Negative Screening Results Research Articles

21-Hydroxylase Deficiency Detected in Neonatal Screening: High Probability of False Negativity in Late Onset Form.

Despite the high sensitivity of neonatal screening in detecting the classical form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, one of the unclear issues is identifying asymptomatic children with late onset forms. The aim of this nationwide study was to analyse the association between genotype and screened level of 17-hydroxyprogesterone in patients with the late onset form of 21-hydroxylase deficiency and to quantify false negativity. In the Czech Republic, 1,866,129 neonates were screened (2006-2022). Among this cohort, 159 patients were confirmed to suffer from 21-hydroxylase deficiency, employing the 17-hydroxyprogesterone birthweight/gestational age-adjusted cut-off limits, and followed by the genetic confirmation. The screening prevalence was 1:11,737. Another 57 patients who were false negative in neonatal screening were added to this cohort based on later diagnosis by clinical suspicion. To our knowledge, such a huge nationwide cohort of false negative patients has not been documented before. Overall, 57 patients escaped from neonatal screening in the monitored period. All false negative patients had milder forms. Only one patient had simple virilising form and 56 patients had the late onset form. The probability of false negativity in the late onset form was 76.7%. The difference in 17-hydroxyprogesterone screening values was statistically significant (p<0.001) between severe forms (median 478.8 nmol/L) and milder (36.2 nmol/L) forms. Interestingly, the higher proportion of females with milder forms was statistically significant compared with the general population. A negative neonatal screening result does not exclude milder forms of 21-hydroxylase deficiency during the differential diagnostic procedure of children with precocious pseudopuberty.

Introduction of a Novel Cut-off in Newborn Screening of Galactosemia; a Cohort Study

Background: The current newborn screening for Classic Galactosemia (CG) presents significant challenges, including a low positive rate and a high false-positive rate. Objectives: In this study, we aimed to establish new cut-off values (COVs) for CG screening and introduce a novel approach. Methods: Total galactose (TGAL: The sum of galactose (Gal) and galactose-1-phosphate (G-1-P)) levels of all newborns born in Fars, Iran, from August 2006 to December 2020, were reviewed to establish cut-off ranges. A receiver operating characteristic (ROC) curve analysis was performed to define an optimal COV. Results: Out of 1,187,436 newborns, 4,893 (0.41%) were recalled for further evaluation due to an initial TGAL ≥ 4 mg/dL from a positive screening test, with 160 (3.26%) confirmed to have CG. In the initial negative screening results, nine infants were missed as false negatives. An area under the curve of 0.868 suggested that TGAL is a reliable indicator for distinguishing galactosemia from normal subjects. Receiver operating characteristic curve analysis indicated that a cut-off value (COV) of 5.2 mg/dL provided a sensitivity and specificity of 80.0% and 81.3%, respectively, making it an optimal conservative value for deciding on further recall in the Iranian setting. Additionally, a COV of 7.35 mg/dL demonstrated a sensitivity of 71.3% and specificity of 95.7%, making it a suitable cut-off for immediate referral. Conclusions: We proposed a novel protocol for newborn screening in Iran, establishing a TGAL level of 5.2 mg/dL as a conservative cut-off for CG screening, showing excellent sensitivity while ensuring specificity for recalling suspicious cases. Furthermore, a cut-off of 7.35 mg/dL was identified for prompt consideration of urgent treatment.

Pregnancies with ‘double-positive’ multiple marker screening results: a population-based study in Ontario, Canada

BackgroundMultiple marker screening is offered to pregnant individuals in many jurisdictions to screen for trisomies 21 and 18. On occasion, the result is ‘double-positive’—a screening result that is unexpectedly positive for both aneuploidies. Although this occurs rarely, the paucity of available evidence about the outcomes of these pregnancies hinders patient counselling. This study aimed to investigate the association of double-positive results with preterm birth and other adverse perinatal outcomes.MethodsWe conducted a population-based retrospective cohort study of pregnancies with an estimated date of delivery from September 1, 2016, to March 31, 2021, using province-wide perinatal registry data in Ontario, Canada. Pregnancies with double-positive screening results where trisomies 21 and 18 were ruled-out were compared to pregnancies with screen negative results for both aneuploidies. We used modified Poisson regression models with robust variance estimation to examine the association of double positive results with preterm birth and secondary outcomes.ResultsFrom 429 540 pregnancies with multiple marker screening, 863 (0.2%) had a double-positive result; trisomies 21 and 18 were ruled out in 374 pregnancies, 203 of which resulted in a live birth. Among the pregnancies in the double-positive group resulting in a live birth, the risk of preterm birth was increased compared to pregnancies with a screen negative result: adjusted risk ratio (aRR) 2.6 (95%CI 2.0-3.6), adjusted risk difference (aRD) 10.5% (95%CI 5.4–15.7). In a sensitivity analysis excluding all diagnosed chromosomal abnormalities, the risk of preterm birth remained elevated to a similar degree: aRR 2.6 (95%CI 1.9–3.7), aRD 10.0% (95%CI 4.8–15.3). The risk of other adverse perinatal outcomes was also higher, including the risk of chromosomal abnormalities other than trisomies 21 and 18: aRR 81.1 (95%CI 69.4–94.8), aRD 34.0% (95%CI 29.2–38.8). Pregnancies with double-positive results were also less likely to result in a live birth, even when excluding all diagnosed chromosomal abnormalities; and at increased risk of adverse perinatal outcomes for those resulting in a live birth.ConclusionAlthough rare, double-positive multiple marker screening results are associated with an increased risk of preterm birth and other adverse perinatal outcomes, even when excluding all identified chromosomal abnormalities.

