Evaluating the Diagnostic Performance of Symptom Checkers: Clinical Vignette Study.

BACKGROUND: Medical self-diagnostic tools (or symptom checkers) are becoming an integral part of digital health and our daily lives, whereby patients are increasingly using them to identify the underlying causes of their symptoms. As such, it is essential to rigorously investigate and comprehensively report the diagnostic performance of symptom checkers using standard clinical and scientific approaches. OBJECTIVE: This study aims to evaluate and report the accuracies of a few known and new symptom checkers using a standard and transparent methodology, which allows the scientific community to cross-validate and reproduce the reported results, a step much needed in health informatics. METHODS: We propose a 4-stage experimentation methodology that capitalizes on the standard clinical vignette approach to evaluate 6 symptom checkers. To this end, we developed and peer-reviewed 400 vignettes, each approved by at least 5 out of 7 independent and experienced primary care physicians. To establish a frame of reference and interpret the results of symptom checkers accordingly, we further compared the best-performing symptom checker against 3 primary care physicians with an average experience of 16.6 (SD 9.42) years. To measure accuracy, we used 7 standard metrics, including M1 as a measure of a symptom checker's or a physician's ability to return a vignette's main diagnosis at the top of their differential list, F1-score as a trade-off measure between recall and precision, and Normalized Discounted Cumulative Gain (NDCG) as a measure of a differential list's ranking quality, among others. RESULTS: The diagnostic accuracies of the 6 tested symptom checkers vary significantly. For instance, the differences in the M1, F1-score, and NDCG results between the best-performing and worst-performing symptom checkers or ranges were 65.3%, 39.2%, and 74.2%, respectively. The same was observed among the participating human physicians, whereby the M1, F1-score, and NDCG ranges were 22.8%, 15.3%, and 21.3%, respectively. When compared against each other, physicians outperformed the best-performing symptom checker by an average of 1.2% using F1-score, whereas the best-performing symptom checker outperformed physicians by averages of 10.2% and 25.1% using M1 and NDCG, respectively. CONCLUSIONS: The performance variation between symptom checkers is substantial, suggesting that symptom checkers cannot be treated as a single entity. On a different note, the best-performing symptom checker was an artificial intelligence (AI)-based one, shedding light on the promise of AI in improving the diagnostic capabilities of symptom checkers, especially as AI keeps advancing exponentially.

Serological responses against seasonal influenza viruses in patients with multiple myeloma treated or untreated with daratumumab after two doses of tetravalent vaccine.

OBJECTIVES: Daratumumab-treated myeloma patients may face increased seasonal influenza risk due to weakened postvaccination immune responses, especially with daratumumab treatment. We aimed to assess humoral responses to boosted influenza vaccination in daratumumab-treated or -untreated patients. METHODS: In a single-center study, we evaluated humoral responses (hemagglutination-inhibition assay) one month following a two-injection (4-weeks apart) influenza vaccination (standard dose) in 84 patients with multiple myeloma (40 with daratumumab in the past year). RESULTS: Seroprotection rates (titer ≥1/40) after the second vaccine injection were low across vaccinal subtypes (except for A-H3N2): 71.3% (A-H3N2), 19.7% (A-H1N1pdm09), 9.9% (B-Victoria), 11.3% (B-Yamagata). Only A-H3N2 seroprotection rates significantly increased with the booster in daratumumab-treated patients (30% (12/40) after one injection vs 55% (22/40) after the boost; P = 0.01).After propensity score weighting, daratumumab was not significantly associated with a reduced likelihood of seroprotection against at least one vaccine strain (OR 0.65 [95% CI: 0.22-1.88]). CONCLUSION: While daratumumab treatment did not lead to a significant reduction in seroprotection rates following influenza vaccination, a booster vaccine injection demonstrated potential benefit for specific strains (A-H3N2) in patients undergoing daratumumab treatment. Nevertheless, the overall low response rates in patients with multiple myeloma necessitates the development of alternative vaccination and prophylaxis strategies.

Real-life effectiveness of carfilzomib in patients with relapsed multiple myeloma receiving treatment in the context of early access: The CARMYN study.

