement could be utilized more as an optimal time window for promoting physical activity and health.

Dapagliflozin in Myocardial Infarction without Diabetes or Heart Failure.

Dapagliflozin in Myocardial InfarctionA total of 4017 patients with acute myocardial infarction, but no diabetes or chronic heart failure, were randomly assigned 10 mg of dapagliflozin or placebo. The primary outcome was a composite of death, hospitalization for heart failure, and five cardiometabolic outcomes analyzed using the win ratio method. There were significantly more wins for dapagliflozin than for placebo (win ratio, 1.34; 95% confidence interval, 1.20 to 1.50), which was driven by the cardiometabolic outcomes. The composite of time to cardiovascular death/hospitalization for heart failure was not different between the two groups.

Age-stratified Assessment of Brain Volumetric Segmentation on the Indian Population Using Quantitative Magnetic Resonance Imaging.

BACKGROUND AND PURPOSE: Automated methods for quantifying brain tissue volumes have gained clinical interest for their objective assessment of neurological diseases. This study aimed to establish reference curves for brain volumes and fractions in the Indian population using Synthetic MRI (SyMRI), a quantitative imaging technique providing multiple contrast-weighted images through fast postprocessing. METHODS: The study included a cohort of 314 healthy individuals aged 15-65 years from multiple hospitals/centers across India. The SyMRI-quantified brain volumes and fractions, including brain parenchymal fraction (BPF), gray matter fraction (GMF), white matter fraction (WMF), and myelin. RESULTS: Normative age-stratified quantification curves were created based on the obtained data. The results showed significant differences in brain volumes between the sexes, but not after normalization by intracranial volume. CONCLUSION: The findings provide normative data for the Indian population and can be used for comparative analysis of brain structure values. Furthermore, our data indicate that the use of fractions rather than absolute volumes in normative curves, such as BPF, GMF, and WMF, can mitigate sex and population differences as they account for individual differences in head size or brain volume.

Device-measured physical activity and cardiometabolic health: the Prospective Physical Activity, Sitting, and Sleep (ProPASS) consortium.

BACKGROUND AND AIMS: Physical inactivity, sedentary behaviour (SB), and inadequate sleep are key behavioural risk factors of cardiometabolic diseases. Each behaviour is mainly considered in isolation, despite clear behavioural and biological interdependencies. The aim of this study was to investigate associations of five-part movement compositions with adiposity and cardiometabolic biomarkers. METHODS: Cross-sectional data from six studies (n = 15 253 participants; five countries) from the Prospective Physical Activity, Sitting and Sleep consortium were analysed. Device-measured time spent in sleep, SB, standing, light-intensity physical activity (LIPA), and moderate-vigorous physical activity (MVPA) made up the composition. Outcomes included body mass index (BMI), waist circumference, HDL cholesterol, total:HDL cholesterol ratio, triglycerides, and glycated haemoglobin (HbA1c). Compositional linear regression examined associations between compositions and outcomes, including modelling time reallocation between behaviours. RESULTS: The average daily composition of the sample (age: 53.7 ± 9.7 years; 54.7% female) was 7.7 h sleeping, 10.4 h sedentary, 3.1 h standing, 1.5 h LIPA, and 1.3 h MVPA. A greater MVPA proportion and smaller SB proportion were associated with better outcomes. Reallocating time from SB, standing, LIPA, or sleep into MVPA resulted in better scores across all outcomes. For example, replacing 30 min of SB, sleep, standing, or LIPA with MVPA was associated with -0.63 (95% confidence interval -0.48, -0.79), -0.43 (-0.25, -0.59), -0.40 (-0.25, -0.56), and -0.15 (0.05, -0.34) kg/m2 lower BMI, respectively. Greater relative standing time was beneficial, whereas sleep had a detrimental association when replacing LIPA/MVPA and positive association when replacing SB. The minimal displacement of any behaviour into MVPA for improved cardiometabolic health ranged from 3.8 (HbA1c) to 12.7 (triglycerides) min/day. CONCLUSIONS: Compositional data analyses revealed a distinct hierarchy of behaviours. Moderate-vigorous physical activity demonstrated the strongest, most time-efficient protective associations with cardiometabolic outcomes. Theoretical benefits from reallocating SB into sleep, standing, or LIPA required substantial changes in daily activity.

