Relative Efficacy Research Articles

The cancer premium - explaining differences in prices for cancer vs non-cancer drugs with efficacy and epidemiological endpoints in the US, Germany, and Switzerland: a cross sectional study.

High treatment prices of new cancer drugs are a global public health challenge to patients and healthcare systems. Policymakers in the US and Europe are debating reforms to drug pricing. The objective of this study was to assess whether drug efficacy or epidemiological characteristics (prevalence, incidence, mortality) explain the gap in treatment prices between cancer and non-cancer drugs in the US, Germany, and Switzerland. This cross-sectional study identified all new drugs approved in the US, Germany, and Switzerland between 2011 and 2020. Drug efficacy was extracted from pivotal trials, drug prices from public and commercial databases, and epidemiological characteristics from the Global Burden of Disease (GBD) 2019 study. We used regression models to explain drug prices with drug efficacy and epidemiological characteristics (prevalence, incidence, mortality). The cohort included 181 drugs, including 68 (37.5%) drugs approved for treatment of cancer. A significant negative correlation was found between incidence/prevalence and treatment prices, and a significant positive correlation was observed between mortality and treatment prices for both, cancer and non-cancer drugs. A significant association between relative drug efficacy and treatment prices of drugs was observed, however, less pronounced for cancer drugs. Our regression estimates indicated that after adjusting for efficacy and epidemiological characteristics, cancer drugs were on average approximately three times more expensive compared to non-cancer drugs in all three countries, indicating a cancer premium; i.e., treatment prices of cancer drugs were on average USD 74,412 (95% CI [62,810; 86,015]) more expensive in the US compared to non-cancer drugs, USD 37,770 (95% CI [26,175; 49,367]) more expensive in Germany, and USD 32,801 (95% CI [27,048; 38,555]) more expensive in Switzerland. Our model explained 72% of the variance in observed prices (R2). Drug pricing reforms should target the cancer premium to improve access of patients to cancer drugs as well as to achieve equity across the different therapeutic areas and sustainability in the health care systems. This study was funded by the Swiss National Science Foundation (SNSF, grant number PCEGP1_194607) and the Swiss Cancer Research Foundation (Krebsforschung Schweiz).

Impact of personalized alcohol intake and cognitive feedback on alcohol use behavior in hazardous drinkers: A quasi-randomized trial.

Worldwide, alcohol use is a major contributor to the burden of disease and mortality. A sizeable literature suggests that brief web-based interventions that incorporate personalized normative and/or health consequences feedback are effective at reducing alcohol intake. The relative efficacy of an intervention that also includes individualized feedback about brain health has not been examined, nor has the utility of integrating a smartphone app component. Participants (N = 436, Mage = 21.27) completed baseline protocols (n = 178 recorded alcohol use via an app for 14 days) and were then assigned to one of three feedback conditions using randomized block allocation with stratification based on the total number of standard drinks consumed. Control participants received no feedback; Alcohol Intake Feedback (Alc) participants received personalized information about their alcohol use; Alcohol Intake plus Cognitive Feedback (AlcCog) participants received personalized details about alcohol use plus individualized brain-health information related to impulsivity. The impact of feedback on alcohol consumption behavior was examined as a function of feedback condition and hazardous/non-harmful drinking status (as defined by the World Health Organization) at an 8-week follow-up. Hazardous drinkers in both the Alc and AlcCog conditions reduced their alcohol intake by 31% to 50% more than those in the Control condition. Reductions were not related to whether participants completed web- plus app-based components or web-only components of the intervention. There was no change in the alcohol intake of non-harmful drinkers. This proof-of-concept study showed that hazardous drinkers respond well to brief electronic interventions that incorporate personalized normative and/or health consequences feedback. Further research is required to determine how best to make impulsivity-related brain-health consequences of drinking manifest and how to maximize the potential of smartphones apps.

Milrinone vs Dobutamine for the Management of Cardiogenic Shock: Implications of Renal Function and Injury

BackgroundCardiogenic shock is associated with poor clinical outcomes. There is a paucity of prospective data examining the efficacy and safety of inotropic therapy in patients with cardiogenic shock and renal dysfunction. ObjectivesThis study sought to examine the treatment effect of milrinone compared to dobutamine in relation to renal function. MethodsIn this post hoc analysis of the DOREMI (Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock) trial, we examined clinical outcomes with milrinone compared to dobutamine after stratification based on baseline estimated glomerular filtration rate (eGFR) 60 ml/min/1.73 m2 and acute kidney injury (AKI). The primary outcome was the composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. ResultsBaseline eGFR <60 ml/min/1.73 m2 and AKI were observed in 78 (45%) and 124 (65%) of patients, respectively. The primary outcome and death from any cause occurred in 99 (52%) and 76 (40%) patients, respectively. eGFR <60 ml/min/1.73 m2 did not appear to modulate the treatment effect of milrinone compared to dobutamine. In contrast, there was a significant interaction between the treatment effect of milrinone compared to dobutamine and AKI with respect to the primary outcome (P interaction = 0.02) and death (P interaction = 0.04). The interaction was characterized by lower risk of primary outcome and death with milrinone compared to dobutamine in patients without, but not with, AKI. ConclusionsIn patients requiring inotropic support for cardiogenic shock, baseline renal dysfunction and AKI are common. A modulating effect of AKI on the relative efficacy of milrinone compared to dobutamine was observed, characterized by attenuation of a potential clinical benefit with milrinone compared to dobutamine in patients who develop AKI.

