Incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease in patients with multiple sclerosis initiating disease-modifying therapies: Retrospective cohort study using a frequentist model averaging statistical framework.

Researchers are increasingly using insights derived from large-scale, electronic healthcare data to inform drug development and provide human validation of novel treatment pathways and aid in drug repurposing/repositioning. The objective of this study was to determine whether treatment of patients with multiple sclerosis with dimethyl fumarate, an activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, results in a change in incidence of type 2 diabetes and its complications. This retrospective cohort study used administrative claims data to derive four cohorts of adults with multiple sclerosis initiating dimethyl fumarate, teriflunomide, glatiramer acetate or fingolimod between January 2013 and December 2018. A causal inference frequentist model averaging framework based on machine learning was used to compare the time to first occurrence of a composite endpoint of type 2 diabetes, cardiovascular disease or chronic kidney disease, as well as each individual outcome, across the four treatment cohorts. There was a statistically significantly lower risk of incidence for dimethyl fumarate versus teriflunomide for the composite endpoint (restricted hazard ratio [95% confidence interval] 0.70 [0.55, 0.90]) and type 2 diabetes (0.65 [0.49, 0.98]), myocardial infarction (0.59 [0.35, 0.97]) and chronic kidney disease (0.52 [0.28, 0.86]). No differences for other individual outcomes or for dimethyl fumarate versus the other two cohorts were observed. This study effectively demonstrated the use of an innovative statistical methodology to test a clinical hypothesis using real-world data to perform early target validation for drug discovery. Although there was a trend among patients treated with dimethyl fumarate towards a decreased incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease relative to other disease-modifying therapies-which was statistically significant for the comparison with teriflunomide-this study did not definitively support the hypothesis that Nrf2 activation provided additional metabolic disease benefit in patients with multiple sclerosis.

An Early Assessment of the Real-World Treatment Patterns of Type 2 Diabetes: A Comparison to the 2018 ADA/EASD Consensus Report Recommendations.

INTRODUCTION: Using the American Diabetes Association (ADA) Hyperglycemic Pharmacotherapy Guidelines for type 2 diabetes, we evaluated the medication use patterns in real-world patients with type 2 diabetes in the USA. METHODS: Health care claims among patients with type 2 diabetes were analyzed (IBM® MarketScan® 2007 to 2019 Commercial and Medicare Databases). Diabetes treatment patterns were evaluated for the total patient sample of 580,741 during the year 2019. Prior years' claims data were used to construct patient history and determine clinical groups per the 2018 ADA/EASD consensus statement: atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), heart failure (HF), hypoglycemia (hypo), and obesity. The recommended therapy use rates (RTUR) were calculated for clinical groups. Univariate chi-square tests were performed to compare RTUR within and outside clinical groups. Multivariate logistic regression was used to identify variables associated with recommended therapy use. RESULTS: A large proportion of patients belonged to multiple clinical groups; this was more common in the Medicare cohort. Each clinical group in the Commercial cohort had a substantially higher RTUR than in the Medicare cohort. However, no clinical group achieved > 40% RTUR. The RTUR was the highest in the CKD and obesity groups in the Commercial cohort and in the hypo and obesity groups in the Medicare cohort, but lowest in hypo and HF groups in the Commercial and Medicare cohorts, respectively. CONCLUSION: Prevalence of guideline-aligned treatment use in 2019 was low, particularly since many patients fit into multiple risk groups with established treatment benefits.

Type 2 diabetes pharmacotherapy trends in high-risk subgroups.

