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Modulation of heart rate and heart rate variability during animal-assisted treatment of patients in a minimally conscious state: A randomized controlled crossover study.

BACKGROUND: Animal-assisted treatment (AATx) is a promising and increasingly used approach in neurorehabilitation, yet its psychophysiological effects remain largely unexplored. Patients in a minimally conscious state (MCS) show severely altered consciousness with minimal but definite behavioral signs of awareness. Because behavioral assessment in this population is limited, psychophysiological measures such as heart rate (HR) and heart rate variability (HRV) may offer valuable insights into autonomic regulation during therapy. AIM: The present study investigated whether AATx influences HR and HRV compared to treatment as usual (TAU). METHODS: A randomized controlled crossover design with repeated measures was conducted. HR and HRV data were recorded using an Empatica E4 wristband, and linear mixed-effects models were fitted for each outcome variable. The analytic sample included twenty-one patients with MCS who completed at least one of the four sessions. RESULTS: We found a significant decrease in mean HR (estimate = -12.75, p = .041) and a significant increase in the standard deviation of normal-to-normal intervals (SDNN) (estimate = 15.76, p = .020) during AATx compared to TAU from the pretreatment to the posttreatment phase, indicating enhanced parasympathetic activation and greater autonomic flexibility. Other HRV parameters revealed no significant effects of AATx, though trends were consistent with the hypotheses. CONCLUSIONS: These findings provide preliminary physiological evidence that AATx can modulate autonomic activity in MCS patients. Despite limitations related to sample size and recording quality, the results highlight the potential of AATx as an emotionally engaging intervention in early neurorehabilitation.

Humans

Family-Wise Error Rate Control in Clinical Trials With Overlapping Populations.

We consider clinical trials with multiple, overlapping patient populations that test multiple treatment policies specifically tailored to these populations. Such designs may lead to multiplicity issues, as false statements will affect several populations. For type I error control, often the family-wise error rate (FWER) is controlled, which is the probability to reject at least one true null hypothesis. If the joint distribution of the test statistics is known, the FWER level can be exhausted by determining critical values or adjusted-levels. The adjustment is typically done under the common ANOVA assumptions. However, the performed tests are then only valid under the rather strong assumption of homogeneous null effects, that is, when the null hypothesis applies to all subpopulations and their intersections. We show that under cancelling null effects, when heterogeneous effects cancel out in some or all subpopulations, this procedure does not provide FWER control. We also suggest different alternatives and compare them in terms of FWER control and their power.

Humans

Reliability of resting heart rate measurements in atrial fibrillation.

BACKGROUND: Heart rate (HR) control in atrial fibrillation (AF) is commonly guided by resting HR measurements, usually with 12&#x2011;lead ECG or in-office pulse palpation. OBJECTIVES: We aimed to assess the reliability of resting HR measurements in AF patients with long-term ambulatory ECG and activity monitoring. METHODS: We included patients who had recorded a full-disclosure ambulatory ECG with a mobile cardiac telemetry device equipped with an accelerometer (PocketECG, MEDICALgorithmics, Poland), with at least 95% AF. Resting HR samples (&#x2264;20 per individual/day) were collected as 10-s daytime (8&#xa0;am to 8&#xa0;pm) measurements after &#x2265;10&#xa0;min of rest. These samples were compared to each individual's mean daytime resting HR. RESULTS: In 832 patients (median age 77 (interquartile range (IQR) 69-83) years, 42% women) with a median registration duration of 13&#xa0;days (IQR 7-22), the population mean daytime resting HR was 85 (&#xb1;15) beats per minute (bpm). A single resting HR differed from the mean daytime resting HR by a mean of &#xb1;10.4% (IQR 3.6-14.4%). When the mean daytime resting HR was &#x2265;110&#xa0;bpm, 29% of resting HR samples were&#xa0;<&#xa0;110&#xa0;bpm, and when the mean daytime resting HR was 80-109&#xa0;bpm,11% of samples were&#xa0;&#x2265;&#xa0;110&#xa0;bpm. Resting HR measurement variability decreased to 5.3% (IQR 1.9-7.5%) when four resting HR samples were averaged. CONCLUSION: In patients with AF, a single resting HR measurement often differs substantially from the mean daytime resting HR. When a precise measurement is clinically relevant, repeated resting HR sampling or ambulatory monitoring can address this measurement imprecision.

