Successful expanded clinic network collaboration and patient tracing for retention in HIV care.

BACKGROUND: There are more than 7,800 people living with human immunodeficiency virus (HIV) in Victoria, Australia. Crucial in maximising the individual and population level benefits from antiretroviral therapy (ART) is understanding how to achieve patient retention in care and the factors that drive it. This study was an expansion of a 2015 assessment of HIV-care retention in Victoria, which sought out to determine whether the inclusion of a broader range of HIV-healthcare sites would yield more accurate estimates of retention in HIV-care. We aimed to improve our understanding of HIV-care retention in Victoria, Australia, identify people living with HIV (PLHIV) with unknown outcomes, and attempt to re-engage PLHIV in care. METHODS: A network of 15 HIV-care sites was established in Victoria, Australia across diverse care settings which ranged from low-caseload rural sites to high-caseload metropolitan GP clinics and hospitals. Individuals who had an HIV viral load (VL) performed in both calendar years of 2016 and 2017 were classified as retained in care. Individuals with a VL test in 2016 but not in 2017 were considered to potentially have unknown outcomes as they may have been receiving care elsewhere, have disengaged from care or died. For this group, an intervention of cross-referencing partially de-identified data between healthcare sites, and contact tracing individuals who still had unknown outcomes was performed. RESULTS: For 5223 individuals considered to be retained in care across 15 healthcare sites in the study period, 49 had unconfirmed transfers of care to an alternative provider and 79 had unknown outcomes. After the intervention, the number of unconfirmed care transfers was reduced to 17 and unknown outcomes reduced to 51. These changes were largely attributed to people being reclassified as confirmed transfers of care. Retention in care estimates that did not include the patient outcome of confirmed transfer of care ranged from 76.2 to 95.8% and did not alter with the intervention. However, retention in care estimates which considered confirmed transfers and those that re-entered care at a new site as retained in care significantly increased across five of the sites with estimates ranging from 80.9 to 98.3% pre-intervention to 83.3-100% post-intervention. Individuals whose outcomes remained unknown post-intervention were more often men who have sex with men (MSM) when compared to other categories (person who injects drugs (PWID), combined PWID/MSM, men who identify as heterosexual or unknown) (74.5% vs. 53.5%, [p = 0.06]) and receiving ART at their last HIV-care visit (84.3% vs. 67.8% [p = 0.09]). CONCLUSION: This study confirmed high retention in HIV-care and low numbers of people disengaged from HIV-care in Victoria. This was demonstrated across a larger number of sites with varying models of care than a prior assessment in 2015. These data align with national and state targets aiming for 95% of PLHIV retained in HIV-care.

Using Literature Review and Structured Hybrid Electronic/ Manual Mortality Review to Identify System-Level Improvement Opportunities to Reduce Colorectal Cancer Mortality.

BACKGROUND: Despite colorectal cancer (CRC) screening and survival rates exceeding national averages in the United States, Kaiser Permanente Southern California (KPSC) aimed to identify system-level improvement opportunities to further reduce mortality from CRC. METHODS: To examine modifiable factors contributing to CRC mortality, a structured hybrid electronic/manual mor- tality review was used to examine 50 randomly selected cases among 524 individuals aged 25-75 years diagnosed with stage II, III, or IV CRC after July 2008 who subsequently died. Physicians conducted chart reviews using a standardized data extraction tool based on evidence-based best practices. RESULTS: Eighty-six percent (43) of the 50 decedents were initially diagnosed with stage III or IV CRC; two cases of appendiceal cancer were excluded. Thirty-one percent (15) of the remaining 48 cases presented with no history of screening; 15% (7) had documented iron deficiency anemia and abdominal pain or rectal bleeding; and 6% (3) had no follow-up colonoscopy after positive screening. Eleven (52%) of the 21 patients with initial stage II-III CRC received appropriate surveillance after curative surgery; 57% (12) developed metastases. Adjuvant chemotherapy was offered to 88% (14/16) of patients with stage III (node-positive) CRC; chemotherapy initiation was delayed in 6 patients. Missed opportunities for surgical oncology evaluation occurred among 61% (11/18) of patients with liver metastases at diagnosis. Failure to report clinically significant features on pathology occurred in 2 patients; they received appropriate treatment for other reasons. CONCLUSIONS: Improvement opportunities existed at multiple stages of care, including screening, evaluation of symp toms, timeliness of care, use of adjuvant chemotherapy, and surgical oncology practices.

