ResearchPad - clinical-trial-report https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Effect of 8-Week Aerobic Walking Program on Sexual Function in Women with Rheumatoid Arthritis]]> https://www.researchpad.co/article/elastic_article_15634 Sexual dysfunction is a little-addressed condition in patients with rheumatoid arthritis. Aerobic exercises, including walking, can help alleviate this dysfunction. This study aimed to determine the effect of an 8-week aerobic walking program on sexual function ine patients with rheumatoid arthritis.MethodologyThis clinical trial was conducted on 51 patients with rheumatoid arthritis. At first, patients were selected through nonprobability sampling. They were then allocated into intervention and control groups using block randomization. The walking intervention was performed based on the frequency–intensity–time–type principle forg 8 consecutive weeks. Rosen’s Female Sexual Function Index was used for data collection before, immediately after, and 4 weeks after the intervention. Data collected were analyzed with SPSS 22 using descriptive and inferential statistics and 95% CI.FindingsMean sexual function scores before, after, and 4 weeks after intervention were 17.66±4, 22.88±4.7, and 24.39±5.1 in the intervention group and 17.60±4.24, 17.27±4.66, and 17.39±4.39 in the control group, respectively. Test results showed a significant intergroup difference in mean sexual function score (p<0.05).ConclusionBased on our results, an 8-week aerobic walking program is recommended as an effective way to improve sexual function in women with rheumatoid arthritis. ]]> <![CDATA[Effect of Acupuncture on Pregnancy-Related Insomnia and Melatonin: A Single-Blinded, Randomized, Placebo-Controlled Trial]]> https://www.researchpad.co/article/elastic_article_15602 The aim of the current study is to evaluate the efficacy and safety of acupuncture on sleep quality and overnight melatonin secretion, measured as urinary 6-sulfatoxymelatonin, in pregnant women.Patients and MethodsThis randomized, parallel, single-blinded (participant), controlled trial was conducted on 72 pregnant women with insomnia. Study participants were randomly assigned to either the intervention, 10 sessions of acupuncture treatment over a 3-week period, or control group by block randomization (1:1). Patients in both groups were evaluated at baseline and post-treatment (third week) using the Pittsburgh Sleep Quality Index (PSQI) score (as the primary outcome) and urinary 6-sulfatoxymelatonin.ResultsFifty-five of 72 participants completed the study. There was no statistically significant difference regarding PSQI score and 6-sulfatoxymelatonin level between intervention and control groups at the baseline (P=0.169 and P=0.496). At the end of the study period, treatment with acupuncture significantly improved the PSQI score (P<0.001) with a large effect size of 3.7, as well as 6-sulfatoxymelatonin level (P=0.020) with a medium effect size of 0.6 as compared to the control group. No adverse effects were noted during acupuncture sessions and follow-up visits.ConclusionAcupuncture was shown to significantly improve the sleep quality in pregnant women, possibly through increasing melatonin secretion, and could be recommended as a low-cost and low-risk alternative treatment to pharmacological therapies. ]]> <![CDATA[Effects of Alpha-Lipoic Acid Supplementation on Cardiovascular Disease Risk Factors in β-Thalassemia Major Patients: A Clinical Trial Crossover Study]]> https://www.researchpad.co/article/elastic_article_15550 Thalassemia is one of the most common genetic diseases, and cardiovascular disease (CVD) has been considered as the leading cause of mortality in more than 50% of β-thalassemia patients. The aim of this study was to determine the effects of alpha-lipoic acid (ALA) on CVD risk factors in β-thalassemia major patients.MethodsTwenty β-thalassemia major patients participated in this randomized crossover clinical trial study. Participants were randomly assigned to ALA (600 mg/day) or placebo groups for two 8-wk interventions that were separated by a 3-wk washout period. The CVD risk factors including serum osteoprotegerin (OPG), homocysteine, lipoprotein-associated phospholipase A2 and trimethylamine N-oxide were measured at the beginning and the end of each intervention phase according to the standard protocol.ResultsSerum OPG reduced significantly in the ALA group in all participants (5.38 ± 2.79 to 3.27 ± 2.43 ng/mL, P= .003) and in the male subgroup (5.24 ± 2.56 to 3.13 ± 2.5 ng/mL, P= .015); this reduction was significant in comparison with the placebo group (P= .013). The changes in other CVD risk factors were not significant.ConclusionThe results of this study showed that after 8-wk of ALA consumption, the serum OPG reduced significantly in β-thalassemia major patients. Therefore, controlling the serum OPG level with ALA consumption can be an important complementary therapeutic option to prevent the progression of CVD in β-thalassemia major patients. ]]> <![CDATA[Effectiveness of a Multifaceted Educational Intervention to Enhance Therapeutic Regimen Adherence and Quality of Life Amongst Iranian Hemodialysis Patients: A Randomized Controlled Trial (MEITRA Study)]]> https://www.researchpad.co/article/Nb3a79736-0df0-4f2a-b012-9c2359a5c538

Purpose

A multimodal intervention designed and executed to improve therapeutic regimen adherence and quality of life in a sample of Iranian hemodialysis patients. Its feasibility and impact was assessed post intervention.

