Public perspective on potential treatment intervention harm in clinical trials-terminology and communication.

BACKGROUND: Randomised controlled trials (RCTs) are typically designed to determine beneficial intervention effects. In addition, an important aspect of every trial is to collect data on any potential harmful effects, with the aim of ensuring that the benefit-risk balance is appropriate. The language used by trialists to describe these potential harmful effects is inconsistent. In pharmacological trials, researchers collect adverse events; when a causal relationship is suspected adverse events are further classified as adverse reactions. Academic researchers have moved to collectively refer to these as harm outcomes; the pharmaceutical industry refer to these events as safety outcomes. In trials of complex interventions, phrases such as unintended consequences or effects are used. With the inconsistent use of terminology by researchers and the potential benefits to be gained from harmonising communications, we sought public opinion on terminology used to describe harmful effects and how these outcomes are communicated in the scientific literature, as well as in public facing material on medications. METHODS: We held two in-person public involvement meetings with public partners, in London and Aberdeen in 2023. Both meetings followed a pre-specified format. We provided a background to the topic including the information researchers collect on potential harms in clinical trials and shared examples on how this information gets presented in practice. We then discussed public partners' perspectives on terminology used and communication of intervention harm in academic journals and in public facing materials. A summary of these discussions and the main topics raised by public partners are presented. RESULTS: Public partners endorsed the use of different terms for different situations, preferring the use of 'side-effect' across all contexts and reserving the use of 'harm' to indicate more severe events. Generally, public partners were happy with the type of information presented in public facing materials but discussions revealed that presentation of information on public NHS websites led to misconceptions about harm. CONCLUSION: This work provides a starting point on preferred terminology by patients and the public to describe potential harmful intervention effects. Whilst researchers have tried to seek agreement, public partners endorsed use of different terms for different situations. We highlight some key areas for improvement in public facing materials that are necessary to avoid miscommunication and incorrect perception of harm.

Shining a spotlight on the inclusion of disabled participants in clinical trials: a mixed methods study.

BACKGROUND: It is crucial to include a wide range of the population in clinical trials for the outcome to be applicable in real-world settings. Existing literature indicates that under-served groups, including disabled people, have been excluded from participating in clinical trials without justification. Exclusion from clinical trials exacerbates disparities in healthcare and diminishes the benefits for excluded populations. Therefore, this study was conducted to investigate potential obstacles that prevent disabled people from participating in clinical trials in the United Kingdom (UK). METHODS: The study was carried out through an explanatory sequential mixed methods design. The Imperial Clinical Trials Unit devised and implemented an online questionnaire-based survey (with open/closed-ended questions) and an online focus group discussion. The target population were disabled people, family members/carers of disabled people and staff involved in clinical trials, whereupon the sample was recruited by convenience sampling methods via posters and emails through various networks. The Qualtrics XM survey system was used as the host platform for the online survey, and Microsoft Teams was used for an online focus group discussion. The focus group discussion was conducted to gain a deeper understanding of the themes identified from the survey responses. We analysed responses to the survey via descriptive analysis and used thematic analysis to synthesise the free-text answers from the survey and focus group discussion. RESULTS: We received 45 responses to the survey questionnaire and 5 disabled people took part in a focus group discussion. Our findings highlighted the differences between the perspectives of researchers and those "being researched" and different types of barriers experienced by disabled people: opportunity barriers (inadequate recruitment strategy and ambiguous eligibility criteria), awareness barriers (perception of disability) and acceptance/refusal barriers (available support and adjustment, and sharing of trial results). CONCLUSION: Our findings support perspectives drawn from the Ford Framework regarding the need to consider all barriers, not just up to the point of enrolment into trials but also beyond the point of inclusion in clinical trials. We support calls for the introduction of legislation on including disabled people in clinical trials, implementation of industry/community-wide participatory approaches and the development of guidelines, a combined public-private approach.

Using staged teaching and assessment approaches to facilitate inter-university collaboration and problem-based learning.

