Integrable discretizations of the sine-Gordon equation

The inverse scattering theory for the sine-Gordon equation discretized in space and both in space and time is considered.Comment: 18 pages, LaTeX2

Cardiovascular efficacy and safety of bococizumab in high-risk patients

BACKGROUND Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin– kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of −56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of –59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients. (Funded by Pfizer; SPIRE-1 and SPIRE-2 ClinicalTrials.gov numbers, NCT01975376 and NCT01975389.

An integrable discretization of KdV at large times

An "exact discretization" of the Schroedinger operator is considered and its direct and inverse scattering problems are solved. It is shown that a differential-difference nonlinear evolution equation depending on two arbitrary constants can be solved by using this spectral transform and that for a special choice of the constants it can be considered an integrable discretization of the KdV equation at large times. An integrable difference-difference equation is also obtained.Comment: 12 page

Non-medical use of opioids among HIV-infected opioid dependent individuals on opioid maintenance treatment: the need for a more comprehensive approach

<p>Abstract</p> <p>Background</p> <p>Opioid maintenance treatment (OMT) has a positive impact on substance use and health outcomes among HIV-infected opioid dependent patients. The present study investigates non-medical use of opioids by HIV-infected opioid-dependent individuals treated with buprenorphine or methadone.</p> <p>Methods</p> <p>The MANIF 2000 study is a longitudinal study that enrolled a cohort of 476 HIV-infected opioid-dependent individuals. Data were collected in outpatient hospital services delivering HIV care in France. The sample comprised all patients receiving OMT (either methadone or buprenorphine) who attended at least one follow-up visit with data on adherence to OMT (N = 235 patients, 1056 visits). Non-medical use of opioids during OMT was defined as having reported use of opioids in a non-medical context, and/or the misuse of the prescribed oral OMT by an inappropriate route of administration (injection or sniffing). After adjusting for the non-random assignment of OMT type, a model based on GEE was then used to identify predictors of non-medical use of opioids.</p> <p>Results</p> <p>Among the 235 patients, 144 (61.3%) and 91 (38.9%) patients were receiving buprenorphine and methadone, respectively, at baseline. Non-medical use of opioids was found in 41.6% of visits for 83% of individual patients. In the multivariate analysis, predictors of non-medical use of opioids were: cocaine, daily cannabis, and benzodiazepine use, experience of opioid withdrawal symptoms, and less time since OMT initiation.</p> <p>Conclusions</p> <p>Non-medical use of opioids was found to be comparable in OMT patients receiving methadone or buprenorphine. The presence of opioid withdrawal symptoms was a determinant of non-medical use of opioids and may serve as a clinical indicator of inadequate dosage, medication, or type of follow-up. Sustainability and continuity of care with adequate monitoring of withdrawal symptoms and polydrug use may contribute to reduced harms from ongoing non-medical use of opioids.</p

On dissipationless shock waves in a discrete nonlinear Schr\"odinger equation

It is shown that the generalized discrete nonlinear Schr\"odinger equation can be reduced in a small amplitude approximation to the KdV, mKdV, KdV(2) or the fifth-order KdV equations, depending on values of the parameters. In dispersionless limit these equations lead to wave breaking phenomenon for general enough initial conditions, and, after taking into account small dispersion effects, result in formation of dissipationless shock waves. The Whitham theory of modulations of nonlinear waves is used for analytical description of such waves.Comment: 15 pages, 9 figure

Distributive sharing among HIV-HCV co-infected injecting drug users: the preventive role of trust in one's physician

International audienceThis study, based on data from the MANIF 2000 cohort study, investigates the relationship between the lending of injecting equipment, drug use and experience with HIV care. The sample comprised 224 HIV-HCV-coinfected patients who reported having injected drugs in the previous 6 months and their 538 visits to clinical services. Longitudinal data were collected for medical status, and self-reported risk behaviors. A logistic regression GEE model was used to identify correlates of distributive sharing. After multiple adjustment, patients who reported trust in physicians were significantly less likely to report lending injection equipment while cocaine users were at increased risk. Promoting dialogue between physicians and IDUs may play an important role in HIV-HCV positive prevention

The Zakharov-Shabat spectral problem on the semi-line: Hilbert formulation and applications

The inverse spectral transform for the Zakharov-Shabat equation on the semi-line is reconsidered as a Hilbert problem. The boundary data induce an essential singularity at large k to one of the basic solutions. Then solving the inverse problem means solving a Hilbert problem with particular prescribed behavior. It is demonstrated that the direct and inverse problems are solved in a consistent way as soon as the spectral transform vanishes with 1/k at infinity in the whole upper half plane (where it may possess single poles) and is continuous and bounded on the real k-axis. The method is applied to stimulated Raman scattering and sine-Gordon (light cone) for which it is demonstrated that time evolution conserves the properties of the spectral transform.Comment: LaTex file, 1 figure, submitted to J. Phys.