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Lupus Science & Medicine Oct 2023To investigate the association of medication copayment and treatment adherence to hydroxychloroquine and immunosuppressants for SLE.
OBJECTIVE
To investigate the association of medication copayment and treatment adherence to hydroxychloroquine and immunosuppressants for SLE.
METHODS
We conducted a retrospective analysis of health claims data using Optum's de-identified Clinformatics Data Mart Database. Individuals with SLE continuously enrolled for 180 days from 1 July 2010 to 31 December 2019 were included. Adherence was defined as the proportion of days covered ≥80%. Copayment for a 30-day supply of medication was dichotomised as high (≥$10) or low (<$10). We examined the association between copayment and odds of adherence in multivariable-adjusted logistic regression models, including age, sex, race or ethnicity, comorbidities, educational attainment and household income.
RESULTS
We identified 12 510 individuals (age 54.2±15.5 years; 88.2% female sex), of whom 9510 (76%) were prescribed hydroxychloroquine and 1880 (15%) prescribed hydroxychloroquine and an additional immunosuppressant (azathioprine, methotrexate or mycophenolate mofetil). Median (IQR) 30-day copayments were $8 (4-10) for hydroxychloroquine, $7 (2-10) for azathioprine, $8 (3-11) for methotrexate and $10 (5-20) for mycophenolate mofetil. High copayments were associated with OR of adherence of 0.61 (95% CI 0.55 to 0.68) for hydroxychloroquine, OR 0.44 (95% CI 0.30 to 0.66) for azathioprine and OR 0.69 (95% CI 0.49 to 0.96) for mycophenolate mofetil. For methotrexate, the association was not significant.
CONCLUSION
In a large, administrative health claims database, we identified that high copayments were associated with reduced adherence to commonly prescribed medications for SLE. Incorporating awareness of the burden of copayments and its consequences into healthcare is essential to promote optimal medication adherence.
Topics: Humans; Female; Adult; Middle Aged; Aged; Male; Lupus Erythematosus, Systemic; Hydroxychloroquine; Azathioprine; Methotrexate; Mycophenolic Acid; Retrospective Studies; Immunosuppressive Agents; Medication Adherence
PubMed: 37852670
DOI: 10.1136/lupus-2023-000966 -
Revista Espanola de Enfermedades... Mar 2024A 48-year-old man with a diagnosis of ulcerative colitis 18 years ago, under immunosuppressive treatment with azathioprine in the last 6 years due to corticosteroid...
A 48-year-old man with a diagnosis of ulcerative colitis 18 years ago, under immunosuppressive treatment with azathioprine in the last 6 years due to corticosteroid dependence, was admitted to the Emergency Department due to fever of one week's evolution. Blood tests showed thrombocytopenia, CRP 96.9mg/L, ferritin 3021ng/mL and hypertriglyceridemia. Blood and urine cultures were negative. Viral serologies (hepatitis B and C, HIV, parvovirus, CMV, HSV), atypical bacteria (Borrelia, Chlamydia, Coxiella) and screening for latent tuberculosis were also negative. Thoracoabdominal CT scan only showed splenomegaly. The bone marrow aspirate revealed immature lymphoid cells and a hemophagocyte figure, fulfilling the criteria for hemophagocytic syndrome, starting corticosteroid therapy at a dose of 1mg/Kg. Subsequently, the existence of an intrasinusoidal CD3 + CD5- lymphoid infiltrate and a FISH study with isochromosome 7q was reported, a characteristic pattern of hepatosplenic T-cell lymphoma (HSTCL). The study was completed with liver biopsy appreciating a 70% infiltration of T lymphocytes (50% gamma-delta) therefore the diagnosis was confirmed. Chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide) was started with the aim of considering hematopoietic stem cell transplantation. Unfortunately, the patient died 6 months later.
