Number Of Treatment-related Adverse Events Research Articles

Dynamic toxicity landscape of immunotherapy for solid tumors across treatment lines

ObjectiveImmune checkpoint inhibitors (ICIs) targeting programmed cell death-1/ligand-1 (PD-1/PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), and lymphocyte-activation gene-3 (LAG-3) have been widely studied and applied throughout the course of cancer treatment. This study aimed to provide a comprehensive profile of ICI-associated toxicity and elucidate the toxicity patterns of ICIs across different treatment lines. MethodsIn total, 155 cohorts comprising 24 539 eligible patients were included in the safety analysis. Trial name, registration number, cancer type, trial phase, clinical setting, trial design, regimen, dosing schedule, age, sex and ethnicity distributions, number of patients, number of treatment-related adverse events (trAEs), and number of treatment-related death were extracted. We defined a timeline from the neoadjuvant setting to the third-line setting. We also introduced a synthesizing principle for adverse event rates (SPAER) of immunotherapy to ensure the comparability and reliability across different treatment lines. The study protocol was registered and approved by the PROSPERO protocol review committee (CRD42021242368). ResultsAfter excluding the neoadjuvant setting group, we observed a distinct reduction in the incidence of treatment-related adverse events (trAEs) with an advancement of the line of ICI treatment. The incidence of trAEs was negatively correlated with the line of treatment, irrespective of whether monotherapy or dual-ICI combination therapy was administered. Sensitivity analyses also confirmed the coincident negative correlations. ConclusionIn summary, using a timeline-based concept centered around treatment lines, we revealed the dynamic landscape of ICI-associated toxicity and found that patients treated with ICIs during later lines of therapy may have a lower risk of trAEs.

Current situation and risk factors for Helicobacter pylori eradication failure in Northwest China: a real-world evidence study.

Current situation and risk factors for Helicobacter pylori eradication failure in Northwest China: a real-world evidence study.

Antisecretory factor is safe to use as add-on treatment in newly diagnosed glioblastoma

PurposeGlioblastoma (GBM) is the most common primary malignant brain tumor in adults. Despite the best available treatment, prognosis remains poor. Current standard therapy consists of surgical removal of the tumor followed by radiotherapy and chemotherapy with the alkylating agent temozolomide (TMZ). Experimental studies suggest that antisecretory factor (AF), an endogenous protein with proposed antisecretory and anti-inflammatory properties, may potentiate the effect of TMZ and alleviate cerebral edema. Salovum is an egg yolk powder enriched for AF and is classified as a medical food in the European Union. In this pilot study, we evaluate the safety and feasibility of add-on Salovum in GBM patients.MethodsEight patients with newly diagnosed, histologically confirmed GBM were prescribed Salovum during concomitant radiochemotherapy. Safety was determined by the number of treatment-related adverse events. Feasibility was determined by the number of patients who completed the full prescribed Salovum treatment.ResultsNo serious treatment-related adverse events were observed. Out of 8 included patients, 2 did not complete the full treatment. Only one of the dropouts was due to issues directly related to Salovum, which were nausea and loss of appetite. Median survival was 23 months.ConclusionsWe conclude that Salovum is safe to use as an add-on treatment for GBM. In terms of feasibility, adherence to the treatment regimen requires a determined and independent patient as the large doses prescribed may cause nausea and loss of appetite.Trial registrationClinicalTrials.gov NCT04116138. Registered on 04/10/2019.

Short-term efficacy and adverse effects of collagenase clostridium histolyticum injections, percutaneous needle fasciotomy and limited fasciectomy in the treatment of Dupuytren’s contracture: a network meta-analysis of randomized controlled trials

