Derivation and validation of clinical prediction rules for diagnosis of infectious mononucleosis: a prospective cohort study.

OBJECTIVES: Infectious mononucleosis (IM) is a clinical syndrome that is characterised by lymphadenopathy, fever and sore throat. Although generally not considered a serious illness, IM can lead to significant loss of time from school or work due to profound fatigue, or the development of chronic illness. This study aimed to derive and externally validate clinical prediction rules (CPRs) for IM caused by Epstein-Barr virus (EBV). DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: 328 participants were recruited prospectively for the derivation cohort, from seven university-affiliated student health centres in Ireland. Participants were young adults (17-39 years old, mean age 20.6 years) with sore throat and one other additional symptom suggestive of IM. The validation cohort was a retrospective cohort of 1498 participants from a student health centre at the University of Georgia, USA. MAIN OUTCOME MEASURES: Regression analyses were used to develop four CPR models, internally validated in the derivation cohort. External validation was carried out in the geographically separate validation cohort. RESULTS: In the derivation cohort, there were 328 participants, of whom 42 (12.8%) had a positive EBV serology test result. Of 1498 participants in the validation cohort, 243 (16.2%) had positive heterophile antibody tests for IM. Four alternative CPR models were developed and compared. There was moderate discrimination and good calibration for all models. The sparsest CPR included presence of enlarged/tender posterior cervical lymph nodes and presence of exudate on the pharynx. This model had moderate discrimination (area under the receiver operating characteristic curve (AUC): 0.70; 95% CI: 0.62-0.79) and good calibration. On external validation, this model demonstrated reasonable discrimination (AUC: 0.69; 95% CI: 0.67-0.72) and good calibration. CONCLUSIONS: The alternative CPRs proposed can provide quantitative probability estimates of IM. Used in conjunction with serological testing for atypical lymphocytosis and immunoglobulin testing for viral capsid antigen, CPRs can enhance diagnostic decision-making for IM in community settings.

Top 20 Research Studies of 2022 for Primary Care Physicians.

This article summarizes the top 20 research studies of 2022 identified as POEMs (patient-oriented evidence that matters), excluding COVID-19. Statins for primary prevention of cardiovascular disease produce only a small absolute reduction in a person's likelihood of dying (0.6%), having a myocardial infarction (0.7%), or having a stroke (0.3%) over three to six years. Supplemental vitamin D does not reduce the risk of a fragility fracture, even in people with low baseline vitamin D levels or a previous fracture. Selective serotonin reuptake inhibitors are preferred medical therapy for panic disorder, and patients who discontinue antidepressants are more likely to relapse (number needed to harm = 6) compared with those who continue. Combination therapy using a selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor, or tricyclic antidepressant with mirtazapine or trazodone is more effective than monotherapy for first-line treatment of acute severe depression and when monotherapy fails. Using hypnotic agents for insomnia in adults comes with a significant trade-off between effectiveness and tolerability. In patients with moderate to severe asthma, using a combination of albuterol and glucocorticoid inhalers as rescue therapy reduces exacerbations and need for systemic steroids. Observational research shows an increased risk of gastric cancer in patients taking proton pump inhibitors (number needed to harm = 1,191 over 10 years). The American College of Gastroenterology updated its guideline for gastroesophageal reflux disease, and a new guideline provides sound advice for the evaluation and management of irritable bowel syndrome. Adults older than 60 years with prediabetes are more likely to become normoglycemic than to develop diabetes mellitus or die. Treatment of prediabetes via intensive lifestyle intervention or metformin has no impact on long-term cardiovascular outcomes. Persons with painful diabetic peripheral neuropathy have similar degrees of improvement with monotherapy using amitriptyline, duloxetine, or pregabalin and greater improvement with combination therapy. When communicating with patients about disease risk, most patients prefer numbers over words because people overestimate word-based probabilities. In terms of drug therapy, the duration of an initial varenicline prescription should be 12 weeks. Many drugs can interact with cannabidiol. No important difference was found among ibuprofen, ketorolac, and diclofenac for treatment of acute nonradicular low back pain in adults.

Development and Validation of Simple Risk Scores to Predict Hospitalization in Outpatients with COVID-19 Including the Omicron Variant.

