Initial Date Research Articles

Comparison of the efficacy and safety of mini-percutaneous nephrolithotomy versus retrograde intrarenal surgery for the treatment of kidney stones in overweight or obese patients: a systematic review and meta-analysis.

To discuss the differences in the effectiveness and security of kidney stones in overweight or obese patients by mini percutaneous nephrolithotomy (MiniPCNL) and retrograde intrarenal surgery (RIRS). We exhaustively searched numerous databases, including PubMed, Embase, Web of Science, Cochrane Library, and CNKI, covering all records from their initiation date until September 2023. This included controlled trials focusing on the use of MiniPCNL and RIRS in the treatment of kidney stones in overweight or obese patients. The gathered data was then analyzed using the Review Manager 5.4 software. 9 studies including 1122 patients were included. Meta-analysis showed that: The MiniPCNL group had higher overall complications, grade I complications, length of hospital stay(LOS), first stone-free rate (SFR), and final SFR in obese patients, with no significant difference between the two groups in terms of operative time(OT), hemoglobin drop, and grade II complication rate. There were more overall complications, grade I complications, final SFR, and LOS with MiniPCNL in patients with stones > 2cm compared to no significant difference in grade II complications. MiniPCNL performed in the prone position had higher final SFR, less OT, hemoglobin drop, and no statistically significant difference in overall complications or LOS. Sheaths using > 14F had higher overall complication rates, final SFR, and LOS, and no statistical differences in OT and first SFR between the two modalities. In the MiniPCNL subgroup aged ≤ 50 years, there were higher first SFR, final SFR, and shorter OT, and in the MiniPCNL subgroup aged > 50 years, there were more OT, LOS, and hemoglobin drop, with no statistical difference in overall complications between the two groups. Our study showed that MiniPCNL in obese patients had higher initial SFR and final SFR, fewer procedures, but more postoperative complications, LOS, and grade I complications compared with RIRS. Similar results were seen in patients in the prone position, with stones > 2cm and age ≤ 50 years. [ https://www.crd.york.ac.uk/PROSPERO/ ], identifier PROSPERO (CRD42023467284).

GLP1-RA versus DPP4 inhibitors on cardiovascular outcomes: A three-year real-world analysis

Abstract Background Cardiovascular outcome trials of GLP1-RAs have massively impacted the clinical practice in the management of patients with type 2 diabetes. The cardiovascular protective properties of GLP1-RA compared to DPP4 have been demonstrated in an observational setting before, however recent methodological developments have enabled clinically relevant effect estimation. Aim This study aimed to evaluate the real-world cardiovascular outcomes of GLP1-RA versus DPP4 inhibitors in patients with type 2 diabetes and high cardiovascular risk. Methods In this study, we utilized the Danish nationwide registers to identify new users of GLP1-RA or DPP4 therapies from 2012 to 2022. Participants were required to be either at least 50 years of age and have one or more of the following conditions: hypertension, chronic obstructive pulmonary disease, cardiovascular disease, or chronic renal disease or be at least 60 years of age and have hypertension. Additionally, their glycated hemoglobin (HbA1c) levels needed to be 53 mmol/mol or higher within the year preceding their first prescription date for these therapies. The index date was defined as the initial prescription date, and comorbidities and medicine use were evaluated up to 10 years prior to this date. Individuals who had filled prescriptions for SGLT2 inhibitors within six months prior to their index date were excluded from the study. The outcome of interest was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE). Patients were followed for up to three years until MACE, all-cause mortality, emigration, or until the end of follow-up on December 31, 2022. To assess the three-year risk of MACE, the Aalen Johansson estimator was used. A casual inference framework was employed estimating the three-year average treatment effect using g-formula based on Cox regression with competing risk. Results A total of 26,190 individuals were included, with 19,494 initiating DPP4 inhibitor therapy and 6,696 initiating GLP1-RA therapy. The three-year risk of MACE was 8.56% (95% confidence interval [CI]: 8.11 to 9.00) for the DPP4 initiator group, compared to 4.76% (95% CI: 4.08 to 5.43) for the GLP1-RA initiator group. Emulating what would have happened had all included individuals initiated GLP1-RA treatment versus had all initiated treatment with DPP4, accounting for age, sex, income, education, degree of urbanization, diabetes duration, baseline hba1c level, co-medicine, and co-morbidities, we estimated an three-year average treatment effect of -2.05% (95% CI:-2.92;-1.18) , p-value<0.001) for GLP1-RA initiation versus DPP4 initiation for MACE. Conclusion Our findings suggest that GLP1-RA use is associated with a significantly lower risk of MACE compared to DPP4 inhibitors in a real-world population of patients with type 2 diabetes and high cardiovascular risk. This supports the cardiovascular protective role of GLP1-RA in clinical practice.

Intermittently scanned continuous glucosemonitoring compared with blood glucose monitoring is associated with lower HbA1c and a reduced risk of hospitalisation for diabetes-related complications in adults with type 2 diabetes on insulin therapies.

