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Introduction: Machine learning (ML) methods are promising and scalable alternatives for propensity score (PS) estimation, but their comparative performance in disease risk score (DRS) estimation remains unexplored. Methods: We used real-world data comparing antihypertensive users to non-users with 69 negative control outcomes, and plasmode simulations to study the performance of ML methods in PS and DRS estimation. We conducted a cohort study using UK primary care records. Further, we conducted a plasmode simulation with synthetic treatment and outcome mimicking empirical data distributions. We compared four PS and DRS estimation methods: 1. Reference: Logistic regression including clinically chosen confounders. 2. Logistic regression with L1 regularisation (LASSO). 3. Multi-layer perceptron (MLP). 4. Extreme Gradient Boosting (XgBoost). Covariate balance, coverage of the null effect of negative control outcomes (real-world data) and bias based on the absolute difference between observed and true effects (for plasmode) were estimated. 632,201 antihypertensive users and nonusers were included. Results: ML methods outperformed the reference method for PS estimation in some scenarios, both in terms of covariate balance and coverage/bias. Specifically, XgBoost achieved the best performance. DRS-based methods performed worse than PS in all tested scenarios. Discussion: We found that ML methods could be reliable alternatives for PS estimation. ML-based DRS methods performed worse than PS ones, likely given the rarity of outcomes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical efficacy of Langenlianqiao (LGLQ) oral liquid treatment and provide a reference basis for the clincal treatment of coronavirus disease 2019 (COVID-19). Design: An experimental clinical study was conducted on three groups with confirmed diagnoses of COVID-19. Site: This study was conducted at Changde Hospital. Participants: A total of 253 patients were enrolled in this study. Methods: The patients were divided into the LGLQ treatment group (100 cases), the Lianhuaqingwen (LHQW) treatment group (100 cases) and the placebo control group (53 cases), according to the treatment each group received. The occurrence of major clinical symptoms, the duration of symptom disappearance, the number of days in hospitalisation and the duration of infection were compared among the three groups. Results: Compared with the placebo control group (10.0 [1.2] d, 9.4 [1.3] d), the duration of infection and hospitalisation effectively decreased in the LGLQ group (6.8 [0.6] d, 7.4 [0.8] d) and the LHQW group (6.8 [1.0] d, 7.3 [1.0] d). Furthermore, the incidence of fatigue in the LGLQ group (4.0%) was lower compared to the LHQW group (14.0%) and the placebo control group (15.1%), but this difference was not statistically significant (P = 0.580 for LGLQ vs. LHQW, P = 0.246 for LGLQ vs. placebo). In the treatment of cough, the LGLQ group showed a significantly different effect compared to both the LHQW group (P = 0.014) and the placebo group (P = 0.016). Additionally, for dry cough specifically, LHQW was effective in reducing its incidence compared to the placebo control group (P < 0.05), while LGLQ showed no statistically significant difference from either LHQW (P = 0.39) or the placebo group (P = 0.14). However, neither the LGLQ group nor the LHQW group showed a reduction in the duration of symptom disappearance in patients with pre-existing symptoms (P > 0.05). Conclusions: Compared with the placebo control group, the LGLQ group showed an improvement in the clinical symptoms of COVID-19 and a decrease in the duration of hospitalisation and infection, which confirmed that the LGLQ treatment had the same antiviral effect as the LHQW treatment. This may provide in-depth insights for antiviral therapy research. [ABSTRACT FROM AUTHOR]

This study aimed to assess the efficacy of hyperbaric oxygen therapy (HBOT) in patients with central retinal artery occlusion (CRAO) by analyzing changes in visual acuity (VA) and enhanced depth imaging optical coherence tomography (EDI-OCT) parameters. A comparative retrospective study was conducted by reviewing the medical records of all HBO-treated RAO patients in our department and comparing them with matched RAO patients who did not receive HBO treatment. All patients treated with HBO received treatment within 7 days of the onset of visual symptoms. Baseline characteristics were compared, and VA and OCT parameters were evaluated at baseline and follow-up visits. A total of 50 eyes from 50 patients were included, with 29 eyes in the HBOT group and 21 eyes in the control group. The mean BCVA of the HBOT group at the initial visit was 2.03 logMAR, which improved to 1.55 logMAR at 6 months, with the change being statistically significant (P < 0.01), while the control group's BCVA remained almost unchanged, from 2.1 to 2.11 logMAR (P = 0.762). The central choroidal thickness increased significantly in the HBOT group over the subsequent period. The central fovea, and outer retinal layer thickness in the HBOT group were significantly greater than those in the control group at the 6-month follow-up after treatment. HBOT appears to be effective in improving VA and inducing favorable changes in OCT parameters in patients with CRAO. It helps to preserve retinal layer thickness, especially in the outer retinal layer. [ABSTRACT FROM AUTHOR]

Background: This study aims to evaluate the two-year outcomes of polypoidal choroidal vasculopathy (PCV) treated with conbercept and to investigate the predictive response factors. Methods: Consecutive patients with PCV who received three-loading intravitreal conbercept, followed by as-needed reinjections, were studied retrospectively. The best corrected visual acuity (BCVA), central retinal thickness (CRT) and polyps were evaluated. Patients who achieved dry maculae in month 6 were categorised into the dry group, or otherwise, into the non-dry group. The predictive factors for a dry macula were evaluated. Results: A total of 25 eyes from 25 patients (17 males; mean age: 62.8 ± 6.4 years) were included. At month 24, the average BCVA increased significantly from 49.9 ± 15.0 letters to 57.2 ± 16.0 letters (p = 0.040); the average CRT decreased significantly from 430.16 ± 166.55 μm to 278.31 ± 157.34 μm (p = 0.00), and 88% of the eyes achieved dry maculae. The number of polyps changed from 55 to 20 (fading rate: 63.6%; p < 0.001). The mean number of intravitreal injections was 8.6 ± 5.4. The dry group (10 eyes, 40%) was more likely to have higher branching vascular network vessel density (BVN VD; p = 0.021), submacular haemorrhages (p = 0.011) but lack polyp-related serous pigmented epithelial detachment (PED) (p = 0.037). Conclusions: Conbercept was effective in eyes with PCV at maintaining functional and anatomical improvement. Baseline characteristics, including BVN VD, the presence of polyps with serous PED and submacular haemorrhage, seemed to be related to the response to conbercept. [ABSTRACT FROM AUTHOR]

Background: Patients with severe infection often require careful fluid management. Intravenous linezolid can increase the fluid volume, whereas oral linezolid can effectively limit the fluid volume. However, the differences in the treatment effect and incidence of thrombocytopenia between oral and intravenous linezolid in patients with severe infection remain unclear. Methods: Patients who received linezolid in the intensive care unit of PLA General Hospital from December 2010 to December 2020 were divided into an oral group and intravenous group according to the route of administration, and we further established the PO group and PO-match group by propensity score matching. The anti-infection effect of linezolid and incidence of thrombocytopenia were compared between the two groups. Results: In total, 177 patients were enrolled in the study (59 in PO group and 118 in PO-match group). The microbial clearance rate and clinical cure rate were similar between the two groups (70.0% vs. 79.3%, P = 0.293; 72.9% vs. 83.9%, P = 0.213). The 30-day mortality rate was slightly higher in the PO group than in the PO-match group, but the difference was not statistically significant (13.6% vs. 6.8%, P = 0.138). There was no difference in the incidence of thrombocytopenia between the two groups (62.7% vs. 65.3%, P = 0.739). Conclusions: There were no significant differences in the treatment effect or incidence of thrombocytopenia between oral and intravenous administration of linezolid in patients with severe infection. [ABSTRACT FROM AUTHOR]

