Sham Controlled Research Articles

Renal denervation - radiofrequency vs. ultrasound: insights from a mixed treatment comparison meta-analysis of randomized sham controlled trials.

Multiple randomized trials have shown that renal denervation (RDN) reduces blood pressure (BP) when compared with sham control but the antihypertensive efficacy of radiofrequency vs. ultrasound-based RDN is uncertain. We aimed to compare the outcomes of radiofrequency RDN (rRDN) and ultrasound RDN (uRDN), when compared with sham in patients with hypertension. PubMed, EMBASE, and clinicaltrials.gov databases were searched for randomized sham-controlled trials (RCTs) of rRDN or uRDN or for trials of rRDN vs. uRDN. Primary efficacy outcome was 24-h ambulatory SBP. A mixed treatment comparison meta-analysis was performed comparing the efficacy and safety against sham and against each other. Among 13 RCTs that enrolled 2285 hypertensive patients, rRDN reduced 24-h ambulatory SBP [(MD = 2.34 mmHg; 95% confidence interval (95% CI): 0.72-3.95], office SBP (MD = 5.04 mmHg; 95% CI: 2.68-7.40)], and office DBP (MD = 2.95 mmHg; 95% CI: 1.68-4.22) when compared with sham. Similarly, uRDN reduced 24-h ambulatory SBP (MD = 4.74 mmHg; 95% CI: 2.80-6.67), day-time ambulatory SBP (MD = 5.40 mmHg; 95% CI: 3.68-7.13), night-time ambulatory SBP (MD = 3.84 mmHg; 95% CI: 0.02-7.67), and office SBP (3.98 mmHg; 95% CI: 0.78-7.19) when compared with sham. There was significantly greater reduction in 24-h ambulatory SBP (MD = 2.40 mmHg; 95% CI: 0.09-4.71), day-time ambulatory SBP (MD = 4.09 mmHg; 95% CI: 1.61-6.56), and night-time ambulatory SBP (MD = 5.76 mmHg; 95% CI: 0.48-11.0) with uRDN when compared with rRDN. For primary efficacy outcome, uRDN ranked #1, followed by rRDN (#2), and sham (#3). In hypertensive patients, rRDN and uRDN significantly reduced 24-h ambulatory and office SBP when compared with sham control with significantly greater reduction in ambulatory BP with uRDN than with rRDN at 4 months (mean) of follow-up. A large-scale randomized head-to-head trial of rRDN or uRDN is warranted to evaluate if there are differences in efficacy.

Effect of radiofrequency ablation of genicular nerves on the isokinetic muscle strength of knee joint in patients with osteoarthritis knee: A randomized double-blind sham controlled clinical trial.

This randomised controlled trial evaluated the effect of radiofrequency ablation (RFA) of genicular nerve on muscle strength in osteoarthritis knee patients with chronic pain. Fifty-four patients with chronic knee osteoarthritis, experiencing significant pain (VNRS > 50) and moderate to severe disease (KL grade ≥ 2) were enrolled. Group 1 received RFA of genicular nerves of the affected knee while Group 2 received a sham procedure. The primary outcome was change in knee muscle strength evaluated using isokinetic peak torque(IPT) using IsoforceTM isokinetic dynamometer at 3 months. Secondary outcomes included changes in pain scores, function, perceived effect of the treatment and compliance to physiotherapy. At 3 months, significant difference was observed between IPT of flexor muscle at 60 and 180 degrees between the treatment and the Sham control (p-value = 0.01). No significant difference was observed in the extensor muscle strength. Within-group analysis revealed a significant increase in the IPT values for both extension and flexion at 60 and 180 degrees/sec evident across various time intervals. Group1 consistently reported lower VNRS scores at all time points. WOMAC scores of both groups were significantly different at all timepoints, with higher scores indicating reduced functionality in Group2. The GPE and compliance to physiotherapy were higher in Group1 patients at all times of follow up albeit decreasing trend in later periods. Application of RFA to genicular nerves in chronic OA knee patients resulted in better pain relief, improved functionality and increased muscle strength at extension and flexion at 3 months follow-up.

Evaluation of visual acuity in dry AMD patients after microcurrent electrical stimulation

