Estimates Of Efficacy Research Articles

Pembrolizumab plus cetuximab with neoadjuvant chemotherapy for head and neck squamous cell carcinoma.

Head and neck cancer cells commonly express programmed death ligand 1 (PD-L1) and epidermal growth factor receptor (EGFR), both of which play pivotal roles in the antitumor cellular immune response. Pembrolizumab, a PD-1 inhibitor, and cetuximab, an EGFR inhibitor, are typically effective agents combined with neoadjuvant platinum-based chemotherapy for the treatment of head and neck squamous cell carcinoma (HNSCC). This study aims to evaluate the efficacy and safety of neoadjuvant immunochemotherapy in patients with HNSCC. Patients with HNSCC underwent radical surgery and complete cervical lymph node dissection following neoadjuvant immunochemotherapy at RenJi Hospital from January 2021 to June 2024 were retrospectively analyzed. The primary endpoint was major pathological response (MPR). We further explored the relationship between the efficacy and immune estimators. Twenty-one patients were enrolled in this retrospective study. The MPR was 66.7%, including 11 patients who achieved a pathological complete response (pCR). The overall response rate (ORR) was 90.5%, and the complete response (CR) rate was 28.6%. The oropharynx, as the primary site, was the sensitive tumor type to neoadjuvant immunochemotherapy. The most common adverse event (AEs) was anemia (61.9%). No grade 4 AE or delayed surgery was reported. Laryngeal preservation rates were 90.9% (10/11), and pathological findings confirmed negative surgical margins for all patients. Moreover, pre-treatment peripheral lymphocyte count, monocyte count, and platelet to lymphocyte ratio (PLR) displayed a significant correlation with the treatment response. Pembrolizumab plus cetuximab with chemotherapy for patients with HNSCC is a feasible and safe clinical protocol fulfilling organ preservation and life quality improvement. Pre-treatment peripheral immune estimators could help to screen patients who may respond to the neoadjuvant immunochemotherapy.

Evaluating quasi-experimental approaches for estimating epidemiological efficacy of non-randomised field trials: applications in Wolbachia interventions for dengue

BackgroundWolbachia symbiosis in Aedes aegypti is an emerging biocontrol measure against dengue. However, assessing its real-world efficacy is challenging due to the non-randomised, field-based nature of most intervention studies. This research re-evaluates the spatial–temporal impact of Wolbachia interventions on dengue incidence using a large battery of quasi-experimental methods and assesses each method’s validity.MethodsA systematic search for Wolbachia intervention data was conducted via PUBMED. Efficacy was reassessed using commonly-used quasi-experimental approaches with extensive robustness checks, including geospatial placebo tests and a simulation study. Intervention efficacies across multiple study sites were computed using high-resolution aggregations to examine heterogeneities across sites and study periods. We further designed a stochastic simulation framework to assess the methods’ ability to estimate intervention efficacies (IE).ResultsWolbachia interventions in Singapore, Malaysia, and Brazil significantly decreased dengue incidence, with reductions ranging from 48.17% to 69.19%. IEs varied with location and duration. Malaysia showed increasing efficacy over time, while Brazil exhibited initial success with subsequent decline, hinting at operational challenges. Singapore's strategy was highly effective despite partial saturation. Simulations identified Synthetic Control Methods (SCM) and its variant, count Synthetic Control Method (cSCM), as superior in precision, with the smallest percentage errors in efficacy estimation. These methods also demonstrated robustness in placebo tests.ConclusionsWolbachia interventions exhibit consistent protective effects against dengue. SCM and cSCM provided the most precise and robust estimates of IEs, validated across simulated and real-world settings.

