scholarly journals Assessing Patient Preferences for the Benefits and Risks of Treating for Acute Myeloid Leukemia (AML): A Pilot Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4799-4799 ◽  
Author(s):  
Jaein Seo ◽  
B. Douglas Smith ◽  
Elihu H. Estey ◽  
Ernest S. Voyard ◽  
Bernadette O'Donoghue ◽  
...  
Keyword(s):  
Pilot Study ◽  
Side Effects ◽  
Patient Preferences ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Z Score ◽  
Short Term ◽  
Stakeholder Committee ◽  
Society Research

Abstract Introduction:Acute Myeloid Leukemia (AML) is a blood cancer which progresses rapidly in the absence of treatment. There have been few advances in the treatment of AML over the last three decades. In 2015 the Leukemia and Lymphoma Society (LLS) initiated a research program to assess patient preferences for AML treatments. The aim of this research was to promote patient-focused drug development and inform future regulatory decisions. We sought to develop and pilot a patient-centered survey instrument to assess patient preferences for the benefits and risks of AML treatments. Methods: Development was informed by a targeted literature review and engagement with an expert stakeholder committee (n=12) to guide the clinical accuracy and relevance of the survey instrument. A community stakeholder committee, consisting of patients with AML and caregivers (n=15), provided information about their experiences with AML and various treatments. They also engaged in pretest interviews to test comprehension and ensure it captured the patient experience. A discrete-choice experiment (DCE) was developed spanning 5 benefits and risks, including event-free survival (EFS), complete remission (CR), time in hospital, short-term side effects, and long-term side effects. This DCE consisted of 16 pairs of hypothetical treatments, with participants being asked to identify which treatment they would prefer in each pair. Results of a pilot study with AML patients and caregivers were assessed by Z-score that were derived from a conditional logistic model regressing each attribute upon their choices. Results: The pilot included 18 patients and 8 caregivers with a mean age of 50 years (range=24-81). Most participants were college educated (n=22), Caucasian (n=19), privately insured (n=21), and employed (n=13). Participants valued CR the most (Z-score=7.95, p<0.001), followed by EFS (5.32, p<0.001). They were most averse to time in hospital (-3.41, p=0.001), followed by long-term side effects (-3.03, p=0.002) and short-term side effects (-1.99, p=0.047), which was marginally significant. Conclusions: This study demonstrates the value of rigorous community engagement in developing survey instruments to measure patient preferences. The results of this pilot study demonstrate the ability of our DCE to measure treatment preferences of AML patients and caregivers. Given this success, we are currently engaged in a nationally study where we will recruit a larger and more diverse sample. The results of this national study will inform drug developers and regulatory decision makers. Disclosures Seo: The Leukemia & Lymphoma Society: Research Funding. Voyard:The Leukemia & Lymphoma Society: Employment. O'Donoghue:The Leukemia & Lymphoma Society: Employment. Bridges:The Leukemia & Lymphoma Society: Research Funding.

scholarly journals Quantifying Patient Preferences for Treatment Outcomes in AML: A Discrete-Choice Experiment

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 718-718
Author(s):  
Daniel R. Richardson ◽  
Jaein Seo ◽  
B. Douglas Smith ◽  
Elihu H. Estey ◽  
Bernadette O'Donoghue ◽  
...  
Keyword(s):  
Side Effects ◽  
Drug Development ◽  
Treatment Outcomes ◽  
Patient Preferences ◽  
Choice Experiment ◽  
Event Free Survival ◽  
Short Term ◽  
Free Survival ◽  
Trade Offs

