Initiation Of Treatment In Patients Research Articles

Abstract PO4-17-04: CDK 4/6 inhibitor switching patterns in Swedish patients with metastatic breast cancer: 5-year update from the SIRI study

Abstract Background: CDK 4/6 inhibitors (CDK 4/6i) combined with endocrine therapy is a well-established treatment option in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). However, there is limited evidence on switching patterns within this class of drugs. The Swedish Ibrance Registries Insights (SIRI) study investigated CDK 4/6i switching patterns in real-world setting using a nationwide cohort of MBC patients. Methods: This was a retrospective study utilizing population-based Swedish Health Data Registers. The overall cohort included all breast cancer patients ≥ 18 years with ≥ 1 dispensation of palbociclib from January 2017 – June 2022. This subgroup analysis focused on patients with ≥ 1 dispensation of either ribociclib or abemaciclib in addition to palbociclib. Minimum follow-up was 3 months. CDK 4/6-I sequencing patterns in total and over time as well as time from the first CDK 4/6i to the subsequent, was investigated. No information on the reason for switching was available. Results: Out of a total 2314 patients with ≥ 1 dispensation of palbociclib, 256 patients (11%) had ≥ 1 dispensation of either ribociclib or abemaciclib, either prior to (60% of cases) or following (40 % of cases) palbociclib treatment. The share of patients with dispensation of > 1 CDK 4/6i increased over the study period from 7% of the patients initiating treatment in 2017 to 15% in 2021. Of the total 2161 patients initiating CDK 4/6i treatment on palbociclib, about 5% were subsequently prescribed another CDK 4/6i. The median age at treatment initiation in patients with > 1 dispensed CDK 4/6-i was similar to the overall study cohort (67.1 vs 68.4 years). Half of the patients identified with > 1 CDK 4/6i were initiated on ribociclib and prescribed palbociclib subsequently. The second and third most common switches were palbociclib to abemaciclib (25%) and palbociclib to ribociclib (10%), respectively. Seven patients received all three CDK 4/6i. In terms of time to subsequent CDK 4/6i, 108 patients (42%) were prescribed a subsequent CDK 4/6i within three months of treatment initiation with ribociclib-palbociclib being the most common sequence in 74 patients whereas 17%, 8%, and 4% of switches happened 4-6, 7-9, and 10-12 months after treatment initiation, respectively. Seventy-two patients (28%) had a dispensation of a subsequent CDK 4/6i more than 12 months after initiation of the first CDK 4/6i, with palbociclib-abemaciclib being the most common switch. Conclusions: A relatively high proportion of Swedish patients treated with CDK4/6i is switched from one to another CDK 4/6i soon after treatment initiation, implying that this strategy might be applied mainly, but not solely, due to adverse events. The increased trend over time might be associated with the regulatory approval of new CDK4/6i over time. Future studies should focus on the potential impact of switching CDK 4/6i on treatment effectiveness and toxicity as these issues have yet not been clarified. Declaration of Interest: This study is sponsored by Pfizer. AV has reported receiving research funding from Roche. HL has reported receiving consultant/advisory fees from Lilly, Novartis, Daichii, Pfizer, MSD, Pierre Fabre, Astra-Zeneca and research funding from Roche. MJ and DN are employees of Pfizer. RL and ML are employees of Quantify Research and were paid consultants to Pfizer for this research. Table. Table. Citation Format: Henrik Lindman, Antonis Valachis, Rosa Lauppe, Mathias Lilja, Daniel Nyqvist, Maria Jakobsson. CDK 4/6 inhibitor switching patterns in Swedish patients with metastatic breast cancer: 5-year update from the SIRI 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 PO4-17-04.

Comparison of time to treatment initiation of specialty medications between an integrated health system specialty pharmacy and external specialty pharmacies.

Specialty medications are commonly dispensed through specialty pharmacies equipped to meet unique monitoring and dispensing requirements. Integrated health system specialty pharmacies (HSSPs) coordinate with health system providers to deliver specialty medications to patients and ameliorate barriers to care. However, payors may restrict specialty medication fills to specialty pharmacies external to the health system, potentially leading to delayed treatment. To compare time to treatment initiation among patients whose specialty medications were transferred to external pharmacies and patients whose medications were filled at an internal HSSP. This was a retrospective, propensity-matched cohort study examining time to treatment initiation in patients with a specialty medication referral to the University of Kentucky HealthCare Specialty Pharmacy between July 1, 2021, and July 1, 2022. Patients were classified into cohorts by receipt of dispensing services from the internal HSSP or an external specialty pharmacy. Data collected via chart review included insurance type, reason for prescription transfer, dates of service (including prescription order, transfer, and receipt of medication), and whether a prior authorization or clinical intervention was performed. Subgroup analyses were performed for patients requiring a prior authorization or clinical intervention. The Wilcoxon signed-rank test was used to assess for statistically significant differences in time to treatment initiation between cohorts. A total of 560 patients with external transfers were identified for inclusion into the study, and after exclusion criteria were applied, 408 external transfer patients were propensity matched 1:1 to 408 patients with internal fills (total n = 816). Time to treatment initiation was significantly longer in the external transfer cohort as compared with the internal fill cohort, (18 days vs 12 days; P < 0.0001). The internal fill cohort had a greater mean days from provider order to the medication being ready to fill compared with the external transfer cohort (10 days vs 6 days; P < 0.0001). The internal fill cohort had fewer mean days from the medication being ready to fill to patient receipt of the medication as compared with the external transfer cohort (2 days vs 12 days; P < 0.0001). Similar findings were observed in the subgroup analyses. Average time to treatment initiation was 6 days shorter for patients whose specialty medications were filled at this HSSP compared with externally transferred patients. Delays in therapy can cause a negative impact on patient care and disease state management, with increased concern for specialty populations. The results of this study highlight the need for continued discussion about policies that limit patient choice to in-network pharmacies.

