Propensity Score-adjusted Analysis Research Articles

Prescription Patterns of Sodium-Glucose Cotransporter 2 Inhibitors and Cardiovascular Outcomes in Patients with Diabetes Mellitus and Heart Failure.

The benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and type 2 diabetes mellitus (T2DM) has been unequivocally proven in randomized, controlled trials. However, real-world evidence assessing the implementation of SGLT2i in clinical practice and their benefit in HF outside of highly selected study populations is limited. Patients with HF and T2DM admitted to the cardiology ward of the Medical University of Vienna between 01/2014 and 04/2020 were included in the present analysis. All first-time prescriptions of SGLT2i were identified. The outcome of interest was cardiovascular mortality. The median follow-up time was 2.3years. Out of 812 patients with T2DM and HF (median age 70.4 [IQR 62.4-76.9] years; 70.3% males), 17.3% received an SGLT2i. The frequency of SGLT2i prescriptions significantly increased over the past 6years (+ 36.6%, p < 0.001). In propensity score-adjusted pairwise analyses, SGLT2i treatment was inversely associated with long-term cardiovascular mortality in patients with HFrEF presenting with an adjusted HR of 0.33 (95%CI: 0.13-0.86; p = 0.024). Despite large outcome trials showing a cardiovascular benefit, SGLT2i remain underutilized in clinical practice in patients with T2DM and HF. National and European Medical Agency remuneration regulations would allow more patients at high risk to receive these cardiovascular protective drugs. Most importantly, an SGLT2i therapy was associated with a survival benefit in patients with HFrEF.

Timing matters: Otological symptoms and Parkinson's disease

IntroductionOtological symptoms contribute to the disability of established Parkinson's disease (PD). We sought to evaluate whether prodromal onset may affect PD progression. MethodsA retrospective cohort design was used to compare time to advanced disease, defined as a Hoehn & Yahr stage ≥3 in consecutive PD patients with history of auditory and/or vestibular symptoms appearing before versus after PD onset. Time from PD onset to H&Y ≥ 3 was determined using Cox proportional hazards, with adjusted results summarized as hazards ratio (HR). ResultsAfter adjusting for age at PD onset, there was a lower risk of progression to advanced disease in patients with prodromal otological symptoms compared to those with otological symptoms after PD onset (HR = 0.34; 95%CI: 0.15–0.75, p = 0.008). This association remained significant after adjusting for age at PD onset and MDS-UPDRS III (HR = 0.25; 95% CI: 0.10–0.63, p = 0.003) and propensity score-adjusted analysis (HR = 0.46; 95% CI: 0.24–0.91, p = 0.025). ConclusionProdromal otological symptoms might be associated with a reduced risk of motor progression in PD.

Clinical Outcomes of Pencil Beam Scanning Proton Therapy in Locally Advanced Non-Small Cell Lung Cancer: Propensity Score Analysis.

Simple SummaryWe analyzed the oncologic outcomes and toxicities after intensity-modulated radiation therapy (IMRT) or pencil beam scanning proton therapy (PBSPT) in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiation therapy. Due to an imbalance in baseline characteristics between IMRT and PBSPT, we used propensity score-based statistical analysis. Regarding radiation therapy planning, PBSPT exhibited superior sparing of the lung, heart, and spinal cord compared to intensity-modulated (photon) radiotherapy in patients with advanced NSCLC. However, PBSPT resulted in higher incidence of grade 3 or more dermatitis and esophagitis compared to IMRT. Despite declined baseline lung function, PBSPT demonstrated a comparable rate of symptomatic radiation pneumonitis compared to IMRT. PBSPT could be an effective and safe treatment technique with comparable locoregional control.This study compared the efficacy and safety of pencil beam scanning proton therapy (PBSPT) versus intensity-modulated (photon) radiotherapy (IMRT) in patients with stage III non-small cell lung cancer (NSCLC). We retrospectively reviewed 219 patients with stage III NSCLC who received definitive concurrent chemoradiotherapy between November 2016 and December 2018. Twenty-five patients (11.4%) underwent PBSPT (23 with single-field optimization) and 194 patients (88.6%) underwent IMRT. Rates of locoregional control (LRC), overall survival, and acute/late toxicities were compared between the groups using propensity score-adjusted analyses. Patients treated with PBSPT were older (median: 67 vs. 62 years) and had worse pulmonary function at baseline (both FEV1 and DLCO) compared to those treated with IMRT. With comparable target coverage, PBSPT exhibited superior sparing of the lung, heart, and spinal cord to radiation exposure compared to IMRT. At a median follow-up of 21.7 (interquartile range: 16.8–26.8) months, the 2-year LRC rates were 72.1% and 84.1% in the IMRT and PBSPT groups, respectively (p = 0.287). The rates of grade ≥ 3 esophagitis were 8.2% and 20.0% after IMRT and PBSPT (p = 0.073), respectively, while corresponding rates of grade ≥ 2 radiation pneumonitis were 28.9% and 16.0%, respectively (p = 0.263). PBSPT appears to be an effective and safe treatment technique even for patients with poor lung function, and it does not jeopardize LRC.