The real-life retrospective observational study CARMYN aimed at investigating the long-term efficacy and safety of carfilzomib in combination with dexamethasone and lenalidomide (KRd, 159 patients). These patients (62% in first and 38% in second relapse, median age 62 yo) were treated between 02/2014 and 02/2017. Most had been pre-exposed to bortezomib (98.2%) and to an IMID (75.4%). At the time of collection, 90% had permanently discontinued carfilzomib. Data collection was conducted from January to July 2021 in 27 participating sites, after a median of 39 months follow-up. For patients treated with KRd, an overall response rate of 78.4% translated in a median progression free survival (PFS) of 24.0 months (95% CI 18.8-27.6) and a median overall survival (OS) of 51.1 months (95% CI 41.3-not reached). Results were poorer but difficult to interpret in the small cohort of Kd recipients. The study is one of the longest real-life studies of carfilzomib treatment in patients in first or second relapse. CARMYN confirmed the real-life long-term efficacy of carfilzomib in combination with lenalidomide and dexamethasone with results similar to those of clinical trials. The KRd regimen is thus an option to consider for late relapses in the current context of MM management.

Parents' perceptions of their children's mental health during COVID-19: Evidence from Canada.

OBJECTIVE: This study examined several factors affecting the perception of Canadian parents about their children's mental health during COVID-19. The contribution of this research included fresh evidence from examining the demographic and sociological factors influencing children's well-being during COVID-19 using the Canadian context. METHODS: We used a cross-sectional dataset from Statistics Canada titled Impacts of COVID-19 on Canadians - Parenting during the Pandemic (2020). We relied on an ordered logit model and computed the respective odds ratios. RESULTS: Our results showed that parents with a university degree and those working from home are less concerned about their children's mental health. Nonetheless, having a disabled child, belonging to a minority, having children aged six-to fourteen-years old, and having lost a job or experienced a drop in working hours increased parents' worry. Additionally, having worries about being connected with family and friends, being concerned about work-life balance, feeling lonely at home, and waiting for the reopening of childcare services all increased the likelihood of parents' anxiety about their child's mental health. When running the analysis by province, we saw that being an immigrant and belonging to a minority increased parents' worry only in Ontario and British Columbia. CONCLUSIONS: Policymakers are encouraged to foster working-from-home practices as working from home has been linked to less worry about child mental health, mainly among mothers, as indicated in our gender heterogeneity analysis. In addition, it is advised that families with a disabled child, and families belonging to a minority received additional support. Lastly, policymakers are advised to consider the social cost of preventive measures and incorporate this into any future preventative policymaking as the social impact variables were robust across all models.

Direct Exchange of PerfluoroCarbon Liquid for Silicone Oil: A Surgical Technique to Control Pressure and Avoid Retinal Slippage.

BACKGROUND/PURPOSE: Perfluorocarbon heavy liquid (PFCL) is used in vitreoretinal surgery to flatten the unsupported detached retina before insertion of silicone oil in cases of giant retinal tear or relaxing retinectomy. Direct exchange of PFCL for silicone oil is recommended to reduce retinal slippage when compared with fluid-air exchange, but it is commonly regarded as a difficult procedure. We describe our technique for direct PFCL-silicone oil exchange using a 20-gauge drainage cannula, reliably avoiding the complications of retinal slippage and high intraoperative intraocular pressure. METHODS: We present a consecutive case series of patients undergoing PFCL-oil exchange and explain, using Poiseuille's equation for laminar fluid flow through a cannula, the rationale for using a 20-gauge drainage cannula rather than smaller gauges to avoid high intraocular pressure. RESULTS: Twenty-six patients underwent PFCL-oil exchange from February 1, 2019, to September 30, 2019. There was no intraoperative retinal slippage or pressure-related complications. Postoperatively 20 patients underwent oil removal. Six suffered retinal redetachment, and 14 remained attached. The vision postoil removal ranged from 6/6 to hand movements. CONCLUSION: We are confident that the PFCL-oil exchange technique described here is reliable and safe. The use of a 20-gauge drainage cannula is recommended regardless of vitrectomy gauge.

