How I treat pain in hematologic malignancies safely with opioid therapy.

The field of malignant hematology has experienced extraordinary advancements with survival rates doubling for many disorders. As a result, many life-threatening conditions have since evolved into chronic medical ailments. Paralleling these advancements have been increasing rates of complex hematologic pain syndromes, present in up to 60% of patients with malignancy who are receiving active treatment and up to 33% of patients during survivorship. Opioids remain the practice cornerstone to managing malignancy-associated pain. Prevention and management of opioid-related complications have received significant national attention over the past decade, and emerging data suggest that patients with cancer are at equal if not higher risk of opioid-related complications when compared with patients without malignancy. Numerous tools and procedural practice guides are available to help facilitate safe prescribing. The recent development of cancer-specific resources directing algorithmic use of validated pain screening tools, prescription drug monitoring programs, urine drug screens, opioid use disorder risk screening instruments, and controlled substance agreements have further strengthened the framework for safe prescribing. This article, which integrates federal and organizational guidelines with known risk factors for cancer patients, offers a case-based discussion for reviewing safe opioid prescribing practices in the hematology setting.

Psychologic wellness of PA, NP, and physician hospitalists during the COVID-19 pandemic.

OBJECTIVES: Hospitalists, comprising PAs, NPs, and physicians, manage patients hospitalized with COVID-19. To guide the development of support programs, this study compared the psychologic wellness of hospitalist PAs, NPs, and physicians during the COVID-19 pandemic. METHODS: We surveyed hospitalists in 16 hospitals at Mayo Clinic, from May 4 to 25, 2020. We used PROMIS surveys for self-reported global well-being (two single-item measures), anxiety, social isolation, and emotional support, before and during the pandemic. Linear and logistic regression models were adjusted for personal and professional factors. RESULTS: The response rate was 52.2% (N = 154/295). In adjusted linear regression models, the change in scores (before minus during pandemic) for anxiety, social isolation, and emotional support was similar for PAs and NPs compared with physicians. In adjusted logistic regression models, physicians, compared with PAs and NPs, had a higher odds of top global well-being for mental health (adjusted odds ratio [95% confidence interval]: 2.82 [1.12, 7.13]; P = .03) and top global well-being for social activities and relationships (adjusted odds ratio 4.08 [1.38, 12.08]; P = .01). CONCLUSIONS: During the COVID-19 pandemic, global well-being was lower for PAs and NPs compared with physician hospitalists. These results can guide support programs for hospitalists.

Tobacco use in the Myeloproliferative neoplasms: symptom burden, patient opinions, and care.

BACKGROUND: Patients with Philadelphia-negative Myeloproliferative Neoplasms (MPN) suffer from numerous symptoms and decreased quality of life. Smoking is associated with an increased symptom burden in several malignancies. The aim of this study was to analyze the association between smoking and MPN-related symptom burden and explore MPN patients' opinions on smoking. METHODS: A total of 435 patients with MPN participated in a cross-sectional internet-based survey developed by the Mayo Clinic and the Myeloproliferative Neoplasm Quality of Life Group. Patients reported their demographics, disease characteristics, tobacco use, and opinions on tobacco use. In addition, MPN-related symptoms were reported via the validated 10-item version of the Myeloproliferative Neoplasms Symptom Assessment Form. RESULTS: Current/former smokers reported worse fatigue (mean severity 5.6 vs. 5.0, p = 0.02) and inactivity (mean severity 4.0 vs. 3.4, p = 0.03) than never smokers. Moreover, current/former smokers more frequently experienced early satiety (68.5% vs. 58.3%, p = 0.03), inactivity (79.9% vs. 71.1%, p = 0.04), and concentration difficulties (82.1% vs. 73.1%, p = 0.04). Although not significant, a higher total symptom burden was observed for current/former smokers (mean 30.4 vs. 27.0, p = 0.07). Accordingly, overall quality of life was significantly better among never smokers than current/former smokers (mean 3.5 vs. 3.9, p = 0.03). Only 43.2% of the current/former smokers reported having discussed tobacco use with their physician, and 17.5% did not believe smoking increased the risk of thrombosis. CONCLUSION: The current study suggests that smoking may be associated with increased prevalence and severity of MPN symptoms and underscores the need to enhance patient education and address tobacco use in the care of MPN patients.