Patients and Methods

This randomized controlled trial (RCT) study was conducted at two hemodialysis wards of the Shahrvand hospital located in Sari, the capital city of the Mazandaran province, north of Iran. The study sample included patients with end-stage renal disease (ESRD) receiving outpatient hemodialysis treatment. Considering 10% attrition, 70 registered patients were randomly categorized into intervention and control groups. The proposed intervention included playing of relevant educational video tracks, conducting eight cognitive behavioral therapy (CBT) group sessions, and telephone-based peer support. Data were collected applying a set of questionnaires including sociodemographic, Beck Depression Inventory (BDI-SF), Multidimensional Scale of Perceived Social Support (MSPSS), Patient Satisfaction with Nursing Care Quality Questionnaire (PSNCQQ), End-Stage Renal Disease Adherence Questionnaire (ESRD-AQ) and the World Health Organization Quality of Life (WHOQOL-SF) scale. Sociodemographic and clinical data were collected at baseline in both groups and the postintervention assessment was performed in the intervention and nonintervention groups after one month and three months.

Results

A significant change in the self-reported depression symptoms (P=0.001), mean social support score (P=0.001), nursing care satisfaction score (P=0.001), quality of life score (P=0.001) and interdialytic weight gain (IDWG) (P=0.001) was observed among the participants in the intervention group compared to the baseline measures. The highest rise in the ESRD-AQ scores within the intervention group was observed after one month of intervention (mean difference=131.88) compared to the baseline values. Same pattern of statistically significant changes in mean scores of the intervention group’s attendants in all subscales of the ESRD-AQ were also ascertained.

Conclusion

This interventional study revealed that inaugurating of a feasible low-cost intervention without need to add major logistic or financial inputs into existing health-care systems, especially in resource limited contexts, is achievable. Findings of this study could provide insights into scientific basis of evidence-informed interventions applicable in the realm of health-care delivery.

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<![CDATA[First-in-human phase I clinical trial of the NY-ESO-1 protein cancer vaccine with NOD2 and TLR9 stimulants in patients with NY-ESO-1-expressing refractory solid tumors]]> https://www.researchpad.co/article/N08b60ceb-51da-4bc0-816d-bad2eba09c2f

Cholesteryl pullulan (CHP) is a novel antigen delivery system. CHP and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen complexes (CHP-NY-ESO-1) present multiple epitope peptides to the MHC class I and II pathways. Adjuvants are essential for cancer vaccines. MIS416 is a non-toxic microparticle that activates immunity via the nucleotide-binding oligomerization domain 2 (NOD2) and TLR9 pathways. However, no reports have explored MIS416 as a cancer vaccine adjuvant. We conducted a first-in-human clinical trial of CHP-NY-ESO-1 with MIS416 in patients with NY-ESO-1-expressing refractory solid tumors. CHP-NY-ESO-1/MIS416 (μg/μg) was administered at 100/200, 200/200, 200/400 or 200/600 (cohorts 1, 2, 3 and 4, respectively) every 2 weeks for a total of 6 doses (treatment phase) followed by one vaccination every 4 weeks until disease progression or unacceptable toxicity (maintenance phase). The primary endpoints were safety and tolerability, and the secondary endpoint was the immune response. In total, 26 patients were enrolled. Seven patients (38%) continued vaccination in the maintenance phase. Grade 3 drug-related adverse events (AEs) were observed in six patients (23%): anorexia and hypertension were observed in one and five patients, respectively. No grade 4–5 drug-related AEs were observed. Eight patients (31%) had stable disease (SD). Neither augmentation of the NY-ESO-1-specific IFN-γ-secreting CD8+ T cell response nor an increase in the level of anti-NY-ESO-1 IgG1 was observed as the dose of MIS416 was increased. In a preclinical study, adding anti-PD-1 monoclonal antibody to CHP-NY-ESO-1 and MIS416 induced significant tumor suppression. This combination therapy is a promising next step.

Electronic supplementary material

The online version of this article (10.1007/s00262-020-02483-1) contains supplementary material, which is available to authorized users.

