Number Of Trials Research Articles

A meta‐analysis of clinical studies of moxibustion for pressure ulcer healing

AbstractIn this study, we aimed to evaluate the effect of moxibustion on pressure ulcers. A thorough search was performed for articles published from database inception up to 14 December 2023. Randomized controlled trials, which evaluated the effects of moxibustion were included. Finally, 11 relevant trails that enrolled a total of 795 participants met inclusion criteria. The results of meta‐analysis suggested beneficial effects of moxibustion for pressure ulcer compared with control on the response rate (RR: 1.21; 95% CI: 1.13–1.29; p = 0.82; I2 = 0%), healing time (MD: −5.69; 95% CI: −9.58 to −1.80; p<0.05; I2 = 97%) and pressure ulcer scale for healing scores (MD: −1.13; 95% CI: −1.36 to −0.89; p = 0.79; I2 = 0%). The evidence suggests that moxibustion possesses satisfactory efficacy in promoting healing of pressure ulcers. However, due to the small number of trials included in this study, as well as the small sample size and high risk of bias, we were unable to draw firm conclusions about the effectiveness of moxibustion for pressure ulcers.

Effects of dry needling on pain, range of motion and function in patients with upper cross syndrome

Background: In upper cross syndrome, upper trapezius, levator scapulae, sub occipital, sternocleidomastoid, pectoralis major and minor become tight. Whereas, the phasic muscle including lower and middle trapezius, deep neck flexor and serratus anterior muscle weaken. Objectives: To determine the effects of dry needling on pain, range of motion and function in upper cross syndrome. Methods: This randomized clinical trial was conducted at Sheikh Zaid Hospital Rahim yar khan. Ethical approval REC/RCRS/20/1049 was obtained from Riphah International University Lahore. Group A was treated with dry needling along with conventional therapy and group B was treated with conventional therapy and 34 subjects were allocated in both groups. The duration of study was of 2 weeks with 1 session per week. The pre and post intervention scores were taken for Visual analogue scale, Neck disability index and neck range of motion. The data was analyzed using SPSS 25. Results: There was no significant difference (p<0.05) between groups based on demographic data at baseline. The BMI in group A was 24.38(1.14) and in group B 23.19(2.59). The mean difference of VAS in group A was 2.89(1.68) with CI [1.98, 3.76] (p<0.05) and in group B was 2.87(1.03) with CI [2.33,3.42] (p<0.05). The mean difference for NDI in group A was 21.25(10.85) with CI [15.46, 27.03] (p<0.05) and in Group B was 14.68(8.42) with CI [10.20,19.17] (p<0.05). In VAS and NDI between group analysis did not show significant result (p>0.05). Conclusion: Dry needling along with conventional therapy only improves range of motion but in term of pain and functionality, dry needling and conventional therapy are equally effective. Clinical Trial Number: NCT04674904

Meta-Analysis of Social Presence Effects on Stroop Task Performance.

In this paper, we conducted a meta-analytic review to examine the impact of social presence on individuals' performance on the Stroop task, shedding light on the cognitive processes underlying social facilitation. We followed PRISMA guidelines to identify and include 33 relevant studies in a multivariate random-effects meta-analysis. Our results show that social presence reliably modulates Stroop interference (a measure of cognitive control); specifically, participants exhibit lower Stroop interference when performing the task in the presence of others compared to performing it in isolation. We also found that the strength of the effect varies depending on the type of social presence: it is stronger with an attentive audience compared to an inattentive one, and null with an evaluative audience. Additionally, different features of the Stroop task itself moderate the effect; the effect is stronger for the classic version of the task compared to the semantic version, and for experiments that use mixed within-block trials compared to those with homogenous blocks. We also observed a negative relationship between the number of trials and the magnitude of the effect. Overall, these findings provide insights into the mechanisms by which the presence of others affects performance on the Stroop task, and how they align with social facilitation theories.

