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Methods | Across three double-blind, placebo-controlled, within-subject experiments, cocaine (0, 125, 250 mg/70 kg; | PMC10006272 | ||
Results | Data were well modeled by the demand curve function, with significantly higher intensity (purchasing at low prices) for active drug doses compared to placebo for all experiments. Unit-price analyses revealed more persistent consumption across prices (lower | PMC10006272 | ||
Conclusions | Orderly demand curve data revealed differences across drug and placebo conditions, and relations to real-world measures of drug spending, and subjective effects. Unit-price analyses enabled parsimonious comparisons across doses. Results lend credence to the validity of the Blinded-Dose Purchase Task, which allows for c... | PMC10006272 | ||
Supplementary Information | The online version contains supplementary material available at 10.1007/s00213-023-06334-6. | PMC10006272 | ||
Keywords | PMC10006272 | |||
Introduction | substance-related | Behavioral economics offers a broad framework for understanding how the behavior of an organism is maintained by reinforcers (Hursh, In a standard laboratory preparation, demand curves are generated with fixed-ratio (FR) schedules to model the price of a commodity, often a drug (e.g., Johnson & Bickel, Simulated purcha... | PMC10006272 | |
Methods | PMC10006272 | |||
Compliance with ethical standards | Johns Hopkins University Institutional Review Board approved these studies, and these studies were performed in accordance with the 1964 Declaration of Helsinki. Participants provided their written informed consent. | PMC10006272 | ||
Participants | Secondary data were drawn from three separate experimental laboratory decision-making protocols involving double-blind drug administration of either cocaine hydrochloride (Demographic characteristics across cocaine, methamphetamine, and alcohol studiesVariables reported as mean (± | PMC10006272 | ||
Cocaine administration study participants | Participation criteria have been reported in detail previously (Johnson et al., | PMC10006272 | ||
Methamphetamine administration study participants | Participation criteria have been reported in detail previously (Berry et al., | PMC10006272 | ||
Alcohol administration study participants | Participation criteria have been reported in detail previously (Johnson et al., | PMC10006272 | ||
General laboratory procedures | Each of these studies consisted of double-blind, randomized, within-subject, placebo-controlled sessions involving nontreatment-seeking individuals. Study duration consisted of three experimental laboratory sessions for the cocaine and methamphetamine groups (placebo and two active doses) and two experimental laborator... | PMC10006272 | ||
Drug administration procedures | For each study, the drugs were prepared in an onsite pharmacy. Subjective drug effects were assessed throughout the session (see primary sources for each study’s time course and additional session timing details). The Blinded-Dose Purchase Task (described in more detail below) was administered at the end of the session... | PMC10006272 | ||
Cocaine | During three drug administration sessions, participants orally ingested, with water, a size 00 opaque capsule containing either 0 (placebo), 125 mg/70 kg, or 250 mg/70 kg of cocaine hydrochloride. Across sessions, the capsules appeared identical and were each filled completely with a combination of cellulose and/or coc... | PMC10006272 | ||
Methamphetamine | During three drug administration sessions, participants orally ingested, with water, a size 00 opaque capsule containing either 0 (placebo), 20 mg, or 40 mg of d-methamphetamine hydrochloride (Mylan, Inc.) and cellulose. Across sessions, the capsules appeared identical. Each participant received each condition once acr... | PMC10006272 | ||
Alcohol | Placebo- and alcohol-containing solutions were prepared in an onsite pharmacy. A weight-based administration procedure was used to determine the volume of a 1 g/kg alcohol dose (USP 95% ethanol; Letco Medical, Decatur, AL) or water to be mixed in grapefruit juice. Total solution volume was determined per bodyweight so ... | PMC10006272 | ||
Assessments | PMC10006272 | |||
