Uncontrolled Comorbidities Research Articles

Real-world experience: a retrospective pediatric chart review to determine why patients and caregivers discontinue oral immunotherapy

BackgroundOral immunotherapy (OIT) is an increasingly utilized management strategy for IgE-mediated food allergy. Despite promising efficacy and effectiveness, there is still a lack of data surrounding the reasons for discontinuation of OIT. The primary reason stated in the literature for discontinuation is adverse gastrointestinal effects. Social factors contributing to OIT discontinuation have not been well reported. We hypothesize that social considerations are significant contributors to treatment discontinuation.MethodsWe completed a retrospective chart review of 50 patients treated in community pediatric allergy practices who discontinued OIT out of 507 patients who were started on OIT between October 1, 2017-October 27, 2022. Reasons for discontinuation were identified and classified into five main categories: unsafe care decisions, anxiety, adverse effects of OIT, uncontrolled comorbidity and social factors. Categories were not exclusive.Results507 patients were started on OIT, with data available for 50 patients who discontinued OIT, aged 10 months to 18 years and 2 months. The overall discontinuation rate was 9.8%, of which 40 patients (80%) discontinued during buildup, 9 patients (18%) discontinued during maintenance and one patient on two food OIT discontinued one food during buildup and one during maintenance (2%). Thirty-four patients (68%) had multiple reasons for discontinuing OIT. Social factors were the most common reason for discontinuation and were identified in 32 patients (64%). Twenty-four patients (48%) discontinued OIT due to adverse effects. Gastrointestinal symptoms were the most prevalent, while anaphylaxis contributed to discontinuation in 15 patients (30%). Anxiety led to discontinuation in 17 patients (34%).ConclusionsOur data highlights the importance of social factors and anxiety in the success of OIT completion. Our results support the need to consider not only the patient’s medical history, but also their social history and support networks when selecting patients who are good candidates for OIT to optimize the successful completion of OIT.

Biologics for eosinophilic otitis media: a retrospective case study in a multidisciplinary center.

Eosinophilic otitis media (EOM) is a difficult-to-treat otitis media characterized by eosinophilic accumulation in the middle ear mucosa and effusion. It is refractory to conventional treatments and is strongly associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The diagnostic criteria for EOM were established by IINO in 2011. With the recognition of type 2 inflammatory diseases, the gold standard of treatment is the systemic and topical administration of corticosteroids. Recently, several retrospective studies have demonstrated the efficacy of biologic treatments in EOM. We aimed to share our experience regarding the response of EOM after the use of biologics. This is a retrospective observational analysis including patients with refractory EOM treated with different biologics (benralizumab, omalizumab, mepolizumab, dupilumab) for concomitant severe asthma, urticaria and/or severe uncontrolled CRSwNP from 2011 to 2023. Treatment effectiveness in terms of EOM severity was measured using medical Global Evaluation of Treatment Effectiveness (GETE). We illustrated 4 clinical cases of uncontrolled comorbid EOM and demonstrated the complexity of multidisciplinary medical pathway with good response to biologics. We also observed that response to EOM and CRSwNP does not always follow that of asthma. The results of our small sample were consistent with those found in the literature and showed control of EOM with biologics. We need a larger multicentric sample and methodology to confirm these results and to compare the efficacy of different biologics.

Cardiometabolic Co-morbidity Burden and Circulating Biomarkers in Patients With Chronic Coronary Disease in the ISCHEMIA Trials

Cardiometabolic co-morbidities, diabetes (DM), hypertension (HTN), and obesity contribute to cardiovascular disease. Circulating biomarkers facilitate prognostication for patients with cardiovascular disease. We explored the relation between cardiometabolic co-morbidity burden in patients with chronic coronary disease and biomarkers of myocardial stretch, injury, inflammation, and platelet activity. We analyzed participants from the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trials biorepository with plasma biomarkers (N-terminal probrain natriuretic peptide, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein, interleukin-6, soluble CD40 ligand, and growth differentiation factor-15) and clinical risk factors (hemoglobin A1c [HbA1c], systolic blood pressure [SBP], and body mass index [BMI]) at baseline. We defined cardiometabolic co-morbidities as DM, HTN, and obesity at baseline. Co-morbidity burden is characterized by the number and severity of co-morbidities. Controlled co-morbidities were defined as HbA1c <7% for those with DM, SBP <130 mm Hg for those with HTN, and BMI <30 kg/m2. Severely uncontrolled was defined as HbA1c ≥8%, SBP ≥160 mm Hg, and BMI ≥35 kg/m2. We performed linear regression analyses to examine the association between co-morbidity burden and log-transformed biomarker levels, adjusting for age, gender, estimated glomerular filtration rate controlled for hemodialysis, and left ventricular ejection fraction. A total of 752 participants (mean age 66 years, 19% women, 84% White) were included in this analysis. Self-reported Black race, current smokers, history of myocardial infarction, and heart failure had a greater cardiometabolic co-morbidity burden. The presence of ≥1 severely uncontrolled co-morbidity was associated with significantly higher baseline levels of high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein, interleukin-6, and growth differentiation factor-15 than participants with no co-morbidities. In conclusion, increasing cardiometabolic co-morbidity burden in patients with chronic coronary disease is associated with higher levels of circulating biomarkers of myocardial injury and inflammation.