Humans

Effect of atenolol versus ivabradine on heart rate variability in patients of schizophrenia with clozapine-induced tachycardia: a randomized controlled trial.

BACKGROUND: A third of schizophrenia cases are resistant to antipsychotics, where clozapine is the only FDA-approved medication. Clozapine use is often limited by intolerable adverse effects. Persistent tachycardia occurs in approximately 25-54% patients receiving clozapine. Heart rate variability (HRV) is a non-invasive, clinically relevant marker of autonomic nervous system functioning. Atenolol and Ivabradine are usually prescribed for clozapine-induced tachycardia (CIT), although evidence guiding their optimal use remains limited. AIM: This study aimed to compare the effects of atenolol versus ivabradine on HRV in patients with treatment-resistant schizophrenia (TRS) receiving clozapine. METHODS: This open-label randomised clinical trial, conducted at a tertiary-care center over 20 months, involved TRS patients on clozapine for more than three months and having persistent tachycardia. Twenty patients received atenolol 25mg once-daily, while twenty received ivabradine 5mg twice-daily for two months. The primary outcome was the change in the frequency domain of HRV, while the secondary outcomes were time-domains, central and peripheral blood pressure, pulse rate and treatment-emergent adverse events (TEAE). RESULTS: While both drugs significantly reduced pulse-rates (atenolol: -20.56&#xb1;13.00, p<0.001; ivabradine: -21.855&#xb1;12.873, p<0.001). Within-group analysis showed that, the atenolol group had significant improvements in high-frequency [HF] power (p=0.048) and LF/HF ratio (p=0.044), along with a non-significant trend towards increased total power (p=0.053); no significant within-group changes were observed in the ivabradine group. CONCLUSION: No significant between-group differences in HRV parameters were established between atenolol and ivabradine. Ivabradine could be a viable option in patients where atenolol is either contraindicated or not tolerated. Future larger multicentric studies are needed for greater generalisability. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06505668.

Humans

Retention strategies and participant retention rates among prospective longitudinal pregnancy cohorts: a systematic mapping review.

Prospective longitudinal pregnancy cohorts can answer questions about fetal and early life exposures and later health outcomes; however, there are challenges to retaining participants in longitudinal studies, particularly over life transitions like the birth of a child. Optimal methods for retaining participants in longitudinal research are unclear. A systematic mapping review was conducted to identify prospective cohort studies and randomized controlled trials that enrolled pregnant participants and their infants. Data on retention rates and 17 retention strategies was extracted. A random effects meta-analysis generated pooled annual retention rates inversely weighted to the number of baseline participants. Spearman rank coefficients were used to assess correlation between strategy use and retention. A random-effects meta-regression was used to determine if select retention strategies were associated with participant retention. We identified 130 studies, involving 472 022 pregnancies. A downward trend in pooled mean retention rates were observed. Studies utilized an average of 6.8 (SD 3.9) retention strategies. Statistically significant associations were not observed between strategy use and retention rates at follow-up (p&#x202f;>&#x202f;0.05). Prospective studies of pregnant people and their infants used multiple retention strategies. Participant retention rates declined over time, suggesting that additional factors may influence study participation in the postpartum period.

Humans

Music therapy in artificial insemination by husband: Effects on psychological distress and clinical pregnancy rate.

