Clinical trial transparency update: an assessment of the disclosure of results of company-sponsored trials associated with new medicines approved in Europe in 2012

Background:

The objective of this study was to assess the timely disclosure of results of company-sponsored clinical trials related to all new medicines approved by the European Medicines Agency (EMA) during 2012. This is an extension of the previously reported study of trials related to all new medicines approved in Europe in 2009, 2010 and 2011, which found that over three-quarters of all these trials were disclosed within 12 months and almost 90% were disclosed by the end of the study.

Methods:

The methodology used was exactly as previously reported. Various publicly available information sources were searched for both clinical trial registration and disclosure of results. All completed company-sponsored trials related to each new medicine approved for marketing by the EMA in 2012, carried out in patients and recorded on a clinical trials registry and/or included in an EMA European Public Assessment Report (EPAR), were included. Information sources were searched between 1 May and 31 July 2014.

Outcome measures and results:

The main outcome measure was the proportion of trials for which results had been disclosed on a registry or in the scientific literature either within 12 months of the later of either first regulatory approval or trial completion, or by 31 July 2014 (end of survey). Of the completed trials associated with 23 new medicines licensed to 17 different companies in 2012, results of 90% (307/340) had been disclosed within 12 months, and results of 92% (312/340) had been disclosed by 31 July 2014.

Conclusions:

The disclosure rate within 12 months of 90% suggests the industry is now achieving disclosure in a timely manner more consistently than before. The overall disclosure rate at study end of 92% indicates that the improvement in transparency amongst company-sponsored trials has been maintained in the trials associated with new medicines approved in 2012.     

Pulmonary Embolism Response Team activation during the COVID-19 pandemic in a New York City Academic Hospital: a retrospective cohort analysis

Journal of Thrombosis and Thrombolysis - Coronavirus disease 2019 (COVID-19) is associated with increased rates of deep vein thrombosis (DVT) and pulmonary embolism (PE). Pulmonary Embolism...     

Impact of bariatric surgery and weight loss medications in adults with type 1 diabetes in the T1D Exchange Clinic Registry

AimTo investigate the impact of bariatric surgery and weight loss medications in adults with type 1 diabetes.Materials and methodsSubjects enrolled in the T1D Exchange (T1DX) Clinic Registry age ≥ 18 years with a diabetes duration of ≥1 year were included in the analysis (n = 13,501). Data for participants (n = 37) with bariatric surgery after diabetes onset were assessed before and after surgery and also compared to a matched control group. Data for participants who reported the use of FDA-approved weight loss medications (n = 483) were assessed before starting, during use, and after stopping the medications and also compared to a matched control group. Variables of interest included BMI, HbA1c, blood pressure, lipid profile, rates of acute complications. Data were analyzed using linear mixed models.ResultsBariatric surgery resulted in BMI reduction from 38.8 ± 9.1 kg/m² to 33.3 ± 6.7 kg/m² (P = 0.006) and HbA1c reduction from 8.8 ± 1.3% (73 ± 14.2 mmol/mol) to 8.1 ± 1.1% (65 ± 12.0 mmol/mol) (P = 0.05). Weight loss medications were not associated with weight loss or better glycemic control although stopping liraglutide favored weight gain. Both interventions were not associated with a significant change in blood pressure or lipid profile. There were no adverse events associated with the use of weight loss medications.ConclusionsBariatric surgery is effective for weight loss and may improve glycemic control in selected patients. Weight loss medications are not associated with diabetes improvement. A trial with liraglutide may be attempted for weight control, but weight loss medications in general do not show a significant effect.     

