Non-optimal Treatment Research Articles

Non-Optimal Treatment in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated With Tyrosine Kinase Inhibitors (TKI) in the United States: A Claims Data Analysis

Non-Optimal Treatment in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated With Tyrosine Kinase Inhibitors (TKI) in the United States: A Claims Data Analysis

CML-205 Non-Optimal Treatment in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated With Tyrosine Kinase Inhibitors (TKI) in the United States: A Claims Data Analysis

CML-205 Non-Optimal Treatment in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated With Tyrosine Kinase Inhibitors (TKI) in the United States: A Claims Data Analysis

Incremental Healthcare Resource Utilization and Costs Associated with Non-Optimal Treatment in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Tyrosine Kinase Inhibitors (TKI) in Early Lines of Therapy in the United States (US)

Introduction: TKIs are the standard of care for CML-CP. Although effective TKI options are available in early lines of therapy of CML, patients may experience intolerance or resistance to TKI leading to non-optimal treatment (NOPT). This retrospective cohort study assessed the incremental healthcare resource utilization (HRU) and medical costs associated with NOPT in patients with CML treated in first-line (1L) or second-line (2L) TKI therapy in the US. Methods: Adult patients with CML who received 1L TKI therapy with imatinib, dasatinib, nilotinib, or bosutinib (1L cohort), and those who received 2L TKI therapy with imatinib, dasatinib, nilotinib, bosutinib, or ponatinib (2L cohort), in 2012 or later, were selected from the OptumInsight Clinformatics database (01/2007-06/2022). Patients were required to have ≥2 years of continuous health plan coverage post-1L/2L initiation (1L/2L index date). Patients were classified in NOPT subgroup if they met one of the following criteria: 1) treatment discontinuation/switch within the first 6 months post-index, or 2) temporary treatment interruption and/or dose reduction within the first 6 months post-index followed by treatment discontinuation within the first 12 months post-index, or 3) low treatment adherence (proportion of days covered [PDC] ≤50%). Patients were classified in the reference (REF) subgroup if they met one of the following criteria: 1) high treatment adherence (PDC >90%) and no treatment discontinuation, 2) high treatment adherence (PDC >90%) and treatment discontinuation occurring more than 12 months post-index. All-cause HRU (inpatient [IP] admissions, outpatient [OP] visits, and emergency department [ED] visits) and associated medical costs (2022 USD) were measured during the 2 years post-index and reported per-patient-per-year (PPPY). Incremental HRU and costs of NOPT (vs. REF) were estimated using multivariable Poisson regressions and two-part models (adjusted for age, gender, race, region, health plan type, time from CML diagnosis to index date, and Darkow Disease Complexity Index), respectively. Adjusted incidence rate ratios (IRR) and mean cost differences (Δ) were reported along with p-value, estimated using bootstrap technique. All analyses were conducted separately in the 1L and 2L cohorts. Results: Of 2,043 patients that initiated 1L TKI therapy in 2012 or later, 197 patients were included in NOPT subgroup (median age: 69 years; 52.3% female; 68.5% White) and 284 in REF subgroup (median age: 62 years; 40.1% female; 74.6% White). Patients in NOPT subgroup had 80% more IP admissions (adjusted IRR=1.8; p <0.001) with twice more IP days (adjusted IRR=2.0; p=0.024), 30% more OP visits (adjusted IRR=1.3; p=<0.001) in the first 2 years post-index, as compared to REF subgroup. Consistently, patients in NOPT subgroup had higher medical costs (adjusted Δ=$13,551 PPPY; p=0.012) mainly driven by higher IP costs (adjusted Δ =$5,989 PPPY; p=0.028) along with numerically higher OP costs (adjusted Δ=$5,483 PPPY; p=0.060) in the first 2 years post-index, as compared to REF subgroup ( Figure 1). Of 586 patients that initiated 2L TKI therapy in 2012 or later, 69 patients were included in NOPT subgroup (median age: 67 years; 60.9% female; 76.8% White) and 72 in REF subgroup (median age: 68 years; 51.4% female; 69.4% White). Patients in NOPT subgroup had 3 times more IP admissions (adjusted IRR=3.1; p <0.001) with almost 7 times more IP days (adjusted IRR=6.7; p<0.001), 80% more ED visits (adjusted IRR=1.8; p=0.036), and numerically more OP visits (adjusted IRR=1.2; p=0.056) in the first 2 years post-index, as compared to REF subgroup. Consistently, patients in NOPT subgroup had higher medical costs (adjusted Δ=$30,962 PPPY; p=0.008) mainly driven by higher OP costs (adjusted Δ=$8,380 PPPY; p=0.016) and higher ED costs (adjusted Δ=$4,332 PPPY; p=0.012) along with numerically higher IP costs (adjusted Δ=$14,063 PPPY; p=0.100) in the first 2 years post-index, as compared to REF subgroup ( Figure 1). Conclusions: In this study of patients with CML-CP non-optimal treatment resulting in early treatment discontinuation/switch or dose interruptions/reduction in the first 6 months from treatment initiation or low adherence with the currently approved TKIs in 1L and 2L therapy for CML was associated with significant incremental economic burden. This highlights the need for more tolerable therapeutic options early in the treatment course.

