Compassionate Treatment Research Articles

Sociology and Animal Studies: Human Responses to Animal Loss in Times of Disaster

A number of attempts have been made to include animals in explorations in the humanities and social sciences. This is a response to the gap where animals are much-neglected entities in the said disciplines. There have been debates pertaining to the inclusion of animals in scholarly discourses in the field of sociology. Notably, human exceptionalism has been one of the key ideological drivers which prevent a more inclusive consideration of animals in the study of our social world. The anthropocentric view of the world and society has put the needs and status of humans above all other animals. This line of thinking has implications on how humanity relates and interacts with animals in a broader context. In times of crisis, humans relegate animals as conveniently expendable or an inconvenient afterthought, which easily leads to instances of animal abandonment and even abuse. However, there has been a collective shift in the way acts of animal abandonment are perceived on social media. This article examined the responses on social media pertaining to animal abandonment during the onslaught of typhoon Vamco in the Philippines in 2020. More specifically, two themes were analyzed: outrage against negligence and compassionate treatment of animals. While this article looks specifically at the abandonment of animals, the project invites further reflection on the notions of environmental ethics and the species boundary.

Acceptability, Compliance, and Safety of Non-small Cell Lung Cancer Cachectic Participants Continuing Compassionate Access in the ACCeRT Clinical Study

Objective: Cancer cachexia is defined as: a ‘multifactorial syndrome’, and it has been suggested that a multitargeted approach is required in its management. High prevalence is seen within non-small cell lung cancer, and patients may continue to experience cachexia post end of anti-cancer treatment, and in the late/end stage.Material and Methods: Participants who had completed week 20/End of Trial visit in the main Auckland’s Cancer Cachexia evaluating Resistance Training (ACCeRT) study were invited to continue with treatment under compassionate use. Participants could continue with 2.09 g of eicosapentaenoic acid (EPA), 300 mg COX-2 inhibitor (celecoxib), once daily; plus two sessions per week of progressive resistance training (PRT), and 20 g oral essential amino acids (EAA); high in leucine, in a split dose over three days post each session. Data was collected on the acceptability, compliance and adherence to medication/PRT sessions. Secondary endpoints included: change in body weight and fat free mass, handgrip and leg strength, the Functional Assessment of Anorexia/Cachexia Therapy, Multidimensional Fatigue Symptom Inventory-Short Form, World Health Organization Quality of Life — BREF, Glasgow prognostic score, and pro-inflammatory cytokines.Results: All six participants, who completed the main ACCeRT study, opted to continue with compassionate use. Acceptability remained high, with overall compliance to last study/PRT visit of 81.0% for EPA, 98.8% for celecoxib, 78.9% for PRT and 77.2% for EAA. Participants continued to lose body weight and Fat-Free Mass, along with reduced albumin and increased C-Reactive protein levels. Mean time on compassionate study treatment was 78 days, and with a mean overall survival of 257 days (140 + 117).Conclusion: Non-small cell lung cancer (NSCLC) cachectic patients are willing to be enrolled onto a multi-targeted treatment regimen, and may benefit from cachexia symptom management even during their late/refractory stage.

Pandemia COVID-19. ¿Qué hemos aprendido en este tiempo?

Since the COVID-19 pandemic was declared in March 2020, we have learned a lot about the SARS-CoV-2 coronavirus, and its role in pediatric pathology.Children are infected in a rate quite similar to adults, although in most cases they suffer mild or asymptomatic symptoms. Around 1% of those infected require hospitalization, less than 0.02% require intensive care, and mortality is very low and generally in children with comorbidities. The most common clinical diagnoses are upper or lower respiratory infections, gastrointestinal infection and, more seriously, multisystemic inflammatory syndrome (MIS-C). Most episodes do not require treatment, except for MIS-C. Remdesivir has been widely used as a compassionate treatment and its role has yet to be defined.The newborn can become infected, although vertical transmission is very low (<1%) and it has been shown that the baby can safely cohabit with its mother and be breastfed. In general, neonatal infections have been mild.Primary care has supported a very important part of the management of the pandemic in pediatrics. There has been numerous collateral damage derived from the difficulty of access to care and the isolation suffered by children. The mental health of the pediatric population has been seriously affected. Although it has been shown that schooling has not led to an increase in infections, but rather the opposite. It is essential to continue maintaining the security measures that make schools a safe place, so necessary not only for children's education, but for their health in general.

