Variety Of Methodological Problems Research Articles

Critical Appraisal of the Literature for Adjuvant Chemoradiation for p16+ Oropharynx Cancer: Definitive Management of Head-and-Neck Squamous Cell Carcinoma

The presence of extracapsular spread (ECS) in traditional head and neck cancer generally results in the use of adjuvant chemoradiation (CRT). The NCCN level of evidence for this recommendation is “Category 1”, ie, “based upon high-level evidence”. In the case of oropharynx cancer (OPC), this recommendation and the clinical research from which it is based do not reflect p16 status. Increasing number of observational studies report that p16+ OPC patients have more favorable outcomes and require less aggressive treatment than traditional OPC patients. We reviewed and critically appraised the research upon which the recommendation for adjuvant CRT is based and assessed its relevance in the p16+ era. A review and critical appraisal of the published articles for trials RTOG 9501 and EORTC 22931, the collaborative comparative analysis of both trials, and the long-term follow-up of RTOG 9501 was performed. Particular attention was given to the design, conduct, analysis, results reporting, and generalizability using standard methodological criteria. A variety of methodological problems were identified. The study populations included a variety of sub sites (oral cavity, oropharynx, larynx, hypopharynx) and in RTOG 9501 included a preponderance of good prognosis sites in the CRT arm. In neither trial was p16 status determined and overall severity of comorbidity reported. Multiple patients were excluded after randomization. Results were presented as relative and not absolute effects. Univariate and unplanned sub-group analyses presented for positive margin and/or ECS; effect of CRT on ECS alone not reported. Multivariable analyses, appropriate for heterogeneity in patient and tumor factors, not done. No patient-reported outcomes reported. Impact of sample size and possibility of spurious findings with sub-group analyses not acknowledged. This critical appraisal of the literature on the role of adjuvant CRT in OPC patients with ECS identified multiple problems. Flaws in trial conduct and analysis, along with other shortcomings, undermine internal validity. Results of the trials are not generalizable to newly diagnosed patients in the p16+ era. The literature upon which the guidelines for the use of adjuvant CRT are based is neither methodologically sound nor relevant to the current management of p16+ OPC patients with ECS.

Affective Modulation of the Startle Reflex Is an Ineffective Methodology to Examine Depression-Linked Interpretative Biases

Cognitive theory predicts that depression is associated with a bias to interpret ambiguous information in a mood-congruent fashion. This negative interpretative bias may serve as a maintenance factor for the continuation of a depressed mood state. The majority of studies investigating such interpretative biases suffer from a variety of methodological problems. This research has utilized an objective physiological measure involving the affective modulation of the human eye blink reflex in 25 depressed and 25 control subjects by depressive, depressive-ambiguous, and distorted stimuli. Almost half of the depressed subjects suffered from a comorbid anxiety disorder. In contrast to previous research utilizing the same methodology, depressed participants did not react differently to non-depressed participants in terms of their blink reflex response to the various stimuli types. This outcome is ascribed to the exclusion of anxiety-related stimuli in the current study. Depression-related stimuli failed to augment blink amplitudes in both subject groups. Therefore, affective modulation of the startle reflex is an ineffective methodology for the detection of depression-linked interpretative biases, as there is no difference to how individuals react to depressive and neutral stimuli. In this study, patients diagnosed with social anxiety disorder reacted to difficult-to-identify stimuli with augmented blink amplitudes, interpreted as an anxiety response.

REporting recommendations for tumor MARKer prognostic studies (REMARK)

Despite years of research and hundreds of reports on tumor markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodologic problems have been cited to explain these discrepancies. Unfortunately, many tumor marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results. The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomized trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, pre-planned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

