Delays in treatment intensification with oral antidiabetic drugs and risk of microvascular and macrovascular events in patients with poor glycaemic control: An individual patient simulation study.

AIMS: To use the Archimedes model to estimate the consequences of delays in oral antidiabetic drug (OAD) treatment intensification on glycaemic control and long-term outcomes at 5 and 20 years. MATERIALS AND METHODS: Using real-world data, we modelled a cohort of hypothetical patients with glycated haemoglobin (HbA1c) ≥8%, on metformin, with no history of insulin use. The cohort included 3 strata based on the number of OADs taken at baseline. The first add-on in the intensification sequence was a sulphonylurea, next was a dipeptidyl peptidase-4 inhibitor, and last, a thiazolidinedione. The scenarios included either no delay or delay, based on observed and extrapolated times to intensification. RESULTS: At 1 year, HbA1c was 6.8% for patients intensifying without delay, and 8.2% for those delaying intensification. For no delay vs delay, risks of major adverse cardiac events, myocardial infarction, heart failure and amputations were reduced by 18.0%, 25.0%, 13.7%, and 20.4%, respectively, at 5 years; severe hypoglycaemia risk, however, increased to 19% for the no delay scenario vs 12.5% for delay. At 20 years, the results showed similar trends to those at 5 years. CONCLUSIONS: Timing of intensification of OAD therapy according to guideline recommendations led to greater reductions in HbA1c and lower risks of complications, but higher risks of hypoglycaemia than delaying intensification. These results highlight the potential impact of timely treatment intensification on long-term outcomes.

Functional traits explain variation in plant life history strategies.

Ecologists seek general explanations for the dramatic variation in species abundances in space and time. An increasingly popular solution is to predict species distributions, dynamics, and responses to environmental change based on easily measured anatomical and morphological traits. Trait-based approaches assume that simple functional traits influence fitness and life history evolution, but rigorous tests of this assumption are lacking, because they require quantitative information about the full lifecycles of many species representing different life histories. Here, we link a global traits database with empirical matrix population models for 222 species and report strong relationships between functional traits and plant life histories. Species with large seeds, long-lived leaves, or dense wood have slow life histories, with mean fitness (i.e., population growth rates) more strongly influenced by survival than by growth or fecundity, compared with fast life history species with small seeds, short-lived leaves, or soft wood. In contrast to measures of demographic contributions to fitness based on whole lifecycles, analyses focused on raw demographic rates may underestimate the strength of association between traits and mean fitness. Our results help establish the physiological basis for plant life history evolution and show the potential for trait-based approaches in population dynamics.

ASSOCIATION BETWEEN HYPOGLYCEMIA AND FALL-RELATED FRACTURES AND HEALTH CARE UTILIZATION IN OLDER VETERANS WITH TYPE 2 DIABETES.

OBJECTIVE: To examine the association between hypoglycemia and fall-related outcomes in older patients with type 2 diabetes mellitus (T2DM). METHODS: This retrospective cohort study used electronic medical records of T2DM patients (≥65 years) from the Veterans Integrated Service Network 16 (VISN 16) data warehouse (01/01/2004-06/30/2010). Patients in nonhypoglycemia group (non-HG) were 1:1 randomly matched with patients in hypoglycemia group (HG) by age (±5 years), sex, race, and medical center location. Fall-related events (i.e., fractures and head injuries) were identified, with a fall being the external cause within ±2 days. McNemar tests and generalized estimating equation (GEE) models were used to compare fall-related events in the 1-year outcome period after the index date (i.e., date of first hypoglycemic episode). We also examined fall-related healthcare utilization. RESULTS: A total of 4,215 patients in each group were studied, with the mean age of 76.5 years (SD: 5.85). The mean Charlson comorbidity index (CCI) scores were 5.73 (SD: 2.95) in the HG and 4.34 (SD: 2.40) in the non-HG. The HG had significantly higher rates of fall-related events than non-HG, 27 (0.64%) versus 1 (0.02%) and 89 (2.11%) versus 21 (0.50%) events within 30 days and 1 year, respectively. GEE models confirmed the elevated risk of fall-related events after controlling for sociodemographic and clinical characteristics, comorbidities, and medication use (adjusted odds ratio [aOR]: 2.70; 95% confidence interval [CI]: 1.64-4.47). The HG patients were more likely to have emergency department (ED) visits, hospital admissions, and long-term care placement compared to their counterparts. CONCLUSION: Hypoglycemia is associated with worse fall-related outcomes among the elderly veterans.

