STUDY QUESTION How often do large randomized clinical trials that have been registered with ClinicalTrials.gov remain unpublished after trial completion, and how often are the results from ...unpublished studies available on ClinicalTrials.gov? SUMMARY ANSWER Among the 585 randomized trials with at least 500 participants registered and completed prior to 2009, a published manuscript containing trial results could not be identified for 171 (29%) trials. Of these unpublished studies, 133 (78%) also had no results available in the ClinicalTrials.gov results database. WHAT IS KNOWN AND WHAT THIS PAPER ADDS It is known that non-publication of trial results is common among small studies across a wide range of clinical topics. This paper shows that non-publication is also an important problem among large clinical trials.
Objective: The optimal resuscitation approach during the initial treatment of hypotensive trauma patients remains unknown, but some clinical trials have observed a survival benefit from restricting ...fluid administration prior to definitive hemorrhage control. We sought to characterize emergency medical services (EMS) protocols for the administration of intravenous fluids in this setting. Methods: Publicly accessible statewide EMS protocols for the treatment of hypotensive trauma patients were included and characterized by: 1) goal of fluid administration, 2) dosing strategy, 3) maximum dose, 4) type of fluid, and 5) specific protocols for head trauma, if present. Results: Of the 27 states with a publicly available, statewide protocol, 21 have a numeric systolic blood pressure (SBP) target for resuscitation. Of these, 16 describe a goal of maintaining SBP ≥90 mmHg with or without additional goals, three specify a goal that is less than 90 mmHg, and two specify a goal ≥100 mHg. Dosing strategies also vary and include both standard bolus strategies (200 mL, 250 mL, 500 mL, and 1 L with repeat) as well as weight-based strategies (20 mL/kg). Nine states specify a maximum dose of 2 L without medical control. Fifteen protocols recommend the use of normal saline, 1 recommends the use of lactated Ringer's, and 11 recommend the use of either normal saline or lactated Ringer's. Nine states have distinct protocols for patients with head trauma, all of which indicate maintaining a higher SBP than for trauma patients without head trauma. Conclusion: State EMS protocols for fluid administration for hypotensive trauma patients vary in regard to SBP goal, fluid dose, and fluid type. Clinical trials to determine the optimal use of intravenous fluids for hypotensive trauma patients are needed to define the optimal approach.
Objective
To investigate the structural brain abnormalities and their diagnostic accuracy through qualitative and quantitative analysis in term born and very preterm birth or with very low birth ...weight (VP/VLBW) adults.
Methods
We analyzed 3-T MRIs acquired in 2011–2013 from 67 adults (27 term born controls, mean age 26.4 years, 8 females; 40 VP/VLBWs, mean age 26.6 years, 16 females). We compared automatic segmentations of the white matter, deep gray matter and cortical gray matter, manual corpus callosum measurements and visual ratings of the ventricles and white matter with
t
tests, logistic regression, and receiver operator characteristic (ROC) curves.
Results
Automatic segmentation correctly classified 84% of cases; visual ratings correctly classified 63%. Quantitative volumetry based on automatic segmentation revealed higher ventricular volume, lower posterior corpus callosum, and deep gray matter volumes in VP/VLBW subjects compared to controls (
p
< 0.01). Visual rating and manual measurement revealed a thinner corpus callosum in VP/VLBW adults (
p
= 0.04) and deformed lateral ventricles (
p
= 0.03) and tendency towards more “dirty” white matter (
p
= 0.06). Automatic/manual measures combined with visual ratings correctly classified 87% of cases. Stepwise logistic regression identified three independent features that correctly classify 81% of cases: ventricular volume, deep gray matter volume, and white matter aspect.
Conclusion
Enlarged and deformed lateral ventricles, thinner corpus callosum, and “dirty” white matter are prevalent in preterm born adults. Their visual evaluation has low diagnostic accuracy. Automatic volume quantification is more accurate but time consuming. It may be useful to ask for prematurity before initiating further diagnostics in subjects with these alterations.
Key Points
• Our study confirms prior reports showing that structural brain abnormalities related to preterm birth persist into adulthood.
• In the clinical practice, if large and deformed lateral ventricles, small and thin corpus callosum, and “dirty” white matter are visible on MRI, ask for prematurity before considering other diagnoses.
• Although prevalent, visual findings have low accuracy; adding automatic segmentation of lateral ventricles and deep gray matter nuclei improves the diagnostic accuracy.
Purpose
The aim of this study was to analyze sex differences in outcome after thrombectomy for acute ischemic stroke in clinical practice in a large prospective multicenter registry.
Methods
Data of ...consecutive stroke patients treated with thrombectomy (June 2015–April 2018) derived from an industry-independent registry (German Stroke Registry–Endovascular Treatment) were prospectively analyzed. Multivariable binary logistic regression analyses were applied to determine whether sex is a predictor of functional independence outcome (defined as a modified Rankin scale mRS 0–2) 90 days after stroke.
Results
In total, 2316 patients were included in the analysis, 1170 (50.5%) were female and 1146 (49.5%) were male. Women were older (median age 78 vs. 72 years;
p
< 0.001) and more frequently had a prestroke functional impairment defined by mRS >1 (24.8% vs. 14.1%;
p
< 0.001). In unadjusted analyses, independent outcome at 90 days was less frequent in women (33.2%) than men (40.6%;
p
< 0.001). Likewise, mortality was higher in women than in men (30.7% vs. 26.4%;
p
= 0.024). In adjusted regression analyses, however, sex was not associated with outcome. Lower age, a lower baseline National Institutes of Health Stroke Scale score, a higher Alberta Stroke Program Early CT score, prestroke functional independence, successful reperfusion, and concomitant intravenous thrombolysis therapy predicted independent outcome.
