Non-pharmaceutical Therapy Research Articles

Clinical phenotype and management of sound-induced pain: Insights from adults with pain hyperacusis

Pain hyperacusis, also known as noxacusis, causes physical pain in response to sounds that do not bother most people. How sound causes excruciating pain that can last for weeks or months is not well understood, resulting in a lack of effective treatments. To gain insight into the underlying mechanisms of the condition, 32 adults attended a virtual focus group to describe their sound-induced pain. Focus group data were used to develop three follow-up surveys that aimed to identify the most common symptoms of pain hyperacusis as well as the participants’ use of therapies for pain relief. All participants endorsed negative effects of pain hyperacusis on psychosocial and physical function. Most reported sound-induced burning (80.77%), stabbing (76.92%), throbbing (73.08%), and pinching (53.85%) sensations that occur either in the ear or elsewhere in the body. Participants have used numerous pharmaceutical and non-pharmaceutical interventions to alleviate their pain with varying degrees of pain relief. Benzodiazepines and nerve blockers emerged as the most effective analgesic options while non-pharmaceutical therapies were largely ineffective. Symptoms and therapeutic approaches were generally consistent with peripheral mechanistic theories of pain hyperacusis (e.g., trigeminal nerve involvement). An interdisciplinary approach to clinical studies and the development of animal models are needed to identify and treat the pathological mechanisms of pain hyperacusis. PerspectiveThis article presents the physical and psychosocial consequences of debilitating sound-induced pain (i.e., pain hyperacusis) and the interventions that sufferers have sought for pain relief. The results are largely consistent with peripheral mechanistic theories (e.g., trigeminal nerve involvement) and will guide future work to investigate neural mechanisms and effective therapies.

Impact of Dance or Music and Meditation on the Progression of Parkinson Disease With Mild or Moderate Severity: Protocol for a Pilot Randomized Controlled Trial.

Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by motor dysfunctions and nonmotor symptoms. Current treatments do not alter disease progression, highlighting the need for alternative therapies. Music, dance, and mindfulness meditation have shown the potential to improve symptoms and quality of life in patients with PD. This study aims to evaluate the effectiveness of dance or music and meditation on PD progression, cognitive functions, mood, behavior, and caregiver burden. This study is a single-blinded, longitudinal, parallel, randomized controlled trial. The participants consist of 30 patients with mild to moderate PD residing in Mumbai, India, who can physically participate in the activities. The exclusion criteria include advanced PD, severe balance issues, age >80 years, and other movement disorders. Participants in the intervention group will engage in dance or music sessions and guided meditation thrice weekly for 6 months. The control group will continue their usual activities and medication. The primary outcome is the progression of PD symptoms, measured using the Unified Parkinson's Disease Rating Scale I-III, and quality of life, measured using the Parkinson's Disease Questionnaire-39. The secondary outcomes include cognitive functions (Mini-Mental State Examination), mood (Beck Depression Inventory and Parkinson Anxiety Scale), mobility (timed up and go and Berg Balance Test), behavioral disorders (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale), and caregiver burden (Zarit Burden Interview and Parkinson's Disease Questionnaire-Carer). Data collection was completed in February 2024, with 28 participants finishing the study (intervention group: n=15, 54% and control group: n=13, 46%). Data analysis is underway, with results expected to be published in December 2024. This study aims to provide significant insights into the effectiveness of dance or music and meditation in improving the quality of life and slowing the progression of PD. The findings are anticipated to support using these nonpharmaceutical therapies as complementary approaches to managing PD. CTRI/2023/03/051064; https://tinyurl.com/2xdus53j. DERR1-10.2196/59018.

Acupuncture-assisted therapy for prolonged disorders of consciousness: study protocol for a randomized, conventional-controlled, assessor-and-statistician-blinded trial.

