Heterogeneity In Baseline Characteristics Research Articles

Residual or recurrent mitral regurgitation predicts mortality following transcatheter edge-to-edge mitral valve repair

ObjectiveAlthough regurgitant mitral valves can be repaired through surgical or transcatheter approaches, contemporary comparative outcomes are limited with the impact of residual and recurrent mitral regurgitation (MR) on clinical outcomes being poorly defined. We hypothesized that moderate (2+) or greater residual or recurrent (RR) MR—regardless of type of repair—predicts worse clinical outcomes. MethodsOur institutional experience of 660 consecutive patients undergoing mitral valve repair (2015-2021) consisting of 393 surgical mitral valve repair (SMVr) and 267 transcatheter edge-to-edge mitral valve repair (TEER) was studied. The echocardiographic impact of RRMR (2+) following both SMVr and TEER on death and reintervention was evaluated. ResultsPatients averaged 67.8 ± 14.2 years (SMVr = 63.8 ± 13.3 vs 73.6 ± 13.6, P < .0001) and 62.1% were male. Baseline clinical and demographic data were vastly different between the 2 groups. Residual or recurrent 2+ or greater MR developed in 25% (n = 68) of patients who received TEER compared with 6% (n = 25) of SMVr (P < .0001). Reintervention (9.3% vs 2.4%, P = .002) and death (37.9% vs 10.4%, P < .0001) rates at 3-years were greater among the TEER group versus SMVr group. Given the heterogeneity in baseline characteristics and difference in survival, each cohort was analyzed separately, stratified by RRMR, using multivariable modeling to identify predictors of repeat reintervention and death. There were too few events of RRMR in the SMVr cohort for evaluation. For the TEER subgroups, we observed greater long-term mortality, but not reintervention among those with RRMR., Hypertension was the strongest predictor of death and obesity was for reintervention. ConclusionsPatients undergoing SMVr and TEER are vastly different with respect to baseline patient characteristics and clinical outcomes, with patients who undergo TEER being much greater risk with poorer prognosis. Moderate or greater RRMR predicted worse long-term survival but not reintervention among patients who received TEER. Given the difference in survival among patients with RRMR following TEER, care must be taken to ensure that patients entering clinical trials and receiving TEER should have a high probability of achieving mild or less MR as seen in contemporary surgical results.

Psilocybin-induced changes in cerebral blood flow are associated with acute and baseline inter-individual differences

Research into the use of psilocybin for the treatment of psychiatric disorders is a growing field. Nevertheless, robust brain–behavior relationships linking psilocybin-induced brain changes to subjective drug-induced effects have not been established. Furthermore, it is unclear if the acute neural effects are dependent on individual heterogeneity in baseline characteristics. To address this, we assessed the effects of three oral doses of psilocybin vs. placebo on cerebral blood flow (CBF) using arterial spin labeling in healthy participants (N = 70; n = 31, 0.16 mg/kg; n = 10, 0.2 mg/kg; n = 29, 0.215 mg/kg). First, we quantified psilocybin-induced changes in relative and absolute CBF. Second, in an exploratory analysis, we assessed whether individual baseline characteristics and subjective psychedelic experience are associated with changes in CBF. Psychological and neurobiological baseline characteristics correlated with the psilocybin-induced reduction in relative CBF and the psilocybin-induced subjective experience. Furthermore, the psilocybin-induced subjective experience was associated with acute changes in relative and absolute CBF. The results demonstrated that inter-individual heterogeneity in the neural response to psilocybin is associated with baseline characteristics and shed light on the mechanisms underlying the psychedelic-induced altered state. Overall, these findings help guide the search for biomarkers, paving the way for a personalized medicine approach within the framework of psychedelic-assisted therapy.

