Development of a Model to Identify Febrile Children at Low Risk for Multisystem Inflammatory Syndrome.

OBJECTIVES: The case definition for multisystem inflammatory syndrome in children (MIS-C) is broad and encompasses symptoms and signs commonly seen in children with fever. Our aim was to identify clinical predictors that, independently or in combination, identify febrile children presenting to the emergency department (ED) as low risk for MIS-C. METHODS: We conducted a retrospective single-center study of otherwise healthy children 2 months to 20 years of age presenting to the ED with fever and who had a laboratory evaluation for MIS-C between April 15, 2020, and October 31, 2020. We excluded children with a diagnosis of Kawasaki disease. Our outcome was an MIS-C diagnosis defined by the Centers for Disease Control and Prevention criteria. We conducted multivariable logistic regression analyses to identify variables independently associated with MIS-C. RESULTS: Thirty-three patients with and 128 patients without MIS-C were analyzed. Of those with MIS-C, 16 of 33 (48.5%) had hypotension for age, signs of hypoperfusion, or required ionotropic support. Four variables were independently associated with the presence of MIS-C; known or suspected SARS CoV-2 exposure (adjusted odds ratio [aOR], 4.0; 95% confidence interval [CI], 1.4-11.9) and the following 3 symptoms and signs: abdominal pain on history (aOR, 4.8; 95% CI, 1.7-15.0), conjunctival injection (aOR, 15.2; 95% CI, 5.4-48.1), and rash involving the palms or soles (aOR, 12.2; 95% CI, 2.4-69.4). Children were at low risk of MIS-C if none of the 3 symptoms or signs were present (sensitivity 87.9% [95% CI, 71.8-96.6]; specificity 62.5% [53.5-70.9], negative predictive value 95.2% [88.3-98.7]). Of the 4 MIS-C patients without any of these 3 factors, 2 were ill-appearing in the ED and the other 2 had no cardiovascular involvement during their clinical course. CONCLUSIONS: A combination of 3 clinical symptoms and signs had moderate to high sensitivity and high negative predictive value for identifying febrile children at low risk of MIS-C. If validated, these factors could aid clinicians in determining the need to obtain or forego an MIS-C laboratory evaluation during SARS-CoV-2 prevalent periods in febrile children.

Discriminating Multisystem Inflammatory Syndrome in Children Requiring Treatment from Common Febrile Conditions in Outpatient Settings.

OBJECTIVES: To examine whether patients with multisystem inflammatory syndrome in children (MIS-C) demonstrated well-defined clinical features distinct from other febrile outpatients, given the difficulties of seeing acute care visits during the severe acute respiratory syndrome coronavirus 2 pandemic and the risks associated with both over- and underdiagnosis of MIS-C. STUDY DESIGN: This case-controlled study compared patients diagnosed with and treated for MIS-C at a large urban children's hospital with patients evaluated for fever at outpatient acute care visits during the peak period of MIS-C. Symptomatology and available objective data were extracted. Comparisons were performed using t tests with corrections for multiple comparisons, and multivariable logistic regression to obtain ORs. RESULTS: We identified 44 patients with MIS-C between April 16 and June 10, 2020. During the same period, 181 pediatric patients were evaluated for febrile illnesses in participating outpatient clinics. Patients with MIS-C reported greater median maximum reported temperature height (40°C vs 38.9, P < .0001), and increased frequency of abdominal pain (OR 12.5, 95% CI [1.65-33.24]), neck pain (536.5, [2.23-129,029]), conjunctivitis (31.3, [4.6-212.8]), oral mucosal irritation (11.8, [1.4-99.4]), extremity swelling or rash (99.9, [5-1960]), and generalized rash (7.42, [1.6-33.2]). Patients with MIS-C demonstrated lower absolute lymphocyte (P < .0001) and platelet counts (P < .05) and greater C-reactive protein concentrations (P < .001). CONCLUSIONS: Patients treated for MIS-C due to concern for potential cardiac injury show combinations of features distinct from other febrile patients seen in outpatient clinics during the same period.

Supporting a Culture of Wellness: Examining the Utility of the Residency Program Community Well-Being Instrument in the Medical Training and Work Environment.

