Generalized Gamma Model Research Articles

Osteochondroplasty with or without labral repair is more cost-effective than arthroscopic lavage with or without labral repair for treatment of young adults with femoroacetabular impingement: A cost-utility analysis based on data from a randomized controlled trial

ObjectivesThe objective of this study was to conduct a cost–utility analysis of osteochondroplasty with or without labral repair compared to arthroscopic lavage with or without labral repair for femoroacetabular impingement (FAI) from a Canadian public payer perspective. MethodsA Markov model was constructed to compare the lifetime quality-adjusted life years (QALYs) and costs of the two treatment strategies. The target population was surgical FAI patients aged 36 years. The primary data source was patient-level data from the Femoroacetabular Impingement Randomised Controlled Trial, which evaluated the efficacy of the surgical correction of FAI via arthroscopic osteochondroplasty with or without labral repair compared to arthroscopic lavage with or without labral repair in Canada. Long-term data were extrapolated using a generalized gamma model. The primary outcome was the incremental cost-effectiveness ratio, calculated by dividing the difference in costs by the difference in QALYs between osteochondroplasty and lavage, with or without labral repair. Probabilistic sensitivity analyses and one-way sensitivity analyses were used to characterize uncertainty of model parameters and assumptions. ResultsOver a lifetime horizon, osteochondroplasty, with or without labral repair, had a greater expected benefit (0.63 QALYs gained per patient) and lower costs ($955.89 saved per patient), as compared with lavage with or without labral repair. Probabilistic sensitivity analyses demonstrated that the probability of osteochondroplasty, with or without labral repair, being cost-effective was 90.5% at a commonly used willingness-to-pay threshold of $50,000/QALY in Canada. Across all one-way sensitivity analyses, osteochondroplasty with or without labral repair remained a cost-effective option. ConclusionOver a lifetime time horizon, osteochondroplasty, with or without labral repair, is a cost-effective treatment strategy for young adults with FAI. Future research involving real-word data is needed to further validate these findings. Level of evidenceIII.

Reduced human fecundity attributable to ambient fine particles in low- and middle-income countries

BackgroundExposure to ambient fine particulate matter (PM2.5) has been associated with reduced human fecundity. However, the attributable burden has not been estimated for low- and middle-income countries (LMICs), where the exposure–response function between PM2.5 and the infertility rate has been insufficiently studied. ObjectiveThis study examined the associations between long-term exposure to PM2.5 and human fecundity indicators, namely the expected time to pregnancy (TTP) and 12-month infertility rate (IR), and then estimated PM2.5-attributable burden of infertility in LMICs. MethodsWe analyzed 164,593 eligible women from 100 Demographic and Health Surveys conducted in 49 LMICs between 1999 and 2021. We assessed PM2.5 exposures during the 12 months before a pregnancy attempt using the global satellite-derived PM2.5 estimates produced by Atmospheric Composition Analysis Group (ACAG). First, we created a series of pseudo-populations with balanced covariates, given different levels of PM2.5 exposure, using a matching approach based on the generalized propensity score. For each pseudo-population, we used 2-stage generalized Gamma models to derive TTP or IR from the probability distribution of the questionnaire-based duration time for the pregnancy attempt before the interview. Second, we used spline regressions to generate nonlinear PM2.5 exposure–response functions for each of the two fecundity indicators. Finally, we applied the exposure–response functions to estimate number of infertile couples attributable to PM2.5 exposure in 118 LMICs. ResultsBased on the Gamma models, each 10 µg/m3 increment in PM2.5 exposure was associated with a TTP increase by 1.7 % (95 % confidence interval [CI]: -2.3 %–6.0 %) and an IR increase by 2.3 % (95 %CI: 0.6 %–3.9 %). The nonlinear exposure–response function suggested a robust effect of an increased IR for high-concentration PM2.5 exposure (>75 µg/m3). Based on the PM2.5-IR function, across the 118 LMICs, the number of infertile couples attributable to PM2.5 exposure exceeding 35 µg/m3 (the first-stage interim target recommended by the World Health Organization global air quality guidelines) was 0.66 million (95 %CI: 0.061–1.43), accounting for 2.25 % (95 %CI: 0.20 %–4.84 %) of all couples affected by infertility. Among the 0.66 million, 66.5 % were within the top 10 % high-exposure infertile couples, mainly from South Asia, East Asia, and West Africa. ConclusionPM2.5 contributes significantly to human infertility in places with high levels of air pollution. PM2.5-pollution control is imperative to protect human fecundity in LMICs.

