Grey literature in meta-analyses of randomized trials of health care interventions

BACKGROUND: The inclusion of grey literature (i.e. literature that has not been formally published) in systematic reviews may help to overcome some of the problems of publication bias, which can arise due to the selective availability of data. OBJECTIVES: To review systematically research studies, which have investigated the impact of grey literature in meta-analyses of randomized trials of health care interventions. SEARCH STRATEGY: We searched the Cochrane Methodology Register (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to 20 May 2005), the Science Citation Index (June 2005) and contacted researchers who may have carried out relevant studies. SELECTION CRITERIA: A study was considered eligible for this review if it compared the effect of the inclusion and exclusion of grey literature on the results of a cohort of meta-analyses of randomized trials. DATA COLLECTION AND ANALYSIS: Data were extracted from each report independently by two reviewers. The main outcome measure was an estimate of the impact of trials from the grey literature on the pooled effect estimates of the meta-analyses. Information was also collected on the area of health care, the number of meta-analyses, the number of trials, the number of trial participants, the year of publication of the trials, the language and country of publication of the trials, the number and type of grey and published literature, and methodological quality. MAIN RESULTS: Five studies met the inclusion criteria. All five studies showed that published trials showed an overall greater treatment effect than grey trials. This difference was statistically significant in one of the five studies. Data could be combined for three of the five studies. This showed that, on average, published trials showed a 9% greater treatment effect than grey trials (ratio of odds ratios for grey versus published trials 1.09; 95% CI 1.03-1.16). Overall there were more published trials included in the meta-analyses than grey trials (median 224 (IQR 108-365) versus 45(IQR 40-102)). Published trials had more participants on average. The most common types of grey literature were abstracts (55%) and unpublished data (30%). There is limited evidence to show whether grey trials are of poorer methodological quality than published trials. AUTHORS' CONCLUSIONS: This review shows that published trials tend to be larger and show an overall greater treatment effect than grey trials. This has important implications for reviewers who need to ensure they identify grey trials, in order to minimise the risk of introducing bias into their review.

Source of funding and results of studies of health effects of mobile phone use: systematic review of experimental studies

OBJECTIVES: There is concern regarding the possible health effects of cellular telephone use. We examined whether the source of funding of studies of the effects of low-level radiofrequency radiation is associated with the results of studies. We conducted a systematic review of studies of controlled exposure to radiofrequency radiation with health-related outcomes (electroencephalogram, cognitive or cardiovascular function, hormone levels, symptoms, and subjective well-being). DATA SOURCES: We searched EMBASE, Medline, and a specialist database in February 2005 and scrutinized reference lists from relevant publications. DATA EXTRACTION: Data on the source of funding, study design, methodologic quality, and other study characteristics were extracted. The primary outcome was the reporting of at least one statistically significant association between the exposure and a health-related outcome. Data were analyzed using logistic regression models. DATA SYNTHESIS: Of 59 studies, 12 (20%) were funded exclusively by the telecommunications industry, 11 (19%) were funded by public agencies or charities, 14 (24%) had mixed funding (including industry), and in 22 (37%) the source of funding was not reported. Studies funded exclusively by industry reported the largest number of outcomes, but were least likely to report a statistically significant result: The odds ratio was 0.11 (95% confidence interval, 0.02-0.78), compared with studies funded by public agencies or charities. This finding was not materially altered in analyses adjusted for the number of outcomes reported, study quality, and other factors. CONCLUSIONS: The interpretation of results from studies of health effects of radiofrequency radiation should take sponsorship into account.

The PRO-AGE study: an international randomised controlled study of health risk appraisal for older persons based in general practice

