Multicenter Randomized Trial Research Articles

International Tailored Chemotherapy Adjuvant (ITACA) trial, a phase III multicenter randomized trial comparing adjuvant pharmacogenomic-driven chemotherapy versus standard adjuvant chemotherapy in completely resected stage II-IIIA non-small-cell lung cancer

Several strategies have been investigated to improve the 4% survival advantage of adjuvant chemotherapy in early-stage non-small-cell lung cancer (NSCLC). In this investigator-initiated study we aimed to evaluate the predictive utility of the messenger RNA (mRNA) expression levels of excision repair cross complementation group 1 (ERCC1) and thymidylate synthase (TS) as assessed in resected tumor.Seven hundred and seventy-three completely resected stage II-III NSCLC patients were enrolled and randomly assigned in each of the four genomic subgroups to investigator's choice of platinum-based chemotherapy (C, n = 389) or tailored chemotherapy (T, n = 384). All anticancer drugs were administered according to standard doses and schedules. Stratification factors included stage and smoking status. The primary endpoint of the study was overall survival (OS).Six hundred and ninety patients were included in the primary analysis. At a median follow-up of 45.9 months, 85 (24.6%) and 70 (20.3%) patients died in arms C and T, respectively. Five-year survival for patients in arms C and T was of 65.4% (95% CI (confidence interval): 58.5% to 71.4%) and 72.9% (95% CI: 66.5% to 78.3%), respectively. The estimated hazard ratio (HR) was 0.77 (95% CI: 0.56-1.06, P value: 0.109) for arm T versus arm C. HR for recurrence-free survival was 0.89 (95% CI: 0.69-1.14, P value: 0.341) for arm T versus arm C. Grade 3-5 toxicities were more frequently reported in arm C than in arm T.In completely resected stage II-III NSCLC tailoring adjuvant chemotherapy conferred a non-statistically significant trend for OS favoring the T arm. In terms of safety, the T arm was associated with better efficacy/toxicity ratio related to the different therapeutic choices in the experimental arm.

182 A Multi-Center Randomized Trial of Capsule Endoscopy to Reduce Admissions in Emergency Department Patients With Low Risk Upper Gastrointestinal Bleed

In US emergency departments (EDs), the provider has limited ability to evaluate for common and serious conditions of the gastrointestinal (GI) mucosa such as a bleeding peptic ulcer. Despite the fact that many bleeding lesions are self-limited, the majority of these patients require emergency hospitalization for an upper endoscopy (EGD). Our objective is to determine if ED risk stratification with Video Capsule Endoscopy (VCE) reduces need for hospitalization for low-to-moderate risk patients with suspected upper GI bleeding. A prospective multi-center randomized control trial was designed to investigate the safety of ED risk stratification with VCE. Stable ED patients with suspected upper GI bleeding were randomized to one of two treatment arms: (1) an experimental arm which included VCE risk stratification and brief ED observation versus (2) a standard of care arm which included an admission for inpatient EGD. Patients were followed for 30 days for safety outcomes. A total of 24 patients were enrolled in the study. In the experimental group, 2/11 (18.2%) patients were admitted to the hospital; and, in the standard of care group, 10/13 (76.9%) patients were admitted to the hospital (p=0.012). There was no difference in safety at day 7 and day 30 after index ED visit. ED risk stratification with VCE leads to fewer hospitalizations without an increase in adverse events.

Outcomes of Using Different Generations of Telescopic Intramedullary Nails in Lower Limbs in Management of Osteogenesis Imperfecta Patients. A Systematic Review

