Key lifestyles and health outcomes across 16 prevalent chronic diseases: A network analysis of an international observational study.

Background: Central and bridge nodes can drive significant overall improvements within their respective networks. We aimed to identify them in 16 prevalent chronic diseases during the coronavirus disease 2019 (COVID-19) pandemic to guide effective intervention strategies and appropriate resource allocation for most significant holistic lifestyle and health improvements. Methods: We surveyed 16 512 adults from July 2020 to August 2021 in 30 territories. Participants self-reported their medical histories and the perceived impact of COVID-19 on 18 lifestyle factors and 13 health outcomes. For each disease subgroup, we generated lifestyle, health outcome, and bridge networks. Variables with the highest centrality indices in each were identified central or bridge. We validated these networks using nonparametric and case-dropping subset bootstrapping and confirmed central and bridge variables' significantly higher indices through a centrality difference test. Findings: Among the 48 networks, 44 were validated (all correlation-stability coefficients >0.25). Six central lifestyle factors were identified: less consumption of snacks (for the chronic disease: anxiety), less sugary drinks (cancer, gastric ulcer, hypertension, insomnia, and pre-diabetes), less smoking tobacco (chronic obstructive pulmonary disease), frequency of exercise (depression and fatty liver disease), duration of exercise (irritable bowel syndrome), and overall amount of exercise (autoimmune disease, diabetes, eczema, heart attack, and high cholesterol). Two central health outcomes emerged: less emotional distress (chronic obstructive pulmonary disease, eczema, fatty liver disease, gastric ulcer, heart attack, high cholesterol, hypertension, insomnia, and pre-diabetes) and quality of life (anxiety, autoimmune disease, cancer, depression, diabetes, and irritable bowel syndrome). Four bridge lifestyles were identified: consumption of fruits and vegetables (diabetes, high cholesterol, hypertension, and insomnia), less duration of sitting (eczema, fatty liver disease, and heart attack), frequency of exercise (autoimmune disease, depression, and heart attack), and overall amount of exercise (anxiety, gastric ulcer, and insomnia). The centrality difference test showed the central and bridge variables had significantly higher centrality indices than others in their networks (P < 0.05). Conclusion: To effectively manage chronic diseases during the COVID-19 pandemic, enhanced interventions and optimised resource allocation toward central lifestyle factors, health outcomes, and bridge lifestyles are paramount. The key variables shared across chronic diseases emphasise the importance of coordinated intervention strategies.

Acupressure can reduce preoperative anxiety in adults with elective surgery: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Preoperative anxiety is prevalent amongst adults with elective surgery and is associated with multiple detrimental perioperative physiological effects. Increasing studies support the effectiveness of acupressure in managing preoperative anxiety. However, the magnitude of acupressure's positive association with preoperative anxiety is still unclear due to a lack of rigorous evidence synthesis. OBJECTIVE: To estimate the efficacy of acupressure on preoperative anxiety and physiological parameters amongst adults scheduled for elective surgery. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Search terms were combined for acupressure and preoperative anxiety in PubMed, Cochrane Library, EMBASE, CINAHL, China National Knowledge Infrastructure, and WanFang Data Knowledge Service Platform to search for eligible randomised controlled trials from the inception of each database through September 2022. METHODS: Pairs of researchers independently screened and extracted data from included studies. The risk of bias was assessed using the Cochrane risk of bias tool Version 2.0. Meanwhile, random-effects meta-analysis of overall effects and prespecified subgroup (i.e., surgery types, intervention providers, and acupressure stimulation tools) was conducted using Review Manager Software 5.4.1. Meta-regression was performed to explore study-level variables that may contribute to heterogeneity using STATA 16. RESULTS: Of 24 eligible randomised controlled trials, there were a total of 2537 participants from 5 countries contributed to this synthesis. When comparing acupressure with usual care or placebo, acupressure showed a large effect size for preoperative anxiety (SMD = -1.30; 95%CI = -1.54 to -1.06; p < 0.001; I2 = 86%). The significant mean reduction of heart rate, and systolic and diastolic blood pressure was -4.58 BPM (95%CI = -6.70 to -2.46; I2 = 89%), -6.05 mmHg (95%CI = -8.73 to -3.37; p < 0.001; I2 = 88%), and -3.18 mmHg (95%CI = -5.09 to -1.27; p = 0.001; I2 = 78%), respectively. Exploratory subgroup analyses showed significant differences in surgery types and acupressure stimulation tools, whilst the intervention providers (i.e., healthcare professionals and self-administered) showed no statistically significant difference for acupressure therapy. None of the predefined participants and study-level characteristics moderated preoperative anxiety through meta-regression. CONCLUSION: Acupressure appears efficacious as a therapy for improving preoperative anxiety and physiological parameters amongst adults with elective surgery. Self-administered acupressure, which is effective with a large effect, may be considered as an evidence-based approach to managing preoperative anxiety. Hence, this review aids in the development of acupressure in different types of elective surgeries and the improvement of the rigour of acupressure therapy.

