Prevalence, patterns, and predictors of patient-reported non-motor outcomes at 30 days after acute stroke: Prospective observational hospital cohort study.

BACKGROUND: Adverse non-motor outcomes are common after acute stroke and likely to substantially affect quality of life, yet few studies have comprehensively assessed their prevalence, patterns, and predictors across multiple health domains. AIMS: We aimed to identify the prevalence, patterns, and the factors associated with non-motor outcomes 30 days after stroke. METHODS: This prospective observational hospital cohort study-Stroke Investigation in North and Central London (SIGNAL)-identified patients with acute ischemic stroke or intracerebral hemorrhage (ICH) admitted to the Hyperacute Stroke Unit (HASU) at University College Hospital (UCH), London, between August 1, 2018 and August 31, 2019. We assessed non-motor outcomes (anxiety, depression, fatigue, sleep, participation in social roles and activities, pain, bowel function, and bladder function) at 30-day follow-up using the Patient-Reported Outcome Measurement Information System-Version 29 (PROMIS-29) scale and Barthel Index scale. RESULTS: We obtained follow-up data for 605/719 (84.1%) eligible patients (mean age 72.0 years; 48.3% female; 521 with ischemic stroke, 84 with ICH). Anxiety (57.0%), fatigue (52.7%), bladder dysfunction (50.2%), reduced social participation (49.2%), and pain (47.9%) were the commonest adverse non-motor outcomes. The rates of adverse non-motor outcomes in ⩾ 1, ⩾ 2 and ⩾ 3 domains were 89%, 66.3%, and 45.8%, respectively; in adjusted analyses, stroke due to ICH (compared to ischemic stroke) and admission stroke severity were the strongest and most consistent predictors. There were significant correlations between bowel dysfunction and bladder dysfunction (κ = 0.908); reduced social participation and bladder dysfunction (κ = 0.844); and anxiety and fatigue (κ = 0.613). We did not identify correlations for other pairs of non-motor domains. CONCLUSION: Adverse non-motor outcomes were very common at 30 days after stroke, affecting nearly 90% of evaluated patients in at least one health domain, about two-thirds in two or more domains, and almost 50% in three or more domains. Stroke due to ICH and admission stroke severity were the strongest and most consistent predictors. Adverse outcomes occurred in pairs of domains, such as with anxiety and fatigue. Our findings emphasize the importance of a multi-domain approach to effectively identify adverse non-motor outcomes after stroke to inform the development of more holistic patient care pathways after stroke.

Low serum 25­hydroxy-vitamin D levels are associated with cognitive impairment in multiple sclerosis.

BACKGROUND: Cognitive impairment frequently affects people with multiple sclerosis (MS). Low vitamin D has been associated with cognitive dysfunction in different neurodegenerative diseases, and, in MS, with motor disability and disease activity. We aim to investigate associations between vitamin D and cognitive status in MS. METHODS: In this cross-sectional study, we included 181 MS patients, recruited consecutively at the MS Unit of the Policlinico Federico II University Hospital of Naples, Italy, between January and April 2022, with serum 25­hydroxy (25-OH) vitamin D measurements using Chemiluminescence-ImmunoAssay, and cognitive assessment using the Brief International Cognitive Assessment for MS (BICAMS), which includes Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT-II) and Brief Visuospatial Memory Test-Revised (BVMT-R). We collected demographics (age, sex, education), and clinical variables (disease duration, disease subtype, expanded disability status scale (EDSS), disease modifying treatment, relapses in previous 12 months, vitamin D supplementation, comorbidities). For a subset of patients (n = 41, 23.2% of the total sample), we collected Beck Depression Inventory-II, Beck Anxiety Inventory, and Modified Fatigue Impact Scale. RESULTS: At univariable linear regression models, serum 25-OH-vitamin D levels were 0.9 ng/mL higher for each unit increase of SDMT adjusted scores (Coeff=0.93; 95%CI=0.81, 1.04; p<0.01), 0.7 ng/mL higher for each unit increase of CVLT-II adjusted scores (Coeff=0.68; 95%CI=0.53, 0.83; p<0. 01), 0.6 ng/mL higher for each unit increase of BVMT-R adjusted scores (Coeff=0.58; 95%CI=0.43, 0.73; p<0.01), -9.63 ng/mL lower for each impaired BICAMS test (Coeff=-9.63; 95%CI=-11.48, -7.79; p<0.01), and -2.2 ng/mL lower for each unit increase of EDSS (Coeff=-2.16; 95%CI=-3.57, -0.75; p<0.01). At multivariable linear regression models, we confirmed associations between 25-OH-vitamin D and EDSS (Coeff=-2.09; 95%CI=-4.45, -0.43; p<0.01), SDMT (Coeff=0.75; 95%CI=0.60, 0.90; p<0.01), and CVLT-II (Coeff=0.14; 95%CI=0.01, 0.28; p = 0. 04). Results remained unchanged when including depression, anxiety and fatigue scores. CONCLUSIONS: Lower serum 25-OH-vitamin D was associated with worse cognitive function in MS. Future studies should consider longitudinal variations in cognitive function in relation to vitamin D supplementation.

