RESUMEN

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is a non-invasive modality that utilizes electrical currents to modulate pain in populations with acute and chronic pain. TENS has been demonstrated to produce hypoalgesic effects in postoperative pain, fibromyalgia, knee osteoarthritis, and healthy subjects. Transcutaneous auricular vagus nerve stimulation (TaVNS) is a non-invasive modality that modulates the vagus nerve by stimulating its auricular branches. The effects of the combination of TENS and TaVNS on producing an analgesic response have not been studied. Considering that TENS and TaVNS both stimulate similar analgesic pathways but through different means of activation, we can hypothesize that a combination of both methods can produce a more pronounced analgesic response. Therefore, the objective of this study is to assess the hypoalgesic effect of a combination of TENS and TaVNS in pain-free subjects. METHODS/DESIGN: The study will be a simple crossover design conducted at the University of Hartford. Subjects will be recruited from the University of Hartford population via oral communication, digital flyers, and posters on campus. Thirty participants will undergo two sessions in a crossover manner with one week in between. During one session, the participants will receive TENS with active TaVNS and the other session will be a placebo procedure (TENS with placebo TaVNS). The order of these sessions will be randomized. Importantly, the pressure pain threshold (PPT) and heat pain threshold (HPT) assessors will be blinded to the treatment category. For active TaVNS, a frequency of 25 Hz will be applied with a pulse duration of 200 µs. For placebo TaVNS, the intensity will be increased to a sensory level and then decreased to 0 mA. High-frequency TENS of 100 Hz will be applied in both sessions, with a pulse duration of 200 µsec, asymmetrical biphasic square waveform, and intensity of maximal tolerance without pain. TENS and TaVNS will be turned on for 30 min after a baseline measurement of outcomes. TENS and TaVNS will then be turned off, but the electrodes will remain on until completion of post-treatment assessment. Pressure pain threshold, heat pain threshold, blood pressure, oxygen saturation, and heart rate will be tested 4 times: Once pre-intervention, once during intervention, once immediately after the intervention, and once 15 min post-intervention. Statistical analysis of the data obtained will consider a significance level of p < 0.05. DISCUSSION: This study will provide evidence concerning the combined effects of TENS and TaVNS on pain threshold in pain-free participants. Based on the outcomes, a greater understanding of how TENS and TaVNS, when used in conjunction, can modulate pain pathways. TRIAL REGISTRATION: ClinicalTrials.gov NCT06361381. Registered on 09 April 2024.

Asunto(s)

RESUMEN

Background: Economic inequity systematically affects Black emerging adults (BEA), aged 18-24, and their healthy trajectory into adulthood. Guaranteed income (GI)-temporary, unconditional cash payments-is gaining traction as a policy solution to address the inequitable distribution of resources sewn by decades of structural racism and disinvestment. GI provides recipients with security, time, and support to enable their transition into adulthood and shows promise for improving mental and physical health outcomes. To date, few GI pilots have targeted emerging adults. The BEEM trial seeks to determine whether providing GI to BEA improves financial wellbeing, mental and physical health as a means to address health disparities. Methods/design: Using a randomized controlled crossover trial design, 300 low-income BEA from San Francisco and Oakland, California, are randomized to receive a $500/month GI either during the first 12-months of follow-up (Phase I) or during the second 12-months of a total of 24-months follow-up (Phase II). All participants are offered enrollment in optional peer discussion groups and financial mentoring to bolster financial capability. Primary intention-to-treat analyzes will evaluate the impact of GI at 12 months among Phase I GI recipients compared to waitlist arm participants using Generalized Estimating Equations (GEE). Primary outcomes include: (a) financial well-being (investing in education/training); (b) mental health status (depressive symptoms); and (c) unmet need for mental health and sexual and reproductive health services. Secondary analyzes will examine effects of optional financial capability components using GEE with causal inference methods to adjust for differences across sub-strata. We will also explore the degree to which GI impacts dissipate after payments end. Study outcomes will be collected via surveys every 3 months throughout the study. A nested longitudinal qualitative cohort of 36 participants will further clarify how GI impacts these outcomes. We also discuss how anti-racism praxis guided the intervention design, evaluation design, and implementation. Discussion: Findings will provide the first experimental evidence of whether targeted GI paired with complementary financial programming improves the financial well-being, mental health, and unmet health service needs of urban BEA. Results will contribute timely evidence for utilizing GI as a policy tool to reduce health disparities. Clinical trial registration: https://clinicaltrials.gov, identifier NCT05609188.

