Nonsignificant Research Articles

Comparative Evaluation of Pain Perception with Conventional and Septoject XL Needle in 6-8-year-old Children: A Randomized Controlled Trial.

To evaluate and compare pain perception with Septoject XL and conventional needles in 6-8 years old children. In this split-mouth randomized controlled trial, a single-blinded study, 24 children (6-8 years) were assigned at random to receive the local anesthetic (LA) injection for treatment needs either with Septoject XL or conventional needle for the first visit in one of the quadrants, while during the second visit in a different quadrant with the other one. Children's pain levels were assessed during each visit using an objective sound eye motor (SEM) scale and subjective Wong-Baker faces rating scale (FRS). The mean objective score rating using SEM for the conventional needle (3.8 ± 2.35) and Septoject XL needle (3.3 ± 2.01) was not found to be statistically significant among the two study groups Septoject XL or conventional needle (Z score-0.996, p = 0.3). Using the Wilcoxon test, the mean subjective rating score was not found to be statistically significant among the two study groups [Z score = 0.636 and p-value = 0.524, nonsignificant (NS)]. In the gender-wise comparison of male (n =15), (6.8667 ± 91548) and female (n = 9), (6.8889 ± 1.05409), NS mean ages of male and female study participants was observed (p = 0.873). Statistically, NS difference was observed in the pain perception while administration of LA using Septoject XL or conventional needle in 6-8-year-old children. This research can be useful in the selection of the gauge of the needle to be used while planning the treatment for different behavior groups.

The Eff ect of Testosterone Gel for Patients with Poor Ovarian Response Prior to IVF Cycles: Is It really Eff ective?

Background: Classically, poor women respond with old maternal age and little ovarian standby. Though, some females unpredictably have little reply to measured ovarian stimulation. Aim of the Study: To evaluate the eff ectiveness of transdermal testosterone gel (TTG) before controlled ovarian stimulation (COS) in poor responders undergoing intracytoplasmic sperm injection (ICSI). Methods: An interventional prospective randomized control trial that included 60 females who were defi nite as unfortunate responders undergoing an intracytoplasmic sperm injection (ICSI) procedure. The population was divided into two groups. Approximately 30 patients received 10 mg TTG that was applied daily for 21 days in the cycle preceding COS for ICSI Transdermal testosterone gel (TTG) pretreatment group, while the other 30 patients are the control group. All patients were assessed for their AFC again and to begin in-vitro futilization (IVF) treatment with the beginning of the menstrual cycle. Serum testosterone was measured again in the study group. The primary outcome is the number of retrieved oocytes while the secondary outcome is the number and quality of embryos transferred, chemical gestation rate. Results: No important diff erences in sociodemographic features between both groups compared. Also there was an increase in total number of oocytes in the study group but again, this diff erence was statically non-signifi cant. Although the total dose of gonadotrophin (GT) and the duration of stimulation days were less in study group but this was statically non-signifi cant. No diff erences experiential regarding number and grading of embryos, chemical pregnancy rate nor clinical pregnancy rate. Conclusion: Pretreatment of transdermal testosterone at a dose of 10 mg/day for 21 days not upsurge the number of oocyte retrieved nor the number of embryos or pregnancy rate to a signifi cant level in poor responders undergoing ICSI

A Comparative Assessment of Adoption Behaviour of Tribal and Non-tribal Rice growers in Assam

Rice (Oryza sativa L.) is the principal diet of majority of the population. A large portion of rural community of Assam depends on rice farming for their livelihood. Baksa district of Assam has enormous potentiality in rice production. Although the district is being blessed with favourable agro climatic conditions, yet the advantages could not be harnessed in terms of yield. To meet the growing demands of rice, one best possible route is to adopt improved technology in HYV rice. As a good number of tribal farmers are prevalent in the district, therefore the study attempts to explore the adoption behaviour of tribal and nontribal rice farmers along with the associated factors in the adoption process. A total of 160 respondents (104 non-tribal and 56 tribal farmers) were selected as the fi nal sample by proportionate random sampling method. The fi ndings showed that above seventy percent of farmers had overall medium adoption level. However, a total of (73.13%) of non- tribal and only 51.78 per cent tribal farmers exhibited medium level of adoption. The “t value” was found to be non-signifi cant. Overall age, family size, operational land holding. training exposure, social participation, economic motivation and scientifi c orientation of the farmers had a positive and signifi cant association with the extent of adoption in case of HYVs. Further, these signifi cant and nearly signifi cant variables were taken for Tobit analysis to see the infl uence of these factors on extent of adoption of HYVs, where only training exposure showed a positive and signifi cant contribution towards adoption of HYVs.

