Non-significant Outcomes Research Articles

Abstract 183: Outcomes for Major Trauma Patients in Counties Without Trauma Centers Are Worse: Nationwide Population-Based Research in Taiwan

Background: Some articles proved indirect-transfer the major trauma patients to the trauma centers had non-significant different outcomes with the patients direct-transfer to the centers. But the outcomes for the major trauma patients in the counties without trauma centers still can be worse. So we did a population based research by using the NHIRD data for the results. Methods: From the claim data of one million beneficiaries of Taiwan National Health Insurance during the year of 2006 to 2008, all of the trauma patients were identified from the database by the ICD-9-CM system. ICDMAP-90 was used for calculating the Injury Severity Score (ISS) as the variable controlling the disease severity. The patients of major trauma were defined as ISS more than fifteen. We used the diagnosis one year before the trauma admission for calculating Charlson Comorbidity Index (CCI). The first hospitals and the second transferred hospitals that the major trauma patients admitted, and the areas of the first hospitals were recognized in our data bank. The condition of transfer, age, genders, intubation, ICU admission, ISS, CCI, and the triage classifications were adjusted in a logistic regression model for further analysis. Results: There were 2497 major trauma patients (ISS more then 15). The total mortality rate was 12.49%. The variables like age, intubation, ICU admission, ISS and CCI were significant for mortality, but the condition of transfer was not significant in our model. After controlling all the factors, the major trauma patients that first admitted in the areas with no trauma centers have a significant higher risk of mortality (OR=1.73, P=0.005). Conclusions: Our results hint that, although indirect-transfer for the major trauma patients have insignificant difference in mortality with the direct transfer patients, the counties with no trauma centers have significant higher mortality rates in major trauma patients. Further researches are needed for investigating the possible reasons.

Addendum to the article: Misuse of null hypothesis significance testing: Would estimation of positive and negative predictive values improve certainty of chemical risk assessment?

We argued recently that the positive predictive value (PPV) and the negative predictive value (NPV) are valuable metrics to include during null hypothesis significance testing: They inform the researcher about the probability of statistically significant and non-significant test outcomes actually being true. Although commonly misunderstood, a reported p value estimates only the probability of obtaining the results or more extreme results if the null hypothesis of no effect was true. Calculations of the more informative PPV and NPV require a priori estimate of the probability (R). The present document discusses challenges of estimating R.

Bias due to selective inclusion and reporting of outcomes and analyses in systematic reviews of randomised trials of healthcare interventions.

Bias due to selective inclusion and reporting of outcomes and analyses in systematic reviews of randomised trials of healthcare interventions.

Origin and therapy for hypertriglyceridaemia in type 2 diabetes.

Hypertriglyceridaemia (HTG) is a risk factor for cardiovascular disease (CVD) in type 2 diabetes and is caused by the interaction of genes and non-genetic factors, specifically poor glycaemic control and obesity. In spite of statin treatment, residual risk of CVD remains high in type 2 diabetes, and this may relate to HTG and atherogenic dyslipidemia. Treatment of HTG emphasises correcting secondary factors and adverse lifestyles, in particular, diet and exercise. Pharmacotherapy is also required in most type 2 diabetic patients. Statins are the first-line therapy to achieve recommended therapeutic targets of plasma low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol. Fibrates, ezetimibe and n-3 fatty acids are adjunctive treatment options for residual and persistent HTG. Evidence for the use of niacin has been challenged by non-significant CVD outcomes in two recent large clinical trials. Further investigation is required to clarify the use of incretin-based therapies for HTG in type 2 diabetes. Extreme HTG, with risk of pancreatitis, may require insulin infusion therapy or apheresis. New therapies targeting HTG in diabetes need to be tested in clinical endpoint trials. The purpose of this review is to examine the current evidence and provide practical guidance on the management of HTG in type 2 diabetes.