We assessed the impact of initiating intermittently scanned continuous glucose monitoring (isCGM) compared with capillary blood glucose monitoring (BGM) on HbA1c levels and hospitalisations for diabetes-related complications in adults with insulin-treated type 2 diabetes in Sweden. This retrospective comparative cohort study included adults with type 2 diabetes who had a National Diabetes Register initiation date for isCGM after 1 June 2017. Prescribed Drug Register records identified subgroups treated with multiple daily insulin injections (T2D-MDI) or basal insulin (T2D-B), with or without other glucose-lowering drugs. The National Patient Register provided data on hospitalisation rates. We identified 2876 adults in the T2D-MDI group and 2292 in the T2D-B group with an isCGM index date after 1 June 2017, matched with 33,584 and 43,424 BGM control participants, respectively. The baseline-adjusted difference in the change in mean HbA1c for isCGM users vs BGM control participants in the T2D-MDI cohort was -3.7 mmol/mol (-0.34%) at 6 months, and this was maintained at 24 months. The baseline-adjusted difference in the change in HbA1c for isCGM users vs BGM control participants in the T2D-B cohort was -3.5 mmol/mol (-0.32%) at 6 months, and this was also maintained at 24 months. Compared with BGM control participants, isCGM users in the T2D-MDI cohort had a significantly lower RR of admission for severe hypoglycaemia (0.51; 95% CI 0.27, 0.95), stroke (0.54; 95% CI 0.39, 0.73), acute non-fatal myocardial infarction (0.75; 95% CI 0.57, 0.99) or hospitalisation for any reason (0.84; 95% CI 0.77, 0.90). isCGM users in the T2D-B cohort had a lower RR of admission for heart failure (0.63; 95% CI 0.46, 0.87) or hospitalisation for any reason (0.76; 95% CI 0.69, 0.84). This study shows that Swedish adults with type 2 diabetes on insulin who are using isCGM have a significantly reduced HbA1c and fewer hospital admissions for diabetes-related complications compared with BGM control participants.

2023: a soil odyssey–HeAted soiL-Monoliths (HAL-Ms) to examine the effect of heat emission from HVDC underground cables on plant growth

BackgroundThe use of renewable energy for sustainable and climate-neutral electricity production is increasing worldwide. High-voltage direct-current (HVDC) transmission via underground cables helps connect large production sides with consumer regions. In Germany, almost 5,000 km of new power line projects is planned, with an initial start date of 2038 or earlier. During transmission, heat is emitted to the surrounding soil, but the effects of the emitted heat on root growth and yield of the overlying crop plants remain uncertain and must be investigated.ResultsFor this purpose, we designed and constructed a low-cost large HeAted soiL-Monolith (HAL-M) model for simulating heat flow within soil with a natural composition and density. We could observe root growth, soil temperature and soil water content over an extended period. We performed a field trial-type experiment involving three-part crop rotation in a greenhouse. We showed that under the simulated conditions, heat emission could reduce the yield and root growth depending on the crop type and soil.ConclusionsThis experimental design could serve as a low-cost, fast and reliable standard for investigating thermal issues related to various soil compositions and types, precipitation regimes and crop plants affected by similar projects. Beyond our research question, the HAL-M technique could serve as a link between pot and field trials with the advantages of both approaches. This method could enrich many research areas with the aim of controlling natural soil and plant conditions.

Effectiveness of endoscopic papillectomy with stent placement in pancreatic and bile ducts for treating duodenal papillary adenoma: a retrospective study

BackgroundDuodenal papillary adenoma, a potentially malignant benign tumor is primarily treated with endoscopic papillectomy. Despite its efficacy, endoscopic papillectomy has a high complication rate. This study investigates whether pancreatic duct and common bile duct stent placement can mitigate these complications.MethodsIn a retrospective observational analysis, 79 patients with duodenal papillary adenoma, treated with endoscopic papillectomy at our center, were studied. The cohort included patients who underwent endoscopic papillectomy with no stents placement, common bile duct stent placement alone, pancreatic duct stent placement alone, or stents placement in both ducts. We assessed the outcomes of endoscopic papillectomy, including complete resection rate and recurrence rate as the primary and secondary outcomes respectively. In the meantime, the incidence of complications were also analysed as the safety outcomes.ResultsComplete resection rates did not significantly differ between patients with or without stent placement (85.7% P group vs. 89.2% N-P group, P = 0.64). Early complication rates were similar across groups. However, significant reduction in common bile duct stenosis was observed in the stenting group (0% B group vs. 10.5% N-B group, P = 0.03). Furthermore, stent placement correlated with lower adenoma recurrence rates during follow-up (2.4% P group vs. 16.2% N-P group, P = 0.03; 2.4% B group vs. 15.8% N-B group, P = 0.04).ConclusionsPancreatic duct and common bile duct stent placement in endoscopic papillectomy may decrease late complications, particularly common bile duct stenosis, and reduce the recurrence of duodenal papillary adenoma.Trial registrationThis study received approval from the Institutional Review Board and Ethics Committee of Beijing Friendship Hospital (Approval No. BFHHZS20230203), and retrospectively registered in www.ClinicalTrials.gov (NCT06301048, Initial Release date: 02/18/2024, Last Public Release date: 03/03/2024).