BackgroundTo assess micro current to improve vision for dry age-related macular degeneration. Dry age-related macular degeneration is a major cause of blindness, disability, and severe erosion of quality of life, throughout the world. Beyond nutritional supplementation, there is no approved therapy.MethodsThis was a prospective randomized sham controlled clinical trial for participants with confirmed dry AMD with documented visual loss. Participants were randomized three to one, to receive transpalpebral external micro current electrical stimulation with the MacuMira device. The Treatment group received four treatments in the first two weeks, and two further treatments at weeks 14 and 26. Differences in BCVA and contrast sensitivity (CS) were estimated with mixed-effects repeated measures analysis of variance.ResultsChange of visual acuity with ETDRS assessment of number of letters read (NLR) and contrast sensitivity at week 4 and 30, compared to the first visit, between 43 treatment and 19 sham control participants. The Sham Control group had NLR of 24.2 (SD 7.1) at baseline, 24.2 (SD 7.2) at 4 weeks, and 22.1 (SD7.4) at 30 weeks. The Treatment group had NLR of 19.6 (SD 8.9) at baseline, 27.6 (SD 9.1) at 4 weeks, and 27.8 (SD 8.4) at 30 weeks. The change in NLR from baseline in the Treatment compared to the Sham control group was 7.7 (95% CI 5.7, 9.7, p < 0.001) at 4 weeks and 10.4 (95% CI 7.8, 13.1, p < 0.001) at 30 weeks. There were similar benefits in CS.ConclusionsThis pilot study of transpalpebral microcurrent demonstrated improved visual measures and is very encouraging as a potential treatment for dry AMD.Trial Registration: NCT02540148, ClinicalTrials.gov.

The association between ischemic preconditioning and exercise performance: a systematic review and meta-analysis

Purpose: The present work was performed to provide an updated and comprehensive systematic review and meta-analysis on the potential ergogenic effects associated with ischemic preconditioning (IPC). In this context, this systematic review and meta-analysis aimed to determine the magnitude of the potential ergogenic effect of IPC and the influence of descriptive factors that contribute to the variability of its potential ergogenic effect. We hypothesized that IPC would be associated with improved exercise performance, and putative factors would modulate this association. Methods: On October 17, 2022, a systematic search of three databases (PubMed, Scopus, and Web of Science) was performed. The electronic search yielded 2,876 unique records, of which 79 were included in analyses after abstract and full-text screening. Eligible study designs included within subjects cross-over, sham controlled study, with a randomized or counter balanced study design. Prespecified analyses aimed to determine whether the ergogenic effect of IPC is influenced by: 1) exercise parameters (type of exercise, fraction of inspired oxygen, and muscle group(s) involved in exercise) and 2) IPC parameters (dosage, duration, and timing before onset of exercise). Results: The meta-analysis model demonstrated that exercise performance was improved with IPC compared to the sham control (pooled standard paired difference (SPD), 0.156; 95% confidence interval (CI), 0.084 to 0.227; Z = 4.258; P &lt; 0.001; n = 105). Both remote IPC (pooled SPD, 0.219; 95% CI, 0.071 to 0.368; Z = 2.894; P = 0.004) and local IPC (pooled SPD, 0.159; 95% CI, 0.088 to 0.231; Z = 4.386; P &lt; 0.001) demonstrated ergogenic effects on performance. Subgroup analyses based on the fraction of inspired oxygen level revealed improved exercise performance in normoxic (pooled SPD, 0.169; 95% CI, 0.100 to 0.237; Z = 4.805; P &lt; 0.001) but not hypoxic (pooled SPD, 0.160; 95% CI, -0.029 to 0.349; Z = 1.659; P = 0.097) conditions. The most notable improvement in exercise performance following IPC was demonstrated during cycling (pooled SPD, 0.116; 95% CI, 0.023 to 0.209; Z = 2.454; P = 0.014), running (pooled SPD, 0.180; 95% CI, 0.056 to 0.303; Z = 2.847; P = 0.004), and leg press (pooled SPD, 0.421; 95% CI, 0.034 to 0.808; Z = 2.131; P = 0.033) performance tests. Conclusion: Overall, IPC demonstrated a clear ergogenic effect on exercise performance across various exercise modalities under normoxic environmental conditions. The enhanced exercise performance following IPC was most pronounced in aerobic tests of performance which predominantly recruited large muscle groups in the lower extremities: cycling, running, and leg press. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of auricular acupressure on postpartum blues: A randomized sham controlled trial

AimTo investigate the effect of auricular acupressure on the severity of postpartum blues. MethodsA randomized sham controlled trial was conducted from February to November 2021, with 74 participants who were randomly allocated into two groups of either routine care + auricular acupressure (n = 37), or routine care + sham control (n = 37). Vacaria seeds with special non-latex adhesives were used to perform auricular acupressure on seven ear acupoints. There were two intervention sessions with an interval of five days. In the sham group, special non-latex adhesives without vacaria seeds were attached in the same acupoints as the intervention group. Severity of postpartum blues, fatigue, maternal-infant attachment, and postpartum depression were assessed. ResultsAuricular acupressure was associated with significant effect in reduction of postpartum blues on 10th and 15th days after childbirth (SMD = −2.77 and −2.15 respectively), postpartum depression on the 21st day after childbirth (SMD = −0.74), and maternal fatigue on 10th, 15th and 21st days after childbirth (SMD = −2.07, −1.30 and −1.32, respectively). Also, maternal-infant attachment was increased significantly on the 21st day after childbirth (SMD = 1.95). ConclusionAuricular acupressure was effective in reducing postpartum blues and depression, reducing maternal fatigue, and increasing maternal-infant attachment in the short-term after childbirth. Trial registrationRegistered prospectively in Iranian Registry of Clinical Trials (ID: IRCT20180218038789N2).

