Risk of discontinuation of risperidone after exposure to potentially interacting drugs: a nested case-control study in patients with schizophrenia

BACKGROUND: The cytochrome P450 (CYP) 2D6 and 3A4 isozymes play an important role in the metabolism of risperidone. Concurrent use of drugs that inhibit or induce the action of these enzymes may increase or decrease levels of risperidone, thereby increasing the risk for discontinuation of risperidone or the need for supplemental treatment to control disease symptoms. OBJECTIVE: This study examined the association between exposure to potentially interacting drugs and nonpersistence in a cohort of patients with schizophrenia newly starting treatment with risperidone. METHODS: The data for this nested case-control study were obtained from the administrative health databases of the Régie de l'Assurance Maladie de Québec. The base cohort included patients aged > or = 15 years who began treatment with risperidone between July 2001 and December 2004. Cases consisted of those who were nonpersistent with risperidone either through drug discontinuation or the addition of/switch to a different atypical antipsychotic; noncases were those who persisted with risperidone through the end of their follow-up period. Exposure to CYP-inhibiting or CYP-inducing medications in the 1-, 3-, and 6-month windows before nonpersistence was compared between cases and noncases. The association between exposure to interacting medications and nonpersistence was analyzed using conditional logistic regression models to account for matching by time on treatment. RESULTS: The base cohort included 20,840 patients, of whom 59.2% were female and 57.7% were aged > or = 65 years. Nonpersistence occurred in 10,913 patients (52.4%) during the study period. Between 40% and 50% of patients were exposed to potential CYP inhibitors, and 6% to 10% were exposed to potential CYP inducers. Exposure to CYP inhibitors over 3 and 6 months was associated with an increase in risk for nonpersistence of approximately 10% (odds ratio [OR] for 3-month exposure = 1.10 [95% CI, 1.06-1.14]; OR for 6-month exposure = 1.11 [95% CI, 1.07-1.15]), whereas exposure to CYP inducers was not associated with a significant change in risk. Exposure to potentially interacting drugs was more likely to lead to nonpersistence while patients were still new to risperidone (ie, in the first month of treatment). For instance, the OR for 6-month exposure to inhibiting drugs was 1.20 (95% CI, 1.04-1.39) in the 1st month of treatment and 1.11 (95% CI, 1.01-1.20) between the 6th and 12th months. CONCLUSION: In this study, use of medications that are potential inhibitors of CYP2D6 and CYP3A4 appeared to be associated with an increased risk of nonpersistence with risperidone, particularly while patients were still new to treatment.     

Iron chelation therapy: Clinical effectiveness,economic burden and quality of life in patients with iron overload

INTRODUCTION: This study of UK patients examines clinical, healthrelated quality of life (HRQOL) and economic outcomes associated with iron chelation therapy (ICT). Desferrioxamine (DFO) (Desferal(R); Novartis, Switzerland) and Deferiprone (Ferriprox(R); Apotex, Canada) are ICTs used to treat iron overload. DFO requires 8-to 12-hour infusions a minimum of five times per week. Deferiprone is administered in an oral daily regimen. Although pharmacologically efficacious, clinical effectiveness of ICT within the real-world setting is yet to be fully elucidated. METHODS: A naturalistic cohort study of 60 patients (betathalassaemia, n=40; sickle cell disease, n=14; myelodysplastic syndromes, n=6; 63% female) receiving ICT in four UK treatment centres was conducted. Serum ferritin level data were abstracted from medical charts. Compliance, HRQOL, satisfaction and resource utilisation data were collected from interviews. Maximum ICT costs were estimated using the resource utilisation data associated with DFO. RESULTS: Mean serum ferritin levels, generally, remained elevated despite ICT. Compliance was suboptimal and HRQOL scores were lower than population norms. The total estimated mean weighted annual per-patient cost of DFO treatment was approximately pound19,000. DFO-related equipment, DFO drug, and home healthcare were estimated to account for 43%, 19% and 24% of costs, respectively. Other more minor components of total annual costs were for in-patient infusions, ICT home delivery services and monitoring costs. CONCLUSION: Generally, patients are not achieving target serum ferritin thresholds despite chronic treatment for iron overload. ICT appears to negatively impact HRQOL; compliance with ICT is poor; and, in the case of DFO, treatment costs well exceed the cost of DFO alone. These results suggest that current ICT in the real-world setting is suboptimal with respect to various clinical, HRQOL and economic outcomes.     

Anterior versus posterior pin placement of pelvic C-clamp in relationship to anatomical structures: a cadaver study

OBJECTIVES: The objective of this study was to compare anterior and posterior pin placement of the pelvic C-clamp with specific reference to the proximity of the sciatic nerve, sciatic notch, hip joint capsule, and superior gluteal neurovascular bundle. METHODS: The pelvic C-clamp (Synthes, Paoli, PA) was applied to eight extracted pelvic specimens and five full cadavers (26 hips in total). Anterior and posterior pin placements were measured in relationship to the described anatomical structures. RESULTS: In 100% of the hips the distance from the posterior pin to the hip joint capsule was in 21 (80.8%), 23 (88.5%), and 20 (76.9%) of the hips, the anterior pin distances were greater than the posterior pin distances to the sciatic nerve, sciatic notch, and superior gluteal neurovascular bundle, respectively. CONCLUSIONS: Anterior pin placement is further from all anatomical structures studies with the exception of the hip joint capsule. The posterior pin was closer to the sciatic nerve, sciatic notch, and superior gluteal neurovascular bundle in all cases. Clinical decision-making for C-clamp placement should be individualised on a case-by-case basis.     

Numerical aberrations of chromosome 8 detected by conventional cytogenetics and fluorescence in situ hybridization in individuals from northern Brazil with gastric adenocarcinoma

Gastric cancer is the third most frequent type of neoplasia and the second most important cause of cancer-related death in the world. In northern Brazil, the state of Pará shows a high incidence of this disease and the capital ranks among cities with the highest incidence of stomach cancer in the world. To evaluate chromosomal aberrations implicated in gastric carcinogenesis, we analyzed 16 samples of gastric adenocarcinoma by fluorescence in situ hybridization using a chromosome 8 alpha-satellite probe and by direct chromosomal analysis techniques. All lesions were classified as at advanced stages according to the recommendations of the Union Internationale Contre le Cancer (UICC). Trisomy 8 was the main finding of this study, observed in all cases. There was no significant difference between chromosome 8 ploidy and localization, stage, or histological type of adenocarcinoma in our sample. The high incidence of alterations we found in chromosome 8 may be a regional characteristic, related to the high incidence of this neoplasm in Pará state and a strong influence of external factors, such as eating habits. This aberration may comprise a cytogenetic subgroup of this neoplasm. Additional investigations are necessary to confirm the involvement of chromosome 8 and to identify genes in this chromosome related to gastric carcinogenesis.     

Dexmedetomidine as sole sedative for awake intubation in management of the critical airway

We report a series of successful awake fiberoptic intubations in patients with critical (unstable, difficult) airways using the alpha(2)-agonist, dexmedetomidine. Dexmedetomidine has several desirable pharmacologic properties, including sedation, anxiolysis, hypnosis, analgesia, amnesia, antisialagogue effects, and a unique respiratory-sparing effect. Dexmedetomidine appears to be a useful agent for sedation during awake fiberoptic intubation in difficult airway patients.