Second malignancy probabilities in prostate cancer patients treated with SBRT and other contemporary radiation techniques

BackgroundProstate radiotherapy has been associated with an increased risk of developing a second malignancy (SM). However, relative SM probabilities following treatment with contemporary radiation techniques such as stereotactic body radiotherapy (SBRT) or moderately hypofractionated intensity modulated radiotherapy (HF-IMRT) remain unknown. MethodsA cohort analysis was performed of men from a nationally representative database with localized prostate cancer with at least 60 months of follow-up comparing SM probability amongst men receiving either radical prostatectomy (RP), conventionally fractionated intensity-modulated radiotherapy (CF-IMRT), HF-IMRT, brachytherapy (BT), or SBRT, using multivariable logistic models, which were used to generate predicted probabilities. Additionally, propensity score-adjusted pairwise assessments of modalities were performed. ResultsFor 303,432 patients included in the study, median follow-up was 9.08 years (IQR 7.01–11.21). Predicted rates of SM by treatment modality and adjusted odds ratios (AOR) for development of SM (referent: RP) were: 6.0% for RP (AOR n/a), 7.1% for CF-IMRT (AOR 1.20, 95%CI 1.14–1.25, P < 0.001), 7.3% for HF-IMRT (AOR 1.25, 95%CI 1.01–1.55, P = 0.045), 6.6% for BT (AOR 1.11, 95%CI 1.07–1.16, P < 0.001), and 5.7% for SBRT (AOR 0.95, 95%CI 0.81–1.12, P = 0.567). On propensity score-adjusted analysis, SBRT was associated with lower odds of SM compared to CF-IMRT (AOR 0.78, 95%CI 0.66–0.93, P = 0.005); no significant difference was found when SBRT was compared to RP (AOR 0.86, 95%CI 0.73–1.03, P = 0.102). ConclusionsConventionally fractionated intensity-modulated radiotherapy, moderately hypofractionated intensity-modulated radiotherapy, and brachytherapy but not stereotactic body radiotherapy were associated with increased probability of a second malignancy compared to radical prostatectomy. Patients treated with SBRT may be at lower risk of second malignancy due to improved conformality, radiobiological differences or patient selection. The possibility that SBRT in select patients may minimize the probability of SM underscores the need for assessment of second malignancy risk in prospective studies of SBRT.

Direct discharge from the emergency department of simple stable injuries: a propensity score-adjusted non-inferiority trial

BackgroundRecent studies suggest a large proportion of musculoskeletal injuries are simple stable injuries (SSIs). The aim of this study was to evaluate whether direct discharge (DD) from the emergency department...

FOLFOXIRI plus Bevacizumab Versus FOLFOX plus Panitumumab for Metastatic Left-Sided RAS/BRAF Wild-Type Colorectal Cancer: Which "Side" Are You On?

This commentary focuses on the results of the study by Pietrantonio et al., which evaluated the clinical conundrum of triplet versus doublet chemotherapy in combination with targeted therapy for metastatic left-sided RAS/BRAF wild-type colorectal cancer and appears in this issue. Both FOLFOXIRI [fluorouracil, leucovorin, oxaliplatin, and irinotecan] plus bevacizumab and FOLFOX [fluorouracil, leucovorin, and oxaliplatin] plus panitumumab have shown impressive activity in this population; however, the two have not been directly compared. The article by Pietrantonio et al. presents a propensity score-adjusted analysis using information from five previous randomized trials and provides best available evidence comparing these regimens. This commentary will discuss their results and how their findings fit in current treatment paradigms.