A first-in-human phase 1 trial of T cell membrane-anchored tumor targeted IL12 (ATTIL12) -T cell therapy in advanced/metastatic soft tissue and bone sarcoma.

TPS11586 Background: Interleukin-12 (IL12) is a cytokine that induces antitumor immune response and immune memory by activation of NK cells, induction of IFNg, and maturation of DC cells in the tumor microenvironment (TME). However, prior clinical experience with IL12 has been limited by toxicities including cytokine release syndrome (CRS) and hepatotoxicity. We developed a novel tumor-targeted IL12 gene (ttIL12) that encodes the p35 and p40 VNTANST fusion subunits that targets cell surface vimentin (CSV). Vimentin is expressed intracellularly in many normal and neoplastic mesenchymal cells but our group discovered that intracellular vimentin is often flipped to the cell surface (referred to as CSV) across multiple tumor types.2 Preclinical studies demonstrated efficacy and induction of long-term memory of ttIL12 against metastatic osteosarcoma with reduced toxicity in immune competent models.3 However, ttIL12 had limited efficacy in treating large volume tumors and did not completely eliminate toxic peripheral cytokines. To address this, our team generated a membrane anchored ttIL12 to arm T cells known as attIL12-T cell therapy. We hypothesize attIL12 will minimize toxic cytokines in peripheral tissues but promote induction of INFg/TNFa in the TME to decrease the toxicity and boost efficacy. Methods: This is a phase 1 trial of attIL12-T cells in patients (pts) with locally advanced or metastatic soft tissue or bone sarcomas to assess safety, maximal tolerated dose (MTD) and recommended phase 2 dose (RP2D). Pts in part A (dose finding) will be enrolled using a Bayesian optimal interval (BOIN) design in up to 6 dose levels. Part B (dose expansion) will evaluate preliminary efficacy in 10 additional pts with osteosarcoma treated at the RP2D. Treatment:Pts will undergo leukapheresis to collect peripheral blood mononuclear cells (PBMCs) for generation of attIl12-T cells. Bridging therapy is permitted but not required. Pts will receive cyclophosphamide (Cy) IV prior to planned T cell administration. attIL12 T cells will be administered at the specified dose level IV in a single infusion (dose level 1 and 2) or 2 serial doses (dose level 3-6) on day 0 and day 14. Pts will be monitored for toxicity and response evaluation. Pts will also undergo pre-treatment/on-treatment tumor biopsies for translational and correlative analysis. Eligibility:Pts must be ≥ 12 years of age, have a confirmed diagnosis of locally advanced or metastatic sarcoma, evaluable disease, received at least 1 prior line of standard systemic therapy, ECOG PS 0-1, and adequate organ function to tolerate immune-effector cell therapy. Pts with known sensitivity to Cy, active/prior autoimmune disease, uncontrolled CNS disease, or other uncontrolled comorbidities that pose potential safety risk will be excluded. Enrollment to cohort 1 began in Dec 2023. Clinical trial information: NCT05621668 .

Validation of a Predictive Model of Vaginal Birth after Caesarean Section in Pakistani Women.

To determine the frequency of successful trials of vaginal birth after Caesarean section (VBAC) using the Flamm and Geiger model. Observational study. Place and Duration of the Study: Obstetrics and Gynaecology Unit II of Dr. Ruth K.M. Pfau Civil Hospital, Karachi, Pakistan, from August 2022 to January 2023. Women with singleton pregnancy having cephalic presentation, previous one lower segment caesarean section (LSCS), and without any contraindication for vaginal delivery were included. Women bearing foetus having estimated weight >3.5kg, morbid obesity, multiple pregnancies, non-cephalic presentation, placenta praevia, abruptio placentae, uncontrolled maternal comorbidities, or had previous two or more Caesarean sections were excluded. Flamm and Geiger score was applied to record observations of successful and unsuccessful trials. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the score were calculated by ROC curve, along with its area under the curve (AUC) and Youden's index curve, with 95% confidence interval. This study included 258 participants. Successful vaginal delivery was possible in 125 (48.4%) participants, whereas 133 (51.6%) underwent emergency Caesarean section. Cervical dilatation and effacement were the main factors assessing the success. The Flamm and Geiger score of >5 had an area under the curve of 0.813 (0.762-0.864). The score's sensitivity was 75% (67-82%), specificity 76% (68-82%), and PPV of 75% with an accuracy of 76%. The Flamm and Geiger score of >5 demonstrated high sensitivity, specificity, PPV, and accuracy in predicting later successful vaginal birth. It is recommended as a promising and valuable tool for assessing VBAC's success in low-resource countries. Vaginal birth after caesarean, Flamm and Geiger Model, Indication of caesarean, trial of labour after caesarean, VBAC risk scoring criteria.

A prospective study of changes in bone health in adult cancer patients treated with pelvic radiotherapy.