Relationship between symptom burden and disability leave among patients with myeloproliferative neoplasms (MPNs): findings from the Living with MPN patient survey.

Patients with myeloproliferative neoplasms (MPNs) experience burdensome symptoms that negatively affect their quality of life. How MPN symptoms relate with medical disability leave (MDL) among patients with the disease has not been previously examined. Using data collected from the Living with MPNs patient survey, symptom burden and functional status were compared in patients who reported taking MDL due to their MPN versus patients who reported no changes in employment status. Among 592 patients who were employed full- or part-time at diagnosis, 24.8% reported taking ≥ 1 MDL and 49.4% reported no change in employment status as a result of their MPN. Of the patients who took MDL, 29.9% took ≥ 2 MDLs, and most patients (62.6%) did not return to work. All 10 symptoms comprising the MPN Symptom Assessment Form were significantly more frequent and severe in patients who took MDL compared with those who had no employment change. Furthermore, functional impairments were also significantly more frequent among patients who went on MDL versus those with no employment change. Effective management of MPN-related symptoms may reduce disability leave among patients with high symptom burden.

Associations between gender, disease features and symptom burden in patients with myeloproliferative neoplasms: an analysis by the MPN QOL International Working Group.

The myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and myelofibrosis, are distinguished by their debilitating symptom profiles, life-threatening complications and profound impact on quality of life. The role gender plays in the symptomatology of myeloproliferative neoplasms remains under-investigated. In this study we evaluated how gender relates to patients' characteristics, disease complications and overall symptom expression. A total of 2,006 patients (polycythemia vera=711, essential thrombocythemia=830, myelofibrosis=460, unknown=5) were prospectively evaluated, with patients completing the Myeloproliferative Neoplasm-Symptom Assessment Form and Brief Fatigue Inventory Patient Reported Outcome tools. Information on the individual patients' characteristics, disease complications and laboratory data was collected. Consistent with known literature, most female patients were more likely to have essential thrombocythemia (48.6% versus 33.0%; P<0.001) and most male patients were more likely to have polycythemia vera (41.8% versus 30.3%; P<0.001). The rate of thrombocytopenia was higher among males than females (13.9% versus 8.2%; P<0.001) and males also had greater red-blood cell transfusion requirements (7.3% versus 4.9%; P=0.02) with shorter mean disease duration (6.4 versus 7.2 years, P=0.03). Despite there being no statistical differences in risk scores, receipt of most therapies or prior complications (hemorrhage, thrombosis), females had more severe and more frequent symptoms for most individual symptoms, along with overall total symptom score (22.8 versus 20.3; P<0.001). Females had particularly high scores for abdominal-related symptoms (abdominal pain/discomfort) and microvascular symptoms (headache, fatigue, insomnia, concentration difficulties, dizziness; all P<0.01). Despite complaining of more severe symptom burden, females had similar quality of life scores to those of males. The results of this study suggest that gender contributes to the heterogeneity of myeloproliferative neoplasms by influencing phenotypic profiles and symptom expression.

Comprehensively understanding fatigue in patients with myeloproliferative neoplasms.

