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PLoS Medicine Jun 2024Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting...
BACKGROUND
Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. We conducted a multicenter, randomized, partially blinded Phase I clinical trial to evaluate the safety and serum concentrations of VRC07-523LS, administered in multiple doses and routes to healthy adults without HIV.
METHODS AND FINDINGS
Participants were recruited between 2 February 2018 and 9 October 2018. A total of 124 participants were randomized to receive 5 VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), subcutaneous (SC) (T4: 2.5 mg/kg, T5: 5 mg/kg), or intramuscular (IM) (T6: 2.5 mg/kg or P6: placebo) routes at 4-month intervals. Participants and site staff were blinded to VRC07-523LS versus placebo for the IM group, while all other doses and routes were open-label. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum PK. Neutralization activity was measured in a TZM-bl assay and antidrug antibodies (ADAs) were assayed using a tiered bridging assay testing strategy. Injections and infusions were well tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusion reactions reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals [95% CIs]) following the first administration were 29.0 μg/mL (25.2, 33.4), 58.5 μg/mL (49.4, 69.3), and 257.2 μg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 μg/mL (8.8, 13.3) and 22.8 μg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 μg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM (95% CIs) concentrations immediately prior to the second administration were 3.4 μg/mL (2.5, 4.6), 6.5 μg/mL (5.6, 7.5), and 27.2 μg/mL (23.9, 31.0) with IV dosing; 0.97 μg/mL (0.65, 1.4) and 3.1 μg/mL (2.2, 4.3) with SC dosing, and 2.6 μg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titers, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A single participant was found to have low titer ADA at a lone time point. VRC07-523LS has an estimated mean half-life of 42 days across all doses and routes (95% CI: 40.5, 43.5), over twice as long as VRC01 (15 days).
CONCLUSIONS
VRC07-523LS was safe and well tolerated across a range of doses and routes and is a promising long-acting bnAb for inclusion in HIV-1 prevention regimens.
TRIAL REGISTRATION
ClinicalTrials.gov/ NCT03387150 (posted on 21 December 2017).
PubMed: 38913710
DOI: 10.1371/journal.pmed.1004329 -
Microbiology Spectrum Jun 2024Vaginal colonization by fungi may elicit genital inflammation and enhance the risk of adverse reproductive health outcomes, such as HIV acquisition. Cross-sectional...
Vaginal colonization by fungi may elicit genital inflammation and enhance the risk of adverse reproductive health outcomes, such as HIV acquisition. Cross-sectional studies have linked fungi with an absence of bacterial vaginosis (BV), but it is unclear whether shifts in vaginal bacteria alter the abundance of vaginal fungi. Vaginal swabs collected following topical metronidazole treatment for BV during the phase 2b, placebo-controlled trial of LACTIN-V, a -based live biotherapeutic, were assayed with semi-quantitative PCR for the relative quantitation of fungi and key bacterial species and multiplex immunoassay for immune factors. Vaginal fungi increased immediately following metronidazole treatment for BV (adjusted = 0.0006), with most of this increase attributable to . Vaginal fungi were independently linked to elevated levels of the proinflammatory cytokine interleukin (IL) 17A, although this association did not remain significant after correcting for multiple comparisons. Fungal relative abundance by semi-quantitative PCR returned to baseline levels within 1 month of metronidazole treatment and was not affected by LACTIN-V or placebo administration. Fungal abundance was positively associated with species, negatively associated with BV-associated bacteria, and positively associated with a variety of proinflammatory cytokines and chemokines, including IL-17A, during and after study product administration. Antibiotic treatment for BV resulted in a transient expanded abundance of vaginal fungi in a subset of women which was unaffected by subsequent administration of LACTIN-V. Vaginal fungi were positively associated with species and IL-17A and negatively associated with BV-associated bacteria; these associations were most pronounced in the longer-term outcomes.IMPORTANCEVaginal colonization by fungi can enhance the risk of adverse reproductive health outcomes and HIV acquisition, potentially by eliciting genital mucosal inflammation. We show that standard antibiotic treatment for bacterial vaginosis (BV) results in a transient increase in the absolute abundance of vaginal fungi, most of which was identified as . Vaginal fungi were positively associated with proinflammatory immune factors and negatively associated with BV-associated bacteria. These findings improve our understanding of how shifts in the bacterial composition of the vaginal microbiota may enhance proliferation by proinflammatory vaginal fungi, which may have important implications for risk of adverse reproductive health outcomes among women.