Outcome-Reporting Bias in Education Research

Outcome-reporting bias occurs when primary studies do not include information about all outcomes measured in a study. When studies omit findings on important measures, efforts to synthesize the research using systematic review techniques will be biased and interpretations of individual studies will be incomplete. Outcome-reporting bias has been well documented in medicine and has been shown to lead to inaccurate assessments of the effects of medical treatments and, in some cases, to omission of reports of harms. This study examines outcome-reporting bias in educational research by comparing the reports of educational interventions from dissertations to their published versions. We find that nonsignificant outcomes were 30% more likely to be omitted from a published study than statistically significant ones.

Guidance to detect, evaluate and prevent the problem of selective reporting in trial publications

Many aspects of a trial may be incompletely reported, including the outcomes collected and the full set of analyses undertaken. Selective reporting bias occurs when the inclusion of outcomes or analyses in the report is based on the results. We review and summarise the empirical evidence from studies that have assessed the selective reporting of outcomes and analyses and provide guidance to trialists to help reduce this problem. Methods Two systematic reviews of studies that have examined randomised trials for i) evidence for publication bias or selective reporting of outcomes and ii) evidence for selective reporting of analyses. An international collaboration of experts will be brought together in July to discuss the available evidence alongside current reporting guidance for trials. Recommendations are being produced with regards to raising the awareness and safeguarding trial publications against selective reporting. Results From twenty studies, of which four were newly identified, the evidence in the first systematic review demonstrated an association between statistically significant results and publication. Statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). A further seventeen studies consider aspects of selective reporting such as statistical analyses; subgroup analyses and composite outcomes. Conclusions This work highlights the evidence of selective reporting and demonstrates the importance of pre-specifying outcomes, analyses and reporting strategies during the planning and design of a clinical trial, for the purposes of minimising bias when findings are reported.

How often are invasion-induced ecological impacts missed?

Managers and policy makers depend on empirical research to guide and support biosecurity measures that mitigate introduced species’ impacts. Research contributing to this knowledge base generally uses null hypothesis significance testing to determine the significance of data patterns. However, reliance on traditional statistical significance testing methods, combined with small effect and sample size and large variability inherent to many impact studies, may obscure effects on native species, communities or ecosystems. This may result in false certainty of no impact. We investigated potential Type II error rates and effect sizes for 31 non-significant empirical evaluations of impact for introduced algal and crustacean species. We found low power consistently led to acceptance of Type II errors at rates 5.6–19 times greater than Type I errors (despite moderate to large effect sizes). Our results suggest that introduced species for which impact studies have statistically non-significant outcomes (often interpreted as “no impact”) may potentially have large impacts that are missed due to small sample or effect sizes and/or high variation. This alarming willingness to “miss” impacts has severe implications for conservation efforts, including under-managing species’ impacts and discounting the costs of Type II errors.

Systematic review of the empirical evidence of study publication bias and outcome reporting bias - an updated review.

BackgroundThe increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias and outcome reporting bias have been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making.Methodology/Principal FindingsIn this update, we review and summarise the evidence from cohort studies that have assessed study publication bias or outcome reporting bias in randomised controlled trials. Twenty studies were eligible of which four were newly identified in this update. Only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Fifteen of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40–62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies.ConclusionsThis update does not change the conclusions of the review in which 16 studies were included. Direct empirical evidence for the existence of study publication bias and outcome reporting bias is shown. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials.

Misuse of null hypothesis significance testing: would estimation of positive and negative predictive values improve certainty of chemical risk assessment?

Although generally misunderstood, the p value is the probability of the test results or more extreme results given H0 is true: it is not the probability of H0 being true given the results. To obtain directly useful insight about H0, the positive predictive value (PPV) and the negative predictive value (NPV) may be useful extensions of null hypothesis significance testing (NHST). They provide information about the probability of statistically significant and non-significant test outcomes being true based on an a priori defined biologically meaningful effect size. The present study explores the utility of PPV and NPV in an ecotoxicological context by using the frequently applied Daphnia magna reproduction test (OECD guideline 211) and the chemical stressor lindane as a model system. The results indicate that especially the NPV deviates meaningfully between a test design strictly following the guideline and an experimental procedure controlling for α and β at the level of 0.05. Consequently, PPV and NPV may be useful supplements to NHST that inform the researcher about the level of confidence warranted by both statistically significant and non-significant test results. This approach also reinforces the value of considering α, β, and a biologically meaningful effect size a priori.

