Bulk Depolymerization of Methacrylate Polymers via Pendent Group Activation.

In this study, we present an efficient approach for the depolymerization of poly(methyl methacrylate) (PMMA) copolymers synthesized via conventional radical polymerization. By incorporating low mol % phthalimide ester-containing monomers during the polymerization process, colorless and transparent polymers closely resembling unfunctionalized PMMA are obtained, which can achieve >95% reversion to methyl methacrylate (MMA). Notably, our catalyst-free bulk depolymerization method exhibits exceptional efficiency, even for high-molecular-weight polymers, including ultrahigh-molecular-weight (106-107 g/mol) PMMA, where near-quantitative depolymerization is achieved. Moreover, this approach yields polymer byproducts of significantly lower molecular weight, distinguishing it from bulk depolymerization methods initiated from chain ends. Furthermore, we extend our investigation to polymethacrylate networks, demonstrating high extents of depolymerization. This innovative depolymerization strategy offers promising opportunities for the development of sustainable polymethacrylate materials, holding great potential for various applications in polymer science.

Selective Electrochemical Modification and Degradation of Polymers.

We demonstrate that electrochemical-induced decarboxylation enables reliable post-polymerization modification and degradation of polymers. Polymers containing N-(acryloxy)phthalimides were subjected to electrochemical decarboxylation under mild conditions, which led to the formation of transient alkyl radicals. By installing these redox-active units, we systematically modified the pendent groups and chain ends of polyacrylates. This approach enabled the production of poly(ethylene-co-methyl acrylate) and poly(propylene-co-methyl acrylate) copolymers, which are difficult to synthesize by direct polymerization. Spectroscopic and chromatographic techniques reveal these transformations are near-quantitative on several polymer systems. Electrochemical decarboxylation also enables the degradation of all-methacrylate poly(N-(methacryloxy)phthalimide-co-methyl methacrylate) copolymers with a degradation efficiency of >95 %. Chain cleavage is achieved through the decarboxylation of the N-hydroxyphthalimide ester and subsequent ß-scission of the backbone radical. Electrochemistry is thus shown to be a powerful tool in selective polymer transformations and controlled macromolecular degradation.

Impact of the COVID-19 Pandemic on Healthcare Workers' Risk of Infection and Outcomes in a Large, Integrated Health System.

BACKGROUND: Understanding the impact of the COVID-19 pandemic on healthcare workers (HCW) is crucial. OBJECTIVE: Utilizing a health system COVID-19 research registry, we assessed HCW risk for COVID-19 infection, hospitalization, and intensive care unit (ICU) admission. DESIGN: Retrospective cohort study with overlap propensity score weighting. PARTICIPANTS: Individuals tested for SARS-CoV-2 infection in a large academic healthcare system (N = 72,909) from March 8-June 9, 2020, stratified by HCW and patient-facing status. MAIN MEASURES: SARS-CoV-2 test result, hospitalization, and ICU admission for COVID-19 infection. KEY RESULTS: Of 72,909 individuals tested, 9.0% (551) of 6145 HCW tested positive for SARS-CoV-2 compared to 6.5% (4353) of 66,764 non-HCW. The HCW were younger than the non-HCW (median age 39.7 vs. 57.5, p < 0.001) with more females (proportion of males 21.5 vs. 44.9%, p < 0.001), higher reporting of COVID-19 exposure (72 vs. 17%, p < 0.001), and fewer comorbidities. However, the overlap propensity score weighted proportions were 8.9 vs. 7.7 for HCW vs. non-HCW having a positive test with weighted odds ratio (OR) 1.17, 95% confidence interval (CI) 0.99-1.38. Among those testing positive, weighted proportions for hospitalization were 7.4 vs. 15.9 for HCW vs. non-HCW with OR of 0.42 (CI 0.26-0.66) and for ICU admission: 2.2 vs. 4.5 for HCW vs. non-HCW with OR of 0.48 (CI 0.20-1.04). Those HCW identified as patient facing compared to not had increased odds of a positive SARS-CoV-2 test (OR 1.60, CI 1.08-2.39, proportions 8.6 vs. 5.5), but no statistically significant increase in hospitalization (OR 0.88, CI 0.20-3.66, proportions 10.2 vs. 11.4) and ICU admission (OR 0.34, CI 0.01-3.97, proportions 1.8 vs. 5.2). CONCLUSIONS: In a large healthcare system, HCW had similar odds for testing SARS-CoV-2 positive, but lower odds of hospitalization compared to non-HCW. Patient-facing HCW had higher odds of a positive test. These results are key to understanding HCW risk mitigation during the COVID-19 pandemic.