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<![CDATA[The Effect of Peer Support on Hope Among Patients Under Hemodialysis]]> https://www.researchpad.co/article/N51a4d918-d6aa-4100-b816-64e083bf4294

Introduction

Providing social support for patients under hemodialysis treatment can reduce their psychological, social, and physical problems. The present study aimed at determining the effect of peer support on hopefulness in patients under hemodialysis.

Methods

This clinical trial with a pre/posttest design was conducted on 128 patients who had referred to the hemodialysis centers of Shiraz University of Medical Sciences in 2019. The patients were randomly divided into an intervention and a control group. The patients in the intervention group were supported by their peers for eight weeks and were provided with the usual care, but the controls were only provided with the usual care. The data were collected using Snyder Hope Scale. Then, the data were entered into the SPSS software, version 18 and were analyzed using independent t-test and paired t-test.

Results

At baseline, the participants in both groups were similar with respect to the mean scores of hope and its subscales (p>0.05). However, there was a significant difference between the two groups in terms of hope and its subscales eight weeks after the intervention (p<0.001).

Conclusion

The results confirmed the effect of peer support on increasing hope among the patients under hemodialysis. Peer support in informational, emotional, instrumental, and spiritual forms could create a positive incentive and increase hope among the patients.

Clinical Trial Number

This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT20190126042498N1).

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<![CDATA[Comparison Between PPOS and GnRHa-Long Protocol in Clinical Outcome with the First IVF/ICSI Cycle: A Randomized Clinical Trial]]> https://www.researchpad.co/article/N794dabf9-16b9-43a1-ba2c-783bf39b022c

Purpose

To investigate whether progestin-primed ovarian stimulation (PPOS) can be an alternative as gonadotrophin-releasing hormone agonist (GnRHa) long protocol for infertile women with normal ovarian reserve during IVF/ICSI.

Methods

A prospective randomized controlled trial (RCT) including 257 patients was conducted between 1 August 2017 to 1 January 2018. Computerized randomization was performed to assign participants into two treatment groups at a 1:1 ratio: PPOS (130 patients) or GnRHa long protocol (127 patients) followed by their first IVF/ICSI with fresh/frozen embryo transfer. The primary outcome was the number of oocytes retrieved. Patients with normal ovarian reserve undergoing their first IVF/ICSI procedure were included. The embryological and clinical outcomes were measured. Only the first embryo transfer cycle was followed-up.

Results

Basic characteristics such as infertility duration, age, and body mass index (BMI) were comparable in both groups. No significant difference was found in the number (mean ± SD) oocytes retrieved [11.8 ± 6.5 for PPOS vs 11.3 ± 5.6 for GnRHa long protocol] or viable embryos [4.5 ± 3.0 for PPOS vs 4.2 ± 2.9 for GnRHa long protocol] between the groups. No patient from either group experienced a premature LH surge during the whole process of ovarian stimulation. Besides, there was no moderate or severe ovarian hyperstimulation syndrome during the ovarian stimulation in PPOS group while three patients suffered it in the GnRHa long protocol group. There was no significant difference in the clinical pregnancy rate of the first embryos transfer cycle between the two groups.

Conclusion

PPOS in combination with embryo cryopreservation as an ovarian stimulation regimen was as effective as GnRHa long protocol during controlled ovarian stimulation (COH) under different endocrinal mechanisms. It can also achieve comparable embryological and clinical outcomes while reducing the incidence of moderate and severe ovarian hyperstimulation syndrome (OHSS) and HMG dosage. It can be an alternative of the treatments for infertile patients with normal ovarian reserve undergoing IVF as well as traditional protocols.

Trial Registration Number

ChiCTR-INR-17012089.

Trial Registration Date

Chictr.org.cn: 23 July 2017.

Date of First Patient’s Enrollment

1 August 2017.

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<![CDATA[Autologous monocyte-derived DC vaccination combined with cisplatin in stage III and IV melanoma patients: a prospective, randomized phase 2 trial]]> https://www.researchpad.co/article/N238970f6-50ce-411c-980f-56203b393896

Background

Autologous dendritic cell (DC) vaccines can induce tumor-specific T cells, but their effect can be counteracted by immunosuppressive mechanisms. Cisplatin has shown immunomodulatory effects in vivo which may enhance efficacy of DC vaccination.

Methods

This is a prospective, randomized, open-label phase 2 study (NCT02285413) including stage III and IV melanoma patients receiving 3 biweekly vaccinations of gp100 and tyrosinase mRNA-loaded monocyte-derived DCs with or without cisplatin. Primary objectives were to study immunogenicity and feasibility, and secondary objectives were to assess toxicity and survival.

