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1.
Journal of Medical Internet Research ; 24(5):e33591, 2022.
Article in English | MEDLINE | ID: covidwho-1834163

ABSTRACT

BACKGROUND: Although well recognized for its scientific value, data sharing from clinical trials remains limited. Steps toward harmonization and standardization are increasing in various pockets of the global scientific community. This issue has gained salience during the COVID-19 pandemic. Even for agencies willing to share data, data exclusivity practices complicate matters;strict regulations by funders affect this even further. Finally, many low- and middle-income countries (LMICs) have weaker institutional mechanisms. This complex of factors hampers research and rapid response during public health emergencies. This drew our attention to the need for a review of the regulatory landscape governing clinical trial data sharing. OBJECTIVE: This review seeks to identify regulatory frameworks and policies that govern clinical trial data sharing and explore key elements of data-sharing mechanisms as outlined in existing regulatory documents. Following from, and based on, this empirical analysis of gaps in existing policy frameworks, we aimed to suggest focal areas for policy interventions on a systematic basis to facilitate clinical trial data sharing. METHODS: We followed the JBI scoping review approach. Our review covered electronic databases and relevant gray literature through a targeted web search. We included records (all publication types, except for conference s) available in English that describe clinical trial data-sharing policies, guidelines, or standard operating procedures. Data extraction was performed independently by 2 authors, and findings were summarized using a narrative synthesis approach. RESULTS: We identified 4 articles and 13 policy documents;none originated from LMICs. Most (11/17, 65%) of the clinical trial agencies mandated a data-sharing agreement;47% (8/17) of these policies required informed consent by trial participants;and 71% (12/17) outlined requirements for a data-sharing proposal review committee. Data-sharing policies have, a priori, milestone-based timelines when clinical trial data can be shared. We classify clinical trial agencies as following either controlled- or open-access data-sharing models. Incentives to promote data sharing and distinctions between mandated requirements and supportive requirements for informed consent during the data-sharing process remain gray areas, needing explication. To augment participant privacy and confidentiality, a neutral institutional mechanism to oversee dissemination of information from the appropriate data sets and more policy interventions led by LMICs to facilitate data sharing are strongly recommended. CONCLUSIONS: Our review outlines the immediate need for developing a pragmatic data-sharing mechanism that aims to improve research and innovations as well as facilitate cross-border collaborations. Although a one-policy-fits-all approach would not account for regional and subnational legislation, we suggest that a focus on key elements of data-sharing mechanisms can be used to inform the development of flexible yet comprehensive data-sharing policies so that institutional mechanisms rather than disparate efforts guide data generation, which is the foundation of all scientific endeavor.

2.
Midwives ; 25:42-49, 2022.
Article in English | ProQuest Central | ID: covidwho-1823700

ABSTRACT

Workplace reps – stewards, health and safety, learning and MSW advocates – are the RCM's front line, supporting, advising, representing, sharing information and caring whileworking alongside members Midwife Mary Ann Gillan has been a steward for the RCM Fife Branch for five years My motivation is getting people a fair deal and advocating for them. [...]over the past two years we've had a huge issue in Fife with staff not being paid correctly for annual leave dating back to 2008 – but, working with other unions, we were able to come to an agreement for the back pay owed. With help from the regional offi cer, we were able to get them to delay implementation and go back to the beginning, work more with midwives and follow the right processes. Recently we were able to get funding from the Welsh Union Learning Fund for a training course run by the charity Birthrights focusing on facilitating a woman's right to informed choice and consent;we're currently off ering an aromatherapy course in collaboration with another Welsh RCM branch.

3.
BMJ Open ; 12(4), 2022.
Article in English | EMBASE | ID: covidwho-1822070

ABSTRACT

Introduction Treatment-resistant schizophrenia (TRS) is associated with significant impairment of functioning and high treatment costs. Identification of patients at high risk of TRS at the time of their initial diagnosis may significantly improve clinical outcomes and minimise social and functional disability. We aim to develop a prognostic model for predicting the risk of developing TRS in patients with first-episode schizophrenia and to examine its potential utility and acceptability as a clinical decision tool. Methods and analysis We will use two well-characterised longitudinal UK-based first-episode psychosis cohorts: Aetiology and Ethnicity in Schizophrenia and Other Psychoses and Genetics and Psychosis for which data have been collected on sociodemographic and clinical characteristics. We will identify candidate predictors for the model based on current literature and stakeholder consultation. Model development will use all data, with the number of candidate predictors restricted according to available sample size and event rate. A model for predicting risk of TRS will be developed based on penalised regression, with missing data handled using multiple imputation. Internal validation will be undertaken via bootstrapping, obtaining optimism-adjusted estimates of the model's performance. The clinical utility of the model in terms of clinically relevant risk thresholds will be evaluated using net benefit and decision curves (comparative to competing strategies). Consultation with patients and clinical stakeholders will determine potential thresholds of risk for treatment decision-making. The acceptability of embedding the model as a clinical tool will be explored using qualitative focus groups with up to 20 clinicians in total from early intervention services. Clinicians will be recruited from services in Stafford and London with the focus groups being held via an online platform. Ethics and dissemination The development of the prognostic model will be based on anonymised data from existing cohorts, for which ethical approval is in place. Ethical approval has been obtained from Keele University for the qualitative focus groups within early intervention in psychosis services (ref: MH-210174). Suitable processes are in place to obtain informed consent for National Health Service staff taking part in interviews or focus groups. A study information sheet with cover letter and consent form have been prepared and approved by the local Research Ethics Committee. Findings will be shared through peer-reviewed publications, conference presentations and social media. A lay summary will be published on collaborator websites.

