Factors Associated With Oral Mucositis Severity in Children Who Have Received Chemotherapy.

Oral mucositis (OM) is a major complication for pediatric oncology patients undergoing cancer therapy. This paper aimed to report on the relationship between OM severity and various patient factors as well as to compare 2 scales used to assess OM severity. The severity of 68 separate episodes of OM in 47 pediatric oncology patients who had received chemotherapy was regularly assessed using the Children's International Mucositis Evaluation Scale (ChIMES) and World Health Organization (WHO) scale. The mean time from the start of the patients' chemotherapy block to the onset of OM was 8.4 days (±4.0), the median duration of OM was 7.0 days (4.0, 10.5) and median admission duration was 7.0 days (4.5, 13.5). There was a significant relationship between the severity of OM and the duration of symptoms ( P <0.001), patient's admission length ( P <0.001) and low neutrophil count. With decreasing neutrophil count, the severity of OM and number of pain medications used increased. Neutrophil count recovery coincided with resolution of OM. No significant relationship was found between OM severity and the child's cancer diagnosis. The 2 scales used to measure OM severity showed substantial agreement.

An update on Heck's disease-a systematic review.

BACKGROUND: Previous research has suggested an ethnic association of Heck's disease with a prominent genetic and familial inheritance pattern, but no systematic review has been reported, which has collected all the evidence in one paper. The aim was estimation of the updated age estimates and gender predilection of this disease and also questioning its proposed link to ethnic and geographical factors. METHODS: Heck's disease from 1966 until present are tabulated, including various descriptive characteristics. After removal of duplicates and adhering to all the inclusion criteria, we shortlisted 95 case reports. The quality assessment of all included studies has been done following STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) guidelines. RESULTS: We found an age range of 3-92 years (mean: 23.1 years) with a male to female ratio of 3:4. Geographical distribution revealed one of the main findings of this study, which was an increased incidence of Heck's disease in the European region. CONCLUSIONS: As already observed and established, there is a much greater prevalence of this disease in the indigenous populations of the world and more research should be encouraged to understand the correct transmission and pattern of spread of this disease.

Implementation and evaluation of social determinants of health practice models within community pharmacy.

BACKGROUND: While community pharmacies are an ideal setting for social needs screening and referral programs, information on social risk assessment within pharmacy practice is limited. OBJECTIVES: Our primary objective was to describe 2 social determinant of health (SDOH) practice models implemented within community pharmacies. The secondary objective was to evaluate implementation practices utilizing the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. PRACTICE DESCRIPTION: Two pharmacy groups participated in a 3-month study, one in New York (9 pharmacies) and another in Missouri (1 pharmacy). The New York pharmacies implemented an SDOH specialist practice model, in which pharmacy staff members facilitate the program. The Missouri pharmacy implemented a community health worker (CHW) model by cross training their technicians. Each pharmacy developed their program using the Community Pharmacy Enhanced Services Network Care Model. PRACTICE INNOVATION: Both programs expanded the technician role to take on additional responsibilities. The SDOH specialist model partnered with a local independent practice association to create a social needs referral program using a technology platform for closed-loop communication. All workflow steps of the self-contained CHW program were completed within the pharmacy, placing additional responsibility on the CHW and pharmacy staff. EVALUATION METHODS: RE-AIM framework dimensions of Reach, Effectiveness, and Adoption. RESULTS: Social challenges were identified in 49 of 76 (65%) generated SDOH screenings. The most prevalent social needs reported were affordability of daily needs (33%) and health care system navigation (15%). While most pharmacy staff indicated that workflow steps were clearly defined, assessments and referral tools were identified as potential gaps. While approximately 50% of pharmacy staff were comfortable with their assigned roles and in addressing SDOH challenges, physical and mental health concerns required additional education for intervention. CONCLUSION: The successful implementation of community pharmacy SDOH programs connected patients with local resources. Community pharmacies are ideally positioned to expand their public health footprint through SDOH interactions that consequently improve patient care.

Choice of faecal immunochemical test matters: comparison of OC-Sensor and HM-JACKarc, in the assessment of patients at high risk of colorectal cancer.