The Circular Electron–Positron Collider (CEPC) in China can also work as an excellent powerful synchrotron light source, which can generate high‐quality synchrotron radiation. This synchrotron radiation has potential advantages in the medical field as it has a broad spectrum, with energies ranging from visible light to X‐rays used in conventional radiotherapy, up to several megaelectronvolts. FLASH radiotherapy is one of the most advanced radiotherapy modalities. It is a radiotherapy method that uses ultra‐high dose rate irradiation to achieve the treatment dose in an instant; the ultra‐high dose rate used is generally greater than 40 Gy s−1, and this type of radiotherapy can protect normal tissues well. In this paper, the treatment effect of CEPC synchrotron radiation for FLASH radiotherapy was evaluated by simulation. First, a Geant4 simulation was used to build a synchrotron radiation radiotherapy beamline station, and then the dose rate that the CEPC can produce was calculated. A physicochemical model of radiotherapy response kinetics was then established, and a large number of radiotherapy experimental data were comprehensively used to fit and determine the functional relationship between the treatment effect, dose rate and dose. Finally, the macroscopic treatment effect of FLASH radiotherapy was predicted using CEPC synchrotron radiation through the dose rate and the above‐mentioned functional relationship. The results show that the synchrotron radiation beam from the CEPC is one of the best beams for FLASH radiotherapy. [ABSTRACT FROM AUTHOR]

Vacuum preloading is a commonly adopted method for improving soft ground. During the preloading period, the applied vacuum pressure is constant or multistaged, implying that the vacuum pump must work continuously with constant or increasing operating power. To reduce the energy consumption of the vacuum pump, a new loading strategy of cyclic vacuum loading was proposed in this study, whereby the pump is periodically switched on and off, and hence the vacuum pressure ascends and descends accordingly. To guide the design of cyclic vacuum preloading, a large-strain radial consolidation theory incorporating the shifting of the consolidation status of ground soil from normally consolidated to overconsolidated (and vice versa) was established in the present study. Based on the established theory, the treatment effects of cyclic vacuum loading can be quantitatively determined, including the ground settlement and the degree of consolidation, while the energy consumption can be simply determined by multiplying the power by the operating time of the vacuum pump, which works only during the ascending stage of cyclic vacuum pressure. Two cases of the cyclic vacuum preloading strategy were evaluated herein, that is, the complete cyclic vacuum loading and combined cyclic/constant vacuum loading cases. Finally, experimental tests were conducted to demonstrate the energy-saving effect of cyclic vacuum preloading. Compared to the conventional vacuum preloading strategy (i.e., constant vacuum pressure), the energy consumption of the cyclic vacuum loading strategy can be drastically reduced (80% reduction), while the treatment effects remain basically unaffected. [ABSTRACT FROM AUTHOR]

Abstract Background This study aims to evaluate the two-year outcomes of polypoidal choroidal vasculopathy (PCV) treated with conbercept and to investigate the predictive response factors. Methods Consecutive patients with PCV who received three-loading intravitreal conbercept, followed by as-needed reinjections, were studied retrospectively. The best corrected visual acuity (BCVA), central retinal thickness (CRT) and polyps were evaluated. Patients who achieved dry maculae in month 6 were categorised into the dry group, or otherwise, into the non-dry group. The predictive factors for a dry macula were evaluated. Results A total of 25 eyes from 25 patients (17 males; mean age: 62.8 ± 6.4 years) were included. At month 24, the average BCVA increased significantly from 49.9 ± 15.0 letters to 57.2 ± 16.0 letters (p = 0.040); the average CRT decreased significantly from 430.16 ± 166.55 μm to 278.31 ± 157.34 μm (p = 0.00), and 88% of the eyes achieved dry maculae. The number of polyps changed from 55 to 20 (fading rate: 63.6%; p

Abstract This study aimed to assess the efficacy of hyperbaric oxygen therapy (HBOT) in patients with central retinal artery occlusion (CRAO) by analyzing changes in visual acuity (VA) and enhanced depth imaging optical coherence tomography (EDI-OCT) parameters. A comparative retrospective study was conducted by reviewing the medical records of all HBO-treated RAO patients in our department and comparing them with matched RAO patients who did not receive HBO treatment. All patients treated with HBO received treatment within 7 days of the onset of visual symptoms. Baseline characteristics were compared, and VA and OCT parameters were evaluated at baseline and follow-up visits. A total of 50 eyes from 50 patients were included, with 29 eyes in the HBOT group and 21 eyes in the control group. The mean BCVA of the HBOT group at the initial visit was 2.03 logMAR, which improved to 1.55 logMAR at 6 months, with the change being statistically significant (P

Abstract Objective To evaluate the clinical efficacy of Langenlianqiao (LGLQ) oral liquid treatment and provide a reference basis for the clincal treatment of coronavirus disease 2019 (COVID-19). Design An experimental clinical study was conducted on three groups with confirmed diagnoses of COVID-19. Site This study was conducted at Changde Hospital. Participants A total of 253 patients were enrolled in this study. Methods The patients were divided into the LGLQ treatment group (100 cases), the Lianhuaqingwen (LHQW) treatment group (100 cases) and the placebo control group (53 cases), according to the treatment each group received. The occurrence of major clinical symptoms, the duration of symptom disappearance, the number of days in hospitalisation and the duration of infection were compared among the three groups. Results Compared with the placebo control group (10.0 [1.2] d, 9.4 [1.3] d), the duration of infection and hospitalisation effectively decreased in the LGLQ group (6.8 [0.6] d, 7.4 [0.8] d) and the LHQW group (6.8 [1.0] d, 7.3 [1.0] d). Furthermore, the incidence of fatigue in the LGLQ group (4.0%) was lower compared to the LHQW group (14.0%) and the placebo control group (15.1%), but this difference was not statistically significant (P = 0.580 for LGLQ vs. LHQW, P = 0.246 for LGLQ vs. placebo). In the treatment of cough, the LGLQ group showed a significantly different effect compared to both the LHQW group (P = 0.014) and the placebo group (P = 0.016). Additionally, for dry cough specifically, LHQW was effective in reducing its incidence compared to the placebo control group (P 0.05). Conclusions Compared with the placebo control group, the LGLQ group showed an improvement in the clinical symptoms of COVID-19 and a decrease in the duration of hospitalisation and infection, which confirmed that the LGLQ treatment had the same antiviral effect as the LHQW treatment. This may provide in-depth insights for antiviral therapy research.

The Circular Electron–Positron Collider (CEPC) in China can also work as an excellent powerful synchrotron light source, which can generate high-quality synchrotron radiation. This synchrotron radiation has potential advantages in the medical field as it has a broad spectrum, with energies ranging from visible light to X-rays used in conventional radiotherapy, up to several megaelectronvolts. FLASH radiotherapy is one of the most advanced radiotherapy modalities. It is a radiotherapy method that uses ultra-high dose rate irradiation to achieve the treatment dose in an instant; the ultra-high dose rate used is generally greater than 40 Gy s−1, and this type of radiotherapy can protect normal tissues well. In this paper, the treatment effect of CEPC synchrotron radiation for FLASH radiotherapy was evaluated by simulation. First, a Geant4 simulation was used to build a synchrotron radiation radiotherapy beamline station, and then the dose rate that the CEPC can produce was calculated. A physicochemical model of radiotherapy response kinetics was then established, and a large number of radiotherapy experimental data were comprehensively used to fit and determine the functional relationship between the treatment effect, dose rate and dose. Finally, the macroscopic treatment effect of FLASH radiotherapy was predicted using CEPC synchrotron radiation through the dose rate and the above-mentioned functional relationship. The results show that the synchrotron radiation beam from the CEPC is one of the best beams for FLASH radiotherapy.

