Binomial Proportion Test Research Articles

Multiethnic Trends in Early Onset Colorectal Cancer.

Current characteristics of early onset colorectal cancer (EOCRC) in the United States have been mainly studied in Whites, African Americans, and Hispanics, but little is known in regard to EOCRC in Asians and Native Hawaiians in the US. EOCRC was examined in Hawaii's multiethnic population. Data from the Hawaii Tumor Registry was used to analyze colorectal cancer (CRC) cases diagnosed in Hawaii from 2000-2019 by subsite, age, gender, ethnicity, and stage. Ethnicity analyses were limited to 3524 CRC cases, diagnosed between 2015-2019. Average annual 5-year age-adjusted incidence and mortality rates, average annual percent change over time, and 5-year survival were evaluated. Group comparisons utilized Chi-square and binomial proportion tests. Overall CRC incidence and mortality declined and were more pronounced for colon than rectal/rectosigmoid junction cancers. Colon cancer incidence rates significantly increased 1.46-fold for cases diagnosed under 45 years of age and rectal/rectosigmoid cancers significantly increased 1.54-fold for cases 45-54 years of age. CRC incidence increased sharply for females aged 45-54 years from 2000-2009 to 2010-2019, and increases in colon and rectal/rectosigmoid cancer among individuals aged 45-54 were higher for females. Among both sexes, the increase in rectal/rectosigmoid cancer incidence for individuals under 55 years was highest for stage I cancers. Overall, the mean (SD) age of CRC diagnosis was 5-10 years earlier for Native Hawaiians (60.6 [13.3] years) compared with Japanese, Chinese, Filipinos, Whites, and Other Asians (p < 0.001). Native Hawaiians constituted a greater proportion of CRC diagnosed under age 55 years and, conversely, a smaller proportion of cases 55 years and older compared with Japanese, Chinese, Filipinos, Whites, and Other Asians. Native Hawaiians had a significantly higher CRC-related mortality rate (14.5 per 100,000 [95% CI: 12.4, 16.8]) compared with Japanese (10.7 per 100,000 [95% CI: 9.3, 12.3]) and a significantly lower CRC survival rate (62.2% [95% CI: 59.1, 65.2]) compared with Japanese (71.9% [95% CI: 69.9, 73.8]), Filipinos (71.9% [95% CI: 69.2, 74.4]), Chinese (70.2% [95% CI: 65.5, 74.4]), Whites (69.3% [95% CI: 67.1, 71.4]), and Other Asians (71.7% [95% CI: 66.2, 76.5]). In our diverse US population, Native Hawaiians contribute disproportionately to EOCRC and present 5-10 years earlier than Whites, Japanese, Chinese, and Filipinos. EOCRCs are increasing faster in females than males in Hawaii, which differs from trends in the general US population. Emerging ethnic disparities in EOCRC in the US speak to the need for studies on targeted interventions and ethnic-specific risk factors for EOCRC.

Optic Nerve Sheath Meningiomas: A National Surveillance, Epidemiology, and End Results (SEER) Database Analysis.

Optic nerve sheath meningioma (ONSM) is a rare optic nerve cancer with considerable morbidity. This national analysis validates previously known ONSM concepts while providing insight into novel risk factors. The Surveillance, Epidemiology, and End Results (SEER) Program was queried from 2000 to 2019 for all histologic subtypes of meningioma primary to the optic nerve. Relevant clinical and demographic variables were analyzed. Asymptotic one-sample test for binomial proportions and Cox proportional hazards modeling evaluated the significance of factor associations. A total of 51 ONSM cases were extracted. A greater proportion of cases were observed in females (N = 37, 73% , P < 0.001) and individuals with age 50 years or more (N = 29, 57% , P < 0.001); the mean number of months from diagnosis to treatment was 4.6 months (SD 4.1, range 13). Psychosocial epidemiologic parameter analysis demonstrated a greater proportion of patients with married status on diagnosis (N = 31, 61% , P < 0.001), listed total family income between $55,000 and $74,999 (N = 24, 47% , P < 0.001). Relative to cases diagnosed clinically only, cases diagnosed radiologically without microscopic confirmation experienced decreased all-cause mortality (HR = 0.041, P = 0.050). Our SEER national analysis affirms previously characterized ONSM concepts. Upon ONSM diagnosis and if needed, treatment protocols are not significantly delayed. Novel psychosocial factors for ONSM were identified, including marital status, total family income, and non-Hispanic white race. Additional ONSM diagnostics may reduce longitudinal mortality burden.

