The COVID-19 pandemic's impact on all-cause mortality disparities in Medicare: By race, income, chronic health, mental/behavioral health, disability.

BACKGROUND: The Medicare-enrolled population is heterogeneous across race, ethnicity, age, dual eligibility, and a breadth of chronic health, mental and behavioral health, and disability-related conditions, which may be differentially impacted by the COVID-19 pandemic. OBJECTIVE: To quantify changes in all-cause mortality prior-to and in the first year of the COVID-19 pandemic across Medicare's different sociodemographic and health-condition subpopulations. METHODS: This observational, population-based study used stratified bivariate regression to investigate Medicare fee-for-service subpopulation differences in pre-pandemic (i.e., 2019 versus 2016) and pandemic-related (2020 versus 2019) changes in all-cause mortality. RESULTS: All-cause mortality in the combined Medicare-Advantage (i.e., managed care) and fee-for-service beneficiary population improved by a relative 1% in the ten years that preceded the COVID-19 pandemic, but then escalated by a relative 15.9% in 2020, the pandemic's first year. However, a closer look at Medicare's fee-for-service subpopulations reveals critical differences. All-cause mortality had actually been worsening prior to the pandemic among most psychiatric and disability-related condition groups, all race and ethnicity groups except White Non-Hispanic, and Medicare-Medicaid dual-eligible (i.e., low-income) beneficiaries. Many of these groups then experienced all-cause mortality spikes in 2020 that were over twice that of the overall Medicare fee-for-service population. Of all 61 chronic health conditions studied, beneficiaries with schizophrenia were the most adversely affected, with all-cause mortality increasing 38.4% between 2019 and 2020. CONCLUSION: This analysis reveals subpopulation differences in all-cause mortality trends, both prior to and in year-one of the COVID-19 pandemic, indicating that the events of 2020 exacerbated preexisting health-related inequities.

Gender Differences in the Relationship Between Food Insecurity and Body Mass Index Among Adults in the USA.

BACKGROUND: In the USA, nearly 40% of adults ≥ 20 years have a body mass index (BMI) ≥ 30, and 11% of households are reported as food insecure. In adults, evidence shows women are more likely than men to be food insecure. Among adults with food insecurity, differences in BMI exist between men and women with women reporting higher BMI. Factors associated with this difference in BMI between genders are less understood. OBJECTIVE: The aim of this study was to assess gender differences in the relationship between food insecurity and BMI. DESIGN: Hierarchical models were analyzed using a general linear model by entering covariates sequentially in blocks (demographics, lifestyle behaviors, comorbidities, and dietary variables) and stratified by gender. PARTICIPANTS: The sample included 25,567 adults in the USA from the National Health and Nutrition Examination Survey (NHANES), 2005-2014. MAIN MEASURES: The dependent variable was BMI, and food insecurity was the primary predictor. KEY RESULTS: Approximately 51% of the sample was women. Food insecure women were significantly more likely to have higher BMI compared to food secure women in the fully adjusted model after controlling for demographics (ß = 1.79; 95% CI 1.17, 2.41); demographic and lifestyle factors (ß = 1.79; 95% CI 1.19, 2.38); demographic, lifestyle, and comorbidities (ß = 1.21; 95% CI 0.65, 1.77); and demographic, lifestyle, comorbidities, and dietary variables (ß = 1.23; 95% CI 0.67, 1.79). There were no significant associations between food insecure and food secure men in the fully adjusted model variables (ß = 0.36; 95% CI - 0.26, 0.98). CONCLUSION: In this sample of adults, food insecurity was significantly associated with higher BMI among women after adjusting for demographics, lifestyle factors, comorbidities, and dietary variables. This difference was not observed among men. More research is necessary to understand this relationship among women.

PROGRESSION OF PARTIAL POSTERIOR VITREOUS DETACHMENT OVER TIME.