AimsDupuytren’s contracture (DC) is a chronic debilitating fibroproliferative disorder.Common treatment options include collagenase clostridium histolyticum injections (CI), percutaneous needle fasciotomy (NF) and limited fasciectomy (LF). Superiority of one specific treatment remains controversial. This study aims to assess the short-term efficacy and safety of CI, NF, and LF for the treatment of DC.MethodsWe included randomized controlled trials of CI compared with placebo, NF and LF for patients with DC. PubMed, Embase and the Cochrane Library were searched from inception to August 2021. Contracture reduction rates in treated joints (within 0–5° of full extension within 30 days), relative reduction in total passive extension deficit (TPED), occurrence of one or more adverse events and number of treatment-related adverse events per patient were the outcomes of interest. The Cochrane risk-of-bias tool was employed for quality assessment of the studies. A network meta-analysis was performed using MetaXL.ResultsNine studies met our inclusion criteria (n = 903). Overall, risk bias was mixed and mostly low. Short term TPED reduction achieved with LF was superior compared to CI and NF. Although CI achieved greater TPED reduction compared to NF, it was associated with the highest risk of overall adverse effects. The analyzed data was limited to a maximum three-year follow-up period and therefore insufficient for long-term outcome evaluation.ConclusionsIn DC, LF may be able to provide patients with severe disease, superior flexion contracture release postoperatively. CI is a valid treatment alternative to NF, however the higher risk of overall adverse effects must be considered. The quality-of-evidence is limited due to short-term follow-up periods and a lack of standardized definitions of complications and adverse events.

Induction therapy for pediatric onset class IV lupus nephritis: Mycophenolate Mofetil versus Cyclophosphamide.

Class IV lupus nephritis (LN) is one of the most frequent and severe types of involvement in pediatric systemic lupus erythematosus. Gold standard treatment consists of intravenous (i.v.) Cyclophosphamide (CYC) associated with corticosteroids. Recent studies in adultshave shown similar efficacy of oral Mycophenolate Mofetil (MMF) with fewer adverse events. Our aim was to compare the efficacy and tolerance of CYC and MMF as induction therapy in childrenwith class IV LN. We conducted a retrospective study of children diagnosed with class IV LN who started oral MMF or i.v. CYCtreatmentat Necker Enfants MaladesHospital (Paris, France). The study included33 patients, 17 treated with oral MMF (51%) and 16 with i.v. CYC (48%). The characteristics at treatment induction did not significantly differ between the two groups except for the neurological involvement, that was only present in the CYC group. Complete remission was obtained in 9/17 (53%) children treated with MMF versus 10/16 (71%) treated with CYC (p = 0.46). Relapse was observed in 59% of patients receiving MMF versus 50% receiving CYC (p = 0.87), after a median of 3.4years and 4.7years after the beginning of treatment, respectively(p = 0.41). During the 6.5years of follow-up, we observed no significant difference regarding the number of treatment-related adverse events between the two groups (p = 0.48). We report similar efficacy and tolerance of MMF or CYC as induction therapy of class IV LN in children. However, the long-term adverse events such as infertility could not be systematically evaluated in this retrospective pediatric study. Overall,however,considering the long-term safety profile reported in the literature,we suggest that MMF may be used as first-line induction therapy in LN.

Inhaled Nitric Oxide for the Treatment of Acute Bronchiolitis: A Multicenter Randomized Controlled Clinical Trial to Evaluate Dose Response.

Rationale: Inhaled nitric oxide (iNO) has potential antiinflammatory, antimicrobial, and antiviral properties for patients with lower respiratory tract infections. Objectives: We compared the safety and efficacy of iNO administered in two concentrations in addition to standard supportive treatment (SST) compared with SST alone with the aim of improving clinical outcomes of infants with bronchiolitis. Methods: In this prospective, multicenter, double-blind, randomized controlled study, 89 infants hospitalized with moderate to severe bronchiolitis were randomly assigned to three treatment groups: 150 ppm NO plus SST (group 1), 85 ppm NO plus SST (group 2), and the control treatment (O2/air plus SST) (group 3). Treatment was given for 40 minutes, four times each day, for up to 5 days. The primary endpoint was time to reach "fit for discharge." This was a composite endpoint composed of both reaching a sustained oxygen saturation ≥92% on room air and reaching a clinical score ⩽5. Secondary endpoints included time to reach sustained oxygen saturation ≥92% on room air, time to clinical score ⩽5, and time to hospital discharge. Safety was assessed by the number of treatment-related adverse events (AEs) or serious AEs. Time-to-event efficacy outcomes were analyzed using a Cox proportional hazards regression model. Hazard ratios (HR) describe how many times more likely an individual is to experience an event, if such an individual receives NO rather than the control treatment during the observational period. Results: Group 1 demonstrated significant efficacy for time to reach fit to discharge compared with groups 2 (HR, 2.11; P = 0.041) and 3 (HR, 2.32; P = 0.049). Group 1 also demonstrated significant efficacy for time to hospital discharge compared with groups 2 (HR, 2.01; P = 0.046) and 3 (HR, 2.28; P = 0.043). No significant differences were observed between groups 2 and 3 for either endpoint. There were no differences between treatment groups in time to reach a clinical score ⩽5. The iNO therapy was well tolerated, with no treatment-related serious AEs. Conclusions: Treatment with high-dose intermittent iNO at 150 ppm showed reduced time to clinical improvement compared with 85 ppm or control treatment of hospitalized infants with acute bronchiolitis. The 150-ppm iNO dose is well tolerated, with significant benefit compared with both standard therapy and 85 ppm iNO, improving respiratory outcomes and reducing length of stay. Clinical trial registered with www.clinicaltrials.gov (NCT04060979).

