The Predictive Value of Mutation Screening for Anticipating COVID-19 Waves

Emerging SARS-CoV-2 strains continue to generate difficulties for authorities and health care professionals worldwide due to enhanced transmissibility and/or immune response evasion. The appearance of the Alpha and Delta strains has been associated with substantial increases in the number of COVID-19 cases and associated deaths. Whole Genome Sequencing (WGS) continues to be the gold standard for molecular surveillance of the pandemics but other assays such as mutation genotyping can be used to reduce costs and allocated time. This study investigates the efficiency of mutation screening tests compared to WGS and their predictive value to anticipate future waves. A very high degree of fidelity for this type of assay was found, regardless of the method used. The positive predictive value (PPV) of 4/5 markers was over 95% for the detection of Alpha and Delta variants. By estimating the prevalence of the Alpha and Delta strains using genotyping assays and fitting the data to a mathematical model, a five week period between the point of exponential growth of variant prevalence and a drastic increase in case numbers was found. For that reason, raising awareness about the efficacy of mutation screening could help authorities adopt better measures in the future.

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DETEKSI MOLEKUL MUTASI GEN rpoB MYCOBACTERIUM TUBERCULO SIS PADA DAHAK DENGAN POL YME RASE CHAIN REACTION DAN SINGLE STRAND CONFORMATION POLYMORPHISM

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v16i2.973 ◽

2018 ◽

Vol 16 (2) ◽

pp. 81

Author(s):

P B Notopuro ◽

J Nugraha ◽

H Notopuro

Keyword(s):

Drug Resistance ◽

Predictive Value ◽

Gold Standard ◽

Molecular Detection ◽

Culture Method ◽

Tuberculosis Infection ◽

Rifampicin Resistance ◽

Multi Drug Resistance ◽

Very High ◽

Resistance Detection

Tuberculosis is a chronic infectious disease which is found in the developing as well as the developed country. This disease is oneof the community health problems which become the priority programs in the national as well as international health. In the lasttwo decades, they can be found in the emergency tuberculosis problems that is related with the Multi Drug Resistance (MDR) Strain.The detection of rifampicin resistance in M. tuberculosis infection can help clinical laboratory to find the MDR strain. Related to thisproblem the proportional culture method is still the gold standard for rifampicin resistance detection for M. tuberculosis infection. Butthis method needs 4−6 weeks to obtain the result, while its sensitivity is not very high. The development of the molecular detection forM. tuberculosis rifampicin resistance in a direct clinical specimen such as sputum, cerebrospinalfLuid, etc. will give an improvement inthe diagnosis, because it has an accurate, fast, sensitive and a specific result. Isolates from twenty six of M. tuberculosis derived fromthe sputum of tuberculosis patients that have failed the tuberculosis treatment, were examined with the proportional culture method.In this study PCR-SSCP were used for the molecular detection of rifampicin resistancy using direct sputum samples. The proportionalculture method was used as a gold standard for the rifampicin resistance detection. A set of primers was directed to conserve the regionof rpoB gene of M. tubercuLosis. This RNA polymerase gene was encondes?, which is bound on rifampicin. A 157-bp fragment wasamplified by PCR and analyzed by SSCP technique. The sensitivity of PCR-SSCP is 80% (high), its specificity is 95.2% (very high), thepositive predictive value is 80% and the negative predictive value is 95.2%. Statistically there were no significant difference between theresult of PCR-SSCP and the proportional culture method. Based on the study result, the molecular detection technique for rifampicinresistance on M. tuberculosis infection can be used as the screening device /means for Multi Drug Resistance Tuberculosis (MDR-TB),while the clinician waits the culure result.

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Validation of a 3D Camera System for Cycling Analysis

Sensors ◽

10.3390/s21134473 ◽

2021 ◽

Vol 21 (13) ◽

pp. 4473

Author(s):

Robson Dias Scoz ◽

Thiago Roberto Espindola ◽

Mateus Freitas Santiago ◽

Paulo Rui de Oliveira ◽

Bruno Mazziotti Oliveira Alves ◽

...