Minimal Protective Antibody Titers Elicited in Sheep by RVFV MP-12 and arMP-12ΔNSm21/384 Vaccine Candidates

The live attenuated Rift Valley Fever Virus (RVFV) vaccine candidates, RVFV MP-12, and the recombinant derivative, RVFV arMP-12ΔNSm21/384 (MP-12NSm-del), are among the most promising next-generation domestic ruminant vaccine candidates. While both vaccines consistently elicit protective neutralizing Antibodies (nAb) in domestic ruminants, the minimal protective antibody titer is unknown. Therefore, we conducted studies to determine the minimal protective nAb titers elicited in sheep by these vaccines using a mouse model. The approach involved the transfer of sera obtained from sheep vaccinated with the MP-12 and MP-12NSm-del vaccines to 6- to 8-week-old BALB/c mice. The sheep nAb titers ranged from 20 to 640 at the time of transfer. A blood sample was obtained from each mouse 24 hours post-transfer to determine the nAb titer 2 hours before challenging each animal with a lethal dose of virulent RVFV (strain ZH501). All challenged mice were observed daily for 21 days for morbidity and mortality. The lowest nAb titer that protected the animals was interpreted as an estimate of the minimal protective efficacy of the vaccine. The results indicated that nAb titers as low as 10 to 20 elicited by the MP-12 and MP-12NSm-del vaccine candidates in sheep 10 days post-vaccination afforded protection to the mice. However, the nAbs elicited in one sheep by MP-12 before day 10 post-vaccination and ranging in titer from < 5 to 40 only afforded protection to 3 out of 18 mice, and therefore suggested that innate and/or the cellular immune response were also needed for protection during early RVFV infection. The findings further support these RVFV candidate vaccines as potential veterinary vaccines for domestic ruminants and offer a promising BALB/c mouse RVFV challenge model as a surrogate for evaluating the protective nAb response elicited by RVFV vaccines.

Efficacy assessment in crop protection: a tutorial on the use of Abbott’s formula

In 1925, the American entomologist Walter Sidney Abbott proposed an equation for assessing efficacy, and it is still widely used today for analysing controlled experiments in crop protection and phytomedicine. Typically, this equation is applied to each experimental unit and the efficacy estimates thus obtained are then used in analysis of variance and least squares regression procedures. However, particularly regarding the common assumptions of homogeneity of variance and normality, this approach is often inaccurate. In this tutorial paper, we therefore revisit Abbott’s equation and outline an alternative route to analysis via generalized linear mixed models that can satisfactorily deal with these distributional issues. Nine examples from entomology, weed science and phytopathology, each with a different focus and methodological peculiarity, are used to illustrate the framework.

Malignancy progression and treatment efficacy estimation of osteosarcoma patients based on in vitro cell culture model and analysis

BackgroundOsteosarcoma (OS) usually happens in patients under 20 years old and is notorious for its low survivorship and limb loss. Personalized medicine is a viable approach to increase the efficiency of chemotherapy which is the main prognostic factor for survivorship after surgical treatment. MethodsIn this five-year prospective observational study, we collected primary cells of osteosarcoma from 15 patients, and examined the correlation between clinical characters of patients and cell properties characterized using various in vitro assays. The properties including genes expression, pro-angiogenic capability and anti-cancer drug response are characterized respectively by using RT-PCR, tube formation assay, osteogenesis assay and drug testing on 3D tumor spheroid model. ResultThe results suggest that OS patients with higher MMP9 expression levels have higher probability to develop skip metastasis (p = 0.041). The 3D tumor spheroid test based on the median lethal dose from 2D culture provides some prognostic value. Patients do not response well to methotrexate (MTX) show higher percentage of high pathology grade (p = 0.009) and lung metastasis (p = 0.044). Also, patients respond well to ifosfamide (IFO) have higher probability to achieve high tumor necrosis rate (p = 0.007). ConclusionThe association between cell properties and clinical characters of patients provided by our data can act as potential prognostic factors to help physicians to develop effective personalized chemotherapy for osteosarcoma treatments.