Single vs Bilateral Lung Transplant in the Management of Patients With Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Lung transplantation is recommended for select patients with end-stage chronic obstructive pulmonary disease (COPD). However, a consensus has not been reached regarding the optimal choice of lung transplantation: single lung transplants (SLTs) vs bilateral lung transplants (BLTs). This meta-analysis aimed to evaluate the safety and efficacy of SLT compared with BLT in managing end-stage COPD. Cochrane, Embase, PubMed, and Scopus were searched for articles by 2 independent reviewers using the Preferred Reporting Items for Systematic Reviews and Meta-analysis system. The review was registered prospectively with PROSPERO (CRD42022343408). Seven studies of 311 screened met the eligibility criteria, with a total of 10,652 patients with end-stage COPD, SLT (n=6233), or BLT (n=4419). Overall survival rates of BLT group were more favorable than SLT group at 1 (odds ratio [OR]=1.29, 95% CI: 1.16, 1.43, I2=0%), 5 (OR=1.46, 95% CI: 1.35, 1.58, I2=23%), and 10 years (OR=1.71, 95% CI: 1.57, 1.87, I2=12%) as well as the hazard ratio (HR=0.73, 95% CI: 0.70, 0.76, I2=40%). Subgroup analysis on survival rates of alpha-1 antitrypsin deficiency also displayed a trend favoring BLT compared with SLT at 1 (OR=1.60, 95% CI: 1.24, 2.08, I2=28%), 5 (OR=1.84, 95% CI: 1.50, 2.26, I2=42%), and 10 years (OR=1.98, 95% CI: 1.59, 2.48, I2=47%) as well as the HR (HR=0.67, 95% CI: 0.35, 1.28, I2=82%). Compared with SLT, BLT seems to demonstrate more favorable trends in survival rates for the management of end-stage COPD. Despite the promising results, the groups have significant heterogeneity in baseline characteristics. Further prospective studies with extended follow-up periods are needed to ascertain the efficacy of treatment.

Hearing Aids Combined With Educational Counseling Versus Educational Counseling Alone for Tinnitus Treatment in Patients With Hearing Loss: A Longitudinal Follow-Up Study.

The effect of hearing aids (HAs) and educational counseling (EC) or their combination on tinnitus is ambiguous. This study aimed to investigate whether the combined use of HAs and EC is more effective than EC alone on tinnitus relief. A total of 72 adults with chronic, bothersome tinnitus and coexisting sensorineural hearing loss completed at least 1-month and 3-month follow-up. After receiving EC and HA prescriptions, 21 participants selected to purchase HAs (i.e., the HA + EC group), whereas the remaining 51 refused to use HAs despite recommendations (i.e., the EC group). Tinnitus severity was measured by Tinnitus Handicap Inventory (THI), Tinnitus Evaluation Questionnaire (TEQ), and Visual Analog Scale (VAS) for loudness. The primary outcome measure was THI, and tinnitus relief was defined as a 20-point or more reduction in THI. A generalized linear mixed model was used to confirm that the heterogeneity in baseline characteristics between groups did not interfere with the results. The THI, TEQ, and VAS scores decreased significantly after treatments, and both groups yielded a similar trend of reduction. There were no significant differences in the incidence of tinnitus relief and time-to-event curves between the two groups. In addition, the length of follow-up did not affect treatment effectiveness. There was insufficient evidence to support the superiority of the combined use of HA and EC for tinnitus over EC with no device.

Perioperative and oncological outcomes of uniportal versus three-port thoracoscopic segmentectomy for lung cancer: a propensity score matching analysis.

With an increasing amount of small nodules being detected, segmentectomy has recently received a great deal of attention. We have previously reported the feasibility and safety of uniportal segmentectomy. This study aims to further compare the perioperative and oncological outcomes of uniportal and three-port thoracoscopic segmentectomy in lung cancer patients. Patients undergoing thoracoscopic segmentectomy for lung cancer from January 2014 to March 2021 were enrolled. Clinical data were collected from the Western China Lung Cancer Database, a prospectively maintained database at the Department of Thoracic Surgery, West China Hospital. Propensity score matching (PSM) was used to reduce the heterogeneity in baseline characteristics. Perioperative outcomes, 1-, 3-, and 5-year overall survival (OS), and progression-free survival (PFS) were compared. Of the 10,063 lung cancer patients who underwent thoracoscopic lung resection, 2,630 patients receiving segmentectomy were selected (uniportal: 400; three-port: 2,230). After matching, similar results were found between the 2 groups (uniportal: 400; three-port: 1,200) regarding the number of lymph nodes harvested, the length of postoperative hospital stays, chest tube drainage volume, and postoperative complication rate. The mean follow-up duration was 27 months. Uniportal regimen showed similar 1- (100% vs. 99.9%, P=0.36), 3- (100% vs. 90.4%, P=0.20), 5-year OS (97.7% vs. 99.4%, P=0.78), as well as PFS, with the three-port regimen. Uniportal video-assisted thoracoscopic segmentectomy is proven to be safe and feasible, and the perioperative outcomes and oncological results were similar between the uniportal and three-port regimens.