Wearable transcutaneous electrical nerve stimulation (actiTENS®) is effective and safe for the treatment of knee osteoarthritis pain: a randomized controlled trial versus weak opioids.

Introduction:Despite their poor tolerance, especially in the elderly, weak opioids (WO) remain commonly prescribed for patients with knee osteoarthritis (KOA). We compared the efficacy and safety of a new wearable transcutaneous electrical nerve stimulation (W-TENS) device with WO for the treatment of moderate-to-severe, nociceptive KOA chronic pain.Methods:The study was a non-inferiority, multicentric, prospective, randomized, single-blind, controlled, 2-parallel groups Trial. A total of 110 patients with KOA were included (Kellgren-Lawrence radiographic grade ⩾2; American College of Rheumatology criteria), with chronic moderate-to-severe nociceptive pain (mean 8-day pain intensity (PI) ⩾ 4 on an 11-point numerical rating scale), in failure to non-opioid analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs). Patients with neuropathic pain were excluded. The co-primary endpoints were mean PI at 3 months (M3) and number of potentially treatment-related adverse events (TRAEs). Secondary outcomes included Western Ontario MAC Master University function subscale (range, 0–68), additional pain and quality of life measures, and responder rates.Results:The non-inferiority of W-TENS was demonstrated in both the per protocol (PP) and intent-to-treat (ITT) populations. At M3, PI in PP population was 3.87 (2.12) compared with 4.66 (2.37) [delta: −0.79 (0.44); 95% CI (−1.65, 0.08)] in W-TENS and WO groups, respectively. A planned superiority analysis showed a significant superiority of W-TENS over WO on PI at M3 (p = 0.0124). The number of TRAEs was significantly lower in the W-TENS group (n = 7) than in the WO group (n = 36) (p < 0.001). Other secondary outcomes also favored W-TENS.Conclusion:W-TENS was more effective and better tolerated than WO in the treatment of chronic nociceptive KOA pain and offers an interesting non-pharmacological analgesic alternative in the management of KOA.Trial Registration: ClinicalTrials.gov: NCT03902340

A randomized phase I pharmacokinetic trial comparing the potential biosimilar adalimumab (CinnoRA®) with the reference product (Humira®) in healthy volunteers

ABSTRACT Background CinnoRA® (CinnaGen, Iran) is a biosimilar candidate for the reference adalimumab, Humira® (AbbVie, USA). This study aimed to compare the pharmacokinetics, safety, and tolerability of these products in healthy participants. Research design and methods In this phase-I, randomized, double-blind trial, 74 healthy adult volunteers were randomized in a 1:1 ratio to receive a single 40 mg subcutaneous injection of CinnoRA® or Humira®. Serum concentrations of adalimumab were analyzed using a validated enzyme-linked immunosorbent assay and were evaluated by non‐compartmental methods. Pharmacokinetic equivalence between groups was determined using the standard equivalence margins of 0.80 to 1.25. Results The baseline characteristics were similar between study groups. Mean values of area under the serum concentration-time curve from time zero to infinity (AUCinf) and maximum serum concentration (Cmax) were similar in study groups and the 90% confidence intervals for the geometric mean ratios of AUCinf and Cmax were within the prespecified equivalence margins. There were no deaths and the total number of treatment-related adverse events was not statistically different between groups (p-value = 0.19). Conclusions The results clearly showed the pharmacokinetic similarity of the biosimilar adalimumab to the originator. CinnoRA® was safe and well-tolerated in healthy volunteers, with no significant differences in safety from the reference product. Trial Registration The trial is registered at ClinicalTrials.gov (# NCT03273192).