Designing and delivering digital learning (e-Learning) interventions in nursing and midwifery education: A systematic review of theories.

AIMS /OBJECTIVES: To identify and synthesise theories that support the design and delivery of digital learning interventions in nursing and midwifery education. BACKGROUND: A range of educational and other theories are used to support nursing and midwifery education, including when e-learning interventions are being designed and delivered. However, there is a limited understanding of how theory is applied across the wide range of digital learning interventions to inform pedagogical research and practice. DESIGN: A systematic review. METHODS: CINAHL, ERIC, MEDLINE and PubMed were searched using key terms. Studies were screened by independent reviewers checking the title, abstract and full text against eligibility criteria. Due to the theoretical focus of the review, critical appraisal was not undertaken. Data were extracted and synthesised using a descriptive approach. RESULTS: Thirty-four studies were included. Twenty theories were identified from a range of scientific disciplines, with the Technology Acceptance Model and Theory of Self-Efficacy employed most often. Theoretical frameworks were used to inform and explain how the digital learning interventions were designed or implemented in nursing and midwifery education. The sample were mainly undergraduate nursing students and the digital learning interventions encompassed animation, blended approaches, general technologies, mobile, online, virtual simulation and virtual reality applications which were used mainly in university settings. CONCLUSIONS: This systematic review found a range of theories that support the design and delivery on digital learning interventions in nursing and midwifery education. While a single theory, the Technology Acceptance Model, tended to dominate the literature, the evidence base is peppered with numerous theoretical models that need to be examined more rigorously to ascertain their utility in improving the design or implementation of digital forms of learning to improve pedagogical research and practice in nursing and midwifery.

Effectiveness of auricular acupoint therapy targeting menstrual pain for primary dysmenorrhea: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Primary dysmenorrhea (PD) is a global public health concern affecting women's health and quality of life, leading to productivity loss and increased medical expenses. As a non-pharmacological intervention, auricular acupoint therapy (AAT) has been increasingly applied to treat PD, but the overall effectiveness remains unclear. AIMS: The aim of this review was to synthesize the effects of AAT targeting menstrual pain among females with PD. METHODS: Eight databases (PubMed, EMBASE, AMED, CINAHL Plus, Cochrane Library, Web of Science, China National Knowledge Infrastructure and Wanfang Data) and three registries (ClinicalTrials.gov, ISRCTN Registry and the Chinese Clinical Trial Registry) were searched to identify existing randomized controlled trials (RCTs) from inception to 21 August 2022. Two reviewers independently screened, extracted the data, and appraised the methodological quality and the evidence strength using the Cochrane risk-of-bias tool for randomized trials (RoB 2) and the GRADE approach. RESULTS: A total of 793 participants from 11 RCTs were included. Despite substantial heterogeneity, AAT was more effective in reducing menstrual pain and related symptoms than placebo and nonsteroidal anti-inflammatory medications (NSAIDs). No significant subgroup differences were found between study locations as well as invasiveness, duration, type, acupoints number, ear selection and provider of AAT. Only minor adverse effects of AAT were reported. LINKING EVIDENCE TO ACTION: AAT can help women with PD, particularly those who are refrained from pharmaceuticals. Primary healthcare professionals, including nurses, can be well-equipped to provide evidence-based and effective AAT for people with PD. AAT can be used in a broader global clinical community. To provide an optimal effect and have wider usability, a unified practice standard is required, which would necessitate further adaptation of clinical care of people with PD. AAT effectively decreased menstrual pain and other accompanying symptoms of PD. More research is needed to identify effective AAT features and explore optimal therapy regimes for PD.

Perceptions of Using Instant Messaging Apps for Alcohol Reduction Intervention Among University Student Drinkers: Semistructured Interview Study With Chinese University Students in Hong Kong.

