Pre-specified Limit Research Articles

Chewing gum to treat postoperative nausea and vomiting in female patients: a multicenter randomized trial.

Postoperative nausea and vomiting (PONV) is common after general anesthesia, with consequences for patient outcomes, satisfaction with care and healthcare costs. Our aim was to compare a new treatment, chewing gum, with a widely-used intravenous agent, ondansetron, to treat PONV in female patients in the post anesthesia care unit (PACU). We conducted a multicenter, randomized, controlled non-inferiority trial in 17 hospitals in Australia and New Zealand. Female patients aged ≥12 years undergoing volatile anesthetic-based general anesthesia for laparoscopic or breast surgery were enrolled. Protocolized anti-emetic prophylaxis was administered. Patients who developed PONV in the PACU were randomized to either 15 min of chewing gum or 4 mg of intravenous ondansetron. The primary outcome was cessation of nausea, retching or vomiting, with no recurrence nor rescue medication for 2 h after administration of the randomized intervention (i.e., complete response). Of 865 enrolled patients, 218 were randomized. In a per-protocol analysis, 50 of 105 (47.6%) ondansetron-treated patients compared with 31 of 103 (30.1%) chewing gum-treated patients achieved the primary outcome (absolute risk difference [95% confidence interval (CI)] -17.3 [-30.4 to -4.3] %), not reaching our prespecified non-inferiority limit. Time to complete response was longer for patients randomized to chewing gum (hazard ratio [95% CI] 0.53 [0.34, 0.83]), and they were more likely to receive antiemetics in the 24 h after surgery (absolute risk difference [95% CI] 14.07 [1.65, 26.49]). Chewing gum cannot be recommended as an alternative to ondansetron for treatment of PONV in female patients administered antiemetic prophylaxis.

Operative versus Nonoperative Treatment of Proximal Hamstring Avulsions

BackgroundOperative treatment is widely used for acute proximal hamstring avulsions, but its effectiveness compared with that of nonoperative treatment has not been shown in randomized trials.MethodsIn this noninferiority trial at 10 centers in Sweden and Norway, we enrolled patients 30 to 70 years of age with a proximal hamstring avulsion in a randomized trial and a parallel observational cohort. Treatments were operative reinsertion of the tendons or nonoperative management. The primary end point was the Perth Hamstring Assessment Tool (PHAT) at 2 years of follow-up. Secondary outcomes included scores on the Lower Extremity Functional Scale (LEFS).ResultsA total of 119 patients were enrolled in the randomized trial and 97 patients in the observational cohort. In the per-protocol analysis of the randomized trial, the mean (±standard deviation) PHAT scores were 79.9±19.5 and 78.5±19.4 in the operative and nonoperative groups, respectively (PHAT scores range from 0 to 100, with higher scores indicating higher function). The prespecified noninferiority limit of 10 points was not crossed (mean difference, −1.2; 95% confidence interval [CI], −8.6 to 6.2; P=0.009 for noninferiority). Analyses of secondary outcomes, including a mean difference in the LEFS score of −1.6 (95% CI, −5.2 to 2.0), aligned with the primary outcome. The observed numbers of adverse events in the randomized trial were nine in the operative group versus three in the nonoperative group (odds ratio, 0.3; 95% CI, 0.1 to 1.2). In the analysis of the observational cohort, the mean PHAT score difference between the nonoperative and operative treatment groups was −2.6 (95% CI, −9.9 to 4.6).ConclusionsIn patients 30 to 70 years of age with proximal hamstring avulsions, nonoperative treatment was noninferior to operative treatment. (Funded by Afa Försäkring and others; ClinicalTrials.gov number, NCT03311997.)