Asunto(s)

RESUMEN

OBJECTIVES: Overuse and misuse of antibiotics are major factors in the development of antibiotic resistance in primary care institutions of rural China. In this study, the effectiveness of a Health Information System-based, automatic, and confidential antibiotic feedback intervention was evaluated. METHODS: A randomized, cross-over, cluster-controlled trial was conducted in primary care institutions. All institutions were randomly divided into two groups and given either a three-month intervention followed by a three-month period without any intervention or vice versa. The intervention consisted of three feedback measures: a real-time pop-up warning message of inappropriate antibiotic prescriptions on the prescribing physician's computer screen, a 10-day antibiotic prescription summary, and distribution of educational manuals. The primary outcome was the 10-day inappropriate antibiotic prescription rate. RESULTS: There were no significant differences in inappropriate antibiotic prescription rates (69.1% vs. 72.0%) between two groups at baseline (P = 0.072). After three months (cross-over point), inappropriate antibiotic prescription rates decreased significantly faster in group A (12.3%, P < 0.001) compared to group B (4.4%, P < 0.001). At the end point, the inappropriate antibiotic prescription rates decreased in group B (15.1%, P < 0.001) while the rates increased in group A (7.2%, P < 0.001). The characteristics of physicians did not significantly affect the rate of antibiotic or inappropriate antibiotic prescription rates. CONCLUSION: A Health Information System-based, real-time pop-up warnings, a 10-day prescription summary, and the distribution of educational manuals, can effectively reduce the rates of antibiotic and inappropriate antibiotic prescriptions.

Asunto(s)

RESUMEN

BACKGROUND AND AIMS: Smoking fewer cigarettes per day may increase the chances of stopping smoking. Capping the number of cigarettes per pack is a promising policy option, but the causal impact of such a change is unknown. This study aimed to test the hypothesis that lowering cigarette pack sizes from 25 to 20 reduces the number of cigarettes smoked. DESIGN: This randomized controlled cross-over trial had two 14-day intervention periods with an intervening 7-day period of usual behaviour. Participants purchased their own cigarettes. They were instructed to smoke their usual brand from either one of two sizes of pack in each of two 14-day intervention periods: (a) 25 cigarettes and (b) 20 cigarettes. Participants were randomized to the order in which they smoked from the two pack sizes (a-b; b-a). SETTING: Canada. PARTICIPANTS: Participants were adult smokers who smoked from pack sizes of 25, recruited between July 2020 and June 2021. Of 252 randomized, 240 (95%) completed the study and 236 (94%) provided sufficient data for the primary analysis. MEASUREMENTS: Cigarettes smoked per participant per day. FINDINGS: Participants smoked fewer cigarettes per day from packs of 20 cigarettes [n = 234, mean = 15.7 standard deviation (SD) = 7.1] than from packs of 25 (n = 235, mean = 16.9, SD = 7.1). After adjusting for pre-specified covariates (baseline consumption and heaviness of smoking), modelling estimated that participants smoked 1.3 fewer cigarettes per day [95% confidence interval (CI) = -1.7 to -0.9], equivalent to 7.6% fewer (95% CI = -10.1 to -5.2%) from packs of 20 cigarettes. CONCLUSIONS: Smoking from packs of 20 compared with 25 cigarettes reduced the number of cigarettes smoked per day.