To compare the functional and radiological outcome between external fixation and volar plating for the treatment of intraarticular distal end radius fractures

Background: Fracture of distal radius may be stable that is extra-articular, non-comminuted without distal radio ulnar joint disruption or unstable that is intra-articular, comminuted displaced with distal radio ulnar joint disruption. Complications of unstable fractures are shortening due to bone loss or due to resorption of the cancellous bone from metaphysis, resistant deformity, residual pain, late collapse, radio carpal arthritis and gross functional impairment. Aims and Objective: The purpose of this study to compare the relative efficacy of external fixation versus plating with regard to functional and radiological outcome. Materials and Methods: Total of 60 patients having intraarticular distal end radius fracture were included in this study and was equally divided into two groups, one group treated by external fixator other group with volar locking compression plate with or without augmentation by k-wire. Follow-up was done after 2 weeks, 4 weeks, 6 weeks and 3 ,6 and 12 months. The radiological evaluation was performed with Sarmiento’s Modification of Lindstrom’s Criteria. With the Modified Mayo Wrist Score, the patient’s functional outcomes were assessed and both groups were compared. Results: In this study we found that volar plate group had good to excellent outcome in 73% cases and 07% with fair outcome however with external fixator group found good to excellent in 50% cases and poor in 17% cases. Conclusion: In our study, we showed that the use of an external fixator and a volar locking plate for the treatment of intraarticular distal radial fractures were reliable. The relative simplicity of use, low surgical exposure, and decreased surgical trauma are benefits of external fixation. Despite these volar locking plates augmented with or without k wire had a good to excellent results in terms of early rehabilitation and less complications related to wrist joint. External fixator with ligamentotaxis provide significant good results in communited intraarticular distal end radius fracture.

Evaluation of the performance of F-layer peak height models used in IRI-2016 over the Indian equatorial and low latitudes

The performance of different height models (BSE-1979, AMTB-2013, and SHU-2015) in the International Reference Ionosphere (IRI-2016) is evaluated over the Indian equatorial and low latitude sectors. The impact of deviations in the modelled hmF2 on the estimation of electron density profiles and the Total Electron Content (TEC) is examined using the three different hmF2 methods in IRI-2016. For this study digisonde observations over Trivandrum (8.5 °N, 76.9 °E) and Ahmedabad (23.0 °N, 72.5 °E) along with GPS observations over Colombo (6.8 °N, 79.8 °E) and Ahmedabad during a high solar activity year 2014 are considered. A comparison of electron density profiles between digisonde and IRI-2016 at both the equatorial station, Trivandrum, and the low latitude station, Ahmedabad, revealed significant deviations with higher deviations in the post sunset hours at the equator. The three height methods have shown significant differences in their predictions of hmF2 at both locations. At the equator, the SHU-2015 method shows better estimates closer to the measurement values, than the other two methods except at Pre-Reversal Enhancement (PRE) time, during which, the AMTB-2013 method shows better performance. At the low latitude station, the newly added methods (SHU-2015 and AMTB-2013) do not indicate any improvements in estimating the hmF2. The availability of three different height methods in IRI-2016 is exploited to understand the modifications if any, in the ionospheric height structure and TEC for different hmF2 methods and the corresponding results are presented. As the variations in hmF2 are used to derive vertical drift on many occasions in the absence of incoherent scatter radar, this study is significant in assessing the relative efficacy of the three height models and hence useful to understand various ionospheric processes over the low/equatorial latitudes.

