Withdrawal Decisions Research Articles

Contextual Modulation of Binary Decisions in Dyadic Social Interactions

The present experimental design allowed binary decisions (i.e., to choose between proactive approaching or withdrawing behavior). These decisions were made on complex social interaction scenarios displayed on videos. The videos were taken from a first-person perspective. They were preceded by one sentence each that provided additional information about the context of the displayed scenario. The sentence preceding the video and the video jointly provided a context of emotional valence. That context varied from trial to trial. We observed that provocative and threatening videos produced predominantly fear and anger responses. Fear was associated with withdrawal decisions, while anger led to approach decisions. Negative contextual information increased the probability of approach decisions in aggressive provocative videos; positive contextual information enhanced the chance of approach decisions in socially positive videos. In neutral situations, displayed in videos, the probability of the approach behavior was reduced in case of negative contextual information. Yet, the probability for approach behavior was increased if positive contextual information preceded neutral videos. Our experimental setup provided a paradigm that can be adapted and accommodated for the examination of future research questions on social decisions in multidimensional, complex social situations.

Foreign Divestment during Postmerger Integration: Antecedents of MNE Foreign Divestment

This study extends research on foreign divestment by considering it within the broader context of corporate restructuring, exploring how MNE M&As affect divestment of foreign affiliates. Drawing from agency and organizational theories, I claim that the postmerger integration process reduces managerial and organizational barriers to foreign divestment and thereby increases the likelihood of foreign divestment. I confirm this prediction using data from a sample of foreign affiliates in Korea during 2006–2019. The positive relationship between MNE M&As and foreign divestment is stronger for majority-owned foreign affiliates, for which managers have made more commitments and therefore are generally less likely to make a withdrawal decision. In contrast, the relationship is weaker when a focal affiliate is the parent MNE’s sole affiliate in a host country.

Attitude of Libyan Pharmacist In Western Regionof Libya Toward Zantac With drawal

Post-marketing drug withdrawals can be associated with various events, ranging from safety issues such as reported deaths or severe side-effects, to a multitude of non-safety problems including lack of efficacy, manufacturing, regulatory or business issues. During the last century, the majority of drugs voluntarily withdrawn from the market or prohibited by regulatory agencies was reported to be related to adverse drug reactions. Understanding the under lying mechanisms of toxicity is of utmost importance for current and future drug discovery. A questioner review about Libyan pharmacist attitude toward Zantac withdrawal in the western region of Libya. Thedata then was evaluated by Microsoft Excel software for analysis. The total number of responses received was 67, and these responses were from different cities in the west of Libya during 6months study 2020. Highlighting the different sources of knowledge regarding the withdrawal decision, 64.1 % got the information through social media. 32.8 % of the pharmacists after getting the information regarding Ranitidine withdrawal returned it to the company from which bought it. 83.6% of the pharmacist when asked about ranitidine cause of drawing clarified that the ranitidine contains carcinogenic substances. 37.3% of participants mentioned that pharmacovigilance means the detection of problems related to drugs after marketing and use by patients. The aim of this work is to know whether Libya really has drug control and how to deal with medicines that are withdrawn from the market by international organizations andto analyze the know ledgeand attitudeof Libyan pharmacists in western region of Libya about Zantac withdrawn from the market. From the results of a questionnaire conducted in the western regions about knowledge and attitude of Libyan pharmacists toward Zantac withdraw from the market, we concluded that a small percentage of Zantac products have been withdrawn and the doctors are still prescribing and pharmacists are dispensing ranitidine, whether it is OTC or POM.

Thalidomide and Dexamethasone Maintenance after Autologous Stem Cell Transplantation in Newly Diagnosed Korean Multiple Myeloma Patients: A Prospective Multi-Center Study in Asia

