Study Design Quality Research Articles

Meta-analysis: Problems with Russian Publications.

Meta-analysis is a powerful tool to identify Evidence Based medical technologies (interventions) for use in every day practice. Meta-analysis uses statistical approaches to combine results from multiple studies in an effort to increase power (over individual studies), improve estimates of the size of the effect and/or to resolve uncertainty when reports disagree. Meta-analysis is a quantitative, formal study design used to systematically assess previous research studies to derive conclusions from this research. Meta-analysis may provide more precise estimate of the effect of treatment or risk factor for a disease, or other outcomes, than any individual study contributing to the pooled analysis.We have quite a substantial number of Russian medical publications, but not so many Meta-Analyses published in Russian. Russian publications are cited in English language papers not so often. A total of 90% of clinical studies included in published Meta-Analyses incorporate only English language papers. International studies or papers with Russian co-authors are published in English language. The main question is: what is the problem with inclusion of Russian medical publications in Meta-Analysis? The main reasons for this are the following: 1) It is difficult to find Russian papers, difficult to work with them and to work with Russian journals:a. There are single Russian Biomedical Journals, which are translated into English and are included in databases (PubMed, Scopus and other), despite the fact that all of them have English language abstracts.b. The majority the meta-analyses authors use in their work different citation management software such as the Mendeley, Reference Manager, ProCite, EndNote, and others. These citation management systems allow scientists to organize their own literature databases with internet searches and have adds-on for the Office programs what makes process of literature citation very convenient. The Internet sites of the majority of International Journals have built-in tools for saving citations to reference manager software. The majority of articles in Russian journals cannot be captured by citation management systems: they do not have special coding of articles descriptors.c. Some journals still have PDF files of the whole journal issue without dividing it into articles and do not provide any descriptors, making manual time-consuming input of information the only possibility. Moreover the context search of the article content is unavailable for search engines.2) The quality of research. This problem has been discussed for more than twenty years already. Still we have too many publications of poor quality of study design and statistical analysis. With the exception of pharmacological clinical tails, designed and supervised by international Pharma industry, many interventional studies, conducted in Russia, have methodological flaws inferring a high risk of bias:a. Absence of adequate control,b. No standard endpoints, duration of therapy and follow up,c. Absence of randomization and blinding,d. Low power of studies: sample sizes are calculated (if calculated at all) in such a way, that the main goal is to have as small sample size as possible. Very often statisticians have to solve the problem how to substantiate a small number of subjects, that sponsor could afford, instead of calculating the needed sample size to reach enough power.e. No standards of statistical analysis.f. Russian journals do not have standards for description and presentation of study results, in particular, results of statistical analysis (a reader even cannot see what is presented: standard deviation (SD) or standard error of the mean (SEM).We have a long standing experience in analysis of methodological and statistical quality of Russian biomedical publications and have found up to 80% publications with statistical and methodological errors and high risk of bias.In our practice, we had tried to perform two Meta-analyses for two local pharmaceutical products for prevention of stroke recurrence. For the first product, we did not found even two single Russian language studies suitable for the analysis (incomparable populations, different designs, endpoints, doses etc.). For the second product, only four studies had comparable populations and standard internationally approved scales for effectiveness analysis. However, the combinations of scales, the length of treatment and follow up differed widely, so that we could combine the results of only 2 or 3 studies for each end point. Russian researchers have to follow internationally recognised standards in study design, selection of endpoint, timelines and therapy regimens, data analysis and presentation of results. Russian journals need to develop consolidate rules for authors of clinical trials and epidemiological research of result reporting close to international standards. In this case the international Network EQUATOR (Enhancing the QUAlity and Transparency Of health Research http://www.equator-network.org/) is one to be taken into account. In addition, Russian Journals have to improve their online information for better interaction with search engines and citation managers.

Quality of Animal Experiments in Anti-Angiogenic Cancer Drug Development--A Systematic Review.

