Novel adipokine fibroblast growth factor 21 is increased in rheumatoid arthritis.

Fibroblast growth factor-21 (FGF-21) has been recently characterized as a new adipokine. The aim of this study was to assess FGF-21 levels in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to study the relationship between FGF-21, disease activity and metabolic status. The levels of FGF-21 in serum and synovial fluid samples from 38 patients with RA and 42 control individuals with OA were determined by ELISA. Patients were assessed for disease activity using the disease activity score (DAS28), a serum glucose and lipid profile. Age, sex and BMI-adjusted FGF-21 levels in the serum (p=0.024) and synovial fluid (p=0.010) samples were significantly higher in patients with RA when compared with OA. The levels of FGF-21 in the serum significantly correlated with the levels in the synovial fluid. Serum and synovial fluid FGF-21 levels adjusted for confounders correlated positively with C-reactive protein. The levels of FGF-21 were positively correlated with BMI in patients with RA; however, the levels were not associated with disease activity or lipid profiles. Furthermore, serum FGF-21 levels were significantly higher in seropositive compared with seronegative RA patients. This work shows that patients with seropositive RA have increased levels of FGF-21. The results suggest that FGF-21 is related to BMI but not disease activity or lipid profiles in patients with RA.

Drug-induced thrombocytopenia: a systematic review of published case reports.

PURPOSE: To determine the strength of clinical evidence for individual drugs as a cause of thrombocytopenia. DATA SOURCES: All English-language reports on drug-induced thrombocytopenia. STUDY SELECTION: Articles describing thrombocytopenia caused by heparin were excluded from review. Of the 581 articles reviewed, 20 were excluded because they contained no patient case reports. The remaining 561 articles reported on 774 patients. DATA EXTRACTION: Two of the authors used a priori criteria to independently review each patient case report. Two hundred fifty-nine patient case reports were excluded from further review because of lack of evaluable data, platelet count of 100000 cells/microL or more, use of cytotoxic or nontherapeutic agents, occurrence of drug-induced systemic disease, or occurrence of disease in children. For the remaining 515 patient case reports, a level of evidence for the drug as the cause of thrombocytopenia was assigned. Data on bleeding complications and clinical course were recorded. DATA SYNTHESIS: The evidence supported a definite or probable causal role for the drug in 247 patient case reports (48%). Among the 98 drugs described in these reports, quinidine was mentioned in 38 case reports, gold in 11, and trimethoprim-sulfamethoxazole in 10. Of the 247 patients described in the case reports, 23 (9%) had major bleeding and 2 (0.8%) died of bleeding. CONCLUSIONS: Many reports of drug-induced thrombocytopenia do not provide evidence supporting a definite or probable causal relation between the disease and the drug. Future patient case reports should incorporate standard criteria to clearly establish the etiologic role of the drug.

A hospital-based pharmacy intervention program for pneumococcal vaccination.

BACKGROUND: Current pneumococcal vaccination rates are well below national goals. OBJECTIVE: To determine whether pneumococcal vaccination rates could be increased with a hospital pharmacy-based program using simple chart reminders. METHODS: On a daily basis, inpatient records on general medicine and cardiology services at an academic medical center were reviewed to determine which patients were eligible to receive pneumococcal vaccine. Eligible inpatients were interviewed, and the percentage of nonvaccinated inpatients given vaccine during hospitalization was determined. During an intervention period, reminders were placed on charts after the interview requesting a vaccine when indicated. RESULTS: Of 447 inpatients, 224 (50.1%) had 1 or more indications for receiving pneumococcal vaccine. Only 64 (28.6%) had been previously vaccinated. One hundred fifty-eight (70.5%) of 224 vaccine-eligible patients had a prior hospitalization within the previous 5 years. Previous hospitalization was not significantly associated with having (48 [30.4%] of 158) or not having (16 [24.2%] of 66; P=.35) been vaccinated prior to admission. During the observational period, 0 of 80 vaccine-eligible, nonvaccinated inpatients were vaccinated before discharge. In comparison, 23 (28.8%) of 80 inpatients were vaccinated after a chart reminder (P<.001). During the intervention period, vaccination rates were 10-fold higher on general medicine services than on cardiology services. CONCLUSIONS: A hospital-based pharmacy vaccination program that relied on simple chart reminders was significantly associated with increased vaccination rates among inpatients at risk for invasive pneumococcal disease.

Ranitidine bismuth citrate in the treatment of Helicobacter pylori infection and duodenal ulcer.

