scholarly journals Inhaled aztreonam improves symptoms of cough and sputum production in patients with bronchiectasis: a post hoc analysis of the AIR-BX studies

2020 ◽  
Vol 56 (1) ◽  
pp. 2000608
Author(s):  
Megan L. Crichton ◽  
Mike Lonergan ◽  
Alan F. Barker ◽  
Oriol Sibila ◽  
Pieter Goeminne ◽  
...  
Keyword(s):  
Linear Models ◽  
Response To Treatment ◽  
Symptom Scale ◽  
Trial Duration ◽  
Patient Response ◽  
Improve Symptom ◽  
Sputum Production ◽  
Inhaled Antibiotics ◽  
Post Hoc ◽  
Specific Symptoms

IntroductionInhaled antibiotics may improve symptom scores, but it is not known which specific symptoms improve with therapy. Item-level analysis of questionnaire data may allow us to identify which specific symptoms respond best to treatment.MethodsPost hoc analysis of the AIR-BX1 studies and two trials of inhaled aztreonam versus placebo in bronchiectasis. Individual items from the quality of life bronchiectasis (QOL-B) respiratory symptom scale, were extracted as representing severity of nine distinct symptoms. Generalised linear models were used to evaluate changes in symptoms with treatment versus placebo from baseline to end of first on-treatment cycle and mixed models were used to evaluate changes across the full 16-week trial.ResultsAztreonam improved cough (difference 0.22, 95% CI 0.08–0.37; p=0.002), sputum production (0.30, 95% CI 0.15–0.44; p<0.0001) and sputum colour (0.29, 95% CI 0.15–0.43; p<0.0001) versus placebo equating to a 20% improvement in cough and 25% improvement in sputum production and colour. Similar results were observed for cough, sputum production and sputum purulence across the trial duration (all p<0.05). Patients with higher sputum production and sputum colour scores had a greater response on the overall QOL-B (difference 4.82, 95% CI 1.12–8.53; p=0.011 for sputum production and 5.02, 95% CI 1.19–8.86; p=0.01 for sputum colour). In contrast, treating patients who had lower levels of bronchitic symptoms resulted in shorter time to next exacerbation (hazard ratio 1.83, 95% CI 1.02–3.28; p=0.042).ConclusionBaseline bronchitic symptoms predict response to inhaled aztreonam in bronchiectasis. More sensitive tools to measure bronchitic symptoms may be useful to better identify inhaled antibiotic responders and to evaluate patient response to treatment.

scholarly journals Changes in respiratory symptoms during 48-week treatment with ARD-3150 (inhaled liposomal ciprofloxacin) in bronchiectasis: results from the ORBIT-3 and -4 studies

2020 ◽  
Vol 56 (4) ◽  
pp. 2000110
Author(s):  
James D. Chalmers ◽  
David Cipolla ◽  
Bruce Thompson ◽  
Angela M. Davis ◽  
Anne O'Donnell ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Respiratory Symptoms ◽  
Mixed Model ◽  
Bacterial Load ◽  
Minimum Clinically Important Difference ◽  
Symptom Improvement ◽  
Symptom Scale ◽  
Inhaled Antibiotics ◽  
Post Hoc ◽  
Relationship Of

