The use of artificial intelligence to optimize medication alerts generated by clinical decision support systems: a scoping review.

OBJECTIVE: Current Clinical Decision Support Systems (CDSSs) generate medication alerts that are of limited clinical value, causing alert fatigue. Artificial Intelligence (AI)-based methods may help in optimizing medication alerts. Therefore, we conducted a scoping review on the current state of the use of AI to optimize medication alerts in a hospital setting. Specifically, we aimed to identify the applied AI methods used together with their performance measures and main outcome measures. MATERIALS AND METHODS: We searched Medline, Embase, and Cochrane Library database on May 25, 2023 for studies of any quantitative design, in which the use of AI-based methods was investigated to optimize medication alerts generated by CDSSs in a hospital setting. The screening process was supported by ASReview software. RESULTS: Out of 5625 citations screened for eligibility, 10 studies were included. Three studies (30%) reported on both statistical performance and clinical outcomes. The most often reported performance measure was positive predictive value ranging from 9% to 100%. Regarding main outcome measures, alerts optimized using AI-based methods resulted in a decreased alert burden, increased identification of inappropriate or atypical prescriptions, and enabled prediction of user responses. In only 2 studies the AI-based alerts were implemented in hospital practice, and none of the studies conducted external validation. DISCUSSION AND CONCLUSION: AI-based methods can be used to optimize medication alerts in a hospital setting. However, reporting on models' development and validation should be improved, and external validation and implementation in hospital practice should be encouraged.

Longitudinal metabolite profiling of Streptococcus pneumoniae-associated community-acquired pneumonia.

INTRODUCTION: Longitudinal biomarkers in patients with community-acquired pneumonia (CAP) may help in monitoring of disease progression and treatment response. The metabolic host response could be a potential source of such biomarkers since it closely associates with the current health status of the patient. OBJECTIVES: In this study we performed longitudinal metabolite profiling in patients with CAP for a comprehensive range of metabolites to identify potential host response biomarkers. METHODS: Previously collected serum samples from CAP patients with confirmed Streptococcus pneumoniae infection (n = 25) were used. Samples were collected at multiple time points, up to 30 days after admission. A wide range of metabolites was measured, including amines, acylcarnitines, organic acids, and lipids. The associations between metabolites and C-reactive protein (CRP), procalcitonin, CURB disease severity score at admission, and total length of stay were evaluated. RESULTS: Distinct longitudinal profiles of metabolite profiles were identified, including cholesteryl esters, diacyl-phosphatidylethanolamine, diacylglycerols, lysophosphatidylcholines, sphingomyelin, and triglycerides. Positive correlations were found between CRP and phosphatidylcholine (34:1) (cor = 0.63) and negative correlations were found for CRP and nine lysophosphocholines (cor = - 0.57 to - 0.74). The CURB disease severity score was negatively associated with six metabolites, including acylcarnitines (tau = - 0.64 to - 0.58). Negative correlations were found between the length of stay and six triglycerides (TGs), especially TGs (60:3) and (58:2) (cor = - 0.63 and - 0.61). CONCLUSION: The identified metabolites may provide insight into biological mechanisms underlying disease severity and may be of interest for exploration as potential treatment response monitoring biomarker.

Exploring the impact of patient-specific clinical features on osimertinib effectiveness in a real-world cohort of patients with EGFR mutated non-small cell lung cancer.

Osimertinib is prescribed to patients with metastatic non-small cell lung cancer (NSCLC) and a sensitizing EGFR mutation. Limited data exists on the impact of patient characteristics or osimertinib exposure on effectiveness outcomes. This was a Dutch, multicenter cohort study. Eligible patients were ≥18 years, with metastatic EGFRm+ NSCLC, receiving osimertinib. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. Kaplan-Meier analyses and multivariate Cox proportional hazard models were performed. In total, 294 patients were included. Primary EGFR-mutations were mainly exon 19 deletions (54%) and p.L858R point mutations (30%). Osimertinib was given in first-line (40%), second-line (46%) or beyond (14%), with median PFS 14.4 (95% CI: 9.4-19.3), 13.9 (95% CI: 11.3-16.1) and 8.7 months (95% CI: 4.6-12.7), respectively. Patients with low BMI (<20.0 kg/m2 ) had significantly shorter PFS/OS compared to all other subgroups. Patients with a high plasma trough concentration in steady state (Cmin,SS ; >271 ng/mL) had shorter PFS compared to a low Cmin,SS (<163 ng/mL; aHR 2.29; 95% CI: 1.13-4.63). A significant longer PFS was seen in females (aHR = 0.61, 95% CI: 0.45-0.82) and patients with the exon 19 deletion (aHR = 0.58, 95% CI: 0.36-0.92). A trend towards longer PFS was seen for TP53 wild-type patients, while age did not impact PFS. Patients with a primary EGFR exon 19 deletion had longer PFS, while a low BMI, male sex and a high Cmin,SS were indicative for shorter PFS and/or OS. Age was not associated with effectiveness outcomes of osimertinib.