Design and Simulation of a Passive Absorber to Reduce Measured Postural Tremor Signal.

Tremor is a semirhythmic oscillatory movement of a body part caused by alternating simultaneous contractions of an antagonistic muscle group. Medical and surgical treatments used to reduce the symptoms of involuntary tremor can cause negative side effects. This study examined the ability of passive vibration absorbers in reducing the amplitude of postural tremor (PT). Inertial measurement unit (IMU) was used to record PT signals at the forearm and hand of a patient. IMU signal was used to excite an upper limb modeled to represent the flexion-extension vibrational motion at the joints. Equations of motion were solved numerically to obtain a response that fits the measured tremor signal. Passive tuned mass damper (TMD) was modeled as a cantilever beam and a screw placed along its length, at a position reflecting its operational frequency. Natural frequency of the TMD was derived for different mass positions and validated numerically and experimentally. Modal damping ratio of the TMD, for each mass position, was also estimated. Mass position and damping coefficient of the TMD were optimized depending on the minimization in the power spectral density (PSD) of angular displacement amplitude at the wrist joint. Optimized three-TMD system of 28.64 g total effective mass with the estimated modal damping ratio reduced 83.1% of the PSD of the angular displacement amplitude. This study showed the performance ability of a lightweight passive absorber in controlling the involuntary tremor of a system excited by the measured tremor signal of a patient.

Anti-SARS-CoV-2 antibody response after 2 and 3 doses of BNT162b2 mRNA vaccine in patients with lymphoid malignancies.

OBJECTIVES: COVID-19 patients affected by haematological malignancies have a more severe course of the disease and higher mortality, prompting for effective prophylaxis. The present study aims to evaluate the humoral response after mRNA vaccination as well as the impact of a third vaccine dose in patients with lymphoid malignancies. METHODS: We conducted a single-centre study, evaluating the serological responses of mRNA vaccination amongst a cohort of 200 patients affected by lymphoid malignancies after two or three doses using an industrial SARS-CoV-2 serology assay for anti-receptor binding domain (RBD) Spike IgG detection and quantification. RESULTS: Among patients with plasma cell disorders, 59 of 96 (61%) had seroconversion (anti-RBD >50 AU/mL), and recent anti-CD38 therapies were associated with lower serological anti-RBD IgG concentrations (median IgG concentration 137 (IQR 0-512) AU/mL vs. 543 (IQR 35-3496) AU/mL; p < 0.001). Patients with B-cell malignancies had a lower seroconversion rate (20/84, 24%) mainly due to the broad usage of anti-CD20 monoclonal antibodies; only 2 of 53 (4%) patients treated by anti-CD20 antibodies during the last 12 months experienced a seroconversion. A total of 78 patients (44 with plasma cell disorders, 27 with B-cell malignancies, and 7 with other lymphomas) received a third dose of vaccine. The seroconversion rate and antibody concentrations increased significantly, especially in patients with plasma cell disorders, where an increment of anti-RBD IgG concentrations was observed in 31 of 44 (70%) patients, with an anti-RBD concentration median-fold increase of 10.6 (IQR 2.4-25.5). Its benefit in B-cell malignancies is uncertain, with only 2 of 25 (8%) patients having seroconverted after the vaccine booster, without increased median antibody concentration. DISCUSSION: A third mRNA vaccine dose significantly improved humoral responses among patients with plasma cell disorders, whereas the effect was limited among patients with B-cell malignancies.

The effects of prostaglandins and endocannabinoids on iris arterial vascularization in Wistar rats - Experimental analysis.