Identification of Multivariable microRNA and Clinical Biomarkers Panels to Predict Imatinib Response in Chronic Myeloid Leukemia at Diagnosis

Imatinib Mesylate (IM) was once hailed as the magic bullet for chronic myeloid leukemia (CML) and remains a front-line therapy for CML to this day alongside other tyrosine kinase inhibitors (TKIs). However, TKI treatments are rarely curative and while they demonstrate efficacy in managing the disease, patients are often required to receive life-long treatment or risk experiencing relapse. Patients also frequently harbor innate TKI-resistance mechanisms to front-line IM therapy and without prior screening, patients can spend precious months on non-optimal treatment before transitioning to other therapeutic strategies. Thus, there is a growing interest in studying biomarkers in patients which can predict TKI response upon diagnosis. CML has unique microRNA (miRNA) expression profiles at different stages of the disease and in response to TKI-treatment. We previously generated global transcriptome profiles on treatment-naïve CD34 + CML cells with known subsequent imatinib (IM) responses and identified several differentially expressed miRNAs in IM-nonresponders as compared to IM-responders. We also reported that IM response could be predicted in treatment-naïve CD34 + cells by an in vitro colony forming cell (CFC) assay. Additionally, we previously analyzed patient data from the ENESTxtnd clinical trial to show that miRNA expression combined with CFC output data could accurately predict Nilotinib response in patients. In this study, we used a Cox Proportional Hazard (CoxPH) analysis to identify 22 out of a pool of 35 pre-validated miRNAs which were associated with IM nonresponse in CD34 + CML cells of 80 patients at diagnosis. These patients were later classified as IM-responders or IM-nonresponders based on the latest European LeukemiaNet (ELN) guidelines. Interestingly, a Welch t-test revealed 16 of these 22 IM-response associated miRNAs to be differentially expressed between IM-responders and IM-nonresponders. Between IM-responders and IM-nonresponders we also found 7 clinical parameters that were associated with IM-response of which 3 matched parameters had significantly different values including CFC assay outputs ( p=0.0015), Sokal scores ( p=0.0070) and white blood cell counts (WBC, p=0.0028). We then trained a machine learning model employing the random-forest (RF), gradient-boosting (GBM) and naïve-bayes (NB) algorithms with different combinations of the 16 miRNAs with and without the clinical parameters of these patients to identify panels with high predictive performance based on area-under-curve (AUC) values of receiver-operating-characteristic (ROC) and precision-recall (PR) curves. Notably, the multivariable panel consisting of both miRNAs and clinical features (AUC-ROC RF=0.83, GBM=0.83, NB=0.84, AUC-PR RF=0.68, GBM=0.67, NB=0.70) performed better than either miRNA (AUC-ROC RF=0.72, GBM=0.73, NB=0.78, AUC-PR RF=0.49, GBM=0.51, NB=0.4) or clinical (AUC-ROC RF=0.82, GBM=0.84, NB=0.84, AUC-PR RF=0.64, GBM=0.67, NB=0.64) panels alone. Interestingly, 2 miRNAs in this panel, miR-185 and miR-145, were also significant classifiers for our Nilotinib predictive study suggesting that expression patterns of these miRNAs may have predictive properties for multiple TKI responses. Thus, we show that predictive accuracy of biomarkers may be supplemented by inclusion of multivariable parameters, and our findings may inform future studies on developing predictive panels for more optimized treatment plans in the clinic.