It is not known if inhaled antibiotics improve respiratory symptoms in patients with bronchiectasis. In the recent phase-3 ORBIT trials, 48 weeks' treatment with ARD-3150 (inhaled liposomal ciprofloxacin) did not significantly improve symptoms using the prespecified method of analysis comparing baseline symptoms to those after 48 weeks, when patients had been off treatment for 28 days. This method of analysis does not take account of possible improvements in symptoms while on active treatment.A post hoc analysis of two identical randomised trials of ARD-3150 (ORBIT-3 and -4) administered 28 days on and 28 days off in patients with bronchiectasis and chronic Pseudomonas aeruginosa infection. The quality-of-life bronchiectasis respiratory symptom scale (QOL-B-RSS), which has a one-week recall period, was administered every 28 days. We examined whether respiratory symptoms improved during on-treatment periods and the relationship of changes in QOL-B-RSS to changes in bacterial load using a mixed-model repeated measures approach.ARD-3150 treatment resulted in a significant improvement in respiratory symptoms during the on-treatment periods with concordant results between ORBIT-3 (estimate 1.4 points, se 0.49; p=0.004) and ORBIT-4 (estimate 1.1 point, se 0.41; p=0.006). The proportion of patients achieving a symptom improvement above the minimum clinically important difference was higher with ARD-3150 compared with placebo during on-treatment cycles (p=0.024). Changes in respiratory symptoms were correlated with changes in bacterial load in the treatment group (r=−0.89, p<0.0001). Individual estimates for decrements in the QOL-B RSS during exacerbation were −9.4 points (se 0.91) in ORBIT-3 and −10.8 points (0.74) in ORBIT-4 (both p<0.0001).Inhaled ARD-3150 resulted in significant improvements in respiratory symptoms during the on-treatment periods which were lost during off-treatment periods. These results supports the concept that reducing bacterial load can improve respiratory symptoms in patients with bronchiectasis.

scholarly journals Telomere Architecture Correlates with Aggressiveness in Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1969
Author(s):  
Aline Rangel-Pozzo ◽  
Pak Yu ◽  
Sadhana LaL ◽  
Yasmin Asbaghi ◽  
Luiza Sisdelli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Genomic Instability ◽  
Clinical Decision Making ◽  
Three Dimensional ◽  
Clinical Decision ◽  
Response To Treatment ◽  
Average Intensity ◽  
Patient Response ◽  
Smoldering Multiple Myeloma

The prognosis of multiple myeloma (MM), an incurable B-cell malignancy, has significantly improved through the introduction of novel therapeutic modalities. Myeloma prognosis is essentially determined by cytogenetics, both at diagnosis and at disease progression. However, for a large cohort of patients, cytogenetic analysis is not always available. In addition, myeloma patients with favorable cytogenetics can display an aggressive clinical course. Therefore, it is necessary to develop additional prognostic and predictive markers for this disease to allow for patient risk stratification and personalized clinical decision-making. Genomic instability is a prominent characteristic in MM, and we have previously shown that the three-dimensional (3D) nuclear organization of telomeres is a marker of both genomic instability and genetic heterogeneity in myeloma. In this study, we compared in a longitudinal prospective study blindly the 3D telomeric profiles from bone marrow samples of 214 initially treatment-naïve patients with either monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or MM, with a minimum follow-up of 5 years. Here, we report distinctive 3D telomeric profiles correlating with disease aggressiveness and patient response to treatment in MM patients, and also distinctive 3D telomeric profiles for disease progression in smoldering multiple myeloma patients. In particular, lower average intensity (telomere length, below 13,500 arbitrary units) and increased number of telomere aggregates are associated with shorter survival and could be used as a prognostic factor to identify high-risk SMM and MM patients.

Using Mixture of Normal Distributions to Detect Treatment Effects when the Frequentist Method Fails

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Anthony Orlando
Keyword(s):  
Dose Response ◽  
Linear Models ◽  
Controlled Trial ◽  
Response To Treatment ◽  
Double Blind ◽  
Underlying Assumption ◽  
Normal Distributions ◽  
Efficacy Measure ◽  
Baseline Weight ◽  
Mixture Of Normal Distributions

