Proportion Of Tests Research Articles

Central Compartment Involvement in T3 & T4 Papillary Thyroid Carcinoma

Background: Lymphatic metastasis in papillary thyroid cancer (PTC) is common; however, the extent of central compartment lymph nodes dissection (CCD) is controversial and requires the knowledge of pattern for central compartment (level VI) lymph nodes metastasis (CCM).
 Objective: To determine the frequency of central compartment (level VI) lymph node metastasis in T3 & T4 papillary thyroid carcinoma.
 Methods: This study was conducted in the Department of Otolaryngology-Head &Neck Surgery, BSMMU, Dhaka, from January 2019 to June 2020. A total of 31 cases of T3 & T4 PTC were selected after obtaining clearance and approval from the IRB of BSMMU; the subjects were included based on the inclusion and exclusion criteria. After taking informed written consent detailed history and examination was done. Ultrasound neck and fine-needle aspiration cytology was taken from all thyroid swelling. All patients had underwent total thyroidectomy with central compartment dissection. The data were analyzed by computer-based statistical software SPSS version 26. Results were expressed as frequency and percentage. Z proportion test was done as applicable.
 Results: In this study, mean (±SD) tumor size was 3.66 (±1.34) cm. 20 (64.52%) had T3 and 11 (35.48%) T4 PTC. 11 (35.48%) had N0, 20 (64.52%) N1a and 8 (25.81%) N1b. 20 (64.52%) had overall central compartment lymph nodes metastasis. Among T3 papillary thyroid carcinoma, 12 (60%) had overall central compartment lymph nodes metastasis, and inT4 papillary thyroid carcinoma, 8 (72.7%) had overall central compartment lymph nodes metastasis. This difference was not statistically significant.
 Conclusion: The frequency of central compartment (level VI) lymph node metastasis (CCM) is high (64.52%) in T3 & T4 papillary thyroid carcinoma. So central compartment (level VI) should be dissected in advanced (T3 & T4) papillary thyroid carcinoma.
 Bangladesh J Otorhinolaryngol 2022; 28(2): 149-156

Evaluation of Extensions of Sinonasal Malignancy by Clinical, Surgical & CT Scan Findings

Background: Sinonasal malignancies are challenging not only from diagnostic view point but also from therapeutic aspects. Owing to the rarity of the lesions, delayed clinical presentations and poor prognosis there is lack of large experience.
 Objectives: Aim of this study is to assess Evaluation of extensions of sinonasal malignancy by correlating clinical and surgical findings with CT scan.
 Methods: A Cross Sectional study was carried out in the Department of Otolaryngology-Head and Neck Surgery, Sylhet M.A.G Osmani Medical College Hospital, Sylhet, from August 2019 to July 2021. A total 30 subjects were included in this study based on inclusion and exclusion criteria. A data collection form was designed and prepared including general characteristics of subjects and reviewed clinically, radiologically and surgically. All the data were compiled and sorted properly and the numerical data were analyzed statistically by using Statistical Package for Social Sciences (SPSS-26). The result was expressed as frequency and percentage and displayed with figure and table. Z proportion test, Spearman’s rho correlation coefficient test and Diagnostic accuracy test of clinical, CT and surgical finding were performed as applicable. For all comparisons p value of <0.05 was considered as significant.
 Results: In this study, CT findings was positively related with clinical and surgical findings. But this relation was strongly significant with surgical findings. In this study, clinical evaluation was 28.8% Sensitive and 100% Specific. Positive predictive value (PPV) was 100% and negative predictive value (NPV) was 9.1%. CT evaluation was 78.6% Sensitive and 100% Specific. Positive predictive value (PPV) was 100% and negative predictive value (NPV) was 25%. Surgical evaluation was 92.9% sensitive and 100% Specific. Positive predictive value (PPV) was 100% and negative predictive value (NPV) was 50%.
 Conclusion: It can be concluded that CT findings was directly correlated with clinical and surgical findings. But this relation was strongly significant with surgical findings.
 Bangladesh J Otorhinolaryngol 2022; 28(2): 171-179

Abstract PD5-03: PD5-03 Comparison of a personalized sequencing assay and digital PCR for circulating tumor DNA based Molecular Residual Disease detection in early-stage triple negative breast cancer in the cTRAK-TN trial