Asunto(s)

RESUMEN

BACKGROUND/AIM: Ultraviolet-B (UV-B) radiation initiates vitamin D synthesis in the skin, making sun exposure a major source of vitamin D. We aimed to determine whether office lighting containing ultra-low levels of UV-B radiation could modify the winter decline in vitamin D status in the UK, while being safe and well tolerated. PATIENTS AND METHODS: Twenty commercial office desk lamps were modified with the addition of UV-B LEDs. Ten hospital office administrative staff received UV-modified lamps with UV-on, and 10 staff received identical placebo lamps with UV switched off, in a double-blind, cross-over pilot study during the winter of 2021/22. Circulating 25-hydroxyvitamin D [25(OH)D] was measured every 4 weeks for 20 weeks: at baseline and during an 8-week trial period, 4-week washout, and a cross-over 8-week trial period. RESULTS: The linear regression combining the complete datasets for phase 1 and 2 of the trial showed that an 8-week UV light intervention significantly increased 25OHD by 7.13 nmol/l with a p-Value=0.02, compared to the placebo group. Similar results were confirmed by cross-over analyses using the datasets of those completing both phases of the trial both with and without using the inverse probability weighing method to handle dropouts. CONCLUSION: The UV-B-modified lighting was well-tolerated and safe with weekly doses of UV-B of 0.5 - 0.9 Standard Erythema Dose [SED=100 Jm-2 erythema weighted UV radiation] measured at chest level. This ultra-low dosing was effective in reducing the winter decline in vitamin D status.

Asunto(s)

RESUMEN

BACKGROUND: Patients with chronic idiopathic axonal polyneuropathy (CIAP) can have neuropathic pain that significantly impacts quality of life. Oral neuropathic pain medication often has insufficient pain relief and side effects. Topical phenytoin cream could circumvent these limitations. The primary objectives of this trial are to evaluate (1) efficacy in pain reduction and (2) safety of phenytoin cream in patients with painful CIAP. The main secondary objective is to explore the usefulness of a double-blind placebo-controlled response test (DOBRET) to identify responders to sustained pain relief with phenytoin cream. METHODS: This 6-week, enriched enrollment randomized double-blind, placebo-controlled triple cross-over trial compares phenytoin 20%, 10% and placebo cream in 48 participants with painful CIAP. Enriched enrollment is based on a positive DOBRET in 48 participants who experience within 30 minutes ≥2 points pain reduction on the 11-point numerical rating scale (NRS) in the phenytoin 10% cream applied area and ≥1 point difference in pain reduction on the NRS between phenytoin 10% and placebo cream applied area, in favour of the former. To explore whether DOBRET has predictive value for sustained pain relief, 24 DOBRET-negative participants will be included. An open-label extension phase is offered with phenytoin 20% cream for up to one year, to study long-term safety. The main inclusion criteria are a diagnosis of CIAP and symmetrical neuropathic pain with a mean weekly pain score of ≥4 and <10 on the NRS. The primary outcome is the mean difference between phenytoin 20% versus placebo cream in 7-day average pain intensity, as measured by the NRS, over week 2 in DOBRET positive participants. Key secondary outcomes include the mean difference in pain intensity between phenytoin 10% and phenytoin 20% cream, and between phenytoin 10% and placebo cream. Furthermore, differences between the 3 interventions will be evaluated on the Neuropathic Pain Symptom Inventory, EuroQol EQ5-5D-5L, and evaluation of adverse events. DISCUSSION: This study will provide evidence on the efficacy and safety of phenytoin cream in patients with painful CIAP and will give insight into the usefulness of DOBRET as a way of personalized medicine to identify responders to sustained pain relief with phenytoin cream. TRIAL REGISTRATION: ClinicalTrials.gov NCT04647877 . Registered on 1 December 2020.