INTRODUCTION: Outpatient physicians need guidance to support decisions regarding hospitalization of COVID-19 patients and how closely to follow outpatients. Thus, we sought to develop and validate simple risk scores to predict hospitalization for outpatients with COVID-19 that do not require laboratory testing or imaging. METHODS: We identified outpatients 12 years and older who had a positive polymerase chain reaction test for SARS-CoV-2. Logistic regression was used to derive a risk score in patients presenting before March, 2021, and it was validated in a cohort presenting from March to September 2021 and an Omicron cohort from December, 2021 to January, 2022. RESULTS: Overall, 4.0% of 5843 outpatients in the early derivation cohort (before 3/1/21), 4.2% of 3806 outpatients in the late validation cohort, and 1.2% in an Omicron cohort were hospitalized. The base risk score included age, dyspnea, and any comorbidity. Other scores added fever, respiratory rate and/or oxygen saturation. All had very good overall accuracy (AUC 0.85-0.87) and classified about half of patients into a low-risk group with < 1% hospitalization risk. Hospitalization rates in the Omicron cohort were 0.22%, 1.3% and 8.7% for the base score. Two externally derived risk scores identified more low risk patients, but with a higher overall risk of hospitalization than our novel risk scores. CONCLUSIONS: A simple risk score suitable for outpatient and telehealth settings can classify over half of COVID-19 outpatients into a very low risk group with a 0.22% hospitalization risk in the Omicron cohort. The Lehigh Outpatient COVID Hospitalization (LOCH) risk score is available online as a free app: https://ebell-projects.shinyapps.io/LehighRiskScore/.

Top 20 Research Studies of 2021 for Primary Care Physicians.

This article summarizes the top 20 research studies of 2021 identified as POEMs (patient-oriented evidence that matters) that did not address the COVID-19 pandemic. Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists prevent adverse cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and also reduce all-cause and cardiovascular mortality. Most older adults (mean age, 75 years) with prediabetes do not progress to diabetes. Among patients in this age group with type 2 diabetes treated with medication, an A1C level of less than 7% is associated with increased risk of hospitalization for hypoglycemia, especially when using a sulfonylurea or insulin. For patients with chronic low back pain, exercise, nonsteroidal anti-inflammatory drugs, duloxetine, and opioids were shown to be more effective than control in achieving a 30% reduction in pain, but self-discontinuation of duloxetine and opioids was common. There is no clinically important difference between muscle relaxants and placebo in the treatment of nonspecific low back pain. In patients with chronic pain, low- to moderate-quality evidence supports exercise, yoga, massage, and mindfulness-based stress reduction. For acute musculoskeletal pain, acetaminophen, 1,000 mg, plus ibuprofen, 400 mg, without an opioid is a good option. Regarding screening for colorectal cancer, trial evidence supports performing fecal immunochemical testing every other year. For chronic constipation, evidence supports polyethylene glycol, senna, fiber supplements, magnesium-based products, and fruit-based products. The following abdominal symptoms carry a greater than 3% risk of cancer or inflammatory bowel disease: dysphagia or change in bowel habits in men; rectal bleeding in women; and abdominal pain, change in bowel habits, or dyspepsia in men and women older than 60 years. For secondary prevention in those with established arteriosclerotic cardiovascular disease, 81 mg of aspirin daily appears to be effective. The Framingham Risk Score and the Pooled Cohort Equations both overestimate the risk of cardiovascular events. Over 12 years, no association between egg consumption and cardiovascular events was demonstrated. Gabapentin, pregabalin, duloxetine, and venlafaxine provide clinically meaningful improvements in chronic neuropathic pain. In patients with moderate to severe depression, initial titration above the minimum starting dose of antidepressants in the first eight weeks of treatment is not more likely to increase response. In adults with iron deficiency anemia, adding vitamin C to oral iron has no effect. In children with pharyngitis, rhinosinusitis, acute bronchitis, or acute otitis media, providing education combined with a take-and-hold antibiotic prescription results in 1 in 4 of those children eventually taking an antibiotic.

External Validation of the COVID-NoLab and COVID-SimpleLab Prognostic Tools.

Our objective was to externally validate 2 simple risk scores for mortality among a mostly inpatient population with COVID-19 in Canada (588 patients for COVID-NoLab and 479 patients for COVID-SimpleLab). The mortality rates in the low-, moderate-, and high-risk groups for COVID-NoLab were 1.1%, 9.6%, and 21.2%, respectively. The mortality rates for COVID-SimpleLab were 0.0%, 9.8%, and 20.0%, respectively. These values were similar to those in the original derivation cohort. The 2 simple risk scores, now successfully externally validated, offer clinicians a reliable way to quickly identify low-risk inpatients who could potentially be managed as outpatients in the event of a bed shortage. Both are available online (https://ebell-projects.shinyapps.io/covid_nolab/ and https://ebell-projects.shinyapps.io/COVID-SimpleLab/).