Abstract Background: Treatment of acute myeloid leukemia (AML) remains a significant challenge: induction chemotherapy is associated with substantial toxicities, and most patients will eventually die related to their disease. While inducing complete remission (CR) has historically been the primary aim of most treatment regimens, it is unknown to what extent patients would be willing to trade-off the chance at remission for other outcomes such as a reduced toxicity profile. Clinicians routinely make such decisions for patients by selecting less intense regimens for elderly patients or those with significant comorbidities, or when remission may not be clinically relevant or likely achievable. Patient preferences for treatment outcomes often inform shared decision making at the bedside and are increasingly recognized by the FDA and industry as a critical aspect to incorporate into drug development. As part of a patient-focused drug development initiative led by The Leukemia & Lymphoma Society (LLS), we sought to quantify patient preferences for treatment outcomes in AML. Methods: In collaboration with diverse stakeholders (including patients, clinicians, industry representatives, and the LLS staff), a survey instrument was developed to quantify patient preferences for treatment outcomes in AML. A discrete-choice experiment (DCE), in which participants made choices between 9 pairs of hypothetical treatments, was utilized with five attributes: event-free survival, complete remission, time in hospital, short-term side effects, and long-term side effects. All attributes were tiered to three clinically relevant levels. A national survey was conducted and analyzed using a conditional logistic regression. Elicited preference weights, reflecting the desirability for individual attributes, were aggregated into preference estimates. Sub-group analysis compared outcomes based on remission status. Results: The survey was sent to 896 patients with AML who were identified through the LLS database. Three-hundred and twenty-two patients participated in the survey; 294 completed the DCE. Most patients were white (89.4%), married (74.7%), college-educated (74.4%), and privately-insured (76.9%). The majority of patients had received an allogeneic stem cell transplant (63.8%) and nearly all (95.0%) were in remission. The mean time since diagnosis was 8.0 years (range = 1 - 40). Mean age was 56.8 years (Standard Deviation = 12.4). Based on the DCE, CR was identified by patients to be the most important attribute (Preference estimates, 10% increase in CR = 1.05, Standard Error (SE) = 0.06), followed by severity of long-term side effects (1-step increase = -0.52, SE = 0.05), event-free survival (6 months increase = 0.29, SE = 0.02), severity of short-term side effects (1-step increase = -0.33, SE = 0.04), and time in hospital (1 month increase = -0.12, SE = 0.03). These preference estimates suggest that patients were willing to accept a 1-step increase in severity of short-term side effects for a 3% increase in chance at CR. Patients would be willing to accept a 5% decrease in the chance at CR for a 1-step decrease in long-term side effects. Patients equivalently valued an additional 3 more months in the hospital to a 3% increase in chance of CR. They valued a 10% increase in chance of CR as approximately the same as 22 months of event-free survival. No differences were seen between patients currently in remission and those not in remission. Patients found the questions easy to understand (79%), easy to answer (68%), and relevant to them (72%). Conclusions: In addition to demonstrating the feasibility of a DCE in eliciting patient preferences and creating the first large dataset of its kind, this study illustrates that AML patients are willing to make trade-offs regarding treatment outcomes. While patients most highly value the chance at CR, they were willing to forgo small increases in the probability of remission to improve other outcomes, especially long-term side effects. Demonstrating patients' willingness to make such trade-offs becomes critical as incremental gains in CR with novel treatments may come with significantly increased toxicities. These data will be important to inform shared decision making, drug development and approval. Prospective studies using DCE may be helpful to guide individual treatment recommendations. Figure. Figure. Disclosures Seo: Evidera/PPD: Employment. O'Donoghue:The Leukemia & Lymphoma Society: Employment. Bridges:The Leukemia & Lymphoma Society: Research Funding.

scholarly journals Understanding the Collateral Damage of Treating Acute Myeloid Leukemia: An Estimate of Patient-Reported Side Effect Rates from a National Survey

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3573-3573
Author(s):  
Norah Crossnohere ◽  
Daniel R. Richardson ◽  
B. Douglas Smith ◽  
Crystal Reinhart ◽  
Bernadette O'Donoghue ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Side Effects ◽  
Hair Loss ◽  
Myeloid Leukemia ◽  
Collateral Damage ◽  
Short Term ◽  
Patient Reported ◽  
Chemo Brain ◽  
Acute Myeloid