Real-world patient characteristics and use of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis: a cross-national study

IntroductionRheumatoid arthritis (RA) is associated with significant morbidity and economic burden. This study aimed to compare baseline characteristics and patterns of anti-inflammatory drug use and disease-modifying anti-rheumatic drug (DMARD) use among patients with RA in Southern Italy versus the United States.MethodUsing Caserta Local Health Unit (Italy) and Optum’s de-identified Clinformatics® Data Mart (United States) claims databases, patients with ≥ 2 diagnosis codes for RA during the study period (Caserta: 2010–2018; Optum: 2010–2019) were identified. Baseline patient characteristics, as well as proportion of RA patients untreated/treated with NSAIDs/glucocorticoids/conventional DMARDs (csDMARDs)/biological/targeted synthetic DMARDs (b/tsDMARDs) during the first year of follow-up, and the proportion of RA patients with ≥ 1 switch/add-on between the first and the second year of follow-up, were calculated. These analyses were then stratified by age group (< 65; ≥ 65).ResultsA total of 9227 RA patients from Caserta and 195,951 from Optum databases were identified (two-thirds were females). During the first year of follow-up, 45.9% RA patients from Optum versus 79.9% from Caserta were exclusively treated with NSAIDs/glucocorticoids; 17.2% versus 11.3% from Optum and Caserta, respectively, were treated with csDMARDs, mostly methotrexate or hydroxychloroquine in both cohorts. Compared to 0.6% of RA patients from Caserta, 3.2% of the Optum cohort received ≥ 1 b/tsDMARD dispensing. Moreover, 61,655 (33.7%) patients from Optum cohort remained untreated compared to 748 (8.3%) patients from the Caserta cohort. The subgroup analyses stratified by age showed that 42,989 (39.8%) of elderly RA patients were untreated compared to 18,666 (24.9%) young adult RA patients in Optum during the first year of follow-up. Moreover, a higher proportion of young adult RA patients was treated with b/tsDMARDs, with and without csDMARDs, compared to elderly RA patients (Optum<65: 6.4%; Optum≥65: 1.0%; P-value < 0.001; Caserta<65: 0.8%; Caserta≥65: 0.1%; P-value < 0.001). Among RA patients untreated during the first year after ID, 41.2% and 48.4% RA patients from Caserta and Optum, respectively, received NSAIDs, glucocorticoids, and cs/b/tsDMARDs within the second year of follow-up. Stratifying the analysis by age groups, 50.6% of untreated young RA patients received study drug dispensing within the second year of follow-up, compared to only 36.7% of elderly RA patients in Optum. Interestingly, more young adult RA patients treated with csDMARDs during the first year after ID received a therapy escalation to b/tsDMARD within the second year after ID in both cohorts, compared to elderly RA patients (Optum<65: 7.8%; Optum≥65: 1.8%; Caserta<65: 3.2%; Caserta≥65: 0.6%).ConclusionsMost of RA patients, with heterogeneous baseline characteristics in Optum and Caserta cohorts, were treated with anti-inflammatory/csDMARDs rather than bDMARDs/tsDMARDs during the first year post-diagnosis, especially in elderly RA patients, suggesting a need for better understanding and dealing with barriers in the use of these agents for RA patients.Key Points• Substantial heterogeneity in baseline characteristics and access to bDMARD or tsDMARD drugs between RA patients from the United States and Italy exists.• Most of RA patients seem to be treated with anti-inflammatory/csDMARD drugs rather than bDMARD/tsDMARD drugs during the first year post-diagnosis.• RA treatment escalation is less frequent in old RA patients than in young adult RA patients.• An appropriate use of DMARDs should be considered to achieve RA disease remission or low disease activity.

One-Third of European Patients With Axial Spondyloarthritis Reach Pain Remission With Routine Care Tumor Necrosis Factor Inhibitor Treatment.