Applying precision methods to treatment selection for moderate/severe depression in person-centered experiential therapy or cognitive behavioral therapy

Objective To develop two prediction algorithms recommending person-centered experiential therapy (PCET) or cognitive–behavioral therapy (CBT) for patients with depression: (1) a full data model using multiple trial-based and routine variables, and (2) a routine data model using only variables available in the English NHS Talking Therapies program. Method Data was used from the PRaCTICED trial comparing PCET vs. CBT for 255 patients meeting a diagnosis of moderate or severe depression. Separate full and routine data models were derived and the latter tested in an external data sample. Results The full data model provided the better prediction, yielding a significant difference in outcome between patients receiving their optimal vs. non-optimal treatment at 6- (Cohen’s d = .65 [.40, .91]) and 12 months (d = .85 [.59, 1.10]) post-randomization. The routine data model performed similarly in the training and test samples with non-significant effect sizes, d = .19 [−.05, .44] and d = .21 [−.00, .43], respectively. For patients with the strongest treatment matching (d ≥ 0.3), the resulting effect size was significant, d = .38 [.11, 64]. Conclusion A treatment selection algorithm might be used to recommend PCET or CBT. Although the overall effects were small, targeted matching yielded somewhat larger effects.

Recovery and Characterization of Spermatozoa in a Neotropical, Terrestrial, Direct-Developing Riparian Frog (Craugastor evanesco) through Hormonal Stimulation.

The Vanishing Rainfrog (Craugastor evanesco) is an endemic and critically endangered frog species of Panama. It is suspected that 90% of the population has disappeared from the wild. Frogs were collected from the wild and brought to a Captive Breeding Program; however, accomplishing regular reproductive events for this species has been difficult. The objective of this study was to determine the effect of hormonal stimulation on the production and quality of C. evanesco spermatozoa, aiming to develop an efficient and safe sperm collection protocol as a tool to help reproduce this endangered species. Mature males received intra-peritoneal injections with one of six hormone treatments, including des-Gly10, D-Ala6, Pro-NHEt9-GnRH-A, Amphiplex or hCG. Urine samples were collected at 10 different time points post-injection. Quality assessments included sperm concentration, percentage motility, percentage forward progressive motility (FPM), osmolality, pH and morphology analysis. Our results indicate that the optimal treatment for the collection of highly concentrated sperm samples of C. evanesco is 4 µg/gbw GnRH, followed by Amphiplex and 2 µg/gbw GnRH as sub-optimal treatments and finally, 6 µg/gbw GnRH and 5 and 10 IU/gbw hCG as non-optimal treatments. GnRH-A at 4 μg/gbw and Amphiplex stimulated the production of samples with the highest sperm concentrations and quality, despite Amphiplex producing lower percentages of intact acrosome and tail. In contrast, hCG concentrations were not reliable inducers of sperm production, consistently showing lower concentrations, higher percentages of sperm abnormalities and more acidic spermic urine than that induced by Amphiplex and GnRH-A. Morphological assessments revealed that C. evanesco spermatozoa have a filiform shape with a large acrosome on the anterior part of an elongated head, a small midpiece and a long tail with two filaments joined together by an undulating membrane.

TUMEURS GRELIQUES QUELLES DIVERSITES HISTOLOGIQUE ?