OBJECTIVES: Currently, NICE recommends the use of faecal immunochemical test (FIT) at faecal haemoglobin concentrations (f-Hb) of 10 µg Hb/g faeces to stratify for colorectal cancer (CRC) risk in symptomatic populations. This f-Hb cut-off is advised across all analysers, despite the fact that a direct comparison of analyser performance, in a clinical setting, has not been performed. METHODS: Two specimen collection devices (OC-Sensor, OC-S; HM-JACKarc, HM-J) were sent to 914 consecutive individuals referred for follow up due to their increased risk of CRC. Agreement of f-Hb around cut-offs of 4, 10 and 150 µg Hb/g faeces and CRC detection rates were assessed. Two OC-S devices were sent to a further 114 individuals, for within test comparisons. RESULTS: A total of 732 (80.1%) individuals correctly completed and returned two different FIT devices, with 38 (5.2%) CRCs detected. Median f-Hb for individuals diagnosed with and without CRC were 258.5 and 1.8 µg Hb/g faeces for OC-S and 318.1 and 1.0 µg Hb/g faeces for HM-J respectively. Correlation of f-Hb results between OC-S/HM-J over the full range was rho=0.74, p<0.001. Using a f-Hb of 4 µg Hb/g faeces for both tests found an agreement of 88.1%, at 10 µg Hb/g faeces 91.7% and at 150 µg Hb/g faeces 96.3%. A total of 114 individuals completed and returned two OC-S devices; correlation across the full range was rho=0.98, p<0.001. CONCLUSIONS: We found large variations in f-Hb when different FIT devices were used, but a smaller variation when the same FIT device was used. Our data suggest that analyser-specific f-Hb cut-offs are applied with regard to clinical decision making, especially at lower f-Hb.

A systematic review and meta-analysis of the prevalence of human papillomavirus infection in Indigenous populations - A Global Picture.

BACKGROUND AND AIM: Recent trends have shown a decline in the rates of human papillomavirus (HPV)-associated cervical cancer in the vaccinated population but there has been a spike in the HPV-associated oropharyngeal, anal and penile cancers in the majority of the unvaccinated population which are young and middle-aged males. Indigenous populations at an international level carry a disproportionate burden of most diseases. The aim of this meta-analysis was to ascertain the worldwide prevalence of HPV infection in Indigenous populations stratified by sex and site and to document the most commonly reported HPV types. METHODS: Published articles on HPV infection in Indigenous populations from PubMed, Scopus, EMBASE and Web of Science were systematically searched from inception until 23 December 2019. RESULTS: A total of 41 studies were included in the final analysis. The pooled worldwide prevalence of HPV infection (for both oral and genital sites, both males and females) in Indigenous populations was 34.2% (95% CI: 28.9%-39.8%). Subgroup analysis (geographical) showed that the pooled prevalence for African Indigenous, American Indigenous and Asian-Oceanic Indigenous populations were 33.0% (95% CI: 12.8%-57.1%), 33.0% (95% CI: 27.4%-38.9%) and 33.3% (95% CI: 0.17.5%-51.3%), respectively. CONCLUSION: There are not enough data on the burden of the infection carried by males especially with respect to highly suspicious sites like oropharynx. Also, we conclude an overall high prevalence of HPV infection in the Indigenous populations and increasing their susceptibility to benign and malignant manifestations of HPV.

Addressing social determinants of health in community pharmacy: Innovative opportunities and practice models.

Social determinants of health (SDoH) account for up to 90% of health outcomes, whereas medical care accounts for only 10%-15%; despite this disparity, only 24% of hospitals and 16% of physician practices screen for the 5 social needs. Community-embedded and highly accessible, pharmacies are uniquely positioned to connect individuals to local community and social resources and thereby address SDoH. In this article, we explore novel community pharmacy practice models that address SDoH, provide real-world examples of these models, and discuss pathways for reimbursement and sustainability. A number of innovative community pharmacy practice models that focus on social issues are currently being explored. These include integrating community health workers (CHWs) or SDoH specialists, wherein CHWs are frontline public health workers who can effectively bridge the health care system and their community, whereas SDoH specialists are pharmacy team members trained with substantial SDoH knowledge and how to use it to connect pharmacy patients to community resources. Three community pharmacy networks have implemented pilot programs using either a CHW or SDoH specialist model. An essential component for program success in all cases has been partnership development and increased interdependence between the pharmacies, local community organizations, and the public health sector. New payment models and financial incentives will be necessary to expand and sustain these programs. A potential Approach may be the use of Z codes, a subset of ICD-10-CM codes specific to assessing SDoH. Although opportunities are developing for community pharmacies to play a major role in sustainably addressing SDoH, additional work is needed before there is a widespread acceptance of pharmacies becoming service referral destinations for patients with social needs. Evaluation of these models on a wider scale will be necessary to fully evaluate their effectiveness, costs, and implementation within different community pharmacy settings.

MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy.

BACKGROUND: Mucositis is a significant toxicity of cancer therapy with numerous systemic sequelae. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for the management of mucositis. METHODS: The literature was reviewed systematically to identify interventions for mucositis. Studies were rated according to the presence of major and minor flaws according to previously published criteria. The body of evidence for each intervention and in each treatment setting was assigned a level of evidence based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible. RESULTS: The guideline covers evidence from 1197 publications related to oral or gastrointestinal mucositis. Thirteen new guidelines were developed for or against the use of various interventions in specific treatment settings, and 11 previous guidelines were confirmed after aa review of new evidence. Thirteen previously established guidelines were carried over because there was no new evidence for these interventions. CONCLUSIONS: The updated MASCC/ISOO Clinical Practice Guidelines for mucositis provide professional health caregivers with a clinical setting-specific, evidence-based tool to help with the management of mucositis in patients who have cancer.

Systematic review of growth factors and cytokines for the management of oral mucositis in cancer patients and clinical practice guidelines.

PURPOSE: To update the clinical practice guidelines for the use of growth factors and cytokines for the prevention and/or treatment of oral mucositis (OM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: recommendation, suggestion, and no guideline possible. RESULTS: A total of 15 new papers were identified within the scope of this section and were merged with 51 papers that were reviewed in the previous guidelines update. Of these, 14, 5, 13, 2, and 1 were randomized controlled trials about KGF-1, G-CSF, GM-CSF, EGF, and erythropoietin, respectively. For the remaining agents there were no new RCTs. The previous recommendation for intravenous KGF-1 in patients undergoing autologous hematopoietic stem cell transplantation (HSCT) conditioned with high-dose chemotherapy and TBI-based regimens is confirmed. The previous suggestion against the use of topical GM-CSF for the prevention of OM in the setting of high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation remains unchanged. CONCLUSIONS: Of the growth factors and cytokines studied for the management of OM, the evidence supports a recommendation in favor of KGF-1 and a suggestion against GM-CSF in certain clinical settings.

Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial.

BACKGROUND: The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and aspirin both have proof of concept for colorectal cancer chemoprevention, aligned with an excellent safety profile. Therefore, we aimed to test the efficacy of EPA and aspirin, alone and in combination and compared with a placebo, in individuals with sporadic colorectal neoplasia detected at colonoscopy. METHODS: In a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial, patients aged 55-73 years who were identified during colonoscopy as being at high risk in the English Bowel Cancer Screening Programme (BCSP; ≥3 adenomas if at least one was ≥10 mm in diameter or ≥5 adenomas if these were <10 mm in diameter) were recruited from 53 BCSP endoscopy units in England, UK. Patients were randomly allocated (1:1:1:1) using a secure web-based server to receive 2 g EPA-free fatty acid (FFA) per day (either as the FFA or triglyceride), 300 mg aspirin per day, both treatments in combination, or placebo for 12 months using random permuted blocks of randomly varying size, and stratified by BCSP site. Research staff and participants were masked to group assignment. The primary endpoint was the adenoma detection rate (ADR; the proportion of participants with any adenoma) at 1 year surveillance colonoscopy analysed in all participants with observable follow-up data using a so-called at-the-margins approach, adjusted for BCSP site and repeat endoscopy at baseline. The safety population included all participants who received at least one dose of study drug. The trial is registered with the International Standard Randomised Controlled Trials Number registry, number ISRCTN05926847. FINDINGS: Between Nov 11, 2011, and June 10, 2016, 709 participants were randomly assigned to four treatment groups (176 to placebo, 179 to EPA, 177 to aspirin, and 177 to EPA plus aspirin). Adenoma outcome data were available for 163 (93%) patients in the placebo group, 153 (85%) in the EPA group, 163 (92%) in the aspirin group, and 161 (91%) in the EPA plus aspirin group. The ADR was 61% (100 of 163) in the placebo group, 63% (97 of 153) in the EPA group, 61% (100 of 163) in the aspirin group, and 61% (98 of 161) in the EPA plus aspirin group, with no evidence of any effect for EPA (risk ratio [RR] 0·98, 95% CI 0·87 to 1·12; risk difference -0·9%, -8·8 to 6·9; p=0·81) or aspirin (RR 0·99 (0·87 to 1·12; risk difference -0·6%, -8·5 to 7·2; p=0·88). EPA and aspirin were well tolerated (78 [44%] of 176 had ≥1 adverse event in the placebo group compared with 82 [46%] in the EPA group, 68 [39%] in the aspirin group, and 76 [45%] in the EPA plus aspirin group), although the number of gastrointestinal adverse events was increased in the EPA alone group at 146 events (compared with 85 in the placebo group, 86 in the aspirin group, and 68 in the aspirin plus placebo group). Six upper-gastrointestinal bleeding events were reported across the treatment groups (two in the EPA group, three in the aspirin group, and one in the placebo group). INTERPRETATION: Neither EPA nor aspirin treatment were associated with a reduction in the proportion of patients with at least one colorectal adenoma. Further research is needed regarding the effect on colorectal adenoma number according to adenoma type and location. Optimal use of EPA and aspirin might need a precision medicine approach to adenoma recurrence. FUNDING: Efficacy and Mechanism Evaluation Programme, a UK Medical Research Council and National Institute for Health Research partnership.

