Efficacy and Safety of Chinese Medicine Resuscitation Pack for Enhanced Recovery after Bronchoscopy: A Randomized, Single-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients. METHODS: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation. RESULTS: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group. CONCLUSIONS: Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299).

Efficacy and safety of Link Natural Sudarshana, an Ayurvedic herbal preparation in COVID-19 patients: A phase II multicenter double-blind randomized placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: In vitro and in vivo studies have shown anti-viral and immunomodulatory actions in components of many traditional medicines. Various constituents of traditional medicines have been found to be effective against coronavirus disease (COVID-19) in several clinical trials and in-silico studies. Sudarshana cúrna, a polyherbal Ayurvedic medicine, has been used over thousands of years for a variety of infectious fevers. AIMS OF THE STUDY: This study aimed to evaluate the efficacy and safety of Link Natural Sudarshana (LNS) tablets, in patients with COVID 19 disease. LNS is a polyherbal preparation comprising 49 medicinal plants included in the Sudarshana cúrna. MATERIALS AND METHODS: A randomized parallel-group double-blind placebo-controlled multi-center phase II clinical trial was conducted in patients with mild to moderate COVID-19 disease. They were randomly allocated to intervention and control groups. The intervention group received LNS tablets whereas the control group received placebo tablets for 10 days or until the patient was discharged from the hospital. All patients received standard symptomatic treatment. The primary outcome, a reduction in mean log viral load was assessed at day 5 of treatment. The secondary outcomes, clinical progression and safety, were assessed by, monitoring changes in symptoms daily on a Likert scale ranging from 1 to 4 and laboratory tests respectively. RESULTS: A total of 171 patients (treatment group 83, control group 88) completed the trial. There were no significant differences between the baseline status of the two groups except that body mass index was significantly higher in the placebo group. The mean log viral load reduction at day 5 was higher in the treatment group (2.20 ± 1.67) compared to the placebo group (1.93 ± 1.80), with a mean difference of -0.278. This difference was not statistically significant at the 5% significant level. Reduction of mean cumulative symptom score, which included 16 symptoms graded according to severity, was higher in the treatment group compared to the placebo group. This difference was not statistically significant. None of the study participants developed hypoxia. Among the 7 lymphopenia patients in the placebo group, 3 continued to have lymphopenia at day 10, whereas 9 lymphopenia patients in the treatment group, reverted to normal counts. C reactive proteins (CRP) showed a greater reduction in the treatment group. None reported adverse effects. No significant changes occurred in hematological and biochemical parameters that assessed safety. CONCLUSIONS: LNS is safe to use in COVID-19 patients and accelerated the decline in viral load, relieved symptoms, reduced CRP levels and reversed lymphopenia earlier, when compared to the placebo.

Acupuncture for Japanese Katakori (Chronic Neck Pain): A Randomized Placebo-Controlled Double-Blind Study.

Background and Objectives: Although acupuncture is listed as a beneficial treatment for neck/shoulder stiffness, which has increased with the spread of information technology, to date, evidence of its efficacy under double-blind conditions has not been shown. This study aimed to assess whether acupuncture treatment with superficial skin piercing is superior to placebo treatment. Materials and Methods: A randomized, double-blind (practitioner-patient) placebo-controlled trial was performed at a single center with four arms (ISRCTN76896018). Four hundred patients with essential neck/shoulder stiffness were randomly assigned to penetrating needle treatment (acupuncture ritual and skin penetration), skin-touch needle treatment (acupuncture ritual and skin touch), no-touch needle treatment (acupuncture ritual alone), and no-treatment control. Each of the six acupuncturists applied a needle to each of the four acupoints in the neck/shoulder of 50 patients. Results: Each of the three treatments significantly (p = 0.01) improved neck/shoulder stiffness compared with the no-treatment control immediately and 24 h after treatment. There was a significant improvement in penetrating needle treatment over no-touch needle treatment 24 h later. However, there was no significant difference between the penetrating and skin-touch and skin-touch vs. no-touch. Conclusions: All treatments that received the ritual of acupuncture were better than the no-treatment control. Only genuine acupuncture involves the specific effects of needle insertion into the body. The acupuncture ritual had a significant impact on the subjective improvement of neck/shoulder stiffness; however, improvement with ritual alone versions of placebo acupuncture was not maintained as with superficial skin piercing. Our study provides important evidence of acupuncture efficacy and information regarding inert no-touch placebo control in acupuncture research.

The effect of lavender aroma for anxiety disorder: a study protocol for a multicenter, double-masked, randomized, placebo-controlled clinical trial.

