Required Rescue Therapy Research Articles

Abstract TP27: Aspiration Success With Adapt Technique: Rate, Predictors, and Outcome

Introduction: First Aspiration Pass Technique (ADAPT) was shown to be effective, safe and cost effective. However, around third of patients treated with aspiration technique require rescue therapy. Objective: report the rate of aspiration success (AS), investigate the predictors of aspiration success and the effect of aspiration success on the functional and hemorrhagic outcome. Methods: We interrogated our prospectively collected database which included all patients who presented with large vessel occlusion between 1/2013 and 12/2017 and were treated with ADAPT technique. Baseline characteristics, procedural and outcome variables were collected. Functional outcome was assessed using modified rankin scale (mRS). Hemorrhagic transformation was classified based on ECASS radiological criteria. Logistic regression was used to determine predictors of AS and investigate the effect of AS on outcomes. Results: A total of 510 patients were included in analysis. 333 patients (65%) achieved successful recanalization using only aspiration technique. On multivariate analysis, pretreatment tPA and ICA occlusion were associated with AS. mRS 0-2 was achieved in higher proportion of patients in AS group (42 % vs. 31%; p<0.001) and mortality was lower in AS group (14.7% vs. 29%, p<0.001). The difference remained significant after controlling for potential confounders. Conclusion: AS was associated with better functional outcome and lower mortality rate. Both IV tPA and ICA occlusion were predictors of aspiration success.

Multicenter randomized phase 3 study of a sustained-release intracanalicular dexamethasone insert for treatment of ocular inflammation and pain after cataract surgery

To assess the efficacy and safety of a sustained-release intracanalicular dexamethasone insert for the treatment of postoperative ocular inflammation and pain in patients having cataract surgery. Twenty-one United States sites. Prospective multicenter randomized parallel-arm double-masked vehicle-controlled phase 3 study. Patients with planned clear corneal cataract surgery were randomized (1:1) to receive dexamethasone insert or placebo, and the treatment was placed in the canaliculus of the eye immediately after surgery (Day 1). The primary efficacy endpoints were complete absence of anterior chamber cells at Day 14 and complete absence of pain at Day8. The study comprised 438 adult patients (216 in the treatment arm and 222 in the placebo arm). At Day 14, significantly more patients had an absence of anterior chamber cells in the dexamethasone insert arm compared with placebo (52.3% versus 31.1%; P<.0001). At Day 8, significantly more patients had an absence of ocular pain in the dexamethasone insert arm compared with placebo (79.6% versus 61.3%; P<.0001). The dexamethasone insert arm showed no increase compared with placebo in incidence of all adverse events or ocular adverse events. Twice as many placebo patients required rescue therapy, compared with treated patients at Day14. Both primary endpoints were successfully met. In addition, patients receiving the dexamethasone insert experienced a decrease in inflammation after surgery as early as Day 4 through Day 45, and a decrease in pain as early as one day after surgery(Day 2) through Day 45. The dexamethasone insert was well-tolerated, and the adverse events profile was similar to placebo.

Extended neuromuscular blockade in acute respiratory distress syndrome does not increase mortality

BackgroundNeuromuscular blockade (NMB) is often utilized in the treatment of acute respiratory distress syndrome (ARDS). Its use for a period of 48 h has been shown to improve mortality in randomized control trials. We aimed to characterize outcomes associated with a prolonged NMB. We hypothesized that the duration of NMB would not be associated with increased mortality. Materials and methodsThis was a retrospective review from June 2014 to October 2016 of patients admitted to the surgical intensive care unit and receiving cisatracurium for ARDS. Patients paralyzed for ≤ 48 h (SHORT) were compared to those paralyzed for longer durations (LONG). Primary outcome was mortality. Parametric and nonparametric tests were utilized for the purposes of the comparison. A multivariate logistic regression model was utilized to adjust for differences. ResultsOf 73 patients meeting inclusion criteria, 32 (44%) were SHORT and 41 (56%) LONG. Compared to the LONG cohort, those in SHORT were older (60 versus 52 years, P = 0.04) but were comparable with respect to sex, acute physiology and chronic health evaluation IV scores, presence of concurrent pneumonia, and the use of vasopressors. SHORT patients were less likely to require rescue therapy with inhaled nitric oxide (28% versus 66%, P < 0.01). Overall mortality was 60%. There was no difference in the adjusted odds for mortality (adjusted odds ratio: 0.57, P = 0.33). Secondary outcomes including deep venous thrombosis and pneumonia did not differ between the two groups. ConclusionsExtended NMB for ARDS was not associated with increased mortality. Discontinuation of this modality should not be based solely on the duration of therapy.

