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Hypertension increases the risk of cardiovascular disease in the elderly. Although treating hypertension can reduce the risk of cardiovascular disease and its related mortality, it is also challenging because these patients could have frailty, orthostatic hypotension (OH) and resistant hypertension (RHTN), which makes them more susceptible to treatment-related adverse events. Identifying such patients and tailoring the choice of drugs and blood pressure targets is crucial to balance the harms and benefits. The Clinical Frailty Scale is recommended to assess elderly patients with hypertension and frailty. For very frail patients, unnecessary medications should be deprescribed to avoid adverse events. Hypertension and OH frequently co-occur in the elderly, and recognizing and managing OH is essential to prevent falls and adverse events. The management of blood pressure in elderly patients with frailty, OH, and RHTN is complex, requiring the patients, their family and caregivers to be involved in decision-making to ensure that treatment plans are well-informed and aligned with the patient's needs., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Despite the increased accessibility and availability of technology in recent years, equality and access to health-related technology remain limited to some demographics. In particular, patients who are older or from rural communities represent a large segment of people who are currently underusing mobile health (mHealth) solutions. System usability continues to hinder mHealth adoption among users with nontraditional digital literacy., Objective: This study aims to investigate if state-of-the-art mobile app interfaces from open-source libraries provide sufficient usability for rural patients with cancer, with minimal design changes and forgoing the co-design process., Methods: We developed Assuage (Network Reconnaissance Lab) as a research platform for any mHealth study. We conducted a pilot study using Assuage to assess the usability of 4 mobile user interfaces (UIs) based on open-source libraries from Apple's ResearchKit and CareKit. These UIs varied in complexity for reporting distress symptoms. Patients with cancer were recruited at the Markey Cancer Center, and all research procedures were conducted in person. Participants completed the distress assessment using a randomly selected UI in Assuage with little to no assistance. Data were collected on participant age, location, mobile app use, and familiarity with mHealth apps. Participants rated usability with the System Usability Scale (SUS), and usability issues were documented and compared. A one-way ANOVA was used to compare the effect of the UIs on the SUS scores., Results: We recruited 30 current or postsurgery patients with cancer for this pilot study. Most participants were aged >50 years (24/30, 80%), from rural areas (25/30, 83%), had up to a high school education (19/30, 63%), and were unfamiliar with mHealth apps (21/30, 70%). General mobile app use was split, with 43% (14/30) of the patients not regularly using mobile apps. The mean SUS score across the UIs was 75.8 (SD 22.2), with UI 3 and UI 4 achieving an SUS score ≥80, meeting the industry standard for good usability of 80. Critical usability issues were related to data input and navigation with touch devices, such as scale-format questions, vertical scrolling, and traversing multiple screens., Conclusions: The findings from this study show that most patients with cancer (20/30, 67%) who participated in this study rated the different interfaces of Assuage as above-average usability (SUS score >68). This suggests that Apple's ResearchKit and CareKit libraries can provide usable UIs for older and rural users with minimal interface alterations. When resources are limited, the design stage can be simplified by omitting the co-design process while preserving suitable usability for users with nontraditional technical proficiency. Usability comparable to industry standards can be achieved by considering heuristics for interface and electronic survey design, specifically how to segment and navigate surveys, present important interface elements, and signal gestural interactions., (©Alyssa Donawa, Christian Powell, Rong Wang, Ming-Yuan Chih, Reema Patel, Ralph Zinner, Eliah Aronoff-Spencer, Corey E Baker. Originally published in JMIR Formative Research (https://formative.jmir.org), 26.09.2024.)

To achieve a consensus on optimal blood pressure (BP) targets for older adults remains challenging, necessitating a trade-off between cardiovascular benefits and the risk of impaired organ perfusion. Evidence suggests that age and frailty have a minimal influence on the cardiovascular benefits of intensive BP control in community-dwelling elderly. Nonetheless, an increased incidence of acute kidney injury with intensive BP control has been observed in octogenarians. Therefore, it is recommended to maintain systolic BP below 130 mmHg for hypertensive patients aged 65-80 years. If well-tolerated, a systolic BP target below 120 mmHg can be recommended for patients with chronic kidney disease (CKD). However, no conclusive evidence supports a stringent BP target for patients aged 80 years and older. The selection of antihypertensive medications for elderly patients requires consideration of their cardiovascular condition and potential contraindications. Combination therapy may be necessary to achieve the desired BP target. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are the primary choices for patients with CKD. Newer generation mineralocorticoid receptor antagonists may further reduce the risk of cardiovascular or renal events in this population. In conclusion, managing hypertension in elderly patients requires a personalized approach that balances cardiovascular benefits with potential risks, considering individual health profiles and tolerability., Competing Interests: Declaration of competing interest None, (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

This paper reports the results of a hybrid effectiveness-implementation randomized trial that systematically varied levels of human oversight required to support the implementation of a digital medicine intervention for persons with mild-to-moderate alcohol use disorder (AUD). Participants were randomly assigned to three groups representing possible digital health support models within a health system: self-monitored use (SM; n = 185), peer-supported use (PS; n = 186), or a clinically integrated model CI; (n = 187). Across all three groups, the percentage of self-reported heavy drinking days dropped from 38.4% at baseline (95% CI [35.8%, 41%]) to 22.5% (19.5%, 25.5%) at 12 months. The clinically integrated group showed significant improvements in mental health and quality of life compared to the self-monitoring group (p = 0.011). However, higher attrition rates in the clinically integrated group warrant consideration in interpreting this result. Results suggest that making a self-guided digital intervention available to patients may be a viable option for health systems looking to promote alcohol risk reduction. This study was prospectively registered at clinicaltrials.gov on 7/03/2019 (NCT04011644)., (© 2024. The Author(s).)

Secondary hypertension in the elderly poses many challenges and requires a comprehensive diagnostic and management approach. This review explores the prevalence, diagnostic strategies, and treatment modalities for secondary hypertension in elderly patients, focusing on etiologies including primary aldosteronism, renal vascular disease, renal parenchymal disease, obstructive sleep apnea, thyroid disorders, Cushing's syndrome, pheochromocytomas and paragangliomas, and drug-induced hypertension. Key considerations include age-related changes in physiology and atypical presentations of underlying conditions necessitating thorough screening with a combination of clinical evaluation, laboratory tests, and imaging studies. Collaboration among healthcare providers is essential to ensure a timely diagnosis and personalized management tailored to the unique needs of elderly patients. Further research is needed to address knowledge gaps and optimize clinical strategies for managing secondary hypertension in this population., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Context: Patient misperceptions are a strong barrier to early palliative care discussions and referrals during advanced lung cancer treatment., Objectives: We developed and tested the acceptability of a web-based patient-facing palliative care education and screening tool intended for use in a planned multilevel intervention (i.e., patient, clinician, system-level targets)., Methods: We elicited feedback from advanced lung cancer patients (n = 6), oncology and palliative care clinicians (n = 4), and a clinic administrator (n = 1) on the perceived relevance of the intervention. We then tested the prototype of a patient-facing tool for patient acceptability and preliminary effects on patient palliative care knowledge and motivation., Results: Partners agreed that the intervention-clinician palliative care education and an electronic health record-integrated patient tool-is relevant and their feedback informed development of the patient prototype. Advanced stage lung cancer patients (n = 20; age 60 ± 9.8; 40% male; 70% with a technical degree or less) reviewed and rated the prototype on a five-point scale for acceptability (4.48 ± 0.55), appropriateness (4.37 ± 0.62), and feasibility (4.43 ± 0.59). After using the prototype, 75% were interested in using palliative care and 80% were more motivated to talk to their oncologist about it. Of patients who had or were at risk of having misperceptions about palliative care (e.g., conflating it with hospice), 100% no longer held the misperceptions after using the prototype., Conclusion: The palliative care education and screening tool is acceptable to patients and may address misperceptions and motivate palliative care discussions during treatment., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Aging-associated cardiovascular diseases depend on the longitudinal deterioration of stem cell dynamics. The entire mechanism behind it is not completely understood. However, many studies suggest that endocrine pathways, particularly the insulin-like growth factor-1(IGF1) signaling pathway are involved in cardioprotection, especially in stem-cell treatments. Here, we investigated the role of a co-chaperone, carboxyl-terminus of Hsp70 interacting protein (CHIP) in the aspects of growth factor secretion and receptor stabilization in mesenchymal stem cells (MSCs). Briefly, we overexpressed CHIP in rat adipose-derived stem cells (rADSCs) and explored the consequences in vitro , and in vivo , in spontaneously hypertensive rats (SHR). Our data revealed that CHIP overexpression in rADSCs promoted the secretion of insulin-like growth factor-1 (IGF1) and IGF binding protein-3 (IGFBP3) as per immunoblot/cytokine array analysis. We also found that these results were dependent on the nuclear translocation of signal transducer and activator of transcription 3 (STAT3) in rADSCs. Further, the CHIP co-chaperone was also involved in the stabilization of the receptor of IGF1 (IGF1R); interactions between the beta transmembrane region of IGF1R, and the tetracopeptide repeat (TPR) domain of CHIP were evident. Importantly, after the transplantation of lentiviral CHIP overexpression of rADSCs (rADSCs CHIP-WT ) into nine months aging-SHR led to an increase in their cardiac function - increased ejection fraction and fractional shortening (≈15% vs. control SHR) - as well as a decrease in their heart size and heart rate, respectively. Altogether, our results support the use of CHIP overexpressing stem cells for the mitigation of cardiac hypertrophy and remodeling associated with late-stage hypertension.

