Triage Screening Research Articles

Clinical performance of Onclarity HPV assay and Cobas HPV test in detection of cervical precancer and cancer in Chinese women

ObjectiveThe Roche Cobas (Cobas) and BD Onclarity (Onclarity) human papillomavirus (HPV) assays are convenient, PCR-based, HPV DNA tests; currently, data on performance of Onclarity in Chinese women is limited. We aimed to evaluate the clinical performance of Onclarity for detecting cervical lesions in Chinese women. MethodsIn total, 1122 women were enrolled into this study. Exfoliated cervical cells were collected in PreservCyt medium and were tested using Cobas and Onclarity. Cytology and histology were interpreted by senior cytologists and a panel of pathologists, respectively, at Cancer Hospital, Chinese Academy of Medical Sciences. ResultsThe assays showed excellent concordance for HPV16 (kappa = 0.91, 95% CI: 0.85–0.97) and for 12 other high-risk types (HPV31/33/35/39/45/51/52/56/58/59/66/68, kappa = 0.84, 95% CI: 0.78–0.90), and very good concordance for HPV18 (kappa = 0.75, 95% CI: 0.69–0.81). No difference for ≥CIN2 sensitivity was observed between Onclarity and Cobas (both 90.5%); and the <CIN2 specificity for detection was similar between Onclarity (84.2%, 95% CI: 81.6–86.4) and Cobas (80.4%, 95% CI: 77.6–82.8). When combined with cytology triage, the colposcopy referral rate point estimate was slightly lower for Onclarity (9.0%) than for Cobas (11.0%), with the same ≥CIN2 sensitivity of 75.0% (95% CI: 53.1–88.8) for Onclarity and Cobas. ConclusionsOnclarity exhibited comparable screening performance and triage efficiency compared to Cobas in detection of cervical lesions in Chinese women.

P16/Ki-67 dual-stained cytology used for triage in cervical cancer opportunistic screening.

ObjectiveTo evaluate the efficiency of p16/Ki-67 dual stain used as a triage in cervical cancer screening.MethodsIn this study, we did 468 p16/Ki-67 dual stain in human papillomavirus (HPV) 16/18-positive or 12 other high-risk HPV (OHR-HPV) positive Thinprep cytologic test (TCT) atypical squamous cells of undetermined significance (ASCUS)/ lower-grade squamous intraepithelial lesion (LSIL) women. We evaluated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the triage test.ResultsThe sensitivity, specificity, PPV and NPV of p16/Ki-67 dual stain in HPV 16/18-positive women were 91.5%/68.4%, 77.0%/75.0%, 73.9%/59.1% and 92.8%/81.8%. In 12 OHR-HPV positive TCT ASCUS/LSIL women, the results were 79.1%/95.0%, 88.5%/66.7%, 88.5%/70.4% and 89.2%/94.1%. The risk of precancerous lesions in p16/Ki-67 dual stain positive cases was much higher than before, and the negative cases had lower risk. Besides, there was no cervical intraepithelial neoplasia (CIN) III case missed after triaged by p16/Ki-67 dual-stained cytology. In p16/Ki-67 dual-stained cytology positive women with benign pathology or CIN I, the 1-year progression rate is 20.5% and in p16/Ki-67 dual-stained cytology negative women, the 1-year progression rate is 5.6%.Conclusionshr-HPV genotyping test plays an important role in cervical cancer screening. p16/Ki-67 dual stain may be a promising triage test. As for chronic cervicitis or CIN I patients, a positive p16/Ki-67 dual-stained cytology suggests a high risk in progression and need to be followed up closely.

Revised Triage and Surveillance Protocols for Temporary Emergency Department Closures in Tertiary Hospitals as a Response to COVID-19 Crisis in Daegu Metropolitan City.

