Explore the vast range of titles available.

The World Health Organization recommends the screening of all people living with HIV for tuberculosis (TB) disease, followed by TB treatment, or isoniazid preventive therapy (IPT) when TB is excluded. However, the difficulty of reliably excluding TB disease has severely limited TB screening and IPT uptake in resource-limited settings. We conducted an individual participant data meta-analysis of primary studies, aiming to identify a sensitive TB screening rule. We identified 12 studies that had systematically collected sputum specimens regardless of signs or symptoms, at least one mycobacterial culture, clinical symptoms, and HIV and TB disease status. Bivariate random-effects meta-analysis and the hierarchical summary relative operating characteristic curves were used to evaluate the screening performance of all combinations of variables of interest. TB disease was diagnosed in 557 (5.8%) of 9,626 people living with HIV. The primary analysis included 8,148 people living with HIV who could be evaluated on five symptoms from nine of the 12 studies. The median age was 34 years. The best performing rule was the presence of any one of: current cough (any duration), fever, night sweats, or weight loss. The overall sensitivity of this rule was 78.9% (95% confidence interval [CI] 58.3%-90.9%) and specificity was 49.6% (95% CI 29.2%-70.1%). Its sensitivity increased to 90.1% (95% CI 76.3%-96.2%) among participants selected from clinical settings and to 88.0% (95% CI 76.1%-94.4%) among those who were not previously screened for TB. Negative predictive value was 97.7% (95% CI 97.4%-98.0%) and 90.0% (95% CI 88.6%-91.3%) at 5% and 20% prevalence of TB among people living with HIV, respectively. Abnormal chest radiographic findings increased the sensitivity of the rule by 11.7% (90.6% versus 78.9%) with a reduction of specificity by 10.7% (49.6% versus 38.9%). Absence of all of current cough, fever, night sweats, and weight loss can identify a subset of people living with HIV who have a very low probability of having TB disease. A simplified screening rule using any one of these symptoms can be used in resource-constrained settings to identify people living with HIV in need of further diagnostic assessment for TB. Use of this algorithm should result in earlier TB diagnosis and treatment, and should allow for substantial scale-up of IPT.

Objective To study the effect of cervical screening on incidence of cervical cancer as a function of age with particular focus on women screened under the age of 25.Design Population based case-control study with prospectively recorded data on cervical screening.Setting Selected centres in the United Kingdom.Participants 4012 women aged 20-69 with invasive cancer diagnosed in participating centres and two controls per case individually matched on age and area of residence.Main outcome measures Odds ratios for strength of association between cervical cancer and screening at particular ages.Results There is no evidence that screening women aged 22-24 reduced the incidence of cervical cancer at ages 25-29 (odds ratio 1.11, 95% confidence interval 0.83 to 1.50). Similar results were seen for cancers restricted to squamous carcinoma or FIGO (International Federation of Gynaecology and Obstetrics) stage IB or worse, but the numbers are insufficient to provide narrow confidence intervals. Screening was associated with a 60% reduction of cancers in women aged 40, increasing to 80% at age 64. Screening was particularly effective in preventing advanced stage cancers.Conclusions Cervical screening in women aged 20-24 has little or no impact on rates of invasive cervical cancer up to age 30. Some uncertainly still exists regarding its impact on advanced stage tumours in women under age 30. By contrast, screening older women leads to a substantial reduction in incidence of and mortality from cervical cancer. These data should help policy makers balance the impact of screening on cancer rates against its harms, such as overtreatment of lesions with little invasive potential.