Gunshot Trauma Patients Have Higher Risk of PTSD Compared With Blunt Trauma and Elective Populations: A Retrospective Comparative Study of Outpatient Orthopaedic Care.

Posttraumatic stress disorder (PTSD) has been extensively studied in patients who have experienced natural disasters or military conflict, but there remains a substantial gap in knowledge about the prevalence of PTSD after civilian orthopaedic trauma, especially as related to firearms. Gun violence is endemic in the United States, especially in urban centers, and the mental impact is often minimized during the treatment of physical injuries. (1) Do patients who experience gunshot wound (GSW) trauma have higher PTSD screening scores compared with patients with blunt or other trauma (for example, motor vehicle and motorcycle accidents or stab wounds) and those with elective conditions (for example, arthritis, tendinitis, or nerve compression)? (2) Are PTSD scores correlated with pain scores in patients with GSW trauma, those with non-GSW trauma, and patients with elective orthopaedic symptoms? We performed a retrospective study of adults older than 18 years of age presenting to an orthopaedic clinic over an 8-month period between August 2021 and May 2022. All patients presenting to the clinic were approached for inclusion (2034 patients), and 630 new or postoperative patients answered study surveys as part of routine care. Patients were divided into three cohorts based on the orthopaedic condition with which they presented, whether gunshot trauma, blunt trauma, or elective orthopaedic symptoms. Overall, the results from 415 patients were analyzed, including 212 patients with elective orthopaedic symptoms, 157 patients with non-GSW trauma, and 46 patients with GSW trauma. Clinical data including demographic information were collected at the time of appointment and abstracted along with results from the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, short screening questionnaire, which uses a 7-item scale scored from 0 to 7 (with higher scores representing worse symptoms), and from the numeric rating scale for pain (range 0 to 10). Both questionnaires were routinely administered by medical assistants at patient intake. The proportions of patients completing PTSD scoring were 45% (95) in the elective group, 74% (116) in the group with non-GSW trauma, and 85% (39) in the group with GSW trauma (p = 0.01). We compared the PTSD scores across the three groups and then dichotomized the scores as a negative versus positive screening result at a value of ≥ 4 with further comparative analysis. The correlation between pain and PTSD scores was also evaluated. Patients with GSW trauma had higher mean ± SD PTSD scores compared with those who had non-GSW trauma (4.87 ± 4.05 versus 1.75 ± 2.72, mean difference 3.21 [95% CI 1.99 to 4.26]; p < 0.001) and those who presented with elective conditions (4.87 ± 4.05 versus 0.49 ± 1.04, mean difference 4.38 [95% CI 3.50 to 5.26]; p < 0.001). When dichotomized for positive or negative PTSD screening results, patients with GSW trauma had a higher risk of having PTSD (64% [25 of 39]) compared with patients with non-GSW trauma (27% [31 of 116], relative risk 2.40 [95% CI 1.64 to 3.51]; p < 0.001) and compared with patients with elective conditions (4% [4 of 95], relative risk 15.22 [95% CI 5.67 to 40.87]; p < 0.001). Pain scores were correlated with PTSD scores only for patients with non-GSW trauma (ρ = 0.37; p < 0.0001). No correlation with pain scores was present for patients with GSW (ρ = 0.24; p = 0.16) or patients with elective conditions (ρ = -0.04; p = 0.75). In an orthopaedic clinic population, the prevalence of positive screening for PTSD was highest in the population sustaining gunshot trauma as compared with blunt or other trauma and elective orthopaedic conditions. Interestingly, pain scores correlated with PTSD screening only in the patients with non-GSW trauma. These differences suggest a substantial difference in the populations at risk of PTSD after trauma. Overall, the psychological impacts of gun trauma are poorly understood. The next step would be to prospectively study the differences and timelines of PTSD screening in patients with GSW trauma in comparison with patients with blunt or other trauma to better define the treatment needs in this population. Level III, prognostic study.