BackgroundWhen an emergency-care patient is diagnosed with an emerging infectious disease, hospitals in Korea may temporarily close their emergency departments (EDs) to prevent nosocomial transmission. Since February 2020, multiple, consecutive ED closures have occurred due to the coronavirus disease 2019 (COVID-19) crisis in Daegu. However, sudden ED closures are in contravention of laws for the provision of emergency medical care that enable the public to avail prompt, appropriate, and 24-hour emergency medical care. Therefore, this study ascertained the vulnerability of the ED at tertiary hospitals in Daegu with regard to the current standards. A revised triage and surveillance protocol has been proposed to tackle the current crisis.MethodsThis study was retrospectively conducted at 6 level 1 or 2 EDs in a metropolitan city where ED closure due to COVID-19 occurred from February 18 to March 26, 2020. The present status of ED closure and patient characteristics and findings from chest radiography and laboratory investigations were assessed. Based on the experience from repeated ED closures and the modified systems that are currently used in EDs, revised triage and surveillance protocols have been developed and proposed.ResultsDuring the study period, 6 level 1 or 2 emergency rooms included in the study were shut down 27 times for 769 hours. Thirty-one confirmed COVID-19 cases, of whom 7 died, were associated with the incidence of ED closure. Typical patient presentation with respiratory symptoms of COVID-19 was seen in less than 50% of patients, whereas abnormal findings on chest imaging investigations were detected in 93.5% of the study population. The chest radiography facility, resuscitation rooms, and triage area were moved to locations outside the ED, and a new surveillance protocol was applied to determine the factors warranting quarantine, including symptoms, chest radiographic findings, and exposure to a source of infection. The incidence of ED closures decreased after the implementation of the revised triage and surveillance protocols.ConclusionTriage screening by emergency physicians and surveillance protocols with an externally located chest imaging facility were effective in the early isolation of COVID-19 patients. In future outbreaks of emerging infectious diseases, efforts should be focused toward the provision of continued ED treatment with the implementation of revised triage and surveillance protocols.

Sensitivity and specificity of a Middle East respiratory syndrome screening tool used in the emergency department

Background: Middle East respiratory syndrome coronavirus (MERS-CoV) infection becomes a global health issue because of its ability to spread rapidly, especially in healthcare settings. Improper triage of MERS-CoV-infected patients in the emergency department (ED) increases the risk of infection in healthcare providers and other patients. Having a good triage screening tool would improve early detection and isolation of suspected infected patients, thus preventing future outbreaks. Materials and Methods: This is a retrospective cohort study performed in a large urban, academic ED in a tertiary care center in Riyadh, Saudi Arabia. The aim of the study was to assess the accuracy of the triage screening tool used in the ED. A convenience sample of 734 patients visiting the ED during the 2015 MERS-CoV outbreak was included. Patients deemed positive were isolated and underwent MERS-CoV polymerase chain reaction (PCR) testing. Patients deemed negative were followed up via phone after two weeks of their ED visit. They were checked for the development of symptoms and whether the patients sought medical advice in another hospital or underwent MERS-CoV PCR testing. Results: The sensitivity of the screening tool for detecting PCR-positive MERS-CoV infection was 100% (95% confidence interval [CI]: 15.8–100), and the specificity was 78.2% (95% CI: 75.1–81.2). Conclusions: The ED triage screening tool used during the 2015 MERS-CoV outbreak is highly sensitive. It is effective for early detection of infection in the ED, thus allowing timely isolation of suspected patients.

204 Screening for Balance and Vision Symptoms in Triage to Enhance Identification of Strokes in the Emergency Department

Prompt identification of stroke is essential as primary interventions such as tissue plasminogen activator (tPA) and thrombectomies are extremely time sensitive. Time is brain and stroke screening scales such as the FAST (Face, Arms, Speech, Time) exam are critical in efforts towards early identification and aggressive treatment. Although FAST has commendable sensitivity and specificity, its ability in identifying posterior circulation strokes, which often only present with balance and visual symptoms, has been challenged. To address this, an augmented stroke screening scale, BE-FAST, was developed with the inclusion of two additional criteria (Balance, Eyes) to enhance stroke detection. The primary objective of this study was to evaluate the sensitivity, specificity, and impact on stroke core measures with the implementation of the BE-FAST scale in comparison to FAST in triage of a community emergency department (ED). An observational before-and-after quality improvement (QI) study was conducted for the two-month period before and after October 8th, 2018 when a formal BE-FAST triage screening educational module was taught to all ED clinical staff. The study sample included all patients who had stroke alerts activated based on their presenting symptoms in the ED. These patients were then divided into two groups: pre-intervention with FAST and post-intervention with BE-FAST criteria. Extensive chart review was then performed to collect the following variables: age, sex, primary identifying symptoms, time to stroke alert, time to CT/CTA, confirmation of stroke as final discharge diagnosis and hospital mortality. Categorical data were compared using the chi-square test for association, and between-group mean differences were compared by calculating t-tests for independent measures and analysis of variance. 155 total stroke alerts were included in the study, with 69 in the pre-intervention and 86 in the post-intervention group. Mean ages for both study groups were similar (68.3, SD=17.0 and 64.3, SD=15.5) with a similar preponderance of females (60.9% and 62.8%). In the pre-intervention group, 29 (36.2%) had acute strokes and presented with ≥1 FAST criteria. In the post-intervention group, 27 (31.4%) had acute strokes, with 23 (85.2%) presenting with ≥1 FAST, and 26 (96.30%) with ≥1 BE-FAST criteria. FAST rendered a sensitivity of 84% and BE-FAST 88%; however, with the additional two criterions, specificity declined from 30% to 16% respectively. Description of sample demographics, times and outcomes are detailed in Table 1. BE-FAST demonstrates potential for improved stroke screening sensitivity, although in the setting of a community ED, this did not outperform FAST in a statistically significant manner. Yet, given the significant burden of long-term deficits and opportunities for early interventions, the identification of even a single additional stroke is arguably clinically significant. Larger trials evaluating the efficacy of BE-FAST should be conducted before widespread implementation into stroke protocols.