Ohwia caudata (Thunb.) H. Ohashi (Leguminosae) also called as "Evergreen shrub" and Artemisia argyi H.Lév. and Vaniot (Compositae) also named as "Chinese mugwort" those two-leaf extracts frequently used as herbal medicine, especially in south east Asia and eastern Asia. Anthracyclines such as doxorubicin (DOX) are commonly used as effective chemotherapeutic drugs in anticancer therapy around the world. However, chemotherapy-induced cardiotoxicity, dilated cardiomyopathy, and congestive heart failure are seen in patients who receive DOX therapy, with the mechanisms underlying DOX-induced cardiac toxicity remaining unclear. Mitochondrial dysfunction, oxidative stress, inflammatory response, and cardiomyocytes have been shown to play crucial roles in DOX-induced cardiotoxicity. Isoliquiritigenin (ISL, 10 mg/kg) is a bioactive flavonoid compound with protective effects against inflammation, neurodegeneration, cancer, and diabetes. Here, in this study, our aim is to find out the Artemisia argyi (AA) and Ohwia caudata (OC) leaf extract combination with Isoliquiritigenin in potentiating and complementing effect against chemo drug side effect to ameliorate cardiac damage and improve the cardiac function. In this study, we showed that a combination of low (AA 300 mg/kg; OC 100 mg/kg) and high-dose(AA 600 mg/kg; OC 300 mg/kg) AA and OC water extract with ISL activated the cell survival-related AKT/PI3K signaling pathway in DOX-treated cardiac tissue leading to the upregulation of the antioxidant markers SOD, HO-1, and Keap-1 and regulated mitochondrial dysfunction through the Nrf2 signaling pathway. Moreover, the water extract of AA and OC with ISL inhibited the inflammatory response genes IL-6 and IL-1β, possibly through the NFκB/AKT/PI3K/p38α/NRLP3 signaling pathways. The water extract of AA and OC with ISL could be a potential herbal drug treatment for cardiac hypertrophy, inflammatory disease, and apoptosis, which can lead to sudden heart failure., (© 2023 Wiley Periodicals LLC.)

Doxorubicin (DOX), an effective chemotherapeutic drug, has been used to treat various cancers; however, its cardiotoxic side effects restrict its therapeutic efficacy. Fisetin, a flavonoid phytoestrogen derived from a range of fruits and vegetables, has been reported to exert cardioprotective effects against DOX-induced cardiotoxicity; however, the underlying mechanisms remain unclear. This study investigated fisetin's cardioprotective role and mechanism against DOX-induced cardiotoxicity in H9c2 cardiomyoblasts and ovariectomized (OVX) rat models. MTT assay revealed that fisetin treatment noticeably rescued DOX-induced cell death in a dose-dependent manner. Moreover, western blotting and TUNEL-DAPI staining showed that fisetin significantly attenuated DOX-induced cardiotoxicity in vitro and in vivo by inhibiting the insulin-like growth factor II receptor (IGF-IIR) apoptotic pathway through estrogen receptor (ER)-α/-β activation. The echocardiography, biochemical assay, and H&E staining results demonstrated that fisetin reduced DOX-induced cardiotoxicity by alleviating cardiac dysfunction, myocardial injury, oxidative stress, and histopathological damage. These findings imply that fisetin has a significant therapeutic potential against DOX-induced cardiotoxicity., (© 2023 John Wiley & Sons Ltd.)

Background: Smartphone-based apps are increasingly used to prevent relapse among those with substance use disorders (SUDs). These systems collect a wealth of data from participants, including the content of messages exchanged in peer-to-peer support forums. How individuals self-disclose and exchange social support in these forums may provide insight into their recovery course, but a manual review of a large corpus of text by human coders is inefficient., Objective: The study sought to evaluate the feasibility of applying supervised machine learning (ML) to perform large-scale content analysis of an online peer-to-peer discussion forum. Machine-coded data were also used to understand how communication styles relate to writers' substance use and well-being outcomes., Methods: Data were collected from a smartphone app that connects patients with SUDs to online peer support via a discussion forum. Overall, 268 adult patients with SUD diagnoses were recruited from 3 federally qualified health centers in the United States beginning in 2014. Two waves of survey data were collected to measure demographic characteristics and study outcomes: at baseline (before accessing the app) and after 6 months of using the app. Messages were downloaded from the peer-to-peer forum and subjected to manual content analysis. These data were used to train supervised ML algorithms using features extracted from the Linguistic Inquiry and Word Count (LIWC) system to automatically identify the types of expression relevant to peer-to-peer support. Regression analyses examined how each expression type was associated with recovery outcomes., Results: Our manual content analysis identified 7 expression types relevant to the recovery process (emotional support, informational support, negative affect, change talk, insightful disclosure, gratitude, and universality disclosure). Over 6 months of app use, 86.2% (231/268) of participants posted on the app's support forum. Of these participants, 93.5% (216/231) posted at least 1 message in the content categories of interest, generating 10,503 messages. Supervised ML algorithms were trained on the hand-coded data, achieving F 1 -scores ranging from 0.57 to 0.85. Regression analyses revealed that a greater proportion of the messages giving emotional support to peers was related to reduced substance use. For self-disclosure, a greater proportion of the messages expressing universality was related to improved quality of life, whereas a greater proportion of the negative affect expressions was negatively related to quality of life and mood., Conclusions: This study highlights a method of natural language processing with potential to provide real-time insights into peer-to-peer communication dynamics. First, we found that our ML approach allowed for large-scale content coding while retaining moderate-to-high levels of accuracy. Second, individuals' expression styles were associated with recovery outcomes. The expression types of emotional support, universality disclosure, and negative affect were significantly related to recovery outcomes, and attending to these dynamics may be important for appropriate intervention., (©Ellie Fan Yang, Rachel Kornfield, Yan Liu, Ming-Yuan Chih, Prathusha Sarma, David Gustafson, John Curtin, Dhavan Shah. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.08.2023.)

Background: Diabetic cardiomyopathy is a progressive disease caused by inexplicit mechanisms, and a novel factor, insulin-like growth factor II receptor-α (IGF-IIRα), may contribute to aggravating its pathogenesis. We hypothesized that IGF-IIRα could intensify diabetic heart injury., Methods and Results: To demonstrate the potential role of IGF-IIRα in the diabetic heart, we used (SD-TG [IGF-IIRα]) transgenic rat model with cardiac-specific overexpression of IGF-IIRα, along with H9c2 cells, to study the effects of IGF-IIRα in the heart under hyperglycemic conditions. IGF-IIRα was found to remodel calcium homeostasis and intracellular Ca 2+ overload-induced autophagy disturbance in the heart during diabetes. IGF-IIRα overexpression induced intracellular Ca 2+ alteration by downregulating phosphorylated phospholamban/sarcoplasmic/endoplasmic reticulum calcium-ATPase 2a (PLB/SERCA2a), resulting in the suppression of Ca 2+ uptake into the endoplasmic reticulum. Additionally, IGF-IIRα itself contributed to Ca 2+ withdrawal from the endoplasmic reticulum by increasing the expression of CaMKIIδ in the active form. Furthermore, alterations in Ca 2+ homeostasis significantly dysregulated autophagy in the heart during diabetes., Conclusions: Our study reveals the novel role of IGF-IIRα in regulating cardiac intracellular Ca 2+ homeostasis and its related autophagy interference, which contribute to the development of diabetic cardiomyopathy. In future, the present study findings have implications in the development of appropriate therapy to reduce diabetic cardiomyopathy., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Diabetes-induced cardiovascular complications are mainly associated with high morbidity and mortality in patients with diabetes. Insulin-like growth factor II receptor α (IGF-IIRα) is a cardiac risk factor. In this study, we hypothesized IGF-IIRα could also deteriorate diabetic heart injury. The results presented that both in vivo transgenic Sprague-Dawley rat model with specific IGF-IIRα overexpression in the heart and in vitro myocardium H9c2 cells were used to investigate the negative function of IGF-IIRα in diabetic hearts. The results showed that IGF-IIRα overexpression aided hyperglycemia in creating more myocardial injury. Pro-inflammatory factors, such as Tumor necrosis factor-alpha, Interleukin-6, Cyclooxygenase-2, Inducible nitric oxide synthase, and Nuclear factor-kappaB inflammatory cascade, are enhanced in the diabetic myocardium with cardiac-specific IGF-IIRα overexpression. Correspondingly, IGF-IIRα overexpression in the diabetic myocardium also reduced the PI3K-AKT survival axis and activated mitochondrial-dependent apoptosis. Finally, both ejection fraction and fractional shortening were be significantly decrease in diabetic rats with cardiac-specific IGF-IIRα overexpression. Overall, all results provid clear evidence that IGF-IIRα can enhance cardiac damage and is a harmful factor to the heart under high-blood glucose conditions. However, the pathophysiology of IGF-IIRα under different stresses and its downstream regulation in the heart still require further research., (© 2022 Wiley Periodicals LLC.)