Translation from preclinical animal research to clinical bedside has proven to be difficult to impossible in many fields of research (e.g. acute stroke, ALS and HIV vaccination development) with oncology showing particularly low translation rates (5% vs. 20% for cardiovascular diseases). Several investigations on published preclinical animal research have revealed that apart from plain species differences, translational problems can arise from low study quality (e.g. study design) or non-representative experimental conditions (e.g. treatment schedule).This review assessed the published experimental circumstances and quality of anti-angiogenic cancer drug development in 232 in vivo studies. The quality of study design was often insufficient; at least the information published about the experiments was not satisfactory in most cases. There was no quality improvement over time, with the exception of conflict of interest statements. This increase presumably arose mainly because journal guidelines request such statements more often recently.Visual inspection of data and a cluster analysis confirmed a trend described in literature that low study quality tends to overestimate study outcome. It was also found that experimental outcome was more favorable when a potential drug was investigated as the main focus of a study, compared to drugs that were used as comparison interventions. We assume that this effect arises from the frequent neglect of blinding investigators towards treatment arms and refer to it as hypothesis bias.In conclusion, the reporting and presumably also the experimental performance of animal studies in drug development for oncology suffer from similar shortcomings as other fields of research (such as stroke or ALS). We consider it necessary to enforce experimental quality and reporting that corresponds to the level of clinical studies. It seems that only clear journal guidelines or guidelines from licensing authorities, where failure to fulfill prevents publication or experimental license, can help to improve this situation.

Interventions for preventing and treating low-back and pelvic pain during pregnancy.

More than two-thirds of pregnant women experience low-back pain and almost one-fifth experience pelvic pain. The two conditions may occur separately or together (low-back and pelvic pain) and typically increase with advancing pregnancy, interfering with work, daily activities and sleep. To update the evidence assessing the effects of any intervention used to prevent and treat low-back pain, pelvic pain or both during pregnancy. We searched the Cochrane Pregnancy and Childbirth (to 19 January 2015), and the Cochrane Back Review Groups' (to 19 January 2015) Trials Registers, identified relevant studies and reviews and checked their reference lists. Randomised controlled trials (RCTs) of any treatment, or combination of treatments, to prevent or reduce the incidence or severity of low-back pain, pelvic pain or both, related functional disability, sick leave and adverse effects during pregnancy. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We included 34 RCTs examining 5121 pregnant women, aged 16 to 45 years and, when reported, from 12 to 38 weeks' gestation. Fifteen RCTs examined women with low-back pain (participants = 1847); six examined pelvic pain (participants = 889); and 13 examined women with both low-back and pelvic pain (participants = 2385). Two studies also investigated low-back pain prevention and four, low-back and pelvic pain prevention. Diagnoses ranged from self-reported symptoms to clinicians' interpretation of specific tests. All interventions were added to usual prenatal care and, unless noted, were compared with usual prenatal care. The quality of the evidence ranged from moderate to low, raising concerns about the confidence we could put in the estimates of effect. For low-back painResults from meta-analyses provided low-quality evidence (study design limitations, inconsistency) that any land-based exercise significantly reduced pain (standardised mean difference (SMD) -0.64; 95% confidence interval (CI) -1.03 to -0.25; participants = 645; studies = seven) and functional disability (SMD -0.56; 95% CI -0.89 to -0.23; participants = 146; studies = two). Low-quality evidence (study design limitations, imprecision) also suggested no significant differences in the number of women reporting low-back pain between group exercise, added to information about managing pain, versus usual prenatal care (risk ratio (RR) 0.97; 95% CI 0.80 to 1.17; participants = 374; studies = two). For pelvic painResults from a meta-analysis provided low-quality evidence (study design limitations, imprecision) of no significant difference in the number of women reporting pelvic pain between group exercise, added to information about managing pain, and usual prenatal care (RR 0.97; 95% CI 0.77 to 1.23; participants = 374; studies = two). For low-back and pelvic painResults from meta-analyses provided moderate-quality evidence (study design limitations) that: an eight- to 12-week exercise program reduced the number of women who reported low-back and pelvic pain (RR 0.66; 95% CI 0.45 to 0.97; participants = 1176; studies = four); land-based exercise, in a variety of formats, significantly reduced low-back and pelvic pain-related sick leave (RR 0.76; 95% CI 0.62 to 0.94; participants = 1062; studies = two).The results from a number of individual studies, incorporating various other interventions, could not be pooled due to clinical heterogeneity. There was moderate-quality evidence (study design limitations or imprecision) from individual studies suggesting that osteomanipulative therapy significantly reduced low-back pain and functional disability, and acupuncture or craniosacral therapy improved pelvic pain more than usual prenatal care. Evidence from individual studies was largely of low quality (study design limitations, imprecision), and suggested that pain and functional disability, but not sick leave, were significantly reduced following a multi-modal intervention (manual therapy, exercise and education) for low-back and pelvic pain.When reported, adverse effects were minor and transient. There is low-quality evidence that exercise (any exercise on land or in water), may reduce pregnancy-related low-back pain and moderate- to low-quality evidence suggesting that any exercise improves functional disability and reduces sick leave more than usual prenatal care. Evidence from single studies suggests that acupuncture or craniosacral therapy improves pregnancy-related pelvic pain, and osteomanipulative therapy or a multi-modal intervention (manual therapy, exercise and education) may also be of benefit.Clinical heterogeneity precluded pooling of results in many cases. Statistical heterogeneity was substantial in all but three meta-analyses, which did not improve following sensitivity analyses. Publication bias and selective reporting cannot be ruled out.Further evidence is very likely to have an important impact on our confidence in the estimates of effect and change the estimates. Studies would benefit from the introduction of an agreed classification system that can be used to categorise women according to their presenting symptoms, so that treatment can be tailored accordingly.