BackgroundMaintenance is a part of standard practice in multiple myeloma patients receiving induction followed by autologous stem cell transplantation (ASCT). Various regimens including thalidomide, lenalidomide and proteasome inhibitor are used as maintenance treatment. However, few prospective trials have been performed evaluating maintenance treatment in Asian myeloma patients. In this prospective multi-center trial, we evaluated the efficacy and toxicity of thalidomide-based maintenance therapy in Korean myeloma patients.MethodsWe conducted an open-label, prospective, multicenter phase II study. Patients with newly diagnosed multiple myeloma who underwent induction followed by ASCT were enrolled. Patients should not have refractoriness to previous thalidomide if the drug is included in induction regimen, and should have achieved at least partial response (PR) after ASCT. Patients received maintenance treatment of 100mg thalidomide daily for 28 days and 40mg dexamethasone for 4 days. The maintenance therapy was continued for one year unless there were disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was 1-year event-free-survival (EFS). Progression free survival (PFS), overall survival (OS), drug tolerability and safety were also evaluated.ResultsA total of 43 patients were enrolled. One-year EFS rate was 60.47% (95% confidence interval (CI), 44.34-73.26%). Progression-free survival (PFS) was 86.05% at 1-year and 72.09% at 2-year. Overall survival (OS) at 1-year and 2-year was 90.70% and 88.37%, respectively. Among 21 patients who did not acquire complete remission (CR) after ASCT, 4 patients reached CR after maintenance therapy. The maintenance treatment was discontinued in 15 patients (34.9%). The most common cause was adverse events (6 patients) followed by disease progression (4 patients). Rest of the patients terminated the treatment by patient's withdrawal (3 patients) and investigator's decision (2 patients). In each cycle, up to 23.3% of patients experienced dose reduction or delayed medication. Two leading causes of the schedule change were the adverse event and physician's decision. Grade 3 or 4 hematologic adverse events (AE) was upper respiratory infection (20 patients, 46.5%) followed by peripheral neuropathy (19 patients, 44.2%). Among the patients with neuropathy, 2 patients showed more than grade 3 symptom. Two patients showed serious adverse events (pneumonia and fulminant hepatitis). Thromboprophylaxis was performed in 37 patients using aspirin and one patient developed deep vein thrombosis during maintenance.ConclusionsThalidomide and dexamethasone maintenance for transplant eligible, newly diagnosed Korean multiple myeloma patients showed 1-year EFS and OS rate of 60.47% and 90.70% which is similar to the reports from western countries. Thalidomide and dexamethasone were tolerable as maintenance in Asian patients, although high hematologic toxicity draws concern. We concluded that thalidomide-based maintenance therapy is one of suitable option in Asian transplant eligible, newly diagnosed multiple myeloma patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Daratumumab in Combination with Carfilzomib and Dexamethasone in Patients (pts) with Relapsed Multiple Myeloma (MMY1001): An Open-Label, Phase 1b Study

Daratumumab in Combination with Carfilzomib and Dexamethasone in Patients (pts) with Relapsed Multiple Myeloma (MMY1001): An Open-Label, Phase 1b Study

Pembrolizumab Antitumor Activity in Relapsed/Refractory Classical Hodgkin Lymphoma in Keynote-087: Revised Response Criteria for Malignant Lymphoma 2007 Criteria Versus Lugano 2014 Classification

Background: Pembrolizumab, the high-affinity antibody against programmed death 1 (PD-1), demonstrated effective antitumor activity and tolerable safety in patients with relapsed or refractory classical Hodgkin lymphoma (RRcHL) in KEYNOTE-087. The 2014 Lugano classification (Cheson et al. J Clin Oncol . 2014;32:3059-67) for lymphoma provides recommendations designed to improve response evaluation compared with the 2007 Revised Response Criteria for Malignant Lymphoma (Cheson et al. J Clin Oncol. 2007;25:579-86). The Lugano classification assigns more weight to changes seen on positron emission tomography (PET)-computed tomography and introduces the 5-point scale for PET assessment. Whereas Cheson 2007 advised using either an increase in the sum of products of diameters or growth of individual lesions to detect progressive disease (PD), Lugano recognizes that growth of individual lesions is always reflected in the growth of the aggregate value, so the sum need not be evaluated when looking for PD. Bone marrow biopsy is not indicated for routine staging (instead of biopsy for staging, per Cheson 2007), and for fluorodeoxyglucose-avid lymphomas, PET can replace bone marrow biopsy. A comparison of response by Cheson 2007 and Lugano 2014 in KEYNOTE-087 is presented.Methods: The phase 2 multicenter, single-arm KEYNOTE-087 (ClinicalTrials.gov, NCT02453594) study examined the safety and efficacy of pembrolizumab in 3 cohorts of patients with RRcHL. Cohort 1 included patients whose disease progressed after autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); cohort 2, after salvage chemotherapy and BV; cohort 3, after ASCT but who had not received BV after transplantation. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 24 months or until confirmed disease progression, unacceptable toxicity, or investigator or patient decision for withdrawal. Response was assessed every 12 weeks by blinded independent central review (BICR) per the Cheson 2007 criteria and Lugano 2014 classification, with the same reviewers performing both assessments sequentially. Primary end points were safety and objective response rate (ORR) by BICR per Cheson 2007. Key secondary end points included ORR by investigator assessment per Cheson 2007; ORR by BICR per the 2014 Lugano classification; complete response (CR) rate by BICR and investigator review per Cheson 2007 criteria; and CR rate by BICR per the 2014 Lugano classification. All patients who received ≥1 dose of pembrolizumab were included in the analyses. Results from the database cutoff of March 21, 2017, are presented.Results: This study enrolled 210 patients with RRcHL. Baseline characteristics have been reported previously (Chen et al. J Clin Oncol. 2017;35:2125-32). Median follow-up was 15.9 months (range, 1.0-20.9 months). ORR by BICR per Cheson (71%) criteria was similar to that by Lugano classification (73%) (Table). CR rates were slightly higher (25% vs 31%, respectively) and PR rates were slightly lower (47% vs 42%, respectively). ORR by cohort per Cheson was also comparable to that per Lugano classification (cohort 1, 75% and 83%, respectively; cohort 2, 67% for each; cohort 3, 73% and 72%, respectively). Of 150 responders per Cheson, 139 (93%) were responders and 11 (7%) nonresponders per Lugano classification; of 60 nonresponders per Cheson, 45 (75%) were nonresponders and 15 (25%) were responders per Lugano classification. There was 88% agreement between the ORR rates per Cheson 2007 and those per Lugano classification.Conclusions: Pembrolizumab monotherapy demonstrated similarly high ORR rates and higher CR rates across all 3 cohorts of patients with heavily pretreated RRcHL by the Lugano 2014 classification than by the Cheson 2007 criteria. [Display omitted] DisclosuresMoskowitz:Pharmacyclics: Research Funding; Celgene: Consultancy; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Other: Ad Board, Research Funding; Genentech BioOncology: Consultancy. Chen:Genentech: Speakers Bureau; Affimed: Research Funding; Merck: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding; Pfizer: Consultancy; Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding, Speakers Bureau. Armand:Infinity: Consultancy; Merck: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Affimed: Research Funding; Pfizer: Research Funding. Zinzani:Celgene, Roche, Janssen, Gilead, Takeda, BMS, MSD, Servier, Sandoz, Mundipharma: Honoraria; Celgene, Janssen, Gilead, Roche, Takeda, BMS, MSD, Sandoz, Servier, Mundipharma: Speakers Bureau; Merck: Consultancy, Other: Advisory board. Goldmacher:Merck: Employment. Lin:Merck: Employment. Nahar:Merck: Employment. Balakumaran:Merck: Employment, Equity Ownership. Salles:Amgen: Consultancy, Other: Advisory board; Bristol-Myers Squibb: Consultancy, Other: Advisory board; Celgene: Consultancy, Other: Advisory board; Gilead: Consultancy, Other: Advisory board; Janssen: Consultancy, Other: Advisory board; Kite: Consultancy, Other: Advisory board; Merck: Consultancy, Other: Advisory board; Morphosys: Consultancy, Other: Advisory board; Novartis: Consultancy, Other: Advisory board; Roche: Consultancy, Other: Advisory board, Research Funding; Servier: Consultancy, Other: Advisory board.