High Prevalence of Obstructive Sleep‐Disordered Breathing in Pediatric Patients With Turner Syndrome

AbstractObjectiveGirls with Turner syndrome (TS) often have features that have been associated with obstructive sleep‐disordered breathing (oSDB). However, little is known about oSDB in TS. Herein, we aimed to characterize oSDB in young patients with TS and identify associated risk factors.Study DesignRetrospective cross‐sectional study.SettingTertiary care pediatric hospital.MethodsWe reviewed medical records for patients diagnosed with TS seen at our institution between October 1, 2007 and December 31, 2019 with the first outpatient visit before age 6 years. The prevalence of oSDB was compared to the general pediatric population with 1‐sample binomial proportion tests. Clinical characteristics were compared between those diagnosed with oSDB and those without oSDB, and risk factors for oSDB were identified.ResultsOf 151 patients with TS, 73 (48%) were diagnosed with oSDB which is 4‐fold higher than the general pediatric population (12%, P &lt; 0.0001). In the multivariable model, adenoid, tonsillar, and inferior turbinate hypertrophy, birthweight, failure to thrive, and older age at the last clinic visit were all associated with increased odds for oSDB.ConclusionYoung children with TS have a high prevalence of oSDB and thus should be screened for oSDB. Polysomnography should be performed in those with associated risk factors and symptoms oSDB. Treatment of oSDB is imperative as individuals with TS are already at increased risk of behavioral problems, neurocognitive deficits, and growth impairment that may be worsened with oSDB.

P14.11.B A MULTICENTER STUDY OF LOW-INTENSITY FOCUSED ULTRASOUND WITH SYSTEMIC MICROBUBBLE OSCILLATORS FOR BLOOD-BRAIN BARRIER DISRUPTION FOR LIQUID BIOPSY IN GLIOBLASTOMA (LIBERATE)

Abstract BACKGROUND Liquid biopsy in glioblastoma (GBM) is hindered by a lack of requisite circulating-free DNA (cfDNA) levels in blood due to the blood-brain barrier (BBB). This results in challenges to the identification of blood-based biomarkers and the development of novel biomarker-driven systemic therapies. Real-time image-guided low intensity focused ultrasound (LIFU) combined with intravenously administered microbubble oscillators non-invasively causes BBB disruption (BBBD). This clinical trial aimed to evaluate the utility of LIFU for increasing cfDNA in blood for liquid biopsy in GBM. METHODS LIBERATE is a prospective, multi-center, self-controlled, ongoing, pivotal trial evaluating the safety and technical efficacy of LIFU for BBBD to increase cfDNA in blood for GBM. Patients aged 18-80 years with suspected GBM planned for tumor biopsy or resection at ten centers in the US are being included. Patients with multifocal tumors or tumors arising from deep midline, thalamus, cerebellum, or brainstem are excluded. Patients are administered intravenous oscillating microbubbles for enhancing sonication, after which MR-guided BBBD using a 220 kHz LIFU device is performed with real-time acoustic feedback for effective cavitation. Before and after the procedure, phlebotomies and MRI brain are performed to evaluate outcomes. The primary study endpoint is defined, per subject, as the ratio between their cfDNA level in blood 1-hour post-LIFU procedure compared to cfDNA level in blood pre-procedure. The primary study hypothesis is that BBBD with LIFU leads to a ≥2-fold increase in cfDNA in blood. The secondary hypothesis is that there exists ≥75% agreement between biomarker pattern in cfDNA sample from 1-hour post-LIFU sample and biomarker pattern in tumor tissue obtained later. The trial has been powered to evaluate both primary and secondary hypotheses. Based on an assumed true agreement rate of 91% and a one-sided alpha of 0.025, an exact test for binomial proportions provides a sample of N=50 with 84% power for the secondary hypothesis. Exploratory endpoints include (1) sensitivity of detection of known somatic mutations in cfDNA from blood samples collected before and after LIFU, (2) estimation of cfDNA levels post-LIFU in samples collected at 30 minutes, 1 hour, 2 hours, and 3 hours to determine the time of greatest yield, (3) correlation of MRI parameters related to grading of BBBD and biomarkers positive in cfDNA from post-LIFU blood samples. RESULTS Patient enrollment commenced in 2022, and 8 patients have been recruited by 04/11/2023. CONCLUSION Findings from this trial will be critical to liquid biopsy in GBM (Clinical trial information: NCT05383872).

