Initial Delay Research Articles

Impact of integrating traditional care with the modern healthcare system in reducing tuberculosis diagnosis delays in Ethiopia: a clustered randomized controlled study.

Diagnosis and treatment initiation delays for tuberculosis (TB) are significant challenges in resource-limited settings. These delays can result in poor treatment outcomes, disease transmission, and increased costs. This study aimed to assess the effect of integrating traditional care with modern healthcare systems on reducing TB diagnosis delay. A cluster randomized controlled trial was conducted among TB patients, with 510 participants, 255 individuals were assigned to the intervention group and 255 to the control group. Training in the intervention group was provided for both traditional and modern healthcare providers in three rounds to enhance their knowledge, attitudes, and skills in TB screening and referral. A non-parametric independent sample test was used to compare the baseline and end-line data. The effect size was determined using Cohen's d. To account for individual and cluster-level variations, a mixed-effect parametric survival model was employed. Furthermore, conditional (fixed only) and marginal (random effects) graphs were used to compare between the intervention and control groups. A total of 510 participants were included in the baseline study, with a similar number of participants included in the endline study. In the intervention group, the delay in diagnosis was 4.185 per 1000 person-days post-intervention, compared to 4.608 per 1000 person-days pre-intervention. In the control group, the delay for diagnosis was 4.759 per 1000 person-days pre-intervention and 5.031 per 1000 person-days post-intervention. The median time to diagnosis was 135days. The non-parametric comparison showed that the intervention significantly reduced patient delays in the intervention group compared to the control group (p = 0.006), with a Cohen's d effect size of 0.246. The intervention also significantly reduced diagnosis delay in the intervention group compared to the control group (p = 0.036), with a Cohen's d effect size of 0.187. The diagnosis of TB was accelerated by 1.076 times due to the integration of traditional care with the modern healthcare system in the intervention group compared to the control group (δ: 1.076; 95% CI 1.021, 1.134). The involvement of traditional care providers in TB control programs significantly reduced diagnosis delays in Ethiopia. These findings suggest the need for integrating traditional care with modern healthcare systems for the effective prevention of TB in high-burden countries. Clinical trial registration ClinicalTrials.gov ID: NCT05236452.

Views from Multinational Pharmaceutical Companies on Allocation of Clinical Trials in Saudi Arabia—Qualitative Study

Clinical trials conducted by pharmaceutical companies are essential for bridging local research efforts with broader populations, facilitating the transfer of valuable insights and solutions. This study aimed to explore the barriers and facilitators affecting clinical trials in Saudi Arabia from the perspective of key personnel within the pharmaceutical industry and Contract Research Organizations (CROs). We conducted in-depth semi-structured interviews with nine participants, which provided a holistic understanding of the intricate dynamics shaping the landscape of clinical trials in the country. The analysis revealed three prominent themes: operational challenges, complexities in navigating approval hurdles, and the unique value proposition for conducting clinical trials in Saudi Arabia. The participants expressed pride in the local infrastructure but acknowledged existing flaws, particularly in regulatory processes that contribute to delays in trial initiation. They emphasized the importance of conducting clinical trials in areas such as diabetes, crowd management during pilgrimages, and rare diseases, which are prevalent in the region. Despite the limited number of clinical trials registered (354 from 2009 to 2020, with only 1% being phase 1 studies), Saudi Arabia’s total pharmaceutical market exceeds SAR 13 billion, positioning it as the largest market in the region. Stakeholders recognized the country’s potential as a research hub, particularly within the Gulf Cooperative Council (GCC) region. However, to attract more trials and enhance the medical research landscape, it is crucial to address the identified barriers, streamline processes, and improve stakeholder alignment. The findings highlight the need for targeted interventions to overcome these challenges and leverage Saudi Arabia’s investments in healthcare infrastructure since its transformation program launched in 2010. By enhancing the regulatory environment and fostering collaboration among stakeholders, Saudi Arabia can solidify its role as a key player in international clinical research.