Abstract Background: Detection of circulating tumour DNA (ctDNA) in patients (pts) who have completed treatment for early-stage breast cancer is associated with a high risk of future relapse. Identifying those at high risk of subsequent relapse may allow tailoring of further therapy to delay or prevent recurrence. Previous analysis of this cohort showed that tools capable of detecting ctDNA at lower concentrations are needed to increase sensitivity and lengthen the lead time between ctDNA detection and relapse. We compared ctDNA detection via a personalised sequencing assay to dPCR in patients from the cTRAK TN clinical trial. Methods: The cTRAK-TN trial recruited 161 pts into prospective ctDNA surveillance with dPCR, with ctDNA positive pts randomised to 1) CT staging plus pembrolizumab therapy for patients without relapse or 2) observation. Pts had serial post-treatment surveillance plasma samples collected every 3 months for up to 2 years. Whole exome sequencing (WES) was performed on tumor DNA from FFPE samples to design personalised Residual Disease and Recurrence (RaDaR®) multiplex PCR based NGS assays. Retrospectively, plasma DNA extracted from a minimum of 2mls banked plasma, was sequenced with personalised RaDaR assays, and ctDNA detection identified with a proprietary algorithm. dPCR assays tracked 1-2 mutations, as previously described. Primary endpoint was rate of positive ctDNA detection by 12 months from start of surveillance in both assays. Secondary endpoints were agreement in ctDNA detection between RaDaR and dPCR assays and lead-time between ctDNA detection and disease recurrence. Results: Overall, 147 pts and 241 tissue samples were subject to WES, and RaDaR assays were developed for 142 pts with sufficient plasma for testing. RaDaR assays tracked a median of 47 variants (range 33-56) per patient, and a total of 907 timepoints were analysed (median 6 timepoints per pt, range 1-11). With RaDaR, 39.4% (56/142) patients tested ctDNA positive during follow-up, with a median ctDNA detected level of 0.081% estimated variant allele fraction (eVAF). With dPCR, 35.2% (50/142) pts tested ctDNA positive. The ctDNA detection rate by 12 months from the start of ctDNA surveillance was 36.2% (95% CI; 27.6% – 43.7%) with RaDaR and 29.9% (95%CI; 21.6% – 37.3%) with dPCR. The overall test agreement between RaDaR and dPCR assays was 92.7% (95%CI; 90.7% – 94.4%). From a patient perspective, 58.7% pts were ctDNA negative for both assays, 32.9% ctDNA were positive for both assays and 8.6% presented discrepancies. ctDNA was detected by RaDaR but not by dPCR in 9 pts and it was detected by dPCR but not by RaDaR in 3 pts. Among ctDNA positive pts, 55.2% were first detected positive by RaDaR, 5.2% by dPCR, and 39.6% were detected at the same time-point (test of proportions, p< 0.001). The median lead time from ctDNA detection to relapse was 7.1 months (95% CI 5.9 – 15.9%) with RaDaR and 5.7 months (95% CI 3.2% – 7.4%) with dPCR. Conclusion: The RaDaR personalised multi-mutation sequencing assay detected MRD with a longer median lead time prior to relapse, and with higher sensitivity, than dPCR mutation tracking assays. These findings have implications for the choice of ctDNA assay in clinical trials designed to treat patients at the point of MRD detection. Citation Format: Maria Coakley, Prithika Sritharan, Guillermo Villacampa, Claire Swift, Kathryn Dunne, Lucy Kilburn, Katie Goddard, Patricia Rojas, Andy Joad, Warren Emmett, Charlene Knape, Karen Howarth, Peter S. Hall, Catherine Harper-Wynne, Tamas Hickish, Iain Macpherson, Alicia F. Okines, Andrew M. Wardley, Duncan Wheatley, Simon Waters, Rosalind Cutts, Isaac Garcia-Murillas, Judith Bliss, Nicholas Turner. PD5-03 Comparison of a personalized sequencing assay and digital PCR for circulating tumor DNA based Molecular Residual Disease detection in early-stage triple negative breast cancer in the cTRAK-TN trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD5-03.

Abstract OT1-04-02: Anastrozole dose escalation for optimal estrogen suppression in postmenopausal early stage breast cancer: A prospective trial