Pearls & Oy-sters: Syndrome of Inappropriate Antidiuretic Hormone Secretion Presenting as Neuromyelitis Optica Spectrum Disorder Flare.

While it was previously believed that neuromyelitis optic spectrum disorder (NMOSD) mostly affected the optic nerves and the spinal cord, it is increasingly recognized that NMOSD can involve any area of the CNS where aquaporin-4 is highly expressed. These other areas can include the hypothalamus and the circumventricular organs that surround the third and fourth ventricles, serving as osmoregulators. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the most common causes of hyponatremia and has been associated with NMOSD due to these lesions. In this report, we present a case of a patient with known NMOSD, who presented with dizziness, fatigue, and generalized weakness and whose workup revealed hyponatremia in the setting of SIADH and hypothalamic demyelinating lesions. This case illustrates an atypical presentation of NMOSD and the importance of looking for syndromes, such as SIADH. This can guide diagnostic testing, such as getting thin MRI cuts through the hypothalamus and brainstem, as well as advanced management techniques such as immunotherapy.

Case report: Gitelman syndrome with diabetes: Confirmed by both hydrochlorothiazide test and genetic testing.

RATIONALE: Gitelman syndrome (GS) is an autosomal recessive tubulopathy caused by mutations of the SLC12A3 gene. It is characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. Hypokalemia, hypomagnesemia, and increased renin-angiotensin-aldosterone system (RAAS) activity can cause glucose metabolism dysfunction. The diagnosis of GS includes clinical diagnosis, genetic diagnosis and functional diagnosis. The gene diagnosis is the golden criterion while as functional diagnosis is of great value in differential diagnosis. The hydrochlorothiazide (HCT) test is helpful to distinguish GS from batter syndrome, but few cases have been reported to have HCT testing. PATIENT CONCERNS: A 51-year-old Chinese woman presented to emergency department because of intermittent fatigue for more than 10 years. DIAGNOSES: Laboratory test results showed hypokalemia, hypomagnesemia, hypocalciuria and metabolic alkalosis. The HCT test showed no response. Using next-generation and Sanger sequencing, we identified 2 heterozygous missense variants (c.533C > T:p.S178L and c.2582G > A:p.R861H) in the SLC12A3 gene. In addition, the patient was diagnosed with type 2 diabetes mellitus 7 years ago. Based on these findings, the patient was diagnosed with GS with type 2 diabetic mellitus (T2DM). INTERVENTIONS: She was given potassium and magnesium supplements, and dapagliflozin was used to control her blood glucose. OUTCOMES: After treatments, her fatigue symptoms were reduced, blood potassium and magnesium levels were increased, and blood glucose levels were well controlled. LESSONS: When GS is considered in patients with unexplained hypokalemia, the HCT test can be used for differential diagnosis, and genetic testing can be continued to confirm the diagnosis when conditions are available. GS patients often have abnormal glucose metabolism, which is mainly caused by hypokalemia, hypomagnesemia, and secondary activation of RAAS. When a patient is diagnosed with GS and type 2 diabetes, sodium-glucose cotransporter 2 inhibitors (SGLT2i) can be used to control the blood glucose level and assist in raising blood magnesium.

Non-pharmacologic interventions for improving cancer-related fatigue (CRF): A systematic review of systematic reviews and pooled meta-analysis.

INTRODUCTION: Literature encloses numerous systematic reviews (SRs) on nonpharmacologic interventions for improving cancer-related fatigue (CRF). The effect of these interventions remains controversial, and the available SRs have not been synthesized yet. We conducted a systematic synthesis of SRs and meta-analysis to determine the effect of nonpharmacologic interventions on CRF in adults. MATERIAL AND METHODS: We systematically searched 4 databases. The effect sizes (standard mean difference) were quantitatively pooled using a random-effects model. Chi-squared (Q) and I-square statistics (I²) tested the heterogeneity. RESULTS: We selected 28 SRs, including 35 eligible meta-analyses. The pooled effect size (standard mean difference, 95% CI) was -0.67 (-1.16, -0.18). The subgroup analysis by types of interventions showed a significant effect in all the investigated approaches (complementary integrative medicine, physical exercise, self-management/e-health interventions). CONCLUSIONS: There is evidence that nonpharmacologic interventions are associated with CRF reduction. Future research should focus on testing these interventions on specific population clusters and trajectories. PROSPERO REGISTRATION: CRD42020194258.