Background: Results from a clinical trial can either support the efficacy and safety of a new compound or fail to provide such evidence. One reason for ‘non[1]positive’ result is due to the underlying assumption of normality and homogeneity of variances, which are quite often violated when analyzing data from clinical trials, despite randomization. A question of interest is can we obtain more informative results when using mixture of normal distributions or linear models (MLMs) in such cases. Introduction: MLM can be used when traditional methods fail. MLMs “search” within the variability in data to identify components or subgroups of individuals (also known as latent classes) who have common intercepts and common slopes of change in a variable/endpoint of interest but whose intercepts and slopes are different from other subsets of patients. Thus, MLMs can be used to identify subgroups of patients exhibiting differential response to treatment within each treatment arm. The purpose of our study was to examine the usefulness of using MLM in such circumstances. Methods: Data of 155 subjects taken from a Multicenter, randomized, double blind, placebo controlled trial that evaluated the efficacy of Cpn10, administered twice weekly subcutaneously to treat Rheumatoid Arthritis was taken to evaluate the usefulness of MLM. The primary efficacy measure ACR20 was analyzed using a 3-step process: first, MLM was used to estimate RA duration using a 3-component model. The second step took the results of the first step to inform the logistic model and its analyses. Model was fitted with an intercept, MLM components, treatment arm, RA duration (linear and quadratic), dose response (modeled as an interaction effect), age and baseline weight. LOCF was used to impute for missing data. Data was analyzed using MLM and SAS v 9.0. Results: The model was a good fit to the data with a likelihood ratio significant at p=0.026, and a significant increase in the -2log L. We also observed low p-values for those variables that were non normal. Overall and for the 75 mg dose, Cpn 10 was efficacious relative to placebo, p<0.050. We also observed that dose response was significant at p><0.15 Conclusion: The use of MLM adds value because it can be used to understand the disease experience or the value of treatment when traditional statistical methods cannot. Key words: Mixture of linear models, normality, entropy.

Efficacy of local treatments in Prurigo Pigmentosa after Bariatric surgery

2021 ◽  
Vol 07 (02) ◽  
pp. 01-03
Author(s):  
Mezoun Almuhaimeed
Keyword(s):  
Bariatric Surgery ◽  
Clinical Presentation ◽  
Response To Treatment ◽  
Single Female ◽  
Provisional Diagnosis ◽  
Patient Response ◽  
Medical City ◽  
History Of ◽  
Multivitamin Supplements

A 22-year-old single female presented to primary care Wazarat Health Center at Prince Sultan Military Medical City in Riyadh, with a 3 weeks history of itchy erythematous papules and vesicles and papulo-vesicles over the neck, chest, and upper back and face, which started 4 to 5 days after bariatric surgery. The patient on daily multivitamin supplements, vitamin D (50,000 IU, weekly / 2 months). The patient has lost 4kg since the operation, family history of atopy was positive regarding the mother physical examination shows erythematous papules and vesicles and papulo-vesicles over the neck with crust, chest, and upper back, Based on medical history and clinical presentation a provisional diagnosis was Prurigo Pigmentosa. The patient was prescribed topical mometasone furoate cream (BID for one week). Two -week follow-up showed improvement of the eruption. The course of the disease was shorter than usual in such cases the patient response to treatment was reactive to the topical mometasone without taking the oral minocyline, which major of such cases need in the late course of the disease The patient starts to improve within 2 weeks compared to others who need an average of 6 weeks to improve in such cases

scholarly journals Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials

Blood ◽  
2019 ◽  
Vol 133 (10) ◽  
pp. 1020-1030 ◽  
Author(s):  
U. Platzbecker ◽  
P. Fenaux ◽  
L. Adès ◽  
A. Giagounidis ◽  
V. Santini ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Myelodysplastic Syndromes ◽  
Working Group ◽  
Lower Risk ◽  
Response Assessment ◽  
Response To Treatment ◽  
Response Criteria ◽  
Patient Response ◽  
Erythroid Response ◽  
Clinical Responses

Abstract The heterogeneity of myelodysplastic syndromes (MDSs) has made evaluating patient response to treatment challenging. In 2006, the International Working Group (IWG) proposed a revision to previously published standardized response criteria (IWG 2000) for uniformly evaluating clinical responses in MDSs. These IWG 2006 criteria have been used prospectively in many clinical trials in MDSs, but proved challenging in several of them, especially for the evaluation of erythroid response. In this report, we provide rationale for modifications (IWG 2018) of these recommendations, mainly for “hematological improvement” criteria used for lower-risk MDSs, based on recent practical and reported experience in clinical trials. Most suggestions relate to erythroid response assessment, which are refined in an overall more stringent manner. Two major proposed changes are the differentiation between “procedures” and “criteria” for hematologic improvement–erythroid assessment and a new categorization of transfusion-burden subgroups.