Abstract Background According to long-term follow-up data of malignant tumor patients, assessing treatment effects requires careful consideration of competing risks. The commonly used cause-specific hazard ratio (CHR) and sub-distribution hazard ratio (SHR) are relative indicators and may present challenges in terms of proportional hazards assumption and clinical interpretation. Recently, the restricted mean time lost (RMTL) has been recommended as a supplementary measure for better clinical interpretation. Moreover, for observational study data in epidemiological and clinical settings, due to the influence of confounding factors, covariate adjustment is crucial for determining the causal effect of treatment. Methods We construct an RMTL estimator after adjusting for covariates based on the inverse probability weighting method, and derive the variance to construct interval estimates based on the large sample properties. We use simulation studies to study the statistical performance of this estimator in various scenarios. In addition, we further consider the changes in treatment effects over time, constructing a dynamic RMTL difference curve and corresponding confidence bands for the curve. Results The simulation results demonstrate that the adjusted RMTL estimator exhibits smaller biases compared with unadjusted RMTL and provides robust interval estimates in all scenarios. This method was applied to a real-world cervical cancer patient data, revealing improvements in the prognosis of patients with small cell carcinoma of the cervix. The results showed that the protective effect of surgery was significant only in the first 20 months, but the long-term effect was not obvious. Radiotherapy significantly improved patient outcomes during the follow-up period from 17 to 57 months, while radiotherapy combined with chemotherapy significantly improved patient outcomes throughout the entire period. Conclusions We propose the approach that is easy to interpret and implement for assessing treatment effects in observational competing risk data.

Objective Elastic strip is a critical component of rail vibration reduction fasteners, its mechanical performance and fatigue-load bearing capacity are crucial for urban rail transit train operational safety and track service life. Given the frequent occurrence of elastic strip failures, it is necessary to analyze the fracture causes and develop reasonable treatment measures. Method Based on the concentrated fracture of elastic strips in an urban rail transit line section, the fracture type of elastic strips is determined as fatigue fracture through analysis of the breakage. Since chemical composition and physical property analysis of elastic strips fails to reveal any abnormal conditions, the natural frequency of the elastic strips is obtained through simulation and experimental analysis. The vibration characteristics of the track and elastic strips are determined through track dynamic testing in elastic strip fractured section. Based on this, rail corrugation is identified as the main cause of repeated elastic strip fractures. Reasonable treatment measures are formulated accordingly, and the number of elastic strip fractures before and after treatment is statistically analyzed. Result & Conclusion Rail grinding measures can effectively suppress rail corrugation, significantly reducing elastic strip fracture occurrence, further confirming rail corrugation as the main cause of elastic strip fractures.

Abstract Background Patients with severe infection often require careful fluid management. Intravenous linezolid can increase the fluid volume, whereas oral linezolid can effectively limit the fluid volume. However, the differences in the treatment effect and incidence of thrombocytopenia between oral and intravenous linezolid in patients with severe infection remain unclear. Methods Patients who received linezolid in the intensive care unit of PLA General Hospital from December 2010 to December 2020 were divided into an oral group and intravenous group according to the route of administration, and we further established the PO group and PO-match group by propensity score matching. The anti-infection effect of linezolid and incidence of thrombocytopenia were compared between the two groups. Results In total, 177 patients were enrolled in the study (59 in PO group and 118 in PO-match group). The microbial clearance rate and clinical cure rate were similar between the two groups (70.0% vs. 79.3%, P = 0.293; 72.9% vs. 83.9%, P = 0.213). The 30-day mortality rate was slightly higher in the PO group than in the PO-match group, but the difference was not statistically significant (13.6% vs. 6.8%, P = 0.138). There was no difference in the incidence of thrombocytopenia between the two groups (62.7% vs. 65.3%, P = 0.739). Conclusions There were no significant differences in the treatment effect or incidence of thrombocytopenia between oral and intravenous administration of linezolid in patients with severe infection.

Abstract Background Many randomized controlled trials (RCTs) and network meta-analyses have demonstrated that the progression-free survival (PFS) and overall survival (OS) of advanced non-small cell lung cancer (NSCLC) patients can be improved through combination immunotherapy or monotherapies. However, time-dependent analysis of the treatment effect is currently lacking. Thus, we aimed to evaluate the efficacy of first-line immunotherapy, and establish a hazard ratio function to reflect the time-varying progression or mortality risk of patients with NSCLC. Methods Seventeen clinical trials were selected based on search strategy. Baseline characteristics, including the age, sex, smoking status, geographical region, and Eastern Cooperative Oncology Group (ECOG) performance status of patients, were balanced, resulting in ten immunotherapies from nine appropriate clinical trials to conduct treatment effect comparison. Results We found that nivolumab plus ipilimumab (nivo + ipi) improved the PFS and OS over time. The hazard ratio of nivo + ipi, relative to that of pembrolizumab, decreased from 1.11 to 0.36 for PFS, and from 0.93 to 0.49 for OS over a 10-year period. In terms of the response to immunotherapy in patients with different PD-L1 expression levels, patients with PD-L1 > = 50% experienced lower rates of progression and a reduced mortality risk over time. The hazard ratio of patients with PD-L1 > = 50% relative to all of the patients decreased from 0.73 to 0.69 for PFS, and from 0.78 to 0.67 for OS. Conclusions Based on the fact that time-dependent progression and mortality risk existed during the treatment duration, physicians should select a suitable treatment regimen for patients based on the hazard ratio.

Background: According to long-term follow-up data of malignant tumor patients, assessing treatment effects requires careful consideration of competing risks. The commonly used cause-specific hazard ratio (CHR) and sub-distribution hazard ratio (SHR) are relative indicators and may present challenges in terms of proportional hazards assumption and clinical interpretation. Recently, the restricted mean time lost (RMTL) has been recommended as a supplementary measure for better clinical interpretation. Moreover, for observational study data in epidemiological and clinical settings, due to the influence of confounding factors, covariate adjustment is crucial for determining the causal effect of treatment. Methods: We construct an RMTL estimator after adjusting for covariates based on the inverse probability weighting method, and derive the variance to construct interval estimates based on the large sample properties. We use simulation studies to study the statistical performance of this estimator in various scenarios. In addition, we further consider the changes in treatment effects over time, constructing a dynamic RMTL difference curve and corresponding confidence bands for the curve. Results: The simulation results demonstrate that the adjusted RMTL estimator exhibits smaller biases compared with unadjusted RMTL and provides robust interval estimates in all scenarios. This method was applied to a real-world cervical cancer patient data, revealing improvements in the prognosis of patients with small cell carcinoma of the cervix. The results showed that the protective effect of surgery was significant only in the first 20 months, but the long-term effect was not obvious. Radiotherapy significantly improved patient outcomes during the follow-up period from 17 to 57 months, while radiotherapy combined with chemotherapy significantly improved patient outcomes throughout the entire period. Conclusions: We propose the approach that is easy to interpret and implement for assessing treatment effects in observational competing risk data. [ABSTRACT FROM AUTHOR]

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Analyzing treatment or exposure effect is a major research theme in scientific studies. In the current big-data era where multiple sources of data are available, it is of interest to perform a synthesized analysis of treatment effects by integrating information from different data sources or studies. However, studies may contain heterogeneous and incomplete covariate sets, and individual data therein may not be accessible. We apply and extend the generalized meta-analysis method to integrate summary results (e.g., regression coefficients) of outcome and treatment (propensity score, PS) regression analyses across different datasets that may contain heterogeneous covariate sets. The proposed integrated analysis utilizes a reference dataset, which contains data on the complete set of covariates. The asymptotic distribution for the proposed integrated estimator is established. Simulations reveal that the proposed estimator performs well. We apply the proposed method to obtain the causal effect of waist circumference on hypertension by integrating two existing outcomes and PS regression analyses with different sets of covariates. [ABSTRACT FROM AUTHOR]

