Complete DPYD genotyping combined with dihydropyrimidine dehydrogenase phenotyping to prevent fluoropyrimidine toxicity: A retrospective study.

INTRODUCTION: In April 2019, French authorities mandated dihydropyrimidine dehydrogenase (DPD) screening, specifically testing uracilemia, to mitigate the risk of toxicity associated with fluoropyrimidine-based chemotherapy. However, this subject is still of debate as there is no consensus on a standardized DPD deficiency screening test. We conducted a real-life retrospective study with the aim of assessing the impact of DPD screening on the occurrence of severe toxicity and exploring the potential benefits of complete genotyping using next-generation sequencing. METHODS: All adult patients consecutively treated with 5-fluorouracil (5-FU) or its oral prodrug at six cancer centers between March 2018 and February 2019 were considered for inclusion. Dihydropyrimidine dehydrogenase deficiency screening included gene encoding DPD (DPYD) genotyping using complete genome sequencing and DPD phenotyping (uracilemia or dihydrouracilemia/uracilemia ratio) or both tests. Associations between each DPD screening method and (i) severe (grade ≥3) early toxicity and (ii) fluoropyrimidine dose reduction in the second chemotherapy cycle were evaluated using multivariable logistic regression analysis. Furthermore, we assessed the concordance between DPD genotype and phenotype using Cohen's kappa. RESULTS: A total of 551 patients were included. Most patients were tested for DPD deficiency (86%) including DPYD genotyping only (6%), DPD phenotyping only (8%), or both (72%). Complete DPD deficiency was not detected in the study population. Severe early toxicity events were observed in 73 patients (13%), with two patients (0.30%) presenting grade 5 toxicity. Despite the numerically higher toxicity rate in untested patients, the occurrence of severe toxicity was not significantly associated with the DPD screening method (p = 0.69). Concordance between the DPD genotype and phenotype was weak (Cohen's kappa of 0.14). CONCLUSION: Due to insufficient numbers, our study was not able to demonstrate any added value of DPYD genotyping using complete genome sequencing to prevent 5-FU toxicity. The optimal strategy for DPD screening before fluoropyrimidine-based chemotherapy requires further clinical evaluation.

Persistent physical symptoms after COVID-19 infection and the risk of Somatic Symptom Disorder.

OBJECTIVE: Evidence shows that many patients with COVID-19 present persistent symptoms after the acute infection. Some patients may be at a high risk of developing Somatic Symptom Disorder (SSD), in which persistent symptoms are accompanied by excessive and disproportionate health-related thoughts, feelings and behaviors regarding these symptoms. This study assessed the frequency of persistent physical symptoms and SSD and their associated factors in patients with confirmed COVID-19. METHODS: We conducted a longitudinal retrospective study after the first two French lockdowns at the Lille University Hospital (France), including all patients with confirmed COVID-19. Persistent physical symptoms and excessive preoccupations for these symptoms were measured 8 to 10 months after the onset of COVID-19. The combination of the Patient Health Questionnaire-15 and the Somatic Symptom Disorder-B Criteria Scale was used to identify the individuals likely to present with SSD. Two linear regression models were performed to identify sociodemographic and medical risk factors of SSD. RESULTS: Among the 377 patients with a laboratory-confirmed diagnosis, 220 (58.4%) completed the questionnaires. Sixty-five percent of the 220 included patients required hospitalization, 53.6% presented at least one persistent physical symptom and 10.4% were considered to present SSD. Female sex, older age, infection during the second wave and having probable PTSD were significantly associated with the severity of SSD and SSD was associated with a significantly higher healthcare use. CONCLUSIONS: The identification of SSD should encourage clinicians to move beyond the artificial somatic/psychiatric dualism and contribute to a better alliance based on multi-disciplinary care.

Definition of a Practical Taxonomy for Referencing Data Quality Problems in Health Care Databases.