Rapid and sensitive approaches for detecting food fraud: A review on prospects and challenges.

Precise and reliable analytical techniques are required to guarantee food quality in light of the expanding concerns regarding food safety and quality. Because traditional procedures are expensive and time-consuming, quick food control techniques are required to ensure product quality. Various analytical techniques are used to identify and detect food fraud, including spectroscopy, chromatography, DNA barcoding, and inotrope ratio mass spectrometry (IRMS). Due to its quick findings, simplicity of use, high throughput, affordability, and non-destructive evaluations of numerous food matrices, NI spectroscopy and hyperspectral imaging are financially preferred in the food business. The applicability of this technology has increased with the development of chemometric techniques and near-infrared spectroscopy-based instruments. The current research also discusses the use of several multivariate analytical techniques in identifying food fraud, such as principal component analysis, partial least squares, cluster analysis, multivariate curve resolutions, and artificial intelligence.

Artificial intelligence in healthcare: a mastery.

There is a vast development of artificial intelligence (AI) in recent years. Computational technology, digitized data collection and enormous advancement in this field have allowed AI applications to penetrate the core human area of specialization. In this review article, we describe current progress achieved in the AI field highlighting constraints on smooth development in the field of medical AI sector, with discussion of its implementation in healthcare from a commercial, regulatory and sociological standpoint. Utilizing sizable multidimensional biological datasets that contain individual heterogeneity in genomes, functionality and milieu, precision medicine strives to create and optimize approaches for diagnosis, treatment methods and assessment. With the arise of complexity and expansion of data in the health-care industry, AI can be applied more frequently. The main application categories include indications for diagnosis and therapy, patient involvement and commitment and administrative tasks. There has recently been a sharp rise in interest in medical AI applications due to developments in AI software and technology, particularly in deep learning algorithms and in artificial neural network (ANN). In this overview, we enlisted the major categories of issues that AI systems are ideally equipped to resolve followed by clinical diagnostic tasks. It also includes a discussion of the future potential of AI, particularly for risk prediction in complex diseases, and the difficulties, constraints and biases that must be meticulously addressed for the effective delivery of AI in the health-care sector.

Advanced oxidation process for the treatment of industrial wastewater: A review on strategies, mechanisms, bottlenecks and prospects.

Due to its complex and, often, highly contaminated nature, treating industrial wastewater poses a significant environmental problem. Many of the persistent pollutants found in industrial effluents cannot be effectively removed by conventional treatment procedures. Advanced Oxidation Processes (AOPs) have emerged as a promising solution, offering versatile and effective means of pollutant removal and mineralization. This comprehensive review explores the application of various AOP strategies in industrial wastewater treatment, focusing on their mechanisms and effectiveness. Ozonation (O3): Ozonation, leveraging ozone (O3), represents a well-established AOP for industrial waste water treatment. Ozone's formidable oxidative potential enables the breakdown of a broad spectrum of organic and inorganic contaminants. This paper provides an in-depth examination of ozone reactions, practical applications, and considerations involved in implementing ozonation. UV/Hydrogen Peroxide (UV/H2O2): The combination of ultraviolet (UV) light and hydrogen peroxide (H2O2) has gained prominence as an AOP due to its ability to generate hydroxyl radicals (ȮH), highly efficient in pollutant degradation. The review explores factors influencing the efficiency of UV/H2O2 processes, including H2O2 dosage and UV radiation intensity. Fenton and Photo-Fenton Processes: Fenton's reagent and Photo-Fenton processes employ iron ions and hydrogen peroxide to generate hydroxyl radicals for pollutant oxidation. The paper delves into the mechanisms, catalyst selection, and the role of photoactivation in enhancing degradation rates within the context of industrial wastewater treatment. Electrochemical Advanced Oxidation Processes (EAOPs): EAOPs encompass a range of techniques, such as electro-Fenton and anodic oxidation, which employ electrode reactions to produce ȮH radicals. This review explores the electrochemical principles, electrode materials, and operational parameters critical for optimizing EAOPs in industrial wastewater treatment. TiO2 Photocatalysis (UV/TiO2): Titanium dioxide (TiO2) photocatalysis, driven by UV light, is examined for its potential in industrial wastewater treatment. The review investigates TiO2 catalyst properties, reaction mechanisms, and the influence of parameters like catalyst loading and UV intensity on pollutant removal. Sonolysis (Ultrasonic Irradiation): High-frequency ultrasound-induced sonolysis represents a unique AOP, generating ȮH radicals during the formation and collapse of cavitation bubbles. This paper delves into the physics of cavitation, sonolytic reactions, and optimization strategies for industrial wastewater treatment. This review offers a critical assessment of the applicability, advantages, and limitations of these AOP strategies in addressing the diverse challenges posed by industrial wastewater. It emphasizes the importance of selecting AOPs tailored to the specific characteristics of industrial effluents and outlines potential directions for future research and practical implementation. The integrated use of these AOPs, when appropriately adapted, holds the potential to achieve sustainable and efficient treatment of industrial wastewater, contributing significantly to environmental preservation and regulatory compliance.