Abstract Background Osteogenesis imperfecta is a group of heterogeneous disorders with a common characteristic of congenital bone fragility caused by mutations in genes encoding procollagen type I. (COL1A1 and COL1A2). Objectives This study aims to review the outcomes of the use of different generations of telescopic intramedullary nails in lower limbs for management of children with osteogenesis imperfecta (OI) and evaluate the functional outcomes of them. Patients and Methods Methodology: Criteria for considering studies for this review, types of studies: we will include: case series studies, retrospective cohort studies and we will exclude: case reports, cross sectional studies, non English studies. Search results will be conducted to systematic review management software and manually screened for eligibility to be included. PRISMA flowchart will be produced based on the search results and the inclusion/ exclusion criteria. Results One of the highest complications that have been very challenging for the orthopedic surgeons is migration and displacement of the telescopic intramedullary nails and FassierDuval nail has showed to have the lowest migration and displacement incidence rate (10.3%) which was clinically significant according to our statistics which supports the previous literature. On the other hand according to our statistics we found that there is no statistical significance in the cortical perforation of the telescopic nails between the different generations despite it might have been thought before that Bailey-Dubow nail has higher cortical perforation rate as the P value = 0.413. Post operative fractures and telescopic nail bending have shown no statistical significance according to our statistics which differ from each study when taken separately with P value = 0.252 and P value = 0.059 respectively. For the bending results we think that more studies are needed to increase the number of patients as it might show statistical significance according to its P value. Conclusion Fassier-Duval telescopic nail has good outcomes with the least complication rates and a promising generation of telescopic nail but needs a multicenter randomized control trials to conduct a level I evidence based on meta-analysis.

Getting the MOST out of follow-up: a randomized controlled trial comparing 3 monthly nurse led follow-up via telehealth, including monitoring CA125 and patient reported outcomes using the MOST (Measure of Ovarian Symptoms and Treatment concerns) with routine clinic based or telehealth follow-up, after completion of first line chemotherapy in patients with epithelial ovarian cancer

BackgroundPhysical symptoms, anxiety, depression, fear of recurrence, sexual dysfunction, and social withdrawal are common in women after treatment for ovarian cancer. Most patients would like and need help dealing with...

Coaching to increase water intake in CKD 1–5: overview and detailed analysis of three clinical trials

Parallel two-group prospective multicentre randomized trial named “HYD45 — Hydration in CKD 4–5 stages” that enrolled 62 patients with CKD G4–5 was aimed at evaluating of estimated glomerular filtration rate (eGFR) with coaching to increase water intake (CIWI) with the achievement of minimally higher diuresis by 400 mL in 31 patients compared with the CKD G4–5 group without CIWI. The stated duration was 12 months, and the trial was terminated in 6 months due to a more pronounced eGFR drop in the CIWI group, namely –3.3 ml vs. 2 ml in the group without CIWI. eGFR, renal functional reserve (RFR), albumin-to-creatinine ratio, and patient’s quality of life were additionally analyzed in this trial. Finally, three randomized clinical trials were analyzed in which patients with CKD 1–2, 3, and 4–5 received hydration. The results of studies demonstrate the possible efficacy of CIWI in stage 1–2 CKD in patients with normal or increased renal functional reserve. In stage 3 CKD, CIWI showed no benefits, and in stage CKD 4–5, forced hydration resulted in greater renal function loss. Summarizing these data, the authors concluded that it is probably appropriate for healthy people to consume the amount of fluid that provides physiological diuresis of 1.2–1.8 L and urine normal osmolarity. CIWI is often excessive, forced excessive hydration may not promote a healthy lifestyle. CIWI becomes forced excess hydration as kidney function decreases. Possibly, the benefits of CIWI are lost in CKD with the progression of renal function reduction. The effect of CIWI for 12 months may be positive for stage 1 CKD and stage 2 CKD with normal functional renal reserve. CIWI is probably impractical for chronic stages 3–5 CKD. In CKD 4–5, RFR is not preserved, which probably explains the negative effect of CIWI. With CKD G1, the CIWI leads to the optimal preservation of the renal function with the increase of GFR per 1 ml/min/1.73 m2 per year in comparison with the same water intake. In CKD G2, CIWI prevents physiological and pathological loss of renal function, RFR above 50% provides restoration of eGFR in CKD G1–2. Early Coaching to Increase Water Intake in CKD (ECIWIC) trial demonstrates benefits of CIWI in patients with CKD G1–2 and preserved RFR and may be recommended to delay the CKD worsening.

