OBJECTIVE:To investigate the effects of animal-assisted treatment (AAT) on patients undergoing inpatient stroke rehabilitation. PATIENTS AND METHODS:Fifty hospitalized patients with a recent stroke were randomly assigned into either the control or experimental group. Patients in the control group received standard hospital-based stroke rehabilitation, including occupational, physical, and speech therapy. Patients in the experimental group participated in AAT-embedded stroke rehabilitation which involved the standard hospital-based treatment along with treatment sessions augmented with AAT. Patients' emotions, motivation, activity level, and treatment outcomes were assessed using questionnaires, physiological parameters (cardiac activity, salivary cortisol, salivary oxytocin, and tympanic membrane temperature), functional performances, and physical activity level. This study was conducted from February 21, 2023, through February 7, 2024. RESULTS:Results demonstrated that, compared with patients participating in the standard stroke rehabilitation protocol (control), experimental group patients scored significantly higher on the Pittsburgh Rehabilitation Participation Scale (P=.0038), had a significantly higher physical activity counts per minute (P=.023), and remained mobile for a significantly higher percentage of time (P=.006). These results indicated that experimental group patients were more engaged and physically more active during the AAT-embedded stroke rehabilitation. Also, compared with the control group, the experimental group had significantly increased differences of the root mean square of successive differences between consecutive normal heartbeats (P=.04) and the standard deviation of NN intervals between consecutive normal heartbeats (P=.032), indicating improvements in stress response in patients receiving the AAT-embedded sessions. Mood and other physiological responses were not statistically different between groups. CONCLUSION:AAT-embedded stroke rehabilitation involving a therapy dog has a positive effect on patients' activity level, motivation, and their engagement during inpatient stroke rehabilitation.

Objective: Battlefield acupuncture (BFA) has gained widespread clinical use for patients presenting to emergency departments (EDs). This systematic review of randomized controlled trials (RCTs) aims to assess the efficacy and safety of BFA in ED settings. Methods: A literature search was conducted in OVID and Scopus databases for RCTs involving BFA applied in ED settings. The risk of bias was evaluated using the Cochrane Collaboration risk of bias tool, while the methodological quality of RCTs was assessed using the Jadad score. Due to the heterogeneity of the included studies, a qualitative analysis was performed. Results: Seven studies involving 758 patients met the eligibility criteria. Among these, five studies evaluated traditional BFA in conjunction with standard analgesia care, while two studies assessed modified BFA alongside standard care. Most of the included studies were found to have a high risk of bias, leading to an overall classification of low quality according to the Jadad criteria. A descriptive analysis was performed due to heterogeneity in the interventions, observational timepoints, and outcomes reported in the included studies. Positive results were demonstrated in 71% of the studies. The most common conditions documented as the primary ED presentation included back pain, acute abdominal pain, lower extremity pain, neck pain, and acute sore throat. Notably, no severe adverse events were reported. Conclusion: BFA may offer a safe adjunct to standard care for pain management in ED settings. However, the limited methodological rigor and small number of existing RCTs reduce confidence in the current evidence. Well-designed, robust studies are needed to clarify their effectiveness and support stronger clinical recommendations.

BACKGROUND:Massage therapists (MTs) and licensed acupuncturists (LAcs) are increasingly embedded within interdisciplinary care teams in both inpatient and outpatient settings. While not traditionally viewed as diagnostic providers, their extended, hands-on interactions with patients enable them to observe subtle physical and behavioral changes that may support early clinical recognition of underlying health issues. OBJECTIVE:To present a case series in which MTs and LAcs identified abnormal clinical findings during routine care, prompting timely referrals that led to new or expedited diagnoses. METHODS:Seven patient cases were retrospectively reviewed in which observations made by MTs and LAcs-such as localized swelling, tissue changes, or unexplained symptoms-led to further medical evaluation and diagnosis. Each case illustrates the value of sustained patient contact, therapeutic rapport, and clear interdisciplinary communication, supported by structured documentation and referral protocols. RESULTS:In all seven cases, the MTs and LAcs played a pivotal role in accelerating clinical evaluation. Their observations contributed to the identification of conditions ranging from cellulitis, pneumonia, and melanoma to complex diagnoses such as multiple myeloma and arterial occlusion. Effective collaboration with nursing and physician teams through electronic medicine record documentation, internal messaging, and direct paging enabled appropriate and timely escalation of care CONCLUSION: MTs and LAcs, while practicing within their professional scope, can enhance diagnostic awareness through careful observation and patient-centered communication. When supported by institutional infrastructure and interdisciplinary trust, these providers serve as valuable contributors to early detection and care coordination. This case series underscores the importance of formally integrating integrative health practitioners into diagnostic workflows to improve patient outcomes and safety.