Clinical Scores and Formal Triage for Screening of Sepsis and Adverse Outcomes on Arrival in an Emergency Department All-Comer Cohort.

Early recognition of sepsis remains a major challenge. The clinical utility of the Quick Sepsis-Related Organ Failure Assessment (qSOFA) score is still undefined. Several studies have tested its prognostic value. However, its ability to diagnose sepsis is still unknown. Our aim was to compare the performance of qSOFA, systemic inflammatory response syndrome (SIRS) criteria, National Early Warning Score (NEWS), and formal triage with the Emergency Severity Index (ESI) algorithm to identify patients with sepsis and predict adverse outcomes on arrival in an emergency department (ED) all-comer cohort. We included all patients presenting consecutively to the ED during a 3-week period. We used vital signs recorded at triage to calculate the study scores. Two independent assessors retrospectively assigned the primary outcome of sepsis according to Third International Consensus Definitions for Sepsis and Septic Shock criteria in a chart review process. There were 2523 cases included in the analysis and 39 (1.6%) had the primary outcome of sepsis. The area under the curve for sepsis was 0.79 (95% confidence interval [CI] 0.71-0.86) for qSOFA, 0.81 (95% CI 0.73-0.87) for SIRS, 0.85 (95% CI 0.77-0.92) for NEWS, and 0.77 (95% CI 0.70-0.83) for ESI. qSOFA offered high specificity for the prediction of sepsis and adverse outcomes. However, its low sensitivity does not support widespread use as a screening tool for sepsis. NEWS outperformed qSOFA for prediction of adverse outcomes and screening for sepsis.

227 Screening for Frailty in the Emergency Department: Comparison of Tools

Abstract Background Numerous tools exist to screen for frailty in clinical settings but a single international standard has not yet been adopted. Recent research indicates that more than one tool is often deployed by clinicians to diagnose frailty. This study aimed to compare the use of two screening tools in the emergency department and assess the predictive ability of keywords in triage notes to detect frailty. Methods Frailty screening was carried out on 198 individuals (100 female / 98 male) attending the emergency department of a large urban teaching hospital, using the Rockwood Clinical Frailty Scale and the Variable Indicative of Placement Risk (VIP) scale. Average screening time for Rockwood was 43.1 ± 21.7s, whilst average screening time for VIP was 11.8 ± 8.5s. Results were dichotomised to frail, corresponding to Rockwood scores of ≥4 or VIP scores of ≥1, or non-frail (Rockwood=1-3 or VIP=0) for comparisons. Triage notes were reviewed to find keywords associated with frail patients. Results Among 198 individuals screened, 149 (75.3%) were frail according to Rockwood, and 143 (72.2%) according to VIP. 25 (12.6%) of the 198 individuals were categorised as frail according to Rockwood but were non-frail according to VIP. Among these, 8 were female (8% of all female patients; 6 were 75+ years of age, and 2 were under 75) and 17 were male (17.3% of all male patients; 11 were 75+ years of age and 6 were under 75). Keywords associated with frailty were identified from triage notes, across the following categories: Falls/ mobility/ balance; Cognition; Living circumstances; Nutrition; Other frailty-associated conditions; and General deterioration. Conclusion Comparison of the two scales suggests that frailty could be missed if relying on a single index. This effect may be more frequent in men than women. Screening triage notes to identify frailty-associated keywords may be a helpful adjunct to existing tools.

