Deficiencies in reporting inclusion/exclusion criteria and characteristics of patients in randomized controlled trials of therapeutic interventions in pressure injuries: a systematic methodological review.

Wound care is a complex procedure and the related research may include many variables. Deficiencies in the sample inclusion and exclusion criteria may limit the generalizability of randomized controlled trials (RCTs) for wound patients in the real world. This study aimed to evaluate deficiencies in reporting the inclusion and exclusion criteria and the characteristics of patients in RCTs of pressure injuries (PI) therapeutic interventions. We conducted a systematic methodological review in which 40 full text RCTs of PI treatment interventions published in English, from 2008 to 2020, were identified. Data on the general characteristics of the included RCTs and data about inclusion/exclusion criteria and characteristics of patients were collected. The inclusion/exclusion criteria were categorized into five domains (definition of disease, precision, safety, ethical/legal and administrative). Study duration (in weeks) was 8.0 (quartile 1: 2.0; quartile 3: 48.0); only 5.0% of the trials mentioned race, skin colour or ethnicity, and 37.5% reported the duration of the wound. Only 9 (22.5%) studies reported the drugs that the included patients were using and 10 (25.0%) RCTs reported adverse events. The presence of the five domains was observed only in 12.5% of RCTs and only 12 (30.0%) had the precision domain. Much more research is required in systematic assessments of the external validity of trials because there is substantial disparity between the information that is provided by RCTs and the information that is required by clinicians. We concluded that there are deficiencies in reporting of data related to inclusion/exclusion criteria and characteristics of patients of RCTs assessing PI therapeutic interventions.

Treatment of Chronic Venous Ulcers With Heterologous Fibrin Sealant: A Phase I/II Clinical Trial.

Background: Heterologous fibrin sealant (HFS) consists of a fibrinogen-rich cryoprecipitate extracted from Bubalus bubalis buffalo blood and a thrombin-like enzyme purified from Crotalus durissus terrificus snake venom. This study evaluated the safety and immunogenicity of HFS, estimated the best dose, and assessed its preliminary efficacy in the treatment of chronic venous ulcers (CVU). Methods: A phase I/II non-randomized, single-arm clinical trial was performed on 31 participants, accounting for a total of 69 active CVUs. All ulcers were treated with HFS, essential fatty acid, and Unna boot for 12 weeks. The outcomes assessed were: (1) primary safety, immunogenicity analyses, and confirmation of the lowest safe dose; (2) secondary promising efficacy by analyzing the healing process. Immunogenicity was evaluated using the serum-neutralizing (IgM and IgG) and non-neutralizing (IgA and IgE) antibody techniques against the product. The immuno-detection of IgE class antibodies was assessed using dot-blot assay before and at the end of treatment. Positive samples on dot-blot assays were subsequently analyzed by western blotting to verify the results. Results: No severe systemic adverse events related to the use of HFS were observed. Local adverse events potentially related to treatment include ulcer pain (52%), peri-ulcer maceration (16%), peri-ulcer pruritus (12%), critical colonization (8%), peri-ulcer eczema (4%), the opening of new ulcers (4%), and increased ulcerated area 4%). Neutralizing and non-neutralizing antibodies did not show significant deviations at any of the evaluated time points. Blot assays showed that all patients presented negative immunological reactions, either before or after treatment, with the thrombin-like enzyme component. In addition, two participants showed a positive immunological reaction to the cryoprecipitate component, while another two were positive before and during treatment. Regarding the secondary outcomes of preliminary efficacy, a total healing and significant reduction of the area was observed in 47.5 and 22%, respectively. A qualitative improvement was observed in the wound beds of unhealed ulcers. Conclusions: The investigational HFS bioproduct proved to be safe and non-immunogenic with a good preliminary efficacy for the treatment of CVU, according to the protocol and doses proposed. A multicentric phase III clinical trial will be necessary to verify these findings.

Quality of reporting of outcomes in trials of therapeutic interventions for pressure injuries in adults: a systematic methodological survey.