Topics: Male; Humans; Middle Aged; Lymphoma, T-Cell; Immunosuppressive Agents; Azathioprine; Inflammatory Bowel Diseases; Adrenal Cortex Hormones; Liver Neoplasms
PubMed: 37170572
DOI: 10.17235/reed.2023.9472/2023 -
Clinical Medicine (London, England) Nov 2023The presented case highlights a rare instance of relapsing polychondritis (RP) manifesting as seronegative limbic encephalitis, an uncommon neurological complication. A...
The presented case highlights a rare instance of relapsing polychondritis (RP) manifesting as seronegative limbic encephalitis, an uncommon neurological complication. A 70-year-old female patient with a history of RP-related inflammation, along with neuropsychiatric symptoms, was diagnosed through multidisciplinary collaboration. Swift administration of steroid therapy, followed by azathioprine, led to remarkable physical and cognitive recovery. This case emphasises the importance of a multidisciplinary approach in diagnosing and treating complex autoimmune disorders with neurological manifestations.
Topics: Female; Humans; Aged; Limbic Encephalitis; Polychondritis, Relapsing; Azathioprine
PubMed: 38065590
DOI: 10.7861/clinmed.2023-0430 -
Frontiers in Psychiatry 2023Anxiety and depression symptoms are very common in patients with inflammatory bowel disease (IBD). We aimed to explore the impact of anxiety and depression on the...
BACKGROUND
Anxiety and depression symptoms are very common in patients with inflammatory bowel disease (IBD). We aimed to explore the impact of anxiety and depression on the efficacy of medications, as well as IBD-related poor outcomes.
METHOD
This was a prospective longitudinal observational study. Hospital Anxiety and Depression Scale was used to assess anxiety and depression symptoms. Logistic regression analyses were used to assess the association between anxiety/depression and the response to different medications. Kaplan-Meier survival analysis and Cox regression model were applied to analyze the relationship between anxiety/depression and IBD-related poor outcomes, which were defined as urgent IBD-related hospitalization, IBD-related surgery, or death.
RESULTS
A total of 325 IBD patients were enrolled, 118 of whom were treated with corticosteroids, 88 with azathioprine/6-mercaptopurine (AZA/6-MP), and 147 with anti-TNF agents. Anxiety/depression symptoms were found to be significantly related to steroid resistance, but independent of AZA/6-MP and anti-TNF agents nonresponse. There was a significant association between anxiety/depression symptoms and IBD-related poor outcomes. Coexisting with anxiety/depression symptoms was an independent influencing factor of steroid resistance and IBD-related poor outcomes.
CONCLUSION
IBD patients with anxiety/depression symptoms were at a higher risk of developing steroid resistance and IBD-related poor outcomes. Future studies are needed to explore whether interventions for anxiety and depression will improve their response to medications and change their prognosis.
PubMed: 37547213
DOI: 10.3389/fpsyt.2023.1029467 -
Frontiers in Immunology 2023To evaluate the prevalence, incidence, and predictors of herpes zoster (HZ) development in lupus nephritis (LN).
OBJECTIVES
To evaluate the prevalence, incidence, and predictors of herpes zoster (HZ) development in lupus nephritis (LN).
METHODS
This retrospective study included 292 LN patients to determine HZ incidence during the last decades and its correlation with LN activity. LN patients with HZ were matched with LN patients without HZ in a 1:2 ratio based on sex, age, year of LN diagnosis, and LN histological class at kidney biopsy to assess HZ risk factors. Statistical tests included t-test, U-test, and Fisher's test. Univariate and multivariate logistic regression analyses were conducted to identify potential risk factors.
