Simultaneous Interfacial Defect Passivation and Bottom-Up Excess PbI2 Management via Rubidium Chloride in Highly Efficient Perovskite Solar Cells with Suppressed Hysteresis.

In halide perovskite solar cells (PSCs), moderate lead iodide (PbI2) can enhance device efficiency by providing some passivation effects, but extremely active PbI2 leads to the current density-voltage hysteresis effect and device instability. In addition, defects distributed on the buried interface of tin oxide (SnO2)/perovskite will lead to the photogenerated carrier recombination. Here, rubidium chloride (RbCl) is introduced at the buried SnO2/perovskite interface, which not only acts as an interfacial passivator to interact with the uncoordinated tin ions (Sn4+) and fill the oxygen vacancy on the SnO2 surface but also converts PbI2 into an inactive (PbI2)2RbCl compound to stabilize the perovskite phase via a bottom-up evolution effect. These synergistic effects deliver a champion PCE of 22.13% with suppressed hysteresis for the W RbCl PSCs, in combination with enhanced environmental and thermal stability. This work demonstrates that the interfacial defect passivation and bottom-up excess PbI2 management using RbCl modifiers are promising strategies to address the outstanding challenges associated with PSCs.

Enhanced Hole Mobility and Decreased Ion Migration Originated from Interface Engineering for High Quality PSCs with Average FF beyond 80.

Perovskite solar cells (PSCs) have made significant progress in power conversion efficiency (PCE) by optimizing deposition method, composition, interface, etc. Although the two-step method demonstrates the advantage of being easy to operate, too much residual PbI2 not only forms defect centers, but affects the perovskite crystallization by arising more grain boundaries (GBs) due to the easy-to-crystallize nature of PbI2 . And GBs in polycrystalline perovskite usually provide main channel for ion migration, leading to accumulation of charges at the interface to form a barrier, thus reducing carrier mobility and resulting in degradation of perovskite devices. Here, an organic molecule N-(4-acetylphenyl)maleimide (N-APMI) is used to modify interface between perovskite and hole transport layer. X-ray photoelectron spectroscopy, scanning electron microscope, and nuclear magnetic resonance results show that ketone group (CO) in N-APMI forms a strong coordination with Pb2+ , which effectively reduces the residual amount of PbI2 nanoparticles on the perovskite surface, giving rise to improved crystallization of perovskite. Temperature-dependent current response demonstrates that ion migration is effectively suppressed, and hole mobility validly increases from 10.74 to 19.48 cm2 V-1 s-1 , leading to a champion fill factor (FF) of 82.5% (PCE 21.96%), and the maximum PCE of the device improves from 20.09% to 23.03%.

Standardizing the haemoglobin glycation index.

AIMS: A high haemoglobin glycation index (HGI) is associated with greater risk for hypoglycaemia and chronic vascular disease. Standardizing how the HGI is calculated would normalize results between research studies and hospital laboratories and facilitate the clinical use of HGI for assessing risk. METHODS: The HGI is the difference between an observed HbA1c and a predicted HbA1c obtained by inserting fasting plasma glucose (FPG) into a regression equation describing the linear relationship between FPG and HbA1c in a reference population. We used data from the 2005-2016 U.S. National Health and Nutrition Examination Survey (NHANES) to identify a reference population of 18,675 diabetes treatment-naïve adults without self-reported diabetes. The reference population regression equation (predicted HbA1c = 0.024 FPG + 3.1) was then used to calculate the HGI and divide participants into low (<-0.150), moderate (-0.150 to <0.150) and high (≥0.150) HGI subgroups. Diabetes status was classified by OGTTs. RESULTS: As previously reported in multiple studies, a high HGI was associated with black race independent of diabetes status, and with older age, higher BMI and higher CRP in normal and prediabetic but not diabetic participants. The mean HGI was 0.6% higher in self-reported diabetic adults. The HGI was not associated with plasma insulin, HOMA-IR or 2 h OGTT in participants classified as normal, prediabetic or diabetic. CONCLUSIONS: The regression equation derived from this demographically diverse diabetes treatment-naïve adult NHANES reference population is suitable for standardizing how the HGI is calculated for both clinical use and in research to mechanistically explain population variation in the HGI and why a high HGI is associated with greater risk for chronic vascular disease.