A 39 Year mortality study of survivors exposed to sulfur mustard agent: A survival analysis

BackgroundThe primary objective of this study was to analyze the long-term survival of 48,067 chemical warfare survivors who suffered from pulmonary, cutaneous, and ocular lesions in the decades following the Iran-Iraq war. MethodsThe data for this study were obtained from the Veterans and Martyr Affair Foundation (VMAF) database. The survivors were divided into two groups based on whether they were evacuated/admitted (EA) to a hospital or not evacuated/admitted (NEA) to a hospital. The proportional hazard (PH) assumption for age categories, gender, exposure statuses, and eye severity was not satisfied. Therefore, we used a Generalized Gamma (GG) distribution with an Accelerated Failure Time (AFT) model for analysis. ResultsThe study included a total of 48,067 observations, and among them, 4342 (9.03 %) died during the study period. The mean (SD) age of the survivors was 55.99 (7.9) years. The mortality rate increased with age, and higher rates were observed in males. Survival probabilities differed significantly among age categories, provinces, lung severity, and eye severity based on log-rank tests (p-value<0.05 for all). The GG model results showed that higher age and being male were associated with a shorter time to death. The study also found that the mortality rate was significantly higher in the EA group compared to the NEA group. ConclusionThe present study showed no significant difference in survival time between the EA and NEA groups. The findings suggest that pulmonary lesions caused by mustard gas are more likely to be fatal compared to skin and eye lesions. The results also indicate a potential association between survival time and the severity of lung damage.

ANALYSIS OF THE RISK OF RECURRENT WHEEZING IN CHILDREN WITH BRONCHIOLITIS BASED ON THE WEIBULL MATHEMATICAL MODEL

Given the frequency of recurrent wheezing (up to 50 % of cases) in young children during the first year after bronchiolitis, the assessment of the prognostic value of diagnostic biological markers of bronchiolitis requires special attention.According to modern concepts, mast cells, eosinophils, play a significant role in the pathogenesis of bronchiolitis, with degranulation of which the release of cationic proteins (eosinophilic cationic protein (ECP), eosinophil-derived neurotoxin (EDN)) and molecular mediators, namely vascular cell adhesion molecule-1 (VCAM-1), which is a regulator of leukocyte adhesion and transendothelial migration. That is why VCAM-1, ECP and EDN are discussed as important prognostic markers in assessing the risk of recurrent wheezing in children with bronchiolitis.The aim of the study. To analyze the risk factors for recurrent wheezing in children with bronchiolitis, considering allergic history, the influence of external factors (passive smoking, place of residence), levels of VCAM-1, ECP, EDN in the blood serum.Material and Methods. This article is a part of the research work of the Department of Paediatrics No. 1 of Vinnytsia National Medical University named after M.I. Pyrohov on the topic "Optimization of diagnosis and treatment of somatic pathology in children", state registration No. 0115U007075.A clinical examination of 67 infants was carried out. The main group consisted of 34 children with bronchiolitis without a complicated allergic history. The comparison group consisted of 33 children with bronchiolitis who had a burdened allergic history. The average age of the children in the main group was 8.4±1.6 months, and 6.2±1.4 months in the comparison group. The analytical component of the study was based on parametric survival models (Weibull and generalized Gamma models). The analysis of Weibull models was performed in the statistical packages of analytical system R for Mac OS X FAQ, Version 3.1.0 2014-04-10, R. app 1.64 based on the Mac OS X 10.9 platform, 64-bit Intel Core i7 architecture.The study was approved by the Commission on Biomedical Ethics for compliance with the moral and legal rules for conducting medical research at Vinnytsia National Medical University named after M.I. Pyrohov. It was established that the research does not contradict the basic bioethical norms and meets the principles of compliance with the basic provisions of the GCP (1996), the Council of Europe Convention on Human Rights and Biomedicine (04.04.1997), WMA Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects (1964-2008) and Order of the Ministry of Health of Ukraine No. 690 of 23.09.2009 (as amended by Order of the Ministry of Health of Ukraine No. 523 of 12.07.2012). All patients were informed about the purpose and possible consequences of the research procedures. All patients signed an informed written consent to participate in the study prior to the procedure.Results of the study. The risks of recurrent wheezing in children with bronchiolitis according to the Weibull model were allergic history ( β=1,996) mixed feeding, and to an even greater extent artificial feeding ( β=7,832 and β=8,337). High serum levels of ECP β=5,03, EDN β=0,182 and VCAM-1 β=0,0254 are reliable markers of increased risk of recurrent wheezing in children with bronchiolitis. Living in rural areas ( β=-5,8) significantly reduces the risk of recurrent wheezing in children with bronchiolitis compared to children living in urban areas β=0.0162).Conclusions. 1. The levels of VCAM-1, ECP and EDN in the blood serum were recognized as reliable markers for the prognosis of recurrent vesicitis in children with bronchiolitis. The level of EDN ≤ 7 ng/ml in the blood serum is a prognostic marker for the risk of recurrent wheezing in children with bronchiolitis.2. The hypothesis that artificial feeding in children with bronchiolitis with a complicated allergic history confirms and significantly increases the risk of recurrent vesicitis in children with bronchiolitis. The hypothesis about the role of passive smoking exposure in a significant increase in the risk of recurrent wheezing in children with bronchiolitis was confirmed only for patients with EDN levels not exceeding 7 ng/ml in the blood serum.

