scholarly journals Treatment selection using prototyping in latent-space with application to depression treatment

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0258400
Author(s):  
Akiva Kleinerman ◽  
Ariel Rosenfeld ◽  
David Benrimoh ◽  
Robert Fratila ◽  
Caitrin Armstrong ◽  
...  
Keyword(s):  
Treatment Selection ◽  
Depression Treatment ◽  
Major Depressive ◽  
Treatment Allocation ◽  
Extensive Evaluation ◽  
Latent Space ◽  
Number Of Patients ◽  
Clinically Significant ◽  
Training Objective ◽  
Potentially Clinically Significant

Machine-assisted treatment selection commonly follows one of two paradigms: a fully personalized paradigm which ignores any possible clustering of patients; or a sub-grouping paradigm which ignores personal differences within the identified groups. While both paradigms have shown promising results, each of them suffers from important limitations. In this article, we propose a novel deep learning-based treatment selection approach that is shown to strike a balance between the two paradigms using latent-space prototyping. Our approach is specifically tailored for domains in which effective prototypes and sub-groups of patients are assumed to exist, but groupings relevant to the training objective are not observable in the non-latent space. In an extensive evaluation, using both synthetic and Major Depressive Disorder (MDD) real-world clinical data describing 4754 MDD patients from clinical trials for depression treatment, we show that our approach favorably compares with state-of-the-art approaches. Specifically, the model produced an 8% absolute and 23% relative improvement over random treatment allocation. This is potentially clinically significant, given the large number of patients with MDD. Therefore, the model can bring about a much desired leap forward in the way depression is treated today.

scholarly journals 577. Incidence and Outcomes of Positive Outpatient Surveillance Blood Cultures in Hematopoietic Stem Cell Transplant (HSCT) Patients with Graft Versus Host Disease (GvHD) On High Dose ≥ 0.5 mg/kg/day (HD) and Low Dose < 0.5mg/kg/day (LD) Steroid Therapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S353-S354
Author(s):  
Sarah Perreault ◽  
Molly Schiffer ◽  
Jennifer Zhao ◽  
Dayna McManus ◽  
Francine Foss ◽  
...  
Keyword(s):  
Steroid Therapy ◽  
Central Line ◽  
Blood Cultures ◽  
High Dose ◽  
Cell Transplant ◽  
Coagulase Negative Staphylococci ◽  
Hematopoietic Stem ◽  
Surveillance Cultures ◽  
Number Of Patients ◽  
Clinically Significant

Abstract Background Treatment of GvHD with steroids increases the risk of infection in HSCT patients due to additive immunosuppression and may delay the diagnosis of infection due to lack of symptoms. Outpatient surveillance blood cultures in HSCT with GvHD being treated with HD steroids has demonstrated a blood culture positivity rate of 3.5%. Currently, the utility of surveillance cultures in patients receiving LD steroid therapy is unknown. Our practice includes weekly outpatient surveillance cultures for all GvHD patients treated with steroids regardless of the dose. The primary endpoint of this study was to assess the incidence of positive surveillance blood cultures in GvHD patients receiving HD or LD steroids. Secondary endpoints included number of patients treated, hospitalization, 30 day mortality due to infection, and organisms isolated. Methods This was a single-center, retrospective review of GvHD patients at Yale New Haven Hospital between January 2013 and May 2019. Patients were excluded if: lack of signs or symptoms of GvHD, treatment with steroids for any indication other than GvHD, and active GvHD without central line. Cultures from patients receiving antibiotics for concurrent infection were also excluded. Results A total of 71 patients met criteria with 901 blood cultures. On HD, eight patients (14%) had 12 positive cultures (4%), and on LD, 16 patients (25%) had 22 positive cultures (4%) (p=0.15). Treatment occurred in six patients (75%) with four (24%) requiring hospitalization on HD, and 12 patients (75%) with 10 (83%) requiring hospitalization on LD (p=0.45). The median duration of steroid therapy was 93 and 236 days with a median dose of steroids of 1mg/kg/day and 0.15mg/kg/day, respectively. The number of positive cultures/1000 steroid days was 1.2 on HD and 0.5 on LD (RR 2.2). 30 day mortality was only noted in one patient (8%) on LD. The most common organism in both groups was Coagulase-negative staphylococci with all six cultures on HD classified as contaminants and 6/10 cultures requiring treatment on LD. Conclusion Although the relative risk of positive surveillance blood cultures in HD patients compared to LD was twofold higher, there were clinically significant infections identified in the LD group. Disclosures All Authors: No reported disclosures

scholarly journals Asymptotic Properties of Multicolor Randomly Reinforced Pólya Urns