Meeting patients' mental health needs.

Sam Foster, Chief Nurse, Oxford University Hospitals, considers how nurses can provide better care to people with mental health conditions, who are often in a vulnerable position and require compassionate treatment.

1058P Treatment outcomes with unselected autologous tumor infiltrating lymphocytes (TILs) in patients (pts) with checkpoint inhibition–refractory advanced cutaneous melanoma

TIL products made from tumor digests showed a high overall response rate (ORR; 67%) and complete response (CR) rate (19%) and a safety profile consistent with lymphodepletion and high-dose interleukin (IL)-2 in a retrospective analysis of a single-center experience of TILs for compassionate use treatment of advanced cutaneous melanoma (n=21; Hawkins, et al. AACR 2021. ePoster LB150). This subanalysis assesses outcomes for pts who received TILs after prior checkpoint inhibition, a pt subset with limited treatment options.

Compassionate use of anti-IL6 receptor antibodies in critically ill patients with acute respiratory distress syndrome due to SARS-CoV-2.

COVID-19 patients developing the acute respiratory distress syndrome (ARDS) show increased production of pro-inflammatory cytokines, including interleukin-6 (IL-6). The use of humanized monoclonal antibody against interleukin-6 receptor (IL-6R) may represent a potential treatment strategy. We analyzed the effects of compassionate use of tocilizumab and sarilumab on clinical outcome of patients affected by ARDS due COVID-19. This single-center, observational, exploratory study was performed during the acute phase of COVID-19 outbreak, between March 7th and April 21st, 2020 in a University Hospital in Rome, Italy. All consecutive adult patients admitted to the intensive care unit with laboratory-confirmed COVID-19 and fulfilling ARDS criteria were enrolled. Patients who were treated with anti-IL-6R therapy were compared to those who were not, as per clinical decision. Inverse probability weights were applied to weight individual's contribution to survival curves and in the multivariate regression model. Among 105 ARDS patients, 65 received compassionate treatment with anti-IL-6R therapy (43 [66%] Tocilizumab [Hoffmann-La Roche, Basel, Switzerland] and 22 [34%] Sarilumab, respectively], with oxygenation improvement. In the multivariable Cox proportional regression hazards model with propensity score inverse probability weighting, patients who received anti-IL-6R treatment had lower risk of death compared to those who did not, with a hazard ration of 0.34 [95% confidence interval 0.17-0.74], P=0.001. Our data suggested that immune modulator therapy based on anti-human IL-6 receptor monoclonal antibodies might lead to improved outcome in patients with ARDS due to COVID-19. These data support the need for confirmatory randomized trials to assess the effect of immune modulator therapies on mortality.

Functional diagnostics using fresh uncultured lung tumor cells to guide personalized treatments

SummaryFunctional profiling of a cancer patient’s tumor cells holds potential to tailor personalized cancer treatment. Here, we report the utility of fresh uncultured tumor-derived EpCAM+ epithelial cells (FUTCs) for ex vivo drug-response interrogation. Analysis of murine Kras mutant FUTCs demonstrates pharmacological and adaptive signaling profiles comparable to subtype-matched cultured cells. By applying FUTC profiling on non-small-cell lung cancer patient samples, we report robust drug-response data in 19 of 20 cases, with cells exhibiting targeted drug sensitivities corresponding to their oncogenic drivers. In one of these cases, an EGFR mutant lung adenocarcinoma patient refractory to osimertinib, FUTC profiling is used to guide compassionate treatment. FUTC profiling identifies selective sensitivity to disulfiram and the combination of carboplatin plus etoposide, and the patient receives substantial clinical benefit from treatment with these agents. We conclude that FUTC profiling provides a robust, rapid, and actionable assessment of personalized cancer treatment options.