Abstract 11420: A Subgroup Meta-Analysis Comparing the Renal Denervation Sham Controlled Randomized Trials Among Those With Resistant and Nonresistant Hypertension

Introduction: Renal denervation (RD) has been investigated as an invasive blood pressure (BP) lowering treatment for hypertension (HTN). Resistant HTN (RHTN) has been defined as uncontrolled BP despite use of 3 antihypertensive medications of different classes, including a diuretic, at maximum tolerated doses. The impact RD on RHTN remains under investigation. Methods: Ten sham-controlled trials testing RD were included in this trial-level analysis. A prespecified subgroup analysis was conducted to test whether efficacy of RD differed in patients with and without RHTN. The primary endpoints were change in 24-hour ambulatory systolic (SBP) and diastolic (DBP) using raw mean difference (RMD) between sham control and RD. Results: Ten studies (6 RHTN and 4 nonresistant HTN) were identified that included 1,544 participants (1,001 RHTN and 543 essential HTN) with cumulative mean age (±SD) of 56 (±11) years. Cochran risk of bias assessment showed 88% of the domains to be low risk of bias for the RHTN studies and 92% of the domains to be low risk of bias for the nonresistant HTN studies. The RMD for 24-hourr SBP between RD and sham-control was statistically significant for nonresistant HTN trials (-4.19 mmHg; 95% CI -6.07 to -2.30) but was not statistically significant for RHTN trials (-1.86 mmHg; 95% CI - 3.89 to 0.16). Despite the numerical difference in the subgroups, the interaction between subgroups failed to reach statistical significance (p = 0.10). The RMD for 24-hour DBP between RD and sham-control was statistically significant for nonresistant HTN trials (-2.60 mmHg; 95% CI -3.79 to -1.42) but was not statistically significant for RHTN trials (-0.67 mmHg; 95% CI -1.84 to 0.50). The interaction between subgroups was statistically significant (p = 0.02). Discussion: Our analysis indicates RD does not seem to be an efficacious intervention for patients with RHTN. This data may be beneficial for clinicians to consider when assessing patients with RHTN for RD.

Abstract 11428: A Comparison Between Endothelin Receptor Antagonists and Renal Denervation for Resistant Hypertension: A Systematic Review and Meta-Analysis of Sham and Placebo Controlled Trials

Introduction: Endothelin-1 causes vasoconstriction by activation of calcium flux in smooth muscle cells. Use of endothelin receptor antagonists (ERAs) has remained controversial. Renal denervation (RD) has also been investigated as a treatment option for resistant hypertension (RHTN). The efficacy of these two novel treatment strategies was compared. Methods: Placebo-controlled and sham-controlled randomized clinical trials testing ERA or RD as treatments for RHTN were selected. Prespecified subgroup analyses comparing the efficacy of ERA and RD were conducted for outcomes of 24-hour (hr) blood pressure (BP) and office BP. Results: Nine studies (3 ERA and 6 RD) were identified that included 1,708 participants (816 ERA and 892 RD). Cochran risk of bias assessment showed 72% of the domains to be low risk of bias for the ERA studies and 88% of the domains to be low risk of bias for the RD studies. The raw mean difference (RMD) between ERA and placebo control was statistically significant for 24-hr systolic (SBP) (-8.34 mmHg; 95% CI -11.51 to -5.81, 24-hr diastolic (DBP) (-6.77 mmHg; 95% CI -8.90 to -4.63), office SBP (-4.50 mmHg; 95% CI -6.92 to -2.08), and office DBP (-2.01 mmHg; 95% CI -2.13 to -1.88). The RMD between RD and sham control was not statistically significant for 24-hr SBP (-1.85 mmHg; 95% CI -3.88 to 0.18), 24-hr DBP (-0.67 mmHg; 95% CI -1.84 to 0.51), office SBP (-1.93 mmHg; 95% CI -5.17 to 1.31), and office DBP (-1.55 mmHg; 95% CI -3.43 to 0.33). The interaction between the treatment subgroups was statistically significant for 24-hr SBP and DBP, but not for office SBP and DBP. Discussion: ERAs had greater reduction in 24-hr and office BP compared to RD among patients with RHTN. Despite efficacy in reducing BP in RHTN, use of ERAs remains controversial given the cost and side effect profile. RD does not reduce BP among patients with RHTN. Medications are the optimal treatment for RHTN and sham controlled data showing efficacy is needed prior to widespread use and adoption of RD in RHTN.

Application of soft tissue laser in the management of recurrent apthous stomatitis

Apthous ulcers are relatively common pathology and are very painful, so in order to facilitate the relief in pain and healing of these ulcers application of LLT has been done in the present study. The purpose of this study was to assess the efficacy of Low Level Laser Therapy in the treatment of recurrent aphthous ulcers. 30 patients of both sexes and all age groups with two recurrent aphthous ulcers were included in the study. One ulcer in each subject was subjected to Low Level Laser Therapy as study group and one ulcer in each subject was considered for the Sham Control group. The Student’s t-test was used for statistical evaluation of the data. The study group (LLLT) showed a statistically significant reduction in pain as compared to the sham controlled group. Complete resolution of the ulcers in the study group was observed to be 4.7 ± 1.2 days and control group was 8.4 ± 2.6 days. On comparison with the sham group, the complete healing time for the study group (LLLT) was found to be highly significant, with a p value of &lt;0.001.

