This study aimed to detect signals of adverse drug reactions (ADRs) associated with biological disease-modifying antirheumatic drugs (DMARDs) and targeted therapies in rheumatoid arthritis (RA) and ...ankylosing spondylitis (AS) patients. Utilizing the KOrean College of Rheumatology BIOlogics & Targeted Therapy Registry (KOBIO) data, we calculated relative risks, excluded previously reported drug-ADR pairs, and externally validated remaining pairs using US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and single centre's electronic health records (EHR) data. Analyzing data from 2279 RA and 1940 AS patients, we identified 35 significant drug-ADR pairs in RA and 26 in AS, previously unreported in drug labels. Among the novel drug-ADR pairs from KOBIO, 15 were also significant in the FAERS data. Additionally, 2 significant drug-laboratory abnormality pairs were found in RA using CDM MetaLAB analysis. Our findings contribute to the identification of 14 novel drug-ADR signals, expanding our understanding of potential adverse effects related to biological DMARDs and targeted therapies in RA and AS. These results emphasize the importance of ongoing pharmacovigilance for patient safety and optimal therapeutic interventions.
Background
Patients with fibromyalgia (FM) exhibit significant clinical heterogeneity, in terms of physical, social and psychological functions, as well as therapeutic responses. Here, we examined FM ...patients in terms of pain, physical, social and psychological variables to identify clinical subgroups that may be predictive of treatment patterns.
Methods
A total of 313 FM patients were interviewed using a structured questionnaire that included sociodemographic data, current or past FM symptoms and current use of relevant medications. A K‐means cluster analysis was conducted using variables reflecting tender points, the Fibromyalgia Impact Questionnaire, Beck Depression Inventory, State‐Trait Anxiety Inventor and Social Support Scale.
Results
Four distinct clusters were identified in these patients. Group 1 was characterized by high pain levels, severe physical and mental impairment and low social support. Group 2 had moderate pain and physical impairment, mild mental impairment and moderate social support. Group 3 had moderate pain, low physical and moderate mental impairment and low social support. Group 4 had low pain levels, nearly normal physical and mental function and high social support. Group 1 was more often a current or past smoker, more likely to have a variety of symptoms, including swelling, cognitive dysfunction, dizziness, syncope, oesophageal dysmotility, dyspepsia, irritable bladder, vulvodynia and restless leg syndrome.
Conclusions
We identified four subgroups of FM patients based on pain, physical, social and psychological function. These subgroups had different clinical symptoms and medication profiles, suggesting that FM may be better managed using a more comprehensive assessment of an individual patient's symptoms.
Significance
FM patients can be clustered into four distinct subgroups based on clinically measurable variables – pain, physical involvement, psychological function and social support. These subgroups had different clinical symptoms and medication profiles.
Background
Although polymorphisms of the catechol‐O‐methyl transferase (COMT) gene have been implicated in altered pain sensitivity, results concerning the association between COMT gene polymorphisms ...and fibromyalgia (FM) are equivocal. We assessed the associations between COMT single‐nucleotide polymorphisms (SNP) and FM risk and symptom severity.
Methods
In total, 409 FM patients and 423 controls were enrolled. Alleles and genotypes at five positions rs6269 (A>G), rs4633 (C>T), rs4818 (C>G), rs4680 (C>G) and rs165599 (A>G) in the COMT gene were genotyped from peripheral blood DNA.
Results
Alleles and genotypes of the rs4818 COMT gene polymorphism were significantly associated with increased susceptibility to FM. The rs4818 GG genotype was more strongly associated with FM compared to the CC genotype (OR = 1.680, 95% CI: 1.057, 2.672, p = 0.027). Although allele and genotype frequencies did not differ among groups, the rs4633 CT genotype was not associated with the presence of FM following adjustment for age and sex (OR = 0.745; 95% CI: 0.558, 0.995; p = 0.046). However, no association was observed between clinical measures and individual COMT SNPs. In haplotype analysis, there was a significant association between ACG haplotype and FM susceptibility sex (OR = 2.960, 95% CI: 1.447, 6.056, p = 0.003) and the number of tender points (p = 0.046).
