A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder

Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Extramedullary relapses after allogeneic non-myeloablative stem cell transplantation in multiple myeloma patients do not negatively affect treatment outcome

Item does not contain fulltextRecent literature suggests that after non-myeloablative allogeneic (NMA) stem cell transplantation (SCT), the incidence of extramedullary (EM) relapse in multiple myeloma (MM) patients is increased and that these relapses have a poor prognosis. However, numbers on incidence and treatment outcome are scarce. We collected data from 54 relapsed MM patients from a total group of 172 treated with sequential autologous and allogeneic NMA SCT at seven transplantation centres. There were 43 (79.6%) systemic relapses, including 6 with concurrent EM localisation. Five patients had a local EM relapse only. Six patients relapsed with only bone involvement. Patients with deletion of chromosome 13 had a higher incidence of EM relapse (30.8 versus 5.6%, P=0.06). EM relapses were treated with donor lymphocyte infusion, radiotherapy, or chemotherapy, especially with novel agents. The response rate was 45.5%, which was not different when compared to patients without EM disease (54.1%). Overall survival and progression-free survival were not significantly different in patients with EM disease, when compared to those without EM disease. In conclusion, the incidence of relapse with EM disease following allogeneic NMA SCT was 20.4%. There was no negative impact of EM relapse on response rate, overall survival and progression-free survival

Prognostic factors for donor lymphocyte infusions following non-myeloablative allogeneic stem cell transplantation in multiple myeloma.

Item does not contain fulltextIn this retrospective study, we evaluated donor lymphocyte infusions given for relapsed (n=48) or persistent (n=15) myeloma following non-myeloablative allogeneic stem cell transplantation (Allo-SCT). Twenty-four of 63 patients (38.1%) responded: 12 patients (19.0%) with a partial response (PR) and 12 patients (19.0%) with a complete response (CR). Overall survival after donor lymphocyte infusions (DLI) was 23.6 months (1.0-50.7+). Median overall survival for non-responding patients was 23.6 months and has not been reached for the patients responding to DLI. In responders, progression-free survival after DLI was 27.8 months (1.2-46.2+). Patients with a PR had a median progression-free survival of 7.0 months, whereas patients with a CR to DLI had a median progression-free survival of 27.8 months. Major toxicities were acute graft-versus-host disease (GVHD) (38.1%) and chronic GVHD (42.9%). Seven patients (11.1%) died from treatment-related mortality. The only significant prognostic factors for response to DLI were the occurrence of acute and chronic GVHD. There was a trend towards significance for time between transplantation and DLI, and response. Donor lymphocyte infusion following non-myeloablative Allo-SCT is a valuable strategy for relapsed or persistent disease

Poaching in Uganda: Perspectives of Law Enforcement Rangers

Much of prior empirical research examining poachers and poaching strategies have originated from interviews with poachers and wildlife law enforcement officers within North American settings. Few studies have empirically analyzed poacher categories and poaching strategies within an African context. Furthermore, most studies have overlooked important situational elements that influence poacher activities. Based on semi-structured interviews and informal conversations with law enforcement rangers and supervisors and, participant observations of routine day foot patrols, this study presents the findings of an exploratory analysis on poaching in a protected area in Uganda

A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder.

Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS.status: Published onlin

A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder.

Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS