Adverse Treatment Outcomes Research Articles

Prevention of adverse HIV treatment outcomes: machine learning to enable proactive support of people at risk of HIV care disengagement in Tanzania

ObjectivesThis study aimed to develop a machine learning (ML) model to predict disengagement from HIV care, high viral load or death among people living with HIV (PLHIV) with the goal...

The influence of comorbidities on treatment outcomes in patients with tuberculosis

To study the association of comorbidities and treatment outcomes in tuberculosis (TB) patients. A retrospective study includes all TB patients aged 18 years and older registered for treatment in Moscow in period 2021 the end of the 3rd quarter of 2022 using data of regional epidemiological TB monitoring system, a total of 3039 patients. The frequency and spectrum of comorbidities, its impact on the risk of adverse treatment outcome (ATO) and mortality using univariate and regression analysis were assessed. Comorbidities were identified in 1528 (50.3%) patients (95% confidence interval - CI 48.5-52.1); HIV infection (18.0%), chronic nonspecific lung disease (9.6%) and cardiovascular disease (8.2%) were predominant. The presence of comorbid pathology increased the odds of uneffective treatment (odds ratio - OR 2.56, 95% CI 2.22-3.03) and death (OR 2.45, 95% СI 1.67-3.59). Independent risk factors for ATO were HIV infection (OR 4.10, 95% CI 3.36-5.10), substance use (OR 2.57, 95% CI 1.70-3.66), chronic nonspecific lung disease (OR 1.39, 95% CI 1.04-1.88), diabetes mellitus (OR 1.69, 95% CI 1.15-2.48), liver pathology (OR 2.10, 95% CI 1.46-3.03), mental illness (OR 2.01, 95% CI 1.32-3.06). The death rate was 13.4%; the most significant predictors of mortality were HIV infection (OR 3.89, 95% CI 2.42-6.22) and liver disease (OR 1.90, 95% CI 1.27-2.82). A comorbidome model was constructed to assess the importance of different comorbidities for patient prognosis. The presence of comorbidity (predominantly HIV infection and liver disease) is a significant risk factor for ATO and mortality in TB patients, which should be taken into account when organizing and providing TB care to comorbid patients.

A - 146 Psychiatric Drugs Can Precipitate Neuropsychological Predicates of Homicide

Abstract Objective A man inexplicably killed his beloved wife. He had no history of violence, was a prominent member of the community, and gave no indications of the impending horrific act. He had been recently commenced treatment with psychiatric drugs, and his condition deteriorated, culminating in homicide. After his incarceration, he stopped taking psychiatric drugs and his mental health improved. Many practitioners are not aware that psychiatric drugs can create a risk for violence - or precursors of violence - such as anger, hostility, and agitation. This risk is often described on the product label. Method The subject was an intensive care nurse who became exhausted and despondent serving long hours during the Covid epidemic, when many of his patients were put on ventilators and died. He had suffered panic attacks from his difficulty breathing through the respiratory masks. He temporarily left employment and sought psychiatric assistance for his professional “burn-out” condition. After three doses of venlafaxine, he reported side effects including increased anxiety, blood pressure and heart rate. He was then prescribed escitalopram without tapering of the venlafaxine. As his anxiety progressed, he was prescribed escitalopram once daily and buspirone three times daily, yet he continued to deteriorate until the homicide. Results Expert genetic analysis found susceptibility to the psychiatric drugs prescribed. The neuropsychological evaluation, months post-homicide, found excellent neuropsychological function, although psychomotor and processing speed was deficit. Personality testing found no disorders, with a profile inconsistent with violent behavior. Conclusions Prescribers need to monitor patients carefully for potentially adverse and violent outcomes of treatment.

“It's the patient that suffers from poor communication”: Analyzing communication gaps and associated consequences in handover events from nurses’ experiences