BACKGROUND: Infertility treatment can be psychologically burdensome. Evidence on music listening during artificial insemination by husband (AIH) remains limited. We evaluated whether a standardized periprocedural music intervention reduced psychological distress and explored its association with clinical pregnancy. METHODS: In this single-center, open-label randomized trial, 254 women undergoing AIH were allocated 1:1 to routine care or routine care plus two 30-minute music-listening sessions, immediately before and after AIH. The prespecified primary outcome was the continuous 21-item Depression Anxiety Stress Scales (DASS-21) score at follow-up; clinical pregnancy was secondary. DASS-21 was completed at baseline and at day 35 after AIH. Clinical pregnancy was assessed by ultrasonography at days 30 to 35. RESULTS: Continuous DASS-21 anxiety, depression, and stress scores did not differ between groups after adjustment for baseline scores (all P&#x2005;&#x2265;&#x2005;.868). Absolute postintervention differences were 0.01 point or less for anxiety and depression and 0.08 point for stress, indicating neither statistical nor clinically meaningful improvement. Clinical pregnancy occurred in 34/127 participants (26.77%) in the intervention group and 14/127 (11.02%) in the control group (exploratory secondary outcome; P&#x2005;=&#x2005;.001). CONCLUSION: The intervention did not improve the primary psychological outcome. The higher clinical pregnancy rate is hypothesis-generating because the trial was not powered for pregnancy, the proposed psychological mechanism was not demonstrated, and nonspecific attention and other unmeasured factors cannot be excluded. Replication using an attention-matched control, immediate state-anxiety and physiological measures, participant-preference assessment, and live-birth follow-up is required.

Humans

Linked-color imaging with computer-aided detection and the proximal adenoma miss rate: a randomized tandem trial.

BACKGROUND AND AIMS: Linked-color imaging (LCI) aids the detection and characterization of lesions. Computer-aided detection (CADe) systems have been introduced to improve lesion detection during colonoscopy. Although several studies have been reported regarding LCI, few have investigated the combination of LCI and CADe. This study aimed to evaluate the efficacy of LCI with CADe colonoscopy compared to conventional white-light colonoscopy. METHODS: A single-center, randomized tandem trial was conducted. Participants referred for first-time colonoscopy after fecal immunochemical test (FIT)-positive, asymptomatic screening, or surveillance colonoscopy were randomized (1:1) to undergo CADe-assisted colonoscopy of LCI or white-light imaging (WLI) in the right side of the colon. The primary outcome was adenoma miss rate (AMR) in the right side of the colon. Secondary outcomes included polyp miss rate (PMR), diminutive adenoma miss rate (dAMR), sessile serrated lesion miss rate (SSLMR), advanced adenoma miss rate, advanced neoplasia miss rate, flat-type lesion miss rate (FMR), and the differences in miss rates based on expertise. RESULTS: Among 232 randomized participants, 209 were analyzed (LCI/CADe: 102; WLI: 107). AMR (WLI: 39% vs LCI/CADe: 20%; P = .001), PMR (42% vs 18%; P < .001), and dAMR (42% vs 21%; P = .003) were significantly lower in the LCI/CADe arm, particularly among experts. SSLMR (46% vs 0%), advanced AMR (30% vs 0%), advanced neoplasia miss rate (25% vs 0%), and FMR (27% vs 5.6%) were lower in LCI/CADe, although without statistical significance. CONCLUSIONS: Compared to conventional colonoscopy, LCI with CADe colonoscopy resulted in a statistically significant decrease, especially in AMR. (UMIN 000050685).

Humans

A prospective crossover study comparing ICCS-recommended and Palmer-adjusted filling rates in children with spina bifida.

OBJECTIVE: This study aimed to investigate whether the maximal cystometric capacity (MCC) in children with spina bifida (SB) is indeed lower, as predicted by the Palmer formula, and to evaluate the impact of different bladder filling rates on urodynamic parameters. MATERIALS AND METHODS: This prospective, randomized, two-sequence crossover-controlled study included 70 children aged 3-18 years with spina bifida under regular follow-up. In Group 1, the first two bladder fillings were performed at the ICCS-recommended rate, and the third at 75% of that rate (Palmer formula). In Group 2, the sequence was reversed. Urodynamic parameters, including maximal cystometric capacity (MCC), bladder compliance, detrusor activity, filling pressures, and detrusor leak point pressure (DLPP), were analyzed across fillings. RESULTS: Cystometric bladder capacity was lower during fillings performed at the Palmer-adjusted rate compared with those at the ICCS-recommended rate. The proportion of reduced compliance significantly decreased in Group 1 (p = 0.046) but remained unchanged in Group 2. A significant positive correlation was observed between expected bladder capacity (EBC) and measured MCC in both groups (&#x3c1; &#x2248; 0.5-0.6). The highest correlation and agreement were found in Group 1 during the third filling at the Palmer rate (ICC = 0.606). No significant intra- or intergroup differences were observed in detrusor pressure, end-filling pressure, DLPP, or overactive bladder prevalence. CONCLUSION: Bladder filling rate was associated with differences in both cystometric capacity and bladder compliance in children with spina bifida. Fillings performed according to the Palmer formula (approximately 75% of the ICCS-recommended rate) were associated with capacities that more closely approximated age-expected values and with modest differences in bladder compliance. Conversely, faster filling rates did not produce similar benefits. These findings suggest that slower filling strategies may improve measurement consistency and agreement with expected bladder capacity estimates. However, the magnitude and direct clinical impact of these differences should be interpreted cautiously, particularly in light of the potential influence of sequence-related effects.