Entrepreneurial Behavior of Farmers towards Cultivation of Medicinal and Aromatic Plants in the Ujjain District of Madhya Pradesh

The present study was carried out in Ujjain district of Madhya Pradesh with the objectives of to know awareness level, identify factors which encourage farmers towards cultivation of medicinal and aromatic plants and constraints in cultivation, and entrepreneurship in medicinal and aromatic plants. Multistage sampling was adopted for the study to collect data from the farmers. Total 50 farmers were selected randomly for the present study. Findings of the study revealed that majority of the farmers unaware about latest technology and cultivation of the medicinal and aromatic plants in study area. All the factors were found to be signifi cant more profi table than other crops, good marketing opportunity, training and subsidy provided by government, easy availability of planting material, adequate knowledge except (p-value 0.60) good demand and (p-value 0.12) low cost in cultivation of the medicinal and aromatic plants were found to be non-signifi cant. The farmers’ friends or fellow farmers were the major source of information to farmers about cultivation of medicinal and aromatic plants in the study area. Lack of availability of ready market for selling of medicinal and aromatic plants followed by lack of fi nance and credit facility were the major constraints faced by the farmers in the study area.

Long-term antiretroviral therapy mitigates mortality and morbidity independent of HIV tropism: 18 years follow-up in a women's cohort.

CXCR4 (X4)-tropic HIV-1 was found previously to herald CD4 + cell depletion and disease progression in individuals who were antiretroviral-naive or took combination antiretroviral therapy (cART) for less than 5 years. We updated this finding by investigating whether the deleterious effect of X4-tropic strains is mitigated by long-term cART. We examined morbidity and mortality in relation to HIV-1 tropism and cART in 529 participants followed up to 18 years in the Women's Interagency HIV Study; 91% were women of color. Plasma-derived HIV-1 tropism was determined genotypically. We categorized participants according to the number of visits reported on cART after initiation. Group 1: three or less visits, 74% of these participants reporting no cART; group 2: at least four visits and less than 70% of visits on cART; group 3: at least 70% of visits on cART. AIDS mortality rates for participants in each group with X4 virus compared with those with R5 virus exclusively were, respectively: 62 vs. 40% ( P = 0.0088); 23% vs. 22% [nonsignificant (NS)]; 7% vs. 14% (NS). Kaplan-Meier curves showed accelerated progression to AIDS death or AIDS-defining illness in participants with three or less cART visits and X4 viruses ( P = 0.0028) but no difference in progression rates stratified by tropism in other groups. Logistic regression found that HIV-1 suppression for at least 10 semiannual visits (≥5 years total) mitigated X4 tropism's deleterious effect on mortality, controlling for maximal viral load, and CD4 + nadir. Long-term cART markedly mitigated the deleterious effect of X4 viruses on AIDS morbidity and mortality. Mitigation was correlated with duration of viral suppression, supporting HIV-1 suppression as a crucial goal.

Influenza Vaccination in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.

The safety and efficacy of influenza vaccination is not well-studied in cancer patients receiving immune checkpoint inhibitors (ICIs). A systematic review and meta-analysis was performed aiming to summarize available data regarding influenza vaccination in ICI-treated cancer patients. Peer-reviewed studies or nonpeer-reviewed conference abstracts including ICI-treated cancer patients who received at least 1 dose of influenza vaccine were deemed eligible. A systematic search in PubMed/EMBASE was performed until October 26, 2021. Endpoints of interest included mortality as the primary outcome and secondary safety outcomes such as the incidence of immune-related adverse events (irAEs). Twenty-five studies were included in the systematic review, among which 9 were included in the meta-analysis. Meta-analysis of 3 studies (n=589, weighted age 64 y, men 61%, influenza vaccinated 32%) showed pooled odds ratio for death in influenza vaccinated versus nonvaccinated patients at 1.25 [(95% confidence intervals (CI): 0.81-1.92), P=non significant (NS)]. Meta-analysis of 6 studies studies (n=1285, weighted age 60 y, men 59%, influenza vaccinated 48%) showed pooled odds ratio for any irAEs in influenza vaccinated versus nonvaccinated patients at 0.82 [95% CI: 0.63-1.08, P=NS]. Similar results were observed in sensitivity analyses for serious irAEs, as well as when only peer-reviewed studies were included. Influenza vaccination appears to be a safe and reasonable intervention for cancer patients receiving ICIs. Most data are derived from retrospective observational studies. Randomized studies are needed to provide high-quality evidence.