ESPEN practical short micronutrient guideline

BackgroundTrace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. The importance of MNs in common pathologies is recognized by recent research, with deficiencies significantly impacting the outcome. ObjectiveThis short version of the guideline aims to provide practical recommendations for clinical practice. MethodsAn extensive search of the literature was conducted in the databases Medline, PubMed, Cochrane, Google Scholar, and CINAHL for the initial guideline. The search focused on physiological data, historical evidence (for papers published before PubMed release in 1996), and observational and/or randomized trials. For each MN, the main functions, optimal analytical methods, impact of inflammation, potential toxicity, and provision during enteral or parenteral nutrition were addressed. The SOP wording was applied for strength of recommendations. ResultsThe limited number of interventional trials prevented meta-analysis and led to a low level of evidence for most recommendations. The recommendations underwent a consensus process, which resulted in a percentage of agreement (%): strong consensus required of >90% of votes. Altogether the guideline proposes 3 general recommendations and specific recommendations for the 26 MNs. Monitoring and management strategies are proposed. ConclusionThis short version of the MN guideline should facilitate handling of the MNs in at-risk diseases, whilst offering practical advice on MN provision and monitoring during nutritional support.

Impact of preconception and antenatal supplementation with myo-inositol, probiotics, and micronutrients on offspring BMI and weight gain over the first 2 years

BackgroundNutritional intervention preconception and throughout pregnancy has been proposed as an approach to promoting healthy postnatal weight gain in the offspring but few randomised trials have examined this.MethodsMeasurements of weight and length were obtained at multiple time points from birth to 2 years among 576 offspring of women randomised to receive preconception and antenatally either a supplement containing myo-inositol, probiotics, and additional micronutrients (intervention) or a standard micronutrient supplement (control). We examined the influence on age- and sex-standardised BMI at 2 years (WHO standards, adjusting for study site, sex, maternal parity, smoking and pre-pregnancy BMI, and gestational age), together with the change in weight, length, BMI from birth, and weight gain trajectories using latent class growth analysis.ResultsAt 2 years, there was a trend towards lower mean BMI among intervention offspring (adjusted mean difference [aMD] − 0.14 SD [95% CI 0.30, 0.02], p = 0.09), and fewer had a BMI > 95th percentile (i.e. > 1.65 SD, 9.2% vs 18.0%, adjusted risk ratio [aRR] 0.51 [95% CI 0.31, 0.82], p = 0.006). Longitudinal data revealed that intervention offspring had a 24% reduced risk of experiencing rapid weight gain > 0.67 SD in the first year of life (21.9% vs 31.1%, aRR 0.76 [95% CI 0.58, 1.00], p = 0.047). The risk was likewise decreased for sustained weight gain > 1.34 SD in the first 2 years of life (7.7% vs 17.1%, aRR 0.55 [95% CI 0.34, 0.88], p = 0.014). From five weight gain trajectories identified, there were more intervention offspring in the “normal” weight gain trajectory characterised by stable weight SDS around 0 SD from birth to 2 years (38.8% vs 30.1%, RR 1.29 [95% CI 1.03, 1.62], p = 0.029).ConclusionsSupplementation with myo-inositol, probiotics, and additional micronutrients preconception and in pregnancy reduced the incidence of rapid weight gain and obesity at 2 years among offspring. Previous reports suggest these effects will likely translate to health benefits, but longer-term follow-up is needed to evaluate this.Trial registrationClinicalTrials.gov, NCT02509988 (Universal Trial Number U1111-1171–8056). Registered on 16 July 2015.

The Impact of the Ecosystem on Health Literacy Among Rural Communities in Protected Areas: Protocol for a Mixed Methods Study.