BACKGROUND: Anxiety disorder is the most prevalent psychiatric disorder. Benzodiazepines, which are often used for anxiety in patients with anxiety disorder, have various side effects. Lavender, one of the most commonly used essential oils in aromatherapy, has the potential to reduce benzodiazepine use for anxiety disorders. METHODS: This study is a multicenter, double-masked, randomized, placebo-controlled clinical trial. The study will recruit patients aged 20-59 years old with generalized anxiety disorder and panic disorder among anxiety disorders. The bottle containing the test solution (lavender aroma essential oil or distilled water) will be given to the patients. Patients will carry the bottles with them in their daily life and use the drops on tissue paper when anxious. The primary endpoint is the number of times anxiolytics used in 28 days. DISCUSSION: If the use of benzodiazepines could be reduced by sniffing lavender aroma, which is inexpensive and safe, it would contribute not only to the risks associated with benzodiazepine use but also to the health care economy and could even be added as a standard treatment. TRIAL REGISTRATION: University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), ID: UMIN000034422 Registered 17 January 2019.

Effects of iron supplementation to iron depleted and iron replete pregnant Danish women: Defining criteria for identification of women who can manage without supplements: A randomized, placebo-controlled study.

OBJECTIVE: To define criteria based on iron status parameters for the identification of healthy women who do need/do not need iron supplementation during normal pregnancy. METHODS: Randomized, double-blind, placebo-controlled study of 113 women (62 iron-, 51 placebo treated) and their newborns. Iron dose was 66 mg elemental iron as ferrous fumarate daily from 14-18 weeks gestation to delivery. Hemoglobin (Hb), serum (S)-ferritin, S-transferrin saturation percentage, and S-erythropoietin were measured during gestation, prepartum, one week and 8 weeks postpartum. The women were divided in groups according to S-ferritin levels at inclusion:<30,≥30,≥40,≥50 and≥60µg/L. Iron deficiency (ID) was defined as S-ferritin < 15µg/L; iron deficiency anemia (IDA) as S-ferritin < 15µg/L and Hb < 110 g/L. RESULTS: Placebo treated women with S-ferritin levels < 30µg/L at inclusion had a much higher incidence of ID/IDA than placebo treated women with S-ferritin levels≥30,≥40,≥50, and≥60µg/L. S-ferritin levels≥40µg/L were associated with a very low risk of ID/IDA and none of the women with levels≥50 and≥60µg/L displayed ID/IDA. CONCLUSIONS: Women having S-ferritin < 30µg/L in early pregnancy, have a high risk of ID/IDA and should be recommended ferrous iron supplements in appropriate doses. With increasing iron reserves, i.e., increasing S-ferritin, the need for iron supplements diminishes, and placebo treated women having S-ferritin ≥40µg/L seldom develop IDA. Women with S-ferritin levels≥50 and≥60µg/L or higher, have adequate iron reserves and do not need routine iron prophylaxis in pregnancy. The results support the arguments for an individual iron supplementation guided by iron status, to avoid unwanted side effects of unnecessary iron intake.

Glycemic Variability in Patients with Type 2 Diabetes Mellitus (T2DM): The Role of Melatonin in a Crossover, Double-Blind, Placebo-Controlled, Randomized Study.

BACKGROUND: Glycemic variability in patients with type 2 diabetes mellitus (T2DM) may be associated with chronic complications of the disease. Melatonin is a hormone that plays a crucial role in biological rhythms. Previous studies have indicated that individuals with T2DM often exhibit reduced melatonin production. In this study, our objective was to investigate whether nighttime melatonin supplementation could mitigate glycemic variability in these patients. METHODS: Crossover, double-blind, placebo-controlled, randomized study. A total of 30 patients were enrolled in this study. The study included 15 participants who followed the intervention sequence of placebo (7 days)-washout (7 days)-melatonin (3 mg) (7 days), and another 15 participants who followed the sequence of melatonin (3 mg) (7 days)-washout (7 days)-placebo (7 days). During the final three days of the first and third weeks, the participants measured their pre- and postprandial capillary blood glucose levels. This study was reported according to the CONSORT 2010 statement: extension to randomized crossover trials. RESULTS: There was a significant absolute difference in the breakfast blood glucose levels (p = 0.016) on Day 7. The use of melatonin determined a greater positive variation between pre- and postprandial glycemia than the placebo. The difference in glycemic amplitude between post-dinner Day 6 and pre-breakfast Day 7 was also significantly higher in the melatonin group (p = 0.032). CONCLUSIONS: Melatonin increased glycemic variability in individuals with type 2 diabetes mellitus (T2DM). These results can be attributed to the residual daytime effects of melatonin, prospective proximal effects, and damage to the prospective distal effects of exogenous melatonin. Therefore, caution should be exercised when administering melatonin supplementation to patients with T2DM, taking into consideration factors such as dosage, duration of use and genetic considerations.