Acupuncture is a promising non-pharmaceutical complementary therapy in treating prolonged Disorders of consciousness (pDOC), but solid evidence to support its effectiveness and safety is still lacking. Thus, the purpose of this study is to investigate the efficacy and safety of acupuncture-assisted therapy for pDOC patients. A single-center, prospective, randomized, conventional-controlled, assessor-and-statistician-blinded trial has been designed and is being conducted at West China Hospital of Sichuan University. A total of 110 participants will be randomly assigned to the experimental group and the control group in a 1:1 allocation ratio and evaluated using Coma Recovery Scale-Revised (CRS-R) at 8 a.m., 12 p.m., and 4 p.m. on 2 consecutive days before enrollment to determine the consciousness level. The experimental group will receive acupuncture combined with conventional treatment, while the control group will receive only conventional treatment during the trial observation period. The treatment duration of both groups will be 20 days. Among them, the frequency of acupuncture-assisted therapy is once a day, with 10 consecutive sessions followed by a day's rest for a total of 24 days. Data will be collected separately during baseline and after the final treatment. For data analysis, both Full Analysis Set (FAS) and Per Protocol Set (PPS) principles will be performed together by applying SPSS 27.0 software. The primary outcome measures are the changes of CRS-R before and after treatment, while the secondary outcome measures are the changes of Full Outline of Unresponsiveness Scale (FOUR), the changes of Nociception Coma Scale-Revised (NCS-R), the changes of Disability Rating Scale (DRS), the changes of Mismatch Negativity (MMN) and P300 before and after treatment, respectively. This trial aims to rationally assess the consciousness level from multiple 2 perspectives through subjective evaluation and objective detection by selecting several standardized clinical scales combined with Event-Related Potential (ERP) detection technology. In this way, we will be able to reduce the subjectivity of consciousness assessment and objectively evaluate the clinical efficacy of acupuncture-assisted therapy for pDOC. The study, if proven to be effective and safe enough, will provide a favorable evidence to guide medical decision-making choices and future researches. https://www.chictr.org.cn/, identifier ChiCTR2300076180.

Baduanjin Exercise Improves Cognitive Function in Older Adults With Mild Cognitive Impairment: A Systematic Review and Meta-analysis.

As a nonpharmacological method for cognitive rehabilitation, older adults with mild cognitive impairment (MCI) may benefit from Baduanjin exercise (BE), a moderate-intensity aerobic exercise. This meta-analysis was conducted to determine if BE is effective in enhancing cognitive performance in older adults with MCI. Using a combination of topic phrases and free words, systematic searches were executed in nine databases. Review Manager 5.4 was used to retrieve and statistically evaluate the data. Fourteen randomized controlled studies comprising 994 individuals aged ≥60 years were included in the meta-analysis. BE enhanced the general cognitive performance in individuals with MCI as measured by the Montreal Cognitive Assessment (standardized mean difference [SMD] = 2.56; 95% confidence interval [CI], 2.17, 2.96; p < 0.001). The level of memory decline (Wechsler Memory Scale; SMD = 12.46; 95% CI, 8.36, 16.57; p < 0.001), executive function (Trail Making Test; SMD = -7.08; 95% CI, -11.21, -2.94; p < 0.001), and frailty (Edmonton Frailty Scale; SMD = -0.97; 95% CI, -1.30, -0.64; p < 0.001) were all improved with BE for older adults with MCI. This study presented a therapeutic practice guide for using BE for cognitive rehabilitation in older adults. BE notably improves cognitive function in older adults with MCI and can be an excellent nonpharmaceutical therapy option.

Perioperative non-pharmaceutical therapies for insomnia in cancer survivors: a systematic review and network meta-analysis protocol

IntroductionThe presence of perioperative insomnia is common but yet often overlooked among cancer survivors. Non-pharmaceutical therapies have shown promise in treating cancer-related insomnia during the perioperative period; however, the existing...

Clinical phenotype and management of sound-induced pain: Insights from adults with pain hyperacusis.

Pain hyperacusis, also known as noxacusis, causes physical pain in response to everyday sounds that do not bother most people. How sound causes excruciating pain that can last for weeks or months in otherwise healthy individuals is not well understood, resulting in a lack of effective treatments. To address this gap, we identified the most salient physical and psychosocial consequences of debilitating sound-induced pain and reviewed the interventions that sufferers have sought for pain relief to gain insights into the underlying mechanisms of the condition. Adults (n = 32) with pain hyperacusis attended a virtual focus group to describe their sound-induced pain. They completed three surveys to identify common symptoms and themes that defined their condition and to describe their use of pharmaceutical and non-pharmaceutical therapies for pain relief. All participants endorsed negative effects of pain hyperacusis on psychosocial and physical function. Most reported sound-induced burning (80.77%), stabbing (76.92%), throbbing (73.08%), and pinching (53.85%) that occurs either in the ear or elsewhere in the body (i.e., referred pain). Participants reported using numerous pharmaceutical and non-pharmaceutical interventions to alleviate their pain with varying degrees of pain relief. Benzodiazepines and nerve blockers emerged as the most effective analgesic options while non-pharmaceutical therapies were largely ineffective. Symptoms of pain hyperacusis and therapeutic approaches are largely consistent with peripheral mechanistic theories of pain hyperacusis (e.g., trigeminal nerve involvement). An interdisciplinary approach to clinical studies and the development of animal models is needed to identify, validate, and treat the pathological mechanisms of pain hyperacusis.

Subgroups of mild cognitive impairment based on cognitive function among Chinese older adults

Abstract Background: Due to the heterogeneity of mild cognitive impairment (MCI), the key points for nonpharmaceutical therapies cannot be determined. Examining impairment characteristics among different MCI subgroups would therefore be beneficial to the development of nonpharmaceutical therapies. Objective: To characterize the subgroups of older Chinese with MCI and examine factors associated with the membership of distinct subgroups. Methods: This cross-sectional study was conducted between October 2018 and June 2022 in Fujian, East China, with 1017 older adults with MCI deemed eligible. Exclusion criteria included any diagnosis of other neurological or psychiatric conditions that could affect cognition. Participants underwent a neuropsychological test that assessed memory, language, attention, and executive function(s) and completed a questionnaire collecting their socioeconomic and clinical variables. Neuropsychological test scores were transformed into z-scores, which were then examined using latent class analysis. Associations between socioeconomic and clinical variables, and MCI subgroups were assessed using multinomial logistic regression analysis. Results: Three MCI subgroups were identified: G1 “Minimally impairment” (56.64%), G2 “Moderate impairment” (36.28%), and G3 “Worst impairment” (7.08%). Age, place of residence, marriage status, living status, and participation in intellectual activities differed significantly across the 3 MCI subgroups (P&lt;0.05). Compared with the minimally impairment group, participants with the worst impairment were less likely to participate in intellectual activity and more likely to live in a nursing home. Conclusion: Cognitive function is a suitable foundation for establishing classifications among individuals with MCI. Nonpharmalogical therapies may target older adults at higher risk of moderate or worst impairment.

Longitudinal adaptive behavioral outcomes in Ogden syndrome by seizure status and therapeutic intervention.

Ogden syndrome, also known as NAA10-related neurodevelopmental syndrome, is a rare genetic condition associated with pathogenic variants in the NAA10 N-terminal acetylation family of proteins. The condition was initially described in 2011 and is characterized by a range of neurologic symptoms, including intellectual disability and seizures, as well as developmental delays, psychiatric symptoms, congenital heart abnormalities, hypotonia, and others. Previously published articles have described the etiology and phenotype of Ogden syndrome, mostly with retrospective analyses; herein, we report prospective data concerning its progress over time. The current study involves a total of 58 distinct participants; of these, 43 caregivers were interviewed using the Vineland-3 and answered a survey regarding therapy and other questions, 10 of whom completed the Vineland-3 but did not answer the survey, and 5 participants who answered the survey but have not yet performed the Vineland-3 due to language constraints. The average age at the time of the most recent assessment was 12.4 years, with individuals ranging in age from 11 months to 40.2 years. Using Vineland-3 scores, we show decline in cognitive function over time in individuals with Ogden syndrome (n = 53). Sub-domain analysis found the decline to be present across all modalities. In addition, we describe the nature of seizures in this condition in greater detail, as well as investigate how already-available non-pharmaceutical therapies impact individuals with NAA10-related neurodevelopmental syndrome. Additional investigation between seizure and non-seizure groups showed no significant difference in adaptive behavior outcomes. A therapy investigation showed speech therapy to be the most commonly used therapy by individuals with NAA10-related neurodevelopmental syndrome, followed by occupational and physical therapy, with more severely affected individuals receiving more types of therapy than their less-severe counterparts. Early intervention analysis was only significantly effective for speech therapy, with analyses of all other therapies being non-significant. Our study portrays the decline in cognitive function over time of individuals within our cohort, independent of seizure status, and therapies being received, and highlights the urgent need for the development of effective treatments for Ogden syndrome.

Endovascular Applications for the Management of High-Grade Gliomas in the Modern Era.

