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[Risk minimalisation measures for medications; are they incorporated in Dutch clinical guidelines?].Nederlands Tijdschrift Voor Geneeskunde Jun 2024Risk minimisation measures (RMM) are put in place to ensure safe and effective use of medicines. This study assessed whether RMM for five medicines are implemented in...
OBJECTIVE
Risk minimisation measures (RMM) are put in place to ensure safe and effective use of medicines. This study assessed whether RMM for five medicines are implemented in Dutch clinical guidelines.
DESIGN
Descriptive study.
METHOD
Dutch clinical guidelines where treatment with valproate, fluoroquinolones, methotrexate, metformin or fluorouracil was recommended were identified. In those guidelines that had been updated after publication of the RMM, we determined whether RMM-information was included in the guideline.
RESULTS
Out of 50 identified guidelines recommending treatment with one of the five medicines, only 21 (42%) were revised after RMM-implementation. Of these 21 guidelines, 12 (n = 57%) included RMM-related information.
CONCLUSION
Uptake of RMM information in Dutch clinical guidelines is limited and RMM-publication does not prompt guideline updates. This suggests that guidelines alone are not an optimal way to inform health care professionals of new safety warnings.
Topics: Humans; Netherlands; Practice Guidelines as Topic; Drug-Related Side Effects and Adverse Reactions; Methotrexate; Valproic Acid; Fluoroquinolones; Metformin; Risk Management
PubMed: 38888389
DOI: No ID Found -
RMD Open Jun 2024To compare the risk of cardiovascular events among Janus kinase inhibitors (JAKIs), biological disease-modifying antirheumatic drugs (bDMARDs) (tumour necrosis factor...
Increased risk of cardiovascular events under the treatments with Janus kinase inhibitors versus biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a retrospective longitudinal population-based study using the Japanese health insurance database.
OBJECTIVES
To compare the risk of cardiovascular events among Janus kinase inhibitors (JAKIs), biological disease-modifying antirheumatic drugs (bDMARDs) (tumour necrosis factor inhibitors (TNFIs) and non-TNFIs) and methotrexate (MTX) in Japanese patients with rheumatoid arthritis (RA).
METHODS
Using Japanese claims data, patients with RA were enrolled in this study if they had at least one ICD-10 code (M05 or M06), were new users of JAKIs, bDMARDs or MTX between July 2013 and July 2020 and being 18 years old or older. The incidence rate (IR), IR ratio and adjusted hazard ratio (aHR (95% CI)) of cardiovascular events including venous thromboembolism, arterial thrombosis, acute myocardial infarction and stroke were calculated. A time-dependent Cox regression model adjusted for patient characteristics at baseline was used to calculate aHR.
RESULTS
In 53 448 cases, IRs/1000 patient-years of the overall cardiovascular events were 10.1, 6.8, 5.4, 9.1 and 11.3 under the treatments with JAKIs, bDMARDs, TNFIs, non-TNFIs and MTX, respectively. The adjusted HRs of JAKIs for overall cardiovascular events were 1.7 (1.1 to 2.5) versus TNFIs without MTX and 1.7 (1.1 to 2.7) versus TNFIs with MTX.
CONCLUSIONS
Among patients with RA, individuals using JAKIs had a significantly higher risk of overall cardiovascular events than TNFIs users, which was attributed to the difference in the risk between JAKIs and TNFIs versus MTX. These data should be interpreted with caution because of the limitations associated with the claims database.
Topics: Humans; Arthritis, Rheumatoid; Female; Male; Antirheumatic Agents; Middle Aged; Cardiovascular Diseases; Janus Kinase Inhibitors; Japan; Aged; Retrospective Studies; Longitudinal Studies; Methotrexate; Adult; Incidence; Databases, Factual; Risk Factors; Insurance, Health; East Asian People
PubMed: 38886005
DOI: 10.1136/rmdopen-2023-003885 -
Zhurnal Voprosy Neirokhirurgii Imeni N.... 2024Leptomeningeal metastases are lesions of brain and/or spinal cord sheaths by tumor cells. They occur in 5% of patients with solid tumors, although autopsies reveal these...
UNLABELLED
Leptomeningeal metastases are lesions of brain and/or spinal cord sheaths by tumor cells. They occur in 5% of patients with solid tumors, although autopsies reveal these lesions much more often (10-20% of cases). Leptomengeal metastases are an unfavorable prognostic factor. Despite the modern NCCN treatment standards, including intrathecal therapy (ITT), such patients receive only irradiation of the entire brain and/or spinal cord in most cases.