The Effect of Proton Pump Inhibitor Use on the Course of Kidney Function in Patients with Chronic Kidney Disease Stages G3a to G4.

BACKGROUND: Proton pump inhibitors (PPI) are widely used and implicated in the progression of chronic kidney disease (CKD). We evaluated the relation between chronic PPI use in veterans with CKD G3a to G4 and the rate of decline in renal function. METHODS: We accessed the Veteran Affairs Informatics and Computing Infrastructure national database to evaluate the relation between chronic PPI use and rate of decline in renal function in veterans with CKD (eGFR <60 ml/min1.73 m2). We applied Propensity Score Matching to match the PPI group and the no-PPI control group on age, sex, race, and Charlson Comorbidity Index. The final sample included 1406 patients (age: 62.07±7.82, 62.02% Caucasian) in the PPI cohort with a median 4.7 years follow-up and 1425 patients (age: 65.45±6.58, 71.16% Caucasian) in the control cohort with a median 3.9 years follow-up. Kaplan-Meier curve and Cox regression were performed to analyze the associations of PPI use with dialysis, all-cause mortality, metabolic acidosis, and CKD progression. RESULTS: The PPI group had a significantly increased risk of CKD progression, dialysis and all-cause mortality (aHR, 1.83; 95% CI, 1.53 to 2.19; aHR, 1.84; 95% CI, 1.26 to 2.67; and aHR, 1.34; 95% CI, 1.08 to 1.65, respectively). The PPI cohort also had a trend for development of metabolic acidosis (aHR, 1.34; 95% CI, 0.998 to 1.80), although the difference was not statistically significant. CONCLUSIONS: The data suggest that chronic PPI use accelerates progression of kidney disease and is associated with increased mortality in CKD patients.

Glycemic control and risk factors for in-hospital mortality and vascular complications after coronary artery bypass grafting in patients with and without preexisting diabetes.

BACKGROUND: The purpose of this study was to investigate risk factors of in-hospital mortality and vascular complications after coronary artery bypass grafting (CABG), particularly the effect of different glycemic control levels on outcomes in patients with and without previous evidence of diabetes. METHODS: A total of 8682 patients with and without previous diabetes undergoing CABG were categorized into strict, moderate, and liberal glucose control groups according to their mean blood glucose control level <7.8 mmol/L, 7.8 to 10.0 mmol/L, and ≥10.0 mmoL/L after in-hospital CABG. RESULTS: The patients with previous diabetes had higher rates of in-hospital mortality (1.3% vs 0.4%, P < .001) and major complications (7.0% vs 4.8%, P < .001) than those without diabetes. Current diabetes was significantly associated with a higher risk of in-hospital mortality (odds ratio [OR] = 3.14, 95% confidence interval [CI] 1.87-5.27) and major complications (OR = 1.49, 95% CI 1.24-1.80), and smoking and higher low-density lipoprotein cholesterol (LDL-C) levels showed similar results. Among patients with previous diabetes, strict glucose control was significantly associated with an increased risk of in-hospital mortality (OR = 8.32, 95% CI 3.95-17.51) compared with moderate glucose control. Nevertheless, among non-previous diabetic patients with stress hyperglycemia, strict glucose control led to a lower risk of major complications (OR = 0.71, 95% CI 0.52-0.98). CONCLUSIONS: Diabetes status, smoking, and LDL-C levels were modifiable risk factors of both in-hospital mortality and major complications after CABG. Strict glucose control was associated with an increased risk of in-hospital mortality among patients with diabetes, whereas it reduced the risk of major complications among non-previous diabetic patients.

Patient reported outcome data from acromegaly patients treated with injectable somatostatin receptor ligands (SRLs) in routine clinical practice.

