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Toxins May 2024As multiple indications for botulinum toxin injections (BTIs) can coexist for neurological patients, there are to date no description of concomitant injections (CIs) to...
As multiple indications for botulinum toxin injections (BTIs) can coexist for neurological patients, there are to date no description of concomitant injections (CIs) to treat both spasticity and neurogenic detrusor overactivity incontinence (NDOI) in patients with spinal cord injuries (SCIs) and multiple sclerosis (MS). We therefore identified patients followed at our institution by health data hub digging, using a specific procedure coding system in use in France, who have been treated at least once with detrusor and skeletal muscle BTIs within the same 1-month period, over the past 5 years (2017-2021). We analyzed 72 patients representing 319 CIs. Fifty (69%) were male, and the patients were mostly SCI (76%) and MS (18%) patients and were treated by a mean number of CIs of 4.4 ± 3.6 [1-14]. The mean cumulative dose was 442.1 ± 98.8 U, and 95% of CIs were performed within a 72 h timeframe. Among all CIs, five patients had symptoms evocative of distant spread but only one had a confirmed pathological jitter in single-fiber EMG. Eleven discontinued CIs for surgical alternatives: enterocystoplasty (five), tenotomy (three), intrathecal baclofen (two) and neurotomy (one). Concomitant BTIs for treating both spasticity and NDOI at the same time appeared safe when performed within a short delay and in compliance with actual knowledge for maximum doses.
Topics: Humans; Muscle Spasticity; Male; Female; Retrospective Studies; Middle Aged; Urinary Bladder, Overactive; Adult; Spinal Cord Injuries; Multiple Sclerosis; Neuromuscular Agents; Botulinum Toxins, Type A; Urinary Bladder, Neurogenic; Aged; Injections, Intramuscular; Treatment Outcome
PubMed: 38922146
DOI: 10.3390/toxins16060252 -
ELife Jun 2024Accurate prediction of the structurally diverse complementarity determining region heavy chain 3 (CDR-H3) loop structure remains a primary and long-standing challenge...
Accurate prediction of the structurally diverse complementarity determining region heavy chain 3 (CDR-H3) loop structure remains a primary and long-standing challenge for antibody modeling. Here, we present the H3-OPT toolkit for predicting the 3D structures of monoclonal antibodies and nanobodies. H3-OPT combines the strengths of AlphaFold2 with a pre-trained protein language model and provides a 2.24 Å average RMSD between predicted and experimentally determined CDR-H3 loops, thus outperforming other current computational methods in our non-redundant high-quality dataset. The model was validated by experimentally solving three structures of anti-VEGF nanobodies predicted by H3-OPT. We examined the potential applications of H3-OPT through analyzing antibody surface properties and antibody-antigen interactions. This structural prediction tool can be used to optimize antibody-antigen binding and engineer therapeutic antibodies with biophysical properties for specialized drug administration route.
Topics: Deep Learning; Complementarity Determining Regions; Antibodies, Monoclonal; Models, Molecular; Protein Conformation; Single-Domain Antibodies; Humans
PubMed: 38921957
DOI: 10.7554/eLife.91512 -
International Journal of Chronic... 2024Inhaled corticosteroid (ICS) therapy has been demonstrated to reduce the risk of COPD exacerbations. It should only be prescribed to COPD patients who are not adequately... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inhaled corticosteroid (ICS) therapy has been demonstrated to reduce the risk of COPD exacerbations. It should only be prescribed to COPD patients who are not adequately controlled by dual long-acting bronchodilator therapy and who have ≥2 exacerbations per year and a blood eosinophil count ≥300cells/µL. ICS therapy is widely prescribed outside guidelines to COPD patients, making ICS withdrawal an important consideration. This systematic review aims to provide an up-to-date analysis of the effect of ICS withdrawal on exacerbation frequency, change in lung function (FEV) and to determine the proportion of COPD patients who resume ICS therapy following withdrawal.
METHODS
Randomised controlled trials (RCTs) and observational studies which compared ICS withdrawal with ICS continuation treatment were included. Cochrane Central, Web of Science, CINHAL, Embase and OVID Medline were searched. Risk of bias was assessed using the Cochrane RoB2 tool and the Newcastle-Ottawa Scale. Quality assessment of RCTs was conducted using GRADE. Meta-analysis of post-hoc analyses of RCTs of ICS withdrawal, stratified by blood eosinophil count (BEC), was undertaken.
