Low reproducibility of randomized clinical trials methodology related to sampling: a systematic methodological review

Objectives: The reporting of sampling methods in Randomized Clinical Trials (RCTs) allows for research quality assessment, determination of sampling bias, and assures the presence of details necessary for reproducibility in future trials. The purpose of this study was to: (1) determine if sampling methodology was reproducible in RCTs related to musculoskeletal physical therapy (MSKPT) interventions to treat non-specific low back pain (NSLBP) and (2) establish if there was a relationship between sample reproducibility and established measures of research quality.

Methods: Data were collected through a systematic review by a professional librarian. The identified RCTs were assessed for methodological quality by two blinded individual reviewers. Data analysis was performed by a third, blinded researcher; additional comparisons were made based on Journal Impact Factor and PEDro score.

Results: Ninety-nine published peer-reviewed RCTs were identified that met inclusion criteria. Only 29% of the articles were judged to be reproducible based on the reported sampling methodology. There were meaningful correlations between two out of ten of the sampling reporting criteria and the judgement made if the sample was reported in significant detail to allow for replication. There was no relationship between sampling reporting criteria, Journal Impact Factors (JIFs), and Physiotherapy Evidence Database (PEDro) scores.

Discussion: The reporting of sampling methodology needs to be considered to ensure reproducibility and avoid sampling bias. Despite the proliferation of measures of research quality, the overall reporting quality of RCTs continues to be inadequate to allow widespread reproducibility of trials.

Level of Evidence: 1a     

Outcomes following a negative computed tomography pulmonary angiography according to pulmonary embolism prevalence: a meta‐analysis of the management outcome studies

Essentials

• Computed tomographic pulmonary angiography (CTPA) is used to exclude pulmonary embolism.
• This meta‐analysis explores the occurrence of venous thromboembolic events (VTE) after a CTPA.
• Occurrence of VTE after a negative CTPA is ?8% in study subgroups with a prevalence of PE ≥ 40%.
• CTPA may be insufficient to safely rule out VTE as a stand‐alone diagnostic test for this subgroup.

Summary

Background

Outcome studies have reported the safety of computed tomographic pulmonary angiography (CTPA) as a stand‐alone imaging technique to rule out pulmonary embolism (PE). Whether this can be applied to all clinical probabilities remains controversial.

Objectives

We performed a meta‐analysis to determine the proportion of patients with venous thromboembolic events (VTE) despite a negative CTPA according to pretest PE prevalence.

Methods

We searched MEDLINE, EMBASE and the Cochrane Library (January 1990 to May 2017) for outcome studies recruiting patients with suspected PE using CTPA as a diagnostic strategy. The primary outcome was the cumulative occurrence of VTE at 3 months following a negative CTPA.

Results

Twenty‐two different studies were identified. VTE was confirmed in 2.4% of patients (95% CI, 1.3–3.8%) either at the time of the index event or in the 3 months follow‐up. Subgroup analyses suggested that the cumulative occurrence of VTE was related to pretest prevalence of PE, as VTE occurred in 1.8% (95% CI, 0.5–3.7%), 1.4% (95% CI, 0.7–2.3%), 1.0% (95% CI, 0.5–1.8%) and 8.1% (95% CI, 3.5–14.5%) of subgroups of patients with a PE prevalence < 20%, 20–29%, 30–39% and ≥ 40%, respectively. This was further confirmed using meta‐regression analysis.

Conclusions

The negative predictive value of CTPA for VTE varies according to pretest prevalence of PE, and is likely to be insufficient to safely rule out VTE as a stand‐alone diagnostic test amongst patients at the highest pretest probability of VTE. Prospective studies are required to validate the appropriate diagnostic algorithm for this subgroup of patients.

     

Measurement properties and feasibility of clinical tests to assess sit-to-stand/stand-to-sit tasks in subjects with neurological disease: a systematic review

Background

Subjects with neurological disease (ND) usually show impaired performance during sit-to-stand and stand-to-sit tasks, with a consequent reduction in their mobility levels.

Objective

To determine the measurement properties and feasibility previously investigated for clinical tests that evaluate sit-to-stand and stand-to-sit in subjects with ND.