Study of Cardiovascular Parameters and Heart Rate Variability (Frequency Domain Analysis) In 1St Trimester of Normal Pregnant Women and Pregnant Women with Risk Factors for Pih in Western Rajasthan

Background: The role of sympathovagal imbalance (SVI) and CV risk in pregnancy-induced hypertension(PIH) has been reported, and their association during early trimesters of gestation in PIH has not beenstudied. Therefore, in the present study, we have investigated the maternal cardiovascular parameters andfrequency domain indices of Heart rate variability (HRV) between normal pregnant women and women withrisk factors for PIH in their 1st trimester of gestation.Methods: Two hundred twenty subjects each (220 of normotensive pregnant women i.e., control group and220 of pregnant women with risk factor for PIH i.e., study group) of 1st trimester of gestation were recruitedfrom the obstetrics & gynecology department of Umaid hospital, associated with Dr. S. N. Medical College,Jodhpur, Rajasthan. Physical examination was done and anthropometric measurement like height & weightwere taken. The collected data was statistically analyzed using HRV analysis software.Results: Significant difference in body mass index was observed between the two groups. Systolic bloodpressure, Diastolic blood pressure, Pulse pressure, Rate pressure product and Mean arterial pressure of studygroup was significantly higher than control group. Values of LF and LF/HF ratio components of frequencydomain analysis of HRV were significantly increased but HF component is non significantly decrease in 1sttrimester of the pregnant women with risk factor for PIH than normal pregnant women.Conclusion: The present study indicates that the cardiovascular parameters in 1st trimester of pregnantwomen with risk factor for PIH were increased highly significantly than the normal pregnant women. Thehighly significant (HS) (p<0.000) increase in the LF (nu) & LF/HF ratio and non significant (NS) (p<0.552)decrease in HF (nu) of pregnant women with risk factors for PIH was observed than normal pregnant womenthis indicate that sympathetic tone was increased in 1st trimester of pregnant women with risk factor for PIH.Vagal withdrawal and sympathetic exaggeration may be the possible cause of PIH in pregnant women withits risk factors.

Correlative Biological Studies Related to the Response, Peak and Persistence of ARI0002h, an Academic BCMA-Directed CAR-T Cell, with Fractionated Initial Infusion and Booster Dose for Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM)

Correlative Biological Studies Related to the Response, Peak and Persistence of ARI0002h, an Academic BCMA-Directed CAR-T Cell, with Fractionated Initial Infusion and Booster Dose for Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM)

Study of Cardiovascular Parameters and Heart Rate Variability (Frequency Domain Analysis) in 1St Trimester of Normal Pregnant Women and Pregnant Women with Risk Factors for PIH in Western Rajasthan

Background: The role of sympathovagal imbalance (SVI) and CV risk in pregnancy-inducedhypertension (PIH) has been reported, and their association during early trimesters of gestation in PIHhas not been studied. Therefore, in the present study, we have investigated the maternal cardiovascularparameters and frequency domain indices of Heart rate variability (HRV) between normal pregnantwomen and women with risk factors for PIH in their 1st trimester of gestation.Methods: Two hundred twenty subjects each (220 of normotensive pregnant women i.e., control groupand 220 of pregnant women with risk factor for PIH i.e., study group) of 1st trimester of gestation wererecruited from the obstetrics & gynecology department of Umaid hospital, associated with Dr. S. N.Medical College, Jodhpur, Rajasthan. Physical examination was done and anthropometric measurementlike height & weight were taken. The collected data was statistically analyzed using HRV analysissoftware.Results: Significant difference in body mass index was observed between the two groups. Systolic bloodpressure, Diastolic blood pressure, Pulse pressure, Rate pressure product and Mean arterial pressure ofstudy group was significantly higher than control group. Values of LF and LF/HF ratio components offrequency domain analysis of HRV were significantly increased but HF component is non significantlydecrease in 1st trimester of the pregnant women with risk factor for PIH than normal pregnant women.Conclusion: The present study indicates that the cardiovascular parameters in 1st trimester of pregnantwomen with risk factor for PIH were increased highly significantly than the normal pregnant women.The highly significant (HS) (p<0.000) increase in the LF (nu) & LF/HF ratio and non significant (NS)(p<0.552) decrease in HF (nu) of pregnant women with risk factors for PIH was observed than normalpregnant women this indicate that sympathetic tone was increased in 1st trimester of pregnant womenwith risk factor for PIH. Vagal withdrawal and sympathetic exaggeration may be the possible cause ofPIH in pregnant women with its risk factors.