OBJECTIVE: To review the clinical pharmacology of ranitidine bismuth citrate in the treatment of Helicobacter pylori (HP) infection and duodenal ulcer. DATA SOURCES: A MEDLINE search of the English-language literature from 1992 to January 1997 was conducting using the key terms Tritec, ranitidine, and bismuth. References of articles pertaining to treatment of duodenal ulcer or HP were extensively searched for relevant sources. DATA EXTRACTION: All articles pertaining to ranitidine bismuth citrate were considered for inclusion, with emphasis placed on randomized, double-blind trials. Priority was placed on data pertaining to regimens that are currently approved by the Food and Drug Administration for the treatment of duodenal ulcer in conjunction with HP. DATA SYNTHESIS: Each tablet of ranitidine bismuth citrate 400 mg contains 162 mg of ranitidine base, 128 mg of trivalent bismuth, and 110 mg of citrate. It uses the acid-suppressive actions of ranitidine and the antimicrobial and mucosal protective effects of bismuth to eradicate HP. Ranitidine bismuth citrate in conjunction with clarithromycin represents one of four treatment regimens currently approved in the US for duodenal ulcer associated with HP infection. In four double-blind, randomized trials, this agent has achieved HP eradication rates of 73-94% and duodenal ulcer healing rates of 73-89%. It is given twice daily for 28 days, and is associated with very low rates of adverse effects. CONCLUSIONS: Relative to some therapeutic alternatives, ranitidine bismuth citrate plus clarithromycin may be simpler to take and have less adverse effects, but may be more expensive. Compared with omeprazole plus clarithromycin, it is less expensive, may have lower ulcer healing rates, but may be more effective in eradicating HP. The role of ranitidine bismuth citrate will continue to evolve as more patients are treated, and other regimens continue to be tested for duodenal ulcer healing and HP eradication.

Beta-lactam antibiotics: is continuous infusion the preferred method of administration?

OBJECTIVE: To examine the pharmacodynamic properties of the beta-lactam class of antibiotics and the rationale for their continuous infusion (CI), and to explore reasons that this mode of administration has not replaced intermittent infusion as the standard of practice. DATA SOURCES: A Medline search of the English-language literature evaluating CI administration of beta-lactam antibiotics was conducted. Bibliographic searches of these articles also were performed. STUDY SELECTION: Because there were few human trials, all available trials were considered for review. A cross section of clinical trials, animal studies, and in vitro studies examining the impact of the route of antibiotic administration was selected for each pharmacodynamic variable addressed. DATA SYNTHESIS: The support for CI as the preferred method of beta-lactam administration comes primarily from in vitro and animal data. Most beta-lactam antibiotics do not demonstrate concentration-dependent killing and have an appreciable postantibiotic effect only against gram-positive cocci. Their efficacy appears to be optimized by maintaining suprainhibitory concentrations throughout the dosing interval. Therefore, CI of beta-lactams could potentially enhance the efficacy of treatment or allow less drug to be used on a daily basis. This has yet to be demonstrated convincingly in human clinical trials. Comparative trials need to continue to explore the impact of the method of administration on patient outcomes such as duration and cost of therapy, as well as morbidity and mortality. CONCLUSIONS: Results of many animal and in vitro studies suggest that CI may be the optimal method of beta-lactam administration. Clinical trials need to further document the impact of the method of beta-lactam administration on the incidence of adverse effects, emergence of bacterial resistance, and patient outcome. Pharmacodynamic studies defining target beta-lactam concentrations, the practicality of CI in patients requiring multiple intravenous fluids and medications, and the pertinence of this issue when beta-lactam antibiotics are used as sole agents or in combination with other antimicrobials require further exploration.

Patterns of acetaminophen use in alcoholic patients.

Alcoholics may be predisposed to the hepatotoxicity of acetaminophen due to increased activity of the cytochrome P-450 system and decreased hepatic glutathione. To date, scattered case reports provide only a brief sketch of the frequency and pattern of acetaminophen use by alcoholics. To determine these variables, we obtained a detailed ethanol and drug history from patients answering yes to at least one of four questions on the CAGE questionnaire. Patients were classified in terms of their acetaminophen use as nonusers, users as necessary, or regular users. Regular users were further classified as nondaily or daily users, or abusers (> 4 g/day). A total of 64 patients were enrolled in the study. The average number of positive responses to the CAGE questionnaire was 3.27 +/- 0.91. Of the 64 patients, 34 (53.1%) were continuous daily drinkers, 28 (43.8%) binge drinkers, and 2 (3.1%) had completely discontinued using alcohol. By history, 32 (50)% were nonusers of acetaminophen. Of the 32 users, 12 (37.5%) stated they took it as needed and 20 (62.5%) took it regularly. Of the 20 regular users, 7 (35%) were nondaily users, 11 (55%) were daily users, and 2 (10%) were abusers. Approximately 31% of alcoholics used acetaminophen regularly, most on a daily basis, with 1 of every 10 abusing the drug. Of the 64 alcoholics interviewed, 3 (4.7%) fit the drinking and acetaminophen use patterns theoretically associated with hepatotoxicity.