A Systematic Review of Telehealth in Palliative Care: Caregiver Outcomes.

Telehealth interventions have proven efficacy in healthcare, but little is known about the results of such interventions in palliative care. We conducted a systematic review to evaluate caregiver outcomes related to palliative telehealth interventions. We searched multiple databases for articles published between January 2003 and January 2015 related to telehealth in palliative care. Two hundred twenty-one articles were considered; nine of these met study inclusion criteria. Data on study design, population, interventions, methods, outcomes, conclusions, and methodological quality were extracted and evaluated by three investigators. Of the nine studies, five measured caregiver quality of life, three measured caregiver anxiety, and two measured caregiver burden. All the studies measuring caregiver quality of life showed no significant difference after telehealth interventions. The caregiver anxiety score decreased after the intervention in two studies, and one study reported significantly reduced caregiver burden. Although feasibility of or caregiver satisfaction with the telehealth intervention was not the focus of this review, most studies reported such findings. Of the nine studies, the majority were rated as having moderate quality using the Cochrane Collaboration's tool for assessing risk of bias. This systematic review suggests there is evidence of overall satisfaction in caregivers who undergo a telehealth intervention, but outcomes reported were often not substantial. Methodological flaws and small sample sizes negatively affected study quality. More rigorous research to test and evaluate such palliative interventions is needed.

Understanding how environmental enhancement and conservation activities may benefit health and wellbeing: a systematic review.

BackgroundAction taken to enhance or conserve outdoor environments may benefit health and wellbeing through the process of participation but also through improving the environment. There is interest, amongst both health and environmental organisations, in using such activities as health promotion interventions.The objective of this systematic review was to investigate the health and wellbeing impacts of participation in environmental enhancement and conservation activities and to understand how these activities may be beneficial, to whom and in what circumstances or contexts.MethodsA theory-led mixed-method systematic review was used to assess evidence of effect and to identify pathways to change (protocol: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010351/full). Due to the multi-disciplinary, dispersed and disparate body of evidence an extensive multi-stage search strategy was devised and undertaken. Twenty-seven databases and multiple sources of grey literature were searched and over 200 relevant organisations were contacted. The heterogenous evidence was synthesised using a narrative approach and a conceptual model was developed to illustrate the mechanisms of effect. Due to the limited nature of the evidence additional higher order evidence was sought to assess the plausibility of the proposed mechanisms of effect through which health and wellbeing may accrue.ResultsThe majority of the quantitative evidence (13 studies; all poor quality and lower-order study designs) was inconclusive, though a small number of positive and negative associations were observed. The qualitative evidence (13 studies; 10 poor quality, 3 good) indicated that the activities were perceived to have value to health and wellbeing through a number of key mechanisms; including exposure to natural environments, achievement, enjoyment and social contact. Additional high level evidence indicated that these pathways were plausible.ConclusionsDespite interest in the use of environmental enhancement activities as a health intervention there is currently little direct evidence of effect, this is primarily due to a lack of robust study designs. Further rigorous research is needed to understand the potential of the activities to benefit health and environment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-015-2214-3) contains supplementary material, which is available to authorized users.