Abstract 9910: Effect of Renal Denervation in Resistant Hypertension: A Meta-Analysis of Randomized Controlled Trials

Introduction: Resistant hypertension is defined as blood pressure that remains ≥ 140/90 mm Hg despite adherence to at least three maximally tolerated doses of antihypertensive medications, including a diuretic. Catheter based renal denervation has been studied as one of the interventions for blood pressure control in such patients. Data comparing renal denervation versus sham procedure have shown disparate results. This meta-analysis summarizes the current evidence on the effect of sham controlled renal denervation on the treatment of resistant hypertension. Methods: Embase, Pubmed and Cochrane Central databases were searched from inception until May 30, 2021. RCTs comparing catheter based renal denervation with a sham control were included. Outcomes assessed were change in 24h ambulatory systolic blood pressure, change in 24h ambulatory diastolic blood pressure, change in office systolic blood pressure, and change in office diastolic blood pressure. Weighted mean differences (WMD) were calculated and pooled into a random effects model meta-analysis. Results: Seven studies with 1,264 participants were included in the analysis. Catheter based renal denervation was associated with significant decrease in ambulatory systolic blood pressure (WMD: -3.76; 95% CI: -2.44 to -5.09, p value &lt;.00001) and ambulatory diastolic blood pressure (WMD: -1.78; 95% CI: -0.84 to -2.72, p value=0.0002) compared with sham. The reduction in office systolic and office diastolic blood pressure was also significantly greater with catheter renal denervation than sham control (WMD: -5.95; 95% CI: -3.93 to -7.97; p value&lt;0.00001 and WMD: -3.54; 95% CI: -2.35 to -4.72; p value&lt;0.00001). Conclusions: There was significant benefit of renal denervation for resistant hypertension for all the studied outcomes. Based on this data, compliant patients with resistant hypertension who are maxed on lifestyle and pharmacological management may benefit from catheter based renal denervation.

Abstract 17044: Effect of Sham Controlled Renal Denervation in Uncontrolled Hypertension. A Systematic Review and Meta-Analysis

Introduction: Catheter-based ablation of renal artery has been studied as one of the interventions for blood pressure control in patients with uncontrolled hypertension. Previous randomized control trials (RCTs) comparing renal denervation versus sham procedure for the same have shown equivocal results. This meta-analysis summarizes the current evidence on the effect of sham-controlled renal denervation on blood pressure reduction. Methods: Pubmed, Embase and Cochrane Central databases were searched from inception until April 30, 2020. RCTs comparing catheter-based renal denervation with a sham control were included. Outcomes assessed were changes in ambulatory systolic blood pressure, change in ambulatory diastolic blood pressure, change in office systolic blood pressure and change in office diastolic blood pressure. Weighted mean differences (WMD) were calculated and pooled using inverse variance method into a random effect model meta-analysis. Results: Six studies with 1118 participants were included in the analysis. Catheter based renal denervation was associated with significant decrease in ambulatory systolic blood pressure (WMD: -3.71; 95% CI: -2.32 to -5.11, p value &lt;.00001) and ambulatory systolic blood pressure (WMD: -1.71; 95% CI: -0.59 to -2.82, p value=0.003) compared with sham. The reduction in office systolic and office diastolic blood pressure was also significantly greater with catheter renal denervation than sham control (WMD: -5.82; 95% CI: -3.67 to -7.92; p value&lt;0.00001 and WMD: -3.51; 95% CI: -2.29 to -4.73; p value&lt;0.00001 respectively) Conclusion: This meta-analysis showed significant benefit of catheter-based renal denervation for uncontrolled hypertension for all the studied outcomes. Based on this data patients with uncontrolled hypertension, on lifestyle and pharmacological management may benefit from catheter-based renal denervation

Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Depression in Adolescence: A Systematic Review

BackgroundThere is evidence that repetitive transcranial magnetic stimulation (rTMS) is effective for treating adult depression. However, it remains unclear whether rTMS is an effective treatment for adolescent depression. This systematic review examines the existing literature on the effectiveness and acceptability of rTMS in the treatment of adolescent depression. MethodsAfter protocol registration (PROSPERO), we searched PubMed, Embase, PsycINFO, WoS and CENTRAL databases and the grey literature. We included studies that used rTMS in adolescents aged 12–25 years old who had a clinical diagnosis of depression. Study quality was assessed using the Newcastle-Ottawa Scale. ResultsFourteen studies were identified, which included 8 open-trial studies (N = 142 participants) and six studies which performed further post-hoc/follow-up analyses on these open-trial datasets. All studies suffered from multiple biases but reported that rTMS treatment reduced depression scores in adolescents. A single study on theta burst stimulation also found a positive effect. No study to date includes a sham control. Reported side effects of rTMS included scalp pain, headache and dizziness. LimitationsStudy methodologies precluded a meta-analysis. ConclusionsThe current literature signals that rTMS could reduce adolescent depressive symptoms. However, sham controlled randomized trials are needed. These findings suggest that rTMS may be a promising treatment option for adolescents with depression.