BackgroundAlthough routine communication gaps among clinical shift teams significantly account for adverse care and treatment outcomes, existing analysis of the phenomenon remain limited in low middle income countries battling with patient safety issues. This study analyzed the drivers and associated episodic consequences of communication gaps from nurses’ experiences in Ghana. MethodsQualitative design implemented in two referral hospitals. Data collection involved site observations and in-depth interviews with general nurses, midwives, and staff nurses across 3-cycle shift regimes in the emergency, ICU, inpatient wards, and maternity units. A two-stage data analysis was adopted by integrating deductive and inductive codes into broad thematic typologies explaining drivers of communication gaps and the consequences thereof. ResultsCommunication gaps among shift teams were largely driven by a combination of three broad factors: a) Attitudinal elements of poor work ethics, poor documentation, interpersonal conflicts and use of unconventional language that impaired effective communication; b) organizational dynamics of taxing job demands, limited training exposure and lack of formal handover communication procedures which allowed shift teams to adopt default patterns of communication behavior; and c) cultural values, stereotyping and prejudicing behaviors that restricted inclusive interactions among shift teams. These communication gaps produced adverse episodic effects of diagnostic and treatment errors, complications, and extended hospitalizations. ConclusionThe findings underscore the need to develop standard guidelines to direct structured communication alongside equipping shift teams with competences on emotional intelligence to overcome cultural and behavioral adversities that influence communication breakdown.

Characterizing the Links Between Systemic Sclerosis and Breast Cancer.

Systemic sclerosis (SSc) is a complex, autoimmune connective tissue disease that affects multiple organs in the body, culminating in a variance of severity and a reduced quality of life. Breast cancer (BC) also affects patients with SSc, and these two conditions affect a similar demographic. With this systematic review, we aim to characterize the links between SSc and BC. Characterizing possible links between SSc and breast malignancies is important for advancing the understanding of SSc management and comorbidities. In this systematic meta-analysis, a comprehensive literature search was conducted in PubMed using relevant keywords and MeSH terms. The inclusion criteria included an English-language retrospective analysis that characterized patients with SSc with or without BC. Two independent reviewers assessed the study's eligibility based on predetermined criteria. Data extraction included patient antibody measurements, demographics (age and gender), family history, social behaviors (alcohol use and smoking history), concurrent condition treatments, and adverse effects following treatment. Thirteen articles were identified in the literature with relevant data on SSc and BC patients. Studies encompassed research about SSc patients with or without BC and relevant risk factors being measured. SSc was found to have a link to antibodies widely associated with cancer. Adverse treatment outcomes and concurrent conditions of BC were found when patients had a family history of SSc, BC, or an alcohol or smoking history. Our results suggest that the presence of antinuclear antibodies, anti-centromere antibodies, or anti-topoisomerase antibodies in SSc patients is correlated with BC. Out of the three antibodies, ATA seemed to be found more commonly in patients with SSc and malignancy across the studies. This systematic review discusses the link between SSc and BC through patients with relevant clinical markers, medical histories, and treatments. However, further research is necessary to advance the linkage between SSc and BC and determine whether management of one condition may prevent or alleviate the other.

P-685 An artificial intelligence based medication regimen recommendation model for optimizing the treatment outcomes of controlled ovarian stimulation

Abstract Study question Can a machine learning (ML) algorithm suggest an optimal controlled ovarian stimulation (COS) protocol for maximizing the number of retrieved and mature (MII) oocytes? Summary answer Based on historical electronic medical record patient data, using ML algorithm based medication regimen recommendation model may increase the number of retrieved oocytes. What is known already The application of artificial intelligence in the field of reproductive medicine is mainly focused on the image analysis of gamete and embryo, and prediction of treatment outcomes. The research on the optimization of COS process is limited. Previous studies mainly focused on one or several types of COS protocols such as GnRH-a protocol and GnRH-A protocol. And most of them aimed to assist single-node decision-making during COS process such as optimal gonadotropins starting dose and trigger day. Study design, size, duration The data used for developing this model consists of 38,355 COS cycles from women who underwent their first IVF/ICSI treatment in a large fertility center between January 2008 to December 2022, of which 33,853 were used as the model training set and 4,502 were used as the test set. This dataset contains a subset of 8,382 cycles with information about MII oocytes. Participants/materials, setting, methods The goal of model was to recommend the optimal COS protocol based on optimizing COS outcomes. The similarity of patient’s characteristic was used as model input. XGBoost algorithm was constructed to calculate the similarity of COS outcomes. The accuracy was compared with the patient similarity calculation method of KNN+Euclidean distance and KNN+cosine distance using mean absolute error (MAE). The performance of different models in improving the average number of retrieved and MII oocytes was compared. Main results and the role of chance The patient similarity calculation method based on XGBoost had lowest MAE when predicting the number of retrieved oocytes (XGBoost vs KNN+Euclidean distance+k=500 vs KNN+Euclidean distance+k=1000 vs KNN+cosine distance+k=500 vs KNN+cosine distance+k=1000: 3.729 vs 3.810 vs 3.815 vs 3.785 vs 3.788). Including AMH could improve the accuracy of all recommendation models in predicting protocols and the number of retrieved oocytes. When the optimal number of MII oocytes is used as the protocol recommended target, the patient similarity calculation method based on XGBoost had lowest MAE (XGBoost vs KNN+Euclidean distance+k=500 vs KNN+Euclidean distance+k=1000 vs KNN+cosine distance+k=500 vs KNN+cosine distance+k=1000: 2.868 vs 3.397 vs 3.452 vs 3.356 vs 3.395). The COS medication regimen recommended by the patient similarity calculation method based on COS treatment outcomes has resulted in higher numbers of retrieved oocytes in patients compared to those who did not adopt recommendation (P < 0.01). The medication regimen recommended model based on KNN+Euclidean distance algorithm (k = 500) has the best performance in improving the average number of retrieved oocytes（adopt recommendation vs not adopt recommendation: 13.01±6.61 vs 10.09±6.67, P < 0.01）There was no statistical difference in the number of MII oocytes between patients receiving the recommendation and those not adopt recommendation. Limitations, reasons for caution The medication regimen recommendation model is based solely on the predicted number of retrieved and MII oocytes, not including adverse treatment outcomes such as ovarian hyperstimulation syndrome. Moreover, the database used to train and validate the model is from a single fertility center. Wider implications of the findings The recommendation model is helpful to improve the number of retrieved oocytes. Based on the recommended COS protocol, further mining the medication content, medication time distribution and medication sequence transformation from the similar patient set can assist clinicians to develop individualized COS medication regimen for infertile patients. Trial registration number not applicable

