Design and reporting considerations for genetic screening tests

Testing asymptomatic individuals for unsuspected conditions is not new to the medical and public health communities and protocols to develop screening tests are well-established. However, the application of screening principles to inherited diseases presents unique challenges. Unlike most screening tests, the natural history and disease prevalence of most rare inherited diseases in an unselected population are unknown. It is difficult or impossible to obtain a “truth set” cohort for clinical validation studies. As a result, it is not possible to accurately calculate clinical positive and negative predictive values for “likely pathogenic” genetic variants, which are commonly returned in genetic screening assays. In addition, many of the genetic conditions included in screening panels do not have clinical confirmatory tests. All of these elements are typically required to justify the development of a screening test, according to the World Health Organization screening principles. Nevertheless, as the cost of DNA sequencing continues to fall, more individuals are opting to undergo genomic testing in the absence of a clinical indication. Despite the challenges, reasonable estimates can be deduced and used to inform test design strategies. Here, we review test design principles and apply them to genetic screening.

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Design and reporting considerations for genetic screening tests

10.7287/peerj.preprints.27922v2 ◽

2019 ◽

Author(s):

Jill Hagenkord ◽

Birgit Funke ◽

Emily Qian ◽

Madhuri Hegde ◽

Kevin B Jacobs ◽

...

Keyword(s):

Genetic Screening ◽

World Health ◽

Screening Tests ◽

Clinical Indication ◽

Test Design ◽

Design Strategies ◽

Predictive Values ◽

Inherited Diseases ◽

Health Communities ◽

Health Organization

Testing asymptomatic individuals for unsuspected conditions is not new to the medical and public health communities and protocols to develop screening tests are well-established. However, the application of screening principles to inherited diseases presents unique challenges. Unlike most screening tests, the natural history and disease prevalence of most rare inherited diseases in an unselected population are unknown. It is difficult or impossible to obtain a “truth set” cohort for clinical validation studies. As a result, it is not possible to accurately calculate clinical positive and negative predictive values for “likely pathogenic” genetic variants, which are commonly returned in genetic screening assays. In addition, many of the genetic conditions included in screening panels do not have clinical confirmatory tests. All of these elements are typically required to justify the development of a screening test, according to the World Health Organization screening principles. Nevertheless, as the cost of DNA sequencing continues to fall, more individuals are opting to undergo genomic testing in the absence of a clinical indication. Despite the challenges, reasonable estimates can be deduced and used to inform test design strategies. Here, we review test design principles and apply them to genetic screening.

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Design and reporting considerations for genetic screening tests

10.7287/peerj.preprints.27922v3 ◽

2019 ◽

Author(s):

Jill Hagenkord ◽

Birgit Funke ◽

Emily Qian ◽

Madhuri Hegde ◽

Kevin B Jacobs ◽

...

Keyword(s):

Genetic Screening ◽

World Health ◽

Screening Tests ◽

Clinical Indication ◽

Test Design ◽

Design Strategies ◽

Predictive Values ◽

Inherited Diseases ◽

Health Communities ◽

Health Organization

Testing asymptomatic individuals for unsuspected conditions is not new to the medical and public health communities and protocols to develop screening tests are well-established. However, the application of screening principles to inherited diseases presents unique challenges. Unlike most screening tests, the natural history and disease prevalence of most rare inherited diseases in an unselected population are unknown. It is difficult or impossible to obtain a “truth set” cohort for clinical validation studies. As a result, it is not possible to accurately calculate clinical positive and negative predictive values for “likely pathogenic” genetic variants, which are commonly returned in genetic screening assays. In addition, many of the genetic conditions included in screening panels do not have clinical confirmatory tests. All of these elements are typically required to justify the development of a screening test, according to the World Health Organization screening principles. Nevertheless, as the cost of DNA sequencing continues to fall, more individuals are opting to undergo genomic testing in the absence of a clinical indication. Despite the challenges, reasonable estimates can be deduced and used to inform test design strategies. Here, we review test design principles and apply them to genetic screening.