Protected areas are crucial for the maintenance of human health and well-being. They aim to preserve biodiversity and natural resources to secure various ecosystem services that are beneficial to human health. Their ecological characteristics can influence local health literacy. Typically, communities surrounding protected areas have limited economic opportunities due to restriction policies to protect the ecosystem, resulting in socioeconomic disparities. The local community faces obstacles in gaining access to health care facilities and health information due to these limitations. It is difficult for them to locate, comprehend, and apply information and services to make better health-related decisions for themselves and others. This study protocol examines the impact of the ecosystem on health literacy among rural communities in protected areas. This study comprises 5 phases. In phase 1, we conduct a systematic review to identify the issue of health literacy in protected areas. In phase 2, we will collect data from stakeholders in a protected area of Pahang National Park and analyze the results using Net-Map analysis. In phase 3, we will conduct a survey among the adult community in Pahang National Park related to health literacy, socioeconomic status, health expenditure, and quality of life. In phase 4, informed by the results of the survey, we will determine suitable intervention programs to improve health literacy through a focus group discussion. Finally, in phase 5, we will conduct a costing analysis to analyze which intervention program is the most cost-effective. This study was funded by Universiti Sains Islam Malaysia (USIM) and strategic research partnership grants, and enrollment is ongoing. The first results are expected to be submitted for publication in 2024. This is one of the first studies to explore health literacy among rural communities in protected areas and will provide the first insights into the overall level of health literacy in the protected community, potential determinants, and a suitable intervention program with expected cost analysis. The results can be used to promote health literacy in other protected areas and populations. International Standard Randomized Controlled Trial Number Registry ISRCTN40626062; http://tinyurl.com/4kjxuwk5. PRR1-10.2196/51851.

Changes in patient care through flexible and integrated treatment programs in German psychiatric hospitals: meta-analyses based on a series of controlled claims-based cohort studies

BackgroundGlobal treatment budgets, i.e. predefined budgets for patients treated in hospital independent of the setting within the hospital, together with flexible and integrated treatment (FIT) have been introduced in some German psychiatric hospitals since 2013. We investigated pooled changes in inpatient, day-care, outpatient treatment, and continuity of care for patients with mental disorders in 12 FIT-hospitals.MethodsWe conducted a series of 12 controlled cohort studies regarding FIT hospitals using anonymized patient claims data from more than 70 German statutory health insurance funds. Each study compared one FIT-hospital to matched patients from equivalent non-FIT-hospitals (routine care). We included only those patients without treatment in the respective hospital within two years prior to first hospital treatment (either FIT or routine care). We contrasted results between the year prior to with the first and second year after patient’s first treatment (treatment continuity: only group comparison) using multivariate multi-level models. To approximate the difference-in-difference effect in the meta-analysis, we used the interaction terms group (FIT hospital vs. routine care) x time (year before vs. first or second patient year after study inclusion) in the Poisson models.ResultsThe 12 studies included 36,069 patients with 2,358 patients from a Department of child and adolescent psychiatry. The pooled effect revealed a 5.1 days lower increase in inpatient treatment in FIT-hospitals during the first patient year compared to routine care. Results were statistically significant for adult care FIT-hospitals but not for child and adolescent FIT-hospitals. Utilization of day-care treatment increased more in most FIT-hospitals during the first year, while outpatient contacts increased in some and decreased in others. The odds of treatment continuity increased by 1.4 in FIT-hospitals compared to non-FIT-hospitals.ConclusionsGlobal treatment budgets lead to the intended changes in mental health care in the majority of FIT-hospitals compared to routine care in this large real-world evidence study from Germany. For child and adolescent psychiatry, more evidence is needed to draw firm conclusions.Trial registrationThis study was registered in the database “Health Services Research Germany” (trial number: VVfD_EVA64_15_003713).

Standard vs. targeted oxygen therapy prehospitally for chronic obstructive pulmonary disease (STOP-COPD): study protocol for a randomised controlled trial

BackgroundA high concentration of inspired supplemental oxygen may possibly cause hypercapnia and acidosis and increase mortality in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Even so, patients with AECOPD are being treated with high oxygen flow rates when receiving inhalation drugs in the prehospital setting. A cluster-randomised controlled trial found that reduced oxygen delivery by titrated treatment reduced mortality—a result supported by observational studies—but the results have never been reproduced. In the STOP-COPD trial, we investigate the effect of titrated oxygen delivery compared with usual care consisting of high flow oxygen delivery in patients with AECOPD in the prehospital setting.MethodsIn this randomised controlled trial, patients will be blinded to allocation. Patients with suspected AECOPD (n = 1888) attended by the emergency medical service (EMS) and aged > 40 years will be allocated randomly to either standard treatment or titrated oxygen, targeting a blood oxygen saturation of 88–92% during inhalation therapy. The trial will be conducted in the Central Denmark Region and include all ambulance units. The power to detect a 3% 30-day mortality risk difference is 80%. The trial is approved as an emergency trial. Hence, EMS providers will include patients without prior consent.DiscussionThe results will provide evidence on whether titrated oxygen delivery outperforms standard high flow oxygen when used to nebulise inhaled bronchodilators in AECOPD treatment. The trial is designed to ensure unselected inclusion of patients with AECOPD needing nebulised bronchodilators—a group of patients that receives high oxygen fractions when treated in the prehospital setting where the only compressed gas is generally pure oxygen. Conducting this trial, we aim to improve treatment for people with AECOPD while reducing their 30-day mortality.Trial registrationEuropean Union Clinical Trials (EUCT) number: 2022-502003-30-00 (authorised 06/12/2022), ClinicalTrials.gov number: NCT05703919 (released 02/02/2023), Universal trial number: U1111-1278-2162.