Assessing the Benefits and Harms of Pharmacotherapy in Older Adults with Frailty: Insights from Pharmacoepidemiologic Studies of Routine Health Care Data.

The objective of this review is to summarize and appraise the research methodology, emerging findings, and future directions in pharmacoepidemiologic studies assessing the benefits and harms of pharmacotherapies in older adults with different levels of frailty. Older adults living with frailty are at elevated risk for poor health outcomes and adverse effects from pharmacotherapy. However, current evidence is limited due to the under-enrollment of frail older adults and the lack of validated frailty assessments in clinical trials. Recent advancements in measuring frailty in administrative claims and electronic health records (database-derived frailty scores) have enabled researchers to identify patients with frailty and to evaluate the heterogeneity of treatment effects by patients' frailty levels using routine health care data. When selecting a database-derived frailty score, researchers must consider the type of data (e.g., different coding systems), the length of the predictor assessment period, the extent of validation against clinically validated frailty measures, and the possibility of surveillance bias arising from unequal access to care. We reviewed 13 pharmacoepidemiologic studies published on PubMed from 2013 to 2023 that evaluated the benefits and harms of cardiovascular medications, diabetes medications, anti-neoplastic agents, antipsychotic medications, and vaccines by frailty levels. These studies suggest that, while greater frailty is positively associated with adverse treatment outcomes, older adults with frailty can still benefit from pharmacotherapy. Therefore, we recommend routine frailty subgroup analyses in pharmacoepidemiologic studies. Despite data and design limitations, the findings from such studies may be informative to tailor pharmacotherapy for older adults across the frailty spectrum.

Role of renin angiotensin system inhibitors and metformin in Glioblastoma Therapy: a review.

Glioblastoma multiforme (GBM) is a highly aggressive and incurable disease accounting for about 10,000 deaths in the USA each year. Despite the current treatment approach which includes surgery with chemotherapy and radiation therapy, there remains a high prevalence of recurrence. Notable improvements have been observed in persons receiving concurrent antihypertensive drugs such as renin angiotensin inhibitors (RAS) or the antidiabetic drug metformin with standard therapy. Anti-tumoral effects of RAS inhibitors and metformin have been observed in in vitro and in vivo studies. Although clinical trials have shown mixed results, the potential for the use of RAS inhibitors and metformin as adjuvant GBM therapy remains promising. Nevertheless, evidence suggest that these drugs exert multimodal antitumor actions; by particularly targeting several cancer hallmarks. In this review, we highlight the results of clinical studies using multidrug cocktails containing RAS inhibitors and or metformin added to standard therapy for GBM. In addition, we highlight the possible molecular mechanisms by which these repurposed drugs with an excellent safety profile might elicit their anti-tumoral effects. RAS inhibition elicits anti-inflammatory, anti-angiogenic, and immune sensitivity effects in GBM. However, metformin promotes anti-migratory, anti-proliferative and pro-apoptotic effects mainly through the activation of AMP-activated protein kinase. Also, we discussed metformin's potential in targeting both GBM cells as well as GBM associated-stem cells. Finally, we summarize a few drug interactions that may cause an additive or antagonistic effect that may lead to adverse effects and influence treatment outcome.