BACKGROUND: This paper describes the study protocol, the recruitment, and base-line data for evaluating the success of randomisation of the PRO-AGE (PRevention in Older people-Assessment in GEneralists' practices) project. METHODS/DESIGN: A group of general practitioners (GPs) in London (U.K.), Hamburg (Germany) and Solothurn (Switzerland) were trained in risk identification, health promotion, and prevention in older people. Their non-disabled older patients were invited to participate in a randomised controlled study. Participants allocated to the intervention group were offered the Health Risk Appraisal for Older Persons (HRA-O) instrument with a site-specific method for reinforcement (London: physician reminders in electronic medical record; Hamburg: one group session or two preventive home visits; Solothurn: six-monthly preventive home visits over a two-year period). Participants allocated to the control group received usual care. At each site, an additional group of GPs did not receive the training, and their eligible patients were invited to participate in a concurrent comparison group. Primary outcomes are self-reported health behaviour and preventative care use at one-year follow-up. In Solothurn, an additional follow-up was conducted at two years. The number of older persons agreeing to participate (% of eligible persons) in the randomised controlled study was 2503 (66.0%) in London, 2580 (53.6%) in Hamburg, and 2284 (67.5%) in Solothurn. Base-line findings confirm that randomisation of participants was successful, with comparable characteristics between intervention and control groups. The number of persons (% of eligible) enrolled in the concurrent comparison group was 636 (48.8%) in London, 746 (35.7%) in Hamburg, and 1171 (63.0%) in Solothurn. DISCUSSION: PRO-AGE is the first large-scale randomised controlled trial of health risk appraisal for older people in Europe. Its results will inform about the effects of implementing HRA-O with different methods of reinforcement.

Health risk appraisal in older people 2: the implications for clinicians and commissioners of social isolation risk in older people

BACKGROUND: Social isolation is associated with poorer health, and is seen by the World Health Organisation (WHO) as one of the major issues facing the industrialised world. AIM: To explore the significance of social isolation in the older population for GPs and for service commissioners. DESIGN OF STUDY: Secondary analysis of baseline data from a randomised controlled trial of health risk appraisal. SETTING: A total of 2641 community-dwelling, non-disabled people aged 65 years and over in suburban London. METHOD: Demographic details, social network and risk for social isolation based on the 6-item Lubben Social Network Scale, measures of depressed mood, memory problems, numbers of chronic conditions, medication use, functional ability, self-reported use of medical services. RESULTS: More than 15% of the older age group were at risk of social isolation, and this risk increased with advancing age. In bivariate analyses risk of social isolation was associated with older age, education up to 16 years only, depressed mood and impaired memory, perceived fair or poor health, perceived difficulty with both basic and instrumental activities of daily living, diminishing functional ability, and fear of falling. Despite poorer health status, those at risk of social isolation did not appear to make greater use of medical services, nor were they at greater risk of hospital admission. Half of those who scored as at risk of social isolation lived with others. Multivariate analysis showed significant independent associations between risk of social isolation and depressed mood and living alone, and weak associations with male sex, impaired memory and perceived poor health. CONCLUSION: The risk of social isolation is elevated in older men, older persons who live alone, persons with mood or cognitive problems, but is not associated with greater use of services. These findings would not support population screening for individuals at risk of social isolation with a view to averting service use by timely intervention. Awareness of social isolation should trigger further assessment, and consideration of interventions to alleviate social isolation, treat depression or ameliorate cognitive impairment.

Psychometric properties of the MacNew heart disease health-related quality of life instrument in patients with heart failure

RATIONALE, AIMS AND OBJECTIVES: Heart failure (HF) is a severe chronic disease and impairs health-related quality of life (HRQL). While validated specific HRQL instruments are required for evaluation of treatment and rehabilitation in patients with HF, a single validated measure to document changes in HRQL for patients with different heart disease diagnoses would be invaluable. The purpose of this analysis was the psychometric analysis of the German MacNew Heart Disease Questionnaire (MacNew) in HF patients, which has previously been shown to be reliable and valid in patients with myocardial infarction, angina pectoris and arrhythmia. METHODS: We recruited 89 patients (61.7+/-11.5 years; 84.3% male) in two Austrian and one Swiss cardiology department with documented HF (effect sizes 28.9+/-10.1%). The self-administered MacNew, the Short Form-36 (SF-36) and the Hospital Anxiety and Depression Scale were completed. Internal consistency reliability (Cronbach's alpha), discriminative and evaluative validity were assessed. RESULTS: Cronbach's alpha exceeded 0.80. Each MacNew scale differentiated between patients with and without anxiety (3.9+/-1.0 vs. 5.3+/-0.8, all P<0.001), with and without depression (4.2+/-1.2 vs. 5.2+/-0.9 all P<0.03) and by the SF-36 health transition item (deteriorate=4.39, no change=4.95, improve=5.45, all P<0.02). Evaluative validity was demonstrated with effect sizes >0.70 for a subsample attending a 12-week outpatient rehabilitation programme. CONCLUSIONS: The German language version of the MacNew demonstrates consistently acceptable psychometric properties of reliability, validity and responsiveness in patients with documented HF. Together with previous documentation of reliability, validity and responsive, these findings strengthen the argument for the MacNew as a potential 'core' HRQL measure, at least in the German language.

Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared

BACKGROUND: The provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland. METHODS AND FINDINGS: We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/mul in South Africa and 204 cells/mul in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%-97%) in South Africa and 96% (94%-97%) in Switzerland, and 26% (22%-29%) and 27% (24%-31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81-19.2) during months 1-3 and 1.77 (0.90-3.50) during months 4-24. CONCLUSIONS: Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease.

Physical long-term health problems and mental comorbidity: evidence from Vietnam

OBJECTIVE: The mental health of children living in low-income countries remains a neglected research area despite the high burden of disease. This study is one of the first that examines the effects of long-term physical health problems on child mental health disorders in a low-income country and investigates whether this association is modified by the socio-economic status of the child's family. METHODS: Community-based cross-sectional survey of 975 eight-year-old children from 20 sites in Vietnam. Long-term physical health problems were measured by a caregiver report and included conditions such as anaemia, congenital malformation, physical disability and skin problems. Child mental disorders were assessed using the strengths and difficulties questionnaire (SDQ). Generalised estimating equations models were fitted to explore the association between long-term physical health problems and child mental disorders. RESULTS: Vietnamese children who suffer from long-term physical health problems have odds 2:1 times greater than children without long-term physical health problems of having a mental disorder (95% CI 1.2 to 3.6, p = 0.006). No significant interaction with socio-economic status was found. CONCLUSIONS: This study showed a high burden of mental disorders among physically ill children, re-enforcing the idea that there is "no health without mental health". While this association needs to be explored longitudinally, children with long-term health problems may be a visible group for targeted mental-health interventions.

Content comparison of health-related quality of life instruments for obstructive sleep apnea

BACKGROUND AND PURPOSE: Due to the increasing importance of quality of life assessments in obstructive sleep apnea (OSA) patients and due to an increased use of the International Classification of Functioning, Disability and Health (ICF), for comparative purposes it is essential to understand the relationship between health-related quality of life (HRQOL) instruments and the ICF. The purpose of this study was to compare the content covered by OSA-specific instruments using the ICF. PATIENTS AND METHODS: OSA-specific instruments were identified, including the Calgary Sleep Apnea Quality of Life Index, the Functional Outcomes of Sleep Questionnaire, the Obstructive Sleep Apnea Patient-Oriented Severity Index, and the Quebec Sleep Questionnaire, and linked to the ICF by six health professionals according to standardized guidelines. The degree of agreement between health professionals was calculated by means of the kappa statistic. RESULTS: A total of 308 concepts were identified and linked to 78 different ICF categories; 35 categories of the component body function, one category of the component body structure, 38 categories of the component activities and participation, and four categories of the component environmental factors. Only contents within the chapters mental functions, mobility and social life were addressed by all instruments. Forty-seven categories were covered by only one instrument. CONCLUSION: The ICF proved highly useful for the comparison of HRQOL instruments. This analysis may help researchers and clinicians to choose the most appropriate HRQOL instrument for a specific purpose as well as help to compare study outcomes of studies using different instruments for HRQOL assessment.

When one depends on the other: reporting of interaction in case-control and cohort studies

