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Objective To evaluate heterogeneity of treatment effects (HTE) in a trial of exercise-based interventions for knee osteoarthritis (OA). Methods Participants (n=350) were randomized to standard physical therapy (PT; n=140), Internet-Based Exercise Training (IBET; n=142), or wait list control (WL; n=68). We applied QUalitative INteraction Trees (QUINT), a sequential partitioning method, and Generalized Unbiased Interaction Detection and Estimation (GUIDE), a regression tree approach, to identify subgroups with greater improvements in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score over 4-months. Predictors included 24 demographic, clinical and psychosocial characteristics. We conducted internal validation to estimate optimism (bias) in the range of mean outcome differences among arms. Results Both QUINT and GUIDE indicated that for participants with lower body mass index (BMI), IBET was better than PT (improvements of WOMAC ranged from 6.3 to 9.1 points lower) and for those with higher BMI and longer duration of knee OA, PT was better than IBET (WOMAC improvement was 6.3 points). In GUIDE analyses comparing PT or IBET to WL, participants not employed had improvements in WOMAC ranging from 1.8 to 6.8 points lower with PT or IBT vs. WL. From internal validation, there were large corrections to the mean outcome differences among arms; however, after correction some differences remained in the clinically meaningful range. Conclusion Results suggest there may be subgroups who experience greater improvement in symptoms from PT or IBET, and this could guide referrals and future trials. However, uncertainty persists for specific treatment effect size estimates and how they apply beyond this study sample.

BACKGROUND & OBJECTIVES: There are reports of worsening renal functions with sofosbuvir, but there are no comparative data of different direct-acting antivirals (DAAs) on serum creatinine. In this retrospective cohort analysis, we examined the treatment effect of two commonly used regimens, sofosbuvir/ledipasvir (SOF/LDV) and glecaprevir/pibrentasvir (GLE/PIB), on serum creatinine. METHODS: We included all patients treated with SOF/LDV (n = 825) and GLE/PIB (n = 116) between December 1, 2014, and December 31, 2018. An increase of serum creatinine ≥0.3 mg/dL was considered clinically significant. The change of creatinine values from pretreatment to posttreatment between two treatment groups was tested in unadjusted and adjusted generalized linear model, and risk factors associated with creatinine change were assessed. In addition, GLE/PIB-treated patients were matched 1:2 to SOF/LDV-treated patients using propensity scores, and then serum creatinine changes were compared. RESULTS: The mean baseline creatinine was higher in the GLE/PIB group vs. SOF/LDV group (1.39 ± 1.86 vs. 0.91 ± 0.24, P = 0.007). When compared to baseline, serum creatinine at posttreatment week 4 was significantly higher in SOF/LDV group (0.97 ± 0.4 vs.0.91 ± 0.24, P

Background and Purpose: Despite the lower rates of good outcomes and higher mortality in elderly patients, age does not modify the treatment effect of mechanical thrombectomy for large vessel occlusion strokes. We aimed to study whether racial background influences the outcome after mechanical thrombectomy in the elderly population. Methods: We reviewed a prospectively maintained database of patients with acute ischemic stroke treated with mechanical thrombectomy from October 2010 through June 2020 to identify all consecutive patients with age ≥80 years and anterior circulation large vessel occlusion strokes. The patients were categorized according to their race as Black and White. Univariable and multivariable analyses were performed to define the predictors of 90-day modified Rankin Scale and mortality in the overall population and in each race separately. Results: Among 2241 mechanical thrombectomy, a total of 344 patients (median [interquartile range]; age 85 [82–88] years, baseline National Institutes of Health Stroke Scale score of 19 [15–23], Alberta Stroke Program Early CT Score 9 [7–9], 69.5% females) were eligible for the analysis. White patients (n=251; 73%) had significantly lower median body mass index (25.37 versus 26.89, P =0.04) and less frequent hypertension (78.9% versus 90.3%, P =0.01) but more atrial fibrillation (64.5% versus 44.1%, P =0.001) compared with African Americans (n=93; 27%). Other clinical, imaging, and procedural characteristics were comparable between groups. The rates of symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score of 0 to 2, and mortality were comparable among both groups. On multivariable analysis, race was neither a predictor of 90-day modified Rankin Scale score of 0 to 2 (White race: odds ratio, 0.899 [95% CI, 0.409–1.974], P =0.79) nor 90-day mortality (White race: odds ratio, 1.368; [95% CI, 0.715–2.618], P =0.34). Conclusions: In elderly patients undergoing mechanical thrombectomy for acute ischemic stroke, there was no racial difference in terms of outcome.

The present study compared intensity of training between technology-supported and conventional exercises during a regular therapy session in three brain injured patients with arm/hand limitations. Results showed that intensity was higher during technology-supported exercises. Further research with a larger sample is needed to confirm these outcomes and assess its potential relation to treatment effect.

Objective: To explore the therapeutic effects of community health management and nursing strategies for elderly hypertensive patients. Methods: A total of 64 elderly hypertensive patients who were treated in our hospital from March 2020 to March 2021 were selected. The control group took conventional care and guidance. The research group carried out community health management and nursing strategy guidance on the basis of the control group. Then compare the blood pressure levels of the two groups of patients before and after nursing and the patients’ satisfaction with nursing. Results: Through comparison, it can be seen that the diastolic and systolic blood pressure levels of the study group and the control group are not significantly different before nursing. After nursing, the diastolic blood pressure of the patients in the study group was 81.22.1 mmHg and the systolic blood pressure was 126.58.7 mmHg. The diastolic blood pressure of the control group was 90.55.4 mmHg and the systolic blood pressure was 136.412.9 mmHg. There are obvious differences in the comparison of the two sets of data. By comparing the two groups of patients’ satisfactions with nursing care, it can be seen that among the 32 patients in the study group: 31 were very satisfied and basically satisfied, with a satisfaction rate of 96.87%. Among the 32 patients in the control group, 28 were very satisfied and basically satisfied, with a satisfaction rate of 87.5%. The data of the two groups of patients are clearly comparable. Conclusion: Through community health management and nursing strategies, the satisfaction and treatment effect of elderly hypertensive patients can be improved, thereby contributing to the recovery of patients.