Primary malignant tumors of the small intestine are rare tumors. They represent 1 to 5% of all tumors of the digestive tract. The multiplicity of histological types associated with the rarity of these tumors. The small intestine is considered as a clinically silent area and this results in a delay in diagnosis and therefore a non-optimal treatment and a severe prognosis. The objective of our work is to report the epidemiological, diagnostic characteristics of patients with small bowel tumors as well as their endoscopic and histological aspects collected in the hepato-gastroenterology department of the Hassan II University Hospital of Fez. Patient and method:We retrospectively analyzed the clinical records of 8 patients with the diagnosis of small bowel malignancies admitted to our training over a period of 11 years. Results: The average age of our patients was 42 years,The sex ratio M/F was 3, the tumor was revealed by an upper GI hemorrhage in 50%(N: 4) followed by abdominal pain in 37%(N: 3) and koening syndrome in 12%(N: 1). The CT scan showed a parietal thickening in all the cases, of which 1 case showed a mass. Double balloon enteroscopy was performed in 8 patients (100%), the endoscopic aspect revealed an ulcerating process in 75% (N: 6), a tumor of sub-mucosal appearance in 12% (N: 1). An ulcerated jejunal stenosis that could not be crossed in 12% (N:1).the biopsy by enteroscopy had allowed to make the diagnosis in 100% of the cases (N: 8).the histological examination had objectified: lymphomas in 37%( N: 3), GIST in 25% cases (N: 2), adenocarcinomas in 25% cases (N: 2) and neuroendocrine tumor in 12% (N: 1). The evolution was unfavorable in all our cases with a median survival rate of 10 months. Conclusion: Small bowel tumors are rare but interesting because of their great histological diversity. The diagnosis is difficult because of the non-specific symptomatology, In our study the couple imaging -enteroscopy had allowed to establish the diagnosis in all our cases, with predominance of the anatomopathological aspect of lymphoma in 37% of the cases.

Ammonia-Nitrogen Reduction in Low Strength Domestic Wastewater by Polyvinyl Alcohol (PVA) Gel Beads

This study aimed to evaluate the efficacy of polyvinyl alcohol (PVA) gel beads as an immobilized biofilm carrier to enhance the reduction rate of Ammonia-Nitrogen (NH3-N) and Chemical Oxygen Demand (COD) in domestic wastewater. Laboratory scale reactors were developed to assess the reduction levels of ammonia-nitrogen and COD with and without PVA gel beads using optimal and non-optimal treatment mode settings based on operation procedures from the sewage treatment plant in Taman Kajang Utama, Selangor. The treatment method used is an activated sludge sequencing batch reactor with a treatment cycle duration of 288 minutes. The findings showed the ammonia-nitrogen reduction by non-optimal treatment mode is more effective, with a reduced rate of 62.96% to 65.71% compared to optimal treatment mode with a reduced rate of 30.94% and treatment without PVA gel beads (optimal and non-optimal) with a reduced rate of 32.41% to 47.85%. The ammonia-nitrogen reduction rate using PVA gel beads for non-optimal treatment mode was significantly increased from 17.86% to 18.82% and complied with ammonia-nitrogen reduction parameter 10mg/L, Standard A of Environmental Quality (Sewage) Regulations 2009 (EQSR 2009). The rate of COD reduction using the non-optimal treatment mode was also more stable, with a reduced rate of 70.68%. It was also found that the COD reduction rate using PVA gel beads for the non-optimal mode was better than the optimal mode, which was 70.68% compared to 42.0%, and both treatment modes complied with COD reduction parameters 120mg/L, Standard A of EQSR 2009.

Spotlight commentary: Navigating between financial risks and improved treatment outcomes with immune checkpoint inhibitors in cancer patients: The need for biomarker identification and dose optimization.

Spotlight commentary: Navigating between financial risks and improved treatment outcomes with immune checkpoint inhibitors in cancer patients: The need for biomarker identification and dose optimization.

