189 research outputs found
Rethinking clinical trials of transcranial direct current stimulation: Participant and assessor blinding is inadequate at intensities of 2mA
Get PDFCopyright @ 2012 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and 85 reproduction in any medium, provided the original author and source are credited. The article was made available through the Brunel University Open Access Publishing Fund.Background: Many double-blind clinical trials of transcranial direct current stimulation (tDCS) use stimulus intensities of 2 mA despite the fact that blinding has not been formally validated under these conditions. The aim of this study was to test the assumption that sham 2 mA tDCS achieves effective blinding. Methods:
A randomised double blind crossover trial. 100 tDCS-naïve healthy volunteers were incorrectly advised that they there were taking part in a trial of tDCS on word memory. Participants attended for two separate sessions. In each session, they completed a word memory task, then received active or sham tDCS (order randomised) at 2 mA stimulation intensity for 20 minutes and then repeated the word memory task. They then judged whether they believed they had received active stimulation and rated their confidence in that judgement. The blinded assessor noted when red marks were observed at the electrode sites post-stimulation. Results: tDCS at 2 mA was not effectively blinded. That is, participants correctly judged the stimulation condition greater than would be expected to by chance at both the first session (kappa level of agreement (κ) 0.28, 95% confidence interval (CI) 0.09 to 0.47 p = 0.005) and the second session (κ = 0.77, 95%CI 0.64 to 0.90), p = <0.001) indicating inadequate participant blinding. Redness at the reference electrode site was noticeable following active stimulation more than sham stimulation (session one, κ = 0.512, 95%CI 0.363 to 0.66, p<0.001; session two, κ = 0.677, 95%CI 0.534 to 0.82) indicating inadequate assessor blinding. Conclusions: Our results suggest that blinding in studies using tDCS at intensities of 2 mA is inadequate. Positive results from such studies should be interpreted with caution.GLM is supported by the National Health & Medical Research Council of Australia ID 571090
The effects of melatonin administration on KCNQ and KCNH2 gene expressions and QTc interval in pinealectomised rats
Get PDFMelatonin is a hormone secreted from the pineal gland and has different cardiovascular effects. KCNQ genes expressed in aorta related with vascu-lar tone and KCNH2 gene characterised in left ventricle associated with QT duration. The aim of this study was to investigate the effects of melatonin on the regulation of the blood pressure and the relationships between the expressions of aorta KCNQ1-5, left ventricle KCNH2 genes and the QTc interval. For that purpose, 42 male adult Sprague-Dawley rats were devided into six groups; SHAM, SHAM+L-NAME, PLT, PLT+L-NAME, PLT+MEL and PLT+L-NAME+MEL. Pinealectomy operation was applied in PLT groups. L-NAME was added in drinking water (40 mg/kg/day) and melatonin was given subcutanously (5 mg/kg/day). The blood pressure, heart rate (HR) and QTc interval values were recorded on 0, 1st, 7th, 14th and 21st days of experiment. Left ventricle and thoracic aorta samples were obtained to investigate the changes of gene expression levels of KCNQ1-5 and KCNH2, respectively. The increased blood pressure and HR were observed in SHAM+L-NAME, PLT, and PLT+L-NAME groups compared to MEL and SHAM groups (p<0.05). On the other hand, the long QTc interval was recorded in PLT and all L-NAME groups compared to others (p<0.05). The decreases in KCNH2 gene expression levels were observed in groups have QTc prolongation. In conclusion, PLT operation could cause an increasing in blood pressure, HR and QTc duration, melatonin was able to prevent these increasings and could change KCNQ and KCNH2 gene expresion profiles. Further molecular studies are required to evaluate these effects.foundation of COMUBAP (Scientific Research Projects Office of Canakkale Onsekiz Mart University) [TYL-2013-29]This study is supported by the foundation of COMUBAP (Scientific Research Projects Office of Canakkale Onsekiz Mart University, Number: TYL-2013-29) and summarised from Master of Science Thesis of Corresponding Author
Three-year randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema.
No full textPurpose: To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant)
0.7 and 0.35 mg in the treatment of patients with diabetic macular edema (DME).
Design: Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols
were conducted. Data were pooled for analysis.
Participants: Patients (n 1⁄4 1048) with DME, best-corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen
equivalent, and central retinal thickness (CRT) of 300 mm by optical coherence tomography.
Methods: Patientswere randomized in a 1:1:1 ratio to study treatmentwithDEX implant 0.7mg,DEX implant 0.35
mg, or shamprocedure andfollowedfor 3 years (or 39months for patients treatedatmonth36) at40 scheduledvisits.
Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months.