Randomised controlled trials of therapeutic interventions for pressure injuries should include a clear description of outcomes to increase transparency and replicability and improve the construction of scientific evidence. The objective of this study was to assess the completeness of the descriptions of the outcomes of therapeutic interventions in adults with pressure injury (PI) and factors associated with completeness. This was a systematic methodological survey. The completeness of the outcome was assessed according to five criteria: domain (title), specific measure (technique/instrument used), specific metric, or format of the outcome data of each participant that was used for analysis, aggregation (method data from each group were summarised), and time that was used for analysis. Sixty-eight studies were included for analysis. A total of 265 outcomes were reported, and 46 trials (67.6%) had 73 primary outcomes, which were mainly intermediates/substitutes (78.8%). The main outcome evaluated was the ulcer area reduction (36.6%). Approximately 37.2% of the outcomes were incompletely reported, and the least described element was the data aggregation method (72.8%). Only 48.4% of the outcomes with the specified technique had the same reference or validation. Poor quality of reporting outcomes was associated with studies with an older year of publication and a small sample size, single-center studies, and those sponsored by industry. PI studies use many outcomes, mostly surrogates or intermediates, and some of them are incompletely described.

Cellulose biomembrane versus collagenase dressing for the treatment of chronic venous ulcers: a randomized, controlled clinical trial.

Cellulose biomembranes may be used for difficult-to-treat ulcers. To assess the efficacy and safety of cellulose biomembranes compared to a collagenase dressing for the treatment of chronic venous ulcers. A randomized, controlled clinical trial was performed using two groups: one treated with collagenase dressing and the other with cellulose biomembrane over a 90-day (T90) period. Both groups received compression therapy. The primary outcome was reduction in ulcer area at T90. Secondary outcomes were healing status, decrease in devitalized tissue and exudate, vascular fraction, change in quality of life, and safety. We randomized 46 participants with 73 venous ulcers (21 with 36 ulcers in the collagenase group and 25 with 37 ulcers in the biomembrane group). A decrease in ulcer area occurred at T90 in both groups, but the difference was not significant. Complete healing before T90 occurred for seven ulcers in the collagenase group and 12 ulcers in the biomembrane group, without significant difference. However, the biomembrane promoted increased precocious healing (p = 0.02). Improved bed vitality and quality of life was observed as a function of time (p < 0.01), but this was not significant between the groups. Immunohistochemical analysis of CD34 showed an increase in vascular fraction in both groups (p < 0.01), with a higher level in the biomembrane group (p < 0.05). No adverse events were considered related to the products. Cellulose biomembranes, in combination with compressive therapy, are effective and safe for the treatment of venous ulcers and provide results similar to those with collagenase treatment.

Introducing the CONSORT extension to pilot trials: enhancing the design, conduct and reporting of pilot or feasibility trials.

This editorial provides a brief overview of the importance of pilot or feasibility trials or studies, the challenges with current practices in their conduct and reporting, an introduction to the Consolidated Standards of Reporting Trials (CONSORT) extension to pilot trials aimed at improving their reporting, along with some key resources on aspects related to pilot and feasibility studies.

A systematic review of comparisons between protocols or registrations and full reports in primary biomedical research.

BACKGROUND: Prospective study protocols and registrations can play a significant role in reducing incomplete or selective reporting of primary biomedical research, because they are pre-specified blueprints which are available for the evaluation of, and comparison with, full reports. However, inconsistencies between protocols or registrations and full reports have been frequently documented. In this systematic review, which forms part of our series on the state of reporting of primary biomedical, we aimed to survey the existing evidence of inconsistencies between protocols or registrations (i.e., what was planned to be done and/or what was actually done) and full reports (i.e., what was reported in the literature); this was based on findings from systematic reviews and surveys in the literature. METHODS: Electronic databases, including CINAHL, MEDLINE, Web of Science, and EMBASE, were searched to identify eligible surveys and systematic reviews. Our primary outcome was the level of inconsistency (expressed as a percentage, with higher percentages indicating greater inconsistency) between protocols or registration and full reports. We summarized the findings from the included systematic reviews and surveys qualitatively. RESULTS: There were 37 studies (33 surveys and 4 systematic reviews) included in our analyses. Most studies (n = 36) compared protocols or registrations with full reports in clinical trials, while a single survey focused on primary studies of clinical trials and observational research. High inconsistency levels were found in outcome reporting (ranging from 14% to 100%), subgroup reporting (from 12% to 100%), statistical analyses (from 9% to 47%), and other measure comparisons. Some factors, such as outcomes with significant results, sponsorship, type of outcome and disease speciality were reported to be significantly related to inconsistent reporting. CONCLUSIONS: We found that inconsistent reporting between protocols or registrations and full reports of primary biomedical research is frequent, prevalent and suboptimal. We also identified methodological issues such as the need for consensus on measuring inconsistency across sources for trial reports, and more studies evaluating transparency and reproducibility in reporting all aspects of study design and analysis. A joint effort involving authors, journals, sponsors, regulators and research ethics committees is required to solve this problem.