Social Exclusivism Versus Cosmopolitan Acceptance: Competing Constructions of ‘Australian Values’ in Discourse Surrounding People Seeking Asylum

ABSTRACT Australia is highly polarised about its treatment of refugees and asylum seekers, with the available literature indicating that public, political, and media discourse routinely constructs them as culturally incompatible with the broader society. These discourses present refugees and asylum seekers as undesirable ‘others’ and in turn, their deservingness of protection becomes contingent upon arbitrary notions of who gets to belong (and why). Rhetoric about what it means to be Australian pervade these discussions, however little is known about the various linguistic functions these ideas serve. This paper presents the findings arising from Critical Discourse Analysis of interviews with 24 Western Australians. Findings revealed that notions of ‘Australian values’ were regularly called upon to further arguments that both deny and advocate for the nation's acceptance of people seeking asylum. While some constructed ‘Australian values’ as incompatible with asylum seekers’ cultural practices and beliefs, others asserted that open, compassionate, and charitable treatment of people seeking asylum is a key facet of ‘being Australian’. Examined with consideration of the literature on Social Exclusivism and Cosmopolitan Acceptance, I discuss the discursive features of these contrasting ideas, emphasising key implications for both societal and scholarly understandings of Australia’s ongoing asylum debate.

COVID-19: Vaccine Delivery System, Drug Repurposing and Application of Molecular Modeling Approach.

The acute respiratory syndrome coronavirus (SARS-CoV-2) has spread across the world, resulting in a pandemic COVID-19 which is a human zoonotic disease that is caused by a novel coronavirus (CoV) strain thought to have originated in wild or captive bats in the initial COVID outbreak region. The global COVID-19 outbreak started in Guangdong Province, China’s southernmost province. The global response to the COVID-19 pandemic has been hampered by the sheer number of infected people, many of whom need intensive care before succumbing to the disease. The epidemic is being handled by a combination of disease control by public health interventions and compassionate treatment for those who have been impacted. There is no clear anti-COVID-19 medication available at this time. However, the need to find medications that can turn the tide has led to the development of a number of investigational drugs as potential candidates for improving outcomes, especially in the severely and critically ill. Although many of these adjunctive medications are still being studied in clinical trials, professional organizations have attempted to define the circumstances in which their use is deemed off-label or compassionate. It is important to remind readers that new information about COVID-19’s clinical features, treatment options, and outcomes is released on a regular basis. The mainstay of treatment remains optimized supportive care, and the therapeutic effectiveness of the subsequent agents is still being studied.

Compassionate mesenchymal stem cell treatment in a severe COVID-19 patient: a case report

COVID-19 presentations range from cold-like symptoms to severe symptoms with the development of acute respiratory distress syndrome (ARDS). We report on a severe COVID-19 patient who was mechanically ventilated and who developed ARDS and bacterial infection. Because of rapid clinical deterioration and the exhaustion of other treatment options, the family and attending physicians requested a compassionate use of adult allogeneic bone marrow-derived mesenchymal stem cells (MSC) in addition to commonly used immunosuppressive, antiviral, and supportive therapy. The clinical course is discussed thoroughly, with a special emphasis on the safety and effect of MSC therapy. Compassionate MSC treatment, given in three rounds, affected ARDS regression. The patient was discharged from the intensive care unit after 31 days and from hospital after 49 days in a good general condition. MSC treatment was not associated with any side effects and was well tolerated in a three-week period; therefore, it should be studied in larger trials and considered for compassionate use.

