Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark : prospective, nationwide cohort study

Supported by a grant (11645) from the Novo Nordisk Foundation. The funder had no role in the study design; in the collection, analysis and interpretation of data, in the writing of the paper or in the decision to submit the paper for publication.Peer reviewedPublisher PD

Hormonal contraceptive use and risk of pancreatic cancer : A cohort study among premenopausal women

Drs. Mørch and Lidegaard were supported by a grant (No 11645) from the Novo Nordisk Foundation. The funder had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the paper; or in the decision to submit the paper for publication. Correction: Hormonal contraceptive use and risk of pancreatic cancer—A cohort study among premenopausal women; Sedrah Arif Butt, Øjvind Lidegaard, Charlotte Skovlund, Philip C. Hannaford, Lisa Iversen, Shona Fielding, Lina Steinrud Mørch; PLOS, Published: March 28, 2019, https://doi.org/10.1371/journal.pone.0214771Peer reviewedPublisher PD

Systematic review of the effectiveness and cost-effectiveness of HealOzone® for the treatment of occlusal pit/fissure caries and root caries

Objectives: To assess the effectiveness and cost-effectiveness of HealOzone® (CurOzone USA Inc., Ontario, Canada) for the management of pit and fissure caries, and root caries. The complete HealOzone procedure involves the direct application of ozone gas to the caries lesion on the tooth surface, the use of a remineralising solution immediately after application of ozone and the supply of a ‘patient kit’, which consists of toothpaste, oral rinse and oral spray all containing fluoride. Data sources: Electronic databases up to May 2004 (except Conference Papers Index, which were searched up to May 2002). Review methods: A systematic review of the effectiveness of HealOzone for the management of tooth decay was carried out. A systematic review of existing economic evaluations of ozone for dental caries was also planned but no suitable studies were identified. The economic evaluation included in the industry submission was critically appraised and summarised. A Markov model was constructed to explore possible cost-effectiveness aspects of HealOzone in addition to current management of dental caries. Results: Five full-text reports and five studies published as abstracts met the inclusion criteria. The five full-text reports consisted of two randomised controlled trials (RCTs) assessing the use of HealOzone for the management of primary root caries and two doctoral theses of three unpublished randomised trials assessing the use of HealOzone for the management of occlusal caries. Of the abstracts, four assessed the effects of HealOzone for the management of occlusal caries and one the effects of HealOzone for the management of root caries. Overall, the quality of the studies was modest, with many important methodological aspects not reported (e.g. concealment of allocation, blinding procedures, compliance of patients with home treatment). In particular, there were some concerns about the choice of statistical analyses. In most of the full-text studies analyses were undertaken at lesion level, ignoring the clustering of lesions within patients. The nature of the methodological concerns was sufficient to raise doubts about the validity of the included studies’ findings. A quantitative synthesis of results was deemed inappropriate. On the whole, there is not enough evidence from published RCTs on which to judge the effectiveness of ozone for the management of both occlusal and root caries. The perspective adopted for the study was that of the NHS and Personal Social Services. The analysis, carried out over a 5-year period, indicated that treatment using current management plus HealOzone cost more than current management alone for non-cavitated pit and fissure caries (£40.49 versus £24.78), but cost less for non-cavitated root caries (£14.63 versus £21.45). Given the limitations of the calculations these figures should be regarded as illustrative, not definitive. It was not possible to measure health benefits in terms of quality-adjusted life-years, due to uncertainties around the evidence of clinical effectiveness, and to the fact that the adverse events avoided are transient (e.g. pain from injection of local anaesthetic, fear of the drill). One-way sensitivity analysis was applied to the model. However, owing to the limitations of the economic analysis, this should be regarded as merely speculative. For non-cavitated pit and fissure caries, the HealOzone option was always more expensive than current management when the probability of cure using the HealOzone option was 70% or lower. For non-cavitated root caries the costs of the HealOzone comparator were lower than those of current management only when cure rates from HealOzone were at least 80%. The costs of current management were higher than those of the HealOzone option when the cure rate for current management was 40% or lower. One-way sensitivity analysis was also performed using similar NHS Statement of Dental Remuneration codes to those that are used in the industry submission. This did not alter the results for non-cavitated pit fissure caries as the discounted net present value of current management remained lower than that of the HealOzone comparator (£22.65 versus £33.39). Conclusions: Any treatment that preserves teeth and avoids fillings is welcome. However, the current evidence base for HealOzone is insufficient to conclude that it is a cost-effective addition to the management and treatment of occlusal and root caries. To make a decision on whether HealOzone is a cost-effective alternative to current preventive methods for the management of dental caries, further research into its clinical effectiveness is required. Independent RCTs of the effectiveness and cost-effectiveness of HealOzone for the management of occlusal caries and root caries need to be properly conducted with adequate design, outcome measures and methods for statistical analyses