Risk Factors and Mortality Among Women With Interval Breast Cancer vs Screen-Detected Breast Cancer

The risk factors for interval breast cancer (IBC) compared with those for screen-detected breast cancer (SBC) and their association with mortality outcomes have not yet been evaluated among Korean women. To evaluate risk factors associated with IBC and survival among Korean women with IBC compared with those with SBC. This retrospective cohort study used data from the Korean National Health Insurance Service Database. Women who participated in a national mammographic breast cancer screening program between January 1, 2009, and December 31, 2012, were included. Mortality outcomes were calculated from the date of breast cancer diagnosis to the date of death or December 31, 2020. Data were analyzed from March 1 to June 30, 2023. Breast cancer diagnosed within 6 to 24 months after a negative screening result (ie, IBC) or within 6 months after a positive screening result (ie, SBC). Risk factors and survival rates for IBC and SBC. This study included 8702 women with IBC (mean [SD] age, 53.3 [8.6] years) and 9492 women with SBC (mean [SD] age, 54.1 [9.0] years). Compared with SBC, the probability of IBC decreased as mammographic density increased. Lower body mass index, menopausal status, hormone replacement therapy (HRT) use, and lack of family history of breast cancer were associated with a higher likelihood of IBC. When stratified by detection time, younger age at breast cancer diagnosis and family history of breast cancer were associated with an increased likelihood of IBC diagnosed at 6 to 12 months but a decreased likelihood of IBC diagnosed at 12 to 24 months. Overall mortality of IBC was comparable with SBC, but total mortality and cancer-related mortality of IBC diagnosed between 6 and 12 months was higher than that of SBC. The findings of this cohort study suggest that breast density, obesity, and HRT use were associated with IBC compared with SBC. These findings also suggest that higher supplemental breast ultrasound use among Korean women, especially those with dense breasts, could be attributed to a lower incidence of IBC among women with dense breasts compared with women with SBC, due to greater detection. Finally, overall mortality of IBC was comparable with that of SBC.

Malnutrition Screening with Nutritional Risk Screening 2002 prior to Assessment as Part of GLIM Criteria in Patients Undergoing Major Abdominal Surgery for Gastrointestinal Cancer

Introduction: For diagnosing malnutrition as an important modifiable risk factor in surgical cancer patients, GLIM criteria offer a standardised diagnostic pathway. Before assessing malnutrition, it is suggested to screen for malnutrition with an implemented screening tool, i.e., the NRS-2002. Validated data regarding the applied screening tool and its relevance for predicting outcome parameters in surgical patients is sparse. Methods: 260 patients undergoing major abdominal surgery for cancer were retrospectively analysed. Between January 2017 and December 2019, patients were prospectively screened for malnutrition with the Nutritional Risk Score 2002 (NRS). Irrespective of their screening result malnutrition was assessed with GLIM criteria using CT scan at lumbar level 3 for measuring skeletal muscle mass (GLIM MMCT). Patients with negative screening results (NRS ≤2) were analysed regarding their malnutrition assessment and outcome parameters. Results: Thirty four of 67 patients with NRS ≤2, posing no risk for malnutrition, were diagnosed malnourished according to GLIM MMCT (n = 34, 50.7%). 19 patients (55.9%) with NRS ≤2 and malnutrition according to GLIM had at least one complication, 12 patients (35.3%) had a severe complication (Clavien-Dindo grade ≥ 3a), in 26.5% re-laparotomy was necessary, readmission within 1 month in 20.6% of patients, and length of hospital stay was 18.76 ± 12.66, which was in total worse in outcome compared to the whole study group (n = 260). Patients with NRS ≤2 but diagnosed malnourished by GLIM were at significant higher risk to develop a severe complication (OR 2.256, 95% CI: 1.038–4.9095, p = 0.036) compared to patients with NRS ≤2 but not being diagnosed malnourished. The risk for overall complications was significantly increased in patients with malnutrition diagnosed by the GLIM criteria using MMCT (OR 2.028, 95% CI: 1.188–3.463, p = 0.009). Patients screened at risk with NRS ≥3 and diagnosed malnourished by GLIM were also at significant higher risk for developing complications (OR 1.728, 95% CI: 1.054–2.832, p = 0.029). Conclusion: GLIM MMCT is suitable for diagnosing malnutrition and estimating postoperative risk in gastrointestinal cancer patients. Nutritional assessment only in patients with NRS >2 may bear the risk to miss malnourished patients with high risk for poor clinical outcome. In every patient undergoing major cancer surgery, regular assessment of nutritional status regardless of screening result should be performed exploiting CT body composition analysis.

Prevalence and factors associated with methicillin-resistant Staphylococcus aureus colonization on admission to geriatric care units: impact on screening practices

Universal screening for methicillin-resistant Staphylococcus aureus (MRSA) entails additional costs, and there is no consensus for targeted screening for high-risk units. The aims of this study were to determine the prevalence of MRSA in geriatric care units, and to identify the factors associated with MRSA colonization on admission. This retrospective case-control study (1:1) in the geriatric care unit of six Belgian hospitals covered the period from 1st January 2021 to 31st December 2022. Cases were patients with a positive MRSA screening result within 48h of admission to the geriatric care unit, and controls were patients with a negative screening result. In total, 556 patients were included in this study (278 in each group). Prevalence per 100 admissions for the total sample was 2.3 [95% confidence interval (CI) 2.2-2.6]. Significant multi-variate factors associated with MRSA carriage on admission were: history of MRSA, nursing home origin, and chronic skin lesions. Applying these three factors would give an area under the receiver operating characteristic (ROC) curve of 0.73 (95% CI 0.71-0.77), and would allow screening to be carried out in only 55.4% of cases (95% CI 51.2-59.6%). Using these factors as screening criteria in geriatric care units could significantly reduce the number of patients screened for MRSA, while maintaining satisfactory sensitivity and specificity.