Clinical Trial Registration in Physical Therapy Journals: Recommendations from the International Society of Physiotherapy Journal Editors

Clinical trial registration involves placing the protocol for a clinical trial on a free, publicly available, and electronically searchable register. Registration is considered to be prospective if the protocol is registered before the trial commences (ie, before the first participant is enrolled). Prospective registration has several potential advantages. It could help avoid trials being duplicated unnecessarily, and it could allow people with health problems to identify trials in which they might participate. Perhaps more important, however, it tackles 2 big problems in clinical research: selective reporting and publication bias. Selective reporting involves investigators reporting only the most favorable results when they publish a trial, instead of reporting the results for all the outcomes that were measured. Reporting only favorable outcomes can create a misleading appearance of the effect of a therapy in the published literature. For example, imagine that a completely ineffective intervention is tested across several trials, and each trial measures multiple outcomes. Most outcomes will show no significant effect of the intervention. However, occasionally an outcome will show significant benefit or harm simply by chance. If the researchers publish the positive outcomes but not all of the nonsignificant and negative outcomes, readers could interpret falsely that the intervention is beneficial. A similar problem could occur when outcomes are analyzed at multiple time points. Researchers may report that an intervention improves walking speed at 6 months, but fail to mention that it does not improve walking speed at 1, 2, 3, 9, 12, and 24 months. Prospective registration of clinical trials combats this problem in several ways. Journal editors and reviewers can compare the range of outcomes reported in a manuscript against those listed in the registered protocol, requesting that any discrepancies be resolved by following the protocol. Readers also can compare the outcomes in the registered protocol against …

Recommendations From the International Society of Physiotherapy Journal Editors: Clinical Trial Registration in Physiotherapy Journals

Costa, Leonardo O.P.1; Lin, Chung-Wei Christine1; Grossi, Debora Bevilaqua2; Mancini, Marisa Cota2; Swisher, Anne K.3; Cook, Chad4; Vaughn, Dan4; Elkins, Mark R5; Sheikh, Umer6; Moore, Ann7; Jull, Gwendolen7; Craik, Rebecca L.8; Maher, Christopher G.8; de Jesus Guirro, Rinaldo Roberto9; Marques, Amélia Pasqual9; Harms, Michele10; Brooks, Dina11; Simoneau, Guy G.12; Strupstad, John Henry13 Author Information

Persistent and delayed effects of a psycho-educational program for family caregivers at disclosure of dementia diagnosis in a relative: a six-month follow-up study

Abstract Background: Disclosure of a relative’s dementia diagnosis marks the family member’s official entry into the caregiver role, yet caregivers seldom receive support at this early stage in order to facilitate transition. This study (2008–2011) sought to evaluate whether positive effects observed at completion of a psycho-educational program persisted and whether any delayed effects emerged six months later. Methods: French-speaking primary caregivers of relatives diagnosed with dementia in the past nine months were recruited at memory clinics in Quebec (Canada). The 97 participants were blindly assessed using standardized measures before randomization to the experimental or the control group and were evaluated at program completion and six months later on outcomes associated with a healthy role transition. Results: Compared with controls, caregivers in the experimental group at both time points were better able to plan for the future care needs of their relative (p=0.05), made greater use of the coping strategy of reframing (p=0.05), experienced less psychological distress (p=0.05), had better knowledge of available services (those with low and moderate knowledge at baseline (p=0.001 and p=0.01, respectively) and tended to be more efficacious in their caregiver role (p=0.06). No persistent effect regarding preparedness or confidence in dealing with caregiving was observed, and no delayed effect was observed for stress-management coping strategies or informal support family conflicts. Conclusions: Intervention at career onset is key to fostering a healthy caregiver role transition. Greater emphasis should be placed on developing skills concerning non-significant outcomes. This trial was not registered.