Main Outcome Measures: The predefined primary efficacy endpoint for the United States Food and Drug
Administration was achievement of 15-letter improvement in BCVA from baseline at study end. Safety measures
included adverse events and intraocular pressure (IOP).
Results: Mean number of treatments received over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX
implant 0.35 mg, and sham, respectively. The percentage of patients with 15-letter improvement in BCVA from
baseline at study end was greater with DEX implant 0.7 mg (22.2%) and DEX implant 0.35 mg (18.4%) than sham
(12.0%; P 0.018). Mean average reduction in CRT from baseline was greater with DEX implant 0.7 mg (111.6
mm) and DEX implant 0.35 mg (107.9 mm) than sham (41.9 mm; P < 0.001). Rates of cataract-related adverse
events in phakic eyes were 67.9%, 64.1%, and 20.4% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham
groups, respectively. Increases in IOP were usually controlled with medication or no therapy; only 2 patients (0.6%)
in the DEX implant 0.7 mg group and 1 (0.3%) in the DEX implant 0.35 mg group required trabeculectomy.
Conclusions: The DEX implant 0.7 mg and 0.35 mg met the primary efficacy endpoint for improvement in
BCVA. The safety profile was acceptable and consistent with previous reports. Ophthalmology 2014;121:1904-
1914 a 2014 by the American Academy of Ophthalmolog
Vagus nerve stimulation in treatment-resistant depression: A one-year, randomized, sham-controlled trial
No full textBackground: Few treatments are available for individuals with marked treatment-resistant depression (TRD). Objective: Evaluate the safety and effectiveness of FDA-approved adjunctive vagus nerve stimulation (VNS) in patients with marked TRD. Methods: This 12-month, multicenter, double-blind, sham-controlled trial included 493 adults with marked treatment-resistant major depression who were randomized to active or no-stimulation sham VNS for 12 months. The primary outcome was percent time in response across months 3–12, with response defined as a ≥50 % change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS). Several secondary endpoints were evaluated. Results: Overall, 88.4 % of participants completed the trial. Percent time in MADRS response did not distinguish active from sham VNS. However, ratings from on-site clinicians (Clinical Global Inventory–Impression [CGI-I]), patients (Quick Inventory of Depressive Symptomology–Self Report [QIDS-SR]), and offsite masked raters (Quick Inventory of Depressive Symptomology–Clinician [QIDS-C]) revealed antidepressant benefits significantly favoring active VNS. Active VNS demonstrated significantly more percent time in response on the CGI-I (P = 0.004) and QIDS-SR (P = 0.049), and significantly more percent time in partial response (PR; symptom improvement ≥30 %) on the CGI-I (P < 0.001) and QIDS-C (P = 0.006) versus sham VNS. Active VNS exceeded sham VNS in rate of dyspnea (P = 0.035), a known side effect of VNS. No new adverse events were identified. Conclusions: Percent time in MADRS response did not distinguish the treatment groups, but on multiple instruments time in response and PR showed a positive treatment effect. VNS was found safe and effective in participants with marked TRD
Clinical effectiveness of active Alpha-Stim AID versus sham Alpha-Stim AID in major depression in primary care in England (Alpha-Stim-D): a multicentre, parallel group, double-blind, randomised controlled trial
Get PDFCopyright © 2023 The Author(s). Published by Elsevier Ltd.
