Clinical negligence

BACKGROUND: Infections complicating neurosurgery pose unacceptable mortality and morbidity. AIMS: To summarize what is known about the epidemiology, diagnosis and treatment of post-neurosurgical meningitis (PNM). SOURCES: PubMed, references of identified studies and reviews, and personal experience when evidence was lacking. CONTENT: The incidence and pathogen distribution of PNM is highly variable. A shift towards Gram-negative bacteria has been observed with use of antibiotic prophylaxis and antibiotic-coated devices directed mainly against Gram-positive bacteria...

OBJECTIVES: Work-related traumatic brain injuries (TBIs) are not well documented in the literature. Published studies mostly rely on worker databases that fail to provide clinically relevant information. Our objective is to describe the characteristics of hospitalized patients and their work-related TBI. METHODS: We used the Québec provincial trauma and TBI program databases to identify all patients with a diagnosis of work-related TBI admitted to the Montreal General Hospital, a level 1 trauma center, between 2000 and 2014...

The aim of this study was to assess the psychometric properties of the five-level (EQ-5D-5L) in comparison with the standard three-level (EQ-5D-3L) classification systems of the EQ-5D in a sample of psoriatic patients. Psoriatic subjects (n = 396) recruited from 16 private practicing centers from various areas of Greece self-completed the two EQ-5D versions and the Dermatology Life Quality Index, while information was also collected on socio-demographics, clinical characteristics and comorbidities. The EQ-5D-5L and EQ-5D-3L were evaluated in terms of agreement, feasibility, ceiling effects, redistribution properties, inconsistency, informativity, and convergent and known-groups validity...

In view of the clinical importance of hypofractionated radiotherapy, track models which are based on multi-hit events are currently reinvestigated. These models are often criticized, because it is believed that the probability of multi-track hits is negligible. In this work, the probabilities for one- and multi-track events are determined for different biological targets. The obtained probabilities can be used with nano-dosimetric cluster size distributions to obtain the parameters of track models. We quantitatively determined the probabilities for one- and multi-track events for 100, 500 and 1000 keV electrons, respectively...

BACKGROUND: Catheter associated urinary tract infections (CAUTI) account for about 25% of nosocomial infections globally and often result in increased morbidity and healthcare costs. An added concern is the presence of microbial biofilms which are major reservoirs of bacteria, especially antibiotic resistant bacteria, in catheters. Since the practice of the closed drainage system, innovations to combat CAUTI have not produced significant improvements in clinical outcomes. The lack of a robust laboratory platform to test new CAUTI preventive strategies may impede development of novel technologies...

BACKGROUND: Autism Spectrum Disorders (ASD) are highly heritable, but the exact etiological mechanisms underlying the condition are still unclear. METHODS: Using a multiple rater twin design in a large sample of general population preschool twins, this study aimed to (a) estimate the contribution of genetic and environmental factors to autistic traits, controlling for the possible effects of rater bias, (b) to explore possible sex differences in etiology and (c) to investigate the discordance in autistic traits in monozygotic and same-sex dizygotic twin pairs...

Broad spectrum activities, a unique mode of actions and rare resistant variants make antimicrobial peptide (AMP) a potential alternative to antibiotics. However, AMPs still have limitations in clinical development due to their physiological stability, toxicity and manufacturing costs. Cbf-14, derived from cathelicidin-BF has been proven to be effective against drug-resistant bacteria. Herein, a series of Cbf-14 mutants were designed to overcome these limitations. Design strategies included substitutions of lysine (Lys) or leucine (Leu) with similar residues such as ornithine (Orn) and norleucine (Ile), which are unnatural amino acids, to generate AMPs with enhanced therapeutic potential...

OBJECTIVE: The severity of central sleep apnoea (CSA), a common comorbidity in patients with chronic heart failure (CHF) and reduced ejection fraction, markedly decreases from the supine to the lateral sleeping position, with no difference between the left and right positions. The mechanisms responsible for this beneficial effect have not yet been elucidated. METHODS: We tested the hypothesis that CSA attenuation in the left lateral position is due, at least in part, to an improvement in cardiac haemodynamics...

Multi-drug resistant Acinetobacter baumannii (MDR-Ab), an opportunistic pathogen associated with nosocomial and combat related infections, has a high mortality due to its virulence and limited treatment options. Deletion of the thioredoxin gene (TrxA) from a clinical isolate of MDR-Ab resulted in a 100-fold increase in 50% lethal dose (LD50) in a systemic challenge murine model. Thus, we investigated the potential use of this attenuated strain as a live vaccine against MDR-Ab. Mice were vaccinated by subcutaneous (s...

The devastating effects of heavy alcohol drinking have been long time recognized. In the last decades, potential benefits of modest red wine drinking were suggested. In European countries in which red wide intake is not negligible (such as France), the association between cholesterol and cardiovascular (CV) risk was less evident, suggesting the action of some protective molecules in red wine or other foods and drinks. Epidemiological and mechanistic evidence of a J-shaped relationship between red wine intake and CV risk further supported the "French paradox"...