Development and validation of RP HPLC method to determine nandrolone phenylpropionate in different pharmaceutical formulations.

This study describes development and subsequent validation of a reversed phase high performance liquid chromatographic (RP-HPLC) method for the estimation of nandrolone phenylpropionate, an anabolic steroid, in bulk drug, in conventional parenteral dosage formulation and in prepared nanoparticle dosage form. The chromatographic system consisted of a Luna Phenomenex, CN (250 mm x 4.6 mm, 5 microm) column, an isocratic mobile phase comprising 10 mM phosphate buffer and acetonitrile (50:50, v/v) and UV detection at 240 nm. Nandrolone phenylpropionate was eluted about 6.3 min with no interfering peaks of excipients used for the preparation of dosage forms. The method was linear over the range from 0.050 to 25 microg/mL in raw drug (r2 = 0.9994). The intra-day and inter-day precision values were in the range of 0.219-0.609% and 0.441-0.875%, respectively. Limits of detection and quantitation were 0.010 microg/mL and 0.050 microg/mL, respectively. The results were validated according to International Conference on Harmonization (ICH) guidelines in parenteral and prepared nanoparticle formulation. The validated HPLC method is simple, sensitive, precise, accurate and reproducible.

The impact of chronic hepatitis B on quality of life: a multinational study of utilities from infected and uninfected persons.

OBJECTIVES: Chronic hepatitis B (CHB) is a condition that results in substantial morbidity and mortality worldwide because of progressive liver damage. Investigators undertaking economic evaluations of new therapeutic agents require estimates of health-related quality of life (HRQOL). Recently, evidence has begun to accumulate that differences in cultural backgrounds have a quantifiable impact on perceptions of health. The objective was to elicit utilities for six health states that occur after infection with the hepatitis B virus from infected and uninfected respondents living in jurisdictions with low and with high CHB endemicity. METHODS: Standard gamble utilities were elicited from hepatitis patients and uninfected respondents using an interviewer-administered survey in the United States, Canada, United Kingdom, Spain, Hong Kong, and mainland China. Generalized linear models were used to the effect on utilities of current health, age and sex, jurisdiction and, for infected respondents, current disease state. RESULTS: The sample included 534 CHB-infected patients and 600 uninfected respondents. CHB and compensated cirrhosis had a moderate impact on HRQOL with utilities ranging from 0.68 to 0.80. Decompensated cirrhosis and hepatocellular carcinoma had a stronger impact with utilities ranging from 0.35 to 0.41. Significant variation was observed between countries, with both types of respondents in mainland China and Hong Kong reporting systematically lower utilities. CONCLUSIONS: Health states related to CHB infection have substantial reductions in HRQOL and the utilities reported in this study provide valuable information for comparing new treatment options. The observed intercountry differences suggest that economic evaluations may benefit from country-specific utility estimates. The extent that systematic intercountry differences in utilities hold true for other infectious and chronic diseases remains an open question and has considerable implications for the proper conduct and interpretation of economic evaluations.

Impact of schizophrenia and schizophrenia treatment-related adverse events on quality of life: direct utility elicitation.

OBJECTIVE: To examine the impact of schizophrenia, its treatment and treatment-related adverse events related to antipsychotics, on quality of life from the perspective of schizophrenia patients and laypersons. METHODS: Health state descriptions for stable schizophrenia, extra pyramidal symptoms (EPS), hyperprolactinemia, diabetes, weight gain and relapse were developed based on a review of the literature and expert opinion. The quality of life impact of each health state was elicited using a time trade-off instrument administered by interview to 49 stable schizophrenia patients and 75 laypersons. Regression techniques were employed to examine the importance of subject characteristics on health-related utility scores. RESULTS: Patients and laypersons completed the interview in similar times. Stable schizophrenia had the highest mean utility (0.87 and 0.92 for laypersons and patients respectively), while relapse (0.48 and 0.60) had the lowest mean utility. Of the treatment-related adverse events, EPS had the lowest mean utility (0.57 and 0.72, respectively). Age, gender and PANSS score did not influence the utility results independently of health state. On average, patient utilities are 0.077 points higher than utilities derived from laypersons, although the ranking was similar between the two groups. CONCLUSION: Events associated with schizophrenia and treatment of schizophrenia can bring about a significant detriment in patient quality of life, with relapse having the largest negative impact. Results indicate that patients with stable schizophrenia are less willing to trade years of life to avoid schizophrenia-related symptoms compared to laypersons. Both sets of respondents showed equal ability to complete the questionnaire.