Histological analysis of 41 dentigerous cysts in a paediatric population.

BACKGROUND: Dentigerous cysts are usually of developmental nature but may be of inflammatory origin especially in paediatric populations. It is important to understand the histological features of dentigerous cysts to enable accurate diagnosis. The aim of this study is to present epidemiological, clinical features and histopathological features of dentigerous cysts seen in a paediatric tertiary referral hospital. METHOD: The medical, radiographic and histopathology records of the Department of Pathology, Women's and Children's Hospital, Adelaide, Australia, during January 1998 to December 2013 were reviewed for patients with dentigerous cysts. All cases were re-examined by a specialist oral pathologist, consultant paediatric pathologist and paediatric dentistry registrar. RESULTS: Forty-one cases of dentigerous cysts were found. Patients in the permanent dentition were most frequently affected. Male predilection was observed (male:female 2.42:1). The posterior mandible was the most frequently affected region (63.42%) although maxillary canines were the teeth most commonly associated with dentigerous cysts (29.27%). The majority of cases were incidental findings. Squamous epithelium showing pseudoepitheliomatous hyperplasia (46%) was frequently observed and was significantly present with thicker epithelium (P < 0.0001) and an acute and chronic inflammatory infiltrate (P < 0.001). Inflammatory infiltrate was seen in 75.6% of cases. CONCLUSIONS: The current study provides increased knowledge of the histological features of dentigerous cysts in a large retrospective series of paediatric patients and provides further evidence regarding the frequency of inflammatory dentigerous cysts.

The Management of Pediatric Oncology Inpatients With Oral Mucositis.

The purpose of the study was to investigate the management of chemotherapy-induced oral mucositis (OM) in pediatric patients. A total of 68 separate episodes of OM were assessed in 47 children who had received chemotherapy. The severity of the child's OM was assessed using 2 scales, and relevant clinical information was collected. The mean onset time of OM was 8.4 days (±4.0), with a median duration of 7.0 days (4.0, 10.5), with median admission of 7.0 days (4.5, 13.5). The overall adherence to an oral health protocol was 59%, which decreased with more severe OM. A third of patients used chlorhexidine mouthwash only, which was used in preference in cases of severe OM. Almost all patients had some systemic analgesia administered, with a significant increase in patient-controlled analgesia/nurse-controlled analgesia and intravenous ketamine in severe cases. Various types of prophylaxis/treatment of secondary infections and supportive care were associated with the severity of OM. The management of OM in children is important to limit its burden. An oral care protocol was recommended. Chlorhexidine mouthwash can maintain some form of oral care when brushing becomes too uncomfortable in severe OM. Pain management is important for the management of OM, and its intensity increases with increasing severity of OM.

The effect of a single injection of irinotecan on the development of enamel in the Wistar rats.

Cancer is the second most frequent cause of death in children. Because the prognosis for childhood malignancies has improved, attention has now focused on long-term consequences of cancer treatment. The immediate effects of chemotherapy on soft tissues have been well described; however, there is less information about long-term effects of chemotherapy on the development of dental tissues. To test the association between the effect of chemotherapy on enamel development, we examined two groups of rats: one that had received an intraperitoneal dose of 200 mg/kg of irinotecan, whereas the other (control) group had received vehicle only. Rats were killed at 6, 48 and 96 hr post-injection; the mandibles dissected out, fixed for histological evaluation and scanned for mineralization defects by Micro-CT. Our results showed structural changes in the ameloblast layer along with a significant reduction in mineralization and thickness of enamel at 96 hr after chemotherapy. These data demonstrate that irinotecan induces structural changes in forming enamel that become apparent after anticancer chemotherapy treatment.