Effects of warm or cold compresses applied to the legs during hemodialysis on cramps, fatigue, and patient comfort: A placebo-controlled randomized trial.

INTRODUCTION: Muscle cramps and fatigue are common complications in hemodialysis patients and have been associated with reduced patient comfort. Among the complementary therapies advocated for the management of these complications have been the application of warm or cold compresses to the extremities during a hemodialysis treatment. In this study, we compared the effects of warm or cold compresses application on cramping, fatigue, and patient comfort. METHODS: This placebo-controlled randomized trial was done in 69 patients, who were stratified and randomly allocated to three treatment arms. Two of the three groups included an intervention; application of either warm (n = 23) or cold (n = 23) compresses to the extremities during dialysis. The third group served as a placebo control (n = 23). The study period comprised 12 hemodialysis sessions. One week after the completion of the intervention, a follow-up dialysis session was also evaluated. Data were collected at baseline (t0 ), during each of 12 intervention sessions (t1 -t12 ), and at the follow-up session t13 . Cramps, fatigue, and patient comfort were evaluated using the Cramp Episode Follow-up Chart, Piper's Fatigue Scale, and the Hemodialysis Comfort Scale, respectively. RESULTS: In both the intervention and follow-up sessions, cramping and fatigue were lower, and comfort was higher in each of the intervention groups compared to placebo controls Application of warm compresses was superior to use of cold compresses. DISCUSSION: Both warm and cold compress administration reduced muscle cramps, fatigue, and hemodialysis comfort in hemodialysis patients.

The effect of acupressure or reiki interventions on the levels of pain and fatigue of cancer patients receiving palliative care: A randomized controlled study.

OBJECTIVE: Taking pain under control is important to calm the individual and reduce complications. This research was conducted with the aim of determining the effect of Acupressure or Reiki interventions on the levels of pain and fatigue of stage III and IV cancer patients receiving palliative care. METHOD: The research was a single-blind, repeated measures, randomized controlled study. Research data were collected between February and November 2022. The research sample consisted of Acupressure and Reiki intervention groups and a control group with 52 patients in each group for a total of 156 patients. Acupressure or Reiki was applied to their intervention groups for a total of eight sessions of 20 min each over four weeks, once a day on two days a week. Data were collected by means of a patient description form, an analgesic follow-up form, the Numeric Pain Rating Scale, and the Brief Fatigue Inventory. RESULTS: In comparison with the control group, a significant reduction was seen over time in the levels of pain (p < 0.001), analgesic use (p < 0.001), and fatigue (p < 0.001) in the Acupressure or Reiki intervention groups. CONCLUSION: Acupressure or Reiki interventions were found to effective in reducing levels of pain, analgesic use, and fatigue. It was seen that in addition to their use in routine nursing care, both treatments can be accepted as effective nursing interventions that reduce pain and fatigue in stage III and IV cancer patients receiving palliative care.

Acupuncture versus massage for pain in patients living with advanced cancer: a protocol for the IMPACT randomised clinical trial.

INTRODUCTION: Pain, comorbid fatigue and sleep disturbances are common and distressing symptoms for patients with advanced cancer, negatively impacting their quality of life. Clinical guidelines recommend non-pharmacological interventions, including acupuncture and massage, for pain management in adult patients with cancer in adjunct to conventional care. However, high-quality evidence about the comparative effectiveness and long-term durability of these therapies for symptom management is limited. METHODS AND ANALYSIS: We describe the design of a two-arm, parallel group, multicentre randomised controlled trial that investigates the use of acupuncture versus massage for musculoskeletal pain among 300 patients with diverse types of advanced cancer. The primary aim is to evaluate the long-term effectiveness (26 weeks from randomisation) of acupuncture vs massage for pain (primary outcome) and comorbid symptoms (fatigue, sleep disturbance and quality of life). The secondary aim is to identify patient-level demographic characteristics (eg, sex, race, age), clinical factors (eg, insomnia, pain severity) and psychological attributes that are associated with a greater reduction in pain for either acupuncture or massage. Patients will receive weekly acupuncture or massage treatments for 10 weeks, followed by monthly booster sessions up to 26 weeks. The primary endpoint will be the change in worst pain intensity score from baseline to 26 weeks. We will collect validated patient-reported outcomes at multiple time points over 26 weeks. ETHICS AND DISSEMINATION: The Institutional Review Board at Memorial Sloan Kettering Cancer Center in New York approved this protocol. Results will be disseminated via peer-reviewed scientific journals and conference presentations. Our findings will help patients and healthcare providers make informed decisions about incorporating non-pharmacological treatments to manage pain for patients with advanced cancer. TRIAL REGISTRATION NUMBER: NCT04095234.