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Accuracy of Intraoperative Examination in Central Nervous System Lesions: A Study of 133 Cases

Acta Cytologica ◽

10.1159/000495175 ◽

2019 ◽

Vol 63 (3) ◽

pp. 224-232

Author(s):

Ludmila Barbosa de Souza Balsimelli ◽

Jamille Costa de Oliveira ◽

Flora Ávila Adorno ◽

Clarissa Almeida Brites ◽

Giuliano Stefanello Bublitz ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Frozen Section ◽

Final Diagnosis ◽

World Health ◽

Histopathological Diagnosis ◽

Low Grade ◽

Predictive Values ◽

Health Organization ◽

Cns Lesions

Objective: Intraoperative examination is a highly valuable tool for the evaluation of central nervous system (CNS) lesions, helping the neurosurgeon to determine the best surgical management. This study aimed to evaluate the accuracy and to analyze the diagnostic disagreements and pitfalls of the intraoperative examinations through correlation with the final histopathological diagnosis in CNS lesions. Study Design: Retrospective analysis of intraoperative examination of CNS lesions and their final diagnosis obtained during 16 consecutive years. All diagnoses were reviewed and classified according to World Health Organization (WHO) grading for CNS tumors. Squash was performed in 119 cases, while frozen section and both methods were done in 7 cases each. Results: Among the 133 intraoperative examinations considered, 114 (85.7%) presented concordance and 19 (14.3%) diagnostic disagreement when compared with subsequent histopathological examinations. The sensitivity and specificity for the detection of neoplasia in intraoperative examination was 98 and 94%, respectively. The positive and negative predictive values were 99 and 88%, respectively. The accuracy for neoplastic and nonneoplastic disease was 85.7%. Disagreements were more frequent among low-grade (WHO grades I and II) neoplasms and nonmalignant cases. Conclusions: Our results showed good accuracy of the intraoperative assessments for diagnosis of CNS lesions, particularly in high-grade (grades III and IV) lesions and metastatic neoplasms.

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Predicting the community prevalence of schistosomiasis mansoni from the prevalence among 7- to 14-year-olds

Parasitology ◽

10.1017/s0031182099006733 ◽

2000 ◽

Vol 121 (5) ◽

pp. 507-512 ◽

Cited By ~ 6

Author(s):

L. C. RODRIGUES ◽

J. G. WHEELER ◽

R. SHIER ◽

H. L. GUERRA ◽

F. PIMENTA ◽

...

Keyword(s):

Treatment Strategies ◽

Strong Relationship ◽

Community Treatment ◽

World Health ◽

Age Group ◽

Predictive Values ◽

Schistosomiasis Mansoni ◽

Indicator Group ◽

The World ◽

Health Organization

The World Health Organization suggested that the prevalence of Schistosoma mansoni among 7- to 14-year-olds be used to guide treatment strategies in endemic areas. This study explores how well the prevalence in that age group predicted the overall prevalence in the community in data from stool examinations (Kato–Katz method) from 180000 people in 3 municipalities in Brazil in 1984 and 1985. The median prevalence was higher in 1984, before community treatment was introduced. There was a strong relationship between the prevalence among 7- to 14-year-olds and the overall prevalence in the community. We present sensitivities and positive predictive values for the use of prevalence in the indicator group to select communities for mass treatment as recommended by WHO. For a range of assumptions sensitivity and positive predictive value were never both above 80%. We suggest that the estimates of validity presented in this paper inform future evaluations of strategies for S. mansoni control.

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Ethical Aspects of Genetic Screening in Israel

Science in Context ◽

10.1017/s0269889700003112 ◽

1998 ◽

Vol 11 (3-4) ◽

pp. 419-429 ◽

Cited By ~ 11

Author(s):

Michal Sagi

Keyword(s):

World Health Organization ◽

Genetic Screening ◽

Genetic Diseases ◽

Genetic Research ◽

Carrier Screening ◽

World Health ◽

Ethical Aspects ◽

The World ◽

Health Organization

The ArgumentAdvances in genetic research make it possible to identify carriers of a growing number of genetic diseases. The World Health Organization (WHO) published several preconditions for community carrier screening. This paper aims to present some of the dilemmas about screening in Israel and the difficulties in following the WHO's helpful criteria.