NCOG-42. SPEECH-SPECIFIC ERRORS IN LEXICAL RETRIEVAL PREDICT GLIOMA MOLECULAR FEATURES

Abstract Recent work confirms that low and high-grade gliomas, remodel neural circuits which influence speech production. The extent to which speech kinetics and category of speech error during lexical retrieval may predict glioma molecular features remains unknown. Here, we extracted audiovisual speech production from 550 patients totaling over 26,400 individual stimuli to identify correlations with glioma molecular features including IDH, TERT, 1p19q co-deletion, and CDK2AB. Nonparametric statistics were used for analysis. IDH wild-type tumors were more likely to be temporoparietal, while IDH mutant tumors were more likely to be insular (p=0.02). Patients with IDH wild-type glioblastoma exhibited more errors (8.23 vs 3.79, p=0.02), with a higher occurrence of anomia (p=0.004), circumlocution (p=0.034) and general delay (p=0.04) when compared with IDH mutant WHO grade 4 astrocytoma. Binomial logistic regression identified lexical retrieval anomia, circumlocution, and initiation delays as an independent predictor of having an IDH wild-type tumor. Within the IDH mutant group, anomia (p=0.03) and articulation (p=0.014) errors were associated with malignant molecular features (after controlling for prognostic variables such as tumor volume). Binomial logistic regression identified articulation or anomia for picture naming as an independent risk predictor for WHO grade 2 gliomas with greater risk molecular features (based on Ki67 and CDK2AB). Distinct patterns of language errors were observed in patients with IDH wild-type and IDH mutant tumors. Further work is required to elucidate the functional and biological correlates of these findings.

Quality Improvement Initiatives for Pleural Infection Managed with Intrapleural Therapy.

Rationale Pleural infection is associated with significant mortality and its management is complex. Little attention has been given to care process metrics such as management delays, pleural drainage practices, and adequacy of intrapleural therapy administration despite their potential impact on outcomes. Audits revealed gaps in those care processes in our institution. Objectives To assess the impact of quality improvement initiatives on pleural effusion management in adults. Methods We performed a retrospective comparison of patients treated with intrapleural therapy for pleural infection at the McGill University Health Centre before (April 2013-April 2016, N=109) and after interventions (June 2020-June 2021, N=44). Interventions included a pleural drainage policy and order set, an intrapleural therapy protocol and pre-printed order, implementation of intrapleural therapy administration by nurses, local pleural infection guideline development, and an online learning module for physicians. Major outcomes (length of stay, mortality, surgical treatment) and care process metrics (management delays, pleural drainage practices, intrapleural therapy administration) were compared between the two periods. Results After implementation of the interventions, in-hospital mortality and length of stay were unchanged, but surgical management went from 14% to 0% (p=0,01). Delays in drain insertion and intrapleural therapy initiation were not significantly different. Insertion of drains smaller than 12Fr decreased from 51% to 7% (p<0,001). Drain blockage decreased from 20% to 2% (p=0,004). Additional drain insertions went from 62% to 48% (p=0,12). After interventions, 70% of intrapleural therapy doses were given by nurses, the intrapleural therapy protocol was more often adequately followed, less doses were missed, and less extended therapy was prescribed. Complications related to drain insertion and intrapleural therapy were similar between the two periods. Conclusions Following the implementation of multifaceted quality improvement interventions for pleural infection including involvement of nurses in pleural drain flushing and intrapleural therapy, improvements were observed in intrapleural therapy administration, chest drainage practices, and need for surgery. However, length of stay, mortality, and management delays were unchanged.

Factors Associated with the Delay of Early Initiation of Breastfeeding in Hospitals: A Scoping Review

Factors Associated with the Delay of Early Initiation of Breastfeeding in Hospitals: A Scoping Review

Atypical Signs and Symptoms of Giant Cell Arteritis: A Systematic Review.

Giant cell arteritis can present with atypical manifestations that delay treatment and risk severe complications. To comprehensively describe all atypical signs/symptoms of giant cell arteritis. In this systematic review, we searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to October 2022. Primary research articles that included at least one participant with an atypical sign/symptom of biopsy-proven giant cell arteritis were included. Study screening and data extraction were performed in duplicate. The primary outcome was the proportion of participants with atypical giant cell arteritis features. Time to treatment was compared between participants with atypical giant features only and participants with both typical and atypical features. Of 21,828 screened records, 429 studies corresponding to 746 individuals (median [IQR] age 72 [IQR, 66-78] years, 63% female) with at least one atypical feature of GCA were included. Eighty-two percent had both atypical and at least one concurrent typical giant cell arteritis feature, whereas 18% of patients with atypical signs and symptoms only presented with atypical features. Patients with atypical symptoms presented to clinicians earlier than patients with typical features (p < 0.001). There was no difference between groups in proportion to elevated ESR and CRP (82.3% vs. 83.35%, p = 0.91) or mortality rate (8.2% vs. 10.8%, p = 0.42). Patients with atypical features only experienced greater delay in treatment initiation (p < 0.001). The most commonly reported atypical signs/symptoms were vertigo (11.9%), scalp necrosis/ulceration (7.9%), and dry cough (5.8%). Eighteen percent of biopsy-proven giant cell arteritis cases with at least one atypical feature have only atypical features and are more likely to experience delays in treatment. Clinicians should be aware of atypical signs/symptoms of giant cell arteritis and order inflammatory markers early to prevent giant cell arteritis-associated morbidity.