Cancer is a major health problem in today's world. Many patients of pelvic malignancies need treatment by radiation therapy. Post-treatment morbidity due to loss of bone health is less commonly studied. Our study aims at studying the impact of pelvic radiation therapy on bone health including bone mineral density and blood parameters and time of maximum change in Indian patients after pelvic radiotherapy. Patients suffering from histologically confirmed pelvic malignancies were included. Patients having metastasis, primary bone tumor or uncontrolled co-morbid conditions were excluded. Patients were treated with concomitant chemoradiation using conventional fractionation of external beam radiotherapy followed by brachytherapy where indicated. T score and Z score of bone mineral density, serum alkaline phosphatase, vitamin D3, phosphorus and calcium were measured before radiation therapy and 6 weeks, three months, and six months after completion of radiation therapy. A p-value ≤ 0.05 was considered statistically significant. We found that there was a significant decrease in mean Z score and a significant rise of mean serum alkaline phosphatase at three months post radiation therapy. This was associated with an insignificant changes of mean T score, vitamin D3, phosphorus and calcium after radiation therapy. No pelvic insufficiency fractures were detected. In Indian patients, alkaline phosphatase rises, and Z score falls significantly after radiation therapy at three months after treatment. This suggests maximum bone turnover at three months after treatment. Pharmacological intervention, when necessary, may be considered by careful monitoring of patients by this time.

Recommendations for initial diabetic retinopathy screening of diabetic patients using large language model-based artificial intelligence in real-life case scenarios

PurposeTo study the role of artificial intelligence (AI) to identify key risk factors for diabetic retinopathy (DR) screening and develop recommendations based on clinician and large language model (LLM) based AI platform opinions for newly detected diabetes mellitus (DM) cases.MethodsFive clinicians and three AI applications were given 20 AI-generated hypothetical case scenarios to assess DR screening timing. We calculated inter-rater agreements between clinicians, AI-platforms, and the “majority clinician response” (defined as the maximum number of identical responses provided by the clinicians) and “majority AI-platform” (defined as the maximum number of identical responses among the 3 distinct AI). Scoring was used to identify risk factors of different severity. Three, two, and one points were given to risk factors requiring screening immediately, within a year, and within five years, respectively. After calculating a cumulative screening score, categories were assigned.ResultsClinicians, AI platforms, and the “majority clinician response” and “majority AI response” had fair inter-rater reliability (k value: 0.21–0.40). Uncontrolled DM and systemic co-morbidities required immediate screening, while family history of DM and a co-existing pregnancy required screening within a year. The absence of these risk factors required screening within 5 years of DM diagnosis. Screening scores in this study were between 0 and 10. Cases with screening scores of 0–2 needed screening within 5 years, 3–5 within 1 year, and 6–12 immediately.ConclusionBased on the findings of this study, AI could play a critical role in DR screening of newly diagnosed DM patients by developing a novel DR screening score. Future studies would be required to validate the DR screening score before it could be used as a reference in real-life clinical situations.Clinical trial registrationNot applicable.

Citric Acid Treatment of Refractory Chronic Postmastectomy Raw Area During Chemotherapy: A Novel Approach

Background. Wounds at sutured sites are a major postoperative complication. Uncontrolled comorbidities and certain drugs (immunosuppressants and antiproliferative chemotherapeutic agents) hamper the process of wound healing. Sutured wounds need prolonged duration of dressings and management as well as repeated hospital visits. In addition, appropriate reconstructive procedures may be needed to cover the wound. All these factors ultimately add to the cost of care. Case Report. A simple, yet effective option for the management of a refractory chronic postoperative raw area in a surgical case of breast carcinoma is reported. Acceptable wound healing was eventually achieved without disturbing the patient’s chemotherapy cycles, and a major reconstructive procedure was avoided. Conclusion. Citric acid treatment can be a cost-effective, safe, efficient, and novel option to promote faster granulation and epithelialization and may avoid the need for major reconstructive surgery.

Abstract C087: Association of serum lipid profile with prostate cancer risk and aggressiveness in Nigerian men