Longitudinal changes of health-related quality of life in childhood chronic kidney disease.

Few longitudinal studies have evaluated the impact of chronic kidney disease (CKD) duration on health-related quality of life (HRQOL). The study's aim was to determine how HRQOL changes over time in childhood CKD. Study participants were children in the chronic kidney disease in children (CKiD) cohort who completed the pediatric quality of life inventory (PedsQL) on three or more occasions over the course of two or more years. Generalized gamma (GG) mixed-effects models were applied to assess the effect of CKD duration on HRQOL while controlling for selected covariates. A total of 692 children (median age = 11.2) with a median of 8.3years duration of CKD were evaluated. All subjects had a GFR greater than 15ml/min/1.73 m2. GG models with child self-report PedsQL data indicated that longer CKD duration was associated with improved total HRQOL and the 4 domains of HRQOL. GG models with parent-proxy PedsQL data indicated that longer duration was associated with better emotional but worse school HRQOL. Increasing trajectories of child self-report HRQOL were observed in the majority of subjects, while parents less frequently reported increasing trajectories of HRQOL. There was no significant relationship between total HRQOL and time-varying GFR. Longer duration of the disease is associated with improved HRQOL on child self-report scales; however, parent-proxy results were less likely to demonstrate any significant change over time. This divergence could be due to greater optimism and accommodation of CKD in children. Clinicians can use these data to better understand the needs of pediatric CKD patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

A UK cost-effectiveness analysis of trifluridine/tipiracil for heavily pretreated metastatic gastroesophageal cancers.

Background: The current work was designed to estimate the cost-effectiveness of trifluridine/tipiracil (T/T) versus best supportive care (BSC) for patients with advanced stage or metastatic gastroesophageal cancer (mGC) from a UK perspective. Materials & methods: A partitioned survival analysis was undertaken using data from the phase III TAGS trial. A jointly fitted lognormal model was selected for overall survivaland individual generalized gamma models were chosen for progression-free survival and time-to-treatment-discontinuation. The primary outcome was the cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were undertaken to investigate uncertainty. Results: Compared with BSC, T/T was associated with a cost per QALY gained of £37,907. Conclusion: T/T provides a cost-effective treatment option for mGCin the UK setting.