This article describes the segmented module design and problem-based learning approaches employed to enable parts of a higher education environmental health module (course) to be shared between universities in Wales, Northern Ireland, and Australia. The module requires students to identify the needs and assets of a community then design community-based interventions to address problems and undertake an evaluation of those interventions. Accreditation body and the degree program learning outcome requirements in the UK and Australia were found to hold many comparable knowledge, skills, and graduate attribute criteria, eliminating a potential barrier for international learning and teaching collaboration between higher education institutions. Instead, barriers to collaboration were associated with institutional issues and practicalities such as timetabling and assessment requirements. Taking a segmented approach to module design allowed staged and varied levels of collaboration between participating institutions, all delivering modules (courses) with similar learning outcomes. This provided a more sustainable environment to facilitate shared learning and teaching and fostered closer relations between programs, within these constraining factors. Students using problem-based learning and its group-working component exhibited the development of leadership, communication, and independent learning skills.

Barriers and facilitators to the recruitment of disabled people to clinical trials: a scoping review.

INTRODUCTION: Underrepresentation of disabled groups in clinical trials results in an inadequate evidence base for their clinical care, which drives health inequalities. This study aims to review and map the potential barriers and facilitators to the recruitment of disabled people in clinical trials to identify knowledge gaps and areas for further extensive research. The review addresses the question: 'What are the barriers and facilitators to recruitment of disabled people to clinical trials?'. METHODS: The Joanna Briggs Institute (JBI) Scoping review guidelines were followed to complete the current scoping review. MEDLINE and EMBASE databases were searched via Ovid. The literature search was guided by a combination of four key concepts from the research question: (1) disabled populations, (2) patient recruitment, (3) barriers and facilitators, and (4) clinical trials. Papers discussing barriers and facilitators of all types were included. Papers that did not have at least one disabled group as their population were excluded. Data on study characteristics and identified barriers and facilitators were extracted. Identified barriers and facilitators were then synthesised according to common themes. RESULTS: The review included 56 eligible papers. The evidence on barriers and facilitators was largely sourced from Short Communications from Researcher Perspectives (N = 22) and Primary Quantitative Research (N = 17). Carer perspectives were rarely represented in articles. The most common disability types for the population of interest in the literature were neurological and psychiatric disabilities. A total of five emergent themes were determined across the barriers and facilitators. These were as follows: risk vs benefit assessment, design and management of recruitment protocol, balancing internal and external validity considerations, consent and ethics, and systemic factors. CONCLUSIONS: Both barriers and facilitators were often highly specific to disability type and context. Assumptions should be minimised, and study design should prioritise principles of co-design and be informed by a data-driven assessment of needs for the study population. Person-centred approaches to consent that empower disabled people to exercise their right to choose should be adopted in inclusive practice. Implementing these recommendations stands to improve inclusive practices in clinical trial research, serving to produce a well-rounded and comprehensive evidence base.

An Evaluation of the Hand Hygiene Behaviour and Compliance of the General Public When Using Public Restrooms in Northern Ireland (NI) during the Initial Weeks of the Novel Coronavirus (COVID-19) Pandemic.

BACKGROUND: The ongoing novel coronavirus (COVID-19) global pandemic has resulted in significant levels of morbidity and mortality worldwide, particularly among the elderly and immuno-suppressed groups. Although adequate hand hygiene (HH) behaviour and compliance is widely accepted as being the most effective self-protective measure in preventing the spread of diseases like COVID-19, previous research suggests that normal hand hygiene compliance is poor, but generally improves during a disease pandemic. This research aimed to evaluate the hand hygiene behaviour and compliance of the general public in the initial weeks of the COVID-19 pandemic in Northern Ireland (NI). METHODS: This cross-sectional study involved the use of infrared-imaging cameras to observe the hand hygiene behaviour and compliance of the general public when using one set of male and female public restrooms. RESULTS: The findings of this study indicated that the level of hand hygiene compliance of the general public was poor in the initial weeks, with 82.93% overall not washing their hands adequately. CONCLUSIONS: Inadequate HH behaviour and compliance may have added significantly to the rapid rate of spread of COVID-19 in the initial weeks of the pandemic in NI. Current public health campaigns do not appear, based on this study, to have the desired impact and may need to be reviewed or re-enforced in order to achieve the levels of hand hygiene compliance required to slow the spread of COVID-19 and other communicable diseases in the future.