4.
Hemato ; 3(1):111, 2022.
Article in English | ProQuest Central | ID: covidwho-1818069

ABSTRACT

Background. Hypercoagulable state and endothelial cell activation are common alterations in patients with COVID-19. Nevertheless, the hypothesis of persistent hypercoagulability and endothelial cell activation following recovery from COVID-19 remains an unresolved issue. Objectives. To investigate the persistence of endothelial cell activation and hypercoagulability after recovery from COVID-19. Patients/Methods. COVID-19 survivors (n = 208) and 30 healthy individuals were enrolled in this study. The following biomarkers were measured: procoagulant phospholipid-dependent clotting time (PPL-ct), D-Dimer, fibrin monomers (FM), free Tissue factor pathway inhibitor (free-TFP)I, heparinase, and soluble thrombomodulin (sTM). Antibodies against SARS-CoV-2 (IgG and IgA) were also measured. Results. The median interval between symptom onset and screening for SARS-CoV-2 antibodies was 62 days (IQR = 22 days). Survivors showed significantly higher levels of D-Dimers, FM, TFPI, and heparanase as compared to that of the control group. Survivors had significantly shorter PPL-ct. Elevated D-dimer was associated with older age. Elevated FM was associated with female gender. Elevated heparanase was independently associated with male gender. Decreased Procoag-PPL clotting time was associated with female gender. One out of four of COVID-19 survivors showed increase at least one biomarker of endothelial cell activation or hypercoagulability. Conclusions. Two months after onset of COVID-19, a significant activation of endothelial cells and in vivo thrombin generation persists in at least one out of four survivors of COVID-19. The clinical relevance of these biomarkers in the diagnosis and follow-up of patients with long COVID-19 merits to be evaluated in a prospective clinical study.

5.
Clinical Cancer Research ; 27(6 SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1816898

ABSTRACT

Background: The UC San Diego (UCSD) Moores Cancer Center Biorepository (BR) is a College of American Pathologists (CAP)-accredited core providing a full array of biological samples services including tissue biobanking. Informed consent (IC) is obtained through an IRB-approved protocol. The MORE (Minorities Outreach Repository Effort) Initiative was launched in 2018 as an effort to increase the enrollment of minorities, and has since shown an accrual increase 213% as compared with previous years. As the ongoing COVID-19 pandemic has affected enrollment in many research studies we decided to reevaluate subject accrual. Methods: Data analysis was performed for Pre-COVID-19 pandemic enrollment from July 2019 to March 2020 and Post-COVID-19 pandemic enrollment from March 2020 to December 2020. Patients from the oncology clinics were identified by the BR or the treating teams, and pre-screened for potential enrollment. Eligible patients were interviewed by coordinators and an IC was obtained. In the IC, the patients were given the option of sharing the tissues for research with university researchers (UR) and/or for-profit (FP) organizations. Race and ethnicity data were acquired from the Epic electronic medical record (EMR). Patients were interviewed in English, Spanish, Russian, Vietnamese, Farsi, Tagalog, Simplified Chinese, or Arabic. Due to interviewing restrictions during the pandemic, protocol was amended to add added the possibility of remote IC via video/phone teleconferencing. Results: Global patient participation decreased by 30% due to the pandemic, with pre-COVID rates at 107.88 patient/month and Post-COVID rates of 31.25/month (69.56 ±38.31). Enrollment of Hispanic populations has remained remarkably similar (22 %;22.18 ±0.18) for the same period. When compared with pre and post pandemic participation, data showed no significant difference among races (p=0.99). There was a slight increase in the rate of acceptance to share specimens with UR among Hispanics (30% Pre-COVID vs. 33% Post-COVID). The non-Hispanic cohort was associated with an increase (19% vs. 33%, p= 0.33) in their resistance to share with FP collaborations in Post-COVID-19 pandemic participation (Pre- COVID-19 19% vs. Post-COVID-19 30%). Conclusions: The MORE initiative is an efficient and effective way of increasing and sustaining the participation of minorities, despite COVID-19 research restrictions. Our ongoing efforts are focused on enhancing remote consenting methodologies, increasing subjects' participation, and sustaining minority involvement in research for biobanking.

6.
Cliniques mediterraneennes: Psychanalyse et Psychopathologie Freudiennes ; 103(1):55-61, 2021.
Article in French | APA PsycInfo | ID: covidwho-1812729

ABSTRACT

Treatment without consent, isolation rooms, use of mechanical and chemical restraints... illegal practices and conditions in psychiatric hospitals have recently been revealed in several newspapers, official reports, and in French academic literature. Condemned everywhere, the functioning of France's psychiatric system has mobilized the attention of the government, which has been talking a great deal about the importance of mental health and care since the beginning of the covid-19 pandemic. How then did the government choose to react to this catastrophic situation? By introducing restrictions and laws that choke a dying organization, one that is suffocating under the weight of demand and the threat of an inhuman financial reform. (PsycInfo Database Record (c) 2022 APA, all rights reserved) (French) Soins sans consentement, isolement, contention, camisoles mecanique, chimique... La litanie des pratiques et des conditions illegales d'enfermement infligees aux patients dans les services hospitaliers de psychiatrie est egrenee, denoncee depuis des mois dans la litterature, la presse, les rapports parlementaires et administratifs. Denonce de toutes parts, le fonctionnement de la psychiatrie est apparemment l'objet de toute l'attention d'un pouvoir politique qui n'a eu de cesse de rappeler l'importance de la sante mentale et du soin, pendant l'epidemie de Covid-19. Mais comment se traduit cette attention ? Par des restrictions, des condamnations, des lois qui viennent alourdir un systeme qui suffoque sous le poids de demandes qu'il ne peut traiter et la perspective d'une reforme qui, si elle etait mise en oeuvre, enterinerait la fin de l'humanite des soins. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