The effect of thoraco-lumbo-sacral orthosis wear time and clinical risk factors on curve progression for individuals with adolescent idiopathic scoliosis

BACKGROUND CONTEXTThe effectiveness of bracing with a thoraco-lumbo-sacral orthosis (TLSO) for adolescent idiopathic scoliosis (AIS) has been studied extensively, with a growing body of evidence supporting TLSO use. In this study we examine the effect of wear time and other important causal factors affecting curve progression and develop a risk model that can be applied to individual patients and is based on important casual factors. PURPOSEUnderstand the impact of TLSO wear time and other risk factors in order to guide optimal treatment. STUDY DESIGN/SETTINGProspective, multi-center, cohort study Patient SampleIndividuals with a diagnosis of AIS, age of 10 to 16 years, primary Cobb angle of 20 to 45 degrees, Risser 0 to 2, <1 year post menarche if female, who were to be treated with a TLSO OUTCOME MEASURES(1) Rate of primary curve progression, (2) surgery recommendation during TLSO treatment METHODSWear time was monitored with thermochrons. Participants were followed until the end of growth. We examined the causal effects of wear time and baseline skeletal maturity as measured by triradiate cartilage (TRC) status, Cobb angle, and age. We then fit an outcome prediction model (logistic regression) based on important casual factors. RESULTSOur final cohort consisted of 145 individuals (baseline age 12.1–13.4 years). Wear time was an important cause of response to treatment, including an interaction with TRC status. Baseline Cobb angle and age were also meaningful causes of response. The prediction model was accurate (79%) and had good specificity (81%) and moderate sensitivity (68%) and an area under the receiver operating characteristic curve (AUC) of 0.81. Additionally, we were able to independently confirm previous estimates of treatment efficacy, with an odds ratio around 2.0. CONCLUSIONSOur study showed the explicit causal effects of wear time, and baseline skeletal maturity, Cobb angle and age. The risk model we developed can be used for counseling patients and their families regarding TLSO wear and expectations for outcome.

Potential Cost Savings with 60-day Peripheral Nerve Stimulation Treatment in Chronic Axial Low Back Pain.

Chronic axial low back pain (CLBP) that is not responsive to medication management or physical therapy often requires significant clinical intervention. Several interventional pain management options exist, including a 60-day peripheral nerve stimulation (PNS) treatment. This economic evaluation investigated the potential for projected cost savings associated with prioritizing 60-day PNS treatment relative to a 'standard of care' (SOC) approach (where patients do not have access to 60-day PNS). A decision tree (supervised machine learning) model tracked treatment progression across two hypothetical cohorts of US patients with CLBP in whom non-interventional options were ineffective (Cohort A: treatment starting with 60-day PNS followed by any additional interventional and surgical treatments versus Cohort B: standard of care interventional and surgical treatments without access to 60-day PNS). Treatment efficacy estimates were based on published success rates. Conditional on treatment failure, up to two additional interventions were considered within the 12-month time frame in both cohorts. SOC treatment options included epidural injection, radiofrequency ablation (RFA), basivertebral nerve ablation (BVNA), PNS permanent implant (PNS-PI), spinal cord stimulator (SCS) trial/implant, and spinal fusion surgery. Treatment choice probabilities in both cohort algorithms were based on clinician interviews. Costs were based on national Medicare reimbursement levels in the ambulatory surgery center (ASC) setting. Savings reflected the difference in projected costs between cohorts. A Monte Carlo simulation and sensitivity analyses were conducted to generate confidence intervals and identify important inputs. The treatment algorithm which prioritized initial 60-day PNS treatment was projected to save $8056 (95% CI $6112-$9981) per patient during the first year of interventional treatment relative to the SOC approach. Use of the 60-day PNS treatment as an initial interventional treatment in patients with CLBP may result in significant savings for Medicare. Projected savings may be even larger for commercial payers covering non-Medicare patients.

Efficacy of surgical treatments for the management of solitary rectal ulcer syndrome: a network meta-analysis.

