Difference In Time Research Articles

Enhanced Moving Source Localization with Time and Frequency Difference of Arrival: Motion-Assisted Method for Sub-Dimensional Sensor Networks

Localizing a moving source by Time Difference of Arrival (TDOA) and Frequency Difference of Arrival (FDOA) commonly requires at least N+1 sensors in N-dimensional space to obtain more than N pairs of TDOAs and FDOAs, thereby establishing more than 2N equations to solve for 2N unknowns. However, if there are insufficient sensors, the localization problem will become underdetermined, leading to non-unique solutions or inaccuracies in the minimum norm solution. This paper proposes a localization method using TDOAs and FDOAs while incorporating the motion model. The motion between the source and sensors increases the equivalent length of the baseline, thereby improving observability even when using the minimum number of sensors. The problem is formulated as a Maximum Likelihood Estimation (MLE) and solved through Gauss–Newton (GN) iteration. Since GN requires an initialization close to the true value, the MLE is transformed into a semidefinite programming problem using Semidefinite Relaxation (SDR) technology, while SDR results in a suboptimal estimate, it is sufficient as an initialization to guarantee the convergence of GN iteration. The proposed method is analytically shown to reach the Cramér–Rao Lower Bound (CRLB) accuracy under mild noise conditions. Simulation results confirm that it achieves CRLB-level performance when the number of sensors is lower than N+1, thereby corroborating the theoretical analysis.

Trophic interactions between common minke whales (Balaenoptera acutorostrata) and their prey during summer in the northern Barents Sea

Global warming is causing rapid change in marine food webs, particularly at northern latitudes where temperatures are increasing most rapidly. In this study, the diet of common minke whales Balaenoptera acutorostrata was assessed both in terms of short-term (morphological analyses of digestive tract contents) and longer-term (tissue chemical markers: fatty acids and stable isotopes) prey use in the northern Barents Sea to see if they are prey shifting. Samples (blubber cores, muscle, and stomach contents) were obtained from 158 common minke whales taken during Norwegian commercial whaling operations during summer over the period 2016–2020. Two prey items, capelin Mallotus villosus and krill (primarily Thysanoessa sp.), dominated the stomach contents in the entire period of investigation, which included sampling both in June and in August, similar to findings from earlier studies. A few gadoids were also observed in the whale stomachs. Lower blubber fatty acid (FA) contents in 2016/2017 as compared with 2018/2019 were observed. This is most likely explained by differences in sampling time (June in 2016/2017 vs August in 2018/2019, i.e., after a longer feeding period during the summer in the latter case). This explanation also fits with the fact that FA profiles of the 2018/2019 whales were more similar to the FA profiles of the potential prey, presumably reflecting the two months longer assimilation time for these whales. Multidimensional mixing models based on carbon and nitrogen isotope composition of the most likely prey groups suggested that the whales ate mostly krill in four of the five sampling years. In 2018 there were indications of a higher proportion of gadoid fish, showing some dietary flexibility. The trophic level of the whales’ feeding, as interpreted from the nitrogen isotope values, was positively correlated with blubber thickness suggesting that fish-eaters tended to assimilate more energy than whales that focused more exclusively on lower trophic prey. The variation suggested by different dietary analyses methods − stomach contents, fatty acids, and stable isotopes – most likely reflects different turnover times, with muscle stable isotopes likely representing several months of dietary integration, while lipid stores are more dynamic and may represent weeks, and stomach contents represent feeding events during the last few hours. The change in diet of minke whales from small pelagic fishes (in the past) to a greater quantity of krill and demersal fish (seen in this study) suggests that the whales are responding to the ongoing borealization of the Barents Sea ecosystem.

Application of intranasal dexmedetomidine in magnetic resonance imaging of preterm infants: The ED50, efficacy and safety analysis.

Infants undergoing magnetic resonance imaging (MRI) often require pharmacological sedation. Dexmedetomidine serves as a novel sedative agent that induces a unique unconsciousness similar to natural sleep, and therefore has currently been used as the first choice for sedation in infants and young children. To determine the 50% effective dose (ED50) and 95% confidence interval (95%CI) of intranasal dexmedetomidine for MRI in preterm and term infants, and to observe the incidence of adverse events. To explore whether there were differences in ED50 and 95%CI, heart rate (HR) and blood oxygen saturation (SpO2), the induction time and wake-up time and the incidence of adverse events between the 2 groups, so as to provide guidance for clinical safe medication for the meanwhile. A total of 68 infants were prospectively recruited for MRI examination under drug sedation (1 week ≤ age ≤ 23 weeks or weight ≤ 5kg). The children were divided into 2 groups according to whether they had preterm birth experience (Preterm group, Atterm group). The Dixon up-and-down method was used to explore ED50. The basic vital signs of the 2 groups were recorded, and the heart rate and SpO2 were recorded every 5 minutes until the infants were discharged from the hospital. The induction time, wake-up time and adverse events were recorded. The ED50 (95%CI) of intranasal dexmedetomidine in the Preterm group and the Atterm group were 2.23 (2.03-2.66) μg/kg and 2.64 (2.49-2.83) μg/kg, respectively (P < .05). the wake-up time was longer in Preterm group (98.00min) than in Atterm group (81.00 min) (P < .05), the incidence of bradycardia in Preterm group was 3/33, which was higher than that in Atterm group (1/35). There was no difference in the induction time between the 2 groups (P > .05), and there was no significant difference in other adverse events. Intranasal dexmedetomidine can be safely used for sedation in preterm infants undergoing MRI. Compared with term infants, preterm infants have a lower dose of dexmedetomidine, a higher incidence of bradycardia, and a longer weak-up time.

WHO DAIRS WINS?

Periprosthetic joint infection is a serious complication of primary total hip replacement (THR) with significant associated morbidity. In acute infection, Debridement, Antibiotics and Implant Retention (DAIR) may be considered. Current national guidelines recommend a DAIR should be performed by “an experienced arthroplasty surgeon┕ but do not specify the need for this to be a revision arthroplasty surgeon. We investigated outcomes in our NHS Trust of DAIR procedures performed by revision and non-revision arthroplasty surgeons.Infection registry data and patient records were analysed for all DAIR procedures of infected primary THRs between 2017 and 2021. Data collected included details of the primary surgery, the presentation with infection, the DAIR procedure and any subsequent complications including return to theatre at any time point. Routinely collected pre- and post-operative patient reported outcome measures (PROMs) were reviewed.54 periprosthetic joint infections of primary THRs received a DAIR procedure. 41 DAIRs were performed by a revision surgeon and 13 by non-revision surgeons. There was no significant difference in time from primary THR to presentation with infection, time from presentation to DAIR or pre-operative C-reactive protein between the two groups.In 21 (38.9%) patients the DAIR procedure was classed as a treatment failure; 17 patients (31.5%) returned to theatre for further revision surgery, one (2.4%) died related to infection and three (5.6%) had persistent infection but did not receive further surgery. Treatment failure was significantly higher in the non-revision surgeon group (9/13 (69.2%)) than in the revision surgeon group (12/41 (29.3%)) (p = 0.02). Overall, improvement in PROMs after DAIR was seen at both six and 12 months.The overall success rate of DAIR was 61.1% and there was a sustained improvement in PROMs after surgery. However, there was a significant difference in failure rates between revision surgeons and non-revision surgeons.

Abstract PO4-12-11: Patient (pt) time burden with IV vs subcutaneous (SC) administration of trastuzumab/pertuzumab (HP): A time and motion (T+M) substudy of a single arm phase II trial of adjuvant endocrine therapy plus HP for stage I HER2+ breast cancer

Abstract Background: The time required for in-clinic drug administration may have a substantial detrimental impact on breast cancer patients’ quality of life. SC drug administration, as opposed to IV, may reduce this time commitment. The purpose of this study was to estimate the relative difference in time and logistical burden between IV and SC administration of HP. Methods: We prospectively enrolled a pre-specified sub-cohort of pts participating on the ADEPT trial (NCT04569747) to this T+M substudy. The ADEPT trial is an ongoing single arm prospective phase II trial of adjuvant SC HP (for 1 yr) plus endocrine therapy for pts with hormone receptor-positive (HR+) and HER2+ stage I (pT1N0 or pT1N1mi) breast cancer. Pts eligible for ADEPT have completed primary breast surgery and are systemic therapy-naïve. Pts who received cycle 1 of loading SC HP at Dana-Farber Cancer Institute and tolerated SC drug administration were eligible and enrolled consecutively to the T+M substudy until the T+M accrual goal; accrual to the T+M substudy was mandatory for eligible pts. The T+M substudy was a single arm crossover design in which pts received 2 cycles of IV HP, followed by 2 cycles of maintenance dose SC HP. During those 4 treatment (tx) cycles, timepoints in the drug preparation and administration process were captured from the electronic medical record or flowsheets filled out by infusion nurses. The primary endpoint of the T+M substudy was total pt chair time in the infusion area (measured from start of first drug administration to end of final post-drug observation period). Exploratory endpoints included total drug preparation time and total pt tx experience time. A sample size of 22 pts was estimated to provide 86% power with 2-sided alpha 0.05 to detect a difference of 70 mins in the primary endpoint by tx arm (IV vs SC). For all endpoints, the average time across both tx cycles was calculated for each pt, and the overall mean across pts for each of IV and SC administration was computed (with standard deviation). Average times for IV vs SC administration were compared via paired Wilcoxon signed rank tests. Adjustments for multiple comparisons were not included. Results: 22 pts participated on the T+M substudy, and each had timepoints captured during 4 tx cycles (2 IV and 2 SC cycles), for a total of 88 patient-cycles analyzed overall. Pts had median age 58 yrs (range 42-83), and were 96% female, 82% White, 9% Black, 9% Asian; and 100% non-Hispanic. Comparison of time intervals for IV vs SC drug administration is shown in the Table. Mean total pt infusion chair time was 84.3 mins with IV HP, vs 22.5 mins with SC HP, for a difference of 61.8 mins shorter pt time commitment in favor of SC administration (p&amp;lt; 0.0001). The mean total drug preparation time was significantly decreased in favor of SC administration (by 78.2 mins; p&amp;lt; 0.0001); and the total pt tx experience time was significantly decreased in favor of SC administration (by 81.8 mins; p&amp;lt; 0.0001). Conclusions: This prospective T+M study demonstrated that pt infusion chair time is significantly decreased with SC as compared to IV administration of HP, shortening this pt time burden by approximately one hour. SC drug administration is an approach that may help to improve and shorten the pt breast cancer therapy experience and decrease pharmacy burden. Table. SD, standard deviation Citation Format: Adrienne Waks, Noah Graham, Emily Chen, Anna Mae Frey, Victoria Attaya, Ibrahim Abbass, Anita Fung, Jesse Sussell, Patricia Cortazar, Caroline Harvey, Kenneth Almeida, Denise Leth, Wendy Chen, Jose Leone, Susan Schumer, Nabihah Tayob, Sara Tolaney. Patient (pt) time burden with IV vs subcutaneous (SC) administration of trastuzumab/pertuzumab (HP): A time and motion (T+M) substudy of a single arm phase II trial of adjuvant endocrine therapy plus HP for stage I HER2+ breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-11.