RESULTS
Ten RCTs (6642 patients randomised) and 6 observational studies (160,029 patients) were included in the results. When ICS was withdrawn and long-acting bronchodilator therapy was maintained, there was no consistent difference in exacerbation frequency or lung function change between the ICS withdrawal and continuation trial arms. The evidence for these effects was of moderate quality. There was insufficient evidence to draw a firm conclusion on the proportion of patients who resumed ICS therapy following withdrawal (estimated range 12-93% of the participants).
DISCUSSION
Withdrawal of ICS therapy from patients with COPD is safe and feasible but should be accompanied by maintenance of bronchodilation therapy for optimal outcomes.
Topics: Pulmonary Disease, Chronic Obstructive; Humans; Administration, Inhalation; Lung; Adrenal Cortex Hormones; Disease Progression; Forced Expiratory Volume; Treatment Outcome; Bronchodilator Agents; Randomized Controlled Trials as Topic; Observational Studies as Topic; Time Factors; Aged; Drug Administration Schedule; Risk Factors; Middle Aged; Female; Male
PubMed: 38919905
DOI: 10.2147/COPD.S436525 -
Acta Dermatovenerologica Alpina,... Jun 2024Melasma, a chronic acquired skin pigmentation disorder, is characterized by the presence of irregular-edged brown to gray-brown patches with a symmetrical distribution,... (Randomized Controlled Trial)
Randomized Controlled Trial
The effectiveness and safety of 3% tranexamic acid cream vs. 4% hydroquinone cream for mixed-type melasma in skin of color: a double-blind, split-face, randomized controlled trial.
INTRODUCTION
Melasma, a chronic acquired skin pigmentation disorder, is characterized by the presence of irregular-edged brown to gray-brown patches with a symmetrical distribution, primarily on sun-exposed areas such as the face. Topical hydroquinone (HQ) is the gold standard for melasma treatment but has numerous side effects. This study assesses the effectiveness of topical tranexamic acid (TA) as an alternative for melasma treatment.
METHODS
In a double-blind, split-face, randomized controlled trial involving 20 subjects, the effectiveness of 3% TA versus 4% HQ cream was evaluated over 8 weeks. The modified melasma area and severity index (mMASI), melanin index, erythema index, and side effects were assessed. Subjective improvement was measured using the patient global assessment (PtGA).
RESULTS
A significant decline in the mMASI score was observed at weeks 4 and 8 in both groups compared to baseline. There were no statistically significant differences in PtGA scores between the 3% TA group and the 4% HQ group.
CONCLUSIONS
Topical 3% TA is as effective and safe as 4% HQ for treating melasma in the Indonesian population, with potential advantages in terms of side-effect profiles.
Topics: Adult; Female; Humans; Male; Middle Aged; Administration, Cutaneous; Double-Blind Method; Hydroquinones; Melanosis; Severity of Illness Index; Skin Cream; Tranexamic Acid; Treatment Outcome
PubMed: 38918942
DOI: No ID Found -
Asian Pacific Journal of Cancer... Jun 2024Capecitabine has been widely prescribed to treat various cancers. The hand foot syndrome (HFS) is the most troublesome adverse effect. Urea cream has been pre-emptively... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
A Randomized Single-Blinded Phase II Trial Comparing Efficacy and Quality of Life of Topical Aloe Vera Gel Plus Urea Cream Versus Urea Cream Alone for Prevention of Hand Foot Syndrome in Cancer Patients Receiving Capecitabine.
INTRODUCTION
Capecitabine has been widely prescribed to treat various cancers. The hand foot syndrome (HFS) is the most troublesome adverse effect. Urea cream has been pre-emptively co-prescribed, even though its efficacy is doubtful. Aloe vera gel with urea cream might potentiate each other. This trial was intended to prove the efficacy of this combination.