2014 ◽  
Vol 46 (02) ◽  
pp. 585-602 ◽  
Author(s):  
Li-Xin Zhang ◽  
Feifang Hu ◽  
Siu Hung Cheung ◽  
Wai Sum Chan
Keyword(s):  
Asymptotic Behavior ◽  
Rate Of Convergence ◽  
Clinical Studies ◽  
Asymptotic Properties ◽  
Important Application ◽  
Urn Models ◽  
Theoretical Justification ◽  
Treatment Allocation ◽  
Number Of Patients ◽  
Generalized Pólya Urn

The generalized Pólya urn has been extensively studied and is widely applied in many disciplines. An important application of urn models is in the development of randomized treatment allocation schemes in clinical studies. The randomly reinforced urn was recently proposed, but, although the model has some intuitively desirable properties, it lacks theoretical justification. In this paper we obtain important asymptotic properties for multicolor reinforced urn models. We derive results for the rate of convergence of the number of patients assigned to each treatment under a set of minimum required conditions and provide the distributions of the limits. Furthermore, we study the asymptotic behavior for the nonhomogeneous case.

scholarly journals Histology results of systematic prostate biopsies by in-bore magnetic resonance imaging vs. transrectal ultrasound

2020 ◽  
Vol 15 (5) ◽  
Author(s):  
Alon Lazarovich ◽  
Gil Raviv ◽  
Yael Laitman ◽  
Orith Portnoy ◽  
Orit Raz ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Prostate Biopsy ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
Resonance Imaging ◽  
Rectal Examination ◽  
Number Of Patients ◽  
Clinically Significant

Introduction: We aimed to compare systematic biopsies (SBs) of in-bore magnetic resonance-guided prostate biopsy (MRGpB) with those performed under transrectal ultrasound (TRUS) guidance in the clinical setting. Methods: Data on all 161 consecutive patients undergoing prostate biopsy in our institution between November 2017 and July 2019 were retrospectively collected. The patients were referred to biopsy due to elevated prostate-specific antigen (PSA) and/or abnormal digital rectal examination and/or at least one Prostate Imaging Reporting and Data System (PI-RADS) lesion score of ≥3 on multiparametric magnetic resonance imaging (mpMRI). We included patients with PSA levels ≤20 ng/ml and those with 8–12 core biopsies. Histology results of SBs performed by in-bore MRGpB were compared to TRUS SBs. Chi-squared, Fischer’s exact, and multivariate Pearson regression tests were used for statistical analysis (SPSS, IBM Corporation). Results: In total, 128 patients were eligible for analysis. Their median age was 68 years (interquartile range [IQR] 61.5–72), mean prostate size 55±29 cc, and mean PSA and PSA density levels 7.6±3.5 ng/ml and 0.18±0.13 ng/ml/cc, respectively. Thirty-five patients (27.3%) had suspicious digital rectal examination findings. Both biopsy groups were similar for these parameters. Thirty-eight (62.3%) MRGpB patients had a previous biopsy vs. 5 (7.1%) TRUS-SB patients (p<0.0001). The number of patients diagnosed with clinically significant and non-significant disease was similar for both groups. High-risk disease was more prevalent in the TRUS-SB group (22.4% vs. 4.9%, p<0.01). Conclusions: Our data suggest that in-bore MRGpB is no better than TRUS for guiding SBs for the detection of clinically significant prostate cancer.

scholarly journals Use of long acting antipsychotics and relationship to newly diagnosed bipolar disorder: a pragmatic longitudinal study based on a Canadian health registry

2020 ◽  
Vol 10 ◽  
pp. 204512532095711
Author(s):  
Emmanuel Stip ◽  
Syed Javaid ◽  
Jonathan Bayard-Diotte ◽  
Karim Abdel Aziz ◽  
Danilo Arnone
Keyword(s):  
Bipolar Disorder ◽  
Newly Diagnosed ◽  
Limited Data ◽  
Major Depressive ◽  
Haloperidol Decanoate ◽  
Number Of Patients ◽  
Prescribing Trends ◽  
Canadian Health ◽  
Long Acting ◽  
Health Registry