Clinical trial registration in physical therapy journals: recommendations from the International Society of Physiotherapy Journal Editors

Clinical trial registration involves placing the protocol for a clinical trial on a free, publicly available, and electronically searchable register. Registration is considered to be prospective if the protocol is registered before the trial commences (ie, before the first participant is enrolled). Prospective registration has several potential advantages. It could help avoid trials being duplicated unnecessarily, and it could allow people with health problems to identify trials in which they might participate. Perhaps more important, however, it tackles 2 big problems in clinical research: selective reporting and publication bias. Selective reporting involves investigators reporting only the most favorable results when they publish a trial, instead of reporting the results for all the outcomes that were measured. Reporting only favorable outcomes can create a misleading appearance of the effect of a therapy in the published literature. For example, imagine that a completely ineffective intervention is tested across several trials, and each trial measures multiple outcomes. Most outcomes will show no significant effect of the intervention. However, occasionally an outcome will show significant benefit or harm simply by chance. If the researchers publish the positive outcomes but not all of the nonsignificant and negative outcomes, readers could interpret falsely that the intervention is beneficial. A similar problem could occur when outcomes are analyzed at multiple time points. Researchers may report that an intervention improves walking speed at 6 months, but fail to mention that it does not improve walking speed at 1, 2, 3, 9, 12, and 24 months. Prospective registration of clinical trials combats this problem in several ways. Journal editors and reviewers can compare the range of outcomes reported in a manuscript against those listed in the registered protocol, requesting that any discrepancies be resolved by following the protocol. Readers also can compare the outcomes in the registered protocol against …

Response to Resistance Training, Blood Pressure, and Meta-Analyses

We thank Rossi et al1 for their interest in our work2 and appreciate the opportunity to answer their comments.1 Our recent meta-analysis2 aimed to provide an update of the previously published meta-analysis on the effect of resistance training (RT) on blood pressure (BP).3 We included all of the randomized, controlled trials that reported the effect of RT on BP in healthy adults. By contrast, Rossi et al1 suggested that we should only have included articles in which BP was the primary outcome. They referred to Dwan et al4 to state that the inclusion of secondary outcomes might have influenced the effect estimates in our meta-analysis. Concordant to others,5 Dwan et al4 provide evidence for the fact that studies with statistically significant results, as well as statistically significant outcomes, are more likely to be published than studies that report no statistically significant results or nonsignificant outcomes. …

The prevalence and effect of publication bias in orthopaedic meta-analyses

BackgroundMeta-analyses of randomized, controlled trials are considered the highest level-of-evidence, thus strongest source of information. However, questions concerning the validity of meta-analyses in orthopaedic surgery emerged recently. Among the most common sources for errors is publication bias. This describes the fact that studies with small or non-significant outcomes are less likely to be published, thus less likely to be identified and included in systematic reviews and meta-analyses. In this study we asked three questions: (1) Whether publication bias is assessed in orthopaedic meta-analyses, (2) What the actual prevalence of publication bias is, and (3) what effect publication bias has on the outcomes of orthopaedic meta-analyses. MethodsUsing the estimate of 35 ± 20% for the prevalence of publication bias in meta-analyses obtained from earlier research we calculated a required samples size of 22 (plus 20% to account for attrition) and randomly selected 26 orthopaedic meta-analyses. To answer our first question we calculated the percentage of papers that report on formal assessment of publication bias. For our second question we obtained all primary studies (n = 321) from the included meta-analyses and used Egger’s regression to search for evidence for publication bias. Third, we used the trim-and-fill method to assess the impact of publication bias, if present. This method estimates publication bias in a meta-analysis and adds hypothetical studies to reduce this bias; it thus produces an estimate of adjusted, unbiased outcomes that can be compared with the unadjusted, publication-biased outcomes to assess the effect of publication bias. ResultsWe found that only 35% (95% CI 20–57) of all orthopaedic meta-analyses published between 1992 and 2008 in English and German assessed publication bias. Most studies used funnel plots, which are rather insensitive. The prevalence of publication bias, based on a sensitivity analysis, ranged between 12 and 19%. Adjustment for publication bias did not produce significantly different results, but the magnitude of the pooled estimates in the affected meta-analyses changed by 29% (95% CI 0–63) on average. ConclusionWe found a rather low prevalence of publication bias in orthopaedic meta-analyses, but recommend assessing for it and its effects, which might be substantial.