PD13-04 PROSTATE CANCER SPECIFIC MORTALITY IN THE ERSPC TRIAL: WHAT IS THE ROLE OF SCREENING RESULT AND ADHERENCE

PD13-04 PROSTATE CANCER SPECIFIC MORTALITY IN THE ERSPC TRIAL: WHAT IS THE ROLE OF SCREENING RESULT AND ADHERENCE

Abstract P162: Comparison Of The Clinical Effect Of Empagliflozin On Glycemic And Non-glycemic Parameters In Japanese Patients With Type 2 Diabetes And Cardiovascular Disease Treated With Or Without Baseline Metformin

Introduction: Recent treatment guidelines for type 2 diabetes (T2D) recommend sodium-glucose cotransporter 2 (SGLT2) inhibitors to be considered preferentially in patients with T2D at high cardiovascular risk or with cardiovascular disease (CVD), regardless of their diabetes status and prior use of metformin. Hypothesis: We assessed the hypothesis that the therapeutic impact of SGLT2 inhibitors on clinical parameters differs according to the use of metformin. Methods: This was a post hoc analysis of the Effect of Empagliflozin on Endothelial Function in Cardiovascular High Risk Diabetes Mellitus: Multi-Center Placebo-Controlled Double-Blind Randomized (EMBLEM) trial. All participants (n=105; women 31.4%; mean age 64.8 years) had both T2D and DVD and were randomized to either 24 weeks of empagliflozin 10mg daily or placebo. We assessed the effect of empagliflozin on changes from baseline to 24 weeks in glycemic and non-glycemic clinical parameters, according to the baseline use of metformin. Results: Overall, 53 (50.5%) patients received baseline metformin. In the 52 patients treated with empagliflozin (48.1% with baseline metformin), the change from baseline systolic blood pressure was greater in patients receiving metformin, compared to metformin-naïve patients (group difference -8.5 [95%CI -17.7 to 0.6 mmHg], p=0.066). Reduction in body mass index was significantly greater in patients receiving baseline metformin, relative to nonusers (-0.54 [95%CI -1.07 to -0.01] kg/m 2 , p=0.047). The group ratio (baseline metformin users vs. nonusers) of proportional changes in the geometric mean of high-sensitivity Troponin-I was 0.74 (95%CI 0.59 to 0.92, p=0.009). No obvious difference was observed in glycemic parameters, such as fasting plasma glucose and HbA1c, between the baseline metformin users and nonusers. Conclusions: Our findings suggest empagliflozin has a partially different impact on clinical parameters according to whether or not metformin has been used at baseline. As clinical opportunities for prescribing SGLT2 inhibitors are likely to increase, further research is needed to investigate the effect of SGLT2 inhibitors on clinical parameters taking into account the background situation of hypoglycemic agents, such as metformin.

PD03-12 LONG-TERM DECISIONAL REGRET FOR MINORITY MEN DIAGNOSED WITH PROSTATE CANCER: RESULTS FROM A MULTI-CENTERED RANDOMIZED CLINICAL TRIAL OF DECISION AID

PD03-12 LONG-TERM DECISIONAL REGRET FOR MINORITY MEN DIAGNOSED WITH PROSTATE CANCER: RESULTS FROM A MULTI-CENTERED RANDOMIZED CLINICAL TRIAL OF DECISION AID

Editor's Choice – Cost Effectiveness of Primary Stenting in the Superficial Femoral Artery for Intermittent Claudication: Two Year Results of a Randomised Multicentre Trial

Invasive treatment of intermittent claudication (IC) is commonly performed, despite limited evidence of its cost effectiveness. IC symptoms are mainly caused by atherosclerotic lesions in the superficial femoral artery (SFA), and endovascular treatment is performed frequently. The aim of this study was to investigate its cost effectiveness vs. non-invasive treatment. One hundred patients with IC due to lesions in the SFA were randomised to treatment with primary stenting, best medical treatment (BMT) and exercise advice (stent group), or to BMT and exercise advice alone (control group). Patients were recruited at seven hospitals in Sweden. For this analysis of cost effectiveness after 24 months, 84 patients with data on quality adjusted life years (QALY; based on the EuroQol Five Dimensions EQ-5D 3L™ questionnaire) were analysed. Patient registry and imputed cost data were used for accumulated costs regarding hospitalisation and outpatient visits. The mean cost per patient was €11 060 in the stent group and €4 787 in the control group, resulting in a difference of €6 273 per patient between the groups. The difference in mean QALYs between the groups was 0.26, in favour of the stent group, which resulted in an incremental cost effectiveness ratio (ICER) of € 23 785 per QALY. The costs associated with primary stenting in the SFA for the treatment of IC were higher than for exercise advice and BMT alone. With concurrent improvement in health related quality of life, primary stenting was a cost effective treatment option according to the Swedish national guidelines (ICER < €50 000 - €70 000) and approaching the UK's National Institute for Health and Care Excellence threshold for willingness to pay (ICER < £20 000 - £30 000). From a cost effectiveness standpoint, primary stenting of the SFA can, in many countries, be used as an adjunct to exercise training advice, but it must be considered that successful implementation of structured exercise programmes and longer follow up may alter these findings.