Solitary rectal ulcer syndrome (SRUS) is a benign and poorly understood disorder with complex management. Typical symptoms include straining during defaecation, rectal bleeding, tenesmus, mucoid secretion, anal pain and a sense of incomplete evacuation. Diagnosis is based on characteristic clinical symptoms and endoscopic/histological findings. Several treatments have been reported in the literature with variable ulcer healing rates. This study aimed to evaluate the efficacy of different treatments for SRUS. A systematic review and network meta-analysis were performed according to the PRISMA guidelines. Studies in English, French and Spanish languages were included. Papers written in other languages were excluded. Other exclusion criteria were reviews, case reports or clinical series enrolling less than five patients, study duplications, no clinical data of interest and no article available. A systematic literature search was conducted from January 2000 to March 2024 using the following databases: PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus. The biases of the studies were assessed using the Newcastle-Ottawa scale or the Jadad scale when appropriate. Types of treatment and their efficacy for the cure of SRUS were collected and critically assessed. The study's primary outcome was to estimate the rate of patients with ulcer healing. A total of 22 studies with 911 patients (men 361, women 550) diagnosed with SRUS were analysed in the final meta-analysis. The pooled effect estimates of treatment efficacy revealed that surgery showed the highest ulcer healing rate (70.5%; 95% CI 0.57-0.83). Surgery was superior in the cure of ulcers with respect to medical therapies and biofeedback (OR 0.09 and OR 0.14). Solitary rectal ulcer syndrome is a challenging clinical entity to manage. Proficient results have been reported with the surgical approach, suggesting its positive role in cases refractory to medical and biofeedback therapy. Further studies in homogeneous populations are required to evaluate the efficacy of surgery in this setting. (PROSPERO registration number CRD42022331422).

A Bayesian latent-subgroup platform design for dose optimization.

The US Food and Drug Administration launched Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development, calling for the paradigm shift from finding the maximum tolerated dose to the identification of optimal biological dose (OBD). Motivated by a real-world drug development program, we propose a master-protocol-based platform trial design to simultaneously identify OBDs of a new drug, combined with standards of care or other novel agents, in multiple indications. We propose a Bayesian latent subgroup model to accommodate the treatment heterogeneity across indications, and employ Bayesian hierarchical models to borrow information within subgroups. At each interim analysis, we update the subgroup membership and dose-toxicity and -efficacy estimates, as well as the estimate of the utility for risk-benefit tradeoff, based on the observed data across treatment arms to inform the arm-specific decision of dose escalation and de-escalation and identify the OBD for each arm of a combination partner and an indication. The simulation study shows that the proposed design has desirable operating characteristics, providing a highly flexible and efficient way for dose optimization. The design has great potential to shorten the drug development timeline, save costs by reducing overlapping infrastructure, and speed up regulatory approval.

Creating a digital approach for promoting physical activity in pediatric pulmonary hypertension: A framework for future interventions.

Children with pulmonary hypertension (PH) often demonstrate limited exercise capacity. Data support exercise as an effective nonpharmacologic intervention among adults with PH. However, data on exercise training in children and adolescents are limited, and characteristics of the optimal exercise program in pediatric PH have not been identified. Exercise programs may have multiple targets, including muscle deficits which are associated with exercise limitations in both adult and pediatric PH. Wearable accelerometer sensors measure physical activity volume and intensity in the naturalistic setting and can facilitate near continuous data transfer and bidirectional communication between patients and the study team when paired with informatics tools during exercise interventions. To address the knowledge gaps in exercise training in pediatric PH, we designed a prospective, single arm, nonrandomized pilot study to determine feasibility and preliminary estimates of efficacy of a 16-week home exercise intervention, targeting lower extremity muscle mass and enriched by wearable mobile health technology. The exercIse Training in pulmONary hypertEnsion (iTONE) trial includes (1) semistructured exercise prescriptions tailored to the participant's baseline level of activity and access to resources; (2) interval goal setting fostering self-efficacy; (3) real time monitoring of activity via wearable devices; (4) a digital platform enabling communication and feedback between participant and study team; (5) multiple avenues to assess participant safety. This pilot intervention will provide information on the digital infrastructure needed to conduct home-based exercise interventions in PH and will generate important preliminary data on the effect of exercise interventions in youth with chronic cardiorespiratory conditions to power larger studies in the future.

Calcitonin treatment for osteoarthritis and rheumatoid arthritis - a systematic review and meta-analysis of preclinical data.