청소년의 스마트폰중독과 폭력비행의 관계에서 여러 가설들의 검증: 패널자료의 분석

This study examines the relationship between smartphone addiction and online and offline violent delinquency, adds relationships with parents, teachers, and peers, and intends to test four hypotheses for relationships among three variables. There are four hypotheses; first, strain-inducing hypothesis that smartphone addiction has negative influences on relationships with parents, teachers, and peers, which in turn affect both online and offline violent delinquency, second, strain reducing or spurious relationship hypothesis that relationships with parents, teachers, and peers explain both smartphone addiction and violent delinquency and the relationship between smartphone addiction and violent delinquency is spurious, third, opportunity hypothesis that the effects of relationships with parents, teachers, and friends on violent delinquency are mediated by smartphone addiction, and fourth, condition hypothesis that expects the interaction effect between smartphone addiction and relationships with parents, teachers, and peers on violent delinquency. This study tests relative efficacy among four hypotheses by using data from a panel study. Results show that smartphone addiction has effects on both relationships with parents and teachers, but it has not indirect but direct effect on both online and offline violent delinquency, which does not support strain-inducing hypothesis. Instead, relationships with parents and teachers have indirect effects on online violent delinquency through smartphone addiction, which supports opportunity hypothesis, but it is also shown that they have also indirect effects on offline violent delinquency and relationships with teachers and peers have direct effects on online violent delinquency. Results also do not support spurious hypothesis, and it is also shown that condition hypothesis is not supported. Overall, the effect of smartphone addiction is significant on both online and offline violent delinquency.

The multi-sensor-based measurement of machining signals and data fusion to develop predictive tool wear models for TiAlN-PVD coated carbide inserts during end milling of Inconel 617

Machining signals from the Force dynamometer, Acoustic Emission (AE), and Accelerometer are acquired and fused to develop Machine Learning (ML) models for tool wear monitoring of TiAlN-PVD coated carbide inserts. Milling experiments were performed on Inconel 617 with varied process parameter combinations until the tool flank wear met the failure criterion. Support Vector Regression, Random Forest Regression, and Long Short-Term Memory models are developed and compared based on a combination of sensor data fusion for tool wear predictions. It is observed that the Random Forest Regression approach can predict the tool wear with 94% accuracy compared to Support Vector Regression (85%) and Long Short-Term Memory (84%) models while using three-sensor data fusion. Further, the two-sensor data combination was used to test the relative efficacy of all the three developed machine learning tool wear models and found that the force dynamometer and the AE sensor fared better for Random Forest Regression and Long Short-Term Memory models in comparison to Support Vector Regression. For Support Vector Regression-based tool wear predictive models, force dynamometer and accelerometer data fusion performed better.

Parent Versus Individual Cognitive Behavioral Therapy for Youth Anxiety: Protocol for an Overview of Systematic Reviews Over Time

Background Cognitive behavioral therapy (CBT) has shown to be highly effective for treating youth anxiety; yet, there is ongoing debate as to whether involving parents improves outcomes. For example, parents who attend may learn CBT skills to help their child in an ongoing way; yet, they could also distract their child from treatment depending on how they interact. As evidence has accumulated, reviews and meta-analyses have attempted to examine the most effective treatment format. These reviews often have high impact in the field; however, they use varied methodologies and draw on different primary studies. Different formats of CBT for youth anxiety have been developed in relation to parental involvement, including youth-only CBT (Y-CBT; where the youth alone attends treatment), youth and parent or family CBT (F-CBT; where youths and their parents attend together), and, most recently, parent-only CBT (P-CBT; where the parent alone attends). Objective This protocol describes an overview of systematic reviews comparing the relative efficacy of different formats of CBT for youth anxiety (Y-CBT, F-CBT, and P-CBT) over the study period. The protocol will also examine the moderating effects of variables on the efficacy of different formats; for example, youths’ age and long-term outcomes. Methods We will analyze the results of systematic reviews that compare different levels and types of parental involvement in CBT for youth anxiety over the study period. A systematic review of medical and psychological databases (PsycINFO, PubMed, SCOPUS, Web of Science, Cochrane Library, and Embase) will identify reviews comparing the efficacy of different formats of parent involvement in CBT for youth anxiety. Data extraction will include (1) author names (and year of publication), (2) review design, (3) age range, (4) analysis type, (5) conclusions, and (6) moderators. This overview will present the relative efficacy of formats chronologically in a table and then describe the main results longitudinally in a narrative summary. A Measurement Tool to Assess Systematic Reviews, 2nd Edition (AMSTAR 2), quality rating will be given to each review, and the amount of primary study overlap across reviews will be quantified. Results The last search was conducted on July 1, 2022. The reviews were published between 2005 and 2022. We found a total of 3529 articles, of which we identified 25 for the final analysis. Conclusions This overview will compare and report the relative efficacy of Y-CBT, P-CBT, and F-CBT for youth anxiety over the study period, describe the heterogeneity across reviews and primary studies, and consider the moderating effect of relevant variables. It will describe the limitations of an overview, including the potential for nuance in the data to be lost, and provide conclusions and recommendations for conducting systematic reviews regarding parental involvement for CBT for youth anxiety. International Registered Report Identifier (IRRID) RR1-10.2196/48077