1266. Refining Antimicrobial Stewardship by De-escalating Vancomycin Using MRSA (Methicillin Resistant Staphylococcus aureus) Nasal Screening in a Community Hospital Setting

Abstract Background Our institution has prioritized appropriate use of anti-Methicillin-resistant Staphylococcus aureus (MRSA) drugs such as vancomycin. The overuse of anti-MRSA drugs contributes to drug toxicities and development of resistant organisms such as vancomycin-resistant enterococcus (VRE). Recent studies show that MRSA nasal surveillance screening has a high negative predictive value of 96.5% in all types of pneumonia. At our community hospital a decentralized pharmacist-driven MRSA nares screening protocol was novel. We report the results of implementing a MRSA nares screening protocol for vancomycin de-escalation in pneumonia patients. Methods A decentralized pharmacist reviewed patients with a diagnosis of pneumonia and prescribed vancomycin. The pharmacist ensured that a culture-based MRSA nares screen was performed within 48 hours of admission, if not already ordered. If the nares screen returned negative and respiratory cultures did not grow MRSA at 48 hours, the decentralized pharmacist contacted the medical team to recommend discontinuing vancomycin. Reasons for exclusion included a positive respiratory culture for MRSA within the prior 7 days, septic shock, alternative site of MRSA infection, and greater than 48 hours of anti-MRSA therapy at time of swab collection. Results 164 patients were reviewed by pharmacy between 6/16/22 and 4/25/23. 98% of MRSA nares screening had been performed within 48 hours of admission. MRSA screen was ordered by the decentralized pharmacist in 44% of patients. 89% of patients screened were negative for MRSA and reviewed for de-escalation of vancomycin. In 40% of patients, vancomycin was discontinued after recommendations by the decentralized pharmacist, with 95% of the recommendations accepted by the primary hospitalist physician. 37% of patients' vancomycin was discontinued by the attending physician. Overall, 77% of patients with negative MRSA nasal screen results were successfully de-escalated. Conclusion Our data highlights the effectiveness of close physician-pharmacy collaboration. Most nares cultures were negative for MRSA allowing for de-escalation of antibiotics. Pharmacist recommendations were accepted majority of the time. Given the data, we plan to apply this approach for other ongoing stewardship initiatives. Disclosures All Authors: No reported disclosures

Severe lung disease in children with cystic fibrosis missed in newborn screening.

Cystic fibrosis (CF) is now routinely diagnosed through newborn screening (NBS), but the tests employed in the USA have been evolving for two decades as missed cases become recognized and lab methods improve in association with more knowledge about CF genetics. New Jersey was among the first states to implement CF NBS in 2001 when it introduced the original two-tiered method that combined measurements of immunoreactive trypsinogen (IRT) with detection of the principal pathogenic variant (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. With continuation of the IRT/DNA (F508del) algorithm for two decades and identification of screening false negative children, we decided to examine the condition of some missed cases with special attention to their respiratory status. To strengthen the arguments for quality improvement in New Jersey's CF NBS program, we reviewed and evaluated false negative cases to determine the potential extent of preventable patient suffering as a consequence of delayed diagnoses. Five children with CF who had false negative screening results were studied in detail. In each case there was a different cause of the negative screening results. They all had clinically significant/severe lung disease, ranging from chronic cough with CF pathogens on respiratory culture at a young age to respiratory failure. This case series highlights the consequences of false negative screening results, which served as the impetus to upgrade New Jersey's CF NBS algorithm. Implemented changes include lowering the IRT cutoff to 70 ng/mL and expanding to a 139 variant CFTR panel. In 2023, a floating IRT cutoff is anticipated to be implemented.

Prenatal cfDNA Screening for Emanuel Syndrome and Other Unbalanced Products of Conception in Carriers of the Recurrent Balanced Translocation t(11;22): One Laboratory's Retrospective Experience.

Prenatal cell-free DNA screening (cfDNA) can identify fetal chromosome abnormalities beyond common trisomies. Emanuel syndrome (ES), caused by an unbalanced translocation between chromosomes 11 and 22, has lacked a reliable prenatal screening option for families with a carrier parent. A cohort of cases (n = 46) sent for cfDNA screening with indications and/or results related to ES was queried; diagnostic testing and pregnancy outcomes were requested and analyzed. No discordant results were reported or suspected; there were ten true positives with diagnostic confirmation, six likely concordant positives based on known translocations and consistent cfDNA data, and twenty-six true negatives, by diagnostic testing or birth outcomes. For cases with parental testing, all affected ES cases had maternal translocation carriers. Expanded cfDNA may provide reassurance for t(11;22) carriers with screen negative results, and screen positive results appear to reflect a likely affected fetus, especially with a known maternal translocation. Current society guidelines support the use of expanded cfDNA screening in specific circumstances, such as for translocation carriers, with appropriate counseling. Diagnostic testing is recommended for prenatal diagnosis of ES and other chromosome abnormalities in pregnancy. To our knowledge, this cohort is the largest published group of cases with prenatal screening for carriers of t(11;22).

False negatives in the newborn screening for cystic fibrosis in Western Andalusia: Results from a 10-year experience.