BACKGROUND: Interaction refers to the situation in which the effect of 1 exposure on an outcome differs across strata of another exposure. We did a survey of epidemiologic studies published in leading journals to examine how interaction is assessed and reported. METHODS: We selected 150 case-control and 75 cohort studies published between May 2001 and May 2007 in leading general medicine, epidemiology, and clinical specialist journals. Two reviewers independently extracted data on study characteristics. RESULTS: Of the 225 studies, 138 (61%) addressed interaction. Among these, 25 (18%) presented no data or only a P value or a statement of statistical significance; 40 (29%) presented stratum-specific effect estimates but no meaningful comparison of these estimates; and 58 (42%) presented stratum-specific estimates and appropriate tests for interaction. Fifteen articles (11%) presented the individual effects of both exposures and also their joint effect or a product term, providing sufficient information to interpret interaction on an additive and multiplicative scale. Reporting was poorest in articles published in clinical specialist articles and most adequate in articles published in general medicine journals, with epidemiology journals in an intermediate position. CONCLUSIONS: A majority of articles reporting cohort and case-control studies address possible interactions between exposures. However, in about half of these, the information provided was unsatisfactory, and only 1 in 10 studies reported data that allowed readers to interpret interaction effects on an additive and multiplicative scale.

AccessMod 3.0: computing geographic coverage and accessibility to health care services using anisotropic movement of patients

Background Access to health care can be described along four dimensions: geographic accessibility, availability, financial accessibility and acceptability. Geographic accessibility measures how physically accessible resources are for the population, while availability reflects what resources are available and in what amount. Combining these two types of measure into a single index provides a measure of geographic (or spatial) coverage, which is an important measure for assessing the degree of accessibility of a health care network. Results This paper describes the latest version of AccessMod, an extension to the Geographical Information System ArcView 3.×, and provides an example of application of this tool. AccessMod 3 allows one to compute geographic coverage to health care using terrain information and population distribution. Four major types of analysis are available in AccessMod: (1) modeling the coverage of catchment areas linked to an existing health facility network based on travel time, to provide a measure of physical accessibility to health care; (2) modeling geographic coverage according to the availability of services; (3) projecting the coverage of a scaling-up of an existing network; (4) providing information for cost effectiveness analysis when little information about the existing network is available. In addition to integrating travelling time, population distribution and the population coverage capacity specific to each health facility in the network, AccessMod can incorporate the influence of landscape components (e.g. topography, river and road networks, vegetation) that impact travelling time to and from facilities. Topographical constraints can be taken into account through an anisotropic analysis that considers the direction of movement. We provide an example of the application of AccessMod in the southern part of Malawi that shows the influences of the landscape constraints and of the modes of transportation on geographic coverage. Conclusion By incorporating the demand (population) and the supply (capacities of heath care centers), AccessMod provides a unifying tool to efficiently assess the geographic coverage of a network of health care facilities. This tool should be of particular interest to developing countries that have a relatively good geographic information on population distribution, terrain, and health facility locations.

[Smokeless tobacco: a new risk factor for oral health? A review]

Due to migration of different ethnic groups, mainly from Africa and Asia, into Switzerland, many traditional products and habits that have not been seen before were also introduced. Smokeless tobacco (ST)--as one of those habits--is a product of increased use in Switzerland, although no sound epidemiological data are presently available. Numerous studies from North-America, Sweden, Asia and Africa could verify the carcinogenic potency of smokeless tobacco and its effects in the developement of oral cancer and different systemic disorders. For dental professionals and their team it is important to detect ST-associated lesions, and to tell the patients about the potential harmful sequelae of ST products. The present review focusses on the different types of RT products and their effects on oral health.

Bleeding on probing and pocket probing depth in relation to probing pressure and mucosal health around oral implants

OBJECTIVES: To assess the bleeding on probing (BOP) tendency and periodontal probe penetration when applying various probing forces at implant sites in patients with a high standard of oral hygiene with well-maintained peri-implant tissues. MATERIAL AND METHODS: Seventeen healthy patients with excellent oral hygiene in a maintenance program after having been treated for periodontitis or gingivitis were recruited. Missing teeth had been replaced using oral implants. The BOP and probing depth (PPD) were assessed at the mid-buccal, mid-oral, mesial and distal aspects of the buccal surfaces of each implant. Moreover, contralateral teeth were designated and assessed for BOP and PPD in the same locations and at the same observation visits. At each visit, implants and contralateral teeth were randomly assigned to one of the standardized probing forces (0.15 or 0.25 N). The second probing force was applied at the repetition of the examination 7 days later. RESULTS: Increasing the probing pressure by 0.1 N from 0.15 N resulted in an increase of BOP percentage by 13.7% and 6.6% for implants and contralateral teeth, respectively. There appeared to be a significant difference of the mean BOP percentage at implant and tooth sites when a probing pressure of 0.25 N was applied. A significantly deeper mean PPD at implant sites compared with tooth sites was found irrespective of the probing pressure applied. CONCLUSIONS: The results of the present study demonstrated that 0.15 N might represent the threshold pressure to be applied to avoid false positive BOP readings around oral implants. Hence, probing around implants demonstrated a higher sensitivity compared with probing around teeth.