CRP/Albumin Ratio

Identifying hospitalized patients with acute severe ulcerative colitis (ASUC) who will be refractory to corticosteroid therapy and require rescue therapy remains difficult. Hypoalbuminemia worsens with time during hospitalization and is associated with rapid clearance of and reduced response to infliximab (IFX) rescue. Early use of rescue therapy may therefore be more effective. Simple clinical and laboratory predictors of corticosteroid responsiveness would facilitate earlier use of rescue therapy. Retrospective study of a prospectively maintained database of 3600 patients attending a single center was conducted. Patients with histologically confirmed ulcerative colitis admitted with ASUC over a 5-year period from January 2010 to December 2014 were identified. All patients initially received intravenous corticosteroids. Patient demographics were collected; C-reactive protein (CRP) and albumin levels were recorded at baseline and during admission. Receiver operating characteristic statistics were used to determine the optimal stool frequency, CRP, albumin, and CRP/albumin ratio (CAR) to predict steroid response. A total of 124 ASUC patients were admitted during a 5-year period. Median follow-up was 2.3 years. A total of 62 patients (50%) were steroid responsive, 55 patients (44%) received rescue IFX, 22 patients (18%) required colectomy within 30 days of admission, whereas a further 14 (11%) required colectomy during follow-up. By receiver operating characteristic statistics, day 3 CAR was a more accurate marker of steroid responsiveness than day 3 CRP or day 3 albumin alone [area under curve=0.75 (P<0.001)]. The optimal CAR to predict response to steroids on day 3 was 0.85 (sensitivity 70%, specificity 76%). When combined with D3 stool frequency, specificity improved to 83%. If at day 3, CAR was >0.85 and stool frequency was >3, the relative risk of steroid nonresponse was significantly raised at 3.9 (95% confidence interval, 2.1-7.2). Raised D3 CAR is an early predictor of steroid-refractory ASUC. When combined with D3 stool frequency, its predictive ability improves. In patients with predicted steroid nonresponse, early introduction of rescue IFX at this stage may be more effective, before serum albumin falls profoundly.

Long-Term Outcomes of Immunosuppression-Naïve Steroid Responders Following Hospitalization for Ulcerative Colitis.

Requirement for hospitalization in ulcerative colitis (UC) is a marker of severity of disease. However, the paradigm of when to escalate therapy in such patients and the benefits of early immunomodulator initiation is less well established. To examine the benefits of early therapy escalation in immunosuppression-naïve patients hospitalized with severe ulcerative colitis responsive to steroids. We identified hospitalized UC patients who were immunosuppression naïve at index hospitalization and responded to intravenous steroids, not requiring medical or surgical rescue therapy. The 'therapy escalated' group comprised of those who were initiated on immunomodulators within 3months of hospitalization. The need for colectomy at 12months was compared to the 'not escalated' group who remained on non-immunosuppressive therapy. Among 133 immunosuppressive naïve patients hospitalized for ulcerative colitis, 13 (9.8%) who responded to intravenous steroids and did not require rescue therapy underwent colectomy by 1year. Among 123 patients who escalated to either immunomodulators (n = 46, 37%) or remained on non-immunosuppressive therapy (92% on 5-ASA), there was no difference in the need for colectomy at 1year (10.8 vs. 7.8%; multivariate OR 1.29, 95% CI 0.35-4.74). There was also no difference in the time to colectomy between the two groups (p = 0.55). Immunosuppression-naïve ASUC patients who respond to intravenous steroids remain at risk for colectomy. Immunomodulator initiation by 3months did not reduce risk of colectomy at 1year. There is an important need for prospective studies identifying thresholds for therapy escalation in UC.