A Qualified Success: Discovery of a New Series of ATAD2 Bromodomain Inhibitors with a Novel Binding Mode Using High-Throughput Screening and Hit Qualification.

The bromodomain of ATAD2 has proved to be one of the least-tractable proteins within this target class. Here, we describe the discovery of a new class of inhibitors by high-throughput screening and show how the difficulties encountered in establishing a screening triage capable of finding progressible hits were overcome by data-driven optimization. Despite the prevalence of nonspecific hits and an exceptionally low progressible hit rate (0.001%), our optimized hit qualification strategy employing orthogonal biophysical methods enabled us to identify a single active series. The compounds have a novel ATAD2 binding mode with noncanonical features including the displacement of all conserved water molecules within the active site and a halogen-bonding interaction. In addition to reporting this new series and preliminary structure-activity relationship, we demonstrate the value of diversity screening to complement the knowledge-based approach used in our previous ATAD2 work. We also exemplify tactics that can increase the chance of success when seeking new chemical starting points for novel and less-tractable targets.

Australian women's self-perceived barriers to participation in cervical cancer screening: A systematic review.

Australia has recently introduced a new screening program for cervical cancer. There has also been a decline in participation rates for cervical screening. To complete a systematic literature review of the factors that prevent Australian women from participating in cervical screening. Authors searched CINAHL, Medline, SCOPUS and the Cochrane Library to obtain articles discussing Australian women's self-identified barriers to cervical screening. Quantitative studies published in peer-reviewed journals after 1991 were considered. PROSPERO Registration Number: CRD42018105028. The final search produced 1749 studies, with 13 quantitative papers included in the narrative synthesis after screening by two independent reviewers. No articles were excluded due to bias. Self-identified barriers to screening were categorised into personal, practitioner, test-related and logistical factors. The most commonly stated barriers included lack of time, embarrassment, fear of results, irrelevance and male health professionals. The use of HPV triage in cervical screening was not a barrier to screening, however, some women regarded self-collected HPV testing as a barrier. Barriers to self-collection included desire for the general practitioner to complete the test, fear of doing the test incorrectly, wishing to include it in a general check-up and concerns about the test itself. A variety of personal, practitioner, test-related and logistical barriers negatively impact the screening participation of Australian women. Further research into barriers in the Australian population, and women's attitudes towards HPV testing and self-collection is required to create effective health interventions to improve participation in cervical screening.

Using modified sepsis criteria to improve specificity of standardized triage screening for pediatric severe sepsis and septic shock

Background: Effective triage for patients with severe sepsis is critical first step for timely recognition and management. We implemented a standardized pediatric sepsis screening tool based on Goldstein SIRS criteria to streamline our ED triage process in 2013. Although the baseline cohort (N=259) had no patients missed, specificity of our screening tool was only 0.270 for severe sepsis. Implementation of this tool raised concerns for over triage, misappropriation of resources and alert fatigue. We set a goal to …

Using modified sepsis criteria to improve specificity of standardized triage screening for pediatric severe sepsis and septic shock

Using modified sepsis criteria to improve specificity of standardized triage screening for pediatric severe sepsis and septic shock

The burden of 14 hr-HPV genotypes in women attending routine cervical cancer screening in 20 states of Mexico: a cross-sectional study

In Mexico, HPV vaccines available immunize against genotypes 16/18 and 16/18/6/11; however, there is limited surveillance about carcinogenic subtypes in different states of the country that allow evaluating the effectiveness of vaccination and cervical cancer screening programs. Here, we report the regional and age-specific prevalence of 14 hr-HPV genotypes as well as their prevalence in abnormal cytology (from ASCUS to cervical cancer) among Mexican women which were undergoing from cervical cancer screening in the Salud Digna clinics in 20 states of the country. This study includes women with social security from the majority of public health institutions (IMSS, ISSSTE, SEMAR, and PEMEX), and women without social security. For cervical cancer screening, we used the SurePath liquid-based cytology and the BD Onclarity HPV Assay. From December 1, 2016, to August 2, 2018, the hr-HPV prevalence among 60,135 women was 24.78%, the most prevalent types were HPV 16 (4.13%), HPV 31 (4.12%) and HPV 51 (3.39%), while HPV 18 (1.70%) was less prevalent among infected women. Interestingly, the genotypes not covered by current vaccines in Mexico were commonly found in precancerous lesions, evidencing their carcinogenic potential, so it is necessary to increase their surveillance and inclusion in cervical cancer screening triage.