Background: Many randomized controlled trials (RCTs) and network meta-analyses have demonstrated that the progression-free survival (PFS) and overall survival (OS) of advanced non-small cell lung cancer (NSCLC) patients can be improved through combination immunotherapy or monotherapies. However, time-dependent analysis of the treatment effect is currently lacking. Thus, we aimed to evaluate the efficacy of first-line immunotherapy, and establish a hazard ratio function to reflect the time-varying progression or mortality risk of patients with NSCLC. Methods: Seventeen clinical trials were selected based on search strategy. Baseline characteristics, including the age, sex, smoking status, geographical region, and Eastern Cooperative Oncology Group (ECOG) performance status of patients, were balanced, resulting in ten immunotherapies from nine appropriate clinical trials to conduct treatment effect comparison. Results: We found that nivolumab plus ipilimumab (nivo + ipi) improved the PFS and OS over time. The hazard ratio of nivo + ipi, relative to that of pembrolizumab, decreased from 1.11 to 0.36 for PFS, and from 0.93 to 0.49 for OS over a 10-year period. In terms of the response to immunotherapy in patients with different PD-L1 expression levels, patients with PD-L1 > = 50% experienced lower rates of progression and a reduced mortality risk over time. The hazard ratio of patients with PD-L1 > = 50% relative to all of the patients decreased from 0.73 to 0.69 for PFS, and from 0.78 to 0.67 for OS. Conclusions: Based on the fact that time-dependent progression and mortality risk existed during the treatment duration, physicians should select a suitable treatment regimen for patients based on the hazard ratio. [ABSTRACT FROM AUTHOR]

Objectives: If questionnaires contributing to the diagnosis of dry eye disease are to be recommended as alternatives to existing questionnaires, they must be comparable, with similar repeatability and treatment sensitivity. Comparability was thus examined for three common dry eye questionnaires along with identifying the individual questions that most strongly predicted overall scores. Methods: Anonymised data (n = 329) collected via the Ocular Surface Disease Index (OSDI), 5-item Dry Eye Questionnaire (DEQ-5) and Symptom Assessment in Dry Eye (SANDE) questionnaires (including responses to individual questions) from consenting patients were drawn from real-world dry eye clinics/registries in the United Kingdom, Australia and New Zealand; at follow-up, normalised changes were evaluated in 54 of these patients. Treatment data were also analysed from a 6-month, randomised controlled trial assessing artificial tear supplement treatments with 43 responders and 13 non-responders to treatment identified. The questions extracted from the OSDI which form the abbreviated 6-item OSDI were also analysed. Results: The agreement between the questionnaires ranged from r = 0.577 to 0.754 (all p < 0.001). For the OSDI, three questions accounted for 89.1% of the variability in the total score. The correlation between the OSDI and OSDI-6 was r = 0.939, p < 0.001. For the DEQ-5, two questions accounted for 88.5% of the variance in the total score. Normalised treatment changes were also only moderately correlated between the questionnaires (r = 0.441 to 0.595, p < 0.01). For non-responders, variability was 7.4% with both OSDI and OSDI-6, 9.7% with DEQ-5, 12.1% with SANDE-frequency and 11.9% with SANDE-severity scale. For responders, improvement with drops was detected with a 19.1% change in OSDI, 20.2% in OSDI-6, 20.9% in DEQ-5, and 27.5%/23.6% in SANDE-frequency/severity scales. Conclusions: Existing commonly used dry eye questionnaire scores do not show high levels of correlation. The OSDI was the least variable of the questionnaires and while displaying a slightly lower treatment effect than either the DEQ or SANDE, it was more sensitive to detection of a treatment effect. The quicker-to-complete OSDI-6 exhibited essentially the same outcome as the OSDI, with similar variability and treatment sensitivity. [ABSTRACT FROM AUTHOR]

Background: There is limited knowledge regarding the comparative patient-reported outcomes (PROMs) and effect sizes (ESs) across orthopedic elective surgery. Methods: All patient data between January 2020 and December 2022 were collected, and treatment outcomes assessed as a PROM difference between baseline and one-year follow-up. The cohort was divided into subgroups (hand, elbow, shoulder, spine, hip, knee, and foot/ankle). The PROM ESs were calculated for each patient separately, and patients with ES > 0.5 were considered responders. Results: In total, 7695 patients were operated on. The mean ES across all patient groups was 1.81 (SD 1.41), and the largest ES was observed in shoulder patients and the smallest in hand patients. Overall, shoulder, hip, and knee patients had a larger ES compared to hand, spine, and foot/ankle patients (p < 0.0001). The proportion of positive responders ranged between 91–94% in the knee, shoulder, and hip, and 69–70% in the hand, spine, and foot/ankle subgroups. Conclusions: The ESs are generally high throughout elective orthopedic surgery. However, based on our institutional observations, shoulder, hip, and knee patients experience larger treatment effects compared to hand, spine, and foot/ankle patients, among whom there are also more non-responders. The expected treatment outcomes should be clearly communicated to patients when considering elective surgery. Because of the study limitations, the results should be approached with some caution. [ABSTRACT FROM AUTHOR]

IntroductionMachine learning (ML) methods are promising and scalable alternatives for propensity score (PS) estimation, but their comparative performance in disease risk score (DRS) estimation remains unexplored.MethodsWe used real-world data comparing antihypertensive users to non-users with 69 negative control outcomes, and plasmode simulations to study the performance of ML methods in PS and DRS estimation. We conducted a cohort study using UK primary care records. Further, we conducted a plasmode simulation with synthetic treatment and outcome mimicking empirical data distributions. We compared four PS and DRS estimation methods: 1. Reference: Logistic regression including clinically chosen confounders. 2. Logistic regression with L1 regularisation (LASSO). 3. Multi-layer perceptron (MLP). 4. Extreme Gradient Boosting (XgBoost). Covariate balance, coverage of the null effect of negative control outcomes (real-world data) and bias based on the absolute difference between observed and true effects (for plasmode) were estimated. 632,201 antihypertensive users and nonusers were included.ResultsML methods outperformed the reference method for PS estimation in some scenarios, both in terms of covariate balance and coverage/bias. Specifically, XgBoost achieved the best performance. DRS-based methods performed worse than PS in all tested scenarios.DiscussionWe found that ML methods could be reliable alternatives for PS estimation. ML-based DRS methods performed worse than PS ones, likely given the rarity of outcomes.

Farmers in Ethiopia and other sub-Saharan African countries often implement various agricultural land management (ALM) practices to mitigate the negative impact of land degradation, increase crop yield, improve income, and safeguard the security of food. Despite the widespread use of these measures, their effect on crop productivity and related income has received relatively little attention in research, particularly in the context of mixed farming systems. The objective of this study was to assess the effects of ALM practices on crop production and household income in southern Ethiopia. Data was gathered from 423 sampled respondents, which included adopters and non-adopters of ALM practices. This study adopted multistage sampling to gather the data through a survey questionnaire. This study’s findings reveal that ALM strategies have a considerable impact on crop productivity and the incomes of farm households (p

Purpose of the study. Determination of the expression of microRNA‑34, microRNA‑130, microRNA‑148, microRNA‑181, microRNA‑194 and microRNA‑605 in colon tumor tissue depending on the clinical and morphological features of the tumor and the effectiveness of treatment.Materials and methods. The study included 56 patients diagnosed with colorectal cancer aged 43 to 75 years with the average age of 54 years. Taking into account the local prevalence of the process patients received surgical or combined treatment, including neoadjuvant chemotherapy, in the clinics of the Cancer Research Institute, Tomsk NRMC. MicroRNA expression was determined by polymerase chain reaction (PCR) in real time.Results. The obtained information revealed the relation of microRNA‑130 to the tumor size. The development of regional metastases was associated with changes in microRNA‑130, microRNA‑194 and microRNA‑605. The level of histological organization of the tumor was associated with microRNA‑34, microRNA‑130, microRNA‑148, and the response to therapy – with microRNA‑130, microRNA‑148 and microRNA‑605. In addition, according to the study, the significance of microRNA‑130 was revealed, which is associated with tumor spread, histological differentiation and response to antitumor therapy.Conclusion. The features of expression of microRNA‑34, microRNA‑130, microRNA‑148, microRNA‑181, microRNA‑194 and microRNA‑605 associated with clinical and morphological features of colon tumors were revealed. Correlations between the studied indicators are noted, which probably determine the outcome and prognosis of the disease.