The present study aimed to develop a smartphone application (app) that addressed identified barriers to success in voice therapy; accessibility, and poor adherence to home practice. The study objectives were (1) to investigate if app use enhanced adherence to the home practice of voice therapy and (2) to test app usability. Maximizing the effectiveness of voice therapy is vital as voice disorders are detrimental to personal and professional quality of life. A single-blinded randomized clinical trial was completed for the first objective. Participants included normophonic individuals randomly assigned to the app group or the traditional group. The primary outcome measure was adherence measured as the number of missed home practice tasks. The second objective was completed through usability testing and a focus group discussion. The app group ( n = 12) missed approximately 50% less home practice tasks as compared to the traditional group ( n = 13) and these results were statistically significant ( p = 0.04). Dropout rates were comparable between the two groups. Usability results were positive for good usability with high perceived usefulness and perceived ease of use. App use resulted in improved adherence to home practice tasks. App usability results were positive, and participants provided specific areas of improvement which are achievable. Areas for improvement include app engagement and willingness to pay.

Cardiovascular diseases in post-menopausal women are on a rise. Oxidative stress is the main contributing factor to the etiology and pathogenesis of cardiovascular diseases. Diosgenin, a member of steroidal sapogenin, is structurally similar to estrogen and has been shown to have antioxidant effects. Therefore, we aimed to investigate the effects of diosgenin in preventing oxidation-induced cardiomyocyte apoptosis and assessed its potential as a substitute substance for estrogen in post-menopausal women. Apoptotic pathways and mitochondrial membrane potential were measured in H9c2 cardiomyoblast cells and neonatal cardiomyocytes treated with diosgenin for 1[Formula: see text]h prior to hydrogen peroxide (H 2 O 2 ) stimulation. H 2 O 2 -stimulated H9c2 cardiomyoblast cells displayed cytotoxicity and apoptosis via the activation of both Fas-dependent and mitochondria-dependent pathways. Additionally, it led to the instability of the mitochondrial membrane potential. However, the H 2 O 2 -induced H9c2 cell apoptosis was rescued by diosgenin through IGF1 survival pathway activation. This led to the recovery of the mitochondrial membrane potential by suppressing the Fas-dependent and mitochondria-dependent apoptosis. Diosgenin also inhibited H 2 O 2 -induced cytotoxicity and apoptosis through the estrogen receptor interaction with PI3K/Akt and extracellular regulated protein kinases 1/2 activation in myocardial cells. In this study, we confirmed that diosgenin attenuated H 2 O 2 -induced cytotoxicity and apoptosis through estrogen receptors-activated phosphorylation of PI3K/Akt and ERK signaling pathways in myocardial cells via estrogen receptor interaction. All results suggest that H 2 O 2 -induced myocardial damage is reduced by diosgenin due to its interaction with estrogen receptors to decrease the damage. Herein, we conclude that diosgenin might be a potential substitute substance for estrogen in post-menopausal women to prevent heart diseases.

Background: Rural Appalachian residents experience among the highest prevalence of chronic disease, premature mortality, and decreased life expectancy in the nation. Addressing these growing inequities while avoiding duplicating existing programming necessitates the development of appropriate adaptations of evidence-based lifestyle interventions. Yet few published articles explicate how to accomplish such contextual and cultural adaptation., Methods: In this paper, we describe the process of adapting the Make Better Choices 2 (MBC2) mHealth diet and activity randomized trial and the revised protocol for intervention implementation in rural Appalachia. Deploying the NIH's Cultural Framework on Health and Aaron's Adaptation framework, the iterative adaptation process included convening focus groups (N = 4, 38 participants), conducting key informant interviews (N = 16), verifying findings with our Community Advisory Board (N = 9), and deploying usability surveys (N = 8), wireframing (N = 8), and pilot testing (N = 9. This intense process resulted in a comprehensive revision of recruitment, retention, assessment, and intervention components. For the main trial, 350 participants will be randomized to receive either the multicomponent MBC2 diet and activity intervention or an active control condition (stress and sleep management). The main outcome is a composite score of four behavioral outcomes: two outcomes related to diet (increased fruits and vegetables and decreased saturated fat intake) and two related to activity (increased moderate vigorous physical activity [MVPA] and decreased time spent on sedentary activities). Secondary outcomes include change in biomarkers, including blood pressure, lipids, A1C, waist circumference, and BMI., Discussion: Adaptation and implementation of evidence-based interventions is necessary to ensure efficacious contextually and culturally appropriate health services and programs, particularly for underserved and vulnerable populations. This article describes the development process of an adapted, community-embedded health intervention and the final protocol created to improve health behavior and, ultimately, advance health equity., Trial Registration: ClinicalTrials.gov Identifier NCT04309461. The trial was registered on 6/3/2020., (© 2022. The Author(s).)

Oxidized low-density lipoprotein (ox-LDL) is a type of modified cholesterol that promotes apoptosis and inflammation and advances the progression of heart failure. Leucine-zipper and sterile-α motif kinase (ZAK) is a kinase of the MAP3K family which is highly expressed in the heart and encodes two variants, ZAKα and ZAKβ. Our previous study serendipitously found opposite effects of ZAKα and ZAKβ in which ZAKβ antagonizes ZAKα-induced apoptosis and hypertrophy of the heart. This study aims to test the hypothesis of whether ZAKα and ZAKβ are involved in the damaging effects of ox-LDL in the cardiomyoblast. Cardiomyoblast cells H9c2 were treated with different concentrations of ox-LDL. Cell viability and apoptosis were measured by MTT and TUNEL assay, respectively. Western blot was used to detect apoptosis, hypertrophy, and pro-survival signaling proteins. Plasmid transfection, pharmacological inhibition with D2825, and siRNA transfection were utilized to upregulate or downregulate ZAKβ, respectively. Ox-LDL concentration-dependently reduces the viability and expression of several pro-survival proteins, such as phospho-PI3K, phospho-Akt, and Bcl-xL. Furthermore, ox-LDL increases cleaved caspase-3, cleaved caspase-9 as indicators of apoptosis and increases B-type natriuretic peptide (BNP) as an indicator of hypertrophy. Overexpression of ZAKβ by plasmid transfection attenuates apoptosis and prevents upregulation of BNP. Importantly, these effects were abolished by inhibiting ZAKβ either by D2825 or siZAKβ application. Our results suggest that ZAKβ upregulation in response to ox-LDL treatment confers protective effects on cardiomyoblast., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hypertension is the most important modifiable cause of cardiovascular (CV) disease and all-cause mortality worldwide. Despite the positive correlations between blood pressure (BP) levels and later CV events since BP levels as low as 100/60 mmHg have been reported in numerous epidemiological studies, the diagnostic criteria of hypertension and BP thresholds and targets of antihypertensive therapy have largely remained at the level of 140/90 mmHg in the past 30 years. The publication of both the SPRINT and STEP trials (comprising > 8,500 Caucasian/African and Chinese participants, respectively) provided evidence to shake this 140/90 mmHg dogma. Another dogma regarding hypertension management is the dependence on office (or clinic) BP measurements. Although standardized office BP measurements have been widely recommended and adopted in large-scale CV outcome trials, the practice of office BP measurements has never been ideal in real-world practice. Home BP monitoring (HBPM) is easy to perform, more likely to be free of environmental and/or emotional stress, feasible to document long-term BP variations, of good reproducibility and reliability, and more correlated with hypertension-mediated organ damage (HMOD) and CV events, compared to routine office BP measurements. In the 2022 Taiwan Hypertension Guidelines of the Taiwan Society of Cardiology (TSOC) and the Taiwan Hypertension Society (THS), we break these two dogmas by recommending the definition of hypertension as ≥ 130/80 mmHg and a universal BP target of < 130/80 mmHg, based on standardized HBPM obtained according to the 722 protocol. The 722 protocol refers to duplicate BP readings taken per occasion ("2"), twice daily ("2"), over seven consecutive days ("7"). To facilitate implementation of the guidelines, a series of flowcharts encompassing assessment, adjustment, and HBPM-guided hypertension management are provided. Other key messages include that: 1) lifestyle modification, summarized as the mnemonic S-ABCDE, should be applied to people with elevated BP and hypertensive patients to reduce life-time BP burden; 2) all 5 major antihypertensive drugs (angiotensin-converting enzyme inhibitors [A], angiotensin receptor blockers [A], β-blockers [B], calcium-channel blockers [C], and thiazide diuretics [D]) are recommended as first-line antihypertensive drugs; 3) initial combination therapy, preferably in a single-pill combination, is recommended for patients with BP ≥ 20/10 mmHg above targets; 4) a target hierarchy (HBPM-HMOD- ambulatory BP monitoring [ABPM]) should be considered to optimize hypertension management, which indicates reaching the HBPM target first and then keeping HMOD stable or regressed, otherwise ABPM can be arranged to guide treatment adjustment; and 5) renal denervation can be considered as an alternative BP-lowering strategy after careful clinical and imaging evaluation.