Objective To examine the evidence on the benefits and harms of screening for prostate cancer.Design Systematic review and meta-analysis of randomised controlled trials.Data sources Electronic databases including Medline, Embase, CENTRAL, abstract proceedings, and reference lists up to July 2010.Review methods Included studies were randomised controlled trials comparing screening by prostate specific antigen with or without digital rectal examination versus no screening. Data abstraction and assessment of methodological quality with the GRADE approach was assessed by two independent reviewers and verified by the primary investigator. Mantel-Haenszel and inverse variance estimates were calculated and pooled under a random effects model expressing data as relative risks and 95% confidence intervals.Results Six randomised controlled trials with a total of 387 286 participants that met inclusion criteria were analysed. Screening was associated with an increased probability of receiving a diagnosis of prostate cancer (relative risk 1.46, 95% confidence interval 1.21 to 1.77; P<0.001) and stage I prostate cancer (1.95, 1.22 to 3.13; P=0.005). There was no significant effect of screening on death from prostate cancer (0.88, 0.71 to 1.09; P=0.25) or overall mortality (0.99, 0.97 to 1.01; P=0.44). All trials had one or more substantial methodological limitations. None provided data on the effects of screening on participants’ quality of life. Little information was provided about potential harms associated with screening.Conclusions The existing evidence from randomised controlled trials does not support the routine use of screening for prostate cancer with prostate specific antigen with or without digital rectal examination.

Objective To compare trends in breast cancer mortality within three pairs of neighbouring European countries in relation to implementation of screening.Design Retrospective trend analysis.Setting Three country pairs (Northern Ireland (United Kingdom) v Republic of Ireland, the Netherlands v Belgium and Flanders (Belgian region south of the Netherlands), and Sweden v Norway).Data sources WHO mortality database on cause of death and data sources on mammography screening, cancer treatment, and risk factors for breast cancer mortality.Main outcome measures Changes in breast cancer mortality calculated from linear regressions of log transformed, age adjusted death rates. Joinpoint analysis was used to identify the year when trends in mortality for all ages began to change.Results From 1989 to 2006, deaths from breast cancer decreased by 29% in Northern Ireland and by 26% in the Republic of Ireland; by 25% in the Netherlands and by 20% in Belgium and 25% in Flanders; and by 16% in Sweden and by 24% in Norway. The time trend and year of downward inflexion were similar between Northern Ireland and the Republic of Ireland and between the Netherlands and Flanders. In Sweden, mortality rates have steadily decreased since 1972, with no downward inflexion until 2006. Countries of each pair had similar healthcare services and prevalence of risk factors for breast cancer mortality but differing implementation of mammography screening, with a gap of about 10-15 years.Conclusions The contrast between the time differences in implementation of mammography screening and the similarity in reductions in mortality between the country pairs suggest that screening did not play a direct part in the reductions in breast cancer mortality.

Objective To determine the risk of colorectal cancer after screening with flexible sigmoidoscopy.Design Randomised controlled trial.Setting Population based screening in two areas in Norway—city of Oslo and Telemark county (urban and mixed urban and rural populations).Participants 55 736 men and women aged 55-64 years.Intervention Once only flexible sigmoidoscopy screening with or without a single round of faecal occult blood testing (n=13 823) compared with no screening (n=41 913).Main outcome measures Planned end points were cumulative incidence and mortality of colorectal cancer after 5, 10, and 15 years. This first report from the study presents cumulative incidence after 7 years of follow-up and hazard ratio for mortality after 6 years.Results No difference was found in the 7 year cumulative incidence of colorectal cancer between the screening and control groups (134.5 v 131.9 cases per 100 000 person years). In intention to screen analysis, a trend towards reduced colorectal cancer mortality was found (hazard ratio 0.73, 95% confidence interval 0.47 to 1.13, P=0.16). For attenders compared with controls, a statistically significant reduction in mortality was apparent for both total colorectal cancer (hazard ratio 0.41, 0.21 to 0.82, P=0.011) and rectosigmoidal cancer (0.24, 0.08 to 0.76, P=0.016).Conclusions A reduction in incidence of colorectal cancer with flexible sigmoidoscopy screening could not be shown after 7 years’ follow-up. Mortality from colorectal cancer was not significantly reduced in the screening group but seemed to be lower for attenders, with a reduction of 59% for any location of colorectal cancer and 76% for rectosigmoidal cancer in per protocol analysis, an analysis prone to selection bias.Trial registration Clinical trials NCT00119912.