The effect of ear acupressure (auriculotherapy) on sexual function of lactating women: protocol of a randomized sham controlled trial

BackgroundLactation has a negative effect on female sexual function. Hormonal changes during lactation cause changes which might lead to dyspareunia, lack of libido, and anorgasmia. There are various pharmacological and non-pharmacological approaches to treat sexual dysfunction. While pharmacological treatment has multiple unwanted side effects, non-pharmacological therapies such as complementary medicine are a potential safer alternative. The aim of this study is to evaluate the effect of ear acupressure on sexual function of lactating women.Methods/designThis is a randomized clinical trial with a parallel sham control group. In this study, 76 lactating women between 6 months and 1 year after childbirth were referred to health care centers in Qazvin City and would be invited to participate. Participants will be divided into intervention (n = 38) and control (n = 38) groups using simple block randomization. Both intervention and sham control groups will be visited over 10 sessions within a 4-day interval. At each visit, the adhesives containing Vaccaria seed will be adhered for the intervention group, while non-latex-based adhesives with no Vaccaria seeds will be placed on the same ear acupoints for the sham control group. Selected ear acupoints include genitalia (two ear points), pelvic point, master shoulder, and posterior pituitary gland. The women will be asked to hold the seeds on their ears for 3 days and press each ear point three times a day for 20 s. After 3 days, they will be asked to remove the seeds from their ears and rest for 1 day. Sexual function as primary outcome in both groups will be assessed using the Female Sexual Function Index before and immediately after 1 and 2 months after the intervention. Also, Sexual Quality of Life as secondary outcome will be assessed using Sexual Quality of Life-Female (SQOL-F) before and 2 months after intervention. Data will be analyzed using repeated measure ANOVA at the significant level of 0.05.DiscussionThis study is expected to support the impact of ear channel ear acupressure on sexual function in lactating women.Trial registrationIranian Clinical Trial Registration Center IRCT20190626044028N1. Registered on 16 August 2019

Randomized controlled three-arm study of NADA acupuncture for alcohol addiction

IntroductionAlcohol addiction compromises cardiovascular health, possibly due to impaired control of the heart and vasculature by the autonomic nervous system. We aimed to assess the effects of National Acupuncture Detoxification Association (NADA) acupuncture on cardiovascular autonomic functions, psychiatric comorbidities and abstinence in patients addicted to alcohol. Material and methodsA randomized sham controlled three-arm study was undertaken in 72 patients (nine females, aged 43.7 ± 9.2 years, mean ± SD) undergoing in-patient rehabilitation for alcohol addiction. Patients were randomly allocated (1:1:1) to receive twenty 30-minute NADA or sham acupuncture sessions within six weeks or no intervention. They were evaluated for craving, depression, anxiety and autonomic control of the heart (heart rate variability, HRV), vasculature (laser Doppler flowmetry) and sweat glands (sympathetic skin response). Testing was performed at baseline, immediately post intervention (sham intervention or control period, respectively) and another four weeks later. Abstinence was assessed one year after study completion. ResultsPatients in the NADA arm displayed increased HRV immediately post-intervention compared to baseline (SDNN: 72.8 ms ± 34.2 ms vs. 57.9 ms ± 31.2 ms, p = 0.001). This increase was sustained four weeks later (66.2 ms ± 32.4 ms, p = 0.015). HRV remained unaltered following sham or no acupuncture (p = n.s.). Autonomic function of vasculature and sweat glands, psychiatric comorbidities and one-year abstinence did not differ between study arms. ConclusionsNADA acupuncture may improve autonomic cardiac function. However, this improvement appears not to translate into alleviation of psychiatric comorbidities or sustained abstinence.

Do Secondary Progressive Multiple Sclerosis patients benefit from Computer- based cognitive neurorehabilitation? A randomized sham controlled trial