Abstract OBJECTIVE Though prostate cancer (PCa) is the most common cancer and cause of cancer death among Nigerian men, its relationship with serum lipid profiles, a biochemical measurement of dietary fat, has not been explored among Nigerian men. The study aimed to determine the association of serum lipid profile with prostate cancer risk and aggressiveness. METHODS The study was a case-control conducted at University College Hospital, Ibadan, Nigeria. The cases were newly diagnosed prostate cancer patients ages 50-75 years, while the controls were age-matched healthy men with confirmed normal PSA. Participants with uncontrolled comorbidities, poor performance status (ECOG ≥3), and weight loss in the past month were not eligible. The patient characteristics (age, marital status, employment status, highest level of education, high-fat diet, lack of exercise, tobacco smoking, alcohol intake, family history of prostate cancer, comorbidities, and tumor characteristics [PSA at presentation, histology, Gleason score, and stage at presentation] in the cases alone) were collected using an interviewer-administered questionnaire. A serum lipid profile test (including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) was done in all participants. Analysis of the variables was on SPSS version 23.0, with a t-test to compare the serum lipid profile between the case and control groups, a chi-square to compare the sociodemographic and patient characteristics between both groups and an ANOVA test to determine the association between serum lipid profile and Gleason's score (disease grade) or stage of prostate cancer. RESULTS Enrolled in each group were seventy-four participants. The mean age ± standard deviation was 65.0 ± 5.9 years for cases and 63.0 ± 6.5 years for controls. Participants with a high-fat diet (p = 0.006), physical inactivity (p = 0.046), alcohol consumption (p = 0.005), and family history (p = 0.002) were significantly higher in the case group than the controls. A high proportion of the cases had high-grade disease (GS ≥ 8) [39.2%] and stage 4 disease (35.2%). The mean levels of TC (p&amp;lt;0.001) and HDL-C (p&amp;lt;0.001) were significantly higher in the cases. The mean TG increased while HDL-C decreased as the disease stage advanced but with no statistical significance. While the mean TC (p = 0.001) increased significantly with worsening prostate cancer grade, the mean HDL-C was highest in low-grade disease (p &amp;lt;0.001). CONCLUSION Elevated total cholesterol and high-density lipoprotein cholesterol were associated with increased prostate cancer risk. While elevated total cholesterol was associated with high-grade prostate cancer, a high level of high-density lipoprotein cholesterol was associated with the low-grade disease. Hence, regular serum lipid profile tests may be encouraged among Nigerian men for early detection and treatment of any cholesterol derangement to avoid its predisposition to prostate cancer. Citation Format: Kehinde Oluwatosin Adeyinka, Adeniyi Adenipekun, Atara Ntekim, Augustine Oghenewveyin Takure, Rotimi Solomon. Association of serum lipid profile with prostate cancer risk and aggressiveness in Nigerian men [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C087.

Direct economic burden 1 year postoperation in Chinese adult patients with chronic rhinosinusitis with nasal polyps

ABSTRACT Background Chronic rhinosinusitis with nasal polyps (CRSwNP) remains a common and challenging clinical entity, and its economic burden has not been well described in China thus far. Methods A total of 101 CRSwNP patients who underwent endoscopic sinus surgery were included to investigate direct costs in the first year post-surgery. Costs for outpatient visits, medication use, and examination costs were obtained from the Hospital Information System, and differences were compared between subgroups. Multiple linear regression analysis was adopted to investigate the main influencing factors on annual total direct costs for CRSwNP patients. Results Ninety-two subjects completed the study. The individual mean total direct cost for a CRSwNP patient 1 year post-surgery was $742.4. The largest contributors were pharmacy costs ($580.2), followed by examination costs ($108.1) and outpatient visits ($54.1). Total direct costs were higher in subgroups of patients with uncontrolled clinical status, asthma comorbidity, and eosinophilic CRSwNP compared to their counterparts. The main influencing factors were clinical control status (P = 0.016) and asthma comorbidity (P = 0.035). Conclusions The individual mean total direct cost of CRSwNP in 1-year post-surgery was $742.4. Clinical control status and asthma comorbidity influence these costs and are therefore important in guiding health resources allocation for CRSwNP management.

Age-related differences in associations between uncontrolled asthma, comorbidities and biomarkers in adult-onset asthma

Objective Adult-onset asthma is a recognized but heterogeneous phenotype and has been described to associate with poor asthma control. Knowledge about associations between clinical characteristics including comorbidities and control of adult-onset asthma is limited, especially in older populations. We aimed to study how clinical biomarkers and comorbidities are associated with uncontrolled asthma among middle-aged and older individuals with adult-onset asthma. Methods Clinical examinations including structured interview, asthma control test (ACT), spirometry, skin prick test (SPT), blood sampling, and measurement of exhaled fractional nitric oxide (FeNO) was performed in a population-based adult-onset asthma cohort in 2019–2020 (n = 227, 66.5% female). Analyses were performed among all included, and separately in middle-aged (37–64 years, n = 120) and older (≥65 years, n = 107) participants. Results In bivariate analysis, uncontrolled asthma (ACT ≤ 19) was significantly associated with a blood neutrophil count ≥5/µl, BMI ≥30, and several comorbidities. In multivariable regression analysis, uncontrolled asthma was associated with neutrophils ≥5/µl (OR 2.35; 95% CI 1.11–4.99). In age-stratified analysis, BMI ≥30 (OR 3.04; 1.24–7.50), eosinophils ≥0.3/µl (OR 3.17; 1.20–8.37), neutrophils ≥5/µl (OR 4.39; 1.53–12.62) and allergic rhinitis (OR 5.10; 1.59–16.30) were associated with uncontrolled asthma among the middle-aged. Among the older adults, uncontrolled asthma was only associated with comorbidities: chronic rhinitis (OR 4.08; 1.62–10.31), ischemic heart disease (OR 3.59; 1.17–10.98), malignancy (OR 3.10; 1.10–8.73), and depression/anxiety (OR 16.31; 1.82–146.05). Conclusions In adult-onset asthma, comorbidities were strongly associated with uncontrolled asthma among older adults, while clinical biomarkers including eosinophils and neutrophils in blood were associated with uncontrolled asthma among middle-aged.