Conclusion
Women showed a worse functional outcome after thrombectomy for acute ischemic stroke in clinical practice; however, after adjustment for crucial confounders sex was not a predictor of outcome. The difference in outcome thus appears to result from differences in confounding factors such as age and prestroke functional status.
Background
Nonsteroidal anti‐inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of ...NSAID‐induced respiratory symptoms in population across Europe and to assess its association with upper and lower respiratory tract disorders.
Methods
The GA2LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15–74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled. Questionnaires including questions about age, gender, presence of symptoms of asthma, allergic rhinitis, chronic rhinosinusitis, smoking status, and history of NSAID‐induced hypersensitivity reactions were sent to participants by mail. Totally, 62 737 participants completed the questionnaires.
Results
The mean prevalence of NSAID‐induced dyspnea was 1.9% and was highest in the three Polish centers Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%) and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants with chronic rhinosinusitis symptoms (Odds Ratio 2.12; 95%CI 1.78–2.74), asthma symptoms in last 12 months (2.7; 2.18–3.35), hospitalization due to asthma (1.53; 1.22–1.99), and adults vs children (1.53; 1.24–1.89), but was not associated with allergic rhinitis.
Conclusion
Our study documented significant variation between European countries in the prevalence of NSAID‐induced respiratory hypersensitivity reactions, and association with chronic airway diseases, but also with environmental factors.
Patients with a left (LHS) or right hemispheric stroke (RHS) differ in terms of clinical symptoms due to lateralization of specific cortical functions. Studies on functional outcome after stroke and ...endovascular thrombectomy (EVT) comparing both hemispheres showed conflicting results so far. The impact of stroke laterality on patient-reported health-related quality of life (HRQoL) after EVT has not yet been adequately addressed and still remains unclear.
Consecutive stroke thrombectomy patients, derived from a multi-center, prospective registry (German Stroke Registry) between June 2015 and December 2019, were included in this study. At 90 days, outcome after EVT was assessed by the modified Rankin scale (mRS) and HRQoL using the European QoL-five dimensions questionnaire utility-index (EQ-5D-I; higher values indicate better HRQoL) in patients with LHS and RHS. Adjusted regression analysis was applied to evaluate the influence of stroke laterality on outcome after EVT.
In total, 5683 patients were analyzed. Of these, 2953 patients (52.8%) had LHS and 2637 (47.2%) RHS. LHS patients had a higher baseline NIHSS (16 vs. 13, p < 0.001) and a higher ASPECTS (9 vs. 8, p < 0.001) compared to RHS patients. Among survivors, patients with LHS less frequently had a self-reported affected mobility (p = 0.037), suffered less often from pain (p = 0.04) and anxiety/depression (p = 0.032) three months after EVT. After adjusting for confounders (age, sex, baseline NIHSS), LHS was associated with a better HRQoL (ß coefficient 0.04, CI 95% 0.017-0.063; p = 0.001), and better functional outcome assessed by lower values on the mRS (ß coefficient - 0.109, CI 95% - 0.217-0.000; p = 0.049).
Ninety days after EVT, LHS patients have a better functional outcome and HRQoL. Patients with RHS should be actively assessed and treated for pain, anxiety and depression to improve their HRQoL after EVT.
Clinical evidence of the potential treatment benefit of intravenous thrombolysis preceding unsuccessful mechanical thrombectomy (MT) is scarce.
To determine whether intravenous thrombolysis (IVT) ...prior to unsuccessful MT improves functional outcomes in patients with acute ischemic stroke.
Patients were enrolled in this retrospective cohort study from the prospective, observational, multicenter German Stroke Registry-Endovascular Treatment between May 1, 2015, and December 31, 2021. This study compared IVT plus MT vs MT alone in patients with acute ischemic stroke due to anterior circulation large-vessel occlusion in whom mechanical reperfusion was unsuccessful. Unsuccessful mechanical reperfusion was defined as failed (final modified Thrombolysis in Cerebral Infarction grade of 0 or 1) or partial (grade 2a). Patients meeting the inclusion criteria were matched by treatment group using 1:1 propensity score matching.
Mechanical thrombectomy with or without IVT.
Primary outcome was functional independence at 90 days, defined as a modified Rankin Scale score of 0 to 2. Safety outcomes were the occurrence of symptomatic intracranial hemorrhage and death.
After matching, 746 patients were compared by treatment arms (median age, 78 IQR, 68-84 years; 438 women 58.7%). The proportion of patients who were functionally independent at 90 days was 68 of 373 (18.2%) in the IVT plus MT and 42 of 373 (11.3%) in the MT alone group (adjusted odds ratio AOR, 2.63 95% CI, 1.41-5.11; P = .003). There was a shift toward better functional outcomes on the modified Rankin Scale favoring IVT plus MT (adjusted common OR, 1.98 95% CI, 1.35-2.92; P < .001). The treatment benefit of IVT was greater in patients with partial reperfusion compared with failed reperfusion. There was no difference in symptomatic intracranial hemorrhages between treatment groups (AOR, 0.71 95% CI, 0.29-1.81; P = .45), while the death rate was lower after IVT plus MT (AOR, 0.54 95% CI, 0.34-0.86; P = .01).
These findings suggest that prior IVT was safe and improved functional outcomes at 90 days. Partial reperfusion was associated with a greater treatment benefit of IVT, indicating a positive interaction between IVT and MT. These results support current guidelines that all eligible patients with stroke should receive IVT before MT and add a new perspective to the debate on noninferiority of combined stroke treatment.
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