Abstract Introduction: Symptom management is considered a top priority of cancer care. Monitoring patient-reported outcomes (PROs) such as side effects of treatment has been shown to improve quality of life and even prolong survival among cancer patients. For regulators, PROs collected from patients and the caregivers who speak for patients when they are too ill or unable to speak for themselves informs patient-focused drug development (PFDD). PFDD is a key-component of the 21st Century Cures Act that aligns FDA, industry, advocacy and academic partners to accelerate medical product development for those who need it most. We sought to understand the prevalence of side effects experienced by people with acute myeloid leukemia (AML) and to assess differences in the report of side effects from patients across the disease trajectory, including those who were deceased or too ill to directly self-report. Methods : We assessed patient reported prevalence of severe short- and long-term side effects from AML treatments as a part of a national survey. Caregiver reports were included so as to capture the experiences of patients who had either passed away from AML or who were too ill to participate. Participants rated their experience with short-term side effects (nausea, infection, mouth sores, diarrhea, hair loss) and long-term side effects (organ dysfunction, neuropathy, fatigue, chemo brain) as 'none,' 'mild,' 'moderate,' or 'severe.' Prevalence of severe side effects was assessed using descriptive statistics, and differences in likelihood of reporting severe side effects were assessed using logistic regression. Results : A total of 1182 eligible participants completed the survey, including 901 patients and 281 caregivers. Participants were an average of 55 years old (SD=13.0), and 12% were non-white minorities. Patient participants had been diagnosed with AML for 7.7 years (SD=4.7), while patients reported on by caregiver participants had been diagnosed for 5.7 years (SD=4.1). Almost all participants received chemotherapy (98%), and one-fifth received radiation (21%). Hair loss was the most common severe short-term side effect among caregivers (68%) as well as patients (79%, p=0.01). Conversely, patients were less likely than caregivers to report a severe infection (29% vs 36%, p<0.001). Patients and caregivers reported similar rates of other short-term side effects, including mouth sores (33 % vs 34%, p=0.22), diarrhea (29% vs 32%, p=0.07), nausea (27% vs 24%, p=0.26), and rash (20% for both; p=0.80). Patients were consistently less likely to report severe, long-term side effects as compared to caregivers, including fatigue (20% vs 34%, p<0.001), neuropathy (8% vs 15%, p=0.02) and organ dysfunction (5% vs 22%, p<0.001). Patients and caregivers reported similar rates of severe 'chemo brain' (11% vs 15%, p=0.43). Conclusions: AML patients of diverse disease stages experience side effects as well as long-lasting collateral damage from treatments. PRO measures can collect important prevalence data for these events. As compared to their healthier patient counterparts, caregivers reporting on deceased or ill patients demonstrated similar rates of severe short-term side effects, but higher rates of long-term, collateral damages from their treatment. Despite the difficulty in objective quantification, that over 10% of the sample reported severe 'chemo brain' validates the disease community's continued interest in better understanding this experience through PFDD. Disclosures Bridges: The Leukemia & Lymphoma Society: Research Funding.

Determinants of Anthropometric Failure Among Tribal Children Younger than 5 Years of Age in Palghar, Maharashtra, India

2021 ◽  
Vol 42 (1) ◽  
pp. 55-64
Author(s):  
Angeline Jeyakumar ◽  
Swapnil Godbharle ◽  
Bibek Raj Giri
Keyword(s):  
Odds Ratio ◽  
Composite Index ◽  
Z Score ◽  
Short Term ◽  
Cross Sectional Survey ◽  
Crude Odds Ratio ◽  
Cross Sectional ◽  
Independent Variables ◽  
Child Undernutrition