Results

Twenty-two stage III and 32 stage IV melanoma patients were analyzed. Antigen-specific CD8+ T cells were found in 44% versus 67% and functional T cell responses in 28% versus 19% of skin-test infiltrating lymphocytes in patients receiving DC vaccination with and without cisplatin, respectively. Four patients stopped cisplatin because of toxicity and continued DC monotherapy. No therapy-related grade 3 or 4 adverse events occurred due to DC monotherapy. During combination therapy, one therapy-related grade 3 adverse event, decompensated heart failure due to fluid overload, occurred. The clinical outcome parameters did not clearly suggest significant differences.

Conclusions

Combination of DC vaccination and cisplatin in melanoma patients is feasible and safe, but does not seem to result in more tumor-specific T cell responses or improved clinical outcome, when compared to DC vaccination monotherapy.

Electronic supplementary material

The online version of this article (10.1007/s00262-019-02466-x) contains supplementary material, which is available to authorized users.

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<![CDATA[The Effect of Using Olive Oil and Fish Oil Prophylactic Dressings on Heel Pressure Injury Development in Critically Ill Patients]]> https://www.researchpad.co/article/N03b9d4a7-433a-480a-ba45-6bd3a984f333

Introduction and Aim

Prevention of pressure injuries in patients hospitalized in intensive care units is significantly important. Therefore, in the present study, the effect of using olive oil and fish oil prophylactic dressings on the development of heel pressure injuries was investigated.

Methods

The present study was a clinical trial conducted in the intensive care unit of Shahid Beheshti Hospital, in Yasuj. Fifty patients, who were at moderate to high risk of pressure injuries development, were randomly divided into two groups based on the mean score of the Braden scale. In one group, patients’ heels were dressed using olive oil prophylactic dressing, and in the other group, patients’ heels were dressed using fish oil prophylactic dressing. The dressings were changed 3 times a day. Collected data were then analyzed using SPSS v16.

Results

No significant difference was determined in demographic variables among the two groups (p<0.05). In terms of the development of heel pressure injuries, none of the patients in the olive oil and fish oil groups had pressure injuries.

Conclusion

There were no statistically significant differences in either treatment group related to heel pressure injuries outcomes during the 7 days observed in the study. Additionally, both dressings had the same effects. Further studies are recommended in this regard.

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<![CDATA[Comparison of the Pharmacokinetics, Safety, and Tolerability of the Autoinjector (AI) and Pre-Filled Syringe (PFS) of SB4 in Healthy Subjects]]> https://www.researchpad.co/article/Nbb74906d-aaa3-469a-9c35-45f3dfe31b14

Purpose

SB4 is an etanercept biosimilar, approved by the European Commission (EC) and the US Food and Drug Administration (FDA) following a demonstration of equivalent efficacy and safety and comparable quality data to the reference product. This study aimed to demonstrate equivalent pharmacokinetic (PK) profiles, safety, and tolerability between SB4 autoinjector (AI) and SB4 pre-filled syringe (PFS).

Patients and methods

This was an open-label, two-period, two-sequence, single-dose, cross-over study to evaluate bioequivalence of PK profiles, safety, and tolerability between SB4 AI and PFS in healthy adults. Treatment periods were separated by 14 days resulting in a 35-day washout between investigational product (IP) administration in Periods 1 and 2.

Results

A total of 50 subjects were randomized: 24 subjects in Sequence I and 26 in Sequence II, and 6 subjects discontinued from the study. The primary PK endpoints including area under the concentration–time curve from time zero to infinity (AUCinf) and to the last quantifiable concentration (AUClast), and maximum serum concentration (Cmax) were all within the equivalence margin of 80.00–125.00%. Safety and tolerability were comparable between the two treatments.

Conclusion

PK profiles showed that SB4 AI and PFS were bioequivalent in healthy subjects. Safety assessment was also comparable between the two treatments.

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<![CDATA[Ultrasound-Guided Injection of High Molecular Weight Hyaluronic Acid versus Corticosteroid in Management of Plantar Fasciitis: A 24-Week Randomized Clinical Trial]]> https://www.researchpad.co/article/N8d693e30-65f1-49e1-87ae-3e7a9ea6aab2

Background and Aims

Plantar fasciitis (PF) is the leading cause of heel pain in adults. This study was designed to evaluate the effect of hyaluronic acid (HA) injection in reducing the symptoms of PF, compared with corticosteroid (CS) injection as a conventional treatment.