Tolerability of Alternative Dosing Schedules for Sunitinib: A Systematic Review and Meta-Analysis.

PurposeThe standard schedule for sunitinib treatment is 4 weeks on and 2 weeks off (4/2) in first-line treatment for metastatic renal cell carcinoma (mRCC). Schedule modifications, including 2 weeks on and 1 week off (2/1), appear to reduce the total number of treatment-related adverse events (TRAEs) without compromising efficacy. Even though TRAEs can qualitatively differ from each other, it is not clear as to what effects a 2/1 schedule has on individual TRAEs.Materials and MethodsThis meta-analysis included one randomized controlled trial (RCT) and four non-randomized controlled studies (non-RCTs) that compared the two schedules in parallel. The primary objective was to estimate risk of individual adverse events (AEs) with a sunitinib 2/1 schedule versus a 4/2 schedule. Seven representative AEs were evaluated as standard data for the RCT and as weighted pooling data of the non-RCTs. Random effects modelling with Review Manager v5.3 was used to pool study-level data using the inverse-variance of each study as the weight.ResultsThe five selected studies included a total of 484 patients with mRCC. Risk ratios for fatigue for a 2/1 schedule were significantly lower than those for a 4/2 schedule {0.69 [95% confidence intervals (CI), 0.51, 0.95] in the RCT and 0.77 (95% CI, 0.63, 0.94) in the non-RCTs}. Other TRAEs, except diarrhea and anorexia, also tended to decrease in both sets. Efficacy outcomes were comparable between 2/1 and standard schedules.ConclusionThis meta-analysis suggests that a 2/1 schedule of sunitinib lowers the risk of fatigue and the occurrence other AEs without compromising efficacy.

Elimination of hepatitis C virus infection from a hemodialysis unit and impact of treatment on the control of anemia

IntroductionIn the interferon era, the treatment of hepatitis C virus (HCV) infection in patients on haemodialysis (HD) was limited due to the significant number of treatment-related adverse events (AEs). Direct-acting antivirals (DAAs) have demonstrated their efficacy and safety in the treatment of HCV in patients with advanced chronic kidney disease on haemodialysis. The objective of the study was to evaluate the success in eliminating HCV infection from our dialysis unit using DAAs, and to assess the impact of HCV elimination on clinical and analytical outcomes. Patients and methodsThis is a prospective, interventional, single-center study at Hospital Clínic de Barcelona. All HCV-RNA positive patients who received antiviral therapy with DAAs within a 3-year period (2014–2017) were analyzed (n=20). Data on virologic response, adverse events, and biochemical and hematological parameters during and after DAA therapy were analyzed. ResultsAll patients achieved sustained virologic response (SVR) and only 40% of patients presented with mild AEs. None of the patients presented with HCV reinfection after a 1-year follow-up period, and thus HCV was eliminated from our HD unit. SVR was associated with a significant increase in hemoglobin and hematocrit, and a tendency toward the need for lower doses of iron supplementation with no changes in darbepoetin dose. ConclusionHCV infection can be safely eliminated from HD units with the use of DAAs, preventing new infections in patients and healthcare staff. In the short term, the achievement of SVR is associated with an improvement in the control of anemia.

Abstract TP320: A Randomized, Double-blind, Placebo-controlled, Phase I / IIa Clinical Trial for Evaluation of the Safety and Potential Therapeutic Effects After Intravenous Transplantation of Human Umbilical Cord-derived Mesenchymal Stem Cells in Patients With Cerebral Infarction