Background: There is limited data from large naturalistic studies to inform prescribing of long-acting injectable medication (LAIs). Guidance is particularly rare in the case of primary mood disorders. Methods: This study describes prescribing trends of LAIs in 3879 patients in Quebec, Canada, over a period of 4 years. Health register data from the Quebec provincial health plan were reviewed. Results: In this specific registry, 32% of patients who received LAIs drugs for schizophrenia had a confirmed diagnosis of bipolar disorder and 17% had a diagnosis of major depressive disorder. Non-schizophrenia syndromes were preferentially prescribed risperidone long-acting antipsychotic, whereas patients with schizophrenia were prescribed an excess of haloperidol decanoate. Patients with non-schizophrenia disorders prescribed long-acting antipsychotics were more frequently treated in primary care compared with patients with schizophrenia. Conclusion: Data from a large number of patients treated naturalistically in Quebec with long-acting antipsychotics suggests that these compounds, prescribed to treat symptoms of schizophrenia and schizoaffective disorders, were maintained when mood symptoms emerged, even in cases when the diagnosis changed to bipolar disorder. This pragmatic study supports the need to explore this intervention as potential treatment for affective disorders.

Associations Between Burnout and Mental Disorder Symptoms Among Nurses in Canada

2020 ◽  
pp. 084456212097419
Author(s):  
Andrea M. Stelnicki ◽  
Laleh Jamshidi ◽  
Andréanne Angehrn ◽  
Heather D. Hadjistavropoulos ◽  
R. Nicholas Carleton
Keyword(s):  
Major Depressive Disorder ◽  
Mental Disorders ◽  
Depressive Disorder ◽  
Mental Disorder ◽  
Stress Disorder ◽  
Demographic Variables ◽  
Early Career ◽  
Depression Symptoms ◽  
Major Depressive ◽  
Clinically Significant

Background Nurses appear to be at a greater risk of burnout compared to other medical professionals. Higher levels of burnout are significantly associated with higher levels of anxiety, stress, and depression symptoms. Purpose The current study was designed to estimate levels of burnout among Canadian nurses, examine the association between burnout and mental disorder symptoms, and identify characteristics that may increase the risk for reporting symptoms of burnout. Method Canadian nurses ( n = 3257; 94.3% women) were surveyed online in both English and French. The survey assessed current symptoms of burnout and mental disorders (i.e., Posttraumatic Stress Disorder, Major Depressive Disorder, Generalized Anxiety Disorder, Panic Disorder). Results Most nurses (63.2%) reported at least some symptoms of burnout and many (29.3%) reported clinically significant levels of burnout. Age and years of service were the only demographic variables that explained burnout rates. Participants reporting clinically significant levels of burnout were significantly more likely than participants with no burnout to screen positive for all mental disorders, but particularly for Major Depressive Disorder. Conclusions Monitoring burnout may be an effective way to identify nurses at risk of developing symptoms of mental disorders. Younger and early-career nurses are an important group to target for prevention programs.

Efficacy and safety of fampridine for walking disability in multiple sclerosis

2020 ◽  
Vol 10 (5) ◽  
pp. 277-287
Author(s):  
Eva Costa Arpín
Keyword(s):  
Multiple Sclerosis ◽  
Back Pain ◽  
Walking Speed ◽  
Development Phase ◽  
Concomitant Treatment ◽  
Efficacy And Safety ◽  
Real World Setting ◽  
Number Of Patients ◽  
History Of ◽  
Clinically Significant

Fampridine is the only drug approved for the treatment of walking impairment in multiple sclerosis. Around a third of the patients on treatment obtained an improvement in walking speed during the development phase. The effects are clinically significant, appear soon after the start of the treatment and are long-lasting, but disappear soon after the drug is withdrawn. In the real-world setting, the number of patients with a significant response to the treatment seems to be higher (around 70%). The tolerance is good, with mild to moderate, and transient adverse events. The most commonly reported are insomnia, headache, fatigue, back pain, dizziness, nausea and balance disorders. The main contraindications are a history of seizures, renal impairment and concomitant treatment with OCT2 inhibitors.