The Influence of Long-Acting Somatostatin Analogs on 68 Ga-DOTATATE Uptake in Patients With Neuroendocrine Tumors.

PURPOSE: A high SUV max tumor-to-liver ratio (TLR) of 68 Ga-DOTATATE can be used to select patients with neuroendocrine tumors (NETs) for peptide receptor radionuclide therapy (PRRT). In addition, an SUV max TLR ≥ 8.1 is associated with increased progression-free survival in NET patients treated with somatostatin analogs (SSAs). To avoid a theoretical interaction, several guidelines recommend performing PET/CT just before the monthly administration of long-acting SSAs. We aimed to investigate the effect of SSA on the SUV max of 68 Ga-DOTATATE in patients with NET and to identify independent predictors for high SUV max TLR. PATIENTS AND METHODS: For this retrospective study, 192 68 Ga-DOTATATE PET/CT scans of 165 patients without (n = 115) and with (n = 77) SSA (octreotide or lanreotide) in the 3 months before PET/CT were collected and reviewed. The effect of SSA on SUV max values was analyzed by a maximum likelihood mixed model. RESULTS: Patients with SSA had a significantly higher median SUV max TLR than patients without SSA (4.7 [IQR], 3.1-7.7) versus 3.2 [IQR, 2.0-5.4]; P < 0.001). Multivariable logistic regression analysis showed that SSA use was an independent predictor for SUV max TLR ≥ 8.1 (odds ratio, 2.91; 95% confidence interval, 1.26-6.72; P = 0.012). CONCLUSIONS: Our data suggest that higher SSA concentrations do not have a negative effect on 68 Ga-DOTATATE uptake in tumor lesions. In addition, we found that only SSA use was associated with SUV max TLR ≥ 8.1. Our results are consistent with previously conducted studies and in line with the recently published guideline that suggests that the relatively recent use of SSA does not necessitate any delay in 68 Ga-DOTATATE PET/CT imaging.

Real-world outcomes of first-line chemotherapy for unresectable stage III and IV bladder cancer.

PURPOSE: For many malignancies, considerable divergence between the efficacy found in clinical trials and effectiveness in routine practice have been reported (efficacy-effectiveness gap). The purpose of this study was to evaluate the efficacy-effectiveness gap in palliative first-line (1L) chemotherapy treatment (CTx) for urothelial carcinoma of the bladder. METHODS: From seven Dutch teaching hospitals, all patients diagnosed with unresectable stage III (cT2-4aN1-3M0) and IV (cT4b and/or cM1) disease, who received 1L-CTx (for both primary as recurrent disease after radical cystectomy) between 2008 and 2016, were captured. Results were compared with data from seven randomised trials that investigated 1L gemcitabine + cisplatin (GemCis) and/or gemcitabine + carboplatin (GemCarbo). RESULTS: Of the 835 included patients, 191 received 1L-CTx. Median overall survival (mOS) of GemCis patients (N = 88) was 10.4 months [95% CI 7.9-13.0], which was shorter compared to clinical trial findings (range mOS: 12.7-14.3 months) despite comparable clinical characteristics. The mOS of GemCarbo patients (N = 92) was 9.3 months [95% CI 7.5-11.1]. Patients who received GemCarbo had worse prognostic characteristics (higher age, impaired renal function and worse performance status (all P-values < 0.001)) compared to GemCis patients, but were equal in occurrence of dose reductions (24.4% vs. 29.5%, P-value = 0.453), early termination (55.7% vs. 54.1%, P-value = 0.839), clinical best response (P-value = 0.733), and toxicity (68.1% vs. 63.3%, P-value = 0.743). In multivariable regression, GemCis was not superior to GemCarbo (HR 0.90 [95% CI 0.55-1.47], P-value = 0.674). CONCLUSION: There seems to be an efficacy-effectiveness gap in 1L GemCis treatment, despite patients having similar baseline characteristics. Early termination of treatment occurred more often and dose reduction less often compared to clinical trials, hinting towards abandonment of treatment in case of adverse events. Patients treated with 1L GemCis did not have superior survival compared to GemCarbo patients, even though GemCarbo patients had worse baseline characteristics.