HPV testing compared with routine cytology in cervical screening: long-term follow-up of ARTISTIC RCT.

The National Screening Committee (NSC) based its recommendation that human papillomavirus (HPV) testing should replace cytology in primary cervical screening largely on the 2009 follow-up results of the ARTISTIC trial (A Randomised Trial In Screening To Improve Cytology). The NSC must now decide on screening intervals and triage policy. Options include extending the screening interval up to 10 years for human papillomavirus-negative (HPV-) women, delaying recall for human papillomavirus-positive (HPV+) women with normal cytology (as their infections are usually transient), and basing triage on full HPV typing. In ARTISTIC, 24,510 women were recruited who were attending routine cervical cytology in Greater Manchester in 2001-3. The women were randomly allocated between revealing and concealing their HPV test results and were recalled every 3 years. After 2009, the women returned to routine cytological screening with recall every 3 years for those aged < 50 years, and every 5 years for those aged 50-64 years. We have followed the cohort to 2015 through national cancer registration for CIN3 (cervical intraepithelial neoplasia grade 3) and cancer, and through linkage to the cervical screening call-recall system to obtain lifetime cytology records. The analysis comprised 24,496 women at round 1 and 13,591 women at round 2 (which was 30-48 months later). Follow-up via local histology laboratories and national cancer registration identified 505 cases of cervical intraepithelial neoplasia grade 3 or cervical cancer (CIN3+) (including 22 invasive cervical cancers). The cumulative CIN3+ risk 10 years after a negative HPV test [0.31%, 95% confidence interval (CI) 0.18% to 0.49%, in the revealed arm] was similar to that 3 years after negative cytology (0.30%, 95% CI 0.23% to 0.41%, in the concealed arm) and fell sharply with age, from 1.1% (95% CI 0.7% to 1.8%) in those women aged < 25 years to 0.08% (95% CI 0.03% to 0.20%) in those women aged > 50 years. The 10-year cumulative CIN3+ risk following a new HPV infection at round 2 was 3.4% (95% CI 2.1% to 5.4%). The highest risks were associated with type-specific persistent infections that, overall, resulted in a 10-year cumulative CIN3+ risk of 20.4% (95% CI 15.6% to 26.4%). We found a similar level of protection 10 years after a negative HPV test and 3 years after negative cytology. These data support a considerably longer screening interval after a negative HPV test than after a negative cytology test. About three-quarters of women with HPV infection and normal cytology clear their infections within about 3 years. Their risk of CIN3+ within this time frame is low (1.5%), suggesting that the current policy of annual repeat testing and referral after 2 years may be unnecessarily cautious. Approximately 40% of women who remained HPV+ had cleared their initial infection and acquired a new HPV type. The cumulative CIN3+ risks in women with type-specific persistent infections are about six times higher than in women with new infections. Triage strategies based on HPV persistence would, therefore, reduce unnecessary referral of women with new (and largely transient) infections. HPV assays that identify HPV types 31, 33, 45, 52 and 58 in addition to 16 and 18 could be useful in triage as well as in primary HPV testing. Similar results in recent routine HPV screening suggest that our results are generalisable despite changes in cytology and HPV assay methods. We are continuing to follow the ARTISTIC cohort into the new era of primary HPV screening. Future work will focus on the implications of more sensitive HPV testing for primary HPV screening policy and triage of HPV-positive women. Our results suggest that a more sensitive test is needed to detect occult CIN3 at high risk of progression to cancer, but this would substantially increase the overall HPV detection rate. Tests such as DNA (deoxyribonucleic acid) methylation for distinguishing HPV infection from neoplasia will be evaluated on stored samples and on further samples now being collected from women in the cohort who are still being screened. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 28. See the NIHR Journals Library website for further project information.