Asunto(s)

RESUMEN

Intravenous cannulation is experientially traumatic to children. To minimize this, EMLA® is applied on the would-be-cannulated area before IV cannula insertion. However, the time to achieve its maximum efficacy may be affected due to incomplete cutaneous absorption and the duration of application. The latter may be a limiting factor in a busy healthcare facility. The usage of dissolvable maltose microneedles may circumvent this problem by introducing micropores that will facilitate EMLA® absorption. A randomized phase II cross-over trial will be conducted to compare the Visual Analogue Scale (VAS) pain scores and skin conductance algesimeter index between 4 different interventions (1 fingertip unit (FTU) of EMLA® with microneedle patch for 30 min before cannulation; 0.5 FTU of EMLA® with microneedle patch for 30 min; 1 FTU of EMLA® with microneedle for 15 min; 1 FTU of EMLA® with sham patch for 30 min). A total of 26 pediatric patients with thalassemia aged between 6 and 18 years old and requiring blood transfusion will be recruited in this trial. During the visits, the VAS scores and skin conductance algesimeter index at venous cannulation will be obtained using the VAS rulers and PainMonitor™ machine, respectively. The trial will commence in August 2021 and is anticipated to end by August 2022.

RESUMEN

Introduction: Compared to standard hemodialysis (S-HD), postdilution hemodiafiltration (HDF) has been associated with improved survival. Methods: To assess whether intradialytic hemodynamics may play a role in this respect, 40 chronic dialysis patients were cross-over randomized to S-HD (dialysate temperature [Td] 36.5 °C), cooled HD (C-HD; Td 35.5 °C), and HDF (low-volume [LV-HDF)] and high-volume [HV-HDF], both Td 36.5 °C, convection volume 15 liters, and at least 23 liters per session, respectively), each for 2 weeks. Blood pressure (BP) was measured every 15 minutes. The primary endpoint was the number of intradialytic hypotensive (IDH) episodes per session. IDH was defined as systolic BP (SBP) less than 90 mmHg for predialysis SBP less than 160 mmHg and less than 100 mmHg for predialysis SBP greater than or equal to 160 mmHg, independent of symptoms and interventions. A post hoc analysis on early-onset IDH was performed as well. Secondary endpoints included intradialytic courses of SBP, diastolic BP (DBP) and mean arterial pressure (MAP). Results: During S-HD, IDH occurred 0.68 episodes per session, which was 3.2 and 2.5 times higher than during C-HD (0.21 per session, P < 0.0005) and HV-HDF (0.27 per session, P < 0.0005), respectively. Whereas the latter 2 strategies showed similar frequencies, HV-HDF differed significantly from LV-HDF (P = 0.02). A comparable trend was observed for early-onset IDH: S-HD (0.32 per session), C-HD (0.07 per session, P < 0.0005) and HV-HDF (0.10 per session, P = 0.001). SBP, DBP, and MAP declined during S-HD (-6.8, -5.2, -5.2 mmHg per session; P = 0.004, P < 0.0005, P = 0.002 respectively), which was markedly different from C-HD (P < 0.01). Conclusion: Though C-HD and HV-HDF showed the lowest IDH frequency and the best intradialytic hemodynamic stability, all parameters were most disrupted in S-HD. Therefore, the survival benefit of HV-HDF over S-HD may be partly caused by a more beneficial intradialytic BP profile.

RESUMEN

In 1989, Peter Freeman published a paper that challenged a commonly accepted approach for analyzing cross-over trials, the so-called two-stage procedure. Freeman himself recommended using the Bayesian approach of Andy Grieve. The flaws Freeman exposed were serious and led many statisticians to conclude that the procedure was unacceptable. Unfortunately, more than 30 years later, one still encounters its use. This note explains, using a simple simulation, why the two-stage procedure is, indeed, as Freeman showed unacceptable and should not be used.