7.
Indian Journal of Transplantation ; 16(1):3-7, 2022.
Article in English | EMBASE | ID: covidwho-1798826

ABSTRACT

From the context of organ donation, COVID-19 vaccine-induced thrombotic thrombocytopenia (VITT) is important as there is an ethical dilemma in utilizing versus discarding organs from potential donors succumbing to VITT. This consensus statement is an attempt by the National Organ and Tissue Transplant Organization (NOTTO) apex technical committees, India, to formulate the guidelines for deceased organ donation and transplantation in relation to VITT to help in appropriate decision-making. VITT is a rare entity, but a meticulous approach should be taken by the organ procurement organization's (OPO) team in screening such cases. All such cases must be strictly notified to the national authorities (NOTTO) as a resource for data collection and ensuring compliance with protocols in the management of adverse events following immunization. Organs from any patient who developed thrombotic events up to 4 weeks after adenoviral vector-based vaccination should be considered to be linked to VITT and investigated appropriately. The viability of the organs must be thoroughly checked by the OPO, and the final decision in relation to organ use should be decided by the expert committee of the OPO team consisting of a virologist, a hematologist, and a treating team. Considering the organ shortage, in case of suspected/confirmed VITT, both clinicians and patients should consider the riskbenefit equation based on limited experience. An appropriate written informed consent of potential recipients and family members should be obtained before the transplantation of organs from suspected or proven VITT donors.

8.
Journal of Clinical and Diagnostic Research ; 16(SUPPL 2):55, 2022.
Article in English | EMBASE | ID: covidwho-1798723

ABSTRACT

Introduction: Evolution of pedagogy in medical education is mainly due to technological advancement. Medical schools shifted online in response to COVID-19 Pandemic, which lead to decreased student participation, a loss of inclusive hands-on experiences. Aim: Therefore, the current study aimed to determine the students' perception on the virtual anatomy classes that was provided to them in addition to conventional teaching learning method. Materials and methods: A descriptive questionnaire based study conducted during the period of January to September 2021. The participants were 250 medical students from first phase of MBBS. A questionnaire was made using Google Form and finalized after proper validation. It was circulated to students on E-mail and messaging platforms such as Whatsapp, and Telegram. The questionnaire was designed with informed consent and 20 questions which enquire about the socio-demographic profile, their perception about the virtual and conventional method of learning. All the questions were closed ended questions in multiple choice format and 5 points Likert scale. The study was done after getting institutional review board approval. The data was then tabulated and interpreted with descriptive statistics using Microsoft Excel Version 2019. Results: The majority of students (82.4%) agreed that they missed conventional anatomy learning, such as cadaveric trainings, faceto- face lectures, and interaction with mentors. About 83% had a lack of appropriate devices, poor network connectivity as a barrier to their virtual learning. Over 69% of students reported a lack of personal motivation. Finally, more than 79.9% of students chose conventional over virtual method of practical education. Conclusion: In conclusion, virtual learning became inseparable part of medical education, student perception can be useful for making adequate and updated changes to virtual anatomy education.

9.
Journal of Clinical and Diagnostic Research ; 16(SUPPL 2):27, 2022.
Article in English | EMBASE | ID: covidwho-1798711

ABSTRACT

Introduction: Traditional medical curriculum has developed an insurmountable barrier between preclinical and clinical subjects, undermining the significance of basic sciences in clinical contexts. Early Clinical Exposure (ECE) is one such innovative vertical integrated teaching tool which breaks the barrier between basic science learning in preclinical traditional class room and clinical setting. Aims: To assess usefulness to the ECE through vertical integration among medical undergraduate first year MBBS students. To evaluate the perceptions of the medical undergraduate students about the ECE through vertical integration as effective tool of memory retention and skill communication development. Materials and method: It was interventional cross-sectional study in which 250 first year MBBS students had enrolled after taking informed consent, on topic acid base balance and imbalance as basic science correlation conducted in Department of Biochemistry in collaboration with Clinical Departments of General Medicine, Emergency Medicine and Paediatrics. Usefulness of ECE as vertical integration assessed by providing pre-test after traditional class room teaching. Post-test was conducted after ECE session. A validated questionnaire was administered through Google form link among phase I medical students of batch 2019 to 2020 after ECE session. Post session feedback from the students was taken by questionnaire graded on likert's scale. Results: The difference between the mean value of the marks obtained by the pre-test compared with post-test using the MCQ assessment tools was found to be statistically significant (p value being <0.05). One hundred and eighty eight students out of the two hundred and fifty answered the questionnaire (97.6%). The dependability of the scale was 0.50 (Cronbach's alpha -0.5). 98.8% students agreed that ECE as an integrated teaching helped in the retention and acquisition of skill /communication of the basic science knowledge to health and disease. Vertical integration was strongly agreed upon as the best method of teaching and learning by 97.6 % on likert scale. Conclusion: Thus, ECE through vertical integration showed efficient new teaching learning method which had positive influence in retaining knowledge and simultaneous gaining of skills. This method will be very useful in its practical implementation during online classes for ECE module in the threat of COVID-19 situation as well.