The aim of this study was to investigate the efficacy of calcitonin (CT) in animal models of experimental osteoarthritis (OA) and rheumatoid arthritis (RA), as new stabilized CT formulations are currently being introduced. A comprehensive and systemic literature search was conducted in PubMed/MEDLINE and Embase databases to identify articles with original data on CT treatment of preclinical OA and RA. Methodological quality was assessed using the Systematic Review Centre for Laboratory Animal Experimentation's risk of bias tool for animal intervention studies. To provide summary estimates of efficacy, a meta-analysis was conducted for outcomes reported in four or more studies, using a random-effects model. Subgroup analyses were employed to correct for study specifics. Twenty-six studies were ultimately evaluated and data from 16 studies could be analyzed in the meta-analysis, which included the following outcomes: bone mineral density, bone volume, levels of cross-linked C-telopeptide of type I collagen, histopathological arthritis score, and mechanical allodynia. For all considered outcome parameters, CT-treated groups were significantly superior to control groups (P = 0.002; P = 0.01; P < 0.00001; P < 0.00001; P = 0.04). For most outcomes, effect sizes were significantly greater in OA than in RA (P ≤ 0.025). High in-between study heterogeneity was detected. There is preclinical evidence for an antioxidant, anti-inflammatory, antinociceptive, cartilage- and bone-protective effect of CT in RA and OA. Given these effects, CT presents a promising agent for the treatment of both diseases, although the potential seems to be greater in OA.

How to Balance Prognostic Factors in Controlled Phase II Trials: Stratified Permuted Block Randomization or Minimization? An Analysis of Clinical Trials in Digestive Oncology.

In controlled phase II trials, major prognostic factors need to be well balanced between arms. The main procedures used are SPBR (Stratified Permuted Block Randomization) and minimization. First, we provide a systematic review of the treatment allocation procedure used in gastrointestinal oncology controlled phase II trials published in 2019. Second, we performed simulations using data from six phase II studies to measure the impacts of imbalances and bias on the efficacy estimations. From the 40 articles analyzed, all mentioned randomization in both the title and abstract, the median number of patients included was 109, and 77.5% were multicenter. Of the 27 studies that reported at least one stratification variable, 10 included the center as a stratification variable, 10 used minimization, 9 used SBR, and 8 were unspecified. In real data studies, the imbalance increased with the number of centers. The total and marginal imbalances were higher with SBR than with minimization, and the difference increased with the number of centers. The efficiency estimates per arm were close to the original trial estimate in both procedures. Minimization is often used in cases of numerous centers and guarantees better similarity between arms for stratification variables for total and marginal imbalances in phase II trials.

PT22 Consistency Between Comparative Efficacy Estimates from Target Trial Emulations and Their Origin Target Trials: A Meta-Epidemiological Study

PT22 Consistency Between Comparative Efficacy Estimates from Target Trial Emulations and Their Origin Target Trials: A Meta-Epidemiological Study

Current and emerging feral cat management practices in Australia

Context Feral cats are responsible for the decline and extinction of species globally. Predation by feral cats is identified in Australian legislation as a key threatening process. However, clear guidance to local land managers on feral cat management techniques and their impacts, limitations and potential costs can be difficult to find. Aims In this study, feral cat management experts from around Australia identified available management techniques and their average environmental, social, and economic impact for different ecoregions and land-use types. Methods We convened a 1-day structured elicitation workshop with 19 experts and five facilitators. Experts identified the techniques used for feral cat management; the effectiveness, impact, and cost of each method; and the key knowledge gaps associated with feral cat management. Facilitators aided in the design and format of the workshop, led the discussion at each stage and collated the results. Key results Experts identified the following 10 techniques currently used in Australia: aerial baiting; ground baiting; leghold trapping; cage trapping; shooting; tracking with detector dogs; tracking by Indigenous Rangers; habitat modification; resource modification; and exclusion fencing. In general, experts highlighted that permits, legislation and scale of application constrained many of these techniques. Aerial baiting was considered the most effective technique for reducing feral cat populations in natural and production systems. Cage trapping, shooting, or tracking with detector dogs were considered more effective in residential areas. For all techniques, efficacy estimates varied according to the following three broad vegetation structural regions: (1) deserts and xeric shrublands; (2) forests and woodlands; and (3) grasslands, savannas and shrublands. Techniques considered to have the lowest social tolerance and highest impact to non-target native species included aerial baiting, ground baiting and leghold trapping. Techniques considered to have high social tolerance and low impact on non-target species included tracking by Rangers, tracking with detector dogs, and habitat and resource modification. Conclusions Estimates of management action efficacy differ among land-use types and at least three vegetation structural regions. However, social licence, logistic and legislative constraints are the key drivers of the availability of methods for these areas. Implications Feral cat management programs should consider how program strategy can be prioritised on the basis of technique availability, region of use and expected impact.

