Objective. To compare the efficacy and safety of subcutaneous (SC) versus oral administration of methotrexate (MTX) in patients with active rheumatoid arthritis (RA).Methods. MTX-naive patients with active RA (Disease Activity Score in 28 joints >4) were eligible for the study if they had not previously taken biologic agents and had not taken disease-modifying antirheumatic drugs for 2 weeks prior to randomization. Patients were randomly assigned to receive 15 mg/week of MTX either orally (2 7.5-mg tablets plus a dummy prefilled syringe; n ؍ 187 patients) or SC (prefilled syringe containing 10 mg/ml plus 2 dummy tablets; n ؍ 188 patients) for 24 weeks. At week 16, patients who did not meet the American College of Rheumatology criteria for 20% improvement (ACR20) were switched from 15 mg of oral MTX to 15 mg of SC MTX and from 15 mg of SC MTX to 20 mg of SC MTX for the remaining 8 weeks, still in a blinded manner. The primary outcome was an ACR20 response at 24 weeks.Results. At week 24, significantly more patients treated with SC MTX than with oral MTX showed ACR20 (78% versus 70%) and ACR70 (41% versus 33%) responses. Patients with a disease duration >12 months had even higher ACR20 response rates (89% for SC administration and 63% for oral). In 52 of the ACR20 nonresponders (14%), treatment was switched at week 16. Changing from oral to SC MTX and from 15 mg to 20 mg of SC MTX resulted in 30% and 23% ACR20 response rates, respectively, in these patients. MTX was well tolerated. The rate of adverse events was similar in all groups. Conclusion. This 6-month prospective, randomized, controlled trial is the first to examine oral versus SC administration of MTX. We found that SC administration was significantly more effective than oral administration of the same MTX dosage. There was no difference in tolerability.
The Swedish Family-Cancer Database comprises a total of 11.8 million individuals covering the Swedish population of the past 100 years. Version VIII of the Database is described in the present article. Cancer cases were retrieved from the Swedish Cancer Registry for the period 1958-2006, including more than 1 million first primary cancers. The number of familial cancers in offspring is 14,000 when a parent was diagnosed with a concordant (same) cancer and the number of concordant siblings was 6,000. From the year 1993 onwards histopathological data according to the SNOMED classification were used, which entails advantages for certain cancers, such as breast cancer. Even though the specific morphological classification only covers a limited number of years, it does cover most familial cancers in the offspring generation. The Database records the country of birth for each subject. A total of 1.79 million individuals were foreign born, Finns and other Scandinavians being the largest immigrant groups. The cancer incidence in the first-generation immigrants was compared to that in native Swedes using standardised incidence ratios (SIRs) to measure relative risk. The SIRs ranged widely between the immigrant groups, from 1.9-fold for myeloma to 25-fold for melanoma. The differences in SIRs were smaller in the second-generation immigrants. The usefulness and the possible applications of the Family-Cancer Database have increased with increasing numbers of cases, and the numerous applications have been described in some 300 publications. Familial cancer studies are in the stimulating interphase of the flourishing disciplines of genetics and epidemiology.
Diagnosis of BCa is associated with increased risks of dying of various causes, including external causes, heart failure, diseases of pulmonary circulation, and gastrointestinal disease. The study fulfills the gap in knowledge of death causes in BCa patients and suggests to draw more attention to comorbidities.
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