Healthcare use in patients with cardiovascular disease and depressive symptoms - The impact of a nurse-led internet-delivered cognitive behavioural therapy program. A secondary analysis of a RCT.

Background: Depressive symptoms in patients with cardiovascular disease (CVD) can lead to increased healthcare use. In a randomized controlled trial (ClinicalTrials.gov, NCT02778074), we reported that a 9-week internet-delivered cognitive behavioural therapy (iCBT) program (n = 72) compared to an online discussion forum (ODF) (n = 72) had moderate to large effect on depression in CVD outpatients. In this secondary analysis, we aimed to describe and compare the effect of iCBT compared to ODF regarding healthcare use and to identify factors impacting healthcare use in these groups. Methods: Data on healthcare use were retrieved from care data registries in five hospitals in Southeastern Sweden. Results: The year prior to intervention, the iCBT group had a mean of 31 outpatient clinic/primary care contacts per patient compared with 21 contacts the year after. The corresponding numbers for the ODF group were 37 and 25. The decrease was 32 % in both groups and did not differ significantly (p = 0.261 and p = 0.354) between the groups. Regarding hospital admissions, the iCBT group had 0.8 admissions per patient the year before and 0.6 the year after the intervention, a decrease by 25 %, whereas the ODF group had 1.1 and 0.6 admissions respectively, a decrease by 45 %. The difference was not statistically significant (p = 0.270 and p = 0.883) between the groups. Improvement in depressive symptoms post intervention were significantly (Beta = 0.459, p = 0.047) associated with a decrease in number of outpatient contacts in the iCBT group. In the ODF group, better mental health-related quality of life post intervention was significantly (Beta = -0.429, p = 0.045) associated with a decrease in number of hospital admissions. Conclusion: Reduced depressive symptom scores following intervention were associated with lower outpatient service use, but iCBT was not superior compared to ODF. This implicates that reducing depression in CVD patients, regardless of the type of internet-delivered intervention used, is important since it may reduce healthcare use in these patients.

Moderating effect of cardiorespiratory fitness on sickness absence in occupational groups with different physical workloads.

Sickness absence from work has a large adverse impact on both individuals and societies in Sweden and the costs for sickness absence were calculated to 64.6 billion Swedish kronor (approx. 5.6 billion in Euros) in 2020. Although high cardiorespiratory fitness may protect against potential adverse effects of high physical workload, research on the moderating effect of respiratory fitness in the relation between having an occupation with high physical workload and sickness absence is scarce. To study the moderating effect of cardiorespiratory fitness in the association between occupation and psychiatric, musculoskeletal, and cardiorespiratory diagnoses. Data was retrieved from the HPI Health Profile Institute database (1988-2020) and Included 77,366 participants (mean age 41.8 years, 52.5% women) from the Swedish workforce. The sample was chosen based on occupational groups with a generally low education level and differences in physical workload. Hurdle models were used to account for incident sickness absence and the rate of sickness absence days. There were differences in sickness absence between occupational groups for musculoskeletal and cardiorespiratory diagnoses, but not for psychiatric diagnoses. In general, the association between occupation and musculoskeletal and cardiorespiratory diagnoses was moderated by cardiorespiratory fitness in most occupational groups with higher physical workload, whereas no moderating effect was observed for psychiatric diagnoses. The study results encourage community and workplace interventions to both consider variation in physical workload and to maintain and/or improve cardiorespiratory fitness for a lower risk of sickness absence, especially in occupations with high physical workload.

A Novel System for the Device-Based Measurement of Physical Activity, Sedentary Behavior, and Sleep (Motus): Usability Evaluation.