Sarcopenia is a Novel Predictor of the Need for Rescue Therapy in Hospitalized Ulcerative Colitis Patients.

Acute severe ulcerative colitis [ASUC] affects one in four patients with UC. Clinical parameters perform modestly in predicting the need for rescue therapy. Sarcopenia and visceral adiposity predict natural history in Crohn's disease, but the role of such metabolic factors on ASUC outcomes is unknown. The aim of this study was to define the effect of sarcopenia and visceral adiposity on outcomes in ASUC. We studied patients hospitalized for ASUC who underwent an abdominal CT scan during the hospitalization. Quantification of skeletal muscle mass and visceral adiposity was performed by radiologists blinded to the outcome. Sarcopenia was defined as a skeletal muscle index of <55 cm2/m2 for men and <39 cm2/m2 for women. The primary outcome of interest was need for medical or surgical rescue therapy. Our study included 89 patients with ASUC, among whom 39 [43.8%] patients required medical rescue therapy or surgery. Two-thirds of the cohort [70%] met the definition of sarcopenia [81% men, 48% women]. Patients with sarcopenia had similar disease characteristics and laboratory parameters to those with a normal muscle mass. However, a larger proportion of patients with sarcopenia required rescue therapy compared with those without (56% vs 28%, multivariable odds ratio [OR] 3.98, 95% confidence interval [CI] 1.12-14.1). Neither visceral [p = 0.23] nor subcutaneous adiposity [p = 0.53] predicted the need for rescue therapy. Sarcopenia as determined on abdominal CT was a novel predictor of need for rescue therapy in hospitalized UC patients.

Efficacy and Safety of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy in the PLANET Study

Polypoidal choroidal vasculopathy (PCV) is common in Asian populations, but an optimal treatment approach remains to be confirmed. To evaluate intravitreal aflibercept injection (IAI) in participants with PCV and compare IAI monotherapy with IAI plus rescue photodynamic therapy (PDT). This 96-week, double-masked, sham-controlled phase 3b/4 randomized clinical trial was conducted at multiple centers in Australia, Germany, Hong Kong, Hungary, Japan, Singapore, South Korea, and Taiwan from May 2014 to August 2016, and included adults 50 years or older with symptomatic macular PCV and a best-corrected visual acuity of 73 to 24 Early Treatment Diabetic Retinopathy Study letters (20/40-20/320 Snellen equivalent). Participants received 2 mg of IAI at weeks 0, 4, and 8. At week 12, participants with a suboptimal response were randomized 1:1 to receive IAI plus sham PDT (IAI monotherapy) or a "rescue" of IAI plus rescue PDT (IAI/PDT). Participants who did not qualify for rescue received IAI every 8 weeks; those qualifying for rescue received IAI every 4 weeks plus sham/active PDT. When the rescue criteria were no longer met, injection intervals were gradually extended to 8 weeks. Noninferiority of IAI monotherapy to IAI/PDT for mean change in best-corrected visual acuity from baseline to week 52 (95% CI of the difference entirely above -5 letters). Of the 318 participants, the mean (SD) age was 70.6 (8.2) years, 96 (30.2%) were women, and 152 (47.8%) were Japanese. Monotherapy with IAI was noninferior to IAI/PDT for the primary end point (+10.7 vs +10.8 letters, respectively; 95% CI, -2.9 to 1.6; P = .55), with few participants requiring rescue therapy (19 [12.1%] vs 23 [14.3%], respectively). Participants in both treatment groups had similar reductions in central subfield thickness from baseline to week 52 (-137.7 [IAI monotherapy] vs -143.5 μm [IAI/PDT]). At week 52, 49 (38.9%) and 60 participants (44.8%) had no polypoidal lesions observed on indocyanine green angiography in the IAI monotherapy and IAI/PDT groups, respectively. Furthermore, 116 (81.7%) and 136 (88.9%), respectively, had no polypoidal lesions with leakage. The most frequent ocular adverse events were conjunctival hemorrhage (IAI monotherapy, 8 [5.1%]) and dry eye (IAI/PDT, 9 [5.6%]). Improvement in visual and/or functional outcomes was achieved in more than 85% of participants who were treated with IAI monotherapy, with no signs of leakage from polypoidal lesions in more than 80%. As fewer than 15% met the criteria of a suboptimal response to receive PDT, the potential benefit of adding PDT cannot be determined. ClinicalTrials.gov Identifier: NCT02120950.