High-grade gliomas (HGGs) have a poor prognosis and are difficult to treat. This review examines the evolving landscape of endovascular therapies for HGGs. Recent advances in endovascular catheter technology and delivery methods allow for super-selective intra-arterial cerebral infusion (SSIACI) with increasing precision. This treatment modality may offer the ability to deliver anti-tumoral therapies directly to tumor regions while minimizing systemic toxicity. However, challenges persist, including blood-brain barrier (BBB) penetration, hemodynamic complexities, and drug-tumor residence time. Innovative adjunct techniques, such as focused ultrasound (FUS) and hyperosmotic disruption, may facilitate BBB disruption and enhance drug penetration. However, hemodynamic factors that limit drug residence time remain a limitation. Expanding therapeutic options beyond chemotherapy, including radiotherapy and immunobiologics, may motivate future investigations. While preclinical and clinical studies demonstrate moderate efficacy, larger randomized trials are needed to validate the clinical benefits. Additionally, future directions may involve endovascular sampling for peri-tumoral surveillance; changes in drug formulations to prolong residence time; and the exploration of non-pharmaceutical therapies, like radioembolization and photodynamic therapy. Endovascular strategies hold immense potential in reshaping HGG treatment paradigms, offering targeted and minimally invasive approaches. However, overcoming technical challenges and validating clinical efficacy remain paramount for translating these advancements into clinical care.

464 Remote Cognitive Behavioral Therapy Utilizing an In-home Virtual Reality Toolkit (Vx Therapy TM) Reduces Pain, Anxiety, and Depression in Patients With Chronic Cervical and Lumbar Pain: A Potential Opiate Alternative in Multimodal Pain Management

INTRODUCTION: Virtual reality has reduced acute pain through visual and auditory distraction, as well as altered brain neurobiology. VR attenuates pain-induced brain activity without narcotic-related side effects or dependency. Cognitive behavioral therapy (CBT) has demonstrated improved pain-related anxiety, depression, physical disability, resiliency, and quality of life. CBT access remains a challenge in most care communities. METHODS: 145 patients with chronic neck and back pain (63 cervical, 46 non-radicular lumbar, 36 radicular lumbar) enrolled into a 14 week Vx therapy CBT program with therapist guided utilization of an in-home VR system with 50 modules (education, meditation, distraction, entertainment). Pain and anxiety severity scores were recorded before and immediately after VR use as well as time to pain recurrence. PROMIS measures of daily pain intensity, pain behavior, pain interference, anxiety, and depression were recorded at baseline and after 14 weeks of Vx therapy. RESULTS: PROMIS domains were significantly improved after Vx treatment vs baseline for the entire cohort and each subgroup. VR acutely reduced pain during use on average by 33% (p &lt; 0.05) across all 14 weeks lasting a mean 2.5 hours. VR acutely reduced anxiety during use on average by 46% (p &lt; 0.05) across all 14 weeks lasting a mean 2.7 hours. The effect was similar for all three diagnosis groups. CONCLUSIONS: Remote CBT guided in-home VR toolkit (Vx therapyTM) provided effective multi-hour sustained pain relief in patients with chronic neck and back pain with and without radiculopathy. Significant improvement in overall pain, anxiety, and depression and reduced pain interference was observed. This non-invasive, non-pharmaceutical Vx therapy is an ideal option to improve outcomes in post-opioid pain management.

“There is no one who helps you with it”: experiences of people with long COVID regarding medical care, therapeutic measures, and barriers in the German healthcare system: results of a qualitative study with four focus groups

BackgroundMany people experience long-term symptoms such as fatigue, cognitive problems, or shortness of breath after an acute infection with COVID-19. This emerging syndrome, known as long COVID, is new and complex in many aspects. This study aims to collect the experiences of people with long COVID with ambulatory healthcare structures.MethodsFour focus groups were conducted with a total of 23 adults with long COVID in June and July 2022. These discussions were audio-recorded, subsequently transcribed, and analyzed using the qualitative content analysis of Mayring and Kuckartz.ResultsFourteen out of 19 participants who had a primary care encounter regarding their long COVID symptoms did not perceive it as helpful. Many respondents reported that their general practitioners did not take their long COVID symptoms seriously and did not refer them to specialists or made therapeutic recommendations. However, some participants reported that they were prescribed non-pharmaceutical therapies (e.g., group meetings supported by psychotherapists, occupational therapy, etc.) that improved their condition. 14 of 23 respondents perceived care barriers such as providers’ lack of awareness of long COVID, poor access to specialists, a lack of specialized care (e.g., long COVID clinics), or high bureaucratic hurdles for specific healthcare services. To improve medical care, participants suggested campaigns to raise awareness of long COVID among healthcare providers and the general population, increase research and government investments regarding the development of treatment structures for long COVID, expanding existing therapeutic services, and establishing one-stop shops for integrated specialist healthcare for people with long COVID.ConclusionsSeveral implications for healthcare professionals and policymakers can be derived from this study: (1) general practitioners should take the symptoms of long COVID seriously, assume a care coordinating role, make referrals, and establish contact with long COVID clinics; (2) care planners should focus on developing interprofessional evidence-based care and treatment approaches for long COVID; (3) existing care structures such as long COVID outpatient clinics should be expanded. The overarching goal must be to develop consistent guidelines for long COVID diagnosis, care, and treatment.Trial registrationThe study is registered in the German register for clinical trials (DRKS00026007, first registration on 09/09/2021).