Shock index and modified shock index as triage screening tools for sepsis

BackgroundFever is one of the common conditions encountered in the emergency department, which related to a spectrum of diseases severity. Identifying sepsis patients from uncomplicated febrile patients is challenging in the emergency triage areas and pre-hospital settings. ObjectivesAssess the triage shock index (SI) and modified shock index (MSI) in febrile patients as predictors for sepsis and sepsis-related outcomes. DesignA retrospective cohort study. SettingPatients presented to the Emergency Department of King Khalid University Hospital. Patients and methodsThe analysis included all febrile adult patients triaged with a temperature of 38 °C or more from January 2016 to December 2017. Based on triage vital sign we calculate the SI with cut-off levels of ≥0.7 and ≥1 and MSI with cut-off levels of ≥1 and ≥1.3. We report the Relative Risk, Sensitivity, Specificity, Positive and Negative Predictive Values of the predictors. Main outcome measuresSepsis and sepsis-related outcomes such as hyperlactatemia, ICU admission, and 28 days mortality. Sample size274 patients. Results274 patients met our inclusion/exclusion criteria. Of the 274 patients, 252 patient (92%) were septic, 62 patients (22%) had hyperlactatemia, 20 patients admitted to the ICU, and 5 patient died within 28 days. An MSI of ≥1 had a sensitivity of 90% for sepsis predication, 85% for ICU admission and 100% for 28 days mortality. MSI of ≥1.3 showed a specificity (59%–100%) for all the outcomes of interest. Non-significant statistical trends of greater accuracy of MSI over SI. ConclusionMSI and SI were found to be promising predictors in triaging febrile patients. However no single cut-off values of MSI or SI were found to have an optimal accuracy for prediction of sepsis and sepsis-related outcomes. Further studies are required to assess the incorporation of MSI in a multi-item scaling system for the prediction of sepsis and its related outcomes. LimitationsSmall single center study and the results may not be generalizable.

Utilizing Data to Improve Sepsis Identification in Targeted Populations

Background: Children’s Memorial Hermann Hospital (CMHH) joined the Improving Pediatric Sepsis Outcomes (IPSO) collaborative in July 2016 with successful data importation beginning Summer 2017. At the beginning of the collaborative, generalized triage screening provided a 30% positive screening rate, and the baseline mortality at 30 days per 1,000 admissions for patients admitted from the Emergency Center (EC) to the pediatric intensive care unit was 0.67. Extensive data analysis revealed that 37% of the patients seen in the emergency department with intent to treat and 100% of attributable deaths related to sepsis at CMHH were identified as complex chronic children who were technology dependent. Methods: Based on the collected data and variable regression analysis utilizing Six Sigma methodology, the problem was defined as the risk for sepsis in the chronic complex patient population who are technology dependent indicated the need for accurate screening. As part of the IPSO collaborative goals of increasing early identification, the CMHH IPSO team worked with the EC nurses to create a triage algorithm to improve the identification of sepsis in this population (Fig. 1). Education was done, and Plan–Do–Study–Act cycle implementation began in January 2018 with the final rollout of the algorithm in the EC of March 2018. Results: Accurate screening of this population increased from a mean of 30%–75% after intervention, resulting in a decrease in mortality for inpatients admitted from the EC to the pediatric intensive care unit to zero/1,000 through the last reported data cycle of December 2018 (Fig. 2). Conclusion: Utilization of data analysis resulted in a defined problem and a targeted intervention resulting in the elimination of sepsis attributed mortality in the targeted population.Fig. 1.: Sepsis triage algorithm.Fig. 2.: Sepsis mortalities per 1,000 admissions—day 3.

Diagnostic Performance of Carbon Monoxide Testing by Pulse Oximetry in the Emergency Department.