Pembrolizumab (pembro) monotherapy for previously untreated advanced hepatocellular carcinoma (HCC): Phase 2 KEYNOTE-224 study.

4074 Background: Results from cohort 1 of KEYNOTE-224, an open-label, single-arm, multi-country phase 2 trial, demonstrated that pembro monotherapy was efficacious and tolerable in patients (pts) with advanced HCC previously treated with sorafenib. Here, we report results from KEYNOTE-224 cohort 2, which enrolled pts with advanced HCC and no prior systemic therapy. Methods: Eligible pts in cohort 2 had radiologically, histologically, or cytologically confirmed, incurable HCC not amenable or refractory to locoregional therapy, Child Pugh A liver disease, measurable disease based on RECIST 1.1 by blinded independent central review (BICR), ECOG PS 0-1, and BCLC stage C or B. Pts received pembro 200 mg IV Q3W for ̃2 years or until disease progression, unacceptable toxicity, consent withdrawal, or investigator decision. Primary endpoint was ORR (RECIST 1.1 by BICR). Secondary endpoints included DOR, DCR, TTP, PFS, OS, and safety/tolerability. Response was assessed every 9 weeks. Efficacy and safety were assessed in pts who received ≥1 dose of study treatment. DOR was assessed in responders. The estimate and 95% CI of the ORR and DCR were based on the Clopper-Pearson method. Kaplan-Meier method was used to estimate OS, PFS, and DOR. A sample size of ̃50 pts was chosen to provide acceptable precision for the assessment of ORR. Results: Cohort 2 enrolled 51 pts. The median time from the first dose to data cutoff (July 31, 2020) was 21 (range, 17-23) mo. The median age of pts was 68 (range, 41-91) years, one pt was HBV+, 80% had alcohol use, 8% were HCV+, 18% had vascular invasion, 35% had extrahepatic disease, 33% had BCLC Stage B disease, and 67% had BCLC Stage C HCC. ORR was 16% (95% CI, 7-29) and was similar across most subgroups. Median DOR was not reached (range, 3-20+ mo); 70% were estimated to have response duration ≥12 mo. Best overall responses were 0 CR, 8 (16%) PRs, 21 (41%) SDs, and 17 (33%) PDs; response was not evaluable or not assessed for 5 (10%) pts. DCR was 57%. The median TTP was 4 (95% CI, 3-8) mo. The median PFS was 4 (95% CI, 2-6) mo, and median OS was 17 (95% CI, 8-NA) mo. PFS rate at 18 mo was 16%, and OS rate at 18 mo was 46%. Treatment-related AEs (TRAEs) occurred in 27 (53%) pts; the most common TRAEs were diarrhea, fatigue, hypothyroidism, and myalgia. Grade ≥3 TRAEs occurred in 7 (14%) pts. TRAEs led to treatment discontinuation in 6% of pts. Immune-mediated AEs and infusion reactions occurred in 11 (22%) pts. One treatment-related death occurred due to myocarditis, with associated immune-related hepatitis. Conclusions: In pts with advanced HCC and no prior systemic therapy, pembro monotherapy provided durable anti-tumor activity, promising overall survival, and demonstrated a safety profile consistent with that previously observed for pembro in advanced HCC. These findings support further evaluation of pembro-based regimens for the treatment of HCC in the frontline setting. Clinical trial information: NCT02702414.