Differential metabolic host response to pathogens associated with community-acquired pneumonia.

Background: Metabolic changes induced by the host immune response to pathogens found in patients with community-acquired pneumonia (CAP) may provide insight into its pathogenesis. In this study, we characterized differences in the host metabolic response to common CAP-associated pathogens. Method: Targeted metabolomic profiling was performed on serum samples obtained from hospitalized CAP patients (n = 119) at admission. We quantified 347 unique metabolites across multiple biochemical classes, including amines, acylcarnitines, and signaling lipids. We evaluated if unique associations between metabolite levels and specific CAP-associated pathogens could be identified. Results: Several acylcarnitines were found to be elevated in C. burnetii and herpes simplex virus and lowered in M. pneumoniae as compared to other pathogens. Phenylalanine and kynurenine were found elevated in L. pneumophila as compared to other pathogens. S-methylcysteine was elevated in patients with M. pneumoniae, and these patients also showed lowered cortisol levels in comparison to almost all other pathogens. For the herpes simplex virus, we observed a unique elevation of eicosanoids and several amines. Many lysophosphatidylcholines showed an altered profile in C. burnetii versus S. pneumoniae, L. pneumophila, and respiratory syncytial virus. Finally, phosphatidylcholines were negatively affected by the influenza virus in comparison to S. pneumoniae. Conclusions: In this exploratory analysis, metabolites from different biochemical classes were found to be altered in serum samples from patients with different CAP-associated pathogens, which may be used for hypothesis generation in studies on differences in pathogen host response and pathogenesis of CAP.

Latent class analysis-based subgroups and response to corticosteroids in hospitalised community-acquired pneumonia patients: a validation study.

In patients with community-acquired pneumonia, LCA can identify robust prognostic subgroups based on clinical and inflammatory parameters. Yet, these subgroups have not proven robust in predicting response to adjunctive dexamethasone treatment. https://bit.ly/3O5eaxz.

Real-world palbociclib effectiveness in patients with metastatic breast cancer: Focus on neutropenia-related treatment modification strategies and clinical outcomes.

INTRODUCTION: In addition to clinical trials, real-world data is needed to verify the effectiveness of the CDK 4/6 inhibitor palbociclib. The primary aim was to examine real-world variation in treatment modification strategies for neutropenia and its relation to progression-free survival (PFS). The secondary aim was to assess if there is a gap between real-world and clinical trial outcomes. MATERIALS AND METHODS: In this multicenter, retrospective observational cohort study 229 patients were analyzed who started palbociclib and fulvestrant as second- or later-line therapy for HR-positive, HER2-negative metastatic breast cancer in the Santeon hospital group in the Netherlands between September 2016 and December 2019. Data were manually retrieved from patients' electronic medical records. PFS was examined using the Kaplan-Meier method to compare neutropenia-related treatment modification strategies within the first three months after neutropenia grade 3 - 4 occurred, as well as patients' eligibility to have participated in the PALOMA-3 clinical trial or not. RESULTS: Even though treatment modification strategies differed from those in PALOMA-3 (dose interruptions: 26 vs 54%, cycle delays: 54 vs 36%, and dose reductions: 39 vs 34%), these did not influence PFS. Patients who were PALOMA-3 ineligible experienced a shorter median PFS than those who were eligible (10.2 vs. 14.1 months; HR 1.52; 95% CI 1.12 - 2.07). An overall longer median PFS was found compared to PALOMA-3 (11.6 vs. 9.5 months; HR 0.70; 95% CI 0.54 - 0.90). CONCLUSION: This study suggests no impact of neutropenia-related treatment modifications on PFS and confirms inferior outcomes outside clinical trial eligibility.