Treatment of COVID-19 olfactory dysfunction with olfactory training, palmitoylethanolamide with luteolin, or combined therapy: a blinded controlled multicenter randomized trial

PurposeFew evidence-based therapies are available for chronic olfactory dysfunction after COVID-19. This study investigated the relative efficacy of olfactory training alone, co-ultramicronized palmitoylethanolamide with luteolin (um-PEA–LUT, an anti-neuroinflammatory supplement) alone, or combined therapy for treating chronic olfactory dysfunction from COVID-19.MethodsThis double-blinded controlled, placebo-controlled multicenter randomized clinical trial was conducted in 202 patients with persistent COVID-19 olfactory dysfunction of > 6 month duration. After a screening nasal endoscopy, patients were randomized to: (1) olfactory training and placebo; (2) once daily um-PEA–LUT alone; (3) twice daily um-PEA–LUT alone; or (4) combination of once daily um-PEA–LUT with olfactory training. Olfactory testing (Sniffin’ Sticks odor identification test) was performed at baseline and at 1, 2, and 3 months. The primary outcome was recovery of over three points on olfactory testing, with outcomes compared at T0, T1, T2 and T3 across groups. Statistical analyses included one-way ANOVA for numeric data and chi-square for nominal data.ResultsAll patients completed the study, and there were no adverse events. At 90 days, odor identification scores improved by > 3 points in 89.2% of patients receiving combined therapy vs. 36.8% receiving olfactory training with placebo, 40% receiving twice daily um-PEA–LUT alone, and 41.6% receiving once daily um-PEA–LUT alone (p < 0.00001). Patients receiving treatment with um-PEA–LUT alone demonstrated subclinical improvement (< 3 point odor identification improvement) more often than patients receiving olfactory training with placebo (p < 0.0001.)ConclusionsOlfactory training plus once daily um-PEA–LUT resulted in greater olfactory recovery than either therapy alone in patients with long-term olfactory function due to COVID-19.Trial registration20112020PGFN on clinicaltrials.gov.Level of evidence1b (Individual Randomized Clinical Trial).

Ginger (Zingiber officinale Roscoe) preparations for prophylaxis of postoperative nausea and vomiting: A Bayesian network meta-analysis

Ethnopharmacological relevanceGinger has been proposed for prevention of postoperative nausea and vomiting (PONV), however it remains equivocal whether ginger can be an alternative option and which certain preparation is optimal for PONV prophylaxis. Aim of the studyWe conducted a network meta-analysis (NMA) to compare and rank relative efficacy for PONV control among all available ginger preparations collected in the databases. MethodsEligible records were identified by retrieving Medline (via Pubmed), Embase, Web of Science, CENTRAL, CNKI, WHO ICTRP and ClinicalTrials.gov for randomized controlled trials that investigated the efficacy of ginger therapies for the prophylaxis of PONV. A bayesian NMA within random-effects models was implemented. Certainty of evidence for estimates was investigated following GRADE framework. We prospectively registered the protocol (CRD 42021246073) in PROSPERO. ResultsEighteen publications comprising 2199 participants with PONV were identified. Ginger oil (RR [95%CI], 0.39 [0.16, 0.96]) appeared to have the highest probability of being ranked best to decrease the incidence of postoperative vomiting (POV), with statistical significance compared with placebo, based on high to moderate confidence in estimates. With regard to reducing postoperative nausea (PON), statistically superiority was not observed in ginger regimens compared with placebo based on moderate to low certainty of evidence. Reduction in antemetic use and nausea intensity were noticed in ginger powder and oil. Ginger was significantly associated with better efficacy for Asian, older age, higher dosage, preoperative administration, hepatobiliary and gastrointestinal surgery. ConclusionsGinger oil appeared to be superior to other ginger treatments for the prophylaxis of POV. With regard to reducing PON, ginger preparations indicated no obvious advantages.

The Efficacy of Hypnotic Analgesic Suggestions in Chronic Nociplastic Pain: A Randomized Controlled Trial

ABSTRACT This blinded study evaluated the relative efficacy of three hypnosis sessions in 60 patients with chronic nociplastic pain allocated randomly to one of two conditions: hypnosis with analgesic suggestions, or hypnosis with nonspecific suggestions. Pain intensity, pain quality, and pain interference as outcome measures were assessed before and after treatment. A mixed-design analysis of the variance model showed no significant differences between groups. According to the adjusted model, large effect size improvements in pain intensity and pain quality emerged for both conditions but were only meaningful for patients not taking pain medications. Analgesic suggestions may not play a primary role in beneficial outcomes of hypnosis at the beginning of chronic pain management since both interventions demonstrated similar positive effects. Future studies should investigate the efficacy of the hypnosis components over longer treatment periods.