Time to Treatment Intensification After Monotherapy Failure and Its Association With Subsequent Glycemic Control Among 93,515 Patients With Type 2 Diabetes.

OBJECTIVE: The goal of this study was to evaluate the association between the timing of treatment intensification and subsequent glycemic control among patients with type 2 diabetes in whom monotherapy fails. RESEARCH DESIGN AND METHODS: This retrospective analysis of the U.K. Clinical Practice Research Datalink database focused on patients with type 2 diabetes and one or more HbA1c measurements ≥7% (≥53 mmol/mol) after ≥3 months of metformin or sulfonylurea monotherapy (first measurement meeting these criteria was taken as the study index date). Baseline (6 months before the index date) characteristics were stratified by time from the index date to intensification (early: <12 months; intermediate: 12 to <24 months; late: 24 to <36 months). Intensification was defined as initiating after the index date one or more noninsulin antidiabetes medication in addition to metformin or a sulfonylurea. Association between time to intensification and subsequent glycemic control (first HbA1c <7% [<53 mmol/mol] after intensification) was evaluated using Kaplan-Meier analyses and Cox proportional hazard models that accounted for baseline differences. RESULTS: Of the 93,515 patients who met the study criteria (mean age 60 years; ∼59% male; 80% taking metformin), 23,761 (25%) intensified <12 months after the index date; 11,908 (13%) intensified after 12 to <24 months; and 7,146 (8%) intensified after 24 to <36 months. Patients who intensified treatment ≥36 months after the index date (n = 9,638 [10%]) and those with no evidence of treatment intensification during the observable follow-up period (n = 41,062 [44%]) were not included in further analyses. The median times from intensification to control were 20.0, 24.1, and 25.7 months, respectively, for the early, intermediate, and late intensification cohorts. After adjustment for baseline differences, the likelihood of attaining glycemic control was 22% and 28% lower for patients in the intermediate and late intensification groups, respectively, compared with those intensifying early (P < 0.0001). CONCLUSIONS: Earlier treatment intensification is associated with shorter time to subsequent glycemic control, independent of whether patients initiate first-line treatment with metformin or a sulfonylurea.

Utilization of Standard and Target-Specific Oral Anticoagulants Among Adults in the United Kingdom With Incident Atrial Fibrillation.

New oral anticoagulants (OACs) and updated risk stratification have the potential to improve the quality of care for patients with atrial fibrillation (AF). To describe the time from AF diagnosis to the initiation of an OAC, characteristics associated with treatment, and the incidence of switching OACs, we conducted this retrospective cohort study of 23,018 adults with incident AF receiving care between 2010 and 2014 in 647 primary care practices participating in the United Kingdom Clinical Practice Research Datalink. In patients with moderate to high stroke risk (CHA2DS2-VASc ≥ 2), the median time from diagnosis to OAC initiation decreased from 10 to 2 months. Among 980 at very low stroke risk (CHA2DS2-VASc = 0), 29% received OAC prescriptions after 90 days. Being prescribed an OAC was associated with a history of stroke or transient ischemic attack (relative risk 1.3); severe dementia or psychosis was most associated with not being prescribed an OAC (relative risk 0.3). After 1 year, the risk of OAC switching was higher for patients initiating dabigatran (19%) than warfarin (6%), rivaroxaban (8%), or apixaban (9%). The prescribing of OACs in moderate-to-high-risk patients in the United Kingdom increased annually; 1/3 of very low-risk patients were prescribed OACs contrary to guidance. In conclusion, future research should refine decision-making tools to minimize the unwanted effects of underutilization and overutilization of OACs.

Health-related quality-of-life implications of cardiovascular events in individuals with type 2 diabetes mellitus: A subanalysis from the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-TIMI 53 trial.