PURPOSE: We investigated interindividual differences in the rate of change of posterior vitreous detachment (PVD) stage and vitreomacular adhesion area (VMAA). Crosssectional studies demonstrated increasing PVD stage and decreasing VMAA with age, but population-level means may mask interindividual variation in the rate of change. METHODS: We retrospectively evaluated PVD stage and VMAA in asymptomatic eyes of subjects who underwent repeated optical coherence tomography screening for high-risk medication use or isolated retinal disease in the fellow eye. A Turnbull estimator modeled changes in the PVD stage, and linear mixed models evaluated VMAA change. RESULTS: We evaluated 101 eyes of 101 subjects. Seventy-six eyes remained in the same stage. Twenty-three eyes progressed to a higher stage. Modeling of longitudinal data predicts that at age 30, time to convert to Stage 4 is 26 years; at age 40, it is 16 years; at age 50, it is 9 years; and at age 60, it is 8 years. In 37 eyes with Stage 1 partial PVD, VMAA decreased at a similar rate. The average population level decline in VMAA was 0.13 mm2/year. CONCLUSION: Individuals vary in age at which they progress to complete PVD. In early partial PVD, VMAA decreases at a similar rate across individuals.

Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia.

BACKGROUND: Older patients with acute myeloid leukemia (AML) have a dismal prognosis, even after treatment with a hypomethylating agent. Azacitidine added to venetoclax had promising efficacy in a previous phase 1b study. METHODS: We randomly assigned previously untreated patients with confirmed AML who were ineligible for standard induction therapy because of coexisting conditions, because they were 75 years of age or older, or both to azacitidine plus either venetoclax or placebo. All patients received a standard dose of azacitidine (75 mg per square meter of body-surface area subcutaneously or intravenously on days 1 through 7 every 28-day cycle); venetoclax (target dose, 400 mg) or matching placebo was administered orally, once daily, in 28-day cycles. The primary end point was overall survival. RESULTS: The intention-to-treat population included 431 patients (286 in the azacitidine-venetoclax group and 145 in the azacitidine-placebo [control] group). The median age was 76 years in both groups (range, 49 to 91). At a median follow-up of 20.5 months, the median overall survival was 14.7 months in the azacitidine-venetoclax group and 9.6 months in the control group (hazard ratio for death, 0.66; 95% confidence interval, 0.52 to 0.85; P<0.001). The incidence of complete remission was higher with azacitidine-venetoclax than with the control regimen (36.7% vs. 17.9%; P<0.001), as was the composite complete remission (complete remission or complete remission with incomplete hematologic recovery) (66.4% vs. 28.3%; P<0.001). Key adverse events included nausea of any grade (in 44% of the patients in the azacitidine-venetoclax group and 35% of those in the control group) and grade 3 or higher thrombocytopenia (in 45% and 38%, respectively), neutropenia (in 42% and 28%), and febrile neutropenia (in 42% and 19%). Infections of any grade occurred in 85% of the patients in the azacitidine-venetoclax group and 67% of those in the control group, and serious adverse events occurred in 83% and 73%, respectively. CONCLUSIONS: In previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone. The incidence of febrile neutropenia was higher in the venetoclax-azacitidine group than in the control group. (Funded by AbbVie and Genentech; VIALE-A ClinicalTrials.gov number, NCT02993523.).

Standard 6-mm Compared with Widefield 16.5-mm OCT for Staging of Posterior Vitreous Detachment.

PURPOSE: To assess whether 6-mm OCT scans, which image the macula, can distinguish complete from partial posterior vitreous detachment (PVD) in comparison with 16.5-mm OCT scans, which image the macula, optic nerve, and mid periphery. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: We compared 6-mm and 16.5-mm scans in 157 eyes of 157 retina clinic patients (mean age, 50 years; range, 10-64 years) with diabetic retinopathy (36%), no retinal disease (19%), and various retinal conditions (45%). We also analyzed 16.5-mm scans in 35 healthy eyes (asymptomatic fellow eyes of patients with unilateral retinal conditions; mean age, 46 years; range, 9-63 years). METHODS: Each participant underwent Heidelberg Spectralis imaging with the standard lens (6-mm scan) and/or the 55° lens (16.5-mm scan). On 6-mm scans, we classified eyes as stage 3 partial PVD when the posterior vitreous cortex was visualized without visible attachment. On 16.5-mm scans, we classified eyes as stage 3 when the vitreous was attached at the optic nerve and separated from the macula. On both scan types, we classified eyes as stage 4 when neither the premacular bursa nor the posterior vitreous cortex were visualized. We assessed the accuracy of this system for detecting complete PVD on 6-mm scans by calculating test characteristics using 16.5-mm scans as a reference standard. MAIN OUTCOME MEASURE: Posterior vitreous detachment stage (0-4). RESULTS: Posterior vitreous detachment stage was identical in 6-mm and 16.5-mm scans in 88% of eyes. Compared with 16.5-mm scans, 6-mm scans detected complete PVD (vs. earlier stages 0-3) with 91% sensitivity and 99% specificity. Seven eyes were classified as no PVD on 6-mm scans and were classified as partial PVD on 16.5-mm scans because vitreoretinal separation was localized to the mid periphery. All 16.5-mm scans showed some degree of PVD, including scans from 9 participants between 9 and 20 years of age. CONCLUSIONS: Six-millimeter scans distinguished complete from partial PVD with good sensitivity and specificity but missed the earliest stages of PVD, which occur in the mid periphery. Posterior vitreous detachment may begin as early as the second decade of life.