Establishing Climate Change on Rainfall Trend, Variation and Change Point Pattern in Umuahia, Nigeria

This study investigates the prevailing conditions of changing climatic trends and change point dates in Umuahia, Nigeria, using daily annual maximum series (AMS) rainfall data spanning 31 years. The Indian Meteorological Department (IMD) was employed to downscale the time series data into durations ranging from 5 minutes to 24 hours. Mann-Kendall (MK) trend and Sen's Slope Estimator (SSE) tests revealed a statistically significant increasing trend across all durations. The Sen's Slope magnitude ranged from 0.1373 mm/year for 5-minute duration to 0.9045 mm/year for 24-hour duration, corresponding to a variation rate of 9.05 mm/decade for the 24-hour duration. Trend change-point analysis, utilizing Distribution-free CUSUM and Sequential Mann-Kendall tests, identified 2002 as the initial rainfall change-point date. These results provide robust evidence of positive changing climatic conditions for rainfall in Umuahia, indicating that non-stationary Intensity-Duration-Frequency (IDF) modelling may be more appropriate for flood risk management and urban planning in this area.

Effect of non-invasive brain stimulation on post-stroke cognitive impairment: a meta-analysis.

Previous studies have suggested that repetitive transcranial magnetic stimulation (rTMS) may be an effective and safe alternative treatment for post-stroke cognitive impairment (PSCI). Similarly, the application of transcranial direct current stimulation (tDCS) during stroke rehabilitation has been shown to improve cognitive function in PSCI patients. However, there have been conflicting results from some studies. Therefore, this study aims to conduct a meta-analysis to evaluate the effects of tDCS and rTMS on PSCI. The meta-analysis search for articles published from the initial availability date to 5 February 2024 in databases. The extracted study data were entered into STATA 12.0 software for statistical analysis. This meta-analysis provides evidence that both rTMS and tDCS have a positive impact on general cognitive function in PSCI patients [immediate effect of rTMS: standard mean difference (SMD) = 2.58, 95% confidence interval (CI) = 1.44 to 3.71; long-term effect of rTMS: SMD = 2.33, 95% CI = 0.87-3.78; immediate effect of tDCS: SMD = 2.22, 95% CI = 1.31-3.12]. Specifically, rTMS was found to significantly improve attention, language, memory, and visuospatial functions, while it did not show a significant therapeutic effect on executive function (attention: SMD = 3.77, 95% CI = 2.30-5.24; executive function: SMD = -0.52, 95% CI = -3.17-2.12; language: SMD = 3.43, 95% CI = 1.50-5.36; memory: SMD = 3.52, 95% CI = 1.74-5.30; visuospatial function: SMD = 4.71, 95% CI = 2.61-6.80). On the other hand, tDCS was found to significantly improve executive and visuospatial functions but did not show a significant improvement in attention function and memory (attention: SMD = 0.63, 95% CI = -0.30-1.55; executive function: SMD = 2.15, 95% CI = 0.87-3.43; memory: SMD = 0.99, 95% CI = -0.81-2.80; visuospatial function: SMD = 2.64, 95% CI = 1.04-4.23). In conclusion, this meta-analysis demonstrates that both rTMS and tDCS are effective therapeutic techniques for improving cognitive function in PSCI. However, more large-scale studies are needed to further investigate the effects of these techniques on different cognitive domains in PSCI.

ANALYSING THE RATE OF RECURRENCE AND LEPTOMENINGEAL DISEASE IN POSTERIOR FOSSA BRAIN METASTASES FOLLOWING POSTOPERATIVE RADIOTHERAPY- SINGLE CENTRE EXPERIENCE

Abstract AIMS The management of posterior fossa brain metastases is complex and necessitates a multidisciplinary approach involving neurosurgeons and oncologists. Post-operative radiotherapy (PORT) to surgical cavity has demonstrated positive oncologic outcomes as well as preserving cognitive function when compared to conventional whole brain radiation therapy. However, larger post-operative volumes in posterior fossa and greater target volume uncertainty due to presence of pseudomeningocele may result in an increased risk of local recurrence (LR) and leptomeningeal disease (LMD). The aim of this retrospective single centre study was to determine the rates of LR and LMD in patients with posterior fossa metastases who underwent PORT to surgical cavity. METHOD Retrospective analysis of data of patient who underwent PORT in between 2017-2022, for posterior fossa brain metastases at our centre. Clinical, imaging and radiotherapy data was collected from electronic medical records. Statistical analysis was performed using SPSS Statistics version 28.0.1. RESULTS We identified 42 patients meeting the study criteria. The median age of the patients was 60.5 years. 71.4% of patients were females, while 28.6% were males. 52.4% of patients had pseudomeningocoele on their radiotherapy planning scans. The median time gap between the date of surgery and initiation of radiotherapy was 34.5 days. 20 out of 42 (47.6%) patients had local recurrence of a posterior fossa brain metastasis and 7 out of 42 (16.7%) patients developed LMD. Out of 7 patients with LMD, 4 patients had pseudomeningocoele present at the time of PORT. The timing of radiotherapy after surgery (≤4 weeks or >4 weeks) showed no statistically significant impact on LR (p-value: 0.413, log-rank test). CONCLUSION The risk of LR remains high despite PORT. This study highlights the challenges in management of posterior fossa metastases. High LR and LMD rates underscore the need for improved treatment strategies.