OBJECTIVE
To evaluate the effectiveness of ITT in patients with leptomeningeal metastases in breast cancer.
MATERIAL AND METHODS
Twenty-five patients with breast cancer and leptomeningeal metastases underwent intrathecal administration of methotrexate between 2016 and 2022. Intrathecal chemotherapy was administered through lumbar puncture. We performed an intensive course (intrathecal methotrexate 15 mg 2 times a week for 1 month (8 injections), then intrathecal methotrexate 15 mg 1 time a week (4 injections), and then 15 mg 1 time a month until progression or unacceptable toxicity).
RESULTS
The median duration of ITT was 2.5 months. Complete neurological responses were observed in 3 out of 25 (12%) patients, partial neurological response - in 15 out of 25 (60%) patients, progression of neurological symptoms - in 7 (28%) patients. The number of complete cytological responses was observed in 6 out of 25 (24%) patients. The median overall survival after ITT was 6.7 months.
CONCLUSION
Effectiveness of ITT is confirmed by higher quality of life (72% of patients), complete cytological responses (24%) and improvement in neuroimaging data. This is an important criterion for severe patients with limited treatment options. First-stage ITT before whole-brain irradiation is preferable, as this approach increases overall survival by 3 months. Undoubtedly, ITT is a treatment option that can be used in routine clinical practice for lesions of brain and spinal cord sheaths.
Topics: Humans; Female; Breast Neoplasms; Middle Aged; Injections, Spinal; Adult; Meningeal Neoplasms; Methotrexate; Aged; Meningeal Carcinomatosis; Antimetabolites, Antineoplastic
PubMed: 38881013
DOI: 10.17116/neiro20248803131 -
Cutaneous Rosai-Dorfman disease: a systematic review and reappraisal of its treatment and prognosis.Archives of Dermatological Research Jun 2024Cutaneous Rosai Dorfman disease (CRDD) is a rare histiocytic disorder that shows distinctive clinical presentation and prognosis. Sufficient data is currently lacking... (Review)
Review
Cutaneous Rosai Dorfman disease (CRDD) is a rare histiocytic disorder that shows distinctive clinical presentation and prognosis. Sufficient data is currently lacking regarding evidence-based management of CRDD. This systematic review aims to provide a comprehensive overview of CRDD, focusing on treatment approaches and outcomes. PubMed and Scopus databases were searched for studies on CRDD from June 1st, 2013 to May 31st, 2023. Articles describing cases of CRDD confirmed with histological examination were eligible for inclusion. All interventions for CRDD were analyzed. The primary outcome measure was the response of cutaneous lesions to treatment including complete response (CR), partial response (PR), and no response. The secondary outcome measures were mortality rate, relapse rate, and the occurrence of adverse events related to CRDD treatment. Eighty-seven articles describing 118 CRDD cases were included. The mean age was 48.2±16.8 years. The sex ratio (F/M) was 1.53. Nodular (46.6%) erythematous (45.3%) lesions, located on the face (38.1%) were the most prevalent presentations. Associated hematological malignancies were noted in 8 (6.8%) cases. Surgical excision was the most prevalent intervention (51 cases) with CR in 48 cases. Systemic corticosteroids were used in 32 cases with 20 CR/PR, retinoids in 10 cases with 4 CR/PR, thalidomide in 9 cases with 5 CR/PR, methotrexate in 8 cases with 7 CR/PR while observation was decided in 10 cases with 6 CR/PR. Factors independently associated with the absence of response to treatment were facial involvement (OR = 0.76, p = 0.014), and cutaneous lesion size (OR = 1.016, p = 0.03). This systematic review shows distinctive clinical characteristics of CRDD and provides insights into the appropriate management of the disease. It allowed a proposal of a treatment algorithm that should be interpreted in the context of current evidence and would help practitioners in treating this rare disease.
Topics: Humans; Histiocytosis, Sinus; Prognosis; Treatment Outcome; Female; Skin; Male; Middle Aged; Adrenal Cortex Hormones; Retinoids; Skin Diseases; Methotrexate; Adult
PubMed: 38878198
DOI: 10.1007/s00403-024-02982-6 -
Archives of Dermatological Research Jun 2024Keratoacanthoma (KA) is a benign neoplasm that affects mainly photodamaged skin. It is locally destructive and may rarely spread. Surgery is not always suitable and... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Keratoacanthoma (KA) is a benign neoplasm that affects mainly photodamaged skin. It is locally destructive and may rarely spread. Surgery is not always suitable and usually disfiguring. Thus, non-operative modalities represent good alternatives.