Assessing the impact of unmeasured confounding in external control arms via tipping point analyses.

e23065 Background: Estimates of the comparative efficacy of new therapies from single-arm settings can be obtained in advance of RCTs through use of external control arms (ECAs).[1] ECAs are collections of patients with the index disease who were treated outside of the single-arm trial, whose measured baseline attributes are matched to the single-arm trial patients and whose outcomes are compared to trial patients’ to estimate comparative efficacy. Without randomization, observed treatment-outcome associations may be confounded by unmeasured patient attributes. Applying established statistical methods, we estimate the magnitude and prevalence of unmeasured confounding required to move an apparently favorable hazard ratio (HR) to the “tipping point” where the new drug is no longer associated with a favorable survival statistically or clinically. Methods: Studying previously reported patients with multiple myeloma treated with an experimental therapy in a clinical trial (N = 290) and patients treated with standard of care therapy from a rigorously matched ECA (N = 290), we applied the method of Lin et al. to adjust the observed treatment effect (HR and 95% CIs) for overall survival to reflect the impact of a (set of) unmeasured confounder(s).[1,2] Lin’s formula incorporates both the unmeasured confounder’s theoretical association with mortality and its prevalence according to treatment group (i.e., single-arm trial vs. ECA). Results: The observed treatment effect for the single-arm trial treated vs. ECA patients was HR 0.76 (95% CI 0.63-0.91). We estimated the impact of an unmeasured confounder (where HR for overall survival of those patients with and without the confounder is set to 1.5) by its prevalence in each group. When the prevalence of the unmeasured confounder is balanced across groups there is no change in the observed treatment effect. When the presence of the confounder is 70% for ECA patients and absent in the trial patients, the clinical tipping point occurs with loss of the favorable HR (i.e., HR 1.02, 95% CI: 0.85-1.23). Conclusions: While novel analytic methods like ECAs have the potential to accelerate drug development, the lack of randomization raises concern for potential unmeasured confounding. Applying Lin’s method, we illustrate that the impact of unmeasured confounding on HR estimates from a single-arm trial vs.an ECA is a function of both the association with mortality and asymmetries in prevalence. Consistency in the efficacy conclusion for all clinically tenable assumptions indicates a qualitatively reliable conclusion. Friends of Cancer Research whitepaper (2019): available online at https://www.focr.org/sites/default/files/Panel-1_External_Control_Arms2019AM.pdf. Lin D, Psaty B, Kronmal R. Assessing the sensitivity of regression results to unmeasured confounders in observational studies. Biometrics.1998; 54:948–963.

Pilot evaluation of portable scalp cooling for chemotherapy-associated alopecia in early-stage breast cancer.