To investigate the distribution of patient-reported outcomes (PROs) in patients with axial spondyloarthritis (axSpA) initiating a tumor necrosis factor inhibitor (TNFi), to assess the proportion reaching PRO "remission" across registries and treatment series, and to compare patients registered to fulfill the modified New York (mNY) criteria for ankylosing spondylitis (AS) vs patients with nonradiographic axSpA (nr-axSpA). Fifteen European registries contributed PRO scores for pain, fatigue, patient global assessment (PtGA), Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Health Assessment Questionnaire (HAQ) from 19,498 patients with axSpA. Changes in PROs and PRO remission rates (definitions: ≤ 20 mm for pain, fatigue, PtGA, BASDAI, and BASFI; ≤ 0.5 for HAQ) were calculated at 6, 12, and 24 months of treatment. Heterogeneity in baseline characteristics and outcomes between registries were observed. In pooled data, 6 months after the start of a first TNFi, pain score was reduced by approximately 60% (median at baseline/6/12/24 months: 65/25/20/20 mm) in patients on treatment. Similar patterns were observed for fatigue (68/32/30/25 mm), PtGA (66/29/21/20 mm), BASDAI (58/26/21/19 mm), BASFI (46/20/16/16 mm), and HAQ (0.8/0.4/0.2/0.2). Patients with AS (n = 3281) had a slightly better response than patients with nr-axSpA (n = 993). The Lund Efficacy Index (LUNDEX)-adjusted remission rates at 6 months for pain/fatigue/PtGA/BASDAI/BASFI/HAQ were 39%/30%/38%/34%/35%/48% for the AS cohort and 30%/21%/26%/24%/33%/47% for the nr-axSpA cohort. Better PRO responses were seen with a first TNFi compared to a second and third TNFi. Patients with axSpA starting a TNFi achieved high PRO remission rates, most pronounced in those fulfilling the mNY criteria and for the first TNFi.

Biliopancreatic Limb Length as a Potential Key Factor in Superior Glycemic Outcomes After Roux-en-Y Gastric Bypass in Patients With Type 2 Diabetes: A Meta-Analysis.

Optimal length of biliopancreatic (BP) and Roux limb in Roux-en-Y gastric bypass (RYGB) for improved glycemic control are not known. To investigate how the lengths of the BP and Roux limbs in RYGB differentially affect postoperative glycemic outcomes in patients with type 2 diabetes. We conducted a systematic literature search using the PubMed, Embase, and the Cochrane Library databases. We included studies that reported glycemic outcomes after RYGB and lengths of the BP and Roux limbs. A total of 28 articles were included for data extraction. Glycemic outcomes after RYGB were assessed on the basis of two definitions: remission and improvement. We categorized the included studies into four groups according to the BP and Roux limb lengths. The type 2 diabetes remission/improvement rates were as follows: long BP-long Roux group 0.80 (95% CI 0.70-0.90)/0.81 (0.73-0.89), long BP-short Roux group 0.76 (0.66-0.87)/0.82 (0.75-0.89), short BP-long Roux group 0.57 (0.36-0.78)/0.64 (0.53-0.75), and short BP-short Roux group 0.62 (0.43-0.80)/0.53 (0.45-0.61). Meta-regression analysis also showed that a longer BP limb resulted in higher postoperative type 2 diabetes remission and improvement rates, whereas a longer Roux limb did not. There was no significant difference or heterogeneity in baseline characteristics, including diabetes-related variables, among the four groups. Not all included studies were randomized controlled trials. Longer BP limb length led to higher rates of type 2 diabetes remission and improvement by 1 year after RYGB in comparisons with the longer Roux limb length.

Prognostic implications of extranodal extension in papillary thyroid carcinomas: A propensity score matching analysis and proposal for incorporation into current tumor, lymph node, metastasis staging