Comparison of live birth rates following the transfer of day-6 blastocysts on the 6th versus 7th day of progesterone exposure in hormone replacement treatment–frozen embryo transfer cycles

Objective: The duration of progesterone exposure is critical for establishing and maintaining a pregnancy in hormone replacement treatment (HRT)–frozen embryo transfer (FET) cycles. This study compared the live birth rates (LBRs) of patients undergoing day-6 warmed blastocyst transfer on either the 6th or 7th day of progesterone administration in HRT-FET cycles.Methods: A retrospective cohort study was conducted using data from the central registry of Indira IVF Hospital Private Limited. In total, 2,633 patients who underwent day-6 blastocyst transfer cycles with HRT-FET were identified. The cycles were categorized based on the timing of the day-6 blastocysts transfer: P+6 vs. P+7 (initiation date: P+1). Propensity scores were calculated. The primary outcome measure was the LBR.Results: Following propensity score matching, a total of 1,401 patients were included in the final analysis (P+6: n=1,212; P+7: n=189). The number of previous attempts was significantly higher in the P+6 group, whereas the rate of preimplantation genetic testing for aneuploidy was significantly higher in the P+7 group. The LBRs were 59.2% and 54.5% in the P+6 and P+7 groups, respectively (p=0.21). Multivariate regression analysis revealed that the number of previous in vitro fertilization attempts (odds ratio [OR], 3.246; 95% confidence interval [CI], 2.429 to 4.337; p<0.001), the number of blastocysts transferred (OR, 2.011; 95% CI, 1.461 to 2.768; p<0.01), and endometrial thickness on the day of progesterone initiation (OR, 1.143; 95% CI, 1.022 to 1.28; p=0.02) were independent predictors of live birth.Conclusions: The LBRs were comparable in patients who underwent day-6 warmed blastocyst transfer on day 6 or 7 post-progesterone initiation in HRT-FET cycles.

The ‘Recency’ of Data Used in Anti-dumping Investigations in South Africa

The Agreement on the Implementation of Article VI of the General Agreement on Tariffs and Trade 1994 does not specify how recent the data must be to the date of initiation of the anti-dumping investigation. In South Africa, dumping is regulated by the International Trade Administration Act 71 of 2002 and the Anti-Dumping Regulations of 2003 (ADR). The ADR states that the period of investigation for dumping must end at least six months before the date of initiation of the investigation. This issue is significant since most dumping instigations in South Africa turn on the calculation of the margin of dumping. This article explores the requirement of the ‘recency’ of the data that is used in an anti-dumping determination in South Africa. As a general rule, it is accepted that an anti-dumping investigation employs historical data, and use of that information does not in itself make the data unreliable. However, it is required that the most recent data are used when it is available rather than outdated data. In essence, the data used must be inherently time-linked to current dumping. JEL Codes: F10, F13, F14, F17, F19

6866 Real-world implications and limitations of GLP-1 prescriptions in adolescents

Abstract Disclosure: G. Castano: None. S. Sisley: None. Background: Glucagon-like-peptide-1 agonists (GLP1), approved for adolescents ≥ 10 years in 2019 for type 2 diabetes (T2D) and ≥ 12 years in 2020 for obesity, require adequate dose titration and have known side effects. There is little information on insurance approval, adherence to titration regimens, or the side effects of liraglutide in clinical practice. Methodology: We performed a retrospective review of all patients <18 years old who were prescribed GLP-1 at a large children’s hospital. We collected demographic information, prescription orders, insurance approval, and drug initiation dates. For individuals who completed at least 26±8 weeks of treatment, we also collected dose titration, side effects, and insulin doses. Results:599 patients were prescribed GLP-1 from 2019 to 2023, with a mean age of 14.99±2.1 years, 58% female, 58% public insurance, and 74% (n=442) with T2D. The cohort was comprised of 63% White, 30% Black, and 2.3% Asian individuals, with 52% of Hispanic ethnicity. 90% of prescriptions were for liraglutide, and 10% for other GLP1 analogs, including exenatide, dulaglutide, and semaglutide. Insurance denied 41% (n=244) of prescriptions, with more denials in those without T2D, 64% vs 32% in patients with T2D.Whereas private insurance denied more prescriptions than Medicaid in patients with T2D (54% vs 27%), the reverse was true for patients without T2D ( 55% private vs 69% Medicaid). Patients lost to follow-up in the first 3 months accounted for 22% (n=135) of the cohort, even though 48% (n=66) of those patients had insurance approval.Those who had insurance approval and took liraglutide for at least 26 weeks accounted for 34% (n=204) of the cohort. Of the patients with T2D, 50% (n=95) titrated to 1.8mg by their first follow-up appointment (1-3 months after prescription start), 33% (n=62) by 6 months, and 17% (n=32) never reached 1.8mg. In patients prescribed a higher dose of liraglutide (3.0 mg daily), 42% (n=8) titrated to 3mg over 5 weeks as prescribed, and 52% (n=10) never reached 3mg, with only one of them not reaching 1.8 mg.Most patients (82%, n=169) had no side effects documented in their charts. From those with side effects reported, GI problems (nausea, vomiting, diarrhea) were noted in 12% (n=25), and 2% (n=4) reported injection site reactions. Side effects that required medication discontinuation included hypoglycemia (n=1), mild pancreatitis (n=1), and severe pancreatitis (n=2). Conclusion: In clinical practice, despite FDA approval, insurance coverage of liraglutide is limited. Almost half of the patients require extra time to reach full doses of liraglutide, with one-third never reaching full treatment doses. Severe pancreatitis may be a previously unpublished side effect. More research is needed to understand how real-world adherence and side effects of liraglutide affect clinical outcomes. Presentation: 6/1/2024