E-Autopsy: Using Structured Hybrid Manual/Electronic Mortality Reviews to Identify Quality Improvement Opportunities.

BACKGROUND: Mortality reviews are a foundation of inpatient quality improvement (QI), but low levels of harm among a random or sequential sample may not yield actionable improvement opportunities. To increase the efficiency of mortality reviews at identifying QI opportunities, Kaiser Permanente Southern California (KPSC) developed a condition-specific hybrid electronic/manual chart review called the "e-autopsy." METHODS: KPSC hospital deaths are filtered electronically by predetermined criteria. Teams consisting of a registered nurse and physician trained in QI at each hospital then manually review selected charts using a structured data-extraction tool to identify gaps in provision of evidence-based care. Results are aggregated and studied to identify improvement opportunities. RESULTS: E-autopsy has identified opportunities amenable to system improvements. The first e-autopsy of all KPSC members who died with a ruptured abdominal aortic aneurysm (AAA) in a KPSC hospital indicated that many patients meeting criteria had not been screened for AAA. This study showed KPSC leaders the value of point-of-care electronic decision support to increase evidence-based AAA screening and of a tracking system for patients with positive results. Screening among high-risk patients in 2012 increased by more than 8,000 individuals, compared with the annual average during the previous four years. E-autopsies have also been conducted of patients who died with aspiration pneumonia; after unplanned transfers to the ICU; and after diagnosis of colon cancer. CONCLUSION: E-autopsy reveals actionable opportunities to improve care systems, complementing other QI activities. This hybrid electronic/manual process can be applied to a wide variety of patient conditions and settings.

Assessing antibiotic prescribing in nurse practitioners: Applied cognitive task analysis.

Background: Prescribing antibiotics is a demanding and complex task where decision-making skills are of critical importance to minimize the risk of antimicrobial resistance. Despite its importance, little is known about the decision-making skills and cognitive strategies new Nurse Practitioners (NPs) use when prescribing antibiotics. Objective: To identify the cognitive demands of antibiotic prescribing complexity and to explore the cognitive strategies that new NPs in New Zealand use when prescribing antibiotics. Design: A qualitative approach using Applied Cognitive Task Analysis (ACTA) methodology. Participants: A purposive sample was recruited consisting of five NPs who had been registered within the last five years and were prescribing antibiotics as part of their scope of practice. Methods: In-depth face-to-face interviews consisting of a task diagram interview and a knowledge audit were conducted and analyzed following the ACTA protocol. Results: Four cognitive elements were identified from the data which showed the cognitive demands of prescribing antibiotics, and the cues and strategies NPs use for safe practice. These were: 1 prescribing in the face of uncertainty (complex patients and diagnostic uncertainty); 2 making clinical decisions with insufficient/poor guidance (lack of guidelines, conflicting information); 3 producing an individualized treatment plan in view of clinical and non-clinical patient factors (patient demand/expectation, inadequate patient education, risks versus benefits of antibiotic treatment); 4 ensuring treatment efficacy and continuity of care (ineffective treatment, patient care follow up). Conclusion: The ACTA framework has given insight into the current antibiotic prescribing practice of new NPs, identifying areas where professional development courses and treatment resources can be targeted to support antibiotic prescribing. NPs are likely to benefit from resources that are freely available and reflect national or local antimicrobial data. Further work is also warranted to determine whether targeted education resources and clinical pathways will help with diagnostic uncertainty, and how this could be embedded into existing curricula.

Saving lives by studying deaths: using standardized mortality reviews to improve inpatient safety.

