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Actas Dermo-sifiliograficas Jun 2015Phototherapy is a treatment option for atopic dermatitis recommended by several guidelines. (Review)
Review
BACKGROUND
Phototherapy is a treatment option for atopic dermatitis recommended by several guidelines.
OBJECTIVE
To perform a systematic review of the efficacy of different modalities of phototherapy and photochemotherapy in moderate to severe atopic dermatitis.
MATERIAL AND METHODS
We considered all randomized clinical trials (RCTs) performed in patients with atopic dermatitis, and accepted all outcome measures. Articles were identified via an online search of the MEDLINE (via Ovid) and Embase databases and the Cochrane Central Register of Controlled Trials. We also searched for clinical trials registered in Current Controlled Trials and in the World Health Organization's International Clinical Trials Registry Platform.
RESULTS
Twenty-one RCTs (961 patients) were included in the qualitative analysis. Two of the trials included children and adolescents (32 patients). The efficacy of narrow-band UV-B and UV-A1 phototherapy was similar for the different outcome measures contemplated. Two RCTs assessed the efficacy of psoralen plus UV-A therapy (PUVA). No serious adverse events were described. In general, the publications reviewed were characterized by a high risk of bias and poor reporting of methodology and results.
CONCLUSIONS
There is evidence for the use of narrow-band UV-B and UV-A1 phototherapy in moderate to severe atopic dermatitis. Evidence supporting the use of PUVA in atopic dermatitis is scarce and there is little information on the use of phototherapy in childhood. For the purpose of future studies, it would be advisable to use comparable criteria and scales for the evaluation of disease severity and patients, to standardize radiation methods, and to establish a minimum follow-up time.
Topics: Adolescent; Adult; Child; Controlled Clinical Trials as Topic; Dermatitis, Atopic; Humans; PUVA Therapy; Phototherapy; Randomized Controlled Trials as Topic; Treatment Outcome; Ultraviolet Therapy
PubMed: 25728564
DOI: 10.1016/j.ad.2014.12.017 -
Journal of Clinical Epidemiology Dec 2014The degree of bias in randomized clinical trials varies depending on whether the outcome is subjective or objective. Assessment of the risk of bias in a clinical trial... (Review)
Review
OBJECTIVES
The degree of bias in randomized clinical trials varies depending on whether the outcome is subjective or objective. Assessment of the risk of bias in a clinical trial will therefore often involve categorization of the type of outcome. Our primary aim was to examine how the concepts "subjective outcome" and "objective outcome" are defined in methodological publications and clinical trial reports. To put this examination into perspective, we also provide an overview of how outcomes are classified more broadly.
STUDY DESIGN AND SETTING
A systematic review of methodological publications providing a classification of clinical trial outcomes and a descriptive study of how outcomes were classified in 200 PubMed indexed clinical trial reports published in 2012.
RESULTS
We identified 90 methodological publications with some form of a classification of outcomes. Three distinct definitions were provided for subjective outcome: (1) dependent on assessor judgment, (2) patient-reported outcome, or (3) private phenomena (ie, phenomena only assessable by the patient). Of the 200 clinical trial reports, 12 used the term "subjective" and/or "objective" about outcomes, but no clinical trial reports explicitly defined the terms.
CONCLUSION
The terms "subjective" and "objective" are ambiguous when used to describe outcomes in randomized clinical trials. We suggest that the terms should be defined explicitly when used in connection with the assessment of risk of bias in a clinical trial, in metaepidemiological research, and generally in the reporting of clinical trials. We also suggest that adding an explicit clarification of the terms in future versions of the Cochrane Handbook might further strengthen its important role in guiding review authors.