A Matched Case-Case-Control Study of the Impact of Clinical Outcomes and Risk Factors of Patients with IMP-Type Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae in Japan.

IMP-type carbapenemase, found in various Gram-negative bacteria, has been increasingly detected worldwide. We aimed to study the outcomes and risk factors for acquisition of IMP-type carbapenemase-producing carbapenem-resistant Enterobacteriaceae (IMP-CRE), as this has not been evaluated in detail. We conducted a matched case-case-control study of patients from whom IMP-CRE isolates were obtained. All patients who tested positive for IMP-CRE were included; they were matched with patients with carbapenem-susceptible Enterobacteriaceae (CSE) and with controls at a ratio of 1:1:2. The risk factors for acquisition for the CRE and CSE groups and mortality rates, which were calculated using multivariate logistic regression models with weighting according to the inverse probability of propensity scores, were compared. In total, 192 patients (96 patients each in the CRE and CSE groups, with 130 Enterobacter cloacae isolates and 62 Klebsiella sp. isolates) were included. The IMP-11 type was present in 43 patients, IMP-1 in 33, and IMP-60 and IMP-66 in 1 each; 31 patients with CRE (32.3%) and 34 with CSE (35.4%) developed infections. Multivariate analysis identified the following independent risk factors: gastrostomy, history of intravenous therapy or hemodialysis, and previous exposure to broad-spectrum β-lactam antibiotics, including penicillin with β-lactamase inhibitors, cephalosporins, and carbapenems. In propensity score-adjusted analysis, mortality rates for the CRE and CSE groups were similar (15.0% and 19.5%, respectively). We found that IMP-CRE may not contribute to worsened clinical outcomes, compared to CSE, and gastrostomy, previous intravenous therapy, hemodialysis, and broad-spectrum antimicrobial exposure were identified as risk factors for CRE isolation. Fluoroquinolone and aminoglycosides are potentially useful antibiotics for IMP-CRE infections.

Impact of a surgical approach for implantation of durable left ventricular assist devices in patients on extracorporeal life support.

The aim of this study was to evaluate the impact of the surgical approach on the postoperative outcome in patients who underwent left ventricular assist device (LVAD) implantation after having received veno-arterial extracorporeal life support (va-ECLS) using data from a European registry (ECLS-VAD). Five hundred and thirty-one patients were included. A propensity score-adjusted outcome analysis was performed, resulting in 324 patients in the full sternotomy (FS) group and 39 in the less invasive surgery (LIS) group. The surgery lasted in median 236 min in the FS group versus 263 min in the LIS group (p = 0.289). The median chest tube output during the first 24 h was similar in both groups. Patients who underwent implantation with an FS required more blood products during the first 24 postoperative hours (median 16 vs. 12, p = 0.033). The incidence of revision due to bleeding was also higher (35.5 vs. 15.4%, p = 0.016). A temporary postoperative right ventricular assist device was necessary in 45.1 (FS) versus 23.1% (LIS) of patients, respectively (p = 0.067). No stroke occurred in the LIS group during the first 30 days after surgery (7.4% in the FS group). The incidence of stroke and of renal, hepatic, and respiratory failure during the follow-up was similar in both groups. The 30-day and one-year survival were similar in both groups. LIS for implantation of a durable LVAD in patients on va-ECLS implanted for cardiogenic shock is associated with less revision due to bleeding, less administration of blood products and absence of perioperative stroke, with no impact on survival.

A multicenter propensity score analysis of FOLFIRINOX vs gemcitabine plus nab-paclitaxel administered to patients with metastatic pancreatic cancer: results from the NAPOLEON study.

Fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX, FFX) and gemcitabine plus nab-paclitaxel (GnP) are considered standard treatments for patients with metastatic pancreatic cancer. Direct comparisons are not available that establish which is optimal. We conducted a propensity score-adjusted analysis of patients with metastatic pancreatic cancer to identify the therapeutic advantages of these standard therapies. We used clinical data as part of a multicenter retrospective study of patients with unresectable or recurrent pancreatic cancer treated with FFX or GnP (NAPOLEON study). FFX and GnP were initially administered to 102 and 153 patients, respectively. The GnP group comprised more patients of advanced age, worse performance status, lower body mass index, recurrence, and lower albumin concentrations. Median overall survival (OS) and progression-free survival (PFS) were 11.5months and 5.8months in the FFX group and 11.1months and 5.9months in the GnP group, respectively. Propensity score-adjusted analysis indicated that the administration of FFX or GnP was not independently associated with OS (adjusted hazard ratio [HR] 1.06; 95% confidence interval [CI] 0.76-1.47; P = 0.73). Similarly, the difference in PFS was not significant between groups (adjusted HR 0.93; 95% CI 0.68-1.26; P = 0.62). Gastrointestinal disorders were more common in the FFX group, whereas the frequencies of hematological, nervous system, and skin disorders were higher in the GnP group. The efficacies of FFX and GnP were comparable, although safety profiles differed and should be considered in selecting treatment.

Effectiveness of In-Hospital Cholecalciferol Use on Clinical Outcomes in Comorbid COVID-19 Patients: A Hypothesis-Generating Study.

Little information is available on the beneficial effects of cholecalciferol treatment in comorbid patients hospitalized for COVID-19. The aim of this study was to retrospectively examine the clinical outcome of patients receiving in-hospital high-dose bolus cholecalciferol. Patients with a positive diagnosis of SARS-CoV-2 and overt COVID-19, hospitalized from 15 March to 20 April 2020, were considered. Based on clinical characteristics, they were supplemented (or not) with 400,000 IU bolus oral cholecalciferol (200,000 IU administered in two consecutive days) and the composite outcome (transfer to intensive care unit; ICU and/or death) was recorded. Ninety-one patients (aged 74 ± 13 years) with COVID-19 were included in this retrospective study. Fifty (54.9%) patients presented with two or more comorbid diseases. Based on the decision of the referring physician, 36 (39.6%) patients were treated with vitamin D. Receiver operating characteristic curve analysis revealed a significant predictive power of the four variables: (a) low (<50 nmol/L) 25(OH) vitamin D levels, (b) current cigarette smoking, (c) elevated D-dimer levels (d) and the presence of comorbid diseases, to explain the decision to administer vitamin D (area under the curve = 0.77, 95% CI: 0.67–0.87, p < 0.0001). Over the follow-up period (14 ± 10 days), 27 (29.7%) patients were transferred to the ICU and 22 (24.2%) died (16 prior to ICU and six in ICU). Overall, 43 (47.3%) patients experienced the combined endpoint of transfer to ICU and/or death. Logistic regression analyses revealed that the comorbidity burden significantly modified the effect of vitamin D treatment on the study outcome, both in crude (p = 0.033) and propensity score-adjusted analyses (p = 0.039), so the positive effect of high-dose cholecalciferol on the combined endpoint was significantly amplified with increasing comorbidity burden. This hypothesis-generating study warrants the formal evaluation (i.e., clinical trial) of the potential benefit that cholecalciferol can offer in these comorbid COVID-19 patients.

Comparison of Oncologic Outcomes between Carbon Ion Radiotherapy and Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer.

Simple SummaryLung cancer is a leading cause of cancer-related death. Stereotactic body radiotherapy (SBRT) is the standard treatment for inoperable early-stage non-small cell lung cancer (NSCLC). Carbon ion radiotherapy (CIRT) is a safe and effective treatment for early-stage NSCLC. However, there is no direct comparison study between these treatments. The present study aimed to compare oncologic outcomes after CIRT and SBRT for early-stage NSCLC in a single-institutional and contemporaneous cohort. We demonstrated favorable overall survival and local control in the CIRT group compared to those in the SBRT group using log-rank tests and Cox regression analyses for 89 patients. In addition, these results were validated in propensity score-adjusted analyses. The present retrospective comparison study showed a positive efficacy profile of CIRT, which is beneficial in the management of early-stage NSCLC.Lung cancer is a leading cause of cancer-related deaths worldwide. Radiotherapy is an essential treatment modality for inoperable non-small cell lung cancer (NSCLC). Stereotactic body radiotherapy (SBRT) is the standard treatment for early-stage NSCLC because of its favorable local control (LC) compared to conventional radiotherapy. Carbon ion radiotherapy (CIRT) is a kind of external beam radiotherapy characterized by a steeper dose distribution and higher biological effectiveness. Several prospective studies have shown favorable outcomes. However, there is no direct comparison study between CIRT and SBRT to determine their benefits in the management of early-stage NSCLC. Thus, we conducted a retrospective, single-institutional, and contemporaneous comparison study, including propensity score-adjusted analyses, to clarify the differences in oncologic outcomes. The 3-year overall survival (OS) was 80.1% in CIRT and 71.6% in SBRT (p = 0.0077). The 3-year LC was 87.7% in the CIRT group and 79.1% in the SBRT group (p = 0.037). Multivariable analyses showed favorable OS and LC in the CIRT group (hazard risk [HR] = 0.41, p = 0.047; HR = 0.30, p = 0.040, respectively). Log-rank tests after propensity score matching and Cox regression analyses using propensity score confirmed these results. These data provided a positive efficacy profile of CIRT for early-stage NSCLC.