PubMed: 38912808
DOI: 10.1128/spectrum.03501-23 -
Heliyon Jun 2024Clinical benefit of Alpha-Proteinase Inhibitor (Human) (A-PI) products for Alpha-antitrypsin deficiency (AATD) is uncertain, based on a systematic review of... (Review)
Review
Clinical benefit of Alpha-Proteinase Inhibitor (Human) (A-PI) products for Alpha-antitrypsin deficiency (AATD) is uncertain, based on a systematic review of observational studies and randomized controlled trials (RCTs) in AATD of Alpha-Proteinase Inhibitor (Human) (A-PI) products. At the recommended dose, A-PI products raise its serum concentration but do not normalize levels. Observational studies suggest A-PI might modestly slow progression of airflow limitation in patients with intermediate airflow obstruction, a finding not confirmed by three placebo-controlled RCTs of limited power, which showed non-significant rates of forced expiratory volume in 1 s (FEV) change favoring placebo. These RCTs found trends favoring A-PI in loss of high-resolution computerized tomographic (HRCT) lung density. While two meta-analyses of HRCT lung density change in RCTs achieved significance favoring A-PI arms, clinical benefit remains uncertain. HRCT lung density measurements don't distinguish changes in measured density due to fluid shifts into and out of the lungs and changes in lung inflammation from those due to progressive loss of alveolar mass. A meta-analysis of RCTs found exacerbations significantly increased in A-PI groups compared to placebo. No RCTs have shown favorable effects of A-PI on mortality, FEV, 6-min walking distance, quality of life, change in diffusion capacity of carbon monoxide (DL, or exacerbation frequency. A fourth RCT comparing two dose regimens of A-PI is underway. RCTs have not provided evidence of clinical benefit in terms of how patients feel, function, or survive. Results have implications for the design of future clinical trials of A-PI and potentially other products targeting AATD-associated emphysema.
PubMed: 38912501
DOI: 10.1016/j.heliyon.2024.e31183 -
Frontiers in Neurology 2024Treatment for post-traumatic greater occipital neuralgia (GON) includes serial injections of steroid/anesthetic. While these injections can alleviate pain, effects can...
BACKGROUND
Treatment for post-traumatic greater occipital neuralgia (GON) includes serial injections of steroid/anesthetic. While these injections can alleviate pain, effects can be transient, frequently lasting only 1 month. As a potential alternative, platelet-rich plasma (PRP) injections are an emerging biological treatment with beneficial effects in peripheral nerve disorders. We investigated the feasibility, safety, and effectiveness of a single PRP injection for post-traumatic GON in comparison to saline or steroid/anesthetic injection.
METHODS
In this pilot randomized, double-blinded, placebo-controlled trial, 32 adults with post-traumatic GON were allocated 1:1:1 to receive a single ultrasound-guided injection of (1) autologous PRP (2) steroid/anesthetic or (3) normal saline. Our primary outcome was feasibility (recruitment, attendance, retention) and safety (adverse events). Exploratory measures included headache intensity and frequency (daily headache diaries) and additional questionnaires (headache impact, and quality of life) assessed at pre-injection, 1 week, 1 month, and 3 months post-injection.
RESULTS
We screened 67 individuals, 55% were eligible and 95% of those participated. Over 80% of daily headache diaries were completed with 91% of participants completing the 3-month outcome questionnaires. No serious adverse events were reported. There were no significant differences between groups for headache intensity or frequency. Headache impact on function test-6 scores improved at 3 month in the PRP ( = -9.7, 95% CI [-15.6, -3.74], = 0.002) and saline ( = -6.7 [-12.7, -0.57], = 0.033) groups but not steroid/anesthetic group ( = 0.135).
CONCLUSION
PRP is a feasible and safe method for treating post-traumatic GON with comparable results to saline and steroid/anaesthetic. Further trials with larger sample sizes are required.https://clinicaltrials.gov/, identifier NCT04051203.
PubMed: 38911584
DOI: 10.3389/fneur.2024.1400057 -
Integrative Medicine Research Sep 2024Auricular acupuncture (AA) has been widely used in overweight and obesity management due to its safety and effectiveness. The combination of other acupuncture therapies...
Adding thread-embedding acupuncture to auricular acupuncture enhances short-term weight reduction in overweight and obesity: A double-blinded, randomized, sham-controlled trial.
BACKGROUND
Auricular acupuncture (AA) has been widely used in overweight and obesity management due to its safety and effectiveness. The combination of other acupuncture therapies with thread-embedding acupuncture (TEA) has shown enhanced effects. However, there is a lack of evidence regarding AA plus TEA for overweight and obesity. This study was conducted to address this question.