Access to high-dimensional data has made the use of machine learning in causal inference more common in recent years. The double/debiased machine learning (DML) estimator for the treatment effect i...

A common assumption of data analysis in clinical trials is that the patient population, as well as treatment effects, do not vary during the course of the study. However, when trials enroll patients over several years, this hypothesis may be violated. Ignoring variations of the outcome distributions over time, under the control and experimental treatments, can lead to biased treatment effect estimates and poor control of false positive results. We propose and compare two procedures that account for possible variations of the outcome distributions over time, to correct treatment effect estimates, and to control type-I error rates. The first procedure models trends of patient outcomes with splines. The second leverages conditional inference principles, which have been introduced to analyze randomized trials when patient prognostic profiles are unbalanced across arms. These two procedures are applicable in response-adaptive clinical trials. We illustrate the consequences of trends in the outcome distributions in response-adaptive designs and in platform trials, and investigate the proposed methods in the analysis of a glioblastoma study.

BACKGROUND Port-wine stain (PWS) is a congenital capillary malformation that often occurs on the face. Feasible and quantitative evaluation of facial port-wine stain (FPWS) can significantly impact its clinical management and aid in future research. AIM To develop and validate an easy-to-use scoring system for FPWS evaluation. METHODS A facial port-wine stain area and severity index (FSASI) scoring system was proposed. To determine the FSASI score, the face was divided into four regions: forehead, right malar, left malar, and perioral. The severity of FPWS in each region was evaluated by three factors: percentage of the area affected, lesion color, and thickness. To evaluate the intra- and inter-rater reliability of FSASI, two separate FSASI assessments on 111 clinical pictures were conducted by each rater in a one-week interval, and the results from 6 independent raters at different time points were compared. Validity of the FSASI scores was assessed by comparing it with physician global assessment (PGA) and traditional classification data. Validity of the area and color elements of FSASI was also determined. The changes in FSASI scores after vascular-targeted photodynamic therapy (V-PDT) were analyzed to evaluate the treatment effect. RESULTS The FSASI scoring system showed good intra- and inter-rater reliability (ICC >0.75, p

PURPOSE Plasma circulating tumor DNA (ctDNA) analysis is routine for genotyping of advanced non–small-cell lung cancer (NSCLC); however, early response assessment using plasma ctDNA has yet to be well characterized. MATERIALS AND METHODS Patients with advanced EGFR-mutant NSCLC across three phase I NCI osimertinib combination trials were analyzed in this study, and an institutional cohort of patients with KRAS-, EGFR-, and BRAF-mutant advanced NSCLC receiving systemic treatment was used for validation. Plasma was collected before treatment initiation and serially before each cycle of therapy, and key driver mutations in ctDNA were characterized by droplet digital polymerase chain reaction. Timing of plasma versus imaging response was compared in a separate cohort of patients with EGFR-mutant NSCLC treated with osimertinib. Across cohorts, we also studied ctDNA variability before treatment start. RESULTS In the NCI cohort, 14/16 (87.5%) patients exhibited ≥ 90% decrease in mutation abundance by the first on-treatment timepoint (20-28 days from treatment start) with minimal subsequent change. Similarly, 47/56 (83.9%) patients with any decrease in the institutional cohort demonstrated ≥ 90% decrease in mutation abundance by the first follow-up draw (7-30 days from treatment start). All 16 patients in the imaging cohort with radiographic partial response showed best plasma response within one cycle, preceding best radiographic response by a median of 24 weeks (range: 3-147 weeks). Variability in ctDNA levels before treatment start was observed. CONCLUSION Plasma ctDNA response is an early phenomenon, with the majority of change detectable within the first cycle of therapy. These kinetics may offer an opportunity for early insight into treatment effect before standard imaging timepoints.

Objectives: The effect of stimulants on anxiety domains has not been systematically studied. We assessed prospectively the impact of stimulant treatment in children with attention-deficit/hyperacti...

Exploring the effects of uterine imaging and hysteroscopy of endometrial polyps, this article has chosen the treatment effect of 50 cases of intrauterine polyps to observe hysteroscopy. The results showed that the diagnosis and sensitivity, specificity, positive, negative, and consistency were passed through various diagnostic methods ( P < 0.05 ). The diagnostic sensitivity of antidiagnosis combination and series combination was 90.0%, 64.0%, 96.0%, 92.0%, 80.0%, 80.0%, 88.0%, and 92.0%, parallel diagnosis with high sensitivity, significantly higher than simple diagnosis ( P < 0.05 ). Therefore, in the clinical treatment of endometrial polyps, hysteroscopic surgery is a safe and effective treatment, which can remove endometrial quality, improve the clinical symptoms of patients, and reduce the interference and postoperative recovery process of surgical trauma.

Despite advances in drug and catheter ablation therapy, long-term recurrence rates for ventricular tachycardia remain suboptimal. Cardiac stereotactic body radiotherapy (SBRT) is a novel treatment that has demonstrated reduction of arrhythmia episodes and favorable short-term safety profile in treatment-refractory patients. Nevertheless, the current clinical experience is early and limited. Recent studies have highlighted variable duration of treatment effect and substantial recurrence rates several months postradiation. Contributing to these differential outcomes are disparate approaches groups have taken in planning and delivering radiation, owing to both technical and knowledge gaps limiting optimization and standardization of cardiac SBRT.In this report, we review the historical basis for cardiac SBRT and existing clinical data. We then elucidate the current technical gaps in cardiac radioablation, incorporating the current clinical experience, and summarize the ongoing and needed efforts to resolve them.Cardiac SBRT is an emerging therapy that holds promise for the treatment of ventricular tachycardia. Technical gaps remain, to be addressed by ongoing research and growing clincial experience.