The Evolution of Minimally Invasive Donor Hepatectomy: Robotic vs Laparoscopic and Open Right Lobe Procurement. A Multicenter Study on 1194 Donor Hepatectomies

Background: Laparoscopic and robotic Minimally invasive donor hepatectomies (MIDH) are increasingly performed, especially in Eastern countries. We conducted a retrospective, multicenter, propensity score-adjusted analysis on right lobe MIDH by comparing the robotic approach to the laparoscopic and open ones assessing feasibility, safety, and early outcomes. Methods: From January 2016 until December 2020, 1194 donors underwent right hepatectomy performed with a robotic (n=92), laparoscopic (n=306), and open approach (n=796) at six high volume centers. Propensity score matching (1:1:2) was performed to make donors comparable for sex, age, and body mass index (BMI), and recipients comparable for sex, age, BMI, liver disease, presence of HCC, MELD and graft-to-recipient-body weight ratio. Perioperative donor outcomes were analyzed, with complications classified according to Clavien-Dindo, and postoperative pain measured through a visual analog scale. Recipients' outcomes were also analyzed. Results: Ninety-two donors undergoing robotic surgery were matched and compared to 92 and 184 donors undergoing laparoscopic and open surgery. Conversions to open surgery occurred during 1 (1.1%) robotic and 2 (2.2%) laparoscopic procedures. Robotic procedures had a longer operative time than laparoscopic and open procedures (p < 0.001). The first graft warm ischemic time was also longer during robotic procedures. However, the robotic approach was associated with reduced donor blood losses (p<0.001). Postoperative mortality was nihil. No differences were observed in major complications (Clavien-Dindo ≥ IIIa). Donors undergoing robotic hepatectomy had less postoperative pain than those undergoing laparoscopic and open procedures (p<0.001). Fifty recipients of robotic-procured grafts were matched to 50 and 100 recipients of laparoscopic and open surgery procured grafts, respectively. There were no differences in terms of postoperative complicationns and 90 days mortality. After a mean follow-up of 18 months, recipients' survival was similar (p=0.455). Conclusions: In high volume centers, robotic right lobe procurement is a safe procedure for both donors and recipients. Despite an increased operative time, a robotic approach is associated with reduced intraoperative blood losses and postoperative pain, compared to the laparoscopic and open approaches. Recipients’ outcomes are independent of the surgical approach used for graft procurement.

Cardiovascular risk in patients with spondyloarthritis and association with anti-TNF drugs.

