Defining Optimal Triage Strategies for hrHPV Screen-Positive Women-An Evaluation of HPV 16/18 Genotyping, Cytology, and p16/Ki-67 Cytoimmunochemistry.

Background: Several options for the triage of high-risk HPV screen-positive (hrHPV+) women were assessed.Methods: This study incorporated CIN2+ cases and controls, all of whom tested hrHPV+ and whose results of liquid-based cytology (LBC), HPV16/18 genotyping, and p16/Ki67 cytoimmunochemistry were available. Sensitivity and specificity for the CIN2+ of these triage tests were evaluated.Results: Absolute sensitivities of HPV 16/18 typing, LBC, and p16/Ki-67 cytoimmunochemistry for CIN2+ detection were 61.7%, 68.3%, and 85.0% for women with hrHPV+ clinician-taken samples. Respective specificities were 70.5%, 89.1%, and 76.7%. The absolute accuracy of the triage tests was similar for women with a hrHPV+ self-sample. P16/Ki-67 cyto-immunochemistry was significantly more sensitive than LBC although significantly less specific.Conclusions: All three single-test triage options, if positive, exceed the threshold of 20% risk at which colposcopy would be indicated. However, none of them conferred a post-test probability of CIN2+ <2%; which would permit routine recall. P16/Ki-67 cytoimmunochemistry on HPV16/18 negative women had a post-test probability of CIN2+ of 1.7% and 0.6% if also LBC negative.Impact: This is one of the few studies to directly compare the performance of triage strategies of hrHPV+ women, in isolation and combinations. It is the only study assessing triage strategies in women who test hrHPV+ in self-taken vaginal samples. A combined triage option that incorporated HPV 16/18 typing prior to p16/ki-67 cytoimmunochemistry in HPV 16/18-negative women yielded a post-test probability of CIN2+ of >20%, whereas women who tested negative had a probability of CIN2+ of <2%. Cancer Epidemiol Biomarkers Prev; 26(11); 1629-35. ©2017 AACR.

Cobas 4800 HPV detection in the cervical, vaginal and urine samples of women with high-grade CIN before and after treatment.

AIMS: To assess the performance of a clinically validated human papillomavirus (HPV) test (the Cobas 4800 HPV test) in urine and self-taken vaginal specimens within a colposcopy population and to assess HPV prevalence before and after treatment across the different biospecimens. METHODS: A total of 100 women attending a colposcopy clinic provided three biospecimens (a clinician-taken liquid-based cytology sample (LBC), a self-taken vaginal sample and a urine sample) for HPV testing. HPV prevalence and concordance was compared across the biospecimens and clinical performance relative to the detection of cervical intraepithelial neoplasia (CIN)2+ and CIN3+ was assessed. A total of 39 women retuned at 6 months for a post-treatment follow-up appointment, and HPV concordance in all biospecimens was measured relative to their original HPV status. RESULTS: 65 cases of CIN2+ were detected in the baseline population; sensitivity for CIN2+ was 92% (82 to 97) for the vaginal and the LBC sample and 80.0 (68% to 88%) for the urine sample. In the follow-up (post treatment) population, women were twice as likely to be HPV positive in their urine or vaginal sample compared with the equivalent LBC sample. CONCLUSIONS: Vaginal and LBC samples showed very similar performance for the detection of CIN2+ in this population using the Cobas HPV test; further validation of these findings in screening contexts will be of value. Self-taken samples may have less utility in a 'test of cure' setting-given the higher prevalence of HPV relative to LBC.

C-reactive protein and risk of colorectal adenomas or serrated polyps: a prospective study.

Serum C-reactive protein (CRP) is a sensitive marker of systemic inflammation. Because there is a well-recognized relationship between local inflammation and colorectal cancer, we aimed to evaluate whether serum CRP levels were associated with the occurrence of colorectal adenomas and serrated polyps using data from a large adenoma prevention trial. A total of 930 participants with a history of colorectal adenomas were enrolled in a randomized trial of calcium supplementation (1,200 mg/day) for the prevention of colorectal adenomas. Outcomes in this analysis are metachronous adenomas (and advanced neoplasms specifically), and serrated polyps at follow-up colonoscopy. High-sensitivity CRP levels were measured 1 year following baseline colonoscopy. Multivariate analysis was performed to estimate risk ratios (RR) using Poisson regression, controlling for potential confounders. We measured serum CRP levels in 689 participants (mean CRP, 3.62 ± 5.72 mg/L). There was no difference in CRP levels with respect to calcium versus placebo treatment assignment (P = 0.99). After adjustment for potential confounders, we found no association between CRP level and risk of recurrent adenoma or advanced lesion [quartile 4 vs. quartile 1: RR, 95% confidence interval (CI) = 0.99 (0.73-1.34) and 0.92 (0.49-1.75), respectively]. Similarly, no association was seen between CRP levels and risk of serrated polyps or proximal serrated polyps [quartile 4 vs. quartile 1: RR (95% CI) = 1.32 (0.85-2.03) and 1.19 (0.54-2.58), respectively]. In conclusion, this large prospective colorectal adenoma chemoprevention study found no significant relationship between CRP levels and occurrence of adenomas, advanced neoplasms, or serrated polyps.

