Non-clinical Parameters Research Articles

Cardiac imaging correlates and predictors of stroke in patients with atrial fibrillation: a meta-analysis.

New nonclinical parameters are needed to improve the current stroke risk stratification schemes for patients with atrial fibrillation. This study aimed to summarize data on potential cardiac imaging correlates and predictors of stroke or systemic embolism in patients with atrial fibrillation. MEDLINE, EMBASE, and Web of Science were searched to identify all published studies providing relevant data through 16 November 2022. Random effects meta-analysis method was used to pool estimates. We included 64 studies reporting data from a pooled population of 56 639 patients. Left atrial spontaneous echo-contrast [adjusted odds ratio (aOR) 3.32, 95% confidence interval (CI) 1.98-5.49], nonchicken wing left atrial appendage (LAA) morphology (aOR 2.15, 95% CI 1.11-4.18), left atrial enlargement (aOR 2.12, 95% CI 1.45-3.08), and higher LAA orifice diameter (aOR 1.56, 95% CI 1.18-2.05) were highly associated with stroke. Other parameters associated with stroke included higher left atrial sphericity (aOR 1.14, 95% CI 1.01-1.29), higher left atrial volume (aOR 1.03, 95% CI 1.01-1.04), higher left atrial volume index (aOR 1.014, 95% CI 1.004-1.023), lower left atrial reservoir strain [adjusted hazard ratio (aHR) 0.86, 95% CI 0.76-0.98], higher left ventricular mass index (aOR 1.010, 95% CI 1.005-1.015) and E / e' ratio (aOR 1.12, 95% CI 1.07-1.16). There was no association between LAA volume (aOR 1.37, 95% CI 0.85-2.21) and stroke. These cardiac imaging parameters identified as potential predictors of thromboembolism may improve the accuracy of stroke risk stratification schemes in patients with atrial fibrillation. Further studies should evaluate the performance of holistic risk scores including clinical factors, biomarkers, and cardiac imaging.

Predictors of Intracranial Hemorrhage Volume Expansion in Patients Receiving Factor Xa Inhibitors in ANNEXA‐4: Time and Severity Matter Most

Background Andexanet alfa, a specific reversal agent for factor Xa inhibitors, resulted in effective hemostasis in 79% of patients with intracranial bleeding in the ANNEXA‐4 (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors) trial (NCT02329327). However, little is known about predictors associated with hematoma expansion in patients with factor Xa inhibitor–associated intracranial hemorrhage (ICrH) receiving andexanet alfa. Methods The ANNEXA‐4 trial was a prospective, single‐arm, open‐label study of andexanet alfa in patients with acute major bleeding within 18 hours after taking a factor Xa inhibitor. Hematoma volumes at baseline and 12 hours after andexanet alfa treatment were measured using a computerized‐assisted volumetric method. Univariable and multivariable logistic regression analyses of clinical and nonclinical parameters were performed to identify factors predictive of different volumes of hematoma expansion. To this end, an ICrH Expansion Scale was developed. Results Overall, 305 ANNEXA‐4 study patients with baseline and follow‐up imaging were included, 15.7% of whom showed evidence of any ICrH expansion ≥6‐mL. Patients with ≥6‐mL ICrH expansion had a significantly ( P< 0.05) higher proportion of ICrH with multiple compartment involvement (36% versus 14.3%); shorter times from symptom onset to baseline computed tomography (median, 1.6 hours [interquartile range (IQR), 1.2–4.3 hours] versus 3.7 hours [IQR, 1.6–7.0 hours]); lower Glasgow Coma Scale scores (14 [IQR, 12–15] versus 15 [IQR, 14–15]); higher systolic blood pressure 15 minutes before andexanet alfa bolus (mean, 151.6 mm Hg [SD, 24.1 mm Hg] versus 143.3 mm Hg [SD, 22.3 mm Hg]); and larger median baseline ICrH volumes (29.3 mL [IQR, 13.3–50.8 mL] versus 8.6 mL [IQR, 2.1–22.4 mL]). Multivariable analysis confirmed shorter symptom onset‐to‐computed tomography time and larger ICrH volume as independent predictors of ≥6‐mL growth and ICrH Expansion Scale change. Lower Glasgow Coma Scale showed a trend ( P = 0.06) as an independent predictor of ≥6‐mL growth but was an independent predictor of ICrH Expansion Scale change. Conclusion Shorter time from symptom onset to computed tomography, larger hematoma volumes, and lower Glasgow Coma Scale score at presentation increased the risk of ICrH expansion in patients with factor Xa inhibitor–associated ICrH treated with andexanet alfa.