INTRODUCTION: Health care information systems can generate and/or record huge volumes of data, some of which may be reused for research, clinical trials, or teaching. However, these databases can be affected by data quality problems; hence, an important step in the data reuse process consists in detecting and rectifying these issues. With a view to facilitating the assessment of data quality, we developed a taxonomy of data quality problems in operational databases. MATERIAL: We searched the literature for publications that mentioned "data quality problems," "data quality taxonomy," "data quality assessment," or "dirty data." The publications were then reviewed, compared, summarized, and structured using a bottom-up approach, to provide an operational taxonomy of data quality problems. The latter were illustrated with fictional examples (though based on reality) from clinical databases. RESULTS: Twelve publications were selected, and 286 instances of data quality problems were identified and were classified according to six distinct levels of granularity. We used the classification defined by Oliveira et al to structure our taxonomy. The extracted items were grouped into 53 data quality problems. DISCUSSION: This taxonomy facilitated the systematic assessment of data quality in databases by presenting the data's quality according to their granularity. The definition of this taxonomy is the first step in the data cleaning process. The subsequent steps include the definition of associated quality assessment methods and data cleaning methods. CONCLUSION: Our new taxonomy enabled the classification and illustration of 53 data quality problems found in hospital databases.

Mental Health Symptoms of University Students 15 Months After the Onset of the COVID-19 Pandemic in France.

Importance: The Conséquences de la pandémie de COVID-19 sur la santé mentale des étudiants (COSAMe) survey was conducted among university students in France during the COVID-19 pandemic and found that although there was a slight decrease in anxiety, depression, and stress between the first lockdown (T1) and 1 month after it ended (T2), the prevalence of suicidal ideation had increased between these periods and 1 in 5 students had probable posttraumatic stress disorder (PTSD) at T2. These results emphasize the need to explore the long-term consequences of the COVID-19 pandemic. Objectives: To measure the prevalence of mental health symptoms among university students in France 15 months after the first lockdown (T3) and to identify factors associated with outcomes. Design, Setting, and Participants: This cross-sectional study reports data from the third measurement time of the repeated COSAMe survey, which took place from July 21 to August 31, 2021, through an online questionnaire sent to all French university students. Main Outcomes and Measures: The prevalence of suicidal thoughts, PTSD (PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] [PCL-5]), stress (Perceived Stress Scale), anxiety (State-Trait Anxiety Inventory), and depression (Beck Depression Inventory) at T3 were gender- and degree-standardized and compared with prevalence rates at T1 and T2. Multivariable logistic regression analyses identified risk factors. Results: A total of 44 898 students completed the questionnaires. They were mainly women (31 728 [70.7%]), and the median (IQR) age was 19 (18-21) years. Standardized prevalence rates of stress, anxiety, depression, suicidal thoughts, and PTSD were 20.6% (95% CI, 20.2%-21.0%), 23.7% (95% CI, 23.3%-24.1%), 15.4% (95% CI, 15.1%-15.8%), 13.8% (95% CI, 13.5%-14.2%), and 29.8% (95% CI, 29.4%-30.2%), respectively. Compared with the decreased prevalence rates at T2, there was an increase at T3 for stress (2.5% increase), anxiety (13.9% increase), and depression (22.2% increase). The prevalence of suicidal ideation continued to increase from T1 (10.6%) to T3 (13.8%), and the prevalence of probable PTSD increased from 1 in 5 students to 1 in 3 students between T2 and T3. Female and nonbinary participants; participants without children and living in an urban area; and those with financial difficulties, a chronic condition, psychiatric history, COVID-19 history, social isolation, and low perceived quality of information received were at risk of all poor outcomes at T3 (eg, stress among women: adjusted OR, 2.18; 95% CI, 2.05-2.31; suicidal thoughts among nonbinary respondents: adjusted OR, 5.09; 95% CI, 4.32-5.99; anxiety among students with children: adjusted OR, 0.68; 95% CI, 0.56-0.81; depression among students living in a rural area: adjusted OR, 0.80; 95% CI, 0.75-0.85). Conclusions and Relevance: These results suggest severe long-lasting consequences associated with the pandemic on the mental health of students. Prevention and care access should be a priority.

Evolution in French University Students' Mental Health One Month After the First COVID-19 Related Quarantine: Results From the COSAMe Survey.