Cystic fibrosis (CF) is the most common autosomal recessive disorder in the Caucasian population, with an incidence of 1:5000 live births. In 2011, the screening of CF was implemented in the Andalusian Public Health newborn screening program by using immunoreactive trypsinogen and chloride sweat test (IRT/IRT/sweat test) determinations. Since then, 79 children have been diagnosed with CF in our health area (Western Andalusia). The aim of this study was to evaluate the efficiency of this screening method and to examinate the characteristics of those CF infants who had a negative screening but who were later diagnosed. In the 2011-2021 period 462,049 newborns were screened for CF using a two-step IRT determination and chloride sweat test. Sixty-threeinfants were diagnosed with CF in our health area thanks to the screening, and 15 CF children had a negative screening result and were finally diagnosed by molecular sequencing of the CFTR gene. The most frequent symptoms that led to the diagnosis of those false negative (FN) patients were hyponatremic dehydration (mean age 9.75 ± 1.5 months) and recurrent wheezing (mean age 24 ± 14.5 months). The molecular analysis of the CFTR gene on those FN showed a diversity of genotypes, identifying more than 10 different mutations. CONCLUSION: The rate of FN patients obtained in this study is inadmissibly high, and the protocol used in this region has not been updated despite the advances in genetic testing in the past 10 years. An improvement on CF newborn screening should be implemented, adding molecular analysis of the CFTR gene.

Evaluation of an AI Model to Assess Future Breast Cancer Risk.

Background Accurate breast cancer risk assessment after a negative screening result could enable better strategies for early detection. Purpose To evaluate a deep learning algorithm for risk assessment based on digital mammograms. Materials and Methods A retrospective observational matched case-control study was designed using the OPTIMAM Mammography Image Database from the National Health Service Breast Screening Programme in the United Kingdom from February 2010 to September 2019. Patients with breast cancer (cases) were diagnosed following a mammographic screening or between two triannual screening rounds. Controls were matched based on mammography device, screening site, and age. The artificial intelligence (AI) model only used mammograms at screening before diagnosis. The primary objective was to assess model performance, with a secondary objective to assess heterogeneity and calibration slope. The area under the receiver operating characteristic curve (AUC) was estimated for 3-year risk. Heterogeneity according to cancer subtype was assessed using a likelihood ratio interaction test. Statistical significance was set at P < .05. Results Analysis included patients with screen-detected (median age, 60 years [IQR, 55-65 years]; 2044 female, including 1528 with invasive cancer and 503 with ductal carcinoma in situ [DCIS]) or interval (median age, 59 years [IQR, 53-65 years]; 696 female, including 636 with invasive cancer and 54 with DCIS) breast cancer and 1:1 matched controls, each with a complete set of mammograms at the screening preceding diagnosis. The AI model had an overall AUC of 0.68 (95% CI: 0.66, 0.70), with no evidence of a significant difference between interval and screen-detected (AUC, 0.69 vs 0.67; P = .085) cancer. The calibration slope was 1.13 (95% CI: 1.01, 1.26). There was similar performance for the detection of invasive cancer versus DCIS (AUC, 0.68 vs 0.66; P = .057). The model had higher performance for advanced cancer risk (AUC, 0.72 ≥stage II vs 0.66 <stage II; P = .037). The AUC for detecting breast cancer in mammograms at diagnosis was 0.89 (95% CI: 0.88, 0.91). Conclusion The AI model was found to be a strong predictor of breast cancer risk for 3-6 years following a negative mammographic screening. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Mann and Sechopoulos in this issue.

Factors Associated With Nonadherence to Lung Cancer Screening Across Multiple Screening Time Points