A systematic review of salicylates in foods: estimated daily intake of a Scottish population.

Several studies suggest that natural salicylates in plant-based foods may benefit health. However, large variation in published values of the salicylate content of foods means that relating dietary intakes to disease risk is problematical. Consequently, we have systematically reviewed the available literature using prescribed selection criteria. By combining these literature values with in-house analysis, we have constructed a food composition database describing median salicylate values for 27 different types of fruits, 21 vegetables, 28 herbs, spices and condiments, 2 soups and 11 beverages. Application of a validated food frequency questionnaire estimated median dietary intakes of 4.42 (range 2.90-6.27) and 3.16 (2.35-4.89) mg/day for Scottish males and females, respectively. Major dietary sources of salicylates were alcoholic beverages (22%), herbs and spices (17%), fruits (16%), non-alcoholic beverages including fruit juices (13%), tomato-based sauces (12%) and vegetables (9%). Application of the database to populations with differing dietary habits and disease risk profiles may provide further evidence for the role of dietary salicylates in the prevention of chronic diseases.

Serum salicylate levels and risk of recurrent colorectal adenomas.

BACKGROUND: Intake of aspirin is associated with reduction in risk of colorectal adenoma and carcinoma. Some plants contain salicylates, and individuals not taking aspirin may have measurable salicylate levels. However, the association between serum salicylate level and recurrence of adenoma in nonusers of aspirin has not been studied. METHODS: We measured serum salicylate levels in participants in a randomized controlled trial with calcium supplementation for the prevention of colorectal adenomas. Generalized linear models were used to assess the association between serum levels and adenoma risk during the follow-up period of the trial. RESULTS: We did not find an association with recurrence of adenomas or advanced adenomas with serum salicylate levels at year 1 among nonusers of aspirin. There was no effect modification of the chemopreventive effect of calcium supplementation in reducing risk of recurrent adenomas or advanced adenomas. CONCLUSIONS: Among nonusers of ASA, serum salicylate levels are not associated with risk of recurrence of adenomas. IMPACT: Serum salicylate levels can be detected in individuals not taking aspirin, but the levels may be too low to confer protection from risk of recurrent adenomas.

The natural history of acute upper respiratory tract infections in children.

AIM: To describe the natural history of acute upper respiratory tract infections (AURIs) in primary-school children, by recording their daily symptoms. BACKGROUND: AURIs in children are one of the most common reasons for people seeking advice from general practitioners (GPs); however, little is known about the natural history of AURIs in terms of the length and severity of symptoms, because the majority of illnesses are contracted at home. METHOD: After an initial pilot study to test the feasibility of parents recording symptoms in a diary based on the Canadian Acute Respiratory Illness and Flu Scale (CARIFS), a random selection of primary schools operating in the region was carried out in order to minimise selection bias. Meetings were arranged at the 20 schools to obtain written consent from parents and to give out diaries with a stamped addressed envelope. The diaries recorded daily symptom severity for one episode of AURI, and the data were analysed using SPSS programmes. FINDINGS: Diaries were returned from 223 children, of whom 146 had had an AURI. The average age was eight years, and there were almost equal numbers of boys and girls. The most frequent symptoms were runny nose, cough, feeling unwell and sore throat. There was a biphasic distribution with systemic symptoms in the first three days characterised by fever, poor sleep, irritability, not playing and headache. By day four, symptoms localising the infection to the upper respiratory tract appeared with runny nose, cough, sore throat and poor appetite; these continued into the second and occasionally third week. Most symptoms lasted for 5-11 days, with a median length for all symptoms of seven days. Symptoms defined by parents tended to be scored less for severity than symptoms defined by children.

Reflective testing: what do patients think?

