Patients' experiences of clinical trial participation involving a product remotely assessing study drug adherence.

Background: The participation of patients in clinical trials is crucial for the development of healthcare. There are several challenges in the recruitment of trial participants with acute medical conditions. The registry-based randomized DAPA-MI clinical trial recruited patients during hospitalization for myocardial infarction and provided study drugs in bottles with smart caps that used wireless technology to transmit monitoring data. This interview study aimed to investigate patients' experience of participation in a clinical trial and their attitude to the new bottle cap technology. Methods: A subset of patients participating in the DAPA-MI trial were recruited from four hospitals in Sweden. Semi-structured interviews were conducted and analysed using manifest content analysis. Results: Video interviews were performed including 21 patients (four women and 17 men). The median age was 59 years (range 44-80). Four categories of patients' experiences were identified. A willingness to contribute consisted of patients' positive attitudes to participation and to be a part of development and research. The perception of information emphasized the value of the oral information as well as the importance of time for reflection. Be in a vulnerable condition highlighted the impaired ability to perceive and remember in the acute medical condition. Adaptation to a new technology described the overall positive experiences of the smart bottle cap to evaluate adherence. Conclusions: Patients' experiences of trial participation were in general positive but some challenges in the acute setting of a myocardial infarction were revealed. The smart bottle cap was well accepted, despite some handling difficulties.

Sex differences in potential triggers of myocardial infarction.

Aims: Internal and external triggers affect seasonal and circadian variations of myocardial infarction (MI). We aimed to assess sex differences in the common triggers of MI. Methods and results: A nationwide, retrospective, cross-sectional postal survey study was conducted. Individuals who experienced a MI during holidays and weekdays were identified through the SWEDEHEART registry. Twenty-seven potential MI triggers were rated in regards to occurring more or less than usual during the last 24 h before the MI. Three areas were covered: activities, emotions, and food or alcohol consumption. A logistic regression model was used to identify sex differences for each trigger and odds ratios (ORs) were reported. Four hundred and fifty-one patients, of whom 317 were men, responded. The most commonly reported triggers were stress (35.3%), worry (26.2%), depression (21.1%), and insomnia (20.0%). Women reported emotional triggers including sadness [OR 3.52, 95% confidence interval (CI) 1.92-6.45], stress (OR 2.38, 95% CI 1.52-3.71), insomnia (OR 2.31, 95% CI 1.39-3.81), and upset (OR 2.69, 95% CI 1.47-4.95) to a greater extent than men. Outdoor activity was less reported by women (OR 0.35, 95% CI 0.14-0.87). No significant sex differences were found in other activities or food and alcohol consumption. Conclusion: Self-experienced stress and distress were higher among women prior to MI compared with men. Understanding sex perspectives in acute triggers may help us find preventive strategies and reduce the excess numbers of MI.

Effect of a Lifestyle-Focused Web-Based Application on Risk Factor Management in Patients Who Have Had a Myocardial Infarction: Randomized Controlled Trial.