Screening with low-dose computed tomography (CT) has been shown to reduce mortality from lung cancer in randomized clinical trials in which the rate of adherence to follow-up recommendations was over 90%; however, adherence to Lung Computed Tomography Screening Reporting & Data System (Lung-RADS) recommendations has been low in practice. Identifying patients who are at risk of being nonadherent to screening recommendations may enable personalized outreach to improve overall screening adherence. To identify factors associated with patient nonadherence to Lung-RADS recommendations across multiple screening time points. This cohort study was conducted at a single US academic medical center across 10 geographically distributed sites where lung cancer screening is offered. The study enrolled individuals who underwent low-dose CT screening for lung cancer between July 31, 2013, and November 30, 2021. Low-dose CT screening for lung cancer. The main outcome was nonadherence to follow-up recommendations for lung cancer screening, defined as failing to complete a recommended or more invasive follow-up examination (ie, diagnostic dose CT, positron emission tomography-CT, or tissue sampling vs low-dose CT) within 15 months (Lung-RADS score, 1 or 2), 9 months (Lung-RADS score, 3), 5 months (Lung-RADS score, 4A), or 3 months (Lung-RADS score, 4B/X). Multivariable logistic regression was used to identify factors associated with patient nonadherence to baseline Lung-RADS recommendations. A generalized estimating equations model was used to assess whether the pattern of longitudinal Lung-RADS scores was associated with patient nonadherence over time. Among 1979 included patients, 1111 (56.1%) were aged 65 years or older at baseline screening (mean [SD] age, 65.3 [6.6] years), and 1176 (59.4%) were male. The odds of being nonadherent were lower among patients with a baseline Lung-RADS score of 1 or 2 vs 3 (adjusted odds ratio [AOR], 0.35; 95% CI, 0.25-0.50), 4A (AOR, 0.21; 95% CI, 0.13-0.33), or 4B/X, (AOR, 0.10; 95% CI, 0.05-0.19); with a postgraduate vs college degree (AOR, 0.70; 95% CI, 0.53-0.92); with a family history of lung cancer vs no family history (AOR, 0.74; 95% CI, 0.59-0.93); with a high age-adjusted Charlson Comorbidity Index score (≥4) vs a low score (0 or 1) (AOR, 0.67; 95% CI, 0.46-0.98); in the high vs low income category (AOR, 0.79; 95% CI, 0.65-0.98); and referred by physicians from pulmonary or thoracic-related departments vs another department (AOR, 0.56; 95% CI, 0.44-0.73). Among 830 eligible patients who had completed at least 2 screening examinations, the adjusted odds of being nonadherent to Lung-RADS recommendations at the following screening were increased in patients with consecutive Lung-RADS scores of 1 to 2 (AOR, 1.38; 95% CI, 1.12-1.69). In this retrospective cohort study, patients with consecutive negative lung cancer screening results were more likely to be nonadherent with follow-up recommendations. These individuals are potential candidates for tailored outreach to improve adherence to recommended annual lung cancer screening.

Significant Incidental Findings in the National Lung Screening Trial

Low-dose computed tomography (LDCT) lung screening has been shown to reduce lung cancer mortality. Significant incidental findings (SIFs) have been widely reported in patients undergoing LDCT lung screening. However, the exact nature of these SIF findings has not been described. To describe SIFs reported in the LDCT arm of the National Lung Screening Trial and classify SIFs as reportable or not reportable to the referring clinician (RC) using the American College of Radiology's white papers on incidental findings. This was a retrospective case series study of 26 455 participants in the National Lung Screening Trial who underwent at least 1 screening examination with LDCT. The trial was conducted from 2002 to 2009, and data were collected at 33 US academic medical centers. Significant incident findings were defined as a final diagnosis of a negative screen result with significant abnormalities that were not suspicious for lung cancer or a positive screen result with emphysema, significant cardiovascular abnormality, or significant abnormality above or below the diaphragm. Of 26 455 participants, 10 833 (41.0%) were women, the mean (SD) age was 61.4 (5.0) years, and there were 1179 (4.5%) Black, 470 (1.8%) Hispanic/Latino, and 24 123 (91.2%) White individuals. Participants were scheduled to undergo 3 screenings during the course of the trial; the present study included 75 126 LDCT screening examinations performed for 26 455 participants. A SIF was reported for 8954 (33.8%) of 26 455 participants who were screened with LDCT. Of screening tests with a SIF detected, 12 228 (89.1%) had a SIF considered reportable to the RC, with a higher proportion of reportable SIFs among those with a positive screen result for lung cancer (7632 [94.1%]) compared with those with a negative screen result (4596 [81.8%]). The most common SIFs reported included emphysema (8677 [43.0%] of 20 156 SIFs reported), coronary artery calcium (2432 [12.1%]), and masses or suspicious lesions (1493 [7.4%]). Masses included kidney (647 [3.2%]), liver (420 [2.1%]), adrenal (265 [1.3%]), and breast (161 [0.8%]) abnormalities. Classification was based on free-text comments; 2205 of 13 299 comments (16.6%) could not be classified. The hierarchical reporting of final diagnosis in NLST may have been associated with an overestimate of severe emphysema in participants with a positive screen result for lung cancer. This case series study found that SIFs were commonly reported in the LDCT arm of the National Lung Screening Trial, and most of these SIFs were considered reportable to the RC and likely to require follow-up. Future screening trials should standardize SIF reporting.

A new efficient multi-stage strategy based on the complementarity of ultrafiltration and high resolution biochromatogram for the screening of skin-whitening candidates from the fibrous root of Bletilla striata

Ultrafiltration-high performance liquid chromatography (UF-HPLC) and high resolution biochromatogram (HR-biochromatogram), have been proven to be effective methods for the rapid discovery of enzyme inhibitors in natural medicines. In attempt to conquer false-positive and false- negative screening results, a new multi-stage strategy based on the complementarity of UF-HPLC and HR-biochromatogram has been proposed for the fast screening of tyrosinase inhibitory components using the fibrous root of Bletilla striata as a case study. For the first two stages, UF- HPLC and HR-biochromatogram, were applied individually for the screening of high-affinity tyrosinase ligands and tyrosinase inhibitors. After that, the inconsistent results, which yielded two potential active fractions, indicated a third stage screening. Thus, a “strengthen” biochromatogram was established to microfractionate the concentrated extract and further evaluate the tyrosinase inhibitors. The complementarity nature of two different screening methods was firstly explored to distinguish tyrosinase inhibitors from the fibrous root of Bletilla striata. As a result, four compounds were screened, isolated and characterized as new potent tyrosinase inhibitors. The screening results were verified by tyrosinase inhibition assays, melanin inhibitory in zebrafish and molecular docking. All compounds possessed much higher tyrosinase inhibition than α-arbutin, especially, 1-(4- Hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene-2,7-diol demonstrated stronger tyrosinase inhibition than kojic acid. This study presented a new screening strategy which had a great potential in rapidly and efficiently exploring tyrosinase inhibitors in complex mixtures. Moreover, it is the first time to reveal the skin-whitening nature of the fibrous root of B. striata, which indicating the promising prospect in the full utilization of B. striata plant.

