A cost-utility and cost-effectiveness analysis of an acute pain service

STUDY OBJECTIVE: To analyze, from a societal perspective, the cost-effectiveness and cost-utility of acute pain management after inception of a nurse-based Acute Pain Service (APS) in a general hospital. DESIGN: Open, observational, interventional study. SETTING: Postanesthesia care unit and surgical wards of a university hospital center. PATIENTS: 1975 surgical inpatients who had undergone various types of surgery. INTERVENTIONS: Visual analog scale (VAS) pain scores and all systemic analgesics prescribed by anesthesiologists and administered by ward nurses were recorded before and after APS inception. All costs (drugs, disposal, and working time of nurses) related to the APS were identified. Pain measurements were performed by VAS every 4 hours over 3 consecutive days post-surgery and transformed into a health state scale, with 0 being equivalent to absence of pain and 10 to the worst imaginable pain.Using these data, analgesic effectiveness (cost-utility analysis) was expressed as postoperative pain days averted (PPDA) in the two surveys. To perform the cost-effectiveness analysis, we focused on postoperative complications, duration of hospital stay, and postoperative mortality rate. (Note: At the time of the study, 1 EURO = 0.85 US dollars.) MAIN RESULTS: VAS pain scores decreased in the post-APS phase (p < 0.001). One the first day, PPDA was 0.075, on the second day PPDA was 0.05, and the third day PPDA was 0.0375. Cost of analgesic drugs and disposal, as well as nursing hours, increased. The incremental cost of pain management after APS inception amounted to 19 EURO per patient per day, resulting in an incremental cost-effectiveness ratio of 350.77 EURO per PPDA gained. The cost-effectiveness analysis showed minor improvement (reduction of postoperative complication rate in some surgical specialties). Duration of hospital stay and postoperative mortality rate did not change. CONCLUSIONS: A hospital-wide, comprehensive, postoperative pain management program provides an overall positive result for the health care system by improving postoperative pain and morbidity. This service is cost-effective, costing 19 EURO per patient per day. A cost-utility analysis for short-term assessment of quality of life showed no benefit in determining usefulness of such a pain management program.     

Comparison of conventional bacteriology with nucleic acid amplification (amplified mycobacterium direct test) for diagnosis of tuberculous meningitis before and after inception of antituberculosis chemotherapy

The role of nucleic acid amplification techniques in the rapid diagnosis of tuberculous meningitis remains uncertain. We compared the performance of Ziehl-Neelsen (ZN) staining, the Gen-Probe amplified Mycobacterium tuberculosis direct test (MTD), and culture with 341 cerebrospinal fluid specimens from 152 adults (73 with and 79 without tuberculous meningitis) before and after inception of antituberculosis chemotherapy. The sensitivity, specificity, and positive and negative predictive values of ZN staining before treatment were 34/66 (52%), 79/79 (100%), 34/34 (100%), and 79/111 (71%), compared with 25/66 (38%), 78/79 (99%), 25/26 (96%), and 79/120 (66%) for MTD. The sensitivity of combined ZN staining and MTD (either positive) was 45/66 (68%). The sensitivity of staining and culture fell more rapidly than that of MTD after the start of treatment: after 5 to 15 days of treatment, MTD was more sensitive than ZN staining (12/43 [28%] versus 2/43 [2%]; P = 0.013). Slower bacterial clearance was observed if M. tuberculosis was resistant to isoniazid and/or streptomycin: resistant organisms were more likely to be cultured from cerebrospinal fluid after 2 to 5 days of treatment than fully sensitive organisms (P < 0.001). The sensitivities of ZN staining, MTD, and the two tests combined were improved by repeated sampling to 38/59 (64%), 35/59 (59%), and 49/59 (83%), respectively. In conclusion, ZN staining of the cerebrospinal fluid is at least as good as MTD for the rapid diagnosis of tuberculosis and is much faster and less expensive. However, the combination of these methods on serial samples detects more cases. Alternative tests are still urgently required.     

Delayed facial palsy after vestibular schwannoma resection: the role of viral reactivation. Our experience in 8 cases

OBJECTIVE: To study the role of herpes virus reactivation in the onset of more than three days-delayed facial paralysis (FP) following vestibular schwannoma (VS) surgery and advocate a specific medical management. MATERIAL AND METHODS: Retrospective study on 8 cases from a series of 348 patients operated on of a VS between 1996 and 2002. Seven of the eight patients were given intravenously acyclovir (30 mg x kg(-1) x d(-1) for 5 days) and methyl-prednisolone (2 mg x kg(-1) x d(-1) for 7 days). A serologic testing looking for specific anti-herpes simplex viruses type 1 and 2 (HSV-2) and varicella-zoster virus (VZV) antibodies at the onset of the FP and 2 weeks later could be done in only 3 cases. RESULTS: Mean delay of FP onset was 8.75 days. Mean time for recovery with intravenous treatment was 90 days. All treated patients had a House and Brackmann grade 1 recovery. The last one had only a grade 3 after 400 days of evolution: he could not be treated because of postoperative transient psychiatric problems. Serologic testing revealed in those patients in whom it could be done either a high level of anti-HSV or -VZV antibodies at the time of onset or a dramatic increase in anti-HSV or anti-VZV antibodies between the two samples, strongly suggesting a HSV or VZV reactivation. CONCLUSION: HSV or VZV reactivation can be evocated in most cases of delayed FPs arising in the postoperative course of VSs, suggesting usefulness of emergency-given steroid and acyclovir intravenous regimen to block virus replication and fight secondary oedema and inflammation causative of nerve lesions. Evoked reactivation mechanism is comparable to that already suspected in delayed FP arising with the same delay in middle ear surgical procedures.     