Publication planning: promoting an ethics of transparency and integrity in biomedical research.

Biomedical research should include plans to communicate complete and accurate results to the scientific community and the public in a timely manner. All too often, however, such planning is lacking until after data have been generated. We developed a collaborative professional statement following review of the indexed biomedical literature and relevant professional society guidelines. Planning for publications before, during and after biomedical research studies are conducted promotes the timely dissemination of accurate and comprehensive results. Effective publication planning accounts for the work of all contributors, encourages full transparency and contributes to overall scientific integrity. Although the most obvious contribution of publication planning is to result dissemination, the best planning may also help improve the overall quality of research study design and the overall integrity of study conduct by keeping the final audience in the forefront of the investigators' attention. Publication planning can help biomedical researchers achieve and maintain high standards of transparency and integrity. Table 1 below highlights briefly some of the aspects to be included in a publication plan.

Does colorectal cancer risk perception predict screening behavior? A systematic review and meta-analysis.

Although health behavior theories postulate that risk perception should motivate colorectal cancer (CRC) screening, this relationship is unclear. This meta-analysis aims to examine the relationship between CRC risk perception and screening behavior, while considering potential moderators and study quality. A search of six databases yielded 58 studies (63 effect sizes) that quantitatively assessed the relationship between CRC risk perception and screening behavior. Most included effect sizes (75 %) reported a positive association between CRC risk perception and screening behavior. A random effects meta-analysis yielded an overall effect size of z = 0.13 (95 % CI 0.10-0.16), which was heterogeneous (I (2) = 99 %, τ(2) = 0.01). Effect sizes from high-quality studies were significantly lower than those from lower quality studies (z = 0.02 vs. 0.16). We found a small, positive relationship between CRC risk perception and reported screening behavior, with important identified heterogeneity across moderators. Future studies should focus on high quality study design.

Pharmaceutical treatment studies in autism and ADHD: A design based review of study quality

The overall design quality of studies conducted on psychotropic substances prescribed to autism spectrum disorder and attention deficit hyperactivity disorder children is reviewed. Searches were conducted on Medline and Cochrane Controlled Trials Register. Peer-reviewed, published studies, written in English were included. Only studies that focused on children, had a minimal sample size of ten participants, and were conducted between 1994 and 2004 were included in the review. Two hundred and eighty one studies were identified and reviewed with 184 (65.5%) focused primarily on methylphenidate, with the remaining 97 studies examined stimulants, antipsychotics, antidepressants, alpha agonists, anxiolytics, and mood stabilizers. Of these, 152 (54.1%) did not employ optimal double blind placebo controlled design and 106 (37.7%) were conducted with less than 30 participants. The upper quartile for median study duration across all medications examined was 9.75 weeks for double-blinded studies and 16 weeks for all studies. Many pharmacotherapy studies conducted on children with autism spectrum disorder and attention deficit hyperactivity disorder are of limited duration, weak quality design and may be seriously underpowered. The issue of follow-up is rarely adequately addressed. These findings raise both safety and efficacy questions that have yet to be adequately studied.

Gait Retraining for Injured and Healthy Runners Using Augmented Feedback: A Systematic Literature Review.

