Managed care COVID-19 outcomes in a population health program.

OBJECTIVES: To determine (1) factors linked to hospitalizations among managed care patients (MCPs), (2) outcome improvement with use of outpatient off-label treatment, and (3) outcome comparison between MCPs and a mirror group. STUDY DESIGN: Retrospective cohort study comparing MCPs with an age- and gender-matched mirror group in Florida from April 1, 2020, to May 31, 2020. METHODS: A total of 38,193 MCPs in a Florida primary care group were monitored for COVID-19 incidence, hospitalization, and mortality. The highest-risk patients were managed by the medical group's COVID-19 Task Force. As part of a population health program, the COVID-19 Task Force contacted patients, conducted medical encounters, and tracked data including comorbidities and medical outcomes. The MCPs enrolled in the medical group were compared with a mirror group from the state of Florida. RESULTS: The mean (SD) age among the MCPs was 67.9 (15.2) years, and 60% were female. Older age and hypertension were the most important factors in predicting COVID-19. Obesity, chronic kidney disease (CKD), and congestive heart failure (CHF) were linked to higher rates of hospitalizations. Patients prescribed off-label outpatient medications had 73% lower likelihood of hospitalization (P < .05). Compared with the mirror group, MCPs had 60% lower COVID-19 mortality (P < .05). CONCLUSIONS: MCPs have risk factors similar to the general population for COVID-19 incidence and progression, including older age, hypertension, obesity, CHF, and CKD. Outpatient treatment with off-label medicines decreased hospitalizations. A comprehensive population health program decreased COVID-19 mortality.

Current Understanding of COVID-19 Clinical Course and Investigational Treatments.

Importance: Currently, there is no unified framework linking disease progression to established viral levels, clinical tests, inflammatory markers, and investigational treatment options. Objective: It may take many weeks or months to establish a standard treatment approach. Given the growing morbidity and mortality with respect to COVID-19, this systemic review presents a treatment approach based on a thorough review of scholarly articles and clinical reports. Our focus is on staged progression, clinical algorithms, and individualized treatment. Evidence Review: We followed the protocol for a quality review article proposed by Heyn et al. (1). A literature search was conducted to find all relevant studies related to COVID-19. The search was conducted between April 1, 2020, and April 13, 2020, using the following electronic databases: PubMed (1809 to present); Google Scholar (1900 to present); MEDLINE (1946 to present), CINAHL (1937 to present); and Embase (1980 to present). The keywords used included COVID-19, 2019-nCov, SARS-CoV-2, SARS-CoV, and MERS-CoV, with terms such as efficacy, seroconversion, microbiology, pathophysiology, viral levels, inflammation, survivability, and treatment and pharmacology. No language restriction was placed on the search. Reference lists were manually scanned for additional studies. Findings: Of the articles found in the literature search, 70 were selected for inclusion in this study (67 cited in the body of the manuscript and 3 additional unique references in the Figures). The articles represent work from China, Japan, Taiwan, Vietnam, Rwanda, Israel, France, the United Kingdom, the Netherlands, Canada, and the United States. Most of the articles were cohort or case studies, but we also drew upon other information, including guidelines from hospitals and clinics instructing their staff on procedures to follow. In addition, we based some decisions on data collected by organizations such as the CDC, FDA, IHME, IDSA, and Worldometer. None of the case studies or cohort studies used a large number of participants. The largest group of participants numbered <500 and some case studies had fewer than 30 patients. However, the review of the literature revealed the need for individualized treatment protocols due to the variability of patient clinical presentation and survivability. A number of factors appear to influence mortality: the stage at which the patient first presented for care, pre-existing health conditions, age, and the viral load the patient carried. Conclusion and Relevance: COVID-19 can be divided into three distinct stages, beginning at the time of infection (Stage I), sometimes progressing to pulmonary involvement (Stage II, with or without hypoxemia), and less frequently to systemic inflammation (Stage III). In addition to modeling the stages of disease progression along with diagnostic testing, we have also created a treatment algorithm that considers age, comorbidities, clinical presentation, and disease progression to suggest drug classes or treatment modalities. This paper presents the first evidence-based recommendations for individualized treatment for COVID-19.

Type 2 diabetes: Evolving concepts and treatment.

In view of new information, we are revising the way we think about and treat diabetes mellitus. In this new view, the insulin-producing beta cells are key, and preserving beta-cell function is paramount. These insights, together with recent outcome studies provide compelling arguments regarding treatments of choice.

A Unified Pathophysiological Construct of Diabetes and its Complications.

Advances in understanding diabetes mellitus (DM) through basic and clinical research have helped clarify and reunify a disease state fragmented into numerous etiologies and subtypes. It is now understood that a common pathophysiology drives the diabetic state throughout its natural history and across its varied clinical presentations, a pathophysiology involving metabolic insults, oxidative damage, and vicious cycles that aggravate and intensify organ dysfunction and damage. This new understanding of the disease requires that we revisit existing diagnostics and treatment approaches, which were built upon outmoded assumptions. 'The Common Pathophysiologic Origins of Diabetes Mellitus and its Complications Construct' is presented as a more accurate, foundational, and translatable construct of DM that helps make sense of the hitherto ambiguous findings of long-term outcome studies.

The Time Is Right for a New Classification System for Diabetes: Rationale and Implications of the ß-Cell-Centric Classification Schema.

