Charlotte Vrinten

The structure and demographic correlates of cancer fear

BackgroundCancer is often described as the ‘number one’ health fear, but little is known about whether this affects quality of life by translating into high levels of worry or distress in everyday life, or which population groups are most affected. This study examined the prevalence of three components of cancer fear in a large community sample in the UK and explored associations with demographic characteristics.MethodsQuestions on cancer fear were included in a survey mailed to a community sample of adults (n = 13,351; 55–64 years). Three items from a standard measure of cancer fear assessed: i) whether cancer was feared more than other diseases, ii) whether thinking about cancer caused discomfort, and iii) whether cancer worry was experienced frequently. Gender, marital status, education, and ethnicity were assessed with simple questions. Anxiety was assessed with the brief STAI and a standard measure of self-rated health was included.ResultsQuestionnaire return rate was 60% (7,971/13,351). The majority of respondents agreed or strongly agreed that they feared cancer more than other diseases (59%), and felt uncomfortable thinking about it (52%), and a quarter (25%) worried a lot about cancer. All items were significantly inter-correlated (r = .35 to .42, p’s < .001), and correlated with general anxiety (r = .16 to .28, p’s < .001) and self-rated health (r = -.07 to -.16, p’s < .001). In multivariable analyses including anxiety and general health, all cancer fear indicators were significantly higher in women (ORs between 1.15 and 1.48), respondents with lower education (ORs between 1.40 and 1.66), and those with higher general anxiety (ORs between 1.50 and 2.11). Ethnic minority respondents (n = 285; 4.4%) reported more worry (OR: 1.85).ConclusionsMore than half of this older adult sample in the UK had cancer as greatest health fear and this was associated with feeling uncomfortable thinking about it and worrying more about it. Women and respondents with less education or from ethnic minority backgrounds were disproportionately affected by cancer fear. General anxiety and poor health were associated with cancer fear but did not explain the demographic differences.

Cancer Fear: Facilitator and Deterrent to Participation in Colorectal Cancer Screening

Background: Cancer fear has been associated with higher and lower screening uptake across different studies, possibly because different aspects of cancer fear have different effects on intentions versus behavior. The present study examined associations of three aspects of cancer fear with intention and uptake of endoscopic screening for colorectal cancer. Methods: A subsample of UK Flexible Sigmoidoscopy (FS) Trial participants received a baseline questionnaire that included three cancer fear items from a standard measure asking if: (i) cancer was feared more than other diseases, (ii) cancer worry was experienced frequently, and (iii) thoughts about cancer caused discomfort. Screening intention was assessed by asking participants whether, if invited, they would accept an invitation for FS screening. Positive responders were randomized to be invited or not in a 1:2 ratio. The behavioral outcome was clinic-recorded uptake. Control variables were age, gender, ethnicity, education, and marital status. Results: The questionnaire return rate was 60% (7,971/13,351). The majority (82%) intended to attend screening; 1,920 were randomized to receive an invitation, and 71% attended. Fearing cancer more than other diseases (OR = 2.32, P < 0.01) and worrying a lot about cancer (OR = 2.34, P < 0.01) increased intentions to attend screening, but not uptake. Finding thoughts about cancer uncomfortable did not influence intention, but predicted lower uptake (OR = 0.72, P < 0.01). Conclusions: Different aspects of cancer fear have different effects on the decision and action processes leading to screening participation. Impact: Knowledge of the different behavioral effects of cancer fear may aid the design of effective public health messages. Cancer Epidemiol Biomarkers Prev; 24(2); 400–5. ©2015 AACR.

What do people fear about cancer? A systematic review and meta‐synthesis of cancer fears in the general population

Cancer has long inspired fear, but the effect of fear is not well understood; it seems both to facilitate and to deter early diagnosis behaviours. To elucidate fears behavioural effects, we systematically reviewed and synthesised qualitative literature to explore what people fear about cancer.

Cancer fear and fatalism among ethnic minority women in the United Kingdom

Background:Cancer fear and fatalism are believed to be higher in ethnic minorities and may contribute to lower engagement with cancer prevention and early detection. We explored the levels of cancer fear and fatalism in six ethnic groups in the United Kingdom and examined the contribution of acculturation and general fatalism.Methods:A cross-sectional survey of 720 White British, Caribbean, African, Indian, Pakistani, and Bangladeshi women (120 of each) was conducted. Three items assessed cancer fear and two cancer fatalism. Acculturation was assessed using (self-reported) migration status, ability to speak English, and understanding of health leaflets; general fatalism with a standard measure.Results:Relative to White British women, African and Indian women were more fearful of cancer, Bangladeshi women less fearful, and Pakistani and Caribbean women were similar to White British women. Cancer fatalism was higher in all the ethnic minority groups compared with White British women. Less acculturated women were less likely to worry (ORs 0.21–0.45, all P<0.05) or feel particularly afraid (ORs 0.11–0.31, all P<0.05) but more likely to feel uncomfortable about cancer (ORs 1.97–3.03, all P<0.05). Lower acculturation (ORs 4.30–17.27, P<0.05) and general fatalism (OR 2.29, P<0.05) were associated with the belief that cancer is predetermined.Conclusions:In general, cancer fear and fatalism are more prevalent among ethnic minority than White British women and even more so in less acculturated ethnic minorities. This may affect their participation in cancer prevention and early detection.