Development of predictive risk models for major adverse cardiovascular events among patients with type 2 diabetes mellitus using health insurance claims data.

BACKGROUND: There exist several predictive risk models for cardiovascular disease (CVD), including some developed specifically for patients with type 2 diabetes mellitus (T2DM). However, the models developed for a diabetic population are based on information derived from medical records or laboratory results, which are not typically available to entities like payers or quality of care organizations. The objective of this study is to develop and validate models predicting the risk of cardiovascular events in patients with T2DM based on medical insurance claims data. METHODS: Patients with T2DM aged 50 years or older were identified from the Optum™ Integrated Real World Evidence Electronic Health Records and Claims de-identified database (10/01/2006-09/30/2016). Risk factors were assessed over a 12-month baseline period and cardiovascular events were monitored from the end of the baseline period until end of data availability, continuous enrollment, or death. Risk models were developed using logistic regressions separately for patients with and without prior CVD, and for each outcome: (1) major adverse cardiovascular events (MACE; i.e., non-fatal myocardial infarction, non-fatal stroke, CVD-related death); (2) any MACE, hospitalization for unstable angina, or hospitalization for congestive heart failure; (3) CVD-related death. Models were developed and validated on 70% and 30% of the sample, respectively. Model performance was assessed using C-statistics. RESULTS: A total of 181,619 patients were identified, including 136,544 (75.2%) without prior CVD and 45,075 (24.8%) with a history of CVD. Age, diabetes-related hospitalizations, prior CVD diagnoses and chronic pulmonary disease were the most important predictors across all models. C-statistics ranged from 0.70 to 0.81, indicating that the models performed well. The additional inclusion of risk factors derived from pharmacy claims (e.g., use of antihypertensive, and use of antihyperglycemic) or from medical records and laboratory measures (e.g., hemoglobin A1c, urine albumin to creatinine ratio) only marginally improved the performance of the models. CONCLUSION: The claims-based models developed could reliably predict the risk of cardiovascular events in T2DM patients, without requiring pharmacy claims or laboratory measures. These models could be relevant for providers and payers and help implement approaches to prevent cardiovascular events in high-risk diabetic patients.

Utility of the Psychosocial Assessment of Candidates for Transplantation in Patients Undergoing Continuous-Flow Left Ventricular Assist Device Implantation.

PURPOSE: Psychosocial assessment of patients comprises an important element in the selection process of appropriate candidates for left ventricular assist device (LVAD) implantation. We sought to determine the association of the well-validated psychosocial assessment of candidates for transplantation (PACT) scale to clinical outcomes post-LVAD implantation. MATERIALS AND METHODS: The PACT scale was used retrospectively to reconstruct psychosocial profiles of all patients who underwent a continuous-flow LVAD implantation for all indications at our institution between March 2008 and August 2012 (N = 230). Psychosocial elements including social support, psychological health, lifestyle factors, comprehension of the operation, and follow-up were evaluated. The primary outcome was overall survival, and the secondary outcomes were hospital readmission, pump thrombosis, hemolysis, gastrointestinal (GI) bleeding, and LVAD driveline infections. RESULTS: The mean age of patients was 55.3 years, with 83% being male; 58% (N = 135) were bridge to transplant and 42% (N = 95) were destination therapy. Up to 1-year post-LVAD implant, there were no statistical differences among the 5 PACT candidate groups in terms of survival ( P = .79), hospital readmissions ( P = .55), suspected or confirmed pump thrombosis ( P = .31), hemolysis ( P = .43), GI bleeding ( P = .71), or driveline infections ( P = .06). CONCLUSIONS: In this single-center retrospective review, post hoc reconstruction of psychosocial profiles using the PACT scale and independent assessment of postimplant outcomes, including survival and adverse events, did not show any association. However, given the small number of patients in the low score PACT groups as well as limited duration of follow-up, further studies are required to elucidate the association.