The current classification system presents challenges to the diagnosis and treatment of patients with diabetes mellitus (DM), in part due to its conflicting and confounding definitions of type 1 DM, type 2 DM, and latent autoimmune diabetes of adults (LADA). The current schema also lacks a foundation that readily incorporates advances in our understanding of the disease and its treatment. For appropriate and coherent therapy, we propose an alternate classification system. The ß-cell-centric classification of DM is a new approach that obviates the inherent and unintended confusions of the current system. The ß-cell-centric model presupposes that all DM originates from a final common denominator-the abnormal pancreatic ß-cell. It recognizes that interactions between genetically predisposed ß-cells with a number of factors, including insulin resistance (IR), susceptibility to environmental influences, and immune dysregulation/inflammation, lead to the range of hyperglycemic phenotypes within the spectrum of DM. Individually or in concert, and often self-perpetuating, these factors contribute to ß-cell stress, dysfunction, or loss through at least 11 distinct pathways. Available, yet underutilized, treatments provide rational choices for personalized therapies that target the individual mediating pathways of hyperglycemia at work in any given patient, without the risk of drug-related hypoglycemia or weight gain or imposing further burden on the ß-cells. This article issues an urgent call for the review of the current DM classification system toward the consensus on a new, more useful system.

Efficacy and safety of linagliptin in Hispanic/Latino patients with type 2 diabetes mellitus: a pooled analysis from six randomized placebo-controlled phase 3 trials.

OBJECTIVE: The number of individuals diagnosed with type 2 diabetes mellitus is expected to rise disproportionately in Hispanic/Latino populations. We therefore aimed to assess the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin specifically in Hispanic/Latino patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: Data from 745 patients who self-identified their ethnicity as Hispanic or Latino were pooled from six randomized, placebo-controlled phase 3 trials. Participants received linagliptin (5 mg/day) or placebo as monotherapy, or in combination with other oral antidiabetes drugs for 18 or 24 weeks. RESULTS: The placebo-adjusted mean change (95% CI) in glycated hemoglobin from baseline (mean 8.2%) was -0.63% (-0.77 to -0.48; p<0.0001) at week 18, and -0.58% (-0.74 to -0.42; p<0.0001) at week 24. The placebo-adjusted mean change (95% CI) in fasting plasma glucose from baseline was -11.7 mg/dL (-19.3 to -4.0; p=0.0028) at week 18 and -14.1 mg/dL (-22.0 to -6.3; p=0.0004) at week 24. Hypoglycemia incidence was 17.4% with linagliptin and 21% with placebo. In patients not receiving concomitant sulfonylurea, the hypoglycemia incidence was 10.1% with linagliptin and 19.4% with placebo. The overall incidence of adverse events (AEs), drug-related AEs, and serious AEs with linagliptin was similar to placebo (AEs 67.6% vs 68.9%; drug-related AEs 15.1% vs 18.7%; serious AEs 3.6% vs 3.0%). The mean body weight remained unchanged in both groups. CONCLUSIONS: In Hispanic/Latino patients with inadequately controlled type 2 diabetes mellitus, linagliptin provided clinically meaningful improvements in glycemic control without weight gain or increased risk of hypoglycemia.

Evaluating treatment algorithms for the management of patients with type 2 diabetes mellitus: a perspective on the definition of treatment success.

BACKGROUND: Traditional treatment of type 2 diabetes mellitus (T2DM) has focused on correcting hyperglycemia. However, T2DM is often accompanied by other conditions and risk factors, including hypertension, overweight/obesity, and dyslipidemia, that affect morbidity and mortality. A broader view toward treating the array of physiologic derangements may provide significant long-term outcomes benefits. OBJECTIVE: This perspective paper reviews recent data regarding the pathophysiology of T2DM, evaluates current treatment recommendations/algorithms, and discusses potential risks and benefits associated with the various therapeutic options and their combinations. METHODS: Information was obtained by a search of the PubMed and Embase databases using the key words type 2 diabetes mellitus, glycosylated hemoglobin, pathophysiology of type 2 diabetes, glycemic control, antidiabetes therapy, multifactorial therapy, and treatment algorithms for the period of 1985 to 2010. A representative number of relevant articles dealing with these topics was then selected for review. RESULTS: Three recently proposed treatment algorithms, the American Diabetes Association/European Association for the Study of Diabetes less well-validated algorithm, the American Association of Clinical Endocrinologists/American College of Endocrinology algorithm, and the DeFronzo algorithm, were compared and contrasted. Metformin is usually the first oral agent to be used when not contraindicated because of its ability to suppress hepatic glucose production. Some recommended agents, such as sulfonylureas, drive ß-cell failure even as they improve glycosylated hemoglobin. Others, such as glucagon-like peptide-1 (GLP-1) receptor agonists and thiazolidinediones, support and enhance ß-cell function. Also, some agents predispose to weight gain (eg, sulfonylureas and insulin), whereas others are weight neutral (eg, dipeptidyl-peptidase-4 inhibitors) or result in weight loss (eg, GLP-1 receptor agonists, pramlintide). Finally, the impact of these agents on associated cardiovascular risk factors is varied. Agents that improve glycemic control while favorably affecting blood lipid levels and/or systemic blood pressure may lead to improvements in morbidity and mortality. Attention to the mechanisms of action and associated consequences of the numerous pharmacologic treatment choices may provide clinicians a better selection of agents in treating patients with T2DM. CONCLUSIONS: Physicians should evaluate the array of treatment options available for patients with T2DM. An aggressive regimen including metformin, a thiazolidinedione, and a GLP-1 receptor agonist may improve insulin sensitivity and enhance ß-cell function. Addressing the pathophysiologic defects associated with T2DM, as well as the various associated cardiovascular risk factors, with combination therapy may slow the natural progression of the disease and development of its associated complications.