Predation of eggs and incubating females in willow ptarmigan Lagopus l. lagopus

Nest predation is a major cause of reproductive loss in many ground-nesting birds. During 15 consecutive years the predation of nests and females throughout the incubation season were recorded in a willow ptarmigan Lagopus l. lagopus population in central Norway. The temporal predation patterns, factors affecting the predation probability and age-specific nesting patterns in this species were studied. There was a large annual variation in predation rate of both nests (0-50%) and incubating females (0-29%) in this area during the study period. The mean annual predation rate of nests (15%) was on average three times higher than the predation of incubating willow ptarmigan females (5%). Predation rate was not constant throughout the incubation season, and the nest predation rate increased with increasing number of available nests. The predation events started after the mean initiation day of incubation, and coincided with the highest number of available nests. None of the parameters we tested in a logistic regression analysis (physical condition, nest cover, experience and date for initiation of egg-laying) could predict the predation probability of nests and incubating females. However, “good” nest cover tended to have some predictive value on the predation probability. Yearling incubating females had significantly lower physical body condition than adults, and also there were differences in choice of nest site in relation to cover between the two age groups. Initiation of egg-laying in adult females tended to be distributed more evenly over the season, whereas yearling females had a more aggregated egg-laying pattern, compared to adults.

Accelerating access: The power of gold carding in reducing treatment delays.

114 Background: Delays in time to treatment initiation (TTI) for cancer patients have been shown to impact survival/mortality/outcomes, and cause patient distress. The process of obtaining prior authorizations (PA) often leads to significant treatment delays, affecting patient outcomes and posing administrative challenges for healthcare providers. PAs have become a ubiquitous part of modern healthcare, aimed at ensuring appropriate utilization of medical treatments and reducing costs. In recent years, the concept of gold carding (GC), a practice where payers waive PA on services and prescription drugs ordered by providers with a proven track record of PA approvals based on guideline concordance or pathway adherence, has gained attention as a potential solution to provide administrative relief to all stakeholders affected by the PA process. This abstract seeks to explore the impact of GC on TTI for a large multi-site community-based oncology practice in The US Oncology Network having a GC contract with a regional payer. Methods: Using administrative claims data from 2021 to 2023, we derived a population of cancer patients who initiated chemotherapy as their first treatment, calculated the TTI (time from the date of first consultation to the date of treatment initiation), and compared TTI between GC and non-GC patients. Results: The average TTI for 4,836 patients that met the inclusion criteria was 26.3 days. Patients initiating therapy under a GC eligible payer coverage started therapy 4.5 days earlier (22.13 days vs 26.68 days, p<0.00001, Kruskal–Wallis test). 80% of GC eligible patients started their treatment within 30 days of their initial consultation. Conclusions: The findings indicate that gold carding has the potential to expedite the time to treatment initiation for cancer patients. Further research is needed to quantify the cost savings, patient and provider satisfaction, and other intangible benefits from GC. Gold carding offers a viable approach to balance guideline concordant care with lowering administrative burden. We enthusiastically support legislative reforms that encourage gold carding and selectively implement prior authorization requirements based on stratification of health care providers’ performance and adherence to evidence-based medicine. Patient Count Average TTI (days) GC 401 22.13 Commercial 217 21.13 Managed Medicare 184 23.32 Non-GC 4435 26.68 Commercial 1610 25.41 Managed Medicare 1405 27.37 Medicare 959 26.48 Managed Medicaid 254 29.06 Medicaid 112 29.54 All Other 95 30.15

Optimising outcomes for frail patients with oesophagogastric (OG) cancers: The impact of dose reduction and comprehensive geriatric assessment.

303 Background: Delivery of appropriate management of elderly patients with OG malignancies in the palliative setting remains challenging and unpredictable. Incidence of OG cancers increases markedly with age, and there are growing numbers of elderly, frail and medically complex patients referred to oncology services for treatment. An adaptive approach to their management is required, tailored to their complex medical needs. The GO2 study sought to optimise chemotherapy delivery in this cohort and demonstrated that upfront dose reductions do not reduce progression-free survival in OG cancers. We analysed the treatment and outcome of elderly patients undergoing first-line palliative chemotherapy at our centre, with or without comprehensive geriatric assessment (CGA). Methods: We retrospectively analysed the records of patients over the age of 75 treated at our centre between May 2011 and March 2023. Progression-free survival (PFS) was calculated from the date of treatment initiation to date of radiological progression, or 19 th March 2024 if patients had not progressed. Overall survival (OS) was calculated from treatment initiation to date of death per the electronic health record, or 19 th March 2024 if patients had not died. Grade 3 (G3) toxicities and dose reductions (DRs) were identified from medical records. Statistical analyses were performed using R v4.3.3. Results: 82 patients were included in the analysis. Overall median PFS was 6.5 months (1-107 months) and median OS was 10 months (1-107 months). Patients who qualified for chemotherapy with immunotherapy had improved PFS (median 16 months, range 2-27 months) and OS (median 16 months, range 10-27 months). G3 toxicities were increased in patients without upfront DR (44% vs. 30%). The most significant predictor for survival in multivariate analysis was performance status (PS), which was associated with worse PFS (hazard ratio 2.66, range 1.35–5.35, p = 0.004), and OS (hazard ratio 6.13, range 2.79–13.44, p < 0.001). Age was not associated with survival. Consistent with the GO2 trial, there was no association between upfront DR and PFS (p = 0.13) or OS (p = 0.72). 38% of patients underwent CGA as part of their workup for chemotherapy. These patients were more likely to have upfront DR (61% vs. 47%). In this cohort, G3 toxicity rates were comparable in patients with PS 0-1 who underwent CGA (39% vs. 35%). In patients with PS ≥ 2, G3 toxicity rates were higher in those who did not undergo CGA (67% vs. 30%). Conclusions: Upfront DR in elderly patients is safe and does not impact survival but does reduce the burden of toxicity. PS, rather than age, is a better predictor of survival and treatment outcome. CGA may help mitigate toxicity burden in patients with poor performance status.