Predictors of Short-term Survival in Cardiogenic Shock Patients Requiring Left Ventricular Support Using the Impella CP or 5.0

BackgroundPercutaneous ventricular assist devices (pVADs) have been used to support patients who are in cardiogenic shock (CS). There is limited data on 30-day mortality predictors in patients supported by an Impella pVAD. MethodsAll CS patients requiring left-sided Impella implantation in Harefield Hospital (Greater London, United Kingdom) between 2017 and 2020 were included in the current study. Logistic regression analysis was used to identify predictors of 30-day mortality. ResultsA total of 92 patients were included. The mean age was 53.8 ± 14.9 years, and 78.3% were male. CS etiology was predominantly acute coronary syndromes (44.6%), followed by decompensated dilated cardiomyopathy (28.3%). Survival at 30 days was 63% (58 of 92). Deceased patients had a lower left ventricular ejection fraction (LVEF) (15.1 ± 9.6 vs 21.8 ± 14.2, P < 0.001), higher serum lactate levels (2.8[1.6 to 5.4] vs 1.45 [1.08 to 3.53], P = 0.012), a higher percentage of prolonged invasive ventilation (> 24 hours) (64.7% vs 13.8%, P < 0.001), and worse renal and liver function. Serum lactate, baseline LVEF, and prolonged ventilation (> 24 hours) were independent predictors of 30-day survival with an area under the curve of 0.85 (95% confidence interval 0.769 to 0.930), P < 0.001. ConclusionsIn the current retrospective registry of patients requiring Impella pVAD implantation, independent 30-day mortality predictors included serum lactate, baseline LVEF, and prolonged invasive ventilation (> 24 hours). These parameters could highlight patients who would benefit from earlier mechanical circulatory support escalation or neurologic assessment to inform withdrawal decisions.

Pairwise Comparison in Repeated Scores-Application in Palliative Cancer Patients

In clinical studies, subjects or patients might be exposed to a succession of diagnostic tests or medication over time and interest is on determining whether there is progressive remission of conditions, disease or symptoms that have measured collectively as quality of life or outcome scores. In addition, subjects or study participants may be required, perhaps early in an experiment, to improve significantly in their performance rates at the current trial relative to an immediately preceding trial, otherwise the decision of withdrawal or dropping out is ineviTable. The common research interest would then be to determine some critical minimum marginal success rate to guide the management in decision making for implementing certain policies. Success rates lower than the minimum expected value would indicate a need for some remedial actions. In this article, a method of estimating these rates is proposed assuming the requirement is at the second trial of any particular study. Pairwise comparisons of proportions of success or failure by subjects is considered in repeated outcome measure situation to determine which subject or combinations is responsible for the rejection of the null hypothesis. The proposed method is illustrated with the help of a dataset on palliative care outcome scores (POS) of cancer patients.

Withdrawal of Combination Immunotherapy in Paediatric Inflammatory Bowel Disease-An International Survey of Practice.

To assess current practices around the use of combination immunosuppression in paediatric inflammatory bowel disease (PIBD) with a focus on the subsequent withdrawal process. A web-based, 43-question survey. Surveys were completed by 70 paediatric gastroenterologists (PGs) from 27 nations across Europe, North America, Oceania and Asia from 62 centres covering approximately 15,000 PIBD patients (median of 200 patients [interquartile range (IQR) 130-300] per centre). Routine use of co-immunosuppression was significantly higher with infliximab (IFX) versus adalimumab (ADL) ([61/70, 87.1%] compared with [23/70, 32.9%]; P < 0.01). Thiopurines (azathioprine [AZA] or 6-mercaptopurine) were the preferred option overall for co-immunosuppression. They were favoured with either IFX or ADL (76% and 77%, respectively) and in both ulcerative colitis (UC) and Crohn disease (CD) (84% and 69%) compared with methotrexate (MTX).Immunomodulators were the preferred choice as the initial drug to be withdrawn from the combination therapy rather than anti-tumour necrosis factor-alpha (anti-TNFα) therapy (59/67, 88% [P < 0.01]). The most common withdrawal time was after 6-12 months, with this decision usually based on clinical assessment rather than a scheduled withdrawal time (51/67, 76% vs 16/67, 24%). Indicators of mucosal healing and therapeutic drug monitoring results tended to be the most important "clinical factors" in the withdrawal decision (P = 0.05). Most PG's favour initial withdrawal of immunomodulator (usually thiopurines) rather than biologic therapy in the step-down process, usually after 6-12 months based on sustained clinical remission. This survey precedes an in-depth, multicentre study of clinical outcomes of withdrawal of co-immunosuppression in PIBD.

