Adverse Treatment Outcomes Research Articles

Repurposing Diflunisal as an Anti-Virulence Agent Against Staphylococcus aureus

Abstract Infections refractory to standard antibiotic therapy are contributing to adverse treatment outcomes in patients suffering from deep-seated bacterial infections caused by increasingly resistant pathogens. Adjunctive strategies targeting bacterial virulence factors have been considered to supplement the host immune response in fighting the infection. Previous studies suggest that the FDA-approved anti-inflammatory drug diflunisal inhibits Staphylococcus aureus (SA) α-toxin expression by its interaction with the response regulator AgrA. We investigated the broader anti-virulence properties of diflunisal against pathogenic strains of SA and established proof-of-concept for its efficacy in blocking SA virulence. Our studies reveal that diflunisal inhibits α-toxin production, sensitizes SA to cationic antibiotics and human antimicrobial peptides, inhibits the production of the golden pigment staphyloxanthin, and reduces biofilm formation. Molecular docking simulations revealed potential interactions between diflunisal and AgrA binding sites. In addition, sequence alignment of the SA AgrA response regulator demonstrated similarities to other response regulators involved in controlling virulence factor expression. Appreciation of the antivirulence properties of diflunisal supports a therapeutic strategy distinct from structurally similar compounds, such as salicylic acid. The repurposing of diflunisal may mitigate disease severity and provide a unique adjunctive tool in the treatment of SA infection.

P0401 The IBD-disk accurately assesses disability and psychological burden at IBD diagnosis and predicts adverse outcomes in both UC and Crohn’s disease during the first year of treatment

Abstract Background Inflammatory bowel disease (IBD) is linked with increased prevalence of mental health diseases (MHD), particularly anxiety and depression. How this influences treatment outcomes is poorly studied at IBD diagnosis. The IBD disk is a patient-reported outcome measure that quantifies disease-associated disability. We aimed to determine if the disk can be used pre-diagnosis to screen for mental health symptoms and predict treatment outcomes. Methods Patients with suspected IBD were seen in a rapid-access clinic. An IBD disk was completed upon review, pre-diagnosis. A subgroup simultaneously completed the Hospital Anxiety and Depression scale (HADS). Repeat disks were completed after diagnosis, with 12-month outcomes collected prospectively. Results 188 patients completed a baseline disk (97 Crohn’s disease [CD], 91 Ulcerative colitis [UC]), 95 completed a simultaneous HADS and 82 completed a repeat disk. Both a pre-existing MHD diagnosis (CD 22%, UC 11%, X2 p=0.049) and an active anti-depressant prescription (CD 16%, UC 7%, X2 p=0.035) were more common at CD diagnosis than UC. The ‘Emotions’ domain correlated with HADS depression (rs=0.607 p<.001), anxiety (rs=0.586 p<.001) and reliably identified HADS defined moderate-severe depression (Area under the curve 0.873). A score ≥7 identified all patients meeting this HADS threshold (Sensitivity 100%, specificity 60.5%, Youden’s index 0.601). This is shown in Figure 1. Whilst the IBD Disk did not outperform traditional disease severity indices, elevated baseline disk scores in UC predicted the subsequent need for advanced therapies (p=0.019), persistent active disease at 12 months (p=0.023) and need for inpatient treatment (p<.001). In CD, elevated disk scores predicted need for advanced therapies (p=0.014), persistent active disease (p=0.015) and showed a weak association with the need for surgical resection within 12 months (p=0.064). These results are summarised in Table 1. After diagnosis and treatment, ongoing disability and psychological symptoms were driven by disease activity. In both UC and CD, the ‘Emotions’ domain fell significantly in those in remission at first follow-up (CD p<.001; UC p=0.008) but was unchanged when the disease remained active (CD p=0.71; UC p=0.72). Conclusion The IBD disk reliably screens for symptoms of depression and anxiety and identifies risk of adverse treatment outcomes at IBD presentation. Its use in the outpatient setting can support holistic disease assessment and identify those who are most likely to benefit from additional psychological support. Moreover, particularly in UC patients, elevated baseline IBD disk scores should prompt the consideration of treatment escalation early in the disease course.