A genre-based approach in ESP classes to teaching clinical communication focusing on breaking bad news to patients

Healthcare professionals have the responsibility to regularly convey difficult information such as unfavourable diagnoses, as well as adverse treatment outcomes. While this task can be uncomfortable, successfully carrying it out plays a crucial role in determining patient outcomes (Sweeney et al. 2011: 230). This necessity has led to the creation of evidence-based protocols such as SPIKES developed by Baile et al. (2000). The goal of the paper is to explore the suitability of the genre-based approach for the study and teaching of medical English, focusing on the integration of the selected clinical communication tool into the ESP classroom. As this study stems from the ESP practitioner’s experience and its outcomes will directly influence her future ESP classroom teaching, action research has been conducted. The feasibility of using an authentic clinical tool in an ESP lesson was assessed through a two-step methodology: i) devising an ESP task based on the SPIKES protocol, emphasizing linguistic elements, and ii) obtaining student feedback focusing on the perceived usefulness of the tool. Overall, the collected data indicate that students acknowledged the significance of effective clinical communication for successful therapeutic practice. However, given the fact that medical English is inconveniently scheduled in a pre-clinical phase of their curriculum, they also exhibited a certain level of hesitancy, unsurprisingly, when it came to readiness in handling serious communication scenarios.

Factors associated with unfavorable treatment outcomes among multidrug-resistant tuberculosis patients, Sierra Leone: a cross-sectional secondary data analysis

BackgroundGlobally, multidrug-resistant tuberculosis (MDR-TB) is a major public health problem. The tuberculosis rate in Sierra Leone is 298 per 100,000 people, and Sierra Leone is considered a country with a high burden of tuberculosis. In Sierra Leone, there are few studies on the outcomes of MDR-TB treatment, especially those exacerbated by COVID-19. We identified factors associated with unfavorable treatment outcomes among people with MDR-TB in Sierra Leone.MethodsWe conducted a cross-sectional study to analyze hospital-based MDR-TB data from 2017 to 2021. Demographic, clinical, and treatment outcome data were extracted from the main MDR-TB referral hospital database. We defined unfavorable outcomes as patients who died, were lost to follow-up, or defaulted. We calculated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) to identify predictors of the outcomes of MDR-TB treatment.ResultsBetween 2017 and 2021, 628 people with MDR-TB were reported at Lakka Hospital; 441 (71%) were male, with a median age of 25 years (interquartile ranges: 17–34). Clinically, 21% of the 628 MDR-TB patients were HIV positive, and 413 were underweight (66%). 70% (440) of MDR-TB patients received tuberculosis treatment. The majority of patients, 457 (73%), were treated with a short treatment regimen, and 126 (20%) experienced unfavorable outcomes. Age 45 years or younger (aOR = 5.08; CI:1.87–13.82), 21–45 years (aOR = 2.22; CI:140–3.54), tuberculosis retreatment (aOR = 3.23; CI:1.82–5.73), age group, HIV status (aOR = 2.16; CI:1.33–3.53), and malnourishment status (aOR = 1.79; CI:1.12–2.86) were significantly associated with unfavorable treatment outcomes for DR-TB patients.ConclusionThis analysis revealed a high proportion of unfavorable treatment outcomes among MDR-TB patients in Sierra Leone. Malnourishment, TB retreatment, HIV coinfection, and age 45 years or younger were associated with unfavorable outcomes of MDR-TB treatment. Increasing patients’ awareness, mainly among young people, heightens treatment adherence and HIV monitoring by measuring the amount of HIV in patient blood, which can reduce adverse treatment outcomes in Sierra Leone and other sub-Saharan African countries.

Risk factors for poor treatment outcomes among opioid-dependent clients taking methadone in Mombasa, Kenya.