Comparison Between the Kansas City Cardiomyopathy Questionnaire and New York Heart Association in Assessing Functional Capacity and Clinical Outcomes.

OBJECTIVE: The Kansas City Cardiomyopathy Questionnaire (KCCQ) has emerged as a patient-centered heart failure-specific health status measure. It currently lacks routine and widespread use in clinical practice and trials. The purpose of this study was to examine the correlation between KCCQ and cardiopulmonary exercise testing (CPET) parameters and clinical outcomes, compared with the New York Heart Association functional classification (NYHA). METHODS AND RESULTS: We performed a single-centered observational analysis of 432 patients who presented to the Heart Failure Department, completed the KCCQ, and underwent CPET. The 1-year clinical outcome assessed was a composite of mortality, heart failure hospitalization, and need for heart transplantation or left ventricular assist device. In the KCCQ, the physical limitation domain had a correlation with peak VO2 similar to NYHA (r = 0.48; P < .001; and r = -0.48; P < .001; respectively), and slightly better correlation with ventilatory threshold (r = 0.42; P < .001; and r = -0.40; P < .001; respectively). According to model validation, the KCCQ physical limitation domain and NYHA were similar predictors of peak VO2 (r2 = 0.229; and r2 = 0.227; respectively). KCCQ predicted the specified 1-year clinical outcome (hazard ratio 0.75, 95% confidence interval 0.69-0.82; P < .001) and provided incremental predictive ability when added to a model that included NYHA, with a net reclassification index of 76.1% (P < .001). CONCLUSIONS: KCCQ and NYHA provide similar assessment of functional capacity. KCCQ predicts 1-year clinical outcomes, providing incremental value over NYHA. These findings support its routine use in clinical care, as well as its potential to serve as a measure in clinical trials.

Treatment of anemia with darbepoetin alfa in systolic heart failure.

BACKGROUND: Patients with systolic heart failure and anemia have worse symptoms, functional capacity, and outcomes than those without anemia. We evaluated the effects of darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anemia. METHODS: In this randomized, double-blind trial, we assigned 2278 patients with systolic heart failure and mild-to-moderate anemia (hemoglobin level, 9.0 to 12.0 g per deciliter) to receive either darbepoetin alfa (to achieve a hemoglobin target of 13 g per deciliter) or placebo. The primary outcome was a composite of death from any cause or hospitalization for worsening heart failure. RESULTS: The primary outcome occurred in 576 of 1136 patients (50.7%) in the darbepoetin alfa group and 565 of 1142 patients (49.5%) in the placebo group (hazard ratio in the darbepoetin alfa group, 1.01; 95% confidence interval, 0.90 to 1.13; P=0.87). There was no significant between-group difference in any of the secondary outcomes. The neutral effect of darbepoetin alfa was consistent across all prespecified subgroups. Fatal or nonfatal stroke occurred in 42 patients (3.7%) in the darbepoetin alfa group and 31 patients (2.7%) in the placebo group (P=0.23). Thromboembolic adverse events were reported in 153 patients (13.5%) in the darbepoetin alfa group and 114 patients (10.0%) in the placebo group (P=0.01). Cancer-related adverse events were similar in the two study groups. CONCLUSIONS: Treatment with darbepoetin alfa did not improve clinical outcomes in patients with systolic heart failure and mild-to-moderate anemia. Our findings do not support the use of darbepoetin alfa in these patients. (Funded by Amgen; RED-HF ClinicalTrials.gov number, NCT00358215.).

Outcomes for Patients With Diabetes After Continuous-Flow Left Ventricular Assist Device Implantation.