BACKGROUND: Acromegaly patients managed on Somatostatin receptor ligands (SRLs), the most common first-line pharmacotherapy for acromegaly, may still experience acromegaly symptoms such as headache, sweating, fatigue, soft tissue swelling, and joint pain, even those with normal IGF-1. Additionally, treatment with SRLs may cause injection site reactions and other side effects such as gastro-intestinal (GI) symptoms. This study utilized patient-reported outcome measures to examine the burden associated with acromegaly and its treatment for patients receiving a stable dose of long-acting SRLs in routine clinical practice. METHODS: US acromegaly patients on a stable dose of SRL seen by their treating healthcare provider in the past 12 months completed a one-time online survey including the Acro-TSQ, an acromegaly-specific tool for assessing symptom burden and treatment satisfaction and convenience. RESULTS: One hundred five patients were enrolled (mean age 49.9 years, 79.1% female). Patients experienced numerous symptoms, including > 80% who experienced joint pain, acro-fog, swelling of soft tissue, and fatigue/weakness. Many symptoms occurred constantly, while some occurred at the end of the injection cycle, even among those with IGF-1 < = 1.0 ULN. Injection site reactions were common. Patients were moderately satisfied with their current treatment; symptoms and side effects often affected daily activities. On average, patients reported > 3 acromegaly provider visits/year. CONCLUSIONS: Despite receiving a stable dose of SRL and regular visits with an acromegaly healthcare provider, US acromegaly patients in routine clinical practice, and even the subgroup with normal IGF-1, report significant burden of disease and treatment.

Racial and sex differences in the polymorphisms of the endocannabinoid receptor genes in obesity.

BACKGROUND: Obesity is a global epidemic and prevalence of obesity is higher in African Americans (AAs) compared to Caucasians. The endocannabinoid system (EC) and polymorphism in the endocannabinoid receptor type 1 (CNR1) gene 3813A/G and 4895A/G and in the fatty acid amide hydrolase (FAAH) are associated with obesity. The objective was to explore racial and sex differences in these polymorphisms and the biochemical abnormalities seen in obesity. METHODS: A cross-sectional study of 667 subjects (53.67% female; 49.18% AA; 69.72% were obese (body mass index [BMI] ≥30)) were screened for CNR1 3813, 4895 and FAAH 385 polymorphisms using a real-time polymerase chain reaction (PCR) system. RESULTS: Subjects with FAAH 385 polymorphisms were more likely to be obese (75.14% vs. 67.81, P = 0.046). There were no significant sex differences for CNR1 3813 and CNR1 4895; or between obese and control group. AAs had higher prevalence of CNR1 3813 (OR, 2.80, 95% CI, 1.95-4.04) and FAAH 385 (OR, 2.48, 95% CI, 1.82-3.38). Association between African American race and the three genotypes persisted after adjustment of all the variables (P < 0.001). CONCLUSION: FAAH 385 polymorphism is more likely seen in obese and in older subjects. AAs had higher prevalence of CNR1 3813 and FAAH 385 polymorphisms; and lower prevalence of CNR1 4895 polymorphism. These findings may explain some of the racial differences, but not the sex differences in the clinical expression of obesity.

Does the Encounter Type Matter When Defining Diabetes Complications in Electronic Health Records?

BACKGROUND: Electronic health records (EHRs) and claims records are widely used in defining type 2 diabetes mellitus (T2DM) complications across different types of health care encounters. OBJECTIVE: This study investigates whether using different EHR encounter types to define diabetes complications may lead to different results when examining associations between diabetes complications and their risk factors in patients with T2DM. RESEARCH DESIGN: The study cohort of 64,855 adult patients with T2DM was created from EHR data from the Research Action for Health Network (REACHnet), using the Surveillance Prevention, and Management of Diabetes Mellitus (SUPREME-DM) definitions. Incidence of coronary heart disease (CHD) and stroke events were identified using International Classification of Diseases (ICD)-9/10 codes and grouped by encounter types: (1) inpatient (IP) or emergency department (ED) type, or (2) any health care encounter type. Cox proportional hazards regression was used to estimate associations between diabetes complications (ie, CHD and stroke) and risk factors (ie, low-density lipoprotein cholesterol and hemoglobin A1c). RESULTS: The incidence rates of CHD and stroke in all health care settings were more than twice the incidence rates of CHD and stroke in IP/ED settings. The age-adjusted and multivariable-adjusted hazard ratios for incident CHD and stroke across different levels of low-density lipoprotein cholesterol and hemoglobin A1c were similar between IP/ED and all settings. CONCLUSION: While there are large variations in incidence rates of CHD and stroke as absolute risks, the associations between both CHD and stroke and their respective risk factors measured by hazard ratios as relative risks are similar, regardless of alternative definitions.

