Deep Brain Stimulation Compared With Contingency Management for the Treatment of Cocaine Use Disorders: A Threshold and Cost-Effectiveness Analysis

ObjectivesCocaine is the second most frequently used illicit drug worldwide (after cannabis), and cocaine use disorder (CUD)-related deaths increased globally by 80% from 1990 to 2013. There is yet to be a regulatory-approved treatment. Emerging preclinical evidence indicates that deep brain stimulation (DBS) of the nucleus accumbens may be a therapeutic option. Prior to expanding the costly investigation of DBS for treatment of CUD, it is important to ensure societal cost-effectiveness.AimsWe conducted a threshold and cost-effectiveness analysis to determine the success rate at which DBS would be equivalent to contingency management (CM), recently identified as the most efficacious therapy for treatments of CUDs.Materials and MethodsQuality of life, efficacy, and safety parameters for CM were obtained from previous literature. Costs were calculated from a societal perspective. Our model predicted the utility benefit based on quality-adjusted life-years (QALYs) and incremental-cost-effectiveness ratio resulting from two treatments on a one-, two-, and five-year timeline.ResultsOn a one-year timeline, DBS would need to impart a success rate (ie, cocaine free) of 70% for it to yield the same utility benefit (0.492 QALYs per year) as CM. At no success rate would DBS be more cost-effective (incremental-cost-effectiveness ratio <$50,000) than CM during the first year. Nevertheless, as DBS costs are front loaded, DBS would need to achieve success rates of 74% and 51% for its cost-effectiveness to exceed that of CM over a two- and five-year period, respectively.ConclusionsWe find DBS would not be cost-effective in the short term (one year) but may be cost-effective in longer timelines. Since DBS holds promise to potentially be a cost-effective treatment for CUDs, future randomized controlled trials should be performed to assess its efficacy.     

Choledochal cyst: case reports and current concepts

Choledochal cyst is an unusual but serious condition which most commonly affects Oriental people. Recent experience of three patients with this condition in whom diagnosis was made by ultrasound examination is reported. Cholangiography (ERCP or PTC) was performed in two of the cases to define the anatomy. All three cases were successfully managed by cyst excision and biliary reconstruction by Roux-en-Y hepaticojejunostomy. The rationale for and importance of cyst excision are discussed.     

Gamma-glutamyl transpeptidase activity during carcinogenesis of hamster buccal pouch epithelium

Gamma-glutamyl transpeptidase (GGT) activity has been demonstratedhistochemically in a number of experimentally induced neoplasmsand has been suggested as a label for potential precursors forthe development of squamous cell carcinomas. This study exploresthe kinetics of GGT-stained cell populations, their correlationwith the hypothesized initiated cells and evidence of malignanttransformation of epithelium in hamster buccal pouch by a 15-weekregime of tri-weekly topical application of 7,12-dimethylbenz[a]anthracene(DMBA) in mineral oil. GGT-positive foci were detected histochemicallyin tissue sections as early as 1 week after application of thecarcinogen, when there was no morphological evidence of dysplasia.The average number of the GGT-positive foci in each experimentalperiod was found to increase with time. Even though the majorityof the foci were small, consisting of only a single cell ora small group of cells, a few larger GGT-positive lesions werenoted, particularly in the later period of the experiment. Atotal of 66 grossly visible neoplasms were found. Thirty-sevenof these were submitted for GGT staining. Thirty-two (86.5%)of these showed patchy GGT activity, primarily in the superficialepithelial cells and/or the keratin. In the non-neoplastic epithelium,the GGT staining could involve any or all layers of cells. GGTactivity was not detected in untreated or mineral oil-treatedmucosa. The results of this study support the hypothesis thatGGT activity may label potential precursors for the developmentof squamous cell carcinomas.     

Nonspecific mitochondrial disease with epilepsy in children: diagnostic approaches and epileptic phenotypes

OBJECTIVES: This study sought to characterize epileptic phenotypes in children with nonspecific mitochondrial disease (MD) and to evaluate MD diagnostic approaches. METHODS: A retrospective analysis of the medical, electroencephalogram, and laboratory records of 142 patients with epilepsy was performed. The patients were evaluated for MD, and 124 patients were included in the final cohort. The MD criteria used included an oral glucose lactate stimulation test (OGLST) and urine organic acid/plasma amino acid (UOA/PAA) assays as metabolic indicators of modified Walker criteria, as suggested by Bernier et al. (Neurology 59:1406-1411, 2002). RESULTS: Twenty-two patients were classified as having definite MD (9), probable MD (5), possible MD (6), or pyruvate dehydrogenase (PDH) deficiency (3), including one patient which showed a respiratory chain (RC) defect and PDH deficiency. Seven out of eight patients in whom significant RC defects were observed showed complex I defects. In 14 patients, epileptic seizures start at infantile ages. Of 17 patients who substantially presented generalized seizures, 4 patients started with partial seizures. Five patients consistently presented only partial seizures. The OGLST and UOA/PAA assays were useful for a more precise diagnosis of MD, although low positive predictive value of the OGLST was regrettable. No patient was classified as definite MD by Walker's original criteria, but the use of our revised MD criteria resulted in the classification of nine additional patients as definite MD. CONCLUSIONS: MD manifested considerable diverse epileptic phenotypes and should be considered in the differential diagnosis of epilepsy in children with unexplained encephalomyopathy and progressive and fluctuating clinical courses.     

