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We develop a novel control function approach in models where the treatment variable has bunching at one corner of its support. This situation typically arises when the treatment variable is a constrained choice and some observations choose the corner solution. The method exploits distributional shape restrictions but makes no exclusion restrictions. We provide estimators and establish their asymptotic behavior, prove the convergence of the bootstrap, and develop tests of the identification assumptions. An application reveals that watching television has no effect on cognitive skills and a negative effect on noncognitive skills in children. [ABSTRACT FROM AUTHOR]

To date, nutritional epidemiology has relied heavily on relatively weak methods including simple observational designs and substandard measurements. Despite low internal validity and other sources of bias, claims of causality are made commonly in this literature. Nutritional epidemiology investigations can be improved through greater scientific rigor and adherence to scientific reporting commensurate with research methods used. Some commentators advocate jettisoning nutritional epidemiology entirely, perhaps believing improvements are impossible. Still others support only normative refinements. But neither abolition nor minor tweaks are appropriate. Nutritional epidemiology, in its present state, offers utility, yet also needs marked, reformational renovation. Changing the status quo will require ongoing, unflinching scrutiny of research questions, practices, and reporting—and a willingness to admit that "good enough" is no longer good enough. As such, a workshop entitled "Toward more rigorous and informative nutritional epidemiology: the rational space between dismissal and defense of the status quo" was held from July 15 to August 14, 2020. This virtual symposium focused on: (1) Stronger Designs, (2) Stronger Measurement, (3) Stronger Analyses, and (4) Stronger Execution and Reporting. Participants from several leading academic institutions explored existing, evolving, and new better practices, tools, and techniques to collaboratively advance specific recommendations for strengthening nutritional epidemiology. [ABSTRACT FROM AUTHOR]

A meta-analysis is substantial for integrating the findings of all related studies into one consistent research to establish a knowledge bank of a common issue. Although several studies have examined the impact of the individual aspect of human capital on farmers' technical efficiency, the composite impact was not synthesized. Therefore, our analysis examines the key determinants driving systematic variations in technical efficiency estimates from 268 food-crop farming studies published recently in peer-reviewed journals. Our results have supported our hypothesis that human capital increases farming efficiency. The studies' location indicates the importance of farmer beliefs, trust in their institutions and land accumulation to increase food-crop farmer technical efficiency. Our findings contribute to the applied agricultural economics literature by theoretically systematizing literature on human capital in accordance with social and natural capitals in agricultural productivity and empirically validating the technical efficiency in food-crop farming studies toward developing agricultural sustainability in harmony with our biosphere. [ABSTRACT FROM AUTHOR]

ehaviour change is a key to addressing many health and healthcare problems and interventions have been designed to improve health outcomes. These behaviour change interventions have been evaluated in many ways, including randomised controlled trials, and over recent decades there has been considerable progress in the conduct and reporting these studies. This paper is a personal retrospection on the changes occurring that have resulted in our current improved methods and their potential for future advancement. There has been steady development of methods for conducting trials, including advances in statistical methods enabled by increase computing power and programmes, greater attention to the recruitment of participants and in the specification of outcomes. Trial reporting has improved, largely due to publication of guidelines for reporting interventions and trials, but until recently the reporting of behaviour change interventions has been quite limited. Developments in the specification of active ingredients of these interventions, the behaviour change techniques, has transformed our ability to report interventions in a manner that facilitates evidence synthesis and enables replication and implementation. However, further work using ontological approaches is needed to adequately represent the evidence contained in the mass of accumulated studies. Meanwhile, attention is gradually being paid to the comparator groups in trials leading to better reporting but with continuing challenges about how control groups are selected. These developments are important for the advancements of behavioural science – but also in consolidating the expertise needed to address global social, environmental and health challenges. [ABSTRACT FROM AUTHOR]

Whether gamification is an organized structure that contributes to student achievement, a simple pontification process or total nonsense is a matter of debate. In such, this study was conducted to provide a scientific answer while exhibiting the gamification effect on student achievement with the meta-analysis method, which is based on experimental research that investigates the effect of gamification on student achievement between 2010 and 2016. As a result of the completed meta-analysis, a common effect size value that was estimated by compiling experimental studies was found to be 0.557. This value shows that gamification has a moderately positive (Cohen, 1988) effect on student achievement. It is exhibited that there is no publication bias regarding determining the effect's validity. Calculated 0.557 Hedges' g value's omega square equivalent is.072. This value shows that gamification has added 7.2% positive value to academic achievement according to 45 experimental results involving 3,487 students from different countries. [ABSTRACT FROM AUTHOR]

Consistently defined, accurate, and easily accessible cost data are a valuable resource to inform efficiency analyses, budget preparation, and sustainability planning in global health. The Global Health Cost Consortium (GHCC) designed the Unit Cost Study Repository (UCSR) to be a resource for standardised HIV and TB intervention cost data displayed by key characteristics such as intervention type, country, and target population. To develop the UCSR, the GHCC defined a typology of interventions for each disease; aligned interventions according to the standardised principles, methods, and cost and activity categories from the GHCC Reference Case for Estimating the Costs of Global Health Services and Interventions; completed a systematic literature review; conducted extensive data extraction; performed quality assurance; grappled with complex methodological issues such as the proper approach to the inflation and conversion of costs; developed and implemented a study quality rating system; and designed a web-based user interface that flexibly displays large amounts of data in a user-friendly way. Key lessons learned from the extraction process include the importance of assessing the multiple uses of extracted data; the critical role of standardising definitions (particularly units of measurement); using appropriate classifications of interventions and components of costs; the efficiency derived from programming data checks; and the necessity of extraction quality monitoring by senior analysts. For the web interface, lessons were: understanding the target audiences, including consulting them regarding critical characteristics; designing the display of data in "levels"; and incorporating alert and unique trait descriptions to further clarify differences in the data. [ABSTRACT FROM AUTHOR]