P532 Efficacy of combination therapy with cyclosporin and vedolizumab in inflammatory bowel diseases refractory to anti-TNF agents

Vedolizumab it is a promising agent in IBD patients refractory to anti-TNF therapy. However, a potential slower response has been documented in both GEMINI 2 and 3 trials, and also in clinical settings. Because of the slower onset of action of vedolizumab, monotherapy does not seem to be effective in more severe cases of IBD. However, cyclosporin is an effective “rescue therapy” which may serve as a rapidly acting “bridge” to maintenance therapy with the slowly acting agents such as thiopurines in patients with severe UC. The aim of the study to report our experiences with the use of combined cyclosporine and vedolizumab therapy in active IBD failed to respond to anti TNF therapy. Vedolizumab was registered in Hungary in 2016. Data were collected retrospectively from the Hungarian Registry on Vedolizumab therapy. We assessed clinical and endoscopic disease activity with CDAI and Mayo Score. Clinical outcome and safety profile was registrated. Six of 106 vedolizumab-treated patients (four colonic CD, two UC) diagnosed with moderate-to-severe IBD requiring rescue therapy received intravenous cyclosporine of 4 mg/kg for 5 days following oral treatment a mean of 69 days before the initiation of vedolizumab. The reason for late initiation of vedolizumab therapy was the awaiting time of the evaluation process. Cyclosporine levels were closely monitored and adjusted if needed. Mean values of CD activity index and partial Mayo score were 276 and 8, respectively. Three patients received concomitant immunomodulator therapy and 3 had azathioprine intolerance. Primary and secondary non-response to previous anti-TNF therapy was reported in two and four patients, while two patients developed infusion reaction. Combination therapy was effective in all cases and cyclosporine was discontinued after a mean of 130 days. After the induction phase of vedolizumab, control colonoscopy was performed. One patient had complete mucosal healing, the other patients had moderate regression in mucosal inflammation. Side-effect of cyclosporine occurred in one patient leading to the discontinuation of the drug after the third infusion of vedolizumab. After the induction phase of vedolizumab, one patient underwent colectomy because of severe CD. On the basis of our data we do think that cyclosporin therapy is a useful and safe option in combination with vedolizumab induction therapy in moderate-to-severe activity of IBD.

Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity

Anti-vascular endothelial growth factor (VEGF) therapies are a novel treatment option in retinopathy of prematurity (ROP). Data on dosing, efficacy, and safety are insufficient. To investigate lower doses of anti-VEGF therapy with ranibizumab, a substance with a significantly shorter systemic half-life than the standard treatment, bevacizumab. This randomized, multicenter, double-blind, investigator-initiated trial at 9 academic medical centers in Germany compared ranibizumab doses of 0.12 mg vs 0.20 mg in infants with bilateral aggressive posterior ROP; ROP stage 1 with plus disease, 2 with plus disease, or 3 with or without plus disease in zone I; or ROP stage 3 with plus disease in posterior zone II. Patients were recruited between September 2014 and August 2016. Twenty infants were screened and 19 were randomized. All infants received 1 baseline ranibizumab injection per eye. Reinjections were allowed in case of ROP recurrence after at least 28 days. The primary end point was the number of infants who did not require rescue therapy at 24 weeks. Key secondary end points included time-to-event analyses, progression of physiologic vascularization, and plasma VEGF levels. Stages of ROP were photodocumented and reviewed by an expert committee. Nineteen infants with ROP were enrolled (9 [47.4%] female; median [range] postmenstrual age at first treatment, 36.4 [34.7-39.7] weeks), 3 of whom died during the study (1 in the 0.12-mg group and 2 in the 0.20-mg group). Of the surviving infants, 8 (88.9%) (17 eyes [94.4%]) in the 0.12-mg group and 6 (85.7%) (13 eyes [92.9%]) in the 0.20-mg group did not require rescue therapy. Both ranibizumab doses were equally successful in controlling acute ROP (Cochran-Mantel-Haenszel analysis; odds ratio, 1.88; 95% CI, 0.26-13.49; P = .53). Physiologic intraretinal vascularization was superior in the 0.12-mg group. The VEGF plasma levels were not systematically altered in either group. This pilot study demonstrates that ranibizumab is effective in controlling acute ROP and that 24% of the standard adult dose (0.12 mg) appears equally effective as 40% (0.20 mg). Superior vascularization of the peripheral retina with 0.12 mg of ranibizumab indicates that the lower dose may be favorable. Unchanged plasma VEGF levels point toward a limited systemic drug exposure after ranibizumab. clinicaltrials.gov Identifier: NCT02134457 and clinicaltrialsregister.eu Identifier: 2013-002539-13.