Low-intensity focused ultrasound with systemic microbubble oscillators for blood-brain barrier disruption for liquid biopsy in glioblastoma (LIBERATE).

TPS2084 Background: Liquid biopsy in glioblastoma (GBM) is hindered by a lack of requisite circulating-free DNA (cfDNA) levels in blood due to the blood-brain barrier (BBB). This results in challenges to the identification of blood-based biomarkers and the development of novel biomarker-driven systemic therapies. Real-time image-guided low intensity focused ultrasound (LIFU) combined with IV microbubble oscillators (DEFINITY), non-invasively causes BBB disruption (BBBD). This clinical trial aims to evaluate the utility of LIFU for increasing cfDNA in blood for liquid biopsy in GBM. Methods: LIBERATE is a prospective, multi-center, self-controlled, ongoing, pivotal trial evaluating safety and technical efficacy of LIFU for BBBD to increase cfDNA in blood for GBM. Patients aged &gt;18-80 years with suspected GBM planned for tumor biopsy or resection at eleven centers in North America are being included. Patients with multifocal tumors or tumors arising from deep midline, thalamus, cerebellum, or brainstem are excluded. Patients are administered IV oscillating microbubbles for enhancing sonication, after which MR-guided BBBD using a 220 kHz LIFU device is performed with real-time acoustic feedback for effective cavitation. Before and after procedure, phlebotomies and MRI brain are performed to evaluate outcomes. The primary study endpoint is defined, per subject, as the ratio between their cfDNA level in blood 1-hour post-LIFU compared to cfDNA level in blood pre-procedure. The primary study hypothesis is that BBBD with LIFU leads to ≥2-fold increase in cfDNA in blood. The secondary hypothesis is that there exists ≥75% agreement between biomarker pattern in cfDNA sample from 1-hour post-LIFU sample and biomarker pattern in tumor tissue obtained later. The trial has been powered to evaluate both primary and secondary hypotheses. Based on an assumed true agreement rate of 91% and a one-sided alpha of 0.025, an exact test for binomial proportions provides a sample of N=50 with 84% power for the secondary hypothesis. Exploratory endpoints include (1) sensitivity of detection of known somatic mutations in cfDNA from blood samples collected before and after LIFU, (2) estimation of cfDNA levels post-LIFU in samples collected at 30 minutes, 1 hour, 2 hour, and 3 hour to determine time of greatest yield, (3) correlation of MRI parameters related to grading of BBBD and biomarkers positive in cfDNA from post-LIFU blood samples. Patient enrollment commenced in 2022 and 7 patients have been recruited by 02/13/2023. Clinical trial information: NCT05383872 .

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&amp;lt; 1.3 pg/mL or E2&amp;lt; 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.

Pathway to Healing and Recovery: Alleviation of Survivor Worries in Sexual Assault Nurse Examiner-Led Sexual Assault Telehealth Examinations

IntroductionThe purpose of this study is to understand the pre-examination worries of individuals who experience sexual assault, and whether those worries were experienced or resolved during a telehealth-enabled, sexual assault nurse examiner-led sexual assault examination. MethodsPatient surveys were administered to understand pre-examination worries, whether those worries were ultimately experienced during the consultation, and patient perceptions of care quality, telehealth consultation, and whether the examination helped individuals feel better. Data analysis was conducted using descriptive statistics and binomial proportion tests. ResultsSurveys were collected from 74 adolescents and adults who obtained sexual assault care at 6 rural and 2 suburban hospitals. Study findings showed individuals overcome substantial worries to access care, with 66% having at least 1 worry and 41% endorsing 3 or more pre-examination worries. Most participants felt believed (83%) and did not feel judged (88%) or blamed (85%) during their examination. Analysis of pre-examination worries and worry resolution during the examination showed 88% to 100% resolution of worries related to being believed, judged, blamed or lacking control. Participants highly rated the quality of care received (92%) and 84% stated the examination helped them feel better, suggesting a sexual assault nurse examiner-led examination is an important step toward recovery and healing. DiscussionThese findings have implications for emergency department support for sexual assault nurse examiner-led care and public health messaging to demystify sexual assault care, allay fears, and highlight care benefits.

Long-term impact of a geriatric prescribing context.