There is a crisis in the foundations of statistical inference. I believe that this crisis will eventually be resolved by regarding the subjective Bayesian paradigm as ideal in principle but often using standard procedures which are not subjective Bayesian for well-defined standard circumstances. As a step toward this resolution, this article looks at the question of what properties statistical inferences might reasonably be expected to have and argues that the use of p-values should be restricted to pure significance testing. The value judgments presented are supported by a range of examples. [ABSTRACT FROM AUTHOR]

Frequent glucose monitoring is a fundamental part of diabetes management, and good glucose control is important for long-term health outcomes. New types of electrochemical sensors that allow for continuous glucose monitoring (CGM) have become an important tool for diabetes management, although they still have drawbacks such as short lifetime and a need for frequent calibration. Other technologies are still being researched for CGM, in an attempt to replace the electrochemical sensors. Optical methods have several advantages for CGM, including potentially long sensor lifetimes and short measurement times, and many developments have been made over the last decades. This paper will review optical measurement methods for CGM, their challenges, and the current research status. The different methods will be compared, and the future prospects for optical methods will be discussed. [ABSTRACT FROM AUTHOR]

Brief social-psychological interventions, like the values affirmation (VA), that target individual feelings of competency and buffer against social threats, have been shown to effectively reduce achievement gaps in randomised controlled trials. In the current study, underrepresented minority and first-generation college students in their first university semester (N = 496) were randomly assigned to receive the VA electronically or complete an online survey (control). Results revealed: (a) VA participants did not engage with the intervention in a manner typical of past VA studies that delivered the intervention as a class activity; (b) VA students had lower semester grade point averages (GPAs) than control students; and (c) contrary to previous studies, neither stereotype threat nor social belonging moderated the effectiveness of the VA. These findings further emphasise the importance of the context within which the VA is delivered and highlight the challenges that accompany increasing the reach of the VA through a widespread, online delivery. [ABSTRACT FROM AUTHOR]

This cohort study aimed to provide normative Y Balance Test scores for an elite Rugby Union population, while investigating the effect player age groups (senior/under-20), playing positions (forwards/backs) and anthropometrics (height and body mass) had on performance. Two-hundred and sixty-one elite male under-20 (n = 50) and senior (n = 211) players completed baseline Y Balance Test during the 2015/2016 season. One-way ANCOVA and post-hoc t-tests were used to investigate the effect playing position, player group, height and weight had on performance. The cohort was then stratified into groups (age group and/or playing position), and normative percentiles were presented. There was a statistically significant difference (p < 0.05) in Y Balance Test performance between playing positions, when controlling for age group. This difference did not remain when controlling for player body mass. Post-hoc analysis demonstrated that backs had a longer normalised reach distance, with medium-large and small-medium effect sizes for the under-20 and senior cohorts respectively. The one-way ANCOVA analysis suggests that this difference is likely due to the larger differences in player body mass between forward and back playing positions. The normative values presented in this paper may be used by clinicians and researchers to aid injury prevention and rehabilitation strategies. [ABSTRACT FROM AUTHOR]

Efforts to address a reproducibility crisis have generated several valid proposals for improving the quality of scientific research. We argue there is also need to address the separate but related issues of relevance and responsiveness. To address relevance, researchers must produce what decision makers actually need to inform investments and public policy—that is, the probability that a claim is true or the probability distribution of an effect size given the data. The term responsiveness refers to the irregularity and delay in which issues about the quality of research are brought to light. Instead of relying on the good fortune that some motivated researchers will periodically conduct efforts to reveal potential shortcomings of published research, we could establish a continuous quality-control process for scientific research itself. Quality metrics could be designed through the application of this statistical process control for the research enterprise. We argue that one quality control metric—the probability that a research hypothesis is true—is required to address at least relevance and may also be part of the solution for improving responsiveness and reproducibility. This article proposes a "straw man" solution which could be the basis of implementing these improvements. As part of this solution, we propose one way to "bootstrap" priors. The processes required for improving reproducibility and relevance can also be part of a comprehensive statistical quality control for science itself by making continuously monitored metrics about the scientific performance of a field of research. [ABSTRACT FROM AUTHOR]

There are more than 700 articles exploring assessment in geography education. However, these papers vary in the degree to which recommendations and conclusions are based on research evidence. Globally, evidence-based practice is being prioritised, making it essential to understand exactly what the empirical research around this topic is saying. A systematic review provides a rigorous method for achieving such a task. This paper quantifies and systematically accounts for the proportion and scope of articles dedicated to assessment in geography education. We conclude that clarity is required regarding: (1) the essential geographical knowledge and skills students should develop; (2) the nature of the learning progressions in each of these areas; and (3) the types and formats of assessment instruments that will provide valid and reliable measures of this progress. [ABSTRACT FROM AUTHOR]

