Impact of Weight Change on Glycemic Control and Metabolic Parameters in T2D: A Retrospective US Study Based on Real-World Data.

INTRODUCTION: Weight loss has been identified as a key strategy for improving glycemic and metabolic outcomes in people with type 2 diabetes (T2D). However, the long-term, real-world impact of weight loss on these outcomes remains unclear. This study aimed to investigate (1) the association between weight loss and glycemic control, (2) association between weight loss and metabolic parameters, and (3) predictors of weight loss and how weight change trajectory varies based on index body mass index (BMI). METHODS: A retrospective, longitudinal cohort study using the linked IQVIA Ambulatory electronic medical records and PharMetrics® Plus databases was performed from January 1, 2010 through December 31, 2019 in adults with T2D. Participants were categorized into 1-year and 5-year follow-up cohorts based on their observed weight change over time. Longitudinal values for vital signs and laboratory parameters, including BMI, weight, glycated hemoglobin (HbA1c), and metabolic parameters (liver enzymes and cholesterol), were reported at index date and every 6 months post index date. Multivariable logistic regression analysis was used to evaluate the factors associated with weight loss. RESULTS: Of 1,493,964 people evaluated, 1,061,354 (71%) and 308,320 (20.6%) were classified into the 1-year and 5-year follow-up cohorts. Average HbA1c reductions of 1.2% and 0.5% were observed among people who lost ≥ 15% of index weight in the 1-year and 5-year follow-up cohorts, respectively. Higher weight loss percentages were associated with numerically greater improvements in metabolic parameters. The presence of bariatric surgery and higher index BMIs were identified as the strongest predictors of ≥ 15% and ≥ 10% weight loss in both follow-up cohorts. CONCLUSION: Results from this study suggest that modest and sustained weight loss can lead to clinically meaningful improvements in glycemic and metabolic parameters among people with T2D. These findings highlight the importance of weight management in managing T2D and preventing its associated complications.

Real-Life Anemia Management Among Patients with Non-Dialysis-Dependent Chronic Kidney Disease in Three European Countries.

Background: Anemia is prevalent among patients with chronic kidney disease (CKD), yet current evidence indicates that treatment may not adhere to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. We aimed to document the management of patients with non-dialysis-dependent (NDD)-CKD receiving erythropoiesis-stimulating agent (ESA) therapy in Europe. Methods: This retrospective, observational study extracted information from medical records in Germany, Spain, and the UK. Eligible patients were adults with NDD-CKD stages 3b-5 who initiated ESA therapy for anemia between January and December 2015. Anemia was defined as hemoglobin (Hb) <13.0 g/dL (males) or <12.0 g/dL (females). Data regarding ESA treatment, treatment response, concomitant iron therapy and blood transfusions were extracted up to 24 months post-ESA initiation, and data on CKD progression until abstraction date. Results: Eight hundred and forty-eight medical records were abstracted. Approximately 40% received no iron therapy prior to ESA initiation. At ESA initiation, mean ± standard deviation Hb level was 9.8 ± 1.0 g/dL. Most patients received darbepoetin alfa, and switching between ESAs was rare (8.5% of patients). Concomitant intravenous and oral iron therapy was prescribed for 36% and 42% of patients, respectively, during initial ESA therapy. Mean Hb levels reached the target level (10-12 g/dL) within 3-6 months of ESA initiation. Hb, transferrin saturation, and ferritin levels were infrequently monitored from 3 months post-ESA initiation. Rates of blood transfusion, dialysis, and diagnosis of end-stage renal disease were 16.4%, 19.3%, and 24.6%, respectively. Rates of kidney transplant and death were 4.8% and 8.8%, respectively. Conclusion: Among ESA-treated patients, ESA initiation was in accordance with KDIGO guidelines, but subsequent monitoring of Hb and iron deficiency were suboptimal.

Practice patterns and perspectives regarding treatment for symptoms of menopause: qualitative interviews with US health care providers.

OBJECTIVE: To document health care providers' views regarding treatments for symptoms associated with menopause and discussions with patients about symptoms and treatment decisions. Results informed development of a data collection form for a retrospective medical record review (reported separately). METHODS: Registered US gynecologists or primary care providers from all US regions were identified from local association directories and an in-house database and were invited to participate in a qualitative interview if they consulted with three or more patients per week presenting with menopausal symptoms. Participants provided demographic data, information about patients' symptoms, and health care provider and patient views on prescription and nonprescription therapies. Key concepts/themes from interviews were identified. RESULTS: Participating health care providers (10 gynecologists, 10 primary care providers) agreed there are effective treatment options for menopausal symptoms, particularly vasomotor symptoms and vaginal dryness and/or atrophy. Health care providers reported that treatment was generally dictated by symptoms that interfered with quality of life and/or daily activities, although patients often had symptoms for months before presentation. All health care providers said they prescribe hormone and/or nonhormone therapies for treatment of menopausal symptoms; half stated that they typically inquire about patients' nonprescription therapy use, and 45% recommend specific nonprescription therapies. The most commonly cited barriers to initiation of any therapy for menopausal symptoms were patient concerns about risks and financial considerations (ie, insurance or cost). CONCLUSIONS: US health care providers reported prescribing therapies for menopausal symptoms and noted that these therapies were perceived as generally effective; however, barriers to initiation of prescription therapy exist, and new treatment options are needed.