scholarly journals The Weighed Core Symptom Scale and Prediction of ADHD in Adults – Objective Measures of Remission and Response to Treatment with Methylphenidate

2013 ◽  
Vol 9 (1) ◽  
pp. 171-179
Author(s):  
Hanna Edebol ◽  
Lars Helldin ◽  
Torsten Norlander
Keyword(s):  
Adult Adhd ◽  
Response Rate ◽  
Optimal Dose ◽  
Response To Treatment ◽  
Therapeutic Effects ◽  
Modified Release ◽  
Symptom Scale ◽  
Core Symptom ◽  
Two Measures

Objective: Two measures of the response rate and the optimal treatment response for adult ADHD were evaluated using methylphenidate. The hypotheses were that Prediction of ADHD (PADHD) defines remission, the Weighed Core Symptom (WCS) scale registers direct effects of medication and that WCS may indicate the optimal dose level during titration. Design: PADHD and WCS were analyzed at baseline and after intake of low doses of either short-acting or modified-release formulations of methylphenidate, MPH (Study I), during titration with modified-release formulations of MPH (18/27, 36, 54, 72 mg) and at three months follow-up (Study II). Patients: Study I consisted of 63 participants (32 females) and Study II consisted of 10 participants (6 females) diagnosed with ADHD and who was to start with treatment. Outcome measures: Prediction of ADHD (PADHD) indicates the occurrence of ADHD (No, Yes) and the Weighed Core Symptom scale (WCS) quantifies ADHD from 0 to 100 (max-min). Results: The number of clinical cases of ADHD decreased after methylphenidate treatment according to PADHD. WCS increased (p < 0.001) from 9.75 (SD = 12.27) to 47.50 (SD = 29.75) with about 10 mg of methylphenidate (N = 63). During titration, symptoms improved after 18/27 mg and 36 mg of methylphenidate and baseline-follow up comparisons showed WCS increments (p = 0.005) from 31.00 (N = 10, SD = 26.85) to 69.00 (N = 10, SD = 22.34). Conclusions: PADHD defined remission and WCS measured therapeutic effects of methylphenidate in adult ADHD.

scholarly journals Genetic Variations Associated with Long-Term Treatment Response in Bipolar Depression

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1259
Author(s):  
Gerard Anmella ◽  
Silvia Vilches ◽  
Jordi Espadaler ◽  
Andrea Murru ◽  
Isabella Pacchiarotti ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Major Depression ◽  
Bipolar Depression ◽  
Scientific Evidence ◽  
Term Treatment ◽  
Response To Treatment ◽  
Clinical Predictors ◽  
Patient Response ◽  
Long Term Treatment ◽  
The Impact

Several pharmacogenetic-based decision support tools for psychoactive medication selection are available. However, the scientific evidence of the gene-drug pairs analyzed is mainly based on pharmacogenetic studies in patients with major depression or schizophrenia, and their clinical utility is mostly assessed in major depression. This study aimed at evaluating the impact of individual genes, with pharmacogenetic relevance in other psychiatric conditions, in the response to treatment in bipolar depression. Seventy-six patients diagnosed with bipolar disorder and an index major depressive episode were included in an observational retrospective study. Sociodemographic and clinical data were collected, and all patients were genotyped using a commercial multigene pharmacogenomic-based tool (Neuropharmagen®, AB-Biotics S.A., Barcelona, Spain). Multiple linear regression was used to identify pharmacogenetic and clinical predictors of efficacy and tolerability of medications. The pharmacogenetic variables response to serotonin-norepinephrine reuptake inhibitors (SNRIs) (ABCB1) and reduced metabolism of quetiapine (CYP3A4) predicted patient response to these medications, respectively. ABCB1 was also linked to the tolerability of SNRIs. An mTOR-related multigenic predictor was also associated with a lower number of adverse effects when including switch and autolytical ideation. Our results suggest that the predictors identified could be useful to guide the pharmacological treatment in bipolar disorder. Additional clinical studies are necessary to confirm these findings.