Delays in diagnosis and treatment initiation of ATTR cardiac amyloidosis: a real-world data analysis

Abstract Introduction Cardiac amyloidosis (CA) is a serious condition characterized by the accumulation of abnormal protein deposits in the heart muscle, leading to functional impairments and, ultimately, heart failure. Transthyretin amyloid cardiomyopathy (ATTR-CM) is the most common form encountered in CA diagnosis with previously underestimated prevalence. ATTR-CM poses a diagnostic challenge, with a substantial number of cases diagnosed late and at advanced stages. The availability of specific pharmacological treatment using the transthyretin-stabilizer tafamidis further emphasizes the need for timely diagnosis. Here, we aim to assess delays in diagnosis and initiation of therapy in a real-world collective of patients with ATTR-CM. Methods All individuals diagnosed from 01/2018 to 05/2023 with ATTR-CM at our university hospital, Germany, were systematically assessed for eligibility in this study. Specifically, we enrolled patients who were undergoing transthyretin stabilizer therapy. The investigation aimed to determine the duration, in days, from the initial suspicion of heart disease to the definitive diagnosis of ATTR-CM. It was also investigated whether the diagnosis of ATTR-CM was made more quickly over time as awareness increased. Additionally, the study assessed the time elapsed until patients received pharmacological therapy following the confirmed diagnosis. The study was approved by the local ethics committee (23-11500-BO). Results After screening of 194 consecutive patients, 154 were included in the analysis, while 40 patients were excluded due to insufficient records. The results of this study reveal that a median of 300 (113-962) days elapsed from the initial suspicion of amyloidosis to the final confirmation. Initial indications of CA often presented as nonspecific symptoms such as unclear dyspnea (16.2% n=25), abnormal echocardiography (75.3% n=116), or, in rare cases, incidental findings (8.4% n=13). Following the diagnosis, an additional median of 84 (46-163.5) days passed before the first prescription of a transthyretin stabilizer. To assess an improvement of ATTR-CM diagnosis over time, we stratified the data into tertiles by date of first diagnosis. The results showed a gradually decrease in medium time to diagnosis of 466 (181-1035) days in the earliest tertile (2018-2019) to 389 (141-1508) days in the most recent tertile (2022-2023) (p&amp;lt;0.001). Conclusion This study shows a major healthcare deficit and underscores the medical need for improved screening procedures and diagnostic modalities to expedite the timely diagnosis of CA, as early identification of the condition is crucial for enhancing the quality of life for patients and preventing life-threatening complications.

Verification about the usefulness of early cardiac rehabilitation initiation in patients with congestive heart failure requiring hospitalization

Abstract Background It is a well-known fact that for patients with decompensated congestive heart failure (CHF) who require hospitalization, starting cardiac rehabilitation (CR) early after hospitalization has a positive impact on their clinical course. To maintain their activity and nutritional status through the early mobilization by efficient medical care, we have introduced our own clinical pathway(PATH) for CHF since August 2015. In PATH, the initiation of CR early after admission was stipulated. With PATH introduction, starting time of CR was significantly earlier and the average hospitalization period for CHF cases was also significantly reduced. However, there are still some cases applied PATH who are unable to start CR early after admission for various reasons. Purpose We examined whether the clinical course after admission differs depending on the timing of CR initiation even in CHF cases applied PATH. Methods We enrolled 933 patients admitted with CHF for the first time from August 2015 to July 2023, applied PATH, started physical therapy (PT) as CR, and discharged alive. We divided them into two groups based on when they started PT, Early-group (649 cases: Starting time is within the 3rd hospital day) and the Late-group (284 cases: Starting time is after the 4th hospital day). And we investigated patient background, clinical data at admission, and clinical course after admission for all cases, and examined the differences in each item between the two groups. Results There were no differences in patient characteristics or clinical data at admission between the two groups (Table 1). On the other hand, although there was no difference in the performance rate of each acute treatment between the two groups, the performance duration of each treatment in cases introduced was significantly shorter in Early-group. Furthermore, the average meal (side dish) intake rate on the 2nd to 4th hospital days after admission was significantly higher in Early-group, and the average length of hospitalization was significantly shorter in the Early-group (Figure 1). Conclusions For 8 years, we have strived to begin cardiac rehabilitation interventions early after hospitalization with introduction of our own clinical pathway. However, we found that even with the introduction of the clinical pathway, cardiac rehabilitation was started on or after the 4th hospital day in 30% of all cases. And we found that in these cases, each treatment during the acute phase was prolonged, nutritional intake was inadequate, and the length of hospitalization tended to be prolonged. The delay in initiation of rehabilitation was thought to be related to factors such as the timing of hospitalization (admission on holidays or public holidays) or the location of hospital management (ICU management in severe cases). It seemed necessary to create a system that would allow cardiac rehabilitation to be started flexibly even in such situations.Table1Figure 1