An Investigation of the General Population's Self-Reported Hand Hygiene Behaviour and Compliance in a Cross-European Setting.

Every year, thousands of people from the UK travel to other countries for work and leisure. Europe, and particularly Spain, is one of the most popular travel destinations for people from the UK. However, it is known that travel to other countries can enhance the risk of communicable disease transmission from person to person, especially when a new one emerges. Adequate hand hygiene behaviour and compliance is widely accepted as being a simple, effective method in preventing the spread of communicable diseases that may be contracted during travel abroad. There is a well-established body of work investigating hand hygiene practice and compliance in community settings, but no recent studies have examined the hand hygiene practice and compliance of the general population when travelling abroad or in a cross-European context. The findings of this study indicated that most UK members of the general population when travelling abroad have a good level of understanding of the importance of adequate hand hygiene practice and compliance and its role regarding communicable disease prevention and control. As such, self-reported levels of compliance were high. Similar findings were made for Spanish members of the general population. However, while self-reported perceptions of adequacy of hand hygiene performance were relatively high, particularly among UK respondents, this was not supported by responses specifically focused on hand hygiene behaviour. However, differences in self-reported adequacy regarding the importance of handwashing versus hand drying, the number of steps that should be followed and the length of time that should be spent washing and drying hands were found for each group. This suggests that self-reported compliance may reflect intention to practice hand hygiene rather than true compliance. It also suggests that there are gaps in knowledge regarding the adequate method of hand hygiene among the cohort as a whole, and indeed these differences may account be a factor in for the high transmission rates of communicable disease when travelling abroad.

A Comprehensive Patient and Public Involvement Program Evaluating Perception of Cannabis-Derived Medicinal Products in the Treatment of Acute Postoperative Pain, Nausea, and Vomiting Using a Qualitative Thematic Framework.

Introduction: Cannabis-derived medicinal products (CDMPs) have antiemetic properties and in combination with opioids have synergistic analgesic effects in part signaling through the delta and kappa opioid receptors. The objective of this patient and public involvement program was to determine perception of perioperative CDMPs in our local population to inform design of a clinical trial. Methods: A qualitative evaluation was conducted utilizing a focus group, semistructured interviews and a community event. Analysis was conducted through the framework methodology. Verbatim transcriptions were coded categorically into analytical frameworks for thematic analysis. Emergent themes and associated degree of consensus/dissent were determined. The participant cohort was composed of a group of patients and relatives representative of the target population (M:F=1:1, age range 33-85). Results: Most common coding categories in thematic analysis framework included side-effect profile, trial schedule of events, and safety. Consensus was that potential benefits of CDMPs were attractive compared with the known risk profile of opioid use. Decrease in opioid dependence was agreed to be an appropriate clinical end-point for a randomized controlled clinical trial and there was concurrence of positive opinion of a therapeutic schedule of 5 days. Negative CDMP perceptions included addiction, dysphoria, and adverse effects in psychiatric subpopulations. Sublingual or oral administration was the most acceptable route of administration, with some expressing that inhalation delegitimizes therapeutic properties. Conclusions: The perception of postoperative CDMP therapy was overwhelmingly positive in this West London population. The data from this thematic analysis will inform protocol development of clinical trials to determine analgesic and antiemetic efficacy of CDMPs.

The Effectiveness of a Poster Intervention on Hand Hygiene Practice and Compliance When Using Public Restrooms in a University Setting.