Efforts to address a reproducibility crisis have generated several valid proposals for improving the quality of scientific research. We argue there is also need to address the separate but related issues of relevance and responsiveness. To address relevance, researchers must produce what decision makers actually need to inform investments and public policy—that is, the probability that a claim is true or the probability distribution of an effect size given the data. The term responsiveness refers to the irregularity and delay in which issues about the quality of research are brought to light. Instead of relying on the good fortune that some motivated researchers will periodically conduct efforts to reveal potential shortcomings of published research, we could establish a continuous quality-control process for scientific research itself. Quality metrics could be designed through the application of this statistical process control for the research enterprise. We argue that one quality control metric—the probability that a research hypothesis is true—is required to address at least relevance and may also be part of the solution for improving responsiveness and reproducibility. This article proposes a "straw man" solution which could be the basis of implementing these improvements. As part of this solution, we propose one way to "bootstrap" priors. The processes required for improving reproducibility and relevance can also be part of a comprehensive statistical quality control for science itself by making continuously monitored metrics about the scientific performance of a field of research. [ABSTRACT FROM AUTHOR]

This article is a critical overview of recent contributions on the dietary corrections and the foods that have been claimed to delay or hinder the onset of diabetic nephropathy (DN) and its progression to end-stage renal disease. Innovative dietary and behavioral approaches to the prevention and therapy of DN appear to be the most captivating in consideration of the rather well-established protocols for glucose and blood pressure control in use. In addition to restricted caloric intake to contrast obesity and the metabolic syndrome, adjustments in the patient's macronutrients intake, and in particular some degree of reduction in protein, have been long considered in the prevention of DN progression. More recently, the focus has shifted to the source of proteins and the content of glycotoxins in the diet as well as to the role of specific micronutrients. Few clinical trials have specifically addressed the role of those micronutrients associated with diet proteins that show the most protective effect against DN. Research on clinical outcome and mechanisms of action of such micronutrients appears the most promising in order to develop both effective intervention on nutritional education of the patient and selection of functional foods capable of contrasting the onset and progression of DN. [ABSTRACT FROM AUTHOR]

The Cochrane risk of bias tool (RoB) is a widely used measure for methodological quality of randomized controlled trials. This paper discusses RoB’s rationale and risk of bias domains, reports on its application in current psychotherapy meta-analyses, and offers comments regarding the application of RoB in the context of psychotherapy outcome research. Our suggestions include focusing on patient’s and therapist’s expectations when judging the domain “blinding of personnel and participants” and paying greater attention to the domain “selective outcome reporting” and to matters of “treatment implementation.” [ABSTRACT FROM AUTHOR]

Aims: To evaluate the effectiveness and feasibility (i.e. tolerability, adherence) of functional electrical stimulation (FES) for the upper extremity (UE) in a two-year-old child with perinatal stroke.Methods: Forty hours of FES over eight weeks was prescribed. FES to the hemiplegic triceps, extensor carpi radialis longus and brevis, extensor carpi ulnaris and extensor digitorum was timed with reaching during play. Assessments were performed before, during, and two months post-intervention. UE function (Melbourne Assessment 2 (MA2), Assisting Hand Assessment (AHA)) and spasticity (Modified Tardieu with electrogoniometry and electromyography) were measured. The mother completed a semi-structured interview post-intervention. Descriptive statistics were used for adherence and UE measures. A repeated-measures ANOVA compared Modified Tardieu parameters (e.g. catch angle) over time. Conventional content analysis was used for the interview data.Results: The child completed 39.2/40 hours. Immediately post-intervention, improvements were observed on MA2's Range of Motion subscale and catch angle (Modified Tardieu,p< 0.001). Two months post-intervention, improvements were observed on MA2's Accuracy and Fluency subscales. No change in AHA score occurred. Three themes emerged from the interview: (1) Ingredients for program success; (2) Information about the FES device; and (3) The child's response.Conclusions: UE FES was feasible in a two-year-old child with hemiplegia. [ABSTRACT FROM AUTHOR]

Background: Observational studies suggest an association between dietary fiber intake and risk of Barrett's esophagus and esophageal cancer. However, the results are inconsistent.Objective: To conduct a meta-analysis of observational studies to assess this association.Design: All eligible studies were identified by electronic searches in PubMed and Embase through February 2015. Dose-response, subgroup, sensitivity, and publication bias analyses were performed.Results: A total of 15 studies involving 16,885 subjects were included in the meta-analysis. The pooled odds ratio for the highest compared with the lowest dietary fiber intake was 0.52 (95% CI, 0.43-0.64). Stratified analyses for tumor subtype, study design, geographic location, fiber type, publication year, total sample size, and quality score yielded consistent results. Dose-response analysis indicated that a 10-g/d increment in dietary fiber intake was associated with a 31% reduction in Barrett's esophagus and esophageal cancer risk. Sensitivity analysis restricted to studies with control for conventional risk factors produced similar results, and omission of any single study had little effect on the overall risk estimate.Conclusions: Our findings indicate that dietary fiber intake is inversely associated with risk of Barrett's esophagus and esophageal cancer. Further large prospective studies are warranted. [ABSTRACT FROM AUTHOR]

Cognitive Behavioural Therapy (CBT) is a widely used psychotherapeutic intervention for suicide prevention despite its efficacy for suicide prevention in adults remaining ambiguous. Reluctance or inability to access face-to-face help suggests that e-health delivery may be a valuable resource for suicidal people. The aim of this study was to systematically review and conduct meta-analysis on research assessing the efficacy of CBT delivered via face-to-face and e-health for suicidal ideation and behaviour. A comprehensive literature search of MEDLINE, PsycINFO, Scopus, PubMed and The Cochrane Central Register of Controlled Trials was conducted. From 764 identified articles, 26 met the inclusion criteria for investigating CBT for suicidal ideation and behaviours in adult populations. Data were extracted on study characteristics and meta-analysis was performed where possible. There was a statistically significant, small to medium effect for face-to-face delivered CBT in reducing suicidal ideation and behaviour although there was significant heterogeneity between the included studies. CBT delivered via e-health was not found to be efficacious for reducing suicidal ideation and behaviour in adults though the number of studies reviewed was small. [ABSTRACT FROM AUTHOR]

The article offers information on the innovation in a learning healthcare system helps to explain position by illuminating the conceptual and practical flaws that follow from drawing a sharp distinction between research and treatment innovation. It mentions both research and innovation are governed by the scientific method; and also mentions moving to implement a learning health care system fosters innovation.