OBJECTIVE
To assess and compare the efficacy of intralesional methotrexate (MTX) and 5-flurouracil (5-FU) in the treatment of KA.
PATIENTS AND METHODS
Randomized controlled trial included 20 patients with biopsy proven KA divided into 2 equal groups; group (A) received intralesional MTX, 25 mg/ml and group (B) received intralesional 5-FU, 50 mg/ml every 2 weeks till complete clearance or for a maximum 5 sessions.
RESULTS
In the MTX group, complete clearance was observed in 7 patients (70%) compared to 8 patients (80%) in the 5- FU group with no statistically significant difference. However, the median number of injections needed to achieve complete response in the MTX group was 3 sessions versus only 2 sessions in the 5-FU group.
LIMITATIONS
the small sample size due to the relatively low incidence of KAs in our population.
CONCLUSION
Intralesional therapy is a good alternative to surgery in selected cases of KA. Both drugs showed comparable efficacy, but 5-FU may give faster results, hence increasing patient satisfaction and compliance.
Topics: Humans; Methotrexate; Fluorouracil; Keratoacanthoma; Female; Male; Middle Aged; Injections, Intralesional; Aged; Treatment Outcome; Adult; Antimetabolites, Antineoplastic; Aged, 80 and over
PubMed: 38878177
DOI: 10.1007/s00403-024-03139-1 -
PloS One 2024Emulation of the "target trial" (TT), a hypothetical pragmatic randomized controlled trial (RCT), using observational data can be used to mitigate issues commonly...
Designing target trials using electronic health records: A case study of second-line disease-modifying anti-rheumatic drugs and cardiovascular disease outcomes in patients with rheumatoid arthritis.
BACKGROUND
Emulation of the "target trial" (TT), a hypothetical pragmatic randomized controlled trial (RCT), using observational data can be used to mitigate issues commonly encountered in comparative effectiveness research (CER) when randomized trials are not logistically, ethically, or financially feasible. However, cardiovascular (CV) health research has been slow to adopt TT emulation. Here, we demonstrate the design and analysis of a TT emulation using electronic health records to study the comparative effectiveness of the addition of a disease-modifying anti-rheumatic drug (DMARD) to a regimen of methotrexate on CV events among rheumatoid arthritis (RA) patients.
METHODS
We used data from an electronic medical records-based cohort of RA patients from Northwestern Medicine to emulate the TT. Follow-up began 3 months after initial prescription of MTX (2000-2020) and included all available follow-up through June 30, 2020. Weighted pooled logistic regression was used to estimate differences in CVD risk and survival. Cloning was used to handle immortal time bias and weights to improve baseline and time-varying covariate imbalance.
RESULTS
We identified 659 eligible people with RA with average follow-up of 46 months and 31 MACE events. The month 24 adjusted risk difference for MACE comparing initiation vs non-initiation of a DMARD was -1.47% (95% confidence interval [CI]: -4.74, 1.95%), and the marginal hazard ratio (HR) was 0.72 (95% CI: 0.71, 1.23). In analyses subject to immortal time bias, the HR was 0.62 (95% CI: 0.29-1.44).
CONCLUSION
In this sample, we did not observe evidence of differences in risk of MACE, a finding that is compatible with previously published meta-analyses of RCTs. Thoughtful application of the TT framework provides opportunities to conduct CER in observational data. Benchmarking results of observational analyses to previously published RCTs can lend credibility to interpretation.
Topics: Humans; Arthritis, Rheumatoid; Antirheumatic Agents; Electronic Health Records; Cardiovascular Diseases; Female; Male; Middle Aged; Methotrexate; Aged; Treatment Outcome; Randomized Controlled Trials as Topic; Comparative Effectiveness Research; Adult
PubMed: 38875273
DOI: 10.1371/journal.pone.0305467 -
Frontiers in Immunology 2024The intricate immune mechanisms governing mucosal healing following intestinal damage induced by cytotoxic drugs remain poorly understood. The goal of this study was to...