Prevalence and causes of prescribing errors: the prescribing outcomes for trainee doctors engaged in clinical training (PROTECT) study

Objectives Study objectives were to investigate the prevalence and causes of prescribing errors amongst foundation doctors (i.e. junior doctors in their first (F1) or second (F2) year of post-graduate training), describe their knowledge and experience of prescribing errors, and explore their self-efficacy (i.e. confidence) in prescribing. Method A three-part mixed-methods design was used, comprising: prospective observational study; semi-structured interviews and cross-sectional survey. All doctors prescribing in eight purposively selected hospitals in Scotland participated. All foundation doctors throughout Scotland participated in the survey. The number of prescribing errors per patient, doctor, ward and hospital, perceived causes of errors and a measure of doctors' self-efficacy were established. Results 4710 patient charts and 44,726 prescribed medicines were reviewed. There were 3364 errors, affecting 1700 (36.1%) charts (overall error rate: 7.5%; F1:7.4%; F2:8.6%; consultants:6.3%). Higher error rates were associated with : teaching hospitals (p&#60;0.001), surgical (p = &#60;0.001) or mixed wards (0.008) rather thanmedical ward, higher patient turnover wards (p&#60;0.001), a greater number of prescribed medicines (p&#60;0.001) and the months December and June (p&#60;0.001). One hundred errors were discussed in 40 interviews. Error causation was multi-factorial; work environment and team factors were particularly noted. Of 548 completed questionnaires (national response rate of 35.4%), 508 (92.7% of respondents) reported errors, most of which (328 (64.6%) did not reach the patient. Pressure from other staff, workload and interruptions were cited as the main causes of errors. Foundation year 2 doctors reported greater confidence than year 1 doctors in deciding the most appropriate medication regimen. Conclusions Prescribing errors are frequent and of complex causation. Foundation doctors made more errors than other doctors, but undertook the majority of prescribing, making them a key target for intervention. Contributing causes included work environment, team, task, individual and patient factors. Further work is needed to develop and assess interventions that address these.</p

Investigating the missing data mechanism in quality of life outcomes: a comparison of approaches

Background: Missing data is classified as missing completely at random (MCAR), missing at random (MAR) or missing not at random (MNAR). Knowing the mechanism is useful in identifying the most appropriate analysis. The first aim was to compare different methods for identifying this missing data mechanism to determine if they gave consistent conclusions. Secondly, to investigate whether the reminder-response data can be utilised to help identify the missing data mechanism. Methods: Five clinical trial datasets that employed a reminder system at follow-up were used. Some quality of life questionnaires were initially missing, but later recovered through reminders. Four methods of determining the missing data mechanism were applied. Two response data scenarios were considered. Firstly, immediate data only; secondly, all observed responses (including reminder-response). Results: In three of five trials the hypothesis tests found evidence against the MCAR assumption. Logistic regression suggested MAR, but was able to use the reminder-collected data to highlight potential MNAR data in two trials. Conclusion: The four methods were consistent in determining the missingness mechanism. One hypothesis test was preferred as it is applicable with intermittent missingness. Some inconsistencies between the two data scenarios were found. Ignoring the reminder data could potentially give a distorted view of the missingness mechanism. Utilising reminder data allowed the possibility of MNAR to be considered.The Chief Scientist Office of the Scottish Government Health Directorate. Research Training Fellowship (CZF/1/31