Different therapies of Chinese herbal medicine for diarrhea-predominant irritable bowel syndrome: A network meta-analysis of double-blinded, placebo-controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Shuganjianpi Therapy (SGJP), Jianpi Therapy (JP), Shugan Therapy (SG), Jianpiwenshen Therapy (JPWS), and Shuganjianpiwenshen Therapy (SGJPWS), consisting of formulas from Chinese herbal medicine (CHM), have been tremendously applied to irritable bowel syndrome (IBS). However, it remains uncertain when exploring the preferable option among different CHM therapies for diarrhea-predominant irritable bowel syndrome (IBS-D). AIM OF THE STUDY: To compare and rank the efficacy and safety of different CHM therapies for IBS-D. MATERIALS AND METHODS: We searched randomized, double-blinded, placebo-controlled trials through mainstream databases from their inception to October 31, 2022. Eligible randomized controlled trials (RCTs) applied one of the CHM therapies as the experimental group and placebo as the control group. Two authors independently extracted data into a form and evaluated the quality of the retrieved articles by the Cochrane Risk of Bias Tool. At least one of the following outcomes was assessed: Serotonin, Neuropeptide Y (NPY), Incidence of Adverse Events (AE), and Irritable Bowel Syndrome-Severity Scoring System (IBS-SSS) with its subscales of Severity of Abdominal Pain (SAP), Frequency of Abdominal Pain (FAP), Severity of Abdominal Distension (SAD), Dissatisfaction with Bowel Habits (DBH), and Interference with Quality of Life (IQOL). A Bayesian network meta-analysis on a random-effect model was conducted using R 4.2.2 software. RESULTS: 1367 records were retrieved from databases in an initial search. Fourteen studies involving six interventions with 2248 participants were identified. Provided pairwise comparisons, the surface under the cumulative ranking curve (SUCRA) ranking, and cluster analysis, JPWS was the best option for ameliorating clinical symptoms simultaneously, which included IBS-SSS, SAP, FAP, SAD, DBH, and IQOL. As for AE, JPWS contributed to fewer adverse events than others as well. In respect of serum indicators, we noticed the dominance of SGJP in regulating both serotonin and NPY. CONCLUSIONS: JPWS and SGJP were the most prominent CHM therapies for IBS-D in terms of clinical symptoms, including abdominal pain, distension, bowel habits, and improvement of quality of life. The effect of JP and SG for IBS-D required further investigation. As a potential candidate, SGJP may well treat IBS-D by mediating dysmotility, visceral hypersensitivity, and the gut-brain axis with an increase of NPY and a reduction of serotonin. For safety, JPWS was ideal for the fewest adverse events in the treatment of IBS-D. On account of a small sample size and possible geographical publication bias, more double-blinded and placebo-controlled trials with larger samples worldwide would be necessary for strengthening current evidence.

Efficacy and safety of tenapanor in hemodialysis patients with hyperphosphatemia: A systematic review and meta-analysis of randomized placebo-controlled trials.

BACKGROUND: The effects of tenapanor in reducing serum phosphorus in hemodialysis patients with hyperphosphatemia are uncertain and no relevant meta-analysis has been conducted. We performed a meta-analysis of randomized placebo-controlled trials to evaluate the efficacy and safety of tenapanor. METHODS: All randomized controlled trials of tenapanor were searched up to 1 August 2022. The primary endpoint was the change in serum phosphorus level from baseline with tenapanor and placebo. Data on drug-related adverse events (AEs), gastrointestinal AEs and diarrhea were collected to determine the safety of tenapanor. RESULTS: There were 533 patients throughout five trials that were eligible. Tenapanor significantly lowered blood phosphorus level by 1.79 mg/dl in the mean difference than the placebo. Diarrhea, gastrointestinal AEs, and drug-related AEs were more severe than placebo. CONCLUSIONS: This meta-analysis showed that although drug side effects were common, tenapanor significantly reduced serum phosphorus level in hemodialysis patients.