Within public health, and increasingly other areas of social policy, there are widespread calls to increase or improve the use of evidence for policy-making. Often these calls rest on an assumption that increased evidence utilisation will be a more efficient or effective means of achieving social goals. Yet a clear elucidation of what can be considered “good evidence” for policy is rarely articulated. Many of the current discussions of best practise in the health policy sector derive from the evidence-based medicine (EBM) movement, embracing the “hierarchy of evidence” that places experimental trials as pre-eminent in terms of methodological quality. However, a number of problems arise if these hierarchies are used to rank or prioritise policy relevance. Challenges in applying evidence hierarchies to policy questions arise from the fact that the EBM hierarchies rank evidence of intervention effect on a specified and limited number of outcomes. Previous authors have noted that evidence forms at the top of such hierarchies typically serve the needs and realities of clinical medicine, but not necessarily public policy. We build on past insights by applying three disciplinary perspectives from political science, the philosophy of science and the sociology of knowledge to illustrate the limitations of a single evidence hierarchy to guide health policy choices, while simultaneously providing new conceptualisations suited to achieve health sector goals. In doing so, we provide an alternative approach that re-frames “good” evidence for health policy as a question of appropriateness. Rather than adhering to a single hierarchy of evidence to judge what constitutes “good” evidence for policy, it is more useful to examine evidence through the lens ofappropriateness. The form of evidence, the determination of relevant categories and variables, and the weight given to any piece of evidence, must suit the policy needs at hand. A more robust and critical examination of relevant and appropriate evidence can ensure that the best possible evidence of various forms is used to achieve health policy goals. [ABSTRACT FROM PUBLISHER]

The pharmaceutical market is experiencing significantly amplified research and development costs, as well as increasing price and other competitive pressures. This article presents a much-needed systematic review of the literature relevant to pharmaceutical marketing. The authors find that the order-of-entry effect is critical in the sector, but that both early- and late-entry strategies can be effective when coupled with the appropriate marketing strategies. Within this context, the present study reveals that promotion policy is the most relevant, followed by price policy, with product design policy surprisingly only third in importance. Distribution (place) is the least relevant in the pharmaceutical context. These findings are used to drive an agenda for future research in pharmaceutical marketing. [ABSTRACT FROM PUBLISHER]

To demand ‘evidence-based medicine’ and ‘evidence-based research’ has become almost a dogma for researchers and policy-makers in Western cultures. A critical analysis shows that the original intention of the term ‘evidence-based’ was to aim to use the best existing evidence (emphasising that research should be planned and interpreted in a methodologically correct way), while recognising that, in some areas, experimental research would be neither sensible nor feasible. However, as the paradigm has become established, three dubious and commonly coexisting additional connotations have become prominent in practice: ‘proven beyond doubt’, ‘exclusively relying on experimental research’ and ‘any conclusions based on empirical data’. Drawing on examples from renowned publications that demand an ‘evidence-based alcohol policy’, this article argues that much of what is presented as ‘evidence-based policy’ should more appropriately be labelled ‘policy-based evidence’. [ABSTRACT FROM PUBLISHER]

The article discusses research ethics and the limitations associated with use of fecal microbiota transplantation (FMT) in other therapeutic uses. Topics discussed include information on the Common Rule and Council for International Organizations of Medical Sciences (CIOMS) guidelines; impact of the infancy of research on the human microbiome; and use of FMT in conditions like inflammatory bowel disease, irritable bowel syndrome and obesity.

Exposure to inorganic arsenic (As) through drinking water is a major international public health issue. We carried out a systematic review of the existing literature examining the association between the risk of bladder cancer in humans and exposure to arsenic through drinking water. We searched electronic databases for studies published from January 2000 up to April 2013. Eight ecological studies, six case-control studies, four cohort studies and two meta-analyses were identified. The vast majority of the studies were carried out in areas with high arsenic concentrations in drinking water such as southwestern and northeastern Taiwan, Pakistan, Bangladesh, Argentina (Cordoba Province), USA (southeastern Michigan, Florida, Idaho) and Chile. Most of the studies reported higher risks of bladder cancer incidence or mortality in areas with high arsenic concentrations in drinking water compared to the general population or a low arsenic exposed control group. The quality assessment showed that among the studies identified, arsenic exposure was assessed at the individual level only in half of them and only three assessed exposure using a biomarker. Further, five out of eight ecological studies presented results with adjustment for potential confounders except for age; all cohort and case-control studies presented results with adjustment for cigarette smoking status in the analysis. The majority of the studies with varying study designs carried out in different areas provided evidence of statistically siginificant increases in bladder cancer risk at high concentrations of arsenic (>50 μg L−1). Assessing bladder cancer risk at lower exposure concentrations requires further investigation. [ABSTRACT FROM AUTHOR]