Hypothesis: Cord has tremendous amount of stem cells that are easier and safer to obtain. The purpose of this study is to investigate the safety and the potential therapeutic effects per dose of human umbilical cord-derived mesenchymal stem cells(Cordstem-ST) IV transplantation in acute cerebral infarction. Methods: This study consist two treatment cohorts: Cohort 1 is one episode of IV Cordstem-ST 2.0 x 10^8 cells or placebo injection on day 0. Cohort 2 is two episodes of IV Cordstem-ST 2.0 x 10^8 cells or placebo injections on day 0 and day 7. Total 18 patients were enrolled and nine patients were allocated in each Cohort. Initially, we non-randomly non-blindly injected Cordstem-ST in initial 3 patients among 2 cohorts to investigate safety evaluation for KFDA requirement. And then we processed randomized, double-blind, placebo-controlled study in remaining 12 patients. Among 12 patients, the ratio of placebo and Cordstem-ST is 1:2 in each cohort. Patients were eligible for acute ischemic stroke patients within 7 days of stroke onset involving anterior circulation territory confirmed by the diffusion weighted MRI and NIHSS score between 5 and 20. Primary outcome measured by number of treatment related-adverse events during 6 months period. Secondary outcome measured improvement in clinical function as assessed by NIHSS, mRS, and BI compared to baseline at 6 months. Other studies including brain imaging (MR volumetry, tractogram, PET), immunochemistry (including biochemical markers), neuropsychological, and genetic studies were performed. Results: We finished this study for 18 patients. All patients had no serious adverse effects. Now, we are processing for rechecking final data and constructing about statistical analyzing methods before opening data randomization. Within 1-2 weeks, all data will be locked for blocking data correction. And then, randomization of data will be opening and we will evaluate primary and secondary outcomes according to schedule of pre-planned statistical analysis. We will present final results in 2018 ISC. Conclusions: We processed this study without any significant problems. Although, up to now, opening process of randomization has not been arrived, we are anticipating announcement of good results in 2018 ISC.

Potassium oxalate oral rinses for long-term relief from dentinal hypersensitivity: Three randomised controlled studies

ObjectivesTo evaluate effectiveness of oral rinses containing dipotassium oxalate monohydrate (KOX) in relieving dentinal hypersensitivity (DH) after 8 w use adjunctive to brushing. MethodsThree 8-week, randomised, controlled, double-blind, parallel-group, single-centre studies were conducted in adults with DH. In each study, participants were randomised to one of two experimental rinses or a placebo in a matrix design, such that each experimental rinse was evaluated in two studies. Rinses A (pH 4.5) and B (pH 7.0) contained 1.5% KOX and were fluoride-free; Rinse C (pH 4.5) contained 2.0% KOX and 45 ppm fluoride as NaF; the placebo rinse (pH 4.5) did not contain KOX or fluoride. Participants brushed with a fluoride dentifrice for 1 min, briefly rinsed with water, then rinsed with their assigned oral rinse for 1 min twice daily for 8 w. DH was assessed at baseline and following 4 and 8 w use by response to an evaporative (air) stimulus (evaluated by Schiff sensitivity score and a 10-point visual rating scale) and a tactile stimulus (Yeaple probe). ResultsAll rinses in each study were associated with statistically significant improvements from baseline in measures of DH after 4 and 8 w treatment. However, between-treatment comparisons were inconsistent across the studies, with only Study 3 demonstrating a significant difference between the experimental (Rinses B and C) and placebo rinses. A number of treatment-related adverse events (all mild) were reported. ConclusionsRinses containing 1.5–2.0% KOX did not consistently demonstrate a benefit over placebo in relieving DH after 8 w use. Clinical significanceWhile favourable results were found in one of the investigations, this suite of studies shows that the possibility of inconsistent results exists even with the best designed and executed trials.

The efficacy of multiple versus single hyaluronic acid injections: a systematic review and meta-analysis

BackgroundIntra-articular hyaluronic acid (IA-HA) is a common therapy used to treat knee pain and suppress knee inflammation in knee osteoarthritis (OA), typically prescribed in regimens ranging from a single injection to 5 weekly injections given once weekly. We conducted a systematic review to determine the efficacy of IA-HA, with subgroup analyses to explore the differences in knee pain and adverse events (AEs) across different dosing regimens.MethodsWe conducted a systematic search of the literature to identify studies evaluating IA-HA for the management of knee OA compared to IA-saline. Primary outcome measure was the mean knee pain score at 13 Weeks (3 months) or 26 weeks (6 months). Secondary outcome was the number of treatment-related AEs and treatment-related serious adverse events (SAEs). We evaluated differences in levels of pain and AEs/SAEs between dosing regimens compared to IA-Saline.ResultsThirty articles were included. Overall, IA-HA injections were associated with less knee pain compared to IA-Saline injections for all dosing regimens. 2–4 injections of IA-HA vs. IA-Saline produced the largest effect size at both 3-months and 6-months (Standard mean difference [SMD] = −0.76; −0.98 to −0.53, 95% CI, P < 0.00001, and SMD = −0.36; −0.63 to −0.09 95% CI, P = 0.008, respectively). Additionally, single injection studies yielded a non-significant treatment effect at 3 and 6 months, while ≥5 5 injections demonstrated a significant improvement in pain only at 6 months. Five or more injections of IA-HA were associated with a higher risk of treatment-related AEs compared to IA-Saline (Risk ratio [RR] = 1.67; 1.09 to 2.56 95% CI, p = 0.02), which was a result not seen within the 1 and 2–4 injection subgroups.ConclusionOverall, 2–4 and ≥5 injection regimens provided pain relief over IA-Saline, while single injection did not. Intra-articular injections of HA used in a 2–4 injection treatment regimen provided the greatest benefit when compared to IA-Saline with respect to pain improvement in patients with knee OA, and was generally deemed safe with few to no treatment-related AEs reported across studies. Future research is needed to directly compare these treatment regimens.