Methods

In this triple-blind, randomized, clinical trial, 75 patients who had the symptoms of PF for at least 3 months were randomly divided into two groups of 38 and 37 individuals. Then, each patient received either a single injection of high molecular weight (>2000 kDa) HA (1 mL HA 20 mg + 1 mL lidocaine 2%) or CS (1 mL methylprednisolone 40 mg + 1 mL lidocaine 2%) under the ultrasonography (US) guidance. Visual analog scale (VAS), foot ankle ability index (FAAI), pressure pain threshold (PPT), functional foot index (FFI), and plantar fascia thickness (PFT) were measured using US at baseline, 6 weeks and 24 weeks after the injection. Eventually, at the end of the treatment period, the patients’ satisfaction was measured. Intention to treat analysis was used to assess the results.

Results

After 24 weeks of follow-up, results from 60 subjects were fully obtained; however, results of 73 patients included into intention to treat analysis in the sixth-week follow-up. In both groups, VAS, PFT and FFI decreased, while FAAI and PPT increased significantly (P <0.001). At the baseline and at the 24th-week, no significant difference between the two groups was observed in any of the variables. However, a comparison between the baseline and the sixth-week results shows a prominent decrease in PPT and PFT in the CS group compared to the HA group (P = 0.004 and P = 0.011). Finally, there were no statistical differences between the two groups in treatment satisfaction (P = 0.618).

Conclusion

Both CS and HA were effective modalities for PF and can improve pain and function with no superiority in 24th-week follow-ups, although CS seems to have a faster trend of improvement in the short term.

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<![CDATA[MRI Changes After Platelet Rich Plasma Injection in Knee Osteoarthritis (Randomized Clinical Trial)]]> https://www.researchpad.co/article/N540a1dc9-bbbc-4a96-ad8c-96a91e50d75a

Purpose

Few papers have studied the objective effects of PRP on cartilage. In this study, we investigated the effect of PRP on cartilage characteristics by special MRI sequencing in knee osteoarthritis (IRCT registration number: 2014020413442N6).

Patients and methods

In this double blind randomized clinical trial, patients with bilateral knees osteoarthritis-grade 1, 2, and 3 were included in the study. Each patient's knees were randomly allocated to either control or treatment groups. PRP was injected in two sessions with 4 week intervals in PRP group. The VAS (visual analog scale) and WOMAC (Western Ontario and McMaster Universities Arthritis Index) were utilized and MRI was performed for all patients, before, and 8 months after treatment. The MRI sequences taken were transverse 3D TRUFISP and coronal and sagittal fat saturated proton-density. Imaging was scored according to four cartilage characteristics.

Results

46 knees (from 23 patients) were included in this study. 23 knees in the case group and 23 knees in control group were studied. All patients were female with mean age of 57.57±5.9 years. Mean total WOMAC and VAS changes before and after treatment in control group were 11.61±8.5 and 1.3±1.1 respectively. In PRP group, mean total WOMAC and VAS changes showed better improvement with 20±12.3 and 3.2±1.6 respectively (P-value <0.05). In PRP group, all of the radiologic variables (patellofemoral cartilage volume, synovitis and medial and lateral meniscal disintegrity), with the exception of subarticular bone marrow abnormality, had significant improvement (P-value <0.05). In a comparison between the two groups, patellofemoral cartilage volume and synovitis had significantly changed in the PRP group (P-value <0.05).

Conclusion

In this study, in addition to the effect of PRP on VAS and WOMAC, there was a significant effect on radiologic characteristics (patellofemoral cartilage volume and synovitis). For further evaluation, a longer study with a larger sample size is recommended.

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<![CDATA[Safety, Tolerability, and Pharmacokinetics of Adrenomedullin in Healthy Males: A Randomized, Double-Blind, Phase 1 Clinical Trial]]> https://www.researchpad.co/article/Ncc9ef7a6-ae89-46c6-b62a-56df3d31a433

Background

Adrenomedullin (AM), an endogenous vasodilative peptide, has immunomodulative effects and acts as an accelerator of mucosal regeneration in the digestive tract. AM has shown beneficial effects in rodent models of inflammatory bowel disease and patients with ulcerative colitis. The present study aimed to evaluate the pharmacodynamic properties and safety of AM in healthy male adults in a phase 1 clinical trial.

Methods

This phase 1, randomized, double-blind, single-center study was conducted on healthy males aged 20–65 years. Subjects received either a placebo, 3 ng/kg/min AM, 9 ng/kg/min AM, or 15 ng/kg/min AM via continuous 12-h intravenous infusion. Other subjects received either placebo or 15 ng/kg/min AM for 8 h per day for 7 days. Adverse events (AEs), vital signs, physical examinations, laboratory tests, electrocardiograms (ECG), and pharmacokinetics were assessed.