Background: Recent shifts to telemedicine and remote patient monitoring demonstrate the potential for new technology to transform health systems; yet, methods to design for inclusion and resilience are lacking., Objective: The aim of this study is to design and implement a participatory framework to produce effective health care solutions through co-design with diverse stakeholders., Methods: We developed a design framework to cocreate solutions to locally prioritized health and communication problems focused on cancer care. The framework is premised on the framing and discovery of problems through community engagement and lead-user innovation with the hypothesis that diversity and inclusion in the co-design process generate more innovative and resilient solutions. Discovery, design, and development were implemented through structured phases with design studios at various locations in urban and rural Kentucky, including Appalachia, each building from prior work. In the final design studio, working prototypes were developed and tested. Outputs were assessed using the System Usability Scale as well as semistructured user feedback., Results: We co-designed, developed, and tested a mobile app (myPath) and service model for distress surveillance and cancer care coordination following the LAUNCH (Linking and Amplifying User-Centered Networks through Connected Health) framework. The problem of awareness, navigation, and communication through cancer care was selected by the community after framing areas for opportunity based on significant geographic disparities in cancer and health burden resource and broadband access. The codeveloped digital myPath app showed the highest perceived combined usability (mean 81.9, SD 15.2) compared with the current gold standard of distress management for patients with cancer, the paper-based National Comprehensive Cancer Network Distress Thermometer (mean 74.2, SD 15.8). Testing of the System Usability Scale subscales showed that the myPath app had significantly better usability than the paper Distress Thermometer (t 63 =2.611; P=.01), whereas learnability did not differ between the instruments (t 63 =-0.311; P=.76). Notable differences by patient and provider scoring and feedback were found., Conclusions: Participatory problem definition and community-based co-design, design-with methods, may produce more acceptable and effective solutions than traditional design-for approaches., (©Eliah Aronoff-Spencer, Melanie McComsey, Ming-Yuan Chih, Alexandra Hubenko, Corey Baker, John Kim, David K Ahern, Michael Christopher Gibbons, Joseph A Cafazzo, Pia Nyakairu, Robin C Vanderpool, Timothy W Mullett, Bradford W Hesse. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 12.04.2022.)

People with low health literacy are more likely to use mobile apps for health information. The choice of mHealth apps can affect health behaviors and outcomes. However, app descriptions may not be very readable to the target users, which can negatively impact app adoption and utilization. In this study, we assessed the readability of mHealth app descriptions and explored the relationship between description readability and other app metadata, as well as description writing styles. The results showed that app descriptions were at eleventh- to fifteenth-grade level, with only 6% of them meeting the readability recommendation (third- to seventh-grade level). The description readability played a vital role in predicting app installs when an app had no reviews. The content analysis showed copy-paste behaviors and identified two potential causes for low readability. More work is needed to improve the readability of app descriptions and optimize mHealth app adoption and utilization., (©2021 AMIA - All rights reserved.)

Background: The extent of human interaction needed to achieve effective and cost-effective use of mobile health (mHealth) apps for individuals with mild to moderate alcohol use disorder (AUD) remains largely unexamined. This study seeks to understand how varying levels of human interaction affect the ways in which an mHealth intervention for the prevention and treatment of AUDs works or does not work, for whom, and under what circumstances., Objective: The primary aim is to detect the effectiveness of an mHealth intervention by assessing differences in self-reported risky drinking patterns and quality of life between participants in three study groups (self-monitored, peer-supported, and clinically integrated). The cost-effectiveness of each approach will also be assessed., Methods: This hybrid type 1 study is an unblinded patient-level randomized clinical trial testing the effects of using an evidence-based mHealth system on participants' drinking patterns and quality of life. There are two groups of participants for this study: individuals receiving the intervention and health care professionals practicing in the broader health care environment. The intervention is a smartphone app that encourages users to reduce their alcohol consumption within the context of integrative medicine using techniques to build healthy habits. The primary outcomes for quantitative analysis will be participant data on their risky drinking days and quality of life as well as app use from weekly and quarterly surveys. Cost measures include intervention and implementation costs. The cost per participant will be determined for each study arm, with intervention and implementation costs separated within each group. There will also be a qualitative assessment of health care professionals' engagement with the app as well as their thoughts on participant experience with the app., Results: This protocol was approved by the Health Sciences Minimal Risk Institutional Review Board on November 18, 2019, with subsequent annual reviews. Recruitment began on March 6, 2020, but was suspended on March 13, 2020, due to the COVID-19 pandemic restrictions. Limited recruitment resumed on July 6, 2020. Trial status as of November 17, 2021, is as follows: 357 participants were enrolled in the study for a planned enrollment of 546 participants., Conclusions: The new knowledge gained from this study could have wide and lasting benefits related to the integration of mHealth systems for individuals with mild to moderate AUDs. The results of this study will guide policy makers and providers toward cost-effective ways to incorporate technology in health care and community settings., Trial Registration: ClinicalTrials.gov NCT04011644; https://clinicaltrials.gov/ct2/show/NCT04011644., International Registered Report Identifier (irrid): DERR1-10.2196/31109., (©Linda S Park, Ming-Yuan Chih, Christine Stephenson, Nicholas Schumacher, Randall Brown, David Gustafson, Bruce Barrett, Andrew Quanbeck. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 18.02.2022.)

To identify the core structure of 2-aminoethoxydiphenyl borate (2-APB) responsible for the anti-oxidative and protective effect on the ischemia/reperfusion (I/R)-induced heart injury, various 2-APB analogues were analyzed, and several antioxidant assays were performed. Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Myocardial infarct size was quantified using triphenyl tetrazolium chloride (TTC) staining. The levels of tumor necrosis factor-alpha (TNF-α) and cleaved-caspase-3 protein were evaluated as an indicator for the anti-inflammatory and anti-apoptotic effect, respectively. Our data show that 2-APB, diphenylborinic anhydride (DPBA) and 3-(diphenylphosphino)-1-propylamine (DP3A) all exerted the anti-oxidative activity, but only 2-APB and DPBA can scavenge H 2 O 2 . 2-APB and DPBA can potently inhibit hydrogen peroxide (H 2 O 2 )- and hypoxanthine/xanthine oxidase (HX/XOD)-induced increases in intracellular H 2 O 2 and H9c2 cell death. 2-APB and DPBA were able to decrease the I/R-induced adult rat cardiomyocytes death, myocardial infarct size, and the levels of malondialdehyde (MDA) and creatine kinase-MB (CK-MB). Our results suggest that the two benzene rings with a boron atom comprise the core structure of 2-APB responsible for the anti-oxidative effect mediated through the reaction with H 2 O 2 and generation of phenolic compounds, which in turn reduced the I/R-induced oxidative stress and injury in the rat heart.

Objectives: The Kimny guiding catheter is a single universal guiding catheter used for performing percutaneous coronary intervention (PCI) in both the right coronary artery (RCA) and the left coronary artery (LCA). Although this guiding catheter has been shown to yield high procedural success rates in nonemergent conditions, its feasibility for patients with ST-segment elevation myocardial infarction (STEMI) remains unknown and therefore needs to be further investigated., Materials and Methods: We retrospectively enrolled 62 consecutive STEMI patients who underwent primary PCI using the Kimny guiding catheter from January 2016 through December 2017. We then evaluated the rates of engagement and procedural success for PCI of the LCA and RCA with the Kimny guiding catheter., Results: Primary PCI of the infarct-related artery (IRA) by means of the Kimny guiding catheter proved to be successful in 61 of the STEMI patients (98.3%). Besides, the procedural success rate was found to be 100% (44/44) for the LCA and 94.4% (17/18) for the RCA ( P = 0.293). With regard to contralateral (non-IRA) angiography, engagement rates of 97.4% (38/39) and 100% (18/18) were obtained for the RCA and LCA, respectively, ( P = 1.0). No coronary artery ostial dissection was observed during the procedures. The mean number of total catheters used for each patient turned out to be only 1.035., Conclusion: Using the Kimny guiding catheter for primary PCI is feasible and results in high procedural success rates, particularly for the treatment of the LCA, with fewer catheters, and at a lower cost., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Tzu Chi Medical Journal.)