Abstract WP126: Predictors Of Intracranial Hemorrhage Volume Expansion In Patients Receiving Factor Xa Inhibitors In The Annexa-4 Trial

Introduction: Andexanet, a specific reversal agent for FXa inhibitors, showed an effective hemostasis in 82% of patients with major bleeding in the ANNEXA-4 trial. However, little is known about the predictors associated with hematoma expansion in patients with FXa inhibitor-associated intracranial hemorrhage (ICrH) receiving andexanet. Methods: ANNEXA-4 was a prospective, single-arm, open-label study of andexanet in patients with acute major bleeding within 18h after taking a FXa inhibitor. Hematoma volumes at baseline and 12h after andexanet treatment were measured utilizing a computerized-assisted volumetric method. Univariate and multivariate logistic regression analyses of baseline clinical and non-clinical parameters were performed to identify factors predictive of different volumes of hematoma expansion. Results: A total of 305 patients with both baseline and follow-up imaging were included (mean age 80 years; 60.2% with intracerebral hemorrhage; 55.4% taking apixaban; 32.5% taking rivaroxaban). Overall median baseline hematoma volume was 10.4 mls (IQR 2.7-28.1) and time from symptom onset to baseline CT was 3.3h (1.5-6.8). Mean baseline anti-FXa activity levels were 148 ng/mL (SD 107.5). In follow up scans, 48 cases (15.7%) showed evidence of ICrH expansion ≥6 mls. Utilizing a four category ICrH Expansion Scale as the dependent variable, ordinal logistic regression identified Glasgow Coma Scale (GCS) score (OR 0.79; 95% CI 0.64-0.97), baseline ICrH volume (OR 1.02; 95% CI 1.01-1.04) and time from symptom onset to CT (OR 0.73 (0.53-0.99) as significant predictors of ICrH expansion. Baseline anti-FXA activity (OR 1.54; 95% CI 0.95-2.51; p value 0.08) and multiple compartment ICrH (OR 2.32; 95% CI 0.98-5.51; p value 0.06) showed trend as predictors of ICrH expansion. ICrH expansion dichotomized by ≥6 mls or <6 mls as dependent variable, identified similar predictors of ICrH expansion. Conclusions: Shorter time from onset of symptoms to CT, lower GCS score and larger hematoma volumes at presentation increased the probability of ICrH expansion in FXa-associated ICrH treated with andexanet. These findings can inform the eligibility criteria of clinical trials targeting hemostatic efficacy in patients with FXa-associated ICrH.

An Assessment of the Profile and Predictors of Outcomes in COVID-19 Patients Hospitalized in a Tertiary Care Institute in Central India

BackgroundCoronavirus disease 2019 (COVID-19) is the largest pandemic that has affected people around the globe. Various researches have been conducted worldwide, but there is a scarcity of data from Central India on the relationship between several risk factors for infection and mortality. Our study assessed the predictors and patient profiles of those with COVID-19, which will aid in prioritizing patient treatment and preventive measures.MethodsA retrospective study was done between March and December 2020. The study included 5,552 COVID-19 patients admitted to the All India Institute of Medical Sciences (AIIMS), Raipur. A validated questionnaire form provided by the WHO was used. Data for multiple clinical and nonclinical parameters were collected, and analysis was done using SPSS version 26 (IBM Corp., Armonk, NY, USA) and STATA version 12 (StataCorp LLC, College Station, TX, USA). Mortality and risk assessment of patients was done using multivariate logistic regression.ResultIn our study cohort of 5,552 COVID-19 patients, the median age was found to be 47 years (interquartile range (IQR): 31-60 years; range: 14-100 years), and 3,557 (64%) were male. Predominantly, patients presented with fever (41.30%), cough (40.20%), and dyspnea (29.29%). The major comorbidities were hypertension (29.70%), diabetes (25.40%), and chronic cardiac disease (5.79%). The common complications were liver dysfunction (26.83%), viral pneumonitis (23.66%), acute renal injury (15.25%), and acute respiratory distress syndrome (ARDS) (13.41%). In multivariate analysis, age (more than 40 years) (odds ratio (OR): 2.63; 95% confidence interval (CI): 1.531-4.512; p<0.001), diabetes (OR: 1.61; 95% CI: 1.088-2.399; p=0.017), obesity (OR: 6.88; 95% CI: 2.188-12.153; p=0.004), leukocytosis (OR: 1.74; 95% CI: 1.422-2.422; p<0.001), lymphocytopenia (OR: 2.54, 95% CI: 1.718-3.826; p<0.001), thrombocytopenia (OR: 1.15; 95% CI: 1.777-8.700; p=0.001), and ferritin concentration > 1,000 ng/mL (OR: 4.67; 95% CI: 1.991-10.975; p<0.001) were the independent predictors of mortality among COVID-19 patients.ConclusionThe leading comorbidities in our study were hypertension, followed by diabetes. Patients who were 40 years or older, obese patients, and diabetic patients have a higher mortality risk. The poor prognostic predictors in COVID-19 patients were high ferritin levels (>1,000 ng/mL), leukocytosis, lymphocytopenia, and thrombocytopenia.