Systematic literature review. This review sought to determine the efficacy of real-time visual and/or auditory feedback for modifying kinematics and kinetics during running gait. Real-time visual and auditory feedback has gained popularity in the clinical and research settings. Rehabilitation time and injury prevention may be improved when clinicians are able to modify running mechanics in a patient population. A thorough search of PubMed, CINAHL, and Web of Science from 1989 to January 2015 was performed. The search sought articles that examined real-time visual or auditory feedback for the purposes of modifying kinematics or kinetics in injured or healthy runners. Study design and methodological quality were rated using a 20-point scale. Ten studies were identified for inclusion in the review, 2 of high and 8 of moderate methodological quality. There was a consensus in the literature that the use of real-time feedback is effective in reducing variables related to ground reaction forces, as well as in positively modifying previously identified risky lower extremity kinematic movement patterns in healthy runners and those with patellofemoral pain and chronic exertional compartment syndrome. No one method of feedback was identified as being superior. Mirror and 2-dimensional video feedback were identified as potential methods for running-gait modification in a clinical setting. In conjunction with traditional therapeutic interventions, real-time auditory and visual feedback should be considered for treating injured runners or addressing potentially injurious running mechanics in a healthy population.

Getting Our ACT Together

Abstract Results that cannot be replicated during drug trials cost pharma companies millions. Katrina Gore and Phil Stanley describe a tool developed by Pfizer to improve the quality of preclinical study design and analysis

Assessment of patient empowerment--a systematic review of measures.

BackgroundPatient empowerment has gained considerable importance but uncertainty remains about the best way to define and measure it. The validity of empirical findings depends on the quality of measures used. This systematic review aims to provide an overview of studies assessing psychometric properties of questionnaires purporting to capture patient empowerment, evaluate the methodological quality of these studies and assess the psychometric properties of measures identified.MethodsElectronic searches in five databases were combined with reference tracking of included articles. Peer-reviewed articles reporting psychometric testing of empowerment measures for adult patients in French, German, English, Portuguese and Spanish were included. Study characteristics, constructs operationalised and psychometric properties were extracted. The quality of study design, methods and reporting was assessed using the COSMIN checklist. The quality of psychometric properties was assessed using Terwee’s 2007 criteria.Findings30 studies on 19 measures were included. Six measures are generic, while 13 were developed for a specific condition (N=4) or specialty (N=9). Most studies tested measures in English (N=17) or Swedish (N=6). Sample sizes of included studies varied from N=35 to N=8261. A range of patient empowerment constructs was operationalised in included measures. These were classified into four domains: patient states, experiences and capacities; patient actions and behaviours; patient self-determination within the healthcare relationship and patient skills development. Quality assessment revealed several flaws in methodological study quality with COSMIN scores mainly fair or poor. The overall quality of psychometric properties of included measures was intermediate to positive. Certain psychometric properties were not tested for most measures.DiscussionFindings provide a basis from which to develop consensus on a core set of patient empowerment constructs and for further work to develop a (set of) appropriately validated measure(s) to capture this. The methodological quality of psychometric studies could be improved by adhering to published quality criteria.

Research Design and Statistical Methods in Indian Medical Journals: A Retrospective Survey

Good quality medical research generally requires not only an expertise in the chosen medical field of interest but also a sound knowledge of statistical methodology. The number of medical research articles which have been published in Indian medical journals has increased quite substantially in the past decade. The aim of this study was to collate all evidence on study design quality and statistical analyses used in selected leading Indian medical journals. Ten (10) leading Indian medical journals were selected based on impact factors and all original research articles published in 2003 (N = 588) and 2013 (N = 774) were categorized and reviewed. A validated checklist on study design, statistical analyses, results presentation, and interpretation was used for review and evaluation of the articles. Main outcomes considered in the present study were – study design types and their frequencies, error/defects proportion in study design, statistical analyses, and implementation of CONSORT checklist in RCT (randomized clinical trials). From 2003 to 2013: The proportion of erroneous statistical analyses did not decrease (χ2=0.592, Φ=0.027, p=0.4418), 25% (80/320) in 2003 compared to 22.6% (111/490) in 2013. Compared with 2003, significant improvement was seen in 2013; the proportion of papers using statistical tests increased significantly (χ2=26.96, Φ=0.16, p<0.0001) from 42.5% (250/588) to 56.7 % (439/774). The overall proportion of errors in study design decreased significantly (χ2=16.783, Φ=0.12 p<0.0001), 41.3% (243/588) compared to 30.6% (237/774). In 2013, randomized clinical trials designs has remained very low (7.3%, 43/588) with majority showing some errors (41 papers, 95.3%). Majority of the published studies were retrospective in nature both in 2003 [79.1% (465/588)] and in 2013 [78.2% (605/774)]. Major decreases in error proportions were observed in both results presentation (χ2=24.477, Φ=0.17, p<0.0001), 82.2% (263/320) compared to 66.3% (325/490) and interpretation (χ2=25.616, Φ=0.173, p<0.0001), 32.5% (104/320) compared to 17.1% (84/490), though some serious ones were still present. Indian medical research seems to have made no major progress regarding using correct statistical analyses, but error/defects in study designs have decreased significantly. Randomized clinical trials are quite rarely published and have high proportion of methodological problems.