Introduction: The COVID-19 related quarantine had negative psychological effects among University students. Evidence from previous epidemics suggests that negative psychological effects of quarantine measures can last or even worsen after the quarantine lift. The objective of this study was to assess the evolution of students' mental health and to identify factors associated with mental health outcomes 1 month after the lift of the lockdown. Materials and Methods: This repeated cross-sectional study collected data during the first quarantine in France (T1, N = 68,891) and 1 month after its lift (T2, N = 22,540), through an online questionnaire sent to all French University students. Using cross-sectional data, we estimated prevalence rates of suicidal thoughts, severe anxiety (State-Trait Anxiety Inventory, State subscale), depression (Beck Depression Inventory), and stress (Perceived Stress Scale) at T1 and T2. Using longitudinal data (N = 6,346), we identified risk factors of poor mental health outcomes among sociodemographic characteristics, precariousness indicators, health-related data, information on the social environment, and media consumption, adjusting for baseline mental health status. Results: We found lower prevalence rates of severe stress (21.7%), anxiety (22.1%), and depression (13·9%) one month after the quarantine compared to the quarantine period (24.8%, 27.5%, and 16.1%, respectively). The prevalence rate of suicidal thoughts increased from 11.4 to 13.2%. Regardless of the existence of symptoms during quarantine, four factors were systematically associated with poor mental health outcomes 1 month after the quarantine was lifted: female gender, a low feeling of integration before the quarantine period, a low quality of social ties during the quarantine, and a history of psychiatric follow-up. Conclusions: The prevalence rates of severe stress, anxiety, and depression, although being lower than during the first lockdown, remained high after its lift. The prevalence rate of suicidal ideation increased. This stresses the need to consider the enduring psychological impact of the pandemic on students as a critical public health issue.

Goupile: A New Paradigm for the Development and Implementation of Clinical Report Forms.

Despite the increasing computerization of hospital information systems, segments of patient care are still in paper format. Data extracted automatically from the hospital databases for one specific project are thus supplemented by data collected manually. Data collection tools are usually developed entirely, which requires computer knowledge and is tedious, or automatically from metadata or drag and drop controls, which is limiting in terms of functionality. To facilitate this manual collection, we developed a free and open-source tool for creating forms that does not require advanced computer skills, offers rich features, and is quickly implemented, tested and deployed. It was implemented for 15 projects and supported thousands of daily users for a complex interactive study at the national level.

Long-Term Outcomes and Prognostic Factors of Patients with Metastatic Solid Tumors Admitted to the Intensive Care Unit.

INTRODUCTION: Admission of metastatic cancer patients to the intensive care unit (ICU) poses medical and ethical challenges in the absence of reliable prognostic tools to guide decision-making. MATERIAL AND METHODS: We retrospectively analyzed the medical charts of 129 consecutive patients with metastatic solid tumors admitted to the ICU between January and September 2014 and identified prognostic factors (PFs) using Cox models. RESULTS: The mean patient age at ICU admission was 58.9 years (range, 25-81 years; males, 51%). Performance status (PS) was 0-1 and 2-3 in 61% and 39% of the patients, respectively. The most prevalent cancers were lung cancer (20%), sarcoma (17%), and breast cancer (16%). ICU admission was attributable to the cancer itself (53%), cancer treatment toxicity (43%), and comorbidities (37%). The median overall survival (OS) after ICU admission was 2.6 months; 15% of the patients died during the ICU stay. Poor PFs for OS were PS >1 before ICU admission (p = 0.007) and ICU admission for the cancer itself (p < 10-3). After ICU discharge, 58% and 42% of the patients received systemic treatment within 12 months and showed good PS recovery, respectively. Multiple organ failure and a multidisciplinary decision to limit therapeutic efforts were poor PFs for reinitiation of systemic treatment (p = 0.2 and 0.006, respectively), and the latter was also a poor PF for PS recovery (p = 0.004). DISCUSSION: In the ICU, the OS of adult patients with solid tumors was similar to that of the noncancer population. For ICU admissions related to the cancer itself, the prognosis is poor.

Mental health among medical, healthcare, and other university students during the first COVID-19 lockdown in France.