Background:Olfactory dysfunction (OD) is a common symptom in patients with coronavirus disease 2019 (COVID-19) with limited treatment options. Objective:This pilot study aimed to investigate an acupuncture protocol in patients with COVID-19 related OD. Methods:Thirty patients were randomized into 2 groups. The standard group was treated with budesonide nasal irrigation and olfactory training. The acupuncture group received ten sessions of acupuncture therapy in addition to the standard group treatment. Olfaction was assessed using the University of Pennsylvania Smell Identification Test, 10-point visual analog scale, and Sino-Nasal Outcome Test at baseline and after 3 months of treatment. Differences between study arms were compared using Fisher's exact and Wilcoxon rank sum tests. Results:Eighteen of the 30 (60%) enrolled patients completed the study, including 11 (73%) in the standard and 7 (47%) in the acupuncture group. Reasons for participant drop-out included cost of travel and time constraints. There were no acupuncture complications. Conclusions:Acupuncture as an adjunct therapy for COVID-19 related OD is well tolerated. Subsequent studies with larger sample sizes are needed to assess the effect of acupuncture on OD.

BACKGROUND:Robust data are essential for clinical and epidemiological research, yet in chronic spontaneous urticaria (CSU), certain patient groups, such as the elderly or comorbid patients, are often underrepresented. In clinical trials, strict inclusion and exclusion criteria frequently limit recruitment, making it difficult to achieve sufficient statistical power. Similarly, real-world observational studies may lack sufficient sample sizes for robust analysis. To address these limitations, we generated synthetic patient data that reflect these groups' clinical characteristics and variability. This approach enables more comprehensive analyses, facilitates hypothesis testing in otherwise inaccessible populations, and supports the generation of evidence where traditional data sources are insufficient. METHODS:A tree-based decision model was applied to generate synthetic data based on an existing set of real-world data (RWD) from the Chronic Urticaria Registry (CURE). Descriptive characteristics and association strength between relevant RWD variables and their synthetic counterparts were analyzed as indicators of replication accuracy, providing insight into how closely the synthetic data aligns with the RWD. Finally, we determined the minimum sample size required to generate high-quality synthetic data. RESULTS:The algorithm produced extensive synthetic data records, closely mirroring patient demographics and disease clinical characteristics. Smaller subgroups of the data were equally replicated and followed the same distribution as RWD. Known associations and correlations between disease-specific factors (disease control) and risk factors (age) yielded similar results, with no significant difference (p > 0.05). The lowest threshold at which synthetic data could be generated while maintaining high accuracy in RWD was identified to be 25%, enabling a fourfold increase in the synthetic population. CONCLUSION:Synthetic data could replicate RWD with reasonable accuracy for patients with CSU down to 25% of the original population size. This method has the potential to extend small patient subgroups in clinical and epidemiological research.