A review of technology-based interventions to maintain weight loss.

For many decades, healthcare providers and researchers have developed weight-loss interventions to help people achieve weight loss. Unfortunately, it is typical for people to lose weight quickly during the intervention period but then slowly regain weight until they return to their approximate baseline. Technology-based maintenance interventions are among the newest approaches to long-term weight loss. Several advantages make technology helpful for maintaining weight loss. The purpose of this article was to review and critique the randomized controlled trials of technology-based weight-loss maintenance interventions (WLMIs) for adults. A systematic search through electronic databases and a manual citation search were conducted. Limited numbers of controlled trials published since 2000 that included randomization, and technology-based WLMIs were identified. The characteristics of the eight studies were diverse. The average score of study design quality was moderate. The results of the effectiveness of technology-based WLMIs were mixed. Technology-based WLMIs are more likely to be effective than usual care but not more effective than personal contact. Based on the review, guidelines were established for the selection and potential success of technology-based WLMIs. The effectiveness of technology-based maintenance interventions for weight loss varied, and potential strategies and approaches are discussed to improve their effectiveness. Further studies are needed to better evaluate and refine the efficacy of technology-based WLMIs.

Systematic review: patient-reported outcomes in chronic hepatitis C--the impact of liver disease and new treatment regimens.

Treatment for chronic hepatitis C (CH-C) is rapidly changing and moving away from an interferon and ribavirin-based therapy to interferon-free ribavirin-free all oral regimens. These regimens are simpler and shorter to administer with very high efficacy rates and better side effect profiles. As advances in the treatment of CH-C occur, it is imperative to capture both clinical outcomes (efficacy and safety) as well as patient-reported outcomes (PROs). In fact, PROs assesses and quantifies the impact of these regimens on patient experience. PROs assess patients' health-related quality of life (HRQOL) especially in the realms of fatigue and neuropsychiatric issues such as depression which can affect treatment adherence and work productivity. To review the literature related to PRO's in HCV patients and summarise the impact of CH-C and its treatment on PROs. Databases Ovid MEDLINE and PubMed were searched from 1990 to October 2014 using a combination of MEsh, thesaurus terms and relevant text words: hepatitis C, CH-C, treatment, quality of life, health-related quality of life, fatigue, work productivity, adherence, patient-reported outcomes, direct acting anti-viral agents and second generation direct acting anti-viral agents. Each manuscript was assessed for pertinence to the issue of PROs in CH-C as well as the quality of study design and publications. From the literature, it is evident that CH-C patients have baseline PRO impairment. Furthermore, treatment with interferon with or without ribavirin and first generation DAAs causes additional PRO burden which can negatively impact treatment adherence and indirectly, treatment efficacy and work productivity. The new treatment regimens with interferon- and ribavirin-free regimens not only have very high efficacy, but also result in the improvement of PRO scores as early as 2 weeks into treatment as well as possibly better adherence to treatment regimens. CH-C and its treatment have been associated with patient-reported outcome impairment. The new IF-free and RBV-free regimens are associated with high efficacy and substantial improvement of patient-reported outcomes in clinical trial setting. Although very encouraging, more data are needed to assess patient-reported outcomes, adherence and work productivity of CH-C patients in the real world setting of clinical practice.

Systematic review: Preventive and therapeutic applications of metformin in liver disease.