BACKGROUND: Patients with myeloproliferative neoplasms (MPNs) experience a high persistence, prevalence, and severity of fatigue. There is currently only limited information regarding factors that contribute to fatigue in patients with MPNs. METHODS: A 70-item, Internet-based survey regarding fatigue was developed by MPN investigators and patients/advocates and hosted by the Mayo Clinic Survey Research Center. RESULTS: Fatigue was found to be prevalent and severe among international survey respondents (1788 respondents). Higher body mass index (P<.001), current use of alcohol (P<.001), and current tobacco use (P = .0025) were found to be significantly associated with greater fatigue. Moderate/severe fatigue was present more frequently in those individuals who did not exercise compared with those who reported exercising at least once per week (P<.001). Medical comorbidities found to be significantly associated with greater fatigue included restless leg syndrome (P = .006), diabetes mellitus (P = .045), fibromyalgia (P < 0.001), chronic fatigue syndrome (P = .006), and chronic kidney disease (P = .02). Current use of antidepressants (P<.001), antihistamines (P = .0276), antianxiety medications (P = .0357), and prescription pain medications (P<.001) were found to be associated with worsened fatigue. Nearly 25% of respondents scored > 2 on the Patient Health Questionnaire, indicating a high probability of depression. Higher Brief Fatigue Inventory score, Myeloproliferative Neoplasm Total Symptom Score, and individual symptom items were all associated with a higher likelihood of depressive symptoms (P<.0001). CONCLUSIONS: The management of fatigue should be multifactorial, with a comprehensive assessment and treatment plan to address all modifiable fatigue etiologies. Patients with MPNs likely have a higher prevalence of mood disturbances compared with the general population, suggesting the need to assess and intervene in this domain.

The role of sexuality symptoms in myeloproliferative neoplasm symptom burden and quality of life: An analysis by the MPN QOL International Study Group.

BACKGROUND: Patients with myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and myelofibrosis, are faced with oppressive symptom profiles that compromise daily functioning and quality of life. Among these symptoms, sexuality-related symptoms have emerged as particularly prominent and largely unaddressed. In the current study, the authors evaluated how sexuality symptoms from MPN relate to other patient characteristics, disease features, treatments, and symptoms. METHODS: A total of 1971 patients with MPN (827 with essential thrombocythemia, 682 with polycythemia vera, 456 with myelofibrosis, and 6 classified as other) were prospectively evaluated and patient responses to the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ C30) were collected, along with information regarding individual disease characteristics and laboratory data. Sexuality scores were compared with an age-matched, healthy control population. RESULTS: Overall, patients with MPN were found to have greater sexual dysfunction compared with the healthy population (MPN-SAF score of 3.6 vs 2.0; P<.001), with 64% of patients with MPN describing some degree of sexual dysfunction and 43% experiencing severe symptoms. The presence of sexual symptoms correlated closely with all domains of patient functionality (physical, social, cognitive, emotional, and role functioning) and were associated with a reduced quality of life. Sexual problems also were found to be associated with other MPN symptoms, particularly depression and nocturnal and microvascular-related symptoms. Sexual dysfunction was more severe in patients aged >65 years and in those with cytopenias and transfusion requirements, and those receiving certain therapies such as immunomodulators or steroids. CONCLUSIONS: The results of the current study identify the topic of sexuality as a prominent issue for the MPN population, and this area would appear to benefit from additional investigation and management. Cancer 2016;122:1888-96. © 2016 American Cancer Society.

Therapy for myeloproliferative neoplasms: when, which agent, and how?

Myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocythemia, and myelofibrosis (MF) (both primary and secondary), are recognized for their burdensome symptom profiles, life-threatening complications, and risk of progression to acute leukemia. Recent advancements in our ability to diagnose and prognosticate these clonal malignancies have paralleled the development of MPN-targeted therapies that have had a significant impact on disease burden and quality of life. Ruxolitinib has shown success in alleviating the symptomatic burden, reducing splenomegaly and improving quality of life in patients with MF. The role and clinical expectations of JAK2 inhibition continues to expand to a variety of investigational arenas. Clinical trials for patients with MF focus on new JAK inhibitors with potentially less myelosuppression( pacritinib) or even activity for anemia (momelotinib). Further efforts focus on combination trials (including a JAK inhibitor base) or targeting new pathways (ie, telomerase). Similarly, therapy for PV continues to evolve with phase 3 trials investigating optimal frontline therapy (hydroxyurea or IFN) and second-line therapy for hydroxyurea-refractory or intolerant PV with JAK inhibitors. In this chapter, we review the evolving data and role of JAK inhibition (alone or in combination) in the management of patients with MPNs.

Distinct clustering of symptomatic burden among myeloproliferative neoplasm patients: retrospective assessment in 1470 patients.