Effects of resveratrol supplementation on bone quality: a systematic review and meta-analysis of randomized controlled trials

BackgroundThe results from clinical trials have revealed that the effects of resveratrol supplementation on bone mineral density (BMD) and bone biomarkers are inconsistent. Our objective was to determine the effects of resveratrol supplementation on BMD and serum bone biomarkers.MethodsPubMed, Cochrane library, EMBASE, Web of science and Scopus were searched up to August 24, 2020. Two reviewers independently performed the articles search and screen according to defined selection criteria. The study quality of the randomized controlled trials (RCTs) was evaluated with the Cochrane scoring system. Heterogeneity among studies was examined by Cochrane Q test. Retrieved data were pooled after mean differences (MD) were computed between two groups for BMD and serum biomarkers. Subgroup analyses were performed to evaluate a potential difference in terms of dose of resveratrol and intervention duration. Sensitivity analysis was executed by omitting studies with imputed values in order to evaluate the influence of these studies on the overall results.ResultsTen eligible studies involving 698 subjects were included in this meta-analysis with 401 participants receiving resveratrol and 297 receiving placebo. Supplementation of resveratrol had no statistically significant effects on areal bone mineral density (aBMD) at lumbar spine (MD: -0.02, 95% CI: − 0.05, 0.01, p = 0.26, I2 = 6%), total hip BMD (MD: -0.01, 95% CI: − 0.04, 0.02, p = 0.65, I2 = 0%), and whole body BMD (MD: 0.00, 95% CI: − 0.02, 0.02, p = 0.74, I2 = 0%). Supplementation of resveratrol also did not result in significant change in bone serum markers, including serum alkaline phosphatase (ALP), bone alkaline phosphatase (BAP), osteocalcin (OCN), procollagen I N-terminal propeptide (PINP), C-terminal telopeptide of type I collagen (CTX) and parathyroid hormone (PTH). Subgroup analysis showed the effect of resveratrol supplementation on BMD and serum bone markers were similar in trails of different doses, intervention duration, and pathological conditions of the participants.ConclusionResveratrol supplementation did not show any significant effect on BMD or serum bone markers with the current evidence. Further investigation with more well-organized multicentre randomized trial is warranted.

Comment on: Systemic versus oral and systemic antibiotic prophylaxis (SOAP) study in colorectal surgery: prospective randomized multicentre trial.

Comment on: Systemic versus oral and systemic antibiotic prophylaxis (SOAP) study in colorectal surgery: prospective randomized multicentre trial.

Goal-directed fluid therapy in emergency abdominal surgery: a randomised multicentre trial

BackgroundMore than 50% of patients have a major complication after emergency gastrointestinal surgery. Intravenous (i.v.) fluid therapy is a life-saving part of treatment, but evidence to guide what i.v. fluid strategy results in the best outcome is lacking. We hypothesised that goal-directed fluid therapy during surgery (GDT group) reduces the risk of major complications or death in patients undergoing major emergency gastrointestinal surgery compared with standard i.v. fluid therapy (STD group). MethodsIn a randomised, assessor-blinded, two-arm, multicentre trial, we included 312 adult patients with gastrointestinal obstruction or perforation. Patients in the GDT group received i.v. fluid to near-maximal stroke volume. Patients in the STD group received i.v. fluid following best clinical practice. Postoperative target was 0–2 L fluid balance. The primary outcome was a composite of major complications or death within 90 days. Secondary outcomes were time in intensive care, time on ventilator, time in dialysis, hospital stay, and minor complications. ResultsIn a modified intention-to-treat analysis, we found no difference in the primary outcome between groups: 45 (30%) (GDT group) vs 39 (25%) (STD group) (odds ratio=1.24; 95% confidence interval, 0.75–2.05; P=0.40). Hospital stay was longer in the GDT group: median (inter-quartile range), 7 (4–12) vs 6 days (4–8.5) (P=0.04); no other differences were found. ConclusionCompared with pressure-guided i.v. fluid therapy (STD group), flow-guided fluid therapy to near-maximal stroke volume (GDT group) did not improve the outcome after surgery for bowel obstruction or gastrointestinal perforation but may have prolonged hospital stay. Clinical trial registrationEudraCT number 2015-000563-14; the Danish Scientific Ethics Committee and the Danish Data Protection Agency (REG-18-2015).