10.
Journal of Clinical and Diagnostic Research ; 16(SUPPL 1):20-21, 2022.
Article in English | EMBASE | ID: covidwho-1798695

ABSTRACT

Background: Covid-19 has enforced education system across India and the world indeed, to suspend physical classrooms and shift to online classes. While faculty grapples with new ways of managing this sudden transition to online education, students are left clinging on to electronic gadgets. Online education is not as easy as using laptop or phone. There are challenges with this form of education, which are faced at both ends of the spectrum by students as well as faculty. Hence, there was a need to find out the perception of medical faculty regarding tectonic shift from traditional to online teaching during COVID 19 pandemic. Description: An observational, prospective and cross-sectional study was conducted among the faculty of medical domain with online teaching experience during COVID 19 pandemic. Out of 269 faculty participated: 29% Professors, 22% Associate Professors, 25% Assistant Professors and 15% Teachers and others 9%. Institutional Ethics Committee approval was obtained prior to the study. Google form with questionnaire and Informed consent with link were shared with faculty all over the globe. The online facilitation system for students (modified) with 20 questions was used as questionnaire with three subscales: (a) student-related issues, (b) instructor-related issues, and (c) institutional-related issues. SPSS version 21, ANOVA test used for statistical analysis. Where, designation and demographic details considered as independent variables and faculty perception as dependent variable. Outcome: 269 subjects from medical domain comprising of faculty from Medical 89%, Allied Health Sciences 6% and Nursing 5% participated in this study. Males were 36% and females 67%, within the age group of 25 years and above. More than 50% of the responses were obtained from Biochemists and Physiologists. Seventy-five to 100% of faculty agreed that they do not have any control on students while teaching online, students can access online course from any place in India or world, students use a wider range of resources, technical problems discourage teaching online. Not meeting students face-to-face prevents the teacher from knowing them with respect to academics and emotional perspectives, concerned about receiving lower course evaluations, it is more difficult to motivate students in online environment than in the traditional setting As the age increased the satisfaction, rating has decreased with p value 0.03 (statistically significant) between groups and within the groups. The junior faculty responded with increased mean value rating of satisfaction when compared to the senior faculty. Medical faculty (mean value 2.75) were less satisfied rating with online teaching compared to allied health sciences and nursing (mean value 3.44). Faculties across India and world have responded that they are partially satisfied with online teaching and prefer traditional teaching. Conclusion: Online learning is an exciting new way to learn and has a positive impact on students' education as well as faculty from medical domain during Covid-19 pandemic. Faculty of every age is taking it as a good step during pandemic. The difference was found when perception was compared with the designation and age groups. High-quality online teaching requires candid planning, preparation and more individualised feedback and assistance. Hence, preference is given for traditional teaching.

11.
Pharmacy Education ; 22(2):129-131, 2022.
Article in English | EMBASE | ID: covidwho-1798555

ABSTRACT

Background: The Pandemic Related Pregnancy Stress Scale (PREPS) is an instrument that assesses pandemic-related stress in pregnant women. Objective: This study aimed to validate the Indonesian version of the Pandemic Related Pregnancy Stress Scale (PREPS). Methods: Validation procedures include forward and backward translation, pretest and cognitive interview, construct validity test, and instrument reliability test. Pregnant women involved in this study agreed to participate with informed consent. Results: The results of the construct validity test showed that each item of the PREPS questionnaire statement had an rcount > rtable (α=0.01;df=28), starting from the lowest 0.562 to the largest 0.847, with an rtable value (α=0.01;df = 28) equal to 0.3610. The Cronbach's alpha value of 0.841 indicates good reliability of the scale. Conclusion: The Indonesian version of the PREPS is valid and has good reliability.

12.
Pakistan Journal of Medical and Health Sciences ; 16(2):186-190, 2022.
Article in English | EMBASE | ID: covidwho-1798526

ABSTRACT

Aim: To ascertain the frequency of acceptance and rejection of covid-19 vaccination and the reasons behind their choices among pregnant and breast feeding women visiting outpatient department of a tertiary care setup. Methods: This cross-sectional study was conducted in the Department of Obstetrics and Gynaecology, Jinnah Postgraduate Medical Centre, Unit -1 for a period of one month. All women attending outpatient department during the study, fulfilling the inclusion criteria and willing to participate in the study were included after informed consent. A questionnaire designed to acquire general information about the study participant was filled by the researcher. Data was entered and analyzed using SPSS vr 21.0. Results: Out of 500 enrolled women, 249(49.8%) women were pregnant and 251(51.2%) were breast feeding. 171(34.2%) were vaccinated and 329(65.8%) were unvaccinated. There is a significant association between the concept regarding unavailability of significant data regarding safety during pregnancy and breast feeding or vaccine being harmful during pregnancy and breastfeeding for mother & baby and acceptance of vaccine (p-value < 0.001) Conclusion: Safety concerns regarding the vaccine for pregnant and breast-feeding mothers still hold them from getting vaccinated. Obstetricians and Gynaecologists of the country need to play a vital role in building up the confidence of this population over vaccination and should strongly recommend pregnant and breast feeding women following up in clinics to get vaccinated.