Learning from COVID-19 for Mitigating the Next Possible Pandemic: Nutrition, Lifestyle, Risk Factors and Non-Pharmaceutical Interventions

The COVID-19 pandemic has sparked a paradigm change in pandemic preparedness measures, motivating an investigation of non-pharmaceutical therapies. This research dives into the lessons learned from COVID-19 to strengthen our strategy to prevent future pandemics. The study aimed to extract valuable insights from the COVID-19 experience, extrapolating lessons learned to develop strong strategies that include diet, lifestyle, risk factors and non-pharmaceutical treatments. Nutrition and lifestyle influences on illness susceptibility were studied using a comprehensive examination of scholarly literature, reports and epidemiological studies. Role of essential risk variables was investigated in magnifying pandemic outcomes and the efficiency of non-pharmaceutical treatments in reducing infectious agent transmission. The analysis demonstrates the long-term utility of COVID-19 findings. This review emphasizes the importance of nutrition and lifestyle variables in determining susceptibility to infectious illnesses. Furthermore, a detailed examination of risk variables shows critical predictors of pandemic severity. Most significantly, the findings highlight the effectiveness of non-pharmaceutical measures, emphasizing their vital role in pandemic containment. This study has far-reaching ramifications that advocate for a paradigm change towards comprehensive pandemic preparation using the lessons learned during COVID-19. Research findings highlight the need for a multifaceted strategy, including diet, lifestyle changes, targeted risk reduction and non-pharmaceutical therapies. This study provides a road map for improving global resilience to potential future pandemics, calling for preventative strategies beyond pharmacological remedies.

Effectiveness of photobiomodulation for people with age-related cognitive impairment: a systematic review and meta-analysis.

The increasing incident of age-related cognitive impairment worldwide and the lack of pharmaceutical treatments emphasizes the value of non-pharmaceutical therapy. Emerging evidence suggested photobiomodulation (PBM) is a popular intervention to brain disorder; however, it remains unclear the efficacy of PBM for patients with age-related cognitive impairment. The purpose of this systematic review is to compare the different parameters used in PBM, analyze the beneficial effects of PBM as a potential therapy for age-related cognitive impairment. Five electronic database, PubMed, Web of Science, Cochrane Library, CINAHL, and PsycINFO, were systematically searched from inception to November 2021. Relevant randomized controlled trials (RCTs) were screened and assessed for risk of bias. Eleven RCTs evaluating PBM interventions were included. The systematic review and meta-analysis has been registered in PROSPERO(CRD42022374562). Results showed that PBM had a significant moderated effect on global cognition function (SMD=0.51, 95% CI [0.162, 0.864], p=0.004). We found that multiple wavelength PBM (SMD=0.648, 95% CI [0.220, 1.075], p=0.003) had significant effects while single wavelength PBM was non-significant (SMD=0.385, 95% CI [-0.168, 0.987], p=0.172). Laser effect (SMD=0.682, 95% CI [0.37, 0,994], p<0.001) was larger than LED effect (SMD=0.582, 95% CI [0.269, 0.895], p<0.001). PBM in clinical setting (SMD=0.468, 95% CI [0.050, 0.887], p=0.028) had significant effect, but there was no significant effect of home-used PBM (SMD=0.616, 95% CI [-0.121, 1.354], p=0.101). The pool effect of multi-modality PBM (SMD=0.720, 95% CI [0.027, 1.414], p=0.040) was significantly higher in the studies of transcranial irradiation (SMD=0.616, 95% CI [-0.121, 1.354], p=0.010). Cumulative irradiation time was a moderator between the PBM and cognitive function improvement. Photobiomodulation have the potential to improve cognitive function in aging adults. Cumulative irradiation duration, light source, device type, penetration modality, and intervention site can affect the effectiveness of PBM intervention.