Efficacy of mecasin for treatment of amyotrophic lateral sclerosis: A phase IIa multicenter randomized double-blinded placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disorder characterized by progressive paralysis of voluntary muscles. Mecasin, the extract of modified jakyakgamchobuja-tang-a herbal preparation comprising of Radix Paeoniae Alba, Radix Glycyrrhizae, Radix Aconiti Lateralis Preparata, Radix Salviae Miltiorrhizae, Rhizoma Gastrodiae, Radix Polygalae, Curcuma Root, Fructus Chaenomelis, and Rhizoma Atractylodis Japonicae-shows neuroprotective and anti-neuroinflammatory effects and alleviates the symptoms in patients with ALS. AIM OF THE STUDY: This trial aimed to evaluate the efficacy and safety of mecasin in these patients. MATERIAL AND METHODS: Patients were randomized to receive mecasin 1.6 g daily, mecasin 2.4 g daily, or placebo for 12 weeks. The primary endpoint was the Korean version of ALS Functional Rating Scale-Revised (K-ALSFRS-R) score. The secondary endpoints were muscular atrophy measurements, pulmonary function test results, creatine kinase levels, body weight, safety, and scores of the Medical Research Council (MRC) scale for muscle strength; Visual Analog Scale for pain (VAS pain); Hamilton Rating Scale for Depression; and Fatigue Severity Scale. RESULTS: Among the 30 patients randomized, 24 completed the follow-up. Significant between-group differences were detected in the primary endpoint using the omnibus F-test. The changes in the K-ALSFRS-R score between 12 weeks and baseline were -0·25, -1·32, and -2·78 in the mecasin 1.6 g, mecasin 2.4 g, and placebo groups, respectively. The difference in the K-ALSFRS-R score between the mecasin 1.6 g and placebo groups was 2·53 points (95% confidence interval [CI]: 0·61-4·45), and that between the 2.4 g and placebo groups was 1·46 points (95% CI: 0·48-3·40). However, no significant differences were detected in the secondary endpoints (MRC: dyspnea, p = 0·139; VAS pain, p = 0·916; forced vital capacity, p = 0·373). The incidence of adverse events was similar and low in all groups. CONCLUSIONS: Mecasin may retard symptomatic progression without major adverse effects. A phase IIb study to evaluate its long-term effects in ALS is ongoing.

Efficacy of Curcumin on Cognitive Function Scores in Women with Premenstrual Syndrome and Dysmenorrhea: A Triple-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: To assess the efficacy of a curcumin supplementation on cognitive abilities in women suffering from premenstrual syndrome (PMS) and dysmenorrhea. METHODS: A randomized, triple-blind, placebo-controlled trial was conducted from December 2019 to March 2020. A total of 124 women who had both PMS and dysmenorrhea were enrolled, and were equally and randomly assigned to the curcumin group or placebo group, 62 cases in each. Each subject received either a capsule containing 500 mg of curcuminoid, or a placebo daily, for 10 days (7 days before and until 3 days after the onset of menstrual bleeding) over 3 menstrual cycles. The cognitive abilities questionnaire was used to measures cognitive functions in 7 specific areas. Adverse reactions were monitored during and after the trial in both groups. RESULTS: Administration of curcumin was associated with a significant increase in memory score (P=0.002), inhibitory control and selective attention (P=0.020), and total cognitive ability task (P=0.024). In addition, significant increments were found in scores of memory (3.5±3.1 vs. 0.4±3.8 in the curcumin and placebo groups, respectively; P=0.035), inhibitory control and selective attention (3.0±3.7 vs. 0.4±3.7; P=0.027) and total cognitive abilities (8.3±12.3 vs. 2.2±12.4; P=0.025) in the curcumin group versus placebo groups. Curcumin was safe and well-tolerable in current clinical trial. CONCLUSION: Curcumin has a beneficial efficacy on cognitive function scores in women with PMS and dysmenorrhea, with improvements in memory, inhibitory control and selective attention. (Registration No. IRCT20191112045424N1, available at: https://www.irct.ir ).

Effectiveness and safety of Qingfei Dayuan granules for treating influenza and upper respiratory tract infections manifested by the pulmonary heat-toxin syndrome: A multicenter, randomized, double-blind, placebo-controlled trial.