Efficacy of ginseng oral administration and ginseng injections on cancer-related fatigue: A meta-analysis.

BACKGROUND: Up to 90% of patients who are under the active treatment suffer from cancer-related fatigue (CRF). CRF can persist about 10 years after diagnosis and/or treatment. Accumulating reports support that ginseng and ginseng injections are both potential drugs for the treatment of CRF but few studies put them together for analysis. METHODS: Two reviewers independently extracted data in 3 databases (PubMed, Cochrane Library and China National Knowledge Infrastructure) from their inception to May 24, 2021. The primary outcome was the effect of ginseng in alleviating CRF. The secondary outcome was ginseng in alleviating emotional or cognitive fatigue. Standardized mean difference (SMD) was employed. RESULTS: Twelve studies were included to evaluate efficacy of ginseng oral administration and ginseng injections on CRF. The pooled SMD was 0.40 (95% confidence Interval [95% CI] [0.29-0.51], P < .00001). Six studies were included to evaluate efficacy of ginseng oral administration on CRF and the SMD was 0.29 (95% CI [0.15-0.42], P < .0001). The order was 2000 mg/d, 3000 mg/d, 1000 mg/d and placebo from high efficacy to low. Ten studies were included to evaluate efficacy of ginseng injections on CRF and the SMD was 0.74 (95% CI [0.59-0.90], P < .00001). Emotional fatigue was reported in 4 studies, ginseng oral administration in 2 and ginseng injections in 2. The pooled SMD was 0.12 (95% CI [-0.04 to 0.29], P = .15). Cognitive fatigue was reported in 4 studies focusing on ginseng injections and the SMD was 0.72 (95% CI [0.48-0.96], P < .00001). CONCLUSION: Ginseng can improve CRF. Intravenous injection might be better than oral administration. Ginseng injections may alleviate cognitive fatigue. No evidence was found to support that ginseng could alleviate emotional fatigue.

The Efficacy and Safety of Manual Therapy for Symptoms Associated with Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Background: Multiple sclerosis (MS) is a chronic neurological autoimmune disease, affecting the psychological and physical health of patients. Manual therapies have been proven to relieve pain, strengthen muscles, and improve bladder and bowel problems with a high safety and low adverse event profile. Previous studies have reported the results of manual therapy in alleviating symptoms associated with MS, but the conclusions were controversial. Objective: The purpose of this meta-analysis is to comprehensively analyze and determine the efficacy and safety of manual therapy in relieving symptoms associated with MS. Methods: Eight electronic databases were searched from inception of the database to April 30, 2021. Randomized controlled trials (RCTs) using manual therapy in patients to relieve symptoms associated with MS were considered eligible for this study. Two reviewers independently extracted data using pre-established standards. Results: Finally, 10 eligible RCTs with 631 subjects were included in this meta-analysis. These data establish that massage therapy can significantly ameliorate fatigue, pain, and spasms, while reflexology was only effective in relieving pain in MS patients. No adverse events were reported in eligible RCTs. Conclusions: The present study provides strong evidence that massage therapy could alleviate fatigue, pain, and spasms in MS patients, while reflexology plays a positive role in relieving pain. Physicians could consider massage therapy or reflexology as a safe and effective complementary and alternative treatment. Larger RCTs with higher methodological quality are needed in the future, which aim to provide more meaningful evidence for further proof of efficacy.

Long-Term Effects of Cognitive-Behavioral Therapy and Yoga for Worried Older Adults.