Method

A systematic literature review following the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) protocol was performed. Systematic literature searches of databases (MEDLINE/SCIELO/LILACS/PEDro) were performed to identify relevant studies. In all studies, the following inclusion criteria were assessed: investigation of any measurement property or the feasibility of clinical tests that evaluate sit-to-stand and stand-to-sit tasks in subjects with ND published in any language through December 2012. The COSMIN checklist was used to evaluate the methodological quality of the included studies.

Results

Eleven studies were included. The measurement properties/feasibility were most commonly investigated for the five-repetition sit-to-stand test, which showed good test-retest reliability (Intraclass Correlation Coefficient:ICC=0.94-0.99) for subjects with stroke, cerebral palsy and dementia. The ICC values were higher for this test than for the number of repetitions in the 30-s test. The five-repetition sit-to-stand test also showed good inter/intra-rater reliabilities (ICC=0.97-0.99) for stroke and inter-rater reliability (ICC=0.99) for subjects with Parkinson disease and incomplete spinal cord injury. For this test, the criterion-related validity for subjects with stroke, cerebral palsy and incomplete spinal cord injury was, in general, moderate (correlation=0.40-0.77), and the feasibility and safety were good for subjects with Alzheimer''s disease.

Conclusions

The five-repetition sit-to-stand test was used more often in subjects with ND, and most of the measurement properties were investigated and showed adequate results.     

The decision to prolong life: ethical perspectives of a clinical dilemma

• ? As a result of rapid developments in medical technology, health-care workers are increasingly faced with decisions regarding the prolongation of life and the withdrawal of treatment. Such decisions are often extremely complex and present a moral dilemma: they are further complicated by prevailing politico-economic, social and cultural influences.
• ? This article contrasts deontological and utilitarian philosophical perspectives, and discusses ethical principles which impinge on the decision making process.
• ? A knowledge and understanding of these philosophies and principles are essential to assist clinical practitioners in the examination of moral issues surrounding life and death.

     

Validity and reliability of an internet-based temporal gait assessment tool with healthy adults: a pilot study

OBJECTIVES: To assess in healthy adults the validity and the inter- and intrarater reliability of the Internet-based Shaw Gait Assessment (SGA). DESIGN: Concurrent test-retest reliability and validity study with participants, 4 raters, and the Elite motion analysis system (used as the criterion standard). SETTING: Motion analysis laboratory in a university physical therapy department. PARTICIPANTS: Convenience sample of 16 healthy men and women (age range, 28-53y). INTERVENTION: Each subject performed 2 consecutive walks "at a comfortable pace" on a 6-m walkway. A video camera from the Elite motion analysis system filmed reflective markers, which were attached to subjects' shoes, and the reflective markers provided the criterion standard. Four raters simultaneously recorded each walk by using laptop computers and the SGA. MAIN OUTCOME MEASURES: Paired t test (5% level) for average differences between each test and retest for raters and the Elite; Pearson correlations, limits of agreement, and coefficients of variation (CVs) for validity of the tool; intraclass correlation coefficients (ICCs) for inter- and intrarater reliability. RESULTS: Pearson product moment correlation coefficients between each of the raters and the Elite ranged from .92 to .95 for speed, from .85 to .97 for cadence, from .87 to .92 for step length, from .61 to .84 for left advance limb time, and from .68 to .83 for right advance limb time. Pooled CVs for all variables were below 8% for all raters and the Elite. Pooled ICCs for intrarater reliability were .89 for speed, .99 for cadence, .84 for step length, .76 for left limb advance time, and .84 for right limb advance time. Interrater ICCs were .89 for speed, .82 for cadence, .76 for step length, .66 for left limb advance time, and .81 for right limb advance time. CONCLUSIONS: The SGA is a valid and reliable tool for several key temporal measures of gait in a healthy adult population.     