Dye Aggregate-Mediated Self-Assembly of Bacteriophage Bioconjugates.

One of the central themes of biomolecular engineering is the challenge of exploiting the properties of biological materials. Part of this challenge has been uncovering and harnessing properties of biological components that only emerge following their ordered self-assembly. One biomolecular building block that has received significant interest in the past decade is the M13 bacteriophage. There have been a number of recent attempts to trigger the ordered assembly of M13 bacteriophage into multivirion structures, relying on the innate tendency of M13 to form liquid crystals at high concentrations. These, in general, yield planar two-dimensional materials. Presented here is the production of multivirion assemblies of M13 bacteriophage via the chemical modification of its surface by the covalent attachment of the xanthene-based dye tetramethylrhodamine (TMR) isothiocyanate (TRITC). We show that TMR induces the formation of three-dimensional aster-like assemblies of M13 by providing "adhesive" action between bacteriophage particles through the formation of H-aggregates (face-to-face stacking of dye molecules). We also show that the H-aggregation of TMR is greatly enhanced by covalent attachment to M13 and is enhanced further still upon the ordered self-assembly of M13, leading to the suggestion that M13 could be used to promote the self-assembly of dyes that form J-aggregates, a desirable arrangement of fluorescent dye, which has interesting optical properties and potential applications in the fields of medicine and light harvesting technology.

The Prevalence and Investigation of Risk Factors of Oral Mucositis in a Pediatric Oncology Inpatient Population; a Prospective Study.

BACKGROUND: Oral mucositis can be a frequent and severe complication of chemotherapy in children. It can result in pain, infection, depression, prolonged admission, treatment delays, increase in patient morbidity, and increased costs. AIM: To record the prevalence and severity of oral mucositis among inpatients and explore the relationship of risks factors and the development of oral mucositis. DESIGN: During an 18-month period 643 clinical inpatient assessments were completed on 73 children who were admitted and had received chemotherapy in the last 14 days. RESULTS: There were 43 episodes of oral mucositis in 31 children; 42.5% of the inpatient population. World Health Organization assessment identified 32.6% of episodes were grade 1, 34.9% grade 2, 14.0% grade 3, and 18.6% grade 4. Analysis revealed significant associations between patient diagnosis (P<0.0001), chemotherapy cycles (P<0.0001), day 8 and 9 of the chemotherapy cycle (P<0.05), and neutropenia (P<0.0001) and oral mucositis. Children had increased length of admission with increasing severity of oral mucositis (P=0.0005). CONCLUSIONS: The prevalence of oral mucositis was 42.5% among inpatients and admission length was increased with increasing severity. Patient diagnosis, chemotherapy treatment block, day of chemotherapy cycle, and neutropenic status were shown to influence the risk of developing oral mucositis.

Matrix metalloproteinase expression is altered in the small and large intestine following fractionated radiation in vivo.

PURPOSE: Radiotherapy-induced gut toxicity (RIGT) is associated with significant diarrhoea, pain and rectal bleeding. Matrix metalloproteinases (MMPs) have been reported to be involved in chemotherapy-induced gut toxicity and RIGT following single-dose irradiation in vivo. We therefore proposed MMPs would be involved in the pathobiology of RIGT following fractionated irradiation. METHODS: Dark Agouti rats were treated with fractionated radiation (3 × 2.5 Gy/week for 6 weeks). Rats were killed at 3, 6 and 15 weeks to represent acute and chronic toxicities. Sections of jejunum and colon were immunostained for MMP-1, MMP-2, MMP-9 and MMP-14. Relative mRNA expression in jejunum and colon was quantified by RT-PCR for MMP-1, MMP-2, MMP-9 and MMP-14. Western blotting was also conducted on jejunum and colon tissue collected at week 6 to determine protein levels of pro- and active MMP-2. RESULTS: MMP-2 total protein levels, determined by western blotting, significantly increased in both the jejunum (p = 0.0359) and the colon (p = 0.0134) 6 weeks into the fractionated radiation schedule. MMP-1, MMP-2, and MMP-14 mRNA expression significantly increased in the jejunum. MMP-2 mRNA expression was also significantly increased in the colon. Immunostaining of MMP-2 was observed to be increased in both crypt enterocytes and the lamina propria. CONCLUSIONS: MMP-2 plays a role in the pathobiology of gastrointestinal toxicities following fractionated irradiation. Whilst MMP-1 and MMP-14 mRNA expression was increased, this occurred only in the jejunum, suggesting MMPs are differentially involved in RIGT depending on the intestinal region. Further studies are needed to elucidate the role these mediators play in the development and potentiation of RIGT.