Abstract Introduction: We performed matched case-control studies utilizing cohorts of postmenopausal women with ER+ breast cancer receiving adjuvant aromatase inhibitors (AI) on MA.27 [anastrozole, exemestane] or PreFace [letrozole] to assess the association between estrogen suppression after 6 months of treatment and an early breast cancer (EBC) event within 5 years of AI initiation (Clin Cancer Res 2020;26:2986-98). We found a significant 3.0-fold increase in risk of an EBC event for those taking anastrozole with levels of estrone (E1) ≥1.3 pg/mL and estradiol (E2) ≥0.5 pg/mL, but not for exemestane or letrozole. Given these findings we designed a prospective pharmacodynamic (PD) study to evaluate the impact of anastrozole (1 mg/day: ANA1) on E1 and E2 levels, and among those with inadequate estrogen suppression (IES: E1 ≥1.3 pg/mL and E2 ≥0.5 pg/mL), to evaluate the safety and PD efficacy of high-dose anastrozole (10 mg/day: ANA10), which has been found to be safe in prior clinical trials (Cancer 1998;83:1142-52). Methods: Post-menopausal women with stage I-III, ER ≥1% positive/HER2-negative breast cancer who were candidates for anastrozole were eligible after completion of locoregional therapy and chemotherapy, as clinically indicated. Women who were pre-menopausal at diagnosis were not eligible. All patients received 8-10 weeks of ANA1, after which those with adequate estrogen suppression (AES: E1< 1.3 pg/mL or E2< 0.5 pg/mL) came off study. Those with IES went on to receive ANA10 for 8-10 weeks, followed by letrozole (2.5 mg/day: LET) for 8-10 weeks. All patients were managed at their treating oncologist’s discretion following study discontinuation. E1 and E2 blood levels were measured pre-treatment and after completion of each treatment cycle by a CLIA-approved liquid chromatography with tandem mass spectrometry in the Immunochemical Core Laboratory at Mayo Clinic. With a sample size of 29 patients with IES after ANA1, a one-sided binomial test of proportions with a significance level of 0.05 will have an 87% chance of rejecting the proportion with AES after ANA10 is at most 25% (Ho) when the true proportion is at least 50%. Specifically, the null hypothesis is rejected if the number of women with AES after ANA10 is 12 or more. Data lock was July 6, 2022. Results: Of the 161 women enrolled from April 2020 through May 2022, 3 withdrew consent prior to start of ANA1 and 2 were ineligible; thus, 156 women comprised the study cohort. Median patient age was 64 years (range 44-86), 10% of patients were of Hispanic ethnicity and/or non-white race, and 15% received chemotherapy. Six patients remain on ANA1, and 10 discontinued ANA1 due to refusal (7), adverse event (AE) (2), or COVID-19 (1). Forty-one of the remaining 140 patients (29.3%; 95%CI: 21.9-37.6%) had IES with ANA1. Nine of these 41 patients did not go on to ANA10 due to refusal (6) or AE (3). Of the 32 patients who started ANA10, 8 remain on treatment, 5 discontinued due to refusal (3) or AE (1-grade 2 urinary tract infection; 1-grade 1 palpitations), and 19 had a blood draw 45 days or more after starting ANA10. No grade 3-5 AEs or grade 2 hot flashes or arthralgias were reported. Of these 19 patients, 14 achieved AES with ANA10 (73.7%; 95%CI: 48.8-90.9%). All 19 patients switched to LET of which 3 remain on treatment, 1 is missing E1/E2 data, and 15 had a blood draw 45 days or more after starting LET. Of these 15 patients, 10 maintained AES, 2 acquired AES with LET, and 3 no longer had AES. Anastrozole and letrozole drug levels will be reported at the meeting. Conclusions: Approximately 29% of postmenopausal women with ER+/HER2- BC receiving adjuvant anastrozole 1 mg/daily had IES. A majority of these patients achieved AES with dose escalation to ANA10 without tolerability issues. E1 and E2 levels are logical biomarkers given the mechanism of action of anastrozole, and further study utilizing them to determine the optimal dose of anastrozole for a given patient should be performed. Citation Format: Tufia C. Haddad, Vera Suman, Karthik V. Giridhar, Alvaro Moreno-Aspitia, Donald Northfelt, Brenda Ernst, Kostandinos Sideras, Ciara C. O’Sullivan, Ravinder Singh, Zeruesenay Desta, Jodi Taraba, Barbara Goodnature, Matthew P. Goetz, Liewei Wang, James N. Ingle. Anastrozole dose escalation for optimal estrogen suppression in postmenopausal early stage breast cancer: A prospective trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-04-02.

Lenalidomide Consolidation Added to Rituximab Maintenance Therapy in Patients Remaining PET Positive After Treatment for Relapsed Follicular Lymphoma: A Phase 2 Australasian Leukaemia & Lymphoma Group NHL26 Study.

Lenalidomide Consolidation Added to Rituximab Maintenance Therapy in Patients Remaining PET Positive After Treatment for Relapsed Follicular Lymphoma: A Phase 2 Australasian Leukaemia & Lymphoma Group NHL26 Study.

Abstract P5-14-09: Comparison of cell-free DNA genomics of breast cancer associated-chest wall disease vs. age & subtype matched controls with metastatic breast cancer not involving the chest wall