Socioeconomic differences in the utilization of diagnostic imaging and non-pharmaceutical conservative therapies for spinal diseases

BackgroundA different utilization of health care services due to socioeconomic status on the same health plan contradicts the principle of equal treatment. We investigated the presence and magnitude of socioeconomic differences in utilization of diagnostic imaging and non-pharmaceutical conservative therapies for patients with spinal diseases.MethodsThe cohort study based on routine healthcare data from Germany with 11.7 million patient-years between 2012 and 2016 for patients with physician-confirmed spinal diseases (ICD-10: M40-M54), occupation and age 20 to 64 years. A Poisson model estimated the effects of the socioeconomic status (school education, professional education and occupational position) for the risk ratio of receiving diagnostic imaging (radiography, computed tomography, magnetic resonance imaging) and non-pharmaceutical conservative therapies (physical therapy including exercise therapy, manual therapy and massage, spinal manipulative therapy, acupuncture).ResultsPatients received diagnostic imaging in 26%, physical therapy in 32%, spinal manipulative therapy in 25%, and acupuncture in 4% of all patient-years. Similar to previous survey-based studies higher rates of utilization were associated with higher socioeconomic status. These differences were most pronounced for manual therapy, exercise therapy, and magnetic resonance imaging.ConclusionsThe observed differences in health care utilization were highly related to socioeconomic status. Socioeconomic differences were higher for more expensive health services. Further research is necessary to identify barriers to equitable access to health services and to take appropriate action to decrease existing social disparities.

Bibliometric and visualized analysis of nonpharmaceutical TCM therapies for rheumatoid arthritis over the last 20 years using VOSviewer and CiteSpace software.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that poses a significant threat to a patient's quality of life. Commonly used drugs include glucocorticoids, nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and biological agents; however, there are associated side effects. Complementary and alternative medicines can play positive roles. Bibliometric analysis of herbal medicines for RA has been conducted, but current research trends in nonpharmaceutical traditional Chinese medicine (TCM) therapies for the treatment of RA have not been studied. Here, we conducted a bibliometric analysis of the application of nonpharmaceutical TCM therapies for RA over the last 20 years. We retrieved relevant literature from the Web of Science Core Collection database and used VOSviewer and CiteSpace software for analysis. Visualized maps were then generated to display the relationships between the author, country, institution, and keywords. A total of 567 articles were included in the final analysis. The number of annual publications on nonpharmaceutical TCM interventions for RA increased over the study period. The journal with the highest number of publications on this topic was Evidence-based Complementary and Alternative Medicine; however, Cochrane Database of Systematic Reviews had the most citations. Collaborations were observed among worldwide institutions, with the People's Republic of China playing a dominant role in the research on treatment of RA using nonpharmaceutical TCM therapies. Ernst E was the most productive author, with 11 articles, whereas Green S had the highest number of citations (287) at the time of retrieval. Specific improvements in the efficacy and selection of nonpharmaceutical therapies were the main research hotspots based on citation burst analysis. This study characterizes the trends in the literature for nonpharmaceutical TCM therapy for RA over the past 20 years; showcasing the current research status for relevant researchers and their teams and providing a reference for future research directions.

Exercise ameliorates skeletal muscle insulin resistance by modulating GRK4-mediated D1R expression.

Exercise has been recommended as a nonpharmaceutical therapy to treat insulin resistance (IR). Previous studies showed that dopamine D1-like receptor agonists, such as fenoldopam, could improve peripheral insulin sensitivity, while antipsychotics, which are dopamine receptor antagonists, increased susceptibility to Type 2 diabetes mellitus (T2DM). Meanwhile, exercise has been proved to stimulate dopamine receptors. However, whether the dopamine D1 receptor (D1R) is involved in exercise-mediated amelioration of IR remains unclear. We found that the D1-like receptor antagonist, SCH23390, reduced the effect of exercise on lowering blood glucose and insulin in insulin-resistant mice and inhibited the contraction-induced glucose uptake in C2C12 myotubes. Similarly, the opposite was true for the D1-like receptor agonist, fenoldopam. Furthermore, the expression of D1R was decreased in skeletal muscles from streptozotocin (STZ)- and high-fat intake-induced T2DM mice, accompanied by increased D1R phosphorylation, which was reversed by exercise. A screening study showed that G protein-coupled receptor kinase 4 (GRK4) may be the candidate kinase for the regulation of D1R function, because, in addition to the increased GRK4 expression in skeletal muscles of T2DM mice, GRK4 transgenic T2DM mice exhibited lower insulin sensitivity, accompanied by higher D1R phosphorylation than control mice, whereas the AAV9-shGRK4 mice were much more sensitive to insulin than AAV9-null mice. Mechanistically, the up-regulation of GRK4 expression caused by increased reactive oxygen species (ROS) in IR was ascribed to the enhanced expression of c-Myc, a transcriptional factor of GRK4. Taken together, the present study shows that exercise, via regulation of ROS/c-Myc/GRK4 pathway, ameliorates D1R dysfunction and improves insulin sensitivity.