The medication-related death of a hospitalized older adult elucidated the inappropriateness of medication default doses in our electronic health record (EHR) for older adults. In response, we created and implemented the Geriatric Prescribing Context (GPC), an EHR-based set of age-specific dose and frequency defaults for patients 75 years and older, in July 2017. Inpatient medication orders aligned with GPC defaults and showed significant dose decreases at one year for nine of ten most commonly used medications. This follow-up investigation examined GPC alignment of dose and frequency over the 42-month time period after its implementation. Order data for the ten most commonly used medications at OHSU Hospital were collected retrospectively from July 2016 through December 2020. We used Statistical Process Control charts to assess the proportion of medication orders aligning with the GPC's recommendations. Signals of special cause were evaluated to identify time periods when shifts in process averages likely occurred and suspected shifts were assessed using binomial proportion tests. We used RStudio (RStudio, Inc., version 1.2.5001) and Microsoft Excel (2016) to perform statistical analyses and control charts, respectively. The preimplementation phase of all medications displayed no special causes. After significant initial improvement in 2017, control charts revealed three different patterns of performance. Eight medications maintained the initial improvement with one medication displaying a second significant improvement at a later date. Two medications showed a subsequent decline in performance not statistically different from baseline. Overall, eight of the ten medications were prescribed at more age-friendly doses and frequencies compared to baseline after 42 months. The GPC is an effective method to support safer prescribing for hospitalized older patients, but long-term impacts may be medication-specific. Further investigation is needed to ensure appropriate prescribing across drug classes and understand the GPC's impact on patient outcomes like adverse drug events.

Diagnosis and evaluation of patients treated with acupuncture in the public service

ObjectiveTo verify the effectiveness of acupuncture using Traditional Chinese Medicine tools (pulse and tongue), for several clinical conditions, in the public health service. This is a retrospective clinical study running in a single healthcare referral center in Brazil. Seventy-two patients participated (retrospective review of medical records). Acupuncture treatment was provided at the referral center. Material and methodsThe main outcome measures included the patients' main complaints, sex, pain classification using the verbal rating scale (VRS), observation of the tongue (color change and presence of coating), and pulse palpation, which were used to assess the most affected San Jiao (SJ). The patients' energy status was classified by the acupuncturist as deficient or excessive in the first and last treatment sessions. Chi-squared test, Fisher's exact test, and binomial proportion test were used for comparisons of data. ResultsPatients experienced significant analgesia at the end of treatment than that before treatment (p < 0.01). At the end of treatment, the tongue showed a greater amount of coating in patients with a deficient energy state (p = 0.02) than in those with excess energy (p = 0.70); however, there was no difference in the tongue color (p > 0.05) between both patient groups. Pulse analysis showed an initial difference according to energy status, with reduced pulse in a deficiency state (p < 0.05), and balanced pulse at the end of the treatment (p = 0.48). ConclusionsAcupuncture is a therapeutic option for pain control and improved energy balance.

Comparing Teacher Priorities and Student Uptake in EMI Lectures: An Exploratory Study

English medium instruction (EMI) has been increasing in higher education with broad intentions of stimulating internationalization and cross-cultural learning experiences. This form of education presents opportunities and challenges for teachers and students alike. Key challenges involve various levels of second language (L2) speaking and listening abilities among teachers and students operating in EMI contexts. This exploratory study therefore examines the relationship between the main ideas two EMI lecturers in Sweden intended for their students to learn during lectures and the main ideas that EMI students report learning in the same lectures. Prior to six lectures, the teachers summarized to the researcher the main ideas to be included in the respective lecture. Immediately following the lecture, students provided their own summaries of the main ideas. A keyword analysis comparing the teachers’ intended messages and students’ reports shows that students may not be recognizing and acquiring the main ideas that the teacher intends. Further analysis distinguished two sub-groups of students: those with self-reported Swedish as a first language (L1) and those with self-reported L1s other than Swedish. A binomial proportion test showed that L1 impacted the amount of lecture main idea key words reported by the students in this study. The paper closes with a pedagogic perspective encouraging EMI lecturers to monitor student uptake on a regular basis and adjust their lecture delivery to support better learning and retention of content delivered via EMI.

Development and internal validation of an equation using anthropometric measures to predict correct endotracheal tube insertion depth.