Topics: Humans; Publication Bias; Randomized Controlled Trials as Topic; Research Design; Terminology as Topic; Treatment Outcome
PubMed: 25263546
DOI: 10.1016/j.jclinepi.2014.06.020 -
Annals of Hematology Jan 2016The treatment of Burkitt's lymphoma with rituximab is controversial, and studies that compared the efficacy of chemotherapy alone with chemotherapy plus rituximab have... (Meta-Analysis)
Meta-Analysis Review
The treatment of Burkitt's lymphoma with rituximab is controversial, and studies that compared the efficacy of chemotherapy alone with chemotherapy plus rituximab have not been powered to test differences in overall survival (OS). We conducted this systematic review and meta-analysis to identify the value of rituximab for the treatment of BL to guide treatment decisions. Based on the PubMed, Web of Science, and Cochrane library online electronic databases, all retrospective and randomized clinical trial studies that compared the aforementioned two regimens were included. The pooled hazard ratio and odds ratio were analyzed using Review Manager 5.3. The primary outcome was the 2-year OS. A total of 581 publications were identified using a predetermined search strategy. One randomized controlled trial (RCT) and five retrospective studies, which included 646 cases (351 cases for the chemotherapy with rituximab group and 295 cases for the chemotherapy alone group), fulfilled the selection criteria and were included in the meta-analysis. The chemotherapy with rituximab group was associated with a higher 2-year OS (hazard ratio 0.62, 95 % CI 0.45-0.85, P = 0.003), 2-year progression-free survival (hazard ratio 0.46, 95 % CI 0.43-0.50, P < 0. 001), and complete remission rate (odds ratios 3.26, 95 % CI 1.22-8.66, P = 0.02). In addition, the treatment-related mortality did not significantly differ between the two treatment regimens (odds ratio 1.16, 95 % CI 0.55-2.45, P = 0.69). The meta-analysis indicates that the addition of rituximab to the treatment regimen for Burkitt's lymphoma may be associated with a significant survival benefit and did not increase the mortality compared with chemotherapy alone.
Topics: Adult; Antineoplastic Agents; Burkitt Lymphoma; Clinical Trials as Topic; Humans; Retrospective Studies; Rituximab; Treatment Outcome
PubMed: 26423805
DOI: 10.1007/s00277-015-2501-1 -
Clinical Neuropharmacology 2017The aim of this study was to review the safety and efficacy of aripiprazole as monotherapy and adjunct therapy for the treatment of post-traumatic stress disorder (PTSD). (Review)
Review
OBJECTIVE
The aim of this study was to review the safety and efficacy of aripiprazole as monotherapy and adjunct therapy for the treatment of post-traumatic stress disorder (PTSD).
METHODS
A search of both MEDLINE (1956 to May 2017) and EMBASE (1957 to May 2017) was conducted using the terms "aripiprazole" and "post-traumatic stress disorder," "posttraumatic stress disorder," or "PTSD." Studies evaluating the primary endpoint of PTSD in patients taking aripiprazole as monotherapy or adjunct therapy were analyzed for relevance. Those that met the objective of this study were included for evaluation: 1 placebo-controlled trial; 4 open-label trials; and 1 retrospective chart review.
RESULTS
In patients with a history of PTSD, aripiprazole resulted in significant improvements in the primary outcome, including Clinician-Administered PTSD Symptom Scale or PTSD Checklist-Military scores, in all but 1 study analyzed. Study durations ranged from 10 to 16 weeks. Initial doses of aripiprazole ranged from 2 to 15 mg daily that could be titrated up or down in the range of 2 to 30 mg daily based on efficacy and tolerability. Overall, aripiprazole was well tolerated with the most common treatment-related study discontinuations attributed to the adverse events of anxiety, insomnia, akathisia, asthenia, restlessness, and somnolence.
CONCLUSIONS
Based on the reviewed literature, aripiprazole is a reasonable therapy option as monotherapy or adjunct therapy in patients with PTSD. Larger randomized controlled trials are needed to better understand the role of this atypical antipsychotic in patients with PTSD.
Topics: Antipsychotic Agents; Aripiprazole; Clinical Trials as Topic; Humans; Stress Disorders, Post-Traumatic
PubMed: 29059134
DOI: 10.1097/WNF.0000000000000251 -
JAMA Mar 2017Recent changes in the periodicity of cervical cancer screening have led to questions about the role of screening pelvic examinations among asymptomatic women. (Review)
Review
IMPORTANCE
Recent changes in the periodicity of cervical cancer screening have led to questions about the role of screening pelvic examinations among asymptomatic women.
OBJECTIVE
To systematically review literature on health benefits, accuracy, and harms of the screening pelvic examination for gynecologic conditions for the US Preventive Services Task Force (USPSTF).
DATA SOURCES
MEDLINE, PubMed, and Cochrane Central Register of Controlled Trials for relevant English-language studies published through January 13, 2016, with surveillance through August 3, 2016.
STUDY SELECTION
Two reviewers independently screened abstracts and studies. The search yielded 8678 unique citations; 316 full-text articles were reviewed, and 9 studies including 27 630 patients met inclusion criteria.