A phase 2 study of the combination of decitabine (DAC), venetoclax (VEN), and ponatinib in patients (Pts) with chronic myeloid leukemia (CML) in accelerated phase (AP)/myeloid blast phase (MBP) or Philadelphia-chromosome positive (Ph+) acute myeloid leukemia (AML).

e19044 Background: CML-AP/MBP and Ph+ AML are therapeutic challenges. Based on published pre-clinical data of synergism (Leonard et.al., Sci Transl Med 2016), we hypothesized that combining ponatinib with DAC and VEN might lead to high rates of response and facilitate allogeneic stem cell transplantation (SCT). Methods: The study (NCT04188405) enrolled pts ≥ 18 years of age with CML-AP, CML-MBP or Ph+ AML with ECOG PS ≤ 3 and adequate liver/renal function. Pts with significant uncontrolled cardiovascular comorbidities were excluded. Therapy was with DAC (20 mg/m2/day) x 5 days, VEN (400 mg equivalent dose/day) x 21 days, and ponatinib (45mg/day) x 21 days in cycle 1 and then continuously in cycles 2-24. Each cycle was for 28 days. Ponatinib was reduced to 30mg/day for pts in CR/CRi and to 15 mg/day for pts in CMR. Intrathecal prophylaxis with 4 doses of cytarabine was recommended. The primary objective was to determine the overall response rate (ORR) with the regimen. Results: From Jul 2020 to Jan 2023, 15 pts were treated, 4 with CML-AP, 10 with CML-MBP and 1 with Ph+ AML (Table). 11 pts (73%) had prior TKI exposure, including 4 pts with prior ponatinib. 5 of 13 tested pts (38%) had an ABL1 kinase domain mutation (T315I, Q252H, L384M in 1 pt each and E255K in 2 pts). The median number of cycles received was 3 (range, 1-7). 11 pts (73%) responded; 6 pts (40%) with CR/CRi and 5 (33%) with MLFS. Best response was achieved after cycle 1 in 9 of 11 (82%) responders. All 4 pts with CML-AP responded, and 9 of 11 pts (82%) with prior TKI exposure responded. Four pts underwent subsequent SCT. At a median follow-up of 9.8 months, the median overall survival (OS) was 11.0 months, and the estimated 10-month OS was 63%. The median relapse-free survival was 5.7 months. Among the 11 responders, 5 relapsed (one after SCT), and 6 are in ongoing response (3 after SCT). One pt had a related grade 3 mucositis. No grade 4-5 related non-hematological adverse events were observed. Of the 10 pts who received &gt; 1 cycle of therapy, 5 pts had delay (&gt;1 week) in initiation of subsequent cycles due to cytopenias. The 60-day mortality rate was 0%. Two pts died on study, one from leukemia and one from infection while in MLFS. Conclusions: A triplet combination of DAC, VEN and ponatinib was well-tolerated and resulted in an ORR of 73% in this poor-risk population of pts with advanced Ph+ leukemias. Clinical trial information: NCT04188405 . [Table: see text]

Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine

The protein-based SARS-CoV-2 vaccines FINLAY-FR-2 (Soberana 02) and FINLAY-FR-1A (Soberana Plus) showed good safety and immunogenicity in phase 1 and 2 trials, but the clinical efficacy of the vaccine remains unknown. To evaluate the efficacy and safety of a 2-dose regimen of FINLAY-FR-2 (cohort 1) and a 3-dose regimen of FINLAY-FR-2 with FINLAY-FR-1A (cohort 2) in Iranian adults. A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 6 cities in cohort 1 and 2 cities in cohort 2. Participants included individuals aged 18 to 80 years without uncontrolled comorbidities, coagulation disorders, pregnancy or breastfeeding, recent immunoglobulin or immunosuppressive therapy, and clinical presentation or laboratory-confirmed COVID-19 on enrollment. The study was conducted from April 26 to September 25, 2021. In cohort 1, 2 doses of FINLAY-FR-2 (n = 13 857) or placebo (n = 3462) were administered 28 days apart. In cohort 2, 2 doses of FINLAY-FR-2 plus 1 dose of FINLAY-FR-1A (n = 4340) or 3 placebo doses (n = 1081) were administered 28 days apart. Vaccinations were administered via intramuscular injection. The primary outcome was polymerase chain reaction-confirmed symptomatic COVID-19 infection at least 14 days after vaccination completion. Other outcomes were adverse events and severe COVID-19. Intention-to-treat analysis was performed. In cohort 1 a total 17 319 individuals received 2 doses and in cohort 2 5521 received 3 doses of the vaccine or placebo. Cohort 1 comprised 60.1% men in the vaccine group and 59.1% men in the placebo group; cohort 2 included 59.8% men in the vaccine group and 59.9% in the placebo group. The mean (SD) age was 39.3 (11.9) years in cohort 1 and 39.7 (12.0) years in cohort 2, with no significant difference between the vaccine and placebo groups. The median follow-up time in cohort 1 was 100 (IQR, 96-106) days and, in cohort 2, 142 (137-148) days. In cohort 1, 461 (3.2%) cases of COVID-19 occurred in the vaccine group and 221 (6.1%) in the placebo group (vaccine efficacy: 49.7%; 95% CI, 40.8%-57.3%) vs 75 (1.6%) and 51 (4.3%) in cohort 2 (vaccine efficacy: 64.9%; 95% CI, 49.7%-59.5%). The incidence of serious adverse events was lower than 0.1%, with no vaccine-related deaths. In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of FINLAY-FR-2 and FINLAY-FR-1A, 2 doses of FINLAY-FR-2 plus the third dose of FINLAY-FR-1A showed acceptable vaccine efficacy against symptomatic COVID-19 as well as COVID-19-related severe infections. Vaccination was generally safe and well tolerated. Therefore, Soberana may have utility as an option for mass vaccination of the population, especially in resource-limited settings, because of its storage condition and affordable price. isrctn.org Identifier: IRCT20210303050558N1.