BACKGROUND: Most research on hand hygiene compliance in community settings indicates that compliance is poor. It is not conclusive as to whether poster interventions are effective at improving compliance. METHODS: An independent, self-designed poster intervention was installed in one set of male and female public restrooms in a university campus in the UK. The hand hygiene practice and compliance of the university population was measured via indirect observation over a 60 day period. RESULTS: During the pre-intervention observation period, 51.09% of the university population practiced basic hand hygiene compliance (washed hands with water, soap and dried afterwards), and 7.88% practiced adequate hand hygiene compliance (washed hands with water and soap for 20 s or more and dried afterwards for 20 s or more). During the post-intervention observation period, 55.39% of the university population were observed practicing basic hand hygiene compliance, and 7.97% practicing adequate hand hygiene compliance. Gender differences revealed that more females practiced basic hand hygiene in the post-intervention observation period (62.81%) than during the pre-intervention period (49.23%) and this was statistically significant (χ2 = 13.49, p = < 0.01). DISCUSSION: The poster intervention had a limited effect on improving the basic and adequate hand hygiene compliance of the general population when using public restrooms. The use of independent, self-designed posters to improve hand hygiene practice and compliance is largely ineffective in the short term and should be used with caution in future intervention strategies.

IPET study: an FLT-PET window study to assess the activity of the steroid sulfatase inhibitor irosustat in early breast cancer.

BACKGROUND: Steroid sulfatase (STS) is involved in oestrogen biosynthesis and irosustat is a first generation, irreversible steroid sulfatase inhibitor. A pre-surgical window-of-opportunity study with irosustat was undertaken in estrogen receptor-positive (ER+) breast cancer to assess the effect of irosustat on tumour cell proliferation as measured by 3'-deoxy-3'-[18F] fluorothymidine uptake measured by PET scanning (FLT-PET) and Ki67. METHODS: Postmenopausal women with untreated ER+ early breast cancer were recruited, and imaged with FLT-PET at baseline and after at least 2 weeks treatment with irosustat, 40 mg once daily orally. The primary endpoint was changed in FLT uptake; secondary endpoints included safety and tolerability of irosustat, changes in tumoral Ki67 and steroidogenic enzymes expression and circulating steroid hormone levels. RESULTS: Thirteen women were recruited, and ten started irosustat for 2 weeks, followed by repeat FLT-PET scans in eight. Defining response as decreases of ≥20% in standardized uptake value (SUV) or ≥30% in Ki, 1 (12.5% (95% CI 2-47%, p = 0.001)) and 3 (43% (95% CI 16-75%, p = <0.001) patients, respectively, responded. 6 out of 7 patients had a Ki67 reduction (range = -19.3 to 76.4%), and median percentage difference in Ki67 was 52.3% (p = 0.028). In one patient with a low baseline STS expression, a 19.7% increase in Ki67 was recorded. STS decreases were seen in tumours with high basal STS expression, significant decreases were also noted in aromatase, and 17ß-hydroxysteroid dehydrogenase type 1 and 2. Irosustat was generally well tolerated with all adverse event CTCAE Grade ≤2. CONCLUSIONS: Irosustat resulted in a significant reduction in FLT uptake and Ki67, and is well tolerated. These data are the first demonstrating clinical activity of irosustat in early breast cancer. Baseline expression of STS may be a biomarker of sensitivity to irosustat.

Early endocrine disruptors exposure acts on 3T3-L1 differentiation and endocrine activity.

Introduction: Data from last years suggested that early exposure to endocrine disruptors (EDs) can predispose newborns to endocrine dysfunction of adipocytes, obesity, and associated disorders. The implication of EDs at low doses on adipocyte development has been poorly investigated. For instance, vinclozolin (V) is a dicarboximide fungicide widely used in agriculture since the 90's, alone or in mixture with genistein (G), an isoflavonoid from Leguminosae. This study aims to identify the effect of vinclozolin alone or with genistein, on adipose tissue properties using cell culture. Methods: In steroid-free conditions, 3T3-L1 pre-adipocytes were induced to differentiate in the presence of EDs, singularly or in mixtures, for 2 days. DNA and triglyceride (TG) levels were measured on days 0, 2 and 8 of differentiation. Leptin secretion was measured only on the eighth day. Results: We show that low doses of G (25 µM) and V (0.1 µM) inhibit pre-adipocytes differentiation. This inhibition has been represented by a decreasing in DNA content (µg/well) and decreasing in TG accumulation (mg/mL) in 3T3-L1 cells. Nevertheless, V increased the anti-adipogenic properties of G. Conclusion: This study confirms that EDs singularly or in mixtures, introduced during early stages of life, could affect the differentiation and the endocrine activity of adipocytes, and can act as potential factors for obesity.