Coexistent anemia modulates systemic inflammation and exacerbates disease severity and adverse treatment outcomes in tuberculosis

IntroductionAnemia has been shown to be an independent predictor of disease progression and death in tuberculosis (TB) patients, significantly impacting TB in several ways. This dual burden poses significant challenges for TB control efforts. However, the mechanism by which anemia influences disease severity, bacterial burden, and TB treatment outcomes remains poorly understood.MethodsIn this study, we aimed to compare bacterial burdens, disease severity, and TB treatment outcomes in TB patients with or without anemia. Participants were recruited from Chennai, South India, as part of the prospective Effect of Diabetes on Tuberculosis Severity (EDOTS) study conducted from February 2014 to August 2018. Anemia was defined as hemoglobin (Hb) levels <13 g/dL and <12 g/dL for males and females, respectively. We employed chest X-rays to assess bilateral lung and cavitary diseases and sputum smear grades to measure bacterial loads in TB subjects. Treatment outcomes were defined as favorable or unfavorable. Cytokine profile was measured using multiplex ELISA.ResultsThe study comprised of 483 culture-confirmed TB individuals, with 288 positives for anemia {Median Hb was 11.0 [interquartile range (IQR)], 10.3–12.3} and 195 negatives [Median Hb was 14.3 (IQR), 13.5–15.2]. The study revealed that TB patients with anemia had significantly higher bacterial loads [adjusted prevalence ratio (aPR), 4.01; 95% CI, 2.22–6.63; p < 0.001], cavitary lung lesions [aPR, 3.36; 95% CI, 1.95–5.68; p < 0.001] and unfavorable treatment outcomes [aPR, 1.61; 95% CI, 1.31–2.19; p = 0.046] compared to those without anemia. Our data also show that TB is associated with significantly lower levels of type-1 cytokines (IFNγ and IL-2) but significantly higher levels of pro-inflammatory cytokines (IL-6, IFNα, and IFNβ) and pro-fibrotic factors (VEGF, EGF, FGF-2, and PDGF-AB/BB) in anemic individuals compared to those without anemia.ConclusionsThese findings highlight a clear association between anemia and increased TB severity, elevated bacterial loads, and poor treatment outcomes. Our data also suggest that anemia might be associated with the modulation of cytokine responses, which could impart a detrimental effect on TB pathogenesis.

Nutritional supplementation during tuberculosis treatment to improve clinical symptoms: a double-blinded placebo-controlled randomized trial.

Background and aims. Undernutrition coexists with tuberculosis and is associated with adverse treatment outcomes. Nutrition packages have been incorporated into tuberculosis patient care in some regions but there are little data on its effectiveness. The aim of this study is to evaluate the effect of a nutrition package on the treatment response and nutritional status of tuberculosis patients. Methods. We conducted a double-blinded placebo-controlled randomized trial in 360 pulmonary tuberculosis patients with concurrent diabetes or prediabetes. The participants were randomly assigned to receive a daily nutrition package (112 kcal, 9 g protein, and micronutrients) or a daily placebo package (112 kcal, 3 g protein, and no micronutrients) during tuberculosis treatment. The intervention lasted for six months. All participants received standard pulmonary tuberculosis treatment. The clinical symptoms, sputum smear, chest computed tomography, and nutritional status were monitored during the intervention. Results. The nutrition package improved the expectoration (intervention vs. placebo: 34.1% vs. 48.3% in week 1, 27.8% vs. 45.0% in week 2, 25.9% vs. 38.6% in week 3, 25.6% vs. 35.4% in month 1, 15.3% vs. 22.9% in month 2) and chest pain (2.3% vs. 9.0% in week 3, 3.6% vs. 8.3% in month 1, 4.3% vs. 10.0% in month 2, 1.8% vs. 6.4% in month 4). The nutrition package also increased hemoglobin, albumin, and lymphocyte counts. The nutrition package did not influence the sputum smear conversion in the whole population [hazard ratio (95% CI): 1.031 (0.685, 1.550), P = 0.885], but accelerated the conversion in patients without cavity [2.583 (1.180, 5.656), P = 0.018]. Conclusions. The nutrition package improved the clinical symptoms (e.g. chest pain and expectoration) and alleviated undernutrition (e.g. anemia and hypoproteinemia) among tuberculosis patients. The study was registered at the China Clinical Trial Registry Center (no. ChiCTR1900022294; https://www.chictr.org.cn).