Symptom burden in myeloproliferative neoplasms (MPNs) is heterogeneous even among patients within the same MPN diagnosis. Using cluster analysis from prospectively gathered symptom burden data in 1470 international patients with essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF), we assessed for the presence of clusters and relationship to disease features and prognosis. In MF (4 clusters identified), clusters significantly differed by Dynamic International Prognostic Scoring System (DIPSS) risk (P < .001), leukopenia (P = .009), thrombocytopenia (P < .001), and spleen size (P = .02). Although an association existed between clusters and DIPSS risk, high symptom burden was noted in some low and intermediate-1-risk MF patients. In PV (5 clusters identified), total symptom score increased across clusters (P < .001), but clusters did not significantly differ by PV risk or the risk assessment variable of age. Among ET patients (5 clusters identified), clusters differed by gender (P = .04), anemia (P = .01), and prior hemorrhage (P = .047). Total symptom score increased across clusters (P < .001), but clusters did not significantly differ by International Prognostic Score for ET risk including the risk assessment variables. Significant symptom heterogeneity exists within each MPN subtype, sometimes independent of disease features or prognosis.

Emerging drugs for the treatment of myelofibrosis.

INTRODUCTION: Myelofibrosis (MF) is a myeloproliferative neoplasm associated with significant disease burden composed of splenomegaly, constitutional symptoms and a reduced life expectancy. The advent of targeted treatments has provided new means by which to improve MF associated splenomegaly, symptoms, health-related quality of life and even mortality. AREAS COVERED: We discuss the spectrum of targeted treatments currently under investigation for MF. We furthermore compare their effects on improving anemia, reducing fibrosis and splenomegaly and enhancing symptom control. EXPERT OPINION: MF is a complex disorder, partly attributable to its heterogeneity. Although the severity of patient symptoms correlates with risk category, high symptom burden may also be observed in low-risk patients. Serial use of PRO tools allows clinicians to objectively evaluate the MF symptom burden, compare efficacy of therapies and adjust medications to improve symptom control. Novel targeted agents have proven superior to historic treatment regimens for symptom management. Promising treatment categories include JAK2 inhibitors, histone deacetylase inhibitors, hypomethylating agents, heat shock protein-90 inhibitors, hedgehog inhibitors, PI3-AKT-mTOR inhibitors, antifibrosing agents and telomerase inhibitors. The majority of therapies remain under investigation, either alone or in combination with other treatments. It is anticipated that these agents will be increasingly integrated into standard treatment algorithms for MF symptom management.

Impact of Inflammation on Myeloproliferative Neoplasm Symptom Development.

Myeloproliferative neoplasms (essential thrombocythemia, ET; polycythemia vera, PV; myelofibrosis, MF) are monoclonal malignancies associated with genomic instability, dysregulated signaling pathways, and subsequent overproduction of inflammatory markers. Acknowledged for their debilitating symptom profiles, recent investigations have aimed to determine the identity of these markers, the upstream sources stimulating their development, their prevalence within the MPN population, and the role they play in symptom development. Creation of dedicated Patient Reported Outcome (PRO) tools, in combination with expanded access to cytokine analysis technology, has resulted in a surge of investigations evaluating the potential associations between symptoms and inflammation. Emerging data demonstrates clear relationships between individual MPN symptoms (fatigue, abdominal complaints, microvascular symptoms, and constitutional symptoms) and cytokines, particularly IL-1, IL-6, IL-8, and TNF-α. Information is also compiling on the role symptoms paradoxically play in the development of cytokines, as in the case of fatigue-driven sedentary lifestyles. In this paper, we explore the symptoms inherent to the MPN disorders and the potential role inflammation plays in their development.

Global well-being, anxiety, social isolation, and emotional support among hospitalists during COVID-19 and Mpox outbreaks.