Background:Cardiovascular (CVS) diseases are the leading cause of death worldwide and patients with rheumatic diseases have an increased CVS. CVS risk factors and CVS events are common in spondyloarthritis (SpA). Delineating the CVS risk in patients with SpA and identifying modifiable risk factors would be useful.Methods:Patients with SpA and patients with non-specific back pain (NSBP) were identified in rheumatology and orthopedics clinics, respectively. Clinical information and CVS events were retrieved. Baseline characteristics and incidence rates of CVS events were compared between two groups of patients using an age- and sex-matched cohort. Propensity score adjustment and Cox regression analysis were performed to determine the CVS risk associated with SpA.Results:A total of 5046 patients (SpA 2616 and NSBP 2430) were included from eight centers. Over 56,484 person-years of follow up, 160 strokes, 84 myocardial infarction (MI) and 262 major adverse cardiovascular events (MACE) were identified. Hypercholesterolemia was more prevalent in SpA (SpA 34.2%, NSBP 28.7%, p < 0.01). Crude incidence rates of MACE and stroke were higher in SpA patients. SpA was associated with a higher risk of MACE [hazard ratio (HR) 1.70; 95% confidence interval (CI) 1.29–2.26; p < 0.01] and cerebrovascular events (HR 1.50; 95% CI 1.08–2.07; p = 0.02). SpA patients with anti-TNF use had a reduced risk of MACE (HR 0.37, 95%CI 0.17–0.80, p = 0.01) and cerebrovascular events (HR 0.21, 95%CI 0.06–0.78, p = 0.02) compared with SpA patients without anti-TNF use.Conclusion:SpA is an independent CVS risk factor. Anti-tumor necrosis factor (TNF) drugs were associated with a reduced CVS risk in these patients.

Age Is Associated With the Efficacy of Anticoagulant Therapies Against Sepsis-Induced Disseminated Intravascular Coagulation.

Disseminated Intravascular Coagulation (DIC) commonly complicates sepsis and considerably worsens mortality. Recent studies suggested that anticoagulant therapies improved mortality only in specific sepsis populations, and key pathologies for selecting optimal targets needed to be identified. Anticoagulant activities were naturally altered with aging. This study aimed to evaluate age-related differences in efficacy of anticoagulant therapies in sepsis. This post hoc analysis of a nationwide multicenter cohort study was conducted in 42 intensive care units in Japan. Adult patients with septic DIC were divided into anticoagulant and control groups. Age-related changes in predicted mortality in both groups were compared using a logistic regression model including 2-way interaction terms. Patients were also stratified into 3 subsets based on age, and propensity score-adjusted Cox regression analyses were conducted to examine survival effect of anticoagulants in each subset. We included 1432 patients with septic DIC; 867 patients received anticoagulants and 565 received none. Age-related change in predicted mortality was significantly different between groups (P for interaction = 0.013), and the gap between groups was broad in the younger population. Similarly, in Cox regression analyses, anticoagulant therapies were associated with significantly lower mortality in the subsets of age ≤ 60 and 60-79 (hazard ratios = 0.461, 0.617, P = 0.007, 0.005, respectively), whereas there was no difference in survival between the groups in the subsets of age ≥ 80. The efficacy of anticoagulant therapies for septic DIC might be associated with patient age.

Percutaneous Endoscopic Gastrostomy Reduces Aspiration Pneumonia Rate in Stroke Patients with Enteral Feeding in Convalescent Rehabilitation Wards.

ABSTRACTObjectives:The effect of percutaneous endoscopic gastrostomy (PEG) on the prevention of aspiration pneumonia and improvements in activities of daily living (ADL) for enteral feeding-dependent stroke patients is unclear. We sought to clarify differences in the rates of aspiration pneumonia and ADL improvement between stroke patients receiving PEG and those receiving nasogastric tube feeding (NGT) in convalescent rehabilitation wards.Methods:We assessed 10 years of data from the Kaga Regional Cooperation Clinical Pathway for Stroke, which covers patients in the southern district of Ishikawa Prefecture of Japan. Logistic regression analysis with propensity score adjustment was used to examine how the enteral feeding method affected aspiration pneumonia rates. Linear regression analysis, adjusted by propensity scores, was also performed to ascertain the effect of the enteral feeding method on ADL improvement.Results:Overall, 47 patients with PEG and 49 patients with NGT were analyzed. The incidence of aspiration pneumonia was 4.67 times higher in the NGT group than in the PEG group in the propensity score-adjusted logistic regression analysis (odds ratio 4.67, 95% confidence interval 1.30–16.67, P=0.02). The enteral feeding method had no significant effect on ADL improvement in the propensity score-adjusted linear regression analysis.Conclusions:In convalescent rehabilitation wards, aspiration pneumonia was more likely to occur in stroke patients with NGT than in those with PEG; however, the enteral feeding method did not affect ADL improvement. These results provide a basis for determining the appropriate enteral feeding method for stroke patients who cannot take adequate nutrition orally during convalescence/rehabilitation.