Epidural dexmedetomidine or esketamine versus fentanyl to decrease ropivacaine use for labor analgesia: A randomized non-inferiority study

BackgroundEpidural nonopioid adjuvants also reduce local anesthetic use. We aimed to test the hypothesis that, compared with the present standard fentanyl, the hourly consumption of local anesthetic was at least as good when dexmedetomidine or esketamine was combined with local anesthetic for patient-controlled epidural analgesia (PCEA). MethodsA total of 120 laboring nulliparous subjects requiring labor analgesia were recruited for the final statistical analysis. Subjects were randomized to receive 0.075 % ropivacaine added with one of three equivalent adjuvants: 0.4 μg/mL fentanyl, 0.4 μg/mL dexmedetomidine, or 1.0 mg/mL esketamine. The primary outcome was hourly ropivacaine consumption. Compared with the fentanyl group, a 20 % difference in hourly local anesthetic consumption between the dexmedetomidine and esketamine groups was considered a clinical difference (non-inferiority margin). ResultsThe hourly ropivacaine consumption of the fentanyl group was 12.4 (95 % confidence interval CI 11.2 to 13.6) ml/h, so the prespecified non-inferiority limit was 2.5 ml/h. The hourly ropivacaine consumption of the fentanyl group was not inferior to that of the dexmedetomidine group (12.4 ml/h vs. 11.9 ml/h, risk difference, 0.5; 95 % confidence interval CI, −1.0 to 2.0, meeting criteria for non-inferiority). However, the hourly ropivacaine consumption of the esketamine group was 14.3 ml/h, and that of the fentanyl group was 12.4 ml/h (risk difference, 1.9, 95 % CI, 0.2 to 3.6), failing to confirm non-inferiority with a non-inferiority margin of 20 %. The incidence of pruritus was highest in the fentanyl group, whereas the occurrence of mild dizziness was highest in the esketamine group. ConclusionsIn setting of the conditions of this study, epidural dexmedetomidine was non-inferior compared with epidural fentanyl in combination with ropivacaine for PCEA during labor. Meanwhile, we failed to establish the non-inferiority of epidural esketamine compared with epidural fentanyl in combination with ropivacaine for labor analgesia.

Non-inferiority trials

Superiority trials are designed to test the hypothesis that a given diagnostic or therapeutic strategy is better than (i.e. "superior to") placebo or an active control. Conversely, non-inferiority trials test the hypothesis that a newer (i.e. alternative) strategy is not "unacceptably worse" than a control (i.e. "traditional", or "older") strategy. Non-inferiority trials are increasingly conducted in clinical medicine more often when a "newer" strategy is supposed to offer a relevant advantage in terms other than clinical efficacy (i.e. better tolerability, less cost, simpler regimen, etc.) versus a "gold standard" traditional strategy. The principle underlying non-inferiority trials is that the above advantage justifies the preferential use of the newer strategy in the clinical practice even if the clinical efficacy of the "new" appears to be a bit worse than that of the "old", albeit not unacceptably worse (i.e. not beyond a pre-specified value). The demonstration of non-inferiority requires that the confidence interval of the point estimate (e.g. the hazard ratio) does not cross a pre-specified limit. The definition of such pre-specified limit, the so called "non-inferiority margin", is a pivotal point when planning non-inferiority trials. It denotes the maximally tolerated worse effect of the alternative strategy, compared with the traditional one, required to conclude that an alternative strategy is non-inferior to the traditional "gold standard". The non-inferiority margin is derived from previous trials evaluating the efficacy of the traditional strategy vs placebo. We reviewed the principles and the practical aspects in the design and conduct of non-inferiority trials.

On optimal reinsurance in the presence of premium budget constraint and reinsurer’s risk limit

Abstract In this paper, we propose two new optimal reinsurance models in which both premium budget constraints and the reinsurer’s risk limits are taken into account. To be precise, we assume that the reinsurance premium has an upper bound, and that the admissible ceded loss functions have a pre-specified upper limit. Moreover, we assume that the reinsurance premium principle is calculated by the expected value premium principle. Under the optimality criteria of minimizing the value at risk and conditional value at risk of the insurer’s total risk exposure, we derive the explicit optimal reinsurance treaties, which are layer reinsurance treaties. A new approach is developed to construct the optimal reinsurance treaties. Comparisons with existing studies are also made. Finally, we provide a numerical study based on real data and an example to illustrate the proposed models and results. Our work provides a novel generalization of several known achievements in the literature.