Objectives To review the evidence for an association of white matter hyperintensities with risk of stroke, cognitive decline, dementia, and death.Design Systematic review and meta-analysis.Data sources PubMed from 1966 to 23 November 2009.Study selection Prospective longitudinal studies that used magnetic resonance imaging and assessed the impact of white matter hyperintensities on risk of incident stroke, cognitive decline, dementia, and death, and, for the meta-analysis, studies that provided risk estimates for a categorical measure of white matter hyperintensities, assessing the impact of these lesions on risk of stroke, dementia, and death.Data extraction Population studied, duration of follow-up, method used to measure white matter hyperintensities, definition of the outcome, and measure of the association of white matter hyperintensities with the outcome.Data synthesis 46 longitudinal studies evaluated the association of white matter hyperintensities with risk of stroke (n=12), cognitive decline (n=19), dementia (n=17), and death (n=10). 22 studies could be included in a meta-analysis (nine of stroke, nine of dementia, eight of death). White matter hyperintensities were associated with an increased risk of stroke (hazard ratio 3.3, 95% confidence interval 2.6 to 4.4), dementia (1.9, 1.3 to 2.8), and death (2.0, 1.6 to 2.7). An association of white matter hyperintensities with a faster decline in global cognitive performance, executive function, and processing speed was also suggested.Conclusion White matter hyperintensities predict an increased risk of stroke, dementia, and death. Therefore white matter hyperintensities indicate an increased risk of cerebrovascular events when identified as part of diagnostic investigations, and support their use as an intermediate marker in a research setting. Their discovery should prompt detailed screening for risk factors of stroke and dementia.

Objective To determine whether a decision aid designed for adults with low education and literacy can support informed choice and involvement in decisions about screening for bowel cancer.Design Randomised controlled trial.Setting Areas in New South Wales, Australia identified as socioeconomically disadvantaged (low education attainment, high unemployment, and unskilled occupations).Participants 572 adults aged between 55 and 64 with low educational attainment, eligible for bowel cancer screening.Intervention Patient decision aid comprising a paper based interactive booklet (with and without a question prompt list) and a DVD, presenting quantitative risk information on the possible outcomes of screening using faecal occult blood testing compared with no testing. The control group received standard information developed for the Australian national bowel screening programme. All materials and a faecal occult blood test kit were posted directly to people’s homes.Main outcome measures Informed choice (adequate knowledge and consistency between attitudes and screening behaviour) and preferences for involvement in screening decisions.Results Participants who received the decision aid showed higher levels of knowledge than the controls; the mean score (maximum score 12) for the decision aid group was 6.50 (95% confidence interval 6.15 to 6.84) and for the control group was 4.10 (3.85 to 4.36; P<0.001). Attitudes towards screening were less positive in the decision aid group, with 51% of the participants expressing favourable attitudes compared with 65% of participants in the control group (14% difference, 95% confidence interval 5% to 23%; P=0.002). The participation rate for screening was reduced in the decision aid group: completion of faecal occult blood testing was 59% v 75% in the control group (16% difference, 8% to 24%; P=0.001). The decision aid increased the proportion of participants who made an informed choice, from 12% in the control group to 34% in the decision aid group (22% difference, 15% to 29%; P<0.001). More participants in the decision aid group had no decisional conflict about the screening decision compared with the controls (51% v 38%; P=0.02). The groups did not differ for general anxiety or worry about bowel cancer.Conclusions Tailored decision support information can be effective in supporting informed choices and greater involvement in decisions about faecal occult blood testing among adults with low levels of education, without increasing anxiety or worry about developing bowel cancer. Using a decision aid to make an informed choice may, however, lead to lower uptake of screening.Trial registration ClinicalTrials.gov NCT00765869 and Australian New Zealand Clinical Trials Registry 12608000011381.

