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.     

A Comparison Between Recipients Receiving Matched Kidney and Those Receiving Mismatched Kidney from the Same Cadaver Donor

The optimal allocation of cadaveric kidneys for transplantation with reference to human leukocyte antigen (HLA) match and sharing these organs to a distant center remains controversial. The current analysis was performed using the United Network for Organ Sharing (UNOS) database for cadaveric kidney transplants (Tx) between 1988 and 1997. The graft survivals of zero-mismatch (matched) kidneys with the mate (mismatched) kidneys were compared. There were 2385 donors and 4770 Tx. Significant differences in recipient demographics between matched and mismatched Tx were: fewer African-American race (AA) in the matched group (9.0% vs. 21.9%), higher number of previous Tx (25.5% vs. 14.8%) and elevated mean cold ischemia time (24.0 vs. 22.2 h). Post-Tx dialysis requirements were similar (22.8% vs. 24.1%, p = 0.62) and matched kidneys had to travel more distance (920 vs. 232 miles). Using a Cox model, the matched group had a decreased relative hazard of graft failure of 23.0% (p = 0.0002) or 35% (p < 0.0001) with and without censoring for death. There was significantly better graft survival in the matched recipients in all pairs except AA (matched) and non-AA (mismatched). For older donors (> or = 50 years, n = 1508), the matched grafts survival was marginally significant (p =0.05). Matched kidneys have improved survival compared with the mismatched kidneys despite the longer distance traveled. The benefit of mismatched transplants was predominantly seen in non-AA.     

BK Virus-Specific Antibodies and BKV DNA in Renal Transplant Recipients with BKV Nephritis

We evaluated twenty renal transplant subjects at various stages of BKV nephritis (BKVN) for BKV-specific IgG and IgM antibodies using ELISA technique and BKV-DNA using PCR. They were divided as early onset (n = 7), stabilizing (n = 3), resolved (n = 8) and late onset (n = 2) BKVN. BKV-specific antibodies and BKV-DNA were simultaneously determined. The mean BKV-specific IgG level in early onset and stabilizing BKVN were 64 and 39 EIA units, and were significantly lower than 138 EIA units seen in resolved BKVN, P = 0.007, P = 0.008. The mean BKV-specific IgM levels in stabilizing BKVN was higher than resolved BKVN (130 vs 51 EIA units), P = 0.006. Mean plasma BKV loads for each group were 955,925, 5642 and 42 copies/mL of plasma, respectively. Prospective study in six BKVN cases revealed mean IgG, IgM levels and BKV-DNA at the time of diagnosis of BKVN as 39, 110 EIA units and 586,758 copies/mL of plasma, respectively. After a mean period of 5.2 months, IgG level increased to 120 EIA units (p = 0.0058) and had no detectable viral copies in circulation. Recovery from BKVN and elimination of BKV is associated with the development of BKV-specific IgG antibodies and this provides insight into the role of humoral immunity to BKV in the pathogenesis of BKVN.     

Antimurine antibody formation following OKT3 therapy

OKT3 is an IgG2a murine monoclonal antibody directed against the CD3 antigen receptor of human T lymphocytes. A major concern with OKT3 treatment in solid organ transplant recipients is the development of antimouse antibody, which may preclude retreatment with this agent. We have administered OKT3 on 215 occasions (150 renal, 34 hepatic, 26 cardiac, 5 pancreatic) in 179 patients between April 1982 and December 1988. The mean duration of treatment was 10.5 days (range, 2-22 days). Antimouse antibody data were analyzed on the most recent 133 treatment courses where the antibody status was available pretreatment. Determination of antimouse antibody production was elicited by ELISA technology at days 0, 7, 14, and 28 of OKT3 treatment. Patients were categorized according to the antibody response as follows: (a) absence of antibody; (b) low titer (1:100); or (c) high titer (greater than or equal to 1:1000). Our earlier experience has demonstrated that retreatment with OKT3 is successful in groups a and b. The development of antimurine antibodies was analyzed with regard to the following parameters: (1) The duration of OKT3 treatment; (2) treatment type (prophylactic, primary, or secondary); (3) primary treatment or retreatment; (4) concomitant immunosuppressive regimen (double or triple therapy); (5) dosage of concomitant immunosuppressive drugs; and (6) transplant organ type. The following results were obtained. (1) Duration of treatment had no effect on antibody production (11.0 days in antibody negative and 10.0 days in antibody positive). (2) There was no difference in antibody formation rates for the first treatment of OKT3 when it was used as prophylaxis (26%), primary (19%), or secondary (27%) therapy. (3) Antibody formation rate with first treatment was 29%; with retreatment, patients who were antibody negative following first treatment became positive in 28% of cases, and retreated patients who were low titer positive following first treatment converted to high titer in 57% of cases. (4) Antibody formation was higher in patients receiving double immunosuppressive therapy (36%) than in those receiving triple immunosuppressive therapy (21%) during OKT3 treatment. (5) Concomitant immunosuppression was lower in the antibody-positive group during OKT3 therapy: steroids, 61 mg/day vs. 52 mg/day; azathioprine, 89 mg/day vs. 66 mg/day; CsA, 317 mg/day vs. 186 mg/day. (6) Antibody formation rates were lower in non-renal transplants following first treatment with OKT3 (liver 17%, heart 17%, kidney 28%); this reflects the higher doses of concomitant immunosuppressive therapy used in nonrenal transplants.(ABSTRACT TRUNCATED AT 400 WORDS)     

Neurilemmoma of tongue

Neurilemmoma is usually soimry, benign tumour derived from schwan cells of the Sheaths of peripheral cranial or autonomie nerves. In thehead and neck region it occurs most commonly in association with acoustic nerve within the skuil and is rely fottnd in the oral cavity (1,2). We report here two cases of the iongue diagnosed on histopathohgy.