BACKGROUND:Chronic nonspecific low back pain (CNLBP) is a prevalent, disabling condition worldwide. Tuina, a traditional Chinese manual therapy, has shown potential benefits, but evidence remains limited. OBJECTIVE:This study evaluated the effectiveness and safety of Tuina therapy in managing CNLBP in a U.S. POPULATION: METHODS:A prospective, single-blind, randomized controlled trial was conducted at Mayo Clinic Rochester campus (February 2020-April 2024). 204 participants with CNLBP were randomized into 3 groups: Tuina (N = 68), physical therapy (N = 68), or a combination of both (N = 68). Each group received 6 treatments over 2 months. The primary outcome was pain intensity (VAS); secondary outcomes included disability (ODI), quality of life (SF-36), and adverse events. Additionally, participants completed a satisfaction survey at the end of the trial. Research Electronic Data Capture (REDCap) was used for survey data collection. Data was assessed by analysis of variance (ANOVA) for the multiple repeated measurements, Kruskal-Wallis tests, while Chi-square tests, and Bonferroni correction in SAS software. RESULTS:185 subjects completed the study. Significant decreases in VAS, ODI, and SF-36 Overall Physical scores were found from baseline, to post treatment and follow-up in all groups (P < .05), while there were no significant differences in VAS, ODI, or SF-36 outcomes between the Tuina group and the other 2 groups. There were 4 adverse events observed in the trial, 1 in the Physical therapy group and 3 in the Mixed group. Only 1 transient low back pain after Tuina therapy was observed in the Mixed group but did not require treatment. The high percentage of patients who received the Tuina program was extremely helpful (n = 94/126, 77.0%). The willingness to recommend was significantly higher for Tuina compared to physical therapy (Mixed group [N = 59/62, 95.2%], Tuina group [N = 57/64, 91.9%], and physical therapy group [N = 31/59, 59.6%] (P < .05). CONCLUSION:Tuina therapy showed comparable benefits to physical therapy and combined treatment of both in improving pain, function, and quality of life in patients with CNLBP. With high patient satisfaction and a favorable safety profile, Tuina appears to be a safe and acceptable non-invasive treatment option. Further studies are needed to validate these findings in the future.

BACKGROUND:Chronic hand eczema is a heterogeneous, fluctuating, and long-lasting disease affecting the hands and wrists that substantially affects quality of life. For severe chronic hand eczema, topical corticosteroids are often unsatisfactory and systemic treatment can be required. The aim of the head-to-head, phase 3 DELTA FORCE trial was to evaluate the efficacy and safety of topical delgocitinib cream versus oral alitretinoin, the only currently approved systemic drug for severe chronic hand eczema. METHODS:This randomised, assessor-masked, trial was conducted at 102 trial centres in Austria, Canada, France, Germany, Italy, Norway, Poland, Slovakia, Spain, and the UK. Adults (aged ≥18 years) with severe chronic hand eczema were randomly assigned (1:1) via an interactive response technology system to delgocitinib cream 20 mg/g (twice daily) or alitretinoin 30 mg (once daily) for up to 24 weeks. The primary endpoint was change in Hand Eczema Severity Index (HECSI) score from baseline to week 12. Efficacy of delgocitinib cream versus alitretinoin was assessed in all eligible randomly assigned patients who had available data at baseline, and safety was assessed in all patients exposed to trial treatment. The trial is registered with ClinicalTrials.gov (NCT05259722) and is complete. FINDINGS:Between June 15, 2022, and Dec 5, 2023, 513 (334 [65%] female and 179 [35%] male) patients were randomly assigned to receive delgocitinib cream (n=254) or alitretinoin (n=259). Ten patients were excluded after randomisation due to not meeting eligibility criteria, so the full analysis set consisted of 250 patients in the delgocitinib group and 253 in the alitretinoin group. One patient in the delgocitinib group and three in the alitretinoin group were excluded from the primary analysis as they had missing HECSI data at baseline. A significantly greater least squares mean change in HECSI score from baseline to week 12 was observed with delgocitinib cream (-67·6 [SE 3·4]; n=249) versus alitretinoin (-51·5 [3·4]; n=250; difference -16·1 [95% CI -23·3 to -8·9], p<0·0001). Fewer patients reported adverse events in the delgocitinib group (125 [49%] of 253 patients) than in the alitretinoin group (188 [76%] of 247). The most frequent adverse events were headache (ten [4%] in the delgocitinib group vs 80 [32%] in the alitretinoin group), nasopharyngitis (30 [12%] vs 34 [14%]), and nausea (one [<1%] vs 14 [6%]). INTERPRETATION:Delgocitinib cream showed superior efficacy and a more favourable safety profile versus oral alitretinoin over 24 weeks. These results support the benefit of delgocitinib cream in patients with severe chronic hand eczema. FUNDING:LEO Pharma.