Substance use patterns and subjective drug effects | Information about individual patterns of substance use was obtained during the in-person screening and the following three variables were selected for analysis for insight into real-world use and spending behavior: (1) the average amount of money participants spent on the substance (or drug class) per week in the last ... | PMC10006272 | ||
The Blinded-Dose Purchase Task | At the end of each session, participants in the cocaine and methamphetamine groups completed a blinded purchasing task for hypothetical capsules of that morning’s randomized dose (oral placebo, 125 mg/70 kg, or 250 mg/70 kg for cocaine hydrochloride; oral placebo, 20 mg, or 40 mg for d-methamphetamine hydrochloride). T... | PMC10006272 | ||
Data analysis | Orderliness of dose purchasing task data was evaluated according to previously published criteria (Bruner & Johnson, To conform to distributional assumptions of parametric statistical tests, we performed natural-log (ln) transformations on | PMC10006272 | ||
Results | PMC10006272 | |||
Modeling drug purchasing behavior | Simulated purchasing of each day’s dose varied as an inverse function of increases in price across the three studies (see Fig. Left panel: Blinded-Dose Purchase Task demand curves for active and placebo doses across the cocaine (top), methamphetamine (middle), and alcohol (bottom) studies. Error bars represent standard... | PMC10006272 | ||
Subjective drug effects | There was a significant main effect of dose on peak drug “liking” in the cocaine study (In the methamphetamine study, peak drug “liking” also significantly differed as a function of dose (Finally, in the alcohol study, there were significantly lower ratings of peak “liking” for the placebo than for the 1.0 g/kg active ... | PMC10006272 | ||
Bivariate associations between behavioral economic demand measures, substance use patterns, and subjective drug effects | Correlations describing the degree to which purchase task indices were associated with reported substance use patterns and peak subjective drug effects can be found in Table Bivariate associations between behavioral economic indices, substance use patterns, and peak subjective effectsDrug doses are reported as mg/70 kg... | PMC10006272 | ||
Discussion | Martínez-Loredo | Across all substance administration studies, the Blinded-Dose Purchase Task yielded orderly demand data that showed significantly greater demand in the active dose conditions compared to the placebo conditions using a double-blind, placebo-controlled within-subject design. Demand was significantly correlated with subst... | PMC10006272 | |
Acknowledgements | SWEENEY, BRADLEY | We thank Crystal Barnhouser, Grant Glatfelter, Curtis Bradley, and Katherine Buckheit for protocol assistance; Leticia Nanda, Annie Umbricht, Eric Strain, Andrew Tompkins, and Denis Antoine for medical oversight; and Lauren Nieder for help with manuscript preparation. We also thank Mary M. Sweeney, Evan S. Herrmann, R... | PMC10006272 | |
Author contribution | All authors contributed in a significant way to the manuscript and all authors have read and approved the final manuscript. | PMC10006272 | ||
Funding | ABUSE | We gratefully acknowledge that this research was supported in part by the National Institute on Drug Abuse (NIDA) grants R21DA032717 (MWJ), R01DA032363 (MWJ), and R01DA035277 (MWJ). Support for MSB, GPN, and PSJ was provided by the National Institute on Drug Abuse Grant T32DA007209. MSB gratefully acknowledges that her... | PMC10006272 | |
Declarations | PMC10006272 | |||
Conflict of interest | The authors declare no competing interests. | PMC10006272 | ||
References | PMC10006272 | |||
Background | mantle cell lymphoma | DISEASE, MANTLE CELL LYMPHOMA | Despite high response rates to initial therapy, most patients with mantle cell lymphoma (MCL) experience relapsed or refractory (R/R) disease. Here, we report the efficacy, safety, and pharmacokinetics of the Phase 2, single-arm M20-075 study (NCT04477486) of ibrutinib and venetoclax combination therapy in Japanese pat... | PMC10808627 |
Methods | toxicity | DISEASE, MINIMAL RESIDUAL DISEASE | Patients received 560 mg ibrutinib and 400 mg venetoclax (after a 5-week ramp-up from 20 mg) once daily for up to 104 weeks. Primary endpoint was complete response (CR) rate by independent review committee (IRC). Secondary endpoints included overall response rate (ORR), duration of response (DOR), undetectable minimal ... | PMC10808627 |