Medication use trends among patients with type 2 diabetes from 2015 to 2019 were investigated in relation to the clinical group-specific recommendations from the 2018 American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) consensus report. Data were drawn from a large health insurance claims database representing Commercial (total patient-year count: 2,379,704) and Medicare (total patient-year count: 845,823) insurance programmes (IBM® MarketScan®). The utilization of sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists increased over time but was lower in the Medicare cohort in every year evaluated. Patients diagnosed with obesity received recommended therapies at higher rates than those without obesity. Differences were more modest between those with versus without atherosclerotic cardiovascular disease (ASCVD) or chronic kidney disease, with greater treatment adoption in those without ASCVD in the Medicare cohort. Utilization of recommended treatments was paradoxically lower in those with versus without heart failure, and worse in the Medicare than in the Commercial cohort. Utilization of sulphonylureas was not different in those with versus without severe hypoglycaemia history. In conclusion, utilization of therapies recommended in the guidelines is increasing overall, which is not preferentially guided by ADA/EASD-defined clinical groups, and there exists a persistent gap in utilization between Commercial and Medicare populations.

Evaluating bias control strategies in observational studies using frequentist model averaging.

Estimating a treatment effect from observational data requires modeling treatment and outcome subject to uncertainty/misspecification. A previous research has shown that it is not possible to find a uniformly best strategy. In this article we propose a novel Frequentist Model Averaging (FMA) framework encompassing any estimation strategy and accounting for model uncertainty by computing a cross-validated estimate of Mean Squared Prediction Error (MSPE). We present a simulation study with data mimicking an observational database. Model averaging over 15+ strategies was compared with individual strategies as well as the best strategy selected by minimum MSPE. FMA showed robust performance (Bias, Mean Squared Error (MSE), and Confidence Interval (CI) coverage). Other strategies, such as linear regression, did well in simple scenarios but were inferior to the FMA in a scenario with complex confounding.

Practical recommendations on double score matching for estimating causal effects.

Unlike in randomized clinical trials (RCTs), confounding control is critical for estimating the causal effects from observational studies due to the lack of treatment randomization. Under the unconfoundedness assumption, matching methods are popular because they can be used to emulate an RCT that is hidden in the observational study. To ensure the key assumption hold, the effort is often made to collect a large number of possible confounders, rendering dimension reduction imperative in matching. Three matching schemes based on the propensity score (PSM), prognostic score (PGM), and double score (DSM, ie, the collection of the first two scores) have been proposed in the literature. However, a comprehensive comparison is lacking among the three matching schemes and has not made inroads into the best practices including variable selection, choice of caliper, and replacement. In this article, we explore the statistical and numerical properties of PSM, PGM, and DSM via extensive simulations. Our study supports that DSM performs favorably with, if not better than, the two single score matching in terms of bias and variance. In particular, DSM is doubly robust in the sense that the matching estimator is consistent requiring either the propensity score model or the prognostic score model is correctly specified. Variable selection on the propensity score model and matching with replacement is suggested for DSM, and we illustrate the recommendations with comprehensive simulation studies. An R package is available at https://github.com/Yunshu7/dsmatch.

Predicting optimal treatment regimens for patients with HR+/HER2- breast cancer using machine learning based on electronic health records.

Aim: To predict optimal treatments maximizing overall survival (OS) and time to treatment discontinuation (TTD) for patients with metastatic breast cancer (MBC) using machine learning methods on electronic health records. Patients/methods: Adult females with HR+/HER2- MBC on first- or second-line systemic therapy were eligible. Random survival forest (RSF) models were used to predict optimal regimen classes for individual patients and each line of therapy based on baseline characteristics. Results: RSF models suggested greater use of CDK4 & 6 inhibitor-based therapies may maximize OS and TTD. RSF-predicted optimal treatments demonstrated longer OS and TTD compared with nonoptimal treatments across line of therapy (hazard ratios = 0.44∼0.79). Conclusion: RSF may help inform optimal treatment choices and improve outcomes for patients with HR+/HER2- MBC.

Multilevel network meta-regression for population-adjusted treatment comparisons.