Investigating the interrelatedness of clinical and non-clinical parameters affecting outcomes in COVID-19 patients: a retrospective study

ABSTRACT The COVID-19 pandemic has affected millions globally. Several studies have been carried out to uncover factors affecting the severity of the resulting infection. Available location-specific data concerning the affective demographics as well as clinical aspect of the disease remains limited. In this study, a number of non-clinical as well as the clinical parameters were investigated for their role in adverse progression of the disease in patients admitted to intensive care unit (ICU) in a private tertiary hospital in Peshawar. The prevalence of comorbidities hypertension and diabetes as well as mortality was higher in age group of 70–79 years. Dyspnea was significantly linked to sepsis, invasive ventilation, and mortality; its late presentation, i.e. 15 to 20 days was significantly associated with mortality (p-value < 0.02). Acute kidney injury and acute respiratory distress syndrome were found to be the most strongly associated with sepsis and septic shock. Neither remdesivir nor tocilizumab was effective in preventing the infection-related complications, invasive ventilation, and mortality. Overall, dyspnea was found to be an indicator of the worst progression of the disease. Furthermore, while some parameters were closely linked, others were not.

Statistical and machine learning analysis of non-clinical factors impacting emergency room delays

IntroductionPlenty is known about the clinical factors impacting the time patients spend in emergency departments (EDs), but less is known about associated non-clinical factors. Here we fill this knowledge gap through a statistical and machine learning (ML) analysis of the non-clinical factors impacting ED length of stay (LoS). MethodsData from adult patients visiting the tertiary healthcare organization ED, Riyadh between January 2017 and October 2019 were subjected to logistic regression and multiple ML classification models to predict non-clinical factors associated with delayed ED LoS (>6 h). ResultsThere were 352,230 emergency visits by 135,185 patients. Most were under 6 h, with only 18% exceeding that benchmark. In logistic regression analysis, weekend visits, in the summer, by elderly male patients were associated with delayed ED LoS. The results of this study and the analysis of non-clinical factors in general can be used to aid in administrative decisions in EDs, such as deciding the number of staff per shift or provide the patients with the expected LoS to help them make decisions whether to stay or leave. ConclusionLogistic regression revealed some associations between ER LoS and the included factors. However, ML models showed disappointing performance with the included non-clinical predictive variables. Further research to examine the impact of both clinical and non-clinical parameters on ED delay is now needed.

Clinical and Non-Clinical Determinants of the Effect of Mechanical Thrombectomy and Post-Stroke Functional Status of Patients in Short and Long-Term Follow-Up.