An Intrastate Approach to the Withdrawal from International Organizations

Abstract When international organizations take measures that seem to go against the national interests of a Member State, is withdrawal inevitable? What do past cases reveal about how the extreme decision of withdrawal has been contained? This article examines the case of Brazil and the Inter-American Commission on Human Rights, which is part of the Organization of American States (OAS). Having received a harsh decision by the Commission, Brazil first threatened to leave OAS, but later mobilized diplomatic strategies to reform its Commission. What happened between a first reaction that considered withdrawal and the final decision to work to reform the system? The article advances the argument that containing international organization withdrawal benefits from the convergence and mutual reinforcement provided by internationally engaged institutions, bureaucrats committed to multilateralism, and a democratic leadership. The case helps to recognize the relevant intrastate variables that play out in the decision-making process that may eventually lead to withdrawal.

Pembrolizumab (pembro) monotherapy for previously untreated advanced hepatocellular carcinoma (HCC): Phase II KEYNOTE-224 study.

297 Background: Results from cohort 1 of KEYNOTE-224, an open-label, single-arm, multi-country phase II trial, demonstrated that pembro monotherapy was efficacious and tolerable in patients (pts) with advanced HCC previously treated with sorafenib. Here, we report results from KEYNOTE-224 cohort 2, which enrolled pts with advanced HCC and no prior systemic therapy. Methods: Eligible pts in cohort 2 had radiologically, histologically, or cytologically confirmed, incurable HCC not amenable or refractory to locoregional therapy, Child Pugh A liver disease, measurable disease based on RECIST 1.1 by blinded independent central review (BICR), ECOG PS 0-1, and BCLC stage C or B. Pts received pembro 200 mg IV Q3W for ~2 years or until disease progression, unacceptable toxicity, consent withdrawal, or investigator decision. Primary endpoint was ORR (RECIST 1.1 by BICR). Secondary endpoints included DOR, DCR, TTP, PFS, OS, and safety/tolerability. Response was assessed every 9 weeks. Efficacy and safety were assessed in pts who received ≥1 dose of study treatment. DOR was assessed in responders. The estimate and 95% CI of the ORR and DCR were based on the Clopper-Pearson method. Kaplan-Meier method was used to estimate OS, PFS, and DOR. A sample size of ~50 pts was chosen to provide acceptable precision for the assessment of ORR. Results: Cohort 2 enrolled 51 pts. The median time from the first dose to data cutoff (July 31, 2020) was 21 (range, 17-23) mo. The median age of pts was 68 (range, 41-91) years, one pt was HBV+, 80% had alcohol use, 8% were HCV+, 18% had vascular invasion, 35% had extrahepatic disease, 33% had BCLC Stage B disease, and 67% had BCLC Stage C HCC. ORR was 16% (95% CI, 7-29) and was similar across most subgroups. Median DOR was not reached (range, 3-20+ mo); 70% were estimated to have response duration ≥12 mo. Best overall responses were 0 CR, 8 (16%) PRs, 21 (41%) SDs, and 17 (33%) PDs; response was not evaluable or not assessed for 5 (10%) pts. DCR was 57%. The median TTP was 4 (95% CI, 3-8) mo. The median PFS was 4 (95% CI, 2-6) mo, and median OS was 17 (95% CI, 8-NA) mo. PFS rate at 18 mo was 16%, and OS rate at 18 mo was 46%. Treatment-related AEs (TRAEs) occurred in 27 (53%) pts; the most common TRAEs were diarrhea, fatigue, hypothyroidism, and myalgia. Grade ≥3 TRAEs occurred in 7 (14%) pts. TRAEs led to treatment discontinuation in 6% of pts. Immune-mediated AEs and infusion reactions occurred in 11 (22%) pts. One treatment-related death occurred due to myocarditis, with associated immune-related hepatitis. Conclusions: In pts with advanced HCC and no prior systemic therapy, pembro monotherapy provided durable anti-tumor activity, promising overall survival, and demonstrated a safety profile consistent with that previously observed for pembro in advanced HCC. These findings support further evaluation of pembro-based regimens for the treatment of HCC in the frontline setting. Clinical trial information: NCT02702414.