Humans

The combined and independent influence of food texture and a 'mindful eating' instruction on eating rate and food intake among Dutch primary schoolchildren.

Eating rate (ER), the amount of food consumed per unit of time, is a key determinant of food intake, with faster ER associated with larger meal size. Research in adults has shown that both sensory properties like texture, and instructions can influence ER and intake. However, their independent and combined effect on ER and intake in children remain poorly understood. This study examined the effects of food texture and a 'mindful eating' instruction on ER and food intake in children. Children (N&#xa0;=&#xa0;73), 38 boys, aged 4-12 years, participated in a 4-week cluster-randomized incomplete cross-over study conducted during regular school lunches. Using a 2&#xd7;3 factorial design, children were exposed to two levels of food texture (softer vs. harder whole-grain buns) and three types of instructions (none, control, 'mindful'). Linear mixed models with repeated measures were used, adjusting for sex and group. As the interaction between food-texture and type of instructions was non-significant, it was excluded from the final models. Results revealed a strong main effect of food texture on ER and food intake (all p&#xa0;<&#xa0;0.001), where compared with softer buns, harder buns were associated with a slower eating rate (&#x394;&#xa0;=&#xa0;-6.67&#xa0;g/min, SE&#xa0;=&#xa0;0.59) and reduced food intake (&#x394;&#xa0;=&#xa0;-70&#xa0;g, SE&#xa0;=&#xa0;8). In contrast, type of instruction had no significant effect on ER or intake (p&#xa0;=&#xa0;0.85). Our findings demonstrate that food texture exerts a dominant influence on children's eating rate and food intake, highlighting texture modification as a potential leverage point for influencing ER and intake in children.

Humans

Impact of oxytocin discontinuation on fetal heart rate and uterine contractility: A pre-specified ancillary analysis embedded within a randomized trial.

INTRODUCTION: Oxytocin is widely used to augment uterine contractions during labor. However, its use has been associated with fetal heart rate (FHR) abnormalities and neonatal morbidity, which may be reduced by discontinuing oxytocin during labor. We aimed to assess the impact of oxytocin discontinuation at the onset of the active phase of labor on FHR patterns and uterine contractility. MATERIAL AND METHODS: This study is a pre-specified ancillary analysis of the STOPOXY trial, a multicenter, randomized, open-label, controlled superiority trial conducted in 21 French maternity units between January 2020 and January 2022, which aimed to assess the impact of oxytocin discontinuation during active labor on neonatal morbidity. Participants who received oxytocin before 4&#x2009;cm dilation were randomly assigned (1:1) to either oxytocin discontinuation or oxytocin continuation. For the present analysis, we included women from the per-protocol discontinuation group of the parent trial. Inclusion was restricted to the six centers with electronic cardiotocography storage where valid cardiotocography recordings were available for at least 1&#x2009;h before and 1&#x2009;h after oxytocin discontinuation. Using a paired before-and-after design, FHR parameters (classified according to FIGO criteria) and uterine activity were compared during the 60&#x2009;min preceding versus the 60&#x2009;min following oxytocin discontinuation by independent obstetricians blinded to neonatal outcomes. Changes in FHR pattern were categorized as no change, improvement, or deterioration. RESULTS: 284 women fulfilled the eligibility criteria. Following oxytocin discontinuation, mean FHR increased (135 vs. 137.5&#x2009;bpm; p&#x2009;<&#x2009;0.002) and FHR variability significantly changed (p&#x2009;=&#x2009;0.010), with a lower rate of reduced variability (3.9% vs. 2.5%) and a higher rate of normal variability (48.2% vs. 53.3%). The proportion of tracings with decelerations significantly decreased (64.1% vs. 48.6%; p&#x2009;<&#x2009;0.001). Uterine activity decreased, with fewer uterine contractions (4.0 vs. 3.5 contractions per 10&#x2009;min; p&#x2009;<&#x2009;0.001). CONCLUSIONS: Among women receiving oxytocin during early labor, discontinuation at the onset of the active phase was associated with improved FHR patterns and reduced uterine activity, suggesting a lower fetal stress and tachysystole. Further studies are needed to assess whether these changes affect labor management or maternal experience.