Effect of C-MAC Video Laryngoscope-aided intubations Using D-Blade on Incidence and Severity of Postoperative Sore Throat.

Background:Video laryngoscope-aided intubations require less force to align oral, pharyngeal, and laryngeal planes to visualize the glottis opening during intubation.Aim:The primary objective of the study was to assess the incidence and severity of postoperative sore throat (POST) in patients who were intubated with C-MAC video laryngoscope using D-blade versus traditional Macintosh laryngoscope.Settings and Design:This prospective, randomized, open label study was conducted in a tertiary care institution.Subjects and Methods:A total of 130 patients undergoing short elective laparoscopic surgeries lasting <2 h were recruited. All patients received general anesthesia as per a standardized protocol. Laryngoscopy was performed using traditional Macintosh laryngoscope in Group M and with Storz® C-MAC video laryngoscope using D-Blade in Group V. The endotracheal tube cuff pressure was maintained at 20–22 cm of H2O intraoperatively.Statistical Analysis Used:Pearson's Chi-square test, Fisher's exact test, and Independent sample t-test were used in this study.Results:As compared to Group M, number of patients who had POST, hoarseness of voice, and cough was significantly low in Group V at 2, 6, 12, and 24 h. Severity, as well as the incidence of all these symptoms, showed a downward trend in both groups with time. Significantly more number of patients in Group M required rescue therapy for POST (44.6% as compared to 7.7%, P < 0.001).Conclusion:C-MAC video laryngoscope-aided intubations using D-blade significantly reduced the incidence and severity of POST, hoarseness of voice, and cough following orotracheal intubation as compared to use of traditional Macintosh laryngoscope.

Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study

Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229. Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56·6 [SEM 4·5] vs 68·3 [4·5]; rank-based treatment difference -11·7, 95% CI -24·3 to 0·96; p=0·0698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy. The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed. Alexion Pharmaceuticals.

Risk Factors for Rescue Therapy in Crohn's Patients Maintained on Infliximab After Withdrawal of the Immunomodulator: A Long-Term Follow-Up.

Usefulness of thiopurine and scheduled infliximab combination therapy in non-immunomodulator (IM)-naïve Crohn's disease (CD) patients and theoptimal length of dual therapy are still debated. To determine proportion of patients developing disease flare requiring rescue therapy and risk factors associated with disease flare after de-escalation of IM from combination therapy. Adult CD patients in clinical remission on combination therapy were identified from a large single-center database between 2002 and 2009. Patients who had their IM stopped in the absence of adverse events were included. Association between clinical and demographic variables and time until rescue therapy was analyzed using Cox-proportional hazard models. Forty-three CD patients on combination therapy in clinical remission at time of IM de-escalation were identified and followed up for a median duration of 61.6months (range 5.4-129.5). Median duration of remission on combination therapy prior to IM de-escalation was 12.0months (range 4-74). Thirty-one patients (72.1%) required rescue therapy during follow-up. On multivariable analysis, age at diagnosis <16years versus >40years (HR 4.55, 95% CI 1.18-17.62, p=0.028), using methotrexate instead of azathioprine in combination with infliximab (HR 3.37, 95% CI 1.14, 9.96, p=0.028), and duration of combination therapy <6months (HR 5.68, 95% CI 1.58, 20.36, p=0.007) increased risk forrescue therapy. A large proportion of CD patients on combination therapy experienced a flare following IM withdrawal. Young age at diagnosis, short duration of combination therapy, and methotrexate use were independent predictors of the need for rescue therapy.