Carbon monoxide (CO) exposure causes roughly 40,000 emergency department (ED) visits annually and is commonly misdiagnosed. Whereas the standard method of carboxyhemoglobin (HbCO) measurement utilizes blood gas analysis, a noninvasive, FDA-cleared alternative exists. We evaluated the performance of pulse oximetry (SpCO) for identification of CO exposure in ED patients. We compared pulse oximetry to blood HbCO levels in a prospective observational study of adult and pediatric subjects recruited from the ED. Nurses screened a convenience sample of patients and referred those with SpCO ≥ 10% to research staff. Researchers also approached individuals who presented with signs and symptoms of CO toxicity. We determined diagnostic performance with a Bland-Altman analysis and calculated sensitivity and specificity for detection of elevated HbCO at thresholds of ≥ 10% and ≥ 15%. To optimize the potential sensitivity of SpCO for detection of CO toxicity, research technicians performed 3 SpCO readings within 5 min of the blood draw for laboratory measurement. A positive SpCO test was defined as any SpCO ≥ 10%. 42,000 patients were screened, 212 were evaluated, and 126 subjects were enrolled. Median HbCO level was 6% (range 1.6-21.9%). Limits of agreement were -10.3% and 8.1%. Of 23 individuals with elevated HbCO ≥ 10%, 13 were not suspected based on clinical assessment. Critically elevated HbCO was present in 6 individuals. Based on our a priori threshold of 10% for a positive test, pulse oximetry identified 14 of 23 subjects with HbCO ≥ 10%, with a sensitivity of 61% (95% CI 39-80%) and a specificity of 86% (95% CI 78-92%), and 5 of 6 subjects with HbCO ≥ 15%, with a sensitivity of 83% (95% CI 36-100%) and a specificity of 81% (95% CI 73-87%). Pulse oximetry underestimated HbCO and produced false negative results (ie, SpCO < 10% for all three measurements) in 17% of ED subjects with elevated HbCO ≥ 15%. Triage screening with pulse oximetry detected cases of elevated HbCO that were not suspected by the clinical provider.

Colposcopic Evaluation of Visual Inspection with Acetic Acid Positive Cases of Unhealthy Cervix

Cervical cancer is the commonest form of cancer in women in virtually all developing countries1. It is the third most common cancer among women worldwide2. Almost 80% of cervical cancer occurs in developing countries. In developed nations, the figure for invasive cervical cancer are much lower due to adaptation of different screening tests1. All sexually active women are at risk of acquiring a Human Papilloma Virus (HPV) infection which may lead to cervical cancer in the future3. Cervical cancer is a preventable disease as the different screening, diagnostic and therapeutic procedures are effective. The screening procedures are VIA (Visual inspection of cervix with acetic acid), Pap’s smear and HPV DNA test. Colposcopy is the triage in screening, taking colpospoy directed biopsy as well as treatment of CIN such as cold coagulation, cryotherapy, and LEEP (Loop electro-surgical excision procedure)4. Objective: To study the role of Colposcopy in the evaluation VIA positive cases of unhealthy cervix, to localize the leisons to obtain the biopsies from the selected areas and detection of precancerous lesion of cervix for early management. Meterials and Methods: This was a prospective observational study done among 306 married women aged 18-65 years who had clinically unhealthy cervix attending the VIA and colposcopy clinic in Department of Obstetrics and Gynaecology of Sir Salimullah Medical College and Mitford Hospital from January 2015 to December 2016. All the patients were subjected to VIA test. Colposcopic evaluation done in VIA positive cases and the findings were noted. Colposcopy directed biopsy was taken from colposcopically suspected areas. Results: Out of 306 cases, 63 women had positive VIA tests and 233 women had negative VIA tests. Colposcopic evaluation were undertaken among 63 VIA positive cases. Colposcopy directed punch biopsy revealed that 28 (60.32%) cases had positive lesions like CIN or invasive carcinoma and 25 (39.68%) had neither CIN or invasive lesions . Among positive leisons about 30.16% had CINI, 1.59 % had CIN II, 0% had CIN III and 28.57% had invasive carcinoma. In this study sensitivity and specificity of colposcopy examination of VIA positive cases were found 94.74% and 56% respectively. Conclusion: It is evident that colposcopy plays a very important role in the evaluation of VIA positive cases of unhealthy cervix. So that early diagnosis and treatment of preinvasive and early invasive carcinoma of cervixis is possible. So wide use of colposcopy in screening program of Bangladesh speciallly in the VIA positive cases can reduce the many young women’s morbidity and mortality.&#x0D; J Bangladesh Coll Phys Surg 2019; 37(2): 60-65

Variability in intensive care unit length of stay after liver transplant: Determinants and potential opportunities for improvement