Prophylactic Antibiotic Use in Open Fractures: An Evidence-Based Guideline

Prolonged courses of broad-spectrum antibiotics are often cited as the standard of care for prevention of infective complications of open fractures. The origins of these recommendations are obscure, however, and multi-drug-resistant systemic infections attributable to antibiotic overuse are common life-threatening problems in current intensive care unit practice. To review systematically the effects of prophylactic antibiotic administration on the incidence of infections complicating open fractures. Computerized bibliographic search of published research and citation review of relevant articles. All published clinical trials claiming to evaluate, or cited elsewhere as being authoritative regarding, the role of antibiotics in open fracture management were identified and then evaluated according to published guidelines for evidence-based medicine. Only small studies (<20 patients), practice surveys, pharmacokinetic studies, and reviews or duplicative publications presenting primary data already considered were excluded from analysis. Information on demographics, study dates, fracture grade, antibiotic type, duration and route of administration, surgical interventions, infection-related outcomes, and the methodologic quality of the studies was extracted by the authors. The primary results were submitted to the Therapeutic Agents Committee of the Surgical Infection Society for review prior to creation of the final consensus document. Current antibiotic management of open fractures is based on a small number of studies that generally are more than 30 years old and do not reflect current management priorities in trauma and critical care. With a few noteworthy exceptions, these primary studies suffer from a variety of methodologic problems, including co-mingling of prospective and retrospective data sets, absence of or inappropriate statistical analysis, lack of blinding, or failure of randomization. The data support the conclusion that a short course of first-generation cephalosporins, begun as soon as possible after injury, significantly lowers the risk of infection when used in combination with prompt, modern orthopedic fracture wound management. There is insufficient evidence to support other common management practices, such as prolonged courses or repeated short courses of antibiotics, the use of antibiotic coverage extending to gram-negative bacilli or clostridial species, or the use of local antibiotic therapies such as beads. Large, randomized, blinded trials are needed to prove or disprove the value of these traditional approaches. Such trials should be performed in patients with high-grade fractures who (1) are well-stratified according to the degree of local injury and (2) undergo standardized fracture and wound management. Trials also must be powered to study the effects of extended antibiotic coverage on nosocomial infections. Antibiotic regimens confirmed to improve local fracture outcomes in such studies could then be used rationally, balancing the risks of local fracture-related infections and of multi-drug-resistant systemic infections to achieve optimal global outcomes.

Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK)

Despite years of research and hundreds of reports on tumor markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often, initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodologic problems have been cited to explain these discrepancies. Unfortunately, many tumor marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results. The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomized trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, preplanned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

REporting recommendations for tumor MARKer prognostic studies (REMARK)

Despite years of research and hundreds of reports on tumor markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons why multiple studies of the same marker lead to differing conclusions. A variety of methodological problems have been cited to explain these discrepancies. Unfortunately, many tumor marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results. The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomized trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, preplanned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines provide helpful suggestions on how to present data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

REporting recommendations for tumour MARKer prognostic studies (REMARK)

Despite years of research and hundreds of reports on tumour markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodological problems have been cited to explain these discrepancies. Unfortunately, many tumour marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalisability of the study results. The development of guidelines for the reporting of tumour marker studies was a major recommendation of the US National Cancer Institute and the European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. Similar to the successful CONSORT initiative for randomised trials and the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, preplanned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

REporting recommendations for tumour MARKer prognostic studies (REMARK)

Despite years of research and hundreds of reports on tumour markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodologic problems have been cited to explain these discrepancies. Unfortunately, many tumour marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalisability of study results. The development of guidelines for the reporting of tumour marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomised trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, pre-planned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

Individual Investor Sentiment and Stock Returns - What do we learn from individual warrant traders?

There is a huge literature on investor sentiment measures and their relation to stock returns. However, extant sentiment measures are subject to a variety of methodological problems. We propose and empirically test a new measure of individual investor sentiment, that is derived from the market for bank-issued warrants. With our measure we simultaneously avoid several problems of other sentiment measures. We find empirical evidence that there exits an interaction effect between individual investors sentiment and stock market returns in the short-run. Investor sentiment is influenced by the return of big company stocks and their volatility and itself influences the returns of those big companies and even more the returns of small companies. Our findings are consistent with the theory of DeLong, Shleifer, Summers, and Waldmann (1990).

Video game violence: A review of the empirical literature

The popularity of video games, especially violent video games, has reached phenomenal proportions. The theoretical line of reasoning that hypothesizes a causal relationship between violent video-game play and aggression draws on the very large literature on media violence effects. Additionally, there are theoretical reasons to believe that video game effects should be stronger than movie or television violence effects. This paper outlines what is known about the relationship between violent video-game playing and aggression. The available literature on virtual reality effects on aggression is discussed as well. The preponderance of the evidence from the existing literature suggests that exposure to video-game violence increases aggressive behavior and other aggression-related phenomena. However, the paucity of empirical data, coupled with a variety of methodological problems and inconsistencies in these data, clearly demonstrate the need for additional research.

Sudden infant death syndrome and parental smoking--a literature review.

There are a variety of methodological problems with published studies of parental smoking and sudden infant death syndrome (SIDS), with over-control the most consistent and problematic. Nevertheless, even though this is likely to minimise the true magnitude of relationships, the results are consistent. There are five cohort studies with prospectively collected information on maternal smoking in pregnancy: all show strong and statistically significant relationships that were dose dependent-the more cigarettes the mother had smoked, the more at risk was the baby of SIDS. Similar results have been shown from the case-control studies in which information has been collected retrospectively from parents or birth certificates. There are data from several studies indicating that environmental tobacco smoke (ETS) is also important. Since it has not yet been possible to determine conclusively whether associations are with smoking (or ETS) during pregnancy or postnatally, it is concluded that both should be discouraged.