Physicians are experiencing symptoms of burnout at unprecedented rates. It is essential to assess programmatic factors contributing to physician burnout as actionable items for work climate improvement. Creation of an evidence base of strategies and methods to cultivate a culture of wellness requires iterative assessment, program development and implementation, and evaluation. To serve their function optimally, assessment tools need to be reliable, valid, and sensitive to change. In this Invited Commentary, the authors discuss Vermette and colleagues' report on the Residency Community Well-Being (RCWB) instrument. The authors examine the utility of the RCWB, a novel, validated tool that quantifies the subjective community well-being of an individual residency program and has 3 subscales that measure key aspects of interpersonal interactions among residents, with emphasis on those within the program leadership sphere of influence. The commentary authors recommend further validation of the RCWB, but acknowledge the instrument is a useful contribution to currently available measures in the domains of community well-being, workplace climate, and culture of wellness. Workplace interventions focused on community well-being or culture of wellness are particularly salient ethical and educational priorities for medical training programs. Prioritizing community well-being will help nurture trainees as an investment in the future of medical care, rather than an exploitable resource valued primarily for short-term work demands.

Shifting Perspectives: A Qualitative Study to Understand Family Expectations at the Time of Their Child's Admission.

Purpose: Patient-centered approaches to health care acknowledge the important role that families have in patients' lives. Shared expectations between families and providers have the potential to improve patient and family experience, hospital care, and outcomes. We aimed to understand families' expectations for their child's admission from the vantage point of the start of a hospital stay. Methods: This qualitative research studied families of hospitalized children at a large pediatric tertiary care center. Family members were approached if their child was admitted to the general pediatrics team, was under 18 years of age, had a length of stay less than 5 days, and had an English-speaking family member present. Semi-structured interviews were conducted by study personnel during the inpatient stay and audio-recorded. Written transcripts were independently coded by multiple investigators to generate codes, which were reconciled via triangulation. Codes were translated into broad themes to provide insight into the views of the study population. An accompanying survey included demographic questions. Results: We conducted 20 interviews with 23 parents of hospitalized children. Participants were 83% female, 35% White, 22% Black, 35% Hispanic, and 70% publicly insured. Participant responses led to identification of 4 themes: 1) setting the stage; 2) building trust and credibility; 3) partnering with families; and 4) maintaining frequent and transparent communication. Conclusions: Findings suggest that families' priorities and expectations at the start of their inpatient stay focus on issues of trust, partnership, and communication. These concepts may help providers strengthen communication and create more meaningful partnerships with families.

Selective serotonin reuptake inhibitors associated with increased mortality risk in breast cancer patients in Northern Israel.

BACKGROUND: Approximately one in six women in the USA takes antidepressants and a third use selective serotonin reuptake inhibitors (SSRIs) after breast cancer diagnosis. Recent investigation demonstrated serotonin receptor (5-HTR2B) expression in the breast and serotonin production as an indicator of poor breast cancer prognosis. This study investigates the association between SSRI use at different time intervals relative to breast cancer diagnosis on survival. METHODS: A population-based sample of 6959 consecutive, newly diagnosed breast cancer cases in Northern Israel was included. Patients were recruited from January 2000 and followed up through March 2020. Participants completed risk factor questionnaires regarding medical, reproductive and family history, medication use and health habits. Full prescription data were available through the Israeli national Clalit medical database. Multivariate Cox proportional hazard models were used to determine survival based on time of SSRI use. RESULTS: Use of SSRIs in the 5 years prior to breast cancer diagnosis was associated with a 66% increase in overall mortality (HRadj = 1.66; CI: 1.05-2.63). SSRI use that initiated after breast cancer diagnosis was associated with an 81% increase in mortality (HRadj = 1.81; CI: 1.58-2.06). Use of SSRIs in the 5 years post-diagnosis was associated with a dose-response increase (P < 0.001) in long-term mortality (>5 years). Heavy SSRI use (≥24 prescription fills) after diagnosis was associated with nearly doubling in mortality (HR = 1.99; CI: 1.39-2.83). CONCLUSION: SSRI use prior to and after breast cancer diagnosis is associated with increased mortality in breast cancer patients. Additional research is needed to better understand mechanisms mediating this association.