Abstract PO2-22-10: Surgical outcomes after neoadjuvant chemotherapy with and without immunotherapy in patients with triple negative breast cancer

Abstract Background: The KEYNOTE-522 trial demonstrated that the addition of neoadjuvant pembrolizumab to neoadjuvant chemotherapy (NAC) for the treatment of early-stage triple negative breast cancer (TNBC) significantly improves rates of both pathologic complete response (pCR) and event-free survival. The impact of adding immunotherapy to NAC on surgical outcomes, however, is unknown. The purpose of this study is to compare 90-day surgical complication rates and timing to subsequent adjuvant therapy of patients undergoing neoadjuvant chemotherapy for stage I-III TNBC with and without immunotherapy. Methods: Patients treated at University of California, Los Angeles with neoadjuvant therapy for TNBC between 2018-2022 were identified retrospectively. Patient comorbidities, tumor characteristics, type of surgery, 90-day postoperative minor and major complications, timing to adjuvant therapy, and oncologic outcomes were reviewed and analyzed. Major complications were defined as those requiring reoperation or hospitalization. Results: A total of 44 patients were included, 15 patients received neoadjuvant chemotherapy with immunotherapy (NAC-I) and 29 patients received neoadjuvant chemotherapy alone (NAC). There was no difference in patient comorbidities between the groups. Compared to the NAC group, significantly more patients in the NAC-I group had stage II or III tumors (58.6% vs. 86.7%, respectively, p=0.028). 73% of patients in the NAC-I group underwent mastectomy compared to only 44% of patients in the NAC group (p=0.111). In total, 23 patients underwent reconstruction with mastectomy, 6 patients underwent immediate DIEP flap (4 in NAC-I group and 2 in NAC group) and 17 underwent immediate tissue expander (7 in NAC-I and 10 in NAC group). 80% of patients in the NAC-I experienced a pCR compared to only 44% in the NAC group (p=0.026). A total of 15 patients (34.1%) experienced surgical complications and there was no significant difference in the complication rate between the groups (p= 0.552). Five patients (33%) in the NAC-I group experienced minor complications of seroma requiring aspiration (n=4), cellulitis requiring antibiotics (n=1), or wound dehiscence requiring local wound care (n=2). No patients in the NAC-I group had major complications. Ten patients (33%) in the NAC group experienced complications, including 6 minor complications and 4 major complications including postoperative bleeding or flap necrosis requiring unplanned return to surgery or hyperbaric oxygen treatment. On multivariable regression analysis, controlling for patient characteristics, tumor stage, and preoperative immunotherapy, only younger age was a statistically significant variable associated with increased risk of surgical complications (p=0.012). Median time to adjuvant therapy, including radiation and/or systemic therapy, was similar between NAC-I and NAC groups, at 32 and 36 days, respectively (p=0.37). In the NAC-I group, 14 patients (93.3%) had adjuvant systemic therapy including pembrolizumab alone (n=12), pembrolizumab with olaparib (n=1) or capecitabine alone (n=1). In the NAC group, 11 patients (37.9%) underwent adjuvant systemic treatment including chemotherapy with either capecitabine (n=1), pembrolizumab (n=1), or olaparib (n=2); or single agent capecitabine (n=6) or olaparib (n=1). Conclusions: Despite patients in the NAC-I group having more advanced stage tumors and undergoing more extensive surgery and reconstruction compared to those in the NAC alone group, a significantly higher rate of surgical complications was not observed in the NAC-I group and there was no significant difference in time to adjuvant therapy between the two groups. Similar to results from the KEYNOTE-522 trial, more patients in the NAC-I group experienced a pCR compared to NAC alone. Larger studies are needed to continue to assess and optimize the surgical safety of neoadjuvant immunotherapy with chemotherapy in patients with TNBC. Citation Format: Anouchka Coste Holt, Maurice Berkowitz, Nicholas McAndrew, Courtney Smith, Jennifer Baker, Nimmi Kapoor. Surgical outcomes after neoadjuvant chemotherapy with and without immunotherapy in patients with triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-22-10.

Time Differences From Abnormal Cervical Cancer Screening to Colposcopy Between Insurance Statuses.

Screening and diagnostic follow-up to prevent cervical cancer are influenced by socioeconomic and systemic factors. This study sought to characterize intervals from abnormal cervical cancer screening to colposcopy between practices differing by insurance status at a large, urban academic center. This retrospective cohort study included patients aged 21-65 who presented for colposcopy between January 1, 2021, and January 1, 2022, at the resident and faculty gynecology practices of a single large urban academic medical center. Patient characteristics were compared using t tests or Wilcoxon rank sum tests for continuous measures and χ2 or Fisher exact tests for categorical measures. Intervals from abnormal cervical cancer screening to colposcopy were compared using the Wilcoxon rank sum test and linear regression analysis with multivariable models adjusted for age, cervical cytology result, human papillomavirus result, and HIV status. Resident practice patients were publicly insured and more likely to be Black or Hispanic (p < .0001); rates of high-risk human papillomavirus and smoking were similar. Resident practice patients had longer intervals from abnormal cervical cancer screening to colposcopy compared with faculty practice patients (median 79.5 vs 34 d, p < .0001). On adjusted analysis, resident practice patients faced a 95% longer interval (p < .0001). Publicly insured patients of a resident-based practice faced significantly longer intervals from abnormal cervical cancer screening to colposcopy than faculty practice patients at a single urban academic center. Effort to address these differences may be an area of focus in improving health disparities.