OBJECTIVES: Cognitive-behavioral therapy (CBT) and yoga decrease worry and anxiety. There are no long-term data comparing CBT and yoga for worry, anxiety, and sleep in older adults. The impact of preference and selection on these outcomes is unknown. In this secondary data analysis, we compared long-term effects of CBT by telephone and yoga on worry, anxiety, sleep, depressive symptoms, fatigue, physical function, social participation, and pain; and examined preference and selection effects. DESIGN: In this randomized preference trial, participants (N = 500) were randomized to a: 1) randomized controlled trial (RCT) of CBT or yoga (n = 250); or 2) preference trial (selected CBT or yoga; n = 250). Outcomes were measured at baseline and Week 37. SETTING: Community. PARTICIPANTS: Community-dwelling older adults (age 60+ years). INTERVENTIONS: CBT (by telephone) and yoga (in-person group classes). MEASUREMENTS: Penn State Worry Questionnaire - Abbreviated (worry);1,2 Insomnia Severity Index (sleep);3 PROMIS Anxiety Short Form v1.0 (anxiety);4,5 Generalized Anxiety Disorder Screener (generalized anxiety);6,7 and PROMIS-29 (depression, fatigue, physical function, social participation, pain).8,9 RESULTS: Six months after intervention completion, CBT and yoga RCT participants reported sustained improvements from baseline in worry, anxiety, sleep, depressive symptoms, fatigue, and social participation (no significant between-group differences). Using data combined from the randomized and preference trials, there were no significant preference or selection effects. Long-term intervention effects were observed at clinically meaningful levels for most of the study outcomes. CONCLUSIONS: CBT and yoga both demonstrated maintained improvements from baseline on multiple outcomes six months after intervention completion in a large sample of older adults. TRIAL REGISTRATION: www. CLINICALTRIALS: gov Identifier NCT02968238.

Effects of actual and imagined music-cued gait training on motor functioning and brain activity in people with multiple sclerosis: protocol of a randomised parallel multicentre trial.

INTRODUCTION: Motor imagery (MI) refers to the mental rehearsal of a physical action without muscular activity. Our previous studies showed that MI combined with rhythmic-auditory cues improved walking, fatigue and quality of life (QoL) in people with multiple sclerosis (pwMS). Largest improvements were seen after music and verbally cued MI. It is unclear whether actual cued gait training achieves similar effects on walking as cued MI in pwMS. Furthermore, in pwMS it is unknown whether any of these interventions leads to changes in brain activation. The purpose of this study is therefore to compare the effects of imagined and actual cued gait training and a combination thereof on walking, brain activation patterns, fatigue, cognitive and emotional functioning in pwMS. METHODS AND ANALYSIS: A prospective double-blind randomised parallel multicentre trial will be conducted in 132 pwMS with mild to moderate disability. Randomised into three groups, participants will receive music, metronome and verbal cueing, plus MI of walking (1), MI combined with actual gait training (2) or actual gait training (3) for 30 min, 4× per week for 4 weeks. Supported by weekly phone calls, participants will practise at home, guided by recorded instructions. Primary endpoints will be walking speed (Timed 25-Foot Walk) and distance (2 min Walk Test). Secondary endpoints will be brain activation patterns, fatigue, QoL, MI ability, anxiety, depression, cognitive functioning, music-induced motivation-to-move, pleasure, arousal and self-efficacy. Data will be collected at baseline, postintervention and 3-month follow-up. MRI reference values will be generated using 15 matched healthy controls. ETHICS AND DISSEMINATION: This study follows the Standard Protocol Items: Recommendations for Interventional Trials-PRO Extension. Ethical approval was received from the Ethics Committees of the Medical Universities of Innsbruck (1347/2020) and Graz (33-056 ex 20/21), Austria. Results will be disseminated via national and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: DRKS00023978.

Implementing an evidence-based somatic acupressure intervention in breast cancer survivors with the symptom cluster of fatigue, sleep disturbance and depression: study protocol of a phase II randomised controlled trial.