Effect of selective beta-blockade with bisoprolol in the treatment of recent-onset atrial fibrillation

Folia Medica ◽  
2012 ◽  
Vol 54 (2) ◽  
pp. 27-31 ◽  
Author(s):  
Maria N. Negreva ◽  
Atanas P. Penev
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Combined Therapy ◽  
Beta Blockade ◽  
Recent Onset ◽  
Number Of Patients ◽  
Group A ◽  
Clinically Significant ◽  
Group B ◽  
Onset Atrial Fibrillation

ABSTRACT The incidence of atrial fibrillation has been rapidly increasing in recent years. The increased tonus of the sympathetic nervous system is related to the development of atrial fibrillation. OBJECTIVE: To study the effect of bisoprolol, a highly selective beta-blocker, on patients with recent-onset atrial fibrillation (< 48 hours) for regularization of the rhythm using propafenone. PATIENTS AND METHODS: The study includes 164 patients (81 women, 83 men, age 59.09 ± 10.81) with successfully restored sinus rhythm in recent-onset atrial fibrillation. The patients received either propafenone (group A, n = 82) or a combination of propafenone and bisoprolol (group B, n = 82). The studied patients were randomly allocated to the groups. Propafenone was administered intravenously as a 2 mg/kg bolus followed by infusion of 0.0078 mg/kg/min for 120 min and orally in dosage of 300 mg three times every 8 hours if arrhythmia persisted. Bisoprolol was administered in a single dose at the very beginning of propafenone treatment and only in patients from group B at a dose of 5 or 10 mg. Regularization of the rhythm was assessed at the 3rd, 6th, 12th and 24th hour. RESULTS: In the initial stages of regularization the combined therapy restored the sinus rhythm in a greater number of patients in comparison with the monotherapy (at the 6th hour 67.07% in group B versus 48.78% in group A, P < 0.05; at the 12th hour it was 87.80% versus 75.60%, respectively, P < 0.05). CONCLUSION: Early regularization of rhythm in patients with recent-onset atrial fibrillation reduces the likelihood of recurrent episodes of arrhythmia. This makes the application of selective beta-blockade clinically significant.

scholarly journals Uncovering the invisible—prevalence, characteristics, and radiomics feature–based detection of visually undetectable intraprostatic tumor lesions in 68GaPSMA-11 PET images of patients with primary prostate cancer

2020 ◽  
Author(s):  
Constantinos Zamboglou ◽  
Alisa S. Bettermann ◽  
Christian Gratzke ◽  
Michael Mix ◽  
Juri Ruf ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Validation Cohort ◽  
External Validation ◽  
Image Interpretation ◽  
Receiver Operating Curve ◽  
Training Cohort ◽  
Primary Prostate Cancer ◽  
Psma Pet ◽  
Number Of Patients ◽  
Clinically Significant

Abstract Introduction Primary prostate cancer (PCa) can be visualized on prostate-specific membrane antigen positron emission tomography (PSMA-PET) with high accuracy. However, intraprostatic lesions may be missed by visual PSMA-PET interpretation. In this work, we quantified and characterized the intraprostatic lesions which have been missed by visual PSMA-PET image interpretation. In addition, we investigated whether PSMA-PET-derived radiomics features (RFs) could detect these lesions. Methodology This study consists of two cohorts of primary PCa patients: a prospective training cohort (n = 20) and an external validation cohort (n = 52). All patients underwent 68Ga-PSMA-11 PET/CT and histology sections were obtained after surgery. PCa lesions missed by visual PET image interpretation were counted and their International Society of Urological Pathology score (ISUP) was obtained. Finally, 154 RFs were derived from the PET images and the discriminative power to differentiate between prostates with or without visually undetectable lesions was assessed and areas under the receiver-operating curve (ROC-AUC) as well as sensitivities/specificities were calculated. Results In the training cohort, visual PET image interpretation missed 134 tumor lesions in 60% (12/20) of the patients, and of these patients, 75% had clinically significant (ISUP > 1) PCa. The median diameter of the missed lesions was 2.2 mm (range: 1–6). Standard clinical parameters like the NCCN risk group were equally distributed between patients with and without visually missed lesions (p < 0.05). Two RFs (local binary pattern (LBP) size-zone non-uniformality normalized and LBP small-area emphasis) were found to perform excellently in visually unknown PCa detection (Mann-Whitney U: p < 0.01, ROC-AUC: ≥ 0.93). In the validation cohort, PCa was missed in 50% (26/52) of the patients and 77% of these patients possessed clinically significant PCa. The sensitivities of both RFs in the validation cohort were ≥ 0.8. Conclusion Visual PSMA-PET image interpretation may miss small but clinically significant PCa in a relevant number of patients and RFs can be implemented to uncover them. This could be used for guiding personalized treatments.

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