Objective To undertake meta-analysis and compare treatment effects estimated by the intention-to-treat (ITT) method and per-protocol (PP) method in randomized controlled trials (RCTs). PP excludes trial participants who are non-adherent to trial protocol in terms of eligibility, interventions, or outcome assessment. Study design and setting Five high impact journals were searched for all RCTs published between July 2017 to June 2019. Primary outcome was a pooled estimate that quantified the difference between the treatment effects estimated by the two methods. Results are presented as ratio of odds ratios (ROR). Meta-regression was used to explore the association between level of trial protocol non-adherence and treatment effect. Sensitivity analyses compared results with varying within-study correlations and across various study characteristics. Results Random-effects meta-analysis (N = 156) showed that PP estimates were on average 2% greater compared to the ITT estimates (ROR: 1.02, 95% CI: 1.00–1.04, P = 0.03). The divergence further increased with higher degree of protocol non-adherence. Sensitivity analyses reassured consistent results with various within-study correlations and across various study characteristics. Conclusion There was evidence of larger treatment effect with PP compared to ITT analysis. PP analysis should not be used to assess the impact of protocol non-adherence in RCTs. Instead, in addition to ITT, investigators should consider randomization based casual method such as Complier Average Causal Effect (CACE).

Heterogeneous treatment effect (HTE) analysis focuses on examining varying treatment effects for individuals or subgroups in a population. For example, an HTE‐informed understanding can critically guide physicians to individualize the medical treatment for a certain disease. However, HTE analysis has not been widely recognized and used, even given the explosive increase of data availability attributed to the arrival of the Big Data era. Part of the reason behind its underuse is that data are often of high dimension and high complexity, which pose significant challenges for applying conventional HTE analysis methods. To meet these challenges, a newly developed causal forest HTE method has been derived from the random forest machine‐learning algorithm. We conducted a systematic performance evaluation for the causal forest method against the conventional two‐step method by simulating scenarios with different levels of complexity for the analysis. Our results show that causal forest outperforms the conventional HTE method in assessing treatment effect, especially when data are complex (e.g., nonlinear) and high dimensional, suggesting that causal forest is a promising tool for real‐world applications of HTE analysis.

International audience; Background In international trials, glucagon-like protein-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2Is) were effective in improving cardiovascular (CV) outcomes. Methods We assessed the effect of GLP-1RAs and SGLT2Is treatment effect on CV endpoints by geographical region in multiple international trials using random effects weighted least squares meta-regressions. Results The estimated effects of both SGLT2Is and GLP-1RAs on major adverse CV events (MACE) in North America (SGLT2Is n = 12,399, HR 0.90, 95% CI 0.81-1.01; GLP-1RAs n = 12,515, HR 0.95, 95% CI 0.83-1.09) and in Europe (SGLT2Is n = 19,435, HR 0.93, 95% CI 0.85-1.02; GLP-1RAs n = 22,812, HR 0.88, 95% CI 0.79-0.99) were numerically lower but not statistically different to the rest of the world (ROW) (SGLT2Is n = 15,127, HR 0.83, 95% CI 0.75-0.92, p-value for interaction 0.26; GLP-1RAs n = 17,494, HR 0.82, 95% CI 0.73-0.92, p-value for interaction 0.28). Effects of SGLT2Is on heart failure readmission or CV death varied significantly by region (P = 0.0094). The effect of SGLT2Is was significantly smaller in Europe (n = 18,653, HR 0.86, 95% CI 0.78-0.95) than in the ROW (n = 12,463, HR 0.68, 95% CI 0.61-0.76, P = 0.0024). The smaller effect in North America (n = 9776, HR 0.76, 95% CI 0.66-0.87) did not differ significantly from that in the ROW (P = 0.2370). Conclusion The effects of SGLT2Is on HF events are larger in the ROW. Further analyses and studies are needed to better elucidate the differential effects of SGLTIs and GLP-1RAs by geographical regions.

At present, the incidence rate of arteriosclerosis obliterans (LEASO) of the lower extremities is significantly increased by aging and lifestyle changes. It is of great importance to predict the LEASO effectively and accurately by analyzing the imaging data of the lower extremities [1]. At this stage, China has entered the era of big data and artificial intelligence. Medical institutions at all levels can produce a large number of lower limb vascular image data every day. Using big data deep learning technology to intelligently analyze a large number of image data, and then carry out auxiliary diagnosis, so as to improve the diagnosis and treatment effect of LEASO is the focus of clinical research.

Households with children may Tiebout (1956) sort to safe cities. Cities that cut funding for police protection may become less attractive to households with children, spurring housing developers to build smaller houses with fewer rooms. Voting data on police tax levies using regression discontinuity suggests that newly-built houses have more rooms in cities that renew rather than fail their tax levies. The treatment effect peaks in the second year after the tax levy at 1.9 rooms, a sizeable difference over the mean of 6.6 rooms. House size tells a similar story: the difference between newly-built houses in communities that pass and fail public safety tax levies is 317.6 square feet (29.5 square meters), representing 15% of the mean house size in the sample. The results become evident 2 years after the tax levy and persist in the third year before petering out in the fourth year. The effect may stem from communities signaling a decreased commitment to public safety, rather than an increase in the crime rate itself, because cutting small tax levies has about the same effect on house size as cutting large tax levies.