The association of amputations and peripheral artery disease in patients with type 2 diabetes mellitus receiving sodium-glucose cotransporter type-2 inhibitors: real-world study.

The aim of this study was to evaluate the temporal pattern of amputations in patients with type 2 diabetes mellitus (T2DM), the risk of amputations by new and older anti-diabetic drugs (ADDs), and the interplay of peripheral artery disease (PAD) with therapy and amputation risk. Using Centricity Electronic Medical Records from USA, 3293983 patients with T2DM were identified: 169739 received sodium-glucose cotransporter type-2 inhibitors (SGLT-2i; no exposure to incretins); 149826 received glucagon-like peptide 1 receptor agonists [GLP-1RA, no SGLT-2i or dipeptidyl peptidase-4 inhibitor (DPP-4i) exposure]; 448225 received DPP-4i (no exposure to GLP-1RA or SGLT-2i); and 1954353 received other ADDs. The proportion of incident amputations per 10000 adults ranged between 4.7 and 6.8 during 2000-08 and significantly increased to 12.3 in 2017. Over 17211719 person-years follow-up post T2DM diagnosis, the rates per 1000 person-years of any and lower limb amputations (LLAs) were similar between SGLT-2i and incretins [95% confidence interval (CI) range: 1.06-1.67], and significantly higher in other groups (95% CI range: 1.96-2.29). In propensity score-adjusted pairwise analyses, the risk of LLA was not higher in SGLT-2i vs. GLP1-RA [hazard ratio (HR) (95% CI): 0.88 (0.73, 1.05)], and lower in SGLT-2i vs. DPP-4i/other ADD [HR (95% CI): 0.65 (0.56, 0.75)/0.43 (0.37, 0.49)]. The rate of LLA was similar in patients treated with canagliflozin, empagliflozin, or dapagliflozin. Patients with PAD had more than four-fold higher LLA risk (range of 95% CI of HR: 3.6-6.0). The risk of amputation in patients treated with SGLT-2i and incretins was not higher compared with other ADDs. Pre-existing PAD was the greatest driver of amputation risk.

Effectiveness of Chemoradiotherapy for Metachronous Esophageal Squamous Cell Carcinoma

Introduction: Multiple Lugol-voiding lesions (LVLs) in the esophagus increase the risk of synchronous and metachronous development of esophageal squamous cell carcinoma (ESCC). Chemoradiotherapy (CRT) following endoscopic submucosal dissection (ESD) may reduce the incidence of metachronous ESCC, but few studies have investigated this. Therefore, we retrospectively examined the effect of CRT on metachronous ESCC and multiple esophageal dysplasias visible as multiple LVLs. Methods: This study reviewed 146 patients who underwent esophageal ESD and were determined pathologically to have noncurative resection. They were divided into 2 groups: those who received additional CRT (CRT group; n = 64) and those without additional treatment (control group; n = 82). Incidence of metachronous ESCC was analyzed using propensity scores to adjust for patient characteristics. The number of multiple LVLs was also examined. Results: The CRT group was significantly younger than the control group (mean 66.6 vs. 70.6 years, p = 0.011), had significantly deeper tumor invasion (p = 0.013), and had a significantly higher rate of lymphovascular invasion (47.8 vs. 12.2%, p < 0.001). The CRT group also had a significantly higher improvement rate of multiple LVLs (58.1 vs. 2.0%, p < 0.001). The LVLs after CRT had a distinctive irregular crack-shaped appearance. Metachronous ESCC was found in 7 patients (10.9%) in the CRT group and in 17 patients (20.7%) in the control group (p = 0.113). In propensity score-adjusted logistic regression analysis, the odds ratio for metachronous ESCC in the CRT group was 0.316 (p = 0.023). The occurrence rate was significantly lower in the CRT group than in the control group. Discussion/Conclusion: CRT may be effective in preventing metachronous ESCC.

Does Side Really Matter? Survival Analysis among Patients with Right- Versus Left-Sided Colon Cancer: A Propensity Score-Adjusted Analysis.