Background: Patients diagnosed with influenza and upper respiratory tract infections (URTIs) have similar clinical manifestations and biochemical indices and a low detection rate of viral pathogens, mixed infection with diverse respiratory viruses, and targeted antiviral treatment difficulty in the early stage. According to the treatment strategy of "homotherapy for heteropathy" in traditional Chinese medicine (TCM), different diseases with the same clinical symptoms can be treated with the same medicines. Qingfei Dayuan granules (QFDY), a type of Chinese herbal preparation included in the TCM Diagnosis and Treatment Protocol for COVID-19 of Hubei Province issued by the Health Commission of Hubei Province in 2021, are recommended for patients suffering from COVID-19 with symptoms of fever, cough, and fatigue, among others. Additionally, recent studies have shown that QFDY effectively alleviates fever, cough, and other clinical symptoms in patients with influenza and URTIs. Materials and methods: The study was designed as a multicenter, randomized, double-blind, placebo-controlled clinical trial for treatment for influenza and URTIs manifested by pulmonary heat-toxin syndrome (PHTS) with QFDY. A total of 220 eligible patients were enrolled from eight first-class hospitals in five cities of Hubei Province in China and randomly assigned to receive either 15 g of QFDY or a placebo three times a day for 5 days. The primary outcome was the complete fever relief time. Secondary outcomes included efficacy evaluation of TCM syndromes, scores of TCM syndromes, cure rate of each single symptom, incidence of comorbidities and progression to severe conditions, combined medications, and laboratory tests. Safety evaluations mainly involved adverse events (AEs) and changes in vital signs during the study. Results: Compared with the placebo group, the complete fever relief time was shorter in the QFDY group, 24 h (12.0, 48.0) in the full analysis set (FAS) and 24 h (12.0, 49.5) in the per-protocol set (PPS) (p ≤ 0.001). After a 3-day treatment, the clinical recovery rate (22.3% in the FAS and 21.6% in the PPS) and cure rate of cough (38.6% in the FAS and 37.9% in the PPS), a stuffy and running nose, and sneezing (60.0% in the FAS and 59.5% in the PPS) in the QFDY group were higher than those in the placebo group (p < 0.05). The number of patients taking antibiotics for more than 24 h in the placebo group (nine cases) was significantly higher than that in the QFDY group (one case) (p < 0.05). There were no significant differences between the two groups in terms of scores of TCM syndromes, incidence of comorbidities or progression to severe conditions, combined use of acetaminophen tablets or phlegm-resolving medicines, and laboratory tests (p > 0.05). Meanwhile, no significant difference was found in the incidence of AEs and vital signs between the two groups (p > 0.05). Conclusion: The trial showed that QFDY was an effective and safe treatment modality for influenza and URTIs manifested by PHTS because it shortened the complete fever relief time, accelerated clinical recovery, and alleviated symptoms such as cough, a stuffy and running nose, and sneezing during the course of treatment. Clinical trial registration: https://www.chictr.org.cn/showproj.aspx?proj=131702, identifier ChiCTR2100049695.

A Double-Blind, Randomized, Placebo-Controlled Study to Assess the Efficacy of a Nerve Support Formula on Neuropathic Pain in Individuals Suffering from Type II Diabetes Mellitus.

Background: The primary objective of the present study was to evaluate the effects of a Nerve Support Formula NeuropAWAY® on diabetic neuropathic pain. Methods: This double-blind, placebo-controlled, randomized trial was conducted between August 2020 and February 2021. Patients aged ≥40 and ≤65 years with a history of type 2 diabetes (T2D) with a confirmed diagnosis of diabetic neuropathic pain were included in the study. The primary efficacy endpoint was to assess the effect of the 42 days administration of the Nerve Support Formula on the neuropathic pain as assessed by the 11 point Pain Intensity Numeric Rating Scale (PI-NRS). The secondary objectives were to assess the effect on plasma vitamin B12 levels, nerve conduction velocity, blood flow velocity, Brief Pain Inventory, Neuropathy Total Symptom Score, and Insomnia Severity Index. Results: The enrolled study population (n=59) was randomized in two study groups; the Investigational Product (IP) group - Nerve Support Formula (n=27) and placebo group (n=32). The mean age of these participants was 52.63 and 53.72 for IP and placebo group, respectively. The mean (SD) HbA1c levels for IP and placebo group were 8.37 (0.85) and 8.16 (0.86), respectively. By the end of the study (Day 42) the decrease in PI-NRS scores for the IP group was maximal (↓61.32%) and highly significant (p<0.001) in comparison to the placebo group (↑2.47%). Significant improvements (p<0.05) were also noted in the secondary efficacy variables after 42 days of IP intake. Conclusion: The formula was found to be significantly effective as compared to placebo in reducing pain and other sensory symptoms related to the diabetic peripheral neuropathy.

The effectiveness of oxytocin for treating substance use disorders:A systematic review of randomized placebo-controlled trials.