METHODS
A randomized placebo-controlled trial was conducted involving 66 overweight or obese participants, divided into two groups: 33 received AA plus TEA, and 33 received AA plus sham TEA over eight weeks. The primary outcome was body weight (BW) reduction. Secondary outcomes included changes in body mass index (BMI) and waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR), food cravings questionnaire-trait-reduced (FCQ-Tr) and food craving visual analog scale (VAS) scores. Safety outcomes were adverse events (AEs).
RESULTS
After eight weeks, BW decreased by a mean (SD) of -4.45 (1.29) kg and -2.05 (1.33) kg in the AA plus TEA and AA plus sham TEA groups, respectively (MD [95 % CI]: 2.40 [1.75; 3.05]). BMI, WC, WHR, and food craving VAS score decreased significantly more in the AA plus TEA group than in the AA plus sham TEA group. No significant differences were found in FCQ-Tr and HC between groups. Seven AEs were recorded that were mild and resolved without treatment.
CONCLUSION
The addition of TEA to AA is a safe and effective management of overweight and obesity. Further studies should incorporate dietary and lifestyle modifications and follow-up after the intervention to assess long-term effectiveness.
TRIAL REGISTRATION
The study protocol had been registered on ClinicalTrials.gov (NCT06091761).
PubMed: 38911552
DOI: 10.1016/j.imr.2024.101050 -
Drug Design, Development and Therapy 2024
Randomized Controlled Trial
Penehyclidine for Prevention of Postoperative Nausea and Vomiting in Patients Undergoing Gynecological Laparoscopic Surgery Under Combined Intravenous and Inhalation Anesthesia: A Randomized, Double-Blind, Placebo-Controlled Trial [Letter].
Topics: Humans; Double-Blind Method; Laparoscopy; Female; Quinuclidines; Postoperative Nausea and Vomiting; Gynecologic Surgical Procedures; Anesthesia, Inhalation; Antiemetics; Randomized Controlled Trials as Topic; Anesthesia, Intravenous
PubMed: 38911028
DOI: 10.2147/DDDT.S482220 -
Endocrine Journal Jun 2024This study aimed to systematically evaluate the efficacy of liraglutide in treating type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease...
This study aimed to systematically evaluate the efficacy of liraglutide in treating type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) by comparing liraglutide with placebo or other drugs (mainly insulin). The PubMed, Web of Science, and National Library of Medicine databases were systematically searched from their inception until December 1, 2023. A meta-analysis was performed using Stata 15.1 software. A total of 12 studies with 13 outcome measures were included. The meta-analysis results revealed that liraglutide significantly reduced body mass index (mean difference [MD] = -1.06, 95%CI: -1.41, -0.70, p < 0.001), triglycerides (MD = -0.35, 95%CI: -0.61, -0.09, p = 0.0009), visceral adipose tissue (MD = -21.06, 95%CI: -34.58, -7.55, p = 0.002), and subcutaneous adipose tissue (MD = -20.53, 95%CI: -29.15, -11.90, p < 0.001) levels in patients with T2DM and NAFLD. Of the 11 studies, 2 reported the occurrence of adverse reactions, which were primarily gastrointestinal. Compared with placebo and other drugs (e.g., insulin), liraglutide may improve glucose metabolism, lipid and liver function parameters, and visceral and subcutaneous fat in patients with T2DM and NAFLD, thus constituting an effective treatment for these patients.
PubMed: 38910131
DOI: 10.1507/endocrj.EJ24-0168 -
BMJ Open Jun 2024Colposcopy is the most important diagnostic tool to detect cervical precancerous lesions and thereby prevention of cervical cancer. Due to age-dependent changes of the...
Improving diagnostic of cervical dysplasia among postmenopausal women aged ≥50 years using local vaginal oestrogen treatment prior to colposcopy: study protocol for a multicentre randomised controlled trial (the IDEAL study).
INTRODUCTION
Colposcopy is the most important diagnostic tool to detect cervical precancerous lesions and thereby prevention of cervical cancer. Due to age-dependent changes of the cervix, colposcopy is challenging in postmenopausal women, as the majority will have a non-visible transformation zone, resulting in increased risk of missing disease, a diagnostic cone biopsy and prolonged follow-up with repeated colposcopies. This study will be among the first to investigate, if treatment with vaginal oestrogen prior to colposcopy will improve the colposcopy performance, to ensure accurate and timely diagnosis of precancerous cervical lesions among postmenopausal women.