Habitual chewing of areca nut increases the risk of cardiovascular disease mortality, but less report demonstrate the toxic mechanism of areca nut on heart. To investigate toxicity of areca nut on cardiomyocytes, we induced the heart injury with arecoline to evaluate the acute damage of areca nut on heart. Different concentrations of are coline (lowdosage: 5 mg/kg/day and high dosage 50 mg/kg/day) were injected into Sprague-Dawley rat via intra-peritoneal method for 21 days to create negative effects of arecoline on cardiomyocyte. Themyocardial architecture of the rat heart was observed. The arecoline-induced apoptotic proteins were analysed via western blotting. The myocardialarchitecture of heart was injured with arecoline and TUNEL stain was also shown are coline-induced cardiac apoptosis. Arecoline promoted the protein expression of both Fas dependent snd mitochondrial dependent apoptosis. In summary, arecoline induces cardiac toxicity and apoptosis by inducing both death receptor and mitochondria-dependent apoptotic pathways on heart., (© 2021 Wiley Periodicals LLC.)

Diabetes-induced cardiomyocyte apoptosis is one of the major causes of mortality in patients with diabetes. Numerous studies have indicated the beneficial effects of Lactobacillus reuteri GMNL-263. However, the protective effect of Lactobacillus reuteri GMNL-263 in cardiac damage associated with diabetes remains poorly understood. In this study, we aimed to investigate the protective effect of Lactobacillus reuteri GMNL-263 on cardiomyocytes in diabetic rats. Five-week-old male Wistar rats were categorized into normal control group, diabetes group (55 mg/kgw STZ-induced diabetes via intraperitoneal injection), and diabetic animals treated with Lactobacillus reuteri GMNL-263 (10 9  CFU/rat/day, oral administration for 4 weeks). The results were presented that oral administration of a high dose of Lactobacillus reuteri GMNL-263 in diabetic rats activated IGF1R cell survival pathways to decrease the Fas-dependent and mitochondrial-dependent apoptotic pathways induced by hyperglycemia. We found that GMNL-263 significantly attenuated cell apoptosis via the IGF1R survival pathway in diabetic rats. The findings of this study suggest that GMNL-263 treatment maybe an effective therapeutic approach for the prevention of cardiac apoptosis in patients with diabetes., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background: The 2016 President's Cancer Panel called for projects focusing on improving cancer symptom management using connected health technologies (broadband and telecommunications). However, rural communities, like those in Appalachia, may experience a "double burden" of high cancer rates and lower rates of broadband access and adoption necessary for connected health solutions., Purpose: To better understand the current landscape of connected health in the management of cancer symptoms in rural America., Methods: A literature search was conducted using four academic databases (PubMed, CINAHL, MEDLINE, and PsycINFO) to locate articles published from 2010 to 2019 relevant to connected cancer symptom management in rural America. Text screening was conducted to identify relevant publications., Results: Among 17 reviewed studies, four were conducted using a randomized controlled trial; the remainder were formative in design or small pilot projects. Five studies engaged stakeholders from rural communities in designing solutions. Most commonly studied symptoms were psychological/emotional symptoms, followed by physical symptoms, particularly pain. Technologies used were primarily telephone-based; few were Internet-enabled video conferencing or web-based. Advanced mobile and Internet-based approaches were generally in the development phase. Overall, both rural patients and healthcare providers reported high acceptance, usage, and satisfaction of connected health technologies. Ten of the 17 studies reported improved symptom management outcomes. Methodological challenges that limited the interpretation of the findings were summarized., Implications: The review identified a need to engage rural stakeholders to develop and test connected cancer symptom management solutions that are based on advanced mobile and broadband Internet technologies., Competing Interests: This narrative review was prepared by the L.A.U.N.C.H. (Linking & Amplifying User-Centered Networks through Connected Health), a public-private collaborative between the National Cancer Institute (NCI), the Federal Communications Commission (FCC), Amgen, the University of California San Diego Design Lab, and the University of Kentucky Markey Cancer Center. Direct funding support was provided by Westat and Amgen. The authors greatly appreciate the review support provided by Grant Patterson from Amgen, and Michele Ellison, Ben Bartolome, Brayden Parker, and Karen Onyeije from the FCC. The Research Communications Office at the University of Kentucky’s Markey Cancer Center assisted with preparation of this manuscript. This research was also supported by the Biostatistics and Bioinformatics Shared Resource Facilities of the University of Kentucky Markey Cancer Center (P30CA177558). Disclaimer: The opinions expressed by the authors are their own, and this material should not be interpreted as representing the official viewpoint of the Federal Communications Commission, the U.S. Department of Health and Human Services, the National Institutes of Health or the National Cancer Institute. No competing financial or editorial interests were reported by the authors of this paper., (Copyright © 2020 Ming-Yuan Chih, Anna McCowan, Sadie Whittaker, Melinda Krakow, David K. Ahern, Eliah Aronoff-Spencer, Bradford W. Hesse, Timothy W. Mullett, and Robin C. Vanderpool.)

The purpose of this study was to investigate the nature and effects of exchanging emotional support via a smartphone-based support group for patients with alcohol dependence. Of the 349 patients who met the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for alcohol dependence, 153 patients participated in the discussion group within the Addiction-Comprehensive Health Enhancement Support System, a smartphone application aimed at reducing relapse. This was developed to prevent problem drinking by offering individuals in recovery for alcohol dependence automated 24/7 recovery support services and frequent assessment of their symptom status as part of their addiction care. The results showed that receiving emotional support from health care providers improved coping self-efficacy. Giving emotional support and receiving emotional support from health care providers acted as a buffer, protecting patients from the harmful effects of emotional distress on risky drinking. Clinicians and researchers should use the features of smartphone-based support groups to reach out to alcoholic patients in need and encourage them to participate in the exchange of emotional support with others.

Quilted Appalachian Sunset©2011 Jim Harrisjim-harris.pixels.com Nothing tells the story of people working together better than a community quilt. A diversity of talents, colors, and materials brought together through skill and shared purpose. Perhaps never before have we as Americans needed a stronger reminder that many hands make short work of big problems. The work presented here by the L.A.U.N.C.H. Collaborative offers a new framework for health care that could be compared to a digital quilt, powered by community-based participatory design, with lived expertise and the newest advances in broadband-enabled connected health solutions. This work demonstrates the value and need to engage local communities and what can be learned when beneficiaries and traditional caregivers work together to develop healthcare solutions., Competing Interests: Disclaimer: The statements, analyses, and conclusions set forth in this article are those of the named authors and do not necessarily reflect the views of the authors’ respective organizational affiliation or other organizations that are part of the L.A.U.N.C.H. Collaborative, including the FCC and NCI. No competing financial or editorial interests were reported by the authors of this paper., (Copyright © 2020 Melanie McComsey, David Ahern, Robin C. Vanderpool, Timothy W. Mullett, Ming-Yuan Chih, Meghan Johnson, Michele Ellison, Karen Onyeije, Bradford W. Hesse, and Eliah Aronoff-Spencer.)

A meta-analysis of oncology papers from around the world revealed that cancer patients who lived more than 50 miles away from hospital centers routinely presented with more advanced stages of disease at diagnosis, exhibited lower adherence to prescribed treatments, presented with poorer diagnoses, and reported a lower quality of life than patients who lived nearer to care facilities. Connected health approaches-or the use of broadband and telecommunications technologies to evaluate, diagnose, and monitor patients beyond the clinic-are becoming an indispensable tool in medicine to overcome the obstacle of distance., Competing Interests: Disclaimer: The statements, analyses, and conclusions set forth in this commentary are those of the named authors and do not necessarily reflect the views of the authors’ respective organizational affiliation or other organizations that are part of the L.A.U.N.C.H. Collaborative, including the FCC and NCI. No competing financial or editorial interests were reported by the authors of this paper., (Copyright © 2020 Bradford W. Hesse, David Ahern, Michele Ellison, Eliah Aronoff-Spencer, Robin C. Vanderpool, Karen Onyeije, Michael C. Gibbons, Timothy W. Mullett, Ming-Yuan Chih, Victoria Attencio, Grant Patterson, Jessica Boten, Christopher Hartshorn, Ben Bartolome, Katie Gorscak, Melanie McComsey, Alexandra Hubenko, Bin Huang, Corey Baker, and Don Norman.)

