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Biomedicines May 2024Myasthenia gravis (MG), an immune disorder affecting nerve-muscle transmission, often necessitates tailored therapies to alleviate longitudinal symptom fluctuations....
INTRODUCTION
Myasthenia gravis (MG), an immune disorder affecting nerve-muscle transmission, often necessitates tailored therapies to alleviate longitudinal symptom fluctuations. Here, we aimed to examine and compare the treatment cycle intervals and efficacy of efgartigimod in four patients. This case series mainly offers insights into personalized treatment cycle intervals and the efficacy of efgartigimod for patients with MG in our facility in Japan.
METHODS
We retrospectively analyzed four patients with MG (2 patients with early-onset, 1 with late-onset, and 1 with seronegative MG, mainly managed with oral immunosuppressants as prior treatments) who completed four or more cycles of efgartigimod treatment from January 2022 to September 2023. We focused on changes in serum immunoglobulin (IgG) level, acetylcholine receptor antibody (AChR-Ab) titer, and quantitative MG (QMG) score.
RESULTS
Efgartigimod, administered at a median of 5.0 [IQR 5.0, 7.5] weeks between cycles, led to decreased serum IgG levels in all patients and reduced AChR-Ab titers in seropositive patients. All patients showed sustained MG symptom improvement, with considerably reduced QMG scores before efgartigimod treatment. None of the patients required rescue medications or developed treatment-related adverse events.
CONCLUSIONS
Customized efgartigimod administration intervals effectively enhanced clinical outcomes in patients with MG without notable symptom fluctuations, demonstrating the benefits of individualized treatment approaches and validating the safety of efgartigimod during the study period.
PubMed: 38927421
DOI: 10.3390/biomedicines12061214 -
Antibiotics (Basel, Switzerland) Jun 2024In most countries, antibiotics for oral administration are put on the market in fixed packages. When there is no exact unit dispensing of antimicrobials, drug pack size...
In most countries, antibiotics for oral administration are put on the market in fixed packages. When there is no exact unit dispensing of antimicrobials, drug pack size may influence prescribers' choice of treatment duration. The aim of this study was to investigate the accordance of approved antibiotic packages with national guidelines for the treatment of community-acquired pneumonia (CAP). For the purpose of this study, criteria were developed to determine the accordance of approved antibiotic packages for treating CAP (criteria), which are based on recommendations from national guidelines for treating CAP. Subsequently, the accordance of approved antibiotic packages with the number of antibiotic doses resulting from the specified criteria was determined. Of 39 identified therapeutic option-package size combinations, 11 were found to be matched (28.2%), meaning there were no leftover medication units after completing therapy, and 28 were mismatched combinations (71.8%), indicating that there were excess doses of antibiotics remaining at the end of therapy. The results of this research showed a significant non-accordance of the approved antibiotic packages with the national guidelines for the treatment of CAP and, consequently, the creation of a large amount of residues of unit doses of antibiotics in the community.
PubMed: 38927212
DOI: 10.3390/antibiotics13060546 -
Antibiotics (Basel, Switzerland) May 2024Interactions between drugs are a common problem in Intensive Care Unit patients, as they mainly have a critical condition that often demands the administration of... (Review)
Review
Interactions between drugs are a common problem in Intensive Care Unit patients, as they mainly have a critical condition that often demands the administration of multiple drugs simultaneously. Antibiotics are among the most frequently used medications, as infectious diseases are often observed in ICU patients. In this review, the most important antibiotic-drug interactions, based on the pharmacokinetic and pharmacodynamic mechanisms, were gathered together and described. In particular, some of the most important interactions with main groups of antibacterial drugs were observed in patients simultaneously prescribed oral anticoagulants, NSAIDs, loop diuretics, and valproic acid. As a result, the activity of drugs can be increased or decreased, as dosage modification might be necessary. It should be noted that these crucial interactions can help predict and avoid negative consequences, leading to better patient recovery. Moreover, since there are other factors, such as fluid therapy or albumins, which may also modify the effectiveness of antibacterial therapy, it is important for anaesthesiologists to be aware of them.
PubMed: 38927170
DOI: 10.3390/antibiotics13060503 -
BMJ Open Gastroenterology Jun 2024To estimate the strength of association between exposure to selected classes of prescribed medications and the risk of developing iron deficiency anaemia (IDA),...
OBJECTIVE
To estimate the strength of association between exposure to selected classes of prescribed medications and the risk of developing iron deficiency anaemia (IDA), specifically considering oral anticoagulants (OACs), antidepressants, antiplatelet agents, proton pump inhibitors (PPIs) and non-steroidal anti-inflammatories.