12141 Background: Chemotherapy-induced alopecia significantly impacts quality of life (QOL). First-generation scalp cooling systems PAXMAN and Dignicap, while effective in reducing alopecia, are not universally adopted due to their lack of portability. Amma is a second-generation, portable and battery-powered scalp cooling system that offers the opportunity for widespread clinical usage by allowing self-administration and mobility. Here, we report first-in-human outcomes of Amma in a preliminary cohort receiving curative-intent taxane-based chemotherapy for early-stage breast cancer. Methods: We conducted a pilot clinical trial (NCT05508984) of the Amma system at Providence Cancer Institute in Oregon. Key inclusion criteria included: no baseline alopecia [Dean’s scale 0], intent to receive 4-6 cycles of taxane-based, anthracycline-sparing therapy, willingness to participate in quality-of-life questionnaires, and serial scalp photography. The primary outcome was the feasibility of Amma devices for adoption within the clinic ascertained by patient reported outcomes (PRO) and provider feedback. The secondary outcome was efficacy defined as the proportion of subjects achieving &lt; 50% hair loss [Dean’s scale 0-2] at 30 days post-treatment, and tolerability assessed by common terminology criteria for adverse events (CTCAE). Results: 14 participants were enrolled and evaluable from 9/2022-1/2024. Participants received docetaxel/cyclophosphamide (TC x 4, n=10) or weekly paclitaxel/trastuzumab+/- pertuzumab (TH(P), n=4). 93% of participants (n=13/14) successfully completed treatment. One participant discontinued scalp cooling prematurely. Primary efficacy endpoint of &lt;50% hair loss was achieved in 64% participants (n=9/14, [95% CI: 0.39, 0.89]) (TC: n=5/10; TH(P): n=4/4). On the validated “Was it Worth It?” questionnaire, 92% reported the treatment “worthwhile”, 85% would repeat participation, and 100% would recommend it to others. After treatment, 93% reported a similar or increased QOL with participation and 71% deemed the experience “better than expected”, paralleling PRO outcomes from previously published trials using first-generation cooling devices. Provider feedback was favorable regarding feasibility of treatment. Conclusions: Scalp cooling with the portable Amma system was both feasible and effective in this pilot study. Point estimates of efficacy were like those reported for PAXMAN (Dean’s 0-2: 50%) and DigniCap (66%). A follow-up clinical trial is planned with a primary outcome of efficacy in patients receiving taxane-based chemotherapy (NCT06215469, PI: Rugo). Clinical trial information: NCT05508984 .

Molecular subtypes of clear cell renal carcinoma based on PCD-related long non-coding RNAs expression: insights into the underlying mechanisms and therapeutic strategies

BackgroundPCD-related long non-coding RNAs (PRLs) are rarely investigated in relation to clear cell renal carcinoma (ccRCC). As part of this study, we evaluated the immunological potential of PRL signatures as a biomarker for ccRCC prognosis and immunological function.Materials and methodsData were downloaded from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases. A Pearson correlation analysis was conducted on the 27 PCD-associated genes to determine whether lncRNAs were significantly associated with PCD. Kaplan–Meier analysis, biological function identification, immune infiltration analysis, estimation of efficacy of immunotherapy and targeted drug screening, and exploration of the landscape of mutation status were conducted by analyzing the risk scores.ResultsSeven PRLs, LINC02747, AP001636.3, AC022126.1, LINC02657, LINC02609, LINC02154, and ZNNT1, were used to divide patients with ccRCC into groups with high and low risk. High-risk patients had a worse prognosis than low-risk patients, according to the results, and the PRL signature showed promising predictive ability. More immune cells were clustered in the high-risk group, whereas the immune cell function of the low-risk group was significantly suppressed. The high-risk group was less sensitive to immunotherapy, whereas the low-risk group had positive responses to most drugs.ConclusionsCollectively, we established and verified a PRL signature that could competently guide the prognostic survival and immunotherapy of ccRCC. In addition, molecular subtypes were determined for ccRCC based on PRL expression, which may help elucidate the underlying molecular mechanism of ccRCC and develop targeted treatments.

The relationship between young college students' recognition of national COVID-19 crisis governance capabilities and the improvement of national identity: the mediating role of online participation in public health critical events.