MATERIALS AND METHODS
The investigators conducted a randomized single-blinded phase II study. The participants were randomized 1:1 to receive the combination of aloe vera gel and 10% urea cream (n = 30), the experimental A+U arm and 10% urea cream alone (n = 31), the U arm. The sample size was calculated to have 90% power to show the significant 20% reduction in the incidence of HFS grade 2-3 of the combination therapy with alpha level = 0.05. Both the CTCAE criteria version 5 and the dermatology life quality index (DLQI) were assessed to determine the severity of HFS and quality of life, respectively.
RESULTS
Most of the participants had rectal cancer (A+U: 43.3%; U: 41.9%). In the A+U group, 86.7% had grade 0-1 HFS and 13.3% had grade 2-3 HFS. In the U group, 64.5% had grade 0-1 HFS and 35.5% had grade 2-3 HFS (Mann-Whitney U test, p = 0.045). Grade 2-3 HFS was significantly lower in the combination group.
CONCLUSION
Combination of aloe vera gel and 10% urea cream ameliorated the severity of HFS in participants taking capecitabine; however, no significant difference in DLQI between the groups was demonstrated.
Topics: Humans; Capecitabine; Female; Male; Middle Aged; Quality of Life; Hand-Foot Syndrome; Urea; Antimetabolites, Antineoplastic; Single-Blind Method; Plant Preparations; Prognosis; Follow-Up Studies; Adult; Administration, Topical; Aged; Neoplasms; Skin Cream; Aloe
PubMed: 38918684
DOI: 10.31557/APJCP.2024.25.6.2203 -
Scientific Reports Jun 2024Contemporary treatment of vitiligo remains a great challenge to practitioners. The vast majority of currently conducted clinical trials of modern therapeutic methods are... (Randomized Controlled Trial)
Randomized Controlled Trial
Contemporary treatment of vitiligo remains a great challenge to practitioners. The vast majority of currently conducted clinical trials of modern therapeutic methods are focused on systemic medications, while there is only a very limited number of reports on new topical treatment in vitiligo. With their pleiotropic activities statins turned out to be efficient in the treatment of various autoimmune/autoinflammatory disorders. The randomized, double-blind placebo-controlled study of topical administration of the active forms of simvastatin and atorvastatin has been designed to evaluate their efficacy in patients with vitiligo. The study was registered in clinicaltrials.gov (registration number NCT03247400, date of registration: 11th August 2017). A total of 24 patients with the active form of non-segmental vitiligo were enrolled in the study. The change of absolute area of skin lesions, body surface area and vitiligo area scoring index were evaluated throughout the 12 week application of ointments containing simvastatin and atorvastatin. Measurements were performed with planimetry and processed using digital software. Use of active forms of simvastatin and atorvastatin did not result in a significant repigmentation of the skin lesions throughout the study period. Within the limbs treated with topical simvastatin, inhibition of disease progression was significantly more frequent than in the case of placebo (p = 0.004), while the difference was not statistically significant for atorvastatin (p = 0.082). Further studies of topical simvastatin in vitiligo patients should be considered.
Topics: Humans; Vitiligo; Atorvastatin; Simvastatin; Male; Female; Double-Blind Method; Adult; Pilot Projects; Middle Aged; Administration, Topical; Young Adult; Treatment Outcome; Adolescent
PubMed: 38918590
DOI: 10.1038/s41598-024-65722-w -
Scientific Reports Jun 2024In Asian patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) undergoing dialysis, the use of direct oral anticoagulants (DOACs) remains debatable....
In Asian patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) undergoing dialysis, the use of direct oral anticoagulants (DOACs) remains debatable. From the national health insurance claims data in South Korea, we included 425 new users of OAC among patients with non-valvular AF and ESRD undergoing dialysis between 2013 and 2020. Patients were categorized into DOAC (n = 106) and warfarin group (n = 319). Clinical outcomes, including ischemic stroke, myocardial infarction (MI), intracranial hemorrhage (ICH), and gastrointestinal (GI) bleeding, were compared between the two groups using inverse probability of treatment weighting (IPTW) analysis. During the median follow-up of 3.2 years, the incidence of ischemic stroke was significantly reduced in the DOAC compared to the warfarin group [Hazard ratio (HR) 0.07; P = 0.001]. However, the incidence of MI (HR 1.32; P = 0.41) and GI bleeding (HR 1.78; P = 0.06) were not significantly different between the two groups. No ICH events occurred in the DOAC group, although the incidence rate did not differ significantly between the two groups (P = 0.17). In Asian patients with AF and ESRD undergoing dialysis, DOACs may be associated with a reduced risk of ischemic stroke compared with warfarin. The MI, ICH, and GI bleeding rates may be comparable between DOACs and warfarin.