The Retrieval of Drop Size Distribution Parameters Using a Dual-Polarimetric Radar

The raindrop size distribution (DSD) is vital for applications such as quantitative precipitation estimation, understanding microphysical processes, and validation/improvement of two-moment bulk microphysical schemes. We trace the history of the DSD representation and its linkage to polarimetric radar observables from functional forms (exponential, gamma, and generalized gamma models) and its normalization (un-normalized, single/double-moment scaling normalized). The four-parameter generalized gamma model is a good candidate for the optimal representation of the DSD variability. A radar-based disdrometer was found to describe the five archetypical shapes (from Montreal, Canada) consisting of drizzle, the larger precipitation drops and the ‘S’-shaped curvature that occurs frequently in between the drizzle and the larger-sized precipitation. Similar ‘S’-shaped DSDs were reproduced by combining the disdrometric measurements of small-sized drops from an optical array probe and large-sized drops from 2DVD. A unified theory based on the double-moment scaling normalization is described. The theory assumes the multiple power law among moments and DSDs are scaling normalized by the two characteristic parameters which are expressed as a combination of any two moments. The normalized DSDs are remarkably stable. Thus, the mean underlying shape is fitted to the generalized gamma model from which the ‘optimized’ two shape parameters are obtained. The other moments of the distribution are obtained as the product of power laws of the reference moments M3 and M6 along with the two shape parameters. These reference moments can be from dual-polarimetric measurements: M6 from the attenuation-corrected reflectivity and M3 from attenuation-corrected differential reflectivity and the specific differential propagation phase. Thus, all the moments of the distribution can be calculated, and the microphysical evolution of the DSD can be inferred. This is one of the major findings of this article.

Impact of integration time steps of rain drop size distribution on their double-moment normalization: a case study in northern Benin

This study analyzed the sensitivity of the double-moment normalization of rain drop size distributions (DSDs) to their integration time steps. Six DSD datasets measured at different integration time steps were modeled by the double-moment normalization method. Six couples of reference moments are used for the normalization. Three DSD models (gamma, generalized gamma and lognormal) are used for modeling. Statistical criteria are used to assess the estimation of the moments of the DSDs made by the models. As results, the analysis highlighted the dependence of the shape function parameters on the DSD integration time step. It is also noted that the three DSD models are well adapted to the data used. Nevertheless, the generalized gamma model is recommended because of the independence of the moment estimation errors with respect to the integration time step, which is not the case for the other models.

OP236 Evidence Synthesis Of Time-To-Event Outcomes In The Presence Of Non-Proportional Hazards

IntroductionSynthesis of clinical effectiveness is a well-established component of health technology assessment (HTA) combining data from multiple trials to obtain an overall pooled estimate of clinical effectiveness, which may inform an associated economic evaluation. Time-to-event outcomes are often synthesized using effect measures from Cox proportional hazards models assuming a constant hazard ratio over time. However, where treatment effects vary over time an assumption of proportional hazards is not always valid. Several methods have been proposed for synthesizing time-to-event outcomes in the presence of non-proportional hazards. However, guidance on choosing between these methods and the implications for HTA is lacking.MethodsWe applied five methods for estimating treatment effects from time-to-event outcomes, which relax the proportional hazards assumption to a network of melanoma trials, reporting overall survival: restricted mean survival time, an accelerated failure time generalized gamma model, piecewise exponential, fractional polynomial and Royston-Parmar models. We conducted a simulation study to compare these five methods. Simulated individual patient data was generated from a mixture Weibull distribution assuming a treatment-time interaction. Each simulated meta-analysis consisted of five trials with varying numbers of patients and length of follow-up across trials. For each model fitted to each dataset, we calculated the restricted mean survival time at the end of observed follow-up and following extrapolation to a 20-year time horizon.ResultsAll models fitted the melanoma data reasonably well with some variation in the treatment rankings and differences in the survival curves. The simulation study demonstrated the potential for different conclusions from different modelling approaches.ConclusionsThe restricted mean survival time, generalized gamma, piecewise exponential, fractional polynomial and Royston-Parmar models can all accommodate non-proportional hazards and differing lengths of trial follow-up within an evidence synthesis of time-to-event outcomes. Further work is needed in this area to extend the simulation study to the network meta-analysis setting and provide guidance on the key considerations for informing model choice for the purposes of HTA.