BACKGROUND: Mobile instant messaging (IM) apps (eg, WhatsApp and WeChat) have been widely used by the general population and are more interactive than text-based programs (SMS text messaging) to modify unhealthy lifestyles. Little is known about IM app use for health promotion, including alcohol reduction for university students. OBJECTIVE: This study aims to explore university student drinkers' perceptions of using IM apps for alcohol reduction as they had high alcohol exposure (eg, drinking invitations from peers and alcohol promotion on campus) and the proportion of IM app use in Hong Kong. METHODS: A qualitative study was conducted with 20 Hong Kong Chinese university students (current drinkers) with Alcohol Use Disorder Identification test scores of ≥8 recruited using purposive sampling. Semistructured individual interviews were conducted from September to October 2019. Interview questions focused on drinking behaviors, quitting history, opinions toward IM app use as an intervention tool, perceived usefulness of IM apps for alcohol reduction, and opinions on the content and design of IM apps for alcohol reduction. Each interview lasted approximately 1 hour. All interviews were audio-taped and transcribed verbatim. Two researchers independently analyzed the transcripts using thematic analysis with an additional investigator to verify the consistency of the coding. RESULTS: Participants considered IM apps a feasible and acceptable platform for alcohol reduction intervention. They preferred to receive IMs based on personalized problem-solving and drinking consequences with credible sources. Other perceived important components of instant messages included providing psychosocial support in time and setting goals with participants to reduce drinking. They further provided suggestions on the designs of IM interventions, in which they preferred simple and concise messages, chat styles based on participants' preferences (eg, adding personalized emojis and stickers in the chat), and peers as counselors. CONCLUSIONS: Qualitative interviews with Chinese university student drinkers showed high acceptability, engagement, and perceived utility of IM apps for alcohol reduction intervention. IM intervention can be an alternative for alcohol reduction intervention apart from traditional text-based programs. The study has implications for developing the IM intervention for other unhealthy behaviors and highlights important topics that warrant future research, including substance use and physical inactivity. TRIAL REGISTRATION: ClinicalTrials.gov NCT04025151; https://clinicaltrials.gov/ct2/show/NCT04025151?term=NCT04025151.

Artificial intelligence in nursing and midwifery: A systematic review.

BACKGROUND: Artificial Intelligence (AI) techniques are being applied in nursing and midwifery to improve decision-making, patient care and service delivery. However, an understanding of the real-world applications of AI across all domains of both professions is limited. OBJECTIVES: To synthesise literature on AI in nursing and midwifery. METHODS: CINAHL, Embase, PubMed and Scopus were searched using relevant terms. Titles, abstracts and full texts were screened against eligibility criteria. Data were extracted, analysed, and findings were presented in a descriptive summary. The PRISMA checklist guided the review conduct and reporting. RESULTS: One hundred and forty articles were included. Nurses' and midwives' involvement in AI varied, with some taking an active role in testing, using or evaluating AI-based technologies; however, many studies did not include either profession. AI was mainly applied in clinical practice to direct patient care (n = 115, 82.14%), with fewer studies focusing on administration and management (n = 21, 15.00%), or education (n = 4, 2.85%). Benefits reported were primarily potential as most studies trained and tested AI algorithms. Only a handful (n = 8, 7.14%) reported actual benefits when AI techniques were applied in real-world settings. Risks and limitations included poor quality datasets that could introduce bias, the need for clinical interpretation of AI-based results, privacy and trust issues, and inadequate AI expertise among the professions. CONCLUSION: Digital health datasets should be put in place to support the testing, use, and evaluation of AI in nursing and midwifery. Curricula need to be developed to educate the professions about AI, so they can lead and participate in these digital initiatives in healthcare. RELEVANCE FOR CLINICAL PRACTICE: Adult, paediatric, mental health and learning disability nurses, along with midwives should have a more active role in rigorous, interdisciplinary research evaluating AI-based technologies in professional practice to determine their clinical efficacy as well as their ethical, legal and social implications in healthcare.

Effects of Mindfulness Yoga Versus Conventional Physical Exercises on Symptom Experiences and Health-related Quality of Life in People with Parkinson's Disease: The Potential Mediating Roles of Anxiety and Depression.