Prognostic Significance of CHEK2 Mutation in Progression of Breast Cancer

2019 ◽  
Vol 50 (3) ◽  
pp. e36-e41
Author(s):  
Narges Ansari ◽  
Saeid Shahrabi ◽  
Abbas Khosravi ◽  
Reza Shirzad ◽  
Hadi Rezaeean
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Cell Signaling ◽  
Prognostic Significance ◽  
The Body ◽  
Response To Treatment ◽  
Patient Response ◽  
Disease Mutations ◽  
Detection Of Mutations ◽  
Cell Signaling Pathways

Abstract Breast cancer (BC) is one of the most common cancers among women; genetic mutations reflect the development of this disease. Mutations in cell signaling factors can be the main cause of BC development. In this study, we focused on mutations in checkpoint kinase 2 (CHEK2) and their impact as a prognostic factor in the pathogenesis of BC. CHEK2 is controlled in cell signaling pathways through the influence of upstream genes. Also, several downstream genes are regulated by CHEK2. In addition, mutations in CHEK2 lead to resistance of BC cells to chemotherapy and metastasis of cancer cells to other parts of the body. Finally, detection of mutations in CHEK2 can be used as a prognostic factor for patient response to treatment and for targeting downstream molecules of CHEK2 that are involved in the proliferation of breast tumor cells. Mutations such as c.1100delC and I157T can distinguish which patients are susceptible to metastasis.

Performance Effects of Carbohydrate Ingestion Between Bouts of Intense Aerobic Interval Exercise

2020 ◽  
Vol 15 (2) ◽  
pp. 262-267
Author(s):  
Devin G. McCarthy ◽  
Lawrence L. Spriet
Keyword(s):  
Oxygen Consumption ◽  
Perceived Exertion ◽  
Peak Oxygen Consumption ◽  
Trial Duration ◽  
Carbohydrate Ingestion ◽  
Subsequent Performance ◽  
Performance Effects ◽  
Improved Performance ◽  
Post Hoc ◽  
Glycogen Stores

Background: Rest between training sessions can be short for athletes. In these situations, consuming carbohydrate (CHO) postexercise replenishes glycogen stores, which is important for recovery and subsequent performance. Purpose: This study tested whether CHO intake during a 2-hour rest between exercise bouts improved performance in the subsequent bout. Methods: In a randomized, single-blinded, crossover design, 10 recreationally active participants (23 [4] y, 70.8 [6.6] kg, 47.0 [5.4] mL·O2·min−1·kg·body·mass−1) arrived at the lab postprandial and completed 2 exercise bouts separated by a 2-hour rest. Bouts included 5 × 4-minute intervals at ∼80% peak oxygen consumption separated by 2 minutes at ∼40% peak oxygen consumption and ended with an endurance trial to voluntary exhaustion at ∼90% peak oxygen consumption. During intervals 1 and 4 in each bout, expired gases were collected and O2 deficit was estimated. Immediately following bout 1, either a CHO (1.2 g CHO·kg·body·mass−1) or placebo solution was consumed. Results: Endurance trial duration decreased in bout 2 versus 1 in both conditions (P < .01) but was ∼35% longer in bout 2 with CHO versus placebo (interaction, P = .03; post hoc, P = .03). Oxygen uptake increased during interval 4 versus 1 in both bouts (P < .01) but was unaffected by CHO (P ≥ .58). O2 deficit was unaffected by CHO (P = .93), bout, or interval (P ≥ .15). Perceived exertion was higher in bout 2 versus 1 (P < .001) and reduced in intervals 2 and 4 in CHO (P ≤ .01). Conclusions: When rest between training sessions is 2 hours, athletes may improve subsequent performance by consuming CHO during recovery.

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