Clinical characteristics and treatment patterns of new users of dapagliflozin for heart failure with reduced ejection fraction: an observational study programme across 12 countries (EVOLUTION HF)

Abstract Background Clinical trials have shown that dapagliflozin, a sodium–glucose cotransporter-2 inhibitor (SGLT-2i), reduces cardiovascular mortality and worsening heart failure (HF). Adoption of new therapies has historically been slow despite robust evidence. Furthermore, treatment profiles of patients in real-world settings are scarce. Purpose EVOLUTION HF is a multinational study programme that aims to describe clinical characteristics and treatment patterns among patients initiating dapagliflozin for HF with reduced ejection fraction (HFrEF) in routine clinical practice. Methods The EVOLUTION HF primary data study programme consists of prospective, observational, descriptive studies of new users of dapagliflozin for HFrEF in 12 countries (Italy, Portugal, UK and the Central and Eastern Europe and Baltic [CEEBA] region [Bulgaria, Croatia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania and Slovenia]). Patients with type 1 diabetes or prior SGLT-2i treatment were excluded. Clinical characteristics were obtained from electronic health records. A total of 2170/2555 (85%) patients were enrolled from November 2021 to November 2023; 1736 patient profiles were assessed using descriptive statistics in this interim analysis. Results In total, 256, 228, 125 and 1127 new dapagliflozin users were analysed from Italy, Portugal, the UK and the CEEBA region, respectively (Table 1). Across the 12 countries, mean patient age in the studies was 65–70 years. Patients were predominantly male (67–76%) and generally had HF with an ischaemic aetiology (35–56%) and New York Heart Association functional class II (52–85%). Mean left ventricular ejection fraction in the studies was 29–32% and estimated glomerular filtration rate was 61–77 mL/min/1.73m². Hypertension and atrial fibrillation were common comorbidities. Mean time between HF diagnosis and dapagliflozin initiation in the studies was 23–52 months. Background therapy included angiotensin receptor-neprilysin inhibitors (36–72%), angiotensin receptor blockers (4–12%) and angiotensin-converting enzyme inhibitors (9–33%). At 6 and 12 months after dapagliflozin initiation, respectively, treatment discontinuation rates across the CEEBA region were 5.22% (59/1131) and 4.66% (50/1072). Conclusions The EVOLUTION HF primary data study programme provides novel insights into clinical characteristics and treatment patterns in patients with HFrEF initiating dapagliflozin in real-world practice across a broad European population. At dapagliflozin initiation, a large proportion of patients were receiving other HF therapeutics, suggesting dapagliflozin is one of the later therapies to be initiated. Indeed, this study identified a substantial delay (23–52 months) in dapagliflozin initiation following HF diagnosis. Treatment discontinuation rates following dapagliflozin initiation were also low, reinforcing the findings of the EVOLUTION HF secondary data studies.

Association between surgery treatment delays and survival outcomes in patients with esophageal cancer in Hebei, China.

The delays in cancer therapies have the potential to impact disease progression by allowing the unchecked growth and spread of cancer cells. However, the understanding of the association between treatment waiting time and survival outcomes in patients with esophageal cancer (EC) is limited. This study aims to assess the impact of waiting time on survival outcomes among EC patients in Hebei province, which is recognized as one of the high-risk areas for EC in China. A total of 9,977 non-metastatic EC patients who underwent surgical treatment were identified between 2000 and 2020. The survival outcomes of overall survival (OS) and cancer-specific survival (CSS) were determined using the Kaplan-Meier methodology. Univariate and multivariate Cox regression analysis was employed to evaluate the impact of treatment delays on OS and CSS. The average delay time for initiating EC surgical treatment after diagnosis was 1.31 months (95%CI=1.29-1.34). Patients with a long delay (≥ 3 months) intreatment, comprising 9977 EC patients, exhibited significantly lower rates of 3-, 5-, and 10-year OS and CSS compared to those without any delay in treatment initiation. A long delay in EC treatment independently associated with an elevated risk of all-cause and cancer-cause mortality among various patient subgroups, including males, older individuals, single individuals, low-income patients, residents of nonmetropolitan counties, as well as those diagnosed with poorly differentiated and stage IV EC. The long delay of treatment initiation impacts the outcomes of OS and CSS in EC patients. Optimizing treatment timing may enhance life expectancy for individuals diagnosed with EC.

Multilevel Disparities of Sex-Differentiated Human Papilloma Virus-Positive Oropharyngeal Cancers in the United States.