Fear Induced on Withdrawal Decisions in Mexican Hysterectomized Patients and the Suppressive Effects: Case Report

In the current research paper the important effects of suppression were analyzed, specifically the suppressive effects of surgical removal of organs. Due to the high incidence of pre-menopausal women who decide to remove their uterus prophylactically, there is a large number of harmful effects of such removal in the practice of homeopaths. The fear (alleged high probability) of having cancer expressed to their patients by many of the gynecologists is the main cause of these decisions. phrases have even been created such as: the uterus that no longer bears children, for sure will gives cancer. This analysis was done in the clinical case study format, it is difficult to obtain a sample of patients who want to collaborate in an investigation of this type, we must understand that many of the patients are not related to homeopathy, which reduces the possibility of consulting the complications of hysterectomy. And of the patients who, being desperate for not being cured with allopathic remedies, some of them have resorted to homeopathy to treat themselves. Only 4 of this group agreed to participate in this research. The main purpose was to show the complications (and implications) for the health of women after this kind of surgery. The sample of the cases: four women with hysterectomy, all had the same diagnosis prior to surgery: Uterine Fibroids (Fibroids). This being the main cause of alarm in these patients due to the catastrophic allopathic prognosis that is almost a fashion in medical practice, especially in Western countries. Post-surgery: After a while, they all developed a number of important symptoms as a result of the withdrawal. Something very important to analyze in the present article is the miasmatic diagnosis of the symptoms after surgery. In this article we explain the individualized treatment of each patient through the miasmatic orientation approach that is followed in the school Homeopathy of Mexico. The treatment is explained using the understanding that what is more relevant is the miasmatic. The cases with columns are presented where a seriation of symptoms, this is made according to a technique which pretend detect the predominant miasma in each patient. In this article, we explain the individualized treatment of complications in each patient using the approach of miasmatic orientation. It is explained the individualized treatment using the approach of miasmatic procedure. Finally, the results are commented, and future research are recommended.

Severe type-B lactic acidosis in a patient with bilateral renal Burkitt's lymphoma.

Introduction: Lactic acidosis (LA) can be categorized as type A, which occurs in the presence of tissue hypoxia, or type B, occurring in the absence of tissue hypoxia. Hematologic malignancies are an uncommon cause of type B LA. Case presentation: A 63-year-old man, HIV-negative, with a history of diabetes mellitus, hypothyroidism, and non‐alcoholic fatty liver disease (NAFLD), presented to the ED complaining of acute-on-chronic lumbar pain, and was found to have high serum anion gap (AG) LA. The rest of chemistry and infectious workup was within normal limits. Despite bicarbonate therapy and fluid resuscitation, the patient remained with persistent AG metabolic acidosis and increasing lactic acid up to 14.5 mmol/L. An abdominal computerized tomography (CT) revealed multiple bilateral enhancing lesions in the kidneys, as well as gastric wall thickening. Upper gastrointestinal endoscopy with biopsy showed a high-grade Burkitt’s lymphoma. Further staging showed bone marrow involvement and extensive abdominal adenopathy. After two cycles of inpatient chemotherapy with dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab), the patient developed multifocal pneumonia complicated by respiratory failure. Following a prolonged ICU stay, after discussion with the family members, a decision of withdrawal of life-sustaining therapy was reached. Conclusion: Persistent LA, without identifiable causes of tissue hypoxia, should prompt clinicians to suspect non-hypoxic etiologies, including occult high-grade malignancies. Hematological malignancies constitute an extremely rare cause of type-B LA, carrying a poor prognosis.

Influencing factors of farmers’ homestead withdrawal decision based on the technology acceptance model and perceived risk：Evidence from Chongqing

Influencing factors of farmers’ homestead withdrawal decision based on the technology acceptance model and perceived risk：Evidence from Chongqing

Information Disclosure and Financial Fragility

I study how banks and other financial intermediaries can use information disclosure to prevent self-fulfilling bank runs. I begin with a finite-agent version of Diamond and Dybvig (1983) with correlated liquidity shocks and sequential service. I allow the intermediary to inform each investor about the withdrawal decisions of previous investors. Adding information disclosure creates a withdrawal game with sequential signaling, and I argue using examples that it is natural to introduce an equilibrium concept placing restrictions on agents’ off equilibrium beliefs. I use the concept of forward induction equilibrium (Cho, 1987) that generalizes the “intuitive” criterion. I provide conditions under which the induced withdrawal game has a unique forward induction equilibrium and no bank run occurs. In other words, disclosing withdrawal information can promote financial stability.