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PERBEDAAN PENGGUNAAN MEDIA LEAFLET DENGAN VIDEO TENTANG PENGETAHUAN DAN SIKAP SISWA MATERI MAKANAN JAJANAN (Studi Penelitian di SDN Kertajaya IX/215 Kecamatan Gubeng Kota Surabaya Tahun 2018)

GEMA LINGKUNGAN KESEHATAN ◽

10.36568/kesling.v16i3.900 ◽

2018 ◽

Vol 16 (3) ◽

Author(s):

Dina Rakhmawati ◽

Nurhaidah . ◽

Suprijandani .

Keyword(s):

World Health Organization ◽

T Test ◽

Video Data ◽

World Health ◽

P Value ◽

Test Design ◽

Post Test ◽

Health Organization ◽

Paired T Test

Makanan jajanan menurut WHO (World Health Organization) adalah makanan dan minuman yang dipersiapkan dan dijual oleh pedagang kaki lima di jalanan dan tempat-tempat yang ramai atau tempat-tempat umum yang dapat dimakan atau dikonsumsi tanpa pengolahan lebih lanjut. Selama ini masih banyak makanan jajanan yang berpotensi dapat mengganggu kesehatan, seperti keracunan makanan. Dalam upaya menghindari terjadinya keracunan makanan maka perlu meningkatkan pengetahuan dan sikap anak usia sekolah tentang makanan jajanan menggunakan alat bantu atau media promosi, seperti media leaflet dan media video. Penelitian ini bertujuan untuk mengetahui perbedaan penyuluhan menggunakan media leaflet dengan video tentang pengetahuan dan sikap siswa materi makanan jajanan.Jenis penelitian ini merupakan penelitian pra-eksperimental dengan rancangan penelitian yang digunakan adalah pra-eksperimen one group pre-post test design. Sampel dalam penelitian ini sebanyak 51 siswa kelas V pada responden kelompok media leaflet dan 51 siswa kelas V pada responden kelompok media video. Data yang diperoleh selanjutnya dianalisis secara analitik menggunakan paired t test pada program komputer.Hasil penelitian menunjukkan bahwa ada perbedaan yang signifikan rata-rata nilai tingkat pengetahuan tentang makanan jajanan sebelum dengan sesudah dilakukan penyuluhan pada kelompok media leaflet dengan p value (0,032) < α (0,05), sedangkan pada sikap kelompok media leaflet dan pengetahuan serta sikap kelompok media video tidak terdapat perbedaan yang signifikan p value > α (0,05).Kesimpulan dalam penelitian ini diketahui bahwa penggunaan media leaflet dalam penyuluhan lebih baik dibandingkan dengan media video terhadap peningkatan pengetahuan dan sikap responden. Disarankan agar sekolah melakukan penyuluhan secara berkala menggunakan bantuan media leaflet.Kata Kunci : Pengetahuan, Sikap, Media Leaflet dan Video

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COVID19 detection from Radiographs: Is Deep Learning able to handle the crisis?

10.36227/techrxiv.12476426 ◽

2020 ◽

Author(s):

Muhammad Saqib ◽

Saeed Anwar ◽

Abbas Anwar ◽

Lars petersson ◽

Michael Blumenstein

Keyword(s):

Deep Learning ◽

Viral Infection ◽

Viral Infections ◽

State Of The Art ◽

World Health ◽

Screening Tests ◽

Early Screening ◽

Current State ◽

Infection Types ◽

Health Organization

The COVID-19 is a highly contagious viral infection which played havoc on everyone's life in many different ways. According to the world health organization and scientists, more testing potentially helps governments and disease control organizations in containing the spread of the virus. The use of chest radiographs is one of the early screening tests to determine the onset of disease, as the infection affects the lungs severely. This study will investigate and automate the process of testing by using state-of-the-art CNN classifiers to detect the COVID19 infection. However, the viral could of many different types; therefore, we only regard for COVID19 while the other viral infection types are treated as non-COVID19 in the radiographs of various viral infections. The classification task is challenging due to the limited number of scans available for COVID19 and the minute variations in the viral infections. We aim to employ current state-of-the-art CNN architectures, compare their results, and determine whether deep learning algorithms can handle the crisis appropriately. All trained models are available at https://github.com/saeed-anwar/COVID19-Baselines