Plant stanol consumption increases anti-COVID-19 antibody responses, independent of changes in serum cholesterol concentrations: a randomized controlled trial

BackgroundPeople with overweight/obesity generally have impaired immune responses, resulting among others in increased risk of severe complaints and hospitalization after infections with severe acute respiratory syndrome coronavirus 2 (COVID-19), as well as decreased antibody production after vaccinations. Plant stanol ester previously increased the combined IgM/IgG antibody titers toward a hepatitis A vaccination in patients with allergic asthma, but the underlying mechanism is unknown. ObjectivesWe evaluated whether plant stanol ester consumption improved the immune response in subjects with overweight/obesity after a COVID-19 vaccination. MethodsA double-blind, randomized, placebo-controlled trial was performed. Thirty-two subjects with overweight/obesity consumed products with added plant stanols (4 g/d; provided as plant stanol ester) or control ≥2 wk before receiving their COVID-19 vaccination until 4 wk after vaccination. Antibody titers were analyzed weekly and statistically analyzed using mixed models. Serum metabolic markers and cytokine profiles were also analyzed. ResultsIgM concentrations against the COVID-19 Spike protein were increased in the plant stanol ester group compared with the control group, with the largest difference observed 2 wk after vaccination [31.2 (0.43, 62.1) BAU/mL, or +139%; Group × Time: P = 0.031]. Subjects that produced very low IgM antibodies produced, as expected, hardly any IgG antibodies. In those with IgG seroconversion, IgG Spike concentrations were also increased in the plant stanol ester group compared with the control group [71.3 (2.51, 140.1) BAU/mL; Group P = 0.043]. Stimulated cytokine concentrations decreased in the plant stanol ester group compared with the control group in all 3 cytokine domains (that is, proinflammatory, T helper [Th1]/Th17, and Th2/regulatory T cells). Between-group differences in serum LDL cholesterol or other metabolic markers were not observed. ConclusionsConsuming plant stanols (4 g/d) affects immune responses to COVID-19 vaccinations, translating into increased serum anti-COVID-19 IgM concentrations in subjects with overweight/obesity. Only in IgG seroconverted subjects, serum anti-COVID-19 IgG concentrations also increase. These effects are independent of reductions in LDL cholesterol. These results suggest that this high-risk group for COVID-19 complications could benefit from plant stanol consumption.This trial was registered at clinicaltrials.gov as NCT04844346.

The Role of Pharmacovigilance in Investigational New Drug (IND) Clinical Trials

The total number of clinical trials registered so far across India was 63,174. Clinical trials from India accounted for only 8.7% of the total number of trials conducted, while clinical trials from the US accounted for 47% of the total number of trials registered, followed by 24% from the EU and 13.1% from Japan. We can increase the number of clinical trials by ensuring the role of pharmacovigilance in investigational new drug (IND) clinical trials in ensuring safety, efficacy and ethical conduct of pharmaceutical research. As pharmaceutical companies advance novel compounds through clinical development, pharmacovigilance serves as a comprehensive system for the detection, assessment, and mitigation of potential risks associated with investigational drugs. This perspective review explores the multifaceted role of pharmacovigilance in IND clinical trials, emphasizing its significance in safeguarding trial participants and contributing to the overall success of drug development programs. Underscores the critical role of pharmacovigilance in investigational new drug clinical trials From pre-trial planning to post-marketing surveillance, pharmacovigilance is integral in maintaining the safety, integrity, and ethical conduct of clinical research. As an essential component of the drug development process, pharmacovigilance contributes to the overarching goal of delivering safe and efficacious treatments to patients and can be increase the clinical trial participation globally