Risk Factors for Early and Late Onset Preeclampsia in Reunion Island: Multivariate Analysis of Singleton and Twin Pregnancies. A 20-Year Population-Based Cohort of 2120 Preeclampsia Cases

Objectives: To develop a multivariate model for risk factors specific to early onset preeclampsia (EOP) and late onset preeclampsia (LOP) in our entire population (singleton and twin pregnancies). Material and methods: 20 year-observational population-based historical cohort study (2001–2020). All consecutive births delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion’s maternity ward. A standardized validated epidemiological perinatal database was used. Results: During the 20-year period, there were 81,834 pregnancies and 83,497 infants born, 1232 dichorionic and 350 monochorionic twin pregnancies. There were 2120 cases of preeclampsia, of which 2001 were preeclamptic singleton pregnancies and 119 twin pregnancies (incidence 7.5% in twin pregnancies vs. 2.5% singletons, OR 3.0, p < 0.001). Independent risk factors for EOP and LOP in a multivariate model (controlling for the two major confounders: maternal ages—both risks for EOP and LOP, and maternal pre-pregnancy BMI—specific risk factor for LOP) were: history of preeclampsia (adjusted OR (aOR) 11.7 for EOP, 7.8 for LOP, p < 0.0001), chronic hypertension (aOR 7.3 for EOP, 3.9 for LOP, p < 0.0001), history of perinatal death (aOR 2.2 for EOP, p < 0.0001 and 1.48 for LOP, p = 0.007), primipaternity (aOR 3.0 for EOP and 3.6 for LOP, p = 0.001), dizygotic twin pregnancies (aOR 3.7 for EOP, p < 0.0001 and 2.1 for LOP, p = 0.003), monozygotic twin pregnancies (aOR 3.98 for EOP, p = 0.003 and non-significant (NS) for LOP), ovulation induction (aOR 5.6 for EOP, p = 0.004 and NS for LOP), and in vitro fertilization (aOR 2.8 for EOP, p = 0.05 and NS for LOP). Specific to LOP and NS for EOP: renal diseases (aOR for LOP 2.9, p = 0.007) and gestational diabetes mellitus (aOR 1.2, p = 0.04). Conclusions: Maternal ages over 35 years, chronic hypertension, history of preeclampsia, ovulation induction, in vitro fertilizations, history of perinatal deaths and twin pregnancy (in our experience, especially mono zygotic twin pregnancies) are significant risk factors for EOP. New paternity is an independent factor for both EOP and LOP.

Calcium signaling induces a partial EMT.

Epithelial plasticity, or epithelial-to-mesenchymal transition (EMT), is a well-recognized form of cellular plasticity, which endows tumor cells with invasive properties and alters their sensitivity to various agents, thus representing a major challenge to cancer therapy. It is increasingly accepted that carcinoma cells exist along a continuum of hybrid epithelial-mesenchymal (E-M) states and that cells exhibiting such partial EMT (P-EMT) states have greater metastatic competence than those characterized by either extreme (E or M). We described recently a P-EMT program operating invivo by which carcinoma cells lose their epithelial state through post-translational programs. Here, we investigate the underlying mechanisms and report that prolonged calcium signaling induces a P-EMT characterized by the internalization of membrane-associated E-cadherin (ECAD) and other epithelial proteins as well as an increase in cellular migration and invasion. Signaling through Gαq-associated G-protein-coupled receptors (GPCRs) recapitulates these effects, which operate through the downstream activation of calmodulin-Camk2b signaling. These results implicate calcium signaling as a trigger for the acquisition of hybrid/partial epithelial-mesenchymal states in carcinoma cells.

Excess body weight association with various cancer: A United States population-based study 2021.

e18558 Background: Excess body weight (EW) is a rising healthcare issue affecting over two-thirds of the United States (US) population, and it is a risk factor for various cancer. Methods: We used Explorys, IBM, a US database that includes ̃ 73 million patients. We evaluated non-gastrointestinal cancers prevalence based on age (18-64 and ≥ 65 years; for female cancers 18-49 and ≥ 50 years), race; Caucasians (C) and African-Americans (AA), and weight; normal weight (N) with BMI 18.5- 24.9 kg/m2 and EW for BMI ≥ 25 kg/m2. Compared to NW, the odds ratio (OR) and 95% confidence interval (CI) for multiple cancer rates in the EW group were calculated. p-value of <0.001 was considered significant (S) and > 0.001 as non-significant (NS). Results: A population of 26.9 million was included. C 85.6%, AA 14.4%. See table. Conclusions: A strong association between EW and urological cancers (prostate, bladder, renal), non-Hodgkin's lymphoma, multiple myelomas (MM), breast cancer, endometrial cancer, ovarian cancer in C 18-64 yrs but not in C ≥ 65 yrs with the exception for kidney cancer. A similar finding in AA 18-64 yrs for cancers of prostate, renal, breast, uterus, and MM compared to AA ≥ 65 yrs. EW is possibly more oncogenic earlier in life, especially in C.[Table: see text]

The Radiographic Effect of Bone Marrow Aspirate Concentrate on Bone Maturation During Mandibular Distraction Osteogenesis.