DATA EXTRACTION AND SYNTHESIS
Two reviewers rated study quality using USPSTF criteria.
MAIN OUTCOMES AND MEASURES
Morbidity; mortality; diagnostic accuracy for any gynecologic cancer or condition except cervical cancer, gonorrhea, and chlamydia, which are covered by other USPSTF screening recommendations; harms (false-positive rates, false-negative rates, surgery rates).
RESULTS
No trials examined the effectiveness of the pelvic examination in reducing all-cause mortality, reducing cancer- and disease-specific morbidity and mortality, or improving quality of life. Eight studies reported accuracy for the screening pelvic examination: ovarian cancer (4 studies; n = 26 432), bacterial vaginosis (2 studies; n = 930), trichomoniasis (1 study; n = 779), and genital herpes (1 study; n = 779). In the 4 ovarian cancer screening studies, low prevalence of ovarian cancer consistently resulted in low positive predictive values (PPVs) and false-positive rates, with a lack of precision in accuracy estimates (sensitivity range, 0%-100%; specificity range, 91%-99%; PPV range, 0%-3.6%; negative predictive value [NPV] range, ≥99%). Each diagnostic accuracy study for bacterial vaginosis, trichomoniasis, and genital herpes was performed in a high-prevalence population with substantial proportions of symptomatic patients and reported accuracy characteristics for individual physical examination findings (bacterial vaginosis, homogeneous discharge: sensitivity range, 69%-79%; specificity range, 54%-97%; PPV range, 52%-95%; NPV range, 79%-80%; herpes simplex virus, vulvar ulcerations: sensitivity, 20%; specificity, 98%; PPV, 88%; NPV, 57%; trichomoniasis, colpitis macularis: sensitivity, 2%; specificity, 100%; PPV, 100%; NPV, 85%). Surgery rates resulting from an abnormal screening pelvic examination for ovarian cancer ranged from 5% to 36% at 1 year, with the largest study reporting an 11% surgery rate and 1% complication rate within 1 year of a screening pelvic examination with abnormal findings.
CONCLUSIONS AND RELEVANCE
No direct evidence was identified for overall benefits and harms of the pelvic examination as a 1-time or periodic screening test. Limited evidence was identified regarding the diagnostic accuracy and harms of routine screening pelvic examinations in asymptomatic primary care populations.
Topics: Adult; Clinical Trials as Topic; Female; Genital Diseases, Female; Gynecological Examination; Humans; Mass Screening
PubMed: 28267861
DOI: 10.1001/jama.2016.12819 -
Clinical Microbiology and Infection :... Aug 2020As COVID-19 cases continue to rise globally, evidence from large randomized controlled trials is still lacking. Currently, numerous trials testing potential treatment... (Review)
Review
BACKGROUND
As COVID-19 cases continue to rise globally, evidence from large randomized controlled trials is still lacking. Currently, numerous trials testing potential treatment and preventative options are being undertaken all over the world.
OBJECTIVES
We summarized all registered clinical trials examining treatment and prevention options for COVID-19. Additionally, we evaluated the quality of the retrieved studies.
DATA SOURCES
Clinicaltrials.gov, the Chinese Clinical Trial Registry and the European Union Clinical Trials Register were systematically searched.
STUDY ELIGIBILITY CRITERIA
Registered clinical trials examining treatment and/or prevention options for COVID-19 were included. No language, country or study design restrictions were applied. We excluded withdrawn or cancelled studies and trials not reporting therapeutic or preventative strategies for COVID-19.
PARTICIPANTS AND INTERVENTIONS
No restrictions in terms of participants' age and medical background or type of intervention were enforced.
METHODS
The registries were searched using the term 'coronavirus' or 'COVID-19' from their inception until 26 March 2020. Additional manual search of the registries was also performed. Eligible studies were summarized and tabulated. Interventional trials were methodologically analysed, excluding expanded access studies and trials testing traditional Chinese medicine.
RESULTS
In total, 309 trials evaluating therapeutic management options, 23 studies assessing preventive strategies and three studies examining both were retrieved. Finally, 214 studies were methodologically reviewed. Interventional treatment studies were mostly randomized (n = 150/198, 76%) and open label (n = 73/198, 37%) with a median number of planned inclusions of 90 (interquartile range 40-200). Major categories of interventions that are currently being investigated are discussed.
CONCLUSIONS
Numerous clinical trials have been registered since the onset of the COVID-19 pandemic. Summarized data on these trials will assist physicians and researchers to promote patient care and guide future research efforts for COVID-19 pandemic containment.