Improving the young college students' national identity is crucial for ensuring social stability and fostering development during public health critical events such as COVID-19. Young college students' recognition of national COVID-19 crisis governance capabilities can influence their national identity, and online participation in public health criticalevents may serve as a crucial role in shaping this intricate relationship. To investigate this possibility, the present study established an intermediary model to examine the impact of online participation in public health critical events on young college students' recognition of national COVID-19 crisis governance capabilities and improvement of national identity. This cross-sectional survey study employed a convenience sampling method to investigate a total of 3041 young college students in China. The correlations between study variables were analyzed using Spearman's rank correlation. The mediation model was established using PROCESS Model 4 with 5000 bootstrap samples in SPSS. The bias-corrected bootstrap method provided statistical efficacy and identification interval estimation. Young college students' recognition of national COVID-19 crisis governance capabilities (r=0.729, P<0.001) and online participation in public health critical events (r=0.609, P<0.001) were positively correlated with improvement of their national identity. The relationship between these two factors was partially mediated by online participation in public health critical events (Indirect effect estimate=0.196, P<0.001). Online participation in public health critical events played a mediating role in the association between college students' recognition of national COVID-19 crisis governance capabilities and the improvement of national identity. Our findings provide a novel intervention strategy for improving college students' national identity, which is to encourage their online participation in public health critical events.

Mathematical modeling for estimating influenza vaccine efficacy: A case study of the Valencian Community, Spain.

Vaccine efficacy and its quantification is a crucial concept for the proper design of public health vaccination policies. In this work we proposed a mathematical model to estimate the efficacy of the influenza vaccine in a real-word scenario. In particular, our model is a SEIR-type epidemiological model, which distinguishes vaccinated and unvaccinated populations. Mathematically, its dynamics is governed by a nonlinear system of ordinary differential equations, where the non-linearity arises from the effective contacts between susceptible and infected individuals. Two key aspects of this study is that we use a vaccine distribution over time that is based on real data specific to the elderly people in the Valencian Community and the calibration process takes into account that over one influenza season a specific proportion of the population becomes infected with influenza. To consider the effectiveness of the vaccine, the model incorporates a parameter, the vaccine attenuation factor, which is related with the vaccine efficacy against the influenza virus. With this framework, in order to calibrate the model parameters and to obtain an influenza vaccine efficacy estimation, we considered the 2016–2017 influenza season in the Valencian Community, Spain, using the influenza reported cases of vaccinated and unvaccinated. In order to ensure the model identifiability, we choose to deterministically calibrate the parameters for different scenarios and we find the one with the minimum error in order to determine the vaccine efficacy. The calibration results suggest that the influenza vaccine developed for 2016–2017 influenza season has an efficacy of approximately 76.7%, and that the risk of becoming infected is five times higher for an unvaccinated individual in comparison with a vaccinated one. This estimation partially agrees with some previous studies related to the influenza vaccine. This study presents a new integrated mathematical approach to study the influenza vaccine efficacy and gives further insight into this important public health topic.

The effect of differences in trial design on estimates of efficacy of olanzapine in randomized studies

BackgroundDifferences in trial design may affect estimates of efficacy of psychotropic drugs. The purpose of this meta-analysis is to evaluate whether the use of Olanzapine (OLZ) as either investigational or control drug affects the observed efficacy of OLZ. MethodsWe performed a search for Randomized-Controlled Trials (RCTs) in which the efficacy of OLZ is assessed in patients with schizophrenia or schizoaffective disorder. We assessed overall efficacy of OLZ and performed subgroup analyses of studies with OLZ as intervention or comparator. Mixed-effect meta-regression analyses were performed. ResultsOf the 25 RCTs included, OLZ was considered as investigational drug or active control in 13 and 12 studies, respectively. The reduction of PANSS score was greater in trials in which OLZ was used as investigational drug. Multivariate meta-regression models showed that a higher PANSS score at baseline and trial duration were the main predictors of greater PANSS score reduction. ConclusionsTrials with OLZ used as investigational drug differ from those of trials with OLZ as comparator for baseline PANSS scores and study duration; these differences may produce differences in estimates of efficacy. As a consequence, the severity of illness at enrollment and trial duration should be carefully considered to ensure the reliability of indirect comparisons among antipsychotics.