This article addresses the issue of the autonomy of patients who are not treated in standard situations of hospitalisation in institutions, but who receive ambulatory care. Academic and institutional discourses both suggest that the development of out-of-hospital care delivery models promotes patient autonomy. Through a qualitative study based on semi-structured interviews of cancer patients treated using ambulatory chemotherapy in a French hospital we show that some of the constraints usually encountered by patients receiving care in institutions are also observed in patients receiving ambulatory care. They experience a form of cognitive isolation regarding access to information about their health, and their social life appears to be institutionalised. [ABSTRACT FROM AUTHOR]

The objectives of this study were to (1) examine the relationship between total trihalomethanes (TTHM) levels in public water supplies and risk of esophageal cancer occurrence and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water modify the effects of TTHM on risk to develop esophageal cancer. A matched case-control study was used to investigate the relationship between the risk of death attributed to esophageal cancer and exposure to TTHM in drinking water in 53 municipalities in Taiwan. All esophageal cancer deaths in the 53 municipalities from 2006 through 2010 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels in drinking water were collected from Taiwan Environmental Protection Administration. Information on the levels of Ca and Mg in drinking water was obtained from the Taiwan Water Supply Corporation. The municipality of residence for cancer cases and controls was presumed to be the source of the subject's TTHM, Ca, and Mg exposure via drinking water. Relative to individuals whose TTHM exposure level <4.9 ppb, the adjusted odds ratio (OR) with 95% confidence interval (CI) for esophageal cancer was 1.02 (0.84–1.23) for individuals who resided in municipalities served by drinking water with a TTHM exposure ≥4.9 ppb. There was evidence of an interaction between drinking-water TTHM levels and low Ca and Mg intake. Our findings showed that the correlation between TTHM exposure and risk of esophageal cancer development was influenced by Ca and Mg levels in drinking water. This is the first study to report effect modification by Ca and Mg intake from drinking water on the correlation between TTHM exposure and risk of esophageal cancer occurrence. Increased knowledge of the interaction between Ca, Mg, and TTHM in reducing risk of esophageal cancer development will aid in public policymaking and standard setting for drinking water. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in industrialized countries. Chemoprevention is a promising approach, but studies demonstrating their usefulness in large populations are still needed. Among several compounds with chemopreventive ability, cyclooxygenase inhibitors have received particular attention. However, these agents are not without side effects, which must be weighed against their beneficial actions. Early diagnosis is critical in the management of CRC patients, because, in early stages, surgery is curative in >90% of cases. If diagnosis occurs at stages II and III, which is often the case, neoadjuvant chemotherapy and radiotherapy before surgery are, in a few cases, recommended. Because of the high risk of recurrence in advanced cancers, chemotherapy is maintained after tumor resection. Chemotherapy is also indicated when the patient has metastases and in advanced cancer located in the rectum. In the last decade, the use of anticancer drugs in monotherapy or in combined regimens has markedly increased the survival of patients with CRC at stages III and IV. Although the rate of success is higher than in other gastrointestinal tumors, adverse effects and development of chemoresistance are important limitations to pharmacological therapy. Genetic profiling regarding mechanisms of chemoresistance are needed to carry out individualized prediction of the lack of effectiveness of pharmacological regimens. This would minimize side effects and prevent the selection of aggressive, cross-resistant clones, as well as avoiding undesirable delays in the use of the most efficient therapeutic approaches to treat these patients. [ABSTRACT FROM AUTHOR]

The objectives of this study were to (1) examine the relationship between total trihalomethanes (TTHM) levels in public water supplies and risk of development of kidney cancer and (2) determine whether hardness levels in drinking water modify the effects of TTHM on risk of kidney cancer induction. A matched case-control study was used to investigate the relationship between the risk of death attributed to kidney cancer and exposure to TTHM in drinking water in 53 municipalities in Taiwan. All kidney cancer deaths in the 53 municipalities from 1998 through 2007 were obtained. Controls were deaths from other causes and were pair-matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels and levels of hardness in drinking water were also collected. The municipality of residence for cancer cases and controls was presumed to be the source of the subject's TTHM and hardness exposure via drinking water. Relative to individuals whose TTHM exposure level was <4.9 ppb, the adjusted OR (95% CI) for kidney cancer was 0.98 (0.77–1.25) for individuals who resided in municipalities served by drinking water with a TTHM exposure ≥4.9 ppb. However, evidence of an interaction was noted between the use of soft water and drinking water TTHM concentrations. Increased knowledge of the interaction between hardness and TTHM levels in reducing risk of kidney cancer development will aid in public policy decision and establishing standards to prevent disease occurrence. [ABSTRACT FROM PUBLISHER]

The objectives of this study were to (1) examine the relationship between total trihalomethanes (TTHM) levels in public water supplies and death attributed to colon cancer and (2) determine whether magnesium (Mg) levels in drinking water modify the effects of TTHM on risk of colon cancer development. A matched case-control study was used to investigate the relationship between the risk of death attributed to colon cancer and exposure to total trihalomethanes (TTHM) in drinking water in 53 municipalities in Taiwan. All colon cancer deaths of the 53 municipalities from 1998 through 2007 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels in drinking water were collected from Taiwan Environmental Protection Administration. Information on the levels of Mg in drinking water was obtained from the Taiwan Water Supply Corporation. The municipality of residence for cancer cases and controls was presumed to be the source of the subject's TTHM and Mg exposure via drinking water. Relative to individuals whose TTHM exposure levels were <4.9 ppb, the adjusted odds ration (OR) (with 95% confidence interval [CI]) for colon cancer was 1.14 (1.01-1.28) for individuals who had resided in municipalities served by drinking water with a TTHM exposure ≥4.9 ppb. Evidence of an interaction between drinking-water TTHM and Mg intake via drinking water was noted. This is the first study to report an effect modification by Mg intake from drinking water in association between TTHM exposure and risk of colon cancer occurrence. Better knowledge of this modifying factor will help in public policymaking and setting health standards. [ABSTRACT FROM AUTHOR]