The relationship between cost and the recommendation, refusal, and discontinuation of treatment for chronic myeloid leukemia and multiple myeloma in Japan: a cross-sectional exploratory survey

Aims This study aimed to ascertain the number of patients with chronic myelogenous leukemia (CML) and transplant-ineligible patients with multiple myeloma (MM) not recommended by their physicians for optimal drug treatment or who refuse, discontinue, reduce, or skip treatment owing to cost in Japan. Methods A cross-sectional survey was conducted among hematologists, hematologic oncologists, and oncologists in Japan treating ≥1 patient with CML or ≥5 transplant-ineligible patients with MM per year. Results A total of 212 physicians participated: 105 treating patients with CML and 107 treating transplant-ineligible patients with MM. While treatment cost did not lead to non-optimal treatment most patients, physicians reported that they recommended non-optimal treatment to 6.53% of their patients with CML and 1.41% of their transplant-ineligible patients with MM, that 1.51 and 0.35% of their patients, respectively, refused treatment and that 1.97 and 0.71% discontinued treatment owing to treatment cost. However, no significant differences in the effect of treatment cost on recommendation, discontinuation, refusal, or reduction of treatment were observed. Non-recommendation of optimal treatment owing to treatment cost was most common for third-line CML and fourth-line transplant-ineligible MM treatment. Discontinuation due to treatment cost was most common in third-line treatment for both. Conclusion Our results show that non-optimal treatment due to treatment cost occurs among some physicians in Japan for patients with CML and transplant-ineligible patients with MM, but it may be limited to a small percentage of patients. Further research is needed to identify the drivers of treatment decisions for physicians and patients, including those involving treatment cost.

Continuous Decline in Myocardial Infarction and Heart Failure Hospitalizations during the First 12 Months of the COVID-19 Pandemic in Israel.

Background: A decline in cardiovascular hospitalizations was observed during the initial phases of the COVID-19 pandemic. We examine the continuous effect of the COVID-19 pandemic in reducing cardiovascular hospitalization and associated mortality rates during the first year of the pandemic in Israel. Methods: We conduct a retrospective cohort study using the data of Clalit Health Services, the largest healthcare organization in Israel. We divide the Corona year into six periods (three lockdowns and three post-lockdowns) and compare the incidence rates of cardiovascular hospitalizations and 30-day all-cause mortality during each period to the previous three years. Results: The number of non-STEMI hospitalizations during the first year of the pandemic was 13.7% lower than the average of the previous three years (95% CI 11–17%); STEMI hospitalizations were 15.7% lower (95% CI 13–19%); CHF (Congestive heart failure) hospitalizations were 23.9% lower (95%, CI 21–27%). No significant differences in 30-day all-cause mortality rates were observed among AMI (acute myocardial infarction) patients during most of the periods, whereas the annual 30-day all-cause mortality rate among CHF patients was 23% higher. Conclusions: AMI and CHF hospitalizations were significantly lower during the first year of the pandemic relative to 2017–9. Mortality rates were higher in the case of CHF patients but not in the case of AMI patients, possibly due to a change in the clinical acuity of patients arriving at the hospitals. We conclude that targeted public health messaging should be implemented together with proactive monitoring, in order to identify residual disability in patients who may have received non-optimal treatment during the pandemic.

Optimal Data Collection Period for Continuous Glucose Monitoring to Assess Long-Term Glycemic Control: Revisited.

It is not clear how the short-term continuous glucose monitoring (CGM) sampling time could influence the bias in estimating long-term glycemic control. A large bias could, in the worst case, lead to incorrect classification of patients achieving glycemic targets, nonoptimal treatment, and false conclusions about the effect of new treatments. This study sought to investigate the relation between sampling time and bias in the estimates. We included a total of 329 type 1 patients (age 14-86 years) with long-term CGM (90 days) data from three studies. The analysis calculated the bias from estimating long-term glycemic control based on short-term sampling. Time in range (TIR), time above range (TAR), time below range (TBR), correlation, and glycemic target classification accuracy were assessed. A sampling time of ten days is associated with a high bias of 10% to 47%, which can be reduced to 4.9% to 26.4% if a sampling time of 30 days is used (P < .001). Correct classification of patients archiving glycemic targets can also be improved from 81.5% to 91.9 to 90% to 95.2%. Our results suggest that the proposed 10-14 day CGM sampling time may be associated with a high correlation with three-month CGM. However, these estimates are subject to large intersubject bias, which is clinically relevant. Clinicians and researchers should consider using assessments of longer durations of CGM data if possible, especially when assessing time in hypoglycemia or while testing a new treatment.