13.
Critical Care ; 26(SUPPL 1), 2022.
Article in English | EMBASE | ID: covidwho-1793840

ABSTRACT

Introduction: Timeliness of diagnosis and treatment of MIS-C has increased amid the COVID-19 pandemic. Methods: A child was admitted to our clinic (male, 14 years old). He was in contact with a COVID-19 patient 17 days before. Upon admission, the patient complained of a rise in body temperature to 40° C, abdominal pain, vomiting, and diarrhea. Hemorrhagic rash on the skin of the upper and lower extremities, hyperemia of the mucous membrane of the lips and tongue, arterial hypotension were found. Hospitalized at ICU. In laboratory tests: WBC 3.42 × 109/ l, RBC 4 × 1012/ l, HB 111 g/l, HTC 31, PLT 31 × 109/ l, CRP 283 mg/l, PCT 6.66, D-dimer 9.2, LDG 194 U/l, ferritin 989 mcg/l, ALT 54 U/l, GGT 79 IU/l, albumin 32 g/l;proteinuria 0.75 g\l, hematuria. Diagnosis: MIS-C associated with COVID-19. Results: Prescribed: Meropenem 20 mg/kg/d, methylprednisolone 2 mg/kg/d. After 8 h-septic shock. 0.3 μg/kg/min norepinephrine was started. ECG-a violation of repolarization with ST elevation up to 0.3 mm. Echocardiography-a decrease in the left ventricular ejection fraction to 47%, pericardial effusion. Ultrasound examination of the abdominal cavity: hepatosplenomegaly. Dobutamine 3 μg/kg/min was added to the therapy. An increase in PCT up to 19.8 was found. IV IgG 2 g/kg was added to the therapy. On the 3rd day of therapy, regression of all symptoms was obtained. On the 8th day, the child was transferred from the ICU to the pediatric department. On the 12th day he was discharged home. Conclusions: Thus, the timely diagnosis of MIS-C associated with COVID-19 and the appointment of intensive therapy with the inclusion of methylprednisolone and IV IgG allows achieving a positive result in the shortest possible time. Consent to Publish: Written informed consent was obtained from the next of kin.

14.
J Med Ethics ; 2022 Apr 08.
Article in English | MEDLINE | ID: covidwho-1784881

ABSTRACT

Pickering et al's paper argues that the capacity of the decision-maker is the sole consideration in whether a decision should stand, and that the risk of the decision should not be considered. This argument ignores the existence of the player who is of the view that a decision is not wise. This paper argues that patient autonomy is not the sole determinant of whether a person is able to make an unwise decision, particularly in healthcare where there are always others affected by the patient decision. Rather than asserting that patients have an unfettered autonomous choice on clinical decisions this paper argues that these decisions should be looked at through the lens of quality in health care that has proposed four parameters to be balanced; the patient experience, wise use of resources, the effect on public health and the clinician experience.

15.
Cancer Research ; 82(4 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1779467

ABSTRACT

Background: Since the beginning of the covid19 pandemic, clinical and demographic data showed that cancer patients are at high risk of developing severe consequences of Sars-Cov2 disease. For this reason, vaccination is strongly recommended, especially for patients on active treatment. Nevertheless, the efficacy of the Sars-Cov2 vaccine in cancer patients is not fully investigated. Our trial aim to explore the seroconversion in a large series of vaccinated cancer patients undergoing active treatment. Here we present a subgroup analysis concerning patients affected by breast cancer. Methods: The "VAX-on" is a single-center study that enrolled 366 cancer patients who underwent oncological treatment within the last six months. The study was approved by the ethics committee and all patients had to sign specific informed consent to be enrolled. Subjects were vaccinated against Sars-Cov2 with mRNA vaccine BNT162b2 (Comirnaty)-Pfizer BioNTech. Blood samples were obtained to quantify the production of specific anti-Spike IgG antibodies at day 21 from the first dose and at 6-8 weeks after the second dose. The antibody laboratory title cut-off of 50 U.A./mL defined the seroconversion. Results are shown as Mean and Standard Deviation for Scontinuous variable, percentage (%) for categorical ones. The Mann-Whitney test or Chi-Square test were used to compare continuous or categorical groups, respectively. Results: A total of 100 patients with breast cancer were enrolled. Clinical and demographic data are summarized in Table 1. The median age was 60.5 years and the majority had an ECOG PS of 0 (75%). Almost all were women (97%), with advanced cancer in 60% of cases. In early or advanced setting 46% patients were treated with chemotherapy while 54% were on target therapy (also including monoclonal antibody and CDK4/6 inhibitors). The mean antibody title after the first dose of mRNA Comirnaty vaccine was 2185.03±9303.26 U.A./mL (M±SD), while after the second dose the mean antibody title rise to 6492.10±10425.95 (M±SD). After the first dose 61% of patients were considered as immunized, meanwhile after the second dose 86% of patients resulted immunized (defined as an antibody title >50 U.A./mL). In the 9 patients in treatment with steroids (prednisone > 10mg/die or equivalent), there was a trend to a decreased antibody development compared to patients without chronic use of steroids (p 0.06 and 0.05 after the first and second dose, respectively). Of interest, patients using G-CSF (12%) had a significant reduction in the production of Sars-Cov2 antibody after vaccination compared to patients who did not use them (p 0.02 and <0.001 after the first and second dose, respectively), with only 75% resulted positively immunized after the second dose (p=0.04). No differences were seen when comparing patients in advanced with non-advanced stage. Conclusions: Our study demonstrated 86% seroconversion in cancer patients after the second dose of mRNA vaccine regardless of disease stage or type of cancer treatment received. Further evaluations are needed to define whether the use of corticosteroids and G-CSF have an impact on seroconversion.