RESULTS
HZ occurred after LN diagnosis in 66 patients (prevalence 22.6%) with an average of 8.7 years (range 0.2-28.4 years). Although with the potential limitations of the retrospective nature and the extensive duration of the study, the incidence of HZ was 15.6/1,000 person-years, increasing from 6.9 before 1980 to 16.0 in the 1990s and 43.9 after 2010. HZ onset was unrelated to LN activity. LN was active in 43% of cases and quiescent in the other 57% of cases at HZ diagnosis. The percentage of patients who developed lupus flares during the year after HZ (18.9%) was not different from that which occurred during the year before HZ (17.2%, p = 0.804). After excluding confounding factors through matching, the univariate analysis suggested that cyclosporin during induction therapy (p = 0.011) and higher cumulative doses of glucocorticoids (GCs; >50 g, p = 0.004), cyclophosphamide (CYC; >5 g, p = 0.001), and mycophenolate mofetil (MMF > 1,000 g, p = 0.007) predisposed patients to HZ. Univariate and multivariate analyses revealed a protective role of azathioprine (p = 0.008) and methylprednisolone pulses (p = 0.010) during induction therapy.
CONCLUSIONS
HZ occurs unpredictably throughout the course of LN, underscoring the importance of continuous monitoring for these patients. In addition, the incidence of HZ seems to have increased in recent decades. Induction therapy with azathioprine and methylprednisolone pulses appears to provide protection, while higher cumulative doses of GCs, CYC, and MMF increase susceptibility.
Topics: Humans; Lupus Nephritis; Immunosuppressive Agents; Azathioprine; Retrospective Studies; Treatment Outcome; Mycophenolic Acid; Herpes Zoster; Methylprednisolone
PubMed: 38077357
DOI: 10.3389/fimmu.2023.1293269 -
Clinical Journal of Gastroenterology Aug 2023Several vaccines have been developed for coronavirus disease 2019 (COVID-19) and are used worldwide. Here we report a case of severe acute hepatitis induced by COVID-19... (Review)
Review
Several vaccines have been developed for coronavirus disease 2019 (COVID-19) and are used worldwide. Here we report a case of severe acute hepatitis induced by COVID-19 vaccination. A 54-year-old woman received two doses of the Pfizer-BioNTech COVID-19 mRNA vaccine and an additional dose of the Moderna COVID-19 mRNA vaccine. Seven days after the third dose, she noticed fatigue, appetite loss and dark urine. Laboratory tests were consistent with severe liver injury and jaundice. Anti-smooth muscle antibody and HLA-DR4 were positive; thus, we suspected that she had autoimmune hepatitis (AIH). Intravenous methylprednisolone followed by oral prednisolone were administered. Because remission was not achieved, we performed percutaneous liver biopsy. Histologically, pan-lobular inflammation with moderate infiltration of lymphocytes and macrophages, interface hepatitis, and rosette formation were present. We regarded these findings as confirmation of the diagnosis of AIH. As she had not responded to corticosteroids, we added azathioprine. Liver biochemistry tests gradually improved, and prednisolone could be tapered without relapse of AIH. Dozens of cases of AIH after COVID-19 vaccination have been reported. Corticosteroids were effective in most cases, but some patients have died from liver failure after vaccination. This case illustrates the efficacy of azathioprine for steroid-refractory AIH induced by COVID-19 vaccination.
Topics: Female; Humans; Middle Aged; Adrenal Cortex Hormones; Azathioprine; COVID-19; COVID-19 Vaccines; Hepatitis, Autoimmune; mRNA Vaccines; Prednisolone; Vaccination
PubMed: 37029249
DOI: 10.1007/s12328-023-01794-x -
Cureus May 2024Crohn's disease is a type of inflammatory bowel disease (IBD) that typically presents in the second or third decade of life. There are various pharmaceutical therapies...