Oxytocin is gaining traction in the treatment of various substance use disorders (SUD). We performed a systematic review assessing the efficacy of oxytocin for treating different SUD. The electronic databases MEDLINE, EMBASE, CENTRAL, and the Cochrane Database of Systematic Reviews were searched for randomized controlled trials examining the effects of oxytocin vs. placebo in SUD samples. Quality assessment was conducted using a Cochrane validated checklist. A total of 17 trials with unique samples were identified. These were conducted on participants with SUD involving alcohol (n = 5), opioids (n = 3), opioids and/or cocaine/other stimulants (n = 3), cannabis (n = 2), or nicotine (n = 4). Across the SUD-groups, oxytocin reduced withdrawal symptoms (3/5 trials), negative emotional states (4/11 trials), cravings (4/11 trials), cue-induced cravings (4/7 trials), and consumption (4/8 trials). Sixteen trials had an overall considerable risk of bias. In conclusion, although oxytocin showed some promising therapeutic effects, the findings are too inconsistent and the trials too heterogeneous to derive any firm conclusions. Sounder methodological and well-powered trials are warranted.

Immune-related microRNAs in breast milk and their relation to regulatory T cells in breastfed children.

BACKGROUND: The immunomodulatory capacity of breast milk may partially be mediated by microRNAs (miRNA), small RNA molecules that regulate gene expression on a post-transcriptional level and are hypothesized to be involved in modulation of immunological pathways. Here, we evaluate the expression of immune-related miRNAs in breast milk after pre- and postnatal supplementation with Limosilactobacillus reuteri and omega-3 (ω-3) polyunsaturated fatty acids (PUFAs), and the association to infant regulatory T cell (Treg) frequencies. METHODS: One-hundred and twenty women included in a double-blind, randomized, placebo-controlled allergy intervention trial received L. reuteri and/or ω-3 PUFAs daily from gestational week 20. Using Taqman qPCR, 24 miRNAs were analyzed from breast milk obtained at birth (colostrum) and after 3 months (mature milk) of lactation. The proportion of activated and resting Treg cells were analyzed in infant blood using flow cytometry at 6, 12, and 24 months. RESULTS: Relative expression changed significantly over the lactation period for most of the miRNAs; however, the expression was not significantly influenced by any of the supplements. Colostrum miR-181a-3p correlated with resting Treg cell frequencies at 6 months. Colostrum miR-148a-3p and let-7d-3p correlated with the frequencies of activated Treg cells at 24 months, as did mature milk miR-181a-3p and miR-181c-3p. CONCLUSION: Maternal supplementation with L. reuteri and ω-3 PUFAs did not significantly affect the relative miRNA expression in breast milk. Interestingly, some of the miRNAs correlate with Treg subpopulations in the breastfed children, supporting the hypothesis that breast milk miRNAs could be important in infant immune regulation. TRIAL REGISTRATION: ClinicalTrials.gov-ID: NCT01542970.

A proposal from the liver forum for the management of comorbidities in non-alcoholic steatohepatitis therapeutic trials.

The current document has been developed by the Liver Forum who mandated the NAFLD-Associated Comorbidities Working Group - a multistakeholder group comprised of experts from academic medicine, industry and patient associations - to identify aspects of diverse comorbidities frequently associated with non-alcoholic steatohepatitis (NASH) that can interfere with the conduct of therapeutic trials and, in particular, impact efficacy and safety results. The objective of this paper is to propose guidance for the management of relevant comorbidities in both candidates and actual participants in NASH therapeutic trials. We relied on specific guidelines from scientific societies, when available, but adapted them to the particulars of NASH trials with the aim of addressing multiple interacting requirements such as maintaining patient safety, reaching holistic therapeutic objectives, minimising confounding effects on efficacy and safety of investigational agents and allowing for trial completion. We divided the field of action into: first, analysis and stabilisation of the patient's condition before inclusion in the trial and, second, management of comorbidities during trial conduct. For the former, we discussed the concept of acceptable vs. optimal control of comorbidities, defined metabolic and ponderal stability prior to randomisation and weighed the pros and cons of a run-in period. For the latter, we analysed non-hepatological comorbid conditions for changes or acute events possibly occurring during the trial, including changes in alcohol consumption, in order to detail when specific interventions are necessary and how best to manage concomitant drug intake in line with methodological constraints. These recommendations are intended to act as a guide for clinical trialists and are open to further refinement when additional data become available.