BACKGROUND: The impact of cardiovascular complications on health-related quality-of-life (HRQoL) in type 2 diabetes mellitus has not been clearly established. Using EQ5D utility data from SAVOR-TIMI 53, a large phase IV trial of saxagliptin versus placebo, we quantified the impact of cardiovascular and other major events on HRQoL. METHODS: EQ5D utilities were recorded annually and following myocardial infarction (MI) or stroke. Utilities among patients experiencing major cardiovascular events were analyzed using linear mixed-effects regression, adjusting for baseline characteristics (including EQ5D utility), and compared to those not experiencing major cardiovascular events. Mean utility decrements with standard errors (SE) were estimated as the difference in utility before and after the event. FINDINGS: The mean EQ5D utility of the sample was 0.776 at all time points, and did not differ by treatment. However, mean baseline and month 12 utilities among those with a major cardiovascular event were 0.751 and 0.714. Mean utilities were 0.691 within 3months of, 0.691 3-6months after, and 0.714 6-12months after, a major cardiovascular event. Cardiovascular event-specific utility decrements were 0.05 (0.007) for major cardiovascular events over the same time periods. Decrements of 0.051 (0.012; myocardial infarction), 0.111 (0.022; stroke), 0.065 (0.014; hospitalization for heart failure) 0.019 (0.024; hospitalization for hypoglycemia) were estimated; all coefficients were statistically significant. INTERPRETATION: Consistent with clinical outcomes reported elsewhere, saxagliptin did not improve HRQoL. Cardiovascular complications were associated with significantly decreased HRQoL, most substantial earlier after the event. FUNDING: BMS/AZ.

A retrospective study of persistence, adherence, and health economic outcomes of fixed-dose combination vs. loose-dose combination of oral anti-diabetes drugs.

OBJECTIVE: To compare outcomes between patients with type 2 diabetes mellitus (T2DM) using fixed-dose combination (FDC) and loose-dose combination (LDC) products. METHODS: This retrospective cohort study used MarketScan Commercial and Medicare Supplemental data from January 1, 2009-December 31, 2013. The identified population included patients with T2DM and ≥1 additional oral anti-diabetic prescription (of the same regimen [FDC/LDC] as the index prescription) within 12 months following the fill date. Persistence (no ≥30-day gap) and adherence (medication possession ratio [MPR] ≥0.8) were assessed as primary end-points; secondary end-points included hypoglycemia, healthcare resource utilization, and costs. RESULTS: Of 23,361 patients identified, 12,590 (53.9%) were on FDC therapy and 10,771 (46.1%) were on LDC therapy. FDC patients had a significantly lower rate of non-persistence (67.9% vs. 73.4%, p < 0.0001) and a significantly higher rate of adherence to therapy (57.0% vs. 50.7%, p < 0.0001) when compared to LDC patients. Average time to non-persistence was significantly longer among FDC vs. LDC patients (207.1 vs. 186.3 days, p < 0.0001). After adjusting for baseline characteristics, the odds of non-persistence were 21% lower with FDC vs. LDC therapy (OR = 0.79, 95% CI = 0.74-0.85, p < 0.0001), with a 28% higher odds of adherence (OR = 1.28, 95% CI = 1.20-1.36, p < 0.0001). Differences in most secondary outcomes significantly favored FDC therapy, including total predicted monthly all-cause costs ($1008 vs. $1053; p = 0.006) and T2DM-related costs ($142 vs. $155; p < 0.001). LIMITATIONS: Cohort classification was based on prescription claims data. The lack of clinical data limits assessment of potential influencers of FDC vs. LDC decisions, residual confounding was possible, and diabetes-related medical costs only captured claims with a primary diagnosis for diabetes. The results may not be generalizable to populations such as Medicaid. CONCLUSION: Management of T2DM using FDC therapies provides a compliance benefit relative to LDC therapies that may translate to reductions in healthcare utilization and costs.

Association Between Weight Change, Clinical Outcomes, and Health Care Costs in Patients with Type 2 Diabetes.