Findings

All 24 subjects in the single-dose test completed the study. Of the 12 subjects in multiple dosing test, one from the AM group withdrew owing to a headache. No serious AEs were reported. Hemodynamic parameters were well maintained in all subjects. Slight ECG abnormalities were observed in the single-dose test. The plasma concentration of AM progressively increased in a dose-dependent manner and reached Cmax at the end of administration. Plasma AM rapidly returned to baseline concentrations after termination, with a T1/2 of under 60 min.

Interpretation

This is the first phase 1 trial in healthy men evaluating the safety of AM. Our results demonstrate the safety and tolerability of AM for subsequent Phase 2 trials.

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<![CDATA[Targeting the Autonomic Nervous System Balance in Patients with Chronic Low Back Pain Using Transcranial Alternating Current Stimulation: A Randomized, Crossover, Double-Blind, Placebo-Controlled Pilot Study]]> https://www.researchpad.co/article/Nd210594b-3957-43b4-9cc9-68042d7bd35c

Background

Chronic low back pain (CLBP) is characterized by an alteration in pain processing by the central nervous system that may affect autonomic nervous system (ANS) balance. Heart rate variability (HRV) reflects the balance of parasympathetic and sympathetic ANS activation. In particular, respiratory sinus arrhythmia (RSA) solely reflects parasympathetic input and is reduced in CLBP patients. Yet, it remains unknown if non-invasive brain stimulation can alter ANS balance in CLBP patients.

Objective

To evaluate if non-invasive brain stimulation modulates the ANS, we analyzed HRV metrics collected in a previously published study of transcranial alternating current stimulation (tACS) for the modulation of CLBP through enhancing alpha oscillations. We hypothesized that tACS would increase RSA.

Methods

A randomized, crossover, double-blind, sham-controlled pilot study was conducted to investigate the effects of 10Hz-tACS on metrics of ANS balance calculated from electrocardiogram (ECG). ECG data were collected for 2 mins before and after 40 mins of 10Hz-tACS or sham stimulation.

Results

There were no significant changes in RSA or other frequency-domain HRV components from 10Hz-tACS. However, exploratory time-domain HRV analyses revealed a significant increase in the standard deviation of normal intervals between R-peaks (SDNN), a measure of ANS balance, for 10Hz-tACS relative to sham.

Conclusion

Although tACS did not significantly increase RSA, we found in an exploratory analysis that tACS modulated an integrated HRV measure of both ANS branches. These findings support the further study of how the ANS and alpha oscillations interact and are modulated by tACS.

ClinicalTrials.gov

Transcranial Alternating Current Stimulation in Back Pain – Pilot Study, NCT03243084.

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<![CDATA[Extrafine triple therapy delays COPD clinically important deterioration vs ICS/LABA, LAMA, or LABA/LAMA]]> https://www.researchpad.co/article/5c973b63d5eed0c484966f1f

Background

Current pharmacological therapies for COPD improve quality of life and symptoms and reduce exacerbations. Given the progressive nature of COPD, it is arguably more important to understand whether the available therapies are able to delay clinical deterioration; the concept of “clinically important deterioration” (CID) has therefore been developed. We evaluated the efficacy of the single-inhaler triple combination beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G), using data from three large 1-year studies.

Methods

The studies compared BDP/FF/G to BDP/FF (TRILOGY), tiotropium (TRINITY), and indacaterol/glycopyrronium (IND/GLY; TRIBUTE). All studies recruited patients with symptomatic COPD, FEV1 <50%, and an exacerbation history. We measured the time to first CID and to sustained CID, an endpoint combining FEV1, St George’s Respiratory Questionnaire (SGRQ), moderate-to-severe exacerbations, and death. The time to first CID was based on the first occurrence of any of the following: a decrease of ≥100 mL from baseline in FEV1, an increase of ≥4 units from baseline in SGRQ total score, the occurrence of a moderate/severe COPD exacerbation, or death. The time to sustained CID was defined as: a CID in FEV1 and/or SGRQ total score maintained at all subsequent visits, an exacerbation, or death.

Results

Extrafine BDP/FF/G significantly extended the time to first CID vs BDP/FF (HR 0.61, P<0.001), tiotropium (0.72, P<0.001), and IND/GLY (0.82, P<0.001), and significantly extended the time to sustained CID vs BDP/FF (HR 0.64, P<0.001) and tiotropium (0.80, P<0.001), with a numerical extension vs IND/GLY.

Conclusion

In patients with symptomatic COPD, FEV1 <50%, and an exacerbation history, extrafine BDP/FF/G delayed disease deterioration compared with BDP/FF, tiotropium, and IND/GLY.