Retrieving Rain Drop Size Distribution Moments from GPM Dual-Frequency Precipitation Radar

A novel method for retrieving the moments of rain drop size distribution (DSD) from the dual-frequency precipitation radar (DPR) onboard the global precipitation mission satellite (GPM) is presented. The method involves the estimation of two chosen reference moments from two specific DPR products, namely the attenuation-corrected Ku-band radar reflectivity and (if made available) the specific attenuation at Ka-band. The reference moments are then combined with a function representing the underlying shape of the DSD based on the generalized gamma model. Simulations are performed to quantify the algorithm errors. The performance of methodology is assessed with two GPM-DPR overpass cases over disdrometer sites, one in Huntsville, Alabama and one in Delmarva peninsula, Virginia, both in the US. Results are promising and indicate that it is feasible to estimate DSD moments directly from DPR-based quantities.

Programmed Death-Ligand 1 Tumor Proportion Score and Overall Survival From First-Line Pembrolizumab in Patients With Nonsquamous Versus Squamous NSCLC

IntroductionFor patients with NSCLC receiving immune checkpoint inhibitors, programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) has been validated as a predictive biomarker for improved overall survival (OS). Nevertheless, its histology-specific predictive value in patients with advanced squamous versus nonsquamous cancers remains unclear. To evaluate the differential value of PD-L1 TPS as a predictive biomarker for OS after first-line pembrolizumab in patients with squamous versus nonsquamous NSCLC. MethodsRetrospective, observational study of patients diagnosed with having advanced NSCLC who were treated between October 2015 and April 2019 at community oncology clinics and academic medical centers in a deidentified electronic health record–derived database. Included patients were diagnosed with having advanced or metastatic NSCLC, received treatment with first-line, single-agent pembrolizumab, and had documentation of PD-L1 testing with a numeric result. Exclusion criteria included alterations in EGFR, ALK, and ROS1. The primary end point was OS from start of first-line pembrolizumab therapy by squamous or nonsquamous histology and PD-1 expression level measured by TPS (low, <50% or high, ≥50%). ResultsThe cohort of 1460 patients with NSCLC who received pembrolizumab as a first-line therapy had a mean age of 72 years. Histology was 28% squamous and 72% nonsquamous. PD-L1 expression was low in 13% and high in 87%. No meaningful differences in age, sex, or smoking history were observed by PD-L1 TPS or histology type. A generalized gamma model adjusting for sex and stage at diagnosis found that for patients with nonsquamous histology, high PD-L1 TPS was significantly associated with improved OS by a median OS difference of 8.4 months (p < 0.001). In contrast, for patients with squamous histology, there was no evidence of association between PD-L1 expression level and OS (p = 0.283). PD-L1–related incremental differences in median OS between the patients with squamous and nonsquamous tumors were significantly different (p = 0.034). ConclusionsAmong patients with NSCLC treated with first-line pembrolizumab, high PD-L1 TPS is associated with OS among patients with nonsquamous NSCLC, but not among patients with squamous NSCLC.

A New Double Truncated Generalized Gamma Model with Some Applications

The generalized Gamma model has been applied in a variety of research fields, including reliability engineering and lifetime analysis. Indeed, we know that, from the above, it is unbounded. Data have a bounded service area in a variety of applications. A new five-parameter bounded generalized Gamma model, the bounded Weibull model with four parameters, the bounded Gamma model with four parameters, the bounded generalized Gaussian model with three parameters, the bounded exponential model with three parameters, and the bounded Rayleigh model with two parameters, is presented in this paper as a special case. This approach to the problem, which utilizes a bounded support area, allows for a great deal of versatility in fitting various shapes of observed data. Numerous properties of the proposed distribution have been deduced, including explicit expressions for the moments, quantiles, mode, moment generating function, mean variance, mean residual lifespan, and entropies, skewness, kurtosis, hazard function, survival function, r th order statistic, and median distributions. The delivery has hazard frequencies that are monotonically increasing or declining, bathtub-shaped, or upside-down bathtub-shaped. We use the Newton Raphson approach to approximate model parameters that increase the log-likelihood function and some of the parameters have a closed iterative structure. Six actual data sets and six simulated data sets were tested to demonstrate how the proposed model works in reality. We illustrate why the Model is more stable and less affected by sample size. Additionally, the suggested model for wavelet histogram fitting of images and sounds is very accurate.