Keyword(s):

Gold Standard ◽

Sports Medicine ◽

Pearson Correlation ◽

Intraclass Correlation ◽

Correlation Coefficients ◽

Camera System ◽

Camera Systems ◽

3D Camera ◽

High Degree ◽

Very High

Background: Kinematic analysis aimed toward scientific investigation or professional purposes is commonly unaffordable and complex to use. Objective: The purpose of this study was to verify concurrent validation between a cycling-specific 3D camera and the gold-standard 3D general camera systems. Methods: Overall, 11 healthy amateur male triathletes were filmed riding their bicycles with Vicon 3D cameras and the Retul 3D cameras for bike fitting analysis simultaneously. All 18 kinematic measurements given by the bike fitting system were compared with the same data given by Vicon cameras through Pearson correlation (r), intraclass correlation coefficients (ICC), standard error measurements (SEM), and Bland–Altman (BA) analysis. Confidence intervals of 95% are given. Results: A very high correlation between cameras was found on six of 18 measurements. All other presented a high correlation between cameras (between 0.7 and 0.9). In total, six variables indicate a SEM of less than one degree between systems. Only two variables indicate a SEM higher than two degrees between camera systems. Overall, four measures indicate bias tendency according to BA. Conclusions: The cycling-specific led-emitting 3D camera system tested revealed a high or very high degree of correlation with the gold-standard 3D camera system used in laboratory motion capture. In total, 14 measurements of this equipment could be used in sports medicine clinical practice and even by researchers of cycling studies.

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Effectiveness of thermal screening in detection of COVID-19 among truck drivers at Mutukula Land Point of Entry, Uganda

PLoS ONE ◽

10.1371/journal.pone.0251150 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0251150

Author(s):

Andrew Nsawotebba ◽

Ivan Ibanda ◽

Isaac Ssewanyana ◽

Patrick Ogwok ◽

Francis Ocen ◽

...

Keyword(s):

Body Temperature ◽

Predictive Value ◽

Gold Standard ◽

Truck Drivers ◽

Screening Tests ◽

Test Results ◽

Likelihood Ratios ◽

Data Set ◽

Predictive Values ◽

Point Of Entry

Introduction Despite the limited evidence for its effectiveness, thermal screening at points of entry has increasingly become a standard protocol in numerous parts of the globe in response to the COVID-19 pandemic. We sought to determine the effectiveness of thermal screening as a key step in diagnosing COVID-19 in a resource-limited setting. Materials and methods This was a retrospective cross-sectional study based on a review of body temperature and Xpert Xpress SARS CoV-2 test results records for truck drivers entering Uganda through Mutukula between 15th May and 30th July 2020. All records missing information for body temperature, age, gender, and Xpert Xpress SARS CoV-2 status were excluded from the data set. A data set of 7,181 entries was used to compare thermal screening and Xpert Xpress SARS CoV-2 assay test results using the diagnostic statistical test in STATAv15 software. The prevalence of COVID-19 amongst the truck drivers based on Xpert Xpress SARS CoV-2 assay results was determined. The sensitivity, specificity, positive predictive value, negative predictive value, positive and negative Likelihood ratios were obtained using Xpert Xpress SARS CoV-2 assay as the gold standard. Results Based on our gold standard test, the proportion of persons that tested positive for COVID-19 was 6.7% (95% CI: 6.1–7.3). Of the 7,181 persons that were thermally screened, 6,844 (95.3%) were male. The sample median age was 38 years (interquartile range, IQR: 31–45 years). The median body temperature was 36.5°C (IQR: 36.3–36.7) and only n (1.2%) had a body temperature above 37.5°C. The sensitivity and specificity of thermal screening were 9.9% (95% CI: 7.4–13.0) and 99.5% (95% CI: 99.3–99.6) respectively. The positive and negative predictive values were 57.8 (95% CI: 46.5–68.6) and 93.9 (95% CI: 93.3–94.4) respectively. The positive and negative Likelihood Ratios (LRs) were 19 (95% CI: 12.4–29.1) and 0.9 (95% CI: 0.88–0.93) respectively. Conclusion In this study population, the use of Thermal screening alone is ineffective in the detection of potential COVID-19 cases at point of entry. We recommend a combination of screening tests or additional testing using highly sensitive molecular diagnostics such as Polymerase Chain Reaction.

