***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE Hypoglycemia is associated with serious health outcomes for patients treated for diabetes . However , the outcome of out patients with type 2 diabetes who have experienced hypoglycemia episodes is largely unknown . RESEARCH DESIGN AND METHODS The study population , derived from the National Health Insurance Research Data base released by the Taiwan National Health Research Institutes during 1998–2009 , comprised 77,611 patients with newly diagnosed type 2 diabetes . We design ed a prospect i ve study consisting of r and omly selected hypoglycemic type 2 diabetic patients and matched type 2 diabetic patients without hypoglycemia .  We investigated the relationships of hypoglycemia with total mortality and cardiovascular events , including stroke , coronary heart disease , cardiovascular diseases , and all-cause hospitalization . RESULTS There were 1,844 hypoglycemic events ( 500 in patients and 1,344 out patients ) among the 77,611 patients . Both mild ( outpatient ) and severe ( inpatient ) hypoglycemia cases had a higher percentage of comorbidities , including hypertension , renal diseases , cancer , stroke , and heart disease . In multivariate Cox regression models , including diabetes treatment adjustment , diabetic patients with hypoglycemia had a significantly higher risk of cardiovascular events during clinical treatment periods . After constructing a model adjusted with propensity scores , mild and severe hypoglycemia still demonstrated higher hazard ratios ( HRs ) for cardiovascular diseases ( HR 2.09 [ 95 % CI 1.63–2.67 ] ) , all-cause hospitalization ( 2.51 [ 2.00–3.16 ] ) , and total mortality ( 2.48 [ 1.41–4.38 ] ) . CONCLUSIONS Symptomatic hypoglycemia , whether clinical ly mild or severe , is associated with an increased risk of cardiovascular events , all-cause hospitalization , and all-cause mortality . More attention may be needed for diabetic patients with hypoglycemic episodes The propensity score is the probability of treatment assignment conditional on observed baseline characteristics . The propensity score allows one to design and analyze an observational ( nonr and omized ) study so that it mimics some of the particular characteristics of a r and omized controlled trial . In particular , the propensity score is a balancing score : conditional on the propensity score , the distribution of observed baseline covariates will be similar between treated and untreated subjects . I describe 4 different propensity score methods : matching on the propensity score , stratification on the propensity score , inverse probability of treatment weighting using the propensity score  , and covariate adjustment using the propensity score . I describe balance diagnostics for examining whether the propensity score model has been adequately specified . Furthermore , I discuss differences between regression-based methods and propensity score-based methods for the analysis of observational data . I describe different causal average treatment effects and their relationship with propensity score analyses The objective of this study was to develop a prospect ively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies . A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients . The 1-yr mortality rates for the different scores were : " 0 " , 12 % ( 181 ) ; " 1 - 2 " , 26 % ( 225 ) ; " 3 - 4 " , 52 % ( 71 ) ; and " greater than or equal to 5 " , 85 % ( 82 ) . The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up . The percent of patients who died of comorbid disease for the different scores were : " 0 " , 8 % ( 588 ) ; " 1 " , 25 % ( 54 ) ; " 2 " , 48 % ( 25 ) ; " greater than or equal to 3 " , 59 % ( 18 ) . With each increased level of the comorbidity index , there were stepwise increases in the cumulative mortality attributable to comorbid disease ( log rank chi 2 = 165 ; p less than 0.0001 ) . In this longer follow-up , age was also a predictor of mortality ( p less than 0.001 ) . The new index performed similarly to a previous system devised by Kaplan and Feinstein . The method of classifying comorbidity provides a simple , readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies . Further work in larger population s is still required to refine the approach because the number of patients with any given condition in this study was relatively small OBJECTIVE Hypoglycemia is associated with failure to show cardiovascular benefit and increased mortality of intensive glycemic control in r and omized clinical trials . This retrospective cohort study aim ed to examine the impact of hypoglycemia on vascular events in clinical practice . RESEARCH DESIGN AND METHODS Patients with type 2 diabetes were identified by ICD-9-CM codes ( 250.xx except for 250.x1 and 250.x3 ) between 1 January 2004 and 1 September 2010 from the Veterans Integrated Service Network 16 . Index date was defined as the first date of new antihyperglycemic medications ( index treatment ) . Patients with 1-year preindex records of hypoglycemia , cardiovascular , and microvascular diseases were excluded . The hypoglycemia group was identified by ICD-9-CM codes ( 250.8 , 251.0 , 251.1 , and 251.2 ) within the index treatment period . A propensity score – matched group was used as control subjects . Cardiovascular events , microvascular complications , and all-cause death were compared using Kaplan-Meier analysis and Cox proportional hazards regression model . RESULTS Among the unmatched sample ( N = 44,261 ) , the hypoglycemia incidence rate was 3.57/100 patient-years . The matched sample ( hypoglycemia group : n = 761 ; control group : n = 761 ) had a median follow-up of 3.93 years , mean age of 62.6 ± 11.0 years , and preindex HbA1c of 10.69 ± 2.61 % . The 1-year change in HbA1c was similar ( hypoglycemia group −0.51 vs. control group −0.32 % , P = 0.7244 ) . The hypoglycemia group had significantly higher risks of cardiovascular events ( hazard ratio 2.00 [ 95 % CI 1.63–2.44 ] ) and microvascular complications ( 1.76 [ 1.46–2.11 ] ) but no statistical mortality difference . Patients with at least two hypoglycemic episodes were at higher risks