Efficacy, Effectiveness, and Safety of Interventions for Von Hippel-Lindau Associated Renal Cell Carcinoma: A Systematic Literature Review

Background: A small proportion of renal cell carcinoma (RCC) are associated with hereditary syndromes such as von Hippel-Lindau disease (VHL) and are commonly treated with surgical interventions. More recently, systemic treatments for VHL-associated RCC have been assessed as an alternative to surgery. Methods: A systematic literature review was conducted by searching MEDLINE, EMBASE, and Cochrane Registry of Controlled Trials to collect and interpret published evidence on treatments for VHL-associated RCC patients to better understand the treatment landscape. Results: This review identified 32 primary studies, comprised of single-arm clinical trials and real-world studies assessing systemic, surgical, radiological, or image guided ablation interventions. In clinical trials, treatment with sunitinib and pazopanib showed an objective response in 33% and 52% of RCC lesions respectively. For patients treated with belzutifan, 64% of patients showed an objective response, of which 7% were complete response and 57% were partial responses with a 24-month PFS rate of 96%. In real-world studies, treatment with sunitinib, pazopanib, axitinib, and sorafenib showed an objective response in 40%, 0%, 33%, and 25% of RCC lesions respectively, and all the responses were partial. In the studies assessing surgical, radiological, or image guided ablation interventions primary failure/re-intervention rates ranged from 2% to 84%. Conclusion: Local procedures are still a mainstay in the management of patients with non-metastatic VHL-associated RCC although multiple procedures incur an increasing rate of complications. A limited number of clinical trials and real-world studies evaluated VEGF-TKIs for the treatment of VHL-RCC, while responses were observed, long term treatment was limited by toxicities.

Adjuvant Therapy in Renal Cell Cancer

A number of adjuvant trials have attempted to improve outcomes for patients following nephrectomy for renal cell carcinoma (RCC). This was initially with cytokines and then Vascular Endothelial Growth Factor (VEGF) targeted therapies. More recently, a series of adjuvant immune checkpoint inhibitor (ICI) studies have been published. To date, only the KEYNOTE— 564 study using adjuvant pembrolizumab has positive Disease-Free Survival (DFS) data with an acceptable toxicity profile. There are many negative ICI and anti-VEGF adjuvant trials, which raises uncertainty. Further randomised trials may be required but importantly biomarker studies are needed to identify those individuals who may benefit from adjuvant therapy.

Effect of sesame supplementation on body composition and lipid profile in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials

AimsThe aim of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) that evaluated the impact of sesame supplementation on body weight (BW), body mass index (BMI), triglycerides (TGs), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) in patients with type 2 diabetes mellitus (T2DM). Data synthesisPubMed, Scopus, ISI Web of Science, and Embase were searched without any restrictions until September 2023.Only RCTs reporting the effects of sesame supplementation on body composition and lipid profiles were included, while observational studies and animal models were excluded. The methodological quality of the studies was assessed using the Cochrane risk of bias tool. Out of 997 studies identified, 10 were included in the systematic review and meta-analysis. Our meta-analysis suggested a significant association between sesame supplementation and reduction in TG (weighted mean difference (WMD): −37.61 mg/dl, 95 % CI: −61.48, 13.73), TC (WMD: −32.69 mg/dl, 95 % CI: −47.26, 18.12), and LDL-C (WMD: −28.72 mg/dl, 95 % CI: −44.68, 12.76). However, our meta-analysis indicated that the supplementary intake of sesame had no significant effect on HDL-C, BW, and BMI in patients with T2DM. ConclusionsThis study showed that sesame consumption significantly lowered TG, TC, and LDL-C levels, which may have contributed to the improvement of clinical symptoms in T2DM. However, given the limited number of trials included in the analysis, additional large-scale studies are needed to confirm the effects of sesame consumption on the lipid profile and body composition in patients with T2DM. Prospero codeCRD42023460630.

May the force be with you: exploring force discrimination in chimpanzees using the force-feedback device.