Optimal Consolidation of Polling Locations

Problem definition: Many logistical and financial challenges of facilitating an election lead election officials to consolidate polling locations. However, determining when it is appropriate to consolidate polling locations and how to consolidate polling locations, if necessary, is a difficult and high-stakes decision that influences voter participation. Methodology/results: We formalize the set of constraints and criteria that election officials should follow as the polling location consolidation problem (PLCP), which is formulated as an integer programming model. The PLCP simultaneously selects which polling locations will be used in the upcoming election, reassigns voter precincts to polling locations, and allocates critical resources to the selected polling locations. The PLCP minimizes the increased distance that voters must travel to their updated polling location. Because empirical research also demonstrates the importance of reducing the voters’ wait times, we require that most voters do not wait longer than a prespecified limit, such as 30 minutes, using a chance constraint. We prove that identifying a feasible solution to PLCP is NP-complete, which demonstrates the difficulty in making consolidation decisions, as well as the importance of optimization for this problem. Managerial implications: This paper introduces a structured and transparent approach to support election officials in making informed, data-driven decisions regarding how and when to consolidate polling locations that minimally impact voters and encourage voter participation. The approach could be used to develop preapproved contingency plans that could be employed if there are major disruptions to an election. Supplemental Material: The online supplement is available at https://doi.org/10.1287/msom.2022.0497 .

A cost-effectiveness analysis of the combination of serplulimab with chemotherapy for advanced esophageal squamous cell carcinoma: insights from the ASTRUM-007 trial

BackgroundCombined serplulimab and chemotherapy demonstrated improved clinical survival outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) and PD-L1 combined positive scores (CPS) ≥ 1. The present study aimed to evaluate the economic viability of integrating serplulimab in combination with chemotherapy as a potential therapeutic approach for treating ESCC in China.MethodsA Markov model was constructed to evaluate the economic and health-related implications of combining serplulimab with chemotherapy. With the incremental cost-effectiveness ratio (ICER), costs and results in terms of health were estimated. For assessing parameter uncertainty, one-way and probabilistic sensitivity studies were carried out.ResultsThe combination of serplulimab and chemotherapy yielded incremental costs and QALYs of $3,163 and 0.14, $2,418 and 0.10, and $3,849 and 0.15, respectively, for the overall population as well as patients with PD-L1 CPS1-10 and PD-L1 CPS ≥ 10. This corresponds to ICER values per QALY of $23,657, $23,982, and $25,134. At the prespecified WTP limit, the probabilities of serplulimab with chemotherapy being the preferred intervention option were 74.4%, 61.3%, and 78.1% for the entire patient population, those with PD-L1 1 ≤ CPS < 10, and those with PD-L1 CPS ≥ 10, respectively. The stability of the presented model was confirmed through sensitivity studies.ConclusionsIn conclusion, the combination of Serplulimab and chemotherapy showed excellent cost-effectiveness compared to chemotherapy alone in treating PD-L1-positive patients with ESCC in China.

Optimal scheduling of BESS for congestion management considering reliability and OTS

The present research explores transmission congestion control in Battery based Energy Storage Systems (BESS) integrated grids using Optimal Transmission Switching (OTS). The oversimplification of underlying assumptions in prior OTS-based congestion management strategies leads to excessive line switching which is undesirable. Hence, a novel reliability constrained alternating current optimal power flow (AC-OPF) based OTS is presented to mitigate the line congestion in the BESS integrated grids. The suggested approach is solved to acquire the OTS solution for 24 h time frame with the primary goal of minimising generating costs subjected to ac power flow equality, BESS, reliability, and transmission congestion constraints. The proposed approach makes use of the integer variable to represent the transmission switching operations and is solved by using a mixed-integer non-linear programming (MINLP) solver. The inclusion of reliability constraints ensures the system reliability by limiting the value of load failure probability to a pre-specified limit. The feasibility of this approach is validated by testing it on a standard IEEE test system for various loading scenarios. The results exhibit that coordinated charging/discharging of BESS supports reducing the number of lines switchings required for congestion management compared to the existing approaches, substantially.