PSY22 - Economic Evaluation of Romiplostim Vs Eltrombopag In The Treatment of Adult Patients With Chronic Immune Thrombocytopenia In Mexico

Romiplostim and eltrombopag are both indicated for the treatment of chronic immune thrombocytopenia (ITP) in splenectomized who are refractory to conventional treatments and rescue therapies, and in non-splenectomized where surgery is contra-indicated. The aim of this analysis was to assess the expected costs and outcomes with both therapies for the treatment of chronic ITP from the perspective of the public health system in Mexico. A decision tree model was developed simulating the pathway of splenectomized and non-splenectomised patients with romiplostim or eltrombopag over a time horizon of 24 weeks. The effectiveness was measured by the overall platelet response (OPR) rate (at least 4 weeks with platelet response). The efficacy estimates for eltrombopag were obtained using an adjusted indirect treatment comparison. Only direct medical costs were considered, including drug acquisition, drug administration, laboratory tests, medical visits, and bleeding related events. Sensitivity analysis was conducted to evaluate robustness of the results. All costs were expressed in 2016 US dollars. The proportion of patients achieving OPR was higher with romiplostim (79.6%) than with eltrombopag (37.4%). The cost per treated patient was 30% lower with romiplostim than eltrombopag ($15,860 Vs. $23,212), driven mainly by cost-savings in the bleeding related costs with romiplostim (-50%). The average cost per patient achieving OPR was also lower with romiplostim vs. eltrombopag ($19,916 Vs. $62,107). The results were consistent and robust to variations in the main inputs. The results of this analysis suggest that romiplostim is a dominant treatment strategy vs. eltrombopag in patients with chronic ITP, as it is associated with more than twice as many patients achieving OPR as well as with cost-savings vs. eltrombopag in the bleeding related events, especially in those events requiring rescue therapy with immunoglobulin. Romiplostim is expected to result in significant savings for the healthcare institutions in Mexico.

Inflammatory Bowel Disease Clinical

Inflammatory Bowel Disease Clinical

Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial

Effective treatment of trauma-induced coagulopathy is important; however, the optimal therapy is still not known. We aimed to compare the efficacy of first-line therapy using fresh frozen plasma (FFP) or coagulation factor concentrates (CFC) for the reversal of trauma-induced coagulopathy, the arising transfusion requirements, and consequently the development of multiple organ failure. This single-centre, parallel-group, open-label, randomised trial was done at the Level 1 Trauma Center in Innsbruck Medical University Hospital (Innsbruck, Austria). Patients with trauma aged 18-80 years, with an Injury Severity Score (ISS) greater than 15, bleeding signs, and plasmatic coagulopathy identified by abnormal fibrin polymerisation or prolonged coagulation time using rotational thromboelastometry (ROTEM) were eligible. Patients with injuries that were judged incompatible with survival, cardiopulmonary resuscitation on the scene, isolated brain injury, burn injury, avalanche injury, or prehospital coagulation therapy other than tranexamic acid were excluded. We used a computer-generated randomisation list, stratification for brain injury and ISS, and closed opaque envelopes to randomly allocate patients to treatment with FFP (15 mL/kg of bodyweight) or CFC (primarily fibrinogen concentrate [50 mg/kg of bodyweight]). Bleeding management began immediately after randomisation and continued until 24 h after admission to the intensive care unit. The primary clinical endpoint was multiple organ failure in the modified intention-to-treat population (excluding patients who discontinued treatment). Reversal of coagulopathy and need for massive transfusions were important secondary efficacy endpoints that were the reason for deciding the continuation or termination of the trial. This trial is registered with ClinicalTrials.gov, number NCT01545635. Between March 3, 2012, and Feb 20, 2016, 100 out of 292 screened patients were included and randomly allocated to FFP (n=48) and CFC (n=52). Six patients (four in the FFP group and two in the CFC group) discontinued treatment because of overlooked exclusion criteria or a major protocol deviation with loss of follow-up. 44 patients in the FFP group and 50 patients in the CFC group were included in the final interim analysis. The study was terminated early for futility and safety reasons because of the high proportion of patients in the FFP group who required rescue therapy compared with those in the CFC group (23 [52%] in the FFP group vs two [4%] in the CFC group; odds ratio [OR] 25·34 [95% CI 5·47-240·03], p<0·0001) and increased needed for massive transfusion (13 [30%] in the FFP group vs six [12%] in the CFC group; OR 3·04 [0·95-10·87], p=0·042) in the FFP group. Multiple organ failure occurred in 29 (66%) patients in the FFP group and in 25 (50%) patients in the CFC group (OR 1·92 [95% CI 0·78-4·86], p=0·15). Our results underline the importance of early and effective fibrinogen supplementation for severe clotting failure in multiple trauma. The available sample size in our study appears sufficient to make some conclusions that first-line CFC is superior to FFP. None.