Oil price uncertainty and IPOs

We examine the impact of oil price uncertainty on IPO volume in the oil and gas sector. By using the implied volatility of oil options, a forward looking exogenously determined uncertainty measure, we can clearly identify the effect of uncertainty on the going public decision. Oil price uncertainty has a strong negative relation to IPO volume, a one standard deviation decrease in the implied volatility results in a 25%-29% increase in the number of quarterly IPOs. The effect is concentrated among the price sensitive upstream producers. We further report that uncertainty negatively impacts the IPO withdrawal decision and increases the value to postpone the offering.

Geriatric polytrauma patients should not be excluded from aggressive injury treatment based on age alone

PurposeAge in severely injured patients has been increasing for decades. Older age is associated with increasing mortality. However, morbidity and mortality could possibly be reduced when accurate and aggressive treatment is provided. This study investigated age-related morbidity and mortality in polytrauma including age-related decisions in initial injury management and withdrawal of life-sustaining therapy (WLST).MethodsA 6.5-year prospective cohort study included consecutive severely injured trauma patients admitted to a Level-1 Trauma Center ICU. Demographics, data on physiology, resuscitation, MODS/ARDS, and infectious complications were prospectively collected. Patients were divided into age subgroups (< 25, 25–49, 50–69, and ≥ 70 years) to make clinically relevant comparisons.Results391 patients (70% males) were included with median ISS of 29 (22–36), 95% sustained blunt injuries. There was no difference in injury severity, resuscitation, urgent surgeries, nor in ventilator days, ICU-LOS, and H-LOS between age groups. Adjusted odds of MODS, ARDS and infectious complications were similar between age groups. 47% of patients ≥ 70 years died, compared to 10–16% in other age groups (P < 0.001). WLST increased with older age, contributing to more than half of deaths ≥ 70 years. TBI was the most common cause of death and decision for treatment withdrawal in all age groups.ConclusionsPatients ≥ 70 years had higher mortality risk even though injury severity and complication rates were similar to other age groups. WLST increased with age with the vast majority due to brain injury. More than half of patients ≥ 70 years survived suggesting geriatric polytrauma patients should not be excluded from aggressive injury treatment based on age alone.

Konsekwencje brexitu w dziedzinie prawa prywatnego międzynarodowego

Brexit is a unique phenomenon as no Member State has ever expressed the will to leave the European Union. Never before had the in-depth impact of a Member State withdrawal been analysed. The issue has started to be analysed after the referendum in which the British voted in favour of leaving the European Union. The topic of the potential consequences of Brexit in the field of private international law concerns, inter alia, national jurisdiction in civil and commercial matters, mutual recognition and enforcement of judgments, specific procedures of EU uniform law, judicial cooperation between Member States or the functioning of the e-Justice Portal and dynamic forms. Before a given Member State withdraws from the EU, interested parties should have been informed, inter alia, of how pending proceedings will be conducted starting with the withdrawal day, what about proceedings initiated at the date of withdrawal or later on, and what about the rulings of the courts of the applicant state covered by the exequatur procedure before the withdrawal. Therefore, the primary purpose of the article is to determine the framework for the future relationship between the EU and the UK in the field of private international law. An additional aim of this paper is to better prepare natural and legal persons for the new post-Brexit reality. European integration has brought Europe peace and prosperity and enabled unprecedented cooperation in all areas of common interest. Following the withdrawal decision, the state and its citizens cease to benefit from the acquis communautaire. In fact, the United Kingdom left the European Union on 31 January 2020. As far as private international law is concerned, the United Kingdom has become a third country. Subsequently, on 1 February 2020 a transition period has started and it aims to provide more time for citizens and businesses to adapt. The negotiations on the future partnership between the EU and the UK has started in March 2020, but they were postponed due to the coronavirus COVID-19 pandemic. The relationship between the United Kingdom and the European Union is sometimes compared to love that has passed away, but former lovers must continue to meet from time to time to manage certain common affaires. The analysis of the topic leads to the conclusion that, in fact, Brexit is a unique phenomenon that has no added value.

Abstract CT215: RELAY, ramucirumab plus erlotinib (RAM+ERL) versus placebo plus erlotinib (PBO+ERL) in previously untreated EGFR mutation-positive metastatic NSCLC: Next generation sequencing (NGS) results