Compassionate mesenchymal stem cell treatment in a severe COVID-19 patient: a case report

COVID-19 presentations range from cold-like symptoms to severe symptoms with the development of acute respiratory distress syndrome (ARDS). We report on a severe COVID-19 patient who was mechanically ventilated and who developed ARDS and bacterial infection. Because of rapid clinical deterioration and the exhaustion of other treatment options, the family and attending physicians requested a compassionate use of adult allogenic bone marrow-derived mesenchymal stem cells (MSC) in addition to commonly used immunosuppressive, antiviral, and supportive therapy. The clinical course is discussed thoroughly, with a special emphasis on the safety and effect of MSC therapy. Compassionate MSC treatment, given in three rounds, affected ARDS regression. The patient was discharged from the intensive care unit after 31 days and from hospital after 49 days in a good general condition. MSC treatment was not associated with any side effects and was well tolerated in a three-week period; therefore, it should be studied in larger trials and considered for compassionate use.

Personalized DNA neoantigen vaccine in combination with plasmid IL-12 for the treatment of a patient with anaplastic astrocytoma.

e14561 Background: Tumor neoantigens are epitopes derived from tumor-specific mutations that may be incorporated in personalized vaccines to prime T cell responses. DNA vaccines delivered with electroporation have recently shown strong CD8 and CD4 T cell responses in clinical trials. In preclinical studies, DNA-encoded neoantigen vaccines have shown induction of CD8 T cells against 50% of predicted high affinity epitopes with the ability to impact tumor growth. Methods: Two resection samples from a patient with IDH+ MGMT-methylated anaplastic astrocytoma were subject to whole exome and transcriptome sequencing. Epitopes derived from 27 neoantigens and 3 shared tumor-associated antigens were prioritized and included in a personalized vaccine. The patient was treated with surgery, radiotherapy and temozolomide starting June 2018 and received the first dose of the personalized vaccine in June 2019 under a compassionate use single patient IND application with the FDA. Results: As of February 10, 2021, the patient has received 10 doses of the DNA personalized vaccine. No serious adverse events have been reported. Related adverse events are limited to grade 1 injection site reactions. The patient remains progression-free 32 months after surgery and 20 months after starting vaccination. Three weeks following the third dose, a hyperintense image on the tumor bed was identified, which disappeared on the following MRI, 2 weeks following dose 5, being catalogued as pseudo progression. Ex vivo ELISpot have identified T cell responses to 21/30 epitopes (70%), including 18/27 (67%) neoantigens and 3/3 (100%) shared antigens. Flow cytometry analysis has determined that T cell responses are 92.3% CD8 and 69.2% CD4 (30.8% CD8 only; 61.5% both CD8 and CD4; and 7.7% CD4 only). Conclusions: This compassionate use treatment in an adjuvant setting demonstrates manufacturing feasibility, safety, tolerability, immunogenicity, and suggests potential for persistent clinical response of DNA encoded personalized vaccines. The data supports further investigation of DNA-encoded personalized vaccines into newly diagnosed high-grade gliomas.

Transcatheter Aortic Valve Replacement in Pure Native Aortic Valve Regurgitation: Challenging Pathology Awaiting Specialized Devices.

Patients with aortic incompetence frequently present with anatomical and pathological challenges such as elliptical dilated annulus, dilated aortic root, dilated ascending aorta, and with no calcification in the aortic cusps or annulus. Patients are commonly in graver clinical condition as a result of a long silent clinical course before overt congestive heart failure. All of the above make transcatheter therapies for native aortic valve regurgitation more challenging with poorer outcomes, escalating the risk of insufficient anchoring, prosthesis migration, and residual paravalvular leak compared with current transcatheter aortic valve replacement (TAVR) outcomes for aortic stenosis. There is a need for specialized TAVR devices to address this complex pathology. Surgical aortic valve replacement is the current treatment option and the gold standard for patients with aortic incompetence (AR). Currently, the specific off-label indication for TAVR in pure native AR could be a feasible and reasonable option, as a compassionate treatment is limited to inoperable patients and agreed on by the heart team.

Convalescent plasma from people vaccinated after COVID-19 infection

Plasma collected from previously infected people to passively transfer antibodies to protect or treat humans (convalescent plasma), has been successfully used since the late 19th century to treat diseases such as diphtheria, hepatitis A and B, and Ebola virus disease.1 The absence of effective treatment options for COVID-19 has led to the experimental use of convalescent plasma as a treatment to suppress the viral disease in early and advanced stages. Convalescent plasma has been widely used as a compassionate treatment for critically ill patients with COVID-19.