Cognitive impairment is common in multiple sclerosis (MS), but deficits tend to be more pronounced in progressive MS, negatively impacting daily functional capacity. Despite this, most cognitive rehabilitation (CR) interventions to date have focused on relapsing-remitting MS (RRMS). Moreover, information on the efficacy of CR in progressive MS is limited and controversial. The present study investigated the efficacy of a home based, computer assisted cognitive rehabilitation (HBCACR) intervention (RehaComTM software) exclusively in a Secondary Progressive Multiple Sclerosis (SPMS) sample. This was a randomized, multi site, sham controlled trial. Thirty six (36) individuals with SPMS, naïve to the RehaCom software, with cognitive deficits were randomized to the treatment (IG; n= 19) or control group condition (CG; n=17). Treatment with the RehaCom modules consisted of 24 domain and task specific, 45 minute session's over an 8-week period, three sessions per week, applied by each patient at home. The CG completed non specific computer based activities at home with the same frequency and duration. Primary cognitive outcome measures included the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery, and secondary outcome measures for depression (BDI-FS), fatigue (MFIS), and quality of life (EuroQol EQ-5D) visual analogue scale (VAS). The two groups were well matched on demographic and clinical characteristics, cognitive reserve and severity of cognitive deficits at baseline assessment. At post treatment assessment the IG group showed significant improvements with large effect sizes; in verbal learning [z=-4.759, p <.0005, g=2.898], visuospatial memory [z=-3.940, p <.0005, g=1.699] and information processing speed [z= -4.792, p <.0005, g=2.980], compared with the sham control group. We also found significant between group differences on physical [z=-3.308, p=.001, g= -.604], cognitive [z=-4.011, p <.0005, g=-1.654], psychosocial [z= 3.308, p=.010, g=-.940], and general fatigue impact [z= -2.623, p=.008, g=-.519], depression severity [z=-2.730, p=.006, g=-.519], and quality of life [z= -4.239, p <.0005, g=-1.885] in favor of the treated group. These data provide the first evidence supporting the efficacy of computer based restorative cognitive rehabilitation applied at home exclusively in SPMS patients, suggesting that adaptive neuroplasticity may occur after functional cognitive training in progressive MS. Improved cognitive functioning in combination with mood augmentation appear to have ameliorated fatigue, which impacted daily functioning activity and culminated in improved health related quality of life.

Renal Denervation for Resistant Hypertension in the contemporary era: A Systematic Review and Meta-analysis

Renal denervation (RDN) is a catheter-based ablation procedure designed to treat resistant hypertension (RH). The objective of our study is to determine the effect of RDN on blood pressure and renal function in patients with RH in comparison to medical therapy alone. We performed an extensive literature search for randomized control trials (RCT) reporting office and 24 hr. blood pressure changes and estimated glomerular filtration rate (eGFR) at baseline and 6 months. We calculated a weighted standardized mean difference of blood pressure and renal outcomes between RDN and control groups using random effects models. Our search yielded 608 studies of which we included 15 studies for the final analysis. A total of 857 patients were treated with RDN and 616 patients treated with medical therapy ± sham procedure. Only 5 studies were double-blinded RCT with sham control. The adjusted standardized mean difference in the change in office based systolic and diastolic pressures (p = 0.18; p = 0.14); 24 hr. systolic and diastolic pressures (p = 0.20; p = 0.18); and eGFR (p = 0.20) from baseline to 6 months is statistically insignificant with significant heterogeneity. Subgroup analysis showed that among sham controlled trials, 24 hr. systolic blood pressure showed a modest but statistically significant benefit favoring renal denervation in patients with RH. Our meta-analysis of 15 RCTs showed no significant benefit of RDN on blood pressure control in patients with resistant hypertension. Subgroup analysis of sham control studies showed a modest benefit in 24 hr. systolic blood pressure at 6 months with RDN.

Nuclear Magnetic Coupled Fast Radio Burst Induced Upregulation of Hsp70 in Regeneration of Human Chondrocytes - A Sham Control Study

Manipulating the cell’s inherent vulnerabilities to induce intrinsic changes and re-engineer diseased tissues to drive regeneration is a domain creating significant therapeutic impact through translational medicine. Articular cartilage injuries are recurrently experienced due to trauma, mechanical stress and age-related deterioration. Prevailing mend methods have failed to yield reliable or lasting results. Lack of suitable models that mimic the cellular and extra cellular matrix properties of hyaline cartilage has been one of the reasons for this deficiency. We investigated and observed, joint tissue obtained during total knee replacement surgeries from 7 discrete patients presenting with osteoarthritis and the commonly associated symptoms of inflammation and pain. We used modulated “Nuclear Magnetic Coupled Fast Radio Burst or simply Fast Radio Bursts”, a new modality that seems to trigger the cellular signaling required by the articular cartilage tissue, to mend and regenerate by upregulation of Heat Shock Protein 70. Fast Radio Bursts are high energy, short electromagnetic bursts, in which both electric and magnetic components of the electromagnetic signals are “circularly” polarized. Fast Radio Bursts are produced when a radio signal is traveling through a powerful instantaneous magnetic field on its path to the target. In this Sham controlled study, up-regulation of Hsp 70 protein, to establish its role in an in vitro model was designed to expose 2-Dimensional and 3-Dimensional cultures to Fast Radio Bursts, and compared to a Sham Control, under identical conditions but without exposing Sham Control culture to fast radio bursts. The 2D and 3D reconstructed cartilage tissues were then assessed in both groups. Experiments were conducted to characterize the 2D and 3D cultures to confirm total collagen, fibrillar collagen and proteoglycans, additionally; immunofluorescence and cell viability assay was performed to identify specific bio markers like Collagen 1, Collagen II, Aggrecan, Cell surface Adhesion factor, Hsp70 and cell viability. It could be established in this study that 2D cultures grown in newly defined media and exposed to Fast Radio Burst signals, when compared to 2D cultures grown as Sham culture showed more chondrocyte specific markers and viable matrix properties. In 3D cultures grown similarly also showed better deep layer properties compared to the 3D cultures grown in sham culture. Thus modulated Fast Radio Bursts exposure could play a significant role in specific protein up/down regulation in tissue regeneration.