Conclusions
This large‐scale study suggests that polymorphisms of the COMT gene may be associated with FM risk and pain sensitivity in Korean FM patients. However, our results differed to those of previous studies, suggesting ethnic variation in COMT gene polymorphisms in FM.
What does this study add
By contrast to Caucasian and Latin‐American populations, the COMT gene polymorphisms are associated with FM risk and pain sensitivity in Korean FM patients, suggesting ethnic variation in COMT gene polymorphisms.
Cancer nanomedicine using nanoparticle-based delivery systems has shown outstanding promise in recent decades for improving anticancer treatment. However, limited targeting efficiency, low drug ...loading efficiency and innate toxicity of nanoparticles have caused severe problems, leaving only a few available in the clinic. Here, we newly developed carrier-free nanoparticles of cathepsin B-cleavable peptide (Phe-Arg-Arg-Gly; FRRG)-conjugated doxorubicin (DOX) prodrug (FRRG-DOX) that formed a stable nanoparticle structure with an average diameter of 213 nm in aqueous condition. The carrier-free nanoparticles of FRRG-DOX induced cytotoxicity against cathepsin B-overexpressed tumor cells whereas the toxicity was minimized in normal cells. In particular, the FRRG-DOX nanoparticles showed the successful tumor-targeting ability and enhanced therapeutic efficiency in human colon adenocarcinoma (HT-29) tumor-bearing mice via enhanced permeation and retention (EPR) effect. Furthermore, FRRG-DOX nanoparticles did not present any severe toxicity, such as non-specific cell death and cardiac toxicity, in normal tissues due to minimal expression of cathepsin B. This carrier-free nanoparticles of FRRG-DOX can solve the unavoidable problems of current nanomedicine, such as lower targeting efficiency, toxicity of nanoparticles themselves, and difficulty in mass production that are fatally caused by natural and synthetic nano-sized carriers.
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Background. There have been few reports on the causes and treatment outcomes for nosocomial spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis. Methods. We performed a ...retrospective cohort study to compare the microbiological and clinical characteristics in nosocomial versus community-acquired SBP. All patients with SBP, for whom culture was proven to be positive for SBP at Samsung Medical Center (Seoul, Republic of Korea) from 1 January 2000 through 31 June 2007, were included. Medical records and laboratory data were reviewed. Nosocomial SBP was defined as SBP diagnosed after 72 h of hospitalization. Results. A total of 236 patients with SBP were enrolled (mean age ±SD age, 56.6±10.7 years); 166 patients were women, and 70 were men. Nosocomial and community-acquired SBP occurred in 126 and 110 patients, respectively. Escherichia coli accounted for 102 (43.2%) of 236 isolates, Klebsiella species accounted for 33 isolates (14.0%), and Streptococcus species accounted for 23 isolates (9.8%). The overall 30-day mortality rate for nosocomial SBP was higher than that for community-acquired SBP (58.7% vs. 37.3%; P=.001). Nosocomial isolates of gram-negative organisms were significantly more resistant to third-generation cephalosporins (41% vs. 10.0%; P<.001) and quinolones (50.0% vs. 30.9%; P=.003), compared with community-acquired isolates. Multivariate analysis revealed that nosocomial infection, concomitant hepatocellular carcinoma, presentation with acute renal failure or shock, and resistance to third-generation cephalosporins were significant risk factors for 30-day mortality associated with SBP. Conclusions. Nosocomial SBP has a poorer outcome than community-acquired SBP. The resistance to third-generation cephalosporins for gram-negative organisms, which are more common in nosocomial cases of SBP than in community-acquired cases of SBP, adversely affects the outcome of SBP in patients with liver cirrhosis.
