Early detection of lung cancer: a statement from an expert panel of the Swiss university hospitals on lung cancer screening.

The discussion about setting up a program for lung cancer screening was launched with the publication of the results of the National Lung Screening Trial, which suggested reduced mortality in high-risk subjects undergoing CT screening. However, important questions about the benefit-harm balance and the details of a screening program and its cost-effectiveness remain unanswered. A panel of specialists in chest radiology, respiratory medicine, epidemiology, and thoracic surgery representing all Swiss university hospitals prepared this joint statement following several meetings. The panel argues that premature and uncontrolled introduction of a lung cancer screening program may cause substantial harm that may remain undetected without rigorous quality control. This position paper focuses on the requirements of running such a program with the objective of harmonizing efforts across the involved specialties and institutions and defining quality standards. The underlying statement includes information on current evidence for a reduction in mortality with lung cancer screening and the potential epidemiologic implications of such a program in Switzerland. Furthermore, requirements for lung cancer screening centers are defined, and recommendations for both the CT technique and the algorithm for lung nodule assessment are provided. In addition, related issues such as patient management, registry, and funding are addressed. Based on the current state of the knowledge, the panel concludes that lung cancer screening in Switzerland should be undertaken exclusively within a national observational study in order to provide answers to several critical questions before considering broad population-based screening for lung cancer.

Effectiveness of yearly, register based screening for chlamydia in the Netherlands: controlled trial with randomised stepped wedge implementation

To evaluate the effectiveness of register based, yearly chlamydia screening.

Impact of carotid plaque screening on smoking cessation and other cardiovascular risk factors: a randomized controlled trial

Screening of peripheral atherosclerosis is increasingly used, but few trials have examined its clinical impact. We aimed to assess whether carotid plaque screening helps smokers to improve their health behaviors and cardiovascular risk factors.

The management of ruptured abdominal aortic aneurysms: screening for abdominal aortic aneurysm and incidence of rupture

Twenty-five years have passed since the first randomised controlled trial began its recruitment for screening for abdominal aortic aneurysm (AAA) in men aged 65 and above. Since this and other randomised trials, all launched in the late 80s and 90s of the last century, the epidemiologic profile of abdominal aortic aneurysm may have changed. The trials reported an AAA prevalence in the range of 4-7% for men aged 65 years or more. AAA-related mortality was significantly improved by screening, and after 13 years, the largest trial showed a benefit for all-cause mortality. Screening also was shown to be cost-effective. Today, there are studies showing a substantial decrease of AAA prevalence to sometimes less than 2% in men aged ≥ 65 years and there is evidence that the incidence of ruptured aneurysm and mortality from AAA is also declining. This decline preceded the implementation of screening programmes but may be due to a change in risk factor management. The prevalence of smoking has decreased and there has been improvement in the control of hypertension and a rising use of statins for cardiovascular risk prevention. Additionally, there is a shift of the burden to the older age group of ≥ 75 years. Such radical changes may influence screening policy and it is worth reflecting on the optimum age of screening - it might be better to screen at ages >65 years - or rescreening 5 to 10 years after the first screen.

Impact of Helicobacter pylori eradication on dyspepsia, health resource use, and quality of life in the Bristol helicobacter project: randomised controlled trial