16.
Cancer Research ; 82(4 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1779443

ABSTRACT

Background:. Mammographic screening programmes have been shown to reduce breast cancer mortality. However, they detect many small tumours with favourable biological features which may not progress during a woman's lifetime. These are treated with standard surgery and adjuvant therapies, which have associated morbidities. Thus, there is a need to reduce overtreatment of good prognosis tumours found by screening. Minimally invasive treatment approaches have been described but there is no prospective randomised evidence to support their routine use. Vacuum-assisted excision (VAE) is in widespread use for management of benign lesions and lesions of uncertain malignant potential. SMALL (ISRCTN 12240119) is designed to determine the feasibility of using this approach for treatment of small invasive tumours detected within the UK NHS Breast Screening Programme (BSP). Methods:. SMALL is a phase III multicentre randomised trial comparing standard surgery with VAE for screen-detected good prognosis breast cancers. The main eligibility criteria are age ≥47 years, screen-detected unifocal grade 1 tumours with maximum diameter 15mm, which are strongly ER/PR+ve and HER2-ve, with negative clinical/radiological axillary staging. Patients are randomised 2:1 in favour of VAE or surgery;with no axillary surgery in S the VAE arm. Completeness of excision is assessed radiologically, and if excision is incomplete, patients undergo open surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm but may be omitted following surgery. Co-primary end-points are:1.Non-inferiority comparison of the requirement for a second procedure following excision2.Single arm analysis of local recurrence (LR) at 5 years following VAE. Recruitment of 800 patients over 4 years will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure. This ensures sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. To ensure that the trial as a whole only has 5% alpha, the significance level for each co-primary outcome is set at 2.5% with 90% power. The Data Monitoring Committee will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A QuinteT Recruitment Intervention (QRI) is integrated throughout SMALL to optimise recruitment and informed consent. Recruitment challenges are identified by analysing recruiter/patient interviews and audio-recordings of trial discussions, and by review of screening, eligibility and recruitment data and study documentation. Solutions to address these are developed collaboratively, including individual/group recruiter feedback and recruitment tips documents. Results:. SMALL opened in December 2019, but recruitment halted in 2020 due to suspension of the NHS BSP for 5 months due to COVID-19. As of 1st July 2021, 55 patients had been approached in 10 centres, with 33 patients randomised (randomisation rate 60%). A further 23 centres are in set-up, with 8 suspended due to the pandemic. Drawing from preliminary QRI findings and insights from patient representatives, a recruitment tips document has been circulated (on introducing and discussing SMALL, providing balanced information. on treatment options and explaining randomisation). individual recruiter feedback has commenced, with wider feedback planned shortly. Conclusion:. Despite pandemic-related challenges, SMALL has an excellent recruitment rate to date and is expected to have a global impact on treatment of breast cancer within mammographic screening programmes. SMALL is funded by the UK NIHR HTA programme, award 17/42/32.

17.
Front Public Health ; 10: 824048, 2022.
Article in English | MEDLINE | ID: covidwho-1776020

ABSTRACT

Living kidney donation is the most common type of living-donor transplant. Italian guidelines allow the living donations from emotionally related donors only after clear and voluntary consent expressed by both the donor and the recipient involved. Living donation raises ethical and legal issues because donors voluntarily undergo a surgical procedure to remove a healthy kidney in order to help another person. According to the Italian standards, the assessment of living donor-recipient pair has to be conducted by a medical "third party", completely independent from both the patients involved and the medical team treating the recipient. Starting from the Hospital "Città della Salute e della Scienza" of Turin (Italy) experience, including 116 living kidney donations, the Authors divided the evaluation process performed by the "Third-Party" Commission into four stages, with a particular attention to the potential donor. Living donation procedures should reflect fiduciary duties that healthcare providers have toward their patients, originating from the relationship of trust between physician and patient. In addition to that, the social implications are enormous if one considers the worldwide campaigns to promote public awareness about organ donation and transplantation, and to encourage people to register their organ donation decisions. The systematic process proposed here can be a tool that proactively reduces and controls the risks of coercion, organ trafficking, vitiated consent, insufficient weighting of donative choice, that could arise especially in donors involved in living kidney donation.