A Binomial Test of Group Differences With Correlated Outcome Measures

Building on previous arguments for why educational researchers should not provide effect-size estimates in the face of statistically nonsignificant outcomes (Robinson & Levin, 1997), Onwuegbuzie and Levin (2005) proposed a 3-step statistical approach for assessing group differences when multiple outcome measures are individually analyzed within the same study. One suggested Step 3 strategy was to conduct a binomial (or “sign”) test of the number of between-group outcome mean differences that are in the same direction. However, because multiple measures within a study typically are correlated, the binomial test's independence assumption will be violated. In the present investigation, the authors (a) performed a Monte Carlo simulation study to assess the Type I error behavior of the binomial test under varying degrees of independence-assumption violations, resulting in a table of adjusted critical values; and (b) illustrated use of this table by applying its adjusted critical values to a real research example.

Secondary Prevention: The Ongoing Challenge

Experts recommend the use of cardiac rehabilitation among patients with coronary disease.1 As hospital stays for acute coronary syndromes decrease, cardiac rehabilitation is assuming an increasingly important role in secondary prevention. There is a large amount of data indicating that cardiac rehabilitation improves several important intermediate end points, including exertional ischemic symptoms, depression and hostility scores, sense of wellness, understanding of the disease, and compliance with risk factor modification. With regard to survival, earlier randomized trials assessing the efficacy of cardiac rehabilitation after myocardial infarction have been limited by small sample size. When the results of individual trials were pooled, cardiac rehabilitation was associated with survival gains of 20% to 30%.2, 3 However, as these trials were conducted in the 1980s, it is uncertain that these data can be generalized to contemporary practice. The study by Brotons et al, published in this issue of Revista Espanola de Cardiologia 4 contributes to address this gap in knowledge by evaluating the efficacy of secondary prevention between 2004 and 2005. The authors report on 1224 patients with cardiovascular disease (coronary disease, cerebrovascular disease or peripheral arterial disease) from 42 practices in Spain, similarly distributed between control and intervention, the latter consisting of education and structured intervention based on the patient's risk factor profile. There was no benefit of the intervention on the primary endpoint (all-cause mortality and hospital readmissions) and marginal effects of questionable clinical significance on intermediate endpoints (risk factor profile), except for depression, which exhibited a notable difference between the 2 arms favoring intervention. These results underscore the importance of publishing “negative trials”, despite the prevalent study publication bias whereby statistically significant outcomes are more likely to be reported than non-significant outcomes.5 Indeed, the study generates several important questions.

Obstacles to researching the researchers: a case study of the ethical challenges of undertaking methodological research investigating the reporting of randomised controlled trials.