Tracheal diameter as a predictor of pulmonary function

Tracheal diameter (TD) was measured from standard posterior-anterior (PA) roentgenograms and evaluated as a predictor of pulmonary function. A population of 222 non-smokers with normal chest roentgenograms was analyzed. A subset of the population with the trachea indented two or more mm by the aorta (on PA film), as well as males and females, were analyzed separately. In males without aortic indentation of the trachea, tracheal diameter alone accounted for 28% of the variation in peak expiratory flow rate (PEFR). Age and height accounted for an additional 19% of the variation. Tracheal diameter was second to age as a predictor for forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC), accounting for an additional 10% of the variation in each. However, tracheal diameter did not explain significant variability in the female group. This study supports an upper airway effect on flow at large lung volumes. It also demonstrates that a tracheal diameter, measured from a PA chest film, is a useful predictor of pulmonary function that can be easily applied in population surveys.     

Validation of in vivo myocardial strain measurement by magnetic resonance tagging with sonomicrometry

OBJECTIVES: This study was designed to validate strain measurements obtained using magnetic resonance tagging with spatial modulation of magnetization (SPAMM). We compared circumferential segment shortening measurements (%S) obtained using SPAMM to sonomicrometry %S in a canine model with (n = 28) and without (n = 3) coronary artery ligation. BACKGROUND: Magnetic resonance tagging enables noninvasive measurement of myocardial strain, but such strain measurements have not yet been validated in vivo. METHODS: Circumferential sonomicrometry crystal pairs were placed in apical myocardium at ischemic risk in ligation studies and in adjacent and remote myocardium. The %S was obtained from closely juxtaposed sonomicrometry and SPAMM sites. RESULTS: Paired data were available from 19 of 31 studies. Both methods distinguished remote from ischemic function effectively (p = 0.014 for SPAMM and p = 0.002 for sonomicrometry). SPAMM %S was similar to sonomicrometry %S in ischemic myocardium (2 +/- 3 vs. 0 +/- 3 p = 0.067) but was slightly higher than sonomicrometry %S in remote myocardium (11 +/- 10 vs. 7 +/- 5, p = 0.033). End-systolic (n = 30) and late systolic (n = 34) SPAMM %S correlated well with sonomicrometry %S (r = 0.84, p < 0.0001 and r = 0.88, p < 0.0001). CONCLUSIONS: Magnetic resonance tagging using SPAMM can quantitate myocardial strain in ischemic and remote myocardium. This study validates its application in scientific investigation and clinical assessment of patients with myocardial ischemia.     

Enhanced production of oxygen radicals in nocturnal asthma.

Although the mechanisms of nocturnal worsening of pulmonary function in asthmatics have not been entirely established, airway inflammation is felt to be a major factor in disease severity. Consequently, to determine whether changes in bronchoalveolar lavage (BAL) fluid cellular components and their functions are related to nocturnal airway obstruction, we performed BAL at 4:00 A.M. and at 4:00 P.M. in asthma subjects with (n = 5) and without (n = 10) nocturnal asthma. No significant changes were observed from 4:00 P.M. to 4:00 A.M. in the concentration of total cells or the percentage or concentration of eosinophils or neutrophils in BAL fluid from subjects with or without nocturnal asthma. However, superoxide anion generation by air-space cells from subjects with nocturnal asthma was significantly greater at 4:00 A.M. than at 4:00 P.M. (6.9 +/- 1.7 versus 1.8 +/- 0.5 nmol/500K cells/h, p less than 0.05). Moreover, superoxide production at 4:00 A.M. was greater in subjects with than in those without nocturnal asthma (6.9 +/- 1.7 versus 2.2 +/- 0.6, p less than 0.02). Furthermore, in our group of asthmatics, the change in generation of superoxide anion from 4:00 P.M. to 4:00 A.M. was significantly correlated with the change in FEV1 (r = -0.71, p less than 0.01). We conclude that the development of nocturnal airway obstruction in asthma is associated with enhanced production of oxygen radicals by air-space cells. Because oxygen radicals can cause airway injury and thus enhance bronchial obstruction, it is possible that the release of these reactive compounds is causally associated with nocturnal asthma.     