Abstract PO3-06-04: Clinical Features and Survival Outcomes of Oligometastatic Breast Cancer Patients: The Mayo Clinic Experience

Abstract Background The current definition, prognosis, and optimal treatment (tx) for oligometastatic breast cancer (OMBC) are not fully known. With advances in multimodality breast cancer (BC) tx and overall improvement in patient (pt) outcomes, it is important to identify baseline pt factors that confer better prognosis in OMBC and assess the impact of local/regional tx and metastasis (mets)-directed tx on survival outcomes. Methods We reviewed 105 Mayo Clinic pts with OMBC (up to 5 mets) from 2003 to 2021. Pts were excluded from analysis if they were misidentified as having OMBC (n=6), did not have a primary breast mass (n=1), developed de novo BC during tx (n=1), or were lost to follow up (n=2). Categorical variables were summarized as counts. Continuous variables were reported as medians. Kaplan-Meier method was used to estimate survival and the time from diagnosis to next tx at 1, 3, and 5 years. Log-rank test was used to compare survival rates between baseline factors. Univariate Cox proportional hazards models were performed on both baseline and time-dependent factors. All tests were two-sided with p-value &amp;lt; 0.05 considered statistically significant. Results Total pts included were 95. Median age was 49 (range, 26-86), most (93.6%) pts were White, and 46.8% were postmenopausal. Invasive ductal carcinoma (89.5%) was the most common BC type. Median survival was 10.8 years; 1-, 3-, and 5-year survival rates were 98.9%, 87.7%, and 81%, respectively. 58 pts (61.1%) required a change in tx due to disease progression. No significant survival difference was observed in pre- vs. postmenopausal pts (p=0.71) or in groups based on hormone receptor and/or human epidermal growth factor receptor 2 status. 47 pts (49.5%) received local/regional tx; no significant difference in survival (HR 0.57, 95% CI 0.23-1.40; p=0.217) or time to next tx (HR 0.67, 95% CI 0.39-1.15; p=0.144) was seen in this subgroup. Of these pts, 36 (76.6%) received neoadjuvant chemotherapy and/or immunotherapy, 5 of whom (10.6%) also started endocrine tx preoperatively. Overall, 11/47 pts (23.4%) received neoadjuvant endocrine tx. 20 pts received systemic tx without eventual surgery, and 5 pts got palliative radiation (RT). Biopsy-confirmed mets were noted in 76 pts (80%), with bone-only mets in 50%, 30 pts (31.6%) with viscera-only mets and 7 pts (7.4%) with both bone and visceral mets. 18 pts had suspected mets on imaging but did not undergo biopsy. The hazard of death was 6.34 times higher in pts with both bone and visceral mets than those with bone-only mets (p=0.008). Pts with viscera-only mets had higher survival at 2 and 3 years than pts with bone-only or both bone and visceral mets (p=0.093). Pts with 3 mets (7/76, 7.4%) had decreased survival at 1, 2, and 3 years compared to pts with 1-2 (65/76, 85.5%) mets (p=0.6). 67 pts (70.5%) received mets-directed tx; RT alone was the most common modality (52/67, 77.6%), followed by surgery (6/67, 9%), RT plus surgery (5/67, 7.5%), and ablation alone (3/67, 4.5%). There was no significant difference in survival (HR 1.27, 95% CI (0.53, 3.07), p=0.589) or time to next tx (HR 0.95, 95% CI (0.56, 1.63), p=0.856) in pts who received mets-directed tx. Multivariate analysis was not performed because most findings were not statistically significant in univariate analysis. Conclusions We did not find any significant differences in survival based on characteristics like menopausal status or site or number of mets in pts with OMBC. There was a trend toward improved survival in pts with viscera-only mets, but this finding requires validation. Local/regional and mets-directed tx did not improve survival; however, survival at 1, 3, and 5 years was excellent in this OMBC pt population. Our study was limited by low pt numbers and heterogeneity in the pt population. Findings need validation in larger studies. Citation Format: Tanmayi Pai, Raza Zarrar, Zhongwei Peng, Zhuo Li, Lauren Cornell, Kostandinos Sideras, Rohit Rao, Alvaro Moreno-Aspitia, Saranya Chumsri, Sarah McLaughlin, James Jakub, Emmanuel gabriel, Sanjay Bagaria, Laura Vallow, Santo Maimone, Pooja Advani. Clinical Features and Survival Outcomes of Oligometastatic Breast Cancer Patients: The Mayo Clinic Experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-04.

Abstract PS02-03: Is de-escalation of treatment by omission of radiotherapy associated with fear of cancer recurrence and health-related quality of life in women with early breast cancer? An exploratory study