Background: The Methadone Maintenance Treatment (MMT) program has been proven to be beneficial in reducing illicit opioid use, increasing access to and retention of HIV treatment and other therapies, and reducing HIV transmission, and other drug-related morbidities and mortalities. However, determinants of treatment retention and outcomes for opioid-dependent persons accessing MMT in Kenya are limited. We sought to identify factors contributing to poor treatment outcomes among opioid-dependent persons enrolled in the Mombasa MMT program, between 2017 and 2019. Method: We conducted a retrospective records review for opioid-dependent persons receiving Methadone treatment in the Kisauni MAT clinic enrolled during 2017-2019. We defined poor clinical or health-related treatment outcome as any client Lost-To-Follow-Up (LTFU), turned HIV or Viral hepatitis positive, and/or missed two or more antiretroviral therapy (ART) appointments intake during MMT. Variables abstracted from clinical and pharmacological MMT service delivery tools included socio-demographic characteristics, clinical history, risk factors, and MMT outcomes. Data were analyzed using Epi Info7. We calculated Prevalence Odds Ratios (POR) and 95% Confidence Intervals (CI) to identify factors associated with adverse health outcomes. Results: Of the total 443 eligible records, the mean age was 37years (SD ± 7.2) and males comprised 90.7%. The majority of females clients, 79.1% (34/43), were aged ≤35years, 7.0% (3/43) had no education, 32.6% (14/43) were employed, 39.5% (17/43) were HIV positive and 18.6% (8/43) were HCV-positive. Overall, adverse treatment outcomes were at 27.5% (122/443), namely: LTFU at 22.8% (101/443), new HIV cases at 1.0% (4/391), HCV at 1.2% (5/405), and Hepatitis B Virus (HBV) at 1.2% (5/411), and 1.1% (5/443) died. Of HIV-infected clients linked to Comprehensive Care Clinic (CCC), 3.6% (2/56) defaulted from ART, and 25% (2/8) had detectable Viral Load of those retested. Lack of formal education (POR: 2.7, 95% CI: 1.3-5.7), unemployment (POR: 2.4, 95% CI: 1.4-4.0), and being a Non-Injector (POR: 1.7, 95% CI: 1.0-2.9) were negatively associated with treatment retention. Conclusion: Females were younger, and more educated with higher HIV and HCV prevalence. Being a Non-injector, unemployment, and lack of formal education may increase the likelihood of poor treatment outcomes among MMT clients. Closer monitoring of MMT clients with these characteristics is recommended with the integration of CCC into MMT services.

Myrrh sitz bath for wound healing after hemorrhoidectomy: A retrospective study of adverse effects and treatment outcomes.

Hemorrhoids affect 75% of people worldwide. surgical hemorrhoidectomy remains the definitive intervention for severe cases. Postoperative wound care is critical, and alternative treatments, like Myrrh, are of growing interest due to their potential wound-healing properties. This study aimed to compare the safety, efficacy, and treatment outcomes of Myrrh sitz baths with standard clinical care in promoting wound healing after hemorrhoidectomy. A retrospective cohort study was carried out using medical records from Abha Private Hospital for the period of January-December 2022. The data of patients who underwent hemorrhoidectomy were collected and categorized based on postoperative wound care into two groups: Group A for Myrrh-based wound care as a self-medication and Group B for standard wound care. The study included 67 patients who underwent hemorrhoidectomy. Out of these patients, 52 had standard wound care, while 15 used Myrrh-based wound care as self-treatment without medical advice. The Myrrh group patients were significantly older with more comorbidities. The Myrrh group had significant Grade III wound healing outcomes 9/15 (60%) compared to the standard care group 2/52 (3.8%) (p < 0.001). However, despite the better healing outcomes, the Myrrh group had a significantly higher complication rate 7/15(46.7%) than the standard care group 1/52 (1.9%) (p < 0.001). These results indicate that despite the good healing capacity of Myrrh, cautious usage must be considered. Myrrh sitz baths appear more effective than standard wound care in enhancing healing after hemorrhoidectomy. However, increased complications suggest the necessity for comprehensive evaluation and research on its safety profile. These findings can guide future research and clinical practices related to postoperative wound care.

Patient-related decisional regret: An evolutionary concept analysis.