Non-expert use of the cerebral function monitor for neonatal seizure detection

BACKGROUND: The cerebral function monitor (CFM) is widely used to detect neonatal seizures, but there are very few studies comparing it with simultaneous electroencephalography (EEG). OBJECTIVE: To determine the accuracy of non-expert use of the CFM and to assess interobserver agreement of CFM seizure detection. PATIENTS: Babies admitted to the neonatal intensive care unit at King's College Hospital who were at high risk of seizure and had video-EEG monitoring. METHODS: Video-EEG was used to detect seizures. Each baby had CFM recordings at speeds of 6, 15, and 30 cm/h during the EEG. Four neonatologists, trained in CFM seizure recognition, independently rated one hour CFM samples at three speeds from each baby. Interobserver agreement was quantified using Cohen's kappa. RESULTS: CFM traces from 19 babies with EEG seizures and 21 babies without EEG seizures were analysed. Overall non-expert interpretation of the CFM performed poorly as a seizure detector compared with simultaneous EEG (sensitivities 38% at 6 cm/h; 54% at 15 cm/h; 55% at 30 cm/h). Although babies with seizures were more likely to be correctly classified at higher speeds (p = 0.02), babies without seizures were also more likely to be misclassified (p < 0.001). Agreement between observers was not good at any speed (kappa values from 0.01 to 0.39). The observers usually detected generalised seizures but often missed seizures that were focal, low amplitude, or lasted less than one minute. CONCLUSION: Approximately half of all neonatal seizures may be missed using CFM alone. Neonatal seizures need to be diagnosed, characterised, and quantified first using EEG. The CFM may then be useful for long term monitoring.     

Inventors and their attorneys must beware of their actions before the US Patent and Trademark Office

Inventors and their legal representative have a duty to disclose all material information of which they are aware to the United States Patent and Trademark Office (USPTO). Breach of this duty, combined with an intent to deceive the USPTO, can result in a court finding of inequitable conduct. Consequently, a patent will be rendered unenforceable upon a court's determination of inequitable conduct. To help understand the requirements of the duty of disclosure, a discussion highlighting recent court decisions pertaining to the issue of inequitable conduct is presented.     

Cytotoxic flavonoids and alpha-pyrones from Cryptocarya obovata

One alpha-pyrone, obolactone (1), two chalcones, kurzichalcolactone B (2) and obochalcolactone (3), and two flavanones, oboflavanones A (4) and B (5), have been isolated from the fruits and the trunk bark of Cryptocarya obovata. The structures of the new compounds were elucidated by spectroscopic interpretations. The absolute configuration of obolactone (1) was established by circular dichroism. Obolactone (1) and obochalcolactone (3) display significant activity in in vitro cytotoxic assays against the KB cell line. Biosynthetic pathways for oboflavanones and obochalcolactone are suggested.     

2-Chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU) inhibits prostate carcinoma cell growth via p53-dependent and p53-independent pathways

BACKGROUND: Prostate carcinoma is the most commonly occurring malignancy in men. Although 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU), an analog of the chloroethylnitrosoureas, has been used in the treatment of advanced solid tumors, the molecular mechanisms underlying the antineoplastic activity of this agent are not well understood. In the current study, the authors sought to investigate the effects of SarCNU on prostate carcinoma cell growth in vivo and in vitro. METHODS: Male SCID mice underwent subcutaneous implantation (on both flanks) of human CWR-22 and CWR-22R prostate carcinoma xenografts. Mice were treated with either vehicle or 60 or 80 mg SarCNU per kg body weight for 5 days, with tumor growth being assessed every 3 days. Animals were sacrificed 21 days after the final injection, and tumors subsequently were collected, weighed, and processed for analysis. Immunohistochemical analyses were performed to obtain data on the localization of p53 and p21Cip1/Waf1. Cell counting, terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) assays, cell cycle analyses, Western blotting, and in vitro kinase assays were performed to determine the effects of SarCNU on growth, apoptosis, cell cycle arrest, cell cycle-regulated protein levels, and Cdc-2 activity, respectively. RESULTS: SarCNU reduced tumor incidence and inhibited the growth of CWR-22 and CWR-22R xenografts. In addition, treatment with this agent led to increases in p21Cip1/Waf1 levels and p53 phosphorylation at Ser15. In vitro administration of SarCNU to cells with wild-type p53 (LNCaP and primary CWR-22 cells) and cells with mutant p53 (PC-3 cells) resulted in G2/M arrest and the reduction of cellular Cdc-2 activity. Up-regulation of p53 levels, p53 phosphorylation at Ser15, and p21Cip1/Waf1 levels in primary CWR-22 and LNCaP cells, as well as up-regulation of Cdc-2 phosphorylation at Tyr15 in PC-3 cells, was detected. CONCLUSIONS: SarCNU induced G2/M arrest in prostate carcinoma cells via p53-dependent up-regulation of p21Cip1/Waf1 and p53-independent phosphorylation of Cdc-2 at Tyr15. These findings suggest a potential role for SarCNU in the treatment of prostate malignancies.