Abstract Background: There is growing interest in treatment optimization in early breast cancer (EBC). PROSPECT (ANZ-1002) provided compelling evidence that a combination of pre-operative MRI and pathological features could identify a substantial group of patients with localised EBC in whom radiotherapy (RT) could be safely omitted. The patient experience of de-escalation or its association with health-related quality of life (HRQoL) and fear of cancer recurrence (FCR), was not examined in PROSPECT but is a key consideration of treatment decision-making. We conducted a retrospective, mixed methods, cross-sectional study to explore this association. Methods: Psychometrically validated measures including the Fear of Cancer Recurrence Inventory Short-Form, Depression Anxiety Stress Scale, Breast Cancer Treatment Outcomes Scale, EORTC QLQ-C30 and its breast-specific module, the BR23, and the Decision Regret Scale were completed by three groups of women with early EBC: Women in the PROSPECT clinical trial who underwent pre-surgical MRI and omitted RT (A), women who underwent pre-surgical MRI and received RT (B); and women who received usual care (no MRI, received RT; C). Between group differences were analysed with ANOVA or equivalent non-parametric tests. A subset from each group participated in a semi-structured interview. These data (n=44) were analysed with directed content analysis. Results: Data from 400 women were analysed. Median age was 65 years, and median time since diagnosis was 4.4 years. There were no group differences in neuroticism, mental health, age, medical comorbidities, parity, or time since diagnosis. Significantly lower FCR was observed in Group A (n=125) than in Group B (n=102; p=.002) or Group C (n=173; p=.001), and when participants were categorized by RT status (omitted RT vs received RT; p&amp;lt; .001). The proportion of women with normal FCR was significantly (p &amp;lt; .05) larger in Group A (62%) than in Group B (35%) or Group C (40%). There were no differences between groups on depression and anxiety. Women in Group A had fewer breast symptoms than in Group B (p=.003) and Group C (p= &amp;lt; .001), fewer arm symptoms than in Group B (p=.004) and Group C (p=.011), and better body image than Group C (p=.041). Compared to Groups B and C, Group A performed better on cosmetic (both p&amp;lt; .001), functional (A vs C: p=.011) and breast-specific pain measures (both p&amp;lt; .001). Pre-operative MRI and omission of RT were highly acceptable and decision regret was low. A secondary analysis was conducted to eliminate any potential impact of disease severity on the analysis. All cases (n=126) with any positive nodes, a Grade 3 tumour and tumour size &amp;gt;20mm were removed. The remaining sample comprised 274 women. The results were similar to the primary analysis. Qualitative analysis showed that women who omitted RT viewed this as appropriate treatment, not undertreatment. Women considered RT toxic but endured it as a necessity, if prescribed. Few women experienced ongoing negative effects from RT but there was a tendency to minimize RT treatment burden. Women managed their FCR by having trust in their treatment and faith in the medical advice they received. Conclusions: In the setting of the PROSPECT trial, treatment de-escalation via omitting RT was associated with less FCR, better HRQoL and functional and cosmetic outcomes and was highly acceptable. Clinicians should consider the potential for preserved HRQoL associated with omission of RT in treatment decision-making. Positive perceptions about tailored care, lower treatment burden, and trust in clinicians appear to be protective against FCR. Future studies should include prospective collection of FCR and HRQoL measures. Citation Format: Bruce Mann, Michelle Sinclair, Phyllis Butow, Janemary Hughes, Allan Park, Leslie Gilham, Allison Rose, Lesley Stafford. Is de-escalation of treatment by omission of radiotherapy associated with fear of cancer recurrence and health-related quality of life in women with early breast cancer? An exploratory study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS02-03.

Longitudinal associations of diurnal rest-activity rhythms with fatigue, insomnia, and health-related quality of life in survivors of colorectal cancer up to 5 years post-treatment

BackgroundThere is a growing population of survivors of colorectal cancer (CRC). Fatigue and insomnia are common symptoms after CRC, negatively influencing health-related quality of life (HRQoL). Besides increasing physical activity and decreasing sedentary behavior, the timing and patterns of physical activity and rest over the 24-h day (i.e. diurnal rest-activity rhythms) could also play a role in alleviating these symptoms and improving HRQoL. We investigated longitudinal associations of the diurnal rest-activity rhythm (RAR) with fatigue, insomnia, and HRQoL in survivors of CRC.MethodsIn a prospective cohort study among survivors of stage I-III CRC, 5 repeated measurements were performed from 6 weeks up to 5 years post-treatment. Parameters of RAR, including mesor, amplitude, acrophase, circadian quotient, dichotomy index, and 24-h autocorrelation coefficient, were assessed by a custom MATLAB program using data from tri-axial accelerometers worn on the upper thigh for 7 consecutive days. Fatigue, insomnia, and HRQoL were measured by validated questionnaires. Confounder-adjusted linear mixed models were applied to analyze longitudinal associations of RAR with fatigue, insomnia, and HRQoL from 6 weeks until 5 years post-treatment. Additionally, intra-individual and inter-individual associations over time were separated.ResultsData were available from 289 survivors of CRC. All RAR parameters except for 24-h autocorrelation increased from 6 weeks to 6 months post-treatment, after which they remained relatively stable. A higher mesor, amplitude, circadian quotient, dichotomy index, and 24-h autocorrelation were statistically significantly associated with less fatigue and better HRQoL over time. A higher amplitude and circadian quotient were associated with lower insomnia. Most of these associations appeared driven by both within-person changes over time and between-person differences in RAR parameters. No significant associations were observed for acrophase.ConclusionsIn the first five years after CRC treatment, adhering to a generally more active (mesor) and consistent (24-h autocorrelation) RAR, with a pronounced peak activity (amplitude) and a marked difference between daytime and nighttime activity (dichotomy index) was found to be associated with lower fatigue, lower insomnia, and a better HRQoL. Future intervention studies are needed to investigate if restoring RAR among survivors of CRC could help to alleviate symptoms of fatigue and insomnia while enhancing their HRQoL.Trial registrationEnCoRe study NL6904 (https://www.onderzoekmetmensen.nl/).

Timing of Mifepristone Relative to Misoprostol Critical for Reducing Blood Loss and Need for Surgical Procedure for Induction of Labor in the Second Trimester [ID 2683544

INTRODUCTION: Mifepristone is used in combination with misoprostol to facilitate inpatient induction of labor in the second trimester; however, the optimal interval of time between administration of these drugs is not known. Current practice guidelines recommend an interval of 24–48 hours. METHODS: In a single-institution retrospective chart review study, we examined whether mifepristone administration practices at that institution improved loss induction duration or adverse outcomes. This study was determined to be exempt from IRB approval. RESULTS: Among 267 loss inductions from 2018 to 2022, 54% received mifepristone. When misoprostol-alone inductions are compared to those that also received mifepristone, results demonstrate no difference in time to delivery (15.1 versus 15.9 hours; P=.62) or adverse outcomes, including blood loss greater than 1 L (8.2% versus 13.1%; P=.24) and need for operating room (OR) procedure (15.6% versus 16.6%; P=.86). Importantly, the average interval in this study between administration of mifepristone and misoprostol was 1.3 hours (median, 0.1 hours). Further analysis of those patients who received mifepristone demonstrated improved outcomes only if mifepristone was given at least 3 hours prior to misoprostol, including blood loss greater than 1 L (17.4% versus 0%; P=.0037) and need for OR procedure (21.4% versus 2.7%; P=.0088). There remained no difference in time to delivery (16.0 versus 15.8 hours; P=.94). CONCLUSION: These data demonstrate the importance of the timing of mifepristone and misoprostol administration for loss induction and strongly suggest that at least a 3-hour interval is required to improve adverse outcomes. Further prospective study is warranted to broaden the scope of these findings.