OBJECTIVE: To determine the impact of a community based Helicobacter pylori screening and eradication programme on the incidence of dyspepsia, resource use, and quality of life, including a cost consequences analysis. DESIGN: H pylori screening programme followed by randomised placebo controlled trial of eradication. SETTING: Seven general practices in southwest England. PARTICIPANTS: 10,537 unselected people aged 20-59 years were screened for H pylori infection (13C urea breath test); 1558 of the 1636 participants who tested positive were randomised to H pylori eradication treatment or placebo, and 1539 (99%) were followed up for two years. INTERVENTION: Ranitidine bismuth citrate 400 mg and clarithromycin 500 mg twice daily for two weeks or placebo. MAIN OUTCOME MEASURES: Primary care consultation rates for dyspepsia (defined as epigastric pain) two years after randomisation, with secondary outcomes of dyspepsia symptoms, resource use, NHS costs, and quality of life. RESULTS: In the eradication group, 35% fewer participants consulted for dyspepsia over two years compared with the placebo group (55/787 v 78/771; odds ratio 0.65, 95% confidence interval 0.46 to 0.94; P = 0.021; number needed to treat 30) and 29% fewer participants had regular symptoms (odds ratio 0.71, 0.56 to 0.90; P = 0.05). NHS costs were 84.70 pounds sterling (74.90 pounds sterling to 93.91 pounds sterling) greater per participant in the eradication group over two years, of which 83.40 pounds sterling (146 dollars; 121 euro) was the cost of eradication treatment. No difference in quality of life existed between the two groups. CONCLUSIONS: Community screening and eradication of H pylori is feasible in the general population and led to significant reductions in the number of people who consulted for dyspepsia and had symptoms two years after treatment. These benefits have to be balanced against the costs of eradication treatment, so a targeted eradication strategy in dyspeptic patients may be preferable.

Partner notification of chlamydia infection in primary care: randomised controlled trial and analysis of resource use

OBJECTIVE: To evaluate the effectiveness of a practice nurse led strategy to improve the notification and treatment of partners of people with chlamydia infection. DESIGN: Randomised controlled trial. SETTING: 27 general practices in the Bristol and Birmingham areas. PARTICIPANTS: 140 men and women with chlamydia (index cases) diagnosed by screening of a home collected urine sample or vulval swab specimen. INTERVENTIONS: Partner notification at the general practice immediately after diagnosis by trained practice nurses, with telephone follow up by a health adviser; or referral to a specialist health adviser at a genitourinary medicine clinic. MAIN OUTCOME MEASURES: Primary outcome was the proportion of index cases with at least one treated sexual partner. Specified secondary outcomes included the number of sexual contacts elicited during a sexual history, positive test result for chlamydia six weeks after treatment, and the cost of each strategy in 2003 sterling prices. RESULTS: 65.3% (47/72) of participants receiving practice nurse led partner notification had at least one partner treated compared with 52.9% (39/68) of those referred to a genitourinary medicine clinic (risk difference 12.4%, 95% confidence interval -1.8% to 26.5%). Of 68 participants referred to the clinic, 21 (31%) did not attend. The costs per index case were 32.55 pounds sterling for the practice nurse led strategy and 32.62 pounds sterling for the specialist referral strategy. CONCLUSION: Practice based partner notification by trained nurses with telephone follow up by health advisers is at least as effective as referral to a specialist health adviser at a genitourinary medicine clinic, and costs the same. Trial registration Clinical trials: NCT00112255.

Epidemiological, social, diagnostic and economic evaluation of population screening for genital chlamydial infection