Introduction: The iris vascular supply originates in the anterior and long posterior ciliary arteries. The endothelium influences local blood flow by releasing endothelium relaxing and contracting substances. From a functional perspective, the ocular vascular tonus adjustment is humoral and neural dependent. Objectives: The present article aims to evaluate the possible implications of topical administration of selective COX2 and nonselective COX inhibitors generically named nonsteroidal anti-inflammatory drugs (NSAIDs) and their possible interactions with the endocannabinoid system and the way they could interfere with the vascular tone at the level of ocular iris territory in Wistar rats. Materials and methods: Experimental protocol on Wistar rats was performed in accordance with present laws regarding animal welfare and ethics in animal experiments (Directive 86/ 609EEC/ 1986; Romanian Law 205/ 2004; Romanian Laws 206/ 2004, 471/ 2002 and 9/ 2008; Romanian Order 143/ 400). The studied substances were instilled topically under general anesthesia, and images of the rat iris vessels were captured over a period of 10 minutes. The obtained images were further analyzed using an appropriate hardware and software program. Results: The nonselective NSAIDs induced vascular dilation in the iris vessels, while the selective COX2 inhibitors determined a variable degree of vasoconstriction. Conclusion: In view of the results of this experiment and the added evidence found in literature, we consider that further research will show the potential benefits for the additional use of NSAIDs in ocular pathology, otherwise unaffected by this medication until the present time (for example, glaucoma treatment).

Endocannabinoid System and Ocular Vascularization.

The focus of this review is the role of endocannabinoid system in ocular and systemic circulation. By critically examining preclinical and clinical research, we explore the cannabinoid receptors localization and vascular implications as well as their interaction with other anti-inflammatory drugs. The objective is to transfer knowledge on the use of cannabinoids, specifically their effect on ocular circulation and intraocular pressure, and provide a better understanding of the endocannabinoid system complexity in modulating local and systemic circulations in order to identify potential uses and limitations of cannabinoid-based therapeutics.

Tremor Reduction at the Palm of a Parkinson's Patient Using Dynamic Vibration Absorber.

Parkinson's patients suffer from severe tremor due to an abnormality in their central oscillator. Medications used to decrease involuntary antagonistic muscles contraction can threaten their life. However, mechanical vibration absorbers can be used as an alternative treatment. The objective of this study is to provide a dynamic modeling of the human hand that describes the biodynamic response of Parkinson's patients and to design an effective tuned vibration absorber able to suppress their pathological tremor. The hand is modeled as a three degrees-of-freedom (DOF) system describing the flexion motion at the proximal joints on the horizontal plane. Resting tremor is modeled as dual harmonic excitation due to shoulder and elbow muscle activation operating at resonance frequencies. The performance of the single dynamic vibration absorber (DVA) is studied when attached to the forearm and compared with the dual DVA tuned at both excitation frequencies. Equations of motion are derived and solved using the complex transfer function of the non-Lagrangian system. The absorber's systems are designed as a stainless steel alloy cantilevered beam with an attached copper mass. The dual DVA was the most efficient absorber which reduces 98.3%-99.5%, 97.0%-97.3% and 97.4%-97.5% of the Parkinson's tremor amplitude at the shoulder, elbow and wrist joint.

Posterior reversible encephalopathy syndrome in pediatric hematologic-oncologic disease: literature review and case presentation.

OBJECTIVE: Posterior reversible encephalopathy syndrome (PRES) is a cliniconeuroradiological disease entity, which is represented by characteristic magnetic resonance imaging (MRI) findings of subcortical/cortical hyperintensity in T2-weighted sequences. It is more often seen in parietaloccipital lobes, and is accompanied by clinical neurological changes. PRES is a rare central nervous system (CNS) complication in patients with childhood hematologic-oncologic disese and shows very different neurological symptoms between patients, ranging from numbness of extremities to generalized seizure. In this article, we will review PRES presentation in hematologic-oncologic patients. Then, we will present our patient, a 7-year-old boy with Evans syndrome on treatment with cyclosporine, mycophenolate mofetil (MMF) and prednisone, with seizure episodes and MRI finding in favour of PRES.

Combination of low O(2) concentration and mesenchymal stromal cells during culture of cord blood CD34(+) cells improves the maintenance and proliferative capacity of hematopoietic stem cells.

