Applying the COM-B behaviour model to understand factors which impact 15-16 year old students' ability to protect themselves against acquirement of Human Papilloma virus (HPV) in Northern Ireland, UK.

High-risk strains of Human Papillomavirus (HPV) can lead to the development of a number of cancers including cervical, vulvar, penile, anal and oropharyngeal. HPV vaccination programmes offer the HPV vaccine to males and females 12-13 years old in schools throughout the UK. However, knowledge of HPV remains low in post-primary schools. The aim of this study is to capture 15-16 year old students' perceptions regarding the current provision of HPV education, and whether providing HPV education to 15-16 year olds could influence their intention to be vaccinated and/or future sexual health decisions related to HPV. Between 5th November 2021 and 6th May 2022, seven focus groups were conducted with 34 students in post-primary schools in Northern Ireland, United Kingdom. The data was analysed using the COM-B behaviour model to explore the perceived facilitators and barriers impacting students' ability to protect themselves from acquirement of HPV. Students perceived their knowledge of HPV to be poor and supported the addition of comprehensive mandatory HPV education at 15-16 years old when many of them were becoming sexually active. They identified barriers including lack of parental education, school ethos and religion and insufficient education regarding their legal rights to self-consent to HPV vaccination. Students felt that removal of these barriers would lead to safer sexual practices, increased awareness of the importance of HPV screening and increased HPV vaccination uptake. The recommendations provided by students need to be supported by the Education Authority in conjunction with the Department of Health in order to be successfully implemented into the post-primary school curriculum.

Applying the COM-B behaviour model to understand factors which impact school immunisation nurses' attitudes towards designing and delivering a HPV educational intervention in post-primary schools for 15-17 year old students in Northern Ireland, UK.

INTRODUCTION: Human Papilloma Virus (HPV) is responsible for the development of cervical, vaginal, vulvar, penile, oropharyngeal and anal cancers. Throughout the UK, Immunisation nurses (IMNs) deliver school-based HPV vaccinations to students 12-13 years old. Providing HPV education to 15-17 year old students may promote decision-making regarding their sexual health and award opportunity for unvaccinated students to self-consent to the vaccination. This study aims to explore the perceptions of IMNs regarding the value of providing HPV education to 15-17 year old students and to explore whether IMNs feel that the design/delivery of this education should form part of their professional role. METHODS: Six focus groups were conducted online with IMNs from all five Health and Social Care Trusts in Northern Ireland, UK, between January-June 2021. Data were analysed using the COM-B model to identify factors that might influence IMNs' behaviour towards designing/delivering this education for 15-17 year old students. RESULTS: IMNs were highly motivated to design and deliver this HPV education. Facilitators promoting this behaviour included their specialist training, their previous sexual health teaching experience and their desire to educate young people. Barriers negatively influencing this behaviour included lack of time/resources, parental influences, lack of school support and lack of teaching/presentation skills training. CONCLUSION: IMNs feel that they are the most appropriate professionals to design/deliver HPV education for 15-17 year old students. National policy change, based on collaboration between the Public Health Agency and Education Authority, is a key factor in facilitating IMNs to implement this school-based HPV education intervention.

Experiences of cancer patients in receiving dietary advice from healthcare professionals and of healthcare professionals in providing this advice-a systematic review.

PURPOSE: This systematic review investigated qualitative and quantitative studies exploring patients and healthcare professionals' (HCP) experience of nutrition care throughout the cancer journey. METHODS: Five databases were systematically searched for studies reporting on patient and healthcare professionals' experience of nutrition advice. RESULTS: Fifteen studies including 374 patients and 471 healthcare professionals were included. Findings indicate that patients desire more specific nutrition advice supported by members of the multidisciplinary team and delivered in appropriate and understandable language. Healthcare professionals have highlighted a lack of time, funding, dietetic roles, and knowledge as barriers to integrating nutrition as a standard part of cancer care. Five themes were identified (current provision of nutrition advice, optimal provision of nutrition advice, tension between patient values and nutritional or HCP priorities, providing evidence-based nutrition care, and practical barriers to nutrition advice provision). CONCLUSIONS: Further work is essential to better understand and address identified barriers and improve the provision of nutrition advice to this population. IMPLICATIONS FOR CANCER SURVIVORS: Findings from this review will guide the delivery of nutrition advice for cancer survivors.