BACKGROUND: Despite extensive ongoing quality improvement (QI) efforts, substantial variation existed in hospital standardized mortality ratios (HSMRs) across hospitals in Kaiser Permanente, an integrated health care delivery system. In 2008, Kaiser Permanente developed an efficient and effective method for investigating hospital-level mortality to identify patterns of potential harm. METHODS: The standardized multidisciplinary mortality review process incorporates the Institute for Healthcare Improvement Global Trigger Tools and 2x2 Mortality Matrix, elements of the United Kingdom's National Health Service (NHS) 3x2 matrix, and two groups of questions to "deep dive" into issues of preventable harm and the use of appropriate care settings. Between April 2008 and November 2009, multidisciplinary teams conducted mortality reviews of the 50 most recent inpatient deaths at 11 hospitals in Kaiser Permanente's Southern California region. An electronic chart abstraction tool facilitated rapid analysis of data. De-identified patient narratives portrayed trends and issues from a patient-centered perspective. RESULTS: Ten categories of harm in inpatient deaths were identified, including failure to rescue, to plan, and to communicate; harm that occurred before hospitalization; medication-related events; surgical or procedural-related harm; hospital-acquired infection and pressure ulcers; falls; and "other." Senior leaders at the study hospitals identified 36 quality improvement goals in response. CONCLUSIONS: The mortality review process, which included quantitative data from structured chart abstraction and qualitative description of harm events, efficiently gathered important information on patterns of mortality that was not otherwise available, enabling hospitals to identify trends and focus improvement efforts.

Cost-effectiveness of aliskiren in type 2 diabetes, hypertension, and albuminuria.

The Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) trial demonstrated that adding aliskiren, an oral direct renin inhibitor, at a dosage of 300 mg/d to the highest approved dosage of losartan and optimal antihypertensive therapy reduces albuminuria over 6 mo among patients with type 2 diabetes, hypertension, and albuminuria. The cost-effectiveness of this therapy, however, is unknown. Here, we used a Markov model to project progression to ESRD, life years, quality-adjusted life years, and lifetime costs for aliskiren plus losartan versus losartan. We used data from the AVOID study and the Irbesartan in Diabetic Nephropathy Trial (IDNT) to estimate probabilities of progression of renal disease. We estimated probabilities of mortality for ESRD and other comorbidities using data from the US Renal Data System, US Vital Statistics, and published studies. We based pharmacy costs on wholesale acquisition costs and based costs of ESRD and transplantation on data from the US Renal Data System. We found that adding aliskiren to losartan increased time free of ESRD, life expectancy, and quality-adjusted life expectancy by 0.1772, 0.1021, and 0.0967 yr, respectively. Total expected lifetime health care costs increased by $2952, reflecting the higher pharmacy costs of aliskiren and losartan ($7769), which were partially offset by savings in costs of ESRD ($4860). We estimated the cost-effectiveness of aliskiren to be $30,500 per quality-adjusted life year gained. In conclusion, adding aliskiren to losartan and optimal therapy in patients with type 2 diabetes, hypertension, and albuminuria may be cost-effective from a US health care system perspective.

What is an estimand & how does it relate to quantifying the effect of treatment on patient-reported quality of life outcomes in clinical trials?

BACKGROUND: Published in 2019, a new addendum to the ICH E9 guideline presents the estimand framework as a systematic approach to ensure alignment among clinical trial objectives, trial execution/conduct, statistical analyses, and interpretation of results. The use of the estimand framework for describing clinical trial objectives has yet to be extensively considered in the context of patient-reported outcomes (PROs). We discuss the application of the estimand framework to PRO objectives when designing clinical trials in the future, with a focus on PRO outcomes in oncology trial settings as our example. MAIN: We describe the components of an estimand and take a naïve PRO trial objective to illustrate how to apply attributes described in the estimand framework to inform construction of a detailed clinical trial objective and its related estimand. We discuss identifying potential post-randomization events that alter the interpretation of the endpoint or render its observation impossible (also defined as intercurrent events) in the context of PRO endpoints, and the implications of how to handle intercurrent events in the construction of the PRO objective. Using a simple objective statement, "What is the effect of treatment X on patient's quality of life?", we build up an example estimand statement and also use a previously published phase III oncology clinical trial to illustrate how an estimand for a PRO objective could have been written to align to the estimate framework. CONCLUSION: The use of the estimand framework, as described in the new ICH E9 (R1) addendum guideline will become a key common framework for developing clinical trial objectives for evaluating effects of treatment. In the context of considering PROs, the framework provides an opportunity to more precisely specify and build the rationale for patient-focused objectives. This will help to ensure that clinical trials used for registration are designed and analysed appropriately, enabling all stakeholders to accurately interpret conclusions about the treatment effects for patient-focused outcomes.

