A population-based model for predicting sentinel lymph node (SLN) status for cutaneous melanoma patients and a clinical decision rule (CDR) for sparing a SLN biopsy (SLNB).

9589 Background: Generally, a SLNB is offered to the patient whose likelihood of positivity is ≥ 5%. Using population-based cohorts, we sought to [1] develop and validate a predictive model to estimate the individualized risk (IR) of SLNB positivity (SLNBp) and its confidence interval (CI), [2] evaluate an IR-based CDR to identify patients with sufficiently low IRs to avoid SLNB, and [3] compare the performance of the CDR with that of the 2019 NCCN guideline. Methods: The learning cohort (n = 18,214; SLNBp rate = 10.7%; 2010-2014) and validation cohort (n = 3,924; SLNBp rate = 11%; 2015) included SEER patients 18-99 years old who had a SLNB as part of definitive surgery. A multivariable logistic regression model for SLNBp, including 4 AJCC related-factors (thickness, ulceration, level and mitotic rate) and age, was used to estimate the IR of SLNBp and its one-sided 95% CI. The CDR was defined using the IR and CI and then used to classify patients into 3 categories: SLNB not indicated (IR and upper limit of the one-sided CI < 5%), SLNB indicated (IR and lower limit of the one-sided CI ≥ 5%), and borderline. Results: In the learning cohort all 5 factors were significant in the multivariate model, which had a c-statistic of 0.742 (95%CI, 0.731-0.753). In the validation cohort the model c-statistic was 0.728. Based on the CDR, 21.6%, 56.9%, and 21.5% of patients would not be offered SLNB, would be offered SLNB, or would need further shared decision making. Compared to the guideline, the CDR classified more patients as “SLNB not indicated” (21.6% vs. 7.1%) and fewer as “SLNB indicated” (56.9% vs. 68.5%). Of the 16,137 SLNB negative patients, 3815 (23.6%) would not be offered SLNB based on the CDR compared to 1258 (7.8%) who would not be offered SLNB based on the guideline. The false negative rates associated with “not indicated” by the CDR and guideline were 4.6% and 1.2%, respectively. Conclusions: Use of this CDR rather than the NCCN guideline will spare more low-risk patients the expense and harms of SLNB and increase only marginally their likelihood of a false negative test (still < 5%).

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Real-life clinical sensitivity of SARS-CoV-2 RT-PCR test in symptomatic patients

PLoS ONE ◽

10.1371/journal.pone.0251661 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0251661

Author(s):

Elisa Kortela ◽

Vesa Kirjavainen ◽

Maarit J. Ahava ◽

Suvi T. Jokiranta ◽

Anna But ◽

...

Keyword(s):

Clinical Decision Making ◽

False Negative ◽

Real Life ◽

Clinical Decision ◽

Population Based ◽

Clinical Suspicion ◽

Rt Pcr ◽

Clinical Sensitivity ◽

High Clinical Suspicion ◽

Pcr Test

Background Understanding the false negative rates of SARS-CoV-2 RT-PCR testing is pivotal for the management of the COVID-19 pandemic and it has implications for patient management. Our aim was to determine the real-life clinical sensitivity of SARS-CoV-2 RT-PCR. Methods This population-based retrospective study was conducted in March–April 2020 in the Helsinki Capital Region, Finland. Adults who were clinically suspected of SARS-CoV-2 infection and underwent SARS-CoV-2 RT-PCR testing, with sufficient data in their medical records for grading of clinical suspicion were eligible. In addition to examining the first RT-PCR test of repeat-tested individuals, we also used high clinical suspicion for COVID-19 as the reference standard for calculating the sensitivity of SARS-CoV-2 RT-PCR. Results All 1,194 inpatients (mean [SD] age, 63.2 [18.3] years; 45.2% women) admitted to COVID-19 cohort wards during the study period were included. The outpatient cohort of 1,814 individuals (mean [SD] age, 45.4 [17.2] years; 69.1% women) was sampled from epidemiological line lists by systematic quasi-random sampling. The sensitivity (95% CI) for laboratory confirmed cases (repeat-tested patients) was 85.7% (81.5–89.1%) inpatients; 95.5% (92.2–97.5%) outpatients, 89.9% (88.2–92.1%) all. When also patients that were graded as high suspicion but never tested positive were included in the denominator, the sensitivity (95% CI) was: 67.5% (62.9–71.9%) inpatients; 34.9% (31.4–38.5%) outpatients; 47.3% (44.4–50.3%) all. Conclusions The clinical sensitivity of SARS-CoV-2 RT-PCR testing was only moderate at best. The relatively high false negative rates of SARS-CoV-2 RT-PCR testing need to be accounted for in clinical decision making, epidemiological interpretations, and when using RT-PCR as a reference for other tests.