Effectiveness of Exercise on Fatigue and Sleep Quality in Fibromyalgia: A Systematic Review and Meta-analysis of Randomized Trials.

OBJECTIVES: To determine the effects of exercise on fatigue and sleep quality in fibromyalgia (primary aim) and to identify which type of exercise is the most effective in achieving these outcomes (secondary aim). DATA SOURCES: PubMed and Web of Science were searched from inception until October 18, 2018. STUDY SELECTION: Eligible studies contained information on population (fibromyalgia), intervention (exercise), and outcomes (fatigue or sleep). Randomized controlled trials (RCT) testing the effectiveness of exercise compared with usual care and randomized trials (RT) comparing the effectiveness of 2 different exercise interventions were included for the primary and secondary aims of the present review, respectively. Two independent researchers performed the search, screening, and final eligibility of the articles. Of 696 studies identified, 17 RCTs (n=1003) were included for fatigue and 12 RCTs (n=731) for sleep. Furthermore, 21 RTs compared the effectiveness of different exercise interventions (n=1254). DATA EXTRACTION: Two independent researchers extracted the key information from each eligible study. DATA SYNTHESIS: Separate random-effect meta-analyses were performed to examine the effects from RCTs and from RTs (primary and secondary aims). Standardized mean differences (SMD) effect sizes were calculated using Hedges' adjusted g. Effect sizes of 0.2, 0.4, and 0.8 were considered small, moderate, and large. Compared with usual care, exercise had moderate effects on fatigue and a small effect on sleep quality (SMD, -0.47; 95% confidence interval [CI], -0.67 to -0.27; P<.001 and SMD, -0.17; 95% CI, -0.32 to -0.01; P=.04). RTs in which fatigue was the primary outcome were the most beneficial for lowering fatigue. Additionally, meditative exercise programs were the most effective for improving sleep quality. CONCLUSIONS: Exercise is moderately effective for lowering fatigue and has small effects on enhancing sleep quality in fibromyalgia. Meditative exercise programs may be considered for improving sleep quality in fibromyalgia.

Impact of school-based educational interventions in middle adolescent populations (15-17yrs) on human papillomavirus (HPV) vaccination uptake and perceptions/knowledge of HPV and its associated cancers: A systematic review.

The American Academy of Paediatrics (AAP) divides adolescence into early (12-14 years), middle (15-17 years), and late (18-21 years) stages. School-based HPV educational interventions are largely directed at parents of early adolescents at the time of vaccination. As the average age of first sexual intercourse in high income countries is 15-17 years old, a second educational intervention for middle adolescents could have a strong impact on HPV prevention, providing an opportunity for self-consenting to HPV vaccination in many countries. This paper appraises literature exploring the impact of school-based educational interventions in 15-17 year olds, on HPV vaccination uptake and/or perceptions/knowledge of HPV and its associated cancers. Randomised controlled trials (RCTs) and quasi-experimental designs (QEDs) (2007-2019) were included if they delivered a school-based educational intervention for 15-17 year olds, and the outcome measures included HPV vaccination uptake, knowledge of HPV and associated cancers or perception/attitude regarding self-protection against HPV. Fifteen studies met the inclusion criteria and were assessed for quality using the Quality Assessment Tool for Quantitative Studies. All studies demonstrated a statistically significant improvement in at least one major outcome measure post-intervention, despite the wide range in design of interventions, though only three studies actually measured changes to HPV vaccination uptake. Stakeholder engagement was absent in most intervention designs and many were not grounded in evidenced theory. Content was largely focused on female cervical cancer, rarely discussing oropharyngeal cancer, the most pre-dominant HPV-associated cancer in men. An optimal mixed gender intervention remains to be established for middle adolescents.

Removal of scatter radiation in paediatric cardiac catheterisation: a randomised controlled clinical trial.