Effects of evidence-based strategies to reduce the socioeconomic gradient of uptake in the English NHS Bowel Cancer Screening Programme (ASCEND): four cluster-randomised controlled trials.

BACKGROUND: Uptake in the national colorectal cancer screening programme in England varies by socioeconomic status. We assessed four interventions aimed at reducing this gradient, with the intention of improving the health benefits of screening. METHODS: All people eligible for screening (men and women aged 60-74 years) across England were included in four cluster-randomised trials. Randomisation was based on day of invitation. Each trial compared the standard information with the standard information plus the following supplementary interventions: trial 1 (November, 2012), a supplementary leaflet summarising the gist of the key information; trial 2 (March, 2012), a supplementary narrative leaflet describing people's stories; trial 3 (June, 2013), general practice endorsement of the programme on the invitation letter; and trial 4 (July-August, 2013) an enhanced reminder letter with a banner that reiterated the screening offer. Socioeconomic status was defined by the Index of Multiple Deprivation score for each home address. The primary outcome was the socioeconomic status gradient in uptake across deprivation quintiles. This study is registered, number ISRCTN74121020. FINDINGS: As all four trials were embedded in the screening programme, loss to follow-up was minimal (less than 0·5%). Trials 1 (n=163,525) and 2 (n=150,417) showed no effects on the socioeconomic gradient of uptake or overall uptake. Trial 3 (n=265 434) showed no effect on the socioeconomic gradient but was associated with increased overall uptake (adjusted odds ratio [OR] 1·07, 95% CI 1·04-1·10, p<0·0001). In trial 4 (n=168 480) a significant interaction was seen with socioeconomic status gradient (p=0·005), with a stronger effect in the most deprived quintile (adjusted OR 1·11, 95% CI 1·04-1·20, p=0·003) than in the least deprived (1·00, 0·94-1·06, p=0·98). Overall uptake was also increased (1·07, 1·03-1·11, p=0·001). INTERPRETATION: Of four evidence-based interventions, the enhanced reminder letter reduced the socioeconomic gradient in screening uptake, but further reducing inequalities in screening uptake through written materials alone will be challenging. FUNDING: National Institute for Health Research.

Reducing the socioeconomic gradient in uptake of the NHS bowel cancer screening Programme using a simplified supplementary information leaflet: a cluster-randomised trial.

BACKGROUND: Uptake of colorectal cancer screening is low in the English NHS Bowel Cancer Screening Programme (BCSP). Participation in screening is strongly associated with socioeconomic status. The aim of this study was to determine whether a supplementary leaflet providing the 'gist' of guaiac-based Faecal Occult Blood test (gFOBt) screening for colorectal cancer could reduce the socioeconomic status (SES) gradient in uptake in the English NHS BCSP. METHODS: The trial was integrated within routine BCSP operations in November 2012. Using a cluster randomised controlled design all adults aged 59-74 years who were being routinely invited to complete the gFOBt were randomised based on day of invitation. The Index of Multiple Deprivation was used to create SES quintiles. The control group received the standard information booklet ('SI'). The intervention group received the SI booklet and the Gist leaflet ('SI + Gist') which had been designed to help people with lower literacy engage with the invitation. Blinding of hubs was not possible and invited subjects were not made aware of a comparator condition. The primary outcome was the gradient in uptake across IMD quintiles. RESULTS: In November 2012, 163,525 individuals were allocated to either the 'SI' intervention (n = 79,104) or the 'SI + Gist' group (n = 84,421). Overall uptake was similar between the intervention and control groups (SI: 57.3% and SI + Gist: 57.6%; OR = 1.02, 95% CI: 0.92-1.13, p = 0.77). Uptake was 42.0% (SI) vs. 43.0% (SI + Gist) in the most deprived quintile and 65.6% vs. 65.8% in the least deprived quintile (interaction p = 0.48). The SES gradient in uptake was similar between the study groups within age, gender, hub and screening round sub-groups. CONCLUSIONS: Providing supplementary simplified information in addition to the standard information booklet did not reduce the SES gradient in uptake in the NHS BCSP. The effectiveness of the Gist leaflet when used alone should be explored in future research. TRIAL REGISTRATION: ISRCTN74121020 , registered: 17/20/2012.