Humans

Acute Haemodynamic and Perceptual Responses to Graded Intradialytic Exercise in Patients on Maintenance Haemodialysis: A Randomised Crossover Trial.

BACKGROUND: Acute responses to graded intradialytic exercise in people receiving haemodialysis remain incompletely characterised. OBJECTIVES: To examine acute haemodynamic and perceptual responses to graded intradialytic resistance exercise compared with a non-exercise control condition. DESIGN: Randomised crossover trial. PARTICIPANTS: Forty-eight clinically stable adults receiving maintenance haemodialysis. MEASUREMENTS: Participants completed seated control and graded lower-limb resistance exercise targeting Borg category-ratio 10 ratings of 3, 5 and 7. Systolic and diastolic blood pressure, mean arterial pressure, heart rate, peripheral oxygen saturation, rating of perceived exertion and acute fatigue were measured before, immediately after and 30&#x2009;min after each condition. RESULTS: Responses increased progressively with perceived intensity. Compared with control, higher perceived intensity increased systolic blood pressure by 14.9&#x2009;mmHg (95% confidence interval&#x2009;=&#x2009;12.7-17.0), diastolic blood pressure by 8.4&#x2009;mmHg (6.8-10.0), mean arterial pressure by 10.6&#x2009;mmHg (9.2-12.0) and heart rate by 15.5 beats per minute (12.9-18.1). Rating of perceived exertion increased by 6.7 points (95% confidence interval&#x2009;=&#x2009;6.3-7.1). Mean peripheral oxygen saturation remained between 95.1% and 97.5%, with no value below 90%. Recorded symptoms occurred in 13 out of 48 higher perceived-intensity sessions; no serious adverse events occurred. CONCLUSIONS: Graded, rating-guided intradialytic resistance exercise produced clear acute dose-response haemodynamic and perceptual changes. These findings support supervised individualisation of acute exercise dose but do not establish long-term safety or superiority of higher perceived-intensity training. TRIAL REGISTRATION: Pan African Clinical Trial Registry: PACTR202606476360900.

Humans

Effects of Hydrogen-Rich Water Supplementation on Exercise Performance, Autonomic Nervous System Recovery, and Blood Lactate Concentration During Repeated Sprint Exercise in Male University Athletes.

Hydrogen-rich water (HRW) supplementation has been proposed to exert anti-fatigue effects during exercise; however, its impact on exercise performance and autonomic nervous system (ANS) function during repeated sprinting remains unclear. The aim of this study was to examine the effects of acute pre-exercise HRW ingestion on repeated sprint performance, ANS regulation, and blood lactate concentration. This randomized, single-blind, placebo-controlled crossover study included 13 male university athletes (23.9 &#xb1; 2.0 years). Each participant completed two sessions of 7&#xd7;6-second all-out cycling sprints interspersed with 30-second recovery intervals, with a one-week washout period between sessions. Critical flicker fusion frequency, heart rate, heart rate variability (HRV), and blood lactate were assessed at baseline, during exercise, and at 0-5 min and 10 min post-exercise. Compared to the placebo trial, the HRW trial demonstrated significantly higher average power output (d = 0.61) and significantly lower total work decrement and fatigue index (d = 0.62; d = 0.64). Post-exercise HRV recovery was significantly accelerated in the HRW trial, including RMSSD (d = 0.62), LF/HF ratio (d = 0.82), SampEn (d = 0.79), and DFA&#x3b1;1 (d = 0.79). Blood lactate at 3 min post-exercise was approximately 1 mmol/L lower in the HRW trial (d = 0.64). These findings suggest that acute HRW ingestion attenuates the decline in power output, accelerates ANS recovery, and enhances lactate clearance following repeated sprint exercise.