The intricate immune mechanisms governing mucosal healing following intestinal damage induced by cytotoxic drugs remain poorly understood. The goal of this study was to investigate the role of lymphotoxin beta receptor (LTβR) signaling in chemotherapy-induced intestinal damage. LTβR deficient mice exhibited heightened body weight loss, exacerbated intestinal pathology, increased proinflammatory cytokine expression, reduced IL-22 expression, and proliferation of intestinal epithelial cells following methotrexate (MTX) treatment. Furthermore, LTβRIL-22 mice succumbed to MTX treatment, suggesting that LTβR- and IL-22- dependent pathways jointly promote mucosal repair. Although both LTβR ligands LIGHT and LTβ were upregulated in the intestine early after MTX treatment, LIGHT mice, but not LTβ mice, displayed exacerbated disease. Further, we revealed the critical role of T cells in mucosal repair as T cell-deficient mice failed to upregulate intestinal LIGHT expression and exhibited increased body weight loss and intestinal pathology. Analysis of mice with conditional inactivation of LTβR revealed that LTβR signaling in intestinal epithelial cells, but not in Lgr5 intestinal stem cells, macrophages or dendritic cells was critical for mucosal repair. Furthermore, inactivation of the non-canonical NF-kB pathway member RelB in intestinal epithelial cells promoted MTX-induced disease. Based on these results, we propose a model wherein LIGHT produced by T cells activates LTβR-RelB signaling in intestinal epithelial cells to facilitate mucosal repair following chemotherapy treatment.
Topics: Animals; Intestinal Mucosa; Lymphotoxin beta Receptor; Signal Transduction; Mice; Mice, Knockout; Transcription Factor RelB; Methotrexate; Epithelial Cells; Mice, Inbred C57BL; Interleukin-22; Interleukins
PubMed: 38873613
DOI: 10.3389/fimmu.2024.1388496 -
ACS Applied Materials & Interfaces Jun 2024Atherosclerotic plaques exhibit high cholesterol deposition and oxidative stress resulting from high reactive oxygen species (ROS). These are the major components in...
Atherosclerotic plaques exhibit high cholesterol deposition and oxidative stress resulting from high reactive oxygen species (ROS). These are the major components in plaques and the main pro-inflammatory factor. Therefore, it is crucial to develop an effective therapeutic strategy that can simultaneously address the multiple pro-inflammatory factors removing cholesterol and inhibiting the overaccumulated ROS. In this study, we constructed macrophage membrane-encapsulated biomimetic nanoparticles (MM@DA-pCD@MTX), which not only alleviate cholesterol deposition at the plaque lesion reverse cholesterol transport but also scavenge the overaccumulated ROS. β-Cyclodextrin (β-CD) and the loaded methotrexate (MTX) act synergistically to induce cholesterol efflux for inhibiting the formation of foam cells. Among them, MTX up-regulated the expression of ABCA1, CYP27A1, and SR-B1. β-CD increased the solubility of cholesterol crystals. In addition, the ROS scavenging property of dopamine (DA) was perfectly preserved in MM@DA-pCD@MTX, which could scavenge the overaccumulated ROS to alleviate the oxidative stress at the plaque lesion. Last but not least, MM-functionalized "homing" targeting of atherosclerotic plaques not only enables the targeted drug delivery but also prolongs circulation time and drug half-life. In summary, MM@DA-pCD@MTX emerges as a potent, multifunctional therapeutic platform for AS treatment, offering a high degree of biosafety and efficacy in addressing the complex pathophysiology of atherosclerosis.
Topics: Dopamine; Nanoparticles; Atherosclerosis; Mice; Animals; Biomimetic Materials; Methotrexate; Cholesterol; Macrophages; Reactive Oxygen Species; Humans; Cyclodextrins; RAW 264.7 Cells; Oxidative Stress; Drug Carriers; beta-Cyclodextrins
PubMed: 38867426
DOI: 10.1021/acsami.4c04431 -
Journal of Obstetrics and Gynaecology :... Dec 2024The pre-treatment characteristics of the patient and ectopic pregnancy to determine the patients who are likely to successfully respond to methotrexate (MTX) therapy...
BACKGROUND
The pre-treatment characteristics of the patient and ectopic pregnancy to determine the patients who are likely to successfully respond to methotrexate (MTX) therapy remain controversial. This study investigated the outcomes of ectopic pregnancy after one and two MTX doses and their independent predictors.
METHODS
Retrospective cross-sectional study of women who consented to MTX treatment in 2017-2018 at our institution ( = 317). Of these, patients with Caesarean scar pregnancies were excluded because they require different treatment protocols ( = 25). All patients were treated according to our institution's protocol based on international guidelines and standardised across the three hospitals included in the current study. We retrieved patients' demographics, laboratory, ultrasonography, and clinical characteristics from our hospital database. Serum β-human chorionic gonadotropin (β-hCG) was measured using electrochemiluminescence immunoassay; ectopic pregnancy was diagnosed using ultrasonography (transvaginal probe).