Development and validation of a decision model for the evaluation of novel lung cancer treatments in the Netherlands.

Recent discoveries in molecular diagnostics and drug treatments have improved the treatment of patients with advanced (inoperable) non-squamous non-small cell lung cancer (NSCLC) from solely platinum-based chemotherapy to more personalized treatment, including targeted therapies and immunotherapies. However, these improvements come at considerable costs, highlighting the need to assess their cost-effectiveness in order to optimize lung cancer care. Traditionally, cost-effectiveness models for the evaluation of new lung cancer treatments were based on the findings of the randomized control trials (RCTs). However, the strict RCT inclusion criteria make RCT patients not representative of patients in the real-world. Patients in RCTs have a better prognosis than patients in a real-world setting. Therefore, in this study, we developed and validated a diagnosis-treatment decision model for patients with advanced (inoperable) non-squamous NSCLC based on real-world data in the Netherlands. The model is a patient-level microsimulation model implemented as discrete event simulation with five health events. Patients are simulated from diagnosis to death, including at most three treatment lines. The base-model (non-personalized strategy) was populated using real-world data of patients treated with platinum-based chemotherapy between 2008 and 2014 in one of six Dutch teaching hospitals. To simulate personalized care, molecular tumor characteristics were incorporated in the model based on the literature. The impact of novel targeted treatments and immunotherapies was included based on published RCTs. To validate the model, we compared survival under a personalized treatment strategy with observed real-world survival. This model can be used for health-care evaluation of personalized treatment for patients with advanced (inoperable) NSCLC in the Netherlands.

Prednisone vs methotrexate in treatment naïve cardiac sarcoidosis.

BACKGROUND: Side effects limit the long-term use of glucocorticoids in cardiac sarcoidosis (CS), and methotrexate has gained attention as steroid sparing agent although the supporting evidence is poor. This study compared prednisone monotherapy, methotrexate monotherapy or a combination of both, in the reduction of myocardial Fluorine-18 fluorodeoxyglucose (FDG) uptake and clinical stabilization of CS patients. METHODS AND RESULTS: In this retrospective cohort study, 61 newly diagnosed and treatment naïve CS patients commenced treatment with prednisone (N = 21), methotrexate (N = 30) or prednisone and methotrexate (N = 10) between January 2010 and December 2017. Primary outcome was metabolic response on FDG PET/CT and secondary outcomes were treatment patterns, major adverse cardiovascular events, left ventricular ejection fraction, biomarkers and side effects. At a median treatment duration of 6.2 [5.7-7.2] months, 71.4% of patients were FDG PET/CT responders, and the overall myocardial maximum standardized uptake value decreased from 6.9 [5.0-10.1] to 3.4 [2.1-4.7] (P < 0.001), with no significant differences between treatment groups. During 24 months of follow-up, 7 patients (33.3%; prednisone), 6 patients (20.0%; methotrexate) and 1 patient (10.0%; combination group) experienced at least one major adverse cardiovascular event (P = 0.292). Left ventricular ejection fraction was preserved in all treatment groups. CONCLUSIONS: Significant suppression of cardiac FDG uptake occurred in CS patients after 6 months of prednisone, methotrexate or combination therapy. There were no significant differences in clinical outcomes during follow-up. These results warrant further investigation of methotrexate treatment in CS patients.

Overweight and obesity are not associated with worse clinical outcomes in COVID-19 patients treated with fixed-dose 6 mg dexamethasone.