Observed discordance between outcomes reported by acromegaly patients and their treating endocrinology medical provider.

BACKGROUND: Acromegaly patients, even those with IGF-1 values within the normal range receiving somatostatin receptor ligands (SRLs), often suffer from significant symptoms. It is not known to what extent patients' medical providers are aware of the frequency and severity of acromegaly symptoms or level of treatment satisfaction with SRLs. This study sought to examine the concordance between outcomes reported by acromegaly patients treated with long-acting SRLs and those perceived by their medical provider. METHODS: US acromegaly patients on a stable dose of SRL and seen by their medical provider in the past year completed an online survey which included the Acro-TSQ. Their medical providers were interviewed about the perception of their patient's symptoms, level of control, and general health, and completed relevant portions of the Acro-TSQ. Concordance between patient and medical provider reported data was examined. RESULTS: Medical providers reported that their patients experienced acromegaly symptoms on a regular basis, however, there was poor agreement between patients and medical providers on the frequency, severity, and pattern of symptoms, as well as on the severity of injection site reactions and multiple domains of the Acro-TSQ, with patients generally reporting symptoms and injection site reactions more often and with higher severity than medical providers. CONCLUSIONS: Medical providers were aware that their patients who were receiving a stable dose of SRL regularly experienced acromegaly symptoms. Addressing discordance in patient- and medical provider-reported frequency and severity of acromegaly symptoms and injection site reactions by facilitating better communication may improve care of acromegaly patients.

Effect of metformin on neurodegenerative disease among elderly adult US veterans with type 2 diabetes mellitus.

OBJECTIVE: This study aimed to evaluate the association between metformin treatment and the risk of neurodegenerative disease (ND) among elderly adults with type 2 diabetes mellitus (T2DM). DESIGN/SETTING/PARTICIPANTS: This retrospective longitudinal cohort study examined the effects of the length of metformin exposure on ND among elderly US veterans with T2DM and insulin treatment using the Veterans Affairs electronic medical record database. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary clinical outcome was defined as diagnosis of ND including dementia, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and mild cognitive impairment during the follow-up period. The secondary clinical outcomes were separately measured by AD, PD, HD, dementia and mild cognitive impairment. RESULT: Adjusted by propensity score weight, a total of 5528 patients (mean age, 63.2±10.9 years; male, 98%; white, 60%) with a median follow-up of 5.2 years were selected. Those with ND or other mental disorders at baseline or who were on insulin for less than two-thirds of the study period were excluded. The incidence rate of ND was 11.48 per 1000 person-years among patients with metformin treatment, compared with 25.45 per 1000 person-years for those without metformin. Compared with no metformin use, 2-4 years and >4 years of metformin exposure were significantly associated with lower risk of ND (adjusted HR (aHR)=0.62, 95% CI 0.45 to 0.85; aHR=0.19, 95% CI 0.12 to 0.31, respectively), while metformin exposure in the first 2 years showed no significant influence. CONCLUSION: We conclude that long-term metformin therapy (>2 years) was associated with lower incidence of ND among elderly veterans with T2DM. We need to conduct a study with more representative population and more robust method for causal inferences. Further investigation into the mechanism involved is needed along with randomised trials to confirm a potential neuroprotective effect of metformin.

Correction to: Novel Risk Engine for Diabetes Progression and Mortality in USA: Building, Relating, Assessing, and Validating Outcomes (BRAVO).