Development and Validation of Simple Risk Scores to Predict Hospitalization in Outpatients with COVID-19 Including the Omicron Variant.

INTRODUCTION: Outpatient physicians need guidance to support decisions regarding hospitalization of COVID-19 patients and how closely to follow outpatients. Thus, we sought to develop and validate simple risk scores to predict hospitalization for outpatients with COVID-19 that do not require laboratory testing or imaging. METHODS: We identified outpatients 12 years and older who had a positive polymerase chain reaction test for SARS-CoV-2. Logistic regression was used to derive a risk score in patients presenting before March, 2021, and it was validated in a cohort presenting from March to September 2021 and an Omicron cohort from December, 2021 to January, 2022. RESULTS: Overall, 4.0% of 5843 outpatients in the early derivation cohort (before 3/1/21), 4.2% of 3806 outpatients in the late validation cohort, and 1.2% in an Omicron cohort were hospitalized. The base risk score included age, dyspnea, and any comorbidity. Other scores added fever, respiratory rate and/or oxygen saturation. All had very good overall accuracy (AUC 0.85-0.87) and classified about half of patients into a low-risk group with < 1% hospitalization risk. Hospitalization rates in the Omicron cohort were 0.22%, 1.3% and 8.7% for the base score. Two externally derived risk scores identified more low risk patients, but with a higher overall risk of hospitalization than our novel risk scores. CONCLUSIONS: A simple risk score suitable for outpatient and telehealth settings can classify over half of COVID-19 outpatients into a very low risk group with a 0.22% hospitalization risk in the Omicron cohort. The Lehigh Outpatient COVID Hospitalization (LOCH) risk score is available online as a free app: https://ebell-projects.shinyapps.io/LehighRiskScore/.

High Prevalence of Both Previous Infection with SARS-CoV-2 and Persistent Symptoms.

INTRODUCTION: Universities are unique settings with large populations, congregate housing, and frequent attendance of events in large groups. However, the current prevalence of previous COVID-19 infection in university students, including symptomatic and asymptomatic disease, is unknown. Our goal therefore was to determine the prevalence of previous infection, risk factors for infection, and the prevalence of persistent symptoms following infection among university students. METHODS: This was a cross-sectional study set in a large public university between January 22 and March 22, 2021. We surveyed students about demographics, risk factors, and symptoms, and simultaneously tested their saliva for IgA antibodies to SARS-CoV-2. To estimate the prevalence of previous infection we adjusted our intentional sample of a diverse student population for year in school and age to resemble the composition of the entire student body and adjusted for the imperfect sensitivity and specificity of the antibody test. Univariate and multiple regression analysis was used to identify independent risk factors for infection, and the proportion of students with persistent symptoms following acute infection was determined. RESULTS: A total of 488 students completed the survey, 432 had a valid antibody result, and 428 had both. The estimated prevalence of previous infection for 432 participants with valid antibody results was 41%. Of 145 students in our sample with a positive antibody test, 41.4% denied having a previous positive polymerase chain reaction (PCR) test for SARS-CoV-2 and presumably had an asymptomatic infection; in our adjusted analysis we estimate that approximately 2-thirds of students had asymptomatic infections. Independent risk factors for infection included male sex, having a roommate with a known symptomatic infection, and having two or fewer roommates. More frequent attendance of parties and bars was a univariate risk factor, but not in the multiple regression analysis. Of 122 students reporting a previous symptomatic infection, 14 (11.4%) reported persistent symptoms consistent with postacute COVID-19 a median of 132 days later. CONCLUSIONS AND RELEVANCE: Previous COVID-19 infection, both symptomatic and asymptomatic, was common at a large university. Measures that could prevent resurgence of the infection when students return to campus include mandatory vaccination policies, mass surveillance testing, and testing of sewage for antigen to SARS-CoV-2.

Development and Validation of a Two-Step Predictive Risk Stratification Model for Coronavirus Disease 2019 In-hospital Mortality: A Multicenter Retrospective Cohort Study.