Do health behaviours change after colonoscopy? A prospective cohort study on diet, alcohol, physical activity and smoking among patients and their partners

Objectives: To describe diet, alcohol, physical activity and tobacco use prospectively, that is, before and 10 months after colonoscopy for patients and their partners. Design: Prospective cohort study of health behaviour change in patients and partners. Comparison groups are patients receiving a normal result notification (NRN) versus patients receiving an abnormal result notification (ARN). Patients and partners (controls) are also compared. Setting: 5 Scottish hospitals. Participants: Of 5798 colonoscopy registrations, 2577 (44%) patients met the eligibility criteria of whom 565 (22%) were recruited; 460 partners were also recruited. Measures: International Physical Activity Questionnaire, Scottish Collaborative Group Food Frequency Questionnaire (includes alcohol), smoking status, sociodemographic characteristics, body mass index, medical conditions, colonoscopy result, Multidimensional Health Locus of Control Scale, behaviour-specific self-efficacy scales. Results: 57% of patients were men, with a mean age of 60.8 years (SE 0.5) and 43% were from more affluent areas. 72% (n=387) of patients received an ARN and 28% (n=149) received an NRN. Response rate of the second questionnaire was 68.9%. Overall, 27% of patients consumed < 5 measures of fruit and vegetables/day, 20% exceeded alcohol limits, 50% had low levels of physical activity and 21% were obese. At 10-month follow-up, a 5% reduction in excessive alcohol consumption and an 8% increase in low levels of physical activity were observed among patients; no significant changes occurred in partners. Baseline high alcohol consumption and low physical activity were the strongest predictors of these behaviours at follow-up. Low alcohol self-efficacy and increasing age were associated with poorer health-related behaviours at follow-up for alcohol consumption and physical activity, respectively. Conclusions: Colonoscopy is associated with marginal beneficial changes in some behaviours but not others. Further work is needed to explore how services can optimise increases in beneficial behaviours and mitigate increases in harmful ones

Public views of the uk media and government reaction to the 2009 swine flu pandemic

<p>Abstract</p> <p>Background</p> <p>The first cases of influenza A/H1N1 (swine flu) were confirmed in the UK on 27th April 2009, after a novel virus first identified in Mexico rapidly evolved into a pandemic. The swine flu outbreak was the first pandemic in more than 40 years and for many, their first encounter with a major influenza outbreak. This study examines public understandings of the pandemic, exploring how people deciphered the threat and perceived they could control the risks.</p> <p>Methods</p> <p>Purposive sampling was used to recruit seventy three people (61 women and 12 men) to take part in 14 focus group discussions around the time of the second wave in swine flu cases.</p> <p>Results</p> <p>These discussions showed that there was little evidence of the public over-reacting, that people believed the threat of contracting swine flu was inevitable, and that they assessed their own self-efficacy for protecting against it to be low. Respondents assessed a greater risk to their health from the vaccine than from the disease. Such findings could have led to apathy about following the UK Governments recommended health protective behaviours, and a sub-optimal level of vaccine uptake. More generally, people were confused about the difference between seasonal influenza and swine flu and their vaccines.</p> <p>Conclusions</p> <p>This research suggests a gap in public understandings which could hinder attempts to communicate about novel flu viruses in the future. There was general support for the government's handling of the pandemic, although its public awareness campaign was deemed ineffectual as few people changed their current hand hygiene practices. There was less support for the media who were deemed to have over-reported the swine flu pandemic.</p

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014

A cancer geography paradox?:Poorer cancer outcomes with longer travelling times to healthcare facilities despite prompter diagnosis and treatment: a data-linkage study

This study was funded by Cancer Research UK (Grant number = C10673/A17593). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review or approval of the manuscript; or the decision to submit the manuscript for publication. All authors are independent of Cancer Research UK.Peer reviewedPublisher PD