Discrete-Choice Experiment to Understand the Preferences of Patients with Hormone-Sensitive Prostate Cancer in the USA, Canada, and the UK.

BACKGROUND: Treatment options for patients with metastatic hormone-sensitive prostate cancer (mHSPC) have broadened, and treatment decisions can have a long-lasting impact on patients' quality of life. Data on patient preferences can improve therapeutic decision-making by helping physicians suggest treatments that align with patients' values and needs. OBJECTIVE: This study aims to quantify patient preferences for attributes of chemohormonal therapies among patients with mHSPC in the USA, Canada, and the UK. METHODS: A discrete-choice experiment survey instrument was developed and administered to patients with high- and very-high-risk localized prostate cancer and mHSPC. Patients chose between baseline androgen-deprivation therapy (ADT) alone and experimentally designed, hypothetical treatment alternatives representing chemohormonal therapies. Choices were analyzed using logit models to derive the relative importance of attributes for each country and to evaluate differences and similarities among patients across countries. RESULTS: A total of 550 respondents completed the survey (USA, 200; Canada, 200; UK, 150); the mean age of respondents was 64.3 years. Treatment choices revealed that patients were most concerned with treatment efficacy. However, treatment-related convenience factors, such as route of drug administration and frequency of monitoring visits, were as important as some treatment-related side effects, such as skin rash, nausea, and fatigue. Patient preferences across countries were similar, although patients in Canada appeared to be more affected by concomitant steroid use. CONCLUSION: Patients with mHSPC believe the use of ADT alone is insufficient when more effective treatments are available. Efficacy is the most significant driver of patient choices. Treatment-related convenience factors can be as important as safety concerns for patients.

Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial.

There is an urgent need for first-line treatment options for patients with human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Claudin-18 isoform 2 (CLDN18.2) is expressed in normal gastric cells and maintained in malignant G/GEJ adenocarcinoma cells. GLOW (closed enrollment), a global, double-blind, phase 3 study, examined zolbetuximab, a monoclonal antibody that targets CLDN18.2, plus capecitabine and oxaliplatin (CAPOX) as first-line treatment for CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. Patients (n = 507) were randomized 1:1 (block sizes of two) to zolbetuximab plus CAPOX or placebo plus CAPOX. GLOW met the primary endpoint of progression-free survival (median, 8.21 months versus 6.80 months with zolbetuximab versus placebo; hazard ratio (HR) = 0.687; 95% confidence interval (CI), 0.544-0.866; P = 0.0007) and key secondary endpoint of overall survival (median, 14.39 months versus 12.16 months; HR = 0.771; 95% CI, 0.615-0.965; P = 0.0118). Grade ≥3 treatment-emergent adverse events were similar with zolbetuximab (72.8%) and placebo (69.9%). Zolbetuximab plus CAPOX represents a potential new first-line therapy for patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. ClinicalTrials.gov identifier: NCT03653507 .

Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: Zolbetuximab, a monoclonal antibody targeting claudin-18 isoform 2 (CLDN18.2), has shown efficacy in patients with CLDN18.2-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma. We report the results of the SPOTLIGHT trial, which investigated the efficacy and safety of first-line zolbetuximab plus mFOLFOX6 (modified folinic acid [or levofolinate], fluorouracil, and oxaliplatin regimen) versus placebo plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma. METHODS: SPOTLIGHT is a global, randomised, placebo-controlled, double-blind, phase 3 trial that enrolled patients from 215 centres in 20 countries. Eligible patients were aged 18 years or older with CLDN18.2-positive (defined as ≥75% of tumour cells showing moderate-to-strong membranous CLDN18 staining), HER2-negative (based on local or central evaluation), previously untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma, with radiologically evaluable disease (measurable or non-measurable) according to Response Evaluation Criteria in Solid Tumors version 1.1; an Eastern Cooperative Oncology Group performance status score of 0 or 1; and adequate organ function. Patients were randomly assigned (1:1) via interactive response technology and stratified according to region, number of organs with metastases, and previous gastrectomy. Patients received zolbetuximab (800 mg/m2 loading dose followed by 600 mg/m2 every 3 weeks) plus mFOLFOX6 (every 2 weeks) or placebo plus mFOLFOX6. The primary endpoint was progression-free survival assessed by independent review committee in all randomly assigned patients. Safety was assessed in all treated patients. The study is registered with ClinicalTrials.gov, NCT03504397, and is closed to new participants. FINDINGS: Between June 21, 2018, and April 1, 2022, 565 patients were randomly assigned to receive either zolbetuximab plus mFOLFOX6 (283 patients; the zolbetuximab group) or placebo plus mFOLFOX6 (282 patients; the placebo group). At least one dose of treatment was administered to 279 (99%) of 283 patients in the zolbetuximab group and 278 (99%) of 282 patients in the placebo group. In the zolbetuximab group, 176 (62%) patients were male and 107 (38%) were female. In the placebo group, 175 (62%) patients were male and 107 (38%) were female. The median follow-up duration for progression-free survival was 12·94 months in the zolbetuximab group versus 12·65 months in the placebo group. Zolbetuximab treatment showed a significant reduction in the risk of disease progression or death compared with placebo (hazard ratio [HR] 0·75, 95% CI 0·60-0·94; p=0·0066). The median progression-free survival was 10·61 months (95% CI 8·90-12·48) in the zolbetuximab group versus 8·67 months (8·21-10·28) in the placebo group. Zolbetuximab treatment also showed a significant reduction in the risk of death versus placebo (HR 0·75, 95% CI 0·60-0·94; p=0·0053). Treatment-emergent grade 3 or worse adverse events occurred in 242 (87%) of 279 patients in the zolbetuximab group versus 216 (78%) of 278 patients in the placebo group. The most common grade 3 or worse adverse events were nausea, vomiting, and decreased appetite. Treatment-related deaths occurred in five (2%) patients in the zolbetuximab group versus four (1%) patients in the placebo group. No new safety signals were identified. INTERPRETATION: Targeting CLDN18.2 with zolbetuximab significantly prolonged progression-free survival and overall survival when combined with mFOLFOX6 versus placebo plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Zolbetuximab plus mFOLFOX6 might represent a new first-line treatment in these patients. FUNDING: Astellas Pharma, Inc.

The economic value of knowing BRCA status: universal BRCA testing for breast cancer prevention.

BACKGROUND: This study aimed to estimate the incremental lifetime effects, costs, and net monetary benefit (NMB) of knowing BRCA information by universal genetic testing of all US women without breast cancer turning 40 in a given year, and the cumulative savings or losses of yearly cohort testing over 16 years. We compared two strategies: (1) 'with BRCA information' and (2) 'without BRCA information.' METHODS: Incremental NMB (INMB) was calculated as the monetized benefit per person of knowing BRCA status. The net monetized value (cumulated INMB) of knowing BRCA information was estimated by multiplying the INMB with the eligible population or the year 2020 cohort of US women age 40 and extended for a total of 16 yearly cohorts. RESULTS: Universal testing of the female population at the age of 40 in a given year provided aan INMB of $663/person (payer) and $1,006/person (society).Escalated to the U.S. population of women age 40 , knowing BRCA status resulted in lifetime cumulated INMB of $1.3 billion (payer) and $2.0 billion (society) for the 2020 cohort; and yielded accumulated monetized value of $18.3 billion (payer) and $27.6 billion (society) over 16 yearly cohorts of 40-year-old women. CONCLUSIONS: The universal testing for BRCA status of all US women at age 40 provides compelling short-term and long-term economic value.

The economic value of knowing BRCA status: BRCA testing for optimizing treatment in recurrent epithelial ovarian cancer.

BACKGROUND: This study aimed to estimate the incremental lifetime effects, costs, and net monetary benefit (NMB) of knowing BRCA information for recurrent ovarian cancer (ROC) patients in a given year and the cumulative savings of yearly hypothetical cohort testing over 16 years. We compared two strategies: (1) 'with BRCA information' and (2) 'without BRCA information.' METHODS: Incremental NMB (INMB) was calculated as the average net monetized benefit of knowing BRCA status. The net monetized value (cumulative INMB) of knowing BRCA information was estimated by multiplying the INMB with the eligible ROC patients in year 2020 and extended for potential ROC patients over 16 yearly hypothetical cohorts of ROC patients. RESULTS: Knowing BRCA information for ROC patients provided an additional monetized value of $3,528 in (payer) and $3,194 (society). Escalated to all ROC patients in the U.S. and future incidence ROC estimates, knowing BRCA information resulted in a lifetime cumulative INMB of $35.6 million (payer) and $32.2 million (society) for the 2020 cohort; and yielded an accumulated value of $97.3 million (payer) and $88.0 million (society) over 16 yearly hypothetical cohorts of ROC patients. CONCLUSIONS: The economic value of knowing BRCA status of all U.S. ROC patients provides short-term and long-term evidence for optimizing treatment.