BACKGROUND: Cardiac rehabilitation is central in reducing mortality and morbidity after myocardial infarction. However, the fulfillment of guideline-recommended cardiac rehabilitation targets is unsatisfactory. eHealth offers new possibilities to improve clinical care. OBJECTIVE: This study aims to assess the effect of a web-based application designed to support adherence to lifestyle advice and self-control of risk factors (intervention) in addition to center-based cardiac rehabilitation, compared with cardiac rehabilitation only (usual care). METHODS: All 150 patients participated in cardiac rehabilitation. Patients randomized to the intervention group (n=101) received access to the application for 25 weeks where information about lifestyle (eg, diet and physical activity), risk factors (eg, weight and blood pressure [BP]), and symptoms could be registered. The software provided feedback and lifestyle advice. The primary outcome was a change in submaximal exercise capacity (Watts [W]) between follow-up visits. Secondary outcomes included changes in modifiable risk factors between baseline and follow-up visits and uptake and adherence to the application. Regression analysis was used, adjusting for relevant baseline variables. RESULTS: There was a nonsignificant trend toward a larger change in exercise capacity in the intervention group (n=66) compared with the usual care group (n=40; +14.4, SD 19.0 W, vs +10.3, SD 16.1 W; P=.22). Patients in the intervention group achieved significantly larger BP reduction compared with usual care patients at 2 weeks (systolic -27.7 vs -16.4 mm Hg; P=.006) and at 6 to 10 weeks (systolic -25.3 vs -16.4 mm Hg; P=.02, and diastolic -13.4 vs -9.1 mm Hg; P=.05). A healthy diet index score improved significantly more between baseline and the 2-week follow-up in the intervention group (+2.3 vs +1.4 points; P=.05), mostly owing to an increase in the consumption of fish and fruit. At 6 to 10 weeks, 64% (14/22) versus 46% (5/11) of smokers in the intervention versus usual care groups had quit smoking, and at 12 to 14 months, the respective percentages were 55% (12/22) versus 36% (4/11). However, the number of smokers in the study was low (33/149, 21.9%), and the differences were nonsignificant. Attendance in cardiac rehabilitation was high, with 96% (96/100) of patients in the intervention group and 98% (48/49) of patients receiving usual care only attending 12- to 14-month follow-up. Uptake (logging data in the application at least once) was 86.1% (87/101). Adherence (logging data at least twice weekly) was 91% (79/87) in week 1 and 56% (49/87) in week 25. CONCLUSIONS: Complementing cardiac rehabilitation with a web-based application improved BP and dietary habits during the first months after myocardial infarction. A nonsignificant tendency toward better exercise capacity and higher smoking cessation rates was observed. Although the study group was small, these positive trends support further development of eHealth in cardiac rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov NCT03260582; https://clinicaltrials.gov/ct2/show/NCT03260582. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-018-3118-1.

Christmas holiday triggers of myocardial infarction.

Objectives: Christmas holidays have been associated with the highest incidence of myocardial infarction (MI). We wanted to assess possible triggers of MI during Christmas. Design: A nationwide, retrospective postal survey with case-control design. All individuals suffering an MI during the Christmas holidays 2018 and 2019 in Sweden were identified through the SWEDEHEART registry and a control group matched in age and gender with chronic coronary syndrome who did not seek medical attention during Christmas were asked for participation. Subjects completed a questionnaire asking them to rate 27 potential MI-triggers as having occurred more or less than usual. Results: A total of 189 patients suffering an MI on Christmas Eve, Christmas Day, or Boxing Day, and 157 patients in the control group responded to the questionnaire, representing response rates of 66% and 62%, respectively. Patients with MI on Christmas experienced more stress (37% vs. 21%, p = .002), depression (21% vs. 11%, p = .024), and worry (26% vs. 10%, p < .001) compared to the control group. The food and sweets consumption was increased in both groups, but to a greater extent in the control group (33% vs. 50%, p = .002 and 32% vs. 43%, p = .031). There were no increases in quarrels, anger, economic worries, or reduced compliance with medication. Conclusions: Patients suffering MI on Christmas holiday experienced higher levels of stress and emotional distress compared to patients with chronic coronary syndrome, possibly contributing to the phenomenon of holiday heart attack. Understanding what factors increase the number of MI on Christmas may help reduce the excess number of MIs and cardiovascular burden.

Patient experience of the informed consent process during acute myocardial infarction: a sub-study of the VALIDATE-SWEDEHEART trial.