Objectives: This study used multilevel social determinants of health (SDoH) models to determine how SDoH influence different sexes of patients diagnosed with HPV-positive oropharyngeal squamous cell cancers (OPSCC) across the US. Methods: This was a retrospective cohort study assessing HPV-confirmed patients with oropharyngeal squamous cell cancers from 2010 to 2018 using census-level Yost Index socioeconomic status (SES) score and rurality-urbanicity measures alongside individual-level race-ethnicity while stratifying by biological sex. Age-adjusted multivariate regressions were performed for survival, treatment receipt, and delay of treatment initiation (of 3+ months). Results: Across 14,076 OPSCC-HPV-positive patients, delay of treatment uniquely featured positive predictors for males of black race-ethnicity (OR, 2.07; 95% CI, 1.68-2.54) and poor Yost SES (1.43; 1.24-1.65). Five-year all-cause mortality uniquely showed positive predictors of females of black race-ethnicity (2.74; 1.84-4.71) and of males with poor Yost SES (1.98; 1.79-2.19). Three-year all-cause mortality shared positive predictors across sexes but were exacerbated in females of black race-ethnicity (2.50; 1.82-3.44) compared to males (2.23; 1.91-2.60); this was reversed for poor Yost SES (male, 1.92, 1.76-2.10; female, 1.60, 1.32-1.95). Surgery showed negative predictors of black race-ethnicity that displayed worsened effects in females (0.60, 0.44-0.79) versus males (0.75, 0.66-0.86). First-line radiation receipt uniquely featured negative predictors for males of black race-ethnicity (0.73; 0.62-0.86) with poor Yost SES (0.74; 0.68-0.82). Conclusions: Comprehensive models of multilevel SDoH displayed exacerbated disparity effects of community-level SES in males and black race-ethnicity among female HPV-positive OPSCC patients. These objective comparisons of specific SDoH factors inform providers and policy direction on how to strategically target the most pertinent SDoH factors affecting a rapidly growing cancer population.

Risk Factors and Outcome of Acute Kidney Injury in Children with Diabetic Ketoacidosis

Background: Children with diabetic ketoacidosis (DKA) suffer from several complications. Among them acute kidney injury (AKI) is one of the grave complications. Objectives: To determine the risk factors for development of AKI in children (age &lt;15 years) with DKA and observe the outcome of these children. Method: An observational study was done in Department of Paediatrics, BIRDEM General Hospital, Dhaka, Bangladesh from January 2019 to December 2020. During study period, we observed all children with DKA who developed AKI. Data of clinical and biological variables were taken from hospital records and analysed. The parameters of children with AKI were compared with children with DKA who did not develop AKI. Then outcome of the children with AKI were measured. Statistical analysis was done by using SPSS version 23. Results: Among 73 children with DKA, 16 (21.9%) children developed AKI. Children were divided into two groups, DKA with AKI and DKA without AKI. No statistically significant differences were found in demographic features of children in both groups. We observed that, delay in initiation of treatment, low Glasgow Coma Scale (score- &lt;8), haemodynamic failure, severe acidosis and sepsis were significant risk factors of developing AKI. Out of 16 children with AKI, 9(56.2%) patients needed peritoneal dialysis and 7(43.7%) responded to fluid resuscitation. Complete resolution occurred in 13(81.2%). Total mortality in DKA children was 13(17.8%). Among them 84.6% children died due to AKI. Conclusions: This study documented that 21.9% of children with DKA developed AKI. Among them mortality was 84.5%. BANGLADESH J CHILD HEALTH 2023; VOL 47 (1) : 30-33

A practical approach to febrile cancer patients: Diagnostic stewardship in Oncology units

Introduction Cancer and cytotoxic chemotherapy used for its treatment predispose to severe and often fatal infections. Prompt diagnosis and timely antibiotic therapy are crucial, with delays in therapy initiation having high mortality. Complete blood count (CBC) is an inexpensive, standardized, and preliminary investigation for the management and follow-up of cancer patients with diagnostic and prognostic value. Method We studied the types of infections associated with various cancers treated with chemotherapy, their etiologies and susceptibility patterns, and the hematological profile of these patients as predictors of infection. Results A total of 21 patients (12 solid and 9 hematological malignancies) presented with 31 febrile episodes. White Blood cell count (2079 cells/cu. mm), percentage of neutrophils (52.9%), absolute neutrophil (137.5 cells/cu. mm), and platelet count (1,77,507 cells/cu. mm) were significantly lower in the 11 patients with febrile neutropenia. The absolute lymphocyte count (412.7 cells/cu. mm) was reduced with a strikingly low Neutrophil-to-lymphocyte ratio (NLR) (6.07) in patients with neutropenia. Laboratory and radiological evidence were present in 14/15 episodes of hematological malignancies (p-0.218) whereas unexplained clinical sepsis was common in solid malignancies (p-0.0202). The majority of documented infections were bacterial, caused by gram-negative bacilli, often showing multi-drug resistance. Infectious etiologies were identified in 71.4% of the patients with febrile neutropenia for &gt;5days. Bacterial infections developed within 2 days of neutropenia, whereas viral and fungal infections manifested in prolonged neutropenia. Multi-site infections and higher mortality rates were observed in patients with febrile neutropenia. (p&lt;0.04) Conclusion Febrile neutropenia is a common complication among patients receiving chemotherapy for cancer, with an increased risk of morbidity and mortality. Early, rapid, and accurate diagnosis is key to prompt intervention. Hematological parameters such as Total Leukocyte count, platelet count, NLR, and Platelet-to-lymphocyte ratio are promising biomarkers in conjunction with morphological changes in neutrophils, thus proving that CBC and peripheral smears are simple, easily available, cost-effective, and highly dependable screening tools, especially in resource-poor settings.