BackgroundThe current American Joint Committee on Cancer tumor, lymph node, metastasis cancer staging system for papillary thyroid carcinoma places low weight on extranodal extension. This study examined the prognostic implications of extranodal extension in papillary thyroid carcinoma patients and attempted to design a new staging system incorporating extranodal extension. MethodsWe reviewed data from 6,165 consecutive papillary thyroid carcinoma patients from 2012 to 2018. Patients with extrathyroidal extension or extranodal extension were included and then divided into 3 groups: extrathyroidal extension (papillary thyroid carcinoma with extrathyroidal extension but without extranodal extension, N = 457); extranodal extension (papillary thyroid carcinoma with extranodal extension but without extrathyroidal extension, N = 116); and extrathyroidal extension and extranodal extension (papillary thyroid carcinoma with both extrathyroidal extension and extranodal extension, N = 116). Recurrence-free survival and cancer-specific survival were compared before and after adjusting for differences using propensity score matching owing to observed heterogeneity in baseline characteristics in the original cohort. Recurrence-free survival and cancer-specific survival were also compared between patients with and without extranodal extension after matching at a 1:1 ratio. Cox proportional hazards regression analyses were used to identify the relationships of factors associated with structural recurrent disease in the node-positive subset. Then a new staging system incorporating extranodal extension was established, and the discrimination of the new staging system for recurrence-free survival and cancer-specific survival was investigated. ResultsOf the 6,165 patients with papillary thyroid carcinoma, extrathyroidal extension was found in 573 (9.3%) patients, and extranodal extension was observed in 232 (3.8%) patients. The recurrence-free survival and cancer-specific survival rates of patients with extranodal extension were similar to those of patients with extrathyroidal extension (all P > .05). Patients with extrathyroidal extension and extranodal extension experienced worse recurrence-free survival than patients with extrathyroidal extension or extranodal extension and even worse cancer-specific survival than patients with extrathyroidal extension (all P < .05). The recurrence-free survival and cancer-specific survival rates of patients with extranodal extension were worse than those of patients without extranodal extension (P = .003; P = .048). Cox proportional hazards regression analysis demonstrated that after propensity score matching, extranodal extension (hazard ratio 1.911; 95% confidence interval 1.568–3.609; P < .001) remained an independent predictor of structural recurrent disease in patients with node-positive papillary thyroid carcinoma. After incorporating extranodal extension into the current tumor, lymph node, metastasis classification, the new staging system presented a better discrimination for recurrence-free survival and cancer-specific survival for those with lymph node metastasis. ConclusionPapillary thyroid carcinoma patients with extranodal extension present worse prognosis, and incorporating extranodal extension in tumor, lymph node, metastasis classification identifies poor-risk patients more accurately.

Lower circulating soluble Klotho level is associated with increased risk of all-cause mortality in chronic kidney disease patients: a systematic review and meta-analysis.

This study aimed to investigate the association between circulating soluble Klotho level and risk of all-cause mortality in chronic kidney disease (CKD) patients using systematic review and meta-analysis technique. Potentially eligible studies were identified from Medline and EMBASE databases from inception to March 2020 using a search strategy that consisted of terms for "Klotho" and "Mortality". Eligible study must be a cohort study that consists of one cohort of CKD patients with higher circulating soluble Klotho level and another cohort of CKD patients with lower circulating soluble Klotho level. The study must also report relative risk (RR), incidence rate ratio, hazard risk ratio or standardized incidence ratio with 95% confidence intervals (95% CIs) comparing all-cause mortality between CKD patients with lower circulating soluble Klotho level versus CKD patients with higher circulating soluble Klotho level. If the study divides patients (per circulating soluble Klotho level) into more than two groups, a comparison between the highest and the lowest group would be extracted. Point estimates with standard errors were retrieved from each study and were combined together using the generic inverse variance method. A total of 2964 articles were retrieved. After two rounds of an independent review by two investigators, six prospective cohort studies met the eligibility criteria and were included into the meta-analysis. CKD patients with lower circulating soluble Klotho level had a significantly increased risk of all-cause mortality with the pooled risk ratio of 1.88 (95% CI 1.29-2.74; I2 0%). The funnel plot was fairly symmetric and did not reveal any suggestive evidence of publication bias. The current study found a significant association between lower circulating soluble Klotho level and increased risk of all-cause mortality in CKD patients. However, this meta-analysis carries some limitations, including relatively small sample size, lack of adjustment for potential confounders and between-study heterogeneity in baseline characteristics of the patients and cut-off values used to categorize patients into higher and lower circulating serum Klotho level group.

Retention and response rates in 14 261 PsA patients starting TNF inhibitor treatment-results from 12 countries in EuroSpA.

To investigate TNF inhibitor (TNFi) retention and response rates in European biologic-naïve patients with PsA. Prospectively collected data on PsA patients in routine care from 12 European registries were pooled. Heterogeneity in baseline characteristics between registries were explored (analysis of variance and pairwise comparison). Retention rates (Kaplan-Meier), clinical remission [28-joint count DAS (DAS28) <2.6; 28 joint Disease Activity index for Psoriatic Arthritis ⩽4] and ACR criteria for 20% improvement (ACR20)/ACR50/ACR70 were calculated, including LUNDEX adjustment. Overall, 14 261 patients with PsA initiated a first TNFi. Considerable heterogeneity of baseline characteristics between registries was observed. The median 12-month retention rate (95% CI) was 77% (76, 78%), ranging from 68 to 90% across registries. Overall, DAS28/28 joint Disease Activity index for Psoriatic Arthritis remission rates at 6 months were 56%/27% (LUNDEX: 45%/22%). Six-month ACR20/50/70 responses were 53%/38%/22%, respectively. In patients initiating a first TNFi after 2009 with registered fulfilment of ClASsification for Psoriatic ARthritis (CASPAR) criteria (n = 1980) or registered one or more swollen joint at baseline (n = 5803), the retention rates and response rates were similar to those found overall. Approximately half of >14 000 patients with PsA who initiated first TNFi treatment in routine care were in DAS28 remission after 6 months, and three-quarters were still on the drug after 1 year. Considerable heterogeneity in baseline characteristics and outcomes across registries was observed. The feasibility of creating a large European database of PsA patients treated in routine care was demonstrated, offering unique opportunities for research with real-world data.