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Real-life clinical sensitivity of SARS-CoV-2 RT-PCR test in symptomatic patients

10.1101/2020.11.01.20223107 ◽

2020 ◽

Author(s):

Elisa Kortela ◽

Vesa Kirjavainen ◽

Maarit J. Ahava ◽

Suvi T. Jokiranta ◽

Anna But ◽

...

Keyword(s):

Clinical Decision Making ◽

False Negative ◽

Real Life ◽

Clinical Decision ◽

Population Based ◽

Clinical Suspicion ◽

Rt Pcr ◽

Clinical Sensitivity ◽

High Clinical Suspicion ◽

Pcr Test

AbstractImportanceUnderstanding the false negative rates of SARS-CoV-2 RT-PCR testing is pivotal for the management of the COVID-19 pandemic and it has practical implications for patient management in healthcare facilities.ObjectiveTo determine the real-life clinical sensitivity of SARS-CoV-2 RT-PCR testing.DesignA retrospective study on case series from 4 March – 15 April 2020.SettingA population-based study conducted in primary and tertiary care in the Helsinki Capital Region, Finland.ParticipantsAdults who were clinically suspected of SARS-CoV-2 infection and underwent SARS-CoV-2 RT-PCR testing, and who had sufficient data for grading of clinical suspicion of COVID-19 in their medical records were eligible. All 1,194 inpatients admitted to COVID-19 cohort wards during the study period were included. The outpatient cohort of 1,814 individuals was sampled from epidemiological line lists by systematic quasi-random sampling. Altogether 83 eligible outpatients (4.6%) and 3 inpatients (0.3%) were excluded due to insufficient data for grading of clinical suspicion.ExposuresHigh clinical suspicion for COVID-19 was used as the reference standard for the RT-PCR test. Patients were considered to have high clinical suspicion of COVID-19 if the physician in charge recorded the suspicion on clinical grounds, or the patient fulfilled specifically defined clinical and exposure criteria.Main measuresSensitivity of SARS-CoV-2 RT-PCR by using manually curated clinical characteristics as the gold standard.ResultsThe study population included 1,814 outpatients (mean [SD] age, 45.4 [17.2] years; 69.1% women) and 1,194 inpatients (mean [SD] age, 63.2 [18.3] years; 45.2% women). The sensitivity (95% CI) for laboratory confirmed cases, i.e. repeatedly tested patients were as follows: 85.7% (81.5–89.1%) inpatients; 95.5% (92.2–97.5%) outpatients, 89.9% (88.2–92.1%) all. When also patients that were graded as high suspicion but never tested positive were included in the denominator, the following sensitivity values (95% CI) were observed: 67.5% (62.9–71.9%) inpatients; 34.9% (31.4–38.5%) outpatients; 47.3% (44.4–50.3%) all.Conclusions and relevanceThe clinical sensitivity of SARS-CoV-2 RT-PCR testing was only moderate at best. The relatively high false negative rates of SARS-CoV-2 RT-PCR testing need to be accounted for in clinical decision making, epidemiological interpretations and when using RT-PCR as a reference for other tests.Key PointsQuestionWhat is the clinical sensitivity of SARS-CoV-2 RT-PCR test?FindingsIn this population-based retrospective study on medical records of 1,814 outpatients and 1,194 inpatients, the clinical sensitivity of SARS-CoV-2 RT-PCR was 47.3–89.9%.MeaningThe false negative rates of SARS-CoV-2 RT-PCR testing need to be accounted for in clinical decision making, epidemiological interpretations and when using RT-PCR as a reference for other tests.

