A comparative evaluation was done of efficacy and safety of methotrexate, leflunomide singly and of combination of methotrexate with leflunomide or detralex. A total of 189 patients with rheumatoid arthritis (RA) were examined. A 6-month course of controllable treatment was instituted in them. The time-related course of clinical-and-laboratory indices allowed judgement about efficiency of the treatments administered. The functional condition of the patients was assessed according to HAQ. As to efficacy and toxicity, leflunomide (in a dose of 20 mg/daily) was comparable to methotrexate (7.5 to 10 mg/per week) whereas the combination leflunomide-methotrexate has been shown to considerably accelerate regression of clinical symptoms of RA while the use of detralex in the therapeutic complex proved to enhance efficiency of pharmacotherapy with methotrexate and to reduce the incidence rate of its side effects.
Ectopic pregnancy can be life-threatening. Its treatment has changed radically during the last two decades. The study objective was to evaluate incidence and treatment of ectopic pregnancy in the Icelandic population during the decade 2000-2009.
Information was collected about all diagnosed cases, place and method of treatment and admissions. The annual incidence was calculated with reference to number of pregnancies (n/1000), number of women aged 15-44 years (n/10 000) and by 5-year age groups, comparing the periods 2000-2004 and 2005-2009.
The number of ectopic pregnancies during these 10 years was 836, or 444 during the years 2000-2004 and 392 during 2005-2009. The average annual incidence was 15.6/1000 pregnancies and 12.9/10 000 women. There was an annual incidence reduction from 17.3 to 14.1/1000 pregnancies (p
Three courses of intermediate dose methotrexate, 500 mg/m2 at three weekly intervals have been used as part of sanctuary therapy to 95 out of 112 children with acute lymphocytic leukaemia in Norway in the period August 1975 to December 1979. Eight doses of MTX IT were also used for CNS prophylaxis, the first dose was given on the day of admission. As of July 1, 1980, 75 out of 95 (79%) were still in CCR for a median of 36 months (6-57 months).
We have looked for medication errors involving the use of low-dose methotrexate, by extracting information from Danish sources other than traditional pharmacovigilance databases. We used the data to establish the relative frequencies of different types of errors.
We searched four databases for cases involving low-dose methotrexate between 1999 and 2011: the Danish Patient Safety Databases (DPSD), controlled by the Danish National Agency for Patients' Rights and Complaints, the Patient Compensation Association (PCA), the Danish Poison and Information Centre (DPIC), and the online database of the Department for Patient Complaints (DPC). We categorized the place where the error occurred, the processes and types of error involved, the person responsible, and the clinical outcome.
We identified 173 errors. In 109 (63%), either harm resulted or could not be excluded; of these, 26 (15%) resulted in serious harm, including nine deaths (5%); 53 (31%) involved incorrect daily administration; and 107 (62%) involved a dosing error. Sixteen events (9.2%) concerned insufficient or faulty monitoring, with four serious outcomes and two deaths. Prescription errors involving daily rather than weekly administration, by hospital physicians, were most likely to result in serious outcomes, including deaths. The error mechanism was evaluated in 129 events. Action-based errors comprised 50 % and knowledge-based errors 34 %. Action-based errors were more likely to result in completed errors, whereas knowledge-based errors more often resulted in near misses.
The medication errors in this survey were most often action-based (50%) and knowledge-based (34%), suggesting that greater attention should be paid to education and surveillance of medical personnel who prescribe and monitor methotrexate, particularly physicians, who accounted for 40% of the errors.
To study (i) the drug utilization pattern of anti-rheumatic drugs in pregnant women and expectant fathers and (ii) the association between the use of anti-rheumatic drugs during pregnancy and the risk of congenital malformations.
Pregnancies registered in the Medical Birth Registry of Norway (MBRN) were linked to the Norwegian Prescription Database (NorPD) in the period 2004-2007. Prescriptions for anti-rheumatic drugs issued to women 3 months prior to and during pregnancy and to men 3 months prior to conception were identified. Congenital malformations were recorded according to the European Surveillance of Congenital Anomalies (EUROCAT) guidelines.
