Association between HTR2C gene polymorphisms and the metabolic syndrome in patients using antipsychotics: a replication study.

In two previous studies we found an association between HTR2C polymorphisms and the prevalence of the metabolic syndrome in patients using antipsychotics. In this study, we set out to replicate our findings in a third separate sample of patients. Data for this cross-sectional study came from the ongoing Pharmacotherapy Monitoring and Outcome survey study, investigating the association between schizophrenia and metabolic or cardiovascular risk factors. Primary end point was the prevalence of the metabolic syndrome. Primary determinants were two polymorphisms in the HTR2C gene: rs3813929 (-759 C/T) and rs1414334:C>G. Carriership of the variant rs1414334 C-allele was significantly associated with an increase prevalence of the metabolic syndrome (odds ratio (OR) 3.73; 95% confidence interval (CI) 1.29-10.79, P=0.015). No association was found between the HTR2C -759 C/T polymorphism and the metabolic syndrome. This study confirms previous findings that the variant C-allele of the rs1414334 polymorphism is associated with the metabolic syndrome.

Treatment of refractory SLE with rituximab plus cyclophosphamide: clinical effects, serological changes, and predictors of response.

OBJECTIVE: To evaluate efficacy, serological responses, and predictors of response in patients with severe and refractory systemic lupus erythematosus (SLE) treated with rituximab plus cyclophosphamide. METHODS: 16 patients entered a treatment protocol using rituximab plus cyclophosphamide. Disease activity was assessed by the SLE disease activity index (SLEDAI) and by the British Isles Lupus Assessment Group (BILAG) index. RESULTS: At six months follow up, mean SLEDAI values decreased significantly from (mean (SD)) 12.1 (2.2) to 4.7 (1.1). Clinical improvement (50% reduction in SLEDAI) occurred in all but three patients. All but one patient responded according to BILAG. Remission defined as SLEDAI <3 was achieved in nine of 16 patients. Isotype analysis of anti-dsDNA antibodies revealed preferential decreases of IgG and IgA, but not IgM. Higher absolute numbers of CD19+ cells at baseline were correlated with shorter depletion time (r = -0.6). CONCLUSIONS: The majority of patients improved following rituximab plus cyclophosphamide. The differential downregulation of anti-DNA of the IgG and IgA but not the IgM isotypes supports the hypothesis that cells producing pathogenic autoantibodies are preferentially targeted by the treatment. The fact that greater absolute numbers of CD19+ cells at baseline predict a less impressive clinical and serological response suggests that more flexible dosing could be advantageous.

The potential interaction between oral anticoagulants and acetaminophen in everyday practice.

OBJECTIVE: The drug-drug interaction between oral anticoagulants (especially warfarin) and acetaminophen has been described, but evidence is conflicting and evidence for a similar interaction between acenocoumarol or phenprocoumon and acetaminophen is limited. Therefore, a study was performed to determine the influence of acetaminophen on oral anticoagulation with acenocoumarol or phenprocoumon in everyday practice. METHOD: Included were patients from two Dutch anticoagulant clinics who had used oral anticoagulants for at least three months and who started with acetaminophen (case group) or benzodiazepines (control group). RESULTS: Fifty-four patients were included who had a first prescription of acetaminophen in their pharmacy record (during oral anticoagulant use) and twenty patients with a first prescription of a benzodiazepine (during oral anticoagulant use). The INR (International Normalized Ratio) difference before and after acetaminophen use was not statistically significant between the two groups and showed no dose dependency. CONCLUSION: These data do not demonstrate that acetaminophen, in the dosages used in everyday practice, has a clinically relevant influence on the INR in patients using acenocoumarol or phenprocoumon.

Stabilization of oral anticoagulant therapy in hospitalized patients and characteristics associated with lack of stabilization.

The initiation and stabilization of oral anticoagulant therapy in hospitalized patients in a setting without specialized medical or pharmaceutical advice, was studied. In addition, potential risk factors for lack of stabilization were studied. All patients from three wards (orthopaedic surgery, general surgery and internal medicine) in two Dutch hospitals, who were started on oral anticoagulant therapy and who gave informed consent, were included in this three months prospective follow-up study. When a patient had two consecutive INR's within the range 2-3 during hospitalization (on day 6 or later), he was defined as stable. Stable and unstable patients were compared with respect to age, gender, quetelet index, length of hospital stay, indication for oral anticoagulant therapy, induction dosing schedule of oral anticoagulant therapy, prescribing physician, type of hospital (teaching or non-teaching), concurrently used drugs, concurrently used drugs known to potentially interact with oral anticoagulant therapy (drug-drug interactions that influence INR) and (co)morbidity. A total of 125 patients, who all used acenocoumarol as oral anticoagulant, were recruited in the study. The study population mainly comprised orthopaedic discharges on prophylactic oral anticoagulants. The mean length of hospital stay was 14.5 days (median 11.0, standard deviation (SD) 10.2) for the patients included in the study (patients with a short length of stay < 6 days were excluded from the study, because of the definition of stability). 43 patients (34%) became stable during hospitalization. The second INR within the range was reached after on average 11.1 days (median 10.0, SD 4.5). 18 different induction dosing schedules were used. Differences in apparent risk of INR instability were statistically associated with length of hospital stay (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.78-0.92), concurrent use of musculoskeletal drugs, mainly NSAIDs, (OR 1.68, 95% CI 1.04-2.72) and two individual prescribing physicians (OR 6.61, 95% CI 1.47-29.82 for one physician and OR 0.23, 95% CI 0.06-0.99 for the other physician). This population has a high percentage of instability and reaches stability relatively late. The instability was associated with length of hospital stay, the concurrent use of musculoskeletal drugs (mostly NSAID's) and physician. Most of the unstable patients had INR's below therapeutic range, suggesting a conservative dosing habit. Part of the instability may also be due to the many different physicians who dose their own patients. Interventions to improve dosing may aid in better stabilization in hospitalized patients and thus in reduced length of hospital stay.