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Frequency of serological non-responders and false-negative RT-PCR results in SARS-CoV-2 testing: a population-based study

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-0978 ◽

2020 ◽

Vol 0 (0) ◽

Cited By ~ 3

Author(s):

Rita Christiane Baron ◽

Lorenz Risch ◽

Myriam Weber ◽

Sarah Thiel ◽

Kirsten Grossmann ◽

...

Keyword(s):

Disease Duration ◽

Validation Cohort ◽

Clinical Symptoms ◽

False Negative ◽

Population Based ◽

Initial Presentation ◽

Rt Pcr ◽

Antibody Testing ◽

Disease Symptoms

AbstractObjectivesThe sensitivity of molecular and serological methods for COVID-19 testing in an epidemiological setting is not well described. The aim of the study was to determine the frequency of negative RT-PCR results at first clinical presentation as well as negative serological results after a follow-up of at least 3 weeks.MethodsAmong all patients seen for suspected COVID-19 in Liechtenstein (n=1921), we included initially RT-PCR positive index patients (n=85) as well as initially RT-PCR negative (n=66) for follow-up with SARS-CoV-2 antibody testing. Antibodies were detected with seven different commercially available immunoassays. Frequencies of negative RT-PCR and serology results in individuals with COVID-19 were determined and compared to those observed in a validation cohort of Swiss patients (n=211).ResultsAmong COVID-19 patients in Liechtenstein, false-negative RT-PCR at initial presentation was seen in 18% (12/66), whereas negative serology in COVID-19 patients was 4% (3/85). The validation cohort showed similar frequencies: 2/66 (3%) for negative serology, and 16/155 (10%) for false negative RT-PCR. COVID-19 patients with negative follow-up serology tended to have a longer disease duration (p=0.05) and more clinical symptoms than other patients with COVID-19 (p<0.05). The antibody titer from quantitative immunoassays was positively associated with the number of disease symptoms and disease duration (p<0.001).ConclusionsRT-PCR at initial presentation in patients with suspected COVID-19 can miss infected patients. Antibody titers of SARS-CoV-2 assays are linked to the number of disease symptoms and the duration of disease. One in 25 patients with RT-PCR-positive COVID-19 does not develop antibodies detectable with frequently employed and commercially available immunoassays.

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Obstacles to Claiming Permanence and Injury-Relatedness for “Posttraumatic” Headache

Guides Newsletter ◽

10.1001/amaguidesnewsletters.2009.mayjun02 ◽

2009 ◽

Vol 14 (3) ◽

pp. 3-6

Author(s):

Robert J. Barth

Keyword(s):

Complete Recovery ◽

World Health ◽

Related Factors ◽

Posttraumatic Headache ◽

Sixth Edition ◽

Causative Relationship ◽

Short Period ◽

The One ◽

Health Organization ◽

Subjective Reports

Abstract “Posttraumatic” headaches claims are controversial because they are subjective reports often provided in the complex of litigation, and the underlying pathogenesis is not defined. This article reviews principles and scientific considerations in the AMAGuides to the Evaluation of Permanent Impairment (AMA Guides) that should be noted by evaluators who examine such cases. Some examples in the AMA Guides, Sixth Edition, may seem to imply that mild head trauma can cause permanent impairment due to headache. The author examines scientific findings that present obstacles to claiming that concussion or mild traumatic brain injury is a cause of permanent headache. The World Health Organization, for example, found a favorable prognosis for posttraumatic headache, and complete recovery over a short period of time was the norm. Other studies have highlighted the lack of a dose-response correlation between trauma and prolonged headache complaints, both in terms of the frequency and the severity of trauma. On the one hand, scientific studies have failed to support the hypothesis of a causative relationship between trauma and permanent or prolonged headaches; on the other hand, non–trauma-related factors are strongly associated with complaints of prolonged headache.