Standard network meta-analysis (NMA) and indirect comparisons combine aggregate data from multiple studies on treatments of interest, assuming that any effect modifiers are balanced across populations. Population adjustment methods relax this assumption using individual patient data from one or more studies. However, current matching-adjusted indirect comparison and simulated treatment comparison methods are limited to pairwise indirect comparisons and cannot predict into a specified target population. Existing meta-regression approaches incur aggregation bias. We propose a new method extending the standard NMA framework. An individual level regression model is defined, and aggregate data are fitted by integrating over the covariate distribution to form the likelihood. Motivated by the complexity of the closed form integration, we propose a general numerical approach using quasi-Monte-Carlo integration. Covariate correlation structures are accounted for by using copulas. Crucially for decision making, comparisons may be provided in any target population with a given covariate distribution. We illustrate the method with a network of plaque psoriasis treatments. Estimated population-average treatment effects are similar across study populations, as differences in the distributions of effect modifiers are small. A better fit is achieved than a random effects NMA, uncertainty is substantially reduced by explaining within- and between-study variation, and estimates are more interpretable.

Stated Preferences for Attributes of a CYP2C19 Pharmacogenetic Test Among the General Population Presented with a Hypothetical Acute Coronary Syndrome Scenario.

BACKGROUND: Pharmacogenetic (PGx) testing identifies pharmacotherapeutic risks to permit personalized therapy. Identifying the genetic profile of patients with acute coronary syndrome (ACS) who are considered for therapy with clopidogrel (P2Y12 receptor blockers) and acetylsalicylic acid (ASA) contributes to the treatment paradigm. Patient preferences would inform a collaborative framework and by extension inform healthcare policy formulation. PURPOSE: To quantify stated preferences (willingness to pay) for attributes of a novel point-of-care PGx (CYP2C19) test using a discrete choice experiment (DCE) from the general public in Ontario, Canada, and to identify starting point bias of the cost attribute. METHODS: A web survey was created and included a questionnaire, decision board, and a DCE. DCE choice sets include the following attributes (levels): sample collection (blood, finger prick, and cheek swab), turnaround time for results (1 hr, 3 days, and 1 week), and cost in additional insurance premiums. The presence of starting point bias (cost attribute levels of $0, $1, $5 or $0, $2, $10) in the estimation of willingness to pay (WTP) was tested. RESULTS: Estimates for turnaround time and cost attributes were statistically significant. Coefficients related to the starting point bias were also significant. Approximately 67% of survey participants chose the PGx test compared to status quo treatment options. WTP for a 1 hr turnaround time compared to a 1-week turnaround time was $10.77 (95% CI 9.58 -12.25). CONCLUSION: This translational study shows preference for a point of care PGx test.

Combination of several matching adjusted indirect comparisons (MAICs) with an application in psoriasis.

In health technology assessment (HTA), beside network meta-analysis (NMA), indirect comparisons (IC) have become an important tool used to provide evidence between two treatments when no head-to-head data are available. Researchers may use the adjusted indirect comparison based on the Bucher method (AIC) or the matching-adjusted indirect comparison (MAIC). While the Bucher method may provide biased results when included trials differ in baseline characteristics that influence the treatment outcome (treatment effect modifier), this issue may be addressed by applying the MAIC method if individual patient data (IPD) for at least one part of the AIC is available. Here, IPD is reweighted to match baseline characteristics and/or treatment effect modifiers of published data. However, the MAIC method does not provide a solution for situations when several common comparators are available. In these situations, assuming that the indirect comparison via the different common comparators is homogeneous, we propose merging these results by using meta-analysis methodology to provide a single, potentially more precise, treatment effect estimate. This paper introduces the method to combine several MAIC networks using classic meta-analysis techniques, it discusses the advantages and limitations of this approach, as well as demonstrates a practical application to combine several (M)AIC networks using data from Phase III psoriasis randomized control trials (RCT).

Alternative Weighting Approaches for Anchored Matching-Adjusted Indirect Comparisons via a Common Comparator.