PurposeTo develop, internally validate, and assess the utility of implementing a regression model for determining endotracheal tube (ETT) insertion depth.Research methodsWe recorded height, weight, age, sex, ETT internal diameter (ID), lip marking, and tracheal position from the electronic record from a random subset of 2,000 intubated subjects obtained from 1 January 2009 to 5 May 2012. A multivariable linear regression model was constructed and validated by a nonparametric bootstrapping technique using unrestricted random sampling methods. A prospective pilot of subjects admitted to the pediatric intensive care unit requiring invasive mechanical ventilatory support was conducted from 7 January 2019 to 31 May 2019. Those with spinal and/or skeletal malformations, without a post-intubation chest-x-ray (CXR) order, or whose CXR quality impaired visualizing the carina and ETT tip, were excluded. The validated regression equation determined insertion depth. CXR following intubation determined ETT position. Demographic data were summarized. Two-tailed, one-sample binomial test of proportions assessed differences in the proportion of correct position by the equation.Main findingsFour hundred and seventy-seven subjects included in model construction yielded 10,000 independent samples for internal validation; 55% were female, and the mean age (SD) was 47 (63) months. Bias between bootstrap coefficients and refined model estimates were negligible (P < 0.01). Eleven subjects in the pilot were female (64%), mean age (SD) of 36.7 (38) months. Four protocol violations (36.4%) resulted in malposition. Subsequent repositioning per protocol resulted in 100% correct positioning (P = 0.01).ConclusionThe regression equation [0.8636 * (Ht. 0.6223)] facilitated correct ETT placement. A larger, diverse sample is required for external model validation.

Representation of Women as Editors in Anesthesiology Journals.

Although there has been a considerable increase in the representation of women in medicine, a gender gap still exists with regard to leadership positions. This gender discrepancy has been identified in the field of anesthesiology, in terms of first and senior authorship, as well as in general composition of editorial boards in Anesthesiology and Anesthesia & Analgesia. The goal of this study is to examine the current representation of women in editorial boards of anesthesia journals with respect to the hierarchy of different editorial positions and to assess whether there has been improvement toward equity in recent years. A comprehensive search was performed for anesthesiology journals indexed in the Scimago Journal and Country Rank in May 2020. The editorial boards of the top 20 journals by impact factor were analyzed. Editorial board members were categorized based on their title. Gender was assigned using images or pronouns on research databases or hospital-affiliated websites. The percentage of women within each category was calculated. When available, the year the editors obtained their medical degree was collected. A binomial proportion test was used to analyze the distribution of women overall and among editorial roles, compared to the proportion of women anesthesiologists (26%). A Wilcoxon rank-sum test was used to compare time since medical degree between genders. Additionally, women representation in anesthesiology editorial boards in 2020 was compared to 2010. A total of 19 journals were included in this study, as 1 journal did not disclose editorial board membership. Overall, women occupied 18% of all editorial board positions. All editors-in-chief and assistant/associate/deputy editors-in-chief were men. Women consisted of 17.1% of executive/section/senior editors, 17.9% of editors, and 20.6% of associate/assistant editors. There were significantly fewer women editorial board members than the percentage of women anesthesiologists (18% vs 26%; P < .001). Editorial boards from 2010 were available for 14 journals, and of these journals, women comprised 12% of editorial board members in 2010 compared to 19% in 2020 (P = .001). These findings suggest that in anesthesiology journals, women are underrepresented at all editorial levels, especially at higher levels. As editorial boards have a significant impact on which articles are published by a journal and thereby significant influence on the specialty as a whole, the lack of gender equity in editorial boards should be addressed.

Outcome of Index Pregnancy in Women with Recurrent Pregnancy Loss (RPL).

Recurrent pregnancy loss (RPL) is encountered in 2-5% of Obstetric population and in 50% the cause is unknown and hence it is a challenging situation for the Obstetrician to manage such women. This study was undertaken with the objectives of finding out the causes of RPL, comparing the outcome of index pregnancy between unknown RPL and known RPL and to study the pregnancy outcome with thromboprophylaxis in women with unknown RPL. Prospective observational study involving 323 women was undertaken in a tertiary care Institute South India. Women with two or more pregnancy losses without any live birth were included after ethical clearance and were investigated including thrombophilia screening. SSPS version 20 was used for statistical analysis. Comparison of pregnancy outcomes was determined with binomial test of proportions and pregnancy outcome in unknown RPL was calculated by Fisher's exact test or Chi-square test. The common etiological factors were Thrombophilias (33%), followed by endocrine causes. There was no difference in miscarriage rates and live birth rates but IUGR, Stillbirth and perinatal deaths were significantly more in women with known RPL after interventions. In unknown RPL thromboprophylaxis with combination of aspirin, enoxaparin or progesterone resulted in significantly more term birth rates (93%). Thrombophilias were found to be the most common cause in this cohort of Indian women. In women with unknown RPL, thromboprophylaxis with Aspirin alone results in high incidence of preterm birth. Aspirin combined with Enoxaparin and or Progesterone achieves high live birth rate of term foetuses.