BACKGROUND: Although several studies have reported positive effects of mind-body exercises on symptom management and health-related quality of life (HRQOL) of people living with Parkinson's disease (PD), it is not known whether these effects are attributable to a change in anxiety and depression. PURPOSE: To compare the effects of mindfulness yoga to conventional stretching exercises in a randomized controlled trial while examining potentially mediating effects of anxiety and depression. METHODS: 138 adults with PD were randomized to eight weekly yoga (n = 71) or stretching (n = 67) sessions. Symptom experiences, anxiety and depression, and HRQOL outcomes were assessed at baseline, immediate post-intervention, and 3-month post-intervention. RESULTS: Generalized estimating equation analyses revealed that, compared to stretching, yoga significantly improved patients' nonmotor (time-by-group interaction, T1:ß = -1.99, p = .008; T2:ß = -2.86, p < .001) and motor (time-by-group interaction, T1:ß = -1.77, p = .03) symptom experiences. The mediation analysis found that the changes in anxiety and depression were the mediators in the associations between non-motor experience and HRQOL; while only the changes in depression were found to be the mediator in the relationship between motor experience and HRQOL. CONCLUSIONS: Yoga is superior to conventional stretching exercises in improving nonmotor and motor symptoms in daily living. Reduced anxiety and depression play a role in mediating the positive effects of the mindfulness yoga intervention. To optimize HRQOL, rehabilitation should reinforce psychological care in addition to pharmacological treatments and physical relief of PD symptoms. Future studies are needed to identify strategies for facilitating the implementation and sustainability of mind-body rehabilitation to enhance the quality of care for PD.

Stay mindfully active during the coronavirus pandemic: a feasibility study of mHealth-delivered mindfulness yoga program for people with Parkinson's disease.

IMPORTANCE: Patients with long-term neurological conditions, such as Parkinson's disease (PD), are particularly vulnerable to the public health measures taken to combat the COVID-19 pandemic. The inaccessibility of center-based rehabilitation further aggravated their motor dysfunctions as well as mental distress, leading to exacerbation of motor and non-motor symptoms, high healthcare utilization and worsened health-related quality of life (HRQOL). OBJECTIVE: This study aimed to evaluate the feasibility, safety, and preliminary effects of the mHealth-delivered home-based mindfulness yoga program on functional balance, motor symptoms, mental health and HRQOL in patients with PD. DESIGN, SETTING AND PARTICIPANTS: This prospective, single-arm, non-randomized feasibility study adopted a sequential explanatory mixed-method design. Adults (aged ≥ 18) with a clinical diagnosis of idiopathic Parkinson's disease (Hoehn and Yahr stage I to III) who were able to stand unaided and walk with or without an assistive device were enrolled via convenience sampling. INTERVENTION: Home-based mindfulness yoga training were delivered via video-conferencing software (Zoom) in eight bi-weekly 90-min sessions. MAIN OUTCOMES AND MEASURES: This current study measured functional balance, motor symptoms, perceived balance confidence, perceived freezing of gait symptoms, anxiety and depression, mindfulness and HRQOL using a tele-assessment approach at baseline and 1-week post-intervention. All participants were invited to attend qualitative individual interviews to explore their experience of using online mindfulness yoga program as a lifestyle intervention for PD rehabilitation. RESULTS: Among the ten patients, 80% completed the program with an adherence rate of 98.4%. All participants were able to learn and practice mindfulness yoga following the eight bi-weekly online mindfulness yoga training sessions, without any significant adverse events. Tele-assessment of outcomes were feasible and uneventful. Qualitative feedback revealed participants had a high preference of using the tele-rehabilitation approach to stay mindful and being active, both physically and socially, while confronting the changes brought by COVID-19 pandemic. CONCLUSIONS AND RELEVANCE: The mHealth-delivered home-based mindfulness yoga intervention was feasible, safe, and well-accepted among people with PD to relieve the burden brought by COVID-19 pandemic. Future studies should adopt a design with enhanced rigor, a comparison group, and enlarged sample size to evaluate the efficacy of the program in patients with long-term neurological conditions and/or physical impairments. We recommend a longer intervention duration of at least 8 weeks to enhance the psychophysiological effects.

Lived experience of neuropsychiatric symptoms among females with mild cognitive impairment: A phenomenological study.