Social Cognitive Mediators of Sociodemographic Differences in Colorectal Cancer Screening Uptake

Background. This study examined if and how sociodemographic differences in colorectal cancer (CRC) screening uptake can be explained by social cognitive factors. Methods. Face-to-face interviews were conducted with individuals aged 60–70 years (n = 1309) living in England as part of a population-based omnibus survey. Results. There were differences in screening uptake by SES, marital status, ethnicity, and age but not by gender. Perceived barriers (stand. b = −0.40, p < 0.001), social norms (stand. b = 0.33, p < 0.001), and screening knowledge (stand. b = 0.17, p < 0.001) had independent associations with uptake. SES differences in uptake were mediated through knowledge, social norms, and perceived barriers. Ethnic differences were mediated through knowledge. Differences in uptake by marital status were primarily mediated through social norms and to a lesser extent through knowledge. Age differences were largely unmediated, except for a small mediated effect via social norms. Conclusions. Sociodemographic differences in CRC screening uptake were largely mediated through social cognitive factors. Impact. Our findings suggest that multifaceted interventions might be needed to reduce socioeconomic inequalities. Ethnic differences might be reduced through improved screening knowledge. Normative interventions could emphasise screening as an activity endorsed by important others outside the immediate family to appeal to a wider audience.

Self-Reported And Objectively Recorded Colorectal Cancer Screening Participation In England

Objective To compare self-reported with objectively recorded participation in Faecal Occult Blood testing (FOBt) colorectal cancer (CRC) screening in a national programme. Methods Survey respondents living in England who were eligible for screening were asked in face-to-face interviews if they had ever been invited to do a CRC screening test, how many times they had been invited, and how many times they had participated. National Health Service (NHS) Bowel Cancer Screening Programme (BCSP) records were consulted for respondents who had consented to a record check. The outcome measures were ‘ever uptake’ (responded to ≥1 invitation), ‘repeat uptake’ (responded to ≥2 invitations), and ‘consistent uptake’ (responded to all invitations). Results In the verified group, self-reported ever uptake was highly consistent with recorded ever uptake (87.0% vs. 87.8%). Among those who indicated that they had been invited more than once, self-reported repeat uptake was 89.8% compared with 84.8% recorded repeat uptake. Among those with more than one recorded invitation, self-reported repeat uptake was 72.7% compared with 77.2% recorded repeat uptake, and self-reported consistent uptake was 81.6% compared with 65.6% recorded consistent uptake. Conclusion Our results suggest that people can accurately report whether they have ever taken part in CRC screening. The vast majority of those whose records were verified could also accurately report whether they had taken part in screening at least twice. They were somewhat less accurate in reporting whether they had responded to all screening invitations.

Ephedrine treatment for autoimmune myasthenia gravis

We studied the effect and safety of ephedrine as add-on treatment for patients with myasthenia gravis with acetylcholine receptor antibodies (AChR MG), who do not sufficiently respond to standard treatment. Four patients with AChR MG were included in a placebo-controlled, double-blind, and randomised, multiple crossover series of n-of-1 trials. Each n-of-1 trial consisted of 3 cycles, in which two 5-day intervention periods were followed by 2 days washout. In each cycle, ephedrine 50 mg daily in 2 doses was compared with placebo in the alternate treatment period. Primary outcome was a change in QMG score. Add-on treatment with ephedrine compared with placebo improved QMG score by 1.0 point (95% confidence interval 0.21-1.79), which was significant for the group of trial patients as well as for the population treatment effect. Ephedrine also showed a significant trial average treatment effect for all secondary outcomes, improving MG Composite by 2.7, MG-ADL by 1.0 and VAS score for muscle strength by 1.1. Adverse events were mild and included palpitations, tremor and restlessness. Although all ECGs were normal, ephedrine prolonged the corrected QT interval. Ephedrine as add-on treatment for myasthenia gravis resulted in a small but consistent reduction of symptoms and weakness in patients with moderate disease severity.