INTRODUCTION: The fatigue-sleep disturbance-depression (FSD) symptom cluster, as one of the most common symptom clusters in breast cancer (BC) survivors, can significantly decrease patients' quality of life. Since the management of the FSD symptom cluster has been unsatisfactory with the use of pharmacological treatments alone, non-pharmacological approaches have, therefore, been recommended. Somatic acupressure (SA) is a promising approach given its potential benefits of cancer-related symptom alleviation and the convenience of self-practice. However, research evidence on using acupressure to manage the FSD symptom cluster has been limited. The proposed trial aims to examine the feasibility and preliminary effects of an evidence-based SA intervention for FSD symptom cluster management in BC survivors. METHODS AND ANALYSIS: This study will be a phase II randomised controlled trial with three study arms and 1:1:1 allocation. Fifty-one early-stage BC survivors who are experiencing the FSD symptom cluster will be randomly assigned to a true SA group, a sham SA group or a usual care group. All participants will receive an education booklet regarding FSD symptom cluster management advice as the usual care package. The participants in the true SA group will additionally receive a 7-week self-administered SA intervention. The participants in the sham SA group will additionally receive self-administered light acupressure at non-acupoints with the same frequency, session and duration as the true SA group. The primary outcomes will be feasibility outcomes related to subject recruitment and completion of study questionnaires and interventions. The secondary outcomes will be the effects of SA on fatigue, sleep disturbance, depression and quality of life. Descriptive statistics will be used to present all the outcomes. The secondary outcomes will be analysed using an intent-to-treat approach. ETHICS AND DISSEMINATION: Ethical approvals of this trial have been granted by the Human Research Ethics Committee at Charles Darwin University (H19017) and the Clinical Trial Ethics Committee at The Affiliated Hospital of Southwest Medical University (KY2019039). Findings from this trial will be published in peer-reviewed journals and presented at professional conferences. TRIAL REGISTRATION NUMBER: This trial was registered at ClinicalTrials.gov and the registration number is NCT04118140, with the stage at Recruiting.

Combining Ozonated Autohemotherapy with Pharmacological Therapy for Comorbid Insomnia and Myofascial Pain Syndrome: A Prospective Randomized Controlled Study.

Objective: To examine the efficacy and safety of ozonated autohemotherapy (O3-AHT) combined with pharmacological therapy for comorbid insomnia and myofascial pain syndrome (MPS). Materials and Methods: One hundred and eighteen patients were randomly divided into two groups: the control group (N = 50) and the O3-AHT group (N = 53). Patients in both groups were given the same pharmacological management for three weeks. Patients in the O3-AHT group were treated with ozonated autohemotherapy (the concentration of ozone was 20 µg/ml in the first week, 30 µg/ml in the second week, and 40 µg/ml in the third week) combined with pharmacological therapy. Primary (the insomnia severity index (ISI) and visual analogue scale (VAS)) and secondary outcomes (the Epworth sleepiness scale (ESS), polysomnography data, the anxiety and preoccupation about sleep questionnaire (APSQ), the beck depression index (BDI), and the multidimensional fatigue inventory (MFI)) were examined at pretreatment, posttreatment, 1 month, and 6 months. Results: Fifty patients in the control group and fifty-three patients in the O3-AHT group completed the study. In both groups, insomnia and pain symptoms were relieved significantly compared with pretreatment. Compared with the control group, the O3-AHT group had significantly improved sleep quality, pain, and negative mood at different time points. No adverse complications were observed in either group. Conclusion: Compared with pharmacological therapy alone, ozonated autohemotherapy combined with pharmacological therapy can ameliorate insomnia, reduce pain intensity, improve negative mood, and alleviate fatigue more effectively without serious adverse complications.

Light enhanced cognitive behavioral therapy for insomnia and fatigue during chemotherapy for breast cancer: a randomized controlled trial.

STUDY OBJECTIVES: Sleep problems are common during chemotherapy for breast cancer (BC). We evaluated whether combined brief cognitive behavioral and bright light therapy (CBT-I + Light) is superior to treatment as usual with relaxation audio (TAU+) for insomnia symptoms and sleep efficiency (primary outcomes). METHODS: We randomized women receiving intravenous chemotherapy, stratified by tumor stage and insomnia severity index, to 6-week CBT-I + Light or TAU+. CBT-I + Light included 1 in-person session, 1 telephone call, 7 emails, and 20 min bright light (BL) each morning. TAU+ comprised usual treatment and two emails with relaxation audio tracks. Patient-reported outcomes were assessed at baseline, midpoint (week 3), post (week 6), and 3-month follow-up. RESULTS: Women (N = 101) were randomly assigned to CBT-I + Light or TAU+. The CBT-I + Light group showed significantly greater improvement in insomnia symptoms than the TAU+ group (-5.06 vs -1.93, p = .009; between-group effect size [ES] = .69). At 3-month follow-up, both groups were lower than baseline but did not differ from each other (between-group ES = .18, p = .56). CBT-I + Light had higher patient-reported sleep efficiency than TAU+ immediately after the start of intervention (p = .05) and significantly greater improvement in fatigue (between-group ES = .59, p = .013) and daytime sleep-related impairment (between-group ES = .61, p = .009) than the TAU+ group. CONCLUSIONS: CBT-I + Light had a clinically significant impact on insomnia and fatigue with moderate ESs. Results support offering cognitive behavioral therapy for insomnia and BL therapy during chemotherapy for BC to help manage sleep and fatigue. CLINICAL TRIAL: Australian New Zealand Clinical Trials Registry (http://anzctr.org.au/). Registration number: ACTRN12618001255279.