A Phase Ⅲ Clinical Observation of Yishen Yangxin Anshen Tablets in Treatment of Insomnia with Deficiency of Heart Blood and Insufficiency of Kidney Essence / 中国实验方剂学杂志

ObjectiveTo confirm the clinical efficacy and safety of Yishen Yangxin Anshen tablets in the treatment of insomnia （heart-blood deficiency and kidney-essence insufficiency syndrome）. MethodA randomized block， double-blind， placebo-controlled， multi-center clinical trial design method was adopted， and a total of 480 patients with insomnia due to deficiency of heart blood and insufficiency of kidney essence （treatment group-control group 3∶1） from seven hospitals （Guang'anmen Hospital， China Academy of Chinese Medical Sciences， The First Clinical Hospital， Jilin Province Academy of Traditional Chinese Medicine（TCM）， The Second Affiliated Hospital of Liaoning University of TCM， The First Affiliated Hospital of Henan University of Chinese Medicine， Henan Province Hospital of TCM， Hebei General Hospital， The First Hospital of Hunan University of Chinese Medicine） were enrolled. The treatment group was given Yishen Yangxin Anshen tablets and the control group received placebo tablets （4 tablets/time， 3 times/day， 4 weeks of administration， 4 weeks of follow-up after drug withdrawal）. The sleep dysfunction rating scale （SDRS） score， pittsburgh sleep quality index （PSQI） score， TCM， polysomnography （PSG） indicators from four hospital （Guang'anmen Hospital， China Academy of Chinese Medical Sciences， Henan Province Hospital of TCM， Hebei General Hospital， The First Hospital of Hunan University of Chinese Medicine）， and other efficacy indicators were compared between the two groups before and after treatment. Through general physical examination， laboratory examination， and observation of adverse events， the safety of the drugs was evaluated. ResultThe baseline indexes of the two groups showed no significant difference and thus the two groups were comparable. After treatment， the total score of SDRS in the treatment group was lower than that in the control group （P<0.01）. After drug withdrawal for 4 weeks， the total score of SDRS demonstrated no significant change in the treatment group as compared with that at the end of treatment， indicating that the rebound change of curative effect was not obvious. After treatment， the total score of PSQI in the treatment group decreased as compared with that in the control group （P<0.01）， and the change of total score of PSQI in the treatment group was statistically significant （P<0.05） after drug withdrawal for 4 weeks but small， indicating that the rebound change of curative effect was not obvious. After treatment， the total effective rate about the TCM symptoms in the treatment group was higher than that in the control group （χ2=137.521，P<0.01）. After treatment， the disappearance rates of single indexes in the treatment group， such as difficulty in falling asleep， easily waking up after sleeping， early awakening， short sleep time， dreamfulness， palpitation， forgetfulness， dizziness， mental fatigue， and weakness of waist and knee， increased compared with those in the control group （P<0.01）. After treatment， the treatment group demonstrated fewer awaking times （AT）， longer total sleep time （TST）， lower ATA/TST ratio， and higher sleep efficiency （%） than the control group （P<0.05）. No abnormal value or aggravation related to drugs was observed in either group. The incidence of adverse events in the treatment group and the control group was 5.57% and 8.40% respectively. No serious adverse events or adverse events leading to withdrawal happened in either group. ConclusionYishen Yangxin Anshen tablets is effective and safe for patients with insomnia of deficiency of heart-blood and insufficiency of kidney-essence.

Efficacy of Curcumin on Cognitive Function Scores in Women with Premenstrual Syndrome and Dysmenorrhea: A Triple-Blind, Placebo-Controlled Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To assess the efficacy of a curcumin supplementation on cognitive abilities in women suffering from premenstrual syndrome (PMS) and dysmenorrhea.@*METHODS@#A randomized, triple-blind, placebo-controlled trial was conducted from December 2019 to March 2020. A total of 124 women who had both PMS and dysmenorrhea were enrolled, and were equally and randomly assigned to the curcumin group or placebo group, 62 cases in each. Each subject received either a capsule containing 500 mg of curcuminoid, or a placebo daily, for 10 days (7 days before and until 3 days after the onset of menstrual bleeding) over 3 menstrual cycles. The cognitive abilities questionnaire was used to measures cognitive functions in 7 specific areas. Adverse reactions were monitored during and after the trial in both groups.@*RESULTS@#Administration of curcumin was associated with a significant increase in memory score (P=0.002), inhibitory control and selective attention (P=0.020), and total cognitive ability task (P=0.024). In addition, significant increments were found in scores of memory (3.5±3.1 vs. 0.4±3.8 in the curcumin and placebo groups, respectively; P=0.035), inhibitory control and selective attention (3.0±3.7 vs. 0.4±3.7; P=0.027) and total cognitive abilities (8.3±12.3 vs. 2.2±12.4; P=0.025) in the curcumin group versus placebo groups. Curcumin was safe and well-tolerable in current clinical trial.@*CONCLUSION@#Curcumin has a beneficial efficacy on cognitive function scores in women with PMS and dysmenorrhea, with improvements in memory, inhibitory control and selective attention. (Registration No. IRCT20191112045424N1, available at: https://www.irct.ir ).