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Management of HIV Infection during Pregnancy in the United States: Updated Evidence-Based Recommendations and Future Potential Practices

Infectious Diseases in Obstetrics and Gynecology ◽

10.1155/2016/7594306 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Bassam H. Rimawi ◽

Lisa Haddad ◽

Martina L. Badell ◽

Rana Chakraborty

Keyword(s):

United States ◽

Hiv Infection ◽

Hiv Transmission ◽

The United States ◽

Maternal Serum ◽

World Health ◽

Screening Tests ◽

Virologic Suppression ◽

Perinatal Hiv ◽

Health Organization

All HIV-infected women contemplating pregnancy should initiate combination antiretroviral therapy (cART), with a goal to achieve a maternal serum HIV RNA viral load beneath the laboratory level of detection prior to conceiving, as well as throughout their pregnancy. Successfully identifying HIV infection during pregnancy through screening tests is essential in order to preventin uteroand intrapartum transmission of HIV. Perinatal HIV transmission can be less than 1% when effective cART, associated with virologic suppression of HIV, is given during the ante-, intra-, and postpartum periods. Perinatal HIV guidelines, developed by organizations such as the World Health Organization, American College of Obstetricians and Gynecologists, and the US Department of Health and Human Services, are constantly evolving, and hence the aim of our review is to provide a useful concise review for medical providers caring for HIV-infected pregnant women, summarizing the latest and current recommendations in the United States.

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Determining post-treatment surveillance criteria for predicting the elimination of Schistosoma mansoni transmission

Parasites & Vectors ◽

10.1186/s13071-019-3611-8 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 2

Author(s):

Jaspreet Toor ◽

James E. Truscott ◽

Marleen Werkman ◽

Hugo C. Turner ◽

Anna E. Phillips ◽

...

Keyword(s):

Schistosoma Mansoni ◽

Monitoring And Evaluation ◽

Diagnostic Techniques ◽

Post Treatment ◽

World Health ◽

Infection Prevalence ◽

Predictive Values ◽

Two Samples ◽

Health Organization ◽

Low Prevalence

Abstract Background The World Health Organization (WHO) has set elimination (interruption of transmission) as an end goal for schistosomiasis. However, there is currently little guidance on the monitoring and evaluation strategy required once very low prevalence levels have been reached to determine whether elimination or resurgence of the disease will occur after stopping mass drug administration (MDA) treatment. Methods We employ a stochastic individual-based model of Schistosoma mansoni transmission and MDA impact to determine a prevalence threshold, i.e. prevalence of infection, which can be used to determine whether elimination or resurgence will occur after stopping treatment with a given probability. Simulations are run for treatment programmes with varying probabilities of achieving elimination and for settings where adults harbour low to high burdens of infection. Prevalence is measured based on using a single Kato-Katz on two samples per individual. We calculate positive predictive values (PPV) using PPV ≥ 0.9 as a reliable measure corresponding to ≥ 90% certainty of elimination. We analyse when post-treatment surveillance should be carried out to predict elimination. We also determine the number of individuals across a single community (of 500–1000 individuals) that should be sampled to predict elimination. Results We find that a prevalence threshold of 1% by single Kato-Katz on two samples per individual is optimal for predicting elimination at two years (or later) after the last round of MDA using a sample size of 200 individuals across the entire community (from all ages). This holds regardless of whether the adults have a low or high burden of infection relative to school-aged children. Conclusions Using a prevalence threshold of 0.5% is sufficient for surveillance six months after the last round of MDA. However, as such a low prevalence can be difficult to measure in the field using Kato-Katz, we recommend using 1% two years after the last round of MDA. Higher prevalence thresholds of 2% or 5% can be used but require waiting over four years for post-treatment surveillance. Although, for treatment programmes where elimination is highly likely, these higher thresholds could be used sooner. Additionally, switching to more sensitive diagnostic techniques, will allow for a higher prevalence threshold to be employed.

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