Fathering and Adolescent Adjustment: Variations by Family Structure and Ethnic Background.

The current study investigated how fathering behaviors (acceptance, rejection, monitoring, consistent discipline, and involvement) are related to preadolescent adjustment in Mexican American and European American stepfamilies and intact families. Cross-sectional data from 393 7th graders, their schoolteachers, and parents were used to examine links between different dimensions of fathering and adolescent outcomes. Following an ecological multivariate model, family SES, marital satisfaction, and mothers' parenting were included as controls. In all contexts, fathering had significant effects on adolescent adjustment. Both mothers' parenting and adolescent gender moderated the associations, and we uncovered some provocative nonlinear relations between fathering and adolescent outcomes. The importance of ethnicity and family structure in studies of fathering are highlighted.

Comparison of views of the nature of science between natural science and nonscience majors.

Science educators have the common goal of helping students develop scientific literacy, including understanding of the nature of science (NOS). University faculties are challenged with the need to develop informed NOS views in several major student subpopulations, including science majors and nonscience majors. Research into NOS views of undergraduates, particularly science majors, has been limited. In this study, NOS views of undergraduates in introductory environmental science and upper-level animal behavior courses were measured using Likert items and open-ended prompts. Analysis revealed similarities in students' views between the two courses; both populations held a mix of naïve, transitional, and moderately informed views. Comparison of pre- and postcourse mean scores revealed significant changes in NOS views only in select aspects of NOS. Student scores on sections addressing six aspects of NOS were significantly different in most cases, showing notably uninformed views of the distinctions between scientific theories and laws. Evidence-based insight into student NOS views can aid in reforming undergraduate science courses and will add to faculty and researcher understanding of the impressions of science held by undergraduates, helping educators improve scientific literacy in future scientists and diverse college graduates.

Cervical cancer after multiple negative cytologic tests in long-term members of a prepaid health plan.

OBJECTIVE: To estimate squamous cell cervical cancer incidence within 3.5 years of 1, 2 and > or = 3 consecutive, normal cytologic tests. STUDY DESIGN: Data were from a case-control study of cervical cancer screening efficacy. Long-term members of a prepaid health plan diagnosed with cancer from 1983 to 1995 (the cases) were grouped by number of prior conventional cytologic tests and by time from the last negative screening test to the diagnosis date. Women from the population at risk were estimated by multiplying the timated by multiplying the proportions of women without cancer (the matched controls) in each screening category by the numbers of long-term of the numbers of long-term female members enrolled from male members enrolled from 1983 to 1995. RESULTS: Of an estimated 6,802,641 woman-years of observation, 129 cases were diagnosed within 3.5 years of > or = 21 negative screening test. After > or = 3 consecutive negative tests, incidence per 100,000 woman-years grouped by time from the last negative screening test were: 1.43 (26/1,813,552) 0-18 months later, 4.24 (17/400,584) 19-30 months later and 4.73 (10/211,217) 31- 42 months later. CONCLUSION: The first 18 months after the last negative screening Pap test in women with > or = 3 prior negative tests, cancer incidence increases to an estimated 4-5 per 100,000 woman-years in each of the subsequent 2 years.

Isolation of Pea Thioredoxin f Precursor Protein and Characterization of its Biochemical Properties.