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Real-World Experience of the One-Year Efficacy of Rifaximin Add-On to Lactulose Is Superior to Lactulose Alone in Patients with Cirrhosis Complicated with Recurrent Hepatic Encephalopathy in Taiwan

Journal of Personalized Medicine ◽

10.3390/jpm11060478 ◽

2021 ◽

Vol 11 (6) ◽

pp. 478

Author(s):

Ching Chang ◽

Chien-Hao Huang ◽

Hsiao-Jung Tseng ◽

Fang-Chen Yang ◽

Rong-Nan Chien

Keyword(s):

Hepatic Encephalopathy ◽

Real World ◽

Ammonia Level ◽

Decompensated Cirrhosis ◽

Control Group ◽

Multivariable Logistic Regression Model ◽

Before And After ◽

One Year ◽

The One ◽

Serum Ammonia

Background: Hepatic encephalopathy (HE), a neuropsychiatric complication of decompensated cirrhosis, is associated with high mortality and high risk of recurrence. Rifaximin add-on to lactulose for 3 to 6 months is recommended for the prevention of recurrent episodes of HE after the second episode. However, whether the combination for more than 6 months is superior to lactulose alone in the maintenance of HE remission is less evident. Therefore, the aim of this study is to evaluate the one-year efficacy of rifaximin add-on to lactulose for the maintenance of HE remission in Taiwan. Methods: We conducted a real-world single-center retrospective cohort study to compare the long-term efficacy of rifaximin add-on to lactulose (group R + L) versus lactulose alone (group L, control group). Furthermore, the treatment efficacy before and after rifaximin add-on to lactulose was also analyzed. The primary endpoint of our study was time to first HE recurrence (Conn score ≥ 2). All patients were followed up every three months until death, and censored at one year if still alive. Results and Conclusions: 12 patients were enrolled in group R + L. Another 31 patients were stratified into group L. Sex, comorbidity, ammonia level, and ascites grade were matched while age, HE grade, and model for end-stage liver disease (MELD) score were adjusted in the multivariable logistic regression model. Compared with group L, significant improvement in the maintenance of HE remission and decreased episodes and days of HE-related hospitalizations were demonstrated in group R + L. The serum ammonia levels were significantly lower at the 3rd and 6th month in group 1. Concerning changes before and after rifaximin add-on in group R + L, mini-mental status examination (MMSE), episodes of hospitalization, and variceal bleeding also improved at 6 and 12 months. Days of hospitalization, serum ammonia levels also improved at 6th month. Except for concern over price, no patients discontinued rifaximin due to adverse events or complications. The above results provide evidence for the one-year use of rifaximin add-on to lactulose in reducing HE recurrence and HE-related hospitalization for patients with decompensated cirrhosis.

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Risk Factors for Pneumonia and Death in Adult Patients With Seasonal Influenza and Establishment of Prediction Scores: A Population-Based Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab068 ◽

2021 ◽

Vol 8 (3) ◽

Author(s):

Koichi Miyashita ◽

Eiji Nakatani ◽

Hironao Hozumi ◽

Yoko Sato ◽

Yoshiki Miyachi ◽

...

Keyword(s):

High Risk ◽

Seasonal Influenza ◽

Prediction Models ◽

Validation Cohort ◽

Risk Groups ◽

Population Based ◽

Limited Data ◽

Population Based Study ◽

Relative Risks ◽

Primary Care Settings

Abstract Background Seasonal influenza remains a global health problem; however, there are limited data on the specific relative risks for pneumonia and death among outpatients considered to be at high risk for influenza complications. This population-based study aimed to develop prediction models for determining the risk of influenza-related pneumonia and death. Methods We included patients diagnosed with laboratory-confirmed influenza between 2016 and 2017 (main cohort, n = 25 659), those diagnosed between 2015 and 2016 (validation cohort 1, n = 16 727), and those diagnosed between 2017 and 2018 (validation cohort 2, n = 34 219). Prediction scores were developed based on the incidence and independent predictors of pneumonia and death identified using multivariate analyses, and patients were categorized into low-, medium-, and high-risk groups based on total scores. Results In the main cohort, age, gender, and certain comorbidities (dementia, congestive heart failure, diabetes, and others) were independent predictors of pneumonia and death. The 28-day pneumonia incidence was 0.5%, 4.1%, and 10.8% in the low-, medium-, and high-risk groups, respectively (c-index, 0.75); the 28-day mortality was 0.05%, 0.7%, and 3.3% in the low-, medium-, and high-risk groups, respectively (c-index, 0.85). In validation cohort 1, c-indices for the models for pneumonia and death were 0.75 and 0.87, respectively. In validation cohort 2, c-indices for the models were 0.74 and 0.87, respectively. Conclusions We successfully developed and validated simple-to-use risk prediction models, which would promptly provide useful information for treatment decisions in primary care settings.