Predictors of compliance with antihypertensive therapy in a high-risk medicaid population.

OBJECTIVE: To identify predictors of compliance with antihypertensive combination therapy in a Medicaid population. METHODS: Retrospective medical and pharmacy claims data for Maryland Medicaid patients receiving angiotensin converting enzyme inhibitors (ACEls)/hydrochlorothiazides (HCTZs) or ACEl/calcium channel blockers as fixed-dose combinations or separate agents during the period of January 1, 2002 to December 31, 2004, were analyzed. INCLUSION: Continuously enrolled patients 18 years and older and at least one year of follow-up. Exclusion: Use of fixed-dose combination antihypertensives between January 1, 2002 and June 30, 2002 (to identify incident cohort). Compliance was defined as medication possession ratio greater than or equal to 80%. Multivariate logistic regression was used to predict compliance as a function of age, gender, race, comorbidities (Charlson Comorbidity Index [CCI]), and use of either fixed-dose combination or separate agents. RESULTS: There were 568 patients, 63.73% female, 68.83% African American, median age 52 years, 35.56% on fixed-dose combinations, 72.89% started on ACEI/HCTZ, and 24.82% complied with therapy. Patients younger than 40 years (OR, 0.38; p = .01; 95% CI, 0.18-0.81) and African American (OR, 0.45; p = .0004; 95% CI, 0.29-0.70) were less likely to be compliant than patients older than 60 years and Caucasian, respectively, Patients with a CCI of 1 (OR, 2.11; p = .05; 95% CI, 1.01-4.40) and those on fixed-dose combinations (OR, 1.60; p = .02, 95% CI, 1.06-2.40) were more likely to be compliant than those with higher CCIs and on separate agents, respectively. CONCLUSION: Age, race, comorbidities, and simplified antihypertensive regimens were significant predictors of compliance. Higher compliance rates may enhance cardiovascular disease management outcomes.

Characteristics of Orofacial Clefting in Hawai'i.

Orofacial clefts are birth defects that require a multi-disciplinary approach for repair and ongoing management as there are often concomitant chronic health issues. Orofacial clefts can occur as an isolated finding, in combination with other anomalies, or as part of a genetic syndrome. When occurring as part of a genetic syndrome, the complexity of management increases and has lifelong implications for these individuals, their families, and their health care providers. Understanding factors related to the occurrence of syndromic orofacial clefting is important for birth defect research and for health care needs assessment and planning. Many research groups have addressed these issues by studying different populations and focusing on different questions. This study was a retrospective chart review of children with orofacial clefts cared for at a pediatric tertiary care center in Hawai'i to evaluate the proportion of isolated and syndromic clefts in the unique population of Hawai'i. The prevalence of syndromic and isolated clefts were then correlated with ethnicity and compared to the prevalence in other studies. Our goal was to increase knowledge about orofacial clefting in the population of Hawai'i. The proportion of isolated orofacial clefting in a population of patients with orofacial clefting cared for at a craniofacial clinic is similar to birth defect registry data for the Hawaiian Islands (59% vs 58%). Pacific Islanders in our study and prior study have a lower proportion of isolated clefts, suggesting that there are more craniofacial patients with syndromic and complex needs in this population. Further study is needed to clarify the etiologic factors.

Host and microbiota factors that control Klebsiella pneumoniae mucosal colonization in mice.

Klebsiella pneumoniae is both an opportunistic pathogen and a commensal organism. We have previously reported that K. pneumoniae strain IA565 (KpIA565) is non-pathogenic in a murine model of acute pneumonia. In this study, KpIA565 was inoculated into wild-type mice and found to stably colonize and persist in the nasal cavity and gastrointestinal tract of mice for up to 3weeks post-inoculation. Intranasal inoculation of wild-type or germ-free mice with KpIA565 resulted in similar bacterial levels in the nasal cavity, suggesting KpIA565 nasal colonization is independent of normal nasal microbiota. In contrast, KpIA565 gastrointestinal tract colonization was significantly higher in germ-free mice than in wild-type mice, indicating that members of the endogenous microbiota regulate KpIA565 colonization. In the presence of non-specific dextran sodium sulfate-induced inflammation, KpIA565 gastrointestinal tract colonization was significantly higher when compared to non-DSS treated mice. Interestingly, KpIA565 colonization was unaffected by Citrobacter rodentium-induced gastrointestinal tract inflammation. However, gastrointestinal tract colonization with K. pneumoniae strain IA565 had no impact on the inflammatory histopathology in either colitis model. This study is the first to identify and describe mechanisms influencing the growth and behavior of a murine commensal strain of K. pneumoniae.