Iron supplementation in pregnant Danish women revisited: Effects on prepartum and postpartum iron deficiency, anemia, serum erythropoietin; including iron status, erythropoietin and anthropometrics in newborns. A randomized, placebo-controlled study.

OBJECTIVE: To assess effects of iron supplementation, 66 mg elemental iron daily as ferrous fumarate, on iron status markers during normal pregnancies. METHODS: Randomized, double-blind, placebo-controlled study of 119 women (62 iron-, 57 placebo -treated) and their newborns. Hemoglobin (Hb), serum (S)-ferritin, S-transferrin saturation percentage (TSAT) and S-erythropoietin (S-EPO) were measured at 14-18, 24-27 weeks of gestation, prepartum, 1 and 8 weeks postpartum. RESULT: From 24-27 weeks gestation to 8 weeks postpartum, the iron group had higher Hb, S-ferritin and TSAT than the placebo group; prepartum, 11% had iron deficiency (ID) and 0% iron deficiency anemia (IDA) in the iron group, vs 60% and 18% in the placebo group; 8 weeks postpartum 1.6% in the iron group had ID and 1.6% IDA vs 14% and 7% in the placebo group. S-EPO levels in the iron group were lower than in the placebo group (p < 0.001). Mothers prepartum S-EPO values were correlated to newborns cord S-EPO values (p < 0.001). Newborns to iron treated mothers had higher cord S-ferritin levels than those to placebo treated mothers (p = 0.02). Newborn girls had higher cord S-ferritin levels than boys (p < 0.01). There was no impact of iron supplementation on the length of gestation, placental weight, or newborns birth weight. Birth weight was correlated only with mothers' body weight, length of gestation and placental weight. CONCLUSION: Iron supplementation had a "positive" impact on iron status and Hb both during pregnancy and postpartum, with a low frequency of ID/IDA and also a "positive" influence on newborns iron status.

Effectiveness of Dry Needling in Bothersome Chronic Tinnitus in Patients with Myofascial Trigger Points

Abstract Introduction Therapeutic dry needling (DN) is effective in reducing the discomfort of chronic somatosensory tinnitus in patients with myofascial trigger points (MTP)s. Objective To evaluate the efficacy of DN in chronic somatosensory tinnitus discomfort in patients with MTP. Methods Placebo-controlled paired trial that included 16 patients with a diagnosis of somatosensory chronic tinnitus and with the presence of at least one active or latent MTP. Treatment was performed in two phases: (1) four sessions (one session per week for four consecutive weeks) of placebo DN and (2) four sessions of therapeutic DN with a gap (washout) of 15 days between these phases. Results The Tinnitus Handicap Inventory (THI) variable and its emotional domain had a statistically significant reduction in therapeutic DN when compared with placebo DN (p= 0.024 and p = 0.011, respectively). The tinnitus visual analogic scale (VAS) signaled a reduction in tinnitus discomfort when compared with moments before and after therapeutic DN (p< 0.05). Conclusion The therapeutic DN technique for MTP in patients with chronic tinnitus of somatosensory origin proved effective in reducing symptom discomfort, as measured by the THI (total score) and its emotional domain when compared with placebo DN.

Effect of Catechins on Upper Respiratory Tract Infections in Winter: A Randomized, Placebo-Controlled, Double-Blinded Trial.

Tea catechins are plant-derived compounds that improve immune functions. Previous randomized control trials have demonstrated the efficacy of primarily epi-type catechins against upper respiratory tract infections (URTIs). Green tea can be consumed in several ways, including popular bottled beverages. These beverages, however, require sterilization during manufacturing, which results in catechin isomerization. We conducted a randomized, double-blinded, placebo-controlled trial involving healthy Japanese participants to evaluate whether catechin consumption via bottled beverages has an alleviating effect on the duration and severity of URTIs in winter. The catechin group (490 mg catechin, 0.14%, containing 59% epi-type catechin, n = 55) showed reduced durations of running nose, nasal congestion, and headache, compared with the placebo group (0 mg catechin, n = 54; p = 0.013, 0.018, and <0.001, respectively). Furthermore, when considering physical symptoms, the duration of nasopharyngeal symptoms improved significantly in the catechin group (p < 0.001) compared with that in the control group. The daily consumption of catechin thus reduced the duration and severity of URTIs in healthy men and women. Humans are regularly exposed to several potential infectious threats, and the oral administration of heat-epimerized tea catechins might help prevent and reduce the severity of URTIs.