OBJECTIVES: To investigate epidemiological, social, diagnostic and economic aspects of chlamydia screening in non-genitourinary medicine settings. METHODS: Linked studies around a cross-sectional population-based survey of adult men and women invited to collect urine and (for women) vulvovaginal swab specimens at home and mail these to a laboratory for testing for Chlamydia trachomatis. Specimens were used in laboratory evaluations of an amplified enzyme immunoassay (PCE EIA) and two nucleic acid amplification tests [Cobas polymerase chain reaction (PCR), Becton Dickinson strand displacement amplification (SDA)]. Chlamydia-positive cases and two negative controls completed a risk factor questionnaire. Chlamydia-positive cases were invited into a randomised controlled trial of partner notification strategies. Samples of individuals testing negative completed psychological questionnaires before and after screening. In-depth interviews were conducted at all stages of screening. Chlamydia transmission and cost-effectiveness of screening were investigated in a transmission dynamic model. SETTING AND PARTICIPANTS: General population in the Bristol and Birmingham areas of England. In total, 19,773 women and men aged 16-39 years were randomly selected from 27 general practice lists. RESULTS: Screening invitations reached 73% (14,382/19,773). Uptake (4731 participants), weighted for sampling, was 39.5% (95% CI 37.7, 40.8%) in women and 29.5% (95% CI 28.0, 31.0%) in men aged 16-39 years. Chlamydia prevalence (219 positive results) in 16-24 year olds was 6.2% (95% CI 4.9, 7.8%) in women and 5.3% (95% CI 4.4, 6.3%) in men. The case-control study did not identify any additional factors that would help target screening. Screening did not adversely affect anxiety, depression or self-esteem. Participants welcomed the convenience and privacy of home-sampling. The relative sensitivity of PCR on male urine specimens was 100% (95% CI 89.1, 100%). The combined relative sensitivities of PCR and SDA using female urine and vulvovaginal swabs were 91.8% (86.1, 95.7, 134/146) and 97.3% (93.1, 99.2%, 142/146). A total of 140 people (74% of eligible) participated in the randomised trial. Compared with referral to a genitourinary medicine clinic, partner notification by practice nurses resulted in 12.4% (95% CI -3.7, 28.6%) more patients with at least one partner treated and 22.0% (95% CI 6.1, 37.8%) more patients with all partners treated. The health service and patients costs (2005 prices) of home-based postal chlamydia screening were 21.47 pounds (95% CI 19.91 pounds, 25.99) per screening invitation and 28.56 pounds (95% CI 22.10 pounds, 30.43) per accepted offer. Preliminary modelling found an incremental cost-effectiveness ratio (2003 prices) comparing screening men and women annually to no screening in the base case of 27,000 pounds/major outcome averted at 8 years. If estimated screening uptake and pelvic inflammatory disease incidence were increased, the cost-effectiveness ratio fell to 3700 pounds/major outcome averted. CONCLUSIONS: Proactive screening for chlamydia in women and men using home-collected specimens was feasible and acceptable. Chlamydia prevalence rates in men and women in the general population are similar. Nucleic acid amplification tests can be used on first-catch urine specimens and vulvovaginal swabs. The administrative costs of proactive screening were similar to those for opportunistic screening. Using empirical estimates of screening uptake and incidence of complications, screening was not cost-effective.

Randomised controlled trials of homeopathy in hyperactive children: treatment procedure leads to an unconventional study design. Experience with open-label homeopathic treatment preceding the Swiss ADHD placebo controlled, randomised, double-blind, cross-over trial

BACKGROUND: Treatment of patients with attention deficit hyperactivity disorder (ADHD) with homeopathy is difficult. The Swiss randomised, placebo controlled, cross-over trial in ADHD patients (Swiss ADHD trial) was designed with an open-label screening phase prior to the randomised controlled phase. During the screening phase, the response of each child to successive homeopathic medications was observed until the optimal medication was identified. Only children who reached a predefined level of improvement participated in the randomised, cross-over phase. Although the randomised phase revealed a significant beneficial effect of homeopathy, the cross-over caused a strong carryover effect diminishing the apparent difference between placebo and verum treatment. METHODS: This retrospective analysis explores the screening phase data with respect to the risk of failure to demonstrate a specific effect of a randomised controlled trial (RCT) with randomisation at the start of the treatment. RESULTS: During the screening phase, 84% (70/83) of the children responded to treatment and reached eligibility for the randomised trial after a median time of 5 months (range 1-18), with a median of 3 different medications (range 1-9). Thirteen children (16%) did not reach eligibility. Five months after treatment start, the difference in Conners Global Index (CGI) rating between responders and non-responders became highly significant (p = 0.0006). Improvement in CGI was much greater following the identification of the optimal medication than in the preceding suboptimal treatment period (p < 0.0001). CONCLUSIONS: Because of the necessity of identifying an optimal medication before response to treatment can be expected, randomisation at the start of treatment in an RCT of homeopathy in ADHD children has a high risk of failure to demonstrate a specific treatment effect, if the observation time is shorter than 12 months.

Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial

PURPOSE: The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy. PATIENTS AND METHODS: The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2-positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF > or = 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. RESULTS: Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m(2) v 257 mg/m(2)) or epirubicin (480 mg/m(2) v 422 mg/m(2)) and had a lower screening LVEF and a higher body mass index. CONCLUSION: Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.

Effectiveness of chlamydia screening: systematic review

BACKGROUND: Screening programmes are promoted to control transmission of and prevent female reproductive tract morbidity caused by genital chlamydia. The objective of this study was to examine the effectiveness of register-based and opportunistic chlamydia screening interventions. METHODS: We searched seven electronic databases (Cinahl, Cochrane Controlled Trials Register, DARE, Embase, Medline, PsycINFO and SIGLE) without language restrictions from January 1990 to October 2007 and reference lists of retrieved articles to identify studies published before 1990. We included studies examining primary outcomes (pelvic inflammatory disease, ectopic pregnancy, infertility, adverse pregnancy outcomes, neonatal infection, chlamydia prevalence) and harms of chlamydia screening in men and non-pregnant and pregnant women. We extracted data in duplicate and synthesized the data narratively or used random effects meta-analysis, where appropriate. RESULTS: We included six systematic reviews, five randomized trials, one non-randomized comparative study and one time trend study. Five reviews recommended screening of women at high risk of chlamydia. Two randomized trials found that register-based screening of women at high risk of chlamydia and of female and male high school students reduced the incidence of pelvic inflammatory disease in women at 1 year. Methodological inadequacies could have overestimated the observed benefits. One randomized trial showed that opportunistic screening in women undergoing surgical termination of pregnancy reduced post-abortal rates of pelvic inflammatory disease compared with no screening. We found no randomized trials showing a benefit of opportunistic screening in other populations, no trial examining the effects of more than one screening round and no trials examining the harms of chlamydia screening. CONCLUSION: There is an absence of evidence supporting opportunistic chlamydia screening in the general population younger than 25 years, the most commonly recommended approach. Equipoise remains, so high-quality randomized trials of multiple rounds of screening with biological outcome measures are still needed to determine the balance of benefits and harms of chlamydia screening.

Development of a screening tool predicting the transition from acute to chronic low back pain for patients in a GP setting: protocol of a multinational prospective cohort study

BACKGROUND: Low back pain (LBP) is by far the most prevalent and costly musculoskeletal problem in our society today. Following the recommendations of the Multinational Musculoskeletal Inception Cohort Study (MMICS) Statement, our study aims to define outcome assessment tools for patients with acute LBP and the time point at which chronic LBP becomes manifest and to identify patient characteristics which increase the risk of chronicity. METHODS: Patients with acute LBP will be recruited from clinics of general practitioners (GPs) in New Zealand (NZ) and Switzerland (CH). They will be assessed by postal survey at baseline and at 3, 6, 12 weeks and 6 months follow-up. Primary outcome will be disability as measured by the Oswestry Disability Index (ODI); key secondary endpoints will be general health as measured by the acute SF-12 and pain as measured on the Visual Analogue Scale (VAS). A subgroup analysis of different assessment instruments and baseline characteristics will be performed using multiple linear regression models. This study aims to examine: 1. Which biomedical, psychological, social, and occupational outcome assessment tools are identifiers for the transition from acute to chronic LBP and at which time point this transition becomes manifest. 2. Which psychosocial and occupational baseline characteristics like work status and period of work absenteeism influence the course from acute to chronic LBP. 3. Differences in outcome assessment tools and baseline characteristics of patients in NZ compared with CH. DISCUSSION: This study will develop a screening tool for patients with acute LBP to be used in GP clinics to access the risk of developing chronic LBP. In addition, biomedical, psychological, social, and occupational patient characteristics which influence the course from acute to chronic LBP will be identified. Furthermore, an appropriate time point for follow-ups will be given to detect this transition. The generalizability of our findings will be enhanced by the international perspective of this study. TRIAL REGISTRATION: [Clinical Trial Registration Number, ACTRN12608000520336].