Crohn's disease is a type of inflammatory bowel disease (IBD) that typically presents in the second or third decade of life. There are various pharmaceutical therapies that have been developed to treat the disease's symptoms. However, some patients still do not find relief with these medications and turn to other therapies such as diet modification. The underlying cause of Crohn's disease involves multiple factors such as uncontrolled inflammation and several genetic variants. While most current medication therapies control the symptoms that occur due to this uncontrolled level of inflammation, an anti-inflammatory diet (AID) may actually lower the level of inflammation in the gut and therefore reduce the amount of disease symptoms in Crohn's disease. Some such diets include the IBD-AID, Crohn's disease exclusion diet, and the Groningen AID (GrAID). This report describes a case of treatment-resistant Crohn's disease in a patient who was given all categories of pharmaceutical therapies including prednisone, budesonide, sulfasalazine, olsalazine, 6-mercaptopurine, methotrexate, mesalamine, and adalimumab. These only gave temporary relief of symptoms and eventually failed for various reasons including allergic reaction, insufficient symptom control, and antibody formation against the medication. This prompted the patient to independently research AIDs instead. In conclusion, for patients whose disease is refractory to different treatments, or who develop antibodies to the medication, AIDs may offer a solution to reduce disease symptoms and progression. Education of healthcare professionals and patients alike is vital in order for Crohn's patients to gain the benefits from dietary therapy.
PubMed: 38939280
DOI: 10.7759/cureus.61262 -
Value in Health Regional Issues Nov 2023To evaluate the cost-effectiveness of pharmacological treatment in maintenance therapy for adult heart transplant recipients from the Colombian health system perspective. (Review)
Review
OBJECTIVES
To evaluate the cost-effectiveness of pharmacological treatment in maintenance therapy for adult heart transplant recipients from the Colombian health system perspective.
METHODS
We constructed a decision tree model with a 1-year time horizon. A review of the clinical literature was performed to extract probabilities of health events and acute rejections avoided were used as the health outcome. Costs were calculated from the base-case approximation and were obtained from administrative databases in Colombia (Sistema de Información de Precios de Medicamentos 2020 and Suficiencia 2012-2019), and the prices were adjusted to US dollar 2021.
RESULTS
Two evaluation results were presented. The first evaluates the tacrolimus + azathioprine + corticosteroid (TAC) scheme compared with cyclosporine + azathioprine + corticosteroid (CAC), in which the incremental cost-effectiveness ratio indicates that 1 additional rejection avoided has a cost of US dollar $5461.09 which, compared with the cost-effectiveness threshold in the base case, indicates that the TAC scheme is not a cost-effective (CE) strategy with respect to the CAC scheme. The second result shows the comparison of tacrolimus + mycophenolate mofetil + corticosteroid (TMC) with cyclosporine + mycophenolate mofetil + corticosteroid (CMC) in which TMC was found to be a dominant alternative to CMC.
CONCLUSIONS
The tacrolimus-based immunosuppression scheme is not CE in its TAC scheme, versus CAC, and is dominant in its TMC scheme, versus CMC, sensitivity analyses show that tacrolimus could become a CE alternative in any scheme used against higher cost-effectiveness threshold.