Abstract Background: Breast cancer associated-chest wall disease (CWD) clinically behaves in an aggressive manner. However, little is known about the genomics of CWD. Cell-free DNA (cfDNA) can identify oncogenic mutations in metastatic breast cancer (MBC). We hypothesized that the cfDNA genomics of CWD may vary from MBC cases without CWD. We compared the cfDNA genomics of patients with CWD to that of age and subtype matched MBC controls without CWD. Methods: Patients with MBC at an academic institution who underwent cfDNA testing (Guardant360, next generation sequencing (NGS), 74 gene assay) from 2/2016-2/2021 were identified. Patients with documented CWD (chest wall recurrence with nodules, ulceration, and/or skin metastases on imaging and/or examination) at the time of cfDNA testing (coinciding with MBC diagnosis) were included in the CWD cohort. Age and subtype matched MBC controls without CWD (CON) during the same time period with cfDNA results at MBC diagnosis were identified. A retrospective review was conducted to determine clinical features and cfDNA genomics of CWD and CON. A two-sample test of proportions was used to compare CWD to CON, with p< 0.05 for statistical significance. Results: Thirty-one patients with CWD and 63 CON were identified. Both groups were well-matched in median age at MBC diagnosis (CWD 57 vs. CON 59 years, p=0.93) and subtype distribution (CWD: TNBC 35%, HR+/HER2- 58%, HER2+ 6%; CON: TNBC 29%, HR+/HER2- 65%, HER2+ 6%, p=0.78). Patients also had similar racial distribution in both cohorts (p=0.57). Ninety percent (28/31) of CWD vs. 90% (57/63) of CON had ≥1 mutation detectable in cfDNA (p=0.62). Median number of cfDNA mutations for CWD was 4.5 (range 0-16) vs. 4 (range 0-21) in CON (p=0.32). The most common cfDNA mutations in CWD were TP53 (58%), NOTCH1 (19%), PIK3CA (16%), BRCA1 (13%), NF1 (13%), FGFR2 (13%), ESR1 (13%), STK11 (10%), NTRK1 (10%), APC (10%), and KIT (10%). In comparison, the most common cfDNA mutations in CON were TP53 (54%), PIK3CA (35%), ESR1 (14%), GATA3 (13%), and ATM (11%). Table 1 depicts mutations that varied between CWD and CON which were statistically significant in ≥1 cohort analyzed. In HR+/HER2- MBC, NOTCH1, STK11, NTRK1, DDR2, and NF1 were significantly more common in CWD than CON. For TNBC, NOTCH1 was numerically more common in CWD vs. CON (p=0.06). Conclusions: The cfDNA genomic spectrum of CWD varies from MBC that does not infiltrate the chest wall. Mutations that are associated with metastasis (NOTCH1), inhibition of tumor suppression (STK11), tumor migration (DDR2), proliferation (NTRK1), and endocrine resistance (NF1) were significantly more common in HR+/HER2- CWD than matched controls. Further research is needed to validate these findings and determine the impact of matched targeted therapies for CWD. Table 1 N/A: mutation not observed Citation Format: Neelima Vidula, Lianne Ryan, Andrzej Niemierko, Dejan Juric, Steven J. Isakoff, Francys Verdial, Marjan Azin, Laura A. Petrillo, Beverly Moy, Leif Ellisen, Shadmehr Demehri, Aditya Bardia. Comparison of cell-free DNA genomics of breast cancer associated-chest wall disease vs. age & subtype matched controls with metastatic breast cancer not involving the chest wall [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-14-09.

Effect of inflammatory bowel diseases on household chores.

More than a half of inflammatory bowel disease (IBD) patients experienced a moderate negative effect on their household chores due to their IBD. The negative effect was more common amongst women.

Reference by the Attorney General for Northern Ireland – Abortion Services (Safe Access Zones) (Northern Ireland) Bill [2022]: The proportionality of safe access zone legislation

In an unanimous judgment given by Lord Reed on 7 December 2022, the Supreme Court of the United Kingdom (UKSC) held that clause 5(2)(a) of the Abortion Services (Safe Access Zone) (Northern Ireland) Bill is a proportionate interference with the rights of those who wish to express opposition to abortion services in Northern Ireland. This clause would make it an offence to do an act within the safe access zone with the intention of or being reckless as to the possibility of directly or indirectly influencing a protected person. In this comment, I analyse the reasoning of the UKSC. I consider, first, the clarifications offered by the UKSC on issues related to the proportionality assessment itself. I then turn my attention to the application of the proportionality test by the UKSC to the facts of the reference. I conclude that the reasoning of the UKSC in Reference by the Attorney General for Northern Ireland – Abortion Services (Safe Access Zones) (Northern Ireland) Bill is sound. The UKSC’s decision is relevant to plans to introduce similar legislation in Scotland and to any future human rights based challenges to the English and Welsh Public Order Bill, which will create a similar offence to the one in clause 5(2)(a) of the Northern Ireland Bill when it becomes law later this year. Moreover, the decision is significant because the UKSC had not previously considered the proportionality of safe access zone legislation. The Abortion Services (Safe Access Zone) (Northern Ireland) Bill has now received Royal Assent.

COVID-19 Test Allocation Strategy to Mitigate SARS-CoV-2 Infections across School Districts.

In response to COVID-19, schools across the United States closed in early 2020; many did not fully reopen until late 2021. Although regular testing of asymptomatic students, teachers, and staff can reduce transmission risks, few school systems consistently used proactive testing to safeguard return to classrooms. Socioeconomically diverse public school districts might vary testing levels across campuses to ensure fair, effective use of limited resources. We describe a test allocation approach to reduce overall infections and disparities across school districts. Using a model of SARS-CoV-2 transmission in schools fit to data from a large metropolitan school district in Texas, we reduced incidence between the highest and lowest risk schools from a 5.6-fold difference under proportional test allocation to 1.8-fold difference under our optimized test allocation. This approach provides a roadmap to help school districts deploy proactive testing and mitigate risks of future SARS-CoV-2 variants and other pathogen threats.