This study aims to evaluate the effect of bone marrow aspirate concentrate (BMAC) during distraction on the consolidation period. The study had 2 groups each had 6 patients. In the control, the distraction had no enhancement; while, the study group was enhanced by BMAC. The bone quality and quantity were assessed using cone beam computed tomography (CBCT). The assessment of bone density showed non-significant (NS) (P = 0.06) increase in bone density in the study group (M = 293 ± 100 HU) compared to the control group (M = 176 ± 94 HU). The Assessment of bone volume showed a NS (P = 0.15) increase in bone volume in Study group with average bone volume/total volume (M = 49.47% ± 4.5%) compared to Control group (M = 43.9% ± 7.5%). Further examination is recommended to evaluate the effect of BMAC on the distracted bone. The addition of BMAC made a non-significant improvement in bone quantity and quality.

Laser Needling® and Natural origin, Highly Purifi ed Polynucleotides (PN-HPT™) in Knee Osteoarthrosis: Benefi ts in Physiatry and Sports Medicine

Background and Objectives: The purpose of the paper is to illustrate the real life clinical outcomes of a retrospective cohort of knee Osteoarthritis (OA) patients treated with a novel laser disease management program; at the same time, to defi ne the most effective operative procedure. The new laser technique mimics the in-vitro benefi ts of Low-Level Laser Therapies (LLLT). The study compared the 3month effi cacy and 6-month persistence of clinical and functional benefi ts after application of laser energy either externally with a standard High Power Laser Therapy (HPLT) laser device (AG1 device, FP3 version), or intra-articularly with the patented, low-energy AG8 intra articular fi ber device (ultrasound-guided, same wavelengths, no handpiece). This innovative laser device reduces to one hundredth the applied energy density. The pain suppressing effi cacy of the LLLT-like laser FP3 procedure is intended to act synergically with the strong biorestructuring and pain suppressing effi cacy of natural origin polynucleotides (PN-HPT™ or Highly Purifi ed Technology™) injected before the laser session. PN-HPT™ are widely used in knee OA management for their persistent viscosupplementation properties overlapping those of high molecular weight hyaluronic acid. Trial design: retrospective comparison of:  Short term 3 month effi cacy outcomes on pain and disability  6-month persistence of clinical improvements in two cohorts of patients with severe knee osteoarthritis. The active cohort knee OA patients (105 agonistic or recreative practitioners with persistent knee pain and disability resistant to conventional medical or physical therapies) were treated with an innovative intra articular low-energy AG8 physical therapy protocol (ambulatory “AG8 Protocol 3” combined with a preliminary PN-HPT™ knee injection); the control-cohort patients (109 patients with knee disease of similar severity) were treated with a standard, multi frequency HPLT ambulatory treatment protocol (FP3 device). Outcome parameters: Western Ontario and McMaster Universities (WOMAC) assessments at baseline (T0) and after 2 weeks (T2) and 3 months (T3). Secondary parameters: Nociceptive and neuropathic pain; assessment: standard 10 cm Visual Analogue Scale (VAS) immediately before and at the end of each treatment session. Results: Treatment with the AG8 protocol 3 / PN-HPT™ intra articular combination was associated with strongly signifi cant short term (2 weeks) and medium-term (3 months) benefi ts vs. controls treated with a conventional FP3 extra-articular treatment protocol both for the WOMAC Total Score and WOMAC Pain and Function subscores. Benefi ts for the WOMAC Stiffness subscore were borderline non-signifi cant. The subgroup analysis showed that the 2A (Grade-2 KL primary OA) and 2B (Grade-2 KL secondary (post-surgical) OA) mainly contributed to overall benefi ts. Conclusion: The study showed the intra-articular Laser Needling® technique (ultrasound-guided AG8 laser device, Protocol 3 plus infi ltration of a facilitating agent such as intra-articular PN-HPT™ gel) to be more effective on knee OA pain than the traditional extra-articular FP3 laser technique, with special reference to pain associated with primary OA.