INTRODUCTION: Reflective testing refers to the practice of adding on tests by laboratory staff. Little is known about what patients think of this practice. METHODS: We surveyed patients attending a general practice surgery and patients attending hospital outpatient clinics. We sought their views about the practice of adding on tests and about the information they received from requesting clinicians about their investigations. RESULTS: In both groups of patients, large majorities favoured an approach in which relevant additional tests are performed without consulting the requesting clinician or patient first. Most patients also felt that the requesting clinicians had provided a satisfactory explanation about what tests were to be performed and why. CONCLUSION: Most patients are content to let NHS professionals add on relevant tests if this is felt to be in their interest.

Salicylic acid content of spices and its implications.

This work was done to determine the salicylate content of a variety of commonly used spices and to assess whether this potential dietary source of salicylate was bioavailable. Spices, Indian cooked dishes, and blood and urine samples taken after ingestion of a test meal were investigated for their salicylate content using high-performance liquid chromatography with electrochemical detection. The serum salicylic acid concentrations in samples from villagers in southern India were also measured and have been compared with typical European values. Salicylic acid was determined in all spices (up to 1.5 wt %) and cooked dishes. The salicylate content of blood and urine was shown to increase following consumption of the meal, indicating that this dietary source of salicylic acid was bioavailable. Salicylic acid levels in the serum from rural Indians were significantly (median almost 3-fold) higher than values previously measured in Western vegetarians. Chemoprotective aspirin is rapidly hydrolyzed to salicylic acid, and this phytochemical may contribute to the low cancer incidence in rural India.

Is there a role for dietary salicylates in health?

Acetylsalicylic acid (aspirin; 2-acetoxybenzoic acid) has been used for >100 years for pain relief and to treat inflammatory conditions and fevers. More recently, regular intake has been associated with decreased incidence of certain cancers, particularly colon cancer. After absorption aspirin is very rapidly hydrolysed to salicylic acid (2-hydroxybenzoic acid). The anti-cancer effects of aspirin may be a result of salicylic acid reducing the transcription of prostaglandin H(2)-synthase and thereby the synthesis of pro-inflammatory and potentially-neoplastic prostaglandins. Salicylic acid is widely present in plants and functions as a hormonal mediator of the systemic acquired resistance response to pathogen attack and environmental stress. Thus, it is present in a large range of fruit, vegetables, herbs and spices of dietary relevance. Consequently, the recognised effect of consuming fruit and vegetables on lowering risk of colon cancer may be partly attributable to salicylates in plant-based foods. The present review discusses which types of fruit and vegetables are the richest source of salicylates and whether they are sufficiently released from the food matrix to modify the key cellular events associated with the pathogenesis of colon cancer.

Dietary improvement in people with schizophrenia: randomised controlled trial.

BACKGROUND: People with schizophrenia make poor dietary choices. AIMS: To measure the impact of giving free fruit and vegetables for 6 months on eating habits in schizophrenia. METHOD: We randomly allocated 102 people with schizophrenia in two areas of Scotland to receive free fruit and vegetables for 6 months, supported by instruction in meal planning and food preparation; free fruit and vegetables alone; or to continue as before. Diet was assessed using the Scottish Health Survey questionnaire. Blood samples to measure micronutrients were taken and mental state, body mass index, level of physical activity and future risk of coronary heart disease (CHD) were assessed. RESULTS: After the intervention, those who received free fruit and vegetables, or free fruit and vegetables and associated instruction, were consuming significantly more fruit and vegetables than those in the treatment as usual group. Consumption fell to pre-intervention levels 12 months after the intervention stopped. There was no between-group difference at any time in blood micronutrients, body mass index, physical activity or risk of CHD. CONCLUSIONS: The diet of people with schizophrenia improved when they were given free fruit and vegetables but this was given free fruit and vegetables but this was not sustained after withdrawal of the intervention. A support programme added no benefit.

Increased salicylate concentrations in urine of human volunteers after consumption of cranberry juice.

The aim of this study was to assess whether regular consumption of cranberry juice results in elevations in urinary salicylate concentrations in persons not taking salicylate drugs. Two groups of healthy female subjects (11/group) matched for age, weight, and height consumed 250 mL of either cranberry juice or a placebo solution three times a day (i.e., 750 mL/day) for 2 weeks. At weekly intervals, salicylic acid and salicyluric acid (the major urinary metabolite of salicylic acid) concentrations were determined in urine by HPLC with electrochemical detection. Concentrations of salicylic acid in plasma were also determined. Consumption of cranberry juice was associated with a marked increase (p < 0.001) of salicyluric and salicylic acids in urine within 1 week of the intervention. After 2 weeks, there was also a small but significant (p < 0.05) increase in salicylic acid in plasma. The regular consumption of cranberry juice results in the increased absorption of salicylic acid, an anti-inflammatory compound that may benefit health.