Economic value of knowing BRCA status: BRCA testing for prostate cancer prevention and optimal treatment.

BACKGROUND: We aimed to estimate the incremental lifetime effects, costs, and net-monetary-benefit (NMB) of knowing BRCA information by testing of patients with low-risk localized prostate cancer (PCa) in the US and guiding subsequent screening and treatment, and the cumulative savings or losses of yearly cohort testing over 16 years. We compared two strategies: (1)'with BRCA information' and (2)'without BRCA information.' We also estimated the expected value of perfect information. METHODS: The incremental NMB (INMB) quantified the monetized benefit per person of knowing BRCA status. The net-monetized-value of knowing BRCA information was estimated by multiplying the INMB with the eligible population. RESULTS: The INMBs of knowing BRCA information were $43,357 (payer) and $43,487 (society). in payer and societal perspectives, respectively. Escalated to the eligible patients in 2020, knowing BRCA status resulted in net monetized lifetime value of $1.7 billion (payer and society) for the 2020 cohort; and yielded accumulated net-monetized-value of $28.0 billion (payer) and $28.1 billion (society) over 16 yearly cohorts of eligible PCa patients. CONCLUSIONS: The economic value of knowing BRCA status for all low-risk localized PCa patients in the US provides short-term and long-term evidence for BRCA testing to screen early and optimize treatment.

Safety and Effectiveness of Empagliflozin in Korean Patients with Type 2 Diabetes Mellitus: Results from a Nationwide Post-Marketing Surveillance

Background@#To evaluate the safety and effectiveness of empagliflozin in routine clinical settings, we collected and assessed the clinical profiles of Korean patients with type 2 diabetes mellitus. @*Methods@#This was a post-marketing surveillance study of empagliflozin 10 and 25 mg. Information on adverse events and adverse drug reactions (ADRs) was collected as safety data sets. Available effectiveness outcomes, including glycosylated hemoglobin (HbA1c) level, fasting plasma glucose, body weight, and blood pressure, were assessed. @*Results@#The incidence rate of ADRs was 5.14% in the safety dataset (n=3,231). Pollakiuria, pruritis genital, and weight loss were the most common ADRs. ADRs of special interest accounted for only 1.18%, and there were no serious events that led to mortality or hospitalization. In the effectiveness data set (n=2,567), empagliflozin significantly reduced the mean HbA1c level and body weight during the study period by –0.68%±1.39% and –1.91±3.37 kg (both P<0.0001), respectively. In addition, shorter disease duration, absence of dyslipidemia, and higher baseline HbA1c levels were identified as the clinical features characteristic of a “responder” to empagliflozin therapy. @*Conclusion@#Empagliflozin is a safe and potent glucose-lowering drug in routine use among Korean patients with type 2 diabetes mellitus. It is expected to have better glycemic efficacy in Korean patients with poorly controlled type 2 diabetes mellitus.

Comparative Effectiveness of Carbidopa-Levodopa Enteral Suspension and Deep Brain Stimulation on Parkinson's Disease-Related Pill Burden Reduction in Advanced Parkinson's Disease: A Retrospective Real-World Cohort Study.