Comparison of LUR, satellite LUR and Bayesian NO2 exposure measures on effect estimates of respiratory and allergic disease in a children’s cohort

Background/Aim Effect estimates in air pollution epidemiology studies can vary depending on the exposure method used, due to error. We aimed to compare estimates for respiratory outcomes in a childhood cohort using three exposure methods. Methods We used: an intra-city land use regression (LUR) model; a national satellite-LUR (Sat-LUR) model; and a regional Bayesian blended model (BME); to estimate annual mean NO2, a marker of traffic pollution, for 398 children (8 years) from the Childhood Asthma Prevention Study, Sydney. We collected questionnaire information on current asthma, wheeze, eczema, and rhinitis, and measured spirometry (FEV1, FVC, airway hyper-responsiveness (AHR)), exhaled nitric oxide (eNO), and atopy. We used logistic and linear regression to analyse binary and continuous variables respectively. Adjusted models included covariates chosen using directed acyclic graphs: sex; father’s education; gas cooking; and environmental tobacco smoke. Results The annual NO2 means from LUR, Sat-LUR and BME models were 7.64 (SD 1.82), 8.77 (1.96) and 8.37 (1.81) ppb respectively. We generally found similar and non-significant (NS) effect estimates for most health outcomes across the three exposure methods after adjustment, with a few variations. We found significantly increased OR for any atopy (1.30 (1.02, 1.68)) and house dust mite atopy (1.35 (1.05, 1.74)) for LUR, and increased but NS effects for Sat-LUR and BME. Conversely, ORs were higher for current asthma for BME 1.31 (0.91, 1.69) than for Sat-LUR 1.24 (0.91, 1.68) or LUR 1.08 (0.82, 1.42) (all NS). Estimates for AHR were similarly increased with ORs varying from 24% (LUR) to 27% (BME), although NS. Conclusions Use of the three exposure measures resulted in similar effect estimates, albeit with subtle variations, illustrating the importance of exposure derivation. It is unclear which measure is most accurate and choice will depend on geography of models and cohorts and confidence in model inputs.

A Single Institution Review Of Efficacy Of Neoadjuvant Chemoradiation With Gemcitabine/Abraxane Compared to FOLFIRINOX in Pancreatic Ductal Adenocarcinoma

FOLFIRINOX has improved OS in patients with metastatic pancreatic ductal adenocarcinoma (PDA) and as adjuvant therapy for resected PDA. No randomized data exists to support neoadjuvant chemoradiation (NA CRT) FOLFIRINOX over gemcitabine/abraxane (GA) although overall survival (OS), disease free survival (DFS), and R0 resection rates appear higher than historical data. A single institution retrospective review of all PDA patients from 2012-2020 who received NA CRT with gemcitabine/abraxane (GA) or FOLFIRINOX including those staged as borderline resectable (BR) or unresectable (UR) disease by the institutional tumor board at diagnosis. Information on demographics, cancer diagnosis, treatment, and outcomes were collected. Survival rates were determined by the Kaplan Meier method. At a median follow-up of 13.08 months, 51 PDA patients received NA CRT with GA (62%, n = 32) or FOLFIRINOX (37%, n = 19). The majority had BR disease (69%, n = 35/51), 20% (n = 10/51) had unresectable disease at diagnosis, 8% (n = 4/51) had resectable disease at diagnosis but were recommended NA CRT, and 4% (n = 2) had metastatic liver disease at diagnosis. Median age was higher in the GA group (66 years, range 46-82) compared to FOLFIRINOX (62 years, range 37-80). The FOLFIRINOX group had better performance status with 74% with ECOG 0-1 (n = 14/19) compared to GA with 47% (n = 15/32). Pre-treatment CA 19-9 was available for 42/51 pts with a median CA 19-9 of 188 (range 4-8736, n = 25/32) in GA vs 22 (range <1-2106, n = 17/19) in FOLFIRINOX, but this difference was non-significant (NS). The difference in median GTV was NS with 22.6 cm3 (range 3.2-59.2) in GA compared to 21.1 cm3 (range 3.2-90.7) in FOLFIRINOX and PTV dose coverage was 100% for all patients. All patients received pancreas SBRT with 3300 cGy/5 fractions. Radiographic progression 1 month after NA CRT was seen in 38% of the GA group (n = 12/32) compared to 21% with FOLFIRINOX (n = 4/19). Of note, 2 patients in the FOLFIRINOX group with liver metastases at diagnosis had complete regression of their lesions after starting chemotherapy. In non-metastatic patients, surgery was offered to 47% (n = 15/32) in GA compared to 26% (n = 5/19, 1 died prior to surgery) in FOLFIRINOX. Of those who had surgery, 73% (n = 11/15) had an R0 resection after NA GA with a 9% PCR (n = 1/11) compared to an R0 resection of 75% with FOLFIRINOX (n = 3/4, 1 had unresectable disease at surgery) and a pCR of 33% (1/3). Interestingly, there was 1 FOLFIRINOX patient with initially unresectable disease that proceeded to surgery with an R0 resection. There was no difference in OS or DFS between neoadjuvant GA (MS 20.3 months, median DFS 34.7) compared to FOLFIRINOX (MS 18 months, median DFS 35.4) in the entire cohort or in BR patients. In our institutional experience, we find that neoadjuvant FOLFIRINOX and gemcitabine/abraxane have similar treatment outcomes. FOLFIRINOX converted one unresectable patient to an R0 resection and caused regression of liver metastases in 2 patients.