Asunto(s)

RESUMEN

INTRODUCTION: Dementia is a very common disorder that affects people over 65 years old all over the world. Apart from the cognitive decline, Behavioral and Psychological Symptoms of Dementia (BPSD) are a crucial matter in dementia, because they affect up to 90% of the patients during the course of their illness. Irritability has been found to be a common BPSD and one of the most distressing behaviors for the caregivers. The aim of the current study was to explore the efficacy of a combination of non-pharmacological interventions to treat irritability. METHODS: Sixty patients with different types and stages of dementia with irritability were participated in a cross-over RCT. Three non-pharmacological interventions were used; (a) Validation Therapy (VT)/Psycho-educational program, (b) Aromatherapy/massage and (c) Music Therapy (MT). The study assessed the three non-pharmacological interventions in order to find the most effective combination of the interventions. This study did not compare pharmacological and non-pharmacological treatments. The interventions lasted for five days. There was no drop-out rate. All patients were assessed at baseline using Mini Mental State of Examination (MMSE), Addenbrooke's Cognitive Examination Revised (ACE-R), Geriatric Depression Scale (GDS), Functional Rating Scale for symptoms in dementia (FRSSD), and Neuropsychiatric Inventory (NPI) (sub questions for irritability). Only NPI used for the assessment after each intervention. The analyses used categorical variables, Wilcoxon signed-rank test, Chi-square test and z value score. RESULTS: The most effective combination of non-pharmacological interventions was Aromatherapy/massage (p = 0.003)-VT plus Psycho-educational program (p = 0.014) plus MT (p = 0.018). The same combination was the most effective for the caregivers' burden, too (p = 0.026). CONCLUSIONS: The above combination of non-pharmacological interventions can reduce irritability in patients with dementia and caregivers' burden.

RESUMEN

The changing climate is one of the most important factors affecting public health. Older people are particularly threatened due to their less efficient immune systems. To evaluate the potential benefits of short-term indoor dehumidification on their circulation and cardiopulmonary health, we conducted a random, cross-over experiment with 36 healthy residents of an aged-care center in Chongqing, China in 2020. Vapor compression dehumidifiers were used over two 48-h periods. At the end of each 48 h, we immediately measured sixteen circulatory system biomarkers of inflammation, coagulation, and oxidative stress; lung function; blood pressure; and heart rate. Indoor temperature and relative humidity were monitored throughout the study period. Linear, mixed-effect models were used to associate health endpoints with indoor relative humidity. This intervention study showed that when the indoor relative humidity decreased from 75% to 45%: (1) the coagulation indicators, sCD40l, and PAI-1, decreased significantly, by 58.82% and 23.50%, respectively; (2) the inflammatory indicators, CRP, IL-6, and TNF-α decreased significantly, by 4.09%, 25.78%, and 10.60%, respectively; (3) PEF, FEV1 and FVC were increased significantly by 20.08%, 14.54%, and 15.75% respectively. To the best of our knowledge, this is the first study to examine the impact of short-term dehumidification on clinical and biochemical measures of cardiorespiratory health in humid areas, and our study suggests that RH in the dehumidified rooms (46.9 ± 8.7%) may be healthier than that in humid rooms (75.2 ± 7.9%). Humidity may be involved in the development of atherosclerosis by activating oxidative stress and mediating the secretion of inflammatory indicators. At the same time, platelet activation induced by oxidative stress stimulates thrombosis to increase cardiovascular risk in older people. Conclusion: This intervention study shows that in a Chinese city like Chongqing with serious indoor environmental humidity, indoor short-term dehumidification has obvious cardiopulmonary benefits for the healthy elderly.

Asunto(s)

RESUMEN

Current guidelines lack sufficient evidence to recommend a specific blood pressure lowering strategy to prevent cardiovascular disease after preeclampsia. We conducted a double-blind cross-over trial to identify the most potent antihypertensive strategy: renin-angiotensin-aldosterone system (RAAS) inhibition (losartan), sympathoinhibition (moxonidine), low sodium diet and placebo (n = 10). Due to low inclusion rate our study stopped prematurely. Initiatory analyses showed no significant effect of antihypertensive strategy on office blood pressure and 24-hour blood pressure. However, nocturnal dipping was significantly higher on RAAS inhibition and low sodium diet compared to placebo and sympathoinhibition. Optimal cardiovascular prevention after preeclampsia should be further explored.