User license Creative Commons Attribution (CC BY 4.0).Background Randomised sham-controlled trials of cranial electrostimulation with the Alpha-Stim Anxiety Insomnia and Depression (AID) device have reported improved anxiety and depression symptoms; however, no adequately powered sham-controlled trials in major depression are available. We investigated whether active Alpha-Stim AID is superior to sham Alpha-Stim AID in terms of clinical effectiveness for depression symptoms in major depression. Methods The Alpha-Stim-D trial was a multicentre, parallel group, double-blind, randomised controlled trial, recruiting participants from 25 primary care centres in two regions in England, UK. Eligible participants were aged 16 years or older with a current diagnosis of primary major depression, a score of 10–19 on the nine-item Patient Health Questionnaire, and had been offered or prescribed and reported taking antidepressant medication for at least 6 weeks in the previous 3 months. Main exclusion criteria were contraindications to Alpha-Stim AID device use, having persistent suicidal ideation or self-harm, neurological conditions, a substance use disorder or dependence, an eating disorder, bipolar disorder, or non-affective psychosis, or receiving psychological treatment in the past 3 months. Eligible participants were randomly assigned (1:1, minimised by region, anxiety disorder, and antidepressant use) to 1 h daily use of active (100 μA) or sham Alpha-Stim AID treatment for 8 weeks. Randomisation was via an independent web-based system, with participants, outcome assessors, and data analyst masked to treatment assignment. The primary outcome was change from baseline in score on the 17-item Hamilton Depression Rating Scale (HDRS-17, GRID version) at 16 weeks after randomisation, with participants analysed by intention to treat (ITT; all randomly assigned participants). Safety was assessed in all randomly assigned participants. The trial is registered with the ISRCTN registry (ISRCTN11853110); status completed. Findings Between Sept 8, 2020, and Jan 14, 2022, 236 eligible participants were randomly assigned to active or sham Alpha-Stim AID (n=118 each). 156 (66%) participants were women, 77 (33%) were men, and three (1%) self-reported as other gender; 200 (85%) were White British or Irish; and the mean age was 38·0 years (SD 15·3; range 16–83). 102 (86%) participants in the active Alpha-Stim AID group and 98 (83%) in the sham group were followed up 16 weeks after randomisation. In the ITT population, mean change in GRID-HDRS-17 at 16 weeks was –5·9 (95% CI –7·1 to –4·8) in the active Alpha-Stim AID group and –6·5 (–7·7 to –5·4) in the sham group (mean change difference –0·6 [95% CI –1·0 to 2·2], p=0·46). Among the 236 participants, 17 adverse events were reported in 17 (7%) participants (nine [8%] participants in the active Alpha-Stim AID group; and eight [7%] participants in the sham group). One serious adverse event of suicidal ideation leading to hospitalisation was reported in the sham group, which was judged to be unrelated to the device. Interpretation Active Alpha-Stim AID was safe and acceptable, but no more clinically effective than sham Alpha-Stim AID in major depression. Fundinghttps://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(23)00007-X/fulltex
Immunolocalization of sclerostin synthesized by osteocytes in relation to bone remodeling in the interradicular septa of ovariectomized rats
Get PDFThis study aimed to elucidate whether estrogen deficiency would affect the synthesis of an osteocyte-derived factor, sclerostin, in the mesial region of alveolar bone. Eight 9-week-old Wistar female rats were ovariectomized (OVX) and the other eight rats were Sham-operated (Sham). After 4 weeks, the interradicular septa of mandibular first molar were embedded in paraffin, and then, were histochemically examined. Sclerostin-positive osteocytes were located in a superficial layer of the mesial region of Sham bone, while the OVX mesial region showed a lesser presence of the sclerostin-reactive osteocytes. There was no significant difference in the distribution of estrogen receptor α and TUNEL-positive cells in either Sham or OVX groups. Meanwhile, the Sham mesial region demonstrated many osteoclasts, but the OVX specimens showed numerous osteoclasts in association with intense immunolabeling of the receptor activator of the nuclear factor kB ligand. Complex meshwork of cement lines was seen consistent with irregularly-distributed osteocytic lacunar-canalicular system in the OVX mesial region, compared with those of the Sham specimens. In conclusion, estrogen deficiency appears to inhibit osteocytes for sclerostin synthesis in the mesial region of the interradicular septum, mediated by accelerated bone remodeling, rather than by directly effecting osteocytes
Nuptial food gifts influence female egg production in the scorpionfly Panorpa cognata
Get PDFEngqvist L. Nuptial food gifts influence female egg production in the scorpionfly Panorpa cognata. Ecological Entomology. 2007;32(3):327-332.1. Before copulation, male Panorpa cognata scorpionflies offer females a salivary secretion, which is consumed by the female during copulation. It has previously been demonstrated that this nuptial food gift functions as mating effort by increasing male attractiveness and by increasing ejaculate transfer during copulation.
2. In this study, the effect of saliva consumption on female reproductive output was investigated, and thus the possibility that nuptial food gifts also serve as paternal investment. The experimental design enabled the effect of nuptial gift consumption to be disentangled from other possible effects of multiple mating or increased copula duration.
3. The results showed that saliva consumption increases female egg production by on average 8% (4.5 eggs) per consumed salivary mass, whereas mean egg weight was not influenced.
4. These results have important implications for the evolution and maintenance of both male nuptial gifts and female polyandry in this and other species
Cardiopoietic cell therapy for advanced ischaemic heart failure: Results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial
Get PDFAIMS: Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort.
METHODS AND RESULTS: This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein-Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann-Whitney estimator 0.54, 95% confidence interval [CI] 0.47-0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200-370 mL (60% of patients) (Mann-Whitney estimator 0.61, 95% CI 0.52-0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death.
CONCLUSION: The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted
Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial
No full text© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods: We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK-based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053. Findings: Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants' systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (
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