OBJECTIVE: This study sought to determine if DNA integrity was compromised by ionising radiation from paediatric cardiac catheterisations and if dose optimisation techniques allowed DNA integrity to be maintained. MATERIALS AND METHODS: Children were imaged using either: (i) an anti-scatter grid (current departmental protocol), (ii) no anti-scatter grid or, (iii) no anti-scatter grid and a 15 cm air-gap between the child and the x-ray detector. Dose area product and image quality were assessed, lifetime attributable cancer risk estimates were calculated and DNA double-strand breakages quantified using the γH2AX assay. RESULTS: Consent was obtained from 70 parents/guardians/children. Image quality was sufficient for each procedure performed. Removal of the anti-scatter grid resulted in dose reductions of 20% (no anti-scatter grid) and 30% (15 cm air-gap), DNA double-strand break reductions of 30% (no anti-scatter grid) and 20% (15 cm air-gap) and a reduction of radiation-induced cancer mortality risk of up to 45%. CONCLUSION: Radiation doses received during paediatric cardiac catheterisation procedures resulted in a significant increase in DNA damage while maintaining acceptable image quality and diagnostic efficacy. It is feasible to remove the anti-scatter grid resulting in a reduction in DNA damage to the patient. The γH2AX assay may be used for assessment of dose optimisation strategies in children.

Effects of α-lipoic acid on mtDNA damage after isolated muscle contractions.

INTRODUCTION: Although pharmacological antioxidants have previously been investigated for a prophylactic effect against exercise oxidative stress, it is not known if α-lipoic acid supplementation can protect against DNA damage after high-intensity isolated quadriceps exercise. This randomized controlled investigation was designed to test the hypothesis that 14 d of α-lipoic acid supplementation can attenuate exercise-induced oxidative stress. METHODS: Twelve (n = 12) apparently healthy male participants (age = 28 ± 10 yr, stature = 177 ± 12 cm and body mass = 81 ± 15 kg) were randomly assigned to receive either a daily supplement of 1000 mg of α-lipoic acid (2 × 500-mg tablets) for 14 d (n = 6) or receive no supplement (n = 6) in a double-blinded experimental approach. Blood and muscle biopsy tissue samples were taken at rest and after the completion of 100 isolated and continuous maximal knee extension (minimum force = 200 N, speed of contraction = 60° · s(-1)). RESULTS: Exercise increased mitochondrial 8-hydroxy-2-deoxyguanosine (8-OHdG) concentration in both groups (P < 0.05 vs rest) with a concomitant decrease in total antioxidant capacity (P < 0.05 vs rest). There was a marked increase in blood total antioxidant capacity after oral α-lipoic acid supplementation (P < 0.05 vs nonsupplemented), whereas DNA damage (Comet assay and 8-OHdG), lipid peroxidation, and hydrogen peroxide increased after exercise in the nonsupplemented group only (P < 0.05 vs supplemented). Exercise increased protein oxidation in both groups (P < 0.05 vs rest). CONCLUSIONS: These findings suggest that short-term α-lipoic acid supplementation can selectively protect DNA (but not in muscle mitochondria) and lipids against exercise-induced oxidative stress.

Exercise-induced lipid peroxidation: Implications for deoxyribonucleic acid damage and systemic free radical generation.

Exercise-induced deoxyribonucleic acid (DNA) damage is often associated with an increase in free radicals; however, there is a lack of evidence examining the two in parallel. This study tested the hypothesis that high-intensity exercise has the ability to produce free radicals that may be capable of causing DNA damage. Twelve apparently healthy male subjects (age: 23 ± 4 years; stature: 181 ± 8 cm; body mass: 80 ± 9 kg; and VO(2max) : 49 ± 5 ml/kg/min) performed three 5 min consecutive and incremental stages (40, 70, and 100% of VO(2max) ) of aerobic exercise with a 15-min period separating each stage. Blood was drawn after each bout of exercise for the determination of ex vivo free radicals, DNA damage, protein carbonyls, lipid hydroperoxide (LOOH) concentration, and a range of lipid-soluble antioxidants. Lipid-derived oxygen-centered free radicals (hyperfine coupling constants a(Nitrogen) = 13.7 Gauss (G) and aß(Hydrogen) = 1.8 G) increased as a result of acute moderate and high-intensity exercise (P < 0.05), while DNA damage was also increased (P < 0.05). Systemic changes were observed in LOOH and for lipid-soluble antioxidants throughout exercise (P < 0.05); however, there was no observed change in protein carbonyl concentration (P > 0.05). These findings identify lipid-derived free radical species as possible contributors to peripheral mononuclear cell DNA damage in the human exercising model. This damage occurs in the presence of lipid oxidation but in the absence of any change to protein carbonyl concentration. The significance of these findings may have relevance in terms of immune function, the aging process, and the pathology of carcinogenesis.