This article studies the therapeutic effect and nursing experience of octreotide in treating hypoglycemia in acute pancreatitis. Method: Sixty patients with acute pancreatitis treated in our hospital from January 2019 to February 2020 were selected as the study subjects, and the patients who met the criteria were randomly divided into intervention group (n=30) and control group (n=30).Both groups of patients were treated with octreotide, while the intervention group was given personalized whole-course intervention on the basis of it, to compare the treatment effect of the two groups and the occurrence of hypoglycemia. Results: The total effective rate was 73.33% in the control group and 96.67% in the intervention group. There was a significant difference in data between the intervention group and the control group (P < 0.05). The incidence of hypoglycemia was 26.67% in the control group and 3.33% in the intervention group. The difference between the control group and the intervention group was statistically significant (P < 0.05). The incidence of adverse reactions was 36.67% in the control group and 6.67% in the intervention group. The difference between the control group and the intervention group was statistically significant (P < 0.05). The nursing satisfaction of the patients in the control group was 79.00%, and that of the intervention group was 96.67%. The difference between the intervention group and the control group was statistically significant (P < 0.05). Conclusion: Octreotide has a good effect in the treatment of patients with acute pancreatitis. If personalized whole-course intervention can be given to patients with acute pancreatitis who receive 24-hour octreotide pump drip, the treatment effect, nursing satisfaction, adverse reactions and hypoglycemia can be further improved, and the patient’s condition can be effectively maintained stable and the patient can recover as soon as possible.

Objective Explore the impact of personalized nursing services and hospice care on the quality of life of elderly patients with advanced cancer. Method We selected 80 elderly cancer patients admitted to our hospital from September 2020 to May 2021, and divided these patients into a study group and a control group using a random number table method. The patients in the control group used conventional nursing methods to treat and care for the patients, and the patients in the study group used hospice care measures and combined personalized nursing measures. The quality of life and pain treatment effects of the two groups of patients before and after treatment were compared. Result Before treatment, the quality-of-life scores of the two groups of patients were low, and there was no statistical difference (P>0.05); After treatment, the quality of life of the two groups of patients improved, but compared with the control group, the improvement was more obvious in the study group, and the difference was statistically significant (P

In clinical trials, surrogate endpoints are useful when the endpoint of interest is difficult to measure or requires a long follow-up time. Current methodology for validating surrogate endpoints encounters challenges in the presence of collinearity between the treatment and surrogate endpoint, which is often present in clinical trials. The proposed methods adapt current methodology in the structural framework of path analysis to quantify the validity of a surrogate endpoint. The path analysis framework provides an improved interpretation of treatment effect. Through derivation and simulation we show the proposed path likelihood reduction factor (LRF P ), is less biased and more robust than current methodology in cases of collinearity between the treatment and surrogate endpoint, with notable improvement when surrogacy is weak or moderate. LRF P can be expanded to evaluate multiple correlated surrogate endpoints, which as shown through simulation, is also less biased and more robust than current methodology in the case of collinearity between the treatment and surrogate endpoint.

We propose a simple-to-implement dynamic panel data method to evaluate the impacts of place-based policies. The idea is to exploit both the cross sectional dependence and the serial correlation within a panel and implement a semi difference-in-difference decomposition. Different from the method by Hsiao et al. (2012), the proposed model is easy to implement statistical inferences and can incorporate multiple treated groups at different time thresholds. We use the proposed method to explore the effect of the Free Trade Zone (FTZ) policy implemented in Shanghai at the end of 2013 on local GDP growth rate and compare it with that from Hsiao et al. (2012). The empirical results show that the FTZ does have a positive effect on the local GDP growth rate and it adds 1.2 − 1.8 percent point to the growth rate of the GDP per capita for Shanghai in 2014 which is about one fourth to one third of the total GDP growth rate per capita. This effect largely comes from the growth of the tertiary sector. The results lend support to the duplication of FTZ policy to other cities and provinces in China.

Objectives Knee osteoarthritis (OA) is a leading cause of health-related disability. In the absence of curative non-operative therapies, treatment goals are limited to symptom relief. Data are limited on how patients and physicians prioritise available treatment options. We assessed patients’ preferences for and physicians’ attitudes towards intra-articular treatments including corticosteroids (IACS), an extended-release corticosteroid (TA-ER) and hyaluronic acids (IAHA). Methods We conducted a prospective, IRB-exempt, double-blind survey of patients with and providers who treat knee OA. Respondents were required to have received or prescribed TA-ER in a non-trial setting. We evaluated patients’ OA history, impact of knee OA and treatment preferences, and physicians’ decision-making and prescribing experiences. Results Of the 97 patient participants, mean age was 56 years, 70.0% were women, 75.0% had bilateral knee OA and 46.4% were diagnosed over 5 years ago. Of the 50 physician participants, 42.0% were orthopaedic surgeons, 34.0% were rheumatologists and 60.0%, on average, treat 50+ patients with knee OA per month. Treatment selection factors considered ‘very important’ to patients and physicians included disease severity (88.7%, 82.0%), impact on quality of life (88.7%, 72.0%), disease extent (84.5%, 54.0%) and activity level (80.4%, 64.0%). A majority (93.8%) of patients indicated moderate to severe difficulty with their knees. Fewer patients (76.3%) reported shared decision making compared with physicians (92.0%). Half (50.5%) of the patients reported that they experienced months of pain relief with TA-ER, 27.7% with IACS and 18.8% with IAHA. Physician assessments were consistent but estimated a greater duration of treatment effects than that reported by patients across all therapies. Conclusion While knee OA has a tremendous impact on patients, there are significant unmet treatment needs. The increasing use of patient-reported outcomes will allow patients and physicians to track pain and functional status over time and across therapies, improving shared decision-making.