Humans

Effects of a situational interest-based rotational fitness training program on positive affect in university students: A randomized controlled trial.

BACKGROUND: To evaluate whether a 12-week situational interest-based rotational fitness program improved positive emotional states in university students, to compare module-specific effects, and to examine whether the intervention moderated the heart rate-emotion association. METHODS: In this 2-arm randomized controlled trial, 560 freshmen from 10 Chinese universities were assigned to an experimental (n&#x2005;=&#x2005;280) or control group (n&#x2005;=&#x2005;280). The experimental group completed weekly 90-minute sessions covering strength, endurance, speed, and agility modules; controls received regular physical education. Positive emotional states were assessed using the positive well-being subscale of the Subjective Exercise Experiences Scale through ecological momentary assessment at 3 points per session, yielding over 14,000 observations. Linear mixed-effects models tested group, time, group&#x2005;&#xd7;&#x2005;time, heart rate, and heart rate&#x2005;&#xd7;&#x2005;group effects. Assessors and analysts were blinded. Ethical approval for the trial was granted by the Institutional Review Board of Capital University of Physical Education and Sports (2025A055). RESULTS: Improvement was greater in the experimental group than in controls (EMM change: 1.843 vs 0.505; difference&#x2005;=&#x2005;1.338, 95% confidence interval [CI]: 1.275-1.400, P&#x2005;<&#x2005;.001). At week 12, the raw between-group difference was 1.85 (d&#x2005;=&#x2005;2.23), and all group&#x2005;&#xd7;&#x2005;week interactions from weeks 2 to 12 were significant. Heart rate positively predicted emotional states in controls (B&#x2005;=&#x2005;0.005, 95% CI: 0.003-0.007), but this association was attenuated in the experimental group (interaction B&#x2005;=&#x2005;-0.008, 95% CI: -0.011 to -0.005). Strength and agility showed significant improvements, while endurance produced consistently higher emotional states across assessment points. Heart rate moderation was significant for strength and endurance, but not speed or agility. CONCLUSION: The rotational program improved positive emotional states more than regular physical education, although effects varied by module. Strength showed the most robust benefit. The program also weakened, but did not eliminate, the heart rate-emotion association during more demanding activities.

Humans

Effect of levothyroxine therapy on albuminuria and glomerular function in patients with type 2 diabetes and subclinical Hypothyroidism: a randomized controlled pilot trial.

AIMS: To evaluate the effect of levothyroxine therapy on renal outcomes in patients with type 2 diabetes mellitus (T2DM) and subclinical hypothyroidism (SCH) with background SGLT2 inhibitor therapy. METHODS: In this hypothesis generating open-label, randomized controlled pilot trial, adults with T2DM and SCH were assigned (1:1) to levothyroxine or no levothyroxine therapy and followed for 6&#xa0;months. Primary outcomes were changes in urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). RESULTS: Sixty participants were randomized (30 per group); 24 and 27 completed follow-up in the treatment and control groups respectively. UACR decreased with levothyroxine (-13.09&#xa0;mg/g) and increased in controls (31.84&#xa0;mg/g). The difference was significant in per-protocol (PP)(-44.93&#xa0;mg/g; 95% CI -77.6 to -12.26; p&#xa0;=&#xa0;0.008) but insignificant in intention to treat (ITT)(-35.61&#xa0;mg/g; 95% CI -77.31 to 6.08; p&#xa0;=&#xa0;0.092). eGFR changes were statistically insignificant in both ITT(4.65&#xa0;mL/min/1.73&#xa0;m2; 95% CI -8.3 to 17.6; p&#xa0;=&#xa0;0.472) and PP(7.35&#xa0;mL/min/1.73&#xa0;m2; 95% CI -1.68 to 16.37; p&#xa0;=&#xa0;0.108). Thyroid-stimulating hormone decreased significantly in treatment arm in comparison to control arm (p&#xa0;<&#xa0;0.001) in ITT and PP. No adverse event was reported. CONCLUSIONS: Levothyroxine treatment showed trend toward improving albuminuria and eGFR without reaching statistical significance, suggesting possible renoprotective effect warranting further studies. CLINICAL TRIAL REGISTRATION: This trial is registered with Clinical Trial Registry of India (CTRI/2025/06/089606).