OBJECTIVE: The Coronavirus Disease-19 (COVID-19) pandemic caused a decline in hospitalist wellness. The COVID-19 pandemic has evolved, and new outbreaks (i.e. Mpox) have challenged healthcare systems. The objective of the study was to assess changes in hospitalist wellness and guide interventions. METHODS: We surveyed hospitalists (physicians and advanced practice providers [APPs]), in May 2021 and September 2022, at a healthcare system's 16 hospitals in four US states using PROMIS® measures for global well-being, anxiety, social isolation, and emotional support. We compared wellness score between survey periods; in the September 2022 survey, we compared wellness scores between APPs and physicians and evaluated the associations of demographic and hospital characteristics with wellness using logistic (global well-being) and linear (anxiety, social isolation, emotional support) regression models. RESULTS: In May 2021 vs. September 2022, respondents showed no statistical difference in top global well-being for mental health (68.4% vs. 57.4%) and social activities and relationships (43.8% vs. 44.3%), anxiety (mean difference: +0.8), social isolation (mean difference: +0.5), and emotional support (mean difference: -1.0) (all, p ≥ 0.05). In September 2022, in logistic regression models, APPs, compared with physicians, had lower odds for top (excellent or very good) global well-being mental health (odds ratio [95% CI], 0.31 [0.13-0.76]; p < 0.05). In linear regression models, age <40 vs. ≥40 years was associated with higher anxiety (estimate ± standard error, 2.43 ± 1.05; p < 0.05), and concern about contracting COVID-19 at work was associated with higher anxiety (3.74 ± 1.10; p < 0.01) and social isolation (3.82 ± 1.21; p < 0.01). None of the characteristics showed association with change in emotional support. In September 2022, there was low concern for contracting Mpox in the community (4.6%) or at work (10.0%). CONCLUSION: In hospitalists, concern about contracting COVID-19 at work was associated with higher anxiety and social isolation. The unchanged wellness scores between survey periods identified opportunities for intervention. Mpox had apparently minor impact on wellness.

Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial.

PURPOSE: Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms. PATIENTS AND METHODS: MAJIC-PV is a randomized phase II trial of ruxolitinib versus best available therapy (BAT) in patients resistant/intolerant to hydroxycarbamide (HC-INT/RES). Primary outcome was complete response (CR) within 1 year. Secondary outcomes included duration of response, event-free survival (EFS), symptom, and molecular response. RESULTS: One hundred eighty patients were randomly assigned. CR was achieved in 40 (43%) patients on ruxolitinib versus 23 (26%) on BAT (odds ratio, 2.12; 90% CI, 1.25 to 3.60; P = .02). Duration of CR was superior for ruxolitinib (hazard ratio [HR], 0.38; 95% CI, 0.24 to 0.61; P < .001). Symptom responses were better with ruxolitinib and durable. EFS (major thrombosis, hemorrhage, transformation, and death) was superior for patients attaining CR within 1 year (HR, 0.41; 95% CI, 0.21 to 0.78; P = .01); and those on ruxolitinib (HR, 0.58; 95% CI, 0.35 to 0.94; P = .03). Serial analysis of JAK2V617F variant allele fraction revealed molecular response was more frequent with ruxolitinib and was associated with improved outcomes (progression-free survival [PFS] P = .001, EFS P = .001, overall survival P = .01) and clearance of JAK2V617F stem/progenitor cells. ASXL1 mutations predicted for adverse EFS (HR, 3.02; 95% CI, 1.47 to 6.17; P = .003). The safety profile of ruxolitinib was as previously reported. CONCLUSION: The MAJIC-PV study demonstrates ruxolitinib treatment benefits HC-INT/RES PV patients with superior CR, and EFS as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to EFS, PFS, and OS.

Wellness of hospitalists and hospital medicine advanced practice providers during the COVID-19 pandemic, 2020-2021.