GS23PPAEDIATRIC SURGERY PERFORMED BY GENERAL SURGEONS IN A PROVINCIAL NEW ZEALAND (NZ) HOSPITAL

Purpose To perform an audit of paediatric surgical patients in a provincial general surgical unit. Methodology Data was prospectively recorded using a standardized proforma on all children aged up to 15 yrs, seen between 11th December 2005 and 11th December 2006. Results There were 209 admissions (194 children), median age 8 yrs (6 wks–15 yrs) with 153 (73%) acutes. 37 children (18%) were under 2 yrs. Male : female ratio was 3 : 2. Procedures (n = 119) were appendicectomy (35), inguinal herniotomy (30), skin procedures (29), endoscopy (10), testicular (10) and others (5). The commonest acute and elective operations were appendicectomy and inguinal herniotomy respectively. 51% of operations were acute. There were 10 tertiary hospital transfers (5%) for burns (4), pyloric stenosis (3), intussusseption (1), neonatal inguinal hernia (1) and pyoderma gangrenosum (1). Median age of transfers was 11 months (6 wks–14 yrs). Complications were wound infection (1), post‐operative ileus (2) and infarcted ovary (1). Conclusion There are increasing moves towards centralization in paediatric surgery. 1 With only 4 paediatric tertiary centres in NZ, many general surgeons routinely perform paediatric surgery. A large number of children presented to our surgical department. Around half of these children required surgery and half of operations were acute. There is still a significant need for general paediatric surgery in the provinces and hence close collaboration with specialist paediatric surgeons.     

Fracture risk in monoclonal gammopathy of undetermined significance.

To assess fractures in monoclonal gammopathy of undetermined significance (MGUS), the precursor of multiple myeloma, we followed 488 Olmsted County, MN, residents with MGUS in a retrospective cohort study. There was a 2.7-fold increase in the risk of axial fractures but no increase in limb fractures. The pathophysiologic basis for the increased axial fractures should be determined. INTRODUCTION: Multiple myeloma is often preceded by monoclonal gammopathy of undetermined significance (MGUS). Fractures are common in myeloma as a result of lytic bone lesions, generalized bone loss, and elevated bone turnover from excessive cytokine production. Whether fractures are also increased in MGUS is unknown. MATERIALS AND METHODS: In a population-based retrospective cohort study, 488 Olmsted County, MN, residents with MGUS first diagnosed in 1960-1994 (52% men; mean age, 71.4 +/- 12.8 years) were followed for 3901 person-years; follow-up was censored at progression to myeloma. The relative risk of fractures was assessed by standardized incidence ratios (SIRs), and risk factors were evaluated in proportional hazards models. RESULTS AND CONCLUSIONS: Altogether, 200 patients experienced 385 fractures. Compared with expected rates in the community, statistically significant increases were seen for fractures at most axial sites, for example, vertebrae (SIR, 6.3; 95% CI, 5.2-7.5). There was a slight increase in hip (SIR, 1.6; 95% CI, 1.2-2.2) but not distal forearm fractures (SIR, 0.8; 95% CI, 0.4-1.5). The relative risk (SIR) of any axial fracture was 2.7 (95% CI, 2.3-3.1) compared with only 1.1 (95% CI, 0.9-1.4) for all limb fractures combined. In a multivariate analysis, the independent predictors of any subsequent fracture were age (hazard ratio [HR] per 10-year increase, 1.4; 95% CI, 1.2-1.6) and corticosteroid use (HR, 1.8; 95% CI, 1.2-2.6); greater weight at diagnosis (HR per 10 kg, 0.8; 95% CI, 0.8-0.9), and IgG monoclonal protein (HR, 0.7; 95% CI, 0.5-0.97) were protective. Baseline monoclonal protein level, a determinant of myeloma progression, did not predict fracture risk. Thus, the risk of axial, but not peripheral, fractures is increased among MGUS patients even before progression to myeloma. The pathophysiologic basis for this should be determined because elevated bone turnover, for example, might be treatable.