Adverse drug reactions of non-statin antihyperlipidaemic drugs in China from 1989 to 2019: a national database analysis.

OBJECTIVE: This study aims to understand the adverse drug reactions (ADRs) for non-statin antihyperlipidaemic drugs included in the China Anti-hyperlipidemic Drug Database. DESIGN: An approach of Chinese national database analysis was employed to screen clinical trials involving non-statin antihyperlipidaemic drugs from 1989 to 2019. SETTING: The database was provided by the China National Medical Products Administration Information Centre. PARTICIPANTS: In total, 117 clinical studies with 8800 patients were selected from 2650 clinical trials of the Anti-hyperlipidemic Drug Database. INTERVENTIONS: The non-statin antihyperlipidaemic drugs were divided into three groups: (1) fibrates (fenofibrate, gemfibrozil, bezafibrate, etofylline clofibrate); (2) nicotinic acid and derivatives (niacin, acipimox) and (3) others (probucol, cholestyramine). RESULTS: The results of this study show that first, gastrointestinal symptoms were the most common reactions (6.975%), which account for approximately 50% of the reported cases with ADRs. Second, cholestyramine (16.418%) and gemfibrozil (13.158%) were the most common gastrointestinal side effect-causing non-statin antihyperlipidaemic drugs, which account for one-third of the population. Third, niacin (7.879%) and gemfibrozil (5.000%) were the most likely cause of liver disease symptoms. Finally, niacin (10.909%) and acipimox (18.847%) were the major non-statin antihyperlipidaemic drugs with skin symptoms. CONCLUSION: This study revealed that gastrointestinal symptoms were the most common ADRs of fibrates, probucol and cholestyramine in the Chinese population. For nicotinic acid and derivatives, the ADRs of skin symptoms were the most common in China.

LigaSure versus Conventional Parotidectomy: A Systematic Review and Meta-Analysis.

Surgery with parotidectomy is the preferable treatment for most parotid tumors. Our meta-analysis compared the differences between the use of the LigaSure (LS) device and the conventional suture ligation technique (CT) in parotidectomies. A literature search in databases including EMBASE, MEDLINE, and the Cochrane Library was carried out. Studies including parotidectomy using LS and CT were included with the intraoperative and postoperative parameters collected. Continuous operative time data were measured by mean differences (MDs). Discrete data on postoperative complications, including facial palsy, postoperative bleeding, and salivary complications, were evaluated with risk differences (RDs). All values were reported with 95% confidence intervals (CIs). Five studies were included in our meta-analysis. The pooled analysis demonstrated a significant reduction in operative time in the LS group (MD: -21.92; 95% CI, -30.18 to -13.66). In addition, the analysis indicated that the incidence of postoperative complications, including permanent facial palsy (RD, -0.01; 95% CI, -0.06 to 0.05), temporary facial palsy (RD, 0.00; 95% CI, -0.03 to 0.04), salivary complications (RD, -0.01; 95% CI, -0.08 to 0.06), and postoperative bleeding (RD, -0.02; 95% CI, -0.07 to 0.04), were all similar between the LS group and the CT group. According to the results, the LS device appears to be a safe and useful tool and could shorten the operative time in patients needing parotidectomy.

Innovative Strategies to Fuel Organic Food Business Growth: A Qualitative Research.

This study aimed to identify the factors affecting consumer behavior and customer loyalty toward organic food. Whether consumers seek organic food for a healthy body or more as food for thought continues to be debated. However, since consumers' purchase habits are based on their honest life experiences, which shape the building of a brand, this study reviewed the extant literature to understand the factors influencing the purchasing behavior for organic food. The follow-up problems highlighted in the research are related to organic business marketing strategy. Based on our methodology, we conducted semi-structured interviews to gain themes for qualitative research. The study found that availability, variety, and taste were the top three factors affecting consumers' purchase decisions; surprisingly, neither price nor health-consciousness was the first concern. Using market-led innovation as an innovative lens to understand customer loyalty, this research highlights sustainable and advantageous business practices in the organic food market to enrich the literature on organic food purchasing behavior from multiple stakeholders.

Functional regulation of an outer retina hyporeflective band on optical coherence tomography images.