Glycolysis inhibition partially resets epilepsy-induced alterations in the dorsal hippocampus-basolateral amygdala circuit involved in anxiety-like behavior

Pharmacoresistant temporal lobe epilepsy affects millions of people around the world with uncontrolled seizures and comorbidities, like anxiety, being the most problematic aspects calling for novel therapies. The intrahippocampal kainic acid model of temporal lobe epilepsy is an appropriate rodent model to evaluate the effects of novel interventions, including glycolysis inhibition, on epilepsy-induced alterations. Here, we investigated kainic acid-induced changes in the dorsal hippocampus (dHPC) and basolateral amygdala (BLA) circuit and the efficiency of a glycolysis inhibitor, 2-deoxy D-glucose (2-DG), in resetting such alterations using simultaneous local field potentials (LFP) recording and elevated zero-maze test. dHPC theta and gamma powers were lower in epileptic groups, both in the baseline and anxiogenic conditions. BLA theta power was higher in baseline condition while it was lower in anxiogenic condition in epileptic animals and 2-DG could reverse it. dHPC-BLA coherence was altered only in anxiogenic condition and 2-DG could reverse it only in gamma frequency. This coherence was significantly correlated with the time in which the animals exposed themselves to the anxiogenic condition. Further, theta-gamma phase-locking was lower in epileptic groups in the dHPC-BLA circuit and 2-DG could considerably increase it.

Comparison of perioperative outcomes of different routes of hysterectomies- total abdominal, vaginal and laparoscopic, in a tertiary care hospital in Karachi, Pakistan

Background: This study was conducted to compare the perioperative findings among women undergoing hysterectomy by abdominal (TAH), vaginal (VH) and laparoscopic (TLH) routes. Methods: A 5-year cross-sectional survey was conducted at the Aga Khan University Hospital from January 2015-December 2020 to compare perioperative outcomes of the different routes of hysterectomies. Medical record review of 385 patients who underwent hysterectomy for benign conditions were reviewed and analysed, out of which 195 (50.6%) underwent TAH, 96 (24.9%) VH and 94 (24.4%) were operated laparoscopically. Patients with uncontrolled medical comorbid, history of 2 or more abdominal surgeries and uterine size of more than 14 weeks were excluded from the study. Results: revealed significant difference between the mean hospital stay of patients with TAH having the highest mean stay in days (TAH=4.8±1.01, VH=4.4±0.7 and TLH=3.9±0.82 in days; p&lt;0.01) TLH took comparatively significantly longer operating time than TAH (p=0.0005) and VH groups (p=0.004) however, median estimated blood loss was significantly lower in women who underwent TLH as compare to TAH [median (25th-75th percentile); 100 (50-200)] versus 300 (200-500); p&lt;0.01] and VH [100 (50-200)] versus 250 (100-400); p&lt;0.01]. The incidence of post-operative complications was less than 3% and these were observed in women underwent TAH. Conclusions: VH and TLH have lesser complications and hospitalization days as compared to TAH, making these 2 methods superior. Informed decision making by patient and surgeon’s training together can account for choosing the best method of hysterectomy suitable to the patient.

Reassessment of the Need for Asthmatic Patients for Biologic Treatment in a Tertiary Care Hospital.

Asthma is a common chronic inflammatory airway condition. In difficult-to-treat asthma, poor control can be linked to multiple factors like the presence of uncontrolled comorbidities (e.g. gastroesophageal reflux and allergic rhinitis), as well as to poor inhaler use techniques and adherence.In this study we wanted to evaluate our severe asthma patients already on a biologic treatment with regard to presence of any of these factors. Method:A questionnaire-based study, filled by investigators through direct interview with patients. We included all asthma patients on biologic treatment at King Abdul Aziz Medical City, Riyadh, KSA. Started in October 2020 and ended in December 2020. The questionnaire had a demographic section and sections for asthma symptoms, compliance, inhaler techniques, and comorbidities. Case series of N=38 severe asthma patients showed that majority had partially controlled or uncontrolled asthma (66%). Some 42% had intermediate/high risk for obstructive sleep apnea (OSA) based on the common screening tool "STOPBANG" score. Some 47% of our patients had uncontrolled gastro-esophageal reflux disease (GERD), and majority (80%) had uncontrolled allergic rhinitis. Only half of them demonstrated appropriate inhaler technique. And none of them was found exposed to asthma triggers at the time of interview. Significant number of severe uncontrolled asthmatic patients were shown to be associated with at least one comorbid condition that might be interfering with patients' improvement in asthmatic symptoms. By taking appropriate measures toward management and controlling of those comorbid conditions and also educating patients about technique to use inhalers might show notable improvement in asthmatic patients' condition.