Study of Association of Hypoglycemic Episodes to Various Potential Risk Factors among Type 2 Diabetes Mellitus (T2DM) Patients

Aim: Hypoglycemia is a major barrier to achieving proper glycemic control in type 2 diabetes mellitus patients. This study aims to document the incidence of hypoglycemia in type 2 diabetes mellitus patients and assess its association with potential risk factors. Methods: This is a cross-sectional study conducted in the Medicine outpatient department of a tertiary care hospital in Gujarat, India. A total of 174 patients with confirmed type 2 diabetes mellitus were interviewed using a pretested semi-structured questionnaire- Stanford Hypoglycemia Questionnaire. Patients with hormone-secreting disorders or pregnant women were excluded. Another questionnaire recorded various potential risk factors. Statistical test for proportions was used to assess the association between incidence of hypoglycemia and the risk factors. Results: Majority (92.5%) had a positive history of hypoglycemic events. A significant association was established between frequency of hypoglycemia, and duration of disease, BMI, sedentary lifestyle and insulin usage. Regularity of food intake, drug compliance and alcohol consumption were not significant factors. Conclusion: Increased incidence of hypoglycemia was significantly associated with pharmacological and non-pharmacological factors including insulin therapy, sedentary lifestyle, obesity, and chronicity of the disease. This knowledge shall help medical practitioners to strategize individualized care and maintain glycemic control in diabetic patients.

Abstract P647: Assessing the Current Practice of Home Blood Pressure Reporting During Pregnancy

Background: Hypertension (HTN) during pregnancy is a leading cause of fetal and maternal morbidity and is increasingly prevalent in the United States. Home blood pressure (HBP) monitoring allows for blood pressure surveillance throughout pregnancy and can prompt pregnant women to seek medical attention if their blood pressure exceeds safe thresholds. Objectives: To assess the current practice of HBP reporting in pregnancy. Methods: We enrolled 38 pregnant women at 24-32 weeks gestation with either a chronic HTN diagnosis or systolic blood pressure of 140-159 and 40 pregnant women without HTN between July 2019 and November 2021. Clinic visits (telehealth and in-person) were retrospectively reviewed. Each visit with recordings of HBP was categorized as: exact HBP readings, ranges of readings, or qualitative assessment (e.g., normal) of HBP readings during pregnancy and postpartum. Two-sample test of proportion was used for comparisons. Results: Of the 38 women with HTN, 27 (71%) had at least one recorded HBP in pregnancy or postpartum, compared to 2 (5%) women without HTN. There was a total of 158 prenatal visits with HBP recorded and 39 readings postpartum. Readings were more likely to be reported as an exact HBP in the postpartum period (49%) vs. prenatal period (23%, p = 0.001, Figure ). In the prenatal period, 47% of the visits recording HBP reported a range of readings. Discussion: In this population of pregnant women with HTN, we observed substantial heterogeneity of HBP monitoring and reporting during pregnancy and postpartum. Exact HBP reporting in the postpartum period may be related to fewer postpartum follow-up visits. With an increased focus on remote patient monitoring, digital health tools may be important for standardization of HBP monitoring in clinician reporting. Figure: Number of reports by type prenatal and postpartum. Each mention of HBP monitoring in the medical record was coded as an exact reading reported, a range of readings reported, or a qualitative report (“HBP has been within normal limits”)

Abstract P388: Assessment of a Tailored Peer Mentoring Program Among Medicare Advantage Members With Hypertension

Introduction: Disparities in access to care coupled with chronic conditions that represent 70% of healthcare spending, highlight the importance of accessible support beyond in-person primary care. In this study, we assessed the feasibility of a virtual peer mentoring program, in which individuals who have successfully managed to live with hypertension serve as peer mentors to individuals with the same condition. We measured clinical improvement through possible blood pressure (BP) reductions as well as program engagement and satisfaction among study participants. Methods: The study consisted of 451 participants enrolled in a Medicare Advantage plan with hypertension and/or a recent systolic BP reading ≥140 mmHg. Participants were matched with a peer mentor and provided with virtual one-on-one engagement based on their hypertension management challenges. The program was defined as feasible if the average monthly engagement rate over the 6-month study period was at least 70%. A one-sample proportion test was used to determine feasibility and the Wilcoxon signed rank test assessed changes in BP between the first month and the sixth month after enrollment. Descriptive statistics were generated from the exit survey upon program completion. Results: The average monthly engagement rate was greater than 70% (p < 0.001), indicating program feasibility. 116 individuals (25.7%) had a baseline systolic BP ≥ 140 mmHg, or diastolic BP ≥ 90 mmHg with both first and sixth month BP data. In this cohort, we found statistically significant median reductions in systolic BP >5 mmHg (-7.5 mmHg; p=0.003) as well as diastolic BP (-3.9 mmHg; p<0.001). The program received high satisfaction with a net promoter score of 79. Conclusion: This study showed a virtual peer mentoring program for individuals with hypertension is feasible. Both systolic and diastolic BP improved in the peer-matched group suggesting a beneficial intervention. In addition, the exit survey responses indicated satisfactory and positive experiences in this peer mentoring program.