DESIGN
A case-control study involving the analysis of community repeat prescriptions among subjects referred with IDA, and unmatched controls referred as gastroenterology fast-tracks for other indications. Multivariable logistic regression modelling was used to calculate ORs for the association between IDA presentation and each medication class, adjusted for age, sex and coprescribing. For those classes showing significance, it was also used to calculate risk differences between those in the IDA group with or without haemorrhagic lesions on investigation.
RESULTS
A total of 1210 cases were analysed-409 in the IDA group, and 801 in the control group. Significant associations were identified between presentation with IDA and long-term exposure to PPIs (OR 3.29, 95% CI: 2.47 to 4.41, p<0.001) and to OACs (OR 2.04, 95% CI: 1.29 to 3.24, p=0.002). IDA was not associated with long-term exposure to any of the other three drug classes. In contrast to the relationship with PPIs, the association with OACs was primarily in the IDA sub-group with haemorrhagic lesions.
CONCLUSION
Long-term exposure to PPIs and OACs are independently associated with the risk of developing IDA. There are grounds for considering that these associations may be causal, though the underlying mechanisms probably differ.
Topics: Humans; Anemia, Iron-Deficiency; Case-Control Studies; Female; Male; Proton Pump Inhibitors; Middle Aged; Aged; Anticoagulants; Risk Factors; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Platelet Aggregation Inhibitors; Adult; Logistic Models; Aged, 80 and over
PubMed: 38926132
DOI: 10.1136/bmjgast-2023-001305 -
Gut Jun 2024Food addiction is a multifactorial disorder characterised by a loss of control over food intake that may promote obesity and alter gut microbiota composition. We have...
OBJECTIVE
Food addiction is a multifactorial disorder characterised by a loss of control over food intake that may promote obesity and alter gut microbiota composition. We have investigated the potential involvement of the gut microbiota in the mechanisms underlying food addiction.
DESIGN
We used the Yale Food Addiction Scale (YFAS) 2.0 criteria to classify extreme food addiction in mouse and human subpopulations to identify gut microbiota signatures associated with vulnerability to this disorder.
RESULTS
Both animal and human cohorts showed important similarities in the gut microbiota signatures linked to food addiction. The signatures suggested possible non-beneficial effects of bacteria belonging to the Proteobacteria phylum and potential protective effects of Actinobacteria against the development of food addiction in both cohorts of humans and mice. A decreased relative abundance of the species was observed in addicted humans and of genus in addicted mice. Administration of the non-digestible carbohydrates, lactulose and rhamnose, known to favour growth, led to increased relative abundance of in mice faeces in parallel with dramatic improvements in food addiction. A similar improvement was revealed after oral administration of as a beneficial microbe.
CONCLUSION
By understanding the crosstalk between this behavioural alteration and gut microbiota, these findings constitute a step forward to future treatments for food addiction and related eating disorders.
PubMed: 38926079
DOI: 10.1136/gutjnl-2023-331445 -
Zhongguo Ying Yong Sheng Li Xue Za Zhi... Jun 2024The buccal route has great prospects and possible benefits for the administration of drugs systemically. The present study involves designing, developing and optimising...
The buccal route has great prospects and possible benefits for the administration of drugs systemically. The present study involves designing, developing and optimising the buccal tablet formulation of Enalapril Maleate (EM) by using the QbD approach. We prepared the EM buccal tablets using the dry granulation method. In the QTPP profile, the CQAs for EM buccal tablets are Mucoadhesive strength, swelling index and drug release (dependent variables); the CMAs identified for EM buccal tablets were Carbopol 934P, HPMC-K100M and chitosan (independent variables). Diluent quantity, blending time and compression force were selected as CPPs; the Box-Behnkentdesign was used to evaluate the relationship between the CMAs and CPPs. Based on the DoE, the composition of the optimised formulation of EM BT-18 consists of 20mg of EM, 15 mg of carbopol 934p, 17 mg of HPMC-K100M, 10mg of chitosan, 30 mg of PVP K-30, 1 mg of magnesium stearate, 16 mg of Mannitol, 1 mg of aspartame, and 50 mg of Ethyl cellulose. The optimised formulation of EM BT 18 was found to have a Mucoadhesive strength of 24.32±0.30g. The swelling index was 90.74±0.25% and drug release was sustained up to 10 hours 98.4±3.62% compared to the marketed product, whose release was up to 8 hours. We attempted to design a buccal tablet of Enalapril Maleate for sustained drug release in the treatment of hypertension. Patients who cannot take oral medication due to trauma or unconscious conditions could receive the formulation. Development of a newly P.ceutical product is very time-consuming, extremely costly and high-risk, with very little chance of a successful outcome. Hence, this study showed EM tablets are already available on the market but we have chosen a buccal drug delivery system using a novel approach using QbD tools to target the quality of the product accurately.