Aldosterone antagonism: An emerging strategy for effective blood pressure lowering

Aldosterone antagonists have been available for many decades for the treatment of hypertension, but their use has been mostly limited to patients with classic primary aldosteronism or to combination products with hydrochlorothiazide to minimize risk for hypokalemia. Recently, indications for aldosterone antagonists have been expanded to include congestive heart failure and first-line treatment of mild-to-moderate hypertension. In addition, we have reported that spironolactone has significant antihypertensive benefit when added to existing regimens in patients with resistant hypertension. This benefit was present in patients with and without hyperaldosteronism and was additive to chronic renin-angiotensin blockade with angiotensin-converting enzyme (ACE) inhibitors or angiotensinreceptor blockers (ARBs). Eplerenone, a selective aldosterone antagonist, avoids the androgen and progesterone receptor-related adverse events that sometimes occur with spironolactone, such as breast tenderness, gynecomastia, sexual dysfunction, and menstrual irregularities. In clinical trials, eplerenone has been shown to have antihypertensive benefit in treating mild-to-moderate hypertension similar to other widely used classes of agents. With recent demonstrations of benefit in multiple segments of the hypertensive population, aldosterone antagonists represent emerging opportunity for controlling high blood pressure.     

Electronic Medical Records and Electronic Health Records: Overview for Nurse Practitioners

Electronic medical records (EMRs) and electronic health records (EHRs) have become essential systems by which nurse practitioners (NPs) communicate vital patient information to other members of the health care team as well as to patients. In this article we examine the important distinctions between EMRs and EHRs; review the genesis of these types of records; summarize applicable provisions of the Health Insurance Portability and Accountability Act from a recent legal case centered around NP utilization of EMRs and EHRs; address open patient access to medical information; and examine threats to security. Suggestions are offered on ways in which NPs can safeguard confidential patient information.     

Insomnia with objective short sleep duration is associated with cognitive impairment: a first look at cardiometabolic contributors to brain health

Study ObjectivesInsomnia with objective short sleep duration has been previously associated with adverse cardiometabolic health outcomes as well as poorer cognitive performance in otherwise noncognitively impaired adults. However, studies demonstrating an increased prevalence of cognitive impairment (CI) in this insomnia phenotype are lacking.MethodsWe analyzed data from Penn State Adult Cohort (N = 1,524; 48.9 ± 13.4 years; 53.4% women). Self-reported sleep difficulty was defined as normal sleep (n = 899), poor sleep (n = 453), and chronic insomnia (n = 172). Objective short sleep duration was defined as less than 6-h of sleep, based on in-lab, 8-h polysomnography. CI (n = 155) and possible vascular cognitive impairment (pVCI, n = 122) were ascertained using a comprehensive neuropsychological battery. Analyses adjusted for age, sex, race, education, body mass index, apnea/hypopnea index, smoking, alcohol, psychoactive medication, and mental and physical health problems.ResultsParticipants who reported poor sleep or chronic insomnia and slept objectively less than 6 hours were associated with a 2-fold increased odds of CI (OR = 2.06, 95% confidence limits [CL] = 1.15–3.66 and OR = 2.18, 95% CL = 1.07–4.47, respectively) and of pVCI (OR = 1.94, 95% CL = 1.01–3.75 and OR = 2.33, 95% CL = 1.07–5.06, respectively). Participants who reported poor sleep or chronic insomnia and slept objectively more than 6 hours were not associated with increased odds of either CI (OR = 0.72, 95% CL = 0.30–1.76 and OR = 0.75, 95% CL = 0.21–2.71, respectively) or pVCI (OR = 1.08, 95% CL = 0.42–2.74 and OR = 0.76, 95% CL = 0.16–3.57, respectively).ConclusionsInsomnia with objective short sleep duration is associated with an increased prevalence of CI, particularly as it relates to cardiometabolic health (i.e. pVCI). These data further support that this insomnia phenotype may be a more biologically severe form of the disorder associated with cardiovascular, cerebrovascular, and neurocognitive morbidity.