Uncovered versus covered metallic stents for the management of unresectable malignant distal biliary obstruction: a randomized multicenter trial

Objective The treatment result of the uncovered metallic stent (uncovered MS) and covered metallic stent (covered MS) for unresectable malignant distal biliary obstruction is controversial. This time, we conducted this study to compare the efficacies and complication rates of uncovered MS and covered MS in unresectable malignant distal biliary obstructions at a prospective randomized multicenter trial. Materials and methods From April 2014 to September 2018, patients with unresectable malignant distal biliary obstruction were randomly assigned to 2 groups: the uncovered MS group and the covered MS group. Results 92 treatment results patients were discussed. 48 patients were assigned to the uncovered MS group and 44 cases were assigned to the covered MS group. Both groups showed a drainage effect. No significant difference was found in the drainage effect between the 2 groups. The number of stent occlusion was significantly greater (p = .0467) in uncovered MS (43.8%) comparing with those in covered MS (22.7%). As the cause of stent occlusion, tumor ingrowth was significantly greater (p < .001) in the uncovered MS group (35.4%) than in the covered MS group (2.3%). The median stent patency period was significantly longer (p = .0112) in the covered MS group (455 days) than that of the uncovered MS group (301 days). A significant difference in the median survival period was not found between the 2 groups. Conclusions Covered MS showed the possibility of extending the stent patency period by suppressing tumor ingrowth more than uncovered MS does. The UMIN Clinical Trial Registry number is UMIN000015093.

Long-term outcomes of primary cystocele repair by transvaginal mesh surgery versus laparoscopic mesh sacropexy: extended follow up of the PROSPERE multicentre randomised trial.

To compare the effectiveness and safety of laparoscopic sacropexy (LS) and transvaginal mesh (TVM) at 4 years. Extended follow up of a randomised trial. Eleven centres. Women with cystocele stage ≥2 (pelvic organ prolapse quantification [POP-Q], aged 45-75 years without previous prolapse surgery. Synthetic non-absorbable mesh placed in the vesicovaginal space and sutured to the promontory (LS) or maintained by arms through pelvic ligaments and/or muscles (TVM). Functional outcomes (pelvic floor distress inventory [PFDI-20] as primary outcome); anatomical assessment (POP-Q), composite outcome of success; re-interventions for complications. A total of 220 out of 262 randomised patients have been followed at 4 years. PFDI-20 significantly improved in both groups and was better (but below the minimal clinically important difference) after LS (mean difference -7.2 points; 95% CI -14.0 to -0.05; P = 0.029). The improvement in quality of life and the success rate (LS 70%, 61-81% versus TVM 71%, 62-81%; hazard ratio 0.92, 95% CI 0.55-1.54; P = 0.75) were similar. POP-Q measurements did not differ, except for point C (LS -57 mm versus TVM -48 mm, P = 0.0093). The grade III or higher complication rate was lower after LS (2%, 0-4.7%) than after TVM (8.7%, 3.4-13.7%; hazard ratio 4.6, 95% CI 1.007-21.0, P = 0.049)). Both techniques provided improvement and similar success rates. LS had a better benefit-harm balance with fewer re-interventions due to complications. TVM remains an option when LS is not feasible. At 4 years, Laparoscopic Sacropexy (LS) had a better benefit-harm balance with fewer re-interventions due to complications than Trans-Vaginal Mesh (TVM).

Surgical and Patient Outcomes of Robotic Versus Conventional Laparoscopic Hysterectomy: A Systematic Review.