Subject(s)
Kidney Transplantation , Living Donors , Tissue and Organ Procurement , Humans , Italy , Kidney Transplantation/methods , Kidney Transplantation/psychology , Living Donors/psychology , Risk Assessment , Tissue and Organ Procurement/ethics
18.
Journal of Function Spaces ; 2022, 2022.
Article in English | ProQuest Central | ID: covidwho-1775020

ABSTRACT

Introduction. Dengue remains a public health threat. Clarifying the characteristics of future threats and prioritising intervention towards the highest risk potential can help to control and prevent dengue outbreaks. However, obtaining a consensus from panels of experts is certainly challenging due to the relative subjectivity of experience. Therefore, this article incorporates the fuzzy Delphi method (FDM) within a nominal group technique (NGT) as a multicriteria decision-making tool for (1) describing the characteristics of socioecological attributes (SEAs) with a high risk of causing dengue outbreak and (2) ranking those SEAs as priorities for intervention. Material and Methods. Experts were recruited using a purposive sampling technique. Informed consent was obtained before the start of the study. The NGT process began with an introductory presentation of dengue SEA by the moderator, followed by “silent generation.” Next, each participant provided information in a round-robin fashion. Ideas were collected by the moderator and displayed publicly. All experts were given ample time and space to contribute and justify their ideas without interruption during the discussion step to yield agreeable SEA characteristics. Ultimately, FDM was incorporated in the voting step to ensure rigorous analysis. The study was approved by an ethical committee before its commencement. Results. A total of 10 field experts participated in the study, with a median experience of 7.5 years working on a dengue team. The common characteristics of SEA prone to cause dengue outbreaks were the presence of human-made containers, in high quantities, left unattended, and covered from direct sunlight. Apart from that, all eight SEAs passed the triangulation of fuzzy numbers and defuzzification processes. The average fuzzy numbers ranged between 0.500 and 0.780, and the threshold value (d) ranged from 0.055 to 0.196. Of the potential risk factors identified, experts ranked illegal dumping sites as the most important, followed by old and unused items and construction sites. Conclusion. The NGT process successfully helped to obtain a consensus among the expert panels in describing SEA characteristics. Nevertheless, the integration of FDM offered a robust analysis that validated their ranking in dengue risk prioritisation. Therefore, we strongly recommend the application of FDM to be incorporated in any public health decision-making process.

19.
Blood ; 138(SUPPL 1):1812, 2021.
Article in English | EMBASE | ID: covidwho-1770305

ABSTRACT

Introduction: The use of high-dose post-transplant cyclophosphamide (PTCY) has revolutionized graft-versus-host disease (GVHD) prophylaxis and allowed to successfully reconsider haplotransplant in recent years. As this strategy significantly reduces the incidence of both acute and chronic GVHD, PTCY has been thereafter considered not only in matched settings but also as sole GVHD prophylaxis, at least when considering myeloablative allotransplant using matched sibling (MSD) or unrelated (MUD) donors and bone marrow as source of graft. Here, PTCY, as a sole GVHD prophylaxis, was tested in a reduced-intensity conditioning (RIC) setting, using peripheral blood stem cells (PBSC) as source of graft considering that this platform is currently broadly used worldwide in adults. Methods: This prospective monocentric phase 2 study was designed with the main objective to demonstrate the feasibility and safety of using only PTCY (without cyclosporine A nor mycophenolate mofetyl after transplant) in adults (18-70 years old) eligible for a RIC PBSC transplant with MSD or MUD. The Baltimore platform with 2 days of PTCY 50mg/kg/day on days 3 and 4 post infusion was considered as conditioning regimen, using fludarabine for lymphoid disease or clofarabine for myeloid disease. The primary objective was to appreciate the incidence of corticosteroid-resistant acute grade 3-4 GVHD (CR 3-4 GVHD) within 100 days post-transplant. According to statistical rules, patients have to be included in a step by step fashion (3, 3, 6, 15, 15 and 17 patients) for a total of 59 evaluable patients (meaning having received PTCY), in order to stop the protocol soon enough in case of excessive rate of deleterious severe acute GVHD (graded according to Mount Sinai International Consortium). Thus, the trial had to be stopped in case of documentation of > 2 CR 3-4 GVHD for the first 3 patients, >3 CR 3-4 GVHD for the first 6 patients, > 4 CR 3-4 GVHD for the first 12 patients, > 6 3-4 CR GVHD for the first 27 patients, > 8 CR 3-4 GVHD for the first 42 patients and finally as soon as > 9 CR 3-4 GVHD for the last included patients. All patients gave informed consent. The trial was registered at ClinicalTrials.gov Identifier: NCT03263767. Results: The results of the first 27 first patients (males n=17 and female n=10;median age: 59 years old (yo), range: 26-70) are reported here. They were included between February 2018 and November 2020. Diagnoses were AML (N=8), MDS (N=5), CMML (N=2), myelofibrosis (N=5), CML (N=1), DLBCL (N=1), T-cell lymphoma (N=1), Philadelphia positive B-ALL (N=1), CLL (N=1), lymphoblastic lymphoma (N=1) and mixed phenotype acute leukemia (N=1). Donors were MSD in 10 cases and MUD in 17. Only one primary graft failure was documented in a 61 yo MDS patient with active disease at transplant. He is however still alive in response after autologous reconstitution. With a median follow-up of 17.6 months (range: 10-42) for alive patients at the time of analysis (July 2021), 1-year and 2-year survivals were 80.9+7% and 74.7+9%, respectively, for both OS et DFS. GVHD-free/relapse-free survival (GRFS) at 1-year and 2-year was 58.7+9% and 52.2+10%, respectively. Three relapses (11%) and 6 deaths occurred. Deaths were due to acute GVHD in 4 patients (including 1 with sepsis and 1 with SARS-COVID 19 infection) and relapse in 2. Grade 2, 3 and 4 acute GVHD occurred in 11, 1 and 4 patients, respectively, for a total of 59% of grade 2-4 acute GVHD. CR 3-4 GVHD was observed in all of 5 patients with acute grade 3-4 GVHD and 4 died related to GVHD. Moderate/severe chronic GVHD occurred in 5/22 (22.7%) evaluable patients, including 4 still on immunosuppressive therapy at 40, 28, 25 and 16 months post-transplant. Overall non-relapse mortality (NRM) was 14.8% and related to acute GVHD. However, the number of cases conducting to stop the protocol was not reached. Conclusion: PTCY as a sole GVHD prophylaxis is here demonstrated as possible and relatively safe for adults receiving a matched PBSC Baltimore-based RIC allograft. The very good survivals reported he e may be related to a strong GVL effect associated with the high incidence of acute GVHD. However, because of this high incidence and the fact that NRM was related to GVHD after this first analysis, we have now made an amendment to test the addition to PTCY of one day of anti-thymoglobulin (ATG) 2.5 mg/kg on day-2 for the next 32 patients to be included. This second cohort receiving PTCY+ATG as a sole prophylaxis is ongoing.