Sociodemographic and clinical risk factors associated with in-hospital tuberculosis mortality in Türkiye, 2008-2018.

Tuberculosis (TB) is an infectious disease that can be fatal if left untreated or poorly treated, and it is associated with many morbidities. Deaths may provide better understanding of the associated factors and help guide interventions to reduce mortality. In this study, it was aimed to reveal some of the features that predict hospital mortality in patients with TB and to present some alarming findings for clinicians. Patients who had been hospitalized with the diagnosis of TB between January 2008 and December 2018 were included and analyzed retrospectively. In-hospital mortality because of any TB disease after the initiation of treatment in patients admitted to the TB Ward and the primary cause of mortality were taken as endpoint. A total of 1321 patients with a mean age of 50.1 years were examined. Total mortality was 39.4% (521 deaths) and 13.1% were in-hospital deaths (173 deaths). Of the deaths, 61.8% (n= 107) occurred during the first month after TB treatment were started. On univariate analysis, age over 48.5 years, Charlson comorbidity index, extension of radiological involvement, hypoalbuminemia and lymphopenia were most predictive variables with higher odds ratios (respectively, p<0.001 for all). In-hospital tuberculosis disease mortality is related with older age, cavitary or extensive pulmonary involvement, low albumin levels, unemployment, cigarette smoking and especially those with concomitant malignancy and chronic pulmonary disease.

Abstract 176: Stearic acid induces pro-inflammatory macrophage response important for lung cancer development

Abstract Background Survival is improved with early detection and treatment initiation in patients with lung cancer (LC) emphasizing the importance of tumor initiation and biomarker development in individuals at high risk for developing LC and those with early-stage LC. Recent studies suggest that immunologic and metabolic changes within the microenvironment are pivotal for tumor formation. We recently demonstrated that in patients with resectable, early-stage LC, elevated levels of stearic acid (SA), a long chain fatty acid, and macrophage inflammatory protein 1β (MIP-1β/CCL4) were predictive of tumor affected lung lobes. Therefore, we hypothesize that SA promotes LC initiation through the activation of macrophages (MΦ) and production of proinflammatory cytokines like CCL4. Methods and Results: We performed untargeted metabolomics utilizing LC-MS from the plasma of patients with various stages of LC and found elevated levels of SA in patients with early-stage LC. To further study the mechanistic role of SA in tumorigenesis, cell lines including immortalized lung epithelial, LC cells, and immune (MΦ and T) cells were treated with SA. We found that physiological concentrations of SA did not affect cellular viability. However, in MΦ, SA induced expression of inflammatory (IL6, iNOS), and immunomodulatory (Arg1, CD206) genes suggesting a role for SA in promoting a pro-tumorigenic immunologic state. Additionally, analysis of the secretome from SA stimulated MΦ using single cell proteomic analysis (Isolight, Bruker Cellular Analysis, Inc), indicated a significant enrichment of polyfunctional MΦs with enhanced secretion of enriched effector and stimulatory cytokines. Furthermore, conditioned media derived from SA stimulated MΦ led to increased proliferation, as well as anchorage independent growth, of BEAS2B immortalized lung epithelial cells. Conclusion: Our data demonstrates plasma levels of SA are increased in early-stage compared to late-stage patients with LC. This observation corresponds to our prior data demonstrating enrichment of SA in the tumor affected lobes of patients with early-stage LC. Recent studies demonstrating the induction of inflammatory responses through MΦ activation in obese patients by circulating SA in blood corroborates our observations as well. Our data suggests that the SA effect on MΦ, is critical in LC initiation not only increasing proliferation but also induction of neoplastic transformation of immortalized lung epithelial cells. Furthermore, our data indicates that blood plasma levels of SA, a fatty acid understudied in tumor biology, could also be exploited as a potential biomarker for LC development in individuals at high-risk for LC development as well as those patients with early-stage disease. Citation Format: Amrita Roy, Martin Davis, Samuel Weinberg, Apurva Mallisetty, Alicia Hulbert, Frank D. Weinberg. Stearic acid induces pro-inflammatory macrophage response important for lung cancer development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 176.

Effect of telemonitoring and as-needed patient support on positive airway pressure therapy adherence.