Process synthesis considering sustainability for both normal and non-normal operations: P-graph approach

Process synthesis usually determines the normal operation of the process. In addition to the cost, recently, sustainability has also become essential in selecting the process. In case of failures of some redundant operating units of the process, it may still be operational as a non-normal operation. This work shows that the sustainability performance of a process in non-normal operation can be much worse than that of the normal case.Consequently, during process synthesis, it is essential to consider the sustainability of a process for both normal and non-normal operations. The current work is the first in offering synthesis of a process network taking into account a pre-specified limit of the process sustainability indicator for both normal and non-normal modes. This synthesis procedure is formulated in a general way, to interface with any sustainability indicator, expressed as a scalar, here Sustainable Process Index has been used in the case studies. The presented method is illustrated on two case studies to showcase the capability of synthesizing processes for multiple operation. The obtained results indicate that it is possible to simultaneously reduce environmental impact and process cost by more than 20%, by appropriate modification of the operating modes.

Pafolacianine for intraoperative molecular imaging of cancer in the lung: The ELUCIDATE trial

ObjectiveThe study objective was to determine the clinical utility of pafolacianine, a folate receptor–targeted fluorescent agent, in revealing by intraoperative molecular imaging folate receptor α positive cancers in the lung and narrow surgical margins that may otherwise be undetected with conventional visualization. MethodsIn this Phase 3, 12-center trial, 112 patients with suspected or biopsy-confirmed cancer in the lung scheduled for sublobar pulmonary resection were administered intravenous pafolacianine within 24 hours before surgery. Participants were randomly assigned to surgery with or without intraoperative molecular imaging (10:1 ratio). The primary end point was the proportion of participants with a clinically significant event, reflecting a meaningful change in the surgical operation. ResultsNo drug-related serious adverse events occurred. One or more clinically significant event occurred in 53% of evaluated participants compared with a prespecified limit of 10% (P < .0001). In 38 participants, at least 1 event was a margin 10 mm or less from the resected primary nodule (38%, 95% confidence interval, 28.5-48.3), 32 being confirmed by histopathology. In 19 subjects (19%, 95% confidence interval, 11.8-28.1), intraoperative molecular imaging located the primary nodule that the surgeon could not locate with white light and palpation. Intraoperative molecular imaging revealed 10 occult synchronous malignant lesions in 8 subjects (8%, 95% confidence interval, 3.5-15.2) undetected using white light. Most (73%) intraoperative molecular imaging–discovered synchronous malignant lesions were outside the planned resection field. A change in the overall scope of surgical procedure occurred for 29 of the subjects (22 increase, 7 decrease). ConclusionsIntraoperative molecular imaging with pafolacianine improves surgical outcomes by identifying occult tumors and close surgical margins.

An integrated inventory and distribution planning problem for the blood products: An application for the Turkish Red Crescent

This study considers an integrated inventory planning and distribution problem based on an applied case at the Turkish Red Crescent’s Central Anatolian Regional Blood Center. We define two echelons, the first echelon being the regional blood center and the second echelon being the districts. The blood products are perishable so that the outdated products are disposed of at the end of their lives. We aim to minimize the cost of inventory keeping at both echelons, the shortage, and disposal amounts at the second echelon. We consider two distribution strategies: all deliveries are realized by the regional blood center (current implementation), and the deliveries are directly from the regional blood center or the other districts. We develop a mixed-integer linear programming model for each strategy. Our experimental results show that the decentralized strategy brings significant cost reductions over the centralized strategy. The mathematical model for the centralized distribution strategy can handle large-sized instances. On the other hand, the model for the decentralized distribution strategy is more complex and could not handle large-sized instances in our pre-specified termination limit of two hours. For large-sized instances of the decentralized distribution strategy, we design a decomposition-based heuristic algorithm that benefits from the optimal solutions of the original model and finds near-optimal solutions very quickly.

A Multicenter Randomized Trial Evaluating Fast-Acting Insulin Aspart in the Bionic Pancreas in Adults with Type 1 Diabetes.