BACKGROUND: The early phase of the coronavirus disease 2019 (COVID-19) pandemic had a negative impact on the wellness of hospitalists and hospital medicine advanced practice providers (APPs). However, the burden of the pandemic has evolved and the change in hospitalist and hospital medicine APP wellness is unknown. OBJECTIVE: To evaluate the longitudinal trend in wellness of hospitalists and hospital medicine APPs during the COVID-19 pandemic and guide wellness interventions. DESIGN, SETTING AND PARTICIPANTS: Between May 4, 2020, and June 6, 2021, we administered three surveys to Internal Medicine hospitalists (physicians) and hospital medicine APPs (nurse practitioners and physician assistants) at 16 Mayo Clinic hospitals in four U.S. states. MEASUREMENTS: We evaluated the association of hospitalist and hospital medicine APP characteristics with PROMIS® measures of global wellbeing-mental health, global wellbeing-social activities and relationships, anxiety, social isolation, and emotional support, using logistic and linear regression models. RESULTS: The response rates were 52.2% (n=154/295; May 2020), 37.1% (n=111/299; October 2020) and 35.5% (n=114/321; May 2021). In mixed models that included hospitalist and hospital medicine APP characteristics and survey period, APPs, compared with physicians, had lower odds of top global wellbeing-social activities and relationships (adjusted odds ratio 0.42 [0.22-0.82]; p = .01), whereas survey period showed no association. The survey period showed an independent association with higher anxiety (May 2020 vs. others) and higher social isolation (October 2020 vs. others), whereas profession showed no association. Concern about contracting COVID-19 at work was significantly associated with lower odds of top global wellbeing-mental health and global wellbeing-social activities and relationships, and with higher anxiety and social isolation. Hospitalist and hospital medicine APP characteristics showed no association with levels of emotional support. CONCLUSIONS: In this longitudinal assessment of hospitalists and hospital medicine APPs, concern about contracting COVID-19 at work remained a determinant of wellness. The trend for global wellbeing, anxiety, and social isolation may guide wellness interventions.

Surveillance of Safety of 3 Doses of COVID-19 mRNA Vaccination Using Electronic Health Records.

Importance: Recent reports on waning of COVID-19 vaccine-induced immunity have led to the approval and rollout of additional doses and booster vaccinations. Individuals at increased risk of SARS-CoV-2 infection are receiving additional vaccine doses in addition to the regimen that was tested in clinical trials. Risks and adverse event profiles associated with additional vaccine doses are currently not well understood. Objective: To evaluate the safety of third-dose vaccination with US Food and Drug Administration (FDA)-approved COVID-19 mRNA vaccines. Design, Setting, and Participants: This cohort study was conducted using electronic health record (EHR) data from December 2020 to October 2021 from the multistate Mayo Clinic Enterprise. Participants included all 47 999 individuals receiving 3-dose COVID-19 mRNA vaccines within the study setting who met study inclusion criteria. Participants were divided into 2 cohorts by vaccine brand administered and served as their own control groups, with no comparison made between cohorts. Data were analyzed from September through November 2021. Exposures: Three doses of an FDA-authorized COVID-19 mRNA vaccine, BNT162b2 or mRNA-1273. Main Outcomes and Measures: Vaccine-associated adverse events were assessed via EHR report. Adverse event risk was quantified using the percentage of study participants who reported the adverse event within 14 days after each vaccine dose and during a 14-day control period, immediately preceding the first vaccine dose. Results: Among 47 999 individuals who received 3-dose COVID-19 mRNA vaccines, 38 094 individuals (21 835 [57.3%] women; median [IQR] age, 67.4 [52.5-76.5] years) received BNT162b2 (79.4%) and 9905 individuals (5099 [51.5%] women; median [IQR] age, 67.7 [59.5-73.9] years) received mRNA-1273 (20.6%). Reporting of severe adverse events remained low after the third vaccine dose, with rates of pericarditis (0.01%; 95% CI, 0%-0.02%), anaphylaxis (0%; 95% CI, 0%-0.01%), myocarditis (0%; 95% CI, 0%-0.01%), and cerebral venous sinus thrombosis (no individuals) consistent with results from earlier studies. Significantly more individuals reported low-severity adverse events after the third dose compared with after the second dose, including fatigue (2360 individuals [4.92%] vs 1665 individuals [3.47%]; P < .001), lymphadenopathy (1387 individuals [2.89%] vs 995 individuals [2.07%]; P < .001), nausea (1259 individuals [2.62%] vs 979 individuals [2.04%]; P < .001), headache (1185 individuals [2.47%] vs 992 individuals [2.07%]; P < .001), arthralgia (1019 individuals [2.12%] vs 816 individuals [1.70%]; P < .001), myalgia (956 individuals [1.99%] vs 784 individuals [1.63%]; P < .001), diarrhea (817 individuals [1.70%] vs 595 individuals [1.24%]; P < .001), fever (533 individuals [1.11%] vs 391 individuals [0.81%]; P < .001), vomiting (528 individuals [1.10%] vs 385 individuals [0.80%]; P < .001), and chills (224 individuals [0.47%] vs 175 individuals [0.36%]; P = .01). Conclusions and Relevance: This study found that although third-dose vaccination against SARS-CoV-2 infection was associated with increased reporting of low-severity adverse events, risk of severe adverse events remained comparable with risk associated with the standard 2-dose regime. These findings suggest the safety of third vaccination doses in individuals who were eligible for booster vaccination at the time of this study.