Ephedrine as add-on therapy for patients with myasthenia gravis: protocol for a series of randomised, placebo-controlled n-of-1 trials

Introduction Myasthenia gravis (MG), a rare neuromuscular disease, is often initially treated using acetylcholinesterase inhibitors. Patients who do not respond adequately depend on the use of corticosteroids or other immunosuppressive medication, but these may have serious side effects. Clinical observations suggest that ephedrine can diminish, postpone or even prevent the need for immunosuppressive therapy when added to acetylcholinesterase inhibitors or low-dose prednisone. In the Netherlands, ephedrine is not licensed for MG nor is reimbursement guaranteed. MG is a rare condition, and ephedrine might be indicated only in a subset of patients. Thus, randomised controlled trials comparing large groups are difficult to conduct. We, therefore, aim to aggregate data from a small series of n-of-1 trials (also known as single patient trials) to assess the effect of ephedrine as add-on treatment for MG. Methods and analysis Single-centre, placebo-controlled, double-blind, randomised, multiple crossover n-of-1 studies in 4 adult patients with generalised MG who show inadequate improvement on pyridostigmine and/or immunosuppressive drugs. Each n-of-1 trial has 3 cycles of two 5-day intervention periods. Treatment: 25 mg ephedrine or placebo, twice daily. Main outcome measure: Quantitative Myasthenia Gravis (QMG) test. Statistical analysis: fixed effects linear model for QMG for all patients combined. Secondary outcome measures: Clinical: effects on MG-Composite and MG-Activities of Daily Living (MG-ADL) scales; QMG at individual level; adverse events. Acceptability of trial design: number of patients eligible and enrolled; number of treatment cycles completed; patients’ and caregivers’ experiences. Ethics and dissemination This study was approved by the Medical Ethics Committee of Leiden University Medical Center, No. P14.108. Results of the trial will be reported in a peer-reviewed publication. Regulatory stakeholders will comment on the suitability of the trial for market authorisation and reimbursement purposes. Trial registration number This study is registered under EudraCT number 2014-001355-23, protocol no. 40960, V.1.0, registration date 27 March 2014.

Public understanding of the purpose of cancer screening: A population-based survey:

Objectives In examining informed choice in cancer screening, we investigated public awareness that some screening programmes aim to prevent cancer, while others seek to detect cancer at an early stage. Methods A population-based survey of adults aged 50–70 in England (n = 1433), including data on demographic characteristics and screening experience. Participants were asked to select the main purpose of cervical, breast, and colorectal cancer screening (both faecal occult blood testing and flexible sigmoidoscopy). Results Across all four screening programmes, most people thought the main aim was to catch cancer early (71–78%). Only 18 and 14% knew that cervical screening and flexible sigmoidoscopy, respectively, are primarily preventive. Knowledge of the preventive aspect of these two programmes was low across the board, with few demographic patterns. By contrast, 78 and 73% of the sample were aware that breast screening and the faecal occult blood test, respectively, predominantly aim to detect cancer early. For these programmes, accurate knowledge was socially graded, lower in ethnic minority groups, and positively associated with previous participation in the programmes. Conclusions Our findings suggest that although awareness of the purpose of early detection screening is high, awareness that screening can prevent cancer is low across all demographic groups. Understanding the purpose of screening is a key aspect of informed choice but despite current communication strategies highlighting these differences, people do not seem to have a nuanced understanding of these differing aims. Our findings may be indicative of a broader public scepticism about the preventability of cancer.

Aggregated N-of-1 trials for unlicensed medicines for small populations: an assessment of a trial with ephedrine for myasthenia gravis

BackgroundInexpensive medicines with a long history of use may currently be prescribed off-label for rare indications. Reimbursement is at the discretion of health insurance companies, and may be unpredictable. The example addressed was ephedrine as add-on treatment for myasthenia gravis. Stakeholders from academia, a patient organization, the Dutch National Health Care Institute (NHCI) and Dutch Medicines Evaluation Board (MEB) advised on the trial design. The NHCI and MEB agreed to provide scientific advice on the suitability of the evidence generated by the trial, for regulatory decisions. This paper describes the feasibility of the trial and the utility of its aggregated results.ResultsThe trialists experienced the trial as feasible. Retrospective interviews showed that the trial as performed was acceptable to patients. The treatment effect in the primary outcome measure, muscle strength, was statistically significant when inferred to the population level, though the effect size was modest. Secondary outcomes were statistically significant in a preplanned, fixed effects analysis within the four patients. The NHCI advised that it could potentially make reimbursement decisions based on the Fitting Evidence framework, should the trialists decide to apply for reimbursement. The MEB advised that for a licensing decision, the N-of-1 design is a last-resort option for demonstrating treatment benefit in a rare disease. N-of-1 trials alone do not provide enough evidence on potential risk. The MEB found the current trial inconclusive. It suggested doing a 2-armed trial of longer duration, possibly with a different outcome measure (postponement of corticosteroid use). It suggested engaging a consultancy or commercial sponsor, should the trialists decide to seek market authorization of the drug.ConclusionsIn theory, evidence from aggregated N-of-1 trials is suitable for use in licensing and reimbursement decisions. The current example illustrates differences in interpretation of N-of-1 results by health authorities. In the era of personalized medicine, consensus is required on the interpretation of data from study designs geared to small groups. Demonstrating effectiveness of inexpensive medicines in small populations may require involvement of non-commercial parties, to preserve affordability.