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Electron Microscopy in Molecular Biology

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100060027 ◽

1967 ◽

Vol 25 ◽

pp. 2-3

Author(s):

Cecil E. Hall

Keyword(s):

Electron Microscopy ◽

Molecular Biology ◽

Noise Level ◽

Molecular Structures ◽

Material Structure ◽

The Arts ◽

Shadow Casting ◽

Electron Image ◽

High Degree ◽

Very High

The visualization of organic macromolecules such as proteins, nucleic acids, viruses and virus components has reached its high degree of effectiveness owing to refinements and reliability of instruments and to the invention of methods for enhancing the structure of these materials within the electron image. The latter techniques have been most important because what can be seen depends upon the molecular and atomic character of the object as modified which is rarely evident in the pristine material. Structure may thus be displayed by the arts of positive and negative staining, shadow casting, replication and other techniques. Enhancement of contrast, which delineates bounds of isolated macromolecules has been effected progressively over the years as illustrated in Figs. 1, 2, 3 and 4 by these methods. We now look to the future wondering what other visions are waiting to be seen. The instrument designers will need to exact from the arts of fabrication the performance that theory has prescribed as well as methods for phase and interference contrast with explorations of the potentialities of very high and very low voltages. Chemistry must play an increasingly important part in future progress by providing specific stain molecules of high visibility, substrates of vanishing “noise” level and means for preservation of molecular structures that usually exist in a solvated condition.

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A Low-Noise, High-Gain Quasi-Millimeter-Wave Receiver MMIC with a Very High Degree of Integration Using 3D-MMIC Technology

IEICE Transactions on Electronics ◽

10.1587/transele.e94.c.1548 ◽

2011 ◽

Vol E94-C (10) ◽

pp. 1548-1556 ◽

Cited By ~ 1

Author(s):

Takana KAHO ◽

Yo YAMAGUCHI ◽

Kazuhiro UEHARA ◽

Kiyomichi ARAKI

Keyword(s):

Millimeter Wave ◽

High Gain ◽

Low Noise ◽

High Degree ◽

Very High ◽

Millimeter Wave Receiver

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Multi-Locus Selection and the Structure of Variation at the white Gene of Drosophila melanogaster

Genetics ◽

10.1093/genetics/144.2.635 ◽

1996 ◽

Vol 144 (2) ◽

pp. 635-645 ◽

Cited By ~ 3

Author(s):

David A Kirby ◽

Wolfgang Stephan

Keyword(s):

Drosophila Melanogaster ◽

White Gene ◽

Transcriptional Unit ◽

North American Population ◽

Evolutionary Mechanisms ◽

Locus Selection ◽

Neutral Equilibrium ◽

History Of ◽

High Degree ◽

Very High

Abstract We surveyed sequence variation and divergence for the entire 5972-bp transcriptional unit of the white gene in 15 lines of Drosophila melanogaster and one line of D. simulans. We found a very high degree of haplotypic structuring for the polymorphisms in the 3′ half of the gene, as opposed to the polymorphisms in the 5′ half. To determine the evolutionary mechanisms responsible for this pattern, we sequenced a 1612-bp segment of the white gene from an additional 33 lines of D. melanogaster from a European and a North American population. This 1612-bp segment encompasses an 834bp region of the white gene in which the polymorphisms form high frequency haplotypes that cannot be explained by a neutral equilibrium model of molecular evolution. The small number of recombinants in the 834bp region suggests epistatic selection as the cause of the haplotypic structuring, while an investigation of nucleotide diversity supports a directional selection hypothesis. A multi-locus selection model that combines features from both-hypotheses and takes the recent history of D. melanogaster into account may be the best explanation for these data.

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Fast Proton Conductors from Inorganic-Organic Composites: I. Amorphous Phosphate-Nafion and Silicophosphate-PMA/PWA Hybrids

MRS Proceedings ◽

10.1557/proc-600-299 ◽

1999 ◽

Vol 600 ◽

Author(s):

Yong-Il Park ◽

Jae-Dong Kim ◽

Masayuki Nagai

Keyword(s):

Phosphoric Acid ◽

Proton Conductivity ◽

Proton Conductors ◽

Phosphorus Concentration ◽

High Proton ◽

Proton Source ◽

Drastic Increase ◽

Amorphous Phosphate ◽

Exchange Resins ◽

Very High

AbstractA drastic increase of electrical conductivity was observed in the composite of amorphous phosphate and ion-exchange resins (Nafion) as phosphorus concentration increased. Incorporation of amorphous phosphate into Nafion caused a large increase of conductivity to about 4×10−1S/cm at 23°C. However, the fabricated composite showed very low chemical stability.A high proton conductivity was also observed in a new inorganic-organic hybrids through incorporating PMA(molibdo-phosphoric acid)/PWA(tungsto-phosphoric acid) as a proton source in amorphous silicophosphate gel structure. Obtained gels were homogeneous and chemically stable. Resulting proton conductivity is very high (up to 5.5×10−3S/cm) compared to those of silicophosphate gels.