Summary A retrospective, observational cohort study was conducted to describe the incidence, clinical and microbiological findings and to evaluate risk factors for treatment failure associated with ...prosthetic joint infections (PJIs). We retrospectively reviewed the medical records of all patients undergoing total knee or total hip prosthesis implantation in our institution between 1994 and 2008. Our institution is a 1950-bed tertiary care university hospital and referral centre. A total of 93 patients with PJIs was identified although only 68 patients had undergone prosthesis implantation at our hospital. The overall infection rate was 0.63%. The most common organisms isolated were Gram positive (76.5%), including meticillin-resistant staphylococci. Two-stage arthroplasty was performed in 48 (51.6%) patients, and debridement and retention of the prosthesis in 34 (36.5%) patients. When 43 patients followed up for more than two years after treatment were included in treatment outcome analysis, the overall treatment failure rate was 41.8% (18/43). Staphylococcus aureus infection was the only clinical variable associated with treatment failure (odds ratio: 11.9; 95% confidence interval: 1.07–133.9; P = 0.044), after adjustment for the other variables. In conclusion, S. aureus was the most common pathogen isolated in patients with PJI, and an independent risk factor for treatment failure in patients with PJI.
Several studies conducted in Western countries have shown that obese or overweight patients with fibromyalgia (FM) exhibit more severe symptoms than patients of normal weight. However, there has been ...no study on the relationship between obesity and FM symptom severity in Asian patients. In this study, we evaluated the association between obesity, and other related factors such as socioeconomic status (SES), and FM symptom severity in Korean patients.
A total of 343 participants were enrolled in this prospective cohort study, which used a nationwide survey of FM patients who were followed on an annual basis. We investigated health-related quality of life (QoL) and associated factors, such as demographic characteristics, SES, and physical and psychological function. The FM patients were assessed using the following self-reported questionnaires: the Medical Outcomes Study Short-Form Health Survey, the Fibromyalgia Impact Questionnaire, the Brief Fatigue Inventory, the Beck Depression Inventory, the State-Trait Anxiety Inventory, the Self-Efficacy Scale, and the Social Support Scale.
Of the 343 patients, 76 (22.1%) were obese; these patients did not differ from the non-obese patients in terms of tender points or self-reported questionnaire scores. FM patients with lower SES - as indexed by unemployment, lower income, and education levels - had more severe symptoms, and poorer QoL and function compared to those with higher SES.
In contrast to Western patients, symptom severity in Korean FM patients is associated with SES, but not with obesity.
Objective: To determine whether HLA-DR alleles are associated with the development and clinical features of systemic sclerosis (SSc) in Koreans.
Methods: Seventy-nine patients (74 women and five men; ...45 diffuse types and 34 limited types; mean age at diagnosis 43.9 years) fulfilling the American College of Rheumatology (ACR) classification criteria for SSc were enrolled. The controls were 144 healthy, disease-free Koreans. HLA-DRB1 genotypes were assessed by the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method.
Results: The HLA-DRB1*15 allele was increased in anti-topoisomerase I autoantibody (anti-topo I)-positive SSc patients p = 0.003, p corrected (pcorr) = 0.039, odds ratio (OR) = 3.43, 95% confidence interval (CI) 1.45-8.13 compared with controls. The DRB1*11 allele was also observed more frequently in anti-topo I-positive SSc than in controls (13.3% vs. 4.2%) but not statistically significant (p = 0.053, pcorr = 0.689). In patients with SSc, the DRB1*04 allele was associated with subcutaneous calcinosis (p = 0.048, OR = 4.56, 95% CI 1.07-19.37). Patients with overlap syndrome showed a negative association with the DRB1*04 allele (p = 0.036, OR = 0.26, 95% CI 0.08-0.91).
Conclusion: The HLA-DRB1*15 allele was associated with the development of anti-topo I-positive SSc in Koreans. In addition, the DRB1*04 allele was associated with certain clinical features in SSc patients.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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