Background The COVID-19 pandemic has raised concerns regarding its psychological effect on university students, especially healthcare students. We aimed at assessing the risk of mental health problems according to the type of university studies, by adjusting for potential confounders. Methods We used data from the COSAMe study, a national cross-sectional survey including 69,054 French university students during the first quarantine. The mental health outcomes evaluated were suicidal thoughts, severe self-reported distress (as assessed by the Impact of Events Scale-Revised), stress (Perceived Stress Scale), anxiety (State-Trait Anxiety Inventory, State subscale), and depression (Beck Depression Inventory). Multivariable logistic regression analyzes were performed to test the association between the type of university studies (healthcare studies: medical and non-medical, and non-healthcare studies) and poor mental health outcomes, adjusted for sociodemographic characteristics, precariousness indicators, health-related data, quality of social relationships, and data about media consumption. Results Compared to non-healthcare students (N = 59,404), non-medical healthcare (N = 5,431) and medical students (N = 4,193) showed a lower risk of presenting at least one poor mental health outcome (adjusted OR [95%CI] = 0.86[0.81-0.92] and 0.87[0.81-0.93], respectively). Compared to non-healthcare students, medical students were at lower risk of suicidal thoughts (0.83[0.74-0.93]), severe self-reported distress (0.75[0.69-0.82]) and depression (0.83[0.75-0.92]). Non-medical healthcare students were at lower risk of severe selfreported distress (0.79[0.73-0.85]), stress (0.92[0.85-0.98]), depression (0.83[0.76-0.91]), and anxiety (0.86[0.80-0.92]). Limitations This is a large but not representative cross-sectional study, limited to the first confinement. Conclusions Being a healthcare student is a protective factor for mental health problems among confined students. Mediating factors still need to be explored.

Heimdall, a Computer Program for Electronic Health Records Data Visualization.

INTRODUCTION: Electronic health records (EHR) comprehend structured and unstructured data, that are usually time dependent, enabling the use of timelines. However, it is often difficult to display all data without inducing information overload. In both clinical usual care and medical research, users should be able to quickly find relevant information, with minimal cognitive overhead. Our goal was to devise simple visualization techniques for handling medical data in both contexts. METHODS: An abstraction layer for structured EHR data was devised after an informal literature review and discussions between authors. The "Heimdall" prototype was developed. Two experts evaluated the tool by answering 5 questions on 24 clinical cases. RESULTS: Temporal data was abstracted in three simple types: events, states and measures, with appropriate visual representations for each type. Heimdall can load and display complex heterogeneous structured temporal data in a straightforward way. The main view can display events, states and measures along a shared timeline. Users can summarize data using temporal, hierarchical compression and filters. Default and custom views can be used to work in problem- oriented ways. The evaluation found conclusive results. CONCLUSION: The "Heimdall" prototype provides a comprehensive and efficient graphical interface for EHR data visualization. It is open source, can be used with an R package, and is available at https://koromix.dev/files/R.

Gastric Bypass But Not Sleeve Gastrectomy Increases Risk of Major Osteoporotic Fracture: French Population-Based Cohort Study.

The objective of this work was to investigate the risk of major osteoporotic fracture (MOF; hip, proximal humerus, wrist and distal forearm, and clinical spine) in bariatric surgery patients versus matched controls. Bariatric surgery is associated with an increase in fracture risk. However, it remains unclear whether the same degree of fracture risk is associated with sleeve gastrectomy, which has recently surpassed gastric bypass. Records from the French National Inpatient database were used from 2008 to 2018. Bariatric surgery patients, aged 40 to 65 years, with BMI ≥40 kg/m2 , hospitalized between January 1, 2010 and December 31, 2014, were matched to one control (1:1) by age, sex, Charlson comorbidity index, year of inclusion, and class of obesity (40 to 49.9 kg/m2 versus ≥50 kg/m2 ). We performed a Cox regression analysis to assess the association between the risk of any MOF and, respectively, (i) bariatric surgery (yes/no) and (ii) type of surgical procedure (gastric bypass, gastric banding, vertical banded gastroplasty, and sleeve gastrectomy) versus no surgery. A total of 81,984 patients were included in the study (40,992 in the bariatric surgery group, and 40,992 matched controls). There were 585 MOFs in the surgical group (2.30 cases per 1000 patient-year [PY]) and 416 MOFs in the matched controls (1.93 cases per 1000 PY). The risk of MOF was significantly higher in the surgical group (hazard ratio [HR] 1.22; 95% CI, 1.08-1.39). We observed an increase in risk of MOF for gastric bypass only (HR 1.70; 95% CI, 1.46-1.98) compared with the matched controls. In patients aged 40 to 65 years, gastric bypass but not sleeve gastrectomy or the other procedures increased risk of major osteoporotic fractures. © 2020 American Society for Bone and Mineral Research.