AIMS: To explore the lived experience of neuropsychiatric symptoms (NPS) among females with mild cognitive impairment (MCI). DESIGN: A phenomenological study using individual, semi-structured, telephone-based interviews was conducted to explore how the NPS are aroused, evolve, and affect the overall well-being, illness perception and the corresponding coping responses adopted by females with MCI. METHODS: Twenty-nine participants with MCI were recruited from the community setting in Hong Kong between March and October 2020. Interviews were audio-recorded, transcribed verbatim, and analysed using an interpretative phenomenological analysis approach and constant comparison strategy. RESULTS: Three themes were identified: (1) living vigilant lives with threats and uncertainty, (2) snowballing into further negative emotions and (3) seeking outlets for negative emotions. Our findings suggested that the participants' cognitive, functional and social challenges aroused intense emotional responses such as depression, agitation and anxiety. These noting negative emotions were further perpetuated by maladaptive coping responses, unrealistic expectations from coping strategies and overwhelming disease burden. Various internal and external strategies were adopted to enhance emotional adaptation, of which adopting a positive attitude appeared to be the most promising strategy. CONCLUSION: This study shed light on the challenging experience of MCI. The cognitive afflictions and the resultant impacts on various life domains evoked a cluster of NPS. Support services need to enhance emotional adjustment through alleviating the various life stressors and strengthening the coping resources. IMPACT: Elucidating the lived experience of NPS provides important insights into the development of a more effective, comprehensive and person-centred care planning for the population with MCI. Holistic care planning should extend beyond cognitive health optimization into enhancing disease knowledge, improve emotional coping, rebuild self-identity and bolstering social supports among this preclinical cohort.

Hypohomocysteinemia may increases the risk of dementia and Alzheimer's disease: A nationwide population-based prospective cohort study.

BACKGROUND: Hyperhomocysteinemia has been repeatedly found to increase the risk of dementia. However, the effects of hypohomocysteinemia on the risk of dementia have been barely investigated. If hypohomocysteinemia, like hyperhomocysteinemia, increases the risk of dementia, misuse or overuse of homocysteine-lowing agents such as vitamin supplements may increase the risk of dementia. AIMS: To investigate whether hypohomocysteinemia, like hyperhomocysteinemia, could increase the risk of dementia and Alzheimer's disease (AD) in a large population-based cohort of older adults. METHODS: This prospective cohort study followed 2655 randomly sampled, community-dwelling, non-demented individuals aged 60 years or older from 2010 to 2018. We measured baseline serum total homocysteine (tHcy) levels and examined the effect of serum tHcy on the risks of dementia and AD using Cox proportional hazards models. RESULTS: During the follow-up period (mean = 5.4 years, SD = 0.9), dementia and AD developed in 85 and 64 participants, respectively. Not only the participants with high serum tHcy (≥10.6 µmol/L) but also those with low serum tHcy (≤8.9 µmol/L) were 4-5 times more likely to develop dementia and AD compared to those with serum tHcy levels between 9.0 and 10.5 µmol/L. With the increase in serum tHcy concentration, the use of vitamin supplements decreased, and 41.2% of the participants with low serum tHcy (≤8.9 µmol/L) were taking vitamin supplements. CONCLUSIONS: Not only hyperhomocysteinemia but also hypohomocysteinemia considerably increased the risk of dementia and AD in older adults. The risk of dementia that results from overuse or misuse of vitamin supplements should be acknowledged and homocysteine-lowering health policies should be tailored to consider dementia risks that are associated with hypohomocysteinemia.

Brief mindfulness training for smoking cessation in Chinese women in workplaces: A pilot randomized controlled trial.

INTRODUCTION: Mindfulness training (MT) has shown preliminary efficacy as a behavioral treatment for smoking cessation. We examined the effect of a brief-MT intervention on smoking cessation for Chinese women in workplaces in Hong Kong, China. METHODS: In this pilot randomized controlled trial, 213 daily smokers were recruited from workplaces and computer-randomized into the intervention (n = 114) or control (n = 99) groups. Participants in both groups received a self-help booklet. Participants in the intervention group additionally attended 2 sessions of a brief-MT workshop. The primary outcome was self-reported 7-day point-prevalence abstinence (PPA) at 6 months. Secondary outcomes were biochemically validated abstinence (exhaled CO < 4 ppm and salivary cotinine < 10 ng/mL) and smoking reduction at 6 months. Analyses were done by intention to treat. We conducted a post-trial qualitative evaluation on participants in the intervention group (n = 14). Data were analyzed thematically. RESULTS: At 6-month follow-up, self-reported 7-day PPA were similar between the intervention and control groups (18.4% vs. 21.2%; P = 0.61). Very few participated in biochemical validation (n = 17), and validated abstinence and smoking reduction rates showed no significant difference (5.3% vs. 11.1%, P = 0.12 and 20.2% vs. 20.2%, P = 1.00, respectively). A posteriori analysis showed that brief-MT participants who were psychologically engaged with the intervention had greater 6-month PPA. Qualitative evaluation showed brief-MT reduced stress but its effectiveness was restrained by the insufficient home practice. CONCLUSIONS: This pilot trial on a brief-MT intervention for smoking cessation on Chinese women in workplaces showed feasibility, but improving compliance is needed to maximize the efficacy in future fully powered trials.