Treatment and resource utilization for menopausal symptoms in the United States: a retrospective review of real-world evidence from US electronic health records.

OBJECTIVE: The aim of this study was to generate real-world evidence documenting use of prescription and nonprescription therapies recorded by health care providers for women experiencing vasomotor symptoms (VMS) associated with menopause. METHODS: This noninterventional, retrospective, observational cohort study used data from US patient medical records. Participating health care providers were gynecologists, internal medicine/family physicians, or advanced practice providers who typically saw three or more women per week presenting with menopausal symptoms and could identify eligible medical records; providers were recruited from local medical association directories and from listings from previously conducted research. Eligible women presented January 2016 through December 2019, were 40 to 60 years of age, and reported experiencing bothersome hot flashes at least twice within 24 hours. RESULTS: A total of 283 health care providers provided data for 1,016 women. The most common symptoms at initial presentation were hot flashes (91.2%), sleep problems (49.9%), and vaginal dryness (47.0%). At least one therapy for menopausal symptoms was recorded for 883 women (86.9%), and 611 (60.1%) had documentation of prescription medication, most commonly hormone therapy (70.4%). Nearly 40% of women had no prescription medication documented, and approximately 13% had no therapy documented. Despite experiencing bothersome menopausal symptoms, approximately 50% delayed seeking care for more than 6 months. Women had a mean of 2.1 (SD, 2.0) office visits related to menopause from initial presentation to completion of review, and health care resource utilization did not vary by treatment status. Subgroup analyses indicated nominal differences in treatment use across ethnic groups and varying prescribing patterns for menopausal symptoms by practitioner type and US region. CONCLUSIONS: A high proportion of women with VMS remain untreated even when experiencing bothersome symptoms of menopause. Improved management of VMS is required to provide relief from the symptoms effectively and safely.

Staging Disease Severity Using the Alzheimer's Disease Composite Score (ADCOMS): A Retrospective Data Analysis.

INTRODUCTION: The Alzheimer's disease (AD) composite score (ADCOMS) has been shown to be a more sensitive measure of cognitive change in early AD (i.e., mild cognitive impairment [MCI] and mild AD) than commonly used measures. This study derived ADCOMS value ranges associated with different disease severity stages across the predementia and AD continuum. METHODS: Data from patients enrolled in the Alzheimer's Disease Neuroimaging Initiative were assessed at baseline and month 24. Data were randomly split into derivation and validation samples. Receiver-operating characteristic (ROC) curves of ADCOMS values were generated in the derivation sample to assess the sensitivity and specificity of ADCOMS cutoff values compared with existing disease severity cutoff scores using the Clinical Dementia Rating (CDR) global, CDR Sum of Boxes, Alzheimer's Disease Assessment Scale-Cognitive Subscale, and Mini-Mental State Examination. Optimal ADCOMS cutoff values for each disease stage were compared between the derivation and the validation samples using a χ2 test. The diagnostic accuracy of the derived ADCOMS cutoff values was then assessed. The analyses were repeated for the subset with positive amyloid ß confirmation (Aß +). RESULTS: The following ADCOMS value ranges for the total population and Aß + population were identified: < 0.29 indicative of normal cognition, 0.29 to < 0.45 indicative of MCI, 0.45-0.77 indicative of mild AD, and > 0.77 indicative of at least moderate AD. The reliability of these ADCOMS value ranges was supported by diagnostic accuracy tests and tests indicating no significant difference in the ROC curves between the derivation and validation samples. CONCLUSION: ADCOMS values ranges can be used to assess the severity of cognitive decline. The derived severity threshold score ranges for ADCOMS will enable its use as an endpoint in clinical trials assessing disease progression and clinical outcomes of disease-modifying therapies in persons with MCI or early AD, including patients with Aß + confirmation.

Correlation Between Change in Psoriasis Area and Severity Index and Dermatology Life Quality Index in Patients with Psoriasis: Pooled Analysis from Four Phase 3 Clinical Trials of Secukinumab.