RESULTS
Two ninety-two patients were included in the current analysis. Age, pre-treatment β-hCG levels, sonographic presence of yolk sac, presence of foetal cardiac activity, and pelvic pain were significantly different between patients with successful and unsuccessful outcomes. Younger age (adjusted odds ratio [aOR] 2.33, 95% confidence interval (CI) 1.16-4.66, = .017), no pelvic pain (aOR 2.65, 95%CI 1.03-6.83, = .043), lower initial β-hCG level (aOR 1.32, 95%CI 1.08-1.59, = .005), and absence of foetal cardiac activity (aOR 12.63; 95% CI 1.04-153.6; = .047) were independently associated with success. Treatment failure odds were >2 folds higher for each 10-year age increase ( = .017), 32% higher for each 1000 IU/L increase in initial β-hCG level ( = .005), and >2 folds higher in presence of pelvic pain ( = .043).
CONCLUSIONS
MTX is effective in most patients, averting invasive surgery, which might affect fertility. Pre-treatment β-hCG levels, age, pelvic pain, and foetal cardiac activity was independently associated with outcomes. Research should assess the relationship between the ectopic pregnancy size and treatment outcomes and refine β-hCG titres where treatment would be ineffective.
Topics: Humans; Female; Methotrexate; Pregnancy; Adult; Retrospective Studies; Cross-Sectional Studies; Abortifacient Agents, Nonsteroidal; Chorionic Gonadotropin, beta Subunit, Human; Pregnancy, Tubal; Treatment Outcome
PubMed: 38864434
DOI: 10.1080/01443615.2024.2361456 -
Annals of Saudi Medicine 2024Medical treatment, expectant approaches, and surgical treatment options are available in the treatment of ectopic pregnancy. Regardless of the treatment, in addition to...
BACKGROUND
Medical treatment, expectant approaches, and surgical treatment options are available in the treatment of ectopic pregnancy. Regardless of the treatment, in addition to its effectiveness, the main concern is to limit the risk of relapse and preserve fertility.
OBJECTIVES
Determine the impact of medical or surgical treatment for ectopic pregnancy on future fertility.
DESIGN
Retrospective.
SETTING
Department of obstrtrics and gynecolgy at Ankara Etlik Zübeyde Hanım Women's Health Training and Research Hospital, Ankara, Turkey.
PATIENTS AND METHODS
Patients who were treated for ectopic pregnancy between June 2016 and November 2019 were allocated into two groups. Expectant approach or medical treatment by methotrexate constituted the conservative treatment group while salpingectomy by laparoscopy indicated the surgical treatment group.
MAIN OUTCOME MEASURES
Fertility rates within two years following treatment were evaluated according to treatment options.
SAMPLE SIZE
202 patients.
RESULTS
Of the 202 patients, 128 had medical treatment and 74 patients had surgical treatment for ectopic pregnancy. Of 272 diagnosed with ectopic pregnancy, 70 were excluded for various reasons. Parity and unemployment rate was significantly higher in the surgical treatment (=.006 and =.12, respectively). Moreover, ectopic mass size and serum β-hCG levels were significantly higher in the surgical treatment group (<.001 and <.001, respectively). There were no significant differences between the conservative and surgical treatment groups in time to pregnancy (17.0 months vs 19.0 months, =.255). Similarly, there was no significant difference between the conservative and surgical treatment groups with respect to history of infertility (=.12). There were no significant differences between the conservative and surgical treatment groups in terms of live birth (51.6% vs 44.6%) and ectopic pregnancy (2.3% vs 1.4%) (=.72 for both). There was no significant difference between the conservative and surgical treatment groups with respect to infertility rate (35.9% vs 41.9%, =.72) and admittance to the IVF program (3.9% vs 6.8%, =.39) following ectopic pregnancy treatment.
CONCLUSIONS
Reproductive outcomes did not differ significantly in women undergoing expectant management, medical treatment, and surgery for ectopic pregnancy. This finding suggests that clinicians should not hesitate to act in favor of surgical treatment for ectopic pregnancy even if there were concerns for future fertility.
LIMITATIONS
Retrospective study.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Adult; Methotrexate; Salpingectomy; Conservative Treatment; Pregnancy, Tubal; Laparoscopy; Abortifacient Agents, Nonsteroidal; Turkey; Fertility; Chorionic Gonadotropin, beta Subunit, Human; Fertility Preservation
PubMed: 38853473
DOI: 10.5144/0256-4947.2024.141