Obstructive sleep apnea (OSA) affects patient health and public welfare. Positive airway pressure (PAP) therapy is the preferred treatment of OSA, but therapy adherence rates remain suboptimal. Current literature demonstrates telemonitoring interventions to support improved PAP therapy adherence. To evaluate the effect of interval telemonitoring of PAP therapy data at 2 and 4 weeks after treatment initiation in patients with moderate-to-severe obstructive sleep apnea with as-needed patient support and troubleshooting by telephone consultation. Ninety-nine participants were enrolled in this study, 50 in the control group and 49 in the intervention group. Data were analyzed using descriptive and inferential statistics using SPSS 28.0 software. The primary outcome of interest was 90-day PAP adherence. Mean PAP adherence scores diverged at 90 days after PAP initiation, with the intervention group having a significantly higher mean score (M = 49.24, SD = 38.18) relative to the control group (M = 36.38, SD = 37.69). Likewise, continued PAP usage at 90 days after therapy initiation diverged between participant groups, with the intervention group having a significantly higher mean score (M = 89.80, SD = 30.58) relative to the control group (M = 72.00, SD = 45.36). The intervention resulted in significantly higher mean PAP adherence and a greater percentage of participants demonstrating continued PAP usage at 90 days after therapy initiation but did not result in a statistically significant increase in what is considered and defined as "good PAP adherence" (adherence of ≥70%). Data-triggered telemonitoring protocols offer supplementary support to patients in need and improve PAP adherence.

Serum Cell-Free DNA-based Detection of Mycobacterium avium Complex Infection.

Rationale: Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial (NTM) pulmonary disease (PD), which exhibits increasing global incidence. Current microbiologic methods routinely used in clinical practice lack sensitivity and have long latencies, leading to delays in diagnosis and treatment initiation and evaluation. A clustered regularly interspaced short palindromic repeats (CRISPR)-based assay that measures MAC cell-free DNA (cfDNA) concentrations in serum could provide a rapid means to detect MAC infection and monitor response to antimicrobial treatment. Objectives: To develop and optimize a CRISPR MAC assay for MAC infection detection and to evaluate its diagnostic and prognostic performance in two MAC disease cohorts. Methods: MAC cfDNA serum concentrations were measured in individuals with diagnoses of MAC disease or who had bronchiectasis or chronic obstructive pulmonary disease diagnoses without histories of NTM PD or NTM-positive sputum cultures. Diagnostic performance was analyzed using pretreatment serum from two cohorts. Serum MAC cfDNA changes during MAC PD treatment were evaluated in a subset of patients with MAC PD who received macrolide-based multidrug regimens. Measurements and Main Results: The CRISPR MAC assay detected MAC cfDNA in MAC PD with 97.6% (91.6-99.7%) sensitivity and 97.6% (91.5-99.7%) specificity overall. Serum MAC cfDNA concentrations markedly decreased after MAC-directed treatment initiation in patients with MAC PD who demonstrated MAC culture conversion. Conclusions: This study provides preliminary evidence for the utility of a serum-based CRISPR MAC assay to rapidly detect MAC infection and monitor the response to treatment.

A Real-World Analysis of the Diagnostic Evaluation for Hemophagocytic Lymphohistiocytosis in a Pediatric Population

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome that is often fatal without immunosuppressive treatment to quell the overactive immune response. Accordingly, it is crucial to diagnose HLH promptly and accurately. Nevertheless, diagnosing HLH is challenging due to its phenotypic overlap with other inflammatory conditions. Furthermore, existing HLH diagnostic criteria consist largely of nonspecific clinical and laboratory findings. Together, these factors contribute to significant diagnostic uncertainty, which can delay initiation of treatment in patients who actually have HLH while exposing other patients who do not have HLH to unnecessary immunosuppressive therapy. We sought to better understand how these challenges manifest in a real-world setting and identify opportunities to improve upon existing diagnostic algorithms. To this end, we queried the UCSF Electronic Medical Record Search Engine for clinical notes containing mention of HLH or the related disease, macrophage activation syndrome (MAS), in patients presenting to the UCSF Medical Center between 2008 and 2021. The resulting 2,360 patients were filtered to include only those who were admitted to an inpatient unit and managed by a pediatric care team. Patients with existing malignant, autoimmune, or immunodeficiency conditions were excluded. The resulting 635 patients were divided into an “HLH-diagnosed” group, consisting of 68 patients assigned an ICD-10 code for HLH/MAS, and an “HLH-considered” group, containing the remaining 567 patients without such a code but in whom HLH/MAS was considered on the differential diagnosis. There was an equal distribution of males and females across the cohort. Ages ranged from 0 to 25 years, with no significant difference between groups. Patients in the HLH-diagnosed group were more likely to be deceased at the end of the admission (21% versus 5%, p&amp;lt;0.0001). The most common presenting symptoms were fever, rash, emesis, and fatigue, and there were no differences in the frequency of any presenting features between the two groups. Among the discharge diagnoses for patients in the HLH-considered group, infections were most common (23%), followed by rheumatologic diseases (20%), new malignancies (9%), and fever of unknown origin (8%). We evaluated the performance of the two most commonly used diagnostic algorithms, namely the HLH-2004 criteria and H-score. The HLH-2004 criteria demonstrated a sensitivity of 65% and a specificity of 92%, versus 82% and 83% for the H-score. Patients in the HLH-considered group with newly-diagnosed malignancies had the highest false positivity rate, with 20% testing positive by the HLH-2004 criteria and 34% by the H-score. We also applied these algorithms to patients in the HLH-considered group who were assigned an ICD-10 code for sepsis (n=62). Fifteen and 42% had a false positive result by the HLH-2004 criteria and the H-score, respectively. Given that many HLH-considered patients tested positive by these existing algorithms but were ultimately ruled out based on other clinical data, we sought to create a new model relying only on basic laboratory parameters to help better differentiate HLH-diagnosed and HLH-considered patients. To address this, we performed multivariate logistic regression analysis. Cytopenias and levels of ferritin, triglycerides, and fibrinogen were all significant predictors in univariate analyses and independent predictors in the multivariate analysis. The resulting model produced an area under the curve of 0.86 (0.81-0.90). HLH is commonly considered on the differential diagnosis in hospitalized children, and in our cohort, was ruled out eight times more often than it was diagnosed. Infections, malignancies, and rheumatologic diseases are the most common HLH mimics and cannot be readily distinguished from HLH on the basis of presenting features. Existing diagnostic algorithms showed suboptimal performance in this cohort, particularly in patients with malignancy and sepsis. Our alternative model consisting only of basic laboratory parameters may help streamline the initial diagnostic workup for pediatric patients with concern for HLH and more accurately identify those who require further specialized testing.