A cytochrome P450 2B6 meditated gene therapy strategy to enhance the effects of radiation or cyclophosphamide when combined with the bioreductive drug AQ4N.

BACKGROUND: AQ4N is metabolised in hypoxic cells by cytochrome P450s (CYPs) to the cytotoxin AQ4. Most solid tumours are known to contain regions of hypoxia whereas levels of CYPs have been found to vary considerably. Enhancement of CYP levels may be obtained using gene-directed enzyme prodrug therapy (GDEPT). We have therefore examined the potential of a CYP2B6-mediated GDEPT strategy to enhance the anti-tumour effect of the combination of AQ4N with radiation or cyclophosphamide (CPA). METHODS: In vitro and in vivo transient transfection of human CYP2B6 +/- CYP reductase (CYPRED) was investigated in RIF-1 mouse tumours. Efficacy in vitro was assessed using the alkaline comet assay (ACA). In vivo, the time to reach 4x the treatment volume (quadrupling time; VQT) was used as the end point. RESULTS: When CYP2B6 was transfected into RIF-1 cells and treated with AQ4N under hypoxic conditions there was a significant increase in DNA damage (measured by the ACA) compared with non-transfected cells. In vivo, a single intra-tumoural injection of a CYP2B6 vector construct significantly enhanced tumour growth delay in combination with AQ4N (100 mg/kg) and 10 Gy X-rays. AQ4N (100 mg/kg) and CPA (100 mg/kg) with CYP2B6 and CYPRED also enhanced tumour growth delay; this effect became significant when the schedule was repeated 14 days later (p = 0.0197). CONCLUSIONS: The results show the efficacy of a CYP2B6-mediated GDEPT strategy for bioreduction of AQ4N; this may offer an additional approach to target radiation- and chemo-resistant hypoxic tumours that should enhance overall tumour control.

Bioreductive GDEPT using cytochrome P450 3A4 in combination with AQ4N.

The bioreductive drug, AQ4N, is metabolized under hypoxic conditions and has been shown to enhance the antitumor effects of radiation and chemotherapy drugs. We have investigated the role of cytochrome P450 3A4 (CYP3A4) in increasing the metabolism of AQ4N using a gene-directed enzyme prodrug therapy (GDEPT) strategy. RIF-1 murine tumor cells were transfected with a mammalian expression vector containing CYP3A4 cDNA. In vitro AQ4N metabolism, DNA damage, and clonogenic cell kill were assessed following exposure of transfected and parental control cells to AQ4N. The presence of exogenous CYP3A4 increased the metabolism of AQ4N and significantly enhanced the ability of the drug to cause DNA strand breaks and clonogenic cell death. Cotransfection of CYP reductase with CYP3A4 showed a small enhancement of the effect in the DNA damage assay only. A single injection of CYP3A4 into established RIF-1 murine tumors increased the metabolism of AQ4N, and when used in combination with radiation, three of nine tumors were locally controlled for >60 days. This is the first demonstration that CYPs alone can be used in a GDEPT strategy for bioreduction of the cytotoxic prodrug, AQ4N. AQ4N is the only CYP-activated bioreductive agent in clinical trials. Combination with a GDEPT strategy may offer a further opportunity for targeting radiation-resistant and chemo-resistant hypoxic tumor cells.