Topics: Antiviral Agents; Betacoronavirus; COVID-19; Cell- and Tissue-Based Therapy; Clinical Trials as Topic; Coronavirus Infections; Humans; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; SARS-CoV-2; Treatment Outcome
PubMed: 32454187
DOI: 10.1016/j.cmi.2020.05.019 -
The Journal of Pathology. Clinical... May 2021The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement was developed to provide guidance for inclusion of key methodological... (Meta-Analysis)
Meta-Analysis
The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement was developed to provide guidance for inclusion of key methodological components in clinical trial protocols. However, these standards do not include guidance specific to pathology input in clinical trials. This systematic review aims to synthesise existing recommendations specific to pathology practice in clinical trials for implementation in trial protocol design. Articles were identified from database searches and deemed eligible for inclusion if they contained: (1) guidance and/or a checklist, which was (2) pathology-related, with (3) content relevant to clinical trial protocols or could influence a clinical trial protocol design from a pathology perspective and (4) were published in 1996 or later. The quality of individual papers was assessed using the AGREE-GRS (Appraisal of Guidelines for REsearch & Evaluation - Global Rating Scale) tool, and the confidence in cumulative evidence was evaluated using the GRADE-CERQual (Grading of Recommendations Assessment, Development and Evaluation-Confidence in Evidence from Reviews of Qualitative research) approach. Extracted recommendations were synthesised using the best fit framework method, which includes thematic analysis followed by a meta-aggregative approach to synthesis within the framework. Of the 10 184 records screened and 199 full-text articles reviewed, only 40 guidance resources met the eligibility criteria for inclusion. Recommendations extracted from 22 guidance documents were generalisable enough for data synthesis. Seven recommendation statements were synthesised as follows: (1) multidisciplinary collaboration in trial design with early involvement of pathologists, particularly with respect to the use of biospecimens and associated biomarker/analytical assays and in the evaluation of pathology-related parameters; (2) funding and training for personnel undertaking trial work; (3) selection of an accredited laboratory with suitable facilities to undertake scheduled work; (4) quality assurance of pathology-related parameters; (5) transparent reporting of pathology-related parameters; (6) policies regarding informatics and tracking biospecimens across trial sites; and (7) informed consent for specimen collection and retention for future research.
Topics: Biomarkers; Biopsy; Clinical Trials as Topic; Humans; Pathology, Clinical; Pathology, Molecular; Practice Guidelines as Topic; Predictive Value of Tests; Research Design; Treatment Outcome
PubMed: 33635586
DOI: 10.1002/cjp2.199 -
World Journal of Gastroenterology Aug 2017To performed a systematic review and meta-analysis to determine any possible differences in terms of effectiveness, safety and tolerability between existing... (Meta-Analysis)
Meta-Analysis Review
AIM
To performed a systematic review and meta-analysis to determine any possible differences in terms of effectiveness, safety and tolerability between existing colon-cleansing products in patients with inflammatory bowel disease.
METHODS
Systematic searches were performed (January 1980-September 2016) using MEDLINE, EMBASE, Scopus, CENTRAL and ISI Web of knowledge for randomized trials assessing preparations with or without adjuvants, given in split and non-split dosing, and in high (> 3 L) or low-volume (2 L or less) regimens. Bowel cleansing quality was the primary outcome. Secondary outcomes included patient willingness-to-repeat the procedure and side effects/complications.
RESULTS
Out of 439 citations, 4 trials fulfilled our inclusion criteria ( = 449 patients). One trial assessed the impact of adding simethicone to polyethylene glycol (PEG) 4 L with no effect on bowel cleansing quality, but a better tolerance. Another trial compared senna to castor oil, again without any differences in term of bowel cleansing. Two trials compared the efficacy of PEG high-volume PEG low-volume associated to an adjuvant in split-dose regimens: PEG low-dose efficacy was not different to PEG high-dose; OR = 0.84 (0.37-1.92). A higher proportion of patients were willing to repeat low-volume preparations high-volume; OR = 5.11 (1.31-20.0).
CONCLUSION
In inflammatory bowel disease population, PEG low-volume regimen seems not inferior to PEG high-volume to clean the colon, and yields improved willingness-to-repeat. Further additional research is urgently required to compare contemporary products in this population.