INTRODUCTION: Patients with psoriasis (PsO) experience impaired health-related quality of life due to physical and psychosocial burdens. The objective of this study was to assess the correlation between change in Psoriasis Area and Severity Index (PASI) score and selected Dermatology Life Quality Index (DLQI) domain scores in patients with moderate-to-severe PsO and those with PsO and comorbid psoriatic arthritis (PsA). METHODS: This post hoc analysis of four phase 3 clinical trials included patients with moderate-to-severe PsO randomized to secukinumab 150/300 mg, etanercept, or placebo. Pairwise latent growth models were applied to assess the longitudinal correlation between change in PASI scores and changes in three DLQI domain scores (daily activities, leisure activities, and symptoms/feelings). The initial (baseline to week 12) and sustained (week > 12 to week 52) treatment exposures were analysed by population type (total, PsO only, and PsO with comorbid PsA) and treatment arm (secukinumab, etanercept, or placebo). RESULTS: Among the total population (N = 2401), PASI change was positively correlated with change in each assessed DLQI domain; correlations were weak to moderate over the initial treatment exposure period (ß range, 0.20-0.29; all P < 0.001) and moderate to strong over the sustained exposure period (ß range, 0.63-0.69; all P < 0.001). Similar trends were observed regardless of the presence of comorbid PsA. These relationships were confirmed among patients treated with secukinumab, etanercept, or placebo. CONCLUSIONS: Improvements in PASI scores were directly moderately related to improvements in DLQI domain scores from initiation of treatment and extended over time, regardless of presence of comorbid PsA or treatment received. CLINICAL TRIAL REGISTRATION: ERASURE (NCT01365455), FIXTURE (NCT01358578), FEATURE (NCT01555125), and JUNCTURE (NCT01636687).

The Dollar or Disease Burden: Caps on Healthcare Spending May Save Money, but at What "Cost" to Patients?

OBJECTIVES: Various strategies to address healthcare spending and medical costs continue to be debated and implemented in the United States. To date, these efforts have failed to adequately contain the growth of healthcare cost. An alternative strategy that has elicited rising interest among policymakers is budget caps. As budget caps become more prevalent, it is important to identify which features are needed to ensure success, both in terms of cost reduction and health improvement. METHODS: We explored the impacts of different features of budget caps by comparing hypothetical service level and global budget caps across 3 annual budget cap growth strategies over a 10-year timeframe in 2005-2015 for 8 of the most commonly occurring conditions in the United States. Health was assessed by a measure of disease burden (disability-adjusted life years). RESULTS: The results indicate that budget caps have the potential for creating savings but can also result in patient harm if not designed well. As a result of these findings, 5 principles were developed for designing budget caps and should guide the use of budget caps to address medical spending. CONCLUSIONS: As public discussion grows about the use of budget caps to constrain health spending, it is critical to recognize that the budget cap design and the resulting healthcare provider behavior will determine whether there is potential harm to public health. Budget cap design should consider variability at the condition level, including patient population, improvements in health, treatment costs, and the innovations available, to both create savings and maximize patient health. In assessing the impact of healthcare spending caps on costs and disease burden, we demonstrate that budget cap design determines potential harm to public health.

What's Been The Bang For The Buck? Cost-Effectiveness Of Health Care Spending Across Selected Conditions In The US.

The continued rise in health care spending has led to an intense debate among policy makers and other health care stakeholders on how to best manage increasing costs, leading to a focus on cost increases with little consideration of the associated change in outcomes. We identified the extent to which increased medical intervention spending on seven prevalent chronic conditions in the US over a twenty-year period has been a good investment. The results provide disease-level cost-effectiveness ratios for comparing changes in medical care spending to changes in health outcomes for patients diagnosed with one of the conditions. This study has two key findings: First, dollars spent on medical care can be a source of high value creation, and such investment should continue. Second, significant variability in value exists across diseases, which highlights the need for disease-specific spending approaches.

Assessing Changes in Chronic Spontaneous/Idiopathic Urticaria: Comparisons of Patient-Reported Outcomes Using Latent Growth Modeling.

INTRODUCTION: Assessing the consequences of chronic spontaneous/idiopathic urticaria (CSU) requires the evaluation of health-related quality of life (HRQoL) associated with the severity of CSU signs and symptoms. It is important to understand how signs, symptoms, and HRQoL change over time in CSU. Evidence is lacking on how closely changes in signs and symptoms of CSU are related to changes in HRQoL. The objective of this study was to assess the correlation between changes in patient-reported outcome measures (PROMs) of signs and symptoms, dermatologic quality of life (QoL), and urticaria-specific QoL. METHODS: Latent growth models (LGMs) were applied to longitudinal data from three randomized, Phase 3 clinical trials investigating the efficacy and safety of omalizumab in CSU. RESULTS: A near-perfect association between changes in signs and symptoms and changes in dermatologic and urticaria-specific QoLs was identified in each clinical trial when using LGMs (correlation coefficient range 0.88-0.92). CONCLUSION: Evidence showed that changes in signs and symptoms are closely related to changes in HRQoL. However, analyses were performed on clinical trial results of an extremely effective treatment; a less effective treatment with much smaller changes over time may not show such close correlations. Results suggest that any of these PROMs may be used to understand changes in CSU.