Comparative effectiveness of mRNA-1273 and BNT162b2 against symptomatic SARS-CoV-2 infection.

BACKGROUND: mRNA coronavirus disease 2019 (COVID-19) vaccines are safe and effective, but increasing reports of breakthrough infections highlight the need to vigilantly monitor and compare the effectiveness of these vaccines. METHODS: We retrospectively compared protection against symptomatic infection conferred by mRNA-1273 and BNT162b2 at Mayo Clinic sites from December 2020 to September 2021. We used a test-negative case-control design to estimate vaccine effectiveness (VE) and to compare the odds of symptomatic infection after full vaccination with mRNA-1273 versus BNT162b2, while adjusting for age, sex, race, ethnicity, geography, comorbidities, and calendar time of vaccination and testing. FINDINGS: Both vaccines were highly effective over the study duration (VEmRNA-1273: 84.1%, 95% confidence interval [CI]: 81.6%-86.2%; VEBNT162b2: 75.6%, 95% CI: 72.2%-78.7%), but their effectiveness was reduced during July-September (VEmRNA-1273: 75.6%, 95% CI: 70.1%-80%; VEBNT162b2: 63.5%, 95% CI: 55.8%-69.9%) as compared to December-May (VEmRNA-1273: 93.7%, 95% CI: 90.4%-95.9%; VEBNT162b2: 85.7%, 95% CI: 81.4%-88.9%). Adjusted for demographic characteristics, clinical comorbidities, time of vaccination, and time of testing, the odds of experiencing a symptomatic breakthrough infection were lower after full vaccination with mRNA-1273 than with BNT162b2 (odds ratio: 0.60; 95% CI: 0.55-0.67). CONCLUSIONS: Both mRNA-1273 and BNT162b2 strongly protect against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It is imperative to continue monitoring and comparing available vaccines over time and with respect to emerging variants to inform public and global health decisions. FUNDING: This study was funded by nference.

Durability analysis of the highly effective BNT162b2 vaccine against COVID-19.

COVID-19 vaccines are effective, but breakthrough infections have been increasingly reported. We conducted a test-negative case-control study to assess the durability of protection after full vaccination with BNT162b2 against polymerase chain reaction (PCR)-confirmed symptomatic SARS-CoV-2 infection, in a national medical practice from January 2021 through January 2022. We fit conditional logistic regression (CLR) models stratified on residential county and calendar time of testing to assess the association between time elapsed since vaccination and the odds of symptomatic infection or non-COVID-19 hospitalization (negative control), adjusted for several covariates. There were 5,985 symptomatic individuals with a positive test after full vaccination with BNT162b2 (cases) and 32,728 negative tests contributed by 27,753 symptomatic individuals after full vaccination (controls). The adjusted odds of symptomatic infection were higher 250 days after full vaccination versus at the date of full vaccination (Odds Ratio [OR]: 3.62, 95% CI: 2.52 to 5.20). The odds of infection were still lower 285 days after the first BNT162b2 dose as compared to 4 days after the first dose (OR: 0.50, 95% CI: 0.37 to 0.67), when immune protection approximates the unvaccinated status. Low rates of COVID-19 associated hospitalization or death in this cohort precluded analyses of these severe outcomes. The odds of non-COVID-19 associated hospitalization (negative control) decreased with time since vaccination, suggesting a possible underestimation of waning protection by this approach due to confounding factors. In summary, BNT162b2 strongly protected against symptomatic SARS-CoV-2 infection for at least 8 months after full vaccination, but the degree of protection waned significantly over this period.