Metformin, a biguanide derivative, is the most commonly prescribed medication in the treatment of type 2 diabetes mellitus. More recently, the use of metformin has shown potential as a preventive and therapeutic agent for a broad spectrum of conditions, including liver disease and hepatic malignancies. In this systematic review, we critically analyze the literature behind the potential use of metformin across the spectrum of liver disease and malignancies. The PubMed and Ovid MEDLINE databases were searched from 2000 to March 2015, using a combination of relevant text words and MeSH terms: metformin and mammalian target of rapamycin, hepatitis B virus (HBV), hepatitis B virus (HCV), non-alcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC) or cholangiocarcinoma. The search results were evaluated for pertinence to the issue of metformin in liver disease as well as for quality of study design. Metformin has a number of biochemical effects that would suggest a benefit in treating chronic liver diseases, particularly in the context of insulin resistance and inflammation. However, the literature thus far does not support any independent therapeutic role in NAFLD or HCV. Nonetheless, there is Level III evidence for a chemopreventive role in patients with diabetes and chronic liver disease, with decreased incidence of HCC and cholangiocarcinoma. The use of metformin seems to be safe in patients with cirrhosis, and provides a survival benefit. Once hepatic malignancies are already established, metformin does not offer any therapeutic potential. In conclusion, there is insufficient evidence to recommend use of metformin in the adjunctive treatment of chronic liver diseases, including NAFLD and HCV. However, there is good evidence for a chemopreventive role against HCC among patients with diabetes and chronic liver disease, and metformin should be continued in patients even with cirrhosis to provide this benefit.

How much do we know about the long-term effectiveness of parenting programmes? Advances, shortcomings, and future directions

Purpose – Parenting programmes are seen as feasible and cost-effective in preventing early behavioural problems in children and adolescents. A number of studies have concluded that such programmes are effective in reducing child problem behaviours and improving the skills and well-being of parents. Nevertheless, less is known about long-term programme effects. The paper aims to discuss these issues. Design/methodology/approach – A non-meta-analytic discussion. Findings – Long-term evaluations of parenting programmes suffer from a number of methodological weaknesses resulting in an inability to make robust causal inferences about child and parent outcomes in the longer term. The current evidence is favourable but is likely to be biased by methodological weaknesses. There is a need for more studies of greater methodological strength to obtain conclusive evidence that would guide empirical research, practice and policy. Originality/value – The paper discusses weaknesses in long-term evaluations of parenting programmes and highlights concrete future directions towards improving the quality of study design, evaluation and data analysis.

Power analysis for generalized linear mixed models in ecology and evolution.

‘Will my study answer my research question?’ is the most fundamental question a researcher can ask when designing a study, yet when phrased in statistical terms – ‘What is the power of my study?’ or ‘How precise will my parameter estimate be?’ – few researchers in ecology and evolution (EE) try to answer it, despite the detrimental consequences of performing under- or over-powered research. We suggest that this reluctance is due in large part to the unsuitability of simple methods of power analysis (broadly defined as any attempt to quantify prospectively the ‘informativeness’ of a study) for the complex models commonly used in EE research. With the aim of encouraging the use of power analysis, we present simulation from generalized linear mixed models (GLMMs) as a flexible and accessible approach to power analysis that can account for random effects, overdispersion and diverse response distributions.We illustrate the benefits of simulation-based power analysis in two research scenarios: estimating the precision of a survey to estimate tick burdens on grouse chicks and estimating the power of a trial to compare the efficacy of insecticide-treated nets in malaria mosquito control. We provide a freely available R function, sim.glmm, for simulating from GLMMs.Analysis of simulated data revealed that the effects of accounting for realistic levels of random effects and overdispersion on power and precision estimates were substantial, with correspondingly severe implications for study design in the form of up to fivefold increases in sampling effort. We also show the utility of simulations for identifying scenarios where GLMM-fitting methods can perform poorly.These results illustrate the inadequacy of standard analytical power analysis methods and the flexibility of simulation-based power analysis for GLMMs. The wider use of these methods should contribute to improving the quality of study design in EE.

High-intensity focused ultrasound for treatment of pancreatic cancer: a systematic review.