PurposeRecovery after liver transplant (LT) requires extensive resources, including prolonged intensive care unit stays. The objective of this study was to use an assessment tool to determine if LT recipients remain in ICU beyond designated indications. MethodsRecords from 100 consecutive LTs performed in a single institution were retrospectively reviewed. An admission, discharge, and triage screening (ADT) tool was utilized to assess the indications for each ICU day. Data collected included demographics; pre-, intra-, and post-operative course; and complications. Days not meeting ADT criteria were considered additional ICU days. Results100 patients: mean age 55 years (range 24–78 years) and mean MELD score 30 (range 6–47). Three recipients who died within one week were excluded. Forty-eight (49.5%) patients had a total of 75 additional days on initial ICU stay. Univariate analysis revealed no significant differences between patients with and without additional days. 12/97 (12.4%) patients returned to ICU including 5/48 and 7/49 with and without additional days. ConclusionNearly half of the LT recipients remained in ICU an average of 1.6 additional days. Monitoring of organ function appeared to be the most common reason. Opportunities to improve resource utilization could include transfer to an intermediate/progressive care (“step-down”) unit.

PP62 Cost-Effectiveness Of Cervical Cancer Screening In Estonia

IntroductionIn Estonia, organized cervical cancer screening program is targeted at women aged 30–55(59) years and Pap-tests are taken every five years. Since cervical cancer is associated with human papillomavirus (HPV), a number of countries have introduced the HPV-test as the primary method of screening. The objective of this study was to evaluate the cost-effectiveness of organized cervical cancer screening program in Estonia by comparing HPV- and Pap-test based strategies.MethodsFor the cost-effectiveness analysis, a Markov cohort model was developed. The model was used to estimate costs and quality-adjusted life-years (QALYs) of eight screening strategies, varying the primary screening test and triage scenarios, upper age limit of screening, and testing interval. Incremental cost-effectiveness ratios (ICERs) were calculated in comparison to current screening practice as well as to the next best option. Sensitivity analysis was performed by varying one or more similar parameter(s) at a time, while holding others at their base case value. The analysis was performed from the healthcare payer perspective adopting a five percent annual discount rate for both costs and utilities.ResultsIn the base-case scenario, ICER for HPV-test based strategies in comparison to the current screening practice was estimated at EUR 8,596–9,786 per QALY. For alternative Pap-test based strategies ICER was estimated at EUR 2,332–2,425 per QALY. In comparison to the next best option, HPV-test based strategies were dominated by Pap-test based strategies. At the cost-effectiveness threshold of EUR 10,000 per QALY Pap-testing every three years would be the cost-effective strategy for women participating in the screening program from age 30 to 63 (ICER being EUR 3,112 per QALY).ConclusionsDecreasing Pap-test based screening interval or changing to HPV-test based screening can both improve the effectiveness of cervical cancer screening program in Estonia, but based on the current cost-effectiveness study Pap-test based screening every three years should be preferred.

Inhibition of protein disulfide isomerase in glioblastoma causes marked downregulation of DNA repair and DNA damage response genes.

Aberrant overexpression of endoplasmic reticulum (ER)-resident oxidoreductase protein disulfide isomerase (PDI) plays an important role in cancer progression. In this study, we demonstrate that PDI promotes glioblastoma (GBM) cell growth and describe a class of allosteric PDI inhibitors that are selective for PDI over other PDI family members.Methods: We performed a phenotypic screening triage campaign of over 20,000 diverse compounds to identify PDI inhibitors cytotoxic to cancer cells. From this screen, BAP2 emerged as a lead compound, and we assessed BAP2-PDI interactions with gel filtration, thiol-competition assays, and site-directed mutagenesis studies. To assess selectivity, we compared BAP2 activity across several PDI family members in the PDI reductase assay. Finally, we performed in vivo studies with a mouse xenograft model of GBM combining BAP2 and the standard of care (temozolomide and radiation), and identified affected gene pathways with nascent RNA sequencing (Bru-seq).Results: BAP2 and related analogs are novel PDI inhibitors that selectively inhibit PDIA1 and PDIp. Though BAP2 contains a weak Michael acceptor, interaction with PDI relies on Histidine 256 in the b' domain of PDI, suggesting allosteric binding. Furthermore, both in vitro and in vivo, BAP2 reduces cell and tumor growth. BAP2 alters the transcription of genes involved in the unfolded protein response, ER stress, apoptosis and DNA repair response.Conclusion: These results indicate that BAP2 has anti-tumor activity and the suppressive effect on DNA repair gene expression warrants combination with DNA damaging agents to treat GBM.