An Indirect Comparison between Bosutinib, Nilotinib and Dasatinib in First-Line Chronic Phase Chronic Myeloid Leukemia

IntroductionSeveral randomized controlled trials (RCTs) compare second generation tyrosine kinase inhibitors (TKIs) with imatinib (IM) for the first-line (1L) treatment of chronic phase chronic myeloid leukemia (CP-CML). However, an examination indicated cross-trial heterogeneity in terms of disease and patient characteristics (baseline risk score, age, trial region, and post-baseline IM dose escalation) and outcomes reported (type and time of evaluation). For this reason, a matching adjusted indirect treatment comparison (MAIC) can be used to assess comparative efficacy. The objective of this study was to compare the efficacy of bosutinib (BOS) with nilotinib (NIL) and dasatinib (DAS) in 1L CP-CML via unanchored MAICs.MethodsAs well as heterogeneity in baseline characteristics, differences in the amount of IM dose escalations in earlier clinical pivotal trials (ENESTnd: 15.9% at 12 months; DASISION 20% at 24 months) relative to more recent ones (BFORE: 27.5% and 30.9% at 12 and 24 months, respectively) were observed. Because differences in IM dose-escalation regimens are trial design matters, they cannot be adjusted for using anchored MAICs. Therefore, an unanchored MAIC (which dismisses the common comparator arm, in this case IM) was used.Unanchored MAICs comparing BOS with NIL and DAS were performed to match the summary statistics in the BFORE trial to the reported summary statistics in the ENESTnd (NIL) and the DASISION (DAS) trials. Outcomes assessed included major molecular response (MMR) at 12 months and at any time after 12 months, complete cytogenetic response (CCyR) by 12 months, and deep molecular response (MR4) at 12 months. Statistical significance was assessed based on confidence intervals (CI; significant when CI excludes 1). The sample size of the matching-adjusted BOS population was estimated using the effective sample size (ESS). No adjustments for multiple comparisons were made.ResultsThe MAICs showed an MMR at 12 months of 49.32% (vs 47.13% before the MAIC, N=244, ESS=186) for BOS vs 44% for NIL (OR 1.24, 95% CI [0.87-1.77], N=282) and an MMR at any time of 58.09% (vs 57.79% before MAIC, N=244, ESS=142) for BOS vs 57% for NIL (OR 1.05, 95% CI [0.72-1.5], N=282), and 58.52% (vs 58.16% before MAIC, N=239, ESS=192) for BOS vs 52% for DAS (OR 1.3, 95% CI [0.9-1.88], N=259). BOS had a CCyR by 12 months of 82.59% (vs 82.38% before MAIC, N=244) vs 80% for NIL (OR 1.19, 95% CI [0.75-1.87], N=282, ESS=195) and 80.47% (vs 82.01% before MAIC, N=239, ESS=185) vs 83% for DAS (OR 0.84, 95% CI [0.53-1.35], N=259). MR4 at 12 months was 20.34% (vs 20.49% before MAIC, N=244, ESS=185) for BOS vs 12% for NIL (OR 1.87, 95% CI [1.15-3.05], N=282). MMR and MR4 at month 12 were not reported for DAS.DiscussionThe general MAIC limitations (impact of having access to only marginal covariate distribution, choice of scale for indirect comparisons, choice of target population and sampling variation in the target population) apply to our analyses as well. Nevertheless, indirect comparisons using unanchored MAICs were conducted because cross-trial heterogeneity in patient baseline characteristics could bias the results of a naïve comparison and increases in IM dose escalation over time could bias the results of an anchored MAIC. The unanchored MAICs indicated that BOS was numerically higher than NIL for all response rates examined, however, except for MR4, none were statistically significant. BOS had a numerically higher MMR at any time and a numerically lower CCyR by 12 months compared with DAS, however, neither were statistically significant. BOS therefore seems to be an equally effective TKI as NIL and DAS in the 1L CP-CML setting. These findings, based on statistical methods, should be confirmed by clinical research. DisclosuresMuresan:Ingress-health Nederland BV: Employment. Mamolo:Pfizer: Employment, Equity Ownership. Cappelleri:Pfizer: Employment, Equity Ownership. Crescenzo:Pfizer: Employment. Leip:Pfizer: Employment, Equity Ownership. Viqueira:Pfizer: Employment, Equity Ownership. Heeg:Ingress-health Nederland BV: Employment, Equity Ownership, Research Funding.