Cost-avoidance associated with implementation of an overnight emergency medicine pharmacist at a Level I Trauma, Comprehensive Stroke Center

AimTo investigate the cost-avoidance associated with implementation of an overnight emergency medicine pharmacist (EMP) through documented clinical interventions. DesignRetrospective evaluation of prospectively tracked interventions in a single Level I Trauma, Comprehensive Stroke Center, from November 25, 2020 through March 12, 2021 during expanded emergency medicine service hours (2300–0700). InterventionsOne of 45 clinical patient-care recommendations associated with cost-avoidance were available to be selected and documented by the EMP; more than one intervention was allowed per patient, though one clinical intervention could not be counted as multiple items. Documented services were associated with monetary cost avoidance based upon available literature assessing pharmacy clinical interventions. Differences in time from imaging to systemic thrombolytics and percentage of patients meeting door-to-alteplase benchmarks were compared with and without the availability of EMPs. ResultsOvernight EMPs documented 820 interventions during 107 overnight shifts with a cost avoidance of $612,974. The most common interventions were bedside monitoring (n = 127; $50,694), drug information consultation (97; $11,269), and antimicrobial therapy initiation and streamlining (95; $60,101). When categorizing interventions, 378 (46%; $292,484) were input as hands-on care, 216 (26%; $94,899) as individualization of patient care, 135 (17%; $25,897) as administrative and supportive tasks, 84 (10%; $121,746) as adverse drug event prevention, and 7 (1%; $77,964) as resource utilization. All patients (n = 6) with an acute ischemic stroke during the evaluation period received systemic thrombolytics ≤45 min in the presence of EMPs compared with 50% receiving thrombolytics ≤45 min without EMPs. ConclusionsExpanded overnight coverage by EMPs provided clinical bedside pharmacotherapy expertise to critically ill patients otherwise not available prior to study implementation. Clinical interventions were associated with substantial cost-avoidance.

Enhancing the Efficiency of the Individual Case Safety Report (ICSR) Quality and Compliance through Automation.

Over the past few years, major inspection findings have been identified in the "management of adverse reactions" that may be due to increasing workload in pharmaceutical organizations impacting the correctness of information in individual case safety reports (ICSRs). Although retrospective quality check (Retro-QC) and late submission analyses are important steps in ensuring ICSR quality, their manual application poses several challenges that can be overcome through automation. To improve the efficiency of the Retro-QC analysis and late submission analysis using a computer-operated tool called Compliance and Metrics Management (CMM) tool, and to measure the tool's effectiveness in terms of productivity, time, and cost savings by comparing against the manual process. Time savings were calculated by measuring the difference in time taken during the manual process versus the automated process. Cost savings were measured in terms of hourly remuneration for the time saved. Productivity was calculated as the difference between the number of cases handled in the manual versus automated process. Thus, the overall efficiency was measured in terms of time and cost savings along with increased productivity. Automation resulted in time savings of 49% and cost savings of 43% for Retro-QC analysis, and the productivity level increased by 67%. For late submission analysis, the CMM tool resulted in time savings of 88% and cost savings of 87%. CMM tool enhanced the efficiency of both Retro-QC and late submission analyses by increasing productivity along with time and cost savings. It also reduced the number of errors, thereby enhancing the accuracy of the process and overall compliance.