Letting nature take its course: A qualitative exploration of the illness and adjustment experiences of Hong Kong Chinese people with Parkinson's disease.

Parkinson's disease (PD) is a chronic condition that results in not only physical deterioration but also a spectrum of psychosocial outcomes that demand continuous adjustment and coping. Previous qualitative research into the illness experiences has been conducted mainly in Western populations, yet little is known about Chinese PD patients' adjustment. The aims of this qualitative description study were to (a) understand the illness and adjustment experiences, (b) explore the reasons for psychological distress and (c) discern the adjustment strategies adopted along the course of illness, from the perspective of Hong Kong Chinese PD patients. Individual semi-structured interviews were conducted with 14 patients from January to June, 2016. Data were analysed using thematic analysis. Two themes emerged from the interviews: confronting the changes caused by Parkinson's disease and adjusting to living with Parkinson's disease. Participants reported experiencing turmoil due to progressive loss of functions and abilities, changes in role and identity and unattended emotional needs in the course of their illness. Considering the chronic and fluctuating nature of PD, rehabilitation programs should be applied to address not only the physical symptoms but also the psychological needs of PD patients. Behavioral strategies facilitating active health behaviours and accommodative psychological adjustment are salient to facilitate the holistic well-being of PD patients.

Effects of lifetime cumulative ginseng intake on cognitive function in late life.

BACKGROUND: We investigated the effects of lifetime cumulative ginseng intake on cognitive function in a community-dwelling population-based prospective cohort of Korean elders. METHODS: Community-dwelling elders (N = 6422; mean age = 70.2 ± 6.9 years, education = 8.0 ± 5.3 years, female = 56.8%) from the Korean Longitudinal Study on Cognitive Aging and Dementia were included. Among them, 3918 participants (61.0%) completed the 2-year and 4-year follow-up evaluations. Subjects were categorized according to cumulative ginseng intake at baseline evaluation; no use group, low use (< 5 years) group, and high use (≥ 5 years) group. One-way analysis of covariance (ANCOVA) was conducted to compare the impact of cumulative ginseng intake on baseline Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet neuropsychological battery total score (CERAD total score) and Mini-Mental State Examination (MMSE) score among the three groups while adjusting for potential covariates. A repeated-measures ANCOVA was performed to investigate the impacts on the changes in CERAD total scores and MMSE scores during the 4 years of follow-up. RESULTS: The high use group showed higher CERAD total scores compared to the no use group after controlling for age, sex, education years, socioeconomic status, smoking, alcohol intake, presence of hypertension, stroke history, Geriatric Depression Scale, Cumulative Illness Rating Scale, and presence of the APOE e4 allele (F(2, 4762) = 3.978, p = 0.019). The changes of CERAD total score for 2 or 4 years of follow-up did not differ according to the use of ginseng. CONCLUSIONS: Cumulative ginseng use for longer than 5 years may be beneficial to cognitive function in late life.

Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes.

Pain management would be greatly enhanced by a formulation that would provide local anesthesia at the time desired by patients and with the desired intensity and duration. To this end, we have developed near-infrared (NIR) light-triggered liposomes to provide on-demand adjustable local anesthesia. The liposomes contained tetrodotoxin (TTX), which has ultrapotent local anesthetic properties. They were made photo-labile by encapsulation of a NIR-triggerable photosensitizer; irradiation at 730 nm led to peroxidation of liposomal lipids, allowing drug release. In vitro, 5.6% of TTX was released upon NIR irradiation, which could be repeated a second time. The formulations were not cytotoxic in cell culture. In vivo, injection of liposomes containing TTX and the photosensitizer caused an initial nerve block lasting 13.5 ± 3.1 h. Additional periods of nerve block could be induced by irradiation at 730 nm. The timing, intensity, and duration of nerve blockade could be controlled by adjusting the timing, irradiance, and duration of irradiation. Tissue reaction to this formulation and the associated irradiation was benign.