Utility of device-derived daily activity, a novel digital biomarker, to predict ventricular arrhythmias – data from the CERTITUDE registry

Abstract Background While there have been prior studies showing an association between activity and outcomes, there have been no studies examining the temporal relationship between device-derived daily activity, a novel digital biomarker, and ventricular tachyarrhythmias (VT). Purpose In a big dataset with over 55,000 pacemaker, ICD, and CRT devices, we aimed to identify whether changes in activity predict VT, or else VT predict changes in activity. Methods The CERTITUDE registry comprises a de-identified database of over 55,000 U.S. BIOTRONIK pacemaker, ICD, CRT devices, and loop recorders active on Home Monitoring®. Daily data on leads, arrhythmias, and physiological parameters such as activity are captured. Patient activity is reported daily as percentage active during the day, assessed by a one-axis accelerometer at ∼0.4 Hz frequency. Analysis to ascertain temporal changes in device-derived activity associated with treated VT was performed using the first event per device and 7-day activity windows (baseline, pre- and post-event). Baseline period was defined as 31–38 days prior to VT. VT events were categorized by heart rate (≤200 bpm,&amp;gt;200 bpm) and treatment (shock with or without ATP, ATP alone). Differences in activity between baseline, and pre- and post-VT were analyzed using the binomial proportion test. Results A total of 16,475 devices (9732 ICDs, 6743 CRT-Ds) had activity data available for analysis. The cumulative follow-up duration was 18,355 years (5.6 million days with transmission). Of the 2636 VT events analyzed, 1409 had a heart rate &amp;gt;200 bpm, and 593 were treated with shock. Patients with VT events &amp;gt;200 bpm treated with shock had a significant reduction in activity post-VT with a median −8.7% reduction (IQR −24.6%; 7.3%, p&amp;lt;0.001). However, there was no reduction in activity before the VT&amp;gt;200 bpm (p=0.690) (Figure). VT events &amp;gt;200 bpm treated with ATP alone were not associated with reduction in activity before or after the episode. Similarly, VT events ≤200 bpm treated with shock were also associated with a reduction in activity following the event (−5.8%, IQR −29.5, 12.3%, p=0.003), but not prior to the VT event. Conclusions In this report from the CERTITUDE registry, we have shown a temporal decline in device-derived activity following ventricular arrhythmias&amp;gt;200 bpm and ≤200 bpm treated with a shock, but not in patients treated with ATP. Monitoring device-derived activity post-VT events with a shock could provide relevant clinical information and potentially warrant intensified treatment. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Biotronik

Prehospital Cross-Sectional Study of Drowning Patients Across the United States.

Every year drowning is responsible for 7% of injury-related deaths worldwide, making it the third leading cause of unintentional injury-related death. However, in the United States, little is known regarding the prehospital presentation and management of these patients. The purpose of this study was to describe the drowning population in the United States, with a focus on prehospital time intervals, transport, and cardiac arrest frequency. A retrospective cross-sectional study was performed querying records from emergency medical services encounters across the United States over 30 mo (January 2016 to July 2018) using the ESO (Austin, TX) national emergency medical services data registry. Patients with a dispatch or chief complaint of drowning were included. Descriptive statistics, binomial proportion tests, and general linear and logistic regression models were used. There were 1859 encounters that met the study criteria. Median age was 18 y (n=1855, LQ-UQ 4-46). Pediatric patients accounted for 50% (n=919, 95% CI 47-52). Cardiac arrest occurred in 29% (n=537, 95% CI 27-31), and return of spontaneous circulation occurred in 37% (n=186, 95% CI 32-41). Times were 8±5, 19±17, and 15±10 min (mean±SD) for arrival, on-scene, and transport times, respectively. This national prehospital drowning study demonstrated that despite an 18% fatality rate in drowning encounters, patients were more likely to have return of spontaneous circulation when compared to the overall prehospital national average, with rates higher in pediatric patients. Future studies with outcomes data should focus on identifying factors that improve cardiopulmonary resuscitation success rates.

One year on: assessing the impact of coronavirus disease 2019 on demand for semi-urgent ENT services.