Results | Thirteen patients were treated (FAS | PMC10808627 | ||
Conclusion | Ibrutinib plus venetoclax exhibited high response rates and a well-tolerated safety profile in Japanese patients with R/R MCL. | PMC10808627 | ||
Supplementary Information | The online version contains supplementary material available at 10.1007/s10147-023-02443-6. | PMC10808627 | ||
Keywords | PMC10808627 | |||
Introduction | malignant lymphoma, Mantle cell lymphoma | MALIGNANT LYMPHOMA, MANTLE CELL LYMPHOMA | Mantle cell lymphoma (MCL) represents approximately 3% of all malignant lymphoma cases in Japan and occurs more commonly in elderly men [Prior preclinical investigations in MCL models have reported synergistic anti-tumor activity with ibrutinib and venetoclax combination [ | PMC10808627 |
Patients and methods | PMC10808627 | |||
Study design and patients | DISEASE PROGRESSION, DISEASE | M20-075 is an open-label, single-arm, Phase 2 study (NCT04477486). There were 12 sites that participated in the study, of which eight sites enrolled patients. The full eligibility criteria are described in the Supplementary Materials. Briefly, patients aged 20 years or older with pathologically confirmed MCL with at le... | PMC10808627 | |
Treatment and assessments | toxicity, DLTs, non-hematologic | DISEASE PROGRESSION | Patients were administered 560 mg ibrutinib once daily as a fixed dose from initial administration with concurrent venetoclax (starting with a ramp-up period to mitigate the risk of TLS). Venetoclax ramp-up consisted of four dose increases every 7 days: patients received a starting dose of 20 mg, then proceeded to 50 m... | PMC10808627 |
Endpoints | Clinical response was assessed according to the positron emission tomography criteria of the Lugano classification [ | PMC10808627 | ||
Pharmacokinetics | BLOOD | Blood samples were collected on Week 6 Day 1 for the evaluation of venetoclax and ibrutinib PK. Samples were collected pre-dose (0 h) and at 1, 2, 4, 6 and 8 h post-dose. Pharmacokinetic parameters, including peak plasma concentration (C | PMC10808627 | |
Statistical analyses | The FAS was used for all efficacy endpoints (except endpoints based on assessment by IRC), safety, PK, and baseline analysis. The PPS was used for endpoints based on assessment by IRC and used as appropriate for investigator assessment endpoints. The estimate and 95% confidence interval (CI) for the CR rate, ORR, and u... | PMC10808627 | ||
Results | PMC10808627 | |||
Efficacy outcomes | With a median follow-up of 9.6 months, the ORR was 83% (10 of 12 patients in the PPS; 95% CI 51.6–97.9; Fig. Response rates by IRC (per protocol set). Overall response and duration of treatment. Progression-free survival (full analysis set). Overall survival (full analysis set) | PMC10808627 | ||
Pharmacokinetic outcomes | Pharmacokinetic data were available from 11 patients. Two patients discontinued treatment prior to the PK sampling day (Week 6 Day 1), and no PK data were available for those patients. Steady-state plasma concentration versus time profiles for venetoclax and ibrutinib are provided in the data supplement (Supplemental F... | PMC10808627 | ||
Discussion | chronic lymphocytic leukemia | CHRONIC LYMPHOCYTIC LEUKEMIA | The primary efficacy outcome of CR rate (83%) in this study shows statistically significant superiority of venetoclax and ibrutinib compared to ibrutinib monotherapy (historical CR rate of 12.5%) in Japanese patients with R/R MCL [Prior studies have demonstrated the efficacy of ibrutinib and venetoclax as single-agent ... | PMC10808627 |
Acknowledgements | AbbVie and authors thank all the trial investigators and the patients who participated in this clinical trial. Medical writing assistance was provided by Daniel Roybal, PhD, of Bio Connections, LLC and funded by AbbVie Inc. | PMC10808627 | ||
Author contributions | Conception and design: Koji Izutsu, Hideyuki Honda, Sumiko Okubo. Provision of study materials or patients: Hideki Goto, Koji Izutsu, Satoshi Ito, Masahiro Kizaki, Masaki Yamaguchi, Noriko Fukuhara, Koji Kato, Toko Saito. Collection and assembly of data: Sumiko Okubo, Tomomi Soshin, Jiewei Zeng, Mohamed Badawi, Jeremy ... | PMC10808627 | ||
Funding | AbbVie. | PMC10808627 | ||
Declarations | PMC10808627 | |||