Teaching clinicians practical genomic medicine: 7 years’ experience in a tertiary care center

PurposeIncreased implementation of complex genetic technologies in clinical practice emphasizes the urgency of genomic literacy and proficiency for medical professionals. We evaluated our genomic education model. MethodsWe assessed the 5-day, extended format program, encompassing lectures, videos, interactive tests, practice cases, and clinical exercises. Pre- and post questionnaires assessed knowledge change, using t-tests to compare groups. Satisfaction on program completion and after 3 years were evaluated. Implementation in other centers determined acceptability. ResultsDuring 2012–2018, 774 clinicians from multiple disciplines and career stages attended 35 programs; 334 (43%) attended the 5-day extended format. Evaluations showed significant improvement of genomic literacy (mean 15.05/100 points, p<0.001). Residents initially had higher scores than specialists (pre: 66.3±17.3 vs. 58.7±16.6, respectively, p=0.002); both significantly improved, with specialists “catching up” (post: 79.1±17.2 vs. 75.7±15.9, nonsignificant (NS)); there was a similar trend between fellows and subspecialists (pre: 70±18 vs. 59.4±16.4, respectively, p=0.007; post: 78.6±16.4 vs. 73.2±17.7, respectively, NS). Younger specialists (≤10 years residency) had significantly higher pre- and post scores. Absolute improvement in scores did not depend on medical specialties. ConclusionOur program is effective in improving genomics literacy for clinicians, irrespective of career length or expertise, and could be a model for improving skills in practical genomics for all medical professionals.

Development and Implementation of a Community Paramedicine Program in Rural United States.

IntroductionCommunity paramedicine (CP) is an innovative care model focused on medical management for patients suffering from chronic diseases or other conditions that result in over-utilization of healthcare services. Despite their value, CP care models are not widely used in United States healthcare settings. More research is needed to understand the feasibility and effectiveness of implementing CP programs. Our objective was to develop a CP program to better meet the needs of complex, high-utilizer patients in a rural setting.MethodsWe conducted an observational descriptive case series in a community, 25-bed, critical access hospital and primary care clinic in a rural Wisconsin county. Multiple stakeholders from the local health system and associated ambulance service were active participants in program development and implementation. Eligible patients receiving the intervention were identified as complex or high need by a referring physician. Primary outcomes included measures of emergency department, hospital, and clinic utilization. Secondary measures included provider and patient satisfaction.ResultsWe characterized 32 unique patients as high utilizers requiring assistance in medical management. These patients were enrolled into the program and categorized as high utilizers requiring assistance in medical management. The median age was 76 years, and 68.8% were female. After six months, we found a statistically significant decline in patient utilization for primary care (53.3%, p = .006) and ED visits (59.3%, p = .007), but not for hospitalizations (60%, p = .13, non-significant (NS), compared to the six months preceding enrollment. Overall, the total number of healthcare contacts was increased after implementation (623 before vs 790 after, + 167, +26.8%). Implementation of the CP program resulted in increased overall use of local healthcare resources in patients referred by physicians as high utilizers.ConclusionThe implementation of an in-home CP program targeting high users of healthcare resources resulted in a decrease in utilization in the hospital, ED, and primary care settings; however, it was balanced and exceeded by the number of CP visits. CP programs align well with population health strategies and could be better leveraged to fill gaps in care and promote appropriate access to healthcare services. Further study is required to determine whether the shift in type of healthcare access reduces or increases cost.

Abstract P2-11-04: Prognostic contribution of predicted sensitivity to endocrine therapy (SET) prior to neoadjuvant chemotherapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer

Abstract Background: The SET2,3 index combines an accurate measure of transcription related to both estrogen and progesterone receptors (SETER/PR index) with a baseline prognostic index (BPI) derived from c-T Stage, c-N status and molecular subtype by RNA4 (ESR1, PGR, ERBB2, and AURKA). SET2,3 index was translated from a microarray-based signature to a customized hybridization assay that yields highly reproducible results from routine pathology tissue blocks. Methods: The SET2,3 index was calculated from microarray data prepared from baseline biopsies of HR+/HER2- cancers prior to neoadjuvant taxane-anthracycline chemotherapy followed by adjuvant endocrine therapy in: 1) a test set of 307 samples from the MDACC cohort with 8 years median follow-up (Affymetrix U133A microarrays, Symmans et al JAMA 2011), and 2) an independent blinded validation set of 268 high-risk Mammaprint (MP) samples from the I-SPY2 clinical trial with 3.8 years median follow-up (Agilent 44K microarrays, Agendia). The cut-point for high versus low SET2,3 was defined in the MDACC cohort and then tested in the I-SPY2 cohort. Association between the SET2,3 index and distant relapse-free survival (DRFS) was evaluated in each cohort using multivariate Cox regression models. One model adjusted for residual cancer burden (RCB) after neoadjuvant chemotherapy and its interaction with the SET2,3 index, also including treatment arm (experimental vs. control) in the I-SPY 2 trial. Another model adjusted for other prognostic gene expression signatures (GES) for recurrence score (RS), MP, or endopredict (EP) in the MDACC cohort, and actual MP in the I-SPY2 trial. A third model tested the ability of prognostic GES to substitute for RNA4 subtype (part of BPI) or SETER/PR index as components of the SET2,3 index. Results: Predicted sensitivity to endocrine therapy (SET2,3) and response to neoadjuvant chemotherapy (RCB) were independently prognostic, with nonsignificant (NS) interaction term, in multivariate analyses of the MDACC study: SET2,3 HR 0.26 (p=0.016); RCB HR 2.04 (p&amp;lt;0.001); and validated in the I-SPY2 trial: SET2,3 HR 0.27 (p=0.031); RCB HR 1.68 (p=0.008); treatment arm HR 1.03 (NS). Other GES (RS, MP, EP) were prognostic in univariate analyses, but were NS in multivariate models with SET2,3 index. They could each effectively substitute for RNA4 subtype, but not for SETER/PR index, as a component of SET2,3 index. SET2,3 index (HR 0.39, p=0.002) was prognostic independently of MP score (HR 2.82, p=0.299) in multivariate Cox analysis of the I-SPY2 trial. RCB classes of chemotherapy response were strongly prognostic in cancers with low SET2,3 (MDACC p&amp;lt;0.001, I-SPY2 p&amp;lt;0.001) but were NS in cancers with high SET2,3 (frequency: 41% MDACC, 37% I-SPY2). Conclusions: SET2,3 index of endocrine transcriptional activity in a pre-treatment core biopsy added independent significant prognostic information to any baseline prognostic score and response to neoadjuvant chemotherapy. Approximately 40% of clinical or genomic (MP) high-risk HR+/HER2- cancers had high SET2,3 index, and their response to neoadjuvant chemotherapy (RCB class) was not prognostic. This suggests that SET2,3 index might be used to select appropriate candidates for endocrine-based neoadjuvant treatments in clinical trials. Citation Format: Lili Du, Christina Yau, Lamorna Brown-Swigart, Rebekah Gould, Gillian L Hirst, I-SPY2 Consortium, Marieke van der Noordaa, Isabelle Bedrosian, Rachel M Layman, Vicente Valero, Laura van't Veer, Laura Esserman, W. Fraser Symmans. Prognostic contribution of predicted sensitivity to endocrine therapy (SET) prior to neoadjuvant chemotherapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-11-04.

Comparison of analgesic and hemodynamic effects of nalbuphine versus fentanyl: a randomized, double-blinded interventional study in patients on cardiopulmonary bypass

Background Our study aimed to compare analgesic and hemodynamic effect of Nalbuphine vs fentanyl in patient undergoing cardiac surgery on cardiopulmonary bypass. Study design Prospective, double blind, randomized intervational study. Materials and Methods After ethical committee approval and written informed consent, 60 patients of either sex,aged between 18 to 65 yrs, ASA grade 2nd and 3rd, randomely allocated to each group. Group A received study drug Nalbuphine and group B received Fentanyl. Both the drugs were given 5 min before induction. Repeated doses of study drugs were given when BIS score >60. Haemodynamics parameters were recorded at different time intervels throughout the surgery. After extubation VAS score noted at different time interval and time of first need of analgesic (Rescue analgesia) noted when VAS >3. Statistical analysis All the qualitative data were analysed with chi square test and all the quantitative data were analysed with comparison of mean±SD and unpaired student t-test. The levels of significance and α - error were kept 95 % and 5 % respectively, for all statistical analyses. P values 0.05 as statistically Non Significant (NS). Results The mean heart rate was statistically significantly less in group B at just after intubation and just before going on cardio pulmonary bypass (CPB) & mean arterial pressure (MAP) also was statistically significantly less at just after intubation and just after coming off CPB compare to group A. Duration of analgesia in group A (288±42.13 min) was significantly prolonged as compared with group B (207±50.04 min). This prolongation of duration of analgesia was statistically significant. Conclusion The present study demonstrate the benefit of Fentanyl over Nalbuphine for intraoperatively haemodynamic stability and Nalbuphine is better for post extubation longer duration of analgesia over fentanyl.