This study investigated how the coronavirus disease 2019 pandemic has impacted on presentations to ENT first-on-call services. All appointments to a rapid access triage clinic from 1 June to 31 August in 2019 and 2020 were reviewed retrospectively and their reasons for consultation classified. A binomial proportion test was used to determine whether the proportions of consultations per presentation differed significantly between years. This analysis was repeated with the number of unique patients per presenting complaint. The proportions of nine reasons for consultation differed significantly between 2019 and 2020, including an increase in otitis media and nasal trauma presentations, and a decrease in otitis externa and tonsillitis presentations. Reattendances caused some variation in the frequency of certain diagnoses. Our data suggest a shift in the presentations to first-on-call services, which may be a result of changes in patient behaviour and access to healthcare services.

Pharmacometabolomics identifies candidate predictor metabolites of an L-carnitine treatment mortality benefit in septic shock.

Sepsis‐induced metabolic dysfunction contributes to organ failure and death. L‐carnitine has shown promise for septic shock, but a recent phase II study of patients with vasopressor‐dependent septic shock demonstrated a non‐significant reduction in mortality. We undertook a pharmacometabolomics study of these patients (n = 250) to identify metabolic profiles predictive of a 90‐day mortality benefit from L‐carnitine. The independent predictive value of each pretreatment metabolite concentration, adjusted for L‐carnitine dose, on 90‐day mortality was determined by logistic regression. A grid‐search analysis maximizing the Z‐statistic from a binomial proportion test identified specific metabolite threshold levels that discriminated L‐carnitine responsive patients. Threshold concentrations were further assessed by hazard ratio and Kaplan‐Meier estimate. Accounting for L‐carnitine treatment and dose, 11 1H‐NMR metabolites and 12 acylcarnitines were independent predictors of 90‐day mortality. Based on the grid‐search analysis numerous acylcarnitines and valine were identified as candidate metabolites of drug response. Acetylcarnitine emerged as highly viable for the prediction of an L‐carnitine mortality benefit due to its abundance and biological relevance. Using its most statistically significant threshold concentration, patients with pretreatment acetylcarnitine greater than or equal to 35 µM were less likely to die at 90 days if treated with L‐carnitine (18 g) versus placebo (p = 0.01 by log rank test). Metabolomics also identified independent predictors of 90‐day sepsis mortality. Our proof‐of‐concept approach shows how pharmacometabolomics could be useful for tackling the heterogeneity of sepsis and informing clinical trial design. In addition, metabolomics can help understand mechanisms of sepsis heterogeneity and variable drug response, because sepsis induces alterations in numerous metabolite concentrations.

Does Nature Have a Systematic Sex Bias: Prevalence, Mortality, and Trend of COVID-19

Abstract Background The unprecedented outbreak of a contagious respiratory disease similar to pneumonia caused by a novel coronavirus termed as COVID-19 has led to a pandemic claiming millions of lives worldwide. Potential vaccine candidates are underdevelopment to contain and mitigate the spread of global cases and deaths. Preliminary reports suggest that males and females are affected in cases and deaths differentially. Objective To study the statistical significance of sex and gender bias in COVID-19 infection and deaths across 75 selected countries in the world, specifically for the United States. To summarize, the prevalence and incidence rates of this infectious disease globally segmented by developed, developing, and transitioning countries. Methods Data on sex are collected from the sex-disaggregated data tracker Global Health 50/50, University College London until September 21, 2020, UN COVID-19 and gender monitor, and CDC COVID data tracker. The hypothesis was tested using the binomial proportion test to be 50% within males and females for infection rate and mortality. Prevalence and Incidence rates by sex are illustrated graphically. Results Females in countries with transitioning and developed economies have a higher number of cases and deaths than males, but in developing countries, males have high mortality due to coronavirus. Also, men are at greater risk of worse outcomes if infected with the SARS-Cov-2 virus, including mortality. The differential effect of gender in death counts in the US is statistically significant, with reported p-values < 0.05. In the oldest US population (85+ years), female's death rate is higher due to the virus. Monthly deaths in the US was at its peak during March - April 2020 for both sexes. Conclusion Clinical researchers, health insurance planners can follow the suggested approach outlined here to target a specific population for inaugural vaccination and immunization. Although everyone should follow the CDC guidelines of prevention, it is recommended that the females strictly follow the CDC guidelines due to a higher rate of Covid-19 infection. Also, the effect of age is delineated to help vaccine administration priority.