Sex differences in ambulatory visits for chronic obstructive pulmonary disease, based on the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey from 1995 to 2004.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a rapidly growing public health problem in the United States. It is unclear whether men and women differ in their utilization of ambulatory care or medications prescribed for COPD. OBJECTIVE: To evaluate sex-related trends in physician-office and out-patient department COPD visits from 1995 through 2004. METHODS: We pooled data from the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) to derive national estimates of out-patient ambulatory COPD visits. For trend analysis we stratified the data into 2-year periods and by sex. The main variables of interest were the number of out-patient visits for COPD, patient characteristics, comorbidities, and medications prescribed. RESULTS: From 1995 to 2004, COPD-related out-patient visits increased among women and men; oral corticosteroids and short-acting bronchodilators were the most commonly prescribed drugs for both women and men; and prescriptions for inhaled corticosteroid decreased in both women (from 20% to 11%) and men (from 20 to 17%). In 2004, women surpassed men in out-patient COPD visits. CONCLUSIONS: COPD visits increased among both sexes, but the upward trend in COPD visits among women indicates that COPD is no longer a male-dominated disease. Providers should be aware of this shift in patient demographics and the differences between the sexes in COPD management.

Medication Utilization Patterns and Hypertension-Related Expenditures among Patients Who Were Switched from Fixed-Dose To Free-Combination Antihypertensive Therapy.

Using a retrospective cohort study of medical and pharmacy claims data, we evaluated medication compliance, persistence, and hypertension-related expenditures among patients who were switched from fixed-dose combination (FDC) to free-combination (FC) antihypertensive therapy. An example of a fixed-dose combination product for hypertension would be a valsartan/HCT tablet, and a free-combination product would be a valsartan tablet plus a diuretic tablet.The 7,224 patients identified from January 2003 to December 2005 were matched, in a 1:1 ratio, by propensity scores to controls who remained on their FC antihypertensive medications. Compliance, defined as a medication-possession ratio, was measured over 12 months. Persistence was measured as the percentage of patients who did not experience a lapse in therapy of more than 30 days since their last prescription refill.The patients continuing with FDC therapy had better persistence (42.5% higher; P < 0.002) and compliance (22.1% higher; P < 0.001), compared with patients who were switched to FC therapy. The 22.1% higher compliance rate for patients continuing the FDC regimen was associated with significantly lower expenditures for hypertension-related health care (P < 0.001) and an estimated 5% reduction in hypertension-related expenditures.

Defective innate antibacterial host responses during murine Klebsiella pneumoniae bacteremia: tumor necrosis factor (TNF) receptor 1 deficiency versus therapy with anti-TNF-alpha.

Klebsiella pneumoniae is a leading cause of pneumonia due to gram-negative bacteria. A significant clinical complication of pulmonary infection with K. pneumoniae is peripheral blood dissemination, which results in a systemic infection coincident with the localized pulmonary infection. This study describes the critical importance of tumor necrosis factor (TNF) receptor 1 (TNFR1)-mediated signaling during K. pneumoniae bacteremia. TNFR1-deficient mice displayed a significantly increased mortality rate after intravenous inoculation. Unexpectedly, this increased mortality occurred in the absence of either increased bacterial burden or increased liver injury. However, excessive production of proinflammatory cytokines, including TNF-alpha , was observed in TNFR1-deficient mice, compared with that observed in infected C57BL/6 mice, which suggests that production was dysregulated in the absence of TNFR1 signaling. In contrast, other experiments examined the effect of immunotherapy with anti-TNF-alpha during K. pneumoniae bacteremia. Administration of a neutralizing anti-TNF-alpha antibody completely ablated K. pneumoniae-induced liver injury. This reduction in liver injury failed to translate into an improved survival rate, because mice died of the infection as late as 10 days after infection. Bacterial clearance after neutralization of TNF-alpha was significantly impaired at later time points during infection. Diminished production of liver-associated cytokines and chemokines correlated with impaired bacterial clearance, which suggests that antibacterial immune responses were dampened. These data indicate that the antibacterial host response is dysregulated in mice lacking TNFR1 or TNF-alpha bioactivity.