Long-term quality of life after hepatic resection: health is not simply the absence of disease

BACKGROUND: Due to advances in operative methods and perioperative care, mortality and morbidity following major hepatic resection have decreased substantially, making long-term quality of life (QoL) an increasingly prominent issue. We evaluated whether postoperative diagnosis was associated with long-term QoL and health in patients requiring hepatic surgery for benign or malignant disease. METHODS: QoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and the liver-specific QLQ-LMC21 module. RESULTS: Between 2002 and 2006, 249 patients underwent hepatic surgery for malignant (76%) and benign (24%) conditions. One hundred thirty-five patients were available for QoL analysis after a mean of 26.5 months. There was no statistical difference in global QoL scores between patients with malignant and benign diseases (p = 0.367). Neither the extent of the resection (> or =2 segments vs. <2 segments; p = 0.975; OR = 0.988; 95% CI = 0.461-2.119) nor patient age had a significant influence on overall QoL (p = 0.092). CONCLUSIONS: These results indicate that long-term QoL for patients who underwent liver resection for malignant disease is quite good and that a poor clinical prognosis does not seem to correlate with a poor QoL.

Event-related potential P300 microstate topography during visual one- and two-dimensional tasks in chronic schizophrenics

Reports on left-lateralized abnormalities of component P300 of event-related brain potentials (ERP) in schizophrenics typically did not vary task difficulties. We collected 16-channel ERP in 13 chronic, medicated schizophrenics (25±4.9 years) and 13 matched controls in a visual P300 paradigm with targets defined by one or two stimulus dimensions (C1: color; C2: color and tilt); subjects key-pressed to targets. The mean target-ERP map landscapes were assessed numerically by the locations of the positive and negative map-area centroids. The centroids' time-space trajectories were searched for the P300 microstate landscape defined by the positive centroid posterior of the negative centroid. At P300 microstate centre latencies in C1, patients' maps tended to a right shift of the positive centroid (p<0.10); in C2 the anterior centroid was more posterior (p<0.07) and the posterior (positive) centroid more anterior (p<0.03), but without leftright difference. Duration of P300 microstate in C2 was shorter in patients (232 vs 347 ms;p<0.03) and the latency of maximal strength of P300 microstate increased significantly in patients (C1: 459 vs 376 ms; C2: 585 vs 525 ms). In summary only the one-dimensional task C1 supported left-sided abnormalities; the two-dimensional task C2 produced abnormal P300 microstate map landscapes in schizophrenics, but no abnormal lateralization. Thus, information processing involved clearly aberrant neural populations in schizophrenics, different when processing one and two stimulus dimensions. The lack of lateralization in the two-dimensional task supported the view that left-temporal abnormality in schizophrenics is only one of several task-dependent aberrations.

Social inequality and smoking in young Swiss men: intergenerational transmission of cultural capital and health orientation

OBJECTIVES Smoking is related to income and education and contributes to social inequality in morbidity and mortality. Socialisation theories focus on one's family of origin as regards acquisition of norms, attitudes and behaviours. Aim of this study is to assess associations of daily smoking with health orientation and academic track in young Swiss men. Further, to assess associations of health orientation and academic track with family healthy lifestyle, parents' cultural capital, and parents' economic capital. METHODS Cross-sectional data were collected during recruitment for compulsory military service in Switzerland during 2010 and 2011. A structural equation model was fitted to a sample of 18- to 25-year-old Swiss men (N = 10,546). RESULTS Smoking in young adults was negatively associated with academic track and health orientation. Smoking was negatively associated with parents' cultural capital through academic track. Smoking was negatively associated with health orientation which in turn was positively associated with a healthy lifestyle in the family of origin. CONCLUSIONS Results suggest two different mechanisms of intergenerational transmissions: first, the family transmission path of health-related dispositions, and secondly, the structural transmission path of educational inequality.