BACKGROUND: Previous research suggests that weight loss is associated with decreases in health care costs among individuals with type 2 diabetes mellitus (T2DM) and that weight change can affect clinical measures, including hemoglobin A1c (A1c), low-density lipoprotein cholesterol (LDLC), and blood pressure. Previous research has also demonstrated more pronounced impact of weight change among patients with T2DM who are obese and have no evidence of cardiovascular disease (CVD). OBJECTIVES: To (a) examine the association between weight change and all-cause and diabetes-related health care costs among patients with T2DM; (b) examine the association between weight change and select clinical measures among patients with T2DM; and (c) analyze a subgroup of obese patients with no previous CVD. METHODS: This retrospective, observational cohort study used U.S. insurance claims linked to laboratory and electronic medical records. This study included patients with T2DM aged 18 years or older who added or switched to a nonmetformin antidiabetes medication after metformin monotherapy between January 1, 2007, and June 30, 2012 (date of add/switch was the index date). The primary predictor was percentage weight change (PWC) between a weight measurement at index and a follow-up measurement 6 months later; PWC ranged from negative (weight loss) to positive (weight gain). Outcomes, measured in the 12-month period beginning at the time of follow-up weight measurement, included all-cause and diabetes-related health care costs and achievement of thresholds for A1c, blood pressure, and LDL-C. Multivariable models quantified the association between PWC (linear effect) and study outcomes. RESULTS: A total of 1,520 patients (mean age 55 years; 47% female) were included, with 780 patients (mean age 53 years; 51% female) in the subgroup sample. Mean (SD) index weight and PWC were 224.6 (52.8) lbs and +0.2% (4.7%) in the primary analysis, and 241.3 (47.3) lbs and -0.2% (4.6%) in the subgroup sample. In adjusted analyses, decreasing PWC was associated with decreasing diabetes-specific pharmacy costs (P < 0.001) in the primary analysis sample and with decreasing all-cause pharmacy costs (P = 0.018), diabetes-specific total costs (P = 0.039), diabetes-specific medical costs (P = 0.002), and diabetes-specific pharmacy costs (P < 0.001) in the subgroup sample. PWC was not associated with all-cause total health care costs or all-cause medical costs in either sample. In adjusted analyses, decreasing PWC was also associated with increasing odds of attaining the A1c goals of < 6.5% (P < 0.001) and < 7.0% (P < 0.001) in the primary analysis sample and increasing odds of attaining the A1c goals of < 6.5% (P < 0.001), < 7.0% (P < 0.001), and < 8.0% (P = 0.010) in the subgroup sample. PWC was not associated with any of the other clinical measures in either of the study samples. CONCLUSIONS: This real-world study suggests that among patients with T2DM, weight loss over a short-term (6-month) period is associated with positive impact on attainment of A1c goals and decreased diabetes-specific pharmacy costs over the subsequent 12 months. In the subset of patients who were obese and had no previus CVD, weight loss over the 6-month period was also associated with decreased all-cause pharmacy costs, diabetes-specific medical costs, and diabetes-specific total health care costs. Future research is warranted to examine whether these associations change over longer-term periods of follow-up. DISCLOSURES: This study was sponsored by AstraZeneca and Bristol-Myers Squibb. Truven Health Analytics received funding from Bristol-Myers Squibb and AstraZeneca to conduct this study. Mukherjee is an employee of Bristol-Myers Squibb. Bell and Sternhufvud are employees of AstraZeneca. Johnston, Stott-Miller, and McMorrow are employees of Truven Health Analytics. Nancy Smith is a consultant to Bristol-Myers Squibb and is employed by GreenKey Resources. Study concept was created by Mukherjee, Sternhufvud, Bell, and Johnston. Stott-Miller and McMorrow took the lead in data collection, along with Johnston, with data interpretation performed by Mukherjee, Sternhufvud, Smith, Stott-Miller, and Johnston. The manuscript was written by Mukherjee, Johnston, and Stott-Miller, along with Sternhufvud and Smith, and revised by Mukherjee, Smith, and Johnston, along with Sternhufvud and Stott-Miller.

Cardiovascular Risk Factor Targets and Cardiovascular Disease Event Risk in Diabetes: A Pooling Project of the Atherosclerosis Risk in Communities Study, Multi-Ethnic Study of Atherosclerosis, and Jackson Heart Study.

OBJECTIVE: Controlling cardiovascular disease (CVD) risk factors in diabetes mellitus (DM) reduces the number of CVD events, but the effects of multifactorial risk factor control are not well quantified. We examined whether being at targets for blood pressure (BP), LDL cholesterol (LDL-C), and glycated hemoglobin (HbA1c) together are associated with lower risks for CVD events in U.S. adults with DM. RESEARCH DESIGN AND METHODS: We studied 2,018 adults, 28-86 years of age with DM but without known CVD, from the Atherosclerosis Risk in Communities (ARIC) study, Multi-Ethnic Study of Atherosclerosis (MESA), and Jackson Heart Study (JHS). Cox regression examined coronary heart disease (CHD) and CVD events over a mean 11-year follow-up in those individuals at BP, LDL-C, and HbA1c target levels, and by the number of controlled risk factors. RESULTS: Of 2,018 DM subjects (43% male, 55% African American), 41.8%, 32.1%, and 41.9% were at target levels for BP, LDL-C, and HbA1c, respectively; 41.1%, 26.5%, and 7.2% were at target levels for any one, two, or all three factors, respectively. Being at BP, LDL-C, or HbA1c target levels related to 17%, 33%, and 37% lower CVD risks and 17%, 41%, and 36% lower CHD risks, respectively (P < 0.05 to P < 0.0001, except for BP in CHD risk); those subjects with one, two, or all three risk factors at target levels (vs. none) had incrementally lower adjusted risks of CVD events of 36%, 52%, and 62%, respectively, and incrementally lower adjusted risks of CHD events of 41%, 56%, and 60%, respectively (P < 0.001 to P < 0.0001). Propensity score adjustment showed similar findings. CONCLUSIONS: Optimal levels of BP, LDL-C, and HbA1c occurring together in individuals with DM are uncommon, but are associated with substantially lower risk of CHD and CVD.