Conflict of interest | Venetoclax is being developed in collaboration between AbbVie and Genentech. Ibrutinib is being developed in collaboration between AbbVie and Janssen Research & Development, LLC. The study sponsor funded this study and participated in the study design, research, analysis, data collection, interpretation of data, review... | PMC10808627 | ||
Disclosures | Jiewei, Symbio | ONCOLOGY | Hideki Goto reports lecture fees earned from Kyowa Kirin. Satoshi Ito reports research funding from AbbVie, Amgen, Insight, Novartis, and Zenyaku-Kogyo. Masahiro Kizaki has nothing to declare. Masaki Yamaguchi has nothing to declare. Noriko Fukuhara reports research funding from AbbVie, Bayer, Celgene, Chordia Therapeu... | PMC10808627 |
References | PMC10808627 | |||
Background | SEQUELAE | Edited by: Gilson Dorneles, Hospital Moinhos de Vento, BrazilReviewed by: Bruna Marmett, Hospital Moinhos de Vento, Brazil; Abdel-Hameed Al-Mistarehi, Johns Hopkins Medicine, United StatesThis article was submitted to Digital Public Health, a section of the journal Frontiers in Public HealthNumerous recommendations fro... | PMC9939639 | |
Methods | infection | INFECTION | It was decided to evaluate two forms of hospital rehabilitation: traditional and one provided through virtual reality. Preliminary results are based on a group of 32 patients (20 female and 12 male), of average age 57.8 (4.92) years in the period of 3–6 months after the initial infection. Primary outcomes included anal... | PMC9939639 |
Results | dyspnoea | The analysis of the results showed a statistically significant improvement in both groups with regard to exercise performance expressed as 6MWT distance. Moreover, a statistically significant decrease in dyspnoea levels following the 6MWT was also noted in intergroup comparison, but the between-group comparison reveale... | PMC9939639 | |
Conclusion | SEQUELAE | A 3-weeks inpatients pulmonary rehabilitation program led to improvement of the exercise performance of people with post-acute sequelae of COVID-19, but not lung function. Furthermore, the program was shown to reduce patients' stress levels. A comparison of the traditional form of rehabilitation to the novel form using... | PMC9939639 | |
Introduction | chronic respiratory diseases, SARS-CoV-2 infection, fatigue, shortness of breath | VIRUS, SEQUELAE, SARS-COV-2 INFECTION, CHRONIC RESPIRATORY DISEASE | Over recent years, SARS-CoV-2 infection has been confirmed in millions of people around the world. The virus spreads mainly through the respiratory tract (especially from droplets arising from coughing, sneezing, and talking) and through contaminated surfaces and biological substances (In the initial phase of the epide... | PMC9939639 |
Materials and methods | PMC9939639 | |||
Participants | lung cancer, pneumonia, heart disease, cognitive impairment | PNEUMONIA, HEART DISEASE, POLAND, COVID-19 INFECTION, LUNG CANCER, INSULIN-DEPENDENT DIABETES MELLITUS | The study was conducted among patients with PASC who participated in inpatient pulmonary rehabilitation at the Specialist Hospital in Glucholazy (Poland). These preliminary results included 32 randomly selected patients aged 41–67 years old who met the inclusion criteria and gave written consent to participate in the s... | PMC9939639 |
Intervention | dyspnea, COPD | COPD | A 3-week, five-times-week high-intensity pulmonary rehabilitation program was designed to compare the effectiveness of a traditional form with a VR-led, novel form of therapy. Such programs have been shown to produce clinically significant improvements in exercise capacity, dyspnea, quality of life and lung function in... | PMC9939639 |
Exercise training in VR | The VR group conducted endurance training using the “Virtual Park” software developed by STIIMA-CNR. The scenery depicted a sunny island where the participants conducted a bicycle ride enriched with realistic elements and sound effects to simulate real-life situations. The software was linked to the ergometer so the dy... | PMC9939639 | ||
Relaxation in virtual reality | A VR TierOne device (StolgrafVR station for relaxation. | PMC9939639 | ||
Measurement | infection | INFECTION | At baseline, participants completed a self-administered sociodemographic questionnaire. Questions included gender, marital status, place of residence, education, comorbidities, and history of hospitalization for SARS-CoV2 infection. | PMC9939639 |