20.
Blood ; 138(SUPPL 1):816, 2021.
Article in English | EMBASE | ID: covidwho-1770300

ABSTRACT

Introduction Lymphoid malignancies are a risk factor for severe COVID-19. Vaccination with BNT162b2 protects the general population from severe disease, but recent studies have shown limited seroconversion after vaccination in patients with lymphoid malignancy. This reduced response is likely related to disease and treatment factors altering both humoral and cellular immunity. Assessing response in patients with the indolent lymphomas, Waldenström's Macroglobulinaemia (WM) and Follicular Lymphoma (FL), including cohorts on differing treatment regimens, may help elucidate some of these factors. Australia has had low prevalence of SARS-CoV-2 infection to date, affording a unique opportunity to assess efficacy to vaccination without the confounding impact of endemic infection. Methods Patients with WM and FL and controls were enrolled in a prospective study of immune response after two doses of BNT162b2 administered 21 days apart. The study had Human Research Ethics Committee approval and all patients gave informed consent prior to participation. Recruitment was targeted to obtain comparable proportions of controls to treatment cohorts. PBMC and sera were collected from participants immediately prior to the first dose (T1), at day 21 immediately prior to the second dose (T2), and day 49 (+/-7d) (T3). Immune response was measured by: flow cytometric detection of anti-SARS-CoV-2 spike antibodies (ASAb), performed using our recently validated flow cytometric live cell assay (Tea et.al. PLoS Medicine 2021) with increased sensitivity compared to currently available commercial ELISAs;live virus neutralisation to a panel of SARS-CoV-2 variants of concern;and CD4+and CD8+ antigenspecific T cell responses. Statistical analysis of medians between cohorts were compared by the Mann-Whitney non-parametric test using Graphpad Prism. Initial ASAb IgG data for T1 and T2 is presented here. Complete immune response data at all time points will be available for the ASH meeting. Results Eighty-five participants received their first dose of BNT162b2 from 18 May 2021 to 7 June 2021 with a second dose 21 days later: 72 lymphoma patients (WM and FL) and 13 age-matched healthy volunteers (controls). Of 37 with WM [19 (51.3%) female, median 71 years (IQR 63-74)] 9 were treatment naïve (WMN), 15 had received rituximab-chemotherapy (WMT), and 13 were currently treated with a Bruton Tyrosine Kinase inhibitor (BTKi): 5 ibrutinib, 8 zanubrutinib (WMB). Of 35 patients with FL [16 (45.7%) female, median 65 years (IQR 54-71)], 11 were treatment naïve (FLN), and 24 had received rituximab-chemotherapy (FLT). Of the 13 controls 8 (61.5%) were female, median age 72 years (IQR 57-74)]. No participants had detectable ASAb at T1, confirming no prior SARS-CoV-2 exposure. Figure 1 shows ASAb results at T2. The median mean fluorescence intensity (MFI) of healthy controls: 60802 (IQR 17565 -78443), is higher than all WM: 0 (IQR 0-15010) p<0.0001, and all FL patients: 1687 (IQR 0-25421) p=0.002, Fig 1A. The median MFI of controls was higher than WMN (p=0.036), but not higher than FLN (p=0.28). The median MFI of WMN: 20074 (IQR 5421-35695), is higher than WMB: 0 (IQR 0-4217) p=0.018, but not significantly higher than WMT: 0 (IQR 0-14356) p=0.13, Fig 1B. Median MFI of FLN: 31476 (IQR 19351-51317), is higher than FLT: 0 (IQR 0-32849) p=0.01, Fig 1B. Conclusion These early serological data show measurable ASAb in all healthy controls 21 days post first dose of BNT162b2 vaccination. Treatment naïve patients had a better response than treated patients, and this did not differ significantly to healthy controls in the FL cohort. In WM, patients on BTKi had a significantly reduced response compared to treatment-naïve patients. This same reduction was not observed in the chemotherapy-rituximab cohort, but the characteristics of early responders versus non-responders, including time since last therapy, is being analysed. FL patients treated with chemotherapy-rituximab had a significantly reduced response compared to the treatmentnaïve cohort. Time constraints before the submission deadline prevented reporting of all mature vaccination response data. Measurement of ASAb one month after second vaccination, live virus neutralisation to a panel of SARS-CoV-2 variants of concern, and CD4+ and CD8+ antigen-specific T cell responses at T1, T2 and T3, to fully characterise the immune response to BNT162b2, will be reported at the ASH meeting.

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