Objective: This study evaluated the feasibility and satisfaction of using a wearable brain activity sensing device for stress reduction among patients experiencing Long COVID (LC). Patients and Methods: Patients with LC (N = 45) were invited to participate in an open-label pilot study. Participants were asked to use a brain-sensing electroencephalogram (S-EEG) wearable device (Muse-S™) daily for 90 days and followed for an additional 90 days (180 days total participation). Study enrollment began June 28, 2022, and ended July 28, 2023. Results: Patients were predominantly female (82%), white (96%), and with an average age of 47.6 (±12.5) years. At the end of treatment (90 days), cognition, sleep, self-efficacy, and quality-of-life quality of life improved ( P < .001 to P = .04). In addition, stress and anxiety were significantly reduced ( P < .001). These significant changes persisted by end-of-study (180 days). For stress ( P = .023) and anxiety ( P = .033), a change from the baseline during follow-up was significantly associated with the amount of S-EEG usage. The end-of-study satisfaction survey indicated that patients were very satisfied with the S-EEG device, and 97% planned to continue using it. Conclusion: Results suggest that the S-EEG device improved cognition in LC, which is one of the main severe symptoms we see in our LC clinic. In addition, it helped reduce stress and anxiety. These findings have important clinical implications for LC patients using S-EEG as an adjunct to concurrent LC clinical care which includes pharmacotherapies.

BACKGROUND:Hand eczema (HE) is a common and complex skin disease. A uniform set of core outcomes and related measures for use in clinical trials is lacking, making it difficult to compare results across HE studies. OBJECTIVE:To reach consensus on a set of core domains and subdomains that should be measured in future therapeutic HE trials. METHODS:In 2024, we conducted a two-round online Delphi (eDelphi) survey among international HE experts, including physicians, patients and their relatives, researchers and industry representatives. A domain/subdomain was included in the core set when ≥80% of participants rated is as 'critically important'; 50% agreement or less resulted in its exclusion. Results from 50% to 80% were deemed controversial and subject for further discussion. During a hybrid consensus meeting, the stakeholders reviewed, completed and, if necessary, revised the preliminary eDelphi consensus. RESULTS:In the first and second round of the eDelphi, 208 and 134 persons, respectively, participated. Forty participants from 18 countries attended the consensus meeting. Consensus was reached to include the core domains 'signs of HE' (with five core subdomains), 'symptoms of HE' (two subdomains), 'HE-related quality of life' (four subdomains) and 'HE control over time' (four subdomains). The subdomains 'desquamation/scaling' and 'emotional impact/mental health' remained controversial. Consensus was reached that the domains 'skin barrier function' and 'patient-reported treatment experience' and 28 subdomains should not be part of the core outcome set. CONCLUSIONS:To produce comparable and meaningful results, future trials evaluating the effectiveness of HE treatments should measure signs and symptoms of HE, HE-related quality of life and HE control over time as core outcome domains. The next step of the HE core outcome set initiative (HECOS) is to identify appropriate measurement instruments.