To date, inconsistent results evaluating the effect of parameters on mechanical thrombectomy (MT) outcomes in stroke-patients have been published. This study aimed to identify the key parameters for functional status after MT in stroke-patients in short and long-term follow-up. Method: The study analysis focused on the relevance of selected clinical and non-clinical parameters to the functional status of the patients after MT. Results: 417 stroke-patients (mean age 67.8 ± 13.2 years) were qualified. Atrial fibrillation, and leukocytosis were significant for the neurological status on the first day of stroke (p = 0.036, and p = 0.0004, respectively). The parameters with the strongest effect on the functional status on day 10 were: age (p = 0.009), NIHSS (p = 0.002), hyperglycemia (p = 0.009), the result in TICI (p = 0.046), and first pass effect (p = 0.043). The parameters with the strongest effect on the functional status on day 365 were: age and NIHSS on the first day of stroke (p = 0.0002 and 0.002, respectively). Leukocytosis and the neurological status at baseline were key parameters associated with ICB after MT (p = 0.007 and p = 0.003, respectively). Conclusions: Age and neurological status in the ultra-acute phase of stroke are crucial for the functional status in short and long-term observations of patients treated with mechanical thrombectomy. Atrial fibrillation, hyperglycemia, and inflammatory state are relevant to the short-term post-stroke functional status. First pass effect and the degree of post-interventional reperfusion are important technical parameters to the short-term functional status. Neurological status and white blood count during the acute phase are associated with a high rate of post-procedural intracranial bleeding.

004 Samelisant (SUVN-G3031), Differentiating features over current treatments of narcolepsy

Abstract Introduction Majority of pharmacological agents used in the treatment of narcolepsy have several limitations. Both nonclinical and clinical evidences suggest usefulness of the histamine H3 receptor (H3R) inverse agonists for the treatment of narcolepsy addressing several of the current limitations. Methods Extensive nonclinical studies were carried out for Samelisant (SUVN-G3031) and other pharmacological agents that are currently being used for the treatment of narcolepsy. The nonclinical parameters like inter-species binding affinity, selectivity profile, in vivo and in vitro ADME features, nonclinical efficacy, neurochemistry and safety were compared. Results Samelisant has no inter-species variation in binding affinity at H3R with less than 50% inhibition at 1 µM against 70 other targets. Unlike pitolisant, Samelisant has no significant binding affinity at sigma 1 and 2 receptor. Samelisant has no inhibition and induction liability towards major CYP enzymes and transporters. Pitolisant is reported to be a CYP3A4, CYP2B6, and CYP1A2 inducer and a CYP2D6 and OCT1 inhibitor. Samelisant has robust wake promoting effects. Samelisant showed negligible affinity towards hERG channel with IC50 &amp;gt; 10 µM and had no effects on heart rate or ECG parameters in dog telemetry study. Samelisant did not show convulsion in rats up to the tested dose of 100 mg/kg, p.o. Most of the pharmacological agents used for the treatment of narcolepsy have abuse liability; Samelisant produced no change in the striatal and accumbal dopamine levels in rats suggesting no propensity to induce abuse liability. Unlike competing H3R inverse agonists, Samelisant has no effects on fertility and embryo-fetal development up to the highest tested doses. Conclusion Nonclinical studies demonstrated superiority of Samelisant over pharmacological agents used in the treatment of narcolepsy. Samelisant is currently being evaluated in a Phase 2 study as monotherapy for the treatment of narcolepsy with and without cataplexy (ClinicalTrials.gov Identifier: NCT04072380). Support (if any):

Classification of Distinct Endotypes in Human Skin Scarring: S.C.A.R.-A Novel Perspective on Dermal Fibrosis.

Significance: Skin scarring is a permanent, irreversible end point of cutaneous injury. However, not everyone will acquire the same exact scar type. Skin scarring is generally recognized as complex with significant variability in individuals' scar type and response to treatment. Despite these tangible differences in treatment response, to date there has been no simplified approach in defining spectrum of skin scarring in relation to prediction and outcome post-treatment. Thus, in this study we propose that skin scarring consists of distinct endotypes, which is characterized by their specific pathology. Four distinct scar endotypes can be observed: (1) Stretched (flat), (2) Contracted, (3) Atrophic (depressed), and (4) Raised scarring, which can be abbreviated to S.C.A.R. endotypes. Each of these endotypes can certainly include subphenotypes and each phenotype can be present in more than one endotype. To define these endotypes, we also present a structured approach in assessment of all relevant parameters in skin scar evaluation including clinical (scar symptoms and signs) and nonclinical parameters (device measurements of structural, mechanical, and physiological properties of scars as well as gene and protein laboratory studies). Recent Advances: Scars can be phenotypically characterized based on a multitude of parameters assessed; however, not all scar types will share all the same characteristics. This leads to the question of whether skin scarring is a single disease entity with varying phenotypic characteristics or should be classed as several disease entities that have certain similar parameters. We suggest the latter and propose distinct scarring phenotypes arise mainly owing to genetic and environmental susceptibilities associated with the development of each specific scar endotype. Characteristic features of skin scarring, however, can be objectively and quantitively evaluated and used as an aid in the theranostic goal-directed management of scarring. Critical Issues: The concept of identifying different endotypes is key in formulating personalized treatments with improved outcomes beyond what is achieved with current nonspecific approaches in scar management. This approach has gained interest and significant traction in several other medical conditions including asthma, rheumatoid arthritis, and atopic dermatitis. Future Directions: To begin identifying distinct endotypic features in skin scarring, it is important to have a better understanding of underlying pathological mechanisms leading to further insight into the heterogeneous nature of skin scarring endotypes. This approach may lead to improved theranostic outcomes and further understanding of the pathophysiology of the complex nature of human skin scarring.