Prevalence of resistant hypertension in uncontrolled hypertensive patients seen in consultation

Resistant hypertension is defined by hypertension not controlled in consultation and confirmed by measurement outside the doctor's office, despite a therapeutic strategy comprising adapted hygiene and dietetic rules and antihypertensive triple therapy for at least 4 weeks, at optimal dose, including a thiazide diuretic. Screening for resistant hypertension in internal medicine and cardiology consultation. Prospective study including 1862 hypertensive patients, aged 18 and over, treated for at least one year and referred for uncontrolled hypertension, seen between October 2015–December 2019. The verification of the non-achievement of the blood pressure target was performed in all patients, either by ambulatory blood pressure measurement (ABPM) or by AMT (self-measurement of blood pressure), and revealed a blood pressure target not reached each time. Of the 1862 patients screened, mean age 58 ± 13.4 years, including 838 men (45%), and 1024 women (55%), 896 (48%) were receiving non-optimal treatment, 45% of patients had a BMI greater than 30 kg/m 2 (41% men vs. 59% women), 23% were smokers, and 45% were diabetics. In total, 612 (32.8%) were poor observers and 202 (8.5%). A secondary cause of hypertension was identified in 175 (9.4%) patients. Finally, only 112 patients presented with hypertension requiring quadruple therapy or more, either a prevalence of 6.01% (95% CI: 5.6–7.2). It should be noted that three of our patients benefited from renal denervation practiced in our department, the immediate responses were satisfactory. Less than 15% of the patients referred to our consultation present a true hypertension, and almost half present a pseudo-resistance. The majority of patients with apparently resistant hypertension can achieve the blood pressure goal if they are sensitized, observant, and properly treated.

Syndrome de Guillain-Barré en milieu hospitalier au Togo

RésuméIntroductionLes études sur le syndrome de Guillain-Barré (SGB) sont rares en Afrique subsaharienne caractérisée par un plateau technique médical limité et une fréquence relativement plus élevée de maladies infectieuses.ObjectifsLes objectifs de ce travail sont de décrire les caractéristiques du SGB au Togo à travers une cohorte de patients suivis dans le service de neurologie du CHU Campus de Lomé.MéthodologieL’étude s'est déroulée de mai 2015 à juillet 2019. Les patients présentant un SGB des niveaux 1, 2 ou 3 des critères de certitude diagnostique de Brighton, ont été inclus de façon consécutive. Ils ont été évalués à l'admission puis à 6 mois et à 1 an d’évolution à l'aide du score d'invalidité SGB (GBS score) et du score neuromusculaire du Medical Research Council (MRC sum-score). Les variables qualitatives et quantitatives ont été exprimées, respectivement, en fréquence et en médiane (intervalle interquartile).RésultatsSur 7 012 patients hospitalisés, 28 (0,39%) présentaient un SGB avec une prédominance féminine (20 femmes soit 71%) et un âge médian de 40 (IQ: 27-53) ans. La présentation clinique majoritairement était constituée par des troubles sensitivo-moteurs bilatéraux des membres à prédominance crurale associés à une diplégie faciale et précédés d'un évènement infectieux. A l'admission, la marche était possible (GBS score 0 à 3) chez 11 patients (39%) et le MRC sum score médian était de 28 (IQ: 12-38). La dissociation albumino-cytologique était présente chez 13 des 20 patients ayant eu une ponction lombaire (65%). Les sous-types démyélinisant et axonal ont représenté chacun 47% (9/19 patients ayant eu un électroneuromyogramme). Les immunoglobulines et la corticothérapie par voie intraveineuse ont été respectivement administrées chez 18% (n=5) et 50% (n=14) des patients. La létalité hospitalière était de 11% (n=3). Le MRC sum score médian à six et 12 mois étaient respectivement de 40 (IQ: 38-49) et 51 (IQ: 46-58). À un an d’évolution, la létalité était de 18% (n=5) et 78% (n=14) des 18 survivants pouvaient marcher sans aide dont 17% (n=3) asymptomatiques.ConclusionAu Togo, avec une prévalence hospitalière faible, le SGB reste une affection grave de par sa forte morbi-létalité en lien avec des thérapeutiques non optimales mais aussi un retard de prise en charge.