The Log-Kumaraswamy Generalized Gamma Regression Model with Application to Chemical Dependency Data

The five parameter Kumaraswamy generalized gamma model (Pas coa et al., 2011) includes some important distributions as special cases and it is very useful for modeling lifetime data. We propose an extended version of this distribution by assuming that a shape parameter can take negative values. The new distribution can accommodate increasing, decreasing, bath tub and unimodal shaped hazard functions. A second advantage is that it also includes as special models reciprocal distributions such as the recipro cal gamma and reciprocal Weibull distributions. A third advantage is that it can represent the error distribution for the log-Kumaraswamy general ized gamma regression model. We provide a mathematical treatment of the new distribution including explicit expressions for moments, generating function, mean deviations and order statistics. We obtain the moments of the log-transformed distribution. The new regression model can be used more effectively in the analysis of survival data since it includes as sub models several widely-known regression models. The method of maximum likelihood and a Bayesian procedure are used for estimating the model pa rameters for censored data. Overall, the new regression model is very useful to the analysis of real data.

Effects of Medicaid Health Homes among people with substance use disorder and another chronic condition on health care utilization and spending: Lessons from New York State

IntroductionNew York State implemented a Health Homes (HH) care management program to facilitate access to health services for Medicaid enrollees with multiple chronic conditions. This study assessed the impact of HH on health care utilization outcomes among enrollees who have substance use disorder (SUD). MethodsUsing HH enrollment data and Medicaid claims data 1 year before and after enrollment, this study compared HH enrollees who enrolled between 2012 and 2014 to a statistically matched comparison group created with propensity score methods. Analyses used generalized gamma models, logistic regression models, and difference-in-differences analyses to assess the impact of HH on general (all-cause) health care and SUD-related outpatient, emergency department (ED), hospitalization, and detoxification utilization as well as total Medicaid cost. ResultsThe sample consisted of 41,229 HH enrollees and a comparison group of 39,471 matched patients. HH-enrolled patients who had SUD utilized less SUD-related ED services (average marginal effect (AME) = −1.85; 95% CI = −2.45, −1.24), SUD-related hospitalizations (AME = −1.28; 95% CI: −1.64, −0.93), and detoxification services (AME = −1.30; 95% CI = −1.64, −0.96), relative to the comparison group during the 1 year post-HH enrollment. SUD-related outpatient visits did not change significantly (AME = −0.28; 95% CI = −0.76, 0.19) for enrollees, but general health care outpatient visits increased (AME = 1.63; 95% CI = 1.33, 1.93). ConclusionThese findings provide preliminary evidence that care management programs can decrease ED visits and hospitalizations among people with SUD.

The Transmuted Generalized Gamma Distribution: Properties and Application

The generalized gamma model has been used in several applied areas such as engineering, economics and survival analysis. We provide an extension of this model called the transmuted generalized gamma distribution, which includes as special cases some lifetime distributions. The proposed density function can be represented as a mixture of generalized gamma densities. Some mathematical properties of the new model such as the moments, generating function, mean deviations and Bonferroni and Lorenz curves are provided. We estimate the model parameters using maximum likelihood. We prove that the proposed distribution can be a competitive model in lifetime applications by means of a real data set.

Generalized Zero-Adjusted Models to Predict Medical Expenditures.