Diabetes prevention and the role of risk factor reduction in the Medicare population.

Medicare is keenly aware of the secular changes in weight gain and of the nearly parallel increases in both the incidence and prevalence of type 2 diabetes throughout the U.S. population. The Medicare population, however, differs from the population at large because of its advanced age and frequency of comorbid conditions and/or disability. These factors affect life span as well as participation in and potential benefit from lifestyle modification and risk-factor reduction activities. Further, macrovascular disease is the greatest burden for older beneficiaries with diabetes, and its risks may antedate the appearance of hyperglycemia. Both diabetes prevention and treatment must be considered in this context. Medicare benefits focus on reduction of cardiovascular risk and mitigation of more temporally immediate complications of weight gain and glucose elevation. These preventive services and interventions are described.

A survey of reports of quetiapine-associated hyperglycemia and diabetes mellitus.

OBJECTIVE: To explore the clinical characteristics of hyperglycemia in patients treated with quetiapine. METHOD: A pharmacovigilance survey of spontaneously reported adverse events in quetiapine-treated patients was conducted using reports from the U.S. Food and Drug Administration MedWatch program (January 1, 1997, through July 31, 2002) and published cases using the search terms hyperglycemia, diabetes, acidosis, ketosis, and ketoacidosis. RESULTS: We identified 46 reports of quetiapine-associated hyperglycemia or diabetes and 9 additional reports of acidosis that occurred in the absence of hyperglycemia and were excluded from the immediate analyses. Of the reports of quetiapine-associated hyperglycemia, 34 patients had newly diagnosed hyperglycemia, 8 had exacerbation of preexisting diabetes mellitus, and 4 could not be classified. The mean +/- SD age was 35.3 +/- 16.2 years (range, 5-76 years). New-onset patients (aged 31.2 +/- 14.8 years) tended to be younger than those with preexisting diabetes (43.5 +/- 16.4 years, p = .08). The overall male:female ratio was 1.9. Most cases appeared within 6 months of quetiapine initiation. The severity of cases ranged from mild glucose intolerance to diabetic ketoacidosis or hyperosmolar coma. There were 21 cases of ketoacidosis or ketosis. There were 11 deaths. CONCLUSION: Atypical antipsychotic use may unmask or precipitate hyperglycemia. UPDATE: An additional 23 cases were identified since August 1, 2002, the end of the first survey, by extending the search through November 30, 2003, bringing the total to 69.

Pancreatitis associated with atypical antipsychotics: from the Food and Drug Administration's MedWatch surveillance system and published reports.

STUDY OBJECTIVE: To investigate the relative numbers and clinical characteristics of pancreatitis in patients treated with the atypical antipsychotic agents, clozapine, olanzapine, and risperidone, versus the conventional neuroleptic, haloperidol. DESIGN: Pharmacovigilance study of pooled, spontaneously reported adverse events. SETTING: Government-affiliated drug evaluation center. PATIENTS: One hundred ninety-two patients who developed pancreatitis during treatment with one or more antipsychotic agents. INTERVENTION: Patients were identified with the Food and Drug Administration's MedWatch surveillance program and a MEDLINE search. MEASUREMENTS AND MAIN RESULTS: Most cases of pancreatitis occurred within 6 months after the start of therapy with one or more antipsychotic agents. Of the reports of pancreatitis occurring in conjunction with these drugs, 40%, 33%, 16%, and 12% were in patients receiving treatment with clozapine, olanzapine, risperidone, and haloperidol, respectively. In 50% of the patients receiving haloperidol, an atypical antipsychotic was listed as a concomitant drug. Valproate was administered concomitantly in 23% of patients. Hyperglycemia and acidosis, although uncommon, developed with all the drugs except haloperidol. Twenty-two patients died. In contrast to patients who developed pancreatitis while receiving an atypical antipsychotic, those who developed the disease while receiving haloperidol were women and tended to be older. CONCLUSION: The number of reports involving the three atypical antipsychotic agents and the relative paucity of reports involving haloperidol, despite its more extensive patient exposure, suggest that atypical antipsychotics may precipitate pancreatitis. However, the risk may not be the same with all agents; pancreatitis was reported most frequently with clozapine, followed by olanzapine, and then risperidone. The temporal relationship of the onset of pancreatitis with the start of drug therapy further supports a cause-and-effect relationship.