Impact of Head and Neck Multidisciplinary Clinic on Treatment Package Time During 2 Years of the COVID-19 Pandemic: A Single-Institution Experience.

Prolongation of treatment package time is strongly associated with inferior oncologic outcomes. We examine the effect of creation of a multidisciplinary head and neck clinic on treatment package times. This was a retrospective cohort study evaluating treatment package time in patients receiving adjuvant radiation through a multidisciplinary clinic compared with standard clinics at a single academic institution between 7/31/2020 and 7/31/2022. Adjuvant radiotherapy was administered to 23 patients in multidisciplinary clinic, 68 patients in standard clinic and 17 patients in satellite clinics. Patients seen in multidisciplinary clinic began adjuvant radiation sooner (median 35 vs 41 vs 48 days, p=0.01) with more compact treatment package times (median 78 vs 84 vs 86 days, p=0.003). Nine patient (13%) in standard clinics and 4 patients (24%) at the satellite clinics had adjuvant treatment package times exceeding 100 days. No patient seen in multidisciplinary clinic had treatment package times exceeding 100 days. Colocalization of radiation oncology and otolaryngology care in multidisciplinary clinic substantially improved time to postoperative radiotherapy and treatment package times. This is likely due to the identification of patients requiring adjuvant radiation earlier in their clinical presentation which in turn allowed for advanced planning and minimization of delays in initiation of adjuvant radiation.

Dose and timing effects of caffeine on subsequent sleep: A randomised clinical crossover trial.

To investigate the effect of a typical dose of caffeine and a high dose of caffeine consumed in the morning, afternoon, and evening on subsequent sleep. Using a placebo-controlled, double-blind, randomised crossover design, 23 males (25.3±5.0 years) with a moderate habitual caffeine intake (<300mg∙day-1) completed seven conditions: placebo, and 100 and 400mg of caffeine consumed 12, eight, and four hours prior to bedtime, with a 48-hour washout. In-home partial polysomnography and sleep diaries were used to assess sleep. Linear mixed models estimated the effect of each condition. No significant effect on objective or subjective sleep occurred with the 100mg dose of caffeine compared to the placebo (p>0.05) but significant effects occurred with the 400mg dose (p<0.05). Significant delays in sleep initiation and alterations to sleep architecture were observed when 400mg was consumed within 12 hours of bedtime (p<0.05), and significantly greater sleep fragmentation occurred when 400mg was consumed within eight hours of bedtime (p<0.05). Additionally, perceived sleep quality was significantly reduced when 400mg was consumed four hours prior to bedtime (-34.02%, p=.006) but not at eight or 12 hours. A 100mg dose of caffeine can be consumed up to four hours prior to bedtime, but 400mg may negatively impact sleep when consumed as one dose within 12 hours of bedtime, with the adverse influence on sleep increasing the closer consumption occurs to bedtime. The discrepancy between objective and subjective sleep quality suggests individuals may have difficulty accurately perceiving the influence of caffeine on sleep quality.

Characteristics and prognosis of patients with cardiac sarcoidosis presenting with atrioventricular block and ventricular arrhythmias

Cardiac sarcoidosis (CS) may initially present with life-threatening arrhythmias such as atrioventricular block (AVB) and ventricular arrhythmia (VA), including ventricular tachycardia and ventricular fibrillation. Diagnosing CS is challenging due to subtle or absent findings in routine tests and the low sensitivity of the definitive diagnostic tool, endomyocardial biopsy. CS can also mimic other cardiac conditions such as dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy, and it may occur without any systemic involvement. Consequently, delays in presentation, accurate diagnosis, and initiation of appropriate treatment are frequent. Greater awareness of the condition could improve outcomes for patients with CS. Non-invasive advanced imaging techniques, such as 18F-fluorodeoxyglucose positron emission tomography and cardiac magnetic resonance imaging are essential for diagnosis, although they may not be accessible in all clinical settings. Management of arrhythmias in CS involves conventional therapies in the utilization of antiarrhythmics and non-pharmacological therapy (e.g., implantable devices), but with notable divergences in the use of immunosuppression and a preference for implantable cardioverter defibrillators over permanent pacemakers. This narrative review aimed to outline the clinical features of patients with CS presenting with AVB or VA and examine diagnostic investigations, imaging techniques, treatment approaches, and prognosis based on current research and international guidelines.