Introducing the CONSORT extension to pilot trials: enhancing the design, conduct and reporting of pilot or feasibility trials

This editorial provides a brief overview of the importance of pilot or feasibility trials or studies, the challenges with current practices in their conduct and reporting, an introduction to the Consolidated Standards of Reporting Trials (CONSORT) extension to pilot trials aimed at improving their reporting, along with some key resources on aspects related to pilot and feasibility studies.

Introducing the CONSORT extension to pilot trials: enhancing the design, conduct and reporting of pilot or feasibility trials

This editorial provides a brief overview of the importance of pilot or feasibility trials or studies, the challenges with current practices in their conduct and reporting, an introduction to the Consolidated Standards of Reporting Trials (CONSORT) extension to pilot trials aimed at improving their reporting, along with some key resources on aspects related to pilot and feasibility studies.(AU)

A scoping review of comparisons between abstracts and full reports in primary biomedical research.

BACKGROUND: Evidence shows that research abstracts are commonly inconsistent with their corresponding full reports, and may mislead readers. In this scoping review, which is part of our series on the state of reporting of primary biomedical research, we summarized the evidence from systematic reviews and surveys, to investigate the current state of inconsistent abstract reporting, and to evaluate factors associated with improved reporting by comparing abstracts and their full reports. METHODS: We searched EMBASE, Web of Science, MEDLINE, and CINAHL from January 1st 1996 to September 30th 2016 to retrieve eligible systematic reviews and surveys. Our primary outcome was the level of inconsistency between abstracts and corresponding full reports, which was expressed as a percentage (with a lower percentage indicating better reporting) or categorized rating (such as major/minor difference, high/medium/low inconsistency), as reported by the authors. We used medians and interquartile ranges to describe the level of inconsistency across studies. No quantitative syntheses were conducted. Data from the included systematic reviews or surveys was summarized qualitatively. RESULTS: Seventeen studies that addressed this topic were included. The level of inconsistency was reported to have a median of 39% (interquartile range: 14% - 54%), and to range from 4% to 78%. In some studies that separated major from minor inconsistency, the level of major inconsistency ranged from 5% to 45% (median: 19%, interquartile range: 7% - 31%), which included discrepancies in specifying the study design or sample size, designating a primary outcome measure, presenting main results, and drawing a conclusion. A longer time interval between conference abstracts and the publication of full reports was found to be the only factor which was marginally or significantly associated with increased likelihood of reporting inconsistencies. CONCLUSIONS: This scoping review revealed that abstracts are frequently inconsistent with full reports, and efforts are needed to improve the consistency of abstract reporting in the primary biomedical community.

The framing of research questions using the PICOT format in randomized controlled trials of venous ulcer disease is suboptimal: A systematic survey.

Despite several publications on venous ulcers, there is still a lack of evidence from randomized controlled trials (RCTs) to support certain treatments for patients with this disorder. Well-designed research questions using the PICOT (Population; Intervention; Comparator; Outcome; Time-frame) format in RCTs can improve the quality of research. The objectives of this study were to assess how the PICOT format is used to frame research questions in RCTs published on venous ulcer disease and to determine the factors associated with better adherence to the PICOT format. We conducted a systematic survey of RCTs on venous ulcers published in the PubMed database between January 2009 and May 2016. All RCTs published in English addressing therapeutic interventions for venous ulcer disease in human subjects were included. We examined whether the five elements of the PICOT format were used in formulating the research question and scored them between 0 and 5. The primary outcome of this systematic survey was the percentage of studies that adequately reported all five PICOT elements. Eighty-five (85) RCTs were included with median PICOT score of 3 (IQR = 1.5). Four elements of PICOT were present in 28 reports (32.9%) and only 2 RCTS (2.3%) reported all the PICOT elements. Population and intervention were often appropriately described, in (70/85) 82.4% and (83/85) 97.6% of the studies, respectively; however, comparison intervention and outcome were presented in only (53/85) 62.3% and (48/85) 56.5% of studies, respectively. Very few RCTs (7.1%; 6/85) reported the study time frame. No journal or RCT characteristics were found to be significantly associated with better reporting. Use of the PICOT format to frame research questions in RCTs published on venous ulcers is suboptimal, and our study reinforces the importance of framing a good research question to improve the design of trials and quality of evidence in venous ulcer disease.

Quality of abstracts of randomized control trials in five top pain journals: A systematic survey.