Safety Profile of Collagenase Clostridium Histolyticum Stratified by Degree of Penile Curvature in Patients With Peyronie Disease

To examine the safety of collagenase clostridium histolyticum (CCH) in adult men with penile curvature deformity <30°. CCH is indicated for treatment of Peyronie disease in adult men with palpable plaque and a penile curvature deformity ≥30° at start of therapy; however, during treatment, patients may receive CCH injections when penile curvature deformity is <30°. Patients who received ≥2 CCH treatment cycles in 2 phase 3 studies (Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies I and II) were included. All patients had penile curvature ≥30° at the beginning of treatment and could receive up to 4 treatment cycles. The rate and number of treatment-related adverse events (TRAEs) with CCH treatment were compared between patients with penile curvature deformity ≥30° and penile curvature <30°. The number of CCH treatment cycles included in the current analysis totaled 1204 and 289 cycles in patients with penile curvature deformity ≥30° and <30°, respectively. The incidence of most TRAEs was similar between groups. Rates of penile swelling (21.1% vs 14.5%, P = .007), penile hemorrhage (12.8% vs 8.9%; P = .046), and skin hyperpigmentation (1.0% vs 0.1%; P = .025) were significantly higher in the <30° group. The occurrence of serious TRAEs was similar between groups. No clinically meaningful differences were observed with TRAE rates when CCH injections were administered at penile curvature deformity ≥30° vs CCH injections at penile curvature deformity <30°. These findings highlight the safety of continued CCH injections for patients who have achieved penile curvature deformity <30° after an initial treatment cycle of CCH.

The Effect of Escitalopram on Mood and Cognition in Depressive Alzheimer’s Disease Subjects

Effective treatments to alleviate depression in Alzheimer's disease (AD) have been scarce. To investigate the efficacy and tolerability of escitalopram in the treatment of depression in AD. In this 12-week randomized, double-blind, placebo-controlled trial with open-label, 12-week extension, AD subjects over 50 years of age, with depression defined by Olin's provisional diagnostic criteria, were enrolled. The Cornell Scale for Depression in Dementia (CSDD), and other measures of depression and cognition were repeated. 91 subjects were screened, and 84 were randomized into either the study group or placebo group (n = 42 for both groups). Twenty-four subjects (29%) were unable to finish the study, yielding a per protocol population of 60 subjects (study group: n = 27; placebo group: n = 33). At week 12, differences in measures of depression and cognition between the two groups were not statistically significant. However, exploratory analysis suggested that further research on a subset of subjects with 'definite major depression' (baseline CSDD score ≥18) is needed. The number of treatment-related adverse-events (AE) did not differ between groups (p = 0.83) and no serious treatment-related AE were observed. The use of escitalopram was well tolerated in depressive dementia patients. Future studies focusing on subjects with more severe levels of depression, and with more statistical power, will be needed.