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Testing as Prevention of Resistance in Bacteria Causing Sexually Transmitted Infections—A Population-Based Model for Germany

Antibiotics ◽

10.3390/antibiotics10080929 ◽

2021 ◽

Vol 10 (8) ◽

pp. 929

Author(s):

Andreas Hahn ◽

Hagen Frickmann ◽

Ulrike Loderstädt

Keyword(s):

Sexually Transmitted Infections ◽

False Negative ◽

Population Based ◽

Sexually Transmitted ◽

Test Characteristics ◽

Antibiotic Drugs ◽

False Positive Signal ◽

Antibiotic Drug ◽

Potential Applicability ◽

Sex With Men

Prescribed antibiotic treatments which do not match the therapeutic requirements of potentially co-existing undetected sexually transmitted infections (STIs) can facilitate the selection of antibiotic-drug-resistant clones. To reduce this risk, this modelling assessed the potential applicability of reliable rapid molecular test assays targeting bacterial STI prior to the prescription of antibiotic drugs. The modelling was based on the prevalence of three bacterial STIs in German heterosexual and men-having-sex-with-men (MSM) populations, as well as on reported test characteristics of respective assays. In the case of the application of rapid molecular STI assays for screening, the numbers needed to test in order to correctly identify any of the included bacterial STIs ranged from 103 to 104 for the heterosexual population and from 5 to 14 for the MSM population. The number needed to harm—defined as getting a false negative result for any of the STIs and a false positive signal for another one, potentially leading to an even more inappropriate adaptation of antibiotic therapy than without any STI screening—was at least 208,995 for the heterosexuals and 16,977 for the MSM. Therefore, the screening approach may indeed be suitable to avoid unnecessary selective pressure on bacterial causes of sexually transmitted infections.

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Incorporating false negative tests in epidemiological models for SARS-CoV-2 transmission and reconciling with seroprevalence estimates

Scientific Reports ◽

10.1038/s41598-021-89127-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rupam Bhattacharyya ◽

Ritoban Kundu ◽

Ritwik Bhaduri ◽

Debashree Ray ◽

Lauren J. Beesley ◽

...

Keyword(s):

False Negative ◽

Population Based ◽

Training Data ◽

Epidemiological Models ◽

Rt Pcr ◽

Antibody Prevalence ◽

Igg Antibody ◽

False Negatives ◽

Seir Model ◽

Study Population

AbstractSusceptible-Exposed-Infected-Removed (SEIR)-type epidemiologic models, modeling unascertained infections latently, can predict unreported cases and deaths assuming perfect testing. We apply a method we developed to account for the high false negative rates of diagnostic RT-PCR tests for detecting an active SARS-CoV-2 infection in a classic SEIR model. The number of unascertained cases and false negatives being unobservable in a real study, population-based serosurveys can help validate model projections. Applying our method to training data from Delhi, India, during March 15–June 30, 2020, we estimate the underreporting factor for cases at 34–53 (deaths: 8–13) on July 10, 2020, largely consistent with the findings of the first round of serosurveys for Delhi (done during June 27–July 10, 2020) with an estimated 22.86% IgG antibody prevalence, yielding estimated underreporting factors of 30–42 for cases. Together, these imply approximately 96–98% cases in Delhi remained unreported (July 10, 2020). Updated calculations using training data during March 15-December 31, 2020 yield estimated underreporting factor for cases at 13–22 (deaths: 3–7) on January 23, 2021, which are again consistent with the latest (fifth) round of serosurveys for Delhi (done during January 15–23, 2021) with an estimated 56.13% IgG antibody prevalence, yielding an estimated range for the underreporting factor for cases at 17–21. Together, these updated estimates imply approximately 92–96% cases in Delhi remained unreported (January 23, 2021). Such model-based estimates, updated with latest data, provide a viable alternative to repeated resource-intensive serosurveys for tracking unreported cases and deaths and gauging the true extent of the pandemic.