Topics: Cathartics; Clinical Trials as Topic; Colon; Colonoscopy; Drug Administration Schedule; Humans; Inflammatory Bowel Diseases; Patient Satisfaction; Treatment Outcome
PubMed: 28932092
DOI: 10.3748/wjg.v23.i32.5994 -
Journal of Cachexia, Sarcopenia and... Jun 2024Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary... (Review)
Review
Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary endpoints. To date, there has been no review of the most commonly selected measures or their potential sensitivity to detect changes resulting from the interventions being examined. The aim of this systematic review is to assess the frequency and diversity of body composition measures that have been used in cancer cachexia trials. MEDLINE, Embase and Cochrane Library databases were systematically searched between January 1990 and June 2021. Eligible trials examined adults (≥18 years) who had received an intervention aiming to treat or attenuate the effects of cancer cachexia for >14 days. Trials were also of a prospective controlled design and included body weight or at least one anthropometric, bioelectrical or radiological endpoint pertaining to body composition, irrespective of the modality of intervention (e.g., pharmacological, nutritional, physical exercise and behavioural) or comparator. Trials with a sample size of <40 patients were excluded. Data extraction used Covidence software, and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. This review was prospectively registered (PROSPERO: CRD42022276710). A total of 84 clinical trials, comprising 13 016 patients, were eligible for inclusion. Non-small-cell lung cancer and pancreatic cancer were studied most frequently. The majority of trial interventions were pharmacological (52%) or nutritional (34%) in nature. The most frequently reported endpoints were assessments of body weight (68 trials, n = 11 561) followed by bioimpedance analysis (BIA)-based estimates (23 trials, n = 3140). Sixteen trials (n = 3052) included dual-energy X-ray absorptiometry (DEXA)-based endpoints, and computed tomography (CT) body composition was included in eight trials (n = 841). Discrepancies were evident when comparing the efficacy of interventions using BIA-based estimates of lean tissue mass against radiological assessment modalities. Body weight, BIA and DEXA-based endpoints have been most frequently used in cancer cachexia trials. Although the optimal endpoints cannot be determined from this review, body weight, alongside measurements from radiological body composition analysis, would seem appropriate. The choice of radiological modality is likely to be dependent on the trial setting, population and intervention in question. CT and magnetic resonance imaging, which have the ability to accurately discriminate tissue types, are likely to be more sensitive and provide greater detail. Endpoints are of particular importance when aligned with the intervention's mechanism of action and/or intended patient benefit.
Topics: Humans; Cachexia; Neoplasms; Body Composition; Body Weight; Clinical Trials as Topic
PubMed: 38738581
DOI: 10.1002/jcsm.13478 -
Clinical Breast Cancer Dec 2019Optimal treatment of breast cancer brain metastases (BCBM) is often hampered by limitations in diagnostic abilities. Developing innovative tools for BCBM diagnosis is...
Optimal treatment of breast cancer brain metastases (BCBM) is often hampered by limitations in diagnostic abilities. Developing innovative tools for BCBM diagnosis is vital for early detection and effective treatment. In this study we explored the advances in trial for the diagnosis of BCBM, with review of the literature. On May 8, 2019, we searched ClinicalTrials.gov for interventional and diagnostic clinical trials involving BCBM, without limiting for date or location. Information on trial characteristics, experimental interventions, results, and publications were collected and analyzed. In addition, a systematic review of the literature was conducted to explore published studies related to BCBM diagnosis. Only 9 diagnostic trials explored BCBM. Of these, 1 trial was withdrawn because of low accrual numbers. Three trials were completed; however, none had published results. Modalities in trial for BCBM diagnosis entailed magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), PET-CT, nanobodies, and circulating tumor cells (CTCs), along with a collection of novel tracers and imaging biomarkers. MRI continues to be the diagnostic modality of choice, whereas CT is best suited for acute settings. Advances in PET and PET-CT allow the collection of metabolic and functional information related to BCBM. CTC characterization can help reflect on the molecular foundations of BCBM, whereas cell-free DNA offers new genetic material for further exploration in trials. The integration of machine learning in BCBM diagnosis seems inevitable as we continue to aim for rapid and accurate detection and better patient outcomes.
Topics: Brain Neoplasms; Breast Neoplasms; Clinical Trials as Topic; Female; Humans; Magnetic Resonance Imaging; Neoplastic Cells, Circulating; Positron Emission Tomography Computed Tomography; Prognosis
PubMed: 31262686
DOI: 10.1016/j.clbc.2019.05.018