No news is still good news: well-conducted studies with negative results make for a stronger evidence base

The literature on the subject of treatment of glomerular disease is immense (over 15,000 articles in PubMed as of July, 2008). Negotiating this broad and complex panorama can be a difficult task, especially in relationship to the evaluation of the best evidence for a particular treatment strategy for a specific disease entity occurring in an individual patient. Perfection is not attainable in clinical trials of therapy and every report has some pitfall or limitation. Some studies, however, stand out as excellent examples of design and execution. Unfortunately, in the field of treatment of glomerular disease such studies are relatively uncommon. The good news is that well designed and executed studies of treatment of primary glomerular disease are being reported with increasing frequency in recent years. This has occurred in part because of increased collaboration among groups interested in furthering knowledge in this important area of inquiry, but also because of better recognition of the deficiencies of past efforts to study treatment of glomerular disease in clinical trials. Many interinstitutional collaborative studies have been aided by improvements in trial design and by more complete descriptions of the natural history of untreated disease. One of the main weaknesses of clinical studies of therapy in primary glomerular disease is the small numbers of subjects studied in individual reports. This increases the risks of confounding and of both false positive and false negative results. The purpose of this chapter is to provide a concise analysis of the strengths and weakness of the various approaches to the study of therapeutic efficacy and safety of agents used in primary glomerular disease. The focus will be on observational studies, controlled clinical trials, and meta-analyses of published reports. The specific aims are to equip the discerning reader for improved understanding of the evidence-base for therapy of primary glomerular disease. The details of the specific reports and how they can be integrated into an ‘evidence-based’ approach to therapeutic decision-making are dealt with in the chapters devoted to specific disease entities which follow.

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Citation bias and selective focus on positive findings in the literature on the serotonin transporter gene (5-HTTLPR), life stress and depression

Psychological Medicine ◽

10.1017/s0033291716000805 ◽

2016 ◽

Vol 46 (14) ◽

pp. 2971-2979 ◽

Cited By ~ 19

Author(s):

Y. A. de Vries ◽

A. M. Roest ◽

M. Franzen ◽

M. R. Munafò ◽

J. A. Bastiaansen

Keyword(s):

Serotonin Transporter ◽

Life Stress ◽

Web Of Science ◽

Evidence Base ◽

Transporter Gene ◽

Negative Results ◽

Research Findings ◽

Citation Bias ◽

The Impact ◽

Positive Focus

BackgroundCaspi et al.'s 2003 report that 5-HTTLPR genotype moderates the influence of life stress on depression has been highly influential but remains contentious. We examined whether the evidence base for the 5-HTTLPR–stress interaction has been distorted by citation bias and a selective focus on positive findings.MethodA total of 73 primary studies were coded for study outcomes and focus on positive findings in the abstract. Citation rates were compared between studies with positive and negative results, both within this network of primary studies and in Web of Science. In addition, the impact of focus on citation rates was examined.ResultsIn all, 24 (33%) studies were coded as positive, but these received 48% of within-network and 68% of Web of Science citations. The 38 (52%) negative studies received 42 and 23% of citations, respectively, while the 11 (15%) unclear studies received 10 and 9%. Of the negative studies, the 16 studies without a positive focus (42%) received 47% of within-network citations and 32% of Web of Science citations, while the 13 (34%) studies with a positive focus received 39 and 51%, respectively, and the nine (24%) studies with a partially positive focus received 14 and 17%.ConclusionsNegative studies received fewer citations than positive studies. Furthermore, over half of the negative studies had a (partially) positive focus, and Web of Science citation rates were higher for these studies. Thus, discussion of the 5-HTTLPR–stress interaction is more positive than warranted. This study exemplifies how evidence-base-distorting mechanisms undermine the authenticity of research findings.