BackgroundRecent cohort studies of randomised controlled trials have provided evidence of within-study selective reporting bias; where statistically significant outcomes are more likely to be more completely reported compared to non-significant outcomes. Bias resulting from selective reporting can impact on meta-analyses, influencing the conclusions of systematic reviews, and in turn, evidence based clinical practice guidelines.In 2006 we received funding to investigate if there was evidence of within-study selective reporting in a cohort of RCTs submitted to New Zealand Regional Ethics Committees in 1998/99. This research involved accessing ethics applications, their amendments and annual reports, and comparing these with corresponding publications. We did not plan to obtain informed consent from trialists to view their ethics applications for practical and scientific reasons.In November 2006 we sought ethical approval to undertake the research from our institutional ethics committee. The Committee declined our application on the grounds that we were not obtaining informed consent from the trialists to view their ethics application. This initiated a seventeen month process to obtain ethical approval. This publication outlines what we planned to do, the issues we encountered, discusses the legal and ethical issues, and presents some potential solutions.Discussion and conclusionMethodological research such as this has the potential for public benefit and there is little or no harm for the participants (trialists) in undertaking it. Further, in New Zealand, there is freedom of information legislation, which in this circumstance, unambiguously provided rights of access and use of the information in the ethics applications. The decision of our institutional ethics committee defeated this right and did not recognise the nature of this observational research.Methodological research, such as this, can be used to develop processes to improve quality in research reporting. Recognition of the potential benefit of this research in the broader research community, and those who sit on ethics committees, is perhaps needed. In addition, changes to the ethical review process which involve separation between those who review proposals to undertake methodological research using ethics applications, and those with responsibility for reviewing ethics applications for trials, should be considered. Finally, we contend that the research community could benefit from quality improvement approaches used in allied sectors.

Systematic review of the empirical evidence of study publication bias and outcome reporting bias.

BackgroundThe increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias has been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Until recently, outcome reporting bias has received less attention.Methodology/Principal FindingsWe review and summarise the evidence from a series of cohort studies that have assessed study publication bias and outcome reporting bias in randomised controlled trials. Sixteen studies were eligible of which only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Eleven of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40–62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies.ConclusionsRecent work provides direct empirical evidence for the existence of study publication bias and outcome reporting bias. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials.

Melatonin for the treatment of dementia

Background There are a number of studies that suggest a relationship between decline of melatonin function and the symptoms of dementia. Objectives The review assessed the evidence of clinical effectiveness of melatonin in the treatment of symptoms of dementia. Relevant primary outcomes were cognition, mood, behaviour, functions of daily living, and safety of melatonin use and secondary outcomes were quality of life, morbidity, mortality and length of time to institutionalization and caregiver stress. Search methods The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on 29 June 2009 using the terms: MELATONIN and N-ACETYL-5-METHOXYTRYPTAMINE. The CDCIG Specialized Register contains records from all major health care databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many trials databases and grey literature sources. The search of June 2009 retrieved several studies for consideration by the authors. Selection criteria All relevant, randomized controlled trials in which orally administered melatonin in any dosage was compared with a control group for the effect on managing cognitive, behavioral (excluding sleep), and mood disturbances of people with dementia of any degree of severity. Data collection and analysis Two to three reviewers independently assessed the retrieved articles for relevance and risk of bias, and extracted data from the selected studies. Statistically significant differences in end-points or changes in outcomes from baseline to end of treatment between the melatonin and control groups were examined. Each study was summarized using a measure of effect (e.g. mean difference) and meta-analyses were conducted when appropriate. Main results Five studies met the inclusion criteria. The pooled estimates of MMSE cognitive and ADAS-cognitive change scores from three of these studies revealed non-significant cognitive effects for melatonin treatment. In two of these studies, significant improvements in psychopathological behaviours (e.g., decreased mood symptoms of depression, anxiety and apathy and decreased behavior symptoms of hallucinations, delusions, agitation, irritability, and appetite disturbances), were found from meta-analysis of the change scores from the NPI (7 weeks, 2.5 mg melatonin), and ADAS non-cognitive (4 weeks, 3 mg melatonin) scales. Sensitivity analyses found similar results to those of the original meta-analyses, and thus, supported the effect estimates for non-significant cognitive outcomes. Individual study estimates for treatment effect of 2.5 mg melatonin at one year demonstrated a significant worsening of mood (e.g. decrease in positive affect) as measured by the Philadelphia Geriatric Centre Affect Rating Scale (positive). The remainder of the treatment effects for mood, behavior, and function of daily living were non-significant. There were no reported adverse effects associated with melatonin use. Authors' conclusions The analyses did not support the use of melatonin for treatment of cognitive impairment associated with dementia. Meta-analysis of psychopathologic behavior scale scores suggested that melatonin may be effective in treating these dementia-related disturbances.