Topics: Tablets; Enalapril; Administration, Buccal; Mouth Mucosa; Drug Compounding; Chemistry, Pharmaceutical
PubMed: 38925868
DOI: 10.62958/j.cjap.2024.003 -
Skin Research and Technology : Official... Jul 2024
Topics: Humans; Botulinum Toxins, Type A; Female; Adult; Botulinum Toxins; Neuromuscular Agents
PubMed: 38925591
DOI: 10.1111/srt.13816 -
Biomedicine & Pharmacotherapy =... Jun 2024There is a lack of a systematic understanding of the specific mechanism of action of DL0410 in AD treatment. In this study, the combination of RNA-seq and proteomics was...
There is a lack of a systematic understanding of the specific mechanism of action of DL0410 in AD treatment. In this study, the combination of RNA-seq and proteomics was firstly employed to uncover the mechanism of action of DL0410 in APP/PS1 transgenic mice. The results of behavioral tests showed that oral administration of DL0410 for 8 weeks improved memory and cognition of APP/PS1 mice. DL0410 significantly reduced β-amyloid deposition and resulted in significant upregulation of synaptophysin, PSD95 and NMDAR/ CaMKⅡ signaling pathway in the hippocampus and cortex, indicating that DL0410 improved synaptic plasticity in APP/PS1 mice, which agrees with the results of RNA-seq and proteomics. Furthermore, the enrichment results of differentially expressed genes identified by RNA-seq and proteomics demonstrate the potential protective effects of DL0410 against oxidative stress and mitochondrial dysfunction. As expected, DL0410 dose-dependently ameliorated oxidative damage and markedly increased the expression of PGC-1α, TFAM, SOD1 and SOD2. Mitochondrial high-resolution respirometry results revealed that mitochondrial respiratory function was significantly improved in APP/PS1 mice administered with DL0410. In addition, DL0410 treatment reduced oxidative damage, strengthened antioxidant system and improved mitochondrial function in Aβ-induced HT22 cells. Altogether, our findings suggest the potential of DL0410 as a novel candidate for AD treatment.
PubMed: 38925020
DOI: 10.1016/j.biopha.2024.116940 -
Cancer Medicine Jun 2024Atezolizumab and bevacizumab (Atezo/Bev) combination immunotherapy regimens and direct oral anticoagulants (DOACs) are both associated with bleeding. Therefore,...
AIM
Atezolizumab and bevacizumab (Atezo/Bev) combination immunotherapy regimens and direct oral anticoagulants (DOACs) are both associated with bleeding. Therefore, combining Atezo/Bev regimens with DOACs may exacerbate the bleeding risk. This study investigated the feasibility of the Atezo/Bev regimen in patients taking DOACs.
METHODS
This retrospective study included 141 patients with unresectable hepatocellular carcinoma (HCC) or advanced lung cancer (LC) treated with Atezo/Bev regimens. Patients who used antithrombotic agents other than DOACs were excluded. Bleeding events during the Atezo/Bev regimen were analyzed.
RESULTS
The incidence rates of bleeding of any grade in the DOAC (n = 11) and no antithrombotic agent (NAA) (n = 130) groups were 9.1% and 10.8%, respectively, with no significant differences. Moreover, no significant difference was found in the frequency of bleeding of grade ≥3 between the DOAC and NAA groups. No patients in the DOAC group discontinued the Atezo/Bev regimen because of severe bleeding. Although serum albumin levels, with a hazard ratio (HR) of 0.298 (95% confidence interval [CI]: 0.105-0.847), independently contributed to bleeding events (p = 0.023), DOAC administration did not (HR: 1.357; 95% CI: 0.157-10.54; p = 0.770). Among only patients with HCC (n = 59), none of the five patients taking DOACs experienced bleeding events. A high albumin-bilirubin score (HR: 9.083, 95% CI: 1.118-73.76) was associated with bleeding events (p = 0.039).
CONCLUSIONS
DOACs did not have a considerable effect on bleeding events in the Atezo/Bev regimens for HCC or LC. Under careful surveillance for bleeding, Atezo/Bev regimens may be feasible in patients receiving DOACs.
Topics: Humans; Carcinoma, Hepatocellular; Male; Liver Neoplasms; Female; Antibodies, Monoclonal, Humanized; Retrospective Studies; Lung Neoplasms; Aged; Middle Aged; Feasibility Studies; Hemorrhage; Bevacizumab; Antineoplastic Combined Chemotherapy Protocols; Anticoagulants; Administration, Oral; Aged, 80 and over
PubMed: 38924675
DOI: 10.1002/cam4.7430