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METHODS OF SCREENING FOR TB INFECTION IN CHILDREN AND THEIR ROLE IN THE FORMATION OF RISK GROUPS AND DIAGNOSIS OF THE DISEASE

Российский педиатрический журнал ◽

10.18821/1560-9561-2017-20-2-108-115 ◽

2019 ◽

Vol 20 (2) ◽

pp. 108-115

Author(s):

Elena S. Ovsyankina ◽

M. F. Gubkina ◽

L. V. Panova ◽

N. V. Yukhimenko

Keyword(s):

High Sensitivity ◽

Tuberculin Test ◽

Risk Groups ◽

Evidence Base ◽

Screening Tests ◽

Mantoux Test ◽

Negative Results ◽

Immunological Tests ◽

To Come ◽

The Cost

In the review there are presented possibilities of the application of skin immunological tests -Mantoux test (MT) 2TE, as a specific diagnostic test - intradermal Mantoux tuberculin test with two tuberculin units; PPD-L - injectable form of purified tuberculin in standard dilution. L-tuberculin by Linnikova (MT with 2 TE PPD-L = MT) and samples with recombinant tuberculosis allergen (RTA) for the formation of high-risk groups and diagnosis of TB infection in children. Screening investigations with the use of MT have a high sensitivity (95-98%), which is an advantage of MT as the evidence base. The insufficient sensitivity of the Diaskintest® skin test (DST) preparation has been established by independent researchers (78-85% of cases of active TB are missed). The special attention was shown to have to assess the cost effectiveness of screening tests with RTA. 98% of negative results in the screening with RTA were revealed to be very expensive unreasonably. These patients failed to come in sight of health professionals, although among them there may be cases with different stages of latent TB infections requiring medical supervision by phthisiatrician. To solve the issue concerning mass application of RTA test its safety profile should be studied.

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Reproductive Disorders

Inference: International Review of Science ◽

10.37282/991819.15.6 ◽

2015 ◽

Vol 1 (2) ◽

Author(s):

Michael Fumento

Keyword(s):

Biomedical Research ◽

Bad News ◽

Good News ◽

Reproductive Disorders ◽

Social Scientists ◽

Negative Results ◽

Positive Results

In biomedical research, good news is not only admired but indispensable. Negative results are less likely to be published than positive results; the trend is increasing at the rate of about six percent per year. A 2014 survey of social scientists found them largely unwilling to pass along bad news: “Why bother?” was the most commonly given explanation.

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Negative results of humoral immunity after anti-SARS-CoV-2 vaccination in patient with advanced ovarian cancer treated with maintenance immunotherapy and targeted therapy: a clinical case and а literature review

Malignant tumours ◽

10.18027/2224-5057-2021-11-1-5-8 ◽

2021 ◽

Vol 11 (1) ◽

pp. 5-8

Author(s):

A. A. Rumyantsev

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Clinical Case ◽

Viral Vector ◽

Advanced Ovarian Cancer ◽

Evidence Base ◽

Post Vaccination ◽

Vector Vaccine ◽

Negative Results ◽

Viral Vector Vaccine

Gam-COVID-Vac (Sputnik V, Gamaleya Research Institute of Epidemiology and Microbiology of Ministry of Health of Russian Federation) is an adenovirus viral vector vaccine for COVID-19 which became the very first vaccine against SARS-CoV-2 registered in Russia and worldwide. The vaccine efficacy and safety in cancer patients is unknown. We present a clinical case of the absence of post-vaccination immunity after the use of Gam-COVID-Vac in a patient with advanced ovarian cancer treated with maintenance targeted and immunotherapy and discuss it in the light of the available evidence base on the effectiveness of other anti-SARS CoV-2 vaccines in cancer patients.

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A systematic review on the role of anticonvulsants in the treatment of acute bipolar depression

The International Journal of Neuropsychopharmacology ◽

10.1017/s1461145712000491 ◽

2012 ◽

Vol 16 (2) ◽

pp. 485-496 ◽

Cited By ~ 28

Author(s):

María Reinares ◽

Adriane R. Rosa ◽

Carolina Franco ◽

José Manuel Goikolea ◽

Kostas Fountoulakis ◽

...