Сравнительная эффективность генно-инженерных биологических препаратов в реальной клинической практике по данным МЕРА

Background: the list expansion of genetically engineered biological drugs (GEBD) used for the treatment of ankylosing spondylitis (AS) determines the relevance of studies aimed at comparing them and determining their place in this disease treatment. Real clinical practice studies are the preferred source of this data type. Aim: to evaluate the efficacy of various GEBD in patients with AS according to the Moscow Unified Arthritis Registry (MUAR). Material and methods: the analysis of the MUAR data was carried out. These included clinical cases with GEBD, for which there were data of a completed visit after 6 months or more after the treatment initiation. Parameters values achieved during treatment with various drugs were analyzed. The comparison was conducted during a multivariate analysis with adjustments for the identified confounders. Non-clinical parameters that were reliably and independently associated with the achieved BASDAI index (CRP) values were considered as confounders. Results: the study included 363 treatment episodes with GEBP in 361 patients. As mutually independent significant predictors of the achieved ASDAS (confounders) values, GEBD treatment duration were established until the evaluation of indicators (p&lt;0.001) and the age of the patient (p=0.006). Significant association between the established values of the studied parameters and the used GEBD were found for the achieved ASDAS (p=0.033) and ESR (p=0.007) values. In a pairwise drug comparison using the conservative Šidák correction, the achieved values of ASDAS and ESR during infliximab and adalimumab administration were significantly less than during certolizumab pegol administration. Conclusion: infliximab, adalimumab, etanercept, certolizumab pegol, golimumab, secukinumab in real clinical practice demonstrate generally similar clinical efficacy in the treatment of AS. The effect of golimumab and secukinumab, recently introduced into clinical practice, does not significantly differ from the effect produced by long-term TNF-α inhibitors. Certain disease activity preservation in a significant part of patients gives grounds to continue the search for new treatment methods. KEYWORDS: ankylosing spondylitis, genetically engineered biological drugs, tumor necrosis factor inhibitors, C-reactive protein, confounders, registry. FOR CITATION: Rosochkina E.A., Lukina G.V., Koltsova E.N. et al. Comparative efficacy of genetically engineered biological drugs in real clinical practice according to the Moscow Unified Arthritis Registry (MUAR) data. Russian Medical Inquiry. 2021;5(2):58–63. DOI: 10.32364/2587-6821-2021-5-2-58-63.

RT-PCR Mediated Identification of SARS-CoV-2 Patients from Particular Regions of Bangladesh and the Multi-factorial Analysis Considering Their Pre and Post Infection Health Conditions

Background: SARS-CoV-2 is a type of coronavirus shows bizarre features with fatality rates at 34.4%. The clinical and non-clinical features of COVID-19 might be causative factors for more rapid community spreading compared to MERS and SARS-CoV-1.&#x0D; Objectives: To study the efficacy of RT-PCR based detection of SARS-CoV-2 patients. Besides, the patients' pre and post-infection health conditions depending on selective clinical and nonclinical parameters were analyzed.&#x0D; Materials and Methods: Clinical and non- clinical data were collected from 205 randomly selected COVID-19 patients, identified through RT-PCR from different areas of Bangladesh. The data were analyzed using statistical and analytical tools to illustrate the impact of the pandemic situation on the sufferers. &#x0D; Results: Molecular identification of the patients through RT-PCR has been observed as the most efficient option for detecting SARS-CoV-2 patients. Patients with the smoking habit have been reported to be more prone to the COVID-19 infection; surprisingly the non-smoker female was the worse suffers. The patients aged 60-69 years were the worst sufferers with every adverse health conditions mentioned. Professionally, 28% self-employed male and 8.19% female were infected. The most infected individuals were house wife (32.029%), as next to the health care workers (22.1%). With the increased age group, a decreased number of smokers were found. Nebulization of 5% home and 12% hospital treated patients were provided, with Oxygen for 26% of hospitalized patients. After recovery, combined physical and psychological complications were observed in 19% of male and 11% female. The socioeconomic, environmental and geographical annotations exposed a clear relationship with the rate of infection as revealed from the nonclinical data analysis.&#x0D; Conclusion: RT-PCR proved its specialty in COVID-19 detection. In addition, impacts of different clinical and nonclinical factors on the physical conditions of the nCoV patients were found significant in the research.