Promises and limits of law for a human-centric artificial intelligence

While the concept of human-centric artificial intelligence (AI) has emerged as a key principle to govern AI systems, two obstacles for its implementation remain largely understated. First, the excessive focus on accountability at the design stage of AI systems, overshadowing the fact that human values can be affected at different stages across the AI life cycle. Second, the market-driven approach of current regulatory initiatives, limited in their ability to actively promote human values. In this article, we argue for a twofold approach to tackle these limitations. On one hand, we propose a co-evolutionary and life cycle approach to tackle the lack of accountability of AI systems, showing that this approach can help ensure accountability beyond the design stage by enabling meaningful human control and human-AI interaction across the entire lifecycle of the system. On the other hand, we propose that regulatory initiatives should balance the market-driven approach by giving a more predominant role to human rights and by introducing explicitly the notion of proportionality test. This rebalancing would serve to handle conflicts between the objectives pursued by AI systems circulating in the markets and the need for an effective protection of human rights.

The Abolition of Sex/Gender Registration in the Age of Gender SelfDetermination: An Interdisciplinary, Queer, Feminist and Human Rights Analysis

It is commonly accepted that gender matters (whether cisgender, transgender/trans*, gender non-binary, genderfluid, gender queer, agender, or other) and many are raising awareness about the fact that gender always seems to matter. That gender matters, and always matters, does not necessarily mean, however, that gender needs to be authenticated or endorsed by the state.
 In fact, based on a feminist and queer reading of human rights, this interdisciplinary article asserts that state-sponsored sex/gender assignment through the practice of sex/gender registration must halt. It argues that mandatory (binary) sex/gender registration disproportionately infringes the emerging right to gender identity autonomy and the right to the legal recognition thereof. Most often, our Western heterosexual cultural system of gender, which posits the existence of two oppositional and complementary gender identities, anchored in so-called natural and binary sex, goes hand in hand with material and discursive forms of violence and entails various forms of unequal power dynamics. Hegemonic in nature, the heterosexual cultural system of gender pervasively regulates many (if not every) aspects of all bodies’ lives and being, including by legal means. The law upholds and certifies that specific gender regime, inter alia, by assigning a sex to individuals at birth (through the registration of a claimed evident, objective, natural element to be found on or in the body by inspection). Policies of mandatory (binary) sex/genderregistration therefore constitute the cornerstone of the legalisation of the heterosexual cultural system of gender, which produces not only the conventional feminine and masculine gender identity (i.e. women and men) but also sex (i.e. females and males).
 This article suggests that, as long as the law refuses to go beyond the compulsory male/female (or even male/female/other) framework, it will be complicit in upholding the undesired consequences of the heterosexual cultural system of gender, which affect all persons of whatever gender or physical features. Therefore, undoing remaining forms of global gender injustice, as well as respecting, protecting and fulfilling human rights relating to gender identity, requires the abolishment of sex/gender registration instead of expanding the available gender markers. Indeed, this article finds that current state practices do not pursue a legitimate aim, and even if they do, mandatory sex/gender registration does not pass the proportionality test that is required in the assessment of restrictions of fundamental rights. A human rights analysis of official sex/gender in the age of gender self-determination finds mandatory sex/gender registration to be a disproportionate measure and recommends that states change their current practices. Doing so would be beneficial to cisgender and trans* individuals alike.

Trial in progress: PREPARE—Exploring the activity of pseudoephedrine in treating retrograde ejaculation following retroperitoneal lymph node dissection (RPLND) in survivors of testicular cancer (TC).

TPS432 Background: Retrograde ejaculation is a known complication of RPLND occurring due to interruption of sympathetic nerve fibres intraoperatively. Whilst common immediately after surgery, the prevalence of persistent symptoms, and impact on health-related quality-of-life (HRQoL) in TC survivors is unknown. Whilst few effective treatments are available, alpha-sympathomimetics such as pseudoephedrine may form a viable treatment option due to effects on bladder neck constriction at sexual climax propagating antegrade ejaculation. Existing studies have shown pseudoephedrine may be helpful in individuals with retrograde ejaculation; however, these studies have only included a small number (n=5) of patients following RPLND. Methods: In a two-part, single-arm phase 2 clinical trial, participants with a history of TC receiving follow-up after RPLND at least >6 months prior will be invited to participate. In part A (ACTRN12622000537752), eligible participants complete questionnaires regarding survivorship issues including sexual function and fertility to explore the prevalence of retrograde ejaculation and HRQoL. Questionnaires include EORTC QLQ-C30, sexual function items from EORTC QLQ-TC26, Brief Male Sexual Function Inventory and tailored questions focusing on retrograde ejaculation. 15 out of a planned 50 participants (30%) have been enrolled and completed questionnaires. If retrograde ejaculation is reported, eligible participants are invited to enrol in Part B (ACTRN12622000542796), where if the participant has no contraindications to pseudoephedrine, nor are they receiving testosterone replacement and retrograde ejaculation is confirmed during screening, they receive a short course of pseudoephedrine hydrochloride. Pseudoephedrine will be given 60mg QID for one-day, followed by 60mg 4 hours and 1 hour prior to ejaculation to evaluate changes in ejaculation volume, sperm count within (any) antegrade ejaculate and within the post-ejaculatory urine. The primary endpoint is total sperm count in antegrade ejaculate of at least 39 million (5th centile) following treatment. We assumed that pseudoephedrine is ineffective if <10% of participants achieve a normal sperm count in antegrade ejaculate after treatment. Using an exact binomial power analysis for a one-sample proportion test, a sample size of 25 participants provides >80% power to detect 36% (9 out of 25) of participants achieving a normal sperm count against a reference proportion of 10% at the 0.05 significance level. 4 out of a planned 30 participants (16%) have been enrolled. All participants with retrograde ejaculation will be invited to an optional, semi-structured interview to further evaluate impact(s) of retrograde ejaculation on issues around sexual health, relationships, body image and masculinity. Clinical trial information: ACTRN12622000537752 , ACTRN12622000542796 .