Objectives: An accurate prognostic score to predict mortality for adults with COVID-19 infection is needed to understand who would benefit most from hospitalizations and more intensive support and care. We aimed to develop and validate a two-step score system for patient triage, and to identify patients at a relatively low level of mortality risk using easy-to-collect individual information. Design: Multicenter retrospective observational cohort study. Setting: Four health centers from Virginia Commonwealth University, Georgetown University, the University of Florida, and the University of California, Los Angeles. Patients: Coronavirus Disease 2019-confirmed and hospitalized adult patients. Measurements and Main Results: We included 1,673 participants from Virginia Commonwealth University (VCU) as the derivation cohort. Risk factors for in-hospital death were identified using a multivariable logistic model with variable selection procedures after repeated missing data imputation. A two-step risk score was developed to identify patients at lower, moderate, and higher mortality risk. The first step selected increasing age, more than one pre-existing comorbidities, heart rate >100 beats/min, respiratory rate ≥30 breaths/min, and SpO2 <93% into the predictive model. Besides age and SpO2, the second step used blood urea nitrogen, absolute neutrophil count, C-reactive protein, platelet count, and neutrophil-to-lymphocyte ratio as predictors. C-statistics reflected very good discrimination with internal validation at VCU (0.83, 95% CI 0.79-0.88) and external validation at the other three health systems (range, 0.79-0.85). A one-step model was also derived for comparison. Overall, the two-step risk score had better performance than the one-step score. Conclusions: The two-step scoring system used widely available, point-of-care data for triage of COVID-19 patients and is a potentially time- and cost-saving tool in practice.

Development and Validation of the COVID-NoLab and COVID-SimpleLab Risk Scores for Prognosis in 6 US Health Systems.

PURPOSE: Develop and validate simple risk scores based on initial clinical data and no or minimal laboratory testing to predict mortality in hospitalized adults with COVID-19. METHODS: We gathered clinical and initial laboratory variables on consecutive inpatients with COVID-19 who had either died or been discharged alive at 6 US health centers. Logistic regression was used to develop a predictive model using no laboratory values (COVID-NoLab) and one adding tests available in many outpatient settings (COVID-SimpleLab). The models were converted to point scores and their accuracy evaluated in an internal validation group. RESULTS: We identified 1340 adult inpatients with complete data for nonlaboratory parameters and 741 with complete data for white blood cell (WBC) count, differential, c-reactive protein (CRP), and serum creatinine. The COVID-NoLab risk score includes age, respiratory rate, and oxygen saturation and identified risk groups with 0.8%, 11.4%, and 40.4% mortality in the validation group (AUROCC = 0.803). The COVID-SimpleLab score includes age, respiratory rate, oxygen saturation, WBC, CRP, serum creatinine, and comorbid asthma and identified risk groups with 1.0%, 9.1%, and 29.3% mortality in the validation group (AUROCC = 0.833). CONCLUSIONS: Because they use simple, readily available predictors, developed risk scores have potential applicability in the outpatient setting but require prospective validation before use.

Primary Care Relevant Risk Factors for Adverse Outcomes in Patients With COVID-19 Infection: A Systematic Review.

BACKGROUND: The aim of this systematic review is to summarize the best available evidence regarding individual risk factors, simple risk scores, and multivariate models that use patient characteristics, vital signs, comorbidities, and laboratory tests relevant to outpatient and primary care settings. METHODS: Medline, WHO COVID-19, and MedRxIV databases were searched; studies meeting inclusion criteria were reviewed in parallel, and variables describing study characteristics, study quality, and risk factor data were abstracted. Study quality was assessed using the Quality in Prognostic Studies tool. Random effects meta-analysis of relative risks (categorical variables) and unstandardized mean differences (continuous variables) was performed; multivariate models and clinical prediction rules were summarized qualitatively. RESULTS: A total of 551 studies were identified and 22 studies were included. The median or mean age ranged from 38 to 68 years. All studies included only inpatients, and mortality rates ranged from 3.2% to 50.5%. Individual risk factors most strongly associated with mortality included increased age, c-reactive protein (CRP), d-dimer, heart rate, respiratory rate, lactate dehydrogenase, and procalcitonin as well as decreased oxygen saturation, the presence of dyspnea, and comorbid coronary heart and chronic kidney disease. Independent predictors of adverse outcomes reported most frequently by multivariate models include increasing age, increased CRP, decreased lymphocyte count, increased lactate dehydrogenase, elevated temperature, and the presence of any comorbidity. Simple risk scores and multivariate models have been proposed but are often complex, and most have not been validated. CONCLUSIONS: Our systematic review identifies several risk factors for adverse outcomes in COVID-19-infected inpatients that are often available in the outpatient and primary care settings: increasing age, increased CRP or procalcitonin, decreased lymphocyte count, decreased oxygen saturation, dyspnea on presentation, and the presence of comorbidities. Future research to develop clinical prediction models and rules should include these predictors as part of their core data set to develop and validate pragmatic outpatient risk scores.