BACKGROUND: Adjusted indirect comparisons (anchored via a common comparator) are an integral part of health technology assessment. These methods are challenged when differences between studies exist, including inclusion/exclusion criteria, outcome definitions, patient characteristics, as well as ensuring the choice of a common comparator. OBJECTIVES: Matching-adjusted indirect comparison (MAIC) can address these challenges, but the appropriate application of MAICs is uncertain. Examples include whether to match between individual-level data and aggregate-level data studies separately for treatment arms or to combine the arms, which matching algorithm should be used, and whether to include the control treatment outcome and/or covariates present in individual-level data. RESULTS: Results from seven matching approaches applied to a continuous outcome in six simulated scenarios demonstrated that when no effect modifiers were present, the matching methods were equivalent to the unmatched Bucher approach. When effect modifiers were present, matching methods (regardless of approach) outperformed the Bucher method. Matching on arms separately produced more precise estimates compared with matching on total moments, and for certain scenarios, matching including the control treatment outcome did not produce the expected effect size. The entropy balancing approach was used to determine whether there were any notable advantages over the method proposed by Signorovitch et al. When unmeasured effect modifiers were present, no approach was able to estimate the true treatment effect. CONCLUSIONS: Compared with the Bucher approach (no matching), the MAICs examined demonstrated more accurate estimates, but further research is required to understand these methods across an array of situations.

Evaluating different strategies for estimating treatment effects in observational studies.

Since the introduction of the propensity score (PS), methods for estimating treatment effects with observational data have received growing attention in the literature. Recent research has added substantially to the number of available statistical approaches for controlling confounding in such analyses. However, researchers need guidance to decide on the optimal analytic strategy for any given scenario. To address this gap, we conducted simulations evaluating both well-established methods (regression, PS weighting, stratification, and matching) and more recently proposed approaches (tree-based methods, local control, entropy balancing, genetic matching, prognostic scoring). The simulation scenarios included tree-based and smooth regression models as true data-generation mechanisms. We evaluated an extensive number of analysis strategies combining different treatment choices and outcome models. Key findings include 1) the lack of a single best strategy across all potential scenarios; 2) the importance of appropriately addressing interactions in the treatment choice model and/or outcome model; and 3) a tree-structured treatment choice model and a polynomial outcome model with second-order interactions performed well. One limitation to this initial assessment is the lack of heterogeneous simulation scenarios allowing treatment effects to vary by patient.

The epidemiology and burden of Alzheimer's disease in Taiwan utilizing data from the National Health Insurance Research Database.

PURPOSE: The objectives of this study were to estimate the incidence, cumulative incidence, and economic burden of Alzheimer's disease (AD) in Taiwan, using data from the National Health Insurance Research Database (NHIRD). MATERIALS AND METHODS: This was a retrospective, longitudinal, observational study using data from the Longitudinal Health Insurance Database of the NHIRD. Patients were included in this study if they were 50 years of age or older and their records included a primary or secondary diagnosis of AD. New patients who met inclusion criteria were followed up longitudinally from 2005 to 2010. Costs were calculated for the first year following the diagnosis of AD. RESULTS: Overall, a higher percentage of women than men were diagnosed with AD (54% vs 46%, respectively). The first AD diagnosis occurred most frequently in the age of 75-84 years. The person-year incidence rate increased from 5.63/1,000 persons (95% CI, 5.32-5.94) in 2005 to 8.17/1,000 persons (95% CI, 7.78-8.57) in 2010. The cumulative incidence rate was 33.54/1,000 persons (95% CI, 32.76-34.33) in 2005-2010. The total mean inflated annual costs per patient in new Taiwan dollars (NT$) in the first year of diagnosis ranged from NT$205,413 (2009) to NT$227,110 (2005), with hospitalization representing the largest component. CONCLUSION: AD represents a substantial burden in Taiwan, and based on the observed increase in incidence rate over time, it is likely that this burden will continue to increase. The findings reported here are consistent with previous research. The NHIRD contains extensive real-world information that can be used to conduct research, allowing us to expand our understanding of the incidence, prevalence, and burden of disease in Taiwan.

Propensity score matching and subclassification in observational studies with multi-level treatments.