Asunto(s)

RESUMEN

BACKGROUND: From a recent meta-analysis it appeared that online post-dilution hemodiafiltration (HDF), especially with a high convection volume (HV-HDF), is associated with superior overall and cardiovascular survival, if compared to standard hemodialysis (HD). The mechanism(s) behind this effect, however, is (are) still unclear. In this respect, a lower incidence of intradialytic hypotension (IDH), and hence less tissue injury, may play a role. To address these items, the HOLLANT study was designed. METHODS: HOLLANT is a Dutch multicentre randomized controlled cross-over trial. In total, 40 prevalent dialysis patients will be included and, after a run-in phase, exposed to standard HD, HD with cooled dialysate, low-volume HDF and high-volume HDF (Dialog iQ® machine) in a randomized fashion. The primary endpoint is an intradialytic nadir in systolic blood pressure (SBP) of < 90 and < 100 mmHg for patients with predialysis SBP < 159 and ≥ 160 mmHg, respectively. The main secondary outcomes are 1) intradialytic left ventricle (LV) chamber quantification and deformation, 2) intradialytic hemodynamic profile of SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP), 3) organ and tissue damage, such as the release of specific cellular components, and 4) patient reported symptoms and thermal perceptions during each modality. DISCUSSION: The current trial is primarily designed to test the hypothesis that a lower incidence of intradialytic hypotension contributes to the superior survival of (HV)-HDF. A secondary objective of this investigation is the question whether changes in the intradialytic blood pressure profile correlate with organ dysfunction and tissue damage, and/or patient discomfort. TRIAL REGISTRATION: Registered Report Identifier: NCT03249532 # ( ClinicalTrials.gov ). Date of registration: 2017/08/15.

Asunto(s)

RESUMEN

RATIONALE & OBJECTIVE: Patients with CKD are at elevated risk of metabolic acidosis due to impaired net acid excretion (NAE). Identifying early markers of acidosis may guide prevention in chronic kidney disease (CKD). This study compared NAE in participants with and without CKD, as well as the NAE, blood pressure (BP), and metabolomic response to bicarbonate supplementation. STUDY DESIGN: Randomized order, cross-over study with controlled feeding. SETTING & PARTICIPANTS: Participants consisted of 8 patients with CKD (estimated glomerular filtration rate 30-59mL/min/1.73m2 or 60-70mL/min/1.73m2 with albuminuria) and 6 patients without CKD. All participants had baseline serum bicarbonate concentrations between 20 and 28 mEq/L; they did not have diabetes mellitus and did not use alkali supplements at baseline. INTERVENTION: Participants were fed a fixed-acid-load diet with bicarbonate supplementation (7 days) and with sodium chloride control (7 days) in a randomized order, cross-over fashion. OUTCOMES: Urine NAE, 24-hour ambulatory BP, and 24-hour urine and plasma metabolomic profiles were measured after each period. RESULTS: During the control period, mean NAE was 28.3±10.2 mEq/d overall without differences across groups (P=0.5). Urine pH, ammonium, and citrate were significantly lower in CKD than in non-CKD (P<0.05 for each). Bicarbonate supplementation reduced NAE and urine ammonium in the CKD group, increased urine pH in both groups (but more in patients with CKD than in those without), and increased; urine citrate in the CKD group (P< 0.2 for interaction for each). Metabolomic analysis revealed several urine organic anions were increased with bicarbonate in CKD, including 3-indoleacetate, citrate/isocitrate, and glutarate. BP was not significantly changed. LIMITATIONS: Small sample size and short feeding duration. CONCLUSIONS: Compared to patients without CKD, those with CKD had lower acid excretion in the form of ammonium but also lower base excretion such as citrate and other organic anions, a potential compensation to preserve acid-base homeostasis. In CKD, acid excretion decreased further, but base excretion (eg, citrate) increased in response to alkali. Urine citrate should be evaluated as an early and responsive marker of impaired acid-base homeostasis. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases and the Duke O'Brien Center for Kidney Research. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT02427594.