Time-dependent effect of antipsychotic discontinuation and dose reduction on social functioning and subjective quality of life–a multilevel meta-analysis

Meta-analyses indicate superiority of antipsychotic maintenance treatment over discontinuation within up to 24 months after treatment initiation for patients with schizophrenia-spectrum disorders. In terms of functional recovery, long-term trials show improved functioning after discontinuation, suggesting a time-dependent effect of antipsychotic maintenance. However, these trials were not included in previous meta-analyses. We therefore investigated whether the effect of antipsychotic maintenance treatment vs. discontinuation on social functioning and quality of life varies by trial length. The study was preregistered with PROSPERO (CRD42021248933). PubMed, PsycINFO, Web of Science, Embase and trial registers were systematically searched on 8th November 2021 and updated on 25th June, 2023 and 10th August, 2023 for studies that compared antipsychotic maintenance to discontinuation and reported data on social functioning or subjective quality of life in patients with schizophrenia-spectrum disorders. Risk of bias was assessed with the RoB 2, the ROBINS-I and the RoB-ME tools. Quality of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation approach. We included k=35 studies (N=5924) with follow-ups between one month and 15 years. Overall, maintenance and discontinuation did not differ on social functioning (k=32; n=5330; SMD=0.204; p=0.65; 95% CI [-0.69, 1.10]) or quality of life (k=10; n=943; SMD=-0.004; p=0.97; 95% CI [-0.22, 0.21]), whilst subgroup analyses of middle- (2-5 years; k=7; n=1032; SMD=0.68; 95% CI [0.06, 1.28]) and long-term follow-ups (>5 years; k=2; n=356; SMD=1.04; 95% CI [0.82, 1.27]) significantly favoured discontinuation. However, the quality of evidence was rated as very low. Although our findings suggest a time-dependent decrease in the effect of maintenance treatment on social functioning, interpretation of these findings is limited by the serious risk of bias in middle- and long-term trials. Therefore, any conclusions regarding the long-term benefits of antipsychotic treatment or discontinuation for functional recovery are premature and more high-quality trials tailored to comparing state of the art maintenance treatment vs. discontinuation are needed. None.

Gynecologic cancer care in the first year of the COVID-19 pandemic

ObjectiveTo analyze the impact of the early COVID-19 pandemic on the diagnosis and initiation of treatment for patients with gynecologic cancer. MethodsPatients diagnosed with gynecologic cancer in the National Cancer Database during 2017–2020 were included. For the first aim, incidence rate ratios were calculated to compare gynecologic cancer diagnosis in the first year of the COVID-19 pandemic to the three years prior, and factors associated with a reduction in diagnosis were identified. For the second aim, patients who experienced an 8-week delay in cancer treatment were compared to those who did not. Multivariate logistic regression was used to identify factors associated with treatment delay. Propensity score analysis was utilized to compare the rate of cancer treatment delay in patients who were diagnosed with COVID-19 to those who were not. ResultsThe incidence rate ratio of being diagnosed with gynecologic cancer in 2020 versus 2017–2019 was 0.90 (95%CI 0.90–0.91). Factors associated with increased risk of missed or delayed diagnosis in 2020 included cervical cancer, earlier cancer stage, younger age, lower levels of medical comorbidity, and lack of health insurance. In 2020, factors associated with treatment delay included COVID-19 diagnosis (aOR 1.50, 95%CI 1.35–1.67), in addition to race and ethnicity, insurance type, comorbidity, cancer stage, and primary site. The risk of treatment delay remained significantly elevated in patients diagnosed with COVID-19 after propensity-score matching. ConclusionsGynecologic cancer diagnosis and timely provision of care were negatively impacted during the first year of the COVID-19 pandemic, with certain subgroups at elevated risk.