Hysterectomy is a commonly performed gynecologic surgery that can be associated with significant morbidity and mortality. However, the evolution of the surgical approach, from open to minimally invasive gynecologic surgery (MIGS), has substantially improved patient outcomes by reducing perioperative complications, pain, and length of hospitalization. The evident advantages and the approval of the da Vinci Surgical System by the Food and Drug Administration led to the exponential rise in the use of MIGS. In particular, robotic hysterectomy (RH) witnessed unparalleled popularity compared to other MIGS despite the lack of strong evidence demonstrating its superiority. Therefore, we conducted a systematic review of the literature to evaluate and compare various patient and surgical outcomes of RH with conventional laparoscopic hysterectomy (CLH), including operating time, estimated blood loss, length of hospitalization, overall complications, survival, and cost. Overall, the outcomes were comparable between RH and CLH except concerning cost. RH is significantly more expensive than CLH due to the higher costs of robotic equipment, including disposable instruments, equipment maintenance, and sterilization. Although RH demonstrated comparable outcomes and higher costs, its technical advantages such as improved ergonomics, three-dimensional view, a wider range of wristed mobility, mechanical lifting of robot’s hand, and greater stability might benefit patient subsets (e.g., obesity, large uterine weights >750 g). Therefore, large and multicentered randomized control trials are imperative to determine the most effective surgical approach between RH and other MIGS for different patient subsets.

Weight management and determinants of weight change in patients with coronary artery disease

ObjectiveTo study the effects of a comprehensive secondary prevention programme on weight loss and to identify determinants of weight change in patients with coronary artery disease (CAD).MethodsWe performed a secondary...

Efficacy and safety of the GOLD FORCE multicentre randomized clinical trial: multielectrode phased radiofrequency vs. irrigated radiofrequency single-tip catheter with contact force ablation for treatment of symptomatic paroxysmal atrial fibrillation.

Pulmonary vein isolation (PVI) for atrial fibrillation (AF) has become increasingly safe and effective with the evolution of single-tip ablation catheters aided by contact force sensing (ST-CF) and single-shot devices such as the second-generation pulmonary vein ablation catheter (PVAC) Gold multi-electrode array. The multicentre randomized GOLD FORCE trial was conducted to evaluate non-inferiority of safety and efficacy of PVAC Gold PVI compared to ST-CF ablation for paroxysmal AF. The primary efficacy endpoint documented AF recurrence ≥30 s was assessed by time-to-first-event analysis after a 90-day blanking period using repeated 7-day Holters. Secondary endpoints include acute success and procedural characteristics. Safety endpoints included procedural complications, stroke/transient ischaemic attack (TIA), tamponade, bleeding, and access site complications. Two hundred and eight patients underwent randomization and PVI (103 assigned to PVAC Gold, 105 to ST-CF). Acute success rates were 95% and 97% for PVAC Gold and ST-CF, respectively. At 12 months, AF recurrence was observed in 46.6% of the PVAC Gold group and in 26.2% of the ST-CF group [absolute efficacy difference 20.4% (95% confidence interval, CI 7.5-33.2%), hazard ratio 2.05 (95% CI 1.28-3.29), P = 0.003]. PVAC Gold had significantly shorter procedure and ablation times. Complication rates were 5.7% and 4.9% for PVAC Gold and ST-CF, respectively (P = 0.782). In this multicentre randomized clinical trial, ablation with ST-CF and PVAC Gold ablation catheters non-inferiority for efficacy was not met. AF recurrence was significantly more frequent in the PVAC Gold group compared to single-tip contact force group. Both groups had similarly low rates of adverse events. PVAC Gold ablation had significantly shorter procedure and ablation times.

Medication Errors During Treatment with New Oral Anticancer Agents: Consequences for Clinical Practice Based on the AMBORA Study.