Humans

Comparison of a Modified Regimen of Prophylactic Phenylephrine Boluses Versus Variable Rate Infusion During Elective Cesarean Delivery Under Spinal Anesthesia: A Noninferiority Randomized Double-Blind Study.

BACKGROUND: Prophylactic phenylephrine boluses have been found to be as effective as variable rate infusions during elective cesarean delivery but require a higher number of physician interventions to maintain blood pressure near baseline values. Therefore, there is a need to find a feasible regimen of bolus administration that is equally efficacious to the infusion regimen while at the same time requires a comparable number of physician interventions and is thus non-inferior to the infusion regimen. METHODS: Healthy pregnant women with term, uncomplicated, singleton pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomly divided into two groups. The Bolus group received a phenylephrine bolus 100 &#x3bc;g immediately after spinal anesthesia and then at every systolic blood pressure value <90% of the baseline. The infusion group received a prophylactic variable-rate infusion of phenylephrine beginning at 50 &#x3bc;g/min and titrated to maintain systolic blood pressure at 90-99% of baseline. The primary outcome was the number of physician interventions needed to maintain the target systolic blood pressure; the secondary outcomes included phenylephrine requirements, incidence of hypotension/hypertension/bradycardia, umbilical arterial and venous blood gas analysis, Apgar scores, and maternal complications. The primary outcome was analyzed in terms of non-inferiority using a non-inferiority margin of two interventions. RESULTS: Eighty patients were included in the study. The median (interquartile range [IQR]) number of physician interventions was 6 (5-8) in the infusion group and 3 (2-4) in the bolus group (P < .001). The difference of medians (95% confidence interval [CI]) between the two groups was -3 (-4 to -2). Phenylephrine requirements were higher in the infusion group (630 [426-765] &#x3bc;g) compared to the bolus group (300 [200-400] &#x3bc;g; P < .001). Blood pressure was higher at certain time points in the infusion group, but overall accuracy of blood pressure control was not different between the groups. Incidence of hypotension, hypertension, and bradycardia, neonatal outcomes, and maternal complications did not differ between the groups. CONCLUSIONS: The modified regimen of prophylactic boluses is non-inferior to variable rate prophylactic phenylephrine infusion in terms of physician interventions needed to maintain systolic blood pressure within the target range and maternal and neonatal outcomes.

Humans

Effects of a programmed reflexology therapy on sleep quality, insomnia, and fatigue among individuals with poor sleep quality: evidence for autonomic nervous system modulation.

Poor sleep quality is closely associated with autonomic dysregulation and increased risks of cardiovascular, metabolic, and mental disorders. Foot reflexology is a widely used complementary therapy; however, its physiological mechanisms and comparative efficacy remain insufficiently explored. This study aimed to compare the effects of manual reflexology treatment (MRT) and foot massage equipment (FEM) on autonomic nervous system function, sleep quality, insomnia severity, and fatigue in adults with poor sleep quality. Using a randomized crossover design, 32 participants with poor sleep quality received MRT and FEM interventions for 6 weeks each (once weekly, 30-40&#x202f;min/session). Heart rate (HR), blood pressure, and heart rate variability (HRV; time- and frequency-domain indices) were assessed at weeks 1 and 6 before and after each intervention. Subjective outcomes included the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Fatigue Assessment Scale (FAS). Following MRT, participants demonstrated significantly greater reductions in global PSQI scores and all PSQI components compared with FEM. MRT also resulted in larger improvements in insomnia severity and both mental and physical fatigue. In contrast, FEM primarily improved physical fatigue. Physiologically, MRT induced an immediate decrease in HR and significant increases in HRV time-domain indices (SDNN, RMSSD, pNN50), which were sustained after 6 weeks. Frequency-domain analysis further revealed reduced LF, increased HF, and a lower LF/HF ratio, indicating enhanced parasympathetic activity and cumulative autonomic modulation. In conclusion, programmed manual reflexology, delivered according to the TIDieR framework, is more effective than mechanical foot massage in improving autonomic balance, sleep quality, insomnia severity, and fatigue in individuals with poor sleep quality. These findings support MRT as a feasible and evidence-based non-pharmacological complementary intervention for sleep health promotion. TRIAL REGISTRATION: clinicaltrials.gov; NCT Number: NCT07402460; Registered 3 February 2026.