Keyword(s):

Bipolar Depression ◽

Small Sample Size ◽

Evidence Base ◽

Small Sample ◽

Current Evidence ◽

High Morbidity ◽

Eligibility Criteria ◽

Double Blind ◽

Negative Results

Abstract Despite the high morbidity and mortality associated with bipolar depression, the optimal treatment for this phase is still a matter of debate. The aim of the current review was to provide updated evidence about the efficacy and tolerability of anticonvulsants in the treatment of acute bipolar depression. A comprehensive review of randomized controlled trials (RCTs) evaluating the use of anticonvulsants for the treatment of acute bipolar depression up to June 2011 was conducted by means of the PubMed-Medline database. Eligibility criteria included active comparator-controlled or placebo-controlled randomized studies involving monotherapy or combination therapy. A total of 18 RCTs fulfilled the inclusion criteria. Studies supported the efficacy of divalproex as monotherapy in acute bipolar depression but small sample size was a common methodological limitation. Findings were inconclusive for lamotrigine and carbamazepine although overall lamotrigine may have a beneficial but modest effect. Negative results were found for levetiracetam and gabapentin but the evidence base on these agents is scant. All anticonvulsants were generally well tolerated. No double-blind RCTs were found for the use of other anticonvulsants such as oxcarbazepine, licarbazepine, zonisamide, retigabine, pregabalin, tiagabine, felbamate and vigabatrine in the acute treatment of bipolar depression. To sum up, taking into consideration the efficacy and tolerability profiles of anticonvulsants, current evidence supports the use of divalproex and lamotrigine in the treatment of acute bipolar depression. However, available data for most other anticonvulsants are inconclusive and further RCTs with larger sample sizes are needed before drawing firm conclusions.

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Classifying Disfluencies in Preschool- and School-Age Spanish–English Bilinguals Who Do Not Stutter: An Exploratory Study

Perspectives of the ASHA Special Interest Groups ◽

10.1044/2019_persp-19-00164 ◽

2020 ◽

Vol 5 (1) ◽

pp. 119-130

Author(s):

Raúl Rojas ◽

Farzan Irani

Keyword(s):

Exploratory Study ◽

Evidence Base ◽

Medium Effect ◽

Bilingual Children ◽

Linear Regression Models ◽

Cross Sectional ◽

Total Percentage ◽

Narrative Production ◽

Language Measures ◽

Mean Length Of Utterance

Purpose This exploratory study examined the language skills and the type and frequency of disfluencies in the spoken narrative production of Spanish–English bilingual children who do not stutter. Method A cross-sectional sample of 29 bilingual students (16 boys and 13 girls) enrolled in grades prekindergarten through Grade 4 produced a total of 58 narrative retell language samples in English and Spanish. Key outcome measures in each language included the percentage of normal (%ND) and stuttering-like (%SLD) disfluencies, percentage of words in mazes (%MzWds), number of total words, number of different words, and mean length of utterance in words. Results Cross-linguistic, pairwise comparisons revealed significant differences with medium effect sizes for %ND and %MzWds (both lower for English) as well as for number of different words (lower for Spanish). On average, the total percentage of mazed words was higher than 10% in both languages, a pattern driven primarily by %ND; %SLDs were below 1% in both languages. Multiple linear regression models for %ND and %SLD in each language indicated that %MzWds was the primary predictor across languages beyond other language measures and demographic variables. Conclusions The findings extend the evidence base with regard to the frequency and type of disfluencies that can be expected in bilingual children who do not stutter in grades prekindergarten to Grade 4. The data indicate that %MzWds and %ND can similarly index the normal disfluencies of bilingual children during narrative production. The potential clinical implications of the findings from this study are discussed.

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Bang for Your Buck: A Single-Case Experimental Design Study of Practice Amount and Distribution in Treatment for Childhood Apraxia of Speech

Journal of Speech Language and Hearing Research ◽

10.1044/2019_jslhr-s-18-0212 ◽

2019 ◽

Vol 62 (9) ◽

pp. 3160-3182 ◽

Cited By ~ 4

Author(s):

Edwin Maas ◽

Christina Gildersleeve-Neumann ◽

Kathy Jakielski ◽

Nicolette Kovacs ◽

Ruth Stoeckel ◽

...