In this article, we develop new methods for estimating average treatment effects in observational studies, in settings with more than two treatment levels, assuming unconfoundedness given pretreatment variables. We emphasize propensity score subclassification and matching methods which have been among the most popular methods in the binary treatment literature. Whereas the literature has suggested that these particular propensity-based methods do not naturally extend to the multi-level treatment case, we show, using the concept of weak unconfoundedness and the notion of the generalized propensity score, that adjusting for a scalar function of the pretreatment variables removes all biases associated with observed pretreatment variables. We apply the proposed methods to an analysis of the effect of treatments for fibromyalgia. We also carry out a simulation study to assess the finite sample performance of the methods relative to previously proposed methods.

Increasing body mass index identifies Chinese patients with type 2 diabetes mellitus at risk of poor outcomes.

AIMS: Association between body mass index (BMI) and glycemic control, comorbidities/complications, and health-related quality of life (HRQoL) was assessed in Chinese patients with type 2 diabetes mellitus (T2DM) enrolled in the Diabetes Disease Specific Programme. METHODS: Surveys of 200 physicians and 2052 patients with T2DM captured demographic, clinical, and HRQoL information. Adjusted and unadjusted analyses were conducted across 3 BMI groups; normal (18.5-<24.0, n=998), overweight (24.0-<28.0, n=822), and obese (≥28.0, n=212). RESULTS: There were no between group differences in the achievement of glycated hemoglobin (HbA1c) <7.0% (48mmol/mol); however, compared with the normal BMI group, more obese patients had an HbA1c >9.0% (75mmol/mol; 4.3% vs 10.2%, P=0.002). More obese patients compared with normal BMI patients had hypertension (48.6% vs 35.3%, P<0.001), dyslipidemia (35.4% vs 18.8%, P<0.001), or both hypertension and dyslipidemia (24.1% vs 13.9%, P<0.001). Patients in the obese group reported worse HRQoL and greater effects of diabetes on their daily living. CONCLUSIONS: Obesity in Chinese patients with T2DM results in poor glycemic control, more comorbidities, and worse HRQoL. Management of these patients should include efforts to reduce weight. Selection of weight-neutral or weight-reducing anti-diabetic medications maybe useful in these patients.

Correlation between changes in quality of life and symptomatic improvement in Chinese patients switched from typical antipsychotics to olanzapine.

PURPOSE: The aim of this study was to investigate the correlation between changes in symptoms and changes in self-reported quality of life among Chinese patients with schizophrenia who were switched from a typical antipsychotic to olanzapine during usual outpatient care. PATIENTS AND METHODS: This post hoc analysis was conducted using data from the Chinese subgroup (n=475) of a multicountry, 12-month, prospective, noninterventional, observational study. The primary publication previously reported the efficacy, safety, and quality of life among patients who switched from a typical antipsychotic to olanzapine. Patients with schizophrenia were included if their symptoms were inadequately controlled with a typical antipsychotic and they were switched to olanzapine. Symptom severity was measured using the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions-Severity scale (CGI-S). Health-Related Quality of Life (HRQOL) was assessed using the World Health Organization Quality of Life-Abbreviated (WHOQOL-BREF). Paired t-tests were performed to assess changes from baseline to endpoint. Pearson's correlation coefficients (r) were used to assess the correlations between change in symptoms (BPRS and CGI-S scores) and change in HRQOL (WHOQOL-BREF scores). RESULTS: Symptoms and HRQOL both improved significantly over the 12 months of treatment (P<0.001). Significant correlations were observed between changes from baseline to end of study on the BPRS and the CGI-S and each of the WHOQOL-BREF four domain scores and two overall quality-of-life questions. The correlation coefficients ranged from r=-0.45 to r=-0.53 for the BPRS and WHOQOL-BREF. The correlation coefficients were slightly smaller between the CGI-S and WHOQOL-BREF, ranging from r=-0.33 to r=-0.40. CONCLUSION: For patients with schizophrenia, assessing quality of life has the potential to add valuable information to the clinical assessment that takes into account the patient's own perspective of well-being.