Right- and left-sided colon cancer are increasingly regarded as two independent disease entities based on different gene expression profiles as well as underlying genetic mutations. Data regarding prognosis and survival are heterogeneous and more favorable in cases of left-sided colon cancer. The purpose of this study was to evaluate the long-term oncological outcome for patients with left-sided versus right-sided stage I-III colon cancer. Overall, 318 consecutive patients who underwent surgery for right- or left-sided sided colon cancer between 2001 and 2014 were analyzed. Analysis was performed applying a prospectively maintained database with respect to overall, disease-specific, and relative survival, using Cox regression and propensity score analyses. A total of 155 patients (48.7%) presented with right-sided colon cancer and 163 patients (51.3%) presented with left-sided colon cancer. In risk-adjusted Cox regression analysis, tumor location had no significant impact on overall survival (hazard ratio [HR] 1.53, 95% confidence interval [CI] 0.80-2.92; p = 0.197), disease-specific survival (HR 1.36, 95% CI 0.76-2.44; p = 0.301), and relative survival (HR 1.70, 95% CI 0.89-3.27; p = 0.107). After propensity score matching, the results from risk-adjusted Cox regression analysis were confirmed. Stratified by American Joint Committee on Cancer stage, patients with right-sided stage II colon cancer had a statistically significant superior relative survival compared with patents with left-sided colon cancer. No significant negative impact on overall, disease-specific, or relative survival could be observed in patients with right- versus left-sided colon cancer after risk adjustment, using multivariable Cox regression and propensity score analyses.

Bias Reduction Methods for Propensity Scores Estimated from Error-Prone EHR-Derived Covariates.

As the use of electronic health records (EHR) to estimate treatment effects has become widespread, concern about bias introduced by error in EHR-derived covariates has also grown. While methods exist to address measurement error in individual covariates, little prior research has investigated the implications of using propensity scores for confounder control when the propensity scores are constructed from a combination of accurate and error-prone covariates. We reviewed approaches to account for error in propensity scores and used simulation studies to compare their performance. These comparisons were conducted across a range of scenarios featuring variation in outcome type, validation sample size, main sample size, strength of confounding, and structure of the error in the mismeasured covariate. We then applied these approaches to a real-world EHR-based comparative effectiveness study of alternative treatments for metastatic bladder cancer. This head-to-head comparison of measurement error correction methods in the context of a propensity score-adjusted analysis demonstrated that multiple imputation for propensity scores performs best when the outcome is continuous and regression calibration-based methods perform best when the outcome is binary.

Sacubitril/Valsartan and Sudden Cardiac Death According to Implantable Cardioverter-Defibrillator Use and Heart Failure Cause: A PARADIGM-HF Analysis

ObjectivesThe purpose of this study was to investigate the effect of sacubitril/valsartan therapy on sudden cardiac death (SCD) according to the use of and eligibility for an implantable cardioverter-defibrillator (ICD), stratified by heart failure cause. BackgroundSCD still accounts for a significant proportion of overall mortality in heart failure with reduced ejection fraction (HFrEF). MethodsPatients enrolled in the PARADIGM-HF (Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial (n = 8,399) were evaluated to assess patterns of ICD implantation and eligibility according to clinical guidelines. The impact of ICD (adjusted for propensity of ICD implantation) and sacubitril/valsartan therapy on SCD was evaluated by using cause-specific Cox models and competing risk analysis. ResultsAt baseline, of the 7,145 patients (85%) eligible for ICD implantation, only 1,243 (15%) had an ICD. Use of ICD varied by region with the highest rates in North America (56%) and lowest in Asia-Pacific (1.7%). In a propensity score-adjusted analysis, use of an ICD was associated with a 56% lower risk of SCD in ICD-eligible patients, in both patients with ischemic (p < 0.001) and nonischemic cardiomyopathy (p = 0.02). Sacubitril/valsartan reduced SCD risk in patients with an ICD (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.25 to 0.99) and in those who were eligible for but did not receive an ICD (HR: 0.81; 95% CI: 0.67 to 0.98). This effect was particularly evident in nonischemic cardiomyopathy (p < 0.05), although interaction with the cause of HF was not significant (p = 0.11 in subjects using an ICD and p = 0.25 in eligible nonusers). ConclusionsUse of an ICD was associated with lower rates of SCD, regardless of HF cause but was underused in most regions of the world in the PARADIGM-HF study. Sacubitril/valsartan reduced SCD risk regardless of use of an ICD or eligibility, particularly in ICD users and nonischemic cardiomyopathy.