Randomized, Double-Blind, Active Comparator Pharmacodynamic Study of Platelet Inhibition with Crushed and Integral Formulations of Clopidogrel and Ticagrelor in Acute Coronary Syndrome.

Crushed formulations of specific antiplatelet agents produce earlier and stronger platelet inhibition. We studied the platelet inhibitory effect of crushed clopidogrel in patients with acute coronary syndrome (ACS) and its relative efficacy compared with integral clopidogrel, crushed and integral ticagrelor. We aimed to compare the platelet inhibitory effect of crushed and integral formulations of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS). Overall, 142 patients with suspected ACS were randomly assigned to receive crushed or integral formulations of clopidogrel or ticagrelor. Platelet inhibition at baseline and 1 and 8h was assessed using the VerifyNow assay. High on-treatment platelet reactivity (HTPR) ≥ 235 P2Y12reaction units (PRUs) 1h after the medication loading dose was also determined. The PRU and percentage inhibition median (interquartile range) at 1h for the different formulations were as follows: crushed clopidogrel: 196.50 (155.50, 246.50), 9.36 (- 1.79, 25.10); integral clopidogrel: 189.50 (159.00, 214.00), 2.32 (- 2.67, 19.89); crushed ticagrelor: 59.00 (10.00, 96.00), 75.53 (49.12, 95.18); and integral ticagrelor: 126.50 (50.00, 168.00), 40.56 (25.59, 78.69). There was no significant difference in PRU or percentage platelet inhibition between the crushed and integral formulations of clopidogrel (p=0.990, p=0.479); both formulations of ticagrelor were superior to the clopidogrel formulations (p<0.05). On paired comparison, crushed ticagrelor showed robust early inhibition of platelets compared with the integral formulation (p=0.03). Crushed clopidogrel exhibited the maximal HTPR of 34.3%, but was < 3% for both formulations of ticagrelor. The platelet inhibitory effect of crushed clopidogrel is not superior to integral preparation in patients with ACS. Crushed ticagrelor produced maximal platelet inhibition acutely. HTPR rates in ACS are similar and very low with both formulations of ticagrelor, and maximal with crushed clopidogrel. Clinical Trials Registry of India identifier number CTRI/2020/06/025647.

O-094 Management of subfertility in women with PCOS: expectations, problems and solutions

Abstract Polycystic ovarian syndrome (PCOS) is a common cause of subfertility particularly when anovulation is present. In this circumstance efforts are made to induce ovulation through lifestyle modification, medication, or a combination of both. Other patients with PCOS may be ovulatory but require IVF/ICSI for other causes, including male factor or tubal infertility. In all cases, attention needs to be placed on the underlying metabolic, psychological, and reproductive features that may complicate treatment and subsequent pregnancy. Pregnancy itself has a higher chance of complications and these can be reduced by adequate preconception evaluation and intervention. Recently, the international evidence-based guideline for evaluation and treatment of PCOS has been updated (1) and the infertility section subjected to a literature integrity check to exclude publications that did not meet the highest criteria for incorporation into clinical management. A recent individual patient data meta-analysis has also clarified the relative efficacy of fertility treatments (2). The following conclusions are recommended; 1. Letrozole is the first line drug of choice for ovulation induction based on its efficacy and lower multiple pregnancy rate 2. Clomiphene is an effective drug particularly given a long experience of use and its lower cost 3. Metformin may be valuable for some patients particularly if glucose intolerance is present 4. A combination of clomiphene and metformin may be effective, particularly in overweight individuals 5. Gonadotrophins are an effective treatment in experienced clinics which the resources to undergo adequate monitoring 6. Laparoscopic ovarian surgery may assist some patients and is associated with a lower multiple pregnancy rate and may have long term benefits 7. IVF may be safely conducted with appropriate safeguards to reduce ovarian hyperstimulation syndrome in those where ovulation induction has failed. It should be noted that some of these drugs are “off-label” in many countries and are not recommended in several healthcare systems.There are several areas where further information may lead to altered and improved practice: 1. IVF as a first line therapy may be more effective and allow better control of multiple pregnancy rates. 2. In vitro maturation (IVM) with IVF/ICSI shows increasing success with no or minimal FSH use (3). 3. Bariatric surgery is more readily available and may lead to significant weight loss related ovulation. 4. Newer GLP1 receptor agonists show dramatic weight loss and are being evaluated in PCOS. 5. First line gonadotrophin treatment has been advocated by some proponents. 6. Higher dose and longer use of standard oral agents may help in ovulation induction resistant patients. 7. Inositol and myoinositol are being evaluated as safe, low cost, over the counter alternatives. 8. Alternatives to hCG are available for ovulation induction in oral and IVF cycles. 9. Promising pharmacogenomic approaches may allow individualisation of treatment. While the genomic and environmental aetiology of PCOS remains uncertain, the increasing emphasis on evaluation and assessment of effective therapies for subfertility is advancing rapidly.