Due to the uncertainty of the results of phase II trials, underpowered phase III trials are often planned. In recent literature the conservative approach for sample size estimation was proposed. Some authors, in the parametric framework, make use of the lower bound of the effect size for conservatively estimating the true power, and so the sample sizes. Here, we present a general bootstrap method for conservatively estimating, on the basis of phase II data, the sample size needed for a phase III trial. The method we propose is based on the use of nonparametric lower bounds for the true power of the test. A wide study is shown for comparing the performances of the new method in estimating the power of the Wilcoxon rank-sum test with those given by standard techniques based on the asymptotic normality of the test statistic. Results indicate that when the phase II sample size is around the ideal sample size for the phase III, the bootstrap provides better results than the other techniques. Since the method is general, it could be used for planning clinical trials for testing superiority, for testing noninferiority, and for more complicated situations, e.g., for testing multiple endpoints. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT) and Cranial electrotherapy stimulation (CES) have both been in use for decades; transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), deep brain stimulation (DBS), transcranial Direct Current Stimulation (tDCS), and vagus nerve stimulation (VNS) have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES), depression (ECT, CES, rTMS, VNS, DBS), obsessive-compulsive disorder (OCD) (DBS), essential tremor, dystonia (DBS), epilepsy (DBS, VNS), Parkinson Disease (DBS), pain (CES), and insomnia (CES). To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in reducing anxiety, findings that may suggest possible utility in relieving PTSD-associated anxiety. Treatment of animal models of PTSD with DBS suggests potential human benefit. Additional research and novel treatment options for PTSD are urgently needed. The potential usefulness of brain stimulation in treating PTSD deserves further exploration. [ABSTRACT FROM AUTHOR]

The objectives of this study were (1) to examine the relationship between total trihalomethanes (TTHM) levels in public water supplies and risk of rectal cancer development and (2) to determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the effects of TTHM on risk of developing rectal cancer. A matched cancer case-control study was used to investigate the relationship between the risk of death attributed to rectal cancer and exposure to TTHM in drinking water in 53 municipalities in Taiwan. All rectal cancer deaths in the 53 municipalities from 1998 through 2007 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels in drinking water were collected from the Taiwan Environmental Protection Administration. Information on the levels of Ca and Mg in drinking water was obtained from the Taiwan Water Supply Corporation. The municipality of residence for cancer cases and controls was presumed to be the source of the subject's TTHM, Ca, and Mg exposure via drinking water. Relative to individuals whose TTHM exposure level was <4.9 ppb, the adjusted OR (95% CI) for rectal cancer occurrence was 1.04 (0.88-1.22) for individuals who resided in municipalities served by drinking water with a TTHM exposure ≥4.9 ppb. There was no evidence of an interaction of drinking-water TTHM levels with low Ca intake via drinking water. However, evidence of an interaction was noted between drinking-water TTHM concentrations and Mg intake via drinking water. Our findings showed that the correlation between TTHM exposure and risk of rectal cancer is influenced by Mg in drinking water. Increased knowledge of the interaction between Mg and TTHM in reducing rectal cancer risk will aid in public policymaking and standard setting. [ABSTRACT FROM AUTHOR]

The objectives of this study were (1) to examine the relationship between total trihalomethanes (TTHM) levels in public water supplies and mortality attributed to colon cancer and (2) to determine whether calcium levels (Ca) in drinking water modify the effects of TTHM on risk to develop colon cancer. A matched cancer case-control study was used to investigate the relationship between the risk of death attributed to colon cancer and exposure to TTHM in drinking water in 53 municipalities in Taiwan. All colon cancer deaths in the 53 municipalities from 1998 through 2007 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels in drinking water were collected from the Taiwan Environmental Protection Administration. Information on the levels of Ca in drinking water was obtained from the Taiwan Water Supply Corporation. The municipality of residence for cancer cases and controls was presumed to be the source of the subject's TTHM and Ca exposure via drinking water. Relative to individuals whose TTHM exposure level was <4.9 ppb, the adjusted OR (95% CI) for colon cancer was 1.14 (1.01-1.28) for individuals who resided in municipalities served by drinking water with a TTHM exposure ≥4.9 ppb. Data demonstrated evidence of an interaction between drinking-water TTHM concentrations and Ca intake via drinking water. Our findings showed that the correlation between TTHM exposure and risk of colon cancer development is influenced by Ca in drinking water. Increased knowledge of the interaction between Ca and TTHM in reducing colon cancer risk will aid in public policymaking and standard setting. [ABSTRACT FROM AUTHOR]