Purpose To investigate long-term visual outcome in inferior posterior staphyloma (IPS) in each group classified based on macular complications and to examine the treatment effect for eyes with IPS with choroidal neovascularization (CNV). Design Prospective clinical cohort study. Participants We analyzed 56 eyes of 43 consecutive patients with IPS who were followed for 4 years. Methods We classified eligible eyes into 3 groups based on baseline findings: eyes without CNV or retinal exudate (no-exudate group), eyes without CNV and with retinal exudate (exudate group), and eyes with CNV (CNV group). We investigated the best-corrected visual acuity (BCVA) and associated parameters for 4 years. Results BCVA declined during 4 years only in the exudate group (P = .002), whereas it was maintained for 4 years in the no-exudate and CNV groups (P = .53 and .20, respectively). Baseline BCVA was lower in the CNV group than in the exudate group (P = .004); however, the 4-year BCVA was not (P = .84). The 4-year BCVA was associated with baseline BCVA in all groups. Eyes in the CNV group required 9.0 ± 8.7 anti–vascular endothelial growth factor therapy in 4 years. Conclusions Better baseline BCVA in eyes with exudative IPS without CNV spontaneously declined in 4 years, whereas worse baseline BCVA in eyes with IPS with CNV did not, probably because of treatment for retinal exudate from CNV. Anti–vascular endothelial growth factor therapy would be effective for long-term maintenance of BCVA in eyes with IPS with CNV, similar to other diseases with CNV.

This paper proposes a new quantile regression model to characterize the heterogeneity for distributional effects of maternal smoking during pregnancy on infant birth weight across different the mother's age. By imposing a parametric restriction on the quantile functions of the potential outcome distributions conditional on the mother's age, we estimate the quantile treatment effects of maternal smoking during pregnancy on her baby's birth weight across different age groups of mothers. The results show strongly that the quantile effects of maternal smoking on low infant birth weight are negative and substantially heterogenous across different ages.

Measuring the effect of a treatment on outcomes is an important goal for research in pediatric/congenital interventional cardiology. The breadth of anatomic and physiologic variations, patient ages, and genetic syndromes and noncardiac comorbid conditions all represent sources of potential confounding and effect modification that are major obstacles to this goal. If not accounted for, these factors can obscure the "true" treatment effect and lead to spurious conclusions about the relative efficacy and/or safety of therapies. In this review, we discuss the importance of confounding and effect modification in pediatric/congenital interventional cardiology research. We define these terms and discuss strategies (both in study design and data analysis) to mitigate error introduced by confounding and effect modification. The importance of confounding by indication in pediatric/congenital cardiology is discussed along with specific methods to address it.

Background and Objectives Several drugs which can improve blood flow have been used as treatment options for sudden sensorineural hearing loss (SSNHL) based on the theory that improvement of perfusion into the inner ear will help restore hearing. Lipo-prostaglandin E1 (lipo-PGE1) is a well-known vasodilator that increases peripheral blood flow. The purpose of this study was to investigate the effect of lipo-PGE1 on the recovery of the SSNHL patients with hypertension or diabetes.Subjects and Method We retrospectively analyzed 801 patients who were diagnosed with SSNHL from January 2007 to December 2018. All patients were treated with 48 mg of methylprednisolone for 5 days; some patients received lipo-PGE1, depending on the attending physician. They were divided into four groups according to the presence or absence of hypertension and diabetes. Hearing test was performed again one month after treatment and compared with the test results at the time of diagnosis.Results As a result of comparing the hearing thresholds before and after the treatment in each group, there was a significant improvement in hearing thresholds in all groups (p

Purpose This study aims to measure the occurrence of gentrification and to relate gentrification with housing values. Design/methodology/approach The authors have used Getis-Ord statistics to identify and quantify gentrification in different residential areas in a case study of Stockholm, Sweden. Gentrification will be measured in two dimensions, namely, income and population. In step two, this measure is included in a traditional hedonic pricing model where the intention is to explain future housing prices. Findings The results indicate that the parameter estimate is statistically significant, suggesting that gentrification contributes to higher housing values in gentrified areas and near gentrified neighbourhoods. This latter possible spillover effect of house prices due to gentrification by income and population was similar in both the hedonic price and treatment effect models. According to the hedonic price model, proximity to the gentrified area increases housing value by around 6%–8%. The spillover effect on price distribution seems to be consistent and stable in gentrified areas. Originality/value A few studies estimate the effect of gentrification on property values. Those studies focussed on analysing the impacts of gentrification in higher rents and increasing house prices within the gentrifying areas, not gentrification on property prices in neighbouring areas. Hence, one of the paper’s contributions is to bridge the gap in previous studies by measuring gentrification’s impact on neighbouring housing prices.

Introduction.Traditional antiallergic therapy for atopic dermatitis, including allergen elimination, therapeutic cosmetic skin care, external anti-inflammatory therapy and antihistamines, does not always lead to the desired result. On this basis, the search for new methods of treatment is urgent and promisingAim.To study the clinical efficacy of a combination of Lactobacillus rhamnosus GG and prebiotics in children in the first years of life with atopic dermatitis (AD).Materials and methods. The observed children were divided into 2 parts: 30 children aged from 1 month to 3 years old, patients with AD constituted the main group, it differed in that these patients were synbiotic (combination of Lactobacillus rhamnosus GG and prebiotics) – 1 sachet per day for 14 days. This drug was prescribed as part of complex therapy. The remaining 25 children with AD made up a comparison group, which was characterized by the fact that children received only antiallergic therapy without symbiotic. Clinical methods of blood pressure examination, laboratory instrumental and specific allergological methods were carried out.Results and discussion. Against the background of the therapy in children with blood pressure in the main group, общий overall treatment effect was higher and amounted to 86.6 + 4.0%, and in the comparison group – 76.0 + 3.9%, p Conclusions.The obtained results allow us to recommend a combination of Lactobacillus rhamnosus GG and prebiotics in children in the first years of life as part of complex therapy to increase the effectiveness of treatment.

This post hoc analysis of the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) shows a treatment effect of remdesivir (RDV) on progression to invasive mechanical ventilation (IMV) or death. Additionally, we create a risk profile that better predicts progression than baseline oxygen requirement alone. The highest risk group derives the greatest treatment effect from RDV.