Perceptions of Indian Healthcare Practitioners Regarding the 2022 Outbreak of Monkeypox Disease.

Introduction Although only a few cases of monkeypox have been reported in India so far, it is vital for healthcare practitioners to have sufficient knowledge about its epidemiology, clinical presentation, diagnosis, and management. Therefore, this study aimed to understand the perception of Indian healthcare practitioners regarding the 2022 outbreak of monkeypox disease. Methods A cross-sectional survey was conducted among 500 medical and dental practitioners from various regions of Kerala, India. The Chi-squared test for proportion was used to determine the significant difference in the knowledge levels of the participants. Binary logistic regression (multivariate) was used to understand the knowledge of healthcare professionals regarding the 2022 outbreak of monkeypox disease. Results A total of 424 healthcare professionals completed this survey. Overall, the level of knowledge was good in 64.9% and poor in 35.1% of the participants (p<0.01). Binary logistic regression analysis did not show any statistical significance (p > 0.05) in terms of demographic characteristics. However, in this sample, participants with 6-10 years of work experience were more likely to have improved knowledge scores (odd's ratio OR 1.764). Similarly, participants between the age of 30-40 years were also likely to have improved knowledge scores (OR: 1.065). Conclusions Indian healthcare professionals had an overall good level of knowledge regarding the 2022 outbreak of monkeypox. However, a low level of knowledge was found related to the clinical presentation and immunization of monkeypox. This may be due to the low prevalence of monkeypoxin this region.

Risk Analysis Index and 30-Day Mortality after Brain Tumor Resection: A Multicenter Frailty Analysis of 31,776 Patients from 2012 to 2020.

Introduction The aim of this study was to evaluate the discriminative accuracy of the preoperative Risk Analysis Index (RAI) frailty score for prediction of mortality or transition to hospice within 30 days of brain tumor resection (BTR) in a large multicenter, international, prospective database. Methods Records of BTR patients were extracted from the American College of Surgeons National Surgical Quality Improvement Program (2012-2020) database. The relationship between the RAI frailty scale and the primary end point (mortality or discharge to hospice within 30 days of surgery) was assessed using linear-by-linear proportional trend tests, logistic regression, and receiver operating characteristic (ROC) curve analysis (area under the curve as C-statistic). Results Patients with BTR ( N = 31,776) were stratified by RAI frailty tier: 16,800 robust (52.8%), 7,646 normal (24.1%), 6,593 frail (20.7%), and 737 severely frail (2.3%). The mortality/hospice rate was 2.5% ( n = 803) and was positively associated with increasing RAI tier: robust (0.9%), normal (3.3%), frail (4.6%), and severely frail (14.2%) ( p < 0.001). Isolated RAI was a robust discriminatory of primary end point in ROC curve analysis in the overall BTR cohort (C-statistic: 0.74; 95% confidence interval [CI]: 0.72-0.76) as well as the malignant (C-statistic: 0.74; 95% CI: 0. 67-0.80) and benign (C-statistic: 0.71; 95% CI: 0.70-0.73) tumor subsets (all p < 0.001). RAI score had statistically significantly better performance compared with the 5-factor modified frailty index and chronological age (both p < 0.0001). Conclusions RAI frailty score predicts 30-day mortality after BTR and may be translated to the bedside with a user-friendly calculator ( https://nsgyfrailtyoutcomeslab.shinyapps.io/braintumormortalityRAIcalc/ ). The findings hope to augment the informed consent and surgical decision-making process in this patient population and provide an example for future study designs.