AbstractTo correctly evaluate the effects of treatments, conducting randomized controlled trials (RCTs) is a reasonable approach. However, because it is generally difficult to implement RCTs for all treatments, methods to estimate the treatment effects using observational data have been actively studied and used in various decision-making processes. Observational data accumulated in business activities and elsewhere contains the results of various previously implemented treatments, and correctly estimating the effects of any given treatment without separating the impacts of other treatments is challenging. Against this background, this paper proposes a method to estimate the effects of multiple treatments of various types while considering various causal relationships. Specifically, the proposal is a variational inference method that estimates the effect of multiple treatments using four latent factors estimated from observations, making assumptions that are independent of the type and number of treatments. The proposed method makes it possible to appropriately estimate the effects of measures even in situations with complex causal relationships. In addition, in situations where measures with continuous parameters are being implemented, it is possible to estimate the effects of measures that have not been implemented in the past by treating the content of the measures as a continuous variable.

ObjectiveThe combination of d-methylphenidate and guanfacine (an α-2A adrenergic agonist) may be an effective alternative to either agent as monotherapy in children with attention-deficit/hyperactivity disorder (ADHD). This study investigated the neural mechanisms underlying medication effects using cortical source analysis of electroencephalography (EEG) data.MethodA total of 172 children with ADHD (aged 7-14; 118 boys) completed an 8-week randomized, double-blind, comparative study with 3 treatment arms: d-methylphenidate, guanfacine, or their combination. EEG modulations of brain oscillations at baseline and end point were measured during a spatial working memory task from cortical sources localized within the anterior cingulate (midfrontal) and primary visual cortex (midoccipital), based on previously reported ADHD and control differences. Linear mixed models examined treatment effects on EEG and performance measures.ResultsCombined treatment decreased midoccipital EEG power across most frequency bands and task phases. Several midoccipital EEG measures also showed significantly greater changes with combined treatment than with monotherapies. D-methylphenidate significantly increased midoccipital theta during retrieval, while guanfacine produced only trend-level reductions in midoccipital alpha during maintenance and retrieval. Task accuracy improved with combined treatment, was unchanged with d-methylphenidate, and worsened with guanfacine. Treatment-related changes in midoccipital power correlated with improvement in ADHD severity.ConclusionThese findings show that combined treatment ameliorates midoccipital neural activity associated with treatment-related behavioral improvements and previously implicated in visuo-attentional deficits in ADHD. Both monotherapies had limited effects on EEG measures, with guanfacine further showing detrimental effects on performance. The identified midoccipital EEG profile may aid future treatment monitoring for children with ADHD.Clinical trial registration informationSingle Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder (Project1); https://clinicaltrials.gov/; NCT00429273.Diversity & inclusion statementWe worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure sex and gender balance in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. We actively worked to promote sex and gender balance in our author group.

The Mann–Whitney effect is a measure for comparing survival distributions between two groups. The Mann–Whitney effect is interpreted as the probability that a randomly selected subject in a group survives longer than a randomly selected subject in the other group. Under the independence assumption of two groups, the Mann–Whitney effect can be expressed as the traditional integral formula of survival functions. However, when the survival times in two groups are not independent of each other, the traditional formula of the Mann–Whitney effect has to be modified. In this article, we propose a copula-based approach to compute the Mann–Whitney effect with parametric survival models under dependence of two groups, which may arise in the potential outcome framework. In addition, we develop a Shiny web app that can implement the proposed method via simple commands. Through a simulation study, we show the correctness of the proposed calculator. We apply the proposed methods to two real datasets. [ABSTRACT FROM AUTHOR]

To compare the treatment efficacy of childhood myopia control optical interventions [spectacles, soft contact lenses (SCLs) and orthokeratology (OK) lenses], explore the consistency of treatment efficacies during the treatment period and evaluate the impact of baseline spherical equivalent refraction (SER), axial length (AL) and age on the treatment effect. A literature search of EMBASE, PubMed and Google Scholar databases identified 220 articles published between January 2000 and April 2022, which reported the treatment efficacy by differences in the SER and AL change between intervention and control groups. Thirty‐five articles were included in the analysis. Treatment effect sizes (ESs) were calculated, where more positive and negative directions indicated greater treatment efficacy for SER and AL respectively. For SER, the ESs with peripheral add design spectacles (0.66) and SCLs (0.53) were large but not significantly different between treatment types (p = 0.69). For AL, ESs with peripheral add design spectacles (−0.37), SCLs (−0.55) and OK lenses (−0.93) were large, but OK lenses had a significantly greater effect than peripheral add design spectacles (p ≤ 0.001). ESs were large during the first 12 months of treatment for all interventions [peripheral add design SCLs and OK (F ≥ 5.39, p ≤ 0.01), peripheral add design spectacles (F = 0.47, p = 0.63)] but reduced towards the end of 24–36 months of treatment. Baseline SER had an impact on the treatment effect with peripheral add design spectacles only. Optical interventions are efficacious in controlling childhood myopia progression. However, treatment effects were largest only during the first 12 months of treatment and reduced over time. [ABSTRACT FROM AUTHOR]

Introduction: In research, it is crucial to accurately estimate treatment effects and analyze experimental results. Common methods include comparing outcome differences between different groups and using linear regression models for analysis. However, observational studies may have significantly different distributions of confounding variables between control and treatment groups, leading to errors in estimating treatment effects. Methods: The propensity score methods can address this issue by weighting or matching samples to approximate the scenario of a randomized experiment and allow for more accurate estimation of treatment this paper. Results: We use propensity score methods to analyze three datasets from observational studies and draw conclusions different from those in the original text. Furthermore, we simulate three scenarios, and the results demonstrate the superiority of propensity score methods over methods such as linear regression in addressing selection bias. Discussion: Therefore, it is essential to thoroughly consider the characteristics of the data and select appropriate methods to ensure reliable conclusions in practical data analysis. [ABSTRACT FROM AUTHOR]

AbstractInterference occurs when a unit’s treatment (or exposure) affects another unit’s outcome. In some settings, units may be grouped into clusters such that it is reasonable to assume that interference, if present, only occurs between individuals in the same cluster, that is, there is clustered interference. Various causal estimands have been proposed to quantify treatment effects under clustered interference from observational data, but these estimands either entail treatment policies lacking real-world relevance or are based on parametric propensity score models. Here, we propose new causal estimands based on modification of the propensity score distribution which may be more relevant in many contexts and are not based on parametric models. Nonparametric sample splitting estimators of the new estimands are constructed, which allow for flexible data-adaptive estimation of nuisance functions and are consistent, asymptotically normal, and efficient, converging at the usual parametric rate. Simulations show the finite sample performance of the proposed estimators. The proposed methods are applied to evaluate the effect of water, sanitation, and hygiene facilities on diarrhea among children in Senegal. Supplementary materials for this article are available online, including a standardized description of the materials available for reproducing the work. [ABSTRACT FROM AUTHOR]

Farmers in Ethiopia and other sub-Saharan African countries often implement various agricultural land management (ALM) practices to mitigate the negative impact of land degradation, increase crop yield, improve income, and safeguard the security of food. Despite the widespread use of these measures, their effect on crop productivity and related income has received relatively little attention in research, particularly in the context of mixed farming systems. The objective of this study was to assess the effects of ALM practices on crop production and household income in southern Ethiopia. Data was gathered from 423 sampled respondents, which included adopters and non-adopters of ALM practices. This study adopted multistage sampling to gather the data through a survey questionnaire. This study's findings reveal that ALM strategies have a considerable impact on crop productivity and the incomes of farm households (p<0.05). Moreover, the adoption of integrated physical and biological intervention practices for longer durations resulted in a steady increase in both crop productivity and household incomes. Furthermore, analysis of the effect of long-term treatment indicates that farms show a significant and increasing marginal benefit to production after six years of intervention. These findings imply that integrating ALM practices and maintaining them for an extended period (i.e., 10 years) will help to increase crop productivity and household incomes. Hence, adopting a wider range of physical and biological ALM measures and ensuring their continual adoption are key strategies for improving crop production and increasing household income. This strategy will have significant policy implications and provide a solid foundation for sustainable agricultural development. [ABSTRACT FROM AUTHOR]