Views from the trenches: California family physicians' challenges and resilience factors while providing patient care during the initial wave of COVID-19.

This study examined challenges and factors promoting resilience among 20 California family physicians (FPs) during the first six months of the COVID-19 pandemic. A subset of academic, community, and resident FPs who responded to an online survey also participated in a semi-structured interview that explored concerns, moral distress, burnout, resource needs, support systems, coping strategies, and motivation to continue caring for patients. Thematic analysis was used to identify common themes in participant interviews. Interviewees demonstrated adaptability, resilience, and grit (i.e., commitment to completing a valued goal in the face of setbacks and adversity) despite challenges disrupting patient care, fears for family and self, and frustration due to the politicization of the pandemic. Factors promoting well-being and perseverance included professional and personal support, strong coping skills, and focusing on the meaning derived from practicing medicine. A service orientation that permeates family medicine philosophy and values motivated practitioners to continue to provide patient care while dealing with overwhelming personal and structural challenges. FPs drew strength from their internal coping skills, core family medicine values, and external support, notwithstanding demoralizing effects of mixed messages and politicization of the pandemic. FPs demonstrated resilience and grit in the face of challenges created by the COVID-19 pandemic. Ensuring adequate resources to promote a physically and psychologically healthy workforce while increasing access to care for all patients is crucial to prepare for the next healthcare crisis.

Aroma Acupoint Therapy for Symptom Management with Adolescent Patients: Early Experiences from School-Based Health Centers.

Objectives: The American Academy of Pediatrics has long recognized a need for more resources for integrative medicine for health care providers and for patients. The aim of this study was to introduce Aroma Acupoint Therapy (AAT)-a relatively new integrative medicine modality using essential oils to activate acupoints-and to describe the early experiences of providers using AAT for adolescents at school-based health centers (SBHCs). Materials and Methods: This was a case series of 15 adolescents treated with 1 of 2 AAT specific protocols plus standard medical therapy between April 2018 and February 2019 at SBHCs. Of these 15 patients, ages 12-19, 14 were female. Clinical characteristics and treatment courses were abstracted by retrospective review of the patients' electronic medical records. The main outcomes and measures for this research were clinical characteristics, treatment courses and pre- and post-treatment pain scores for adolescents treated with AAT. Results: All 15 patients had nonspecific symptoms, including headaches, menstrual cramps, nausea, shortness of breath, chest pain, back pain, or dizziness. Pain scores were recorded in 8 of 15 encounters, and suggested improvements in most patients. Subjective documentation by the providers also suggested that most of these patients had reduced symptoms. Conclusions: With the call for nonopiate and integrative approaches to pain management, there is an urgent need to study the effectiveness of such modalities, such as AAT. It is safe, inexpensive, easy to learn, and is well-received by both health care providers and patients.

A Clinical Pathway for Hospitalized Pediatric Patients With Initial SARS-CoV-2 Infection.

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread quickly across the globe, creating unique and pressing challenges for today's physicians. Although this virus disproportionately affects adults, initial SARS-CoV-2 infection can present a significant disease burden for the pediatric population. A review of the literature yields descriptive studies in pediatric patients; however, no evidence-based or evidence-informed guidelines for the diagnosis and treatment of the hospitalized pediatric patient have been published in peer-reviewed journals. The authors, working at a quaternary care children's hospital in the national epicenter of the SARS-CoV-2 pandemic, found an urgent need to create a unified, multidisciplinary, evidence-informed set of guidelines for the diagnosis and management of coronavirus disease 2019 in children. In this article, the authors describe our institutional practices for the hospitalized pediatric patient with confirmed or suspected initial SARS-CoV-2 infection. The authors anticipate that developing evidence-informed and institution-specific guidelines will lead to improvements in care quality, efficiency, and consistency; minimization of staff risk of exposure to SARS-CoV-2; and increased provider comfort in caring for pediatric patients with SARS-CoV-2 infection.

Epidemiology, Clinical Features, and Disease Severity in Patients With Coronavirus Disease 2019 (COVID-19) in a Children's Hospital in New York City, New York.