Risperidone-associated diabetes mellitus: a pharmacovigilance study.

STUDY OBJECTIVE: To explore the clinical characteristics of hyperglycemia in patients treated with risperidone. DESIGN: Pharmacovigilance survey of spontaneously reported adverse events in risperidone-treated patients, with reports of haloperidol-associated hyperglycemia used as a control. SETTING: Government-affiliated drug evaluation center. INTERVENTION: The Food and Drug Administration MedWatch surveillance program was queried (risperidone, 1993-February 2002; haloperidol, late 1970s-February 2002) and results pooled with published cases. MEASUREMENTS AND MAIN RESULTS: We identified 131 reports of risperidone-associated hyperglycemia in addition to seven reports of patients with hyperglycemia who received combined risperidone-haloperidol therapy and six reports of acidosis that occurred in the absence of hyperglycemia. We found 13 reports of haloperidol-associated hyperglycemia and 11 reports of acidosis without hyperglycemia. Of the reports of risperidone-associated hyperglycemia (monotherapy), 78 patients had newly diagnosed hyperglycemia, 46 had exacerbated preexisting diabetes, and 7 could not be classified. Mean +/- SD age was 39.8 +/- 17.4 years (range 8-96 yrs). Patients with new-onset diabetes (mean +/- SD age 34.8 +/- 15.7 yrs) were younger than those with preexisting diabetes (mean +/- SD age 48.8 +/- 17.5 yrs). The overall male:female ratio was 1.5. In most patients, hyperglycemia appeared within 3 months of the start of risperidone therapy. Severity of disease ranged from mild glucose intolerance to diabetic ketoacidosis or hyperosmolar coma. Twenty-six patients with acidosis or ketosis were reported. Four patients died. CONCLUSION: Atypical antipsychotic treatment may unmask or precipitate hyperglycemia. Although such cases attributed to clozapine or olanzapine are more numerous than those associated with risperidone, the number for risperidone-associated hyperglycemia is relatively higher than that observed with the conventional neuroleptic haloperidol.

Olanzapine-associated diabetes mellitus.

STUDY OBJECTIVE: To explore the clinical characteristics of hyperglycemia in patients treated with olanzapine. DESIGN: Retrospective, epidemiologic survey of spontaneously reported adverse events related to olanzapine therapy SETTING: Government-affiliated drug evaluation center. PATIENTS: Two hundred thirty-seven patients with olanzapine-associated diabetes or hyperglycemia. INTERVENTION: One hundred ninety-six cases from January 1994-May 15, 2001, were identified with the United States Food and Drug Administration's MedWatch Drug Surveillance System, and 41 cases published through May 15, 2001, were identified with MEDLINE or through meeting abstracts. MEASUREMENTS AND MAIN RESULTS: Of the 237 cases, 188 were new-onset diabetes, 44 were exacerbations of preexistent disease, and 5 could not be classified. Mean patient age for newly diagnosed cases was 40.7+/-12.9 years and male:female ratio was 1.8. Seventy-three percent of all cases of hyperglycemia appeared within 6 months of start of olanzapine therapy. Eighty patients had metabolic acidosis or ketosis, 41 had glucose levels of 1000 mg/dl or greater, and 15 patients died. When olanzapine was discontinued or the dosage decreased, 78% of patients had improved glycemic control. Hyperglycemia recurred in 8 of 10 cases with rechallenge. CONCLUSIONS: Number of reports, temporal relationship to start of olanzapine therapy, relatively young age, and improvement on drug withdrawal suggest that olanzapine may precipitate or unmask diabetes in susceptible patients.