The cancer diagnostic clinic: A rapid access clinic to improve outcomes for patients with a suspected cancer diagnosis.

77 Background: Patients with suspected cancer often face challenges navigating complex health systems, resulting in delays in diagnosis and time to treatment, which are associated with adverse outcomes and patient dissatisfaction. To improve patient access and bridge this healthcare gap, the Cancer Diagnostic (CDx) clinic was established to streamline the evaluation for patients with a new suspected cancer. The CDx clinic prioritizes expedited cancer evaluation, timely and accurate diagnostic testing, and transition of care to subspecialty Oncologists, to improve the patient experience and cancer-related outcomes. Methods: Leaders in the Abramson Cancer Center (ACC) initiated a pilot project to facilitate timely appointments to Oncologists for patients in the Emergency Department with a new suspected cancer. Patient access lead time and time to diagnosis and treatment were tracked. This pilot was formally expanded across the health system to become the CDx clinic for eligible adult patients with suspicious symptoms, lab abnormalities, or imaging findings concerning for cancer. Patient data was extracted using an EMR-based form and supplemented by chart review. Study period was March 2023 to April 2024 and included socio-demographics, cancer subtype, referral type, time from referral to new patient appointment (access lead time), time from first appointment to diagnosis and treatment (surgery, systemic or radiation therapy), patient retention, complications, and mortality. Results: Over 12 months, 108 patients were evaluated in the CDx clinic. Most patients were male (56%), White (58%), and non-residents of Philadelphia County (65%). There were 8 referrals (range: 6-13) per month with the majority of patients from external referrals (60.2%). Compared to baseline, CDx resulted (median pre/post in days) in similar time to first appointment (7 vs. 7 days), improved time to diagnosis (21 vs. 8 days), and improved time to treatment (42 vs. 29.5 days). 71 patients were diagnosed with cancer with Gastrointestinal (47%) and Thoracic (24%) cancers being most common. 98.6% (70/71) of patients were retained at ACC and transitioned to subspecialty care. 80.3% (57/71) of patients received cancer-directed treatment. After the initial consult date, for the patients diagnosed with cancer, there were 4 ED visits and 20 hospitalizations within 30 days, 19 hospice enrollments, and 16 deaths. Conclusions: The CDx clinic has been a valuable resource for patients with suspected cancer by optimizing time to diagnosis and time to treatment. Additional navigation pathways are underway to expand the CDx patient population to target a more underserved population in an effort to promote health equity in cancer care.

Real-world event-free survival (rwEFS) and overall survival (rwOS) in elderly patients with resected locoregionally advanced head and neck squamous cell carcinoma (LA HNSCC) in the US.

375 Background: Surgery followed by adjuvant radiotherapy (RT) ± systemic therapy (ST) is often recommended for patients (pts) with resectable LA HNSCC with curative intent. This study assessed rwEFS, rwOS, and the correlation between rwEFS and rwOS in elderly pts (≥66 years old at diagnosis) with resected LA HNSCC to better understand unmet needs and inform future clinical trial designs. Methods: This retrospective cohort study utilized linked SEER-Medicare data (2007–2019). Pts with newly diagnosed stage III-IVB (AJCC 6/7th) LA HNSCC (larynx, hypopharynx, oral cavity, or oropharynx) who underwent surgery as primary treatment within 4 months of diagnosis were included. Index date was defined as the primary treatment initiation date. rwEFS was defined as time from index date to first recurrence or death, whichever occurred first. rwOS was defined as time from index date to death. Baseline (12 months prior to index date) factors associated with rwEFS and rwOS were assessed using a Cox proportional hazards model. Correlation between rwEFS and rwOS was assessed using the normal scores rank correlation. Results: A total of 526 pts met the selection criteria (median follow-up: 24.3 months). The median (interquartile range) age at initial diagnosis was 72.6 (68.6-78.8) years, 63.9% were male, 79.5% were white, and 6.1% had stage IVb disease. HPV status and smoking status were not available. Over half of pts received adjuvant RT ± ST following resection. Median rwEFS and 5-year rwEFS were 8.0 months (95% CI: 6.4, 9.2) and 16.3%, respectively. Median rwOS was 32.6 months (95% CI: 26.2, 42.3), with a 5-year rwOS of 37.8%. Older age, primary hypopharynx disease (vs. oropharynx), and higher Charlson Comorbidity Index scores were associated with significantly shorter rwOS. Additionally, surgery followed by RT ± ST (vs. surgery only) and less advanced tumor stage were associated with significantly longer rwEFS and rwOS. The correlation between rwEFS and rwOS was moderate and significantly positive (r = 0.68 [95% CI: 0.62, 0.74], p<0.001). Conclusions: Real-world survival outcomes were modest among elderly pts with surgically managed LA HNSCC, highlighting a population with significant unmet need where more effective therapies are needed. rwEFS was found to have a significant, positive correlation with rwOS, supporting EFS as a predictor for OS in this patient population. Primary treatment and association with rwEFS and rwOS. 1,2,3 Treatment Pattern N (%) HR (95% CI) - rwEFS HR (95% CI) - rwOS Surgery Only 144 (27.4%) - - Surgery followed by RT 172 (32.7%) 0.60 (0.47, 0.78)* 0.77 (0.58, 1.03) Surgery followed by RT + ST 128 (24.3%) 0.49 (0.36, 0.66)* 0.50 (0.34, 0.72)* RT or RT+ST followed by surgery 66 (12.5%) 0.66 (0.47, 0.93)* 0.80 (0.55, 1.18) 1 Treatment modalities with N<11 were not reported. 2 *denotes p < 0.05. 3 denotes reference group.