Abstract RELAY (NCT02411448) showed a superior progression free survival benefit with RAM+ERL versus (v) PBO+ ERL (mPFS 19.4 vs 12.4mo, HR 0.59, p-value &amp;lt;0.0001). We investigated the mutational landscape for potential a) baseline biomarkers and b) treatment emergent (TE) alterations. Eligible patients (untreated metastatic NSCLC, EGFR exon 19 deletion or exon 21 L858R mutation-positive by local testing, ECOG PS of 0 or 1, and without CNS metastases) were randomized to receive ERL (150 mg oral) daily with either RAM (10 mg/kg iv) or PBO Q2W until progressive disease, unacceptable toxicity, withdrawal, non-compliance, or investigator decision. Liquid biopsies (baseline, cycle 4 (C4), and post-treatment discontinuation 30-day follow-up) underwent Guardant360® NGS for pre-specified exploratory biomarker analyses. For baseline analyses, alterations (single nucleotide variants, gene fusions, or copy number changes) in ALK, MET, and TP53 were among the 69 genes with alterations co-occurring at baseline with ex19del or ex21.L858R (not shown). Baseline ALK and MET alterations did not appear to impact the observed PFS or DOR. However, altered baseline TP53 associated with a worse prognosis (p&amp;lt;0.001), and had a trend for better ram efficacy. For evaluating TE alterations, two populations were assessed to address factors like disease progression and ctDNA shedding (footnote). The distribution of TE alterations in the 30-day follow-up samples was similar for RAM+ERL v PBO+ERL (TABLE). Additional results, including associations with baseline characteristics, C4, 30-day follow-up, and PFS will be presented. Understanding the potential clinical impact of co-occurring baseline alterations provides important information to evaluate treatment options. Sample size was limited, but the types and frequency of TE alterations appeared similar between treatment arms. TablePts (≥2 in either treatment group) with treatment emergent alterationsaPop1bPop2bGene NameRAM+ERL (n=36)PBO+ERL (n=60)p-valuecRAM+ERL (n=98)PBO+ERL (n=129)p-valuecEGFRd16 (44)33 (55).3227 (28)47 (36).16TP538 (22)7 (12).1717 (17)16 (12).30NF15 (14)1 (2).027 (7)3 (2).08APC4 (11)1 (2).055 (5)3 (2).26MET3 (8)5 (8)1.006 (6)7 (5).82KRAS2 (6)3 (5).917 (7)3 (2).08FGFR22 (6)2 (3).603 (3)3 (2).73GNAS2 (6)0.052(2)1 (1).41BRAF1 (3)6 (10).163 (3)6 (5).54PI3KA1 (3)4 (7).391 (1)7 (5).06BRCA203 (5).094 (4)6 (5).84ERBB21 (3)3 (5).594 (4)4 (3).69AR02 (3).171 (1)2 (2).73CDK61 (3)2 (3).881 (1)2 (2).73RB11 (3)1 (2).722 (2)3 (2).88CDK41 (3)1 (2).721 (1)2 (2).73SMAD41 (3)1 (2).721 (1)2 (2).73KIT1 (3)1 (2).723 (3)1 (1).19PTEN1 (3)2 (3).882 (2)2 (2).78ARID1A1 (3)1 (2).723 (3)3 (2).73FGFR11 (3)0.162 (2)1 (1).41MAP2K11 (3)0.162 (2)0.07MAPK31 (3)0.162 (2)0.07MTOR01 (2).332 (2)1 (1).41MYC1 (3)0.162 (2)2 (2).78RET00–2 (2)0.07ROS100–2 (2)0.07STK1100–1 (1)2 (2).73Evaluable baseline NGS results were obtained for 390 out of 449 ITT patients (87%).aPts are included in more than one row if alterations arose in more than one gene.bAnalysis population 1 (Pop1, N=96) had disease progression by the 30-day post treatment discontinuation follow-up and had detectable EGFR ex19del or ex21.L858R mutation in baseline and 30 day follow-up blood samples. There is a greater confidence that alterations related to mechanisms of resistance would be detectable in this population since the patients had all progressed by 30-day follow-up and since the EGFR ex19del and ex21.L858R were detectable as shed circulating tumor DNA in the blood. Analysis population 2 (Pop2, N=227) had discontinued study treatment for any reason by the 30-day post treatment discontinuation follow-up and had any alteration detectable at baseline and at 30 day follow-up. Pop2 is a larger population (includes all Pop1 pts) and offers the opportunity to detect less common TE alterations that may not be found in the smaller Pop1. Seven (19%) RAM+ERL v 19 (32%) PBO+ERL of Pop1 and 33 (34%) v 59 (46%) of Pop2 pts had not acquired any of the evaluated alterations.cFisher's exact testdIncludes T790M; the frequencies of TE T790M in RAM+ERL v PBO+ERL for Pop1 were 42% v 50%, respectively, and for Pop2, 19% v 25% Citation Format: Edward Garon, Martin Reck, Kazuto Nishio, John Victor Heymach, Makoto Nishio, Silvia Novello, Luis Paz-Ares, Sanjay Popat, Santiago Ponce Aix, Sameera Wijayawardana, Rebecca R. Hozak, Carla Visseren-Grul, Kazuhiko Nakagawa. RELAY, ramucirumab plus erlotinib (RAM+ERL) versus placebo plus erlotinib (PBO+ERL) in previously untreated EGFR mutation-positive metastatic NSCLC: Next generation sequencing (NGS) results [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT215.