Background: Data on clinical outcome after drug-eluting stent (DES) vs. bare-metal stent (BMS) implantation in patients with end-stage renal disease (ESRD) under hemodialysis are limited and controversial., Methods and results: We identified 4,970 patients under chronic hemodialysis from Taiwan National Health Insurance Research Database (NHIRD) who had their first coronary stenting between 1 January 2007 and 31 December 2012. After 1:1 propensity score matching, we evaluated clinical outcomes for 1,151 patients in the DES group and 1,151 patients in the matched BMS group. We used ICD-9 CM codes or operation code to identify all outcomes in the study cohort after the index procedure. Primary outcomes including composite endpoints of mortality, non-fatal myocardial infarction (MI), non-fatal stroke, and revascularization after the index procedure were similar in both groups (HR, 0.94; 95% CI: 0.81-1.09; P=0.399). The results were consistent in various generations of DES vs. BMS groups. Secondary outcomes including mortality, non-fatal MI, non-fatal stroke, revascularization, cardiovascular death, hospitalization for heart failure, peptic ulcer bleeding or blood transfusion were similar in both groups, except for a lower risk of peptic ulcer disease in the DES group (HR, 0.59; 95% CI: 0.41-0.83; P=0.003) than the BMS group., Conclusions: In patients on chronic hemodialysis, implantation of DES did not have a better clinical outcome than BMS.

Background: Family members absorb much of the care of dementia patients. The burden of care substantially impacts caregivers' health, further straining our healthcare system. By 2050, the incidence of Alzheimer's disease will more than double, increasing the numbers of family caregivers proportionally. Interventions that reduce their burden are needed to preserve their health as well as the viability of the healthcare system., Objective: This paper reports on the development and feasibility testing of a computer-based system intended to improve the lives of caregivers. D-CHESS (Dementia-Comprehensive Health Enhancement Support System) allows users to obtain information, communicate with other caregivers, get help with care decisions, and share information with experts., Method: Thirty-one caregivers were randomly assigned to an intervention group receiving D-CHESS for 6 months or to a control group receiving a caregiving book. Surveys at 0, 2, 4, and 6 months evaluated caregiver burden, family conflict, satisfaction with decisions, social support, loneliness, anxiety, depression, and coping competence., Results: Survey findings suggest D-CHESS participants may perform better on measures of social support, anxiety, loneliness, and coping competence; the groups were equivalent on caregiver burden, decision satisfaction, and depression, and the control group reported less family conflict than the intervention. D-CHESS use data suggested enhancements to system design and content to increase awareness and use of various features., Conclusion: This study suggests that D-CHESS has potential to positively impact family caregivers and that the system merits further development and investigation with a full-scale clinical trial.

Background: Advanced cancer can erode patients' wellbeing. Narrative interventions have improved patients' wellbeing, but might not be feasible for widespread implementation., Objectives: (1) Test the effects of miLivingStory, a telephone-based life review and illness narrative intervention with online resources and social networking, on community-dwelling advanced cancer patients' wellbeing. (2) Explore intervention use and satisfaction., Patients and Setting: Stage III or IV cancer patients having completed initial therapy were randomized to miLivingStory or to an active control group, miOwnResources. Data and Analysis: Primary outcomes measured at baseline, two and four months included subscales for the FACIT-Sp peace and meaning and the POMS-SF depressed, anxious, and angry mood, scored on 0-4-point Likert scales. Linear mixed modeling, controlling for baseline primary outcome scores, tested for group comparisons of repeated outcome measures. Pairwise comparisons tested for within- and between-group differences. Intervention use and satisfaction data were collected automatically and by survey., Results: Eighty-six primarily white, female patients with high baseline wellbeing completed the study. There were no between-group differences at baseline or at two months. At four months, miLivingStory had a direct and positive effect for peace (2.86 vs. 2.57, p = 0.029), a trend effect for lower depressed mood (0.55 vs. 0.77, p = 0.097), and appeared to protect against the control group's declining wellbeing between two and four months. miLivingStory use was low and assessed as helpful to quite helpful., Conclusions: Telephone-based narrative interventions hold promise in improving advanced cancer patients' wellbeing. Further testing of delivery and implementation strategies is warranted.

Background: Despite the near ubiquity of mobile phones, little research has been conducted on the implementation of mobile health (mHealth) apps to treat patients in primary care. Although primary care clinicians routinely treat chronic conditions such as asthma and diabetes, they rarely treat addiction, a common chronic condition. Instead, addiction is most often treated in the US health care system, if it is treated at all, in a separate behavioral health system. mHealth could help integrate addiction treatment in primary care., Objective: The objective of this paper was to report the effects of implementing an mHealth system for addiction in primary care on both patients and clinicians., Methods: In this implementation research trial, an evidence-based mHealth system named Seva was introduced sequentially over 36 months to a maximum of 100 patients with substance use disorders (SUDs) in each of three federally qualified health centers (FQHCs; primary care clinics that serve patients regardless of their ability to pay). This paper reports on patient and clinician outcomes organized according to the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework., Results: The outcomes according to the RE-AIM framework are as follows: Reach-Seva reached 8.31% (268/3226) of appropriate patients. Reach was limited by our ability to pay for phones and data plans for a maximum of 100 patients per clinic. Effectiveness-Patients who were given Seva had significant improvements in their risky drinking days (44% reduction, (0.7-1.25)/1.25, P=.04), illicit drug-use days (34% reduction, (2.14-3.22)/3.22, P=.01), quality of life, human immunodeficiency virus screening rates, and number of hospitalizations. Through Seva, patients also provided peer support to one another in ways that are novel in primary care settings. Adoption-Patients sustained high levels of Seva use-between 53% and 60% of the patients at the 3 sites accessed Seva during the last week of the 12-month implementation period. Among clinicians, use of the technology was less robust than use by patients, with only a handful of clinicians using Seva in each clinic and behavioral health providers making most referrals to Seva in 2 of the 3 clinics. Implementation-At 2 sites, implementation plans were realized successfully; they were delayed in the third. Maintenance-Use of Seva dropped when grant funding stopped paying for the mobile phones and data plans. Two of the 3 clinics wanted to maintain the use of Seva, but they struggled to find funding to support this., Conclusions: Implementing an mHealth system can improve care among primary care patients with SUDs, and patients using the system can support one another in their recovery. Among clinicians, however, implementation requires figuring out how information from the mHealth system will be used and making mHealth data available in the electronic health (eHealth) record. In addition, paying for an mHealth system remains a challenge., (©Andrew Quanbeck, David H Gustafson, Lisa A Marsch, Ming-Yuan Chih, Rachel Kornfield, Fiona McTavish, Roberta Johnson, Randall T Brown, Marie-Louise Mares, Dhavan V Shah. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 30.01.2018.)

Background: External change agents can play an essential role in healthcare organizational change efforts. This systematic review examines the role that external change agents have played within the context of multifaceted interventions designed to promote organizational change in healthcare-specifically, in primary care settings., Methods: We searched PubMed, CINAHL, Cochrane, Web of Science, and Academic Search Premier Databases in July 2016 for randomized trials published (in English) between January 1, 2005 and June 30, 2016 in which external agents were part of multifaceted organizational change strategies. The review was conducted according to PRISMA guidelines. A total of 477 abstracts were identified and screened by 2 authors. Full text articles of 113 studies were reviewed. Twenty-one of these studies were selected for inclusion., Results: Academic detailing (AD) is the most prevalently used organizational change strategy employed as part of multi-component implementation strategies. Out of 21 studies, nearly all studies integrate some form of audit and feedback into their interventions. Eleven studies that included practice facilitation into their intervention reported significant effects in one or more primary outcomes., Conclusions: Our results demonstrate that practice facilitation with regular, tailored follow up is a powerful component of a successful organizational change strategy. Academic detailing alone or combined with audit and feedback alone is ineffective without intensive follow up. Provision of educational materials and use of audit and feedback are often integral components of multifaceted implementation strategies. However, we didn't find examples where those relatively limited strategies were effective as standalone interventions. System-level support through technology (such as automated reminders or alerts) is potentially helpful, but must be carefully tailored to clinic needs.