Objective?Research on the effect of moist wound healing theory in a combination with modern new dressingtreatment in patients diagnosed with pressure ulcers. Method: Selected 30 patients with pressure ulcers from our hospital, which is Shandong Tai’an Municipal Hospital, from January 2019 to January 2021 were divided into experimental group (15 cases, treated with moist wound healing theory combined with modern new dressings) and control group (15 cases, applied conventional treatments). The treatment effect, time of wound edema subsidence, wound healing time, number of dressing changes, granulation tissue growth time, and diameter reduction time were compared between the two groups. Results: The total effective rate of the experimental group (93.33%, 14/15) was higher than that of the control group (53.33%, 8/15), P

This article introduces a crossover design that is often used in clinical studies, with the advantage of comparing treatment effects within one study subject. In particular, the advantages and disadvantages of the two-period, two-sequence crossover design (2 × 2 or AB/BA crossover design), which is widely used in clinical practice, are identified, and the elements necessary for analysis are introduced. This article explains the carryover effect, period effect, sequence effect, and period-by-treatment interaction in a crossover design and examines the analysis commands of SAS along with example data. After confirming the carryover effect using a general linear model, the treatment effect is analyzed using a linear mixed effect model.

BACKGROUND: Data on direct comparison between various drug-eluting stents with short duration dual antiplatelet therapy (DAPT) are limited, especially in patients with acute coronary syndrome (ACS). AIMS: We sought to compare biodegradable polymer biolimus-eluting stents (BP-BES) with durable polymer everolimus-eluting (DP-EES) and zotarolimus-eluting stents (DP-ZES) in patients with ACS according to different durations of DAPT. METHODS: In the SMART-DATE trial, 2,712 patients with ACS underwent randomisation for allocation of DAPT (6 months [n=1,357] or 12 months or longer [n=1,355]) and type of stent (BP-BES [n=901]), DP-EES [n=904], or DP-ZES [n=907]). The primary endpoint was a composite of cardiac death, myocardial infarction, or stent thrombosis. RESULTS: At 18 months, the primary endpoint was attained by 2.6% with BP-BES, 2.0% with DP-EES, and 2.1% with DP-ZES (HR 1.29, 95% CI: 0.70-2.39, p=0.42 for BP-BES vs DP-EES and HR 1.23, 95% CI: 0.67-2.26, p=0.50 for BP-BES vs DP-ZES). The treatment effect of BP-BES for the primary endpoint was consistent among patients receiving 6-month DAPT as well as those receiving 12-month or longer DAPT (BP-BES vs. DP-EES, pinteraction=0.48 and BP-BES vs DP-ZES, pinteraction=0.87). After excluding 179 patients (101 in the BP-BES group) who did not receive allocated DES, the per-protocol analysis showed similar results. CONCLUSIONS: The risk of a composite of cardiac death, myocardial infarction, or stent thrombosis was not significantly different between patients receiving BP-BES versus DP-EES or DP-ZES across a short or prolonged duration of DAPT after ACS.

Primary malignant giant cell tumor of bone is clinically rare, lack of specificity, and often misdiagnosed. Currently, related literature about this tumor remains scarce. One case of primary malignant giant cell tumor of bone was diagnosed and treated in our hospital, and the treatment effect was satisfactory. There was no recurrence or metastasis in 2 years of follow-up. The report is as follows.

Thermal ablation (TA) for benign thyroid nodules (BTNs) is widely accepted as an effective and safe alternative to surgery. However, studies on the long-term outcomes of TA have reported problems with nodule regrowth and symptom recurrence, which have raised the need for adequate control of regrowth. Therefore, a more complete TA with a longer-lasting treatment effect may be required. In this study, we review and discuss long-term outcomes and regrowth of BTNs following TA and evaluate factors affecting the long-term outcomes. We also discuss the management of regrowth based on long-term outcomes.

Efficient biomarker-driven randomized clinical trials are a key tool for implementing precision oncology. A commonly used biomarker phase III design is focused on testing the treatment effect in biomarker-positive and overall study populations. This approach may result in recommending new treatments to biomarker-negative patients when these treatments have no benefit for these patients.

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS) characterized by the accumulation of focal white matter (WM) lesio...

Phase 2 and 3 development failure is one of the key factors for high drug development cost. Robust prediction of a candidate drug's efficacy and safety profile could potentially improve the success rate of the drug development. Therefore, systematic evaluation of the prediction is important for learning and continuous improvement of the prediction. In this article, we proposed a set of unified criteria that allow to evaluate the predictions across different endpoints, indications and development stages: standardized bias (SB), standardized mean squared errors (SMSE), and credibility of prediction. We applied the SB and SMSE to the predicted treatment effects for 54 comparisons in 5 compounds in immunology and diabetes.

Individuals differ in how they respond to a given treatment. In an effort to predict the treatment response and analyze the heterogeneity of treatment effect, we propose a general modeling framework by identifying treatment-covariate interactions honoring a hierarchical condition. We construct a single-step l1 norm penalty procedure that maintains the hierarchical structure of interactions in the sense that a treatment-covariate interaction term is included in the model only when either the covariate or both the covariate and treatment have nonzero main effects. We developed a constrained Lasso approach with two parameterization schemes that enforce the hierarchical interaction restriction differently. We solved the resulting constrained optimization problem using a spectral projected gradient method. We compared our methods to the unstructured Lasso using simulation studies including a scenario that violates the hierarchical condition (misspecified model). The simulations showed that our methods yielded more parsimonious models and outperformed the unstructured Lasso for correctly identifying nonzero treatment-covariate interactions. The superior performance of our methods are also corroborated by an application to a large randomized clinical trial data investigating a drug for treating congestive heart failure (N = 2569). Our methods provide a well-suited approach for doing secondary analysis in clinical trials to analyze heterogeneous treatment effects and to identify predictive biomarkers.