Clinical Variables Impact Time to Inpatient Radiation Oncology Consultation for Spine Metastases: A Single Institution Study

Timely initiation of treatment for patients presenting with spinal metastases is essential for optimal oncologic care. An important rate limiting step for many patients is initiation of radiation oncology consultation. We performed a retrospective single institution study on adult inpatients with spine metastases with or without cord compression from 2018-2021. Variables related to inpatient care were collected. Our primary study endpoint was time to inpatient radiation consultation of less than or equal to 2 days. Our secondary study endpoint was time to magnetic resonance imaging (MRI) order less than or equal to 1 day. Multivariable logistic regression was utilized to determine which variables were associated with our study endpoints. P-values less than 0.05 were considered significant. A total of 160 patients received inpatient care between 2018-2021. The median age of our study population was 68 years. One hundred twenty-one patients (75.6%) underwent initial MRI imaging of their spine. One hundred thirty-nine (86.9%) patients underwent inpatient radiation oncology consultation. Forty-seven patients (29.4%) were non-ambulatory on presentation The median time to inpatient radiation consultation was 1 day (interquartile range [IQR]: 1-3 days). Patients with a diagnosis of cancer at presentation were more likely to have an inpatient radiation consultation within two days (OR: 5.25, 95% CI: 1.64-17.38, p = 0.006). Spine MRIs ordered within 1 day were more likely to lead to radiation oncology consultation within 2 days of presentation (OR: 9.75, 95% CI: 1.83-61.78, p = 0.009). Similarly, surgical consultation within 1 day was more likely to lead to radiation oncology consultation within two days of presentation (OR: 6.60, 95% CI: 1.41 - 35.09, p = 0.019). There was a higher likelihood of ordering a spine MRI within 1 day of presentation for patients with difficulty ambulating (OR: 6.00, 95% CI: 1.78 - 27.51, p = 0.008). Our analysis identifies cancer diagnosis, time to surgical consultation, time to MRI order, and ambulation status as influencing the time to inpatient radiation consultation and spine MRI orders. These variables should be taken into consideration to optimize care for inpatients with spine metastases and cord compression.

The impact of changes in gadolinium-enhancement on disease progression in children with neurofibromatosis type 1-associated optic pathway glioma: a retrospective analysis.

There has been limited investigation of imaging features associated with visual acuity (VA) decline and initiation of treatment for patients with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). To evaluate the association of increased gadolinium enhancement with decline in VA, initiation of chemotherapy, and tumor growth, we performed a retrospective cohort study of children diagnosed with NF1-OPG between January 2006 to June 2016. Two cohorts were defined: a new diagnosis and a longitudinal cohort. Outcomes were examined at 1 and 2 years from initial diagnosis, and 1 and 2 years from initial increase in enhancement in the longitudinal cohort. Eighty patients were eligible; all 80 contributed to the new diagnosis cohort and 73 to the longitudinal cohort. Fifty-six patients (70%) demonstrated enhancing NF1-OPG at diagnosis. 39% of patients in the new diagnosis cohort and 45% of those in the longitudinal cohort developed increased enhancement during the study period. There was no significant association between increases in enhancement and VA decline in the newly diagnosed or longitudinal cohorts, as well as with initiation of treatment in the longitudinal cohort. Although there was an association of enhancement increase with treatment in the new diagnosis cohort, this association was not maintained when stratified by concurrent change in tumor size. Increased gadolinium-enhancement independent of a concurrent increase in tumor size on MRI should not be used as a marker of NF1-OPG progression and does not appear to be associated with visual decline or initiation of chemotherapy.

The Long-Term Use of Diagnostic Subdural Electroencephalogram Electrodes and Subdural Hematoma: A Prospective Cohort Study.

Seizures and status epilepticus (SE) are frequent complications of acute subdural hematoma (aSDH) associated with increased morbidity and mortality. Therefore, we aimed to evaluate whether invasive subdural electroencephalogram recording leads to earlier seizure detection and treatment initiation in patients with aSDH. Prospective, single-center, cohort trial. Neurologic and neurosurgical ICUs of one academic hospital in Germany. Patients with aSDH undergoing surgical treatment. In total, 76 patients were enrolled in this study, 31 patients (40.8%) were assigned to the invasive electroencephalogram (iEEG) monitoring group and 45 patients (59.2%) to control group. The electrode group was implanted with a subdural strip electrode providing up to 7 days of real-time electroencephalogram recording in the neurointensive care unit, whereas the control group received regular normal surface electroencephalograms during the 7-day period. The primary outcomes were the prevalence and time to seizures and SE occurrence. Secondary outcomes included neurologic outcomes assessed using the Glasgow Outcome Scale (GOS) at discharge and 6-month follow-up and the prevalence of focal structural epilepsy within 2 years after discharge. The trial was stopped after a study committee meeting when the prespecified criteria were met. The iEEG and control groups were well-matched for clinical characteristics at admission. Frequencies of seizures and SE detection were significantly higher in the iEEG group than in the control group (61% vs 15.6%; p < 0.001 and 38.7% vs 11.1%; p = 0.005). Time to seizure and SE detection was significantly earlier (median 29.2 vs 83.8 hr; p = 0.018 and 17.2 vs 83.8 hr; p = 0.033) in the iEEG group than in the control group. Favorable outcomes (GOS 4-5) were more frequently achieved in the iEEG group than in the control group (58% vs 31%; p = 0.065). No significant differences were detected in long-term mortality or post-traumatic epilepsy. Invasive subdural electroencephalogram monitoring is valuable and safe for early seizure/SE detection and treatment and might improve outcomes in the neurocritical care of patients with aSDH.