Objective: To evaluate the insulin-only configuration of the iLet® bionic pancreas (BP) using fast-acting insulin aspart (Fiasp®) in adults with type 1 diabetes (T1D). Research Design and Methods: In this multicenter, randomized trial, 275 adults with T1D (18-83 years old, baseline HbA1c 5.3%-14.9%) were randomly assigned 2:2:1 to use the BP with fast-acting insulin aspart (BP-F group, N = 114), BP with aspart or lispro (BP-A/L group, N = 107), or a control group using their standard-care insulin delivery (SC group, N = 54) plus real-time continuous glucose monitoring (CGM). The primary outcome was HbA1c at 13 weeks. The BP-F versus SC comparison was considered primary and BP-F versus BP-A/L secondary. Results: Mean ± standard deviation (SD) HbA1c decreased from 7.8% ± 1.2% at baseline to 7.1% ± 0.6% at 13 weeks with BP-F versus 7.6% ± 1.2% to 7.5% ± 0.9% with SC (adjusted difference = -0.5%, 95% CI -0.7 to -0.3, P < 0.001). CGM-measured percent time <54 mg/dL over 13 weeks with BP-F was noninferior to SC (adjusted difference = 0.00%, 95% CI -0.07 to 0.05, P < 0.001 for noninferiority based on a prespecified noninferiority limit of 1%). Over 13 weeks, mean time in range 70-180 mg/dL (TIR) increased by 14% (3.4 h/day) and mean CGM glucose was reduced by 18 mg/dL with BP-F compared with SC (P < 0.001). Analyses of time >180 mg/dL, time >250 mg/dL, and the SD of CGM glucose all favored BP-F compared with SC (P < 0.001). Differences between BP-F and BP-A/L were minimal, with no difference in HbA1c at 13 weeks (adjusted difference = -0.0%, 95% CI -0.2 to 0.1, P = 0.67) or mean glucose (adjusted difference = -2.0 mg/dL, 95% CI -4.3 to 0.4, P = 0.10). Mean TIR was 2% greater with BP-F than BP-A/L (95% CI 1 to 4, P = 0.005), but the percentages of participants improving TIR by ≥5% were not significantly different (P = 0.49) and there were no significant differences comparing BP-F versus BP-A/L across nine patient-reported outcome surveys. The rate of severe hypoglycemia events did not differ among the three groups. Conclusions: In adults with T1D, HbA1c was improved with the BP using fast-acting insulin aspart compared with standard care without increasing CGM-measured hypoglycemia. However, the effect was no better than the reduction observed with the BP using aspart or lispro. Clinical Trial Registry: clinicaltrials.gov; NCT04200313.

Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes

BackgroundCurrently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting.MethodsIn this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed.ResultsA total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, −0.5 percentage points; 95% confidence interval [CI], −0.6 to −0.3; P<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, −0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P=0.39). No episodes of diabetic ketoacidosis occurred in either group.ConclusionsIn this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.)

A Randomized, Controlled Trial of Treat-and-Extend vs. Pro Re Nata Regimen for Neovascular Age-Related Macular Degeneration.

PurposeTo compare the efficacy and safety of conbercept using a treat-and-extend (T&E) regimen vs. a pro re nata (PRN) regimen in Chinese patients with neovascular age-related macular degeneration (nAMD).MethodsThis was a randomized, multicenter, non-inferiority study. After an initial loading phase of three consecutive monthly intravitreal injections of 0.5 mg Conbercept, the patients were treated to PRN or T&E regimen. The prespecified retreatment criteria was defined as a more than 5-letter decrease in BCVA from the previous visit or any evidence of new retinal hemorrhages, or the presence of any IRF and any SRF of more than 200 μm in height at the sub-foveal center. The primary outcome was the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months, with a prespecified non-inferiority limit of −5 letters.ResultsFrom July 2016 through August 2018, 141 participants were allocated and treated (T&E, n = 69; PRN, n = 72). About one fifth of the overall participants were dropped out during the 12-month follow-up (28/141, 19.9%), and about one thirds of the overall participants were lost during the 24-month follow-up (51/141, 36%). At 2 years, mean BCVA letter improvement was + 4.0 in the T&E group vs. + 5.1 in the PRN group, and T&E regimen was not non-inferior to PRN regimen [difference, −1.169 letters; 95% confidence interval (CI): −6.864 ∼ 4.526]. Subgroup analyses also demonstrate the similar results in PCV patients, naive patients and no-naive patients. The mean decrease in central subfield thickness were 180 ± 165 μm in the T&E group and 247 ± 230 μm in the PRN group, respectively. The patients in the PRN group had required significantly fewer injections than those in the T&E group (12.4 vs. 14.6 injections, P = 0.041). The types and rates of adverse events were comparable in the two treatment groups.ConclusionThese findings suggest that the T&E regimen was not non-inferior to the PRN regimen in patients with nAMD in terms of BCVA outcomes through 24 months.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02802657.