Circulating microRNAs: a novel class of biomarkers to diagnose and monitor human cancers

Specific and sensitive non-invasive biomarkers for the detection of human epithelial malignancies are urgently required to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are 19-24 nt noncoding RNAs that are frequently dysregulated in cancer and have shown great promise as tissue-based markers for cancer classification. Once thought to be unstable RNA molecules, miRNAs are now shown to be stably expressed in serum, plasma, urine, saliva, and other body fluids. Moreover, the unique expression patterns of these circulating miRNAs are correlated with certain human diseases, including various types of cancer. Therefore, tumor-derived miRNAs in serum or plasma are emerging as novel blood-based fingerprints for the detection of human cancers, especially at an early stage. This review presented newly uncovered cellular and molecular mechanisms of the sources and stability of circulating miRNAs, revealing their great potential as a class of highly specific and sensitive biomarkers for tumor classification and prognostication. Meanwhile, this review also addressed certain critical issues that hinder the wide application of this new approach. Some potential challenges for the transition of circulating miRNAs from a research setting to a clinical application were also highlighted, with a future perspective of the incorporation of circulating miRNAs in the field of clinical oncology, especially their great potential from diagnostic to prognostic and predictive applications.     

Apolipoprotein(a) inhibits the conversion of Glu‐plasminogen to Lys‐plasminogen: a novel mechanism for lipoprotein(a)‐mediated inhibition of plasminogen activation

Summary. Background: Elevated plasma concentrations of lipoprotein(a) [Lp(a)] are associated with an increased risk for thrombotic disorders. Lp(a) is a unique lipoprotein consisting of a low‐density lipoprotein‐like moiety covalently linked to apolipoprotein(a) [apo(a)], a homologue of the fibrinolytic proenzyme plasminogen. Several in vitro and in vivo studies have shown that Lp(a)/apo(a) can inhibit tissue‐type plasminogen activator‐mediated plasminogen activation on fibrin surfaces, although the mechanism of inhibition by apo(a) remains controversial. Essential to fibrin clot lysis are a number of plasmin‐dependent positive feedback reactions that enhance the efficiency of plasminogen activation, including the plasmin‐mediated conversion of Glu‐plasminogen to Lys‐plasminogen. Objective: Using acid–urea gel electrophoresis to resolve the two forms of radiolabeled plasminogen, we determined whether apo(a) is able to inhibit Glu‐plasminogen to Lys‐plasminogen conversion. Methods: The assays were performed in the absence or presence of different recombinant apo(a) species, including point mutants, deletion mutants and variants that represent greater than 90% of the known apo(a) isoform sizes. Results: Apo(a) substantially suppressed Glu‐plasminogen conversion. Critical roles were identified for the kringle IV types 5–9 and kringle V; contributory roles for sequences within the amino‐terminal half of the molecule were also observed. Additionally, with the exception of the smallest naturally‐occurring isoform of apo(a), isoform size was found not to contribute to the inhibitory capacity of apo(a). Conclusion: These findings underscore a novel contribution to the understanding of Lp(a)/apo(a)‐mediated inhibition of plasminogen activation: the ability of the apo(a) component of Lp(a) to inhibit the key positive feedback step of plasmin‐mediated Glu‐plasminogen to Lys‐plasminogen conversion.     

Prospective evaluation of tools to assess the psychological response of CPR provision to a relative who has suffered a cardiac arrest: a pilot project

Objectives

We aimed to evaluate assessment tools to measure the psychological impact of providing CPR to a relative. We set out to evaluate the Revised Impact of Event Scale (IES-R) and Texas Inventory of Grief (TIG) for comparing CPR providers and non-providers, and to establish whether research of this nature had a negative impact on the participants. We also collected narrative data from CPR providers.

Methods

Prospective sampling of relatives of patients presenting to hospital who had witnessed their relative have a cardiac arrest and who had performed or witnessed CPR. Participants performed two interviews and completed the IES-R and the TIG.

Results

Twenty-nine cardiac arrest victims presented, with ten relatives enrolled. The IES-R and TIG were feasible, and registered moderate responses from CPR providers and non-providers.There was no significant difference in the IES-R score between CPR providers and non-providers (1.96 vs. 1.04, p = 0.3). There was no significant difference between scores obtained at two different time points (1.75 vs. 1.63, p = 0.43). Participants demonstrated a moderate response on the TIG (mean TIG score 2.8, SD 1.7). Participants did not have a negative perception of study involvement, and actually perceived a benefit from discussion with a health professional.

Conclusion

It is acceptable and achievable to prospectively assess the response of a cardiac arrest victim's relatives to the provision of CPR. The test instruments used were appropriate and feasible. Results suggested a sample size of 48 to achieve a statistically significant result.