While force-feedback devices have been developed in areas such as virtual reality, there have been very few comparative cognitive studies in nonhuman animals using these devices. In addition, although cross-modal perception between vision and touch has been actively studied in nonhuman primates for several decades, there have been no studies of their active haptic perception. In this study, we attempted to train force discrimination in chimpanzees using a force-feedback device modified from a trackball. Chimpanzees were given different levels of force feedback (8.0 vs. 0.5N) when moving the on-screen cursor to the target area by manipulating the trackball and were required to select one of two choice stimuli based on the force cue. The experiment was conducted using a trial-block procedure in which the same force stimulus was presented for a fixed number of trials, and the force stimulus was changed between blocks. The block size was progressively reduced from ten trials. Four chimpanzees were trained, but none reached the learning criterion (80% or more correct responses under the condition that the force stimuli were presented randomly). However, a detailed analysis of the chimpanzees' performance before and after the trial-block switching revealed that their choice behavior could not be explained by a simple win-stay/lose-shift strategy, suggesting that the switching of the force stimuli affected the chimpanzees' choice behavior. It was also found that the chimpanzees performed better when switching from small to large force stimuli than when switching from large to small force stimuli. Although none of the chimpanzees in this study acquired force discrimination, future studies using such force-feedback devices will provide new insights for understanding haptic cognition in nonhuman primates from a comparative cognitive perspective.

Genome-wide DNA methylation status to predict the efficacy of modified (m)-FOLFOXIRI plus cetuximab as initial treatment for RAS wild-type metastatic colorectal cancer: A biomarker study of the DEEPER trial (JACCRO CC-13AR).

152 Background: Genome-wide DNA methylation status (GWMS) has been shown to be a predictor of therapeutic response to anti-EGFR antibody therapies. This study investigated the association between GWMS and clinical outcomes of first-line chemotherapy with anti-EGFR or anti-VEGF antibody agents for metastatic colorectal cancer (mCRC). Methods: Tumor tissues of mCRC patients registered in the JACCRO CC-13AR (clinical trial number: UMIN000018412) were analyzed for GWMS and were classified into low-methylated colorectal cancer (LMCC) and high-methylated colorectal cancer (HMCC). Clinical data were obtained from the randomized phase II trial, DEEPER trial (JACCRO CC-13) [NCT02515734], in which patients were randomly assigned to m-FOLFOXIRI plus cetuximab (CET) arm and m-FOLFOXIRI plus bevacizumab (BEV) arm for treatment. Progression-free survival (PFS), overall survival (OS), depth of response (DpR), and response rate (RR) were analyzed according to GWMS for each treatment arm. Results: One hundred thirty-seven out of 227 patients enrolled in the JACCRO CC-13AR were analyzed. Of these, 122 (89.1%) and 15 (10.9%) were classified in the LMCC and HMCC, respectively; 66 were assigned to the CET arm including 7 HMCCs, and 54 were assigned to the BEV arm including 8 HMCCs. In the CET arm, PFS and OS of the LMCC were significantly longer than those of the HMCC (median PFS 14.3 vs. 4.0 months, hazard ratio [HR] 0.11, 95% CI: 0.05–0.29, P<0.01; median OS 42.7 vs. 13.6 months, HR 0.04, 95% CI: 0.01–0.13, P<0.01). There were no differences in DpR and RR between the LMCC and the HMCC (median DpR 58.1% vs. 46.7%, P=0.45), although RR of the LMCC was numerically higher than that of the HMCC (71.2% vs. 42.9%, P=0.13). In contrast, in the BEV arm, there were no differences in PFS, DpR, and RR between the two groups (median PFS 16.1 vs. 12.2 months, P=0.08; median DpR 48.3% vs. 53.9%, P=0.99; RR 73.0% vs. 75.0%, P=0.91). However, OS of the LMCC was significantly longer than that of the HMCC (median OS 48.9 vs. 24.2 months, HR 0.39, 95% CI: 0.16–0.95, P=0.03). Conclusions: This study showed that GWMS may be a prognostic marker for initial treatment in RAS wild-type mCRC. Also, GWMS correlates to the survival outcomes of m-FOLFOXIRI plus CET as initial treatment for RAS wild-type mCRC. Clinical trial information: 000018412 .