Despite nanomedicine has shown great potential for reverse cancer cells resistance, the suboptimal transport across multiple biological obstacles seriously impedes its reaching targets at an efficacious level, which remains the challenging hurdle for clinical success in resistant cancer therapy. Here, a lipid-based hybrid nanoparticle was designed to efficiently deliver the therapeutics to resistant cells and treat resistant cancer in vivo. The hybrid nanoparticles (D-NPs/TET) are composed of a pH-responsive prodrug 1,2-distearoyl-snglycero-3-phosphoethanolamine (DSPE)-doxorubicin (DOX), a efflux inhibitor tetrandrine (TET) and a surfactant 1,2-distearoyl-snglycero-3-phosphoethanolamine-[methoxy (polyethylene glycol)-2000] (DSPE-mPEG2000), which hierarchically combatted the sequential physiological and pathological barriers of drug resistance, exhibited prolonged blood circulation, high tumor accumulation, and deep tumor parenchyma penetration...

OBJECTIVE: This phase I study of ZYAN1 was conducted to evaluate the safety, tolerability, and pharmacokinetics following oral administration in healthy volunteers. METHODS: The study was a randomized, double-blind, placebo-controlled phase I study carried out in two parts in addition to a third part involving an open-label study to evaluate the food/sex effect. A total of 100 subjects were enrolled into the study as follows: part I-single-dose study with ZYAN1 10, 25, 50, 100, 150, 200, and 300 mg (n = 56); part II-multiple-dose study with every other day dosing of ZYAN1 100, 150, 200, and 300 mg (n = 32); and part III-sex and food effect study with ZYAN1 150 mg (n = 12; open-label)...

Very high energy electrons (VHEE) in the range from 100 to 250MeV have the potential of becoming an alternative modality in radiotherapy because of their improved dosimetric properties compared with 6-20MV photons generated by clinical linear accelerators (LINACs). VHEE beams have characteristics unlike any other beams currently used for radiotherapy: femtosecond to picosecond duration electron bunches, which leads to very high dose per pulse, and energies that exceed that currently used in clinical applications...

BACKGROUND: Clinical trials testing proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have demonstrated an unanticipated but significant lipoprotein (a) (Lp(a))-lowering effect, on the order of 25% to 30%. Although the 50% to 60% reduction in low-density lipoprotein (LDL)-cholesterol (LDL-C) achieved by PCSK9i is mediated through its effect on LDL receptor (LDLR) preservation, the mechanism for Lp(a) lowering is unknown. OBJECTIVE: We sought to characterize the degree of concordance between LDL-C and Lp(a) lowering because of PCSK9i in a standard of care patient cohort...

Red blood cells (RBCs) express a variety of immunomodulatory markers that enable the body to recognize them as self. We have shown that RBC membrane glycophorin A (GPA) receptor can mediate membrane attachment of protein therapeutics. A critical knowledge gap is whether attaching drug encapsulated nanoparticles (NPs) to GPA, and modification with cell penetration peptide (CPP) will impact binding, oxygenation and induce cellular stress. The objective of this study was to formulate copolymer-based NPs containing model fluorescent tagged bovine serum albumin (BSA) with GPA-specific targeting ligands such as ERY1 (ENPs), single chain variable antibody (scFv TER-119, SNPs), and low molecular weight protamine based CPP (LNPs) and determine their biocompatibility using a variety of complementary high-throughput in vitro assays...

BACKGROUND: Patients with congenital heart defects are frequently hospitalized before surgery. This exposes them to a high risk for pathogen colonization. There are limited data on colonization prevalence in the pediatric cardiac population, and limited data concerning its potential role in the risk of developing infections after cardiac surgery. AIM: This study aimed to verify the impact of preoperative colonization on postoperative infections in a population of pediatric cardiac surgery patients coming from Italy and developing countries...

RATIONALE, AIMS, AND OBJECTIVES: Although the issue of monitoring appropriateness of tumour markers (TMs) request in outpatients remains crucial, proper indicators are still demanding. The present study developed and explored indicators of inappropriate TM ordering in outpatients through the data mining of electronic health records (EHRs). METHODS: Carcinoembryonic antigen (CEA), alfa-fetoprotein (AFP), carbohydrate antigen (CA)125, CA15.3, CA19.9, and prostate-specific antigen (PSA) ordered in outpatients during a year were examined by mining EHRs of a Local Health Authority in Italy...

Opioid antagonists, naloxone and naltrexone have long been used in clinical practice and research. In addition to their low selectivity, they easily pass through the blood-brain barrier. Quaternization of the amine group in these molecules, (e.g. methylnaltrexone) results in negligible CNS penetration. In addition, zwitterionic compounds have been reported to have limited CNS access. The current study, for the first time gives report on the synthesis and the in vitro [competition binding, G-protein activation, isolated mouse vas deferens (MVD) and mouse colon assay] pharmacology of the zwitterionic compound, naltrexone-14-O-sulfate...

PUROSE: To calculate theoretical fitting success rates (SR) for a range of typical soft contact lens (SCL) designs using a mathematical model. METHOD: A spreadsheet mathematical model was used to calculate fitting SR for various SCL designs. Designs were evaluated using ocular topography data from 163 subjects. The model calculated SR based on acceptable edge strain (within range 0-6%) and horizontal diameter overlap (range 0.2-1.2mm). Where lenses had multiple base curves (BCs), eyes unsuccessful with the steeper BC were tested with the flatter BC and aggregate SR calculated...

Ostreid herpesvirus-1 microvariants (OsHV-1) cause severe mortalities in farmed Crassostrea gigas in Europe, New Zealand and Australia. Outbreaks are seasonal, recurring in the warmer months of the year in endemic estuaries. The reference genotype and microvariant genotypes of OsHV-1 have been previously detected in the tissues of apparently healthy adult oysters naturally exposed to OsHV-1 in the field. However, the role of such oysters as reservoirs of infection for subsequent mortality outbreaks remains unclear...