Health-related decision-making is a complex process given the variability of treatment options, conflicting treatment plans, time constraints and variable outcomes. This complexity may result in patients experiencing decisional regret following decision-making. Nonetheless, literature on decisional regret in the healthcare context indicates inconsistent characterization and operationalization of this concept. To conceptually define the phenomenon of decisional regret and synthesize the state of science on patients' experiences with decisional regret. A concept analysis. Rodgers' evolutionary method guided the conceptualization of this review. An interdisciplinary literature search was conducted from 2003 until 2023 using five databases, PubMed, CINAHL, Embase, PsycINFO and Web of Science. The search informed how the concept manifested across health-related literature. We used PRISMA-ScR checklist to guide the reporting of this review. Based on the analysis of 25 included articles, a conceptual definition of decisional regret was proposed. Three defining attributes underscored the negative cognitive-emotional nature of this concept, post-decisional experience relating to the decision-making process, treatment option and/or treatment outcome and an immediate or delayed occurrence. Antecedents preceding decisional regret comprised initial psychological or emotional status, sociodemographic determinants, impaired decision-making process, role regret, conflicting treatment plans and adverse treatment outcomes. Consequences of this concept included positive and negative outcomes influencing quality of life, health expectations, patient-provider relationship and healthcare experience appraisal. A conceptual model was developed to summarize the concept's characteristics. The current knowledge on decisional regret is expected to evolve with further exploration of this concept, particularly for the temporal dimension of regret experience. This review identified research, clinical and policy gaps informing our nursing recommendations for the concept's evolution. This concept analysis examines existing literature and does not require patient-related data collection. The methodological approach does not necessitate collaboration with the public.

Tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges.

Tuberculosis (TB) remains a leading cause of death among infectious diseases, particularly in poor countries. Viral infections, multidrug-resistant and ex-tensively drug-resistant TB strains, as well as the coexistence of chronic illnesses such as diabetes mellitus (DM) greatly aggravate TB morbidity and mortality. DM [particularly type 2 DM (T2DM)] and TB have converged making their control even more challenging. Two contemporary global epidemics, TB-DM behaves like a syndemic, a synergistic confluence of two highly prevalent diseases. T2DM is a risk factor for developing more severe forms of multi-drug resistant-TB and TB recurrence after preventive treatment. Since a bidirectional relationship exists between TB and DM, it is necessary to concurrently treat both, and promote recommendations for the joint management of both diseases. There are also some drug-drug interactions resulting in adverse treatment outcomes in TB-DM patients including treatment failure, and reinfection. In addition, autophagy may play a role in these comorbidities. Therefore, the TB-DM comorbidities present several health challenges, requiring a focus on multidisciplinary collaboration and integrated strategies, to effectively deal with this double burden. To effectively manage the comorbidity, further screening in affected countries, more suitable drugs, and better treatment strategies are required.

Abstract PO5-01-09: Exploring cellular heterogeneity of localised breast cancers

Abstract Breast cancer is a heterogeneous disease at multiple levels, ranging from subtype differences between patients (inter-patient heterogeneity) to the diverse composition of malignant cells, heterogeneity of hormone receptor (HR) expression and cellular makeup within single breast cancer samples (intra-tumour heterogeneity). Despite an increase in the number of effective therapies available, many patients will experience an incomplete treatment response and subsequent relapse. These adverse treatment outcomes may be attributed to the often overlooked but critical factor of cellular heterogeneity. In order to gain deeper insights into intra-tumour heterogeneity, we have applied single-cell technologies on a cohort comprising 250 primary, untreated breast cancers. We have optimized methods for tissue cryopreservation, eliminating the need for fresh sample processing, and multiplex tissue profiling. Together, these are cost-efficient processes that allow for improved handling of small tissue sizes, such as biopsies, and reduce batch effect. To ensure accurate and reliable data processing, we have developed a scalable computational workflow that includes benchmarked methods for sample SNP-demultiplexing, doublet detection, high-resolution cell annotation and cellular integration. Finally, we are extending our existing methods1 to study the cellular heterogeneity of breast cancers. Our method, scSubtyper, explores the phenotypic differences between malignant cells within tumours, by comparing each single cell to distinct features associated with different molecular subtypes and assigning each cell to one of these subtypes. Our previous study1 and preliminary results of this project revealed that over 90% of the samples exhibit a mix of malignant cells of different subtypes, and 50% of samples contain cells that have characteristics of all subtypes, demonstrating cellular heterogeneity exists not only exists between malignant cells, but also within malignant cells of a tumour. Our second approach, known as ecotyping, assesses patterns of cell type frequencies across samples and groups them based on similarity of these co-occurences. Our preliminary results have revealed the existence of 5 ecotypes that lack significant associations with samples clinical subtypes. Applying the same approach exclusively within the HR-positive samples identified 4 ecotypes characterized by distinct abundances of immune and stromal cells. This analysis revealed that ecotypes are not a simple surrogate for clinical and molecular subtypes, but their presence could drive different response to treatment. Together, our high-throughput tissue processing and computational approaches to studying intra-tumour heterogeneity are now being applied to our large, well annotated, clinical cohort. Supported by the preliminary results, we hypothesize that this study will play a vital role in optimizing breast cancer patient stratification to improve treatment management and outcome. 1. Wu, Sunny Z., et al. "A single-cell and spatially resolved atlas of human breast cancers." Nature genetics 53.9 (2021): 1334-1347. Citation Format: Beata Kiedik, Daniel Roden, Kate Harvey, Ghamdan Al-Eryani, Sunny Wu, Mun Hui, Sandra O'Toole, Elgene Lim, Charles Perou, Alex Swarbrick. Exploring cellular heterogeneity of localised breast cancers [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 PO5-01-09.