Drug Repurposing Patent Applications October-December 2020.

Drug Repurposing Patent Applications October-December 2020.

Narrative Politics in Policy Discourse: The Debate Over Safe Injection Sites in Philadelphia, Pennsylvania

Safe injection sites are spaces where people who inject drugs can do so under the supervision of staff at the sites who attempt to revive them if they overdose. Public officials in Philadelphia, Pennsylvania, have proposed the sites as a means to reduce opioid overdose deaths in the city, a policy proposal that has been politically and legally contested. This article uses the Narrative Politics model to elucidate the concerns, values, and aspirations of the competing narratives in the public discourse over safe injection sites in Philadelphia. Despite the aspirations expressed within the Harm Reduction narrative to open such a site, opposition from the Nimby (not in my backyard) narrative has, at the time of this research, successfully precluded such a step. Other narratives in the discourse include the Abstinence narrative opposing safe injection sites and the Social Justice narrative opposed to incarceration but also hesitant to wholeheartedly endorse the Harm Reduction narrative for its delayed advocacy of compassionate treatment of people who use drugs now that the face of the person who uses opioids is a white one. In addition to juxtaposing competing narratives against one another and considering their alignments, disagreements, and interactions, the authors consider absences and shared presuppositions. The social construction of the purported drug addict varies in some ways between and among the prevailing narratives; in other ways, all the narratives problematize “addiction” as an affliction that justifies techniques of discipline aimed at caring for and controlling the population.

The Use of Compassionate Ivermectin in the Management of Symptomatic Outpatients and Hospitalized Patients with Clinical Diagnosis of Covid-19 at the Centro Medico Bournigal and at the Centro Medico Punta Cana, Grupo Rescue, Dominican Republic, from May 1 to August 10, 2020

No antiviral has been shown to reduce mortality in SARS-COV-2 patients to date. In the present Retrospective observational study, 3,099 patients with a definitive or highly probable diagnosis of infection due to COVID-19 were evaluated between May 1st to August 10th, 2020, at the Centro Medico Bournigal (CMBO) and the Centro Medico Punta Cana (CMPC), and all received compassionate treatment with Ivermectin and Azithromycin. A total of 2,706 (87.3%) were discharged for outpatient treatment, all with mild severity of the infection. The average between the onset of symptoms and the Emergency Room (ER) visit in outpatients was 3.6 days (Early Treatment). In 2,688 (99.33%) with outpatient treatment, the disease did not progress to warrant further hospitalization and there were no deaths. In 16 (0.59%) with outpatient treatment, it was necessary their subsequent hospitalization to a room without any death. In 2 (0.08%) with outpatient treatment, it was necessary their admission to the Intensive Care Unit (ICU) and 1 (0.04%) patient died. There were 411 (13.3%) patients hospitalized, being admitted at a COVID-19 room with a moderate disease 300 (9.7%) patients of which 3 (1%) died; and with a severe to critical disease were hospitalized in the ICU 111 (3.6%), 34 (30.6%) of whom died. The mortality percentage of patients admitted to the ICU of 30.6% is similar with the percentage found in the literature of 30.9%. Total mortality was 37 (1.2%) patients, which is much lower than that reported in world statistics, which are around 3%, by the time of completion of this study.

Clinical experience of convection-enhanced delivery (CED) of carboplatin and sodium valproate into the pons for the treatment of diffuse intrinsic pontine glioma (DIPG) in children and young adults after radiotherapy.