Importance: Descriptions of the coronavirus disease 2019 (COVID-19) experience in pediatrics will help inform clinical practices and infection prevention and control for pediatric facilities. Objective: To describe the epidemiology, clinical, and laboratory features of patients with COVID-19 hospitalized at a children's hospital and to compare these parameters between patients hospitalized with and without severe disease. Design, Setting, and Participants: This retrospective review of electronic medical records from a tertiary care academically affiliated children's hospital in New York City, New York, included hospitalized children and adolescents (≤21 years) who were tested based on suspicion for COVID-19 between March 1 to April 15, 2020, and had positive results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exposures: Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription-polymerase chain reaction assay. Main Outcomes and Measures: Severe disease as defined by the requirement for mechanical ventilation. Results: Among 50 patients, 27 (54%) were boys and 25 (50%) were Hispanic. The median days from onset of symptoms to admission was 2 days (interquartile range, 1-5 days). Most patients (40 [80%]) had fever or respiratory symptoms (32 [64%]), but 3 patients (6%) with only gastrointestinal tract presentations were identified. Obesity (11 [22%]) was the most prevalent comorbidity. Respiratory support was required for 16 patients (32%), including 9 patients (18%) who required mechanical ventilation. One patient (2%) died. None of 14 infants and 1 of 8 immunocompromised patients had severe disease. Obesity was significantly associated with mechanical ventilation in children 2 years or older (6 of 9 [67%] vs 5 of 25 [20%]; P = .03). Lymphopenia was commonly observed at admission (36 [72%]) but did not differ significantly between those with and without severe disease. Those with severe disease had significantly higher C-reactive protein (median, 8.978 mg/dL [to convert to milligrams per liter, multiply by 10] vs 0.64 mg/dL) and procalcitonin levels (median, 0.31 ng/mL vs 0.17 ng/mL) at admission (P < .001), as well as elevated peak interleukin 6, ferritin, and D-dimer levels during hospitalization. Hydroxychloroquine was administered to 15 patients (30%) but could not be completed for 3. Prolonged test positivity (maximum of 27 days) was observed in 4 patients (8%). Conclusions and Relevance: In this case series study of children and adolescents hospitalized with COVID-19, the disease had diverse manifestations. Infants and immunocompromised patients were not at increased risk of severe disease. Obesity was significantly associated with disease severity. Elevated inflammatory markers were seen in those with severe disease.

Negative Valence Life Events Promote Breast Cancer Development.

BACKGROUND: The influence of stress on breast cancer risk remains unknown. The goal of the present study was to determine the effect of stress in the form of salient positive and negative valence life events (LEs) on primary invasive breast cancer risk. We hypothesized that salient negative LEs would increase breast cancer risk and salient positive LEs would attenuate this increased risk. PATIENTS AND METHODS: We used a case-control design with 664 cases identified through the Cancer Surveillance Program of Orange County and 203 population-based controls. Participants completed a risk factor questionnaire, which included a LE section. Fourteen salient LEs of positive or negative valence were used to quantify stress exposure. A baseline model was constructed, and odds ratios (ORs) were calculated using multivariate unconditional logistic regression. RESULTS: Negative LEs were associated with increased breast cancer risk. The OR for ≥ 4 negative LEs showed a 2.81-fold increase in breast cancer risk (OR, 2.81; 95% confidence interval [CI], 1.47-5.36). A significant dose-response relationship between lifetime negative valence LEs and breast cancer risk was found. Previous personal illness increased breast cancer risk by 3.6-fold (OR, 3.60; 95% CI, 2.50-5.20). In contrast, abortion was associated with a 45% decrease in breast cancer risk (OR, 0.55; 95% CI, 0.34-0.89). Salient positive LEs did not have a significant effect on breast cancer risk. However, they seemed to buffer the adverse effect of salient negative LEs on breast cancer risk. CONCLUSION: The findings from the present study support the role of salient negative LEs in promoting breast cancer development, with a possible buffering effect of salient positive LEs.

Perception matters: Stressful life events increase breast cancer risk.