Prolonged Time-to-antihypertensive Therapy Worsens Organ Damage and Blood Pressure Control in Arterial Hypertension.

Delay in arterial hypertension (AH) diagnosis and late therapy initiation may affect progression towards hypertensive-mediated organ damage (HMOD) and blood pressure (BP) control. We aimed to assess the impact of time-to-therapy on BP control and HMOD in patients receiving AH diagnosis. We analysed data from the Campania Salute Network, a prospective registry of hypertensive patients (NCT02211365). At baseline visit, time-to-therapy was defined as the interval between the first occurrence of BP values exceeding guidelines-directed thresholds and therapy initiation; HMOD included left ventricular hypertrophy (LVH), carotid plaque, or chronic kidney disease. Optimal BP control was considered for average values < 140/90 mmHg. Low-risk profile was defined as grade I AH without additional cardiovascular risk factors. From 14,161 hypertensive patients, we selected 1,627 participants who were not on antihypertensive therapy. This population was divided into two groups based on the median time-to-therapy (≤ 2 years n = 1,009, > 2 years n = 618). Patients with a time-to-therapy > 2 years had higher risk of HMOD (adjusted odds ratio, aOR:1.51, 95%, CI:1.19-1.93, p < 0.001) due to increased risks of LVH (aOR:1.43, CI:1.12-1.82, p = 0.004), carotid plaques (aOR:1.29, CI:1.00-1.65, p = 0.047), and chronic kidney disease (aOR:1.68, CI:1.08-2.62, p = 0.022). Time-to-therapy > 2 years was significantly associated with uncontrolled BP values (aOR:1.49, CI:1.18-1.88, p < 0.001) and higher number of antihypertensive drugs (aOR:1.68, CI:1.36-2.08, p < 0.001) during follow-up. In low-risk subgroup, time-to-therapy > 2 years did not impact on BP control and number of drugs. In hypertensive patients, a time-to-therapy > 2 years is associated with HMOD and uncontrolled BP.

Hybridization of Machine Learning Models for Alzheimers Disease Classification

Alzheimer's disease (AD), is a gradual cognitive decline and memory impairment. It is a major health concern worldwide. Despite intensive research efforts, accurate and early diagnosis remains difficult to achieve, largely due to the complexity of AD pathology and the absence of definitive biomarkers. Existing diagnostic approaches often rely on costly and invasive procedures, leading to delays in diagnosis and treatment initiation, and limiting the effectiveness of therapeutic interventions. To overcome these issues, this work suggests a novel approach for AD classification using EEG signals. EEG signals offer a non-invasive and cost-effective means of assessing brain activity, making them an attractive candidate for biomarker discovery and disease classification. The proposed work integrates preprocessing, feature extraction, and classification methodologies to accurately differentiate between AD, normal/healthy states, and Frontotemporal Dementia (FTD). The proposed solution begins with Sequential Savitzky-Golay filtering (SEQ-SG) to enhance the quality of EEG signals by reducing noise and enhancing relevant features. Subsequently, an Improved Principal Component Analysis (IPCA) approach is employed for feature extraction, incorporating feature scaling using StandardScaler to ensure uniform contribution from all features. Finally, classification is achieved using a hybrid approach named HMLCAD (Hybridization of Machine Learning for Classification of Alzheimer's Disease), which combines Random Forest and Gradient Boosting through a voting classifier ensemble. This methodology offers a promising framework for accurate and early detection of AD, enabling timely intervention and improved patient outcomes.

B-296 Assessment of Clozapine Assay on The Automated, High-performance Beckman AU Analyzer