0155 SUVN-G3031, A Potent and Selective Histamine H3 Receptor Inverse Agonist - Differentiating Features Over Current Treatments of Narcolepsy

Abstract Introduction Majority of pharmacological agents used in the treatment of narcolepsy have several limitations. Both nonclinical and clinical evidences suggest usefulness of the histamine H3 receptor (H3R) inverse agonists for the treatment of narcolepsy and addressing several of the current limitations. Methods Extensive nonclinical studies were carried out for SUVN-G3031 and other pharmacological agents that are currently being used for the treatment of narcolepsy. Nonclinical parameters like inter-species binding affinity, selectivity profile, in vivo and in vitro ADME features, nonclinical efficacy, neurochemistry and safety were compared. Results SUVN-G3031 has no inter-species variation in binding affinity at H3R with less than 50% inhibition at 1 µM against 70 other targets. Unlike pitolisant, SUVN-G3031 has no significant binding affinity at sigma 1 and 2 receptor. SUVN-G3031 has no inhibition and induction liability towards major CYP enzymes and transporters. Pitolisant is reported to be a CYP3A4, CYP2B6, and CYP1A2 inducer and a CYP2D6 and OCT1 inhibitor. SUVN-G3031 has robust wake promoting effects. SUVN-G3031 showed negligible affinity towards hERG channel with IC50 &amp;gt; 10 µM and had no effects on any ECG parameters in dog telemetry study. SUVN-G3031 did not show convulsion in rats up to the tested dose of 100 mg/kg, p.o. Most of the pharmacological agents used for the treatment of narcolepsy have abuse liability; SUVN-G3031 produced no change in the striatal and accumbal dopamine levels in rats suggesting no propensity to induce abuse liability. Unlike competing H3R inverse agonists, SUVN-G3031 has no effects on fertility and embryo-fetal development up to the highest tested doses. Conclusion Nonclinical studies demonstrate superiority of SUVN-G3031 over pharmacological agents currently used in the treatment of narcolepsy. SUVN-G3031 is being evaluated in a Phase 2 study as monotherapy for the treatment of narcolepsy with and without cataplexy (ClinicalTrials.gov Identifier: NCT04072380). Support None

Significance of non-clinical parameters for the clinical manifestation of non-cavitated carious lesions in children with nephrotic syndrome

Significance of non-clinical parameters for the clinical manifestation of non-cavitated carious lesions in children with nephrotic syndrome

Evaluation of clinical and non-clinical parameters among partial and total mastectomy patients

BackgroundMastectomy is a common surgical procedure performed on the breast cancer patients. A number of factors influence the choice regarding the type of mastectomy and postoperative outcomes including survival rate. ObjectiveThe aim of this study is to compare clinical and nonclinical parameters among partial (breast conserving surgery) and total mastectomy patients referred to our center. MethodIn this retrospective study, 279 women who underwent partial or total mastectomy were included. A questionnaire comprising of demographic data such as; age, marital status, employment status, education level and smoking, clinical data such as; grade of tumor, tumor side, breast reconstruction (prosthesis status), biopsy status, involvement of lymph node and postoperative stress and data regarding comorbidities was drafted for all the patients. ResultOverall, 78 and 201 underwent total and partial mastectomy, respectively. Patients who underwent partial mastectomy were significantly younger p < 0.001, underwent radiation and chemotherapy p < 0.001 and p = 0.018, respectively, had significantly greater incidence of heart disease p = 0.012 and were presented with greater postoperative stress p < 0.001. Patients who received total mastectomy were more to receive breast reconstruction (prosthesis) p = 0.035 and had greater lymph node involvement. The grade and side of tumor, employment status, diabetes, smoking, thyroid disease and type of incision was not significant among the two groups. ConclusionOur study concludes that a number of clinical and nonclinical parameters can affect the decision of the type of mastectomy among the patients. Studies regarding postoperative outcomes such as recurrence and mortality need to be added to this data.