BACKGROUND: Diabetes mellitus (DM) is a risk factor for mortality among patients with heart failure as well as for patients who undergo cardiothoracic surgery. However it is unknown whether DM is associated with increased mortality or major complications during continuous-flow left ventricular assist device (CF-LVAD) support. METHODS AND RESULTS: We retrospectively reviewed 300 consecutive adults who received CF-LVADs at a single center in the years 2006-2013; 129 patients had DM before LVAD, as defined by American Diabetes Association criteria (HbA1c ≥6.5% and/or taking DM medications). Compared with the non-DM group, DM patients were older, with a higher pre-LVAD body mass index, more ischemic heart failure etiology, and higher pre-LVAD creatinine. Ninety-three patients died on LVAD support, 43 with DM and 50 without DM (P = .4526). After control for 9 covariates in a Cox proportional hazards model, DM was unassociated with all-cause mortality (hazard ratio 0.883, 95% confidence interval 0.571-1.366; P = .5768). Diabetes was also unassociated with the adverse event end points of stroke/transient ischemic attack, intracerebral hemorrhage, pump thrombosis, and device-related infections. CONCLUSIONS: Diabetes is common in LVAD recipients (43% of the present cohort) but does not increase mortality or rates of major adverse events during CF-LVAD support.

An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resynchronization therapy on morbidity and mortality in patients with symptomatic heart failure.

AIMS: Cardiac resynchronization therapy (CRT) with or without a defibrillator reduces morbidity and mortality in selected patients with heart failure (HF) but response can be variable. We sought to identify pre-implantation variables that predict the response to CRT in a meta-analysis using individual patient-data. METHODS AND RESULTS: An individual patient meta-analysis of five randomized trials, funded by Medtronic, comparing CRT either with no active device or with a defibrillator was conducted, including the following baseline variables: age, sex, New York Heart Association class, aetiology, QRS morphology, QRS duration, left ventricular ejection fraction (LVEF), and systolic blood pressure. Outcomes were all-cause mortality and first hospitalization for HF or death. Of 3782 patients in sinus rhythm, median (inter-quartile range) age was 66 (58-73) years, QRS duration was 160 (146-176) ms, LVEF was 24 (20-28)%, and 78% had left bundle branch block. A multivariable model suggested that only QRS duration predicted the magnitude of the effect of CRT on outcomes. Further analysis produced estimated hazard ratios for the effect of CRT on all-cause mortality and on the composite of first hospitalization for HF or death that suggested increasing benefit with increasing QRS duration, the 95% confidence bounds excluding 1.0 at ∼140 ms for each endpoint, suggesting a high probability of substantial benefit from CRT when QRS duration exceeds this value. CONCLUSION: QRS duration is a powerful predictor of the effects of CRT on morbidity and mortality in patients with symptomatic HF and left ventricular systolic dysfunction who are in sinus rhythm. QRS morphology did not provide additional information about clinical response. CLINICALTRIALSGOV NUMBERS: NCT00170300, NCT00271154, NCT00251251.

Cardiorenal Syndrome: An Evolutionary Appraisal.

A recent American Heart Association Scientific Statement and Presidential Advisory recognized a new syndrome, the cardiovascular-kidney-metabolic syndrome. This expands our understanding of what has been called cardiorenal syndrome by incorporating the pathophysiological interrelatedness of metabolic risk factors into the previous concept of cardiorenal syndrome. Importantly, perturbation of cardiac or renal physiology combines to produce significant detrimental outcomes. The cardiorenal syndrome is a significant part of the cardiovascular-kidney-metabolic syndrome and contributes to health care cost, disability, and mortality. It is a vexing malady that has generated considerable interest. To understand the syndrome evaluation of its teleological origins is important. In life's beginning, eukaryotes acquired exocytosis for excretion, formed tubular secretory systems for clearance, and a mesenchymal nucleic acid vasoform for nutritional distribution. Those structures progressed to cardiovascular and renal systems of evolving organisms, whose migration to rivers and land imposed complex, coordinated, homeostatic roles to maintain intravascular stability. Tissue mineralization of vertebrate endoskeleton added renal calcium balance regulation, which in kidney failure results in cardiovascular calcification. Insight into cardiorenal disease can be traced to ancient Egyptian and Chinese medicine, through the Scientific Revolution, and into current insights regarding human physiology and pathophysiology. The post-World War II epidemic of cardiovascular mortality generated considerable information on cardiovascular disease, which being higher in patients with kidney disease, drew increasing health concerns. The cardiorenal syndrome was formally introduced in this setting with a focus on ultrafiltration to manage volume overload. An evolutionary review of insight into cardiorenal syndrome will help us better understand the new cardiovascular-kidney-metabolic syndrome.