Abstract Background Treatment-resistant schizophrenia (TRS) affects approximately one in three patients with schizophrenia. The timely initiation of clozapine therapy is crucial for achieving remission in TRS patients. However, long turnaround times (TATs) associated with sending clozapine tests to reference laboratories cause significant challenges, leading to delays in treatment initiation and compromising patient outcomes. To address this issue, we implemented in-house clozapine testing on Beckman AU analyzers, aiming to facilitate early clozapine initiation and enhance confidence in prescribing and monitoring clozapine therapy for TRS patients. Methods The Beckman AU clozapine assay is a homogenous competitive nanoparticle agglutination assay. Precision and linearity were assessed for the Beckman AU DxC700 clozapine assay using manufacturer-provided standards. We conducted a correlation study involving 31 samples analyzed on both Beckman AU DxC 700 and LC-MS/MS methods. Data analysis was performed using Deming and Linear regression methods. Additionally, we analyzed 356 clozapine tests performed in-house on Beckman AU DxC700 between March 15th and Sept 10th, 2023, and compared them with 1399 clozapine tests sent to a reference laboratory using the LC-MS/MS method from March 13th, 2020, to March 13th, 2023. Turnaround time was evaluated. Results The Beckman AU DxC700 clozapine assay exhibited excellent performance across the measuring range, with intra-assay and inter-assay coefficients of variation ranging from 1.7-3.6% and 2.2-5.3%, respectively. The assay demonstrated linearity over the five recommended ranges (68-1500 ng/mL) without significant bias observed. The Beckman AU DxC700 and LC-MS/MS clozapine assays displayed excellent correlation (R2=0.948, slope=0.941, intercept=6.3). Implementation of in-house clozapine testing led to a significant reduction in total turnaround time, from 3922 minutes to 116 minutes. The time from sample receipt to results also decreased substantially, from 3894 minutes to 32 minutes. Conclusions The clozapine assay was validated and routinely measured in-house using the Beckman AU DxC700 automated assay. Moreover, we validated the correlation by confirming that the results from Beckman AU DxC had around 6% lower bias comparing with LC-MS/MS. Turnaround time serves as a critical quality indicator for evaluating testing process effectiveness and efficiency, as well as clinician and patient satisfaction. The implementation of in-house clozapine testing significantly improved pre-analytical, analytical, and post-analytical Turnaround times.

Impact of delays in neoadjuvant chemotherapy initiation on pathologic complete response among patients with HER2-positive or triple negative breast cancer.

102 Background: Pathologic complete response (pCR) is used as a surrogate endpoint for overall survival (OS) in high-risk early-stage breast cancer (BC). pCR rates vary according to BC molecular subtype and have the highest association with OS in triple negative BC (TNBC) and HER2-positive (HER2+) BC. In these subgroups, neoadjuvant chemotherapy (NACT) is often the standard of care. We evaluated the association of delays in NACT initiation (NACTI) with pCR. Methods: We conducted a retrospective cohort study using the National Cancer Database. Eligibility included age ≥18 years, diagnosis cT2+ or lymph node positive HER2+ or TNBC between 1/1/2010 – 12/31/2020, who were treated with NACT within 180 days of BC diagnosis. Time to chemotherapy (TTC) was recorded in days. Patients were categorized by receptor status. We used AJCC 7 th and 8 th edition T and N staging to define pCR (pT0 or pTis and pN0 or pN0I-). Delay was defined as TTC &gt; 60 days. Multivariable logistic regression, adjusted for demographic, socioeconomic and tumor characteristics, was used to calculate odds of pCR associated with delays. A sensitivity analysis defining delay &gt;30 and &gt;90 days was also conducted. Results: We identified 105,352 eligible patients, 73% were White, 19% were Black, 3% were Asian, and 4% were Other/Unknown. Median age at diagnosis was 52 years (range 18-90), median TTC was 32 days (range 0-180). There were 56,868 patients with HER2+ BC and 48,484 with TNBC; 9% of patients were delayed &gt; 60 days in each group. Among all HER2+ patients, 39.1% achieved a pCR: 35.0% with delay compared to 39.5% without delay. Among TNBC patients, 30% achieved a pCR: 25% with delay compared to 31% without delay (p &lt; 0.0001 for all). In multivariable analysis, patients with HER2+ disease (OR 0.85, 95%CI 0.79-0.92) and TNBC (OR 0.80, 95%CI 0.73-0.87) were less likely to achieve pCR if delayed &gt; 60 days. In a sensitivity analysis, delay &gt; 30 days was associated with lower likelihood of achieving pCR for all and delay &gt; 90 days was associated with lower likelihood for TNBC (Table). Conclusions: Delays in NACTI &gt;60 days among patients with HER2+ and TNBC BC was an independent predictor of not achieving pCR. Given the known association between socioeconomic factors and delays to initiation of treatment, interventions aimed at reducing delays may reduce disparities in BC outcomes. Future studies to identify causes of delays and the downstream impact are needed to ultimately develop interventions that mitigate these effects among patients with HER2+ or TNBC, where pCR rates are associated with OS. Association of pCR in patients who experience NACTI delay using multivariable logistic regression* n(complete case) = 77,690. Subgroup &gt;30-day Delay in NACTIOR (95% CI) &gt;60-day Delay in NACTIOR (95% CI) &gt;90-day Delay in NACTIOR (95% CI) HER2+n =41,672 0.91 (0.87-0.95) 0.85 (0.79-0.92) 0.93 (0.80-1.07) TNBCn = 36,018 0.87 (0.83-0.92) 0.80 (0.73-0.87) 0.78 (0.65-0.92) *Adjusted for demographic, socioeconomic and tumor characteristics.