Human and animal retinal optical coherence tomography (OCT) images show a hyporeflective band (HB) between the photoreceptor tip and retinal pigment epithelium layers whose mechanisms are unclear. In mice, HB magnitude and the external limiting membrane-retinal pigment epithelium (ELM-RPE) thickness appear to be dependent on light exposure, which is known to alter photoreceptor mitochondria respiration. Here, we test the hypothesis that these two OCT biomarkers are linked to metabolic activity of the retina. Acetazolamide, which acidifies the subretinal space, had no significant impact on HB magnitude but produced ELM-RPE thinning. Mitochondrial stimulation with 2,4-dinitrophenol reduced both HB magnitude and ELM-RPE thickness in parallel, and also reduced F-actin expression in the same retinal region, but without altering ERG responses. For mice strains with relatively lower (C57BL/6J) or higher (129S6/ev) rod mitochondrial efficacy, light-induced changes in HB magnitude and ELM-RPE thickness were correlated. Humans, analyzed from published data captured with a different protocol, showed a similar light-dark change pattern in HB magnitude as in the mice. Our results indicate that mitochondrial respiration underlies changes in HB magnitude upstream of the pH-sensitive ELM-RPE thickness response. These two distinct OCT biomarkers could be useful indices for non-invasively evaluating photoreceptor mitochondrial metabolic activity.

FOS licenses early events in stem cell activation driving skeletal muscle regeneration.

Muscle satellite cells (SCs) are a quiescent (non-proliferative) stem cell population in uninjured skeletal muscle. Although SCs have been investigated for nearly 60 years, the molecular drivers that transform quiescent SCs into the rapidly dividing (activated) stem/progenitor cells that mediate muscle repair after injury remain largely unknown. Here we identify a prominent FBJ osteosarcoma oncogene (Fos) mRNA and protein signature in recently activated SCs that is rapidly, heterogeneously, and transiently induced by muscle damage. We further reveal a requirement for FOS to efficiently initiate key stem cell functions, including cell cycle entry, proliferative expansion, and muscle regeneration, via induction of "pro-regenerative" target genes that stimulate cell migration, division, and differentiation. Disruption of one of these Fos/AP-1 targets, NAD(+)-consuming mono-ADP-ribosyl-transferase 1 (Art1), in SCs delays cell cycle entry and impedes progenitor cell expansion and muscle regeneration. This work uncovers an early-activated FOS/ART1/mono-ADP-ribosylation (MARylation) pathway that is essential for stem cell-regenerative responses.

How Geographical Isolation and Aging in Place Can Be Accommodated Through Connected Health Stakeholder Management: Qualitative Study With Focus Groups.

BACKGROUND: In remote areas, connected health (CH) is needed, but as local resources are often scarce and the purchasing power of residents is usually poor, it is a challenge to apply CH in these settings. In this study, CH is defended as a technological solution for reshaping the direction of health care to be more proactive, preventive, and precisely targeted-and thus, more effective. OBJECTIVE: The objective of this study was to explore the identity of CH stakeholders in remote areas of Taiwan and their interests and power in order to determine ideal strategies for applying CH. We aimed to explore the respective unknowns and discover insights for those facing similar issues. METHODS: Qualitative research was conducted to investigate and interpret the phenomena of the aging population in a remote setting. An exploratory approach was employed involving semistructured interviews with 22 participants from 8 remote allied case studies. The interviews explored perspectives on stakeholder arrangements, including the power and interests of stakeholders and the needs of all the parties in the ecosystem. RESULTS: Results were obtained from in-depth interviews and focus groups that included identifying the stakeholders of remote health and determining how they influence its practice, as well as how associated agreements bring competitive advantages. Stakeholders included people in government sectors, industrial players, academic researchers, end users, and their associates who described their perspectives on their power and interests in remote health service delivery. Specific facilitators of and barriers to effective delivery were identified. A number of themes, such as government interests and power of decision making, were corroborated across rural and remote services. These themes were broadly grouped into the disclosure of conflicts of interest, asymmetry in decision making, and data development for risk assessment. CONCLUSIONS: This study contributes to current knowledge by exploring the features of CH in remote areas and investigating its implementation from the perspectives of stakeholder management. It offers insights into managing remote health through a CH platform, which can be used for preliminary quantitative research. Consequently, these findings could help to more effectively facilitate diverse stakeholder engagement for health information sharing and social interaction.

Smart, Remote, and Targeted Health Care Facilitation Through Connected Health: Qualitative Study.