Anti-tumor necrosis factor-alpha therapy during murine Klebsiella pneumoniae bacteremia: increased mortality in the absence of liver injury.

Klebsiella pneumoniae is a leading cause of gram-negative bacterial pneumonia, often resulting in bacteremia concurrent with the localized pulmonary infection. The beneficial role of tumor necrosis factor (TNF)-alpha during pulmonary infection has been well documented; however, consequences of TNF-alpha production during systemic bacterial infection are controversial. A murine model of K. pneumoniae was developed to address this important issue. Liver-associated TNF-alpha mRNA was induced within 30 min after intravenous bacterial inoculation and remained elevated through 6 h before returning to near-baseline at 24 h postinfection. Intravenous K. pneumoniae infection induced liver cellular injury that was completely ablated when mice were pretreated with a neutralizing anti-TNF-alpha antibody. Interestingly, this reduction in liver injury failed to translate into improved survival. Mice receiving anti-TNF-alpha continued to succumb to the infection even out to day 10 postinfection. Bacterial clearance after TNF-alpha neutralization was significantly impaired at later time points during infection. Correlating with impaired bacterial clearance was diminished production of liver-associated MIP-2, MIP-1alpha, MCP-1, and interferon-gamma. Further evidence of diminished antibacterial immune responses was noted when the activational status of splenic natural killer cells in anti-TNF-alpha-treated mice was examined 24 h postinfection. Natural killer cells displayed decreased CD69 expression. Combined, these data indicate that the beneficial effects of TNF-alpha during systemic K. pneumoniae infection outweigh the detrimental effects of TNF-alpha-mediated hepatocyte cellular injury. Anti-TNF-alpha therapy, although preventing liver injury during blood-borne bacterial infection, results in a dampened anti-bacterial host response, resulting in decreased bacterial clearance and overall survival.

Multicenter retrospective assessment of thiazolidinedione monotherapy and combination therapy in patients with type 2 diabetes: comparative subgroup analyses of glycemic control and blood lipid levels.

BACKGROUND: Thiazolidinediones (TZDs) have contributed to the management of patients with type 2 diabetes mellitus as unique insulin-sensitizing agents. When used as monotherapy or in combination therapy, these drugs not only reduce glycosylated hemoglobin (HbA(1c)) levels, but also effect changes in blood lipid concentrations and have the potential to ameliorate cardiovascular disease risk. Although drugs in the TZD class are perceived to be equivalent clinically, prospective and retrospective studies have demonstrated their ability to modify blood lipid levels. OBJECTIVE: We evaluated and compared the effects of pioglitazone and rosiglitazone monotherapy and combination therapy on blood lipid levels and HbA(1c) in patients with type 2 diabetes. METHODS: We conducted a multicenter retrospective chart review of 1115 records of patients with type 2 diabetes who received pioglitazone or rosiglitazone, alone or in combination with other antidiabetic agents, between August 1, 1999, and August 31, 2000. The review was conducted to evaluate pretreatment and posttreatment levels of triglyceride, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and HbA(1c). RESULTS: All observed demographic characteristics, comorbidities, and concomitant drug use were similar in both treatment cohorts. Of the patients who received pioglitazone, 83% also received >/=1 other antihyperglycemic agent and 59% received some form of antihyperlipidemic therapy. Among those who received rosiglitazone, 81% received concomitant antihyperglycemic medication and 60% received some form of antihyperlipidemic therapy. With pioglitazone, mean levels of serum triglyceride, total cholesterol, and LDL-C decreased and HDL-C increased in most patients, with or without concomitant antihyperglycemic medications; with rosiglitazone, with or without other antidiabetic agents, triglyceride and HDL-C levels decreased, whereas total cholesterol and LDL-C levels increased in most patients. Reductions in HbA(1c) levels and increases in body weight related to each study drug were comparable. CONCLUSIONS: This comparative assessment of pioglitazone and rosiglitazone, based on observational data, reveals that use of these TZDs with other antidiabetic agents was similar in 605 primary care practices in the United States. In both monotherapy and combination treatment regimens, pioglitazone was associated with greater beneficial effects on lipids than was rosiglitazone. Additional studies are needed to determine the long-term outcomes of TZD therapy with concomitant antihyperglycemic medications.

Effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with type 2 diabetes mellitus: a retrospective review of randomly selected medical records.

BACKGROUND: The antihyperglycemic effects of pioglitazone hydrochloride and rosiglitazone maleate are well documented. The results of clinical trials and observational studies have suggested, however, that there are individual differences in the effects of these drugs on blood lipid levels. OBJECTIVE: The present study evaluated the effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with type 2 diabetes mellitus. METHODS: This was a retrospective review of randomly selected medical records from 605 primary care practices in the United States in which adults with type 2 diabetes received pioglitazone or rosiglitazone between August 1, 1999, and August 31, 2000. The outcome measures were mean changes in serum concentrations of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glycosylated hemoglobin (HbA1c) values. RESULTS: Treatment with pioglitazone was associated with a reduction in mean TG of 55.17 mg/dL, a reduction in TC of 8.45 mg/dL, an increase in HDL-C of 2.65 mg/dL, and a reduction in LDL-C of 5.05 mg/dL. Treatment with rosiglitazone was associated with a reduction in mean TG of 13.34 mg/dL, an increase in TC of 4.81 mg/dL, a reduction in HDL-C of 0.12 mg/dL, and an increase in LDL-C of 3.56 mg/dL. With the exception of HDL-C, the differences in mean changes in lipid parameters between treatment groups were statistically significant (P < 0.001, pioglitazone vs rosiglitazone). Reductions in HbA1c were statistically equivalent between treatments (1.04% pioglitazone, 1.18% rosiglitazone). CONCLUSIONS: Treatment with pioglitazone was associated with greater beneficial effects on blood lipid levels than treatment with rosiglitazone, whereas glycemic control was equivalent between the 2 treatments.

Impact of adjunctive thiazolidinedione therapy on blood lipid levels and glycemic control in patients with type 2 diabetes.

OBJECTIVE: This study was undertaken to assess the effect of pioglitazone hydrochloride and rosiglitazone maleate on blood lipid levels and glycemic control when these drugs are used as adjunctive therapy in type 2 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes receiving metformin and/or sulfonylurea (n = 829) were evaluated in this national, multicenter, retrospective study. Medical records from 318 endocrinology practices in the USA were randomly selected and screened for study inclusion. Data related to patient demographics and laboratory data were extracted from medical records and analyzed for primary and secondary outcomes. MAIN OUTCOME MEASURES: The primary study outcome was the mean change in plasma rosiglitazone was associated with no significant triglyceride (TG) levels. Secondary outcome measures included mean changes in total cholesterol (TChol), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) concentrations and hemoglobin A1C levels. RESULTS: With pioglitazone, TG levels declined by a mean of 51.5 mg/dl (P < 0.001), HDL-C levels rose by 3.3mg/dl (P < 0.001), and no change was seen in LDL-C or TChol. Treatment with change in TG levels and a 1.5mg/dl mean increase in HDL-C (P < 0.001). Furthermore, rosiglitazone therapy was associated with an 8 mg/dl mean increase in TChol (P < 0.001), and a 5.8 mg/dl mean increase in LDL-C (P < 0.001). Hemoglobin A1C levels were significantly reduced by approximately 1% within thiazolidinedione (TZD) cohorts (P < 0.001), but were not significantly different between study groups (P = 0.257). CONCLUSIONS: Results from this study suggest that pioglitazone has a more favorable effect on lipid profiles of patients with type 2 diabetes compared with rosiglitazone. In particular, differences were observed in TG and LDL-C levels. Both TZDs were equivalent at reducing hemoglobin A1C levels. These differences in lipid effects may have an impact on cardiovascular outcomes. The full clinical importance of these lipid alterations must be further assessed in prospective trials.