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Development of an Electronic Algorithm to Identify Inappropriate Antibiotic Prescribing for Pediatric Pharyngitis

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.728 ◽

2020 ◽

Vol 41 (S1) ◽

pp. s188-s189

Author(s):

Jeffrey Gerber ◽

Robert Grundmeier ◽

Keith Hamilton ◽

Lauri Hicks ◽

Melinda Neuhauser ◽

...

Keyword(s):

Predictive Value ◽

Gold Standard ◽

Antibiotic Stewardship ◽

Chart Review ◽

Antibiotic Use ◽

Audit And Feedback ◽

Urgent Care ◽

Antibiotic Prescribing ◽

Tract Infections ◽

The Impact

Background: Antibiotic overuse contributes to antibiotic resistance and unnecessary adverse drug effects. Antibiotic stewardship interventions have primarily focused on acute-care settings. Most antibiotic use, however, occurs in outpatients with acute respiratory tract infections such as pharyngitis. The electronic health record (EHR) might provide an effective and efficient tool for outpatient antibiotic stewardship. We aimed to develop and validate an electronic algorithm to identify inappropriate antibiotic use for pediatric outpatients with pharyngitis. Methods: This study was conducted within the Children’s Hospital of Philadelphia (CHOP) Care Network, including 31 pediatric primary care practices and 3 urgent care centers with a shared EHR serving >250,000 children. We used International Classification of Diseases, Tenth Revision (ICD-10) codes to identify encounters for pharyngitis at any CHOP practice from March 15, 2017, to March 14, 2018, excluding those with concurrent infections (eg, otitis media, sinusitis), immunocompromising conditions, or other comorbidities that might influence the need for antibiotics. We randomly selected 450 features for detailed chart abstraction assessing patient demographics as well as practice and prescriber characteristics. Appropriateness of antibiotic use based on chart review served as the gold standard for evaluating the electronic algorithm. Criteria for appropriate use included streptococcal testing, use of penicillin or amoxicillin (absent β-lactam allergy), and a 10-day duration of therapy. Results: In 450 patients, the median age was 8.4 years (IQR, 5.5–9.0) and 54% were women. On chart review, 149 patients (33%) received an antibiotic, of whom 126 had a positive rapid strep result. Thus, based on chart review, 23 subjects (5%) diagnosed with pharyngitis received antibiotics inappropriately. Amoxicillin or penicillin was prescribed for 100 of the 126 children (79%) with a positive rapid strep test. Of the 126 children with a positive test, 114 (90%) received the correct antibiotic: amoxicillin, penicillin, or an appropriate alternative antibiotic due to b-lactam allergy. Duration of treatment was correct for all 126 children. Using the electronic algorithm, the proportion of inappropriate prescribing was 28 of 450 (6%). The test characteristics of the electronic algorithm (compared to gold standard chart review) for identification of inappropriate antibiotic prescribing were sensitivity (99%, 422 of 427); specificity (100%, 23 of 23); positive predictive value (82%, 23 of 28); and negative predictive value (100%, 422 of 422). Conclusions: For children with pharyngitis, an electronic algorithm for identification of inappropriate antibiotic prescribing is highly accurate. Future work should validate this approach in other settings and develop and evaluate the impact of an audit and feedback intervention based on this tool.Funding: NoneDisclosures: None

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Development of an Electronic Algorithm to Target Outpatient Antimicrobial Stewardship Efforts for Acute Bronchitis

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.510 ◽

2020 ◽

Vol 41 (S1) ◽

pp. s32-s32

Author(s):

Ebbing Lautenbach ◽

Keith Hamilton ◽

Robert Grundmeier ◽

Melinda Neuhauser ◽

Lauri Hicks ◽

...