Efficacy of adding acupuncture to Methylphenidate in children and adolescents with attention deficit hyperactivity disorder: A randomized clinical trial

IntroductionAttention deficit hyperactivity disorder (ADHD) is the most prevalent finding in children with behavioral issues. It has been shown that acupuncture, as a complementary medicine, may have some beneficial effects in ADHD treatment; however, the available evidence of its effectiveness are inadequate. This study aimed to investigate the effectiveness of acupuncture treatment in patients with ADHD. MethodsThis double blind randomized sham controlled trial was conducted on patients with confirmed ADHD referred to Ibn-e-Sina Psychiatric Hospital, Mashhad, Iran between January 2017 and June 2017. Patients were randomly allocated into either an acupuncture (experimental group) or a sham acupuncture (control group). All patients received a standard treatment of 0.3–1 mg/kg of Methylphenidate (Ritalin) in 2 or 3 divided doses. Within 4 weeks the intervention group received acupuncture treatment 3 times a week. Sham acupuncture was used for the control group within the same duration as acupuncture group. The treatment outcomes were measured using home version of ADHD-rating scale (RS) and the Continuous Performance Test after 3 weeks. Independent-samples t-test, Pearson Chi-square test, and Paired-samples t-test were used for data analysis with SPSS version 16.0. ResultsThis study was conducted on 59 patients (52 males) with a mean age of 10.64 ± 2.46 years in two groups of experiment (n = 31) and control (n = 28). ADHD-RS total score was significantly more decreased in acupuncture group after 3 weeks (-6.29 ± 7.1 vs. -1.96 ± 6.7; p = 0.007). Also, the hyperactivity and impulsivity was significantly more decreased in the acupuncture group compared to the sham control group (-3.29 ± 3.7 vs. -0.45 ± 4.1; p = 0.005). Furthermore, acupuncture did not considerably change Omission error, Commission error, Reaction Time and Correct hit (p > 0.05). ConclusionOur study showed that acupuncture can significantly improve the parent-report ADHD-RS. Nevertheless, it did not improve the attention deficit. We recommend further investigations with larger sample sizes and longer follow-up. The adverse effects of acupuncture on ADHD patients were not assessed in this study, but should be measured in future studies.

Sham or no sham control: that is the question in trials of renal denervation for resistant hypertension. A systematic meta-analysis

Background: Studies of renal denervation (RDN) in patients with apparent treatment resistant hypertension have been hampered by a number of patient and physician related confounders on blood pressure (BP) including poor drug adherence. It remains uncertain whether RDN lowers BP. We aimed to investigate whether the use of sham control is essential in RDN studies or whether systematic use of 24-hour ambulatory BP provides enough information thereby making an invasive sham control redundant.Methods: We meta-analyzed randomized controlled trials of the BP response to RDN on top of continued or optimized antihypertensive drugs in patients with resistant hypertension. On top of the randomized trials reviewed earlier, we additionally included three studies, one conducted in Spain (24 patients, RDN vs. spironolactone), one conducted in Denmark (69 patients, sham controlled) and one conducted in Netherlands (139 patients, RDN vs. continued treatment). We analyzed 24-hour ambulatory BP in 3 sham controlled studies vs. 7 no sham controlled studies.Results: The updated meta-analysis of 10 studies showed 3.6 mmHg (p = .45) and 1.0 mmHg (p = .54) reductions in office and in 24-hour systolic BP, respectively. Meta-analysis of 24-hour systolic BP in the 3 sham-controlled studies showed a reduction of 2.18 mmHg (95% confidence intervals (CIs) −4.70 to 0.33 mmHg, n = 396 vs. 230, p = .07). For the 7 no sham controlled studies there was no difference in 24-hour systolic BP (+0.38 mmHg; 95% CIs −5.29 to 6.04 mmHg, n = 215 vs. 245, p = .90). The test for sub-group heterogeneity showed no significant interaction (p = .69). Removing one trial at a time produced confirmatory results.Conclusion: The overall meta-analysis of 10 randomized and controlled studies showed no significant effect on BP of RDN in resistant hypertension. Moreover, our analysis does not support the use of sham control but rather suggests extensive use of 24-hour ambulatory BP in studies of RDN in resistant hypertension

Abstract TP146: Vagus Nerve Stimulation Paired With Rehabilitation To Improve Upper Limb Function