Evolution of COVID-19 patients treated with a combination of nutraceuticals to reduce symptomatology and improve prognosis: a multi-centred, retrospective cohort study

Although a vast knowledge has already been gathered on the pathophysiology of COVID-19, there are still limited, non-optimal treatment options. In this context, agents that can act on prophylaxis or as adjuvants to the therapies are of high value. In this paper, we describe a multicentre, retrospective, observational study to describe the course of SARS-CoV-2 disease in patients treated with Immuno Formulation (IF), an add-on therapy developed to decrease duration of clinical symptoms. In parallel, a group of patients that did not receive IF was used for comparison (using standard of care treatment). A total of 39 patients were evaluated for their recovery rate, general symptoms and their severity, and adverse reactions. Throughout the observational period, 90% of patients recovered in the IF cohort and 47.4% in the Control cohort (p=0.0057). From the symptoms with statistically significant differences, the duration of symptoms (i.e., the time to recover from it) was shorter in the IF cohort than in control cohort (in days, average), especially for fever (2.25 x 21.78), dry cough (4.38 x 24.00), dyspnoea (3.67 x 20.00), headache (2.00 x 26.50), diarrhoea (5.25 x 25.25), and weakness (1.92 x 23.30). This demonstrates a potential promising role of IF as adjuvant therapy on the evolution of symptomatology to COVID-19 patients.

Predicting optimal treatment regimens for patients with HR+/HER2- breast cancer using machine learning based on electronic health records

Aim: To predict optimal treatments maximizing overall survival (OS) and time to treatment discontinuation (TTD) for patients with metastatic breast cancer (MBC) using machine learning methods on electronic health records. Patients/methods: Adult females with HR+/HER2-MBC on first- or second-line systemic therapy were eligible. Random survival forest (RSF) models were used to predict optimal regimen classes for individual patients and each line of therapy based on baseline characteristics. Results: RSF models suggested greater use of CDK4 & 6 inhibitor-based therapies may maximize OS and TTD. RSF-predicted optimal treatments demonstrated longer OS and TTD compared with nonoptimal treatments across line of therapy (hazard ratios=0.44∼0.79). Conclusion: RSF may help inform optimal treatment choices and improve outcomes for patients with HR+/HER2-MBC.

Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial

ObjectivesTo compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC).MethodsPragmatic, prospective, cluster-randomised, controlled, open, 1-year trial (NCT03043846). 18 centres were randomised...

Moderators of response to child-based and parent-based child anxiety treatment: a machine learning-based analysis.

Identifying moderators of response to treatment for childhood anxiety can inform clinical decision-making and improve overall treatment efficacy. We examined moderators of response to child-based cognitive-behavioral therapy (CBT) and parent-based SPACE (Supportive Parenting for Anxious Childhood Emotions) in a recent randomized clinical trial. We applied a machine learning approach to identify moderators of treatment response to CBT versus SPACE, in a clinical trial of 124 children with primary anxiety disorders. We tested the clinical benefit of prescribing treatment based on the identified moderators by comparing outcomes for children randomly assigned to their optimal and nonoptimal treatment conditions. We further applied machine learning to explore relations between moderators and shed light on how they interact to predict outcomes. Potential moderators included demographic, socioemotional, parenting, and biological variables. We examined moderation separately for child-reported, parent-reported, and independent-evaluator-reported outcomes. Parent-reported outcomes were moderated by parent negativity and child oxytocin levels. Child-reported outcomes were moderated by baseline anxiety, parent negativity, and parent oxytocin levels. Independent-evaluator-reported outcomes were moderated by baseline anxiety. Children assigned to their optimal treatment condition had significantly greater reduction in anxiety symptoms, compared with children assigned to their nonoptimal treatment. Significant interactions emerged between the identified moderators. Our findings represent an important step toward optimizing treatment selection and increasing treatment efficacy.