Long-term outcome of panic disorder treatment. A review of the literature.

This review was designed to provide a detailed analysis of long-term outcome data from treatment studies for panic disorder, with the goal of ascertaining differential efficacy of the available treatments. Studies were included if they were published after 1980 and if follow-up took place at least 6 months after treatment termination. Thirty-one studies were located. A variety of methodological problems were found in these studies, including lack of clarity of diagnosis, lack of clarity in the treatment administered, and inadequately tracked nonstudy treatments during the study and follow-up periods, which limited the information that could be obtained about long-term outcome. Long-term outcome studies that closely track the additional treatments that patients receive are necessary to draw more definitive conclusions about differential treatment efficacy for panic disorder. Available data suggest that there is limited evidence for long-term maintenance of short-term treatment gains in panic disorder patients in the absence of continued treatment.

Epidemiology of potential association between l-tryptophan ingestion and eosinophilia-myalgia syndrome

This article examines the methodology of the epidemiological studies of the association between l-tryptophan and eosinophilia-myalgia syndrome (EMS) and evaluates the validity of the conclusions from these studies. In the initial case-control studies of l-tryptophantryptophan and EMS there were a variety of methodological problems, including different sources and different exclusion criteria for cases and controls, which could have resulted in selection bias, as well as problems with information bias and confounding. The studies of manufacturer and brand also had similar potential for bias. The l-tryptophan-EMS association is based on two small studies that had important methodological inadequacies. Subsequent studies of brand of l-tryptophan also contained errors in design, which may have produced biased results and call the conclusions into question. The cause of eosinophilia-myalgia syndrome remains unknown.

Neuropsychology of post-polio syndrome.

The sparse literature concerning the psychology of PPS is easy to summarize. Some psychopathology can be observed in PPS, but it is not clear whether it is a reaction to PPS or a by‐product of a concurrent but unrelated disorder. Psychopathology does not seem to be responsible for the onset or intensity of new PPS symptoms. A relationship may exist between the perception of stress, an inability to handle stress, and perceived fatigue in PPS. Neuropsychological studies have been equivocal with patients performing well on some tests and more poorly on others compared to controls. An attempt has been made to link reticular formation and hypothalamic involvement in PPS to decreased attention and arousal and increased fatigue. Higher levels of fatigue have been associated with the presence of hyperintensities on MRI scanning. Unfortunately, a variety of methodological problems are present with most of these studies and indicate that caution should be used in their interpretation (see section on Methodological Considerations).Future studies should adapt more stringent controls in subject selection so that non‐PPS factors that might affect behavior or cognition can be factored out (e.g., hypertension or exogenous depression). Tests specifically designed to evaluate components of attention and motor control can be used to test hypotheses regarding fatigue, arousal, and attention. Our experience is that patients carefully selected to have pure PPS without concurrent medical disease have few complaints about cognition or altered mood. Before we pronounce neuropsychological deficits in PPS patients, more carefully designed studies are required.

A review of current evidence concerning possible reproductive hazard from VDUs

Abstract Widespread concern exists as to the possible hazards to reproduction of work with visual display units or VDUs, the use of which has expanded dramatically in the last 20 years. This is part of a more general concern about the health effects of such technology which is being tackled by ergonomic research recommendations. Concern over a possible hazard to pregnancy appears to have its origins in ‘cluster’ reports, but these are not proof of an effect. Critical review of some eleven studies in this area reveals that there are a variety of methodological problems involved in the design and interpretation of the results of this research, but their authors have generally concluded that they found no evidence of an effect. Research continues, but there are clear indications of a need for prospective studies which will provide reassurance that this technology can be used safely by working women planning a family, and investigate the possible role of factors such as stress and the effect of VDU work on me...

4. Researching the New Industrial Relations

Regardless of judgements about the novelty, permanence or extent of the “new industrial relations”, key features in the USA are a decline in union membership, the declining role of bargaining and a corresponding decrease in its scope; the increasing importance of human resource management; the increasing importance of “high‐tech” industries; the increasing need for a “responsible, flexible” worker; the conscious attempt to avoid and undermine unions by firms through location policies and sophisticated paternalism; the attempt to link pay more directly to the economic performance of the plant or firm through gain‐saving schemes, profit‐sharing and fragmented bargaining. It should not be assumed that these developments are widespread or actually represent a change in the management of people. A variety of methodological problems exist making it difficult to assess whether these features are in themselves “new”, notably those relating to the danger of generalising from specific and isolated cases, the problem of benchmarks, links between managerial intentions and practice, the measurement of attitudinal change and the notion of management strategy in itself. To demonstrate these problems and to provide documentary evidence current practices in the US car industry are examined, particularly to evaluate recent change. A multitude of research methods (including participant observation) are required in order to capture all the dimensions of shop‐floor industrial relations behaviour.