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial

In the ongoing, randomised, double-blind phase 3 TOPAZ-1 study, durvalumab, a PD-L1 inhibitor, plus gemcitabine and cisplatin was associated with significant improvements in overall survival compared with placebo, gemcitabine, and cisplatin in people with advanced biliary tract cancer at the pre-planned intermin analysis. In this paper, we present patient-reported outcomes from TOPAZ-1. In TOPAZ-1 (NCT03875235), participants aged 18 years or older with previously untreated, unresectable, locally advanced, or metastatic biliary tract cancer with an Eastern Cooperative Oncology Group performance status of 0 or 1 and one or more measurable lesions per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) were randomly assigned (1:1) to the durvalumab group or the placebo group using a computer-generated randomisation scheme. Participants received 1500 mg durvalumab or matched placebo intravenously every 3 weeks (on day 1 of the cycle) for up to eight cycles in combination with 1000 mg/m2 gemcitabine and 25 mg/m2 cisplatin intravenously on days 1 and 8 every 3 weeks for up to eight cycles. Thereafter, participants received either durvalumab (1500 mg) or placebo monotherapy intravenously every 4 weeks until disease progression or other discontinuation criteria were met. Randomisation was stratified by disease status (initially unresectable vs recurrent) and primary tumour location (intrahepatic cholangiocarcinoma vs extrahepatic cholangiocarcinoma vs gallbladder cancer). Patient-reported outcomes were assessed as a secondary outcome in all participants who completed the European Organisation for Research and Treatment of Cancer's 30-item Quality of Life of Cancer Patients questionnaire (QLQ-C30) and the 21-item Cholangiocarcinoma and Gallbladder Cancer Quality of Life Module (QLQ-BIL21). We calculated time to deterioration-ie, time from randomisation to an absolute decrease of at least 10 points in a patient-reported outcome that was confirmed at a subsequent visit or the date of death (by any cause) in the absence of deterioration-and adjusted mean change from baseline in patient-reported outcomes. Between April 16, 2019, and Dec 11, 2020, 685 participants were enrolled and randomly assigned, 341 to the durvalumab group and 344 to the placebo group. Overall, 345 (50%) of participants were male and 340 (50%) were female. Data for the QLQ-C30 were available for 318 participants in the durvalumab group and 328 in the placebo group (median follow-up 9·9 months [IQR 6·7 to 14·1]). Data for the QLQ-BIL21 were available for 305 participants in the durvalumab group and 322 in the placebo group (median follow-up 10·2 months [IQR 6·7 to 14·3]). The proportions of participants in both groups who completed questionnaires were high and baseline scores were mostly similar across treatment groups. For global health status or quality of life, functioning, and symptoms, we noted no difference in time to deterioration or adjusted mean changes from baseline were observed between groups. Median time to deterioration of global health status or quality of life was 7·4 months (95% CI 5·6 to 8·9) in the durvalumab group and 6·7 months (5·6 to 7·9) in the placebo group (hazard ratio 0·87 [95% CI 0·69 to 1·12]). The adjusted mean change from baseline was 1·23 (95% CI -0·71 to 3·16) in the durvalumab group and 0·35 (-1·63 to 2·32) in the placebo group. The addition of durvalumab to gemcitabine and cisplatin did not have a detrimental effect on patient-reported outcomes. These results suggest that durvalumab, gemcitabine, and cisplatin is a tolerable treatment regimen in patients with advanced biliary tract cancer. AstraZeneca.

Inhibitory control mediates the effect of high intensity interval exercise on food choice

Exercise is associated with changes in food consumption and cognitive function. The aim of this study was to examine the immediate effects of acute exercise on appetite, food choices, and cognitive processes, and the mediating role of cognitive functioning, namely inhibitory control, working memory, cognitive flexibility and decision making. We compared the effects of high-intensity interval exercise (HIIE) to a resting condition on appetite and food choices, using visual analogue rating scales and a computerised portion selection task. Mediation analysis was performed with exercise/rest condition as a predictor variable and cognitive measures were entered as mediating variables and food choice measures as outcomes. Young women with low activity levels, aged between 18-35 years with a body mass index (BMI) between 18-25 kg/m2, were recruited. Participants (n=30) demonstrated improved performance on a Stroop task following HIIE compared to the rest session, indicating enhanced attentional inhibition. Accuracy on an N-back task was significantly higher after HIIE, indicating an improvement in working memory and response times on the N-back task were shorter after HIIE, suggesting increased processing speed. Delay discounting for food (but not money) was reduced after HIEE but there were no significant on go/no-go task performance. On the trail-making task (a measure of cognitive flexibility), the time difference between trail B and A was significantly lower after HIIE, compared to rest. HIIE reduced rated enjoyment and ideal portion size selection for high energy dense foods. The relationship between exercise and food choices was mediated by inhibition as assessed by the Stoop task. These results suggest that HIIE leads to cognitive benefits and a reduced preference for high-calorie foods and that an enhancement of attentional inhibition may underlie this relationship.

Comparison between in-person, telehealth, and combination visits among veterans treated in a pharmacist-led diabetes management clinic

The Veterans Affairs San Diego Healthcare System converted its pharmacist-run Diabetes Intense Medical Management (DIMM) Clinic to telehealth during the COVID-19 pandemic. Previous studies suggested that in-person DIMM visits improved glycemic control, medication adherence, and patient satisfaction. To explore if these benefits apply to telehealth, we compared glycemic control in veterans with post-COVID-19 telehealth DIMM visits and pre-pandemic in-person DIMM visits. The primary study objective was to evaluate the mean hemoglobin (A1c) change from baseline in cohorts who received telehealth visits, traditional visits, or a combination of both after 12 months of intervention. Secondary objectives included evaluation of all-cause mortality and the average time to mortality (days). A retrospective multi-arm historical cohort control study was conducted to compare 12-month glycemic control among veterans with type 2 diabetes who initiated DIMM care via audio-only telehealth, in-person, or combination between August 2018 and November 2021. Primary endpoint was the 12-month change in A1c from baseline; secondary measures included all-cause mortality and the average time to mortality (days). A total of 44 veterans were included for analysis. At 12 months, the average decrease in A1c from baseline were -0.90% (95% CI: -2.82, 1.01), -1.73% (95% CI: -3.33, -0.14), and -1.42% (95% CI: -2.67, -0.18) for the In-Person, Telehealth, and Combination groups, respectively. No differences in quarterly HbA1c rate of change were reported across the groups. All-cause mortality was highest in the In-person group (15.4%) compared to the Telehealth (4.6%) and the Combination (0.0%) groups; however, these differences were not statistically significant. Lastly, there were no significant differences in average time to death between the groups. Telehealth may be an alternative method of access to pharmacist-led diabetes care that is slowly making its way into our healthcare systems as a permanent fixture.

Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial.

Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone. MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants. Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group. Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone. National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895).