The original article can be found online.

Comparative Effectiveness of Non-cisplatin First-line Therapies for Metastatic Urothelial Carcinoma: Phase 2 IMvigor210 Study Versus US Patients Treated in the Veterans Health Administration.

BACKGROUND: First-line treatments for cisplatin-ineligible patients with metastatic urothelial carcinoma (mUC) include carboplatin-based chemotherapy and checkpoint inhibitors such as atezolizumab (anti-PD-L1). OBJECTIVE: To compare overall survival (OS) among patients with mUC treated in the first-line setting with atezolizumab versus carboplatin-based chemotherapies (any carboplatin-based regimens or carboplatin-gemcitabine). DESIGN, SETTING, AND PARTICIPANTS: Cisplatin-ineligible patients with mUC from the phase 2 trial IMvigor210 (ClinicalTrials.gov NCT02951767) treated with atezolizumab and patients from the Veterans Health Administration (VHA) health care system (2006-2017, with IMvigor210 eligibility criteria applied using proxy measurements) treated according to normal clinical practice. INTERVENTIONS: IMvigor210 cohort 1 patients were treated with atezolizumab, and real-world VHA cohorts were treated with carboplatin-based regimens. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Entropy-balance weighting was applied to balance prespecified baseline patient characteristics. OS was analyzed using weighted Kaplan-Meier and Cox methods. RESULTS AND LIMITATIONS: The median OS was 15.0 mo with atezolizumab (n = 110), 12.1 mo with any carboplatin-based chemotherapy (n = 282), and 8.7 mo with carboplatin-gemcitabine (n = 120). An OS benefit occurred with atezolizumab versus carboplatin-based regimens after 9 mo (hazard ratio [HR] 0.43; p = 0.004) and with atezolizumab versus carboplatin-gemcitabine after 5 mo (HR 0.52; p = 0.005). Study limitations include a predominantly male VHA cohort and ≤24-mo follow-up. Adjustment for confounding, a potential limitation of nonrandomized studies, was limited by the availability of clinical measurements in the VHA data, which allowed for replication of IMvigor210 exclusions in the VHA cohorts. CONCLUSIONS: First-line atezolizumab for cisplatin-ineligible mUC may provide an OS benefit over carboplatin-based treatments after 5-9 mo, depending on the regimen. PATIENT SUMMARY: Many patients with metastatic urothelial carcinoma are ineligible for cisplatin-based chemotherapy. This study compared patients from a clinical trial receiving the immunotherapeutic agent atezolizumab with those in Veterans Health Administration clinical practice receiving carboplatin-based chemotherapy. Atezolizumab provided a survival benefit over chemotherapy after 5-9 mo.

Novel Risk Engine for Diabetes Progression and Mortality in USA: Building, Relating, Assessing, and Validating Outcomes (BRAVO).

BACKGROUND: There is an urgent need to update diabetes prediction, which has relied on the United Kingdom Prospective Diabetes Study (UKPDS) that dates back to 1970 s' European populations. OBJECTIVE: The objective of this study was to develop a risk engine with multiple risk equations using a recent patient cohort with type 2 diabetes mellitus reflective of the US population. METHODS: A total of 17 risk equations for predicting diabetes-related microvascular and macrovascular events, hypoglycemia, mortality, and progression of diabetes risk factors were estimated using the data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (n = 10,251). Internal and external validation processes were used to assess performance of the Building, Relating, Assessing, and Validating Outcomes (BRAVO) risk engine. One-way sensitivity analysis was conducted to examine the impact of risk factors on mortality at the population level. RESULTS: The BRAVO risk engine added several risk factors including severe hypoglycemia and common US racial/ethnicity categories compared with the UKPDS risk engine. The BRAVO risk engine also modeled mortality escalation associated with intensive glycemic control (i.e., glycosylated hemoglobin < 6.5%). External validation showed a good prediction power on 28 endpoints observed from other clinical trials (slope = 1.071, R2 = 0.86). CONCLUSION: The BRAVO risk engine for the US diabetes cohort provides an alternative to the UKPDS risk engine. It can be applied to assist clinical and policy decision making such as cost-effective resource allocation in USA.