Durability analysis of the highly effective mRNA-1273 vaccine against COVID-19.

COVID-19 vaccines are effective, but breakthrough infections have been increasingly reported. We conducted a test-negative case-control study to assess the durability of protection against symptomatic infection after vaccination with mRNA-1273. We fit conditional logistic regression (CLR) models stratified on residential county and calendar date of SARS-CoV-2 PCR testing to assess the association between the time elapsed since vaccination and the odds of symptomatic infection, adjusted for several covariates. There were 2,364 symptomatic individuals who had a positive SARS-CoV-2 PCR test after full vaccination with mRNA-1273 ("cases") and 12,949 symptomatic individuals who contributed 15,087 negative tests after full vaccination ("controls"). The odds of symptomatic infection were significantly higher 250 days after full vaccination compared to the date of full vaccination (Odds Ratio [OR]: 2.47, 95% confidence interval [CI]: 1.19-5.13). The odds of non-COVID-19 associated hospitalization and non-COVID-19 pneumonia (negative control outcomes) remained relatively stable over the same time interval (Day 250 ORNon-COVID Hospitalization: 0.68, 95% CI: 0.47-1.0; Day 250 ORNon-COVID Pneumonia: 1.11, 95% CI: 0.24-5.2). The odds of symptomatic infection remained significantly lower almost 300 days after the first mRNA-1273 dose as compared to 4 days after the first dose, when immune protection approximates the unvaccinated state (OR: 0.26, 95% CI: 0.17-0.39). Low rates of COVID-19 associated hospitalization or death in this cohort precluded analyses of these severe outcomes. In summary, mRNA-1273 robustly protected against symptomatic SARS-CoV-2 infection at least 8 months after full vaccination, but the degree of protection waned over this time period.

Psychological wellness of internal medicine hospitalists during the COVID-19 pandemic.

BACKGROUND: Patients with COVID-19 infection requiring in-hospital care are frequently managed by Internal Medicine hospitalists, comprised of physicians, nurse practitioners and physician assistants. There is sparse information on the psychological impact of the COVID-19 pandemic on Internal Medicine hospitalists. METHODS: We surveyed Internal Medicine hospitalists at Mayo Clinic sites in four states (Arizona, Florida, Minnesota, and Wisconsin). We collected demographic information, and used Patient-Reported Outcomes Measurement Information System (PROMIS®) measures to assess global well-being, anxiety, social isolation, and emotional support. Descriptive statistics were used to compare responses between two periods: prior to the pandemic (before March 15th, 2020), and during the pandemic (March 15 through 30 April 2020). The survey was conducted from May 4-25, 2020. RESULTS: Of 295 Internal Medicine hospitalists, 154 (52%) responded. Fifty-six percent were women (n = 85/154) and 54% were physicians (n = 84/154). Most hospitalists (75%; n = 115/154) reported concerns about contracting COVID-19 infection at work, and 5% (n = 8/154) reported changing where they lived during the pandemic. Most hospitalists (73%; n = 112/154) reported relying primarily on institutional resources for COVID-19 information. During the pandemic, the percentage of participants with excellent or very good global well-being decreased (90% prior to pandemic vs. 53% during pandemic), with increases in mean anxiety (-4.88 [95% confidence interval, - 5.61 to - 4.16]; P<.001) and social isolation (-3.91[95% confidence interval, - 4.68 to - 3.13]; P<.001). During the same period, there was a small decrease in mean emotional support (1.46 [95% confidence interval, 0.83 to 2.09]; P<.001). CONCLUSION: During the COVID-19 pandemic, Internal Medicine hospitalists reported lower global well-being, higher anxiety and social isolation, and a small decrease in emotional support. These results provide a framework to develop programs to support hospitalists and potentially mitigate long-term psychological sequelae including burnout.