SAFETY AND EFFICACY OF SAR97276A FOR TREATING MALARIA: TWO OPEN-LABEL MULTICENTER PHASE II CLINICAL STUDIES IN AFRICAN CHILDREN AND ADULTS

BackgroundSAR97276A, is a choline analogue inhibiting the phospholipid biosynthesis of Plasmodium falciparum. Treatment options for severe malaria are limited and SAR97276A represents a drug candidate for this indication.MethodsThis is a...

Rescue therapies for acute respiratory distress syndrome: what to try first?

Severe respiratory failure due to the acute respiratory distress syndrome (ARDS) might require rescue therapy measures beyond even extended standard care to ensure adequate oxygenation and survival. This review provides a summary and assessment of treatment options that can be beneficial when the standard approach fails. 'Life-threatening' conditions or refractory hypoxemia during mechanical ventilation are more a matter of personal rating than an objective diagnosis based on defined and/or unanimously agreed thresholds that would mandate the use of rescue therapies. Although the outcome might vary with different rescue procedures, most of them will improve oxygenation. Prone positioning maintains a predominant role as rescue therapy in severe hypoxemia and does not only improve oxygenation in but also survival of ARDS patients. Recruitment maneuvers can have temporary positive effects. Inhaled nitric oxide, as well as high-frequency oscillatory ventilation might acutely improve oxygenation and can be used as a 'bridge' to alternative rescue therapies, but neither provides any survival advantage by itself and might even be detrimental. Although increasingly employed in other than the rescue indication, extracorporeal membrane oxygenation should still primarily be used in patients who do not respond to differentiated mechanical ventilation, which includes a careful evaluation of nonextracorporeal membrane oxygenation rescue therapies that might be combined in order to overcome the life-threatening situation. Early involvement of an ARDS or extracorporeal membrane oxygenation center should be considered to ensure optimal care. A well timed, multimodal approach is required for patients with ARDS suffering from life-threatening hypoxemia. Understanding the limits of each type of rescue measure is of vital importance.

Systematic Review of Liposomal Bupivacaine (Exparel) for Postoperative Analgesia.

Management of postoperative pain often requires multimodal approaches. Suboptimal dosages of current therapies can leave patients experiencing periods of insufficient analgesia, often requiring rescue therapy. With absence of a validated and standardized approach to pain management, further refinement of treatment protocols and targeted therapeutics is needed. Liposomal bupivacaine (Exparel) is a longer acting form of traditional bupivacaine that delivers the drug by means of a multivesicular liposomal system. The effectiveness of liposomal bupivacaine has not been systematically analyzed relative to conventional treatments in plastic surgery. A comprehensive literature search of the MEDLINE, PubMed, and Google Scholar databases was conducted for studies published through October of 2015 with search terms related to liposomal bupivacaine and filtered for relevance to postoperative pain control in plastic surgery. Data on techniques, outcomes, complications, and patient satisfaction were collected. A total of eight articles were selected and reviewed from 160 identified. Articles covered a variety of techniques using liposomal bupivacaine for postoperative pain management. Four hundred five patients underwent procedures (including breast reconstruction, augmentation mammaplasty, abdominal wall reconstruction, mastectomy, and abdominoplasty) where pain was managed with liposomal bupivacaine and compared with those receiving traditional pain management. Liposomal bupivacaine use showed adequate safety and tolerability and, compared to traditional protocols, was equivalent or more effective in postoperative pain management. Liposomal bupivacaine is a safe method for postoperative pain control in the setting of plastic surgery and may represent an alternative to more invasive pain management systems such as patient-controlled analgesia, epidurals, peripheral nerve catheters, or intravenous narcotics.