Adult

Exercise with motor cortex high-definition transcranial direct current stimulation enhances cardiovascular efficiency and lower-limb function in multiple sclerosis: A crossover, double-blind, and proof-of-principle study.

Combining exercise with high-definition transcranial direct current stimulation (HD-tDCS) could offer a strategy to help people with Multiple Sclerosis improve outcomes. In this crossover study, participants with MS (Expanded Disability Status Scale &#x2265;3.0, n&#x202f;=&#x202f;12) and controls (n&#x202f;=&#x202f;10) completed baseline testing, followed by three randomized experimental conditions: 1) exercise+active HD-tDCS; 2) exercise+sham HD-tDCS; and 3) HD-tDCS alone. Exercise performance metrics [heart rate, work rate, heart rate-to-work rate (HR/WR) ratio, and perceived exertion] were compared across the exercise conditions. Secondary outcomes included the Symbol Digit Modalities Test (SDMT), Timed 25-Foot Walk (T25F), Nine-Hole Peg Test (9HPT), and acute symptom ratings (fatigue and pain), assessed pre-, immediately post-, and 1h-Post. Cardiovascular efficiency (HR/WR ratio) significantly improved during exercise+HD-tDCS compared to exercise alone, particularly in older MS participants (p&#x202f;=&#x202f;0.010). SDMT declined immediately post HD-tDCS alone, 1h-post-exercise alone, and at both time points during exercise+active HD-tDCS (p&#x202f;<&#x202f;0.05). Both groups increased walking speed only post-exercise+active HD-tDCS, while no condition affected upper-limb function (p&#x202f;<&#x202f;0.05). These results are in line with the tDCS literature in the general population, suggesting that tDCS improves exercise performance and selectively improves engaged motor function. The trade-off between physical and cognitive outcomes underscores the importance of personalized neuromodulation strategies in neurorehabilitation to maximize therapeutic benefits while minimizing adverse effects, and warrants further large-scale, long-term investigations of this approach in MS.

Humans

Short-term effects of foot reflexology on pain, anxiety, and physiological responses in women with shoulder and neck pain: A randomized controlled trial.

OBJECTIVES: Shoulder and neck pain (SNP) is a common musculoskeletal complaint among women and is often accompanied by heightened anxiety. Foot reflexology (FR) is a complementary therapy proposed to promote relaxation and short-term psychophysiological regulation. This study examined the short-term effects of a single session of FR on pain, anxiety, and physiological responses in women with SNP. METHODS: A single-blind randomized controlled trial was conducted with 80 women aged 20-64&#xa0;years in southern Taiwan. Participants were randomly allocated to one of three groups: FR, exercise, or passive rest control. Each group received a single 50-min session. Pain intensity and anxiety were assessed using the Numeric Rating Scale (NRS) and the State-Trait Anxiety Inventory (STAI), respectively. Heart rate and blood pressure were recorded as physiological indicators. Outcomes were measured at baseline, immediately post-intervention, and at 24-h follow-up. RESULTS: Baseline pain, anxiety, and physiological measures did not significantly differ among groups. Immediately after the intervention, both the FR and exercise groups demonstrated greater reductions in pain intensity compared with the passive rest control (P&#xa0;<&#xa0;0.001 and P&#xa0;=&#xa0;0.018, respectively). The FR group additionally showed greater reductions in anxiety and heart rate compared with the passive rest group (P&#xa0;=&#xa0;0.005 and P&#xa0;=&#xa0;0.001, respectively). Pain reduction in the FR group remained significant at the 24-h follow-up (P&#xa0;=&#xa0;0.013), whereas anxiety reductions were not sustained. No significant between-group differences were observed for systolic blood pressure. CONCLUSION: A single session of FR was associated with immediate and short-term reductions in pain, anxiety, and heart rate among women with SNP. Foot reflexology may serve as a supportive, non-pharmacological approach for short-term modulation, although sustained effects require further investigation.

Humans