When I Am Asked: Lisel Mueller's Beginning in Poetry.

Why does anyone write poetry? Lisel Mueller (1924-2020) was a poet, author, and translator with a long and much-decorated career. She and her family fled Nazi Germany in the 1930s and emigrated to the United States, where she would establish herself as a writer. The poem "When I Am Asked" describes the beginning of her journey into poetry, undertaken during a period of grief after the death of her mother. Her writing would come to include nine collections of poetry and myriad accolades, including the 1981 National Book Award and the 1997 Pulitzer Prize for Poetry. Though her ouvre is filled with evocative works, this piece stands out as particularly relevant to physicians and other writers who find solace by expressing themselves through the art of poetry.

Bruegel's Landscape with the Fall of Icarus.

Ovid's Metamorphoses tells the story of Icarus - his tragic flight with man-made wings, the melting of the wax that bound them, and the ensuing fall to his death. This moment has been immortalized across the arts and through several mediums, but none are more notable than Bruegel's Landscape with the Fall of Icarus. Described as a "painter for poets," Bruegel's work served as inspiration for several writers, with this piece in particular providing the basis for ekphrastic poems by W.H. Auden and William Carlos Williams. Though each of these works has a different focus, the unifying theme is that human tragedy is too often placed on the periphery of notice. They are effective reminders to physicians and other healthcare providers about the human aspect of suffering and pain in medicine.

An Obesity-Centric Approach with and Without Anti-Obesity Medications Compared to the Usual-Care Approach to Management of Patients with Obesity and Type 2 Diabetes in an Employer Setting: A Pragmatic Randomized Controlled Trial (EMPOWER-T2D).

INTRODUCTION: This study aimed to compare weight loss and glycated hemoglobin (HbA1c)-reduction effects of two obesity-centric, weight-loss management approaches (with or without anti-obesity medication) versus usual glucose-centric care in patients with obesity and type 2 diabetes. METHODS: Single-center, randomized, open-label, 3-armed, parallel-group, pragmatic, noninferiority trial, July 2020 to August 2022. Adults enrolled in the Cleveland Clinic Employee Health Plan (body mass index [BMI] ≥ 30 kg/m2, type 2 diabetes diagnosis, HbA1c > 7.5%) were randomized to usual glucose-centric management ("Usual-Care" group) or one of two obesity-centric management strategies: participation in a weight management program plus anti-obesity medication ("WMP + AOM" group), or WMP participation without anti-obesity medication ("WMP-Only" group). Primary endpoints were changes in weight and HbA1c, baseline to month 12. RESULTS: Due to enrollment and retention challenges, largely related to COVID-19, only 74/300 planned participants were randomized and the study was terminated early. Participants were predominantly female (59%), median (interquartile range [IQR]) age 53.5 (47, 60) years, 68% white, with baseline median (IQR) BMI and HbA1c of 37.4 (34.2, 42.7) kg/m2 and 8.8% (7.9%, 10.4%), respectively. At month 12, mean (90% confidence interval [CI]) percentage weight change in the Usual-Care, WMP-Only, and WMP + AOM groups was - 4.5% (- 6.5%, - 2.5%), - 6.7% (- 8.7%, - 4.7%), and - 8.7% (- 10.7%, - 6.8%), respectively; mean (90% CI) HbA1c change was - 1.7% (- 2.1%, - 1.2%), - 2.2% (- 2.7%, - 1.8%), and - 2.2% (- 2.6%, - 1.7%), respectively. WMP + AOM was superior to Usual-Care for weight change (P = 0.02); both WMP + AOM and WMP-Only were noninferior (P ≤ 0.01) to Usual-Care for change in HbA1c. CONCLUSIONS: Including anti-obesity medication was associated with superior weight loss with noninferior HbA1c reductions, warranting further evaluation in larger study populations of obesity-focused approaches to type 2 diabetes management. Graphical abstract available for this article. TRIAL REGISTRATION: ClinicalTrials.gov NCT03799198.