Toxicity surveillance in FDA pivotal registration trials for immune checkpoint inhibitors: Are we missing the mark?

215 Background: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for a multitude of malignancies, leading to prolonged survival and durable responses. Despite this, a significant number of patients will develop immune-related adverse events (irAEs) with significant associated morbidity and mortality. A retrospective study has previously demonstrated that 28% of patients can develop IrAEs from 6 months up to 2 years after starting therapy (1). Surveillance for toxicity is essential for understanding the long-term risk associated with ICIs. We aimed to analyze the reporting timeframes used in clinical trials of immuno-oncology agents leading to FDA approval. Methods: In this retrospective study, we interrogated the HemeOnc knowledgebase to curate a list of all clinical trial publications leading to FDA approval from 2011 to 2024. We manually selected from this list any trial including an immune checkpoint inhibitor either as monotherapy or in combination with another systemic therapy. The adverse event follow-up time was then extrapolated by manually reviewing the trial publication, supplemental materials or the trial protocol depending on where this information was listed. All trials were categorized based on trial initiation dates. Results: We identified 175 clinical trials leading to FDA approvals, with trial initiation dates ranging from 2004 to 2019. 165 trials were included in the analysis with 10 being excluded due to lack of language regarding follow-up. 62% of the trials included were Phase III trials with the remaining 38% Phase I/II trials. The median follow-up days for all trials across this timeframe was 90, with a range of 28 to 135. The median follow-up time for AE monitoring increased by nearly 30%, rising from 70 days in 2004 to 90 days in 2013. Subsequently, we observed a consistent median follow-up time of 90 days (28 to 130 days) from that point onward, with no further increase. Conclusions: To our knowledge this is the first systematic review of IrAE monitoring in clinical trials leading to FDA approval. In our study we revealed that, despite advancements in the understanding of IrAEs and their potential for late presentation, registration trials leading to regulatory approval remain inadequately designed to capture chronic and delayed immunotherapy toxicities. As these therapies advance into earlier stages of disease with longer life expectancy, it will be critical for regulatory bodies, study sponsors, and trial investigators to either redesign clinical trials or for there to be an alternative method that comprehensively captures the incidence and pattern of late-presenting toxicities. 1. Durbin, ASCO 2023.

Initiation of Intermittently Scanned Continuous Glucose Monitoring Is Associated With Reduced Hospitalization for Acute Diabetes Events and Cardiovascular Complications in Adults With Type 1 Diabetes.

We assessed the impact of intermittently scanned continuous glucose monitoring (isCGM) compared with blood glucose monitoring (BGM) on rates of hospitalization for metabolic and vascular complications of diabetes and on HbA1c levels for adults with type 1 diabetes. This retrospective study using data from the Swedish National Diabetes Register and the Swedish National Patient Register comprised adults with type 1 diabetes and an isCGM initiation date after 1 June 2017 and matched control individuals using BGM. Hospital admission rates were calculated per 100 person-years of follow-up. We identified 11,822 adults with type 1 diabetes and an isCGM index date after 1 June 2017 and HbA1c baseline values 3-8 months prior to the index date. Compared with 3,007 BGM users, isCGM users had a significantly lower relative risk of hospitalization for hypoglycemia (0.32; 95% CI 0.14, 0.74), diabetic ketoacidosis (0.55; 0.35, 0.87), stroke (0.48; 0.37, 0.64), acute myocardial infarction (0.64; 0.46, 0.91), atrial fibrillation (0.59; 0.38, 0.94), heart failure (0.25; 0.16, 0.39), peripheral vascular disease (0.21; 0.07, 0.62), kidney disease (0.48; 0.35, 0.66), or hospitalization for any reason (0.32; 0.29, 0.35). Compared with BGM users, change in mean HbA1c for isCGM users was -0.30% (-3.3 mmol/mol) at 6 months and -0.24% (-2.6 mmol/mol) at 24 months (both P < 0.001). This study shows that adults with type 1 diabetes in Sweden who initiate isCGM have significantly reduced hospitalization rates for acute diabetes events, kidney disease, and cardiovascular complications, along with improved glucose control, compared with BGM users.