Does participation in a weight control program also improve clinical and functional outcomes for Chinese patients with schizophrenia treated with olanzapine?

OBJECTIVES: This study examined whether participation in a weight control program (WCP) by patients with schizophrenia treated with olanzapine was also associated with improvements in clinical and functional outcomes. METHODS: A post-hoc analysis was conducted using data from the Chinese subgroup (n=330) of a multi-country, 6-month, prospective, observational study of outpatients with schizophrenia who initiated or switched to oral olanzapine. At study entry and monthly visits, participants were assessed with the Clinical Global Impression of Severity, and measures of patient insight, social activities, and work impairment. The primary comparison was between the 153 patients who participated in a WCP at study entry (n=93) or during the study (n=60) and the 177 patients who did not participate in a weight control program (non-WCP). Mixed Models for Repeated Measures with baseline covariates were used to compare outcomes over time. Kaplan-Meier survival analysis was used to assess time to response. RESULTS: Participants had a mean age of 29.0 years and 29.3 years, and 51.0% and 57.6% were female for WCP and non-WCP groups, respectively. Average initiated daily dose for olanzapine was 9.5±5.4 mg. WCP participants gained less weight than non-participants (3.9 kg vs 4.9 kg, P=0.03) and showed statistically significant better clinical and functional outcomes: greater improvement in illness severity (-2.8 vs -2.1, P<0.001), higher treatment response rates (94.1% vs 80.9%, P<0.001), shorter time to response (P<0.001), and greater improvement in patients' insight (P<0.001). Patients who enrolled in a WCP during the study had greater initial weight gain than those who enrolled at baseline (P<0.05), but similar total weight gain. CONCLUSION: Participation in a WCP may not only lower the risk of clinically significant weight gain in olanzapine-treated patients, but may also be associated with additional clinical and functional benefits.

Factors associated with early response to olanzapine and clinical and functional outcomes of early responders treated for schizophrenia in the People's Republic of China.

BACKGROUND: The aims of this analysis were to identify factors associated with early response (at 4 weeks) to olanzapine treatment and to assess whether early response is associated with better longer-term outcomes for patients with schizophrenia in the People's Republic of China. METHODS: A post hoc analysis of a multi-country, 6-month, prospective, observational study of outpatients with schizophrenia or bipolar mania who initiated or switched to treatment with oral olanzapine was conducted using data from the Chinese schizophrenia subgroup (n=330). Factors associated with early response were identified using a stepwise logistic regression with baseline clinical characteristics, baseline participation in a weight control program, and adherence with antipsychotics during the first 4 weeks of treatment. Mixed models for repeated measures with baseline covariates were used to compare outcomes over time between early responders and early nonresponders to olanzapine. RESULTS: One hundred and thirty patients (40%) achieved an early response. Early response was independently predicted by higher baseline Clinical Global Impressions-Severity score (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.15-1.97), fewer years since first diagnosis (OR 0.94, CI 0.90-0.98), a greater number of social activities (OR 1.22, CI 1.05-1.40), participation in a weight control program (OR 1.81, CI 1.04-3.15), and high adherence with antipsychotics during the first 4 weeks of treatment (OR 2.98, CI 1.59-5.58). Relative to early nonresponders, early responders were significantly more likely to meet treatment response criteria at endpoint, had significantly greater symptom improvement (Clinical Global Impressions-Severity), and had significantly greater improvement in functional outcomes (all P<0.05). CONCLUSION: High levels of adherence to prescribed antipsychotics and participation in a weight control program were associated with early response to olanzapine in Chinese patients with schizophrenia. Early response was associated with greater improvement in symptomatic, functional, and quality of life outcomes at 6 months compared with early nonresponse. Current findings are consistent with previous research outside of the People's Republic of China.

Comparison of several multiple imputation strategies for repeated measures analysis of clinical scales: to truncate or not to?