In healthcare research, medical expenditure data for the elderly are typically semicontinuous and right-skewed, which involve a point mass at zero and may exhibit heteroscedasticity. The problem of a substantial proportion of zero values prevents traditional regression techniques based on the Gaussian, gamma, or inverse Gaussian distribution, which may lead to understanding the standard errors of the parameters and overestimating their significance. A common way to counter the problem is using zero-adjusted models. However, due to the right-skewness in the nonzeros' response, conventional zero-adjusted models such as zero-adjusted gamma, zero-adjusted Inverse Gaussian, and classic Tobit may not perform well. Here, we firstly generalize those three types of the conventional zero-adjusted model to solve the problem of right-skewness in health care. The generalized zero-adjusted models are very flexible and include the zero-adjusted Weibull, zero-adjusted gamma, zero-adjusted inverse Gaussian, and classic Tobit models as their special cases. Using the Chinese Longitudinal Healthy Longevity Survey, we find that, according to the AIC, SBC, and deviance criteria, the zero-adjusted generalized gamma model is the best one of these generalized models to predict the odds of zero cost accurately. In order to depict the predictors affecting the amount expenditure, we further discuss the situations where the mean, dispersion of a nonzero amount expenditure and model the probability of a zero amount of ZAGG in terms of predictor variables using suitable link functions, respectively. Our analysis shows that age, health, chronic diseases, household income, and residence are the main factors influencing the medical expenditure for the elderly, but the insurance is not significant. To the best of our knowledge, little study focused on these situations, and this is the first time.

Effect of Statin Use on Inflammation and Immune Activation Biomarkers in HIV-Infected Persons on Effective Antiretroviral Therapy.

Immune activation and inflammation are hallmarks of chronic HIV infection and are etiologically linked to major causes of morbidity and mortality among HIV-infected persons, including coronary artery disease and cancer. Systemic immune activation is dampened, but not resolved, with use of combination antiretroviral therapy (cART). Statins are cardioprotective drugs that also appear to have immunomodulatory and anti-inflammatory properties. We sought to understand the association between statin use, cART, and levels of circulating immune markers in a longitudinal cohort study. From 2004 to 2009, statin use was ascertained in male participants of the Multicenter AIDS Cohort Study (MACS) using interviewer-administered questionnaires. Twenty-four circulating markers of immune activation and inflammation were measured in archived serial samples from a subset of cohort members using multiplex assays. Propensity-adjusted generalized gamma models were used to compare biomarkers' distributions by statin use, and multivariable linear regression models were used to assess the effect of initiating statin on these biomarkers. Overall, 1,031 cART-exposed individuals with HIV infection were included in this study. Statin use was reported by 31.5% of cART-exposed participants. Compared to nonstatin users on cART, statin users on cART had lower levels of IP-10, IL-10, and IL-12p70, and the effect of statin use was decreased in participants using lipophilic statins (atorvastatin, simvastatin, fluvastatin, or lovastatin); these results were statistically significant (p < .05). Among cART users not on aspirin, starting statins decreased levels of high sensitivity c-reactive protein (hsCRP), IL-12p70, and IL-6. Statin therapy is associated with reduced levels of certain biomarkers of immune activation and inflammation in cART users, which may contribute to a lower burden of disease.

PD-L1 tumor proportion score and clinical benefit from first-line pembrolizumab in patients with advanced nonsquamous versus squamous non-small cell lung cancer (NSCLC).

9539 Background: The predictive value of PD-L1 tumor proportion score (TPS) on NSCLC tumor cells as a biomarker for response to PD-(L)1 inhibitors is well established. However, its histology specific value in advanced (a) squamous (Sq) versus nonsquamous (NS) cancers remains unclear. Here, we used real world data to assess the differential value of PD-L1 TPS as a predictive biomarker for overall survival (OS) after first-line pembrolizumab (P) in patients (pts) with Sq versus NS NSCLC. Methods: Inclusion criteria for this analysis of the Flatiron Health EHR-derived de-identified database required that pts were diagnosed with aNSCLC, tested for PD-L1 TPS and received a numerical result, had no alteration in EGFR, ALK, or ROS, and received first-line, single agent P. The primary endpoint was overall survival (OS) from the first dose of P in patients with TPS ≥ 50% (H) compared to patients with TPS &lt; 50% (L). Due to the violation of the proportional hazards assumption, a generalized gamma model of OS was used, adjusting for demographic variables and estimated median OS and their confidence intervals with the bootstrap method. The PD-L1-histology interaction was examined by comparing the differences in median OS (H vs. L) between Sq and NS patients. Results: Of 1560 pts with NSCLC treated from 1/2011 – 5/2019, 1055 had NS and 405 Sq. No meaningful differences in age, gender, or smoking history were seen between PD-L1 H and L pts with either histology. Among NS pts, H had significantly longer OS than L, with unadjusted hazard ratio (HR) of 0.71 (95% CI: 0.53 - 0.94; p = 0.018). Among Sq pts, H was not associated with longer OS than L, with unadjusted HR 0.89 (95% CI: 0.64 - 1.25; p = 0.514). Based on the generalized gamma model, PD-L1 H in Sq patients was associated with a 0.19 year improvement in median OS (95% CI: -0.22-0.49, P = 0.283), whereas PD-L1 H in the NS group was associated with a 0.70 year improvement in OS (95% CI: 0.34-1.05, P &lt; 0.001). The median improvements between the Sq and NS patients were significantly different (P = 0.034), after adjusting for demographic variables. Conclusions: PD-L1 TPS of ≥ 50% predicted longer OS in pts with NS NSCLC treated with first-line P compared to pts whose tumors had a TPS of &lt; 50%. However, no relationship between PD-L1 TPS and OS after first-line P was seen in patients with Sq NSCLC. These data suggest that PD-L1 may not be an appropriate predictive biomarker for checkpoint inhibitor use in NSCLC with squamous histology.