Eficacia comparativa de los apósitos quirúrgicos Micropore™, Tegaderm™ y Lockit plus® para la fijación del catéter epidural lumbar en niños: ensayo controlado aleatorizado de grupo paralelo prospectivo

BackgroundProper fixation of an epidural catheter is necessary for desired drug effect and to prevent catheter displacement. Different techniques have been used for epidural catheter fixation. The aim of the study was to compare the relative efficacy of Micropore™ surgical dressing, Tegaderm™, and Lockit plus® in preventing lumbar epidural catheter migration in children. MethodsWe studied 167 patients aged 5-16 years, for up to 48hrs. after the elective abdominal or lower limb surgery. Patients were randomly assigned to one of three groups: 1) Micropore™ surgical dressing (group M), 2) Tegaderm™ (group T), or 3) Lockit plus® (group L). Incidence and extent of epidural catheter migration in centimetres (cm); was compared at 24 and 48hours post epidural fixation. Correlation between epidural catheter migration and patient characteristics, and relative incidence of complications in three groups was also analysed. ResultsIncidence of catheter migration was 9.6% at 24hours (group M: 7.1%, group T: 21.1% and group L: 0%) and 45.5% at 48hours (group M: 66.1%, group T: 45.6% and group L: 24.1%). After 48hours, absolute migration (mean migration rounded off to the nearest 0.5cm) was least in patients in group L: 0.34cm (1.39) compared to group M 1.22cm (SD: 1.85) group T: 0.94cm (1.94) (p = <0.001). ConclusionUp to 48hours after surgery, the Lockit plus® device demonstrated the less epidural catheter migration when compared to micropore surgical dressing or tegaderm in children undergoing elective abdominal or lower limb surgery.

Relative efficacy of high-pressure versus backpack sprayer applications of 2 natural product-based acaricides for control of host-seeking Ixodes Scapularis and Amblyomma americanum nymphs.

We evaluated the relative effectiveness of the natural product acaricide Essentria IC3 and the entomopathogenic fungal acaricide BotaniGard ES to suppress host-seeking Ixodes scapularis Say and Amblyomma americanum (L.) nymphs when applied with low-pressure backpack and high-pressure sprayers. Essentria IC3 applied by backpack sprayer out-performed high-pressure applications, while the opposite was true for treatments with BotaniGard ES. We were unable to demonstrate consistently greater efficacy using high-pressure applications, and neither of the acaricides or application methods provided substantial (>90%) levels of control at 7 days postapplication.

73-LB: Tirzepatide 5, 10, and 15 mg vs Injectable Semaglutide 0.5 mg for the Treatment of Type 2 Diabetes—An Indirect Treatment Comparison

Semaglutide (sema) 0.5 mg is part of type 2 diabetes (T2D) standard of care as initial maintenance dose. While there has been a study conducted on TZP and sema 1.0 mg, showing TZP superiority, currently there is no head-to-head study comparing TZP and sema 0.5 mg. Therefore, the objective of this analysis was to evaluate the efficacy and safety of TZP and sema 0.5 mg using adjusted indirect comparisons. Adjusted indirect comparisons were performed using the Bucher method to compare the relative efficacy and safety of TZP 5, 10, 15 mg and sema 0.5 mg via a common comparator (sema 1.0 mg) based on trial results from SURPASS-2 (TZP vs sema 1.0 mg) and SUSTAIN 7 (sema 0.5 and 1.0 mg vs dulaglutide 0.75 and 1.5 mg). All TZP doses showed statistically significant greater reductions in HbA1c, weight and BMI from baseline to week 40 compared to sema 0.5 mg (Figure). TZP demonstrated a comparative safety profile for adverse events (AEs) but patients had statistically significant greater odds of treatment discontinuations due to AEs for TZP 10 and 15 mg. All TZP doses demonstrated no statistically significant differences vs sema 0.5 mg in the odds or likelihood of gastrointestinal AEs. In these adjusted indirect comparisons the extent of differences between TZP and sema 0.5 mg regarding HbA1c and weight reductions provide insights on their comparative effectiveness in the absence of a head-to-head study. Disclosure K. M. Pantalone: Consultant; AstraZeneca, Bayer Inc., Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk, Sanofi, Research Support; Bayer Inc., Merck &amp; Co., Inc., Novo Nordisk, Twin Health, Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Merck &amp; Co., Inc., Novo Nordisk. S. Tofe: Advisory Panel; Lilly, Novo Nordisk, Research Support; Lilly, Novo Nordisk, Speaker's Bureau; Lilly, Novo Nordisk. L. Fan: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J. S. Paik: None. K. T. Ranta: Employee; Eli Lilly and Company. H. Sapin: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. B. Osumili: Employee; Eli Lilly and Company. Funding Eli Lilly and Company