Parkinson's Disease and Photobiomodulation: Potential for Treatment.

Parkinson's disease is the second most common neurodegenerative disease and is increasing in incidence. The combination of motor and non-motor symptoms makes this a devastating disease for people with Parkinson's disease and their care givers. Parkinson's disease is characterised by mitochondrial dysfunction and neuronal death in the substantia nigra, a reduction in dopamine, accumulation of α-synuclein aggregates and neuroinflammation. The microbiome-gut-brain axis is also important in Parkinson's disease, involved in the spread of inflammation and aggregated α-synuclein. The mainstay of Parkinson's disease treatment is dopamine replacement therapy, which can reduce some of the motor signs. There is a need for additional treatment options to supplement available medications. Photobiomodulation (PBM) is a form of light therapy that has been shown to have multiple clinical benefits due to its enhancement of the mitochondrial electron transport chain and the subsequent increase in mitochondrial membrane potential and ATP production. PBM also modulates cellular signalling and has been shown to reduce inflammation. Clinically, PBM has been used for decades to improve wound healing, treat pain, reduce swelling and heal deep tissues. Pre-clinical experiments have indicated that PBM has the potential to improve the clinical signs of Parkinson's disease and to provide neuroprotection. This effect is seen whether the PBM is directed to the head of the animal or to other parts of the body (remotely). A small number of clinical trials has given weight to the possibility that using PBM can improve both motor and non-motor clinical signs and symptoms of Parkinson's disease and may potentially slow its progression.

Efficacy and safety of insulin glargine 300 units/mL vs insulin degludec in patients with type 1 and type 2 diabetes: a systematic review and meta-analysis.

Ultra-long-acting insulin analogs [insulin degludec (IDeg) and insulin glargine 300 units/mL (IGla-300)] offer a longer duration of action with less risk of hypoglycemia compared to other long-acting insulins. However, data about the comparative efficacy and safety are inconsistent. We searched CENTRAL, PubMed, Embase, ICTRP Search Portal, and ClinicalTrials.gov on 7 October 2022. Randomized controlled trials (RCTs) comparing the safety and efficacy of IDeg (100 or 200 units/mL) and IGla-300 in patients with type 1 or type 2 diabetes were included. Three review authors independently selected trials, assessed the risk of bias, extracted data, and evaluated the overall certainty of the evidence using GRADE. The primary outcomes were the change in glycated hemoglobin (HbA1c) and any hypoglycemia; the secondary outcomes were the change in fasting plasma glucose (FPG) and severe and nocturnal hypoglycemia. Four open-label RCTs were included (2727 participants), 3 parallel and 1 cross-over. Overall, the risk of bias assessment yielded some concern or high risk. There was a comparable change in HbA1c from baseline to the end of treatment, a mean difference of 0.07% (95% confidence interval (CI) 0.06 - 0.19; p = 0.29; 3 trials; 2652 patients; very low-certainty evidence), and a comparable rate of any hypoglycemia, rate ratio 1.02 (95% CI 0.8 - 1.3; p = 0.87; 3 trials; 2881 patients; very low-certainty evidence). IDeg resulted in more reduction in FPG compared to IGla-300, mean difference of 10.27 mg/dL (95% CI 7.25 - 13.29; p < 0.001; 3 trials; 2668 patients; low-certainty evidence). Similar rates of nocturnal and severe hypoglycemia were observed, rate ratio of 1.13 (95% CI 0.72 - 1.78; p = 0.54; 3 trials; 2668 patients; very low-certainty evidence) and 1.4 (95% CI 0.41 - 4.73; p = 0.59; 2 trials; 1952 patients; very low-certainty evidence), respectively. There is no evidence of a difference between IDeg and IGla-300 in the mean change in HbA1c and the risk of anytime, nocturnal, and severe hypoglycemia. IDeg appeared to cause a higher reduction in FPG compared to IGla-300. However, this finding should be interpreted with caution due to the small number of trials included and their high risk of bias. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022364891, identifier CRD42022364891.

Time-series blood cytokine profiles correlate with treatment responses in triple-negative breast cancer patients.