Statin treatment and outcomes of metastatic pancreatic cancer: a pooled analysis of two phase III studies.

The current analysis aims to evaluate the impact of statin co-treatment on the survival of patients with metastatic pancreatic cancer. This is a pooled analysis of de-identified patient data from two clinical trials (NCT01124786; NCT00844649). Overall and progression-free survival according to patient subsets (patients who received or who did not receive statins) were assessed through Kaplan-Meier analysis and log-rank test. Univariate and multivariate Cox regression analysis was performed to evaluate different factors potentially affecting overall and progression-free survival. Propensity score matching was performed to address heterogeneity in baseline characteristics of different subgroups of patients. A total of 797 patients were assessed in the current study; of which 156 patients received statins and 641 did not receive statins. Using Kaplan-Meier survival estimates, patients who received statins seem to have better overall and progression-free survival compared to patients who did not (P = 0.008; P < 0.001, respectively). In multivariate analysis for factors affecting overall survival, the following factors were associated with worse overall survival: worse performance status (P < 0.001), no statin use (P = 0.044) and multiple sites of metastatic disease (P = 0.023); likewise in multivariate analysis for factors affecting progression-free survival, the following factors were associated with worse progression-free survival: worse performance status (P < 0.001), gemcitabine elaidate chemotherapy (P = 0.015) and no statin use (P = 0.048). Following propensity score matching and using Kaplan-Meier estimates, statin use was also associated with better overall and progression-free survival (P = 0.005; P = 0.040, respectively). Statin use seems to be associated with better overall survival among patients with metastatic pancreatic cancer treated with first-line chemotherapy. Prospective studies designed specifically to assess this potential effect of statins are needed.

DIFFERENCES IN ELIGIBILITY CRITERIA AND BASELINE PATIENT CHARACTERISTICS AMONGST TRIALS OF BIOLOGIC THERAPIES IN ASTHMA

Introduction The understanding of asthma pathophysiology has evolved over time, impacting investigation of asthma biologics. Differences in eligibility criteria amongst trials for patients with diverse asthma severity and phenotypes have resulted in relevant differences in baseline characteristics. A systematic literature review explored these differences. Methods PubMed, EMBASE, Cochrane, ClinicalTrials.gov, and conferences were searched from 2003 onwards. Randomized controlled trials (RCTs) were included with: ≥24 weeks’ duration; biologic (omalizumab [OMA]/dupilumab [DUPI]/benralizumab [BENRA]/mepolizumab [MEPO]/reslizumab [RESLI]) + daily high-dose ICS + ≥1 controller; adults ≥18 years with moderate/severe uncontrolled asthma and evidence of Type 2 inflammation (eg, blood eosinophils). Results 27 RCTs (9 OMA/3 DUPI/6 BENRA/7 MEPO/2 RESLI) were included. Overall, BENRA/MEPO/RESLI trials enrolled patients with more severe asthma than OMA/DUPI (Table 1). Per inclusion criteria, the number of prior exacerbations was higher in BENRA/MEPO versus OMA/DUPI/RESLI trials. Baseline blood eosinophil levels varied between trials, but were highest in RESLI. There was a trend towards higher baseline FEV1 in OMA/RESLI trials compared with others. Most patients received medium/high dose ICS + LABAs, with more patients in MEPO trials receiving maintenance OCS. Conclusions Transitivity, an important assumption in network meta-analysis (NMA), requires populations and study designs be sufficiently similar or have differences that can be adjusted for by accepted methods. Substantial heterogeneity in baseline characteristics existed between trials of asthma biologics and OMA. These characteristics are potential treatment effect modifiers with limited evidence for adjustment. Therefore, comparison of OMA to other asthma biologics through NMA is not clinically valid and inconsistent with best practices. Table 1. Summary of eligibility criteria and baseline patient characteristics across randomized controlled trials of biologic agents in moderate-to-severe asthma.