Effect of models uncertainties on the emission constrained economic dispatch. A prediction interval-based approach

Although electricity is a clean and relatively safe form of energy when it is used, the generation and transmission of electricity have severe effects on the environment. An alternative to diminish the polluting emissions released by the generating units is the Emission Constrained Economic Dispatch (ECED). This is an optimization problem where the total fuel cost is minimized while treating emissions as a constraint with a pre-specified limit. Usually, the fuel cost and emission functions of the generating units must be experimentally derived, introducing then uncertainties in the obtained models. However, these uncertainties are often neglected and the ECED problem is solved considering the coefficients of the functions involved as exact (totally known) values. In this investigation we analyzed the effect of the uncertainties associated to the experimental derivation of the input–output curves of thermal power plants. Particularly, when polynomial models are fitted through multiple linear regression, we proposed an approach that, based on the respectively prediction intervals, can provide solutions immunized, in some sense, against variability in the coefficients estimates. We tested the proposed approach in a real system from the Chilean electrical power network. For the analyzed system we noted that, when uncertainties are not considered, the deterministic optimal solutions can be environmentally infeasible in some scenarios; whereas solutions obtained through the proposed approach, can significantly diminish the risk of environmental violations. The robustness of the prediction interval-based solutions was obtained with a negligible increase of the total fuel cost in all the cases studied.

Optimal maintenance policy for equipment leased with base and extended warranty

ABSTRACT In this paper, we consider an equipment leased with a warranty contract with the possibility to extend the warranty at a given price that depends on its duration. During the warranty period, the lessor (who possesses the equipment) performs and pays for repairs at failure and for preventive maintenance (PM) actions whenever the equipment reliability reaches a specific limit. After the warranty ends, repairs and PM actions are still performed by the lessor, but they are billed to the lessee (who rents the equipment). Furthermore, in case the total average equipment downtime due to repair and PM actions during the lease period surpasses a certain pre-specified limit agreed on in the lease contract, a penalty is supported by the lessor. A mathematical model and numerical procedure are proposed to determine the PM intervals durations that maximise the lessor’s expected total profit during the lease period. The optimal solution is obtained by determining the combination between the optimal equipment reliability threshold that triggers a PM action and the optimal extended warranty period. A numerical example is given to illustrate the use of the proposed model and a sensitivity analysis is performed.

A randomized controlled clinical trial comparing different numbers of acupuncture sessions for migraine.

Acupuncture has shown benefit in preventing migraine attacks, but there has been no clear recommendation about the number of treatment sessions that should be provided. The aim of this study was to examine whether 5 sessions of acupuncture treatment is non-inferior to 10 sessions for migraine. We performed a multicenter, open-label, randomized, controlled clinical trial across five hospitals in Thailand. Migraine patients were randomly assigned into two groups: treatment with 5 sessions of acupuncture (group A) or 10 sessions of acupuncture (group B). Acupuncture was performed twice a week. We measured the number of migraine days, average pain severity according to a 0-10 numeric pain rating scale (NPRS) and quality of life using the EQ-5D-5L questionnaire, comparing 4 weeks after treatment versus baseline. Of 156 patients, 83 and 73 patients were assigned to groups A and B, respectively. Comparing 4 weeks after treatment with baseline, the mean reduction in the number of headache days in groups A and B was 6.4 (95% confidence interval [CI] 4.8 to 7.9) days and 6.4 (95% CI 4.5 to 8.4) days, respectively (p = 0.97). The mean difference between the reduction in headache days of the two groups was -0.1 (95% CI -2.5 to 2.4) days, which included the pre-specified non-inferiority limit of -1. The mean reduction of NPRS scores in groups A and B was 4.5 (95% CI 3.8 to 5.1) and 3.8 (95% CI 3.1 to 4.5), respectively (p = 0.17). Both groups showed an improvement in quality of life. Both 5 and 10 sessions of acupuncture were associated with apparent benefits in terms of preventing migraine attacks, reducing the severity of the headache and improving quality of life, based on comparisons between baseline and follow-up in both study groups. Although we were unable to demonstrate non-inferiority of 5 sessions versus 10 sessions of acupuncture, the effects in the two groups were not significantly different and the temporal effects appeared to last for at least 1 month. TCTR20170612002 (Thai Clinical Trials Registry).