Objectives To assess whether the mortality benefit from screening men aged 65-74 for abdominal aortic aneurysm decreases over time, and to estimate the long term cost effectiveness of screening.Design Randomised trial with 10 years of follow-up.Setting Four centres in the UK. Screening and surveillance was delivered mainly in primary care settings, with follow-up and surgery offered in hospitals.Participants Population based sample of 67 770 men aged 65-74.Interventions Participants were individually allocated to invitation to ultrasound screening (invited group) or to a control group not offered screening. Patients with an abdominal aortic aneurysm detected at screening underwent surveillance and were offered surgery if they met predefined criteria.Main outcome measures Mortality and costs related to abdominal aortic aneurysm, and cost per life year gained.Results Over 10 years 155 deaths related to abdominal aortic aneurysm (absolute risk 0.46%) occurred in the invited group and 296 (0.87%) in the control group (relative risk reduction 48%, 95% confidence interval 37% to 57%). The degree of benefit seen in earlier years of follow-up was maintained in later years. Based on the 10 year trial data, the incremental cost per man invited to screening was £100 (95% confidence interval £82 to £118), leading to an incremental cost effectiveness ratio of £7600 (£5100 to £13 000) per life year gained. However, the incidence of ruptured abdominal aortic aneurysms in those originally screened as normal increased noticeably after eight years.Conclusions The mortality benefit of screening men aged 65-74 for abdominal aortic aneurysm is maintained up to 10 years and cost effectiveness becomes more favourable over time. To maximise the benefit from a screening programme, emphasis should be placed on achieving a high initial rate of attendance and good adherence to clinical follow-up, preventing delays in undertaking surgery, and maintaining a low operative mortality after elective surgery. On the basis of current evidence, rescreening of those originally screened as normal is not justified.Trial registration Current Controlled Trials ISRCTN37381646.

Objectives To quantify the benefits and harms of general health checks in adults with an emphasis on patient-relevant outcomes such as morbidity and mortality rather than on surrogate outcomes.Design Cochrane systematic review and meta-analysis of randomised trials. For mortality, we analysed the results with random effects meta-analysis, and for other outcomes we did a qualitative synthesis as meta-analysis was not feasible.Data sources Medline, EMBASE, Healthstar, Cochrane Library, Cochrane Central Register of Controlled Trials, CINAHL, EPOC register, ClinicalTrials.gov, and WHO ICTRP, supplemented by manual searches of reference lists of included studies, citation tracking (Web of Knowledge), and contacts with trialists.Selection criteria Randomised trials comparing health checks with no health checks in adult populations unselected for disease or risk factors. Health checks defined as screening general populations for more than one disease or risk factor in more than one organ system. We did not include geriatric trials.Data extraction Two observers independently assessed eligibility, extracted data, and assessed the risk of bias. We contacted authors for additional outcomes or trial details when necessary.Results We identified 16 trials, 14 of which had available outcome data (182 880 participants). Nine trials provided data on total mortality (11 940 deaths), and they gave a risk ratio of 0.99 (95% confidence interval 0.95 to 1.03). Eight trials provided data on cardiovascular mortality (4567 deaths), risk ratio 1.03 (0.91 to 1.17), and eight on cancer mortality (3663 deaths), risk ratio 1.01 (0.92 to 1.12). Subgroup and sensitivity analyses did not alter these findings. We did not find beneficial effects of general health checks on morbidity, hospitalisation, disability, worry, additional physician visits, or absence from work, but not all trials reported on these outcomes. One trial found that health checks led to a 20% increase in the total number of new diagnoses per participant over six years compared with the control group and an increased number of people with self reported chronic conditions, and one trial found an increased prevalence of hypertension and hypercholesterolaemia. Two out of four trials found an increased use of antihypertensives. Two out of four trials found small beneficial effects on self reported health, which could be due to bias.Conclusions General health checks did not reduce morbidity or mortality, neither overall nor for cardiovascular or cancer causes, although they increased the number of new diagnoses. Important harmful outcomes were often not studied or reported.Systematic review registration Cochrane Library, doi:10.1002/14651858.CD009009.

The World Health Organization Disability Assessment Schedule (WHODAS 2.0) measures disability due to health conditions including diseases, illnesses, injuries, mental or emotional problems, and problems with alcohol or drugs. The 12 Item WHODAS 2.0 was used in the second Australian Survey of Mental Health and Well-being. We report the overall factor structure and the distribution of scores and normative data (means and SDs) for people with any physical disorder, any mental disorder and for people with neither. A single second order factor justifies the use of the scale as a measure of global disability. People with mental disorders had high scores (mean 6.3, SD 7.1), people with physical disorders had lower scores (mean 4.3, SD 6.1). People with no disorder covered by the survey had low scores (mean 1.4, SD 3.6). The provision of normative data from a population sample of adults will facilitate use of the WHODAS 2.0 12 item scale in clinical and epidemiological research.