INTRODUCTION: In advanced Parkinson's disease (PD), a high pill burden is associated with poor compliance, reduced control of symptoms, and decreased quality of life. We assessed the impact of carbidopa-levodopa enteral suspension (CLES) and deep brain stimulation (DBS) on PD-related pill burden. METHODS: A retrospective cohort analysis was conducted in the IBM MarketScan and Medicare Supplemental databases. Patients with advanced PD, taking only PD medications, and initiating CLES or DBS between 9 January 2015 and 31 July 2019 were identified. CLES patients were matched to DBS patients in a 1:3 ratio based on a propensity score to balance patient characteristics. Pill burden was measured as a 30-day average number of PD-related pills per day and was captured monthly. Pill-free status was evaluated as the percentage of patients receiving CLES or DBS monotherapy. Descriptive statistics were used to compare pill counts and assess the proportion of patients on monotherapy at 6 and 12 months after initiating CLES or DBS. RESULTS: The cohorts included 34 CLES patients matched to 97 DBS patients. A significant reduction in PD-related pill burden was observed at 6 months after initiation of CLES or DBS (∆CLES: -5.62, p < 0.0001; ∆DBS: -1.48, p = 0.0022). PD-related pill burden reduction in CLES patients was significantly greater than in matched DBS patients at 6 months (∆: -4.14, p < 0.0001), which was sustained at 12 months after initiation. At 12 months, nearly three times more CLES patients were pill free than DBS patients (29.41% and 10.31%, respectively, p = 0.0123). CONCLUSIONS: Device-aided therapies such as CLES and DBS are effective in significantly reducing PD-related pill burden. Patients treated with CLES were more likely to achieve pill-free status than patients receiving DBS.

Meta-Analysis of Same-Day Pegfilgrastim Administration Stratified by Myelotoxic Febrile Neutropenia Risk and Tumor Type.

Background: Pegfilgrastim is recommended to be administered at least 24 hours following the completion of chemotherapy, yet some clinicians use a same-day administration protocol. In this meta-analysis, we compared the incidence of chemotherapy-induced (febrile) neutropenia (CIN/FN) as well as CIN/FN-related chemotherapy disruptions in cancer patients provided with pegfilgrastim same-day vs. next-day. Methods: Six databases were searched for comparative studies of same-day vs. next-day pegfilgrastim administration. Fixed or random-effects meta-analyses were conducted to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Results: Thirteen studies were included in this meta-analysis. The FN OR for same-day vs. next-day administration was 1.48 (95% CI = 1.06-2.08) across all cycles, attributable mainly to studies of high FN risk (OR = 2.46, 95% CI = 1.04-5.83) vs. intermediate FN risk regimens (OR = 1.41, 95% CI = 0.95-2.10), and breast cancer (OR = 3.15, 95% CI = 1.24-8.01) vs. non-Hodgkin lymphoma (NHL; OR = 1.48, 95% CI = 0.98-2.23) and gynecologic cancers (OR = 0.64, 95% CI = 0.11-3.85). Where available, ORs for first cycle of chemotherapy, grades 3 and/or 4 CIN, and chemotherapy dose delays or reductions were in line with these findings. Conclusion: In this independent study, same-day pegfilgrastim administration may or may not increase the likelihood of FN, grades 3 and/or 4 CIN, and chemotherapy dose reductions or delays; and this may be a function of the myelotoxicity of the regimens (elevated in high-risk but not intermediate-risk regimens) and tumor type (elevated in breast but not in NHL or gynecologic cancers). With due caution, same-day pegfilgrastim administration may be safe and beneficial in intermediate-risk regimens and selected tumor types.

Sensorineural hearing loss with macrolide antibiotics exposure: a meta-analysis of the association.

OBJECTIVE: Macrolide antibiotics are among the most commonly used antibiotics; the association of macrolide antibiotics exposure with sensorineural hearing loss (SNHL) has been hypothesized. A systematic search was conducted in PubMed, EMBASE and Cochrane Library from inception to 15 July 2019 to identify studies used macrolide antibiotics for any indication. The results were reported as odds ratio (OR) with 95% confidence interval (CI) using random-effects model to derive the association of macrolide antibiotics exposure with SNHL. The objective of this meta-analysis was to estimate the association of macrolide antibiotics exposure and SNHL from up-to-date evidence. KEY FINDINGS: Nine studies met the inclusion criteria. There was no statistically significant association between macrolide antibiotics exposure and SNHL; the OR was 1.20 (95% CI: 0.96 to 1.49). No significant association was found with any of the subgroup meta-analyses. SUMMARY: Whilst the frequency of SNHL was higher with macrolide antibiotics exposure compared with controls, overall, no association was found between macrolide antibiotics and SNHL.