of vascular events than those with one episode ( 1.53 [ 1.10–1.66 ] ) . CONCLUSIONS Hypoglycemia is associated with higher risks of incident vascular events . Patients with hypoglycemia should be monitored closely for vascular events OBJECTIVE To determine whether a history of severe hypoglycemia was associated with an increased risk of subsequent macrovascular events in people with type 2 diabetes and to explore possible mediation of this association by inflammation . RESEARCH DESIGN AND METHODS A cohort of 1,066 adults aged 60–75 years with type 2 diabetes was evaluated prospect ively . Baseline history of severe hypoglycemia and plasma levels of the inflammatory markers C-reactive protein , fibrinogen , interleukin-6 , and tumor necrosis factor-α were recorded . Their association with incident macrovascular events after 4 years was explored . RESULTS At baseline , 87 participants ( 8.2 % ) reported one or more episodes of  severe hypoglycemia  within the preceding year , and at follow-up 99 participants ( 9.3 % ) had suffered a new macrovascular event . Hypoglycemia was associated with increased odds of macrovascular events ( odds ratio [ OR ] 2.11 [ 95 % CI 1.06 , 4.21 ] , P = 0.035 ) , including coronary heart events ( OR 2.44 [ 95 % CI 1.13 , 5.26 ] , P = 0.023 ) , largely due to increased myocardial infa rct ion ( OR 4.02 [ 95 % CI 1.54 , 10.48 ] , P = 0.004 ) . Hypoglycemia was also associated with increased levels of inflammatory markers , including a general inflammation factor derived using principal-components analysis ( P = 0.030 , after adjustment for cardiometabolic risk factors ) . However , the significant association between hypoglycemia and macrovascular events persisted after adjustment for inflammatory markers . CONCLUSIONS The odds of suffering a macrovascular event were higher in patients with type 2 diabetes who had a history of severe hypoglycemia . There was no evidence that a proinflammatory state had a major role in mediating this association BACKGROUND Severe hypoglycemia may increase the risk of a poor outcome in patients with type 2 diabetes assigned to an intensive glucose-lowering intervention .  We analyzed data from a large study of intensive glucose lowering to explore the relationship between severe hypoglycemia and adverse clinical outcomes . METHODS We examined the associations between severe hypoglycemia and the risks of macrovascular or microvascular events and death among 11,140 patients with type 2 diabetes , using Cox proportional-hazards models with adjustment for covariates measured at baseline and after r and omization . RESULTS During a median follow-up period of 5 years , 231 patients ( 2.1 % ) had at least one severe hypoglycemic episode ; 150 had been assigned to intensive glucose control ( 2.7 % of the 5571 patients in that group ) , and 81 had been assigned to st and ard glucose control ( 1.5 % of the 5569 patients in that group ) . The median times from the onset of severe hypoglycemia to the first major macrovascular event , the first major microvascular event , and death were 1.56 years ( interquartile range , 0.84 to 2.41 ) , 0.99 years ( interquartile range , 0.40 to 2.17 ) , and 1.05 years ( interquartile range , 0.34 to 2.41 ) , respectively . During follow-up , severe hypoglycemia was associated with a significant increase in the adjusted risks of major macrovascular events ( hazard ratio , 2.88 ; 95 % confidence interval [ CI ] , 2.01 to 4.12 ) , major microvascular events ( hazard ratio , 1.81 ; 95 % CI , 1.19 to 2.74 ) , death from a cardiovascular cause ( hazard ratio , 2.68 ; 95 % CI , 1.72 to 4.19 ) , and death from any cause ( hazard ratio , 2.69 ; 95 % CI , 1.97 to 3.67 ) ( P<0.001 for all comparisons ) . Similar associations were apparent for a range of nonvascular outcomes , including respiratory , digestive , and skin conditions ( P<0.01 for all comparisons ) . No relationship was found between repeated episodes of severe hypoglycemia and vascular outcomes or death . CONCLUSIONS Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes . It is possible that severe hypoglycemia contributes to adverse outcomes , but these analyses indicate that hypoglycemia is just as likely to be a marker of vulnerability to such events . ( Funded by Servier and the National Health and Medical Research Council of Australia ; Clinical Trials.gov number , NCT00145925 . ) There have been few reports concerning the trends in antidiabetic drug use in Japan . In 2009 , a dipeptidyl peptidase-4 inhibitor ( DPP4I ) , an antidiabetic with a new mechanism of action , was made available . This study was conducted to analyze the antidiabetic prescription trends in Japan in recent years and the influence of DPP4Is on those trends . We used monthly cl aims data obtained from a data base company . Data from patients 20 years of age or older and who were prescribed antidiabetics  were extracted and analyzed . A total of 18,457 patients were prescribed antidiabetics ( mean age , 53.6 ± 11.0 ) .  The sulfonylurea prescription rate decreased while that of biguanides increased . After the introduction of DPP4Is , use of these agents rapidly increased and the rate further increased one year after DPP4I introduction .  DP-P4Is  also became the most prescribed antidiabetics for those prescribed antidiabetics for the first time . The decrease in the use of sulfonylureas  and the increase in the use of biguanides  are in accordance with trends observed in the United States and Europe , and probably reflect Japanese physicians ' awareness of cumulating evidence gained from studies such as the UK Prospect i ve Diabetes Study ( UKPDS ) . The rapid increase in the DPP4I prescription rate might be the result of several factors including their safety profiles , which were highlighted in clinical studies published just prior to the drugs becoming available . However , there is little 
    Output:
    
Our results suggest that severe hypoglycemia is strongly associated with an increased risk of CVD in Japanese patients with T2D , further supporting the notion that avoiding severe hypoglycemia may be important in preventing CVD in this patient population