Functional capacity | The functional capacity assessment included exercise performance (6-minute walk test: 6MWT), spirometry [forced expiratory volume for 1 second (FEV | PMC9939639 | ||
Stress level | The Perceived Stress Scale (PSS-10) is a widely used psychological instrument for measuring the perception of stress (These examinations were performed before the start of rehabilitation and after its completion. | PMC9939639 | ||
Statistical analysis | POLAND | Analyses were performed using Statistica 13 software (StatSoft, Cracow, Poland) and JASP software (JASP Team, Amsterdam, Netherlands) ( | PMC9939639 | |
Results | REGRESSION | The main groups characteristic is presented in Groups characteristic.The analysis of the results showed a statistically significant improvement in both groups with regard to exercise performance expressed as 6MWT distance (CG: Results of the 6-minute walk test.Regarding lung function, the analysis showed essentially no... | PMC9939639 | |
Discussion | cough, desaturation, fatigue, shortness of breath | CRITICAL ILLNESS, COVID-19 INFECTION | In COVID-19 survivors, physical impairment can persist for weeks after COVID-19, such as shortness of breath, desaturation, cough, weakness, and fatigue. Even in the early stages of the pandemic, expert opinions suggested the need for rehabilitation, based on the fact that exercise is feasible and useful in survivors o... | PMC9939639 |
Conclusions | dyspnea | VIRUS, SEQUELAE | From a clinical perspective, this study's results suggest that VR rehabilitation may be an effective intervention for improving exercise performance and reducing dyspnea levels in patients with post-acute sequelae of COVID-19, although VR was not shown to be more effective than standard rehabilitative practices. This i... | PMC9939639 |
Data availability statement | The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. | PMC9939639 | ||
Ethics statement | The studies involving human participants were reviewed and approved by Bioethical Commission Opole Medical Chamber in Opole (Approval Number: 343, 25 November 2021). The patients/participants provided their written informed consent to participate in this study. | PMC9939639 | ||
Author contributions | SR: conceptualization, project administration, and funding acquisition. SR, JS, and RC: methodology. SR and RC: formal analysis. KB, AR, and JS: investigation. SR, AR, and RC: writing—original draft preparation. RC: supervision. All authors: writing—review and editing, meet criteria for authorship as recommended by the... | PMC9939639 | ||
Conflict of interest | The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. | PMC9939639 | ||
Publisher's note | All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or ... | PMC9939639 | ||
References | PMC9939639 | |||
Abstract | PMC10315777 | |||
Background | cancer, GCA, Gastric cardia adenocarcinoma | CANCER, GCA | Gastric cardia adenocarcinoma (GCA) is a highly fatal form of cancer in humans. The aim of this study was to extract clinicopathological data of postoperative patients with GCA from the Surveillance, Epidemiology, and End Results database, analyze prognostic risk factors, and build a nomogram. | PMC10315777 |
Methods | GCA | In this study, the clinical information of 1448 patients with GCA who underwent radical surgery and were diagnosed between 2010 and 2015 was extracted from the SEER database. The patients were then randomly divided into training ( | PMC10315777 | |
Results | REGRESSION | The results of the multivariate Cox regression analysis showed that age, grade, race, marital status, T stage, and log odds of positive lymph nodes (LODDS) were independently associated with cancer‐specific survival in the training cohort. Both the C‐index and AUC values depicted in the nomogram were greater than 0.71.... | PMC10315777 | |
Conclusions | GCA | Race, age, marital status, differentiation grade, T stage, and LODDS are independent predictors of CSS in patients with GCA after radical surgery. Our predictive nomogram constructed based on these variables demonstrated good predictive ability.The nomogram for postoperative patients with GCA we constructed has good pr... | PMC10315777 | |