BACKGROUND: Societies around the world are aging. Widespread aging creates problems for social services and health care practices. In this light, research on connected health (CH) is becoming essential. CH refers to a variety of technological measures that allow health care to be provided remotely with the aim of increasing efficiency, cost-effectiveness, and satisfaction on the part of health care recipients. CH is reshaping health care's direction to be more proactive, more preventive, and more precisely targeted and, thus, more effective. CH has been demonstrated to have great value in managing and preventing chronic diseases, which create huge burdens on health care and social services. In short, CH provides promising solutions to diseases and social challenges associated with aging populations. However, there are many barriers that need to be overcome before CH can be successfully and widely implemented. OBJECTIVE: The research question of this study is as follows: How can CH facilitate smart, remote, and targeted health care? The objective is to identify how health care can be managed in more comprehensive ways, such as by providing timely, flexible, accessible, and personalized services to preserve continuity and offer high-quality seamless health care. METHODS: A qualitative approach was used based on 60 multistage, semistructured stakeholder interviews. RESULTS: The results can be divided into two functions of CH: ecosystem and platform. On the one hand, the interviews enabled the authors to develop a stakeholder classification and interaction diagram. These stakeholders interacted sequentially to provide technology-based content to end users. On the other hand, interviewees reflected on how CH serves as a platform to address remote monitoring and patient self-management. In the Discussion section, three innovation strategies are discussed to reflect the manner in which CH promotes smart, timely, and precise health care. CONCLUSIONS: This study indicates that it is essential to continually revise CH business models, given the ongoing and rapid changes in technology across groups of CH stakeholders. We also found that global trends toward smart, timely, and precise health care shape what individuals expect from products and services, providing firms with unique opportunities for growth.

"Nomen Omen": Exploring Connected Healthcare through the Perspective of Name Omen.

Background: The evolution of names, from "medical informatics" to "connected health", implies that the evolvement of technology in health care has been shifted from technology-oriented to healthcare-oriented implementation. Connected healthcare, a healthcare platform of remote monitoring and self-management through technological measures, is suggested to contribute to the efficiency, cost-effectiveness, and satisfaction of healthcare recipient enhancement. However, limited understanding of related connected health (CH) terminology may constrain its implementation. Whether CH is a buzzword only or a practice that can contribute to an aging society is controversial. Objective: This study aims to distinguish CH-related terminology and to identify the trend of CH through reviewing its definition, initiation, development, and evolvement, in order to offer management insights and implications. The objective is to understand what is connected and who is cared about in the connected health model so that better applications can be addressed for the benefit of society. Method: This study reviews the evolution of names, from "medical informatics" in the 1970s to "connected health" after 2000, as well as relevant literature of CH, including e-health, telemedicine, telehealth, telecare, and m-health, to discover the trend of technology-related healthcare innovations. Results: The current status and issues facing accessibility, quality, and cost were presented. Its future trends will be explored through reviewing how changes in healthcare are managed, in addition to its operation and practice. Pre-conditions and requirements for implementing CH are identified to select a typical case to study. Findings suggest that areas with a complete business ecosystem-isolated locations, advanced information technology, aging in population, integrated health, and social care system-are prevalent for designing friendly CH environments. Conclusion: The evidence and tendency of technological convergence create a demand for innovation and partnering with start-up companies that offer a competitive advantage in innovation.

Factors Influencing the Application of Connected Health in Remote Areas, Taiwan: A Qualitative Pilot Study.

This pilot study investigated factors influencing the application of connected health (CH) in Taiwanese remote areas. These factors cover issues of cost, infrastructure, technology, business sustainability, business model, collaboration, and communication. It aimed to explore the significance and to assess the feasibility of researching CH in Taiwan. A qualitative exploratory study was conducted by interviewing relevant stakeholders (n = 18). The majority were healthcare providers as most of them are the CH end users. Their feedback was essential in reflecting the effectiveness of CH products and services. Therefore, understanding their views is significant in the design of a successful and user-friendly interactive system. A theoretical framework on the introduction of innovations in healthcare was employed to guide data collection and thematic analysis. Additionally, stakeholders proposed strategies for enhancing the implementation of CH in remote areas. This pilot study also contributed to identifying future directions and information for conducting the multi-stage interviews for collecting the data more effectively. Although the results reveal that the study of CH is meaningful, there is an issue of business sustainability which is obscured by some barriers that need to be addressed. These barriers will be further investigated in the first-stage interview and second-stage interview in future research. The research findings also suggest that strategies and sustainability for CH implementation should be included from the planning phase to benefit all the stakeholders in the CH ecosystem.

Light-Dependent OCT Structure Changes in Photoreceptor Degenerative rd 10 Mouse Retina.