Accuracy of baseline low-dose computed tomography lung cancer screening: a systematic review and meta-analysis.

Screening using low-dose computed tomography (LDCT) is a more effective approach and has the potential to detect lung cancer more accurately. We aimed to conduct a meta-analysis to estimate the accuracy of population-based screening studies primarily assessing baseline LDCT screening for lung cancer. MEDLINE, Excerpta Medica Database, and Web of Science were searched for articles published up to April 10, 2022. According to the inclusion and exclusion criteria, the data of true positives, false-positives, false negatives, and true negatives in the screening test were extracted. Quality Assessment of Diagnostic Accuracy Studies-2 was used to evaluate the quality of the literature. A bivariate random effects model was used to estimate pooled sensitivity and specificity. The area under the curve (AUC) was calculated by using hierarchical summary receiver-operating characteristics analysis. Heterogeneity between studies was measured using the Higgins I2 statistic, and publication bias was evaluated using a Deeks' funnel plot and linear regression test. A total of 49 studies with 157,762 individuals were identified for the final qualitative synthesis; most of them were from Europe and America (38 studies), ten were from Asia, and one was from Oceania. The recruitment period was 1992 to 2018, and most of the subjects were 40 to 75 years old. The analysis showed that the AUC of lung cancer screening by LDCT was 0.98 (95% CI: 0.96-0.99), and the overall sensitivity and specificity were 0.97 (95% CI: 0.94-0.98) and 0.87 (95% CI: 0.82-0.91), respectively. The funnel plot and test results showed that there was no significant publication bias among the included studies. Baseline LDCT has high sensitivity and specificity as a screening technique for lung cancer. However, long-term follow-up of the whole study population (including those with a negative baseline screening result) should be performed to enhance the accuracy of LDCT screening.

Malaysian Women's Viewpoint on HPV Screening and Vaccination: A Study on Barriers.

Cervical cancer is the second most common cancer in low-income countries and the third most common cancer in Malaysia among women aged 15 to 44. This is a huge concern because of the high mortality rate compared to other countries. Cervical cancer is caused by a common sexually transmitted human papillomavirus (HPV). Of cervical cancer cases, 80% are attributed to serotypes 16 and 18; therefore, early detection of premalignant lesions and infections from these viruses is important. Diagnosis can be carried out by polymerase chain reaction (PCR)-based HPV DNA analysis and Pap smear, which act as a viable preventive strategy. (1) Background: This study determined the adoption of the human papillomavirus (HPV) vaccine and the willingness to get vaccinated in Malaysian women. (2) Methods: An online survey was conducted with women from across Malaysia to gather their views on the barriers that prevent them from accessing HPV services. Sentiment analysis was performed to detect and classify the comments into three groups (positive, neutral, and negative). (3) Results: A total of 449 opinions were received, and the findings revealed that 41.3% were not afraid to be diagnosed early, and were prepared to accept positive or negative screening results. In addition, 18.6% of those surveyed indicated that they feared a Pap smear and were very concerned that they would not get good results. Of the respondents, 36% believed in vaccination and preferred to know more about it; 43.24% claimed that their family members were very supportive towards screening and vaccination; and 21.3% felt embarrassed and were afraid to undergo the screening procedure, as they had no prior experience and were unsure of how the procedure was conducted. In addition, 40.5% indicated that they had no concerns about HPV testing and related procedures, as this information is widely available. Only a few respondents (8.1%) talked about the time constraints and busy work schedules that prevented them from going to medical appointments. The survey also revealed that women are prevented from participating in cervical cancer screening and vaccination programs due to a lack of knowledge, shyness, personal rumors, privacy issues, financial issues, a lack of access to medical services, and ignorance and beliefs about rumors spreading online. (4) Conclusion: Results indicate that awareness of HPV and related prevention measures among women is vague and that negative perceptions continue to exist. It is strongly advised to develop a well-designed and knowledge-based application on the efficacy of screening and vaccination among Malaysian women.