Soluble ST2 is a sensitive clinical marker of ulcerative colitis evolution

BackgroundThe ST2/IL-33 pathway has been related to ulcerative colitis (UC), and soluble ST2 (sST2), to disease severity. We tested the potential usefulness of sST2 as a predictive marker of treatment response and patients’ outcome.MethodsTwenty-six patients with active UC were prospectively recruited and grouped according to an endoscopic score and therapy response. Colonoscopic biopsies were collected at baseline and 6 months or when patients showed clinical activity. The protocol was reinitiated in patients requiring rescue therapy. Blood and stool were collected at baseline, 1, 3, 6 and 12 months. Serum and mucosal ST2, and fecal calprotectin (FC) content were determined by ELISA and correlated to Mayo clinical and endoscopic subscore. Intestinal ST2 was evaluated by immunofluorescence. Wilcoxon signed rank test and Spearman correlations (Rs) were applied (p <0.05).ResultsFollow-up was completed in 24 patients. sST2 levels (median and range) varied from 173.5 [136.6–274.0] to 86.5 [54.6–133.2] in responders (p < 0.05), and 336.3 [211.0–403.2] to 385.3 pg/mL [283.4–517.3] in non-responders at baseline and 6 months, respectively. sST2 levels correlated with Mayo clinical and endoscopic subscore, mucosal ST2 and FC (Rs = 0.57, 0.66, 0.74 and 0.42, respectively; p < 0.0001) and showed a trend similar to that of FC in responders. Non-responders revealed an increased ST2 content, restricted to the lamina propria’s cellular infiltrate.ConclusionsConsecutive sST2 measurement to follow changes in inflammatory activity of UC patients who respond or not to treatment identifies sST2, like FC, as a useful biomarker in predicting clinical outcome of UC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-016-0520-6) contains supplementary material, which is available to authorized users.

Risk of clinical deterioration in patients with lupus nephritis receiving rituximab.

Rituximab is a chimeric anti-CD20 monoclonal antibody that is used as an immunosuppressive agent in cyclophosphamide refractory lupus nephritis to induce remission. Although uncontrolled case series suggest efficacy, this is not yet supported by evidence from prospective randomized controlled trials. The objective of this retrospective case series is to report the clinical outcome of seven patients who received rituximab for lupus nephritis in a single centre between 2011 and 2014. One patient had clinical evidence of an uncomplicated response to therapy. A second patient responded well with the first rituximab course, but had transient worsening of renal function and nephrotic syndrome with a second course. The other five patients all had evidence of a clinical deterioration following rituximab. Two had transient worsening of both renal function and nephrotic syndrome, with subsequent evidence of response in one of these. A fifth patient showed evidence of worsening nephrotic syndrome and renal function which then improved but with renal function remaining below the level present before rituximab. A sixth developed rapidly progressive renal failure following rituximab with active nephritis on renal biopsy and required rescue therapy with high dose steroids and cyclophosphamide. A seventh developed a transient worsening of her nephrotic syndrome and an exacerbation of extrarenal symptoms following rituximab. The two patients showing a good response had complete B cell depletion and incomplete depletion may be a factor in the deterioration seen in the other patients. Our experience suggests that rituximab therapy in lupus nephritis is not without risk and patients should be informed of this beforehand. This is particularly important in view of the uncertainty that rituximab will offer a therapeutic benefit.