Purpose: Using optical coherence tomography (OCT) to analyze the effects of light/dark adaptation in a mouse model of inherited photoreceptor degeneration (rd10), and to study dynamics of subretinal fluid during the progress of retinal degeneration. Methods: rd10 and wild-type (WT) C57BL/6J mice were reared in cyclic light or darkness and imaged with Bioptigen UHR-OCT or Spectralis HRA+OCT after adaptation to either light or darkness. Results: OCT images from rd10 mice were analyzed at three progressive stages of degeneration. After light-adaptation, stage I (postnatal age [P]26-29) eyes demonstrated no apparent subretinal fluid. At stage II (P32-38), subretinal fluid was present and restricted to parapapillary area, while at stage III (P44-45) extensive subretinal fluid was present across many retinal areas. Following overnight dark-adaptation, WT eyes showed a large reduction in outer retinal thickness (4.6 ± 1.4 µm, n = 16), whereas this change was significantly smaller in stage I rd10 eyes (1.5 ± 0.5 µm, n = 14). In stage II rd10 eyes, dark-adaptation significantly reduced the extent of subretinal fluid, with the amount of reduction correlating with the amount of fluid pre-existing in the light-adapted state. However, dark-adaptation did not significantly alter the amount of subretinal fluid observed in stage III rd10 mice. In addition, dark-rearing of rd10 mice from P6 to P30 slowed retinal degeneration. Conclusions: Visual experience in the form of light/dark adaptation exerts a significant effect on outer retinal structure in the context of photoreceptor degeneration. This effect may arise from light-dependent alterations in fluid transport across the RPE monolayer, and promote photoreceptor survival as induced by dark-rearing.

Technological Health Intervention in Population Aging to Assist People to Work Smarter not Harder: Qualitative Study.

BACKGROUND: Technology-based health care has been promoted as an effective tool to enable clinicians to work smarter. However, some health stakeholders believe technology will compel users to work harder by creating extra work. OBJECTIVE: The objective of this study was to investigate how and why electronic health (eHealth) has been applied in Taiwan and to suggest implications that may inspire other countries facing similar challenges. METHODS: A qualitative methodology was adopted to obtain insightful inputs from deeper probing. Taiwan was selected as a typical case study, given its aging population, advanced technology, and comprehensive health care system. This study investigated 38 stakeholders in the health care ecosystem through in-depth interviews and focus groups, which provides an open, flexible, and enlightening way to study complex, dynamic, and interactive situations through informal conversation or a more structured, directed discussion. RESULTS: First, respondents indicated that the use of technology can enable seamless patient care and clinical benefits such as flexibility in time management. Second, the results suggested that a leader's vision, authority, and management skills might influence success in health care innovation. Finally, the results implied that both internal and external organizational governance are highly relevant for implementing technology-based innovation in health care. CONCLUSIONS: This study provided Taiwanese perspectives on how to intelligently use technology to benefit health care and debated the perception that technology prevents human interaction between clinicians and patients.

Nasopharyngeal Carcinoma Diagnostic Challenge in a Nonendemic Setting: Our Experience with 101 Patients.

INTRODUCTION: We studied the presenting symptoms, time intervals, and workup involved in the diagnosis of nasopharyngeal carcinoma in an integrated health care system. METHODS: A retrospective chart review of all patients with a nasopharyngeal carcinoma diagnosis between 2007 and 2010 at Kaiser Permanente Northern California. Main outcome measures included diagnostic time intervals, presenting symptoms, diagnostic accuracy of nasal endoscopy, imaging, and diagnosis at first otolaryngologist (Oto-HNS) visit. RESULTS: This study included 101 patients: 70 (70%) were of Chinese or of Southeast Asian descent. The median time intervals along the diagnostic pathway were symptom onset to primary care physician visit, 6.0 weeks; primary care physician to Oto-HNS, 2.4 weeks; Oto-HNS to pathologic diagnosis, 1.1 weeks; and diagnosis to treatment onset, 5.5 weeks. The most common presenting symptoms were otologic issues (41, 41%), neck mass (39, 39%), nasal issues (32, 32%), and headache/cranial neuropathy (16, 16%). A nasopharyngeal lesion was detected in 54 (53%) patients after the first Oto-HNS visit. Among the initial nasal endoscopy reports, 32 (32%) did not reveal a nasopharyngeal lesion; 32 (32%) initial imaging studies also did not reveal a nasopharyngeal lesion. There was no correlation between diagnostic delay and disease stage. CONCLUSION: Nasopharyngeal carcinoma presenting symptoms are extremely variable, and initial misdiagnosis is common. Median time from symptom onset to treatment was almost six months among patients studied. Nearly one-third of nasopharyngeal cancers were missed with nasal endoscopy and imaging. An understanding of the risk factors, presenting symptoms, and limitations associated with these diagnostic tests is necessary to support earlier detection of this insidious cancer.

Practice patterns in endoscopic dacryocystorhinostomy: survey of the American Rhinologic Society.

BACKGROUND: The introduction of advanced endoscopic techniques has facilitated significant growth in endoscopic dacryocystorhinostomy (EnDCR). The purpose of this study is to evaluate clinical practice patterns of otolaryngologists performing EnDCR. METHODS: A 25-item survey was electronically disseminated to the American Rhinologic Society (ARS) membership from November 17, 2014 to December 14, 2014. The target group encompassed 1157 ARS members. RESULTS: A total of 85 (7.3%) physicians completed the survey. EnDCR was performed by 87% of respondents. The annual average number of EnDCR cases ranged from 1 to 10 in 65% of respondents, 11 to 25 in 15%, 26 to 50 in 6%, and >50 in 1%. A total of 48% of respondents had some to a lot of DCR exposure during training, and 60% had completed a rhinology fellowship. Respondents frequently perform preoperative nasal endoscopy and computed tomography (CT) imaging, but very infrequently perform ophthalmologic workup. Lacrimal stents were used often or always in 80%, with 38% keeping stents in place for 6 to 8 weeks. The mucosal flap preservation technique was used often or always in 40%. Topical antimetabolites were used often or always in only 1%. Ophthalmology was present in most cases to perform lacrimal intubation. Postoperative antibiotics, topical ophthalmic steroids, and oral steroids were prescribed often or always in 62%, 47%, and 23%, respectively. Postoperative endoscopic debridement was performed often or always in 69%. A total of 81% of respondents followed DCR patients for >2 months, with 17% following these patients for >1 year. CONCLUSION: There is widespread integration of EnDCR procedures into rhinologic clinical practice among respondents. EnDCR practice patterns demonstrate moderate variation. In conjunction with evidence-based medicine, these trends can highlight areas of controversy and help advance patient care.

Comprehensive sequencing of PALB2 in patients with breast cancer suggests PALB2 mutations explain a subset of hereditary breast cancer.

BACKGROUND: This study sought to determine the prevalence of PALB2 mutations in a cohort referred for diagnostic testing for hereditary breast cancer. METHODS: Sanger sequencing was used to analyze the entire coding region and flanking introns of PALB2 in anonymized DNA samples from 1479 patients. Samples were stratified into a "high-risk" group, 955 samples from individuals predicted to have a high probability of carrying a mutation in BRCA1 or BRCA2 based on their personal and family history, and a "lower-risk" group consisting of 524 samples from patients with breast cancer, but fewer risk factors for being a BRCA1 or BRCA2 mutation carrier. All patients were known to be negative for deleterious sequence mutations and large rearrangements in BRCA1 and BRCA2. RESULTS: We identified 12 disease-associated PALB2 mutations among the 1479 patients (0.8%). The PALB2 mutations included 8 nonsense, 3 frameshift mutations and a splice-site mutation. The mutation prevalence for the high-risk population was 1.05% (95% CI = 0.5-1.92), whereas that for the lower-risk population was 0.38% (95% CI = 0.05-1.37). We identified 59 PALB2 variants of uncertain significance (VUS) among 57 of the 1479 patients (3.9%). CONCLUSIONS: These results suggest that PALB2 mutations occur at a frequency of ~1% in patients with hereditary breast cancer.

Safety of intranasal Bevacizumab (Avastin) treatment in patients with hereditary hemorrhagic telangiectasia-associated epistaxis.

OBJECTIVES/HYPOTHESIS: Assess for complications of intranasal Bevacizumab application in patients with hereditary hemorrhagic telangiectasia (HHT)-associated epistaxis. STUDY DESIGN: Retrospective chart review. METHODS: In 58 patients presenting with recurrent HHT epistaxis, Bevacizumab was applied intranasally either as a submucosal injection or as a topical spray between October 2006 and June 2010. In many of the injected patients, the potassium titanyl phosphate (KTP) laser was used adjunctively for vessel photocoagulation. A phone interview was performed in July 2010 to assess for treatment complications. RESULTS: Of the 58 treated patients 52 were contacted. Patient surveys were performed 1.5 to 46 months following their initial Bevacizumab treatment. Within the treatment population, five patients had sustained a septal perforation. Notably, these patients were treated early in the study period at which time the cartilaginous septum was often both injected and lasered. Subsequently, the treatment protocol was changed and the cartilaginous septum was neither lasered nor injected. After these changes were made no additional septal perforations were identified. No other adverse events were associated with intranasal Bevacizumab treatment. CONCLUSIONS: Bevacizumab applied as either a submucosal injection or as a topical nasal spray, with or without application of the KTP laser, is a safe treatment regimen. Still, when Bevacizumab injections are performed, the cartilaginous nasal septum should be avoided as patients may develop septal perforations.