Markov process approach for analyzing periodically inspected competing-risk system embodying downtime threshold

ABSTRACT Substantially, most repairable systems undergo ignored failure, i.e. if any failure is repaired quickly then it will not be affecting systems availability. The availability and cost for a periodically examined competing-risk system is studied embedding the downtime threshold concept. If the systems downtime is not more than a pre-specified limit, the system could be considered functional during that downtime period, i.e. the breakdown could be neglected. Contrarily, if the downtime extends that limit, the system is deemed to be functional from outset of failure till the downtime exceeding the preset limit, i.e. the breakdown is deferred. Moreover, the system is presumed to have a functional state and M modes of failure. The point and limiting availabilities are being analyzed for the aforementioned system employing the Markov process approach. Additionally, long-run average cost expression is also acquired for the proposed model. An example of a protection device is then utilized to demonstrate the drafted procedure.

Aqueous chlorhexidine 1% versus 2% for neonatal skin antisepsis: a randomised non-inferiority trial

ObjectiveTo evaluate whether 1% aqueous chlorhexidine gluconate (CHG) when compared with 2% aqueous chlorhexidine gluconate is non-inferior for neonatal skin antisepsis.DesignParallel, blinded, non-inferiority randomised trial.SettingLevel III, academic, neonatal intensive care...

Preemptive intravenous iron therapy versus autologous whole blood therapy for early postoperative hemoglobin level in patients undergoing bimaxillary orthognathic surgery: a prospective randomized noninferiority trial

BackgroundPrevious studies have reported the efficacy and safety of intravenous (IV) iron therapy during the perioperative period as an alternative and adjunct to allogeneic blood transfusion. Preemptive IV iron therapy provides noninferior hemoglobin levels on postoperative day (POD) 1 compared to autologous whole blood therapy (AWBT) in healthy patients who had undergone bimaxillary orthognathic surgery.MethodsThis was a prospective, patient-randomized, noninferiority trial. After excluding 2 patients, 64 patients were divided into two groups: the IV iron therapy group (patients received IV iron infusion 4 weeks before surgery; n = 32) and the AWBT group (2 units of autologous whole blood were collected 4 and 2 weeks before surgery; n = 32). The primary outcome was hemoglobin level on POD 1 and the prespecified noninferiority limit was − 1 g/dL.ResultsBaseline data were comparable, including hemoglobin and iron levels, between the two groups. Immediately before surgery, the levels of hemoglobin, iron, and ferritin were higher in the IV iron group than in the AWBT group. The mean treatment difference (iron group—whole blood group) in hemoglobin level on POD 1 between the two groups was 0.09 (95% CI = − 0.83 to 1.0). As the lower limit of the 95% CI (− 0.83) was higher than the prespecified noninferiority margin (δ = − 1), noninferiority was established. On POD 2, the hemoglobin level became lower in the iron group, which eventually led to greater requirement of allogeneic blood transfusion compared to the whole blood group. However, the iron group did not require allogeneic blood transfusion during or early after surgery, and the whole blood group showed continuously higher incidence of overt iron deficiency compared to the iron group.ConclusionAs collection of autologous whole blood caused overt iron loss and anemia before surgery and intraoperative transfusion of whole blood was not able to prevent the occurrence of persistent iron deficiency after surgery, IV iron therapy was found to have potential benefits for iron homeostasis and subsequent erythropoiesis in healthy patients early after bimaxillary orthognathic surgery.Trial registration: Clinical Research Information Service, Republic of Korea, approval number: KCT0003680 on March 27, 2019. https://cris.nih.go.kr/cris/search/search_result_st01_kren.jsp?seq=15769&sLeft=2<ype=my&rtype=my.