1161MO Lanreotide autogel (LAN) and temozolomide (TMZ) combination therapy in progressive thoracic neuroendocrine tumours (TNETs): ATLANT study results

LAN and TMZ are among the main therapies recommended for progressive TNETs but prospective data are lacking. We present safety and efficacy outcomes of this combination in progressive TNETs. ATLANT was a 12-month, phase II, multicentre, single-arm, open-label study. Eligible patients had unresectable, locally advanced or metastatic, well-differentiated TNETs (bronchial or thymic, typical or atypical carcinoid) with baseline radiological progression (RECIST v1.1) in the previous 12 months. Patients received subcutaneous LAN 120 mg and oral TMZ 250 mg/day over 5 days, every 28 days. Primary endpoint: disease control rate (DCR) at 9 months (RECIST v1.1 complete response, partial response or stable disease [clinically relevant: ≥30%, unacceptable: ≤10%]). Data were analysed using exact binomial proportion tests for one-way tables. Patients (N=40; 60% male) had a mean (SD) age of 64.9 (11.8) years. The primary tumour site was: lung, 90%; thymus, 10% (typical, 20.0%; atypical, 52.5%; carcinoid, 27.5%). Mitotic count (mitoses/2 mm2): <2: 30%; ≥2–<10: 42.5%; ≥10: 2.5%; not done: 25%. Ki-67 expression (N=20): <4%: 10%; 4–<25%: 80%; ≥25%: 10%. TNM staging: primary tumour TX: 5.1%, T0: 46.2%, T1: 7.7%, T2: 12.8%, T3: 10.3%, T4: 17.9%; regional lymph node N0: 56.4%, N1: 2.6%, N2: 23.1%, N3: 17.9%; distant metastasis M0: 5.1%, M1: 94.9%. Locally assessed DCR at 9 months (ITT population; N=40) was 35.0% (95% CI: 20.63; 51.68) (significantly higher than 10% p<0.0001 but not superior to 30% p=0.297). Median progression-free survival was 37.1 (95% CI: 24.1; 52.9) weeks. In total, 97.5% of patients had treatment-emergent adverse events (TEAEs; >90% of TEAEs were Grade 1/2), 9 (22.5%) patients had serious TEAEs (of which 2 were treatment related), 2 TEAEs led to withdrawal of study treatment, and 2 led to death. The observed TEAEs were in line with the known individual drug profiles, and there were no new or unexpected AEs. Most common TEAEs included nausea (52.5%), vomiting (32.5%) and diarrhoea (30.0%). These results suggest that the LAN and TMZ combination was generally well tolerated and could be an effective regimen for managing progressive TNETs.

Differences Between Esophageal and Tracheal Intubation Ultrasound View Proficiency: An Educational Study of Novice Prehospital Providers.

ObjectivesAirway ultrasound is now possible in the prehospital setting due to advances in ultrasound equipment portability. We questioned how well prehospital providers without prior experience could determine both esophageal and tracheal placement of an endotracheal tube in cadavers after a brief training course in ultrasound. MethodsThis educational prospective study at the Simulation Center in Mayo Clinic Jacksonville Florida enrolled 50 prehospital providers. Demographic and practice background information was obtained through surveys. Each participant performed a baseline ultrasound to determine endotracheal tube placement in a cadaver that was randomly assigned to an esophageal or tracheal intubation. Participants then repeated the randomized testing after a 15-minute tutorial. Before and after overall accuracy as well as proportions of correct identification of esophageal and tracheal intubations were determined and compared using standard binomial proportion and McNemar’s tests.Results None of the participants had prior experience of performing airway ultrasound. Baseline group scores were 60% (CI 45%-74%) for overall accuracy (n=50), 55% (CI 32%-76%) for correct identification of an esophageal intubation, and 64% (CI 44%-81%) for correct tracheal detection. Baseline scores were not significantly different from standard binomial distributions. Post-test scores were 82% (CI 69%-91%) for overall accuracy, 96% (CI 80%-100%) for esophageal intubation detection, and 66.7% (CI 45%-84%) for tracheal intubation detection, with corresponding binomial p-values of <0.001, <0.001, and 0.15. P-values for McNemar’s paired test for combined overall accuracy, correct esophageal detection, and correct tracheal detection were 0.04, 0.02, and 0.62, respectively.ConclusionsPrehospital participants without prior ultrasound experience demonstrated significant gains in airway ultrasound proficiency after a limited introductory course. Post-training score increases were largely due to a notable increase in correct esophageal intubation detection rates. Learners did not make significant progress in correctly identifying a tracheal intubation. Airway ultrasound educational design may benefit from added emphasis on the potentially more difficult to recognize tracheal intubation view.