Evaluation of the accuracy of seven intraoral scanners for the full dentate and partially edentulous complete-arch mandibular casts: An in vitro comparison

Statement of problemIntraoral scanners (IOSs) are widely used in dentistry, providing high accuracy in short-range scanning. Nevertheless, when scanning the full dental arch, it remains a challenge. Furthermore, there is a lack of studies reporting the differences in scan accuracy between dental arches with large-span mucosal areas and fully dentate casts or optimal IOS selection for different dental statuses. PurposeThis study aimed to evaluate the accuracy and scanning time of different IOSs for full dentate (FD) and partially edentulous (PE) casts with missing teeth in the #34–#44 range and to determine the IOSs with the optimal clinical adaptability and scanning accuracy for different complete-arch casts. Material and methodsReference scans of two complete-arch (FD and PE) casts were obtained using a laboratory scanner (Ceramill Map 600). Subsequently, the same casts were scanned ten times each by seven IOSs (3Shape Trios 3, CS3600, Planmeca Emerald, iTero Element 5D, Medit i500, BAMBOO B1, and Shining Aoralscan 3), and the scanning time was recorded. The test data were superimposed on the reference scans for the selected areas, and three-dimensional deviations between the reference and test casts (trueness), and between test casts (precision) were determined using reverse engineering software (Geomagic Wrap). The dataset was analyzed using a two-factor analysis of variance with post-hoc Bonferroni tests. ResultsTwo-factor analysis of variance revealed significant differences in accuracy and scanning time for different casts (P<0.001) and IOSs (P<0.001). For the FD cast, the i500 (0.35±0.11 mm trueness) and CS3600 (0.23±0.12 mm precision) performed worse than the remaining scanners. For the PE cast, the BAMBOO B1(0.89±0.58 mm trueness; 0.88± 0.48mm precision) performed worse than the remaining scanners. There were no differences in the accuracy of scanning between the Element 5D and Emerald for both cast types. However, the scanning time differed significantly between the different IOSs (P<0.001). Regardless of the cast type, the fastest and slowest scans were performed by the Trios3 and CS3600 scanners respectively. ConclusionsThe accuracy and scanning time differed between the different IOSs and types of complete-arch casts.

Prospective comparison of two methods for correct ureteral stent placement in pediatric laparoscopic pyeloplasty

Ureteral stent placement during laparoscopic pyeloplasty is a common procedure in pediatric patients. Although an apparently safe maneuver, ascending placement of the stent can lead to complex removal or repositioning reinterventions. In this study we compare two methods for intraoperative verification of correct positioning. Prospective observational study collecting data on laparoscopic pyeloplasties in pediatric patients in our center over three years. We carried out descriptive and univariate comparative analyses. Data were compared between ultrasound and reflux visualized by the catheter after intraoperative salineinjection into the bladder through the urethral catheter. We recorded time to catheter visualization in both ultrasonography and in reflux from the start of bladder instillation, as well as bladder volume at the time of placement verification with each method. Data were collected from 20 patients (15 male and 5 female) with a median age of 48 months. Pyeloplasty was successful in 100% of the sample (as observed by ultrasound and MAG-3), while one patient had postoperative leak requiring nephrostomy placement. Correct distal positioning of the ureteral stent could be verified by intraoperative ultrasound and reflux in all cases. Using reflux, the bladder volume needed to verify correct positioning exceeded the age-related maximum in half the cohort, while on ultrasound, the stent was visualized in the bladder without reaching the maximum bladder capacity for age in any case (p=0.02 comparing percentages). Likewise, mean time to verification was lower with ultrasound than with reflux (61.8s versus 115s), but without these differences reaching statistical significance (p=0.14). The present study is the first to compare two methods to verify the correct positioning of the ureteral stent in laparoscopic pyeloplasties in pediatric patients. Our results show that both intraoperative ultrasound and visualization of reflux are useful methods, although ultrasound requires a lower volume of saline instilled through the bladder catheter for verification. This work can be very useful for the daily clinical practice of urologists and pediatric surgeons. Both intraoperative ultrasound and visualization of reflux are useful methods to verify the correct positioning of the ureteral stent in laparoscopic pyeloplasty of pediatric patients. With ultrasound, a smaller volume is required to check for reflux. Although ultrasound is faster for verification, there are no differences in procedural times.

Efficacy of bone ring grafts for the reconstruction of alveolar ridge deficiencies: a systematic review. Part II: animal trials.

Bone ring (BR) grafts have been introduced to reconstruct alveolar ridge defects with simultaneous implant placement, but their clinical effectiveness remains undetermined. The aim of the current systematic review was to critically appraise evidence from animal studies regarding the effectiveness of BR grafts in alveolar ridge reconstruction and their variations under different surgical protocols. Electronic retrieval of six databases (MEDLINE, Embase, Cochrane Library, ScienceDirect, Web of Science, and Scopus) and citation search until 11 October 2023, for animal studies on bone augmentation employing BR grafts. The outcome variables were total bone area (BA), bone volume (BV), bone-implant contact (BIC), and histology. The protocol was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and prospectively registered with PROSPERO (CRD42023453949). Ten studies were included in the qualitative analysis according to the screening criteria. Two studies demonstrated favorable bone remodeling and osseointegration of the BR with both the implant and pristine bone. A comparative study between autogenous BRs and allogenic BRs reported a higher percentage of BA and BIC at 4 months of healing, but conflicting data were observed at 8 months. Another study indicated a significant advantage of autogenous BRs over bovine and biphasic ceramic BRs in terms of BA and BIC after 5 weeks. Three studies found that using collagen membranes did not significantly affect BA, BV, or BIC when used simultaneously with autogenous BRs during implant placement. Two studies evaluated one-stage and two-stage implant placement in conjunction with BR grafts, revealing similar levels of BA, BV, and BIC except for differences in total treatment time. Furthermore, one study found that the use of mucogingival junction incision and split-thickness flap significantly reduced the incidence of wound dehiscence compared with conventional incision and flap. Vertical bone augmentation surgery utilizing BR grafts with one-stage implant placement yielded histological and histomorphometric outcomes comparable to those achieved with two-stage implant placement or the additional application of collagen membrane.