Epidemiology of hypertension associated with diabetes mellitus.

The clinical impression of an association between hypertension and diabetes mellitus has not been consistently confirmed by epidemiological studies. The variety of methodological problems in this area of research includes the choice of appropriate patient and control groups, the measurement techniques used, and consideration of many possible confounding variables. Several prospective studies have shown that hypertension may be a potent risk factor for diabetic macrovascular and microvascular disease. This relationship may have important preventive implications, and raises the question of the optimal antihypertensive therapy in diabetic patients.

Capillary gas chromatography measurement of oxalate in plasma and urine

Oxalic acid can be measured reliably in urine by colorimetric methods [1] and is useful for the diagnosis of hyperoxaluric states that result in nephrolithiasis. The measurement of plasma oxalic acid has been far more difficult due to its very low concentration in normal plasma and a variety of methodologic problems. Normal plasma oxalic acid, measured by in vivo isotopic dilution, has been reported in the range of —l mo1es/liter (-9 g/dl) [2—4]. Far higher values, obtained by most published methods [5, 6] suggest a lack of specificity that would obscure variations in normal levels. The difficulty in preserving specimens, the lack of a way of monitoring interference, and the need for very large sample volumes makes enzymatic methods [7] less than ideal. Recently, Wolthers and Hayer [81 reported a capillary gas chromatographic method for measuring plasma oxalic acid that gave a normal range closer to that obtained by in vivo isotopic dilution [41. We have adapted and verified this method for measuring urinary and plasma oxalic acid and applied the method to normal adults and patients with primary hyperoxaluria. These patients have been studied during renal insufficiency, during hemodialysis, and with various levels of renal function after renal transplantation. Methods. Urine specimens were collected for 24 hr on ice, acidified to a pH of less than 2.0 with HCI (1:100 v/v), and frozen at —20°C or —70°C until analysis. To triplicate 0.5 ml samples we added malonic acid (15 pg), a further two drops of 6 N HCI, and 1 g NaC1. Heparinized blood was collected on ice, the plasma separated (X2000 g, 20 mm) within 1 hr of collection, and 0.5-ml aliquots acidified with two drops of HC1 and frozen (—70°C) in microfuge tubes (Sarsted). Samples were partially thawed to transfer of the frozen/precipitated sample, containing 2 g of malonic acid and 1 g NaC1, with one rinse of 0.5 ml of 0.1 N HCI. For either urine or plasma aliquots, a 4-mm vigorous solvent extraction with 6 ml of ethyl acetate was performed twice. Ethyl acetate was evaporated at 35°C under anhydrous N2, placed under P205 in vacuo for 30 mm and organic acids derivatized in the same tube with 50 to 150 (urine) or 30 tl (plasma) of 30:1 (v/v) mixture of bis-trimethylsilyltrifluoroacetamide (BSTFA) (Regis Chemical Co., Morton

Work Factors as Potential Causal Agents of Alcohol Abuse

The notion that an individual's work may contribute to alcohol abuse is a central theme in the job-based alcoholism literature. A review of the theoretical formulation and empirical studies on this topic, however, revealed that unequivocal evidence of such linkages is scarce. A variety of methodological problems and the absence of a unifying theory of job-based consumption are blamed for this shortcoming. In an attempt to begin building a causal literature, the methodological problems and some solutions are outlined. In addition, the basis for a theory is presented by proposing three causal pathways: a job requirement pathway, a social influence pathway and a job response pathway. The latter two pathways are discussed in detail and a variety of research areas are outlined.

Drug and alcohol education programs: a review of outcome studies.

Outcome studies of the effectiveness of drug and alcohol education programs are reviewed. Studies were examined that dealt with student populations as well as adult programs. In addition, specific population variables and methods of presentation were evaluated for their impact on the education process. The data indicate that these programs have been ineffective in obtaining the goals of reducing substance abuse or preventing future abuse. Among student populations there is evidence to suggest that these programs may exacerbate the use and sale of drugs and alcohol. The data on programs with adults are more encouraging though far from conclusive. Suggestions for future outcome studies in the area are enumerated with emphasis on the variety of methodological problems that exist in the literature to date.