Identifying differential responders and their characteristics in clinical trials: innovative methods for analyzing longitudinal data.

OBJECTIVES: To present a step-by-step example of the examination of heterogeneity within clinical trial data by using a growth mixture modeling (GMM) approach. METHODS: Secondary data from a longitudinal double-blind clinical drug study were used. Patients received enalapril or placebo and were followed for 2 years during the drug component, followed by a 3-year postdrug component. Primary variables of interest were creatinine levels during the drug component and number of hospitalizations in the postdrug component. Latent growth modeling (LGM) methods were used to examine the treatment response variability in the data. GMM methods were applied where substantial variability was found to identify latent (unobserved) subsets of differential responders, using treatment groups as known classes. Post hoc analyses were applied to characterize emergent subgroups. RESULTS: LGM methods demonstrated a large variability in creatinine levels. GMM methods identified two subsets of patients for each treatment group. Placebo class 2 (7.0% of the total sample) and enalapril class 2 (8.5%) include individuals whose creatinine levels start at 1.114 mg/dl and 1.108 mg/dl, respectively, and show worsening (slopes: 0.023 and 0.017, respectively). Placebo class 1 (43.1%) and enalapril class 1 (41.4%) individuals start with lower creatinine levels (1.082 and 1.083 mg/dl, respectively) and show very minimal change (0.008 and 0.003, respectively). Post hoc analyses revealed significant differences between placebo/enalapril class 1 and placebo/enalapril class 2 in terms of New York Heart Association functional ability, depression, functional impairment, creatinine levels, mortality, and hospitalizations. CONCLUSIONS: GMM methods can identify subsets of differential responders in clinical trial data. This can result in a more accurate understanding of treatment effects.

Application of latent growth and growth mixture modeling to identify and characterize differential responders to treatment for COPD.

OBJECTIVE: To explore the utility of applying growth mixture models (GMMs) in secondary analyses of clinical trials to identify sources of variability in data reported by patients with COPD. METHODS: Analyses were performed on data from two 6-month clinical trials comparing indacaterol and open-label tiotropium or blinded salmeterol and the first six months of a 12-month trial comparing indacaterol and blinded formoterol. Latent growth model (LGM) analyses were conducted to explore the response of the SGRQ Symptoms score from baseline to six months and GMM analyses were evaluated as a method to identify latent classes of differential responders. RESULTS: Variability in SGRQ Symptom scores was found suggesting subsets of patients with differential response to treatment. GMM analyses found subsets of non-responders in all trials. When the responders were analyzed separately from non-responders, there were increased treatment effects (e.g., symptoms score improvement over six months for whole groups: indacaterol=8-12 units, tiotropium=7 units, salmeterol=9 units, formoterol=11 units. Responder subgroup improvement: indacaterol=9-21 units, tiotropium=7 units, salmeterol=10 units, formoterol=20 units). Responders had significantly different baseline SGRQ Symptom scores, smoking history, age, and mMRC dyspnea scores than non-responders. CONCLUSIONS: Patients with COPD represent a heterogeneous population in terms of their reporting of symptoms and response to treatment. GMM analyses are able to identify sub-groups of responders and non-responders. Application of this methodology could be of value on other endpoints in COPD and in other disease areas.

Development of a frequent heartburn index.

PURPOSE: The aim of this study is to develop and validate a brief instrument for the measurement of overall psychosocial impact of frequent heartburn (heartburn experienced 2+ times weekly) in the general U.S. population, yielding a single, composite score. METHODS: Item reduction and psychometric analyses of an existing Frequent Heartburn (FHB) Survey, a 52-item, 13-domain, patient-reported outcomes (PRO) survey assessing the impact of frequent heartburn on psychosocial quality of life. RESULTS: Item reduction resulted in 9 items from the original FHB Survey measuring all domains. All retained items in this full Frequent Heartburn Index (FHBI-Full) had moderate to strong factor loadings on the underlying factor (range: 0.66-0.85) and acceptable overall model fit (CFI = 0.93, SRMR = 0.04). Coefficient alpha was 0.92. A shorter FHBI (FHBI-Brief) was created that excludes the two employment-related items. The FHBI-Brief had a coefficient alpha of 0.90. CONCLUSIONS: Both FHBI versions have good psychometric properties and capture a full range of psychosocial effects of frequent heartburn. Normed national scores for the FHBI are available against which an individual can compare their own FHBI score. The FHBI-Full and FHBI-Brief show promise as PRO instruments that may help individuals and clinicians better understand the effect of frequent heartburn on psychosocial functioning.