Trial registration

The studies are registered in ClinicalTrials.gov: TRILOGY, NCT01917331; TRINITY, NCT01911364; TRIBUTE, NCT02579850.

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<![CDATA[Physicochemical characterization and phase I study of CMAB008, an infliximab biosimilar produced by a different expression system]]> https://www.researchpad.co/article/5c9740bdd5eed0c48496ee7e

Background

Infliximab (Remicade), a chimeric monoclonal antibody against human TNFα, will inevitably face competition from biosimilar products, because of its effectiveness in autoimmune diseases and rapidly increasing market demand. According to guidelines for biosimilar development, the “biosimilar-expression system” may differ from that of the innovator, but more appropriate studies should be carried out to demonstrate the comparability between biosimilar and innovator. CMAB008 is an infliximab biosimilar candidate developed by the State Key Laboratory of Antibody Medicine and Targeted Therapy of China. Infliximab was expressed in SP2/0 cells, while CMAB008 was produced in a CHO-expression system.

Methods

In this study, infliximab and CMAB008 were compared on physicochemical and biological characterizations, including protein content, activity, physiochemical integrity, impurities, additives, and immunogenicity.

Results

The results showed that they were highly similar and comparable, except some differences in glycosylation. As glycosylation profiles can influence immunogenicity and occurrence of allergy or other adverse reactions of antibody therapeutics, primary tolerability and pharmacokinetics of CMAB008 were evaluated. In the phase I clinical trial, plasma concentration of CMAB008 and antidrug antibodies were also measured using ELISA and bridging ELISA, respectively. CMAB008 exhibited favorable clinical tolerability, no adverse events in the 3 mg/kg single-dose group (recommended therapeutic dosage), and no serious adverse events in the multiple-dose group. Also, no injection-site reactions were observed in the experiment.

Conclusion

In summary, CMAB008 might have the potential to be an effective drug compared with infliximab.

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<![CDATA[Effect of specific deep cervical muscle exercises on functional disability, pain intensity, craniovertebral angle, and neck-muscle strength in chronic mechanical neck pain: a randomized controlled trial]]> https://www.researchpad.co/article/5c973e6fd5eed0c48496b78e

Background

Exercise is known to be an important component of treatment programs for individuals with neck pain. The study aimed to compare the effects of semispinalis cervicis (extensor) training, deep cervical flexor (flexor) training, and usual care (control) on functional disability, pain intensity, craniovertebral (CV) angle, and neck-muscle strength in chronic mechanical neck pain.

Methods

A total of 54 individuals with chronic mechanical neck pain were randomly allocated to three groups: extensor training, flexor training, or control. A Thai version of the Neck Disability Index, numeric pain scale (NPS), CV angle, and neck-muscle strength were measured at baseline, immediately after 6 weeks of training, and at 1- and 3 -month follow-up.

Results

Neck Disability Index scores improved significantly more in the exercise groups than in the control group after 6 weeks training and at 1- and 3-month follow-up in both the exten-sor (P=0.001) and flexor groups (P=0.003, P=0.001, P=0.004, respectively). NPS scores also improved significantly more in the exercise groups than in the control group after 6 weeks’ training in both the extensor (P<0.0001) and flexor groups (P=0.029. In both exercise groups, the CV angle improved significantly compared with the control group at 6 weeks and 3 months (extensor group, P=0.008 and P=0.01, respectively; flexor group, P=0.002 and 0.009, respectively). At 1 month, the CV angle had improved significantly in the flexor group (P=0.006). Muscle strength in both exercise groups had improved significantly more than in the control group at 6 weeks and 1- and 3-month follow-up (extensor group, P=0.04, P=0.02, P=0.002, respectively; flexor group, P=0.002, P=0.001, and 0.001, respectively). The semispinalis group gained extensor strength and the deep cervical flexor group gained flexor strength.

Conclusion

The results suggest that 6 weeks of training in both exercise groups can improve neck disability, pain intensity, CV angle, and neck-muscle strength in chronic mechanical neck pain.

Trial registration

NCT02656030

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<![CDATA[A phase 2 randomized, double-masked, placebo-controlled study of novel nonsystemic kinase inhibitor TOP1630 for the treatment of dry eye disease]]> https://www.researchpad.co/article/5c95d2bcd5eed0c48478f55d

Purpose

To evaluate the safety and efficacy of topical TOP1630, a novel nonsystemic kinase inhibitor, in dry eye disease (DED).