Long-term outcomes associated with triple-goal achievement in patients with type 2 diabetes mellitus (T2DM).

AIMS: This study was designed to compare the risk of long-term health outcomes, including microvascular, macrovascular complications and mortality, across 4 cohorts: triple-goal, dual-goal, single-goal, and no-goal achievers. METHODS: A retrospective cohort of 53,120 patients with T2DM were identified (97.51% male, 61.49% whites) from the Veterans Affairs (VA) electronic medical records VISN 16 data warehouse (2004-2010). Propensity score weight (PSW) was used to balance demographic characteristics and complication history at baseline. The PSW adjusted hazard ratios (aHR) from Cox proportional hazard models were used to compare complications and all-cause mortality over an average of 4 years of follow-up. RESULTS: At baseline, 25.43% (13,507) patients achieved triple-goal, while 41.36% (21,972) and 26.37% (14,010) patients achieved dual-goal and single-goal, respectively. During the follow-up period, triple-goal achievement was associated with risk reductions of complications and all-cause mortality when compared to all other groups of achieving dual or single-goal. Across different combinations of dual-goal achievement, the cohort with LDL-C goal achievement had lower risk of complication events and mortality, compared to those that achieved other goals but failed to reach LDL-C goal. CONCLUSIONS: Achievement of triple-goal was associated with better health outcomes among veterans with T2DM compared to those that did not, while LDL-C has more weight of influence. Multi-faceted treatment strategies targeting hypertension, hyperglycemia and hyperlipidemia may improve health outcome in veterans with T2DM.

Outcomes associated with warfarin time in therapeutic range among US veterans with nonvalvular atrial fibrillation.

BACKGROUND: Poor quality of warfarin control (time in therapeutic range [TTR] < 65%) can lead to increased risk of adverse events. The objective of this study was to examine the overall quality of international normalized ratio (INR) control and the association of TTR with clinical outcomes including stroke, major bleeding, and all-cause mortality among US warfarin users. METHODS AND RESULTS: This retrospective observational cohort study utilized the US Veterans Affairs electronic medical records database (VA EMR). Patients with NVAF who newly initiated warfarin from 1 January 2005 to 31 December 2015 were grouped into two cohorts based on TTR <65% or ≥65%. TTR was computed from INR test results. Clinical outcomes assessed were stroke/systemic embolism (SE), hemorrhagic stroke, ischemic stroke, and major bleeding, defined based on hospitalization with those conditions as primary diagnosis, as well as all-cause mortality. Patients were followed from warfarin initiation to the first occurrence of an outcome or censoring. Propensity score weighted time-varying Cox regression was used to evaluate the risk of the clinical events. A total of 127,385 NVAF patients with mean TTR of 51% were included. TTR <65% was observed in 65% of patients. Mean CHA2DS2-VASC score (SD) was 2.9 (1.5) in the low TTR cohort and 2.7 (1.4) in the high TTR cohort. Patients with TTR <65% had a higher risk for any stroke/SE (HR: 1.57; 95% CI: 1.41-1.75), major bleeding (HR: 2.78; 95% CI: 2.55-3.03) and all-cause mortality (HR: 1.73; 95% CI: 1.67-1.79). CONCLUSIONS: The observed quality of warfarin control in VA EMR suggests room for improvement given the association with elevated risk of adverse clinical outcomes.

Patient-centered assessment on disease burden, quality of life, and treatment satisfaction associated with acromegaly.