Impact of dyslipidemia associated with Highly Active Antiretroviral Therapy (HAART) on cardiovascular risk and life expectancy.

We investigated the effect of dyslipidemia associated with highly active antiretroviral therapy on cardiovascular risk and life expectancy among patients who had the human immunodeficiency virus. Dyslipidemia estimates were based on results from a phase 2 randomized trial that compared lipid changes after 32 weeks of therapy with atazanavir with those with nelfinavir (each in combination with stavudine and lamivudine). The resultant increased coronary risk was estimated using Framingham risk equations, and change in life expectancy (after adjustment for mortality due to human immunodeficiency virus) was based on the cardiovascular life expectancy model, which is based on a published Markov's model. Levels of total cholesterol and low-density lipoprotein cholesterol increased significantly more among patients who used nelfinavir (+24% and +28%) than among those who used atazanavir (+4% and +1%). This dyslipidemia increased the risk of coronary disease by 50% over 10 years. The absence of dyslipidemia was estimated to preserve life expectancy 0.15 to 1.53 additional years depending on a patient's age, gender, and other risk factors. There are increasing reports of dyslipidemia and cardiovascular events associated with highly active antiretroviral therapy. Significant increases in blood lipid levels observed with some protease inhibitors are associated with an increase in calculated 10-year coronary risk. Accordingly, minimizing dyslipidemia associated with highly active antiretroviral therapy may preserve life expectancy among adults who have the human immunodeficiency virus.

Changes in lipids over twelve months after initiating protease inhibitor therapy among persons treated for HIV/AIDS.

BACKGROUND: Protease inhibitors are known to alter the lipid profiles in subjects treated for HIV/AIDS. However, the magnitude of this effect on plasma lipoproteins and lipids has not been adequately quantified. OBJECTIVE: To estimate the changes in plasma lipoproteins and triglycerides occurring within 12 months of initiating PI-based antiretroviral therapy among HIV/AIDS afflicted subjects. METHODS: We included all antiretroviral naive HIV-infected persons treated at St-Paul's Hospital, British Columbia, Canada, who initiated therapy with protease inhibitor antiretroviral (ARV) drugs between August 1996 and January 2002 and who had at least one plasma lipid measurement. Longitudinal associations between medication use and plasma lipids were estimated using mixed effects models that accounted for repeated measures on the same subjects and were adjusted for age, sex, time dependent CD4+ T-cell count, and time dependent cumulative use of non-nucleoside reverse transcriptase inhibitors and adherence. The cumulative number of prescriptions filled for PIs was considered time dependent. We estimated the changes in the 12 months following any initiation of a PI based regimen. RESULTS: A total of 679 eligible subjects were dispensed nucleoside analogues and PI at the initiation of therapy. Over a median 47 months of follow-up (interquartile range (IQR): 29-62), subjects had a median of 3 (IQR: 1-6) blood lipid measurements. Twelve months after treatment initiation of PI use, there was an estimated 20% (95% confidence interval: 17% - 24%) increase in total cholesterol and 22% (12% - 33%) increase in triglycerides. CONCLUSIONS: Twelve months after treatment initiation with PIs, statistically significant increases in total cholesterol and triglycerides levels were observed in HIV-infected patients under conditions of standard treatment. Our results contribute to the growing body of evidence implicating PIs in the development of blood lipid abnormalities. In conjunction with the predominance or men, high rates of smoking, and aging of the treated HIV-positive population, elevated lipoproteins and triglycerides may mean that patients such as these are at elevated risk for cardiovascular events in the future.

Do patient or provider characteristics impact management of diabetes?