To explore the efficacy and safety of high-intensity focused ultrasound combined with other physical therapies for the treatment of pancreatic cancer, so as to provide reference for clinical application. The PubMed, EMbase, The Cochrane Library (Issue 11, 2013), CBM, CNKI, and WanFang databases were systematically searched up to November 2013. The randomized controlled trials and clinical controlled trials about the treatment of high-intensity focused ultrasound were included. According to the inclusion and exclusion criteria, two reviewers independently screened the studies, exacted the data, and assessed the quality. The meta-analysis was performed by using the RevMan 5.0 software. A total of 23 studies including 19 randomized controlled trials and four clinical controlled trials were included. Of which 14 studies reported the safety. The results of meta-analyses showed that: the survival rate at 6 months and 12 months, overall efficacy, and clinical benefit rate in high-intensity focused ultrasound plus radiation and chemotherapy group were significantly higher than those in groups treated with three-dimensional conformal radiation therapy (P < 0.05), gemcitabine (P < 0.05), gemcitabine plus cisplatin (P < 0.05), and gemcitabine plus 5-fluorouracil (P < 0.05). The adverse effect caused by high-intensity focused ultrasound plus other therapy was equal to those in the control group. The major high-intensity focused ultrasound-related adverse effect was skin damage and fever. The current evidence suggested that the efficacy of high-intensity focused ultrasound for pancreatic cancer was superior to other therapies. However, the poor quality of trails may reduce the reliability of outcome to some extent. The current evidence suggested that the efficacy of HIFU for pancreatic cancer was superior to other therapies, but with poor quality. Therefore, a standard and unified criterion for the diagnosis and outcome measures of pancreatic cancer is needed, and the quality of study design and implementation should be bettered, so as to improve the high quality of evidence for its clinical application.

Results from a preliminary review of scientific evidence for appropriateness of preparations, dosage forms and other product design elements for older adult patients

The aging population and the growing multimorbidity of the major patient population as well as the advanced (pharmaco)therapeutic treatment options are increasing the complexity of independent drug therapy management and administration. The increased complexity may have an impact on drug adherence (including any need for patients initiated coping strategies), and consequently on the safety and efficacy of the medicine. To overcome adherence issues caused by the design of the medicine, it is crucial that developers consider the age appropriateness of the medicine (route of administration, dosage form, excipients in the composition, frequency of dosing) in meeting patients’ needs to manage their therapy without the support of a care giver. In order to understand the scientific evidence on such age appropriately designed medicines for use by older adults, a literature search was performed in the Medline database (all languages included). The search produced 34 publications that met the inclusion and exclusion criteria for the patient population of 65 years an older. An in-depth analysis of the included publications with respect to the methodological quality (study design, data collection, endpoints chosen) and results showed that none of these publications had adequately investigated the age appropriateness of the medicine for use by older adults. The authors consider that the knowledge gap in this area requires attention of all stakeholders in the healthcare community.

Measurement properties of continuous text reading performance tests.

Measurement properties of tests to assess reading acuity or reading performance have not been extensively evaluated. This study aims to provide an overview of the literature on available continuous text reading tests and their measurement properties. A literature search was performed in PubMed, Embase and PsycInfo. Subsequently, information on design and content of reading tests, study design and measurement properties were extracted using consensus-based standards for selection of health measurement instruments. Quality of studies, reading tests and measurement properties were systematically assessed using pre-specified criteria. From 2334 identified articles, 20 relevant articles were found on measurement properties of three reading tests in various languages: IReST, MNread Reading Test and Radner Reading Charts. All three reading tests scored high on content validity. Reproducibility studies (repeated measurements between different testing sessions) of the IReST and MNread of commercially available reading tests in different languages were missing. The IReST scored best on inter-language comparison, the MNread scored well in repeatability studies (repeated measurements under the same conditions) and the Radner showed good reproducibility in studies. Although in daily practice there are other continuous text reading tests available meeting the criteria of this review, measurement properties were described in scientific studies for only three of them. Of the few available studies, the quality and content of study design and methodology used varied. For testing existing reading tests and the development of new ones, for example in other languages, we make several recommendations, including careful description of patient characteristics, use of objective and subjective lighting levels, good control of working distance, documentation of the number of raters and their training, careful documentation of scoring rules and the use of Bland-Altman analyses or similar for reproducibility and repeatability studies.