Effective treatment of diffuse intrinsic pontine glioma (DIPG) remains a formidable challenge due to inadequate penetration of the blood-brain barrier (BBB) by systemically administered chemotherapies. The BBB can be overcome by directly infusing drugs into pons using method of convection-enhanced delivery (CED). We describe our clinical experience and what we have learned about the safety and feasibility of treating DIPG with intermittent CED of carboplatin and sodium valproate to the pons through the Renishaw Drug Delivery System (RDDS). Retrospective review (2017-2020) of children with DIPG, who following radiotherapy, received compassionate treatment commencing 3.3-10months post-diagnosis (median 4.9months). They received up to 7 cycles of 3-6 weekly pontine infusions of carboplatin (0.12-0.18mg/ml) and sodium valproate (14.4-28.8mg/ml). 13 children 3-19years (mean 6.9years) were treated. There were no surgical complications. With the exception of infusion channels blocking in one device, there were no adverse device effects. Two patients developed persistent 6th nerve palsies, which led to drug concentration reduction in the combination therapy. Subsequently infusion/ drug-related toxicities were transient. Tumour was controlled in pons in 10/13 patients. Median progression-free survival (PFS) was 13.0months, while median overall survival (OS) was 15.3months. Use of the RDDS was safe and well tolerated in all 13 patients. Treatment improved control of pontine disease resulting in longer PFS and OS and merits further evaluation in a clinical trial.

Mesenchymal Stem Cells for the Compassionate Treatment of Severe Acute Respiratory Distress Syndrome Due to COVID 19.

Mesenchymal stem cells (MSC) have received particular attention due to their ability to inhibit inflammation caused by cytokine storm induced by COVID-19. In this way some patients have been treated successfully. The aim of this study was to evaluate the safety and describe the clinical changes after IV administration of allogeneic human umbilical cord MSC (ahUCMSC), in patients with bilateral pneumonia caused by COVID-19, complicated with severe ARDS, as compassionate treatment. This was a pilot, open-label, prospective, longitudinal study. Five patients that did not improve in their clinical conditions after 48 hours of receiving the standard medical management used by the Medical Center and with persistent PaO2/FiO2 less than 100 mmHg were enrolled. ahUCMSC were infused IV, at dose of 1x106 per Kg of body weight over 15 minutes. Patients were monitored after the infusion to detect adverse event. Pa02/FiO2, vital signs, D-dimer, C reactive protein and total lymphocytes were monitored for 21 days after the infusion or until the patient was discharged from the hospital. Descriptive statistics were used with means or medians and standard deviation or interquartile range according to the type of variable. The Wilcoxon’s rank-sum was used for stationary samples. Adverse events occurred in three patients and were easily and quickly controlled. Immediately after the infusion of ahUCMSC, constant rise of PaO2/FiO2 was observed in all patients during the first 7 days, with statistical significance. Three patients survived and were extubated on the ninth day post-infusion. Two patients died at 13 and 15 days after infusion. The infusion of ahUCMSC in patients with severe ARDS caused by COVID-19, was safe, and demonstrated its anti-inflammatory capacity in the lungs, by improving the respiratory function expressed by PaO2 / FiO2, which allowed the survival of 3 patients, with extubation at 9 days.

Comparison of the effectiveness of acceptance and commitment-based therapy and compassion-focused therapy on the quality of life of mothers with gestational diabetes

Introduction: The aim of this study was to compare the effectiveness of acceptance and commitment-based therapy and compassion-focused therapy on the quality of life of mothers with gestational diabetes.Methods: The research method is quasi-experimental with pre-test-post-test-three-group follow-up. The statistical population of the study was all pregnant mothers who referred to Milad Hospital in Tehran in 2019, who were diagnosed with gestational diabetes. In order to form three groups using purposive sampling method (considering the inclusion and exit criteria), 45 patients were selected and then randomly divided into three groups of 15 (acceptance and commitment therapy, compassionate treatment and group Witness) were assigned. Forman and Herbert (2008) acceptance and commitment group training, and Gilbert (2007) self-compassion training were performed for the second experimental group. Also, a three-month follow-up phase was performed on all three groups. The research tool was the quality of life of the World Health Organization (1986). Data analyzed by repeated measure analysis of variance and spss.22. Results: The results showed that acceptance and commitment therapy and compassion-focused therapy had a significant effect on improving the quality of life in mothers with gestational diabetes (p <0.001).Conclusion: As a result, acceptance and commitment therapy has a greater impact on the quality of life of mothers with gestational diabetes than compassion-focused therapy.