Asunto(s)

RESUMEN

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a complex, multifaceted disorder that impairs functional status and quality of life. Current pharmacological treatments are limited. OBJECTIVES: This study investigated the effect of ivabradine (selective blocker of the Ifunny channel in the sinoatrial node) on heart rate, quality of life (QOL), and plasma norepinephrine (NE) levels in patients with hyperadrenergic POTS defined by plasma NE >600 pg/ml and abnormal tilt table test. METHODS: In total, 22 patients with hyperadrenergic POTS as the predominant subtype completed a randomized, double-blinded, placebo-controlled, crossover trial with ivabradine. Patients were randomized to start either ivabradine or placebo for 1 month, and then were crossed over to the other treatment for 1 month. Heart rate, QOL, and plasma NE levels were measured at baseline and at the end of each treatment month. RESULTS: The average age was 33.9 ± 11.7 years, 95.5% were women (n = 21), and 86.4% were White (n = 23). There was a significant reduction in heart rate between placebo and ivabradine (p < 0.001). Patients reported significant improvements in QOL with RAND 36-Item Health Survey 1.0 for physical functioning (p = 0.008) and social functioning (p = 0.021). There was a strong trend in reduction of NE levels upon standing with ivabradine (p = 0.056). Patients did not experience any significant side-effects, such as bradycardia or hypotension, with ivabradine. CONCLUSION: Ivabradine is safe and effective in significantly improving heart rate and QOL in patients with hyperadrenergic POTS as the predominant subtype.

Asunto(s)

Asunto(s)

RESUMEN

OBJECTIVES: To evaluate the feasibility of implementing a clinical trial protocol of the herbal seeds Ziziphus spinosa (ZS) for people with insomnia. DESIGN AND SETTING: A randomized, double-blind, placebo controlled, cross-over feasibility trial in Melbourne, Australia. INTERVENTIONS: After two-week run-in participants were randomized to either ZS (encapsulated granules; 2 g daily) or placebo for four weeks. After four-weeks wash-out, participants swapped to the other treatment for four weeks. MAIN OUTCOME MEASURES: Sleep quality assessed by the Insomnia Severity Index and Pittsburgh Sleep Quality Index (PSQI). Quality of life, mood, functional impairment and sleep parameters were also assessed. RESULTS: Twelve participants were randomized and completed both periods of cross-over (six in each sequence). Feasibility endpoints were acceptable. Improvements for sleep quality measured on the PSQI were statistically significant during the ZS treatment periods compared to placebo (t = -2.276, df = 10, 95 % CI -3.3 to -0.04, p = 0.046). There was no evidence of any significant carryover effects. However, there were period effects. Other outcomes showed no statistically significant difference between the treatments. Subjective sleep parameters measured on sleep diaries showed improvements after ZS in terms of total sleep time, sleep efficiency and sleep onset latency, but not after placebo. ZS was well tolerated with only minor adverse events. CONCLUSIONS: ZS is an acceptable and well-tolerated herbal candidate for the treatment of insomnia. The feasibility objectives of this study were achieved and ZS improved both subjective sleep quality and quantity compared to placebo. ZS should be explored in future clinical trials.

Asunto(s)

RESUMEN

Cardiovascular events occur most frequently in the early morning. Similarly, the release of reticulated platelets (RP) by megakaryocytes has a peak in the late night and early morning. Which aspirin regimen most effectively inhibits platelets during these critical hours is unknown. Hence, the primary objective of this trial was to assess platelet function and RP levels at 8.00 AM, in stable cardiovascular (CVD) patients, during three different aspirin regimens. In this open-label randomized cross-over study subjects were allocated to three sequential aspirin regimens: once-daily (OD) 80 mg morning; OD-evening, and twice-daily (BID) 40 mg. Platelet function was measured at 8.00 AM & 8.00 PM by serum Thromboxane B2 (sTxB2) levels, the Platelet Function Analyzer (PFA)-200® Closure Time (CT), Aspirin Reaction Units (ARU, VerifyNow®), and RP levels. In total, 22 patients were included. At 8.00 AM, sTxB2 levels were the lowest after OD-evening in comparison with OD-morning (p = <0.01), but not in comparison with BID. Furthermore, RP levels were similar at 8.00 AM, but statistically significantly reduced at 8.00 PM after OD-evening (p = .01) and BID (p = .02) in comparison with OD-morning. OD-evening aspirin intake results in higher levels of platelet inhibition during early morning hours and results in a reduction of RP levels in the evening. These findings may, if confirmed by larger studies, be relevant to large groups of patients taking aspirin to reduce cardiovascular risk.