The Role of the Lawton Instrumental Activities of Daily Living (IADL) Scale in Predicting Adverse Events and Outcomes of R-CHOP Treatment in Elderly Patients with Diffuse Large B-Cell Lymphomas (DLBCLs) or Mantle Cell Lymphomas (MCLs): A Prospective Single-Center Study.

The prognostic value of the comprehensive geriatric assessment (CGA) is recognized by many in hematology. However, there is no consensus on the utilization of alternative abbreviated methods to assess disabilities in elderly patients with B-cell non-Hodgkin's lymphomas (B-NHLs). The aim of this study was to prospectively analyze the prognostic value of selected CGA tools in predicting adverse events (AEs) and outcomes of R-CHOP or R-CHOP-like treatment in elderly patients with diffuse large B-cell lymphomas (DLBCLs) or mantle cell lymphomas (MCLs). All patients who participated in this study underwent the Katz Index of Independence in Activities of Daily Living (ADL), the Lawton Instrumental Activities of Daily Living (iADL) scale, the Vulnerable Elders Survey-13 (VES-13), the Groningen Frailty Index (GFI), and the Mini Nutritional Assessment Short Form (MNA-SF) before starting anticancer treatment. Selected clinical predictors were also included in the study. A total of 62 patients with newly diagnosed DLBCLs or MCLs, treated with R-CHOP in the Department of Hematology, Blood Neoplasm and Bone Marrow Transplantation of Wroclaw University Hospital between 1 July 2018, and 1 July 2020, were included in the study. The median age upon initiation of the treatment was 72 years (range: 61-68). Multinomial logistic regression and Cox proportional hazard regression analysis demonstrated that the iADL scale was significantly associated with response to treatment (OR = 1.21, 95% CI: 1.02-1.44, p = 0.03), was inversely related to non-hematological AEs (OR = 0.81, 95% CI: 0.71-0.92, p = 0.001), and was a statistically significant predictor of longer overall survival (OS) (HR = 0.83, 95% CI: 0.79-0.89, p < 0.001) and longer progression-free survival (PFS) (HR = 0.91, 95% CI: 0.83-0.99, p = 0.03). These results underscore the effectiveness of the iADL scale as a quick, easy-to-use, and universal CGA tool for evaluating crucial functional status before treatment in elderly hematological patients with DLBCLs or MCLs.

Prevalence trends, population characteristics and treatment outcomes of tuberculosis combined with diabetes in Southwest China: a register-based retrospective study.

The global situation regarding the prevention and control of pulmonary tuberculosis (PTB) remains challenging. With the ongoing aging population and the increasing prevalence of chronic diseases, the epidemic of comorbid pulmonary tuberculosis and diabetes mellitus (PTB-DM) presents challenges to PTB control. We conducted this study given that current research on PTB-DM has primarily focused on clinical medicine and immunology, with limited reports on the true prevalence of population-wide PTB-DM in specific regions, as well as the heightened risk of PTB-DM co-prevalence due to aging and the high prevalence of DM in Chongqing, Southwest China. This retrospective study used PTB case data from the PTB Information Management System within the China Information System for Disease Control and Prevention (CISDP). The medical records of 112,592 PTB patients registered in Chongqing from 2016 to 2022 were extracted. After excluding patients with incomplete records, those not residing in Chongqing, and individuals still undergoing treatment, a total of 108,003 PTB patients were included in the study. The trend in PTB-DM incidence was analyzed using the Joinpoint regression model, and population and clinical characteristics of patients were described using frequencies (n) and percentages. Chi-squared test and Fisher's exact tests was used to compare groups, and multivariable logistic regression model with stepwise backward elimination based on the Wald test was used to examine risk factors for adverse treatment outcomes. From 2016 to 2022, the incidence rate of PTB in southwest China showed a decreasing trend (AAPC = -10.22, 95% CI: -11.49% ~ -8.94%), while the incidence rate of PTB-DM increased rapidly (AAPC = 14.25, 95% CI: 11.35% ~17.23%). The proportion of PTB-DM among PTB cases increased from 2.96 to 12.28%. PTB-DM patients were characterized by a higher proportion of males and older adult individuals, the age range of the patients was 11 ~ 100 years, with a mean age of 58.21 ± 12.02 years, with multiple positive aetiological results, and lower rates of proactive medical consultation. Among PTB-DM patients, successful outcomes accounted for 80.85%, while unsuccessful outcomes accounted for 19.15%. Although the number of PTB-DM patients with successful treatment outcomes increased overall (AAPC = 12.22, 95% CI: 10.30% ~14.16%), the failure rate showed a gradual upward trend (AAPC = 14.18, 95% CI: 6.53% ~ 27.67%). Older age, retreatment, referral, and multiple positive aetiological results were risk factors for adverse treatment outcomes among PTB-DM patients. The study presents the true prevalence of PTB-DM comorbidity in the general population of Southwest China, revealing a significant upward trend in its prevalence and a higher risk of adverse outcomes among PTB-DM patients. Future efforts should focus on the prevention and control of PTB-DM comorbidity, with early screening and standardized treatment for high-risk groups such as the older adult, as well as implementing comprehensive and effective treatment and management measures for patients.