Overcoming Delays in the Progress against Cancer: Identifying Tobacco Use among Cancer Patients Enrolled in Clinical Trials.

Though smoking causes adverse cancer treatment outcomes and smoking cessation can improve survival, prior literature demonstrates deficits in collecting tobacco use information in clinical trials. Results by Streck and colleagues represent a thorough structured assessment of tobacco use and alternative tobacco product use in patients enrolled in cooperative group trials. Among patients with predominantly non-tobacco related cancers, observations demonstrate that approximately 27% of patients reported using one or more forms of tobacco use after diagnosis. Alternative tobacco use was reported by many patients, including patterns of dual use. Results demonstrate the feasibility of collecting comprehensive structured tobacco use information, and further support the need to address tobacco and cessation even among patients with non-tobacco related cancers. See related article by Streck and colleagues, Cancer Epidemiol Biomarkers Prev 2023;32:1552-57.

Association between TB delay and TB treatment outcomes in HIV-TB co-infected patients: a study based on the multilevel propensity score method.

HIV-tuberculosis (HIV-TB) co-infection is a significant public health concern worldwide. TB delay, consisting of patient delay, diagnostic delay, treatment delay, increases the risk of adverse anti-TB treatment (ATT) outcomes. Except for individual level variables, differences in regional levels have been shown to impact the ATT outcomes. However, few studies appropriately considered possible individual and regional level confounding variables. In this study, we aimed to assess the association of TB delay on treatment outcomes in HIV-TB co-infected patients in Liangshan Yi Autonomous Prefecture (Liangshan Prefecture) of China, using a causal inference framework while taking into account individual and regional level factors. We conducted a study to analyze data from 2068 patients with HIV-TB co-infection in Liangshan Prefecture from 2019 to 2022. To address potential confounding bias, we used a causal directed acyclic graph (DAG) to select appropriate confounding variables. Further, we controlled for these confounders through multilevel propensity score and inverse probability weighting (IPW). The successful rate of ATT for patients with HIV-TB co-infection in Liangshan Prefecture was 91.2%. Total delay (OR = 1.411, 95% CI: 1.015, 1.962), diagnostic delay (OR = 1.778, 95% CI: 1.261, 2.508), treatment delay (OR = 1.749, 95% CI: 1.146, 2.668) and health system delay (OR = 1.480 95% CI: (1.035, 2.118) were identified as risk factors for successful ATT outcome. Sensitivity analysis demonstrated the robustness of these findings. HIV-TB co-infection prevention and control policy in Liangshan Prefecture should prioritize early treatment for diagnosed HIV-TB co-infected patients. It is urgent to improve the health system in Liangshan Prefecture to reduce delays in diagnosis and treatment.

Establishment of glioma prognosis nomogram based on the function of meox1 in promoting the progression of cancer