Partial Normalization of Biomarkers of Inflammation and Immune Activation Among Virally Suppressed Men With HIV Infection and High ART Adherence.

BackgroundThe objective of this study was to investigate whether 100% antiretroviral therapy (ART) adherence in men with HIV (MWH) is associated with normalization of concentrations of biomarkers of inflammation and immune activation compared with HIV-uninfected men.MethodsWe analyzed person-visits with available biomarker data from the Multicenter AIDS Cohort Study (MACS) among MWH receiving ART with HIV RNA <50 copies/mL and among HIV-uninfected men. Self-reported adherence was classified as 100% if no missed ART doses in the past 4 days were reported. We evaluated associations between ART adherence and concentrations of 24 serum biomarkers compared with HIV-uninfected visits using a generalized gamma model, adjusting for potential confounders.ResultsPerson-visits (2565 from MWH reporting 100% ART adherence and 1588 from HIV-uninfected men) from a total of 1469 men were included in the analysis. Serum concentrations of interleukin-6 (IL-6), soluble interleukin-6 receptor (sIL-6R), IL-1β, interferon-γ (IFN-γ), chemokine C-C motif ligand 2 (CCL2), and CCL14 from person-visits among MWH who reported 100% adherence were similar to HIV-uninfected person-visits. Comparatively higher concentrations of 11 biomarkers and lower concentrations of 7 biomarkers were observed in person-visits from MWH who reported 100% ART adherence, compared with HIV-uninfected person-visits.ConclusionsAlthough MWH with virologic suppression who reported 100% ART adherence exhibited overall higher concentrations of biomarkers of inflammation and immune activation compared with HIV-uninfected men, some biomarker concentrations were similar in both groups. These findings suggest that optimal ART adherence could have clinical implications beyond achieving and sustaining viral suppression.

The Flexibility of the Generalized Gamma Distribution in Modeling the Fading Based on Kullback-Leibler and Kolmogorov-Smirnov Criteria

The precision of Rayleigh distribution, as the simplest fading model in Non-Line-of-Sight (NLOS) channels, is low in high-resolution radars and long-distance communication receivers. Many currently-available statistical models with a higher precision, including Nakagami-m, Weibull and generalized hybrid Gamma models, are used to describe the radar clutter and the reflected signals in communication receivers. Although the mentioned models in NLOS channels have more accurate matching with the actual fading, a variety of models and the lack of a comprehensive model in different fading channels make it difficult to select an appropriate model. In this paper, the generalized Gamma model is analyzed and evaluated to demonstrate that it adapts to other fading models. Moreover, it also matches with long-term fading, as well as combined long and short-term fading models. Using a practical sample, it is stated that the generalized Gamma model is also adaptable to the channels to which none of the other available closed-form models are suitable. The simulations and the real data results, approved by Kullback-Leibler and Kolmogorov-Smirnov criteria, prove the claim.