Background: Azvudine has clinical benefits and acceptable safety against COVID-19, including in patients with comorbidities, but there is a lack of available data for its use in older adult patients. This study explored the effectiveness and safety of azvudine in older adults with mild or moderate COVID-19. Methods: This retrospective cohort study included patients aged ≥80 diagnosed with COVID-19 at the Central Hospital of Shaoyang between October and November 2022. According to the therapies they received, the eligible patients were divided into the azvudine, nirmatrelvir/ritonavir, and standard-of-care (SOC) groups. The outcomes were the proportion of patients progressing to severe COVID-19, time to nucleic acid negative conversion (NANC), and the 5-, 7-, 10-, and 14-day NANC rates from admission. Results: The study included 55 patients treated with azvudine (n = 14), nirmatrelvir/ritonavir (n = 18), and SOC (n = 23). The median time from symptom onset to NANC of the azvudine, nirmatrelvir/ritonavir, and SOC groups was 14 (range, 6–25), 15 (range, 11–24), and 19 (range, 18–23) days, respectively. The median time from treatment initiation to NANC of the azvudine and nirmatrelvir/ritonavir groups was 8 (range, 4–20) and 9 (range, 5–16) days, respectively. The median length of hospital stay in the three groups was 10.5 (range, 5–23), 13.5 (range, 10–21), and 17 (range, 10–23) days, respectively. No treatment-related adverse events or serious adverse events were reported. Conclusion: Azvudine showed satisfactory effectiveness and acceptable safety in older adults with mild or moderate COVID-19. Therefore, azvudine could be a treatment option for this special patient population. [ABSTRACT FROM AUTHOR]

Abstract Background Azvudine has clinical benefits and acceptable safety against COVID-19, including in patients with comorbidities, but there is a lack of available data for its use in older adult patients. This study explored the effectiveness and safety of azvudine in older adults with mild or moderate COVID-19. Methods This retrospective cohort study included patients aged ≥80 diagnosed with COVID-19 at the Central Hospital of Shaoyang between October and November 2022. According to the therapies they received, the eligible patients were divided into the azvudine, nirmatrelvir/ritonavir, and standard-of-care (SOC) groups. The outcomes were the proportion of patients progressing to severe COVID-19, time to nucleic acid negative conversion (NANC), and the 5-, 7-, 10-, and 14-day NANC rates from admission. Results The study included 55 patients treated with azvudine (n = 14), nirmatrelvir/ritonavir (n = 18), and SOC (n = 23). The median time from symptom onset to NANC of the azvudine, nirmatrelvir/ritonavir, and SOC groups was 14 (range, 6–25), 15 (range, 11–24), and 19 (range, 18–23) days, respectively. The median time from treatment initiation to NANC of the azvudine and nirmatrelvir/ritonavir groups was 8 (range, 4–20) and 9 (range, 5–16) days, respectively. The median length of hospital stay in the three groups was 10.5 (range, 5–23), 13.5 (range, 10–21), and 17 (range, 10–23) days, respectively. No treatment-related adverse events or serious adverse events were reported. Conclusion Azvudine showed satisfactory effectiveness and acceptable safety in older adults with mild or moderate COVID-19. Therefore, azvudine could be a treatment option for this special patient population.

A method for estimating the conditional average treatment effect under the condition of censored time-to-event data, called BENK (the Beran Estimator with Neural Kernels), is proposed. The main idea behind the method is to apply the Beran estimator for estimating the survival functions of controls and treatments. Instead of typical kernel functions in the Beran estimator, it is proposed to implement kernels in the form of neural networks of a specific form, called neural kernels. The conditional average treatment effect is estimated by using the survival functions as outcomes of the control and treatment neural networks, which consist of a set of neural kernels with shared parameters. The neural kernels are more flexible and can accurately model a complex location structure of feature vectors. BENK does not require a large dataset for training due to its special way for training networks by means of pairs of examples from the control and treatment groups. The proposed method extends a set of models that estimate the conditional average treatment effect. Various numerical simulation experiments illustrate BENK and compare it with the well-known T-learner, S-learner and X-learner for several types of control and treatment outcome functions based on the Cox models, the random survival forest and the Beran estimator with Gaussian kernels. The code of the proposed algorithms implementing BENK is publicly available. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Phase 3 trials using the anti‐amyloid antibodies aducanumab, lecanemab, donanemab, and high‐dose gantenerumab in prodromal and mild Alzheimer's disease dementia were heterogeneous in respect to statistical significance of effects. However, heterogeneity of results has not yet directly be quantified. METHODS: We used Bayesian random effects meta‐analysis to quantify evidence for or against a treatment effect, and assessed the size of the effect and its heterogeneity. Data were extracted from published studies where available and Web based data reports, assuming a Gaussian data generation process. RESULTS: We found moderate evidence in favor of a treatment effect (Bayes factor = 13.2). The effect was moderate to small with −0.33 (95% credible interval −0.54 to −0.10) points on the Clinical Dementia Rating – Sum of Boxes (CDR‐SB) scale. The heterogeneity parameter was low to moderate with 0.21 (0.04 to 0.45) CDR‐SB points. DISCUSSION: Heterogeneity across studies was moderate despite some trials reaching statistical significance, while others did not. This suggests that the negative aducanumab and gantenerumab trials are in full agreement with the expected effect sizes. [ABSTRACT FROM AUTHOR]

Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is very rare, with about 1000 reported cases globally. Removing most TIO culprit tumors requires the evaluation and intervention of orthopedic doctors. However, orthopedic doctors often have a poor understanding of the optical treatment of TIO due to its rarity. In addition, most TIO patients lack specific clinical manifestations. Also, the clinical localization and qualitative diagnosis of TIO are difficult and thus can easily be misdiagnosed and mistreated. Furthermore, the true incidence rate of TIO may be underestimated. Although many breakthroughs have been made in exploring the pathogenesis, clinical diagnosis, and treatment of TIO, rational and standardized orthopedic surgical treatment experience summary and sorting for TIO patients are lacking. In this article, the recent experience and progress in the field of orthopedic surgical treatment for TIO globally have been summarized, providing a theoretical basis and new clinical practice guidance for the rational treatment of TIO patients.

Collective action in the agricultural sector of Peru started in the form of agrarian production cooperatives around 1969. Following the collapse of the collectivisation program in the 1980s, external stakeholders helped to form marketing cooperatives in select sectors to discourage coca leaf production. Nowadays, cooperatives are only active in four sectors: banana, cocoa, coffee, and palm oil. Case study evidence of the performance of cooperatives in Peru is mixed, which raises the need for applied research to inform if cooperatives have been successful as instruments of smallholder development. We address the situation with empirical analysis of comprehensive survey data collected for the 2016-2019 period. Using multiple empirical techniques, we estimate the farm-level treatment effect of selling output to cooperatives. Generally, we find a positive effect of cooperatives on the price received and the quantity sold of their patrons. Palm oil cooperatives, which appear to have started in the recent past, form an exception. Implications of our findings are discussed.