Keyword(s):

Antimicrobial Stewardship ◽

Predictive Value ◽

Gold Standard ◽

Chart Review ◽

Acute Bronchitis ◽

Antibiotic Use ◽

Antibiotic Prescribing ◽

Diagnostic Codes ◽

Icd 10 ◽

The Impact

Background: Antibiotic resistance has increased at alarming rates, driven predominantly by antibiotic overuse. Although most antibiotic use occurs in outpatients, antimicrobial stewardship programs have primarily focused on inpatient settings. A major challenge for outpatient stewardship is the lack of accurate and accessible electronic data to target interventions. We sought to develop and validate an electronic algorithm to identify inappropriate antibiotic use for outpatients with acute bronchitis. Methods: This study was conducted within the University of Pennsylvania Health System (UPHS). We used ICD-10 diagnostic codes to identify encounters for acute bronchitis at any outpatient UPHS practice between March 15, 2017, and March 14, 2018. Exclusion criteria included underlying immunocompromising condition, other comorbidity influencing the need for antibiotics (eg, emphysema), or ICD-10 code at the same visit for a concurrent infection (eg, sinusitis). We randomly selected 300 (150 from academic practices and 150 from nonacademic practices) eligible subjects for detailed chart abstraction that assessed patient demographics and practice and prescriber characteristics. Appropriateness of antibiotic use based on chart review served as the gold standard for assessment of the electronic algorithm. Because antibiotic use is not indicated for this study population, appropriateness was assessed based upon whether an antibiotic was prescribed or not. Results: Of 300 subjects, median age was 61 years (interquartile range, 50–68), 62% were women, 74% were seen in internal medicine (vs family medicine) practices, and 75% were seen by a physician (vs an advanced practice provider). On chart review, 167 (56%) subjects received an antibiotic. Of these subjects, 1 had documented concern for pertussis and 4 had excluding conditions for which there were no ICD-10 codes. One received an antibiotic prescription for a planned dental procedure. Thus, based on chart review, 161 (54%) subjects received antibiotics inappropriately. Using the electronic algorithm based on diagnostic codes, underlying and concurrent conditions, and prescribing data, the number of subjects with inappropriate prescribing was 170 (56%) because 3 subjects had antibiotic prescribing not noted based on chart review. The test characteristics of the electronic algorithm (compared to gold standard chart review) for identification of inappropriate antibiotic prescribing were the following: sensitivity, 100% (161 of 161); specificity, 94% (130 of 139); positive predictive value, 95% (161 of 170); and negative predictive value, 100% (130 of 130). Conclusions: For outpatients with acute bronchitis, an electronic algorithm for identification of inappropriate antibiotic prescribing is highly accurate. This algorithm could be used to efficiently assess prescribing among practices and individual clinicians. The impact of interventions based on this algorithm should be tested in future studies.Funding: NoneDisclosures: None

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Chronic Constrictive Pericarditis

Case Reports in Cardiology ◽

10.1155/2013/957497 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4

Author(s):

Hossein Doustkami ◽

Afshin Hooshyar ◽

Nasrollah Maleki ◽

Zahra Tavosi ◽

Iraj Feizi

Keyword(s):

Cardiac Catheterization ◽

Constrictive Pericarditis ◽

Gold Standard ◽

Elevated Serum ◽

Disease Process ◽

Clinical Suspicion ◽

Rare Clinical Entity ◽

Good Recovery ◽

Prompt Treatment ◽

High Degree

Constrictive pericarditis (CP) is a rare clinical entity that can pose diagnostic problems. The diagnosis of CP requires a high degree of clinical suspicion. The gold standard for diagnosis is cardiac catheterization with analysis of intracavitary pressure curves, which are high and, in end diastole, equal in all chambers. We present a patient with unexplained dyspnea, recurrent right-side pleural effusion, and ascites. Analysis of the ascitic fluid revealed a high protein content and an elevated serum-ascites gradient. Echocardiography, computed tomography, and cardiac catheterization revealed the diagnosis of CP. He underwent complete pericardiectomy and to date has made a good recovery. The diagnosis of CP is often neglected by admitting physicians, who usually attribute the symptoms to another disease process. This case exemplifies the difficulty in diagnosing this condition, as well as the investigation required, and provides a discussion of the benefit and outcomes of prompt treatment.

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