METHODS AND ANALYSIS
A randomised blinded controlled multicentre study. Enrolment will be performed at gynaecology departments in Central Denmark Region and Region of Southern Denmark. A total of 150 postmenopausal women aged ≥50 years referred for colposcopy due to abnormal cervical screening results will be randomised 1:1 to either pretreatment with vaginal application of Vagifem 30 µg or placebo once a day for 14 days prior to colposcopy. The primary outcome will be to compare the percentage of women in the two groups with a visible transformation zone at colposcopy, and biopsies representative of the transformation zone. Secondary outcomes will be the proportion of detected cervical intraepithelial neoplasia grade 2 or higher in the cervical biopsies; the proportion of diagnostics cone biopsies; the patients' report on possible side effects and compliance to the pretreatment.
ETHICS AND DISSEMINATION
The study has been approved by the Central Denmark Region Committee on Biomedical Research Ethics (1-10-72-34-22), the Central Denmark Regions' Research Unit (1-16-02-72-22) and The Danish Health Authority (Danish Medicine Agency; 2022015030). The study's EudraCT number is (1-23-456; 2022-000269-42) and it is registered on www.
CLINICALTRIALS
gov. The local Good Clinical Practice (GCP) unit will supervise and monitor the study closely before, during and after the study period. Findings will be disseminated in peer-reviewed scientific journals and presented in relevant conferences.
TRIAL REGISTRATION NUMBER
NCT05283421.
Topics: Humans; Female; Colposcopy; Uterine Cervical Dysplasia; Postmenopause; Middle Aged; Administration, Intravaginal; Uterine Cervical Neoplasms; Estrogens; Denmark; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Early Detection of Cancer
PubMed: 38910002
DOI: 10.1136/bmjopen-2023-082833 -
BMJ Open Diabetes Research & Care Jun 2024To assess the efficacy of a chitosan-based gel (ChitoCare) for the treatment of non-healing diabetic foot ulcers (DFUs). (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
To assess the efficacy of a chitosan-based gel (ChitoCare) for the treatment of non-healing diabetic foot ulcers (DFUs).
RESEARCH DESIGN AND METHODS
Forty-two patients with chronic DFUs were randomized to the ChitoCare or placebo gel for a 10-week treatment period and 4-week follow-up. The primary study end point was the rate of complete wound closure at week 10, presented as relative rate.
RESULTS
Thirty patients completed the 10-week treatment and 28 completed the 4-week follow-up. The ChitoCare arm achieved 16.7% complete wound closure at week 10 vs 4.2% in the placebo arm (p=0.297), 92.0% vs 37.0% median relative reduction in wound surface area from baseline at week 10 (p=0.008), and 4.62-fold higher likelihood of achieving 75% wound closure at week 10 (p=0.012). Based on the results of the Bates-Jensen Wound Assessment Tool, the wound state at week 10 and the relative improvement from the baseline were significantly better (median 20 vs 24 points, p=0.018, and median 29.8% vs 3.6%, p=0.010, respectively).
CONCLUSIONS
ChitoCare gel increased the rate of the DFU healing process. Several secondary end points significantly favored ChitoCare gel.
TRIAL REGISTRATION NUMBER
NCT04178525.
Topics: Humans; Chitosan; Diabetic Foot; Female; Male; Middle Aged; Gels; Wound Healing; Aged; Follow-Up Studies; Treatment Outcome; Chronic Disease; Double-Blind Method; Prognosis
PubMed: 38909998
DOI: 10.1136/bmjdrc-2024-004195 -
Acta Psychologica Jun 2024The study aimed to examine the effect of mental imagery on sports performance. Specifically, it was tested whether imagining flying (i.e., air travel) increases jumping...
OBJECTIVE
The study aimed to examine the effect of mental imagery on sports performance. Specifically, it was tested whether imagining flying (i.e., air travel) increases jumping performance in a group of female volleyball players.
METHODS
The study included 46 female young athletes (mean age = 15.23 years; standard deviation = 2.4) divided into two groups: the experimental group viewed a three-dimensional video that simulated a flying experience, while the control group watched neutral footage. The jump performance of both groups was measured before and after viewing the videos, using the Vertec Like® instrument to assess jump height. Participants were assessed for their flow disposition, mental imagery skills, and image vividness.
RESULTS
Comparing pre-post jump performance scores, the experimental group showed a significant improvement over the control group, with a medium-large effect size (d = 0.634). There was no significant association between flow disposition, mental imagery skills, image vividness, and pre-post jumping performance differences (respectively: β = -0.107, p = .484; β = -0.008, p = .957; β = 0.024, p = .913).
CONCLUSIONS
These findings suggest that the experience of imagining flying, enhanced with an immersive video, has a positive effect on jumping performance in a one-session study with young female volleyball players. This effect does not appear to be associated with pre-existing characteristics or the vividness of the image itself.
PubMed: 38909396
DOI: 10.1016/j.actpsy.2024.104366