OBJECTIVE: A fixed 6 mg dexamethasone dose for 10 days is the standard treatment for all hospitalised COVID-19 patients who require supplemental oxygen. Yet, the pharmacokinetic properties of dexamethasone can lead to diminishing systemic dexamethasone exposure with increasing body mass index (BMI). The present study examines whether this translates to overweight and obesity being associated with worse clinical outcomes, defined as ICU admission or in hospital death, in COVID-19 patients treated with fixed-dose dexamethasone. METHODS: We conducted a single centre retrospective cohort study in COVID-19 patients who were admitted to a non-ICU ward and were treated with dexamethasone (6 mg once daily for a maximum of ten days) between June 2020 and January 2021. Univariable and multivariable logistic regression analyses were conducted to assess the association between BMI-categories and an unfavourable clinical course (ICU admission and/or in hospital death). Analyses were adjusted for age, comorbidities, inflammatory status, and oxygen requirement at admission. For reference, similar analyses were repeated in a cohort of patients hospitalised before dexamethasone was introduced (March 2020 through May 2020). RESULTS: In patients treated with dexamethasone (n = 385) an unfavourable clinical course was most prevalent in patients with normal weight (BMI < 25) compared to patients with overweight (BMI 25-30) and patients with obesity (BMI ≥ 30) with percentages of 33, 26 and 21% respectively. In multivariable analyses, there was no association between BMI-category and an unfavourable clinical course (respectively with aORs of 0.81 (0.43-1.53) and 0.61 (0.30-1.27) with normal weight as reference). In the reference cohort (n = 249) the opposite was observed with an unfavourable clinical course being most prevalent in patients with overweight (39% vs 28%; aOR 2.17 (0.99-4.76)). In both cohorts, CRP level at admission was higher and lymphocyte count was lower in patients with normal weight compared to patients with obesity. CONCLUSIONS: Overweight and obesity are not associated with an unfavourable clinical course in COVID-19 patients admitted to a non-ICU ward and treated with 6 mg dexamethasone once daily.

Hospital variation in treatment patterns and oncological outcomes for patients with muscle-invasive and metastatic bladder cancer in the Netherlands.

PURPOSE: Population-based studies on treatment patterns in oncology and corresponding clinical outcomes can help identify strategies towards optimal value for patients. This study was performed to describe the variation in treatment patterns and major oncological outcomes for muscle-invasive or metastatic bladder cancer (MIBC/mBC) patients in the Netherlands. METHODS: Patients diagnosed with cT2-4aN0-3M0-1 disease between 2008 and 2016 in seven large teaching hospitals in the Netherlands were included. Baseline characteristics, disease stage, intended and definitive treatment, and oncological outcomes were collected. Patients were categorized based on cTNM-stage: (1) cT2-4aN0M0, (2) cT2-4aN1-3M0 and (3) cT4b and/or M1. RESULTS: The total study population comprised 1853 patients, of which 1303 patients were diagnosed with cT2-4aN0M0 disease. Overall, curative treatment was intended in 81% (range 74-85%, P value = 0.132). Radical cystectomy (RC) and curative radiotherapy (RTx) ranged between hospitals from 42 to 66% and 13 to 27%, respectively (P value < 0.001). For 334 patients staged cT4b and/or M1, frequencies for palliative therapy and best supportive care (no anti-cancer therapy) ranged between hospitals from 20 to 54% and 44 to 71%, respectively (P value < 0.001). There was no association between hospital site and overall survival (OS) in a univariable and multivariable Cox regression for survival analysis (after adjusting for age and cT-stage), for all three cTNM-groups. Neoadjuvant or induction chemotherapy (NAIC) utilization rates before RC ranged from 8 to 38% (P value < 0.001). CONCLUSIONS: There is large inter-hospital variation in treatment intent in MIBC/mBC patients. This variation does not seem to translate to differences in overall survival rates. There is an ongoing trend of increased use of RC. Utilisation of NAIC is relatively low considering European guideline recommendations.

Validation of the PreOperative Score to predict Post-Operative Mortality (POSPOM) in Dutch non-cardiac surgery patients.