Topics: Adult; Humans; Tacrolimus; Cyclosporine; Immunosuppressive Agents; Cost-Benefit Analysis; Colombia; Mycophenolic Acid; Azathioprine; Immunosuppression Therapy; Heart Transplantation; Adrenal Cortex Hormones
PubMed: 37573854
DOI: 10.1016/j.vhri.2023.06.005 -
Molecules (Basel, Switzerland) May 2024The rapid advancements in nanotechnology in the field of nanomedicine have the potential to significantly enhance therapeutic strategies for cancer treatment. There is... (Review)
Review
The rapid advancements in nanotechnology in the field of nanomedicine have the potential to significantly enhance therapeutic strategies for cancer treatment. There is considerable promise for enhancing the efficacy of cancer therapy through the manufacture of innovative nanocomposite materials. Metallic nanoparticles have been found to enhance the release of anticancer medications that are loaded onto them, resulting in a sustained release, hence reducing the dosage required for drug administration and preventing their buildup in healthy cells. The combination of nanotechnology with biocompatible materials offers new prospects for the development of advanced therapies that exhibit enhanced selectivity, reduced adverse effects, and improved patient outcomes. Chitosan (CS), a polysaccharide possessing distinct physicochemical properties, exhibits favorable attributes for controlled drug delivery due to its biocompatibility and biodegradability. Chitosan nanocomposites exhibit heightened stability, improved biocompatibility, and prolonged release characteristics for anticancer medicines. The incorporation of gold (Au) nanoparticles into the chitosan nanocomposite results in the manifestation of photothermal characteristics, whereas the inclusion of silver (Ag) nanoparticles boosts the antibacterial capabilities of the synthesized nanocomposite. The objective of this review is to investigate the recent progress in the utilization of Ag and Au nanoparticles, or a combination thereof, within a chitosan matrix or its modified derivatives for the purpose of anticancer drug delivery. The research findings for the potential of a chitosan nanocomposite to deliver various anticancer drugs, such as doxorubicin, 5-Fluroacil, curcumin, paclitaxel, and 6-mercaptopurine, were investigated. Moreover, various modifications carried out on the chitosan matrix phase and the nanocomposite surfaces to enhance targeting selectivity, loading efficiency, and pH sensitivity were highlighted. In addition, challenges and perspectives that could motivate further research related to the applications of chitosan nanocomposites in cancer therapy were summarized.
Topics: Chitosan; Nanocomposites; Antineoplastic Agents; Silver; Humans; Metal Nanoparticles; Gold; Drug Delivery Systems; Drug Carriers; Neoplasms; Animals
PubMed: 38792255
DOI: 10.3390/molecules29102393 -
Pharmacological Research Feb 2024Lenvatinib is a frontline tyrosine kinase inhibitor for patients with advanced hepatocellular carcinoma (HCC). However, just 25% of patients benefit from the treatment,...
Identification of Fasudil as a collaborator to promote the anti-tumor effect of lenvatinib in hepatocellular carcinoma by inhibiting GLI2-mediated hedgehog signaling pathway.
Lenvatinib is a frontline tyrosine kinase inhibitor for patients with advanced hepatocellular carcinoma (HCC). However, just 25% of patients benefit from the treatment, and acquired resistance always develops. To date, there are neither effective medications to combat lenvatinib resistance nor accurate markers that might predict how well a patient would respond to the lenvatinib treatment. Thus, novel strategies to recognize and deal with lenvatinib resistance are desperately needed. In the current study, a robust Lenvatinib Resistance index (LRi) model to predict lenvatinib response status in HCC was first established. Subsequently, five candidate drugs (Mercaptopurine, AACOCF3, NU1025, Fasudil, and Exisulind) that were capable of reversing lenvatinib resistance signature were initially selected by performing the connectivity map (CMap) analysis, and fasudil finally stood out by conducting a series of cellular functional assays in vitro and xenograft mouse model. Transcriptomics revealed that the co-administration of lenvatinib and fasudil overcame lenvatinib resistance by remodeling the hedgehog signaling pathway. Mechanistically, the feedback activation of EGFR by lenvatinib led to the activation of the GLI2-ABCC1 pathway, which supported the HCC cell's survival and proliferation. Notably, co-administration of lenvatinib and fasudil significantly inhibited IHH, the upstream switch of the hedgehog pathway, to counteract GLI2 activation and finally enhance the effectiveness of lenvatinib. These findings elucidated a novel EGFR-mediated mechanism of lenvatinib resistance and provided a practical approach to overcoming drug resistance in HCC through meaningful drug repurposing strategies.
Topics: Humans; Animals; Mice; Carcinoma, Hepatocellular; Hedgehog Proteins; Antineoplastic Agents; Liver Neoplasms; Cell Line, Tumor; ErbB Receptors; Zinc Finger Protein Gli2; Nuclear Proteins; Phenylurea Compounds; Quinolines; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
PubMed: 38280440
DOI: 10.1016/j.phrs.2024.107082