Women entrepreneurs in Southern Ethiopia: Capacity building programs for women empowerment and challenges in implementation

ABSTRACT This study evaluates the availability of capacity-building programs for women entrepreneurs and investigate the main challenges that women entrepreneurs face. 258 women entrepreneurs were randomly selected from six randomly selected zones in the SNNPR using a two-stage selection technique. Paper Assisted Personal Interview (PAPI) method was used to acquire quantitative data from women entrepreneurs. In addition, key informant interviews and focus group discussions with government officials and women entrepreneurs were conducted. Quantitative data were interpreted using inferential statistics such as proportion tests, pairwise proportion tests, and chi-square test, while qualitative data was analyzed using the thematic method. We found that training, marketplace, and cooperative services are relatively easily provided and implemented, while credit and market information are challenges for women entrepreneurs. Financial constraint is a main problem. Findings show that government and other bodies are working to strengthen the capacity of women entrepreneurs but that implementation is the weak link.

Effect of Silver Diamine Fluoride on Caries Arrest and Prevention

Dental caries is the most common global childhood disease. To control caries, the Centers for Disease Control and Prevention recommends school-based caries prevention, and the World Health Organization lists glass ionomer cement and silver diamine fluoride as essential medicines for oral disease. To determine the noninferiority of silver diamine fluoride with fluoride varnish vs traditional glass ionomer sealants with fluoride varnish after 2 years when provided to children via a school-based health care program. The CariedAway study is an ongoing single-blind, cluster randomized, noninferiority trial conducted between February 1, 2019, and June 1, 2023, among 2998 children in 47 New York City primary schools. Children aged 5 to 13 years of any race and ethnicity were recruited from block-randomized schools. Inclusion criteria for schools were a student population of at least 50% Hispanic or Latino or Latina ethnicity and/or Black race and at least 80% of students receiving free or reduced-cost lunch. Statistical analysis is reported through March 2022. Children received a single application of silver diamine fluoride with fluoride varnish or an active comparator of glass ionomer sealants and atraumatic restorations with fluoride varnish. Primary outcomes were caries arrest and incidence after a 2-year follow-up, assessed using mixed-effects multilevel models and clustered 2-sample proportion tests. The noninferiority margin was 10%. Intention-to-treat analysis was performed using multiple imputation. A total of 2998 children (1566 girls [52.2%]; mean [SD] age at baseline, 6.6 [1.2] years; 1397 Hispanic or Latino or Latina children [46.6%]; 874 [29.2%] with untreated dental caries) were recruited and treated from September 16, 2019, to March 12, 2020. Follow-up observations were completed for 1398 children from June 7, 2021, to March 2, 2022. The mean (SE) proportion of children with arrested caries was 0.56 (0.04) after experimental treatment and 0.46 (0.04) after control treatment (difference, -0.11; 95% CI, -0.22 to 0.01). The mean (SE) proportion of patients without new caries was 0.81 (0.02) after experimental treatment and 0.82 (0.02) after control treatment (difference, 0.01; 95% CI, -0.04 to 0.06). Analysis of imputed data for the full sample did not deviate from per-protocol analyses. There were no adverse events. In this randomized clinical trial, silver diamine fluoride with fluoride varnish was noninferior to sealants and atraumatic restorations with fluoride varnish for caries arrest and prevention. Results may support the use of silver diamine fluoride as an arresting and preventive agent in school-based oral health programs. ClinicalTrials.gov Identifier: NCT03442309.

Does tandem balance test predict cognitive impairment among older adults? Findings from Longitudinal Ageing Study in India, 2017-18.

Ageing entails a decline in physical and functional abilities including a reduced body balance due to complex integration and coordination of sensory acuity, motor control, neural and cognitive functions. This study aimed to examine the association between tandem balance test and cognitive impairment among older Indian adults. The study also examined the gender differentials in the associations with an interaction analysis. Data for this study were drawn from the recent release of the Longitudinal Ageing Study in India (2017-18). The total sample size for the present study included 26,539 older adults age 60years and above. Descriptive statistics and bivariate analysis were used to present the preliminary results. Two sample proportion test was used to evaluate the significance for gender differences. Further, multivariable binary logistic regression analysis was used to evaluate the independent association of balance test performance and cognitive impairment among older adults. Nearly 16% of male and 26% of female older adults could not finish full tandem test in this study. There were significant gender differences in cognitive impairment among older adults (male-6.5% and female-18.9%). The likelihood of cognitive impairment was significantly higher among older adults who could not finish the full tandem test compared to those who finished the tandem test [AOR: 1.22; CI: 1.09-1.36]. The interaction model revealed that older females who could not finish the full tandem test were 2.11 times significantly more likely to be cognitively impaired in reference to older males who finished the full tandem test [AOR: 2.11; CI: 1.81,2.45]. Similarly, older females who finished the full tandem test were 2.42 times significantly more likely to be cognitively impaired in reference to older males who finished the full tandem test [AOR: 2.42; CI: 2.02,2.88]. The findings of the study suggest that healthcare professionals working with older adults should consider the results of a balance test to screen for their risk of cognitive impairment. Results fromthe relationship between failing to finish the tandem test and cognitive impairment may be helpful for identifying older men and women who are at higher risk of experiencing mobility decline and their progression to dementia.