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Unfilled Training Positions in Germany – Regional and Establishment-Specific Determinants

Jahrbücher für Nationalökonomie und Statistik ◽

10.1515/jbnst-2018-0014 ◽

2019 ◽

Vol 239 (4) ◽

pp. 661-701 ◽

Cited By ~ 1

Author(s):

Sandra Dummert ◽

Ute Leber ◽

Barbara Schwengler

Keyword(s):

Related Factors ◽

Factors Affecting ◽

External Conditions ◽

Western Germany ◽

Enterprise Level ◽

Specific Factors ◽

Regional Factors ◽

The One ◽

Training Position ◽

Quantitative Importance

AbstractThe current situation in the German apprenticeship market is characterized by two contradictory developments. On the one hand, establishments are experiencing increasing problems filling the training positions they offer, and the number of vacant training positions is climbing. On the other hand, the transition into training is still difficult for many young people, and the number of unsuccessful vocational training applicants is rising. Hence, matching supply with demand is becoming increasingly difficult in the German job market for training positions. Using the Linked Employer-Employee dataset (LIAB) from the Institute for Employment Research (IAB), our paper provides a closer examination of the phenomenon of unfilled training positions. It presents an overview of the evolution of vacant training positions in eastern and western Germany and attempts to explain the number of vacancies by investigating the factors responsible for the establishments’ inability to fill their training positions. We assume that training position vacancies are due not only to internal company reasons such as firm size or the wage offer for apprentices but also to external conditions such as general regional factors. Therefore, our analysis also considers the situation on the demand side of the labor market within a region. The results of our multilevel mixed-effects estimations show that in addition to characteristics on the enterprise level, regional determinants also affect the share of vacant apprenticeships. With respect to establishment-related factors, mainly characteristics that describe the attractiveness of the firm prove to be important. With regard to regional-specific factors, we find that the availability of school leavers in a region in addition to the level of regional-sectoral competition impacts the recruiting success of establishments. Our analysis also shows that there are remarkable differences between eastern and western Germany concerning both the quantitative importance of unfilled training positions and the factors affecting them.

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Frailty Changes Predict Mortality in 4 Longitudinal Studies of Aging

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa266 ◽

2020 ◽

Author(s):

Erwin Stolz ◽

Emiel O Hoogendijk ◽

Hannes Mayerl ◽

Wolfgang Freidl

Keyword(s):

Mortality Risk ◽

Clinical Decision Making ◽

Frailty Index ◽

Credible Interval ◽

Clinical Decision ◽

Population Based ◽

Time To Event Data ◽

Longitudinal Aging Study Amsterdam ◽

Aging Study ◽

Longitudinal Aging Study

Abstract Background Baseline frailty index (FI) values have been shown to predict mortality among older adults, but little is known about the effects of changes in FI on mortality. Methods In a coordinated approach, we analyzed data from 4 population-based cohorts: the Health and Retirement Study (HRS), the Survey of Health, Ageing and Retirement in Europe (SHARE), the English Longitudinal Survey of Ageing (ELSA), and the Longitudinal Aging Study Amsterdam (LASA), comprising a total of 24 961 respondents (65+), 95 897 observations, up to 9 repeated FI assessments, and up to 23 years of mortality follow-up. The effect of time-varying FI on mortality was modeled with joint regression models for longitudinal and time-to-event data. Results Differences (of 0.01) in current FI levels (hazard ratio [HR] = 1.04, 95% credible interval [CI] = 1.03–1.05) and baseline FI levels (HR = 1.03, 95% CI = 1.03–1.05) were consistently associated with mortality across studies. Importantly, individuals with steeper FI growth also had a higher mortality risk: An increase in annual FI growth by 0.01 was associated with an increased mortality risk of HR = 1.56 (95% CI = 1.49–1.63) in HRS, HR = 1.24 (95% CI = 1.13–1.35) in SHARE, HR = 1.40 (95% CI = 1.25–1.52) in ELSA, and HR = 1.71 (95% CI = 1.46–2.01) in LASA. Conclusions FI changes predicted mortality independently of baseline FI differences. Repeated assessment of frailty and individual’s frailty trajectory could provide a means to anticipate further health deterioration and mortality and could thus support clinical decision making.

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