BACKGROUND: The reporting quality of abstracts of randomized control trials (RCTs) is inadequate despite the publication of consolidated standards of reporting trials extension for abstracts (CONSORT-A). We compared the reporting quality of abstracts in pain journals before and after the publication of CONSORT-A. METHODS: We searched MEDLINE in April-2016 for RCTs published in five pain journals: Pain, Pain Physician, European Journal of Pain, Clinical Journal of Pain and Pain Practice for pre- and post-CONSORT-A period (2005-2007 and 2013-2015). Data were extracted in duplicate from 250 abstracts for compliance with CONSORT-A, and for items known to affect reporting quality: journal endorsement of CONSORT, number of trial centers, sample-size, type of intervention, industry-sponsorship and significance of results. The primary outcome was mean number of items reported and the secondary outcome was the reporting of each item. We used logistic regression and Poisson regression for analyses. RESULTS: Most trials were single centric (76%), had sample size <100 (63%), involved pharmacological intervention (59%) and were non-industry funded (70%). The mean number of items reported was better for 2013-2015 (mean difference 0.94; 95% confidence-interval [CI]: 0.50-1.38, p < 0.001). Post-CONSORT-A, trials were more likely to report as randomized in the title (odds ratio (OR) 2.69; 95% CI 1.61-4.49), describe eligibility criteria and settings (OR 2.47; 95% CI 1.35-4.54), provide effect size and precision for primary outcome (OR 2.47; 95% CI 1.19-5.16), inform harms (OR 1.80; 95% CI 1.05-3.07) and report trial registration (OR 5.13; 95% CI 1.44-18.32). Post-CONSORT-A period (incident rate ratio (IRR) 1.15; 95% CI 1.07-1.24), endorsement of CONSORT statement by the journal (IRR 1.08; 95% CI 1.02-1.14), multi-centric studies (IRR 1.14; 95% CI 1.08-1.20), and studies with pharmacological interventions (IRR 1.07; 95% CI 1.02-1.13) were significantly associated with reporting of more items. CONCLUSIONS: Abstract reporting for trials in pain literature was better in the post-CONSORT-A period, but there is room for improvement.

Framing of research question using the PICOT format in randomised controlled trials of venous ulcer disease: a protocol for a systematic survey of the literature.

INTRODUCTION: Although venous ulcers have a great social and economic impact, there is a lack of evidence from randomised controlled trials (RCTs) to support appropriate management for this disease. Framing the research question using the Population; Intervention; Comparator; Outcome; Time frame (PICOT) format in RCTs can improve the quality of the research design. OBJECTIVES: To evaluate how the PICOT format is used to frame a research question in reports of RCTs of venous ulcer disease and to determine the factors associated with better adherence to the PICOT format in framing the research question. METHODS AND ANALYSES: We will conduct a systematic survey of RCTs on venous ulcers published in the National Institute of Health, PubMed database between January 2009 and May 2016. We will include all RCTs addressing therapeutic intervention for venous ulcer disease involving human subjects, and published in the English language. The selection process will be carried out in duplicate by two independent investigators. First, titles and abstracts will be screened, then full-text articles. We will examine whether the five elements of the PICOT format are used in formulating the research question and give a score between 0 and 5. The primary outcome will be the proportion of studies that have adequately reported all five PICOT elements. DISSEMINATION: This will be the first survey to assess how the PICOT format is used to frame research questions on the management of venous ulcers in reports of RCTs. On completion, this review will be submitted to a peer-reviewed biomedical journal for publication and the findings will also be presented at scientific conferences.

Reporting quality of abstracts of trials published in top five pain journals: a protocol for a systematic survey.

INTRODUCTION: Abstracts of randomised controlled trials (RCTs) are often the first and the only source read in a journal by busy healthcare providers. This necessitates good reporting of abstracts. The quality of reporting of abstracts, though gradually improving over time, is still not uniform across medical journals. Improvement in completeness of reporting of abstracts has been documented in general medical journals after the publication of the consolidated standards of reporting trials (CONSORT) extension for abstracts in 2008. Currently, this aspect has not been assessed with regards to pain journals. This study aims to compare the completeness of reporting of abstracts before and after the publication of CONSORT statement for abstracts in five pain journals. METHODS AND ANALYSES: The abstracts of RCTs published from 1 January 2005 to 31 December 2007 (pre-CONSORT) and from 1 January 2013 to 31 December 2015 (post-CONSORT) will be assessed for the quality of reporting. Studies without abstracts, non-English abstracts, abstracts not reporting on RCTs or on humans and conference abstracts will be excluded. A thorough search of MEDLINE will be carried out in April 2016. All identified studies will be screened for inclusion based on titles and abstracts. Data will be extracted by two sets of independent reviewers for each abstract in duplicate regarding compliance with CONSORT statement for abstracts. Full-text review will be performed to obtain additional characteristics which are likely to affect reporting quality. The unadjusted and adjusted differences in the mean number of items reported will be analysed using a two sample t-test and generalised estimation equation in SPSS. ETHICS AND DISSEMINATION: As far as we know, this is the first study to evaluate reporting quality of abstracts of pain journals based on CONSORT extension for abstracts. The findings of this study will be disseminated by a presentation at a conference and through publication in a peer-reviewed journal. Ethics committee approval was not sought for this survey.