Patients treated with oral anticancer agents (e.g., kinase inhibitors) are a high-risk population for medication errors due to, for example, polymedication, age, and limited adherence. Systematic evaluations regarding frequencies and causes of medication errors and resulting harm are lacking. Our previously published multicenter randomized AMBORA trial revealed that an intensified support by clinical pharmacologists/pharmacists for patients and the treatment team considerably reduced drug-related problems and improved patient-reported outcomes. Using this database, we performed a comprehensive, additional analysis focusing on medication errors related to the patients' complete medication with consideration of the antitumor agents, concomitantly administered drugs, and herb/food intake. Two hundred two patients starting a new oral anticancer drug regardless of the tumor entity were included. Clinical pharmacologists/pharmacists performed advanced medication reviews for 12weeks. Medication errors were characterized regarding type, cause, patient harm, and the involved medicines. We detected 1.7 medication errors per patient (335/202). Of the medication errors (216/335), 64.5% occurred within the concomitant medication. Patients caused 28.4% of the medication errors. There were 67.8% detected immediately after the start of the new oral regimen, and 14.9% resulted in temporary harm. Drug-drug or drug-food interactions accounted for 24.8% of the medication errors. Patients and physicians need to be addressed in strategies for systematic reduction of medication errors during treatment with new oral antitumor drugs. Clinical decision support systems focusing on drug-drug interactions capture only a minority of the medication errors. Specialists with expertise in clinical pharmacology/pharmacy should support both the treating physicians as well as the patients for improved patient safety.

Electrolyzed hydrogen-rich water for oxidative stress suppression and improvement of insulin resistance: a multicenter prospective double-blind randomized control trial.

Electrolyzed hydrogen-rich water (EHW) is known to have suppressive effects on oxidative stress (OS). However, its benefit in type 2 diabetes mellitus (T2DM) remains unclear. This study aimed to investigate the effect of EHW on T2DM. This was a multicenter, prospective, double-blind, randomized controlled trial of 50 patients with T2DM who were assigned to the EHW or filtered water (FW) groups. The primary endpoint was changes in insulin resistance (IR) evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). OS markers such as urinary 8-hydroxy-2'-deoxyguanosine excretion (8-OHdG), plasma diacron-reactive oxygen metabolites (d-ROM), and plasma biological antioxidant potential (BAP) and other clinical data, including serum lactate concentration (lactate), were evaluated. There were no significant differences in the changes in HOMA-IR between the EHW and FW groups. However, lactate levels decreased significantly in the EHW group, and this decrease was significantly correlated with a reduction in HOMA-IR, fasting plasma glucose, and fasting plasma insulin level. Serum lactate level also significantly correlated to decreased insulin bolus secretion after 90min with glucose loading in the EHW subjects with HOMA-IR > 1.73. No EHW treatment-related adverse effects were observed. There were no significant effect of EHW in the change in HOMA-IR in this study; larger-scale and longer-term study are needed to verify the effects of EHW in T2DM patients. The online version contains supplementary material available at 10.1007/s13340-021-00524-3.

Cost-Effectiveness of Peptide Enhanced Bone Graft i-Factor versus Use of Local Autologous Bone in Anterior Cervical Discectomy and Fusion Surgery.

Study DesignWe conducted decision analytical modeling using a Markov model to determine the ICER of i-factor compared to autograft in ACDF surgery.ObjectiveThe efficacy and safety of traditional anterior cervical discectomy and fusion (ACDF) surgery has improved with the introduction of new implants and compounds. Cost-effectiveness of these innovations remains an often-overlooked aspect of this effort. To evaluate the cost-effectiveness of i-FACTOR compared to autograft for patients undergoing ACDF surgery.MethodsThe patient cohort was extracted from a prospective, multicenter randomized control trial (RCT) from twenty-two North American centers. Patients randomly received either autograft (N = 154) or i-Factor (N = 165). We analyzed various real-world scenarios, including inpatient and outpatient surgical settings as well as private versus public insurances. Two primary outcome measures were assessed: cost and utility. In the base-case analysis, both health and societal system costs were evaluated. Health-related utility outcome was expressed in quality-adjusted life years (QALYs). Cost-effectiveness was expressed as an incremental cost-effectiveness ratio (ICER).ResultsIn all scenarios, i-FACTOR reduced costs within the first year by 1.4% to 2.1%. The savings proved to be incremental over time, increasing to 3.7% over an extrapolated 10 years. The ICER at 90 days was $13,333 per QALY and became negative (“dominated”) relative to the control group within one year and onwards. In a threshold sensitivity analysis, the cost of i-FACTOR could theoretically be increased 70-fold and still remain cost-effective.ConclusionThe novel i-FACTOR is not only cost-effective compared to autograft in ACDF surgery but is the dominant economic strategy.