Background: Symptom distress in patients toward the end of life can change rapidly. Family caregivers have the potential to help patients manage those symptoms, as well as their own stress, if they are equipped with the proper resources. Electronic health (eHealth) systems may be able to provide those resources. Very sick patients may not be able to use such systems themselves to report their symptoms but family caregivers could., Objective: The aim of this paper was to assess the effects on cancer patient symptom distress of an eHealth system that alerts clinicians to significant changes in the patient's symptoms, as reported by a family caregiver., Methods: A pooled analysis from two randomized clinical trials (NCT00214162 and NCT00365963) compared outcomes at 12 months for two unblinded groups: a control group (Comprehensive Health Enhancement Support System [CHESS]-Only) that gave caregivers access to CHESS, an online support system, and an experimental group (CHESS+CR [Clinician Report]), which also had CHESS but with a CR that automatically alerted clinicians if symptoms exceeded a predetermined threshold of severity. Participants were dyads (n=235) of patients with advanced lung, breast, or prostate cancer and their respective family caregivers from 5 oncology clinics in the United States of America. The proportion of improved patient threshold symptoms was compared between groups using area-under-the-curve analysis and binomial proportion tests. The proportion of threshold symptoms out of all reported symptoms was also examined., Results: When severe caregiver-reported symptoms were shared with clinicians, the symptoms were more likely to be subsequently reported as improved than when the symptoms were not shared with clinicians (P<.001). Fewer symptom reports were completed in the group of caregivers whose reports went to clinicians than in the CHESS-Only group (P<.001), perhaps because caregivers, knowing their reports might be sent to a doctor, feared they might be bothering the clinician., Conclusions: This study suggests that an eHealth system designed for caregivers that alerts clinicians to worrisome changes in patient health status may lead to reduced patient distress., Trial Registration: Clinicaltrials.gov NCT00214162; https://clinicaltrials.gov/ct2/show/NCT00214162 (Archived by WebCite at http://www.webcitation.org/6nmgdGfuD) and Clinicaltrials.gov NCT00365963; https://clinicaltrials.gov/ct2/show/NCT00365963 (Archived by WebCite at http://www.webcitation.org/6nmh0U8VP)., (©David H Gustafson, Lori L DuBenske, Amy K Atwood, Ming-Yuan Chih, Roberta A Johnson, Fiona McTavish, Andrew Quanbeck, Roger L Brown, James F Cleary, Dhavan Shah. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 14.11.2017.)

This study investigated the role of breast cancer survivors in a computer-mediated social support (CMSS) group for women with breast cancer. Applying a computer-aided content analytic method, the present study examined the differences in support provision between survivors and newly diagnosed patients. This study further investigated the impacts of survivor-provided social support on psychosocial adjustment of newly diagnosed patients. The results revealed that, compared with newly diagnosed patients, breast cancer survivors provided more emotional and informational support. Receiving emotional support from survivors contributed to an improvement in the quality of life and the depression of patients. The effects of survivor-provided informational support were not significant., Competing Interests: Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This article presents an innovative methodology to study computer-mediated communication (CMC), which allows analysis of the multi-layered effects of online expression and reception. The methodology is demonstrated by combining the following three data sets collected from a widely tested eHealth system, the Comprehensive Health Enhancement Support System (CHESS): 1) a flexible and precise computer-aided content analysis; 2) a record of individual message posting and reading; and 3) longitudinal survey data. Further, this article discusses how the resulting data can be applied to online social network analysis and demonstrates how to construct two distinct types of online social networks - open and targeted communication networks - for different types of content embedded in social networks.

In obstructive sleep apnea (OSA), recurrent obstruction of the upper airway leads to intermittent hypoxia (IH) during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON) or to a group receiving 10 weeks of exercise training (EXE). During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE), whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect., Competing Interests: The authors have declared that no competing interests exist.

A breast cancer diagnosis typically results in dramatic and negative effects on an individual's quality of life. Web-based interactive support systems such as the Comprehensive Health Enhancement Support System (CHESS) offer one avenue for mitigating these negative effects. While evidence supports the efficacy of such systems, evaluations typically fail to provide a true test of the theorized model of effects, treating self-determination theory's constructs of competence, relatedness, and autonomy as outcomes rather than mediators. Using path analysis, this study tests the nature of the proposed mediated relationship between system engagement and quality-of-life indicators utilizing data collected from women (N = 90) who participated in the treatment condition of a CHESS randomized controlled trial. Findings support a latent model, indicating that system effects are mediated through an intertwined measure of autonomy, competence, and relatedness.

Pyomyositis is a pyogenic infection of the skeletal muscles causing myalgia and fever in patients. Hematogenous seeding engendered by persistent bacteremia and septic embolism is usually the underlying cause of the disease. Trauma, intravenous drug use, and immunodeficiency are the main predisposing factors.Obturator internus pyomyositis with sciatica has not previously been reported. We report a rare case of a patient with subacute bacterial endocarditis presenting with left buttock pain and sciatica.Computed tomography confirmed the diagnosis of obturator internus pyomyositis. The patient was discharged uneventfully after successful antibiotic treatment.The mortality rate of patients who have pyomyositis comorbid with another condition or disease is extremely high. Early diagnosis and aggressive management are imperative., Competing Interests: The authors have no conflicts of interest to disclose.

The U.S. criminal justice system refers more people to substance abuse treatment than any other system. Low treatment completion rates and high relapse rates among addicted offenders highlight the need for better substance use disorder treatment and recovery tools. Mobile health applications (apps) may fill that need by providing continuous support. In this pilot test, 30 participants in a Massachusetts drug court program used A-CHESS, a mobile app for recovery support and relapse prevention, over a four-month period. Over the course of the study period, participants opened A-CHESS on average of 62% of the days that they had the app. Social networking tools were the most utilized services. The study results suggest that drug court participants will make regular use of a recovery support app. This pilot study sought to find out if addicted offenders in a drug court program would use a mobile application to support and manage their recovery.

Background: With the increasing penetration of digital mobile devices among adolescents, mobile texting messaging is emerging as a new channel for patient-clinician communication for this population. In particular, it can promote active communication between healthcare clinicians and adolescents with asthma. However, little is known about the content of the messages exchanged in medical encounters via mobile text messaging. Therefore, this study explored the content of text messaging between clinicians and adolescents with asthma., Materials and Methods: We collected a total of 2,953 text messages exchanged between 5 nurse case managers and 131 adolescents with asthma through a personal digital assistant. The text messages were coded using a scheme developed by adapting categories from the Roter Interaction Analysis System., Results: Nurse case managers sent more text messages (n=2,639) than adolescents with asthma. Most messages sent by nurse case managers were targeted messages (n=2,475) directed at all adolescents with asthma, whereas there were relatively few tailored messages (n=164) that were created personally for an individual adolescent. In addition, both targeted and tailored messages emphasized task-focused behaviors over socioemotional behaviors. Likewise, text messages (n=314) sent by adolescents also emphasized task-focused over socioemotional behaviors., Conclusions: Mobile texting messaging has the potential to play an important role in patient-clinician communication. It promotes not only active interaction, but also patient-centered communication with clinicians. In order to achieve this potential, healthcare clinicians may need to focus on socioemotional communication as well as task-oriented communication.

How patients used Addiction-Comprehensive Health Enhancement Support System (A-CHESS)1, a mobile health intervention, while quitting drinking is worthy exploring. This study is to explore A-CHESS use patterns prior to the initial lapse reported after discharge from inpatient detoxification programs. 142 patients with alcohol addiction from two treatment agencies in the U.S. were included. A comprehensive set of A-CHESS use measures were developed based on a three-level system use framework and three A-CHESS service categories. In latent profile analyses, three A-CHESS system use patterns-inactive, passive, and active users-were found. Compared to the passive users (with the highest chance of the initial lapse), the active users (with the lowest chance of such behavior) participated more in online social activities, used more sessions, viewed more pages, and used A-CHESS longer. However, the chances of the initial lapse between A-CHESS user profiles were not statistically different. Implications of this finding were provided.

Objective: Informal caregivers (family and friends) of people with cancer are often unprepared for their caregiving role, leading to increased burden or distress. Comprehensive Health Enhancement Support System (CHESS) is a Web-based lung cancer information, communication, and coaching system for caregivers. This randomized trial reports the impact on caregiver burden, disruptiveness, and mood of providing caregivers access to CHESS versus the Internet with a list of recommended lung cancer websites., Methods: A total of 285 informal caregivers of patients with advanced nonsmall cell lung cancer were randomly assigned to a comparison group that received Internet or a treatment group that received Internet and CHESS. Caregivers were provided a computer and Internet service if needed. Written surveys were completed at pretest and during the intervention period bimonthly for up to 24 months. Analyses of covariance (ANCOVAs) compared the intervention's effect on caregivers' disruptiveness and burden (CQOLI-C), and negative mood (combined Anxiety, Depression, and Anger scales of the POMS) at 6 months, controlling for blocking variables (site, caregiver's race, and relationship to patient) and the given outcome at pretest., Results: Caregivers randomized to CHESS reported lower burden, t(84) = 2.36, p = .021, d = .39, and negative mood, t(86) = 2.82, p = .006, d = .44, than those in the Internet group. The effect on disruptiveness was not significant., Conclusions: Although caring for someone with a terminal illness will always exact a toll on caregivers, eHealth interventions like CHESS may improve caregivers' understanding and coping skills and, as a result, ease their burden and mood.