Background: Measuring undernutrition using composite index of anthropometric failure (CIAF) and identifying its determinants in tribal regions is essential to recognize the true burden of undernutrition in these settings. Objective: To determine anthropometric failure and its determinants among tribal children younger than 5 years in Palghar, Maharashtra, India. Methods: A cross-sectional survey employing CIAF was performed in children <5 years to estimate undernutrition in the tribal district of Palghar in Maharashtra, India. Anthropometric measurements, maternal and child characteristics were recorded from 577 mother–child pairs in 9 villages. Results: As per Z score, prevalence of stunting, wasting, and underweight were 48%, 13%, and 43%, respectively. According to CIAF, 66% of children had at least one manifestation of undernutrition and 40% had more than one manifestation of undernutrition. Odds of anthropometric failure were 1.5 times higher among children of mothers who were illiterate (adjusted odds ratio [AOR] =1.57, 95% CI: 1.0-2.3), children who had birth weight >2.5 kg had lesser odds (AOR: 0.63, 95% CI: 0.4-0.9) of anthropometric failure, and children who had initiated early breastfeeding had 1.5 times higher odds of anthropometric failure (crude odds ratio: 1.5, 95% CI: 1.0-2.1). However, when adjusted for other independent variables, the results were not significant. Conclusion: The alarming proportion of anthropometric failure among tribal children calls for urgent short-term interventions to correct undernutrition and long-term interventions to improve maternal literacy and awareness to prevent and manage child undernutrition.

scholarly journals Long-Term Sustained Responses Following Ibrutinib Discontinuation after Frontline Therapy with Obinutuzumab Plus Ibrutinib in Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-34
Author(s):  
Paula A. Lengerke Diaz ◽  
Michael Y. Choi ◽  
Eider F. Moreno Cortes ◽  
Jose V. Forero ◽  
Juliana Velez-Lujan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Side Effects ◽  
Chronic Lymphocytic Leukemia ◽  
Disease Progression ◽  
Research Funding ◽  
Lymphocytic Leukemia ◽  
Combination Regimen ◽  
Grade 3

Single oral targeted therapies have emerged as a standard of care in chronic lymphocytic leukemia (CLL). However, accessibility, side effects, and financial burden associated with long term administration limit their clinical use. Mainly, it is unclear in what clinical situation discontinuation of oral therapy can be recommended. The combination of type II anti-CD20 antibody obinutuzumab-Gazyva® with ibrutinib (GI) has shown a significant progression-free survival benefit in patients (pts) with CLL, including those with high-risk genomic aberrations. We conducted a phase 1b/2, single-arm, open-label trial to evaluate the safety and efficacy of GI as first-line treatment in 32 CLL pts. We report the outcome in pts that discontinued ibrutinib (either after 3 years of sustained complete response (CR) as stipulated in the clinical protocol, or due to other reasons). CLL pts enrolled in this protocol were ≥65 years old, or unfit/unwilling to receive chemotherapy. Pts received GI for six cycles, followed by daily single-agent ibrutinib. The protocol was designed to ensure that pts with a sustained CR after 36 months were allowed to discontinue ibrutinib. The median age was 66 years (IQR 59-73), and 6% of the evaluated pts had 17p deletion. All pts were able to complete the six planned cycles of obinutuzumab. The combination regimen was well-tolerated, and the most common adverse events (&gt;5% CTCAE grade 3-4) were neutropenia, thrombocytopenia, and hyperglycemia. The rate and severity of infusion-related reactions (IRR) were much lower than expected (Grade≥ 3, 3%), and pts without IRR had lower serum levels of cytokines/chemokines CCL3 (P=0.0460), IFN-γ (P=0.0457), and TNF-α (P=0.0032) after infusion. The overall response rate was 100%, with nine pts (28%) achieving a CR, and four pts (12.5%) with undetectable minimal residual disease (uMRD) in the bone marrow, defined as &lt;10-4 CLL cells on multicolor flow cytometry. At a median follow-up of 35.5 months (IQR 24.5-42.7) after starting treatment, 91% of the enrolled pts remain in remission with a 100% overall survival. Sixteen pts have completed a long-term follow-up of 36 months. Six pts showed CR, with three of them achieving uMRD in the bone marrow. Ten of these pts were in PR, and only one had disease progression and started treatment for symptomatic stage I disease with obinutuzumab plus venetoclax. In total, thirteen pts (41%) have stopped ibrutinib, with a median time on treatment prior to discontinuation of 35 months. Five (16%) of these pts had CRs and discontinued after 36 months. Eight additional pts (25%) had PRs and discontinued ibrutinib without being eligible: three pts discontinued prior to 36 months due to toxicities, and five pts discontinued after 36 months (3 due to side effects, and 2 due to financially driven decision). One patient eligible to discontinue ibrutinib, decided to remain on treatment despite sustained CR. After a median follow up time following ibrutinib discontinuation of 8 months (IQR 3.5-17), only two out of 13 pts have progressed (10 and 17 months after Ibrutinib discontinuation). None of the pts that stopped ibrutinib after achieving a CR have shown signs of disease progression. Of note, the pharmaceutical sponsor provided ibrutinib for the first 36 months, after which pts or their insurer became financially responsible. This particular scenario could bias the discontinuation pattern compared to a real world experience. It also provided us with a perspective about diverse factors affecting the treatment choices of pts. In summary, the obinutuzumab plus ibrutinib combination therapy was well-tolerated, with a much lower IRR rate. Efficacy compares favorably with historical controls with all pts responding to therapy, no deaths associated with treatment or disease progression, and a longer than expected time-to-progression after discontinuation of ibrutinib. The rate of ibrutinib discontinuation was higher than reported in the literature, most likely influenced by the protocol design and financial decisions driven by the switch from sponsor-provided ibrutinib to insurance or self-paid medication. Our observations regarding safety, efficacy and lack of disease progression after ibrutinib discontinuation are encouraging, and warrant confirmation in long-term prospective studies. Clinicaltrials.gov Identifier NCT02315768. Funding: Pharmacyclics LLC. Disclosures Choi: AbbVie: Consultancy, Speakers Bureau. Amaya-Chanaga:AbbVie: Ended employment in the past 24 months, Other: Research performed while employed as an investigator of this study at UCSD.. Kipps:Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Castro:Kite Pharma: Research Funding; Pharmacyclics: Research Funding; Fate Therapeutics: Research Funding.