Like many other soluble chloroplastic enzymes, thioredoxin f is nuclear-encoded and expressed as a precursor protein. After synthesis in the cytosol, it is imported into the chloroplast with subsequent cleavage of the transit sequence in the stroma. We report the expression and the partial purification of the recombinant precursor thioredoxin f protein. The prethioredoxin f was found to be located essentially in the insoluble Echerichia coli fraction, but could be renatured after urea treatment followed by dialysis. The renatured protein was active in the dithiothreitol- and thioredoxin-dependent activation of NADP malate dehydrogenase and also of fructose bisphosphatase and in the ferredoxin-thioredoxin-dependent fructose bisphosphatase activation. These data are discussed in relation with the known properties of mature thioredoxin f.

Stage at diagnosis and mortality in patients with adenocarcinoma and adenosquamous carcinoma of the uterine cervix diagnosed as a consequence of cytologic screening.

OBJECTIVE: To determine if cytologic screening is associated with early stage at diagnosis of and decreased mortality from invasive adenocarcinoma and adenosquamous carcinoma of the uterine cervix. STUDY DESIGN: We retrospectively reviewed the medical records of all 169 women diagnosed with invasive adenocarcinoma or adenosquamous carcinoma of the cervix in a prepaid health plan during 1988-1994. Differences in stage and survival were assessed in relation to screening history and symptoms. RESULTS: Among the 169 cases, late-stage disease was present in 19/169 women (11.2%) at the time of diagnosis, and 24/269 (14.2%) women died of the disease during the three-year follow-up period. Women whose cancer was screen detected numbered 48/169 (28.4%) and were less likely to present with late-stage disease than non-screen-detected women: 2/48 (4.2%) versus 17/121 (14.0%) (P = .05). A mortality advantage at three years from diagnosis was associated with screen-detected cancers: 1/48 (2.1%) versus 23/121 (19.0%) (P = .002), and this advantage persisted after controlling for stage at diagnosis. CONCLUSION: Invasive adenocarcinomas and adenosquamous carcinomas of the cervix detected by screening are found at an earlier stage and are associated with lower disease-specific mortality than those not detected by screening.

Screening interval and risk of invasive squamous cell cervical cancer.

To compare the risks of developing invasive squamous cell cervical cancer associated with screening intervals of 1, 2, and 3 years after a negative cervical smear. We conducted a matched case-control study of invasive squamous cell cervical cancer patients (n = 482) diagnosed between 1983 and 1995 among long-term members of a large health maintenance organization. Controls were matched for age, length of membership, and race (n = 934). Screening interval was time between the last negative cervical smear and the case diagnosis date. The main outcome measure was the relative odds of invasive disease associated with 1-year, 2-year, and 3-year intervals. The odds ratio for a 2-year versus a 1-year interval was 1.72 (95% confidence interval 1.12, 2.64, P =.013) and for a 3-year versus a 1-year interval was 2.06 (95% confidence interval 1.21, 3.50, P =.007). The odds ratio for a 3-year versus a 2-year interval was 1.20 (95% confidence interval 0.65, 2.21, P =.561). Controlling for ever having had an abnormal cervical smear or a previous consecutive negative smear did not substantially change these results. In this large health plan, the relative risks of invasive squamous cell cervical cancer were significantly greater for 2-year and 3-year cervical cancer screening intervals compared with a 1-year interval, but not for a 3-year interval compared with a 2-year interval. Our findings need to be placed in the context of the low absolute risks of developing invasive cervical cancer during the first 3 years after a negative cervical smear before making policy recommendation.

The process to develop a meaningful community health assessment in New York State.

Conducting and producing a meaningful Community Health Assessment (CHA) is an important and essential public health service and a mandatory biennial activity for New York State's (NYS) Local Health Departments. The Assessment Initiative project has allowed the NYS Department of Health to better understand and identify strategies to strengthen CHAs and to develop training, education, and technical assistance programs. The Assessment Initiative project has benefited from participation, coordination, and sharing of resources and expertise with other community health improvement initiatives in NYS, including those that emphasize collaborative approaches to health improvement, workforce development, and expanding access to data.