Triple-negative breast cancer (TNBC) is the most heterogeneous breast cancer subtype. Partly due to its heterogeneity, it is currently challenging to stratify TNBC patients and predict treatment outcomes. In this study, we examined blood cytokine profiles of TNBC patients throughout treatments (pre-treatment, during chemotherapy, pre-surgery, and 1 year after the surgery in a total of 294 samples). We analyzed the obtained cytokine datasets using weighted correlation network analyses, protein-protein interaction analyses, and logistic regression analyses. We identified five cytokines that correlate with good clinical outcomes: interleukin (IL)-1α, TNF-related apoptosis-inducing ligand (TRAIL), Stem Cell Factor (SCF), Chemokine ligand 5 (CCL5 also known as RANTES), and IL-16. The expression of these cytokines was decreased during chemotherapy and then restored after the treatment. Importantly, patients with good clinical outcomes had constitutively high expression of these cytokines during treatments. Protein-protein interaction analyses implicated that these five cytokines promote an immune response. Logistic regression analyses revealed that IL-1α and TRAIL expression levels at pre-treatment could predict treatment outcomes in our cohort. We concluded that time-series cytokine profiles in breast cancer patients may be useful for understanding immune cell activity during treatment and for predicting treatment outcomes, supporting precision medicine. The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index-j.htm ) with the unique trial number UMIN000023162. The association Japan Breast Cancer Research Group trial number is JBCRG-22. The clinical outcome of the JBCRG-22 study was published in Breast Cancer Research and Treatment on 25 March 2021. https://doi.org/10.1007/s10549-021-06184-w .

Analysis of the Current Situation of Drug Clinical Trial Institutions in Shaanxi Province

To understand the current situation of institutional registration in Shaanxi Province after the implementation ofregistration system management in drug clinical trial institutions. Relevant information was collected on the “Announcement on the Accreditation of Drug Clinical Trial Institutions” issued by the National Medical Products Administration from 2005 to August 2022, the record management information system of drug and medical device clinical trial institutions, and the drug clinical trial registration and information publicity platform. A retrospective analysis was carried out in terms of institutional development, regional distribution, registered majors, principal investigators, and the number of drug clinical trials. After the implementation of institution registration, the number of drug clinical trial institutions in Shaanxi Province increased by 47.4%, 884 principal investigators were registered, the number of registered majors expanded from 58 qualified to 117, and the professional scope increased by 50.4%. The policy of institution registration is conducive to promoting the rational use of medical resources and the development of drug clinical trial institutions and improving the healthy development of the pharmaceutical industry in Shaanxi Province.

The use of melatonin in the treatment of irritable bowel syndrome: a systematic review of randomized placebo-controlled clinical trials

Introduction. One of the most prevalent functional disorders of the gastrointestinal system, irritable bowel syndrome (IBS), significantly affects patients’ quality of life. At the moment, only symptomatic drugs are used to treat this disorder. Although using melatonin can be thought of as a form of pathogenetic therapy, its efficacy has not yet been conclusively demonstrated. This systematic review of randomized placebo controlled clinical trials reviews current data on the evaluation of the efficacy of melatonin in patients with IBS. Material and research methods. The search and selection of publications was carried out in the PubMed, ScienceDirect, ClinicalTrials.gov, Cochrane Library, eLibrary, medRxiv and International Clinical Trials Registry Platform databases from their publication until October 30, 2022. Results. The inclusion criteria were met by four randomized placebo-controlled trials, totaling 155 participants, and these trials were included in the subsequent analysis. All investigations revealed a considerable reduction in the frequency and severity of bloating, as well as a tendency for other intestinal symptoms to regress. Two trials reported an improvement in patients’ quality of life, albeit one of the studies did not find these changes to be statistically significant, and the other did not assess them. This review demonstrates that melatonin is effective in treating IBS by lowering the frequency and severity of the condition’s symptoms in the vast majority of published RCTs. The poor number and sample size of clinical trials, along with their inadequate methodological quality, prevent us from drawing any firm conclusions about the contribution of melatonin to the improvement of IBS patients’ quality of life. To confirm melatonin’s significance in the treatment of IBS patients, larger studies are required to assess its efficacy and safety when used in various doses.