OBJECTIVE: We aimed to assess the patient experience of informed consent (IC) during acute myocardial infarction (AMI) in a sub-study of the VALIDATE-SWEDEHEART trial. The original trial compared two anticoagulant agents in patients undergoing coronary intervention. A witnessed oral IC was required prior to randomization in patients with ST-segment elevation myocardial infarction, which was subsequently complemented with a written IC after percutaneous coronary intervention. Written consent was obtained before angiography in patients with non-ST-segment elevation myocardial infarction. BACKGROUND: The IC process in patients with AMI is under debate. Earlier trials in this population have required prospective consent before randomization. A trial published some years ago used deferred consent, but the patient experience of this process is poorly studied. METHODS: A total of 414 patients who participated in the main trial were enrolled and asked the following questions: (1) Do you remember being asked to participate in a study? (2) How was your experience of being asked to participate; do you remember it being positive or negative? (3) Would you have liked more information about the study? (4) Do you think it would have been better if you were included in the study without being informed until a later time? RESULTS: Of these patients, 94% remembered being included; 85% of them experienced this positively, 12% were neutral and 3% negative. Regarding more information, 88% did not want further information, and 68% expressed that they wanted to be consulted before inclusion. Of the patients, 5% thought it would have been better to have study inclusion without consent, and 27% considered it of no importance. CONCLUSION: It is reasonable to ask patients for verbal IC in the acute phase of AMI. Most patients felt positively about being asked to participate and had knowledge of being enrolled in a scientific study. In addition they objected to providing IC after randomization and treatment. TRIAL REGISTRATION: VALIDATE-SWEDEHEART European Union Clinical Trials Register: 2012-005260-10. ClinicalTrials.gov: NCT02311231. Registered on 8 Dec 2014.

The Analgesic Effect of Oxygen in Suspected Acute Myocardial Infarction: A Substudy of the DETO2X-AMI Trial.

OBJECTIVES: In this substudy of the DETO2X-AMI (An Efficacy and Outcome Study of Supplemental Oxygen Treatment in Patients With Suspected Myocardial Infarction) trial, the authors aimed to assess the analgesic effect of moderate-flow oxygen supplementation in patients with suspected acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI) and to study the effect of oxygen supplementation on the use of opiates and sedatives during PCI. BACKGROUND: Routine oxygen in normoxemic patients with AMI does not provide clinical benefit. However, oxygen may relieve ischemic pain. METHODS: Patients were randomly allocated to oxygen or ambient air according to the main study protocol. After PCI, peak level of pain during PCI was measured by the Visual Analogue Scale. The total amount of opiates and sedatives was reported. RESULTS: A total of 622 patients were enrolled: 330 in the oxygen group and 292 in the ambient air group. There was no significant difference in peak level of pain (oxygen 4.0 [1.0 to 6.0] vs. air 3.0 [0.6 to 6.0]; p = 0.37), use of opiates (mg) (oxygen 0.0 [0.0 to 3.0] vs. air 0.0 [0.0 to 3.0]; p = 0.31), or use of sedatives between the groups (median [interquartile range]) (oxygen 2.5 [0.0 to 2.5] vs. air 2.5 [0.0 to 2.5]; p = 0.74). CONCLUSIONS: In the present study, the authors did not find any analgesic effect of routine oxygen as compared with ambient air, and no differences in the use of sedatives and opiates during PCI. Our results indicate that moderate-flow oxygen supplementation does not relieve pain in normoxemic patients with suspected AMI undergoing treatment with PCI and should thus not be used for this purpose.

Differences in quality of life modalities give rise to needs of individual support in patients with ALS and their next of kin.

OBJECTIVE: The aim of this study was to examine health-related quality of life (HRQoL), individual QoL, anxiety and depression in patients with amyotrophic lateral sclerosis (ALS) and their next of kin in relation to patients' physical function over time. METHODS: 35 patients and their next of kin were studied using the Short Form-36 Health Survey (SF-36), Schedule for Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), and Hospital Anxiety and Depression Scale (HADS) and patients also by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised and the Norris scale every fourth to sixth month, one to four times. RESULTS: Changes were found over time in both patients and their next of kin in the SF-36 but not in the SEIQoL-DW or HADS. Patients rated worse than their next of kin in the SF-36 physical subscales and next of kin rated worse than the patients in the global QoL score in SEIQoL-DW. Health, hobbies, and total relations were important areas in the SEIQoL-DW among all participants, but some important areas also differed between the patients and their next of kin. In most important areas among the pairs, the next of kin estimated their functioning/satisfaction worse than patients estimated their functioning/satisfaction. SIGNIFICANCE OF RESULTS: There were few changes over time in the QoL among the participants. Although most of the estimates in patients and their next of kin were equal, there were also some differences. These results emphasize the importance of support for both patients and their next of kin and that support ought to be given on both individual bases and together in pairs. The SEIQoL-DW might give signposts in the care through the course of the disease about what should be focused on to increase satisfaction of the important areas of life and might help the person to find coping strategies to handle his or her life situation.