Top POEMs of 2019 Consistent with the Principles of the Choosing Wisely Campaign.

In this article, we discuss the POEMs (patient-oriented evidence that matters) of 2019 judged to be most consistent with the principles of Choosing Wisely, an international campaign to reduce unnecessary testing and treatments. We selected these POEMs through a crowdsourcing strategy of the daily POEMs information service for the Canadian Medical Association's physician members. We present recommendations from these top POEMs of primary research or meta-analysis that identify interventions to encourage or consider avoiding in practice. The recommendations cover musculoskeletal conditions (e.g., do not recommend platelet-rich plasma injections for rotator cuff disease or knee osteoarthritis), respiratory disease (e.g., in clinically stable patients with community-acquired pneumonia, antibiotics can be stopped after five days), screening or preventive care (e.g., patients who take their blood pressure at home or in a pharmacy should know what to do when they have an elevated reading), and miscellaneous topics (e.g., in healthy adults treated for dermatophyte infection, do not obtain baseline or follow-up alanine transaminase level, aspartate transaminase level, or complete blood count). These POEMs describe interventions whose benefits are not superior to other options, are sometimes more expensive, or put patients at increased risk of harm. Knowing more about these POEMs and their connection with the Choosing Wisely campaign will help clinicians and patients engage in conversations better informed by high-quality evidence.

Community Outbreak Investigation of SARS-CoV-2 Transmission Among Bus Riders in Eastern China.

Importance: Evidence of whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), can be transmitted as an aerosol (ie, airborne) has substantial public health implications. Objective: To investigate potential transmission routes of SARS-CoV-2 infection with epidemiologic evidence from a COVID-19 outbreak. Design, Setting, and Participants: This cohort study examined a community COVID-19 outbreak in Zhejiang province. On January 19, 2020, 128 individuals took 2 buses (60 [46.9%] from bus 1 and 68 [53.1%] from bus 2) on a 100-minute round trip to attend a 150-minute worship event. The source patient was a passenger on bus 2. We compared risks of SARS-CoV-2 infection among at-risk individuals taking bus 1 (n = 60) and bus 2 (n = 67 [source patient excluded]) and among all other individuals (n = 172) attending the worship event. We also divided seats on the exposed bus into high-risk and low-risk zones according to the distance from the source patient and compared COVID-19 risks in each zone. In both buses, central air conditioners were in indoor recirculation mode. Main Outcomes and Measures: SARS-CoV-2 infection was confirmed by reverse transcription polymerase chain reaction or by viral genome sequencing results. Attack rates for SARS-CoV-2 infection were calculated for different groups, and the spatial distribution of individuals who developed infection on bus 2 was obtained. Results: Of the 128 participants, 15 (11.7%) were men, 113 (88.3%) were women, and the mean age was 58.6 years. On bus 2, 24 of the 68 individuals (35.3% [including the index patient]) received a diagnosis of COVID-19 after the event. Meanwhile, none of the 60 individuals in bus 1 were infected. Among the other 172 individuals at the worship event, 7 (4.1%) subsequently received a COVID-19 diagnosis. Individuals in bus 2 had a 34.3% (95% CI, 24.1%-46.3%) higher risk of getting COVID-19 compared with those in bus 1 and were 11.4 (95% CI, 5.1-25.4) times more likely to have COVID-19 compared with all other individuals attending the worship event. Within bus 2, individuals in high-risk zones had moderately, but nonsignificantly, higher risk for COVID-19 compared with those in the low-risk zones. The absence of a significantly increased risk in the part of the bus closer to the index case suggested that airborne spread of the virus may at least partially explain the markedly high attack rate observed. Conclusions and Relevance: In this cohort study and case investigation of a community outbreak of COVID-19 in Zhejiang province, individuals who rode a bus to a worship event with a patient with COVID-19 had a higher risk of SARS-CoV-2 infection than individuals who rode another bus to the same event. Airborne spread of SARS-CoV-2 seems likely to have contributed to the high attack rate in the exposed bus. Future efforts at prevention and control must consider the potential for airborne spread of the virus.