The study aimed to assess the economic burden, health-related quality of life (HRQoL), and acromegaly treatment satisfaction in the USA. A web-based, cross-sectional survey was distributed to members of Acromegaly Community. Data related to comorbidities, treatment patterns, and treatment satisfaction were collected. The costs over the past 3 months included out-of-pocket cost, sick leave, leave of absence, direct loss of job due to acromegaly, unemployment, assistance to perform household chores, and family member loss of income. The HRQoL was assessed by Acromegaly Quality of Life (AcroQoL) and EQ-5D-3L questionnaires. Among 106 patients who completed the survey (mean age: 46 years, female: 76.4%), 44.3% presented with ≥5 comorbidities, and 90.6% reporting acromegaly-related symptoms. Compared with the low-symptom group 0-3 (n=41), the 4+ symptoms group (n=65) was more likely to have depression (OR=2.3, 95% CI 1.1 to 5.2) and cardiovascular disease (OR=5.8, 95% CI 2.0 to 16.7), and experienced higher costs (loss of job: $8874 vs $1717, P=0.02; unemployment disability: $17,102 vs $429, P=0.003; household chores: $2160 vs $932, P=0.0003; family members' income loss: $692 vs $122, P=0.03). The high-symptom group had lower HRQoL scores, compared with the low-symptom group (EQ-5D-3L: 0.53 vs 0.75, P<0.0001; AcroQoL: 27 vs 56, P<0.0001). Only 55.7% among patients requiring injections for acromegaly were satisfied. Patients with acromegaly who presented with multiple acromegaly-related symptoms were evidenced to have experienced higher economic burden and poorer quality of life than patients with the same diagnosis but fewer symptoms. The low rate of treatment satisfaction warrants need for further studies.

Cost-effectiveness analysis of dapagliflozin versus glimepiride as monotherapy in a Chinese population with type 2 diabetes mellitus.

OBJECTIVE: To evaluate the long-term cost-effectiveness of dapagliflozin (a novel sodium-glucose co-transporter-2 inhibitor) versus glimepiride (a widely used sulfonylurea), when applied as monotherapy in patients with type 2 diabetes mellitus (T2DM) in China. METHODS: Literature screening, meta-analysis and indirect comparison were used to compare efficacy and safety between dapagliflozin and glimepiride. Direct medication costs and medical expenditure on treating diabetes related comorbidities were calculated based on published and local sources and reported in 2015 Chinese Renminbi (RMB). A discount rate of 3% was applied to both costs and health effects. The Cardiff model, an economic model designed to evaluate the cost-effectiveness of comparator therapies in diabetes, was used to generate outputs including macrovascular and microvascular complications, diabetes-specific mortality, costs and quality-adjusted life years (QALYs) over a time horizon of 40 years from the health provider perspective. Univariate and probabilistic sensitivity analyses were performed to assess uncertainty in the model results. RESULTS: Compared with glimepiride, patients on dapagliflozin gained 1.01 QALYs, at a cost saving of RMB 49,065 in our simulated cohort. This resulted in a cost saving of RMB 48,585 per QALY gained with dapagliflozin. The cost-effectiveness results were robust to various sensitivity analyses including probabilistic sensitivity analysis (PSA). CONCLUSIONS: Compared with glimepiride, dapagliflozin as monotherapy for T2DM is a more cost-effective treatment for T2DM patients on monotherapy in China. The weight control has been identified as the major contributor for the higher cost-effectiveness of dapagliflozin.

State feedback control design for Boolean networks.

BACKGROUND: Driving Boolean networks to desired states is of paramount significance toward our ultimate goal of controlling the progression of biological pathways and regulatory networks. Despite recent computational development of controllability of general complex networks and structural controllability of Boolean networks, there is still a lack of bridging the mathematical condition on controllability to real boolean operations in a network. Further, no realtime control strategy has been proposed to drive a Boolean network. RESULTS: In this study, we applied semi-tensor product to represent boolean functions in a network and explored controllability of a boolean network based on the transition matrix and time transition diagram. We determined the necessary and sufficient condition for a controllable Boolean network and mapped this requirement in transition matrix to real boolean functions and structure property of a network. An efficient tool is offered to assess controllability of an arbitrary Boolean network and to determine all reachable and non-reachable states. We found six simplest forms of controllable 2-node Boolean networks and explored the consistency of transition matrices while extending these six forms to controllable networks with more nodes. Importantly, we proposed the first state feedback control strategy to drive the network based on the status of all nodes in the network. Finally, we applied our reachability condition to the major switch of P53 pathway to predict the progression of the pathway and validate the prediction with published experimental results. CONCLUSIONS: This control strategy allowed us to apply realtime control to drive Boolean networks, which could not be achieved by the current control strategy for Boolean networks. Our results enabled a more comprehensive understanding of the evolution of Boolean networks and might be extended to output feedback control design.