#3664 EVALUATION OF THE INTRODUCTION OF NOVEL POTASSIUM BINDERS IN ROUTINE CARE: THE STOCKHOLM CREATININE MEASUREMENTS (SCREAM) PROJECT

Abstract Background and Aims The pharmacological management of hyperkalemia has traditionally considered sodium polystyrene sulfonate (SPS) and, since late 2018, the novel potassium (K+) binders Patiromer and Sodium Zirconium Cyclosilicate (SZC). This study evaluated their patterns of use, duration of treatment and relative effectiveness in reducing plasma K+ levels in Stockholm´s contemporary routine care. Method Observational study of all adults who newly-filled a prescription for SPS, Patiromer or SZC during 2019–2021 in Stockholm, Sweden. Sweden offers universal healthcare and covers the cost of prescribed medications. We described patient characteristics of new initiators, including their comorbidities, medication use, eGFR and pre-treatment plasma K+ levels. We then quantified treatment duration by evaluating all subsequent dispensations. Lastly, we compared their relative efficacy by evaluating post-treatment K+ during the following 60 days through multivariable logistic regression. Because the frequency and pattern of K+ monitoring differed per patient, we considered the K+ test closest to the end of 15-day intervals. Then, we estimated odds ratios and 95% confidence intervals of maintaining normokalemia (K+&amp;lt;5.1 and &amp;lt;5.5 mmol/L) for the novel binders vs SPS. Results During 2019–2021, 1879 adults started treatment with SPS, and 147 with novel binders (41 with Patiromer and 106 with SZC). The median K+ at initiation for all three treatments was 5.7 mmol/L. Median eGFR was higher among Patiromer initiators (58 mL/min/1.73 m2) than initiators of SZC (31 mL/min/1.73m2) or SPS (37 mL/min/1.73m2). Patients on SPS stayed mean 61 days on treatment, and 14% filled three or more consecutive prescriptions suggesting chronic use. Patients on novel binders stayed mean 109 days on treatment, and 49% filled three or more prescriptions (Panel A). After 15 days of treatment, mean plasma K+ similarly decreased to 4.6 (4.3-5.1) and 4.8 (4.5-5.2) mmol/L in patients with SPS and novel binders, respectively, and this level was maintained during the 60 days post-treatment (Panel B). 76% of SPS users reached a potassium value &amp;lt;5.1 mmol/L at day 15 versus 67% of patients in the novel binder group (between group difference 9%; 95% CI 0.92-2.57; p-value 0.07; Panel C). Furthermore, the proportion of patients with K+ &amp;lt;5.5 mmol/L at day 15 was 91% for SPS and 85% for novel binders (Panel D). In multivariable logistic regression, the odds ratio for novel binders (vs SPS) in reaching K+ targets (K+ &amp;lt;5.1 mmol/L) after 15 days was 0.68 (95% CI 0.4-1.17) and 0.78 (95% CI 0.42-1.44) after 30 days. Conclusion We observe modest use of novel K+ binders in Stockholm's contemporary practice, with longer treatment lengths than SPS. Both SPS and novel binders showed similar efficacy in achieving normal potassium values during the first 15 days of treatment and subsequent 2 months.

Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea.

Antibiotic-associated diarrhea is often managed by the withdrawal of the culprit antibiotics or the administration of alternative antibiotics when a Clostridium difficile infection (CDI) is suspected, an infection that tends to be the most common causative agent of the disease. Probiotics are also gaining popularity as alternative therapies, and it was hypothesized in this article that a Lactobacillus strain is the most efficacious probiotic for the prevention of antibiotic-associated diarrhea. This article conducted a literature review investigating the relative efficacy of the Lactobacillus, Bifidobacterium, and Saccharomyces probiotic strains as effective alternative therapies for antibiotic-associated diarrhea. The literature searched was from the PubMed database. The inclusion filters were: random control trials (RCTs), clinical trials, meta-analysis, last 10 years, full-text articles available in English, and all articles published in peer-reviewed journals. All three probiotic genera had strains that demonstrated significant efficacy in the prevention of antibiotic-associated diarrhea. However, Saccharomyces boulardii I-745 tends to outperform all the strains as the most effective and the one with the fewest, if any, adverse effects. Whenever probiotics are considered for the prevention of antibiotic-associateddiarrhea (AAD) in both pediatric and adult patients, S. boulardii I-745 should probably be prioritized.