OBJECTIVE:To evaluate the safety and effectiveness of a novel nonsurgical integrative treatment, Mokhuri Chuna (MC), in patients with symptomatic degenerative lumbar spondylolisthesis (DLS). PATIENT AND METHODS:This multinational randomized controlled trial was conducted at Mokhuri Oriental Medicine Hospital, Seoul, South Korea, and Mayo Clinic, Rochester, Minnesota, from June 2017, to December 2022. Patients with symptomatic DLS were randomized 1:1 by study site to receive MC or standard care (SC) twice weekly for 5 weeks, followed by a 96-week posttreatment evaluation period. The primary endpoint was change in back pain (VAS). Secondary endpoints included changes in leg pain (VAS), physical function (ODI), health-related quality of life (EQ-5D), walking capacity, and safety. Patients were evaluated at baseline (Week 1), weekly during Week 2 through 6, and at 7, 18, 30, 54, and 102 weeks. Data analysis was performed in April 2024. RESULTS:In the randomized cohort of 115 patients (mean ± SD age, 59.97±10.96 years; 56 females [48.7%]), 58 patients were assigned to MC and 57 to SC. Baseline characteristics were comparable between groups. In the modified intention-to-treat analysis of 112 patients (56 per group), the MC group showed significant improvements in back pain (-10.27; 95% CI, -19.22 to -1.32; P=.02) and leg pain (-11.91; 95% CI, -21.15 to -2.68; P=.01) compared with the SC group. No significant differences were observed in ODI, EQ-5D, or walking capacity. No treatment-related serious adverse events were reported in either group. CONCLUSION:In patients with symptomatic DLS, MC was safe and more effective than SC for relieving back and leg pain, offering a promising nonsurgical treatment option. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT03107468.

BACKGROUND:Chronic spontaneous urticaria (CSU), a disease predominantly affecting females, has limited information available on its differences between females and males of varying ages. OBJECTIVES:To investigate sex differences in age groups regarding disease activity, comorbidities, quality of life (QoL) and treatment patterns in CSU patients. METHODS:We analysed Chronic Urticaria Registry (CURE) data, an international real-world registry for patients with chronic urticaria. Patients were recruited via an online platform using a standardized questionnaire. The data were analysed for demographics, age of onset, duration of urticaria, (Urticaria Activity Score [UAS], Urticaria Control Test [UCT], Chronic Urticaria Quality of Life Questionnaire [CU-Q2oL]), family history, systemic symptoms, aggravating factors, comorbidities, smoking and alcohol consumption, laboratory parameters, burden of disease, treatment distribution and response rates, compliance to treatment and adverse events. Comparisons were made among age groups <13, 13-17, 18-30, 31-50, 51-65 and >65 years. RESULTS:Across 4136 CSU patients (from 58 sites across 29 countries), 2994 (72.4%) were female. Statistically significant female predominance started at age 31 (<0.001). Compared with males, females showed higher rates of angioedema (59.6 vs. 51.7%; p < 0.001), systemic symptoms (34.6 vs. 25.4%; p < 0.001), sleep disturbance (38.9 vs. 32.5%; p < 0.001), QoL impairment (CU-Q2oL score 32 vs. 27.7; p < 0.001) and lower rates of urticaria control than males in all medication categories (p < 0.05 for all). Females had more concomitant diseases, including asthma, thyroid disease, obesity, autoimmune disease, gastrointestinal disease and depression (p < 0.05 for all). The disease was especially more burdensome and refractory in females aged 51-65 years than males, evidenced by more angioedema and systemic symptoms, worse QoL, lower UCT scores and more emergency visits (p < 0.05 for all). However, these differences were not prominent in the elderly females (>65 years). CONCLUSIONS:Compared with males, female CSU patients experience more burdensome disease, which gets worse in midlife. CLINICALTRIALS:gov (or equivalent) listing (if applicable None).

BACKGROUND:Itch is the most bothersome symptom in chronic spontaneous urticaria (CSU) and severely affects quality of life. OBJECTIVE:To analyze factors associated with itch severity, and how itch is associated with quality of life and health care use in CSU. METHODS:We retrieved patient data from the Chronic Urticaria Registry. Patients were categorized by self-reported itch severity (recall period of 7 days). We used ordinal logistic regressions as well as negative binomial and gamma regressions with log link to investigate possible associations. RESULTS:A total of 3,045 patients, 74.3% female, mean age 44.4 years, with no, mild, moderate, or intense itch (16.4%, 25.2%, 32.5%, and 25.9%, respectively) were included. A higher itch rating was associated with symptomatic dermographism (odds ratio [OR] = 1.25; P = .027), malaise (OR = 1.43; P < .001), depression (OR = 1.46; P = .008), and laboratory signs of inflammation (ie, elevated erythrocyte sedimentation rate (OR = 1.57; P = .031) and leukocyte counts (OR = 2.37; P = .004)). Intense itch was associated with worse quality of life (Chronic Urticaria Quality of Life Questionnaire; P < .001) and more patients visiting a general practitioner, allergologist or dermatologist, and the emergency room (P < .001). CONCLUSIONS:Higher itch levels are associated with inflammation and depression and are linked to worse quality of life and increased health care demand. Addressing itch is crucial to reducing the humanistic and societal burden in CSU.