Promotion of health in older people: a randomised controlled trial of health risk appraisal in British general practice

BACKGROUND: there is inadequate evidence to support currently formulated NHS strategies to achieve health promotion and preventative care in older people through broad-based screening and assessment in primary care. The most extensively evaluated delivery instrument for this purpose is Health Risk Appraisal (HRA). This article describes a trial using HRA to evaluate the effect on health behaviour and preventative-care uptake in older people in NHS primary care. METHODS: a randomised controlled trial was undertaken in three London primary care group practices. Functionally independent community-dwelling patients older than 65 years (n = 2,503) received a self-administered Health Risk Appraisal for Older Persons (HRA-O) questionnaire leading to computer-generated individualised written feedback to participants and general practitioners (GPs), integrated into practice information-technology (IT) systems. All primary care staff received training in preventative health in older people. The main outcome measures were self-reported health behaviour and preventative care uptake at 1-year follow-up. RESULTS: of 2,503 individuals randomised, 2,006 respondents (80.1%) (intervention, n = 940, control n = 1,066) were available for analysis. Intervention group respondents reported slightly higher pneumococcal vaccination uptake and equivocal improvement in physical activity levels compared with controls. No significant differences were observed for any other categories of health behaviour or preventative care measures at 1-year follow-up. CONCLUSIONS: HRA-O implemented in this way resulted in minimal improvement of health behaviour or uptake of preventative care measures in older people. Supplementary reinforcement involving contact by health professionals with patients over and above routine clinical encounters may be a prerequisite to the effectiveness of IT-based delivery systems for health promotion in older people.

Does a Pre-Treatment Diagnostic Interview Affect the Outcome of Internet-Based Self-Help for Social Anxiety Disorder? A Randomized Controlled Trial

BACKGROUND: Numerous studies suggest that Internet-based self-help treatments are effective in treating anxiety disorders. Trials evaluating such interventions differ in their screening procedures and in the amount of clinician contact in the diagnostic assessment phase. The present study evaluates the impact of a pre-treatment diagnostic interview on the outcome of an Internet-based treatment for Social Anxiety Disorder (SAD). METHOD: One hundred and nine participants seeking treatment for SAD were randomized to either an interview-group (IG, N = 53) or to a non-interview group (NIG, N = 56). All participants took part in the same 10-week cognitive-behavioural unguided self-help programme. Before receiving access to the programme, participants of the IG underwent a structured diagnostic interview. Participants of the NIG started directly with the programme. RESULTS: Participants in both groups showed significant and substantial improvement on social anxiety measures from pre- to post-assessment (d IG = 1.30-1.63; d NIG = 1.00-1.28) and from pre- to 4-month follow-up assessment (d IG = 1.38-1.87; d NIG = 1.10-1.21). Significant between-groups effects in favour of the IG were found on secondary outcome measures of depression and general distress (d = 0.18-0.42). CONCLUSIONS: These findings suggest that Internet-based self-help is effective in treating SAD, whether or not a diagnostic interview is involved. However, the pre-treatment interview seems to facilitate change on secondary outcomes such as depression and general distress.

Should we perform a screening ECG among asymptomatic adults?

The resting ECG is a safe, low cost and widely available in the clinical investigation of several cardiac symptoms. However, there is controversy regarding the use as a screening tool or routine cardiovascular (CV) risk assessment test among healthy asymptomatic adults. Two recent studies reported that ECG adds supplemental information in the estimation of coronary artery disease (CAD) risk in asymptomatic patients, especially in those with intermediate risk. However, we currently need more data on the impact of ECG on the prevention of clinical CV outcomes, especially in a randomized clinical trial, and on additional costs of testing and treatment. For the time being, routine ECG testing is not recommended for the prevention of CV events among healthy asymptomatic adults.