Antimicrobial Applications of Nanoparticles

2022 ◽  
pp. 269-288
Author(s):  
Ayesha Kanwal ◽  
Zeeshan Ahmad Bhutta ◽  
Ambreen Ashar ◽  
Ashar Mahfooz ◽  
Rizwan Ahmed ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Side Effects ◽  
Antibacterial Agent ◽  
Antibacterial Agents ◽  
The Other ◽  
Drug Resistant ◽  
Short Term ◽  
Human Mortality ◽  
Recent Developments

Human mortality due to drug-resistant infections is becoming more prevalent in our society. Antibiotics are impotent due to abuse and/or misuse, leading to new, more expensive, and more effective medicines and treatments. Therefore, it causes many short-term and long-term side effects in the patient. On the other hand, nanoparticles have exhibited antibacterial activity against various pathogens due to their small size and ability to destroy cells by various mechanisms. Unlike antibiotics for the treatment of patients' diseases and infections, nanomaterials provide an exciting way to limit the growth of microorganisms due to infections in humans. This has led to the development of a number of nanoparticles as active antibacterial agents. Therefore, the authors have carefully reviewed the recent developments in the use of nanomaterials for antibacterial applications and the mechanisms that make them an effective alternate antibacterial agent.

Differential Effects of Worry and Imagery After Exposure to a Stressful Stimulus: A Pilot Study

1995 ◽  
Vol 23 (1) ◽  
pp. 45-56 ◽  
Author(s):  
Gillian Butler ◽  
Adrian Wells ◽  
Hilary Dewick
Keyword(s):  
Pilot Study ◽  
Emotional Processing ◽  
Long Term Effects ◽  
Short Term ◽  
Differential Effects ◽  
Short And Long Term ◽  
Intrusive Cognitions ◽  
Stressful Stimulus ◽  
Do So

Imagery appears to be associated with higher levels of anxiety than does worry. Borkovec has argued that worry could be a way of avoiding distressing imagery and the associated affect. Thus worry could suppress emotional activation, interfere with emotional processing, and contribute to the maintenance of anxiety. This hypothesis suggests that short and long-term effects of worrying after experiencing a distressing stimulus should differ from the effects of engaging in imagery. In the short term, imagery should maintain anxiety while worry should not do so, or should do so less. In the longer term, worry should be a less successful way of reducing anxiety associated with the stimulus than imagery, and should be followed by a greater number of intrusive cognitions (indicating the relative failure of emotional processing). These predictions were tested by asking subjects to worry, engage in imagery or “settle down” after watching a distressing video. The results were broadly consistent with the hypothesis. Other interpretations are also considered.