Changes in Mortality in People With IGT Before and After the Onset of Diabetes During the 23-Year Follow-up of the Da Qing Diabetes Prevention Study.

OBJECTIVE: People with impaired glucose tolerance (IGT) have increased risk of mortality and a high risk of progression to diabetes, but the extent that the excess mortality is associated with IGT per se or is the result of subsequent diabetes is unclear. RESEARCH DESIGN AND METHODS: We compared mortality before and after the development of diabetes among 542 persons with IGT initially who participated in a 6-year lifestyle diabetes prevention trial and were followed-up from 1986 to 2009. RESULTS: During the 23-year follow-up, 174 (32.1%) died, with an overall death rate of 15.9/1,000 person-years. The majority of deaths (74.7%; 130 of 174) occurred after progression to type 2 diabetes, with age-adjusted death rates of 11.1/1,000 person-years (95% CI 8.2-12.0) before and 19.4/1,000 person-years (95% CI 11.9-23.3) after the development of type 2 diabetes. The cumulative mortality was 37.8% (95% CI 33.1-42.2%) in participants who developed type 2 diabetes during first 10 years of follow-up, 28.6% (95% CI 21.6-35.0%) in those who progressed to type 2 diabetes in 10-20 years, and 13.9% (95% CI 7.0-20.3%) in those who did not develop to type 2 diabetes within 20 years. Time-dependent multivariate Cox proportional hazards analyses, with adjustment for baseline age, sex, intervention, and other potential confounding risk factors, showed that the development of type 2 diabetes was associated with a 73% higher risk of death (hazard ratio 1.73 [95% CI 1.18-2.52]). CONCLUSIONS: As elsewhere, IGT is associated with increased risk of mortality in China, but much of this excess risk is attributable to the development of type 2 diabetes.

Effects of antiviral treatment on influenza-related complications over four influenza seasons: 2006-2010.

PURPOSE: The objective of the study is to evaluate the effect of antiviral treatment, pre-existing diseases, and sociodemographic factors on the risk of influenza-related complications and healthcare utilization. METHODS: Case data was obtained from U.S. MarketScan Research Databases. Cases had a clinical diagnosis of influenza between 2006 and 2010 and continuous healthcare insurance from 90 days before to 30 days after diagnosis. Logistic regression models were applied to explore the impact of antiviral treatment on complications and healthcare utilization. Modified generalized estimating equation regression models in propensity score matched samples were used to address the robustness of the study. RESULTS: Analyses included 1,557,437 cases from four influenza seasons. In each season, 34.82%-43.42% of patients received antiviral treatment, mostly oseltamivir. On average, 1.86% of patients were hospitalized, 9.56% visited the emergency room and 41.14% made ≥2 outpatient visits. The incidence of complications ranged from 17.62 to 19.67 per 100 patient-months. The relative risk of complications was increased in patients aged 0-4 years and those with pre-existing diseases, including asthma, Parkinson's disease, and cystic fibrosis. Overall, patients receiving antiviral treatment had an 11% reduction in the risk of complications. Among oseltamivir-treated patients, the risk of complications was significantly reduced by 81% in those treated ≤2 days after diagnosis compared with later. Antiviral treatment significantly reduced the risk of hospitalization, emergency room visits and need for ≥2 outpatient visits by 29%, 24% and 11%, respectively. The propensity score matching method improved the strength of the study. CONCLUSIONS: Early treatment with antivirals, and specifically oseltamivir, significantly reduced the risk of influenza-related complications and healthcare utilization. However, lacking information about disease severity and the time from onset of symptoms to fulfillment of a prescription may bias the outcomes.