Keyword(s):

Single Case ◽

Evidence Base ◽

Distributed Practice ◽

Single Subject ◽

Single Subject Design ◽

Apraxia Of Speech ◽

Childhood Apraxia Of Speech ◽

Opposite Pattern ◽

Massed Practice ◽

Treatment Conditions

Purpose The aim of this study was to examine 2 aspects of treatment intensity in treatment for childhood apraxia of speech (CAS): practice amount and practice distribution. Method Using an alternating-treatments single-subject design with multiple baselines, we compared high versus low amount of practice, and massed versus distributed practice, in 6 children with CAS. Conditions were manipulated in the context of integral stimulation treatment. Changes in perceptual accuracy, scored by blinded analysts, were quantified with effect sizes. Results Four children showed an advantage for high amount of practice, 1 showed an opposite effect, and 1 showed no condition difference. For distribution, 4 children showed a clear advantage for massed over distributed practice post treatment; 1 showed an opposite pattern, and 1 showed no clear difference. Follow-up revealed a similar pattern. All children demonstrated treatment effects (larger gains for treated than untreated items). Conclusions High practice amount and massed practice were associated with more robust speech motor learning in most children with CAS, compared to low amount and distributed practice, respectively. Variation in effects across children warrants further research to determine factors that predict optimal treatment conditions. Finally, this study adds to the evidence base supporting the efficacy of integral stimulation treatment for CAS. Supplemental Material https://doi.org/10.23641/asha.9630599

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Inclusion of Transgender Voice and Communication Training in a University Clinic

Perspectives of the ASHA Special Interest Groups ◽

10.1044/persp2.sig10.109 ◽

2017 ◽

Vol 2 (10) ◽

pp. 109-115 ◽

Cited By ~ 1

Author(s):

Jennifer Oates ◽

Georgia Dacakis

Keyword(s):

Training Program ◽

Clinical Education ◽

Well Being ◽

Evidence Base ◽

Communication Training ◽

Speech Language Pathology ◽

Transgender People ◽

Language Pathology ◽

Effectiveness Of Training ◽

Negative Impacts

Because of the increasing number of transgender people requesting speech-language pathology services, because having gender-incongruent voice and communication has major negative impacts on an individual's social participation and well-being, and because voice and communication training is supported by an improving evidence-base, it is becoming more common for universities to include transgender-specific theoretical and clinical components in their speech-language pathology programs. This paper describes the theoretical and clinical education provided to speech-language pathology students at La Trobe University in Australia, with a particular focus on the voice and communication training program offered by the La Trobe Communication Clinic. Further research is required to determine the outcomes of the clinic's training program in terms of student confidence and competence as well as the effectiveness of training for transgender clients.

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Impairment Questions and Answers

Guides Newsletter ◽

10.1001/amaguidesnewsletters.1999.julaug02 ◽

1999 ◽

Vol 4 (4) ◽

pp. 4-4

Keyword(s):

Symptom Validity ◽

Validity Testing ◽

Symptom Validity Testing ◽

Negative Results ◽

Tunnel Vision ◽

Questions And Answers ◽

Blurry Vision ◽

Fatigue Evaluation ◽

Choice Testing ◽

Rule Out

Abstract Symptom validity testing, also known as forced-choice testing, is a way to assess the validity of sensory and memory deficits, including tactile anesthesias, paresthesias, blindness, color blindness, tunnel vision, blurry vision, and deafness—the common feature of which is a claimed inability to perceive or remember a sensory signal. Symptom validity testing comprises two elements: A specific ability is assessed by presenting a large number of items in a multiple-choice format, and then the examinee's performance is compared with the statistical likelihood of success based on chance alone. Scoring below a norm can be explained in many different ways (eg, fatigue, evaluation anxiety, limited intelligence, and so on), but scoring below the probabilities of chance alone most likely indicates deliberate deception. The positive predictive value of the symptom validity technique likely is quite high because there is no alternative explanation to deliberate distortion when performance is below the probability of chance. The sensitivity of this technique is not likely to be good because, as with a thermometer, positive findings indicate that a problem is present, but negative results do not rule out a problem. Although a compelling conclusion is that the examinee who scores below probabilities is deliberately motivated to perform poorly, malingering must be concluded from the total clinical context.

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