Min Gao,1,2,&ast; Wenhua Sang,1,3,4,&ast; Kun Mi,1,3,4 Jiancong Liu,1,3,4 Yudong Liu,1,3,4 Wenge Zhen,1,3,4 Bang An2 1Department of Affective Disorders II, Hebei Provincial Mental Health Center, Baoding, People’s Republic of China; 2Xianyang Central Hospital, Xianyang Mental Health Center, Xianyang, People’s Republic of China; 3Hebei Key Laboratory of Major Mental and Behavioral Disorders, Baoding, People’s Republic of China; 4The Sixth Clinical Medical College of Hebei University, Baoding, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenhua Sang, Department of Affective Disorders II, Hebei Provincial Mental Health Center, Hebei Key Laboratory of Major Mental and Behavioral Disorders, The Sixth Clinical Medical College of Hebei University, Baoding, People’s Republic of China, Email whsang997169@163.com Bang An, Xianyang Central Hospital, Xianyang Mental Health Center, Xianyang, People’s Republic of China, Email xyanbang@163.comObjective: Only about one-third of depressed patients respond to initial antidepressant treatment. Therefore, it is crucial to find effective predictors of antidepressants. The purpose of our study was to learn the relationship between EEG theta power, theta asymmetry, and the efficacy of escitalopram.Methods: The study included 34 patients with depression. Before and after each patient’s course of treatment, EEG data was gathered. Both the Hamilton Anxiety Scale (HAMA) and the 17-item Hamilton Depression Scale (HAMD-17) were evaluated simultaneously. The natural logarithm of right frontal theta power minus left frontal theta power was used to calculate inter-electrode theta asymmetry (AT).Results: First, our study found no statistically significant difference between intra-electrode theta power and inter-electrode AT before and after treatment (P ≥ 0.05). When we later looked at the data regarding treatment effects, the findings revealed that patients (n = 9) who did not respond to treatment had lower baseline theta power at C4 [6.190 (2.000, 12.990) vs 15.800 (7.255, 22.330), z = − 2.166, P = 0.030]. The two groups had no difference in other electrodes (P ≥ 0.05). The AT of C3/C4 in non-responders (n = 9) was lower [0.012 (0.795) vs 0.733 (0.539), t = − 3.224, P = 0.005]. However, there was no difference in inter-electrode AT between the two groups in F3/F4 and F7/F8 (P ≥ 0.05). We finally show that the theta power at C4 was negatively correlated with HAMD scores before treatment (r = − 0.346, P = 0.045).Conclusion: Our findings determined that increased theta power and positive asymmetry in the right frontal-central area correlate with favourable escitalopram treatment, providing a basis for finding predictive markers for antidepressants.Keywords: depression, EEG, theta power, theta asymmetry, treatment effect

Analyzing treatment or exposure effect is a major research theme in scientific studies. In the current big-data era where multiple sources of data are available, it is of interest to perform a synthesized analysis of treatment effects by integrating information from different data sources or studies. However, studies may contain heterogeneous and incomplete covariate sets, and individual data therein may not be accessible. We apply and extend the generalized meta-analysis method to integrate summary results (e.g., regression coefficients) of outcome and treatment (propensity score, PS) regression analyses across different datasets that may contain heterogeneous covariate sets. The proposed integrated analysis utilizes a reference dataset, which contains data on the complete set of covariates. The asymptotic distribution for the proposed integrated estimator is established. Simulations reveal that the proposed estimator performs well. We apply the proposed method to obtain the causal effect of waist circumference on hypertension by integrating two existing outcomes and PS regression analyses with different sets of covariates.

Abstract Background The estimand for a clinical trial is a precise definition of the treatment effect to be estimated. Traditionally, estimates of treatment effects are based on either an ITT analysis or a per-protocol analysis. However, there are important clinical questions which are not addressed by either of these analyses. For example, consider a trial where patients take a rescue medication. The ITT analysis includes data after use of rescue, while the per-protocol analysis excludes these patients altogether. Neither of these analyses addresses the important question of what the treatment effect would have been if patients did not take rescue medication. Main text Trial estimands provide a broader perspective compared to the limitations of ITT and per-protocol analysis. Trial treatment effects depend on how events occurring after treatment initiation such as use of alternative medication or discontinuation of the intervention are included in the definition. These events can be accounted for in different ways, depending on the clinical question of interest. Conclusion The estimand framework is an important step forward in improving the clarity and transparency of clinical trials. The centrality of estimands to clinical trials is currently not reflected in methods recommended by the Cochrane group or the CONSORT statement, the current standard for reporting clinical trials in medical journals. We encourage revisions to these guidelines.

Abstract Background In the causal analysis of observational studies, covariates should be carefully balanced to approximate a randomized experiment. Numerous covariate balancing methods have been proposed for this purpose. However, it is often unclear what type of randomized experiments the balancing approaches aim to approximate; and this may cause ambiguity and hamper the synthesis of balancing characteristics within randomized experiments. Methods Randomized experiments based on rerandomization, known for significant improvement on covariate balance, have recently gained attention in the literature, but no attempt has been made to integrate this scheme into observational studies for improving covariate balance. Motivated by the above concerns, we propose quasi-rerandomization, a novel reweighting method, where observational covariates are rerandomized to be the anchor for reweighting such that the balanced covariates obtained from rerandomization can be reconstructed by the weighted data. Results Through extensive numerical studies, not only does our approach demonstrate similar covariate balance and comparable estimation precision of treatment effect to rerandomization in many situations, but it also exhibits advantages over other balancing techniques in inferring the treatment effect. Conclusion Our quasi-rerandomization method can approximate the rerandomized experiments well in terms of improving the covariate balance and the precision of treatment effect estimation. Furthermore, our approach shows competitive performance compared with other weighting and matching methods. The codes for the numerical studies are available at https://github.com/BobZhangHT/QReR .

Abstract INTRODUCTION Phase 3 trials using the anti‐amyloid antibodies aducanumab, lecanemab, donanemab, and high‐dose gantenerumab in prodromal and mild Alzheimer's disease dementia were heterogeneous in respect to statistical significance of effects. However, heterogeneity of results has not yet directly be quantified. METHODS We used Bayesian random effects meta‐analysis to quantify evidence for or against a treatment effect, and assessed the size of the effect and its heterogeneity. Data were extracted from published studies where available and Web based data reports, assuming a Gaussian data generation process. RESULTS We found moderate evidence in favor of a treatment effect (Bayes factor = 13.2). The effect was moderate to small with −0.33 (95% credible interval −0.54 to −0.10) points on the Clinical Dementia Rating – Sum of Boxes (CDR‐SB) scale. The heterogeneity parameter was low to moderate with 0.21 (0.04 to 0.45) CDR‐SB points. DISCUSSION Heterogeneity across studies was moderate despite some trials reaching statistical significance, while others did not. This suggests that the negative aducanumab and gantenerumab trials are in full agreement with the expected effect sizes.

Objective: To evaluate the clinical efficacy of a combination treatment of traditional Chinese medicine (TCM) in scalp seborrheic dermatitis (SSD) of differing severity. Methods: Our study included patients with typical SSD who visited the Medical Research Center for Hair and Skin at our hospital. Symptoms were evaluated using a "16‐point scale" developed at the center. Patients who had mild SSD were treated with Pi Fu Kang Xi Ye (PFKXY), those with moderate SSD were treated with PFKXY combined with Run Zao Zhi Yang Jiao Nang (RZZYJN), and those with severe dermatitis were treated with PFKXY and RZZYJN along with garlicin enteric‐coated tablets. Patients were asked to revisit 4 weeks later to evaluate the efficacy. Results: Symptom scores of all patients decreased by (5.48 ± 2.51) after treatment as compared with before treatment, and the results of t‐test and correlation test were significant (p < 0.01). The scores of patients with mild, moderate and severe SSD decreased by 3.14 ± 1.83, 4.90 ± 1.77, and 8.05 ± 2.21, respectively, after treatment as compared with before treatment. Among them, the changes in scores of patients with moderate dermatitis before and after treatment were significant in the t‐test and correlation test (p < 0.01). Conclusion: In this study, the combination treatment of TCM showed significant efficacy in the treatment of mild, moderate, and severe SSD, and the efficacy was stable, especially for patients with moderate SSD. [ABSTRACT FROM AUTHOR]

Abstract Estimating individual treatment effects (ITE) from observational data have become an important topic in various fields. In healthcare, determining the optimal time and amount of the treatment is crucial for improving each patient’s quality of life. However, existing methods mainly focused on estimating treatment effect under static setting with categorical treatments. In this work, we proposed Recurrent Continuous Adversarial Balancing (RCAB), a method that incorporates adversarial learning into a sequence-to-sequence recurrent network to reduce selection bias in dynamic data. Moreover, we reformulated imbalance loss to be appropriate for continuous scenario. RCAB is empirically validated in both synthetic and real-world datasets. The results demonstrate that RCAB outperforms various state-of-the-art methods, and it is applicable to time-series data with any types of treatments.