We evaluated via a simulation study several strategies for imputing missing ordinal outcomes in a longitudinal clinical trial, contrasting methods that involve truncation of imputed values outside plausible ranges with those that do not. Our aim was to identify a preferred imputation strategy for estimating treatment difference at study endpoint. Plausible data were simulated via resampling of existing placebo data sets and adding treatment effect; then different imputation strategies were evaluated under missingness at random (MAR) and varying dropout rates. Our conclusion is that imputation methods based on rounding and truncation lead to larger bias than strategies based on simple methods based on (nontruncated) multivariate normal distribution.

Prognostic factors for patients with advanced non-small cell lung cancer treated with gemcitabine-platinum as first-line therapy in an observational setting in China.

BACKGROUND: This study examined the prognostic factors associated with survival in advanced non-small cell lung cancer (NSCLC) patients receiving gemcitabine-platinum regimens as first-line therapy in real-world clinical settings in China. METHODS: Data was analyzed from a multinational, prospective, non-interventional, observational study of individuals receiving gemcitabine-platinum regimens as first-line therapy for NSCLC, focusing on 300 patients from mainland China. A Cox regression model was used to determine the association of 38 prognostic factors, including patient smoking characteristics, with overall survival. RESULTS: In these 300 patients, the mean age was 58.9 (±10.8) years, with males comprising 71% of the population. Thirty percent of patients had an Eastern Cooperative Oncology Group performance status (PS) of 0 and 70% had a PS of 1. The majority of patients had NSCLC of adenocarcinoma origin (57%). Multivariate Cox regression analyses adjusted for baseline factors revealed that gender, tumor (T) staging, metastasis (M) staging, liver metastases, serum albumin, and superior vena cava obstruction were significant prognostic factors. Smoking during therapy was not significantly associated with survival, although numbers were small for this variable (n = 16). Weight loss of >10% was a significant prognostic factor for adverse events. CONCLUSIONS: Gender, T staging, M staging, liver metastases, superior vena cava obstruction, and serum albumin are prognostic factors affecting overall survival in mainland Chinese patients receiving first-line gemcitabine-platinum regimens for advanced NSCLC. These negative prognostic factors may warrant further investigation in clinical trials.

Do concomitant pain symptoms in patients with major depression affect quality of life even when taking into account baseline depression severity?

BACKGROUND: Patients with major depressive disorder (MDD) may suffer from concomitant pain symptoms. The aim of this study is to determine whether the presence of painful physical symptoms (PPS) influences quality of life when taking into account baseline depression severity. METHODS: Patients with a new or first episode of MDD (n = 909) were enrolled in a 3-month prospective observational study in East Asia. The Hamilton Depression Rating Scale, Clinical Global Impression-Severity score, Somatic Symptom Inventory, and EuroQoL questionnaire-5 Dimensions (EQ-5D) and EQ-Visual Analogue Scale (EQ-VAS) were assessed at baseline and 3 months' follow-up. The presence of PPS was defined as a mean score of ≥2 on the Somatic Symptom Inventory pain-related items. Regression analyses determined predictors of quality of life at 3 months, adjusting for age, sex, depressive symptoms, overall severity, and quality of life at baseline. RESULTS: PPS were present (PPS+) at baseline in 52% of patients. During the 3-month follow-up, EQ-VAS scores improved from 47.7 (standard deviation [SD] 20.6) to 72.5 (SD 20.4), and EQ-5D improved from 0.48 (SD 0.34) to 0.80 (SD 0.26). At 3 months, mean EQ-VAS was 66.4 (SD 21.2) for baseline PPS+ patients versus 78.5 (SD 17.6) for baseline PPS- patients, and mean EQ-5D was 0.71 (SD 0.29) versus 0.89 (SD 0.18). PPS+ at baseline was a significant predictor of quality of life at 3 months after adjusting for sociodemographic and baseline clinical variables. CONCLUSION: The presence of painful physical symptoms is associated with less improvement in quality of life in patients receiving treatment for major depression, even when adjusting for depression severity.