Effect of Light Therapy on Cancer-Related Fatigue: A Systematic Review and Meta-Analysis.

CONTEXT: Light therapy is a non-pharmacological therapy that is currently being studied in cancer-related symptoms and is certificated as a low-risk intervention by FDA. Cancer-related fatigue (CRF) is the most common symptom reported by cancer patients. OBJECTIVE: To examine the effectiveness of light therapy for CRF in cancer patients through a systematic review and meta-analysis. METHODS: We conducted a systematic review of four electronic databases targeted randomized clinical trials evaluating light therapy for CRF (CRD42020215446), from inception to May 2021. The primary outcome was changes of CRF scores; secondary outcomes included depression, sleep, and quality of life (QoL). We quantitatively pooled outcomes using meta-analysis with random-effects models and assessed methodological bias. RESULTS: We identified thirteen RCTs representing 551 cancer patients, encompassing breast (n = 5), ovarian or endometrial (n = 1), multiple myeloma (n = 1), lung (n = 1), or combined (n = 5) cancers. The comparison groups included dim light (n = 12) and waiting list (n = 1). Duration of intervention ranged from 1 to 12 weeks. Light intensities ranged from 417.9 to 12,000 lux. Light therapy was associated with a significant improvement in CRF (SMD = 0.45, P = 0.007), depression (SMD = -0.26, P = 0.03) and sleep difficulty (SMD = -2.46, P = 0.0006); a statistically non-significant trend was observed for QoL (SMD = 0.33, P = 0.09). Funnel plots for CRF suggest not significant publication bias. CONCLUSION: Light therapy could be a feasible and effective option for improving CRF in cancer patients. Larger sample, rigor trials design and a standard protocol of intervention are needed to draw more conclusive conclusions.

Cross-Sectional Associations between Dietary Daily Nicotinamide Intake and Patient-Reported Outcomes in Colorectal Cancer Survivors, 2 to 10 Years Post-Diagnosis.

Supplementation with nicotinamide adenine dinucleotide (NAD+) precursors including dietary nicotinamide has been found to boost tissue NAD+ levels and ameliorate oxidative stress-induced damage that contributes to aging and aging-related diseases. The association between dietary NAD+ precursors and patient-reported health-related outcomes in cancer survivors has not been investigated. This study aimed to determine associations of dietary nicotinamide intake with different patient-reported outcomes in colorectal cancer survivors, 2 to 10 years post-diagnosis. A total of 145 eligible participants were recruited into this cross-sectional study. Dietary nicotinamide intake level was calculated based on data from 7-day food diaries. Fatigue was assessed with the Checklist Individual Strength (CIS), which is a subscale of the cancer-specific European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC), and anxiety and depression were assessed with Hospital Anxiety and Depression Scale (HADS). Oxidative stress marker serum protein carbonyl contents and serum NAD+ levels were measured. A hierarchical linear regression model with confounder adjustment was performed to analyze the association of nicotinamide intake, serum protein carbonyl contents, and NAD+ levels with patient-reported outcomes. The median values of daily nicotinamide intake for male and female participants were 19.1 and 14.4 mg, respectively. Daily dietary nicotinamide intake was associated with a lower level of fatigue (ß: -14.85 (-28.14, -1.56)) and a lower level of anxiety and depression (ß: -4.69 (-8.55, -0.83)). Subgroup analyses by sex showed that a beneficial association between nicotinamide intake and patient-reported outcomes was mainly found in men. To conclude, our findings suggested that higher dietary NAD+ precursor nicotinamide intake was cross-sectionally associated with less patient-reported outcomes in CRC survivors.

Feasibility and Acceptability of Light Therapy to Reduce Fatigue in Adolescents and Young Adults Receiving Cancer-Directed Therapy.