A success in Toxinology translational research in Brazil: bridging the gap.

Basic research is fundamental for discovering potential diagnostic and therapeutic tools, including drugs, vaccines and new diagnostic techniques. On this basis, diagnosis and treatment methods for many diseases have been developed. Presently, discovering new candidate molecules and testing them in animals are relatively easy tasks that require modest resources and responsibility. However, crossing the animal-to-human barrier is still a great challenge that most researchers tend to avoid. Thus, bridging this current gap between clinical and basic research must be encouraged and elucidated in training programmes for health professionals. This project clearly shows the challenges faced by a group of Brazilian researchers who, after discovering a new fibrin sealant through 20 years of painstaking basic work, insisted on having the product applied clinically. The Brazilian government has recently become aware of this challenge and has accordingly defined the product as strategic to the public health of the country. Thus, in addition to financing research and development laboratories, resources were invested in clinical trials and in the development of a virtual platform termed the Virtual System to Support Clinical Research (SAVPC); this platform imparts speed, reliability and visibility to advances in product development, fostering interactions among sponsors, physicians, students and, ultimately, the research subjects themselves. This pioneering project may become a future model for other public institutions in Brazil, principally in overcoming neglected diseases, which unfortunately continue to afflict this tropical country.

Venous ulcer: clinical characteristics and risk factors.

BACKGROUND: Lower limb venous ulceration ranks among the 10 most common medical problems in Western countries and has significant socioeconomic impact. The aim of this study was to identify the risk factors for unhealed, recurrent, and large ulcers and to characterize patients with active or recently healed venous ulcers. METHODS: We identified 97 patients and assessed 103 ulcerated limbs in 90 patients. All patients underwent clinical examination, arterial and venous system evaluation, ankle-brachial index determination, and ultrasound of the affected limb. Clinical characteristics included age, gender, race, ulcer duration, time since first episode, history of recurrence, localization of ulcer, ulcer area, eczema, ochre dermatitis, lipodermatosclerosis, pain, body mass index, and medical history data. Risk factors were identified by univariate analysis and estimated odds ratios. RESULTS: We assessed 90 patients (103 limbs) with active or healed venous leg ulcers, of whom 84.4% were Caucasian and 68.9% were female. Mean age was 56.0 ± 13.3 years. Ulcers had remained unhealed for <1 year in 40.7%. Lipodermatosclerosis, lower limb hyperpigmentation, edema, and eczema were seen in 96.7%, 95.6%, 94.4%, and 51.1% of patients, respectively. Pain was a frequent symptom in 74.4%. Body mass index was assessed in 85 patients: 30.6% were slightly, 36.5% moderately, and 7% severely obese. Patient age >60 years (odds ratio [OR] 4.0), extensive lipodermatosclerosis (OR 8.7), and previous history of ulceration (OR 19.9) were risk factors for unhealed ulcers. Time since first ulcer episode ≥ 2 years (OR 29.2) and incompetence of venous systems (OR 1.6) were risk factors for recurrence. CONCLUSIONS: Longstanding and large ulcers and recurrences are the main problems encountered by venous ulcer patients. Severe lipodermatosclerosis, previous ulcer history, and time since first ulcer episode ≥ 2 years are significant risk factors.

Paracoccidioidomycosis: an unusual presentation in a young girl disclosing an unnoted HIV-infection.

The association of paracoccidioidomycosis with AIDS is apparently less frequent than expected. The authors present an unusual case of paracoccidioidomycosis in a 13-year-old female student which was later found to be the first opportunistic infection in the course of the patient's HIV-infection. The clinical presentation followed an accidental incised wound on the palmar region initially described as a 'sporotrichotic-chancre'. After good response under sulfamethoxazole-trimethoprin, the patient relapsed and presented an associated oral candidiasis. HIV-infection was documented and additional investigation showed CD4(+) T-cells=22/mm(3), CD8(+)=280 cell/mm(3) and viral load=4,043 log. This case report presents an uncommon dermatological-clinical picture in the youngest patient in which such association has been reported to date.