Importance: Patients leaving residential treatment for alcohol use disorders are not typically offered evidence-based continuing care, although research suggests that continuing care is associated with better outcomes. A smartphone-based application could provide effective continuing care., Objective: To determine whether patients leaving residential treatment for alcohol use disorders with a smartphone application to support recovery have fewer risky drinking days than control patients., Design, Setting, and Participants: An unmasked randomized clinical trial involving 3 residential programs operated by 1 nonprofit treatment organization in the Midwestern United States and 2 residential programs operated by 1 nonprofit organization in the Northeastern United States. In total, 349 patients who met the criteria for DSM-IV alcohol dependence when they entered residential treatment were randomized to treatment as usual (n = 179) or treatment as usual plus a smartphone (n = 170) with the Addiction-Comprehensive Health Enhancement Support System (A-CHESS), an application designed to improve continuing care for alcohol use disorders., Interventions: Treatment as usual varied across programs; none offered patients coordinated continuing care after discharge. A-CHESS provides monitoring, information, communication, and support services to patients, including ways for patients and counselors to stay in contact. The intervention and follow-up period lasted 8 and 4 months, respectively., Main Outcomes and Measures: Risky drinking days--the number of days during which a patient's drinking in a 2-hour period exceeded 4 standard drinks for men and 3 standard drinks for women, with standard drink defined as one that contains roughly 14 g of pure alcohol (12 oz of regular beer, 5 oz of wine, or 1.5 oz of distilled spirits). Patients were asked to report their risky drinking days in the previous 30 days on surveys taken 4, 8, and 12 months after discharge from residential treatment., Results: For the 8 months of the intervention and 4 months of follow-up, patients in the A-CHESS group reported significantly fewer risky drinking days than did patients in the control group, with a mean of 1.39 vs 2.75 days (mean difference, 1.37; 95% CI, 0.46-2.27; P = .003)., Conclusions and Relevance: The findings suggest that a multifeatured smartphone application may have significant benefit to patients in continuing care for alcohol use disorders., Trial Registration: clinicaltrials.gov Identifier: NCT01003119.

The chronically relapsing nature of alcoholism leads to substantial personal, family, and societal costs. Addiction-comprehensive health enhancement support system (A-CHESS) is a smartphone application that aims to reduce relapse. To offer targeted support to patients who are at risk of lapses within the coming week, a Bayesian network model to predict such events was constructed using responses on 2,934 weekly surveys (called the Weekly Check-in) from 152 alcohol-dependent individuals who recently completed residential treatment. The Weekly Check-in is a self-monitoring service, provided in A-CHESS, to track patients' recovery progress. The model showed good predictability, with the area under receiver operating characteristic curve of 0.829 in the 10-fold cross-validation and 0.912 in the external validation. The sensitivity/specificity table assists the tradeoff decisions necessary to apply the model in practice. This study moves us closer to the goal of providing lapse prediction so that patients might receive more targeted and timely support., (© 2013.)

Several systems for treating alcohol-use disorders (AUDs) exist that operate on mobile phones. These systems are categorized into four groups: text-messaging monitoring and reminder systems, text-messaging intervention systems, comprehensive recovery management systems, and game-based systems. Text-messaging monitoring and reminder systems deliver reminders and prompt reporting of alcohol consumption, enabling continuous monitoring of alcohol use. Text-messaging intervention systems additionally deliver text messages designed to promote abstinence and recovery. Comprehensive recovery management systems use the capabilities of smart-phones to provide a variety of tools and services that can be tailored to individuals, including in-the-moment assessments and access to peer discussion groups. Game-based systems engage the user using video games. Although many commercial applications for treatment of AUDs exist, few (if any) have empirical evidence of effectiveness. The available evidence suggests that although texting-based applications may have beneficial effects, they are probably insufficient as interventions for AUDs. Comprehensive recovery management systems have the strongest theoretical base and have yielded the strongest and longest-lasting effects, but challenges remain, including cost, understanding which features account for effects, and keeping up with technological advances.

Background: Metabolic syndrome has been shown to be associated with lower levels of plasma N-terminal pro-B-type natriuretic peptide (Nt-proBNP) in the general population. We sought to elucidate the relationship between Nt-proBNP and components of metabolic syndrome in patients with congestive heart failure (CHF)., Methods: Fasting blood samples were obtained from 93 patients in our institution. Plasma levels of Nt-proBNP and other biochemical data were measured. The New York Heart Association (NYHA) classification system (I-IV) was used to define the functional capacity of CHF. Metabolic syndrome and its components were defined using diagnostic criteria from the International Diabetes Federation., Results: Forty-nine patients (52.7%) had CHF. There was a positive correlation between plasma Nt-proBNP levels and NYHA functional capacity in CHF patients. Plasma Nt-proBNP levels increased significantly with each increasing NYHA class of the disease. The prevalence of metabolic syndrome in CHF patients was higher than that in patients without CHF. Most importantly, we found that plasma Nt-proBNP levels were lower in CHF patients with metabolic syndrome attributable to inverse relationships between plasma Nt-proBNP and body mass index (β = -0.297), plasma triglyceride (β = -0.286) and homeostasis model assessment of insulin resistance (HOMA-IR; β = -0.346). Fasting glucose to insulin ratio (FGIR, an insulin sensitivity index) was positively associated with plasma Nt-proBNP levels (β = 0.491), and was the independent predictor of plasma Nt-proBNP levels in CHF patients., Conclusions: Plasma Nt-proBNP levels are inversely associated with metabolic syndrome in CHF patients. Reduced plasma Nt-proBNP levels in CHF patients may lead to impaired lipolysis and metabolic function, and may contribute to the development of metabolic syndrome in CHF patients.

Background: Using available communication technologies, clinicians may offer timely support to family caregivers in managing symptoms in patients with advanced cancer at home., Aim: To assess the effects of an online symptom reporting system on caregiver preparedness, physical burden, and negative mood., Design: A pooled analysis of two randomized trials (NCT00214162 and NCT00365963) was conducted to compare caregiver outcomes at 6 and 12 months after intervention between two randomized, unblinded groups using General Linear Mixed Modeling. Caregivers in one group (Comprehensive Health Enhancement Support System-Only) were given access to an interactive cancer communication system, the Comprehensive Health Enhancement Support System. Those in the other group (Comprehensive Health Enhancement Support System + Clinician Report) received access to Comprehensive Health Enhancement Support System plus an online symptom reporting system called the Clinician Report. Clinicians of patients in the Comprehensive Health Enhancement Support System + Clinician Report group received e-mail alerts notifying them when a symptom distress was reported over a predetermined threshold., Setting/participants: Dyads (n = 235) of advanced-stage lung, breast, and prostate cancer patients and their adult caregivers were recruited at five outpatient oncology clinics in the United States., Results: Caregivers in the Comprehensive Health Enhancement Support System + Clinician Report group reported less negative mood than those in the Comprehensive Health Enhancement Support System-Only group at both 6 months (p = 0.009) and 12 months (p = 0.004). Groups were not significantly different on caregiver preparedness or physical burden at either time point., Conclusions: This study provides new evidence that by using an online symptom reporting system, caregivers may experience less emotional distress due to the Clinician Report's timely communication of caregiving needs in symptom management to clinicians.

Background: In this study, the authors examined the effectiveness of an online support system (Comprehensive Health Enhancement Support System [CHESS]) versus the Internet in relieving physical symptom distress in patients with non-small cell lung cancer (NSCLC)., Methods: In total, 285 informal caregiver-patient dyads were assigned randomly to receive, for up to 25 months, standard care plus training on and access to either use of the Internet and a list of Internet sites about lung cancer (the Internet arm) or CHESS (the CHESS arm). Caregivers agreed to use CHESS or the Internet and to complete bimonthly surveys; for patients, these tasks were optional. The primary endpoint-patient symptom distress-was measured by caregiver reports using a modified Edmonton Symptom Assessment Scale., Results: Caregivers in the CHESS arm consistently reported lower patient physical symptom distress than caregivers in the Internet arm. Significant differences were observed at 4 months (P = .031; Cohen d = .42) and at 6 months (P = .004; d = .61). Similar but marginally significant effects were observed at 2 months (P = .051; d = .39) and at 8 months (P = .061; d = .43). Exploratory analyses indicated that survival curves did not differ significantly between the arms (log-rank P = .172), although a survival difference in an exploratory subgroup analysis suggested an avenue for further study., Conclusions: The current results indicated that an online support system may reduce patient symptom distress. The effect on survival bears further investigation., (Copyright © 2013 American Cancer Society.)