OBJECTIVE: The relationship between psychological stress and breast cancer risk is unclear. The present study sought to understand how stressfulness appraisal of salient Life Events (LEs) influences breast cancer risk. METHODS: A case-control design was used and included 664 female cases identified through the Cancer Surveillance Program of Orange County, CA and 203 female population-based controls. A LE questionnaire determined if events occurred prior to breast cancer diagnosis and if these events were considered to be stressful or not. Multivariate unconditional logistic regression was used to calculate ORs while adjusting for known breast cancer covariates. RESULTS: Cumulative adverse LEs perceived as stressful were associated with increased breast cancer risk in a dose response fashion (OR = 1.63, 95% CI = 1.00-2.66, Ptrend = 0.045). Conversely, events perceived as non-stressful did not have a significant impact on breast cancer risk. Previous personal illness was directly related to increased breast cancer risk, whether perceived as stressful (OR = 2.84, 95% CI = 1.96-4.11) or non-stressful (OR = 3.47, 95% CI = 1.34-8.94). Abortion and relocation were observed to have a protective effect on breast cancer risk only when reported as stressful (OR = 0.54, 95% CI = 0.32-0.92; OR = 0.63, 95% CI = 0.43-0.93, respectively). Pre/Peri-menopausal women who were nulliparous or who had their first child at ≥30 years of age were especially prone to the effects of appraised stress on increased breast cancer risk. CONCLUSIONS: This study underscores the importance of stressfulness appraisal when determining the effect of major LEs on breast cancer risk. Our results support incorporating assessments of perceived stressfulness in future epidemiological investigation of this topic.

Cancer-Incidence, prevalence and mortality in the oldest-old. A comprehensive review.

Chronic health conditions are commonplace in older populations. The process of aging impacts many of the world's top health concerns. With the average life expectancy continuing to climb, understanding patterns of morbidity in aging populations has become progressively more important. Cancer is an age-related disease, whose risk has been proven to increase with age. Limited information is published about the epidemiology of cancer and the cancer contribution to mortality in the 85+ age group, often referred to as the oldest-old. In this review, we perform a comprehensive assessment of the most recent (2011-2016) literature on cancer prevalence, incidence and mortality in the oldest-old. The data shows cancer prevalence and cancer incidence increases until ages 85-89, after which the rates decrease into 100+ ages. However the number of overall cases has steadily increased over time due to the rise in population. Cancer mortality continues to increase after age 85+. This review presents an overview of plausible associations between comorbidity, genetics and age-related physiological effects in relation to cancer risk and protection. Many of these age-related processes contribute to the lowered risk of cancer in the oldest-old, likewise other certain health conditions may "protect" from cancer in this age group.

Pharmacological blockade of memory reconsolidation in posttraumatic stress disorder: three negative psychophysiological studies.

Posttraumatic stress disorder (PTSD) may involve over-consolidated emotional memories of the traumatic event. Reactivation (RP) can return a memory to an unstable state, from which it must be restabilized (reconsolidated) if it is to persist. Pharmacological agents administered while the memory is unstable have been shown to impair reconsolidation. The N-methyl-d-aspartate (NMDA) partial agonist d-cycloserine (DCS) may promote memory destabilization. In the three studies reported here, we investigated whether the ß-adrenergic blocker propranolol or the glucocorticoid (GR) antagonist mifepristone, given at the time of traumatic memory reactivation, could reduce PTSD symptoms and physiological responding during subsequent traumatic imagery. Individuals with PTSD were randomized as follows: Study One: propranolol with memory reactivation (n=10) or without reactivation (n=8); Study Two: reactivation mifepristone (n=13), non-reactivation (NRP) mifepristone (n=15), or double placebo (PL) (n=15); Study Three: reactivation mifepristone plus d-cycloserine (n=16), or two placebos (n=15). Subjects underwent memory retrieval by describing their traumatic event. A week later they engaged in script-driven traumatic mental imagery, while heart rate (HR), skin conductance (SC), and facial electromyogram (EMG) responses were measured. There were no significant group differences in physiological responsivity or change in PTSD symptoms in any of the studies. These results do not support successful blockade of reconsolidation of traumatic memories in PTSD.