INTRODUCTION | tumor, death, GCA, malignant tumor, Gastric cardia adenocarcinoma | MALIGNANT TUMOR, TUMOR, GCA, PRIMARY TUMOR | Gastric cardia adenocarcinoma (GCA) is a commonly diagnosed malignant tumor of the digestive tract.The TNM staging system is currently the primary method used to evaluate patient prognosis and guide clinical treatment approaches.The Surveillance, Epidemiology, and End Results (SEER) database covers over 28% of the popu... | PMC10315777 |
METHODS | PMC10315777 | |||
Patient selection | tumors, adenocarcinoma, cardia | TUMORS, GCA, ADENOCARCINOMA, TUMOR METASTASIS | The specific operational process for extracting information from the SEER database is outlined below: (1) Register for a personal account on the SEER database official website and install the SEER*Stat software; (2) Extract clinical data of patients based on the inclusion and exclusion criteria determined in this study... | PMC10315777 |
Variable collection | tumor, death, adenocarcinoma, N0, Cancer | TUMOR, SIGNET RING CELL CARCINOMA, ADENOCARCINOMA, CANCER | According to the instructions provided by the National Cancer Institute, the code data extracted from the SEER database was translated. The external validation cohort data was obtained through the hospital medical record system. The variables collected in this study were mainly divided into three categories: patient‐re... | PMC10315777 |
Statistical analysis | REGRESSION | SPSS (26.0) and R (4.2.2) software were used for statistical analysis and graph plotting. The X‐tile software determined the optimal cutoff value, and continuous variables were transformed into categorical variables accordingly. Categorical variables were compared between groups using the Fisher's exact test or chi‐squ... | PMC10315777 | |
RESULTS | PMC10315777 | |||
Patient characteristics | GCA | Data of 1448 patients with GCA who underwent curative surgery were extracted from the SEER database, and these patients were randomly assigned to a training set (1013 patients) and an internal validation set (435 patients) at a ratio of 7:3. In the training cohort, the median follow‐up time was 41 months, with 3‐year a... | PMC10315777 | |
Independent prognostic factors | tumor | REGRESSION, TUMOR | The univariate Cox regression analysis showed that race, age, marital status, grade, T stage, N stage, tumor size, and LODDS score were related to CSS. To avoid overfitting, LASSO regression was performed using those eight variables. All eight variables were included in the model, as their coefficients were non‐zero (F... | PMC10315777 |
Establishment of the nomogram | REGRESSION | Based on the results of the multivariate Cox regression analysis, a nomogram was established and is presented in Figure Nomogram predicting CSS of the postoperative patients with GCA.Calibration curves of the nomogram for predicting 3‐year CSS (A) and 5‐year CSS (B) in the training set; the calibration curves of the no... | PMC10315777 | |
Risk stratification based on the nomogram | The risk score was calculated using the nomogram, and patients were categorized into low‐risk and high‐risk groups based on the median value as the cutoff point. The Kaplan–Meier plot (Figure Kaplan–Meier curves for the patients in the low‐ and high‐risk groups based on the risk scores. (A) training cohort; (B) interna... | PMC10315777 | ||
DISCUSSION | cancer | CANCER, GCA | Currently, mainstream studies consider the EGJ to be a region that is separate from both the esophagus and the stomach.Our study aimed to construct a nomogram that accurately predicts the prognosis of postoperative patients with GCA at stages I–III based on a multivariate analysis. The C‐index and AUC values were both ... | PMC10315777 |
CONCLUSIONS | GCA | In conclusion, we utilized clinical data from the SEER database to identify factors associated with survival in postoperative patients with GCA at stages I–III. Subsequently, we developed a nomogram that accurately predicted CSS in patients with GCA who underwent radical surgery. Our findings indicate that the nomogram... | PMC10315777 | |
AUTHOR CONTRIBUTIONS | PMC10315777 | |||
CONFLICT OF INTEREST STATEMENT | The authors have no conflict of interest to declare. | PMC10315777 | ||
ETHICS APPROVAL STATEMENT | The First Affiliated Hospital of Zhengzhou University's Medical Ethics Committee examined and approved this study involving human participants (2023‐KY‐0019‐001). | PMC10315777 | ||
PATIENT CONSENT STATEMENT | As this was a retrospective study, no written informed consent was required. | PMC10315777 |
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