Tissue distribution and urinary excretion of nicotine, cotinine, and hydroxycotinine after multiple oral administration of nicotine to rats for 4 weeks were studied. Physiological change and serum biochemical parameters were also measured to check dysfunction of organs. Significant change of glutathione S-transferase, aspartate aminotransferase, blood urea nitrogen, and physiological parameters indicated the toxicity in liver and kidney, at the dose of 5 and 10 mg/kg/day. Only the concentration and total amount of cotinine, not nicotine or hydroxycotinine, in the liver and the kidney showed a proportional dose-dependent increase and were highly correlated with toxicity. Saturation of metabolizing enzymes for nicotine was estimated by the change of urinary excreted amount ratio between nicotine and its metabolites. Metabolizing enzyme to produce cotinine from nicotine was saturated after multiple oral dosing for 4 weeks in a low dose (1 mg/kg/day), but within 1 week in the dose of 5 and 10 mg/kg/day. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate whether exposure to disinfection by-products (DBP) is associated with colon cancer. A matched case-control study was used to investigate the relationship between the risk of death attributed to colon cancer and exposure to total trihalomethanes (TTHM) in drinking water in 65 municipalities in Taiwan. All colon cancer deaths of the 65 municipalities from 1997 through 2006 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels in drinking water in study municipalities were collected from the Taiwan Environmental Protection Administration. The municipality of residence for cancer cases and controls was assumed to be the source of the subject's TTHM exposure via drinking water. The adjusted odds ratios (OR) for colon cancer death for those with high TTHM levels in their drinking water were 1.02 (0.87-1.2) and 1.04 (0.89-1.21) compared to the lowest group. The results of the present study show that there was no statistically significant association between TTHM in drinking water at levels in this study and risk of death from colon cancer. [ABSTRACT FROM AUTHOR]

Objectives. Over the last few decades, important changes occurred in the pharmacological approach to asthma control. However, the possible link between pharmacologic treatment and asthma death remains controversial. Study Design and Setting. Age-standardized asthma mortality rates were computed over the 1994-2004 period for France, Germany, Spain, the UK, and Italy. Rates for children and young adults 5 to 34 years of age, middle age adults 35 to 64 years of age, and elderly adults ≥ 65 years. Joinpoint regression was performed to identify years where significant changes in mortality trends occurred. Consumption of inhaled long-acting beta-2-agonists (LABA), including inhaled corticosteroids (ICS) when combined with LABAs in a single inhaler, derived from sales estimates. Results. In 1994, the highest asthma mortality rates were in Germany (4.7/100,000), and the lowest ones were in Italy and Spain (0.5/100,000). Steady downward trends were observed in all the countries considered. The largest decline was registered in Germany and the smallest one was in the UK. LABA sales increased steadily since 1994, particularly in France, Spain, and the UK, reaching values around 14 Defined Daily Doses (DDD)/1,000 inhabitants in 2004. Conclusion. While the use of LABAs (with or without ICS) increased over the last decade, asthma mortality declined in major western European countries. [ABSTRACT FROM AUTHOR]

We conducted a systematic review of studies evaluating the diagnostic accuracy of all the ultrasound based tests of ovarian reserve, including antral follicle count (AFC), ovarian volume and stromal blood flow in predicting fertility outcomes and, where appropriate, performed a meta-analysis to determine the predictive_value at each cut-off value described in the literature. Included in the analysis were 17 studies for AFC, six studies for ovarian volume and six studies for stromal blood flow. Meta-analyses showed that women with AFC less than four were 8.7 times more likely not to get pregnant after IVF (two studies; 95% CI, 2.4-31.7) than women with AFC four or more. The sensitivity and specificity of AFC to predict cycle cancellation was 66.7% and 94.7%, respectively. Women with an AFC of less than four were 37 times (two studies; 95% CI, 13.68-100.45) more likely to have their cycle cancelled than women with AFC of four or more. Ovarian volume measurement, at a cut off value of 3 cm3, showed specificity for prediction of cycle cancellation and non-pregnancy of 92% (three studies, 95% CI, 89-94) and 93% (three studies, 95% CI, 87-97), respectively. The clinical value of Doppler studies for ovarian stromal blood flow was unclear. [ABSTRACT FROM AUTHOR]

Reactive chemicals have been used to disinfect drinking waters for over a century. In the 1970s, it was first observed that the reaction of these chemicals with the natural organic matter (NOM) in source waters results in the production of variable, complex mixtures of disinfection by-products (DBP). Because limited toxicological and epidemiological data are available to assess potential human health risks from complex DBP mixture exposures, methods are needed to determine when health effects data on a specific DBP mixture may be used as a surrogate for evaluating another environmental DBP mixture of interest. Before risk assessors attempt such efforts, a set of criteria needs to be in place to determine whether two or more DBP mixtures are similar in composition and toxicological potential. This study broadly characterizes the chemical and toxicological measures that may be used to evaluate similarities among DBP mixtures. Variables are discussed that affect qualitative and quantitative shifts in the types of DBP that are formed, including disinfectants used, their reactions with NOM and with bromide/iodide, pH, temperature, time, and changes in the water distribution system. The known toxicological activities of DBP mixtures and important single DBPs are also presented in light of their potential for producing similar toxicity. While DBP exposures are associated with a number of health effects, this study focuses on (1) mutagenic activity of DBP mixtures, (2) DBP cancer epidemiology, and (3) toxicology studies to evaluate similarity among DBP mixtures. Data suggest that further chemical characterization of DBP mixtures and more systematic study of DBP toxicology will improve the quality and usefulness of similarity criteria. [ABSTRACT FROM AUTHOR]

