Determinants of prescribing meperidine compared to morphine in hospitalized patients

Morphine is a preferred narcotic since meperidine forms toxic metabolites. Determinants of meperidine use have been poorly described. The objective of this study is to explore factors associated with the ordering of meperidine versus morphine. Retrospective chart review of adult patients, randomly selected based on orders for morphine or meperidine. 1552 orders were written for 670 patients. Of these, 36% were for meperidine. In multivariable analysis, the ordering of meperidine was associated with the following variables in decreasing order of importance: physician specialty, total doses received, hospital location, patient race, age and insurance, and physician gender. More orders for meperidine were written for those receiving fewer doses. Though meperidine has little role in the routine management of hospital pain, we found it continues to be used frequently. Importantly, meperidine is ordered more frequently for patients who receive shorter courses of narcotics. Our study suggests that interventions targeted at more appropriate use of meperidine rather than complete elimination might be more acceptable to physicians while minimizing the risk of toxicity.     

Increased prevalence of epilepsy associated with severe falciparum malaria in children

PURPOSE: Multiple, prolonged, generalized, or focal seizures are common in children with severe malaria, with or without coma. In other contexts, such seizures have been associated with the development of epilepsy. The relation between falciparum malaria and epilepsy is undetermined; thus we measured the prevalence and characteristics of epilepsy in children with a history of severe malaria. METHODS: We took a detailed epilepsy history from the parents of 487 children (aged 6-9 years) to compare the prevalence of epilepsy between three exposure groups: children with a history of cerebral malaria (CM), malaria and complicated seizures (M/S), or those unexposed to either complication. Each child had an EEG and was classified as having active, inactive, or no epilepsy. RESULTS: An increased prevalence of epilepsy was seen in children previously admitted with CM [9.2%; OR, 4.4; 95% confidence interval (CI), 1.4-13.7] or M/S (11.5%; OR, 6.1; 95% CI, 2.0-18.3) compared with the unexposed group (2.2%). The most commonly reported seizure types were tonic-clonic (42%), focal becoming secondarily generalized (16%), and both (21%). Twenty-six percent of the active epilepsy group initially had EEG abnormalities. CONCLUSIONS: These results suggest that children exposed to CM or M/S have an increased propensity for epilepsy relative to children unexposed to these complications. The prevalence of epilepsy associated with CM is similar to that reported after other severe encephalopathies. The prevalence associated with M/S is more than twice that reported after complicated febrile seizures.     

Political analysis of rapid change in Uganda's health financing policy and consequences on service delivery for malaria control

The aim of this study was to assess the political and social dynamics resulting from the rapid change in user-fee reforms in Uganda and the effects on service delivery for malaria control. Using political mapping and political risk analysis techniques, the study analysed qualitative and quantitative data obtained from secondary data sources and key actors in the policy arena. The results have shown that the feasibility of user-fees in Uganda was undermined by the absence of strong central government leadership and strategies to manage the politics of the reforms. The resultant rapid change in policy adversely affected the recurrent expenditures of health units that previously relied heavily on cost sharing, which led to a chronic shortage of malaria drugs and undermined the ability of health facilities to hire and motivate staff. The study results demonstrate that in order to contribute positively to healthcare delivery goals for malaria control in endemic countries, user-fees require full ownership and strong political leadership by the central government. Decentralization, when merely used as a strategy to navigate the political risks associated with user-fees, is unlikely to succeed without a centrally coordinated and managed process of policy formulation and acceptance involving wider consultations and political management of interest groups.     

Cyclin D1 amplification and p16(MTS1/CDK4I) deletion correlate with poor prognosis in head and neck tumors

OBJECTIVES/HYPOTHESIS: Cyclin D1, a cell cycle regulator localized to chromosome 11q13, is amplified in several human tumors including head and neck squamous cell carcinoma (HNSCC). Amplification and/or overexpression of cyclin D1 have been correlated to a poor prognosis. Deletion of the p16 gene, localized to 9p21, has also been observed in a significant proportion of HNSCC. The p16 gene regulates cyclin D1-CDK4 activity and prevents retinoblastoma tumor suppressor gene phosphorylation, thereby downregulating cellular proliferation. Detection of cyclin D1 amplification and p16 deletion using a simple and sensitive method will be valuable for the development of effective treatment modalities for head and neck cancer. STUDY DESIGN: We have used fluorescence in situ hybridization (FISH) to study cyclin D1 amplification and p16 gene deletion in head and neck tumors. Both single- and dual-color FISH were performed. METHODS: Paraffin-embedded tissues from 103 patients with HNSCC were analyzed using genomic DNA probes for cyclin D1 and p16. Dual-color FISH was performed with chromosome 11 or 9 centromeric probes as a control. Twenty-eight of these samples were analyzed for p16 expression by immunohistochemistry. RESULTS: Cyclin D1 amplification was observed in 30% (31/103) of patients, and p16 deletion in 52% (54/103). Lack of p16 expression was observed in 64% (18/28) of patients. There was a good correlation between the deletion of p16 sequences and the loss of p16 expression (P = .008). Amplification of cyclin D1 had a statistically significant association with recurrence, distant metastasis, and survival at 36 months. There was a significant association between p16 deletion and the development of distant metastases. Cyclin D1 amplification and p16 deletion together correlated with recurrence, distant metastasis, and survival. CONCLUSIONS: We demonstrate that FISH is a simple and sensitive method for detecting cyclin D1 amplification and p16 deletion in head and neck cancer. Our results suggest that these two genetic aberrations together portend a poorer outcome than either of the abnormalities alone in head and neck cancer.     

Salvage topical therapy for upper tract urothelial carcinoma

Purpose

Topical therapy (TT) for upper tract urothelial carcinoma (UTUC) has been explored as a kidney sparing approach to treat carcinoma in situ (CIS) and as adjuvant for endoscopically treated Ta/T1 tumors. In bladder cancer, data support use of salvage TT for repeat induction. We investigate the outcomes of salvage TT for UTUC in patients ineligible for or refusing nephroureterectomy.

Methods

A single-center retrospective review on patients receiving salvage TT via percutaneous nephrostomy tube or cystoscopically placed ureteral catheters was performed. Primary outcome was response to therapy based on International Bladder Cancer Group criteria.

Results

51 patients with 58 renal units (RUs) received TT. Of these, 17 patients with 18 RUs received the second-line TT, with a median follow-up of 36.5 months (IQR 24.5–67 months). 44% (8/18) received salvage TT for refractory disease and 56% (10/18) as reinduction. 5 RUs with CIS were unresponsive to initial TT and went on to receive salvage TT, of which 20% (1/5) responded. 13 RUs recurred or relapsed following initial TT and received salvage TT for papillary tumors, with 62% (8/13) responding.

Conclusion

Our data provide preliminary clinical rationale for the second-line TT for refractory and recurrent, endoscopically managed papillary UTUC in patients ineligible for or refusing nephroureterectomy. However, refractory upper tract CIS appears to have poor response to salvage TT.