Clinical and Sociodemographic Characteristics of New Residents of Assisted Living: A Nested Case-Control Study

ObjectiveTo examine transitions to an assisted living facility among community-dwelling older adults who received publicly funded home care services. DesignNested case-control study. Setting and ParticipantsLinked, population-level health system administrative data were obtained from adults aged 65 years and older who received home care services in Ontario, Canada, from April 1, 2018, to December 31, 2019. New residents of assisted living were matched on age, sex, and initiation date of home care (± 7 days) to community-dwelling home care recipients in a 1:4 ratio. MethodsClinical and functional status, health service use, sociodemographic variables, and community-level characteristics were examined; conditional logistic regression was used to model associations with a transition to an assisted living facility. ResultsThere were 2427 new residents of assisted living who were matched to 9708 home care recipients [mean (SD) age 85.5 (6.02) years, 72% female]. Most of the new residents were concentrated in urban communities and communities with higher income quintiles. New residents had an increased rate of physician-diagnosed dementia [adjusted hazard ratio (aHR), 1.28; 95% CI, 1.14–1.43], mood disorders (aHR, 1.17; 95% CI, 1.05–1.29), and cardiac arrhythmias (aHR, 1.19; 95% CI, 1.07–1.32). They also had higher rates of mild cognitive impairment (aHR, 1.43; 95% CI, 1.24–1.66), 2 or more falls (aHR, 1.29; 95% CI, 1.11–1.51), participation in activities of long-standing interest in the past 7 days (aHR, 1.29; 95% CI, 1.11–1.50), and a lower rate of a spouse or partner unpaid caregiver vs a child (aHR, 0.66; 95% CI, 0.56–0.79). Conclusions and ImplicationsNew residents of assisted living were mostly women, were cognitively impaired, had clinical comorbidities that could increase their risk of injuries, and had caregivers who were their children. These findings stress the importance of upscaling memory and dementia care in assisted living to address the needs of this population.

The effects of age and frailty on the risks of end-stage renal disease, death, and severe infection in older adults with antineutrophil cytoplasmic antibody-associated vasculitis: a retrospective cohort study

Frailty, a measure of biological age, might predict poor outcomes in older adults better than chronological age. We aimed to compare the effect of age and frailty on end-stage renal disease, death, and severe infection within 2 years of diagnosis in older adults with incident antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This retrospective cohort study included individuals aged 65 years or older from the Mass General Brigham ANCA-associated vasculitis cohort in the USA who were treated between Jan 1, 2002, and Dec 31, 2019. Individuals with a diagnosis of eosinophilic granulomatosis with polyangiitis were excluded from the analysis. Baseline frailty was measured with a claims-based frailty index using data collected in the year before the date of treatment initiation in individuals with at least one health-care encounter before baseline; individuals who did not have an encounter within the 12 months before baseline were classified as pre-frail. Incidence rates of end-stage renal disease or death and severe infections (ie, infections leading to hospital admission or death) at 2 years were estimated, and multivariable analyses were performed to compare the association of age and frailty with these outcomes. Cumulative incidence rates and an additive interaction analysis were used to assess the interaction of age and frailty groupings. Of the 234 individuals included, 136 (58%) were women, 98 (42%) were men, 198 (85%) were White, and 198 (85%) were positive for myeloperoxidase-specific ANCA. Frailty was present in 25 (22%) of 116 individuals aged 65-74 years and 44 (37%) of 118 aged 75 years or older. In the multivariable analysis, an age of 75 years or older was associated with an increased risk of end-stage renal disease or death (hazard ratio [HR] 4·50 [95% CI 1·83-11·09]), however, frailty was not (1·08 [0·50-2·36]). Both an age of 75 years or older (HR 2·52 [95% CI 1·26-5·04]) and frailty (8·46 [3·95-18·14]) were independent risk factors for severe infections. The effect of frailty on the incidence of end-stage renal disease or death was greater in individuals aged 65-74 years (frail vs non-frail or pre-frail incidence rate 7·5 cases vs 2·0 cases per 100 person-years) than in those aged 75 years or older (13·5 cases vs 16·0 cases per 100 person-years). The effect of frailty on the incidence of serious infections varied by age, with large differences observed among both individuals aged 65-74 years (frail vs non-frail or pre-frail incidence rate 38·9 cases vs 0·8 cases per 100 person-years) and individuals aged 75 years or older (61·9 cases vs 12·3 cases per 100 person-years). Despite the observed differences between the age groups, the additive interaction terms were not statistically significant for either frailty and end-stage renal disease or death (p for interaction=0·276) or frailty and serious infections (p for interaction=0·650). Adults with ANCA-associated vasculitis aged 75 years or older had a higher incidence of end-stage renal disease, death, and severe infections within 2 years of diagnosis than adults aged 65-74 years. Frailty, an approximation of biological age, was a risk factor for severe infection. Assessment beyond chronological age could better inform management decisions in older adults with ANCA-associated vasculitis. National Institutes of Health and National Institute of Arthritis and Musculoskeletal and Skin Diseases.