Detection of drug-related adverse events in hospitals

Adverse drug events (ADEs) contribute significantly to patient morbidity and mortality as well as to cost for healthcare providers and society. Since only serious ADEs will result in hospitalisation, the evaluation of ADEs leading to hospitalisation reflects safety and appropriateness of ambulatory prescribing. ADEs occurring during hospitalisation may result from the special clinical situation of hospitalised patients; high degree of severity of diseases (e.g., renal failure, necessity of intensive care) and specific drugs administered only in hospitals. Moreover, the number of diagnostic and therapeutic procedures carried out daily puts the hospitalised patient at an extremely high risk for ADEs.     

Secondary and tertiary sulfonamides: a patent review (2008 – 2012)

Introduction: Secondary and tertiary sulfonamides (R-SO₂NR₁R₂) are defined by the single or double N-alkyl or N-aryl/heteroaryl substitution of the primary sulfonamide respectively. They can be obtained easily by the classical S_N2 or nucleophile acyl substitution displacements using the appropriate synthones. Many classes of compounds used in therapy present the substituted sulfonamide groups and there is also a continuous interest in different fields such as the herbicides herein schematically reported.

Areas covered: The intent of this article is to give a comprehensive overview of the most important patents in the last decade related to pathologies of great interest. All selected patents claim new compounds bearing the secondary or/and tertiary sulfonamide moiety, and state to have biological activities. The article is neither intended for detailed discussions of the sulfonamides mode of action on the specific therapeutic targets, nor for their contribution to the physicochemical properties of the molecules they are introduced into, as the scientific literature in such topics is exhaustive and in many cases, debates are still ongoing. The main fields covered are related to pathologies affecting the CNS, cardiac disorders, anti-virals, inflammation diseases, glaucoma, bone remodeling, anti-cancer, and finally a section is also dedicated to herbicides.

Expert opinion: The insertion of the secondary/tertiary sulfonamide group into the organic scaffolds is chemically straightforward and not associated to particular toxicity in the cells or in the organisms. Therefore, it is possible to create large libraries of compounds, which can be tested for different diseases. As demonstrated by the patents reported in the present review, the research in medicinal chemistry, and other fields, takes big advantages as new leads are created, and might be further developed.     

Veno-arterial CO2 difference and lactate for prediction of early mortality after cardiac arrest

Patients admitted to intensive care after cardiac arrest are at risk of circulatory shock and early mortality due to cardiovascular failure. The aim of this study was to evaluate the ability of the veno-arterial pCO₂ difference (∆pCO₂; central venous CO₂ – arterial CO₂) and lactate to predict early mortality in postcardiac arrest patients. This was a pre-planned prospective observational sub-study of the target temperature management 2 trial. The sub-study patients were included at five Swedish sites. Repeated measurements of ∆pCO₂ and lactate were conducted at 4, 8, 12, 16, 24, 48, and 72 h after randomization. We assessed the association between each marker and 96-h mortality and their prognostic value for 96-h mortality. One hundred sixty-three patients were included in the analysis. Mortality at 96 h was 17%. During the initial 24 h, there was no difference in ∆pCO₂ levels between 96-h survivors and non-survivors. ∆pCO₂ measured at 4 h was associated with an increased risk of death within 96 h (adjusted odds ratio: 1.15; 95% confidence interval [CI]: 1.02–1.29; p = .018). Lactate levels were associated with poor outcome over multiple measurements. The area under the receiving operating curve to predict death within 96 h was 0.59 (95% CI: 0.48–0.74) and 0.82 (95% CI: 0.72–0.92) for ∆pCO₂ and lactate, respectively. Our results do not support the use of ∆pCO₂ to identify patients with early mortality in the postresuscitation phase. In contrast, non-survivors demonstrated higher lactate levels in the initial phase and lactate identified patients with early mortality with moderate accuracy.     

Current Use of Fractional Flow Reserve: A Nationwide Survey

Major medical society guidelines recommend the measurement of fractional flow reserve (FFR) as an aid in choosing percutaneous coronary intervention in patients with stable coronary artery disease. We investigated the measurement of FFR among interventionalists, analyzing operators'' attributes and decision-making processes to reveal differences in their applications of FFR and the reasons for those differences. An electronic survey study of 1,089 interventionalists was performed from 2 February through 6 March 2012, yielding 255 responses. Most respondents were >45 years old (58%), worked primarily in a community hospital (59%), and performed 10 to 30 cases per month (52%). More than half (145/253, 57%) used FFR measurement in less than one third of cases, and 39 of 253 (15%) never used it. There were no differences in use of FFR by age, practice location, or angiogram volume (P >0.05 for all). Respondents used FFR measurement more frequently than intravascular ultrasonography (73% vs 60%) to help guide the decision to stent (P <0.01). Operators reported that their primary reasons for not using FFR were lack of availability (47%) and problems with reimbursement (39%). There was no difference in FFR use by operator age, practice setting, or case volume.     