Introduction: SCLC is an aggressive malignancy with poor outcome. Most patients have disease recurrence despite treatments with multiple modalities. Subtyping of SCLC has been proposed recently, and novel agents targeting specific subtypes are actively being investigated. In this study, we evaluated the plasticity of subtypes in paired pre- and post-treatment samples. The aim was to understand possible subtype evolution after chemotherapy resistance that could lead to alternate targeted therapy strategies. Methods: A total of 68 samples from 32 patients with sufficient paired specimens were identified from 1998 to 2022. ASCL1, NEUROD1, and POU2F3 immunohistochemistry studies were performed on all cases, and subtyping by predominant expression was determined. Subtype comparison in each patient was performed, and expression analysis was performed on the basis of subtypes. Results: Of 32 cases, 28 (88%) had the same subtype in pre- and first post-treatment specimens. Protein expression level of subtype-specific transcription factor remained stable after chemotherapy. Two of five (40%) NEUROD1-predominant SCLC switched to ASCL1-predominant phenotype after treatment. One case had a pitfall of scoring ASCL1 on specimen with marked crushing artifacts. One case revealed the challenge of proper subtyping for samples with borderline POU2F3 expression. Conclusions: Subtype of SCLC generally remains the same after acquiring chemotherapy resistance. Plasticity was observed with rare cases switching from NEUROD1-predominant to ASC1-predominant SCLC. Resubtyping is unnecessary for the consideration of novel subtype-specific targeted agents, except cases with NEUROD1-predominant subtype.

Background: The estimand for a clinical trial is a precise definition of the treatment effect to be estimated. Traditionally, estimates of treatment effects are based on either an ITT analysis or a per-protocol analysis. However, there are important clinical questions which are not addressed by either of these analyses. For example, consider a trial where patients take a rescue medication. The ITT analysis includes data after use of rescue, while the per-protocol analysis excludes these patients altogether. Neither of these analyses addresses the important question of what the treatment effect would have been if patients did not take rescue medication. Main text: Trial estimands provide a broader perspective compared to the limitations of ITT and per-protocol analysis. Trial treatment effects depend on how events occurring after treatment initiation such as use of alternative medication or discontinuation of the intervention are included in the definition. These events can be accounted for in different ways, depending on the clinical question of interest. Conclusion: The estimand framework is an important step forward in improving the clarity and transparency of clinical trials. The centrality of estimands to clinical trials is currently not reflected in methods recommended by the Cochrane group or the CONSORT statement, the current standard for reporting clinical trials in medical journals. We encourage revisions to these guidelines. [ABSTRACT FROM AUTHOR]

Background: In the causal analysis of observational studies, covariates should be carefully balanced to approximate a randomized experiment. Numerous covariate balancing methods have been proposed for this purpose. However, it is often unclear what type of randomized experiments the balancing approaches aim to approximate; and this may cause ambiguity and hamper the synthesis of balancing characteristics within randomized experiments. Methods: Randomized experiments based on rerandomization, known for significant improvement on covariate balance, have recently gained attention in the literature, but no attempt has been made to integrate this scheme into observational studies for improving covariate balance. Motivated by the above concerns, we propose quasi-rerandomization, a novel reweighting method, where observational covariates are rerandomized to be the anchor for reweighting such that the balanced covariates obtained from rerandomization can be reconstructed by the weighted data. Results: Through extensive numerical studies, not only does our approach demonstrate similar covariate balance and comparable estimation precision of treatment effect to rerandomization in many situations, but it also exhibits advantages over other balancing techniques in inferring the treatment effect. Conclusion: Our quasi-rerandomization method can approximate the rerandomized experiments well in terms of improving the covariate balance and the precision of treatment effect estimation. Furthermore, our approach shows competitive performance compared with other weighting and matching methods. The codes for the numerical studies are available at https://github.com/BobZhangHT/QReR. [ABSTRACT FROM AUTHOR]

A conventional evaluation methodology for drinking water pollution focuses on analysing hundreds of compounds, usually by liquid chromatography–tandem mass spectrometry. High-resolution mass spectrometry allows comprehensive evaluation of all detected signals (compounds) based on their elemental composition, intensity, and numbers. We combined target analysis of 192 emerging micropollutants with nontarget (NT) full-scan/MS/MS methods to describe the impact of treatment steps in detail and assess drinking water treatment efficiency without compound identification. The removal efficiency based on target analytes ranged from − 143 to 97%, depending on the treatment section, technologies, and season. The same effect calculated for all signals detected in raw water by the NT method ranged between 19 and 65%. Ozonation increased the removal of micropollutants from the raw water but simultaneously caused the formation of new compounds. Moreover, ozonation byproducts showed higher persistence than products formed during other types of treatment. We evaluated chlorinated and brominated organics detected by specific isotopic patterns within the developed workflow. These compounds indicated anthropogenic raw water pollution but also potential treatment byproducts. We could match some of these compounds with libraries available in the software. We can conclude that passive sampling combined with nontargeted analysis shows to be a promising approach for water treatment control, especially for long-term monitoring of changes in technology lines because passive sampling dramatically reduces the number of samples and provides time-weighted average information for 2 to 4 weeks. [ABSTRACT FROM AUTHOR]

Objective To evaluate the short-term outcomes of thoracic endovascular aortic repair (TEVAR) with outer branched and inner branched endografts in the treatment of Stanford type B aortic dissection (TBAD), and to analyze the effects of endografts on blood flow status of aortic dissection by computational fluid dynamics (CFD). Methods The clinical data of TBAD patients treated with outer branched endograft technology in outer branched endograft group and inner branched endograft technology in inner branched endograft group in Department of Vascular Surgery Tianjin Medical University General Hospital from May 2018 to December 2021 were collected, and the short-term results of two groups were analyzed retrospectively. Based on CT angiography images of patients in two groups, one typical case in each group was selected to construct personalized 3D model and CFD numerical simulation was performed. The parameters including flow field velocity distribution, wall pressure and wall shear stress (WSS) before and after surgery were compared and analyzed. Results A total of 55 cases with TBAD were enrolled, consisting of 49 cased in outer branched endograft group and 6 cases in inner branched endograft group. There was no statistical difference in baseline data between two groups, and surgical success rate were both 100%. Reconstruction of left subclavical artery(LSA) simple was 41(83.7%) cases in outer branched endograft group and all 6 cases in inner branched endograft group. In outer branched endograft group there were 5 cases with reconstruction of left common carotid artery (LCCA) combined with bridging carotic clavical artery, 2 cases with reconstruction of LCCA combined with LSA embolism, and 1 case with reconstruction of LCCA combined with LSA window. Four cases were lost during follow-up in outer branched endograft group. There were no significant differences in the aorta-related mortality rate (P=1.000), branch patency rate (P=1.000) and avoidance of secondary intervention of target vessels between the two groups during the perioperative period and follow-up period (P=0.298). After endograft implantation of two groups the flow field disturbance in dissection lesions improved significantly, aortic blood flow pattern restored normal, and local abnormally increased WSS decreased. However, the interference of inner branch on aortic arch and blood flow of branch was more obvious than that of outer branch. Conclusions Both outer branched endograft and inner branched endograft TEVAR for reconstruction of LSA had good short-term results in the treatment of TBAD. Compared with inner branched endograft, outer branched endograft has a higher anatomical fit and can restore the normal blood flow to a greater extent for aortic arch.