Topics: Humans; Atrial Fibrillation; Kidney Failure, Chronic; Male; Female; Renal Dialysis; Aged; Anticoagulants; Warfarin; Administration, Oral; Middle Aged; Republic of Korea; Incidence; Asian People; Gastrointestinal Hemorrhage; Myocardial Infarction; Ischemic Stroke; Aged, 80 and over
PubMed: 38918543
DOI: 10.1038/s41598-024-65541-z -
Scientific Reports Jun 2024Delivery of therapeutic stem cells to treat bone tissue damage is a promising strategy that faces many hurdles to clinical translation. Among them is the design of a...
Delivery of therapeutic stem cells to treat bone tissue damage is a promising strategy that faces many hurdles to clinical translation. Among them is the design of a delivery vehicle which promotes desired cell behavior for new bone formation. In this work, we describe the use of an injectable microporous hydrogel, made of crosslinked gelatin microgels, for the encapsulation and delivery of human mesenchymal stem cells (MSCs) and compared it to a traditional nonporous injectable hydrogel. MSCs encapsulated in the microporous hydrogel showed rapid cell spreading with direct cell-cell connections whereas the MSCs in the nonporous hydrogel were entrapped by the surrounding polymer mesh and isolated from each other. On a per-cell basis, encapsulation in microporous hydrogel induced a 4 × increase in alkaline phosphatase (ALP) activity and calcium mineral deposition in comparison to nonporous hydrogel, as measured by ALP and calcium assays, which indicates more robust osteogenic differentiation. RNA-seq confirmed the upregulation of the genes and pathways that are associated with cell spreading and cell-cell connections, as well as the osteogenesis in the microporous hydrogel. These results demonstrate that microgel-based injectable hydrogels can be useful tools for therapeutic cell delivery for bone tissue repair.
Topics: Mesenchymal Stem Cells; Osteogenesis; Humans; Hydrogels; Cell Differentiation; Porosity; Alkaline Phosphatase; Cells, Cultured; Cell Encapsulation; Mesenchymal Stem Cell Transplantation; Injections
PubMed: 38918510
DOI: 10.1038/s41598-024-65731-9 -
JAMA Network Open Jun 2024Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are limited.
OBJECTIVE
To assess the effectiveness of sublingual or extended-release injection formulations of buprenorphine for the treatment of OUD among patients with and without fentanyl use.
DESIGN, SETTING, AND PARTICIPANTS
Post hoc analysis of a 24-week, randomized, double-blind clinical trial conducted at 35 outpatient sites in the US from December 2015 to November 2016 of sublingual buprenorphine-naloxone vs extended-release subcutaneous injection buprenorphine (CAM2038) for patients with OUD subgrouped by presence vs absence of fentanyl or norfentanyl in urine at baseline. Study visits with urine testing occurred weekly for 12 weeks, then 6 times between weeks 13 and 24. Data were analyzed on an intention-to-treat basis from March 2022 to August 2023.
INTERVENTION
Weekly and monthly subcutaneous buprenorphine vs daily sublingual buprenorphine-naloxone.
MAIN OUTCOMES AND MEASURES
Retention in treatment, percentage of urine samples negative for any opioids (missing values imputed as positive), percentage of urine samples negative for fentanyl or norfentanyl (missing values not imputed), and scores on opiate withdrawal scales and visual analog craving scales.