BACKGROUND: Device-based measurements of physical behavior, using the current methods, place a large burden on participants. The Motus system could reduce this burden by removing the necessity for in-person meetings, replacing diaries written on paper with digital diaries, and increasing the automation of feedback generation. OBJECTIVE: This study aims to describe the development of the Motus system and evaluate its potential to reduce participant burden in a two-phase usability evaluation. METHODS: Motus was developed around (1) a thigh-worn accelerometer with Bluetooth data transfer; (2) a smartphone app containing an attachment guide, a digital diary, and facilitating automated data transfer; (3) a cloud infrastructure for data storage; (4) an analysis software to generate feedback for participants; and (5) a web-based app for administrators. We recruited 19 adults with a mean age of 45 (SD 11; range 27-63) years, of which 11 were female, to assist in the two-phase evaluation of Motus. A total of 7 participants evaluated the usability of mockups for a smartphone app in phase 1. Participants interacted with the app while thinking aloud, and any issues raised were classified as critical, serious, or minor by observers. This information was used to create an improved and functional smartphone app for evaluation in phase 2. A total of 12 participants completed a 7-day free-living measurement with Motus in phase 2. On day 1, participants attempted 20 system-related tasks under observation, including registration on the study web page, reading the information letter, downloading and navigating the smartphone app, attaching an accelerometer on the thigh, and completing a diary entry for both work and sleep hours. Task completion success and any issues encountered were noted by the observer. On completion of the 7-day measurement, participants provided a rating from 0 to 100 on the System Usability Scale and participated in a semistructured interview aimed at understanding their experience in more detail. RESULTS: The task completion rate for the 20 tasks was 100% for 13 tasks, >80% for 4 tasks, and <50% for 3 tasks. The average rating of system usability was 86 on a 0-100 scale. Thematic analysis indicated that participants perceived the system as easy to use and remember, and subjectively pleasing overall. Participants with shift work reported difficulty with entering sleep hours, and 66% (8/12) of the participants experienced slow data transfer between the app and the cloud infrastructure. Finally, a few participants desired a greater degree of detail in the generated feedback. CONCLUSIONS: Our two-phase usability evaluation indicated that the overall usability of the Motus system is high in free-living. Issues around the system's slow data transfer, participants with atypical work shifts, and the degree of automation and detail of generated feedback should be addressed in future iterations of the Motus system. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/35697.

Accelerometer derived physical activity and subclinical coronary and carotid atherosclerosis: cross-sectional analyses in 22 703 middle-aged men and women in the SCAPIS study.

OBJECTIVES: The aim included investigation of the associations between sedentary (SED), low-intensity physical activity (LIPA), moderate-to-vigorous intensity PA (MVPA) and the prevalence of subclinical atherosclerosis in both coronaries and carotids and the estimated difference in prevalence by theoretical reallocation of time in different PA behaviours. DESIGN: Cross-sectional. SETTING: Multisite study at university hospitals. PARTICIPANTS: A total of 22 670 participants without cardiovascular disease (51% women, 57.4 years, SD 4.3) from the population-based Swedish CArdioPulmonary bioImage study were included. SED, LIPA and MVPA were assessed by hip-worn accelerometer. PRIMARY AND SECONDARY OUTCOMES: Any and significant subclinical coronary atherosclerosis (CA), Coronary Artery Calcium Score (CACS) and carotid atherosclerosis (CarA) were derived from imaging data from coronary CT angiography and carotid ultrasound. RESULTS: High daily SED (>70% ≈10.5 hours/day) associated with a higher OR 1.44 (95% CI 1.09 to 1.91), for significant CA, and with lower OR 0.77 (95% CI 0.63 to 0.95), for significant CarA. High LIPA (>55% ≈8 hours/day) associated with lower OR for significant CA 0.70 (95% CI 0.51 to 0.96), and CACS, 0.71 (95% CI 0.51 to 0.97), but with higher OR for CarA 1.41 (95% CI 1.12 to 1.76). MVPA above reference level, >2% ≈20 min/day, associated with lower OR for significant CA (OR range 0.61-0.67), CACS (OR range 0.71-0.75) and CarA (OR range 0.72-0.79). Theoretical replacement of 30 min of SED into an equal amount of MVPA associated with lower OR for significant CA, especially in participants with high SED 0.84 (95% CI 0.76 to 0.96) or low MVPA 0.51 (0.36 to 0.73). CONCLUSIONS: MVPA was associated with a lower risk for significant atherosclerosis in both coronaries and carotids, while the association varied in strength and direction for SED and LIPA, respectively. If causal, clinical implications include avoiding high levels of daily SED and low levels of MVPA to reduce the risk of developing significant subclinical atherosclerosis.