Although chemical disinfection of drinking water is a highly protective public health practice, the disinfection process is known to produce toxic contaminants. Epidemiological studies associate chlorinated drinking water with quantitatively increased risks of rectal, kidney, and bladder cancer. One study found a significant exposure-response association between water mutagenicity and relative risk for bladder and kidney cancer. A number of studies found that several types of disinfection processes increase the level of mutagens detected by the Salmonella assay. As part of a comprehensive study to examine chlorinated and ozonated/postchlorinated drinking water for toxicological contaminants, the Salmonella mutagenicity assay was used to screen both volatile and nonvolatile organic components. The assay also compared the use of reverse osmosis and XAD resin procedures for concentrating the nonvolatile components. Companion papers provide the results from other toxicological assays and chemical analysis of the drinking water samples. The volatile components of the ozonated/postchlorinated and chlorinated water samples and a trihalomethane mixture were mutagenic to a Salmonella tester strain transfected with a rat theta-class glutathione S-transferase and predominantly nonmutagenic in the control strain. In this study, the nonvolatile XAD concentrate of the untreated water possessed a low level of mutagenic activity. However, compared to the levels of mutagenicity in the finished water XAD concentrates, the contribution from the settled source water was minimal. The mutagenicity seen in the reverse osmosis concentrates was < 50% of that seen in the XAD concentrates. Overall, mutagenic responses were similar to those observed in other North American studies and provide evidence that the pilot plant produced disinfection by-products similar to that seen in other studies. [ABSTRACT FROM AUTHOR]

Random controlled trials on the efficacy of naltrexone and acamprosate in the treatment of alcohol dependence were reviewed, using a Relative Benefit (RB) analysis approach. A total of 42 studies were included, showing acamprosate use demonstrated a modest improvement, with a RB of 1.76 at three month follow-up. Short-term administration of naltrexone significantly reduced the relapse rate, but was not associated with modification in the abstinence rate. There was insufficient data available to ascertain the efficacy of naltrexone and acamprosate over prolonged periods of time, or the effectiveness of the medications relative to each other. [ABSTRACT FROM AUTHOR]

Meta- and pooled analyses are increasingly applied to aggregate the results of a number of studies, especially in health sciences. A typical difficulty is the presence of a publication bias. Usually Egger's regression test and funnel plots are applied to detect such a publication bias. A simulation study was conducted to investigate the quantity of null and negative results required to be omitted to detect a publication bias. In particular, the performance of Egger's test and funnel plots was considered in two scenarios with binary outcomes and expected odds ratios (OR) of 1 and 2, respectively. For both scenarios Egger's test detected only a small fraction of publication biases if few studies were deleted, corresponding to the results of a random deletion. Moreover, if a true null effect is present Egger's test is quite unlikely to detect a publication bias even if a considerable proportion of the null results are missing. Generally, the detection of a publication bias using Egger's test is only likely if both the “true” effect and the bias are large enough. Visual inspection of the funnel plots resulted in a higher fraction of detected publication biases in cases where a bias was present and in cases where studies were randomly deleted, revealing the arbitrariness of this method. Evidence indicates that standard methods for detection of a publication bias do not necessarily detect such a bias; thus, additional tests for publication bias need to be applied. [ABSTRACT FROM AUTHOR]

Perhaps the most valuable contribution of Bayesian methods to health care evaluation involves study design. Drug and medical device clinical trialists are increasingly confronted with data that feature complex correlation structures, and are costly and difficult to obtain. In such settings, Bayesian trial designs are attractive since they can incorporate historical data or information from published literature, thus saving time and expense and minimizing the number of subjects exposed to an inferior treatment. Bayesian designs can also adapt to unexpected changes in the protocol, and allow the investigator to explore the plausibility of various outcome scenarios before any patients are enrolled in the trial. Recently, the FDA Center for Devices has encouraged hierarchical Bayesian statistical approaches which allow for the incorporation of such valuable historical data into the design and analysis of new device trials. The practical application of these methods has only become feasible in the last decade due to advances in computing via Markov chain Monte Carlo (MCMC) methods, especially as implemented in the popular BUGS software package. In this paper we illustrate Bayesian analysis and sample size calculations using BRugs, a function for calling BUGS from R. We provide illustrations in two applied settings where incorporation of available historical information is crucial, one concerning an AIDS drug trial and the other a comparison of left ventricular assist devices (LVADs). [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the reporting quality of key methodological items in randomized controlled trials (RCTs) in four general clinical ophthalmology journals.Methods: The reporting of 11 key methodological items in RCTs published in American Journal of Ophthalmology, Archives of Ophthalmology, British Journal of Ophthalmology and Ophthalmology in the year 2005 was assessed. Results : Sixty-seven eligible RCTs were assessed and the mean number of items reported was 6.3 per RCT. No significant difference in the mean number of items reported was found between the four journals (P = 0.20). The most frequently reported item was ethics approval and informed consent (97.0%), followed by masking status (85.1%), description of withdrawals (76.1%), adverse events (73.1%), and intention-to-treat analysis (71.6%). Details on sequence generation, randomization restriction, allocation concealment, allocation implementation, patient flow diagrams, and sample size calculation were reported in < 50% of the RCTs assessed. Both sample size and page length of the RCTs correlated with the number of methodological items reported (P = 0.024 and P = 0.008, respectively). Conclusions: Similar to other specialties, rooms for improvement exist in the reporting of key methodological items of RCTs in clinical ophthalmic journals. Stricter adoption of the CONSORT statement might enhance the reporting quality of RCTs in ophthalmic journals. [ABSTRACT FROM AUTHOR]