BACKGROUND: Standardized risk assessment tools can be used to identify patients at higher risk for postoperative complications and death. In this study, we validate the PreOperative Score to predict Post-Operative Mortality (POSPOM) for in-hospital mortality in a large cohort of non-cardiac surgery patients. In addition, the performance of POSPOM to predict postoperative complications was studied. METHODS: Data from the control cohort of the TRACE (routine posTsuRgical Anesthesia visit to improve patient outComE) study was analysed. POSPOM scores for each patient were calculated post-hoc. Observed in-hospital mortality was compared with predicted mortality according to POSPOM. Discrimination was assessed by receiver operating characteristic curves with C-statistics for in-hospital mortality and postoperative complications. To describe the performance of POSPOM sensitivity, specificity, negative predictive values, and positive predictive values were calculated. For in-hospital mortality, calibration was assessed by a calibration plot. RESULTS: In 2490 patients, the observed in-hospital mortality was 0.5%, compared to 1.3% as predicted by POSPOM. 27.1% of patients had at least one postoperative complication of which 22.4% had a major complication. For in-hospital mortality, POSPOM showed strong discrimination with a C-statistic of 0.86 (95% CI, 0.78-0.93). For the prediction of complications, the discrimination was poor to fair depending on the severity of the complication. The calibration plot showed poor calibration of POSPOM with an overestimation of in-hospital mortality. CONCLUSION: Despite the strong discriminatory performance, POSPOM showed poor calibration with an overestimation of in-hospital mortality. Performance of POSPOM for the prediction of any postoperative complication was poor but improved according to severity.

Cost-effectiveness of screening smokers and ex-smokers for lung cancer in the Netherlands in different age groups.

OBJECTIVE: We aimed to assess the cost-effectiveness of screening smokers and ex-smokers for lung cancer in the Netherlands. METHODS: A Markov model was used to evaluate the health effects and costs of lung cancer screening from the healthcare perspective. The effects and costs of ten screening scenarios with different start and stop ages of screening were examined across a lifetime horizon in a cohort of 100,000 smokers and ex- smokers 50 years and older. RESULTS: The incremental cost-effectiveness ratios (ICERs) of screening smokers and ex-smokers aged 50-60 years, 50-70 years, and 50 years and older are below the cost-effectiveness threshold of € 20,000 per quality adjusted life year (QALY) gained. Screening 50-60-year-old smokers and ex-smokers was the most cost-effective scenario with an ICER of € 14,094 per QALY gained. However, screening smokers and ex-smokers 50 years and older yielded the highest QALYs and resulted in an ICER of € 16,594 per QALY, which is below the threshold of € 20,000 per QALY. All screening scenarios compared to no screening resulted in CERs between the € 14,000 and € 16,000 per QALY gained. The efficiency frontier showed that screening smokers and ex-smokers in the age groups 70 years and older, 60-70 years, 60 years and older are excluded by extended dominance by no screening, screening smokers and ex-smokers aged 50-60 years and 50-70 years. CONCLUSION: This study showed that lung cancer screening is cost-effective in the Netherlands.

Community-acquired pneumonia subgroups and differential response to corticosteroids: a secondary analysis of controlled studies.

BACKGROUND: Latent class analysis (LCA) has identified subgroups with meaningful treatment implications in acute respiratory distress syndrome. We performed a secondary analysis of three studies to assess whether LCA can identify clinically distinct subgroups in community-acquired pneumonia (CAP) and whether the treatment effect of adjunctive corticosteroids differs between subgroups. METHODS: LCA was performed on baseline clinical and biomarker data from the Ovidius trial (n=304) and the Steroids in Pneumonia (STEP) trial (n=727), both randomised controlled trials investigating adjunctive corticosteroid treatment in CAP, and the observational TripleP cohort (n=201). Analyses were conducted independently in two cohorts (Ovidius-TripleP combined and the STEP trial). In both cohorts, differences in clinical outcomes and response to adjunctive corticosteroid treatment were examined between subgroups identified through LCA. RESULTS: A two-class model fitted both cohorts best. Class 2 patients had more signs of systemic inflammation compared to class 1. In both cohorts, length of stay was longer and in-hospital mortality rate was higher in class 2. In the Ovidius trial, corticosteroids reduced the median length of stay in class 2 (6.5 versus 9.5 days) but not in class 1 (p-value for interaction=0.02). In the STEP trial, there was no significant interaction for length of stay. We found no significant interaction between class assignment and adjunctive corticosteroid treatment for secondary outcomes. CONCLUSIONS: In two independent cohorts, LCA identified two classes of CAP patients with different clinical characteristics and outcomes. Given the different response to adjunctive corticosteroids in the Ovidius trial, LCA might provide a useful basis to improve patient selection for future trials.

The dynamics in applied COVID-19 pharmacotherapy and the influence of national guidance in The Netherlands: a quantitative and qualitative study.