Developing and designing an internet-based support and education program for patients awaiting kidney transplantation with deceased donors through: a Delphi study.

AIMS: The aim of this study was to develop and refine the content and design of an internet-based support and education program for patients awaiting kidney transplantation from deceased donors. DESIGN: A Delphi process was used. METHODS: A prototype internet-based intervention was drafted, based on previous research. The intervention included educational and psychological support to manage the uncertain waiting time and specific education enabling preparation for transplantation and adjustment to life after transplantation. In a two-round Delphi process, patients who had received a kidney transplant from a deceased donor within the last 2 years (n = 27), significant others (n = 6), health-care personnel with renal (n = 20) or transplant (n = 14) expertise, rated importance of content and design aspects of the prototype intervention on a 5-point scale using web questionnaires. A median of ≥ 3 was considered as consensus. Quantitative data was analyzed using descriptive statistics. Free text answers were encouraged and analyzed using deductive content analysis. The STROBE-checklist was used. RESULTS: Consensus was reached for all suggested content and design items in round 1, with median ratings of 4 or 5. Qualitative analysis from round 1 suggested four new content and design items which were rated in round 2, on all which consensus was reached; information about life with young children as relatives, expansion of kidney transplantation specific information, program extension by one week and individualization by making information available based on individual needs. CONCLUSION: There was consensus among heterogenous experts regarding suggested educational and psychological support content and design aspects, and additional content and design aspects were identified for an internet-based support and education program for patients awaiting kidney transplantation from deceased donors.

The effects of internet-based cognitive behavior therapy for depression in cardiovascular disease on symptoms of anxiety: A secondary analysis of a randomized trial.

AIMS: The aims of this study were to evaluate: (I) the short- and long-term effects of the internet-based cognitive behavior (iCBT) program on symptoms of distress and fear disorder in CVD patients, and (II) the association between changes in depression and changes in symptoms of distress and fear disorder from baseline to 12-months follow-up. METHODS AND RESULTS: Secondary analysis of data collected in a randomized controlled study evaluating the effects on depression of an iCBT program compared to an online discussion forum (ODF) in CVD patients (n = 144). Data were collected at baseline, at post-intervention (nine weeks), and at 6- and 12-month follow-up.The results showed that symptoms of distress disorder were statistically significantly more reduced in the iCBT group than the ODF group. For symptoms of fear disorder, no differences were found except for avoidance, which showed a statistically significant reduction in the iCBT group. The long-term analysis in the iCBT group showed that CAQ total score and fear decreased from baseline to 6- and 12-months follow-up respectively. Avoidance and attention both decreased statistically significantly from baseline to post-intervention, but not between post-intervention and 12-months follow-up. CONCLUSION: The results suggest that the iCBT program targeted depression in CVD patients successfully reduced symptoms of distress disorder, and to a lesser extent symptoms of fear disorder. Change in depression was more strongly associated with change in distress than change in fear disorder. REGISTRATION: clinicaltrials.gov NCT02778074.

The clinical relevance of broad mutational screening of myeloproliferative neoplasms at diagnosis.