Diabetes Fact Sheets in Korea, 2020: An Appraisal of Current Status

Background@#This study aimed to investigate the recent prevalence, management, and comorbidities of diabetes among Korean adults aged ≥30 years by analyzing nationally representative data. @*Methods@#This study used data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018, and the percentage and total number of people ≥30 years of age with diabetes and impaired fasting glucose (IFG) were estimated. @*Results@#In 2018, 13.8% of Korean adults aged ≥30 years had diabetes, and adults aged ≥65 years showed a prevalence rate of 28%. The prevalence of IFG was 26.9% in adults aged ≥30 years. From 2016 to 2018, 35% of the subjects with diabetes were not aware of their condition. Regarding comorbidities, 53.2% and 61.3% were obese and hypertensive, respectively, and 72% had hypercholesterolemia as defined by low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL in people with diabetes. Of the subjects with diabetes, 43.7% had both hypertension and hypercholesterolemia. With regard to glycemic control, only 28.3% reached the target level of <6.5%. Moreover, only 11.5% of subjects with diabetes met all three targets of glycosylated hemoglobin, blood pressure, and LDL-C. The percentage of energy intake from carbohydrates was higher in diabetes patients than in those without diabetes, while that from protein and fat was lower in subjects with diabetes. @*Conclusion@#The high prevalence and low control rate of diabetes and its comorbidities in Korean adults were confirmed. More stringent efforts are needed to improve the comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.

Association between Sleep Quality and Painless Diabetic Peripheral Neuropathy Assessed by Current Perception Threshold in Type 2 Diabetes Mellitus

BackgroundIt is known that the painful sensation of diabetic peripheral neuropathy (DPN) results in sleep problems in type 2 diabetes mellitus (T2DM). However, it is not known that the painless DPN also is associated with poor sleep quality in T2DM. The purpose of the current study was to investigate the association between painless DPN and poor sleep quality in T2DM.MethodsA total of 146 patients of T2DM who do not have any painful symptoms of DPN were recruited into the study. Among the patients, painless DPN was diagnosed by using the current perception threshold test. Sleep quality was assessed using the Pittsburgh Sleep Quality Index questionnaire.ResultsThe percentage of painless DPN was significantly higher in the poor sleep quality group than the good sleep quality group (70.0% vs. 35.5%, PP=0.009; 34.3% vs. 18.4%, P=0.029; 40.0% vs. 19.7%, P=0.007, respectively). The association of painless DPN and poor sleep quality remained significant after adjustment for significant covariates (odds ratio, 3.825; 95% confidence interval, 1.674 to 8.742; PConclusionThe current study showed that painless DPN was associated with poor sleep quality. Future studies are required to clarify the pathophysiologic causal relationship between painless DPN and sleep quality.

Association between Sleep Quality and Painless Diabetic Peripheral Neuropathy Assessed by Current Perception Threshold in Type 2 Diabetes Mellitus

BackgroundIt is known that the painful sensation of diabetic peripheral neuropathy (DPN) results in sleep problems in type 2 diabetes mellitus (T2DM). However, it is not known that the painless DPN also is associated with poor sleep quality in T2DM. The purpose of the current study was to investigate the association between painless DPN and poor sleep quality in T2DM.MethodsA total of 146 patients of T2DM who do not have any painful symptoms of DPN were recruited into the study. Among the patients, painless DPN was diagnosed by using the current perception threshold test. Sleep quality was assessed using the Pittsburgh Sleep Quality Index questionnaire.ResultsThe percentage of painless DPN was significantly higher in the poor sleep quality group than the good sleep quality group (70.0% vs. 35.5%, PP=0.009; 34.3% vs. 18.4%, P=0.029; 40.0% vs. 19.7%, P=0.007, respectively). The association of painless DPN and poor sleep quality remained significant after adjustment for significant covariates (odds ratio, 3.825; 95% confidence interval, 1.674 to 8.742; PConclusionThe current study showed that painless DPN was associated with poor sleep quality. Future studies are required to clarify the pathophysiologic causal relationship between painless DPN and sleep quality.

Cost Analysis of Adjunctive Hydrocortisone Therapy for Septic Shock: U.S. Payer Perspective.