821P - Tolerability associated with sunitinib (SU) 2-week on and 1-week off schedule (2/1 schedule) compared with its standard schedule in metastatic RCC (mRCC): Meta-analysis

SU is the 1st line standard treatment for mRCC and it requires 4-week on treatment and 2-week off as a standard schedule for mRCC. The treatment is associated with several adverse events (AEs), such as fatigue, hand-foot syndrome (HFS), neutropenia, thrombocytopenia etc. Schedule modifications of SU including 2/1 schedule are studied and the results provided the total number of treatment-related adverse events decreased in 2/1 schedule without compromising efficacy. However, the effect of 2/1 schedule on individual AEs was not clearly understood. This analysis included 1 randomized controlled trial (RCT): Lee et al. 2015 (RESTORE trial, NCT00570882) and 4 non-randomized controlled studies (non-RCT): Neri et al. 2013, Kondo et al. 2014, Bradarda et al. 2015 and Pan et al. 2015. The primary objective was to estimate risk of individual adverse events in SU 2/1 schedule versus standard one and secondary objectives were to evaluate efficacy outcomes. 7 AEs were evaluated with a standard data of RCT compared with the weighted meta-analysis data (non-RCT meta). Meta-analysis technique, including fixed effects modelling with Review Manager v5.3 was used to pool study-level data using the inverse-variance of each study as the weight. Data cut-off for this analysis: Apr 2015 The selected studies included a total of 484 patients with mRCC, which comprised 74 and 410 from RCT and non-RCTs, respectively. The risk ratio of fatigue and neutropenia for 2/1 schedule vs. standard significantly decreased in both RCT and non-RCT meta (risk ratio (RR) of fatigue: 0.69 [95% confidence intervals (CI) 0.51, 0.95] vs. 0.75 [0.63, 0.89]; RR of neutropenia 0.60 [0.37, 0.99] vs. 0.58 [0.41, 0.83]). Other AEs also tended to decrease in both sets except diarrhea and anorexia. Efficacy outcomes were comparable between 2/1 and standard schedule. This meta-analysis suggests that 2/1 schedule of SU compared to its standard one decreases risk of fatigue and neutropenia and also favoured to control other AEs without compromising efficacy even with limited sources of data. A patient-level meta-analysis to confirm these findings is warranted.

THE EFFECT OF ESCITALOPRAM ON MOOD AND COGNITION IN DEPRESSIVE ALZHEIMER’S DISEASE SUBJECTS

Background Effective treatments to alleviate depression in Alzheimer's disease (AD) have been scarce. Objective To investigate the efficacy and tolerability of escitalopram in the treatment of depression in AD. Methods In this 12-week randomized, double-blind, placebo-controlled trial with open-label, 12-week extension, AD subjects over 50 years of age, with depression defined by Olin's provisional diagnostic criteria, were enrolled. The Cornell Scale for Depression in Dementia (CSDD), and other measures of depression and cognition were repeated. Results 91 subjects were screened, and 84 were randomized into either the study group or placebo group (n = 42 for both groups). Twenty-four subjects (29%) were unable to finish the study, yielding a per protocol population of 60 subjects (study group: n = 27; placebo group: n = 33). At week 12, differences in measures of depression and cognition between the two groups were not statistically significant. However, exploratory analysis suggested that further research on a subset of subjects with 'definite major depression' (baseline CSDD score ≥18) is needed. The number of treatment-related adverse-events (AE) did not differ between groups (p = 0.83) and no serious treatment-related AE were observed. Conclusion The use of escitalopram was well tolerated in depressive dementia patients. Future studies focusing on subjects with more severe levels of depression, and with more statistical power, will be needed.

Efficacy and tolerability of a single-pill combination of telmisartan/ hydrochlorothiazide 80/25 mg in Chinese and Korean patients with moderate to severe hypertension: a subgroup analysis of a randomized, double-blind, active-controlled trial