The physiological approach suggests that an environment associating the mesenchymal stromal cells (MSC) and low O(2) concentration would be most favorable for the maintenance of hematopoietic stem cells (HSCs) in course of ex vivo expansion of hematopoietic grafts. To test this hypothesis, we performed a co-culture of cord blood CD34(+) cells with or without MSC in presence of cytokines for 10 days at 20%, 5%, and 1.5% O(2) and assessed the impact on total cells, CD34(+) cells, committed progenitors (colony-forming cells-CFC) and stem cells activity (pre-CFC and Scid repopulating cells-SRC). Not surprisingly, the expansion of total cells, CD34(+) cells, and CFC was higher in co-culture and at 20% O(2) compared to simple culture and low O(2) concentrations, respectively. However, co-culture at low O(2) concentrations provided CD34(+) cell and CFC amplification similar to classical culture at 20% O(2) . Interestingly, low O(2) concentrations ensured a better pre-CFC and SRC preservation/expansion in co-culture. Indeed, SRC activity in co-culture at 1.5% O(2) was higher than in freshly isolated CD34(+) cells. Interleukin-6 production by MSC at physiologically low O(2) concentrations might be one of the factors mediating this effect. Our data demonstrate that association of co-culture and low O(2) concentration not only induces sufficient expansion of committed progenitors (with respect to the classical culture), but also ensures a better maintenance/expansion of hematopoietic stem cells (HSCs), pointing to the oxygenation as a physiological regulatory factor but also as a cell engineering tool.

Slow-cycling/quiescence balance of hematopoietic stem cells is related to physiological gradient of oxygen.

OBJECTIVE: Regulation of hematopoiesis depends on cytokines, cellular interactions, transcription, and metabolic factors. Among the latter, O(2) has been neglected for a long time. Recently, an increasing number of publications evidenced the regulatory role of physiological low O(2) concentrations (0.1-5%; similar to those in bone marrow) on the in vitro behavior of hematopoietic stem cells. This brief review utilizes the article of Eliasson and colleagues in this Journal to summarize the major results and questions about the relationships between O(2) and hematopoiesis. MATERIALS AND METHODS: In order to be concise and interesting for readers unfamiliar with this field, we selected only the most significant data that either reinforce or contradict the conclusions of Eliasson et al., but we also provide references of reviews with a more detailed bibliography. RESULTS: A critical analysis of some key publications provides partial answers to three important questions: is the term hypoxia appropriate to describe physiological low O(2) concentrations? Is a very low O(2) level sufficient to control the quiescence/slow cycling balance of hematopoietic stem cells? Is the O(2) concentration able to modify the effect of cytokines on hematopoietic stem cells? CONCLUSIONS: We propose to use in situ normoxia instead of the confusing term hypoxia when working with normal cells at physiological low O(2) concentrations. We suggest that a very low O(2) concentration is necessary but not sufficient to induce hematopoietic stem cell quiescence. We review some articles showing that O(2) variations modify the effect of cytokines.

Low O2 concentrations enhance the positive effect of IL-17 on the maintenance of erythroid progenitors during co-culture of CD34+ and mesenchymal stem cells.

Co-culture of haematopoietic cells with a stromal cell layer does not mimic the physiological, micro-environmental niche, whose major feature is a low oxygen (O2) concentration. Thus, in order to study the effects of IL-17 in a context which better approximates the physiological state, we investigated its effects on cell expansion, colony-forming ability, and the phenotypical profile of normal, human blood CD34+ cells co-cultured for five days with MSC layers at various O2 concentrations (20%, 12.5% and 3% O2. We demonstrated that IL-17 enhances CD34+ and total CFC production during the five days of MSC/CD34+ co-culture. This effect depends upon the O2 concentration, reaching its maximum at 3% O2, and is more pronounced on erythroid progenitors (BFU-E). In addition, the stimulation of IL-6 production by IL-17 in MSC cultures and co-cultures is enhanced by low O2 concentration. The expression of some differentiation markers (CD34, CD13 and CD41) on haematopoietic cells in co-cultures also depends upon the oxygen concentration. Our results strengthen the concept that physiological levels of O2 (mistakenly called hypoxia), should be considered as an important environmental factor that significantly influences cytokine activity.