Decreased inducibility of TNF expression in lipid-loaded macrophages.

BACKGROUND: Inflammation and immune responses are considered to be very important in the pathogenesis of atherosclerosis. Lipid accumulation in macrophages of the arterial intima is a characteristic feature of atherosclerosis which can influence the inflammatory potential of macrophages. We studied the effects of lipid loading on the regulation of TNF expression in human monocyte-derived macrophages. RESULTS: In macrophages incubated with acetylated low density lipoprotein (ac-LDL) for 2 days, mRNA expression of TNF in cells stimulated with TNF decreased by 75%. In cell cultures stimulated over night with IL-1beta, lipid loading decreased secretion of TNF into culture medium by 48%. These results suggest that lipid accumulation in macrophages makes them less responsive to inflammatory stimuli. Decreased basal activity and inducibility of transcription factor AP-1 was observed in lipid-loaded cells, suggesting a mechanism for the suppression of cytokine expression. NF-kappaB binding activity and inducibility were only marginally affected by ac-LDL. LDL and ac-LDL did not activate PPARgamma. In contrast, oxidized LDL stimulated AP-1 and PPARgamma but inhibited NF-kappaB, indicating that the effects of lipid loading with ac-LDL were not due to oxidation of lipids. CONCLUSIONS: Accumulation of lipid, mainly cholesterol, results in down-regulation of TNF expression in macrophages. Since monocytes are known to be activated by cell adhesion, these results suggest that foam cells in atherosclerotic plaques may contribute less potently to an inflammatory reaction than newly arrived monocytes/macrophages.

Nitric oxide synthase 2 mRNA expression in relation to p53 and adenomatous polyposis coli mutations in primary colorectal adenocarcinomas.

BACKGROUND: The inducible nitric (NO) synthase 2 (NOS2) is upregulated in breast, brain, colon, and gynecological tumors, which indicate that NO may have a role in tumorigenesis. However, little is known about the role and regulation of NOS2 in colorectal carcinomas. Recent in vitro experiments have implicated that NOS2 is downregulated by p53 accumulation. Virtual analysis of the NOS2 promoter showed putative TCF-4/Lef-1 response elements, which indicate a potential regulation of NOS2 expression by activation of the adenomatous polyposis coli (APC)/beta-catenin pathway. METHODS: NOS2 mRNA expression was investigated in 59 colorectal carcinomas by reverse transcriptase/real-time polymerase chain reaction and related to mutations in the p53, APC, and beta-catenin genes. Presence of NOS2 protein was studied by Western blot, and the localization was studied by immunohistochemistry. Loss of heterozygosity was studied in the region of the NOS2 gene. RESULTS: The NOS2 mRNA and protein expression were significantly higher in tumors than in control tissue. Immunohistochemistry revealed extensive NOS2 staining in the epithelial cells and, to a minor degree, in leukocytes. Increased NOS2 mRNA expression was found in Dukes' stages A and B compared with the C and D stages. No relationship was found between elevated NOS2 expression and loss of heterozygosity in the later stages according to Dukes' classification or mutations in the p53, APC, or beta-catenin genes. CONCLUSIONS: Inactivating mutations in the p53 and APC pathways are not the main explanation for the increased NOS2 expression found in colorectal tumors.