1039-P: Examining Physician Case Studies on Success of Treatment Initiation in Patients with Type 2 Diabetes

Introduction: The Michigan Collaborative for Type 2 Diabetes (MCT2D) is a state-wide quality initiative supported by Blue Cross Blue Shield of Michigan that aims to improve the treatment of diabetes through three initiatives-encouraging increased prescribing of continuous glucose monitoring (CGM), SGLT2i/GLP-1RA medications, and low carbohydrate diet (LCD), defined as 80-130 total grams of carbohydrates per day, with patients on an SGLT2i instructed to stay &amp;gt;100g among 264 primary care practices. The aim of this study was to evaluate physician experience prescribing LCD through case studies. Methods: Each physician participating in MCT2D submitted a case study evaluating their experience implementing MCT2D initiatives. Close-ended questions were assessed using a 4-point scale (Yes, Somewhat, Too Early to Tell, No). Open-ended responses on intervention success were analyzed using a multi-step process of data immersion, generating initial codes, and reorganization. Results: Physicians prescribed a LCD either alone or in combination with CGM and/or SGLT2i/GLP-1RA in 375 of 970 case studies. More than half (51.5%) reported that the intervention(s) achieved the target outcome. Case studies incorporating all three interventions were associated with greater physician satisfaction with results, as compared to diet alone (p&amp;lt;0.01). Five major themes regarding intervention effectiveness were: glycemic control, weight loss, patient motivation, simplification of medications, and combined benefit of multiple interventions. Improvement of blood glucose was reported in 45.9% of LCD alone cases and in 69.1% of cases that involved all three interventions. An increase in patient motivation to achieve improvement in health was most frequently discussed in cases where diet and CGM were combined (67.3%). Conclusion: LCD may have a synergistic effect with the use of CGM and newer medications. These exploratory findings require confirmation through future investigations. Disclosure K.L.Khosrovaneh: None. H.L.Diez: None. C.R.Richardson: Other Relationship; Annals of Family Medicine, JMIR Diabetes, Research Support; Dexcom, Inc., Blue Cross Blue Shield of Michigan, Neilson Foundation. L.Oshman: Stock/Shareholder; Abbott, AbbVie Inc., Merck &amp; Co., Inc., Procter &amp; Gamble, Johnson &amp; Johnson, Eli Lilly and Company. N.Kim: None. J.Rau: None. J.Reiss: None. R.Hisamatsu: None. D.H.Griauzde: None. L.A.Young: None. J.Weisensel: None. J.E.Aikens: None.

Do it fast! Early access to specialized care improved long-term outcomes in rheumatoid arthritis: data from the REAL multicenter observational study

BackgroundEarly rheumatoid arthritis (RA) offers an opportunity for better treatment outcomes. In real-life settings, grasping this opportunity might depend on access to specialized care. We evaluated the effects of early versus late assessment by the rheumatologist on the diagnosis, treatment initiation and long-term outcomes of RA under real-life conditions.MethodsAdults meeting the ACR/EULAR (2010) or ARA (1987) criteria for RA were included. Structured interviews were conducted. The specialized assessment was deemed “early” when the rheumatologist was the first or second physician consulted after symptoms onset, and “late” when performed afterwards. Delays in RA diagnosis and treatment were inquired. Disease activity (DAS28-CRP) and physical function (HAQ-DI) were evaluated. Student’s t, Mann-Whitney U, chi-squared and correlation tests, and multiple linear regression were performed. For sensitivity analysis, a propensity score-matched subsample of early- vs. late-assessed participants was derived based on logistic regression. The study received ethical approval; all participants signed informed consent.ResultsWe included 1057 participants (89.4% female, 56.5% white); mean (SD) age: 56.9 (11.5) years; disease duration: 173.1 (114.5) months. Median (IQR) delays from symptoms onset to both RA diagnosis and initial treatment coincided: 12 (6–36) months, with no significant delay between diagnosis and treatment. Most participants (64.6%) first sought a general practitioner. Notwithstanding, 80.7% had the diagnosis established only by the rheumatologist. Only a minority (28.7%) attained early RA treatment (≤ 6 months of symptoms). Diagnostic and treatment delays were strongly correlated (rho 0.816; p < 0.001). The chances of missing early treatment more than doubled when the assessment by the rheumatologist was belated (OR 2.77; 95% CI: 1.93, 3.97). After long disease duration, late-assessed participants still presented lower chances of remission/low disease activity (OR 0.74; 95% CI: 0.55, 0.99), while the early-assessed ones showed better DAS28-CRP and HAQ-DI scores (difference in means [95% CI]: -0.25 [-0.46, -0.04] and − 0.196 [-0.306, -0.087] respectively). The results in the propensity-score matched subsample confirmed those observed in the original (whole) sample.ConclusionsEarly diagnosis and treatment initiation in patients with RA was critically dependent on early access to the rheumatologist; late specialized assessment was associated with worse long-term clinical outcomes.

Outcomes in patients with retinal vein occlusion with good baseline visual acuity.

Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) are first-line therapy for macular oedema in retinal vein occlusion (RVO). Appropriate management for RVO with good visual acuity at diagnosis has not been evaluated. The purpose of this study is to analyse the visual and anatomic outcomes from anti-VEGF treatment among RVO patients with good vision at baseline. This retrospective cohort study evaluated patients diagnosed with macular oedema secondary to RVO from January 2012 to February 2021 at a tertiary ophthalmic centre. Patients had a Snellen acuity of 20/32 or better at diagnosis. Three cohorts were compared: patients with no anti-VEGF treatment, delayed anti-VEGF treatment (initial injection >30 days post-diagnosis) and immediate anti-VEGF treatment (initial injection ≤30 days post-diagnosis). Central subfield thickness (CST) and best visual acuity (BVA) were collected at diagnosis and 6-, 12- and 24-month follow-up appointments. Among 131 eyes, mean BVA values among treatment groups did not differ at 6-, 12- or 24-month follow up visits (P = 0.521, 0.426, 0.356, respectively). The percentage of eyes with at least a 5-letter BVA decrease at 24 months was 24.1%, 65.0% and 30.8% in the no treatment, delayed and immediate treatment groups respectively (P = 0.010). There was no significant difference in the percentage of eyes with at least a 10% decrease in CST at 24 months among groups (P = 0.095). Close observation with initiation of treatment in patients with good visual acuity with macular oedema secondary to RVO as indicated has similar outcomes in the setting of routine clinical practice.

Periods till psoriatic arthritis onset and diagnosis in Russian patients with moderate to severe psoriasis (according to psoriasis patient registry)

Background. Early detection of psoriatic arthritis in patients with psoriasis remains an unmet medical need. Early diagnosis and treatment initiation in patients with psoriatic arthritis decreases the risk of adverse patient outcomes and improves patients quality of life.&#x0D; Aims. To describe a period between psoriasis and psoriatic arthritis onset and a period between psoriatic arthritis onset and diagnosis in Russian patients with moderate to severe psoriasis.&#x0D; Materials and methods. Analysis of data from the psoriasis patient registry. Patients aged 18 years and older with an established diagnosis of psoriasis and psoriatic arthritis were included in the analysis. Noninclusion criteria: no data on psoriasis and/or psoriatic arthritis onset (for the period between psoriasis and psoriatic arthritis onset description); no data on psoriatic arthritis onset and/or diagnosis (for the period between psoriatic arthritis onset and diagnosis description).&#x0D; Results. Sample size for the descriptive characteristic of period between psoriasis and psoriatic arthritis onset was 891 patients; sample size for the descriptive characteristic of period between psoriatic arthritis onset and diagnosis was 849 patients.&#x0D; Psoriatic arthritis onset preceeded cutaneous manifestation of psoriasis in 2.5% of patients. Concurrent onset of cutaneous psoriasis and psoriatic arthritis (within one year) had 10.7% of patients. In 86.8% of patients, cutaneous manifestation of psoriasis preceded manifestation of psoriatic arthritis.&#x0D; Exclusively of patients with psoriatic arthritis developed before or concurrently with cutaneous manifestation of psoriasis, the mean duration of period between psoriasis and psoriatic arthritis onset was 13.7 10.3 years, the median [IQR] 12 [619] years.&#x0D; In 24% of patients psoriatic arthritis was diagnosed 1 year and more after its onset. The mean (SD) period from signs and|or symptoms onset till psoriatic arthritis diagnosis was 3.9 5.0 years; median [IQR] was 2 [14.5] years.&#x0D; Conclusions. A diagnostic delay in 24% Russian patients with psoriatic arthritis is one year or more. In this subgroup of patients the mean delay in diagnosis of psoriatic arthritis is about 4 years.

P456 Magnetic resonance enterography findings at week 46 after biological treatment predict long-term clinical outcomes in Crohn’s disease patients

Abstract Background Magnetic resonance enterography (MRE) provides an accurate evaluation of transmural lesions in Crohn’s Disease (CD). However, MRE findings associated with poor long-term outcomes in CD are not yet defined. Identification of such parameters would help in defining therapeutic goals. AIMS to identify predictors of long-term clinical outcomes based on MRE findings performed 46 weeks after biological treatment initiation in patients with CD. Methods single-center, prospective, longitudinal study conducted from 2010 to 2019. Patients with CD who had an MRE evaluation 46 weeks after biological treatment initiation and clinical follow-up of at least 3 years were evaluated. Results 89 patients were included with a median follow up of 53 months (IQR 44-76). 59 patients had ileal (66.3%), 26 ileocolic (29.2%) and 4 colonic disease (4.5%). 31 (34.8%) had inflammatory behavior, 27 (30.3%) stricturing, 9 (10.1%) fistulizing and 22 (34.7%) stricturing/fistulizing. 70 (78.7%) were treated with anti-TNFα, 5 (5.6%) vedolizumab and 14 (15.7%) ustekinumab. During follow-up, 25 (28.1%) required surgery, 17 (19.1%) hospitalization, 40 (44.9%) had clinical relapse (CDAI &amp;gt;150), 12 (13.5%) required corticosteroids and 12 (13.5%) required endoscopic dilatation. 32 (36.0%) patients needed resection surgery or endoscopic dilatation. MaRIA score ≥11 in any segment at week 46 was associated with a higher risk of surgery [HR 6.28 (1.42-27.84), p=0,02] or surgery/endoscopic dilatation [HR 3.76 (1.24-11.38), p=0,02]. Relative contrast enhancement (RCE) &amp;gt;103 was associated with higher risk of clinical relapse [HR 1,01 (1.00-1.02), p=0,03] and corticosteroids requirement [HR 1,01 (1.00-1.02), p=0,05]. Conclusion MRE findings at week 46 after biological treatment initiation predict long-term clinical outcomes in CD patients. The main determinants of poor clinical prognosis were MaRIA score ≥11 and RCE &amp;gt;103. Patients with these persistent findings may be candidates for treatment optimization.