Fractionated abdominal irradiation induces intestinal microvascular changes in an in vivo model of radiotherapy-induced gut toxicity.

PURPOSE: Radiotherapy-induced gut toxicity (RIGT) is associated with diarrhoea, pain and rectal bleeding and can occur as an acute or chronic toxicity. The microvasculature has been shown to be altered in the development of RIGT; however, the features are not yet characterized. We hypothesized that apoptosis of microvascular cells would occur early in the gastrointestinal tract following fractionated irradiation, followed by late microvascular changes, including sclerosis and telangiectasis. METHODS: Female Dark Agouti rats were treated with a 6-week fractionated radiation schedule of 3 × 2.5 Gy doses per week localized to the abdomen. At 3, 6 and 15 weeks, the intestines were assessed for markers of acute and chronic injury including morphological changes, collagen deposition, apoptosis and proliferation. RESULTS: Apoptosis of microvascular cells significantly increased at 6 and 15 weeks in the jejunum (p = 0.0026 and p = 0.0062, respectively) and at 6 and 15 weeks in the colon (p < 0.0001 and p = 0.0005, respectively) in rats receiving fractionated radiation to the abdomen. Histopathological changes of the colon microvasculature were also seen from week 3, including thickening of the lamina propria and dilated, thickened, telangiectatic vessels. CONCLUSIONS: Findings of this study provide evidence of regional and timing-specific changes in the intestinal microvasculature in response to fractionated radiotherapy which may play a role in development of both acute and chronic RIGT.

A systematic review of oral herpetic viral infections in cancer patients: commonly used outcome measures and interventions.

PURPOSE: To review the literature for outcome measures for oral viral infections in cancer patients. A secondary aim was to update the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) clinical practice guidelines for the management of oral viral infections in cancer patients. METHODS: Databases were searched for articles published in the English language, 1981-2013. Studies that met the eligibility criteria were reviewed systematically. The data about the outcome measures were classified according to the aim of the study: prevention, treatment, or non-interventional. The results of interventional studies were compared to the 2010 MASCC/ISOO publication. RESULTS: Multiple clinical and laboratory tests were used to measure oral viral infections, with great variability between studies. Most of the studies were about Herpes Simplex Virus (HSV). The outcome measure that was most commonly used was the presence of HSV infection diagnosed based on a combination of suggestive clinical presentation with a positive laboratory result. HSV culture was the most commonly reported laboratory outcome measure. Acyclovir and valacyclovir were consistently reported to be efficacious in the management of oral herpetic infections. No new data on the quality of life and economic aspects was found. CONCLUSIONS: Considering the variability in outcome measures reported to assess oral herpetic infections the researcher should select carefully the appropriate measures based on the objective of the study. Acyclovir and valacyclovir are effective in the management of oral herpetic infections in patients receiving treatment for cancer. Studies on newer anti-viral drugs may be useful to address the issue of anti-viral resistance.

Cytokine-mediated blood brain barrier disruption as a conduit for cancer/chemotherapy-associated neurotoxicity and cognitive dysfunction.

Neurotoxicity is a common side effect of chemotherapy treatment, with unclear molecular mechanisms. Clinical studies suggest that the most frequent neurotoxic adverse events affect memory and learning, attention, concentration, processing speeds and executive function. Emerging preclinical research points toward direct cellular toxicity and induction of neuroinflammation as key drivers of neurotoxicity and subsequent cognitive impairment. Emerging data now show detectable levels of some chemotherapeutic agents within the CNS, indicating potential disruption of blood brain barrier integrity or transport mechanisms. Blood brain barrier disruption is a key aspect of many neurocognitive disorders, particularly those characterized by a proinflammatory state. Importantly, many proinflammatory mediators able to modulate the blood brain barrier are generated by tissues and organs that are targets for chemotherapy-associated toxicities. This review therefore aims to explore the hypothesis that peripherally derived inflammatory cytokines disrupt blood brain barrier permeability, thereby increasing direct access of chemotherapeutic agents into the CNS to facilitate neuroinflammation and central neurotoxicity.