Key influencing factors for the success of external innovation strategies in the biotechnology industry

PurposeNumerous biotechnology and pharmaceutical firms have undergone considerable changes and adapted to the challenge of developing sustainable products and services. However, few studies have explored the factors that contribute to the success of external innovation and value co-creation strategies adopted by biotechnology and pharmaceutical firms. The purpose of this study is to examine how biotechnology and pharmaceutical industries use value co-creation strategies to obtain external resources.Design/methodology/approachThis study developed a conceptual framework based on the relevant literature. The study applied a resource-based approach, dynamic capability theory and a qualitative multiple-case study design to investigate several research questions; semi-structured interviews were conducted with representatives from 11 biotechnology/pharmaceutical firms in Taiwan, and the data extracted from the interview content were axially coded.FindingsThis study revealed that factors such as dynamic marketing capabilities and process optimization contributed to the success of the aforementioned strategies; several propositions were also developed on the basis of the literature review and coded data, thereby providing insights regarding the relative efficacy and propriety of various external innovation and value co-creation strategies and models in various situations and contexts. Firms and technology providers might enter a technology licensing agreement, establish a joint venture company; participate in a merger/acquisition depending on their size, research and development capabilities; or goals and time- and cost-related factors.Originality/valueThe main original contributions of this study are the proposed conceptual framework and the insights provided regarding the relative efficacy and propriety of different external innovation and value co-creation strategies and models in different situations and contexts.

Association of CYP2C19 Loss-of-Function Metabolizer Status With Stroke Risk Among Chinese Patients Treated With Ticagrelor-Aspirin vs Clopidogrel-Aspirin

The Clopidogrel With Aspirin in High-Risk Patients With Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial showed that ticagrelor-aspirin combination therapy reduced the risk of stroke compared with a clopidogrel-aspirin combination among carriers of CYP2C19 loss-of-function (LOF) alleles after a transient ischemic attack (TIA) or minor ischemic stroke. However, the association between the degree of CYP2C19 LOF and ideal treatment allocation remains unknown. To investigate whether the efficacy and safety of ticagrelor-aspirin vs clopidogrel-aspirin are consistent with the expected degree of CYP2C19 LOF after TIA or minor stroke. CHANCE-2 was a multicenter, double-blind, double-dummy, placebo-controlled randomized clinical trial. Patients were enrolled at 202 centers in China from September 23, 2019, through March 22, 2021. Patients with at least two *2 or *3 alleles (*2/*2, *2/*3, or *3/*3) according to point-of-care genotyping were classified as "poor metabolizers," and those with one *2 or *3 allele (*1/*2 or *1/*3) were classified as "intermediate metabolizers." Patients were randomly assigned in a 1:1 ratio to receive ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for days 2-90) or clopidogrel (300-mg loading dose on day 1 followed by 75 mg/d for days 2-90). All patients received aspirin (75- to 300-mg loading dose followed by 75 mg/d for 21 days). The primary efficacy outcome was a new ischemic or hemorrhagic stroke. The secondary efficacy outcome was a composite of new clinical vascular events and individual ischemic stroke events within 3 months. The primary safety outcome was severe or moderate bleeding. Analyses were performed according to the intention-to-treat principle. Of the 6412 patients enrolled, the median age was 64.8 years (IQR, 57.0-71.4 years), and 4242 patients (66.2%) were men. Of the 6412 patients, 5001 (78.0%) were intermediate metabolizers, and 1411 (22.0%) were poor metabolizers. The primary outcome occurred less often with ticagrelor-aspirin vs clopidogrel-aspirin, irrespective of metabolizer status (6.0% [150 of 2486] vs 7.6% [191 of 2515]; hazard ratio [HR], 0.78 [95% CI, 0.63-0.97] among intermediate metabolizers and 5.7% [41 of 719] vs 7.5% [52 of 692]; HR, 0.77 [95% CI, 0.50-1.18] among poor metabolizers; P = .88 for interaction). Patients taking ticagrelor-aspirin had a higher risk of any bleeding event compared with those taking clopidogrel-aspirin, irrespective of metabolizer status: 5.4% (134 of 2486) vs 2.6% (66 of 2512) (HR, 2.14 [95% CI, 1.59-2.89]) among intermediate metabolizers and 5.0% (36 of 719) vs 2.0% (14 of 692) (HR, 2.99 [95% CI, 1.51-5.93]) among poor metabolizers (P = .66 for interaction). This prespecified analysis of a randomized clinical trial found no difference in treatment effect between poor and intermediate CYP2C19 metabolizers. The relative clinical efficacy and safety of ticagrelor-aspirin vs clopidogrel-aspirin were consistent across CYP2C19 genotypes. ClinicalTrials.gov Identifier: NCT04078737.