Introduction: Myeloproliferative neoplasm (MPN) is a heterogenous group of hematological malignancies including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). JAK2V617F is the most frequent driver mutation in all three entities, but in PMF and ET mutations in CALR and MPL are also frequent. Mutations seen in additional genes are also often the same regardless of subtype of MPN. The aim of this study was to analyze a population based MPN cohort for genetic variants with prognostic value that can guide clinical decisions. Methods: MPN patients from Western Sweden diagnosed between 2008-2013 (n=248) were screened for mutations in 54 genes associated with myeloid malignancy. Results: Mutations in the genes SRSF2 and U2AF1 correlated significantly with impaired overall survival but did not correlate to increased risk for vascular events, neither before nor after diagnosis. Rather, mutations in these genes showed an association with disease transformation. Several recurrent gene variants with allele frequency close to 50% were confirmed to be germline. However, none of these variants was found to have an earlier onset of MPN. Discussion: In conclusion, we identified gene mutations to be independent markers of impaired survival in MPN. This indicates the need for more individualized assessment and treatment of MPN patients and a wider gene mutation screening already at diagnosis. This could ensure the identification of patients with high-risk mutations early on. In addition, several genetic variants were also identified as germline in this study but gave no obvious clinical relevance. To avoid conclusions from non-informative genetic variants, a simultaneous analysis of normal cell DNA from patients at diagnosis should be considered.

TINF2 is a major susceptibility gene in Danish patients with multiple primary melanoma.

TINF2 encodes the TINF2 protein, which is a subunit in the shelterin complex critical for telomere regulation. Three recent studies have associated six truncating germline variants in TINF2 that have previously been associated with a cancer predisposition syndrome (CPS) caused by elongation of the telomeres. This has added TINF2 to the long telomere syndrome genes, together with other telomere maintenance genes such as ACD, POT1, TERF2IP, and TERT. We report a clinical study of 102 Danish patients with multiple primary melanoma (MPM) in which a germline truncating variant in TINF2 (p.(Arg265Ter)) was identified in four unrelated participants. The telomere lengths of three variant carriers were >90% percentile. In a routine diagnostic setting, the variant was identified in two more families, including an additional MPM patient and monozygotic twins with thyroid cancer and other cancer types. A total of 10 individuals from six independent families were confirmed carriers, all with cancer history, predominantly melanoma. Our findings suggest a major role of TINF2 in Danish patients with MPM. In addition to melanoma, other cancers in the six families include thyroid, renal, breast, and sarcoma, supporting a CPS in which melanoma, thyroid cancer, and sarcoma predominate. Further studies are needed to establish the full spectrum of associated cancer types and characterize lifetime cancer risk in carriers.

Rationale and design of the DAPA-MI trial: Dapagliflozin in patients without diabetes mellitus with acute myocardial infarction.

BACKGROUND: Therapies that could further prevent the development of heart failure (HF) and other cardiovascular and metabolic events in patients with recent myocardial infarction (MI) represent a large and unmet medical need. METHODS: DAPA-MI is a multicenter, parallel-group, registry-based, randomized, double-blind, placebo-controlled phase 3 trial in patients without known diabetes or established HF, presenting with MI and impaired left ventricular systolic function or Q-wave MI. The trial evaluated the effect of dapagliflozin 10 mg vs placebo, given once daily in addition to standard of care therapy, on death, hospitalization for HF (HHF), and other cardiometabolic outcomes. The primary objective of the trial was to determine, using the win-ratio method, if dapagliflozin is superior to placebo by comparing the hierarchical composite outcome of death, HHF, nonfatal MI, atrial fibrillation/flutter, new onset of type 2 diabetes mellitus, HF symptoms as measured by New York Heart Association Functional Classification at last visit, and body weight decrease ≥5% at last visit. Assuming a true win-ratio of 1.20 between dapagliflozin and placebo, 4,000 patients provide a statistical power of 80% for the test of the primary composite outcome. A registry-based randomized controlled trial framework allowed for recruitment, randomization, blinding, and pragmatic data collection of baseline demographics, medications, and clinical outcomes using existing national clinical registries (in Sweden and the UK) integrated with the trial database. CONCLUSIONS: The trial explores opportunities to improve further the outcome of patients with impaired LV function after MI. The innovative trial design of DAPA-MI, incorporating national clinical registry data, has facilitated efficient patient recruitment as well as outcome ascertainment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04564742.