HUBUNGAN TINGKAT PENGETAHUAN IBU HAMIL TENTANG VAKSINASI CORONA VIRUS DISEASE 2019 DENGAN KESEDIAAN MELAKUKAN VAKSINASI CORONA VIRUS DISEASE 2019

Coronavirus Disease (Covid-19) is an infection that occurs in the respiratory tract due to the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) virus. Protective behavior with vaccination measures is an effort to protect against the spread of Covid-19 which can be done, especially in at-risk groups such as pregnant women. Lack of knowledge, the spread of negative opinions and the high feeling of worry about the impact of Covid-19 vaccination have resulted in a low level of willingness in pregnant women to be vaccinated compared to other populations. This study aims to determine the correlation between the level of knowledge of pregnant women regarding the Covid-19 vaccination and their willingness to carry out the vaccination. This research is included in the type of correlational quantitative research with a cross sectional design. The sample used in this study was 70 pregnant women who were selected using purposive sampling techniques. The sample inclusion criteria are pregnant women who have not been vaccinated against Covid-19 and the exclusion criteria are pregnant women with uncontrolled comorbidities and have a high risk (anemia, hyperemesis gravidarum, and preeclampsia). Data analysis using univariate and bivariate tests with chi-square statistical tests. The results of this study show that the majority of respondents have a high level of knowledge (51,4%) and some are willing to carry out the Covid-19 vaccination (75,7%). Based on the results of the chi-square test, it is known that there is a correlation between the level of knowledge of pregnant women regarding the Covid-19 vaccination and their willingness to be given the Covid-19 vaccine (p-value = 0.000). The conclusion obtained is that when the knowledge about administering the covid-19 vaccine to pregnant women is high, the willingness will also increase to carry out the vaccination.

Alliance A031902 (CASPAR): A randomized phase (ph) 3 trial of enzalutamide with rucaparib/placebo in first-line metastatic castration-resistant prostate cancer (mCRPC).

TPS277 Background: Despite a growing number of treatment options for first-line mCRPC, approximately 40% of patients (pts) have radiographic progression within the first year. Co-inhibition of androgen receptor (AR) and PARP is a promising therapeutic strategy that leverages synthetic lethality induced by impaired double-strand DNA repair. Two phase III studies have shown improvement in radiographic progression-free survival (rPFS) in HRR-mutant pts with abiraterone + PARPi combinations vs abiraterone alone. However, the results in HRR-wild type pts are conflicting, with only one of the studies demonstrating a benefit with the abiraterone + PARPi combination. ENZ + RUCA has shown an acceptable safety profile &amp; no significant drug-drug interactions (S-DDI) in a phase 1b trial. This allows its evaluation in mCRPC. Methods: CASPAR (A031902) is a phase 3 study in which 984 pts will be randomized on a 1:1 basis to ENZ plus RUCA/PBO. HRR gene aberration is not required for enrollment. All pts will undergo next-generation targeted exome sequencing from archival tumor tissue (new biopsy only required if no archival tissue is available). Treatment will be continued until disease progression and crossover is not allowed. Key eligibility criteria are age ≥ 18 years, ECOG PS 0-2, biopsy-proven prostate adenocarcinoma, progressive (PSA or radiographic) disease per Prostate Cancer Working Group 3 guidelines, measurable or non-measurable disease per RECIST 1.1, no prior treatment for mCRPC (prior docetaxel, abiraterone, darolutamide, or apalutamide in non-mCRPC setting is allowed), no significant uncontrolled comorbidity, and no medications with S-DDI with ENZ/RUCA. Hierarchical co-primary endpoints are overall survival (OS) and rPFS. The OS analysis will be undertaken as a primary endpoint if the rPFS endpoint is met. For a one-sided logrank test with a type 1 error rate equal to 0.025, the study has 90% power to detect a hazard ratio (HR) of 0.71 in rPFS (median rPFS of 15 and 21 months in control and combination arms, respectively), and 80% power to detect an HR of 0.80 in OS (median OS of 32 and 40 months, respectively). Key secondary endpoints are rPFS and OS in pts with vs without pathogenic BRCA1, BRCA2, or PALB2 alterations; and differences in adverse events and quality of life (QOL) outcomes between the treatment arms. QOL assessments include Functional Assessment of Cancer Therapy–Prostate (FACT-P), Brief Pain Inventory Short Form (BPI-SF), and EQ-5D-5L. A key correlative endpoint is the sensitivity of ctDNA testing for HRR gene alterations. Enrollment began in July 2021 &amp; the study is available for participation to all US-NCTN sites. Clinical trial information: NCT04455750 .

Abstract A077: Are anthropometric measures associated with prostate cancer in Nigerian men?