RESULTS
Of 428 participants, 123 (subcutaneous buprenorphine, n = 64; sublingual buprenorphine-naloxone, n = 59; mean [SD] age, 39.1 [10.8] years; 75 men [61.0%]) had evidence of baseline fentanyl use and 305 (subcutaneous buprenorphine, n = 149; buprenorphine-naloxone, n = 156; mean [SD] age, 38.1 [11.1] years; 188 men [61.6%]) did not have evidence of baseline fentanyl use. Study completion was similar between the fentanyl-positive (60.2% [74 of 123]) and fentanyl-negative (56.7% [173 of 305]) subgroups. The mean percentage of urine samples negative for any opioid were 28.5% among those receiving subcutaneous buprenorphine and 18.8% among those receiving buprenorphine-naloxone in the fentanyl-positive subgroup (difference, 9.6%; 95% CI, -3.0% to 22.3%) and 36.7% among those receiving subcutaneous buprenorphine and 30.6% among those receiving buprenorphine-naloxone in the fentanyl-negative subgroup (difference, 6.1%; 95% CI, -1.9% to 14.1%), with significant main associations of baseline fentanyl status and treatment group. In the fentanyl-positive subgroup, the mean percentage of urine samples negative for fentanyl during the study was 74.6% among those receiving subcutaneous buprenorphine vs 61.9% among those receiving sublingual buprenorphine-naloxone (difference, 12.7%; 95% CI, 9.6%-15.9%). Opioid withdrawal and craving scores decreased rapidly after treatment initiation across all groups.
CONCLUSIONS AND RELEVANCE
In this post hoc analysis of a randomized clinical trial of sublingual vs extended-release injection buprenorphine for OUD, buprenorphine appeared to be effective among patients with baseline fentanyl use. Patients with fentanyl use had fewer opioid-negative urine samples during the trial compared with the fentanyl-negative subgroup. These findings suggest that the subcutaneous buprenorphine formulation may be more effective at reducing fentanyl use.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02651584.
Topics: Humans; Opioid-Related Disorders; Fentanyl; Male; Female; Administration, Sublingual; Adult; Double-Blind Method; Buprenorphine; Middle Aged; Delayed-Action Preparations; Injections, Subcutaneous; Narcotic Antagonists; Analgesics, Opioid; Opiate Substitution Treatment; Buprenorphine, Naloxone Drug Combination; Treatment Outcome
PubMed: 38916892
DOI: 10.1001/jamanetworkopen.2024.17377 -
International Ophthalmology Jun 2024To assess the effectiveness of a switch to faricimab in individuals affected by DME and previously treated with aflibercept.
PURPOSE
To assess the effectiveness of a switch to faricimab in individuals affected by DME and previously treated with aflibercept.
METHODS
In this retrospective, single-center study, DME patients previously treated with at least 3 injections of aflibercept then switched to faricimab were enrolled. Best corrected visual acuity (BCVA) and central subfield thickness (CST) were recorded at baseline, at the time of the switch and at 6 months follow-up. At transition to faricimab, patients were categorized as "good visual responders" (≥ 5 letters from baseline) or "poor visual responders" (< 5 letters), and as "good anatomical responders" (any reduction in edema compared to baseline) or "poor anatomical responders" (no reduction or worsening of edema). Changes in BCVA and CST were recorded at 6 months after the switch to faricimab.
RESULTS
100 eyes of 100 patients (61 female, 61%) were switched to faricimab after a mean of 6.8 ± 3.3 aflibercept injections. At the 6 months follow-up, only "poor visual responders" (N = 62) demonstrated a meaningful increase in BCVA (Δswitch-6M = + 5 letters; P = 0.007), coupled with a reduction in CST (Δswitch-6M = - 67.9 µm; P = 0.004); participants with "poor anatomical response" upon transitioning exhibited a significant functional gain (Δswitch-6M = + 4.5 letters; p = 0.05) but limited CST enhancements (Δswitch-6M = - 95.1 µm; p = 0.05).
CONCLUSIONS
Faricimab shows a positive impact on anatomical and functional metrics in DME cases refractory to aflibercept.
Topics: Humans; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Female; Male; Retrospective Studies; Macular Edema; Diabetic Retinopathy; Intravitreal Injections; Visual Acuity; Middle Aged; Angiogenesis Inhibitors; Tomography, Optical Coherence; Follow-Up Studies; Aged; Treatment Outcome; Drug Substitution; Vascular Endothelial Growth Factor A
PubMed: 38916818
DOI: 10.1007/s10792-024-03226-2