OBJECTIVES: To conduct a cost analysis of adjunctive hydrocortisone therapy for severe septic shock from the perspective of a third-party payer in the United States. DESIGN: Estimates of outcomes were aggregate data from the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and Activated Protein C and Corticosteroids for Human Septic Shock trials. In these trials, the outcomes of interests were ICU length of stay, vasopressor-free days, ventilation-free days, and the proportion of patients receiving blood transfusion. Each outcome was monetized into a set of mutually exclusive components and was aggregated to estimate the cost-per-patient based on each trial. Cost inputs for each outcome were obtained from literature and adjusted based on the medical care consumer price index. To estimate the budget impact using adjunctive hydrocortisone therapy, per-patient avoided cost was multiplied by expected septic shock annual incidence. Deterministic one-way sensitivity analysis evaluated the robustness of the findings, and Monte Carlo simulation estimated 95% CI of the findings. SETTING: A total of 103 medical-surgical ICU (69 for Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and 34 for Activated Protein C and Corticosteroids for Human Septic Shock). PATIENTS: Adults greater than or equal to 18 years old with septic shock. INTERVENTIONS: Adjunctive hydrocortisone therapy (hydrocortisone at a dose of 200 mg/d for 7 d for Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and hydrocortisone at a 50 mg IV bolus every 6 hr and fludrocortisone as a 50 µg tablet once daily). MEASUREMENTS AND MAIN RESULTS: Per Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock, adjunctive hydrocortisone therapy showed a 90-day monetized benefit of $8,111 (95% CI, $3,914-$12,307) per patient, driven by improvements in ICU-free days, vasopressor-free days, ventilation-free days, and blood transfusion proportion. The total estimated annual impact of adjunctive hydrocortisone therapy, in 2019 dollars, was $750 million. Per Activated Protein C and Corticosteroids for Human Septic Shock, adjunctive hydrocortisone therapy showed a 90-day monetized benefit of $25,539 per patient (95% CI, $22,853-$28,224), driven by improvements in ICU free-days, vasopressor-free days, and ventilation-free days. The total estimated annual impact of adjunctive hydrocortisone therapy, in 2019 dollars, was $2.3 billion. The deterministic one-way sensitivity analysis showed the cost of ICU stays to be the most influential factor in both analyses. The sensitivity analysis using the reported median showed a greater monetized benefit of $10,658 (Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock) and $30,911 (Activated Protein C and Corticosteroids for Human Septic Shock) per patient. CONCLUSIONS: Using adjunctive hydrocortisone therapy yields a significant monetized benefit based on inputs from the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and Activated Protein C and Corticosteroids for Human Septic Shock trials.

Exposure to proton pump inhibitors and risk of pancreatic cancer: a meta-analysis.

Objectives: To estimate the pancreatic cancer risk among subjects exposed versus not exposed to proton pump inhibitors.Methods: The authors searched PubMed, EMBASE, Scopus, Cochrane Library, and clinicaltrials.gov to identify relevant studies. The authors quantified pancreatic cancer risk among subjects exposed versus not exposed to PPIs, expressed as the pooled (adjusted) odds ratio (OR/aOR) and 95% confidence interval (95%CI) in overall and sensitivity analyses.Results: One randomized trial, two cohort, four case-control, and five nested case-control studies with 700,178 subjects (73,985 cases; 626,193 controls) were retained. PPI exposure was associated with pancreatic cancer risk (OR = 1.75, 95%CI = 1.12-2.72, I2 = 99%); confirmed in sensitivity analyses for high-quality studies, observational studies, case-control studies, studies with pancreatic cancer as the primary outcome, and in sensitivity analyses for diabetes and obesity but not for pancreatitis and smoking. This association was independent of the duration and Defined Daily Dose of PPI exposure. Rabeprazole had a singular significant association with pancreatic cancer (OR = 5.40, 95%CI = 1.98-14.703, I2 = 87.9%).Conclusion: The class of PPIs is associated with a 1.75-fold increase in pancreatic cancer risk, confirmed in sensitivity analyses.

Relationship of Sarcopenia with Microcirculation Measured by Skin Perfusion Pressure in Patients with Type 2 Diabetes