OBJECTIVE: At the beginning of the COVID-19 pandemic in the Netherlands, the Dutch Working Party on Antibiotic Policy constructed an advisory document about off-label drug treatment options that was regularly updated with new scientific findings. The aim of this study is to describe the dynamics in applied COVID-19 pharmacotherapy during the first 100 days of the pandemic and to assess how the national advisory document influenced local hospital policies. METHODS: A multicentre observational cohort study was conducted in six hospitals in the Netherlands. Patients with confirmed COVID-19 admitted between 27 February and 7 June 2020 were studied. Drug prescription data were collected and percentages of patients receiving a specific treatment were calculated. These percentages were plotted together with release dates of the national advisory document. Semi-structured in-depth interviews with hospital pharmacists and infectious diseases specialists were conducted to gain insight into the development and implementation of pharmacotherapy treatment protocols in hospitals. RESULTS: Data from 1511 patients (60% men, mean age 66 years) were analysed. From mid-March (hydroxy)chloroquine was being prescribed in all six hospitals to approximately 70% of patients at admission. Frequencies of other off-label treatments were below 2%. In the week of 6 April 2020, the first hospital discontinued prescribing (hydroxy)chloroquine and the last hospital discontinued in the week of 4 May 2020 (total range -19 to +10 days after the national advisory document advised against its use (1 May 2020)). All interviewees (n=6) stated that the hospitals based their policies mainly on the national advisory document but also assessed scientific literature themselves. Order panels were constructed to support prescribing. CONCLUSION: Dutch hospitals opted en masse for (hydroxy)chloroquine as COVID-19 therapy at the start of the pandemic, although the time until the therapy was no longer prescribed differed by several weeks. The fact that hospitals defined pharmacotherapy regimens based on their own assessment of the scientific literature besides the national advisory document can explain this variation.

Development of the First Patient-centred Set of Outcomes for Muscle-invasive and Metastatic Bladder Cancer: A Multicentre Initiative.

BACKGROUND: To improve and compare outcomes in healthcare, it is necessary to standardise outcome measurements. There are no widely accepted standardised outcome measures reflecting quality of care for bladder cancer (BCa) patients. OBJECTIVE: The aim of this study was to create a standardised set of outcomes for patients with muscle-invasive or metastatic BCa, using the value-based healthcare principles. DESIGN SETTING AND PARTICIPANTS: A multidisciplinary working group of 25 healthcare professionals and patient representatives was assembled, to develop the set. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used an online RAND-modified Delphi process to prioritise, discuss, and reach consensus regarding the outcomes, case-mix variables, and treatment factors. RESULTS AND LIMITATIONS: Recognising the heterogeneity of patients with BCa, the working group defined the scope as patients with muscle-invasive and metastatic BCa. A total of 24 outcomes, including ten patient-reported outcomes, were included in the standard set of outcomes, covering survival, complication rates, recurrence of disease, readmissions after treatment, and quality of life (QoL). Fourteen case-mix variables were included. The EQ-5D and European Organisation for Research and Treatment of Cancer quality of life (EORTC-QLQ) questionnaires were recommended to measure QoL. CONCLUSIONS: We developed the first standardised set of patient-centred outcomes for muscle-invasive and metastatic BCa. The sue of this set enables institutions to monitor, compare, and improve the quality of BCa care, on an international level. PATIENT SUMMARY: Our group of healthcare professionals and patient representatives recommended a standardised set of patient-centred outcomes to be followed during the treatment of patients with muscle-invasive or metastatic bladder cancer, in order to monitor, compare, and improve the quality of care.

Metabolomic profiling of microbial disease etiology in community-acquired pneumonia.