Radioactive iodine in differentiated thyroid cancer: a national database perspective.

Radioactive iodine (RAI) is a key component in the treatment of differentiated thyroid cancer. RAI has been recommended more selectively in recent years as guidelines evolve to reflect risks and utility in certain patient subsets. In this study we sought to evaluate the survival impact of radioactive iodine in specific thyroid cancer subgroups. Nationwide retrospective cohort study of patients using the National Cancer Database (NCDB) from 2004 to 2012 and Surveillance, Epidemiology, and End Results (SEER) database from 1992 to 2009 examining patients with differentiated thyroid cancer treated with or without RAI. Primary outcomes included all-cause mortality (NCDB and SEER), and cancer-specific mortality (SEER). Cox multivariate survival analyses were applied to each dataset, and in 135 patient subgroups based on clinical and non-clinical parameters. A total of 199,371 NCDB and 77,187 SEER patients were identified. RAI was associated with improved all-cause mortality (NCDB: RAI hazard ratio (HR) 0.55, P < 0.001; SEER: HR 0.64, P < 0.001); and cancer-specific mortality (SEER: HR 0.82, P = 0.029). Iodine therapy showed varied efficacy within each subgroup. Patients with high-risk disease experienced the greatest benefit in all-cause mortality, followed by intermediate-risk, then low-risk subgroups. Regarding cancer-specific mortality, radioactive iodine therapy was protective in high-risk patients, but did not achieve statistical significance in most intermediate-risk subgroups. Low-risk T1a subgroups demonstrated an increased likelihood of cancer-specific mortality with iodine therapy. The efficacy of RAI in patients with differentiated thyroid cancer varies by disease severity. A negative cancer-specific survival association was identified in patients with T1a disease. These findings warrant further evaluation with prospective studies.

Clinical and socio-demographic characteristics associated with involuntary admissions in Switzerland between 2008 and 2016: An observational cohort study before and after implementation of the new legislation

BackgroundInvoluntary admission (IA) for psychiatric treatment has a history of controversial discussions. We aimed to describe characteristics of a cohort of involuntarily compared to voluntarily admitted patients regarding clinical and socio-demographic characteristics before and after implementation of the new legislation. MethodsIn this observational cohort study, routine data of 15’125 patients who were admitted to the University Hospital of Psychiatry Zurich between 2008 and 2016 were analyzed using a series of generalized estimating equations. ResultsAt least one IA occurred in 4’560 patients (30.1%). Of the 31’508 admissions 8’843 (28.1%) were involuntary. In the final multivariable model, being a tourist (OR = 3.5) or an asylum seeker (OR = 2.3), having a schizophrenic disorder (OR = 2.1), or a bipolar disorder (OR = 1.8) contributed most to our model. Male gender, higher age, prescription of neuroleptics (all OR < 2.0) as well as having a depressive disorder, prescription of psychotherapy, prescription of antidepressants and admission after implementation of the new legislation (all OR > 0.6) were also weakly associated with IA. ConclusionsBesides schizophrenic or bipolar disorders, a small group of patients had an increased risk for IA due to non-clinical parameters (i.e. tourists and asylum seekers). Knowledge about risk factors should be used for the development of multi-level strategies to prevent frequent (involuntary) hospitalizations in patients at risk. On the organizational level, we could show that the new legislation decreased the risk for IA, and therefore may have succeeded in strengthening patient autonomy.

Emerging novel agents for patients with advanced Ewing sarcoma: a report from the Children's Oncology Group (COG) New Agents for Ewing Sarcoma Task Force.