Effect of SP6 Acupressure on First-Period Labor Pain

The process of labor begins with uterine contractions that cause pain and discomfort in laboring mothers. The main problem in laboring mothers is pain. Pain is a single sensation caused by a specific stimulus that is subjective and different for each individual. One of the non-pharmaceutical therapies for overcoming labor pain is acupressure. The aim is to determine the effect of SP6 acupressure on labor pain during the first stage at the Midwife Clinic Nelly M. Harahap Padangsidimpuan City. This study was conducted using a quasi-experimental research method (pseudo-experiment) using a Pretest posttest only design. The number of samples in this study was 20 respondents. sampling method using a purposive sampling technique. Data were analyzed univariately and bivariately. The results of the study found labor pain before the SP6 Acupressure action in laboring mothers at time I with a mean of 6.65 and after the SP6 Acupressure action in laboring mothers at time I with a mean value of 3.05. This study concludes that there is an effect of Acupressure SP6 on labor pain at time I with a p-value of 0.002. It is recommended that laboring women gain knowledge and experience in the implementation of Acupressure SP6 on labor pain at stage I.

Quantitative sensory testing as an assessment tool to predict the response to standard pain treatment in knee osteoarthritis: a systematic review and meta-analysis.

Emerging evidence suggest that quantitative sensory testing (QST) may predict the treatment response to pain-relieving therapies. This systematic review and meta-analysis focus on the predictive value of QST for pain management of knee osteoarthritis (OA). MEDLINE and EMBASE were systematically searched for all studies from year 2000 to 2023 on pretreatment QST and treatment of OA including surgical, pharmaceutical, and nonsurgical and nonpharmaceutical therapies. Preclinical studies and reviews were excluded. The systematic review followed the PRISMA guidelines and was pre-registered on the Open Science Framework website (link: https://osf.io/4FETK/, Identifier: DOI 10.17605/OSF.IO/4FETK). Meta-analysis were conducted to demonstrate the strength of the pre-treatment QST predictions on pain outcomes after OA treatments. Sixteen surgical (all on total knee arthroplasty [TKA], N = 1967), 5 pharmaceutical (4 on non-steroidal anti-inflammatory drugs [NSAIDs], N = 271), and 4 exercise-based therapy studies (N = 232) were identified. Pretreatment QST parameters predicted pain-relieving treatment outcomes in 81% of surgical, 100% of pharmaceutical, and 50% of exercise-based therapy studies. Meta-analyses found pretreatment QST profiles to predicted pain outcomes after TKA (random effects: 0.309, 95% confidence interval [CI]: 0.206-0.405, P < 0.001), NSAIDs (random effects: 0.323, 95% CI: 0.194-0.441, P < 0.001), and exercise-based therapies (random effects: 0.417, 95% CI: 0.138-0.635, P = 0.004). The overall risk of bias for the included studies was low to moderate. This systematic review and meta-analysis demonstrate weak-to-moderate associations between pretreatment QST and pain outcomes after standard OA pain treatments. Based on this work, it is hypothesized that a subset of specific pain sensitive patients with OA exist and that these patients do not respond adequately to standard OA pain treatments.

Effects of yoga vs placebo on inflammation among cancer survivors: A nationwide multicenter phase III randomized controlled trial (RCT).