Introduction: Vagus Nerve Stimulation (VNS) paired with rehabilitation induces movement specific plasticity in rat motor cortex and improves forepaw function in a rat ischemic model compared to rehabilitation alone. A 20 subject first-in-human study in the UK indicated acceptable safety and feasibility of this approach in patients with arm weakness after stroke and showed a significant difference in favour of VNS paired with rehabilitation in the per-protocol analysis (Upper Extremity Fugl Meyer difference of 9.6 points for VNS vs. 3.0 Control; p = 0.038). We conducted a new, double-blind sham controlled study to further assess this technique. Methods: Subjects with chronic moderate to severe upper extremity hemiparesis secondary to ischemic stroke (Upper Extremity Fugl Meyer (UEFM) 20-50) were enrolled at four sites (3 US, 1 UK). After baseline assessments subjects were implanted with a vagus nerve stimulation device if all eligibility criteria were met. Following implantation, randomization was made to either paired VNS (1/2 second, 30 Hz., 0.8 mA, 100 uS stimulation with task-specific movement) or sham control (stimulation only on first 5 movements). All received the same intensive and task-specific rehabilitation and had 18 treatment sessions (2-hourly, 3 times a week for 6-weeks, approximately 50 repetitions per task and 300 to 400 repetition movements per session). Outcomes were assessed on the first and 30 th day following completion of the 6-week therapy course. Results: Sixteen patients (8 female) were implanted (8 VNS, 8 Control). Mean age (SD) was 63.2(6.9), with an average (SD) of 21.7 months (12.9) post stroke. One study related serious adverse event was reported (a wound infection that resolved with IV antibiotics). Blinded results (change in UEFM, WMFT, and UEFM responders for both groups) will be available and presented. Conclusions: A pivotal study of VNS paired with rehabilitation movements will be justified if preliminary results are confirmed.

Effect of Remote Ischaemic preconditioning on Clinical outcomes in patients undergoing Coronary Artery bypass graft surgery (ERICCA study): a multicentre double-blind randomised controlled clinical trial

BackgroundNovel cardioprotective strategies are required to improve clinical outcomes in higher-risk patients undergoing coronary artery bypass graft (CABG) with or without valve surgery. Remote ischaemic preconditioning (RIPC) in which brief episodes of non-lethal ischaemia and reperfusion are applied to the arm or leg has been demonstrated to reduce perioperative myocardial injury (PMI) following CABG with or without valve surgery.ObjectiveTo investigate whether or not RIPC can improve clinical outcomes in this setting in the Effect of Remote Ischaemic preconditioning on Clinical outcomes in patients undergoing Coronary Artery bypass graft surgery (ERICCA) study in patients undergoing CABG surgery.DesignMulticentre, double-blind, randomised sham controlled trial.SettingThe study was conducted across 30 cardiothoracic centres in the UK between March 2010 and March 2015.ParticipantsEligible patients were higher-risk adult patients (aged &gt; 18 years of age; additive European System for Cardiac Operative Risk of ≥ 5) undergoing on-pump CABG with or without valve surgery with blood cardioplegia.InterventionsPatients were randomised to receive either RIPC (four 5-minute inflations/deflations of a standard blood pressure cuff placed on the upper arm) or the sham control procedure (simulated RIPC protocol) following anaesthetic induction and prior to surgical incision. Anaesthetic management and perioperative care were not standardised.Main outcome measuresThe combined primary end point was the rate of major adverse cardiac and cerebral events comprising cardiovascular death, myocardial infarction, coronary revascularisation and stroke within 12 months of randomisation. Secondary end points included perioperative myocardial and acute kidney injury (AKI), intensive care unit and hospital stay, inotrope score, left ventricular ejection fraction, changes in quality of life and exercise tolerance.ResultsIn total, 1612 patients (sham control group,n = 811; RIPC group,n = 801) were randomised in 30 cardiac surgery centres in the UK. There was no difference in the primary end point at 12 months between the RIPC group and the sham control group (26.5% vs. 27.7%; hazard ratio 0.95, 95% confidence interval 0.79 to 1.15;p = 0.58). Furthermore, there was no evidence for any differences in either adverse events or the secondary end points of PMI (72-hour area under the curve for serum high-sensitivity troponin T), inotrope score, AKI, intensive therapy unit and hospital stay, 6-minute walk test and quality of life.ConclusionsIn patients undergoing elective on-pump CABG with or without valve surgery, without standardisation of the anaesthetic regimen, RIPC using transient arm ischaemia–reperfusion did not improve clinical outcomes. It is important that studies continue to investigate the potential mechanisms underlying RIPC, as this may facilitate the translation of this simple, non-invasive, low-cost intervention into patient benefit. The limitations of the study include the lack of standardised pre-/perioperative anaesthesia and medication, the level of missing and incomplete data for some of the secondary end points and the incompleteness of the data for the echocardiography substudy.Trial registrationClinicalTrials.gov NCT01247545.FundingThis project was funded by the Efficacy and Mechanism Evaluation programme, a MRC and NIHR partnership, and the British Heart Foundation.