BackgroundGliomas stand out as highly predominant malignant nervous tumors and are linked to adverse treatment outcomes and short survival periods. Current treatment options are limited, emphasizing the need to identify effective therapeutic targets. The heterogeneity of tumors necessitates a personalized treatment approach with an effective grouping system. Meox1 has been implicated in promoting tumor progression in diverse cancers; nonetheless, its role in gliomas remains unelucidated. Material/methodsUtilized immunohistochemistry to assess the expression of Meox1 protein in glioma tissues. Proliferation and invasion assays were conducted on wild-type and meox1-overexpressed glioma cells using the CCK8 and Transwell assays, respectively. The expression levels of meox1 and its related genes in gliomas were obtained from Chinese Glioma Genome Atlas (CGGA), along with the corresponding patient survival periods. LASSO regression modeling was employed to construct a scoring system for patients with gliomas, categorizing them into high-/low-risk groups. Additionally, a nomogram for predicting the survival period of patients with glioma was developed using multivariate logistic analysis. ResultsWe attempted, for the first time, to demonstrate heightened expression of Meox1 in glioma tumor tissues, correlating with significantly increased invasion and proliferation abilities of glioma cells following meox1 overexpression. The scoring system effectively stratified patients with glioma into high-/low-risk groups, revealing differences in the survival period and immunotherapy efficacy between the two groups. The integration of this scoring system with other clinical indicators yielded a nomogram capable of effectively predicting the survival period of individuals with gliomas. ConclusionsOur study established a stratified investigation system based on the levels of meox1 and its related genes, providing a novel, cost-effective model for facilitating the prognosis prediction of individuals with glioma.

Evaluation of a new two-step frailty assessment of head and neck patients in a prospective cohort

PurposeAssessing frailty, in head and neck cancer (HNC) patients is key when choosing appropriate treatment. Optimal screening is challenging, as it should be feasible and should avoid over-referral for comprehensive geriatric assessment (CGA) This study aims to evaluate the association between geriatric assessment using a new two-step care pathway, referral to geriatrician and adverse outcomes.MethodsThis institutional retrospective analysis on a prospective cohort analysed the multimodal geriatric assessment (GA) of newly diagnosed HNC patients. Uni- and multivariable logistic regression was performed to study the association between the screening tests, and referral to the geriatrician for complete geriatric screening, and adverse outcomes.ResultsThis study included 539 patients, of whom 276 were screened. Patients who underwent the GA, were significantly older and more often had advanced tumour stages compared to non-screened patients. Referral to the geriatrician was done for 30.8% of patients. Of the 130 patients who underwent surgery, 26/130 (20%) experienced clinically relevant postoperative complications. Of the 184 patients who underwent (radio)chemotherapy, 50/184 (27.2%) had clinically relevant treatment-related toxicity. Age, treatment intensity, polypharmacy and cognitive deficits, were independently associated with referral to geriatrician. A medium to high risk of malnutrition was independently associated with acute radiation induced toxicity and adverse outcomes in general.ConclusionThe current study showed a 30.8% referral rate for CGA by a geriatrician. Age, treatment intensity, cognitive deficits and polypharmacy were associated with higher rates of referral. Furthermore, nutritional status was found to be an important negative factor for adverse treatment outcomes, that requires attention.

Age-Related Differences in Vancomycin-Associated Nephrotoxicity and Efficacy in Methicillin-Resistant Staphylococcus aureus Infection: A Comparative Study between Elderly and Adult Patients.

Elderly patients (age ≥ 65 years) are susceptible to methicillin-resistant Staphylococcus aureus (MRSA) infections, with potential for more adverse treatment outcomes or complications compared to younger adults (18-64 years). This study compared vancomycin-associated nephrotoxicity and efficacy in elderly and adult patients and investigated the correlation between vancomycin pharmacokinetic/pharmacodynamic (PK/PD) indices and clinical outcomes. A prospective study was conducted in 10 hospitals in Shanghai from October 2012 to November 2019. A total of 164 patients with MRSA infections were enrolled, including 83 elderly and 81 adult patients. Vancomycin therapeutic drug monitoring (TDM) was performed in all patients, indicating significantly higher vancomycin trough concentrations (Ctrough), 24-h area under the curve (AUC24) values, and AUC24/minimum inhibitory concentration (AUC24/MIC) values in elderly patients compared to adult patients. The incidence of vancomycin-associated nephrotoxicity was nearly three times higher in elderly patients (18.1% vs. 6.2%, p = 0.020), despite similar clinical and microbiological efficacy. Of particular importance, a Ctrough > 20 mg/L was found as an independent factor of nephrotoxicity in elderly patients. Further analysis of patients with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 also revealed that elderly patients had significantly higher vancomycin-related PK/PD indices and more nephrotoxicity than adult patients. In conclusion, elderly patients receiving vancomycin therapy face a higher risk of nephrotoxicity, which requires close vancomycin TDM, especially when the Ctrough exceeds 20 mg/L.