In 154,976 singleton pregnancies, 1461 of the women (0.9%) and 1198 (0.8%) of the known fathers (150,530) were dispensed anti-rheumatic drugs at least once during the study period: 723 had non-steroidal anti-inflammatory drugs (NSAIDs), 633 prednisolone (CS), 119 sulfasalazine (SASP), 101 azathioprine (AZA), 58 hydroxychloroquine (HQC), 37 etanercept (ETAN), eight methotrexate (MTX), two leflunomide (LEF), and three adalumimab (ADA). Odds ratios (ORs) for malformations in children born of women (w) or men (m) who had received the drugs were OR(w) = 1.06 [95% confidence interval (CI) 0.85-1.32] and OR(m) = 1.19 (95% CI 0.93-1.51), respectively, and for major malformation OR(w) = 1.05 (95% CI 0.79-1.40) and OR(m) = 1.26 (95% CI 0.93-1.71), respectively. None of the children whose mother had received MTX, LEF, ETAN, or ADA were reported to be born with major malformations.
This study revealed no major malformations of the alert drugs MTX, LEF, ETAN, or ADA. Although the numbers are limited, this provides important population-based information to both expectant parents and prescribers.
To determine which risk factors are associated with serious pancytopenia associated with low dose methotrexate (MTX) therapy.
All Ottawa area rheumatologists, hematologists and dermatologists were surveyed to obtain cases of pancytopenia associated with low dose MTX therapy between 1981 and 1991. Pancytopenia was defined as white blood cells
BACKGROUND: Treatment of childhood leukemia may cause perfusion defects in the brain observed by SPECT. Perfusion MRI is a novel method to study brain perfusion which has not been used previously in this setting. This study was performed to compare SPECT with perfusion MRI in patients with acute lymphoblastic leukemia (ALL) after treatment. PROCEDURE: Nineteen children or young adults underwent perfusion MRI at the cessation of treatment (n = 9) or 4-8 years after the treatment (n = 10). Seventeen of them also underwent SPECT at the time of MRI (within 0-3 days, n = 14) or a couple of months later (1.5-6 months, n = 3). SPECT images and relative cerebral blood volume (CBV) and cerebral blood flow (CBF) maps from perfusion MRI were analyzed visually. Relative CBV ratios of gray matter to white matter and thalamus to white matter were also calculated from the perfusion MRI. RESULTS: Perfusion MRI did not show any focal perfusion defects, while small defects were observed by SPECT in five of 17 children (29%) in the basal, frontal or temporal areas on the left. No significant differences were observed by perfusion MRI in the relative CBV ratios in the different treatment groups. Time since treatment, age at diagnosis, brain irradiation, or findings in conventional MRI or SPECT did not have any effect on the relative perfusion values either. CONCLUSIONS: SPECT may show small perfusion defects after treatment for childhood leukemia which are not visible by perfusion MRI. The clinical significance or prognosis of these defects is not known.
The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those eligible. Risk of relapse was increased 2.9-fold for patients with the 1199GA variant versus 1199GG (P=0.001), and reduced 61% and 40%, respectively, for patients with the 3435CT or 3435TT variants versus 3435CC (overall P=0.02). The degree of bone marrow toxicity during doxorubicin, vincristine and prednisolone induction therapy was more prominent in patients with 3435TT variant versus 3435CT/3435CC (P=0.01/PA may be a new possible predictive marker for outcome in childhood ALL.
Cites: Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):854-916467099
To determine methotrexate (MTX) use and the degree to which Canadian pediatric rheumatologists adhere to the American College of Rheumatology (ACR) guidelines on monitoring for MTX toxicity.
A 20-item questionnaire was e-mailed to 37 pediatric rheumatologists in 17 centers in Canada. A total of 28 (75.7%) responded.
The oral route (PO) of administration was preferred initially by 78.6% in most cases, but for more severe cases, this fell to 42.8%. Those who chose not to start PO used the subcutaneous route (SQ). When PO was initial treatment, a switch to SQ was undertaken because of dose escalation, lack of efficacy, or GI toxicity. An initial mean dose of 0.35-0.5 mg/kg/wk was prescribed by 51.8%. For 75%, the maximum dose was 1 mg/kg/wk (up to 25 mg). Complete blood count, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were determined by 100% at baseline and in followup; albumin and creatinine by 85.7% at baseline, but by only 71.4% and 67.8%, respectively, in followup. After a change in dose, 96.3% requested blood tests at least monthly; this was extended to every 6 to 8 weeks by 78.6% when the dose was stable. Side effects of recurrent nausea and/or vomiting were reported to occur frequently. No severe toxicity, and in particular no case of cirrhosis, was reported. Prophylactic folate supplementation was prescribed by almost all physicians.
Most Canadian pediatric rheumatologists follow ACR guidelines to monitor for MTX toxicity in children with rheumatic diseases who were prescribed MTX. The variation in monitoring and response to toxicity raises the question whether specific pediatric guidelines should be developed.