The increasing importance of histologic grading in tailoring adjuvant systemic therapy in 30,843 breast cancer patients

PurposeThe large variation in histologic grading of invasive breast cancer (IBC) that has been reported likely influences tailoring adjuvant therapy. The role of grading in therapeutic decision-making in daily practice, was evaluated using the Dutch national guidelines for IBC-management.MethodsSynoptic reports of IBC resection-specimens, obtained between 2013 and 2016, were extracted from the nationwide Dutch Pathology Registry, and linked to treatment-data from the Netherlands Cancer Registry. The relevance of grading for adjuvant chemotherapy (aCT) was quantified by identifying patients for whom grade was the determinative factor. In addition, the relation between grade and aCT-administration was evaluated by multivariate logistic regression for patients with a guideline-aCT-indication.Results30,843 patients were included. Applying the guideline that was valid between 2013 and 2016, grade was the determinative factor for the aCT-indication in 7744 (25.1%) patients, a percentage that even increased according to the current guideline where grade would be decisive for aCT in 10,869 (35.2%) patients. Also in current practice, the indication for adjuvant endocrine therapy (aET) would be based on grade in 9173 (29.7%) patients. Finally, as patients with lower-grade tumors receive aCT significantly less often, grade was also decisive in tailoring aCT de-escalation.ConclusionsIn the largest study published so far we illustrate the increasing importance of histologic grade in tailoring adjuvant systemic breast cancer therapy. Next to playing a key-role in aCT-indication and de-escalation, the role of grading has expanded to the indication for aET. Optimizing histologic grading by pathologists is urgently needed to diminish the risk of worse patient outcome due to non-optimal treatment.

Therapeutic management and outcome of nonagenarians admitted to an intensive care unit for an acute coronary syndrome as compared to octogenarians

The number of very old patients admitted to an intensive care unit (ICU) for acute coronary syndrome (ACS) has increased gradually but these patients are underrepresented in randomised clinical trials. The aim of this study was to analyse mortality of nonagenarians as compared to octogenarians admitted to an ICU for ACS, to describe their management, and to identify prognostic factors. Patients ≥ 80 years admitted to the ICU (Croix-Rousse University Hospital, Lyon) with a diagnosis of ACS from 1st January 2013 to 31st December 2016 were retrospectively included. After exclusion of type 2 ACS, the data for 311 octogenarians and 92 nonagenarians were analysed using Kaplan–Meier curves and a multivariate Cox-regression model. More than 70 % of patients received renin-angiotensin-system blockers, beta-blockers, and statins, without significant difference between nonagenarians and octogenarians. Nonagenarians were significantly less treated by ticagrelor than octogenarians ( P = 0.028). Overall, 97.8 % of patients underwent a coronary angiogram, and 80.4 % percutaneous coronary intervention. At 5 years of follow-up, the survival rate was 62.8 % for nonagenarians as compared to 73.1 % for octogenarians ( P = 0.007) but no significant difference was observed for cardiovascular mortality ( P = 0.171). GRACE score and increased age were significantly associated with higher mortality rate, while renin-angiotensin-system blockers, statins, and ticagrelor were protective factors. Although, overall mortality is higher in patients ≥ 90 years than in those < 90 years, the overall survival reported herein remains acceptable. On top of the effect of age, the difference in prognosis according to age may be partly explained by a non-optimal treatment strategy for older patients.