乙型肝炎疫苗预防接种与疑似不良反应

乙型肝炎(乙肝)是严重危害我国人群健康的传染病，按照2006年全国乙肝血清流行病学调查结果估算，我国总人群中有34％的人感染过HBV，其中HBsAg携带者约为9 300万，每年有大约26万人由于感染HBV导致肝硬化和原发性肝癌死亡?。HBV可通过母婴、血液和性接触三种途径传播，目前尚无有效治愈乙肝的药物，因此接种疫苗成为控制乙肝的关键。     

Socioeconomic Status Is Associated with Provision of Bystander Cardiopulmonary Resuscitation

Objective. Although socioeconomic status (SES) has been linked to multiple health outcomes, there have been few studies of the effect of SES on the provision of bystander cardiopulmonary resuscitation (CPR) during cardiac arrest events and no studies that we know of on the effect of SES on the provision of dispatcher-assisted bystander CPR. This study sought to define the relationship between SES and the provision of bystander CPR in an emergency medical system that includes dispatcher-provided CPR instructions. Methods. This study was a retrospective, cohort analysis of cardiac arrests due to cardiac causes occurring in private residences in King County, Washington, from January 1, 1999, to December 31, 2005. We used the tax-assessed value of the location of the cardiac arrest as an estimate of the SES of potential bystanders as well as multiple measures from 2000 Census data (education, employment, median household income, and race/ethnicity). We also examined the effect of patient and system characteristics that may affect the provision of bystander CPR. Logistic regression models were used to analyze the association of these factors with two outcomes: the provision of bystander CPR with and without dispatcher assistance. Results. Forty-four percent (1,151/2,618) of cardiac arrest victims received bystander CPR. Four hundred fifty-seven people (17.5% of the entire study population, 39.7% of those who received any bystander CPR) received CPR without telephone instructions. A total of 694 people received dispatcher-assisted bystander CPR (25.6% of the entire population, 60.4% of those receiving any bystander CPR). After adjusting for demographic and care factors, we found a strong association between the tax-assessed value of the cardiac arrest location and increased odds of the provision of bystander CPR without dispatcher instructions and bystander CPR with dispatcher assistance compared with no bystander CPR. Conclusions. This study suggests that higher bystander SES is associated with increased rates of bystander CPR with and without dispatcher instructions. CPR training programs that target lower-SES communities and assessment of these training methods may be warranted.     

Emerging role of multimodality imaging in management of inflammatory pericardial diseases

The non-specific and highly variable symptomatology of inflammatory pericardial diseases create clinical challenges in making accurate diagnosis, which often requires the integration of clinical findings, imaging and invasive hemodynamic assessment. Echocardiography is considered to be a first-line imaging test in pericardial diseases. Emerging imaging modalities, especially cardiac MRI allowed better understanding of pericardial anatomy, physiology and, for the first time, enable demonstration of the pericardial inflammation. On the other hand, cardiac computed tomography is excellent tool to define pericardial thickness, pericardial calcification and is useful for preoperative planning once pericardiectomy is indicated especially in the patients with prior cardiac surgery.     

A comprehensive review of intake estimates of di-isononyl phthalate (DINP) based on indirect exposure models and urinary biomonitoring data

Di-isononyl phthalate (DINP) is a high molecular weight general purpose plasticizer used principally in the manufacture of flexible polyvinyl chloride (PVC) articles. DINP metabolites can be measured in biological media such as blood and urine. However, measurement of a substance in the blood or urine does not by itself mean that the chemical causes or is associated with adverse health outcomes. This is particularly pertinent given the advances in modern analytical techniques whereby ever diminishing trace amounts of substances can be detected. Therefore, it is a scientific necessity that risk assessors understand the relationship of biomonitoring data to estimation of exposure so that appropriate comparisons can be made to the no observed adverse effects levels (NOAELs) or other points of departure from toxicological studies in animals. In this paper, estimates of daily DINP intake are calculated for various population segments based on urinary biomonitoring data and are compared to estimates of exposure based on indirect methods and to health-based exposure guidance values. In general, intake estimates converge on a mean of 1–2 μg/kg/day regardless of source of exposure or population cluster; a value 2-orders of magnitude lower than health-based exposure guidance values, ranging from 120 to 290 μg/kg/day, which have been established by regulatory authorities and other authoritative bodies as representing acceptable levels.