Truman Capote as a Poet.

Truman Capote (1924-1984) was a fascinating, entertaining, and much ballyhooed American character who came of age in the mid-Twentieth Century. Some would say he led a tragic life. Often described as a notable novelist, he was more generally a polymath dabbling in nonfiction between his parties. He also was a screenwriter, playwright, actor, and short-story writer. His literary classics include the novella Breakfast at Tiffany's (1958, movie 1961) and true crime nonfiction "novel" (as Capote described it) In Cold Blood (1965, movie 1967). These two efforts became his most famous. But what about his poetry? Was this one of his creative passions?

Old Ironsides.

Dr. Oliver Wendell Holmes Sr. was a 19th century elite physician, curmudgeon, essayist, and poet. His works were numerous, insightful, entertaining, and characteristic of the pre-Civil War, Civil War, and Gilded age eras. Many of his shorter poems are taught in high school as examples of late 19th century works, as they are relatively easy to memorize and understand. Holmes and the Fireside Poets (Emerson, Longfellow, and Lowell, among others) created works that, in their time, were read aloud by fathers and mothers to their family because the poems often centered around values, morals, and historic events. "Old Ironsides" is characteristic of the type of work for which the Fireside Poets became famous. It is an entertaining poem to read, study, and hear, particularly when linking it to the oldest ship in the world, still afloat and sailing around Boston Bay.

Up-Hill: An Allegory.

The Christina Rossetti poem "Up-Hill" (1862) is an exemplary poem of the Victorian era by one of the rare female poets of the time, including Emily Brontë, Elizabeth Browning, Katherine Tynan, and Alice Meynell. Rossetti, typical of the era and the Victorian genre, wrote allegories about faith and love. She came from a distinguished literary family. "Up-Hill" was one of her better-known works.

Do Not Go Gentle Into That Good Night.

Do not go gentle into that good night,Old age should burn and rave at close of day;Rage, rage against the dying of the light. Though wise men at their end know dark is right,Because their works had forked no lightning theyDo not go gentle into that good night. Good men, the last wave by, crying how brightTheir frail deeds might have danced in a green bay,Rage, rage against the dying of the light. Wild men who caught and sang the sun in flight,And learn, too late, they grieved it on its way,Do not go gentle into that good night. Grave men, near death, who see with blinding sightBlind eyes could blaze like meteors and be gay,Rage, rage against the dying of the light. And you, my father, there on the sad height,Curse, bless, me now with your fierce tears, I pray.Do not go gentle into that good night.Rage, rage against the dying of the light. Dylan ThomasThe Poems of Dylan Thomas, New Directions Publishing 1971. This poem is in the public domain.

Does Osler's Aequanimitas Inform Our Contemporary Pursuit of Stillness?

William Osler (1849-1919) was an academic physician who has been revered by many as an accomplished internist of his time. His contributions to the philosophy and practice of medicine foreground characteristics of a compassionate caregiver, including imperturbability and equanimity. This article defines these qualities, argues that Osler demonstrated both, and suggests how today's clinicians can apply these qualities to their own pursuits of stillness in their practices and relationships with patients.

Gertrude Stein: A Physician Who Wasn't to Be.

After a tumultuous time in the United States, including flunking out of medical school in 1901, Gertrude Stein, an iconic American author, art lover, and critic, moved to Paris in 1903 as an avant garde modernist who became a leading and legendary guru in the Parisian art and literature world.