The objective of this study was to determine the association between biases related to attrition, missing data, and the use of intention to treat and changes in effect size estimates in physical therapy randomized trials. A meta-epidemiological study was conducted. A random sample of randomized controlled trials included in meta-analyses in the physical therapy discipline were identified. Data extraction including assessments of the use of intention to treat principle, attrition-related bias, and missing data was conducted independently by two reviewers. To determine the association between these methodological issues and effect sizes, a two-level analysis was conducted using a meta-meta-analytic approach. Three hundred ninety-three trials included in 43 meta-analyses, analyzing 44,622 patients contributed to this study. Trials that did not use the intention-to-treat principle (effect size = -0.13, 95% confidence interval = -0.26 to 0.01) or that were assessed as having inappropriate control of incomplete outcome data tended to underestimate the treatment effect when compared with trials with adequate use of intention to treat and control of incomplete outcome data (effect size = -0.18, 95% confidence interval = -0.29 to -0.08).Researchers and clinicians should pay attention to these methodological issues because they could provide inaccurate effect estimates. Authors and editors should make sure that intention-to-treat and missing data are properly reported in trial reports.

Summary. Purpose. The improvement of the treatment effect of patients with a decompensated form of the chronic venous insufficiency. Reduction of the reatment period in a hospital by application of the complex treatment. Materials and methods. The work was based on the studies of 24 patients who had trophic ulcers on the lower leg. All patients have undergone combined treatment, including scleroobliteration of perforating veins, phototherapy, platelet-derived growth factor, the use of wound closure with a heterograft. Results and discussion. The combined use of phototherapy and platelet-derived growth factor has significantly reduced the duration of all phases of the wound process. The ultrasound-controlled scleroobliteration has helped to remove a pathological reflux in the insolvent tibial perforators. The studies have shown that the use of phototherapy in the treatment of trophic ulcers with the application of the heterograft has contributed to the rapid cleansing of wounds, accelerating the appearance of granulations and epithelialization, has reduced the need for antibacterial therapy and is an alternative to autodermoplasty. Conclusions. The use of the offered technique allows to reach optimum restoration conditions of the affected fabrics trophism, leads to the decrease in the number of complications and reduces the hospitalization period.

PurposeThe purpose of the study is to assess the differential impact of gender and cancer sites on mental burden across different types of cancer and control patients.Design/methodology/approachThe paper is based on a primary survey undertaken in 2015–2016 of 600 cancer and 200 control patients across five hospitals of Nepal. The data was analyzed using propensity score matching methods and treatment effect weighting estimators.FindingsThe authors find that of all the types of patients covered under this study, cervical cancer patients suffered from a greater intensity of anxiety and lack of functional wellbeing. On an average, all other female, male cancer patients, and control patients experience significantly lower intensity of mental burden in the range of 1.83, 2.63 and 3.31, respectively when compared to patients of cervical cancer. The results are robust across all the four treatment effect estimators and through all the measures of mental burden. The implications of suffering from cervical cancer, as a unique gynecological cancer was studied in-depth. An effect size analysis pointed out to the dysfunctional familial relationship as additional causes of concern for cervical cancer patients.Originality/valueAn important finding that emerged is that female cancer patients especially those who have cervical cancer should be given special attention because they appear to be the most vulnerable group. Further work is needed to delineate the reasons behind a cervical cancer patient facing higher amount of stress.

Objectives The aims of this study were to review recent fungal infection case reports published, evaluate the treatment regimens and clinical outcomes, and provide recommendations for future management. Methods A review of case reports published over the last decade was conducted. PubMed was searched to collect the relevant citations using a combination of the key words ("burn," "burned," "burns," "fungal," "fungi," and "fungus") in title or abstract. Case series, reviews, guidelines, and experimental and non-English studies were excluded. Statistical analyses were performed using Microsoft Excel 2019. Results A total of 36 case reports encompassing a total of 44 burn patients with fungal infection were included in the final analysis. Ablative surgeries, including surgical excision, debridement, skin graft, vitrectomy, teeth extraction, valve replacement, or amputation, were performed in 38 cases after the suspicion or identification of fungal infection. Twenty-nine of them were eventually discharged, yielding a survival rate of 76.3%. In the remaining 6 cases, ablative surgery was not mentioned and 3 of them eventually died, yielding a survival rate of 50%. The total mortality was 27.27%. Among the 12 death cases, 1 was infected with Candida albicans, 1 with non-albicans Candida, 2 with Aspergillus spp, 2 with Fusarium spp, 4 with Zygomycetes, and 2 with other fungal species. Conclusions The overall mortality of fungal wound infection is still high in burn patients around the world, especially those infected with non-Candida species. Early diagnosis of fungal infection, early initiation of appropriate antifungal therapy, and effective surgical intervention are key measures to improve the treatment effect and reduce the mortality of fungal infection in burn patients.

Objectives Onasemnogene Abeparvovec-xioi (AVXS-101) is a gene therapy intended for curative treatment of spinal muscular atrophy (SMA) with an expected price of around €2 000 000. The goal of this study is to perform a cost-effectiveness analysis of treatment of SMA I patients with AVXS-101 in The Netherlands including relapse scenarios. Methods An individual-based state-transition model was used to model treatment effect and survival of SMA I patients treated with AVXS-101, nusinersen and best supportive care (BSC). The model included five health states: three health states according to SMA types, one for permanent ventilation and one for death. Deterministic and probabilistic sensitivity analyses were performed. Effects of relapsing to lower health states in the years following treatment was explored. Results The base-case incremental cost-effectiveness ratio (ICER) for AVXS-101 versus BSC is €138 875/QALY, and €53 447/QALY for AVXS-101 versus nusinersen. If patients relapse within 10 years after treatment with AVXS-101, the ICER can increase up to 6-fold, with effects diminishing thereafter. Only relapses occurring later than 50 years after treatment have a negligible effect on the ICER. To comply with Dutch willingness-to-pay reference values, the price of AVXS-101 must decrease to €680 000. Conclusions Based on this model, treatment with AVXS-101 is unlikely to be cost-effective under Dutch willingness-to-pay reference values. Uncertainty regarding the long-term curative properties of AVXS-101 can result in multiplication of the ICER. Decision-makers are advised to appropriately balance these uncertainties against the price they are willing to pay now.