Asunto(s)

RESUMEN

PURPOSE: This randomized cross-over group pilot trial assessed feasibility of recruiting survivors from a long-term follow-up clinic to an exercise group and measured whether outdoor or indoor exercise sessions better supported exercise motivation and behaviors in survivors of cancer. METHODS: Sixteen adolescent and young adult survivors of any cancer completed indoor and outdoor exercise sessions in this randomized cross-over pilot trial. Measures of physical activity, motivation, and fatigue were taken 2 weeks before and 2 weeks after indoor sessions and 2 weeks before and 2 weeks after outdoor sessions. Measures of physical activity and fatigue were also taken during each exercise session. RESULTS: Initial recruiting of 19 participants met recruiting goals. Survivors who attended the most sessions lived an average of 8.7 km closer to the clinic. Objectively measured physical activity intensity was 0.63 metabolic equivalents of a task (METs) per minute greater during outdoor exercise sessions as compared to indoor exercise sessions. There were no meaningful differences in long term, habitual physical activity behavior, motivation, or fatigue in the weeks following the outdoor exercise sessions as compared to the indoor exercise sessions. CONCLUSIONS: This study shows the feasibility of recruiting survivors from a long-term follow-up clinic to community-based exercise groups. Although this brief pilot intervention did not show significant effects on habitual physical activity behavior or motivation in adolescent and young adult survivors of cancer, the greater exercise intensity during the outdoor exercise sessions indicate that holding group exercise sessions for survivors outdoors may promote greater intensity during exercise.

Asunto(s)

RESUMEN

BACKGROUND: The introduction of modern sub-perception modalities has improved the efficacy of spinal cord stimulation (SCS) in refractory pain syndromes of the trunk and lower limbs. The objective of this study was to evaluate the effectiveness of low and high frequency SCS among patients with chronic pain. MATERIAL AND METHODS: A randomised, semi-double-blind, placebo controlled, four period (4 × 2 weeks) crossover trial was conducted from August 2018 to January 2020. Eighteen patients with SCS due to failed back surgery syndrome and/or complex regional pain syndrome were randomised to four treatment arms without washout periods: (1) low frequency (40-60 Hz), (2) 1 kHz, (3) clustered tonic, and (4) sham SCS (i.e., placebo). The primary outcome was pain scores measured by visual analogue scale (VAS) preoperatively and during subsequent treatment arms. RESULTS: Pain scores (VAS) reported during the preoperative period was M (SD) = 8.13 (0.99). There was a 50% reduction in pain reported in the low frequency tonic treatment group (M (SD) = 4.18 (1.76)), a 37% reduction in the 1 kHz treatment group (M (SD) = 5.17 (1.4)), a 34% reduction in the clustered tonic settings group (M (SD) = 5.27 (1.33)), and a 34% reduction in the sham stimulation group (M (SD) = 5.42 (1.22)). The reduction in pain from the preoperative period to the treatment period was significant in each treatment group (p < 0.001). Overall, these reductions were of comparable magnitude between treatments. However, the modality most preferred by patients was low frequency (55% or 10 patients). CONCLUSIONS: The pain-relieving effects of SCS reached significance and were comparable across all modes of stimulation including sham. Sub-perception stimulation was not superior to supra-perception. SCS was characterised by a high degree of placebo effect. No evidence of carryover effect was observed between subsequent treatments. Contemporary neuromodulation procedures should be tailored to the individual preferences of patients.