Efficacy and safety of percutaneous administration of dihydrotestosterone in children of different genetic backgrounds with micropenis

2017 ◽  
Vol 30 (12) ◽  
Author(s):  
Dan Xu ◽  
Liangsheng Lu ◽  
Li Xi ◽  
Ruoqian Cheng ◽  
Zhou Pei ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Side Effects ◽  
Low Doses ◽  
Efficacy And Safety ◽  
Short Term ◽  
Term Study ◽  
Long Term Study ◽  
Percutaneous Administration ◽  
Open Prospective Study

AbstractBackground:Exogenous androgen supplement is an optional treatment for micropenis; however, its use in childhood is controversial due to potential side effects.Methods:Twenty-three children (mean age: 4.07±3.4 years) with micropenis of unknown causes harboring the 46,XY karyotype were recruited in an open prospective study. Androgen receptor (Results:Two patients were found withConclusions:Short term and local application of DHT at low doses in patients with micropenis could accelerate penile growth effectively without evident side effects; however, precautions still need be taken due to the paucity of long term study and the lack of ideal DHT dosage.

scholarly journals Short-term and long-term treatment with propafenone: determinants of arrhythmia suppression, persistence of efficacy, arrhythmogenesis, and side effects in patients with symptoms.

Heart ◽  
1992 ◽  
Vol 67 (6) ◽  
pp. 491-497 ◽  
Author(s):  
M Zehender ◽  
S Hohnloser ◽  
A Geibel ◽  
A Furtwangler ◽  
M Olschewski ◽  
...  
Keyword(s):  
Side Effects ◽  
Term Treatment ◽  
Short Term ◽  
Long Term Treatment

scholarly journals New Scheme of Intermittent Benznidazole Administration in Patients Chronically Infected with Trypanosoma cruzi: a Pilot Short-Term Follow-Up Study with Adult Patients

2015 ◽  
Vol 60 (2) ◽  
pp. 833-837 ◽  
Author(s):  
María Gabriela Álvarez ◽  
Yolanda Hernández ◽  
Graciela Bertocchi ◽  
Marisa Fernández ◽  
Bruno Lococo ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Effects ◽  
Liver Enzymes ◽  
Main Criterion ◽  
Short Term ◽  
Follow Up Study ◽  
End Of Treatment ◽  
Chronic Chagas Disease

ABSTRACTThere is a clinical need to test new schemes of benznidazole administration that are expected to be at least as effective as the current therapeutic scheme but safer. This study assessed a new scheme of benznidazole administration in chronic Chagas disease patients. A pilot study with intermittent doses of benznidazole at 5 mg/kg/day in two daily doses every 5 days for a total of 60 days was designed. The main criterion of response was the comparison of quantitative PCR (qPCR) findings prior to and 1 week after the end of treatment. The safety profile was assessed by the rate of suspensions and severity of adverse effects. Twenty patients were analyzed for safety, while qPCR was tested for 17 of them. The average age was 43 ± 7.9 years; 55% were female. Sixty-five percent of treated subjects showed detectable qPCR results prior to treatment of 1.45 (0.63 to 2.81) and 2.1 (1.18 to 2.78) parasitic equivalents per milliliter of blood (par.eq/ml) for kinetoplastic DNA (kDNA) qPCR and nuclear repetitive sequence satellite DNA (SatDNA) qPCR, respectively. One patient showed detectable PCR at the end of treatment (1/17), corresponding to 6% treatment failure, compared with 11/17 (65%) patients pretreatment (P= 0.01). Adverse effects were present in 10/20 (50%) patients, but in only one case was treatment suspended. Eight patients showed mild adverse effects, whereas moderate reactions with increased liver enzymes were observed in two patients. The main accomplishment of this pilot study is the promising low rate of treatment suspension. Intermittent administration of benznidazole emerges a new potential therapeutic scheme, the efficacy of which should be confirmed by long-term assessment posttreatment.

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