Ewing sarcoma is a small round blue cell malignancy arising from bone or soft tissue and most commonly affects adolescents and young adults. Metastatic and relapsed Ewing sarcoma have poor outcomes and recurrences remain common. Owing to the poor outcomes associated with advanced disease and the need for a clear research strategy, the Children’s Oncology Group Bone Tumor Committee formed the New Agents for Ewing Sarcoma Task Force to bring together experts in the field to evaluate and prioritize new agents for incorporation into clinical trials. This group’s mission was to evaluate scientific and clinical challenges in moving new agents forward and to recommend agents and trial designs to the Bone Tumor Committee. The task force generated a framework for vetting prospective agents that included critical evaluation of each drug by using both clinical and non-clinical parameters. Representative appraisal of agents of highest priority, including eribulin, dinutuximab, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, anti-angiogenic tyrosine kinase inhibitors, and poly-ADP-ribose polymerase (PARP) inhibitors, is described. The task force continues to analyze new compounds by using the paradigm established.

Doses aux organes à risque en radiothérapie conformationnelle et en radiothérapie stéréotaxique : les poumons

Radiation-induced lung disease (RILD) is common after radiation therapy and represents cornerstone toxicities after treatment of thoracic malignancies. From a review of literature, the objective of this article was to summarize clinical and non-clinical parameters associated with the risk of RILD in the settings of normo-fractionated radiotherapy and stereotactic body radiation therapy (SBRT). For the treatment of lung cancers with a normo-fractionated treatment, the mean lung dose (MLD) should be below 15–20Gy. For a thoracic SBRT, V20Gy<10% and MLD<6Gy are recommended. One should pay attention to central tumors and respect specific dose constraints to the bronchial tree. The recent technological improvements may represent an encouraging way to decrease lung toxicities. Finally, our team developed a calculator in order to predict the risk of radiation pneumonitis.

Systematic review: Impact of the new task force criteria in the diagnosis of arrhythmogenic right ventricular cardiomyopathy

BackgroundArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disorder of cardiac desmosomes associated with ventricular arrhythmias and sudden cardiac death. The clinical diagnosis is problematic and relies on a complex criteria composed of clinical and non-clinical parameters. In 2010, the original 1994 Task Force Criteria (TFC) was revised with particular attention given to the imaging parameters. MethodsFive retrospective studies compared the diagnostic concordance between the 1994 and 2010 TFC. Three studies used cardiac magnetic resonance (CMR) and compared major and minor CMR criteria and three studies compared definite ARVC cases; one study assessed both. ResultsThree studies with 1435 patients compared the 1994 imaging and the 2010 CMR criteria. Using the 1994 criteria, 123 (8.6%) and 419 (29.2%) patients satisfied major and minor criteria compared to only 52 (3.6%) and 28 (1.9%) using the 2010 criteria; 57.7% and 94.3% reduction in major and minor criteria (p value, 0.0001 and 0.0001). Three studies with 611 patients assessed for definite ARVC. Using the 1994 and 2010 criteria, 207 (33.9%) and 243 (39.8%) patients satisfied the parameters respectively. This resulted in a statistically significant 17.4% (p value, 0.0379) increase in ARVC cases driven largely by two sub-groups. ConclusionsThe 2010 revised TFC have resulted in a significant reduction in the number of patients that satisfy CMR criteria particularly those that satisfied minor imaging abnormalities using the 1994 criteria. In addition, in certain groups the revised criteria have significantly increased the number of patients diagnosed with definite ARVC.

How to Develop, Validate, and Compare Clinical Prediction Models Involving Radiological Parameters: Study Design and Statistical Methods.

Clinical prediction models are developed to calculate estimates of the probability of the presence/occurrence or future course of a particular prognostic or diagnostic outcome from multiple clinical or non-clinical parameters. Radiologic imaging techniques are being developed for accurate detection and early diagnosis of disease, which will eventually affect patient outcomes. Hence, results obtained by radiological means, especially diagnostic imaging, are frequently incorporated into a clinical prediction model as important predictive parameters, and the performance of the prediction model may improve in both diagnostic and prognostic settings. This article explains in a conceptual manner the overall process of developing and validating a clinical prediction model involving radiological parameters in relation to the study design and statistical methods. Collection of a raw dataset; selection of an appropriate statistical model; predictor selection; evaluation of model performance using a calibration plot, Hosmer-Lemeshow test and c-index; internal and external validation; comparison of different models using c-index, net reclassification improvement, and integrated discrimination improvement; and a method to create an easy-to-use prediction score system will be addressed. This article may serve as a practical methodological reference for clinical researchers.