Clinical, Cytogenetic and Molecular Cytogenetic Outcomes of Cell-Free DNA Testing for Rare Chromosomal Anomalies

The scope of cell-free DNA (cfDNA) testing was expanded to the genome, which allowed screening for rare chromosome anomalies (RCAs). Since the efficiency of the test for RCAs remains below the common aneuploidies, there is a debate on the usage of expanded tests. This study focuses on the confirmatory and follow-up data of cases with positive cfDNA testing for RCAs and cases with screen-negative results in a series of 912 consecutive cases that underwent invasive testing following cfDNA testing. Chorion villus sampling (CVS), amniocentesis (AS), fetal blood sampling, and term placenta samples were investigated using classical cytogenetic and molecular cytogenetic techniques. Out of 593 screen-positive results, 504 (85%) were for common aneuploidies, 40 (6.7%) for rare autosomal trisomies (RATs), and 49 (8.3%) for structural chromosome anomalies (SAs). Of the screen-positives for RATs, 20 cases were evaluated only in fetal tissue, and confined placental mosaicism (CPM) could not be excluded. Among cases with definitive results (n = 20), the rates of true positives, placental mosaics, and false positives were 35%, 45%, and 10%, respectively. Among screen-positives for SAs, 32.7% were true positives. The confirmation rate was higher for duplications than deletions (58.3% vs. 29.4%). The rate of chromosomal abnormality was 10.9% in the group of 256 screen-negatives with pathological ultrasound findings. This study provides further data to assess the efficiency of expanded cfDNA testing for RATs and SAs. The test efficiency for cfDNA seems to be higher for duplications than for deletions, which is evidence of the role of expert ultrasound in identifying pregnancies at increased risk for chromosome anomalies, even in pregnancies with screen-negatives. Furthermore, we discussed the efficiency of CVS vs. AC in screen-positives for RATs.

A Case Report of Delayed Syphilis Diagnosis in Pregnancy

Aims: To report a case of primary genital syphilis in a pregnant woman, which is atypical due to the delayed diagnosis, course of the disease and to emphasize its reasons and clinical management.&#x0D; Presentation of Case: We present a pregnant primiparous woman G1P0A0 complaining of pain and growing lesion in the perineal area. She was misdiagnosed and unsuccessfully treated for the perineal abscess several times. The diagnosis of syphilis was delayed because of the negative prenatal syphilis test result in the first trimester. The negative test result misled doctors into immediately dismissing the diagnosis of syphilis. In addition to the delayed diagnosis, after the correct diagnosis regardless of an appropriate treatment with benzathine penicillin G, the pain and the chancre recurred possibly due to the reinfection during intercourse with an infected partner.&#x0D; Discussion: Diagnosing syphilis may be complicated itself. In this case there were several factors that made the correct diagnosis and successful treatment even more difficult. These were: negative prenatal screening, reinfection and recurrence of the symptoms after treatment.&#x0D; Conclusion: With this case we emphasize the importance to repeat the syphilis testing if the diagnosis of syphilis is suspected, regardless of previous negative first trimester syphilis screening result and importance of sexual partner’s screening and treatment if infected.

The reliability, validity and screening effect of the happiness index scale among inpatients in a general hospital

BackgroundThe Happiness Index Scale (HIS) is a newly developed scale by our group to screen for common psychological illnesses among general hospital inpatients. This study aimed to analyze the reliability, validity and screening effect of the HIS and to explore its clinical application.MethodsFrom April 1, 2021, to December 31, 2021, a total of 8405 continuous inpatients were enrolled from different departments of a large tertiary general hospital with 1385 inpatient beds in Guangzhou, Guangdong Province, China. Using a cross-sectional survey design, each participant was assessed with the Patient Health Questionnaire 9(PHQ-9), Generalized Anxiety Disorder 7 items(GAD-7), Athens Insomnia Scale (AIS), Columbia Suicide Severity Rating Scale (C-SSRS) and HIS within 24 h of admission. McDonald's ω coefficient, the Guttman split-half coefficient and the test–retest reliability coefficient were used to evaluate the reliability of the HIS and the construct validity and criterion validity of the validity tests. Scores on the PHQ-9, GAD-7, AIS, and C-SSRS were used as the gold standard tools to analyze the screening effect of the HIS.ResultsThe HIS exhibited very good reliability, with a McDonald's ω coefficient of 0.825, a Guttman split-half coefficient of 0.920 and a test–retest reliability coefficient of 0.745 (P < 0.05). Confirmatory factor analysis showed a satisfactory model fitting index with a χ2/df = 2.602, a root mean squared error of approximation (RMSEA) of 0.014, a standardized root mean square residual (SRMR) of 0.010, a comparative fit index (CFI) of 0.992, and a Tucker–Lewis index (TLI) of 0.983. The correlation coefficient between the total score of each dimension of the scale and the corresponding criterion was 0.854 ~ 0.949 (P < 0.001). The HIS showed a very good distinguishing effect. The average HIS score of inpatients who screened positive for psychological problems was significantly higher than that of inpatients who screened negative for psychological problems (t = 3790.619, P < 0.001). The effect size was very large (Cohens d = 2.695, 95% CI = 2.630 ~ 2.761). Approximately 90.2% of the positive and negative screening results of the HIS were matched with the gold standard tools, with a kappa value of 0.747 (P < 0.001). The screening effect test showed a sensitivity (true positive rate) of 92.9% and a specificity (true negative rate) of 89.5%.ConclusionThe HIS exhibited satisfactory reliability and validity and a clinically meaningful screening effect with a much shorter version compared to the commonly used screening scales. Thus, it could potentially be useful as the first screening step to rule out psychological conditions for inpatients in general hospitals or to remind medical teams of further psychological concerns.