Impact of diabetes comorbidity on the efficacy and safety of FOLFOX first-line chemotherapy among patients with metastatic colorectal cancer: a pooled analysis of two phase-III studies.

The current analysis aims to provide an evaluation of the impact of diabetes mellitus (DM) on the efficacy and safety of first-line FOLFOX chemotherapy for patients with metastatic colorectal cancer (mCRC). This is a pooled analysis of the comparator arms of two clinical trials (NCT00272051; NCT00305188) which evaluated first-line FOLFOX chemotherapy for patients with mCRC. The overall survival and progression-free survival according to patient subsets (non-diabetic and diabetic patients) were assessed through Kaplan-Meier analysis and log-rank testing. Propensity score matching was additionally conducted to account for heterogeneity in baseline characteristics of different subsets of patients. A total of 756 patients were enrolled in the current analysis; of which 64 patients have pre-existing DM while 692 patients were non-diabetic. Through Kaplan-Meier analysis, no evidence for overall or progression-free survival difference was found among the two patient subsets (P = 0.501; P = 0.960, respectively). Moreover, metformin treatment does not affect overall or progression-free survival among diabetic patients (P = 0.598; P = 0.748, respectively). Repetition of overall and progression-free survival assessment following propensity score matching does not reveal any differences. Comparing diabetic to non-diabetic patients, there were no differences between the two groups in terms of acute oxaliplatin-induced neurological symptoms including cold-induced dysthesia (P = 0.600), laryngeal dysthesia (P = 0.707), jaw pain (P = 0.743) or muscle pain (P = 0.506). Moreover, no difference was seen between the two groups in terms of the incidence of long-term oxaliplatin-induced paresthesia (P = 0.107), highest grade of paresthesia (P = 0.498) or rates of recovery from paresthesia (P = 0.268). Diabetic patients have, however, a shorter time to develop oxaliplatin-induced paresthesia (P = 0.024). DM does not seem to affect overall or progression-free survival of mCRC patients treated with first-line FOLFOX chemotherapy. Moreover, DM does not influence the incidence or severity of oxaliplatin-induced paresthesia in those patients while it might lead to a shorter time to develop oxaliplatin-induced paresthesia compared to non-diabetic patients.

Validity of upfront surgery for patients with unsuspected lymph node metastasis in esophageal cancer: a propensity scoring matching study

BackgroundAlthough neoadjuvant therapy followed by esophagectomy is well-established as being superior to upfront esophagectomy when locoregional lymph node (LN) metastasis is present in esophageal cancer, upfront esophagectomy without neoadjuvant therapy may be performed in patients with LN metastasis due to unreliable preoperative evaluations. However, outcomes in this setting remain unclear. The purpose of the present study was to clarify whether upfront esophagectomy without neoadjuvant therapy in patients with unsuspected lymph node metastasis in esophageal cancer is appropriate.MethodsWe included 215 squamous cell esophageal cancer patients who met the study criteria. Inclusion criteria included complete (R0) and curative surgery cases, intra-thoracic esophageal cancer, preoperative biopsy-proven squamous cell carcinoma, and cases without LN metastasis (WL, cN0 and pN0) or with unsuspected LN metastasis (UL, cN0 and pN1). Exclusion criteria were palliation or salvage cases, other uncured previous or current primary cancers, complete remission cases, and operative mortalities (defined as patients who died during hospitalization or within one month after surgery). We compared 5-year disease- free survival (DFS) between WL and UL. In addition, we investigated the influence of neoadjuvant therapy in UL. To overcome heterogeneity in baseline characteristics between the groups, a propensity matched-analysis based on propensity scores was then carried out to create a cohort of WL with clinical characteristics similar to those in UL.ResultsThe incidence of UL among preoperative N0 patients was 25.6% and the incidence of UL cases who did not receive neoadjuvant therapy was 47.2%. All subjects were stratified into either WL (160 patients) or UL (55 patients). Twenty nine of 55 patients in UL received neoadjuvant therapy before esophagectomy and all patients with LN metastasis received adjuvant therapy after esophagectomy. There was no significant difference in DFS between WL and UL (p = 0.242). Furthermore, there were no significant differences in DFS between cases that received and did not receive neoadjuvant therapy (p = 0.769).ConclusionsUpfront surgery without neoadjuvant therapy in UL is appropriate for patients who can tolerate adjuvant therapy.