Background Hypertension is an important issue in Asia, responsible for up to 66% of cardiovascular disease cases. This randomized controlled trial subgroup analysis compared telmisartan 80 mg (T80)/hydrochlorothiazide 25 mg (H25) single-pill combination with T80 monotherapy, specifically in Chinese and Korean patients. Methods Patients with grade 2/3 hypertension were randomized to receive telmisartan 40 mg (T40)/hydrochlorothiazide 12.5 mg (H12.5) combination or T40 monotherapy for one week, before uptitrating the dose to T80/H25 or T80, respectively, for the remaining 6 weeks. The primary endpoint was systolic blood pressure (SBP) mean change from baseline. Secondary endpoints included mean diastolic blood pressure (DBP) change from baseline, and blood pressure (BP) goal achievement. Adverse events were recorded. Results Of a total 888 patients who were treated, efficacy analyses for Chinese and Korean patients included 127 patients treated with T80/H25 and 54 patients treated with T80. At week 7, mean SBP reductions from baseline were −37.5 mmHg (1 mmHg=0.133 kPa) and −26.9 mmHg in the T80/H25 and T80 groups (adjusted mean difference, −10.6 mmHg; 95% confidence interval (CI), −15.6 to −5.7). Mean DBP reductions were −19.0 and −14.1 mmHg in the T80/H25 and T80 groups (adjusted mean difference, −4.9 mmHg; 95% CI, −8.0 to −1.8). In total, 56.7% of patients receiving T80/ H25 achieved BP goal (&lt;140/90 mmHg) compared with 35.2% receiving T80. SBP goal attainment (&lt;140 mmHg) and DBP goal attainment (&lt;90 mmHg) were also higher in the T80/H25 group compared with the T80 group (SBP: 69.3% vs. 48.1%; DBP: 62.2% vs. 46.3%). A small number of treatment-related adverse events were observed in both T80/H25 (nine patients, 6.9%) and T80 monotherapy (two patients, 3.6%) groups. Conclusions In Chinese and Korean patients with moderate-to-severe hypertension, treatment with T80/H25 provided large reductions in mean SBP and DBP, and high BP goal attainment rates. This once-daily combination is effective and well tolerated in this patient group. (ClinicalTrials.gov identifier NCT00926289)

Adverse Events Associated With Concurrent Chemoradiation Therapy in Patients With Head and Neck Cancer

To assess toxicities, functional outcomes, and health-related quality of life associated with concurrent chemoradiation therapy (CRT) in patients with head and neck cancer. Prospective and retrospective outcomes study. Tertiary care institution. Participants in the longitudinal Outcomes Assessment Project whose head and neck cancer was treated with CRT between February 1, 2000, and March 1, 2007 (n = 104). Patients prospectively provided functional and health-related quality of life information, including data from the 1-year and most current follow-up visits. Medical records were reviewed to determine toxicity and survival rates. Well-defined acute and late toxicities; functional outcomes (diet, dentition, tracheostomies); head and neck cancer-specific, general health, and depression outcomes; and survival rates. Most patients had oropharyngeal or laryngeal tumors (87.5%) and advanced-stage disease (75.0%). Approximately one-half had hematologic toxicities and toxicity-related treatment delays. Approximately one-quarter had neurotoxicities and/or ototoxicites, moist desquamation, pneumonia, nausea and vomiting requiring hospitalization or intravenous fluids, dehydration or malnutrition requiring hospitalization, and mild or moderate fever. Although patients receiving the current intensity-modulated radiation therapy (IMRT) protocol using the Pinnacle(3) planning system had more toxicity-related treatment delays, they had fewer toxicities and better functional and health-related quality of life outcomes compared with those receiving conventional lateral opposing-field radiation or the initial IMRT protocol using the Best nomos PEACOCK planning system. Patients receiving CRT experience a substantial number of treatment-related adverse events, primarily affecting oropharyngeal and laryngeal function, with improvement noted for the current IMRT protocol. Improving dental prosthetic rehabilitation and including evaluations with speech and swallowing pathologists before and during treatment may enhance patient outcomes.

Low-dose estradiol for climacteric symptoms in Japanese women: a randomized, controlled trial

Objectives To investigate two different doses of oral estradiol to reduce the number of hot flushes in Japanese women with climacteric symptoms.Methods Women (n = 211) aged 40–64 years who had experienced natural menopause or bilateral oophorectomy, with ≥ three moderate/severe hot flushes per day in the week before study, were randomized to receive micronized estradiol (E2) 0.5 or 1.0 mg or placebo once daily for 8 weeks. The primary efficacy endpoint was percentage change in mean daily number of hot flushes over 7 days from baseline to final examination.Results Percentage change in mean daily number of hot flushes at final examination was similar for E2 0.5 mg and E2 1.0 mg (−79.58 ± 28.29% vs. −82.49 ± 25.31%, p = 0.555) but was significantly lower with placebo (−57.89 ± 34.15%, p < 0.001 vs. E2, both doses). There was no significant difference in number of treatment-related adverse events occurring in the E2 0.5 and 1.0 mg groups (25% and 36.6%, respectively). The higher E2 dose showed more pronounced effects on symptom severity.Conclusions The dose of 0.5 mg/day was effective as the oral E2 starting dose for treatment of hot flushes in Japanese women.