Effectiveness and Safety of the Regimens Containing Bedaquiline in Patients with TB and HIV-infection

The objective: to analyze effectiveness and safety of bedaquiline administered concurrently with antiretroviral therapy in treatment regimens for patients with such comorbidities as HIV infection and multiple drug resistant and extensively drug resistant tuberculosis.Subjects and Methods. Effectiveness and safety of chemotherapy regimens containing bedaquiline in the treatment of patients in 2017-2019 was analyzed. The study included 40 patients with multiple drug resistant and extensively drug resistant tuberculosis (MDR/XDR-TB) and HIV infection receiving antiretroviral (ART) therapy.Results. Treatment of tuberculosis in this category of patients who completed the main course of chemotherapy was found to be effective in 70.6%. The effectiveness was significantly higher in the following patients: those with intact immune status (88.9% and 51.6%, p=0.04) due to a significant reduction in the proportion of fatal outcomes from 19.4% to 0; those with preserved susceptibility to fluoroquinolones (81.8% and 51.7%, p=0.08) due to a 3.4-fold reduction in the proportion of unfavourable treatment outcomes (from 31.0% to 9.1%) and a 1.9-fold reduction in the proportion of treatment outcomes that could not be evaluated (from 17.2% to 9.1%). The analysis showed good tolerability of bedaquiline included in MDR/XDR-TB treatment regimens in combination with antiretroviral therapy. The frequency of AEs associated with the bedaquiline-containing regimen made 7.5%. When prescribing bedaquiline, preference should be given to ART regimens that do not contain NNRTIs and PIs (the incidence of adverse treatment outcomes when bedaquiline is prescribed in combination with NNRTIs is 1.7 times higher; the incidence of adverse events (AEs) associated with the use of a bedaquiline-containing regimen in combination with PIs is 2.7 times higher than when prescribing ART regimens without PIs (including those associated with bedaquiline – 5.2 times). In 1-3 years after the effective course of chemotherapy with bedaquiline during antiretroviral therapy, tuberculosis relapse rate made 9.1%.

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...

Integrated profile of tumor stage and mutational burden predicts disparate clinical responses to immune checkpoint inhibitors: A risk-benefit study

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, having demonstrated efficacy and leading to regulatory approvals of ICIs in cancers characterized by high tumor mutation burden (TMB). However, there remains a gap in determining their applicability and risk-benefit profile, across the broad spectrum of patients whose tumors harbor varying TMB levels across distinct tumor stages. By interrogating a large contemporary cohort comprised of 10,233 patients with a diagnosis of cancer across all tumor stages and TMB levels, this study revealed significantly improved overall survival (OS) following ICI therapy (p <0.0001) in patients with a combination of ≥10 mut/Mb and stage IV disease. In contrast, ICI therapy is associated with markedly worse OS in patients with low TMB levels <10 mut/Mb and stages I, II, and III cancer. These findings highlight the critical interplay between TMB, tumor stage, and ICI treatment outcomes, underscoring the importance of integrating clinical and genetic characteristics in weighing the risk-benefit balance of ICI therapy. Although maximizing therapeutic benefits is crucial, it is equally important to identify and manage potential risks that may not be immediately apparent. This may require enrolling patients with less-severe or early-stage disease to enable long-term follow‐up with effective clinical surveillance. By comprehensively evaluating the added benefit of improved treatment efficacy and the potential risk of adverse treatment outcome, a risk-benefit profile can optimize immunotherapy regimens, with profound implications for clinical decision-making and regulatory approvals of ICI.

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 &amp;lt; 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 &amp;lt; 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.