OBJECTIVE/BACKGROUND: Fatigue is one of the most consistent and distressing symptoms reported by adolescent/young adult (AYA) oncology patients. Bright white light (BWL) is used to treat fatigue in adult oncology but has not been explored in AYA oncology patients. The purpose of the current study was to determine the feasibility and acceptability of BWL for AYA who were receiving cancer-directed therapy. PARTICIPANTS: 51 AYA patients with newly diagnosed solid tumors, including lymphoma. METHODS: Participants were randomized to dim red light (DRL, n = 25) or BWL (n = 26) from devices retrofitted with adherence monitors for 30 minutes upon awakening daily for 8 weeks. Side effects were assessed via modified Systematic Assessment for Treatment-Emergent Effects (SAFTEE). Participants completed the PedsQL Multidimensional Fatigue Scale. RESULTS: Of patients approached, 73% consented and participated. Mean adherence was 57% of days on study with 30.68 average daily minutes of usage. BWL did not cause more extreme treatment-emergent effects over DRL. Patients in the BWL group demonstrated significant improvement on all fatigue outcomes by both self-report and parent proxy report, which was not observed in the DRL group. CONCLUSIONS: This is the first study to evaluate the feasibility and acceptability of light therapy to reduce fatigue in AYA patients receiving cancer-directed therapy. These findings demonstrate the feasibility and acceptability of the intervention and provide preliminary evidence of the potential benefits of BWL, which warrants further study in a confirmatory efficacy trial.ClinicalTrials.gov Identifier Number: NCT02429063.

Development and validation of a Tai chi intervention protocol for managing the fatigue-sleep disturbance-depression symptom cluster in female breast cancer patients.

OBJECTIVE: To develop an evidence-based tai chi intervention protocol for managing the fatigue-sleep disturbance-depression symptom cluster (FSDSC) in breast cancer (BC) patients. METHODS: The Medical Research Council (MRC) Framework for Developing and Evaluating Complex Interventions (the MRC framework) was utilized to guide the study design. This study focused on Phase І of the MRC framework-the development of the intervention-to develop an evidence-based tai chi intervention protocol for managing the FSDSC in BC patients based on existing research evidence, theories, practice standards/guidelines, and experts' consensus. An extensive literature search was performed to identify current systematic reviews, theories, and practice standards/guidelines that can be utilized to inform the intervention dosage and techniques of tai chi and practice instructions. Content validity assessment was also conducted to assess the content validity of the tai chi protocol through expert panel consensus. The content validity index (CVI) was calculated to identify whether the intervention required further refinement. RESULTS: The components of the tai chi protocol were identified by current research evidence and relevant practice standards/guidelines, including the selection of an appropriate tai chi modality and intensity and the duration of the intervention. The Easy 8 form Yang-style tai chi was selected based on the guidelines of the National Comprehensive Cancer Network, the American College of Sports Medicine, and China's State Commission for Physical Culture and Sports. The intensity and duration of the tai chi intervention were scheduled, respectively, twice per week, with each session lasting about one hour, for eight weeks based on the current systematic review evidence on traditional Chinese exercise for the alleviation of cancer-related symptoms. The practise techniques of tai chi were identified from practise standards released by the State Sport General Administration of China. All the items in the tai chi protocol were determined to be content valid after the first round of rating, with all item-level CVIs at 1.00. The scale-level CVI for the tai chi protocol was also identified as excellent, at 1.00. CONCLUSION: An evidence-based tai chi program for managing the FSDSC in BC patients was developed by following the MRC framework. The results provided a clear specification of the tai chi intervention protocol for healthcare professionals and researchers in the next phase of the study-pilot testing the tai chi intervention protocol for FSDSC management through a preliminary randomized controlled trial.

Feasibility of Patient-Created Orff Chant as a Music-Based Intervention in Supportive Cancer Care.

A cancer diagnosis and subsequent treatment can produce distress symptoms, including pain, anxiety, fatigue, and altered mood. These symptoms can have a negative psychological and physiological impact on patients. Patients may need to engage in supportive care with opportunities for emotional responses associated with the disease and chemotherapy treatment to ameliorate distress symptoms. The purpose of the current study was to assess the feasibility of 2 music-based interventions, 1 traditional and 1 novel, and explore the preliminary efficacy of these interventions as supportive care of cancer patients in outpatient treatment rooms. Supportive care options were: standard care (control), patient-selected singing with accompaniment (traditional), and patient-created chant using the Orff process (novel). Distress outcomes measured were: pain and fatigue using a 0-10 numerical rating scale, the State-Trait Anxiety Inventory (state form), and the Profile of Mood States 2 Short Form (for mood and fatigue). After obtaining consent, participants engaged in a single-session of 1 of 3 conditions lasting approximately 30 min. Feasibility measures indicated that the traditional and novel interventions were appropriate for the setting. Results indicated that although not always statistically significant, there were positive changes in pain, fatigue, anxiety, and mood for the 2 music-based conditions over standard care. Conclusions indicate the patient-selected condition was more impactful for pain, anxiety, and mood, while the patient-created chant using the Orff process was more impactful for fatigue. These conclusions might be clinically relevant for therapists pending cancer-related symptoms present during the assessment.