Statistical analyses of randomized controlled trials (RCTs) yield a causally valid estimate of the overall treatment effect, which is the contrast between the outcomes in two randomized treatment groups commonly accompanied by a confidence interval. In addition, the trial investigators may want to examine whether the observed treatment effect varies across patient subgroups (also called 'heterogeneity of treatment effects'), i.e. whether the treatment effect is modified by the value of a variable assessed at baseline. The statistical approach for this evaluation of potential effect modifiers is a test for statistical interaction to evaluate whether the treatment effect varies across levels of the effect modifier. In this article, we provide a concise and nontechnical explanation of the use of simple statistical tests for interaction to identify effect modifiers in RCTs. We explain how to calculate the test of interaction by hand, applied to a dataset with simulated data on 1,000 imaginary participants for illustration. (C) 2021 The Author(s). Published by Elsevier Inc.

Given the association between deviated inflammatory chemokines, the pathogenesis of autism spectrum disorders (ASD), and our previous findings of the Chanwuyi Lifestyle Medicine Program regarding improved cognitive and behavioral problems in ASD, the present study aims to explore if this intervention can alter pro-inflammatory chemokines concentration. Thirty-two boys with ASD were assigned to the experimental group receiving the Chanwuyi Lifestyle Medicine Program for 7 months or the control group without a change in their lifestyle. The experimental group, but not the control group, demonstrated significantly reduced CCL2 and CXCL8, a trend of reduction in CCL5, and elevation of CXCL9. The experimental group also demonstrated significantly reduced social communication problems, repetitive/stereotypic behaviors, and hyperactive behaviors. The present findings support the potential efficacy and applicability of the Chanwuyi Lifestyle Medicine Program for reducing both behavioral problems and immunological dysfunction in ASD. Further studies are warranted to verify its treatment effect and its association with brain functions.

Introduction Quantitative patient-reported outcome (PRO) measures ideally are analyzed on their original scales and responder analyses are used to aid the interpretation of those primary analyses. As stated in the FDA PRO Guidance for Medical Product Development (2009), one way to lend meaning and interpretation to such a PRO measure is to dichotomize between values where within-patient changes are considered clinically important and those that are not. But even a PRO scale with a cutoff score that discriminates well between responder and non-responders is fraught with some misclassification. Methods Using estimates of sensitivity and specificity on classification of responder status from a PRO instrument, formulas are provided to correct for such responder misclassification under the assumption of no treatment misclassification. Two case studies from sexual medicine illustrate the methodology. Results Adjustment formulas on cell counts for responder misclassification are a direct extension of correction formulas for misclassification on disease from a two-way cross-classification table of disease (yes, no) and exposure (yes, no). Unadjusted and adjusted estimates of treatment effect are compared in terms of odds ratio, response ratio, and response difference. In the two case studies, there was considerable underestimation of treatment effect. Discussion and conclusions The methodology can be applied to different therapeutic areas. Limitations of the methodology, such as when adjusted cell estimates become negative, are highlighted. The role of anchor-based methodology is discussed for obtaining estimates of sensitivity and specificity on responder classification. Correction for treatment effect bias from misclassification of responder status on PRO measures can lead to more trustworthy interpretation and effective decision-making. Clinicaltrials.gov: NCT00343200

Strengthening the pathway to entrepreneurship for high school students could be important in regions of the United States where economic mobility is low. We examine the impact of high school business education on the decision to be a self-employed entrepreneur in two southeastern urban U.S. high schools. We appeal to a potential-outcomes framework to estimate the treatment effect of having taken a business and coding/programming course in high school on actually being a self-employed entrepreneur, and planning to do so in the future. We find evidence that having taken a business course in high school increases the likelihood of actually being a self-employed entrepreneur, and on planning to be one in the future. Our results suggest that, at least in Atlanta and New Orleans, urban high school business education can be effective in increasing the supply of entrepreneurs, which could improve economic mobility in these urban regions. JEL Classification: C14, C21, E10, I26, J01, J20, J40, M13

Summary Background At the clinical trial design stage, assumptions regarding the treatment effects to be detected should be appropriate so that the required sample size can be calculated. There is evidence in the medical literature that sample size assumption can be overoptimistic. The aim of this study was to compare the distribution of the assumed effects versus that of the observed effects as a proxy for overoptimistic treatment effect assumptions at the study design stage. Materials and method Systematic reviews (SRs) published between 1 January 2010 and 31 December 2019 containing at least one meta-analysis on continuous outcomes were identified electronically. SR and primary study level characteristics were extracted from the SRs and the individual trials. Details on the sample size calculation process and assumptions and the observed treatment effects were extracted. Results Eighty-five SRs with meta-analysis containing 347 primary trials were included. The median number of SR authors was 5 (interquartile range: 4–7). At the primary study level, the majority were single centre (78.1%), utilized a parallel design (52%), and rated as an unclear/moderate level of risk of bias (34.3%). A sample size was described in only 31.7% (110/347) of studies. From this cohort of 110 studies, in only 37 studies was the assumed clinical difference that the study was designed to detect reported (37/110). The assumed treatment effect was recalculated for the remaining 73 studies (73/110). The one-sided exact signed rank test showed a significant difference between the assumed and observed treatment effects (P < 0.001) suggesting greater values for the assumed effect sizes. Conclusions Careful consideration of the assumptions at the design stage of orthodontic studies are necessary in order to reduce the unreliability of clinical study results and research waste.