12111 Background: Inflammation, both acute and chronic, is universally associated with primary and secondary cancer development and progression, as well as a myriad of toxicities that negatively affect cancer treatment adherence and survival. The effectiveness of targeting inflammation with non-pharmaceutical therapies such as yoga is not known. As part of a nationwide, multicenter, phase III RCT with cancer survivors, we compared the effects of yoga (Yoga for Cancer Survivors; YOCAS) to a behavioral placebo (survivorship health education) on inflammation (i.e. pro-inflammatory, anti-inflammatory, and overall inflammatory status). Methods: Participants were recruited via the URCC NCORP Research Base in partnership with 23 community oncology practices across the United States. Eligible participants were cancer survivors with insomnia 2-60 months post-treatment. They were randomized to receive YOCAS (gentle Hatha and Restorative yoga, 75-min./session, 2x/week, 4 weeks) or placebo (ASCO survivorship recommendation-based health education, 75-min./session, 2x/week, 4 weeks). Serum samples were collected at baseline and post-intervention to assess inflammation (i.e., pro-inflammatory markers IL-1β, IL-6, TNF-α, IFN-γ and anti-inflammatory markers IL-4, IL-8, IL-10, sTNFRI), via Luminex multiplex assays. Analysis of covariance (ANCOVA) and structural equation modeling (SEM) were used to access yoga's effects on inflammation. Results: 502 survivors (94% female, mean age 56±11 years, 74% breast cancer) were enrolled. ANCOVAs revealed significantly lower levels of pro-inflammatory markers in YOCAS participants compared to placebo participants (IL-1β: -0.07±0.03, p = 0.01; TNF-α: -0.04±0.02, p = 0.08; IFN-γ: -0.07±0.03, p = 0.02) where YOCAS participants exhibited stable pro-inflammatory responses (all p &gt; 0.05) and placebo participants exhibited significant increases in pro-inflammatory responses (all p≤0.05) from baseline to post-intervention. ANCOVAs also revealed a statistical trend toward lower levels of anti-inflammatory markers in YOCAS participants compared to placebo participants (IL-4: -0.06±0.04, p = 0.10; IL-10: -0.06±0.04, p = 0.09; sTNFRI: -0.06±0.04, p = 0.09). SEM also demonstrated significantly lower pro-inflammatory status (-0.16±0.03, p &lt; 0.01), significantly lower anti-inflammatory status (-0.14±0.03, p = 0.03), and significantly lower overall inflammatory status (-0.15±0.03, p = 0.01) in YOCAS participants compared to placebo participants. Conclusions: Our data suggest that YOCAS yoga significantly reduces inflammation among cancer survivors. Clinicians should consider prescribing yoga for survivors experiencing inflammation, which may lead to a high chronic toxicity burden and increased risk of progression, recurrence, and second cancers. Funding: NCI UG1CA189961, R01CA181064, T32CA102618. Clinical trial information: NCT02613364 .

Exercise Therapy for Knee Osteoarthritis: A Systematic Review and Network Meta-analysis.

Exercise is an effective nonpharmaceutical therapy for knee osteoarthritis (KOA). To identify the most effective type of exercise therapy for KOA with regard to pain, stiffness, joint function, and quality of life. Systematic review; Level of evidence, 3. The PubMed, Web of Science, Embase, and Cochrane Library databases were searched, from inception to April 4, 2022. Included were randomized controlled trials that assessed the efficacy on KOA among 5 different exercise therapy groups (aquatic exercise [AE], stationary cycling [CY], resistance training [RT], traditional exercise [TC], and yoga [YG]) and compared with the control group. Outcomes among the groups were assessed with the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), 6-minute walk test (6-MWT), visual analog scale (VAS) for pain, and Knee injury and Osteoarthritis Outcome Score (KOOS); weighted mean differences (WMDs) and 95% confidence intervals were calculated. Network meta-analyses comparing outcomes between all groups and with controls were performed, and group rankings were calculated using the surface under the cumulative ranking curve (SUCRA). A total of 39 studies (N = 2646 participants) were included. Most of the studies failed to blind participants and researchers, resulting in a high risk of performance bias. Significantly worse WOMAC-Pain scores were seen in controls compared with all exercise interventions except AE (WMD [95% CI]: CY, -4.45 [-5.69 to -3.20]; RT, -4.28 [-5.48 to -3.07]; TC, -4.20 [-5.37 to -3.04]; and YG, -0.57 [-1.04 to -1.04]), and worse scores were seen in controls compared with YG regarding WOMAC-Stiffness (WMD, -1.40 [95% CI, -2.45 to -0.34]) and WOMAC-Function (WMD, -0.49 [95% CI, -0.95 to -0.02]). According to the SUCRA, CY was the most effective for improving WOMAC-Pain (80.8%) and 6-MWT (76.1%); YG was most effective for improving WOMAC-Stiffness (90.6%), WOMAC-Function (77.4%), KOOS-Activities of Daily Living (72.0%), and KOOS-Quality of Life (79.1%); AE was the most effective regarding VAS pain (77.2%) and KOOS-Pain (64.0%); and RT was the most effective regarding KOOS-Symptoms (84.5%). All 5 types of exercise were able to ameliorate KOA. AE (for pain relief) and YG (for joint stiffness, limited knee function, and quality of life) were the most effective approaches, followed by RT, CY, and TC.