Background@#Few studies have examined the relationship of sarcopenia with the microcirculation. The current study investigated the relationship of sarcopenia with microcirculatory function, as assessed by skin perfusion pressure (SPP), in type 2 diabetes mellitus (T2DM) patients. @*Methods@#In total, 102 T2DM patients who underwent SPP measurements and bioelectrical impedance analysis (BIA) were enrolled in this cross-sectional study. SPP was assessed using the laser Doppler technique. Sarcopenia was defined as low height-adjusted appendicular muscle mass (men, 50 mm Hg), and an SPP below 50 mm Hg was considered to reflect impaired microcirculation. @*Results@#Fourteen patients (13.7%) were diagnosed with impaired microcirculatory function of the lower limb based on SPP. The prevalence of sarcopenia in all subjects was 11.8%, but the percentage of patients with an SPP ≤50 mm Hg who had sarcopenia was more than triple that of patients with an SPP >50 mm Hg (28.6% vs. 9.1%, P=0.036). A significant positive correlation was found between SPP and appendicular muscle mass adjusted for height (P=0.041 for right-sided SPP). Multiple logistic regression analysis showed that patients with sarcopenia had an odds ratio of 4.1 (95% confidence interval, 1.01 to 24.9) for having an SPP ≤50 mm Hg even after adjustment for confounding factors. @*Conclusion@#These results suggest that sarcopenia may be significantly associated with impaired microcirculation in patients with T2DM. Nonetheless, the small number of patients and wide CI require cautious interpretation of the results.

Recent Updates on Vascular Complications in Patients with Type 2 Diabetes Mellitus

It is well known that patients with type 2 diabetes mellitus (T2DM) are at an increased risk of morbidity and mortality from atherosclerotic cardiovascular (CV) complications. Previously, the concept that diabetes mellitus (DM) is a “coronary artery disease (CAD) risk equivalent” was widely accepted, implying that all DM patients should receive intensive management. However, considerable evidence exist for wide heterogeneity in the risk of CV events among T2DM patients and the concept of a “CAD risk equivalent” has changed. Recent guidelines recommend further CV risk stratification in T2DM patients, with treatment tailored to the risk level. Although imaging modalities for atherosclerotic cardiovascular disease (ASCVD) have been used to improve risk prediction, there is currently no evidence that imaging-oriented therapy improves clinical outcomes. Therefore, controversy remains whether we should screen for CVD in asymptomatic T2DM. The coexistence of T2DM and heart failure (HF) is common. Based on recent CV outcome trials, sodium glucose cotransporter-2 inhibitors and glucagon like peptide-1 receptor agonists are recommended who have established ASCVD, indicators of high risk, or HF because of their demonstrated benefits for CVD. These circumstances have led to an increasing emphasis on ASCVD and HF in T2DM patients. In this review, we examine the literature published within the last 5 years on the risk assessment of CVD in asymptomatic T2DM patients. In particular, we review recent guidelines regarding screening for CVD and research focusing on the role of coronary artery calcium, coronary computed tomography angiography, and carotid intima-media thickness in asymptomatic T2DM patients.

Association between Sleep Quality and Painless Diabetic Peripheral Neuropathy Assessed by Current Perception Threshold in Type 2 Diabetes Mellitus

Background@#It is known that the painful sensation of diabetic peripheral neuropathy (DPN) results in sleep problems in type 2 diabetes mellitus (T2DM). However, it is not known that the painless DPN also is associated with poor sleep quality in T2DM.The purpose of the current study was to investigate the association between painless DPN and poor sleep quality in T2DM. @*Methods@#A total of 146 patients of T2DM who do not have any painful symptoms of DPN were recruited into the study. Among the patients, painless DPN was diagnosed by using the current perception threshold test. Sleep quality was assessed using the Pittsburgh Sleep Quality Index questionnaire. @*Results@#The percentage of painless DPN was significantly higher in the poor sleep quality group than the good sleep quality group (70.0% vs. 35.5%, P<0.001). In the subscale results, stimulus values at 2,000 Hz, hypoesthesia and hyperesthesia were more common in the poor sleep quality group than in the good sleep quality group (45.7% vs. 25.0%, P=0.009; 34.3% vs. 18.4%, P=0.029; 40.0% vs. 19.7%, P=0.007, respectively). The association of painless DPN and poor sleep quality remained significant after adjustment for significant covariates (odds ratio, 3.825; 95% confidence interval, 1.674 to 8.742; P<0.001). @*Conclusion@#The current study showed that painless DPN was associated with poor sleep quality. Future studies are required to clarify the pathophysiologic causal relationship between painless DPN and sleep quality.

Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

BACKGROUND: Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia.METHODS: This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment.RESULTS: After 8 weeks of treatment, the percent changes from baseline in TG (−29.8% vs. 3.6%, P<0.001) and non-HDL-C (−10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups.CONCLUSION: The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.