Patients and methods

A randomized, double-masked, parallel-group trial of 0.1% TOP1630 ophthalmic solution TID or placebo (vehicle without active drug) was conducted in DED subjects (n=61). Key eligibility criteria consistent with enrolling a moderate to severe DED population included >6 months DED history; OSDI© score ≥18; Schirmer’s test score ≤10 and ≥1 mm/5 minutes; tear film break-up time >1 and <7 seconds; and dry eye exacerbation in corneal staining and ocular discomfort in a Controlled Adverse Environment (CAE®). After a 7-day run-in period with placebo TID, eligible subjects were randomized to TOP1630 or placebo for 28 days. No supplemental artificial tears or rescue medication were allowed.

Results

TOP1630 was safe, well-tolerated, and efficacious in treating DED symptoms and signs. No serious adverse events (AEs) or withdrawals due to treatment emergent AEs occurred. Drop comfort scores showed TOP1630 to be comfortable and comparable with placebo. Significant symptom improvements were seen for TOP1630 vs placebo for ocular discomfort (P=0.02 post-CAE), grittiness/foreign body sensation (on four independent assessment scales, each P<0.05), worst DED symptom (diary, P=0.06), and ocular pain (VAS, P=0.03). Sign improvements were seen for total ocular surface (all regions), corneal sum, and conjunctival sum staining with TOP1630 compared with placebo (each P<0.05).

Conclusion

TOP1630 had placebo-like tolerability and produced improvements in multiple symptom and sign endpoints in both environmental and challenge settings. The emergent TOP1630 benefit–risk profile for DED treatment is highly favorable and supports further development.

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<![CDATA[A highly sensitive biosensor based on Au NPs/rGO-PAMAM-Fc nanomaterials for detection of cholesterol]]> https://www.researchpad.co/article/5c79b3fed5eed0c4841e993c

Objective

This study aimed to construct a biosensor using Au nanoparticles (Au NPs) and reduced graphene-polyamide-amine-ferrocene (rGO-PAMAM-Fc) nanomaterials designed for rapid and sensitive detection of cholesterol.

Materials and methods

In this study, a highly sensitive biosensor based on Au NPs/ rGO-PAMAM-Fc nanomaterials was manufactured for detection of cholesterol. The rGO-PAMAM-Fc and Au NPs were modified on the surface of the electrode and then coated with cholesterol oxidase (ChOx) and cholesterol esterase (ChEt) to develop the ChOx&ChEt/Au NPs/rGO-PAMAM-Fc biosensor.

Results

The capability of rGO-PAMAM-Fc nanomaterials in fabricating a more efficient biosensor was validated through stability, selectivity and reproducibility checks. Under optimal conditions, the newly developed biosensor showed a linear relationship with logarithm of cholesterol concentration from 0.0004 to 15.36 mM (R2=0.9986), and a low detection limit of 2 nM was obtained at the signal/noise ratio of 3.

Conclusion

The ChOx&ChEt/Au NPs/rGO-PAMAM-Fc biosensor was successfully applied for the measurement of cholesterol in human serum, which implies that the biosensor has a potential application in clinical diagnostics.

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<![CDATA[Elevated free fatty acid level is associated with insulin-resistant state in nondiabetic Chinese people]]> https://www.researchpad.co/article/5c61b810d5eed0c484938795

Background

Free fatty acids (FFAs) are associated with insulin secretion and insulin resistance. However, the associations among FFAs, obesity, and progression from a normal to a prediabetic state are unclear.

Methods

Nondiabetic subjects (5,952) were divided in two groups according to their body mass index (BMI): obese subjects (BMI ≥24 kg/m2) and nonobese subjects (BMI <24 kg/m2). Clinical and multiple glucolipid metabolism data were collected. The homeostasis model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β) was used. HbA1c level between 5.7% and 6.4% was considered prediabetic. Nonparametric tests, one-way ANOVA, and linear correlation analysis were performed. R and SPSS 23.0 software programs were used to analyze the results.

Results

A U-shaped relationship between FFAs and HOMA-IR was observed. After adjusting for potential confounders, the turning points of FFA levels in the curves were 0.54 mmol/L in the nonobese group and 0.61 mmol/L in the obese group. HOMA-IR levels decreased with increasing FFA concentrations before the turning points (regression coefficient [β]= – 0.9, P=0.0111, for the nonobese group; β=0.2, P=0.5094, for the obese group) and then increased (β=0.9, P=0.0069, for the nonobese group; β=1.5, P=0.0263 for the obese group) after the points. Additionally, our study also identified that FFAs were associated with the prediabetes status in obese individuals.

Conclusion

FFA levels were associated with insulin resistance in nondiabetic subjects, and HOMA-IR in nonobese individuals was more sensitive to FFA changes. Monitoring and controlling plasma FFA levels in obese subjects is significant in decreasing insulin resistance and preventing diabetes.

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