OBJECTIVES: Patients with diabetes often exceed desired glycated hemoglobin (A1C) levels for months prior to medication adjustments. To determine if provider and patient characteristics predict glycemic control and treatment intensification. STUDY DESIGN: Observational retrospective cohort study using electronic medical record data. METHODS: We studied 149 Kaiser Permanente Northwest primary care providers of 14,430 patients with diabetes, of whom 5823 (40.4%) were in optimal control (all A1Cs < 7%) and 2446 (17%) were in poor control (at least 1 A1C > 9%) in 2011. We also identified a subset of 107 primary care providers of 912 patients with diabetes who were initially in optimal control (A1C < 7%) but had a subsequent A1C > 7.5% from 2010 to 2011. We used hierarchical linear modeling to assess both patient and provider characteristics as predictors of glycemic control and treatment intensification after incident hyperglycemia. RESULTS: Patient characteristics associated with optimal control included older age, lower baseline A1C, shorter diabetes duration, and not using insulin (P < .001 for all). The inverse of these variables predicted poor control. No provider characteristics were associated with glycemic control or intensification. Older patients with a greater change in A1C were more likely to have therapy intensified after loss of glycemic control. CONCLUSIONS: Patient, but not provider characteristics, predicted glycemic control and therapy intensification. Improving systems of care such as disease management services may be a better use of resources than focusing on individual providers.

Association between hypoglycemia and fall-related events in type 2 diabetes mellitus: analysis of a U.S. commercial database.

BACKGROUND: Hypoglycemia is a major barrier to achieving optimal glycemic control and managing diabetes successfully in patients with diabetes. Falls are the most significant consequences caused by hypoglycemia episodes. Both hypoglycemia and falls lead to substantial economic burden on the health care system in the United States. OBJECTIVE: To examine the association of hypoglycemia with fall-related outcomes in elderly patients with type 2 diabetes mellitus (T2DM). METHODS: Records were obtained for T2DM patients (N = 1,147,937) from January 1, 2008, to December 31, 2011. The nonhypoglycemia patients were randomly matched 1:1 by age and gender to the hypoglycemia patients. Fall-related events (composite of fall-related outcomes) were defined using ICD-9-CM codes. Conditional logistic regression models were used to compare the fall-related events within 30 days, 90 days, 180 days, and 365 days between the 2 cohorts. RESULTS: A total of 21,613 hypoglycemia patients were matched with 21,613 nonhypoglycemic patients. Patients with hypoglycemia had higher fall-related events within 30 days, 90 days, 180 days, and 365 days (P less than 0.001 for all frequency differences). Conditional logistic regression analyses showed an elevated risk for fall-related events over 365 days (aOR = 1.95, 95% CI = 1.70-2.24). Subgroup analysis showed elevated risk for patients aged less than 75 years and ≥ 75 years. Elevated risks were also seen for individual fall-related outcomes of fractures, head injuries, long-term care placement, and hospital admissions. CONCLUSIONS: The risk of fall-related events over 365 days increased 2-fold among elderly patients with diabetes who experienced hypoglycemia.

Provider beliefs about diabetes treatment have little impact on glycemic control of their patients with diabetes.

OBJECTIVE: To improve the health of people with diabetes, it is essential to identify why patients experience extended periods of poor glycemic control before therapeutic intensification. RESEARCH DESIGN AND METHODS: We surveyed 252 primary care providers at Kaiser Permanente Northwest to determine their beliefs about the glycemic goals of their patients, treatment intensification behavior, and barriers to achieving optimal glycemic control. We linked the responses of 149 providers to the health records of their 18 346 patients with diabetes. RESULTS: Patient glycemic levels were not related to either individualized glycemic goals or provider intensification behavior. Providers' beliefs about diabetic treatment and glycated hemoglobin (HbA1c) goals were poorly associated with patient HbA1c levels. Providers identified patients' resistance to lifestyle behaviors and taking insulin, lack of medication adherence, and psychosocial issues as the main barriers to optimal glycemic control. Lack of time to care for complex patients was also a barrier. Providers who agreed that "current research did not support A1C levels <7%" were less likely to have patients with HbA1c levels <7% (OR=0.87, 95% CI 0.78 to 0.97) and patients of providers who disagreed that "some patients will have an A1C >9% no matter what I do" were 16% more likely to have patients with HbA1c <7% (1.16, 1.03 to 1.30) compared with providers who were neutral about those statements. CONCLUSIONS: Given the consistency of HbA1c levels across providers despite differences in beliefs and intensification behaviors, these barriers may be best addressed by instituting changes at the system level (ie, instituting institutional glycemic targets or outreach for dysglycemia) rather than targeting practice patterns of individual providers.