Abstract Purpose/Objective(s): Despite prostate cancer (PCa) being a public health problem globally, much remains unknown of its etiology. Though obesity is a probable risk factor for prostate cancer measurable by anthropometric indices, its impact on PCa development with other risk factors has not been explored among Nigerian men. This study was designed to test the hypothesis that anthropometric indices are higher in prostate cancer patients compared to age-matched healthy controls. Materials/Methods: The study was a case-control study conducted in four tertiary hospitals in Nigeria. The cases were newly diagnosed prostate cancer patients, while the controls were age-matched healthy men confirmed to be cancer-free with normal PSA. Patients with weight loss (self-reported) in the past month, ECOG ≥3, and uncontrolled comorbidities (diabetes and hypertension) were not eligible. Socio-demographics (age, marital status, ethnicity, the highest level of education, occupation, and employment status) and clinical history (high-fat diet, physical activity, cigarette smoking, alcohol, family history of prostate cancer, and Gleason score [for cases]) using an interviewer-administered questionnaire, and anthropometric measures (weight, height, body mass index, waist circumference, hip circumference, and waist-hip ratio [WHR]) physically measured were obtained from all participants. The socio-demographics and the clinical history were compared between cases and controls using a chi-square test. The comparison of the anthropometric measures between the groups and their correlation with Gleason's score were determined using a t-test. Results: Seventy-three prostate cancer cases (PCa) and seventy-three age-matched healthy controls (Co) were recruited for the study. The mean age was 64.20 years (SD = 6.184). Only the mean WHR was of significant difference between the PCa and the Co (0.98 [SD=0.07] PCa: 0.93 [SD=0.06] Co, p=&amp;lt;0.0001). Forty-three (58.9%) of the cases had high-grade diseases (Gleason Score 8-10). No significant association was found between anthropometric indices and the disease grade. PCa and Co groups differ by regular exercise (32PCa [43.8%]:47Co [64.4%]; p=0.013), family history of PCa (14PCa [19.2%]:2Co [2.7%]; p=0.001), tobacco smoking (28PCa [38.4%]:15Co [20.5%]; p=0.018), and alcohol consumption (57PCa [78.1%]:43Co [58.9%]; p=0.013). Conclusion: Patients with PCa had higher WHR and were more likely physically inactive, have a family history of prostate cancer, smoke tobacco, or drink alcohol. PCa in Nigerian men are predominantly high-grade, and there was no association between Gleason grade and anthropometric indices. Citation Format: Kehinde O. Adeyinka. Are anthropometric measures associated with prostate cancer in Nigerian men? [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A077.

Comparative Effectiveness of Team-Based Care With and Without a Clinical Decision Support System for Diabetes Management : A Cluster Randomized Trial.

Uncontrolled hyperglycemia, hypercholesterolemia, and hypertension are common in persons with diabetes. To compare the effectiveness of team-based care with and without a clinical decision support system (CDSS) in controlling glycemia, lipids, and blood pressure (BP) among patients with type 2 diabetes. Cluster randomized trial. (ClinicalTrials.gov: NCT02835287). 38 community health centers in Xiamen, China. 11132 persons aged 50 years or older with uncontrolled diabetes and comorbid conditions, 5475 receiving team-based care with a CDSS and 5657 receiving team-based care alone. Team-based care was delivered by primary care physicians, health coaches, and diabetes specialists in all centers. In addition, a computerized CDSS, which generated individualized treatment recommendations based on clinical guidelines, was implemented in 19 centers delivering team-based care with a CDSS. Coprimary outcomes were mean reductions in hemoglobin A1c (HbA1c) level, low-density lipoprotein cholesterol (LDL-C) level, and systolic BP over 18 months and the proportion of participants with all 3 risk factors controlled at 18 months. During the 18-month intervention, HbA1c levels, LDL-C levels, and systolic BP significantly decreased by -0.9 percentage point (95% CI, -0.9 to -0.8 percentage point), -0.49 mmol/L (CI, -0.53 to -0.45 mmol/L) (-19.0 mg/dL [CI, -20.4 to -17.5 mg/dL]), and -9.1 mm Hg (CI, -9.9 to -8.3 mm Hg), respectively, in team-based care with a CDSS and by -0.6 percentage point (CI, -0.7 to -0.5 percentage point), -0.32 mmol/L (CI, -0.35 to -0.29 mmol/L) (-12.5 mg/dL [CI, -13.6 to -11.3 mg/dL]), and -7.5 mm Hg (CI, -8.4 to -6.6 mm Hg), respectively, in team-based care alone. Net differences were -0.2 percentage point (CI, -0.3 to -0.1 percentage point) for HbA1c level, -0.17 mmol/L (CI, -0.21 to -0.12 mmol/L) (-6.5 mg/dL [CI, -8.3 to -4.6 mg/dL]) for LDL-C level, and -1.5 mm Hg (CI, -2.8 to -0.3 mm Hg) for systolic BP. The proportion of patients with controlled HbA1c, LDL-C, and systolic BP was 16.9% (CI, 15.7% to 18.2%) in team-based care with a CDSS and 13.0% (CI, 11.7% to 14.3%) in team-based care alone. There was no usual care control, and clinical outcome assessors were unblinded; the analysis did not account for multiple comparisons. Compared with team-based care alone, team-based care with a CDSS significantly reduced cardiovascular risk factors in patients with diabetes, but the effect was modest. Xiamen Municipal Health Commission.