Therapy dogs have been increasingly incorporated into a variety of medical treatment programs to improve patients' treatment outcomes and wellbeing. However, research investigating the stress level of therapy dogs in this setting is limited. This is the first randomized-controlled and prospective study that investigated the wellbeing of therapy dogs in an inpatient stroke rehabilitation program. In this study, 14 therapy dog-handler pairs were embedded in an inpatient stroke rehabilitation program to provide animal-assisted treatment (AAT). These therapy dog-handler pairs actively participated in stroke rehabilitation by walking with the patient, playing fetch with the patient, and being petted/brushed by the patient, amongst various other AAT activities. To measure canine stress responses during the rehabilitation sessions, salivary cortisol and oxytocin concentrations, heart rate and heart rate variability, tympanic membrane temperature, and a behavioral evaluation were recorded before and after interactions with the patient. The results demonstrated that therapy dogs had significantly decreased heart rate and increased heart rate variability after the AAT session. Right tympanic temperature significantly increased after the session, but there was no significant difference in terms of salivary cortisol or oxytocin levels, nor in stress-related behavioral evaluations after the AAT session. Taken together, the results suggest that incorporating AAT into an inpatient stroke rehabilitation program did not induce stress in the therapy dogs, and that the therapy dogs may have been more relaxed after the session.

Itch and pain are two of the most common and burdensome symptoms of Chronic Hand Eczema. Delgocitinib cream, a topical pan-Janus kinase inhibitor, was well tolerated and demonstrated significant improvement in primary and all secondary efficacy endpoints in DELTA-1 (NCT04871711) and DELTA-2 (NCT04872101). The objectives of this analysis were to assess the effect on itch and pain of twice-daily applications of delgocitinib cream 20 mg/g, including early onset of reductions, compared with cream vehicle in the treatment of adults with moderate to severe CHE in a pooled analysis of the pivotal Phase 3 DELTA-1 and DELTA-2 trials. This analysis includes pooled data from DELTA-1 and -2 (delgocitinib cream 20 mg/g [n=639]; cream vehicle [n=321]; twice-daily). The Hand Eczema Symptom eDiary (HESD) captured patient-reported worst severity of itch and pain over the past 24 hours on an 11-point numeric rating scale (0=no itch/pain to 10=severe itch/pain). Changes in itch and pain from baseline were assessed daily during Week (W)1 and weekly from W1-16. For itch, a significant least square (LS) mean reduction from baseline was detected 1 day after patients first applied delgocitinib 20 mg/g (0.75) versus the cream vehicle group (0.32, P<0.001). For pain, a significant LS mean reduction was detected 3 days after the first application of delgocitinib cream (0.98) versus cream vehicle (0.58, P<0.001). The LS mean itch and pain reductions continued for delgocitinib cream-treated patients up to W16 (P<0.001). A clinically meaningful ≥4-point reduction in itch was achieved by significantly more patients applying delgocitinib cream from W2 (14.2%) versus cream vehicle (6.3%, P<0.001) and onwards to W16 (delgocitinib cream: 47.2%; cream vehicle: 21.5%; P<0.001). Similar results for a ≥4-point reduction in pain were observed. Early onset of itch and pain reduction was observed within W1 for delgocitinib-treated patients, with reductions remaining significantly greater versus cream vehicle-treated patients from W1 to W16.