Diagnosis of microbial disease etiology in community-acquired pneumonia (CAP) remains challenging. We undertook a large-scale metabolomics study of serum samples in hospitalized CAP patients to determine if host-response associated metabolites can enable diagnosis of microbial etiology, with a specific focus on discrimination between the major CAP pathogen groups S. pneumoniae, atypical bacteria, and respiratory viruses. Targeted metabolomic profiling of serum samples was performed for three groups of hospitalized CAP patients with confirmed microbial etiologies: S. pneumoniae (n = 48), atypical bacteria (n = 47), or viral infections (n = 30). A wide range of 347 metabolites was targeted, including amines, acylcarnitines, organic acids, and lipids. Single discriminating metabolites were selected using Student's T-test and their predictive performance was analyzed using logistic regression. Elastic net regression models were employed to discover metabolite signatures with predictive value for discrimination between pathogen groups. Metabolites to discriminate S. pneumoniae or viral pathogens from the other groups showed poor predictive capability, whereas discrimination of atypical pathogens from the other groups was found to be possible. Classification of atypical pathogens using elastic net regression models was associated with a predictive performance of 61% sensitivity, 86% specificity, and an AUC of 0.81. Targeted profiling of the host metabolic response revealed metabolites that can support diagnosis of microbial etiology in CAP patients with atypical bacterial pathogens compared to patients with S. pneumoniae or viral infections.

Risk factors for nonvisualization of the sentinel lymph node on lymphoscintigraphy in breast cancer patients.

BACKGROUND: Accurate sentinel lymph node (SLN) staging is essential for both prognosis and treatment in patients with breast cancer. However, the preoperative lymphoscintigraphy may fail to visualize the SLN in some patients. The purpose of this retrospective study was to identify risk factors associated with SLN nonvisualization on lymphoscintigraphy. For this single-center retrospective study, all data of lymphoscintigraphy of SLN procedures from March 2011 to April 2021 were collected and reviewed from the Amsterdam UMC database. RESULTS: A total of 1886 SLN procedures were included in this study. The SLN nonvisualization rate was 25.1% on lymphoscintigraphy at 4 h post-injection. The SLN nonvisualization rate decreased to 9.4% after reinjection. Multivariable analysis showed that age ≥ 70 years (P < 0.001; OR: 2.27; 95% CI: 1.46-3.53), BMI ≥ 30 kg/m2 (P = 0.031; OR: 1.48; 95% CI: 1.04-2.12) and nonpalpable tumors (P = 0.004; OR: 1.54; 95% CI: 1.15-2.07) were independent predictors of SLN nonvisualization. Tumor location, brand of radiopharmaceutical, injected dose and volume, experience of preparer and administrator were not associated with SLN nonvisualization. None of the patient, tumor or tracer characteristics were associated with SLN nonvisualization after radiotracer reinjection. CONCLUSIONS: This study shows that risk factors for SLN nonvisualization in breast cancer patients during preoperative lymphoscintigraphy are age ≥ 70 years, BMI ≥ 30 kg/m2 and nonpalpable tumors. Our results support the notion that SLN lymphoscintigraphy is a very robust technique that does not depend on the experience of the preparer or administrator of the radiotracer.

Development and Evaluation of a Real-World Outcomes-Based Tool to Support Informed Clinical Decision Making in the Palliative Treatment of Patients With Metastatic NSCLC.

PURPOSE: To develop and evaluate a tool for patients with stage IV non-small-cell lung cancer and their thoracic oncologists (TOs) that provides insight into real-world effectiveness of systemic treatments to support informed clinical decision making in the palliative setting. METHODS: A participatory design approach was used to acquire insights from patients and TOs into preferences regarding the content and design of the web-based tool. Implementation was investigated by means of an adoption and usage rate. The appreciation of the tool was evaluated through a telephone survey with patients and a questionnaire for TOs. RESULTS: From clinical data of 2,989 patients with stage IV non-small-cell lung cancer diagnosed in one of the Santeon hospitals, an interface was developed to show treatments plus both real-world outcomes and clinical trial results after selecting patient characteristics (patients like me). This prototype of the tool was finalized after discussion in a focus group with four TOs and semi-structured interviews with six patients. The tool was implemented and used by TOs in three of six Santeon hospitals (50% adoption rate). The tool was used in 48 patients (29% usage rate), of which 17 participated in the telephone survey. Ten TOs responded to the questionnaire. The responses varied from positive reactions on the clear overview of treatment outcomes to statements that the tool rarely changed treatment decisions. Overall, the majority of patients and TOs scored the tool as of added value (71% and 83%, respectively). CONCLUSION: Our real-world data tool in metastatic lung cancer was appreciated in clinical practice by both patients and TOs. However, the efficacy of the implementation can be improved.