COT-18 DATABASE STUDY ON TRENDS IN MEDICAL EXAMINATIONS OF PATIENTS WITH MALIGNANT BRAIN TUMORS

Abstract Background and Purpose Glioblastoma is the most is the poorest prognosis tumor of all carcinomas. Various factors contribute to deterioration for glioblastoma such as age, KPS, and surgical removal level. The most important factors for poor prognosis are that half of patients with glioblastoma have a KPS ≤ 70 at the start of treatment because glioblastoma progresses rapidly. There have been no comprehensive reports on the trends in visits and time to initiation of treatment for patients with glioblastoma. We analyzed the actual clinical course of malignant brain tumor patients using the receipt database with the aim of raising awareness of prompt diagnosis and treatment. Methods Because this study included patient-visit transitions, we utilized receipt data from JMDC Inc., which can be tracked through changes of medical facilities. We analyzed for data for the period January 1, 2005, to March 31, 2022. Results and Discussion The study included 493 patients with malignant neoplasms of brain, aged 18 years or older, who underwent surgery and received radiation or temozolomide. The medical departments that visited for the first time before surgery were general internal medicine, neurosurgery, followed by ophthalmologist, orthopedics, and otolaryngology. The period from the date of the first visit to surgery was 21 days for neurosurgery and 46 days for general internal medicine. The mean time from MRI to surgery was 11 days when surgery was performed at the MRI site, and 22 days when the patient was referred to another hospital after MRI. This study clarified the actual situation when patients with malignant brain tumors visit a department besides neurosurgery. In order to facilitate prompt diagnosis and treatment, it is necessary to raise awareness of the disease among the departments where patients are likely to visit for the first time.

Quantitative lateral flow immunoassay for rapid detection of procollagen type I N-terminal propeptide in the monitoring of osteoporosis treatment

Appropriate follow-up after treatment initiation in patients with osteoporosis is challenging. Serum biomarkers may offer more efficient monitoring of bone mineral density (BMD) than the currently used dual X-ray absorptiometry; however, significant changes in BMD often occur over at least 12 months. During teriparatide treatment for osteoporosis, monitoring with markers such as procollagen type I propeptide (PINP), which is derived from osteoblasts, can provide clinically useful information for disease management. However, rapid and cost-effective methods for detecting serum PINP are lacking, necessitating a point-of-care test (POCT) for enhanced follow-up efficiency in osteoporosis management. For the quantitative detection of PINP, we developed a high-sensitivity lateral flow immunoassay with a stacking pad (sLFIA). We established a calibration equation based on the test line/control line ratio obtained from our PINP sLFIA results of various nonspiked serum samples to calculate the PINP concentrations in 40 serum samples and compared the result with those obtained using a fully automated electrochemiluminescence immunoassay. PINP concentrations between these two methods exhibited excellent correlation (R = 0.991). In addition, we assessed the serum PINP concentrations of patients with osteoporosis treated with teriparatide. At the 3-month follow-up, their PINP levels were nearly twice as high as those at baseline, thus implying that our method can be used for osteoporosis treatment monitoring. Our findings thus indicate that the PINP sLFIA can serve as a POCT for monitoring medication response and managing osteoporosis.

Reporting of Helicobacter pylori associated gastroduodenal diseases: A clinicopathological approach

is one of the most important causes of the varied spectrum of gastroduodenal diseases. It is important to have a collaborative approach between clinicians and pathologists for early initiation of treatment in patients and control the progression of the disease.To evaluate the clinico-histopathological spectrum of gastroduodenal diseases with respect to infection and provide recommendations for reporting and management of the same.All patients of chronic dyspepsia not responding to conventional treatment were subjected to endoscopy, and mucosal biopsy samples were collected. A rapid urease test (RUT) and histopathology was performed on these samples. A histopathological evaluation was done with special reference to the Updated Sydney System for reporting of chronic gastritisThe specificity, sensitivity, positive predictive value, negative predictive value, and diagnostic accuracy of RUT were 97.22%, 94.04%, 98.75%, 87.5%, and 95%, respectively. The specificity, sensitivity, PPV, NPV and diagnostic accuracy of endoscopy were calculated as 98.68%, 88.5%, 95.83%, 96.15% and 96.07% respectively.A clinicopathological approach for diagnosis of associated gastroduodenal diseases which includes clinical assessment, endoscopic evaluation, RUT and histopathological analysis is of prime importance for effective management of such patients.