Opportunities to optimise colistin stewardship in hospitalised patients in South Africa: Results of a multisite utilisation audit.

Background: Colistin is an old antibiotic that has been reintroduced as salvage therapy in hospitalised patients because it is frequently the only agent active against Gram-negative bacteria. Various guidelines for colistin administration have led to confusion in establishing the appropriate dose, which has potential for adverse consequences including treatment failure or toxicity. The emergence and spread of colistin resistance has been documented in South Africa (SA), but no local information exists on how and why colistin is used in hospitals, and similarly, compliance with current dosing guidelines is unknown.

What Does It Take to Search Organized? The Cognitive Correlates of Search Organization During Cancellation After Stroke.

Objectives: Stroke could lead to deficits in organization of visual search. Cancellation tests are frequently used in standard neuropsychological assessment and appear suitable to measure search organization. The current aim was to evaluate which cognitive functions are associated with cancellation organization measures after stroke.

Prism Adaptation in Rehabilitation? No Additional Effects of Prism Adaptation on Neglect Recovery in the Subacute Phase Poststroke: A Randomized Controlled Trial.

Background: Patients with neglect ignore or respond slower to contralesional stimuli. Neglect negatively influences independence in activities of daily living (ADL). Prism adaptation (PA) is one of the most frequently studied treatments, yet there is little evidence regarding positive effects on neglect behavior in ADL.

Software-aided approach to investigate peptide structure and metabolic susceptibility of amide bonds in peptide drugs based on high resolution mass spectrometry.

Interest in using peptide molecules as therapeutic agents due to high selectivity and efficacy is increasing within the pharmaceutical industry. However, most peptide-derived drugs cannot be administered orally because of low bioavailability and instability in the gastrointestinal tract due to protease activity. Therefore, structural modifications peptides are required to improve their stability.

Prognostic modeling of oral cancer by gene profiles and clinicopathological co-variables.

Accurate staging and outcome prediction is a major problem in clinical management of oral cancer patients, hampering high precision treatment and adjuvant therapy planning. Here, we have built and validated multivariable models that integrate gene signatures with clinical and pathological variables to improve staging and survival prediction of patients with oral squamous cell carcinoma (OSCC). Gene expression profiles from 249 human papillomavirus (HPV)-negative OSCCs were explored to identify a 22-gene lymph node metastasis signature (LNMsig) and a 40-gene overall survival signature (OSsig).

A situational analysis of current antimicrobial governance, regulation, and utilization in South Africa.

The Global Action Plan on antimicrobial resistance calls for the use of antimicrobial medicines in human and animal health to be optimized, in tandem with a strengthening of the knowledge and evidence base through surveillance and research. However, there is a paucity of consumption data for African countries such as South Africa. Determining antimicrobial consumption data in low-resource settings remains a challenge.

High-Level Resistance to Colistin Mediated by Various Mutations in the Gene among Carbapenemase-Producing Klebsiella pneumoniae.

Mutations in genes encoding a two-component regulator involved in modifications of lipopolysaccharide were searched for among a collection of colistin-resistant isolates. Four isolates, respectively, producing carbapenemases NDM-1, OXA-181, or KPC-2 showed mutated CrrB proteins compared with those in wild-type strains. Complementation assays with a wild-type CrrB protein restored the susceptibility to colistin in all cases, confirming the involvement of the identified substitutions in the resistance phenotype.

Erratum to: Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].

Crystal structure of ()-4-benzyl-idene-6-phenyl-1,2,3,4,7,8,9,10-octa-hydro-phenanthridine.

The preparation of the title compound, CHN, was achieved by the condensation of an ethano-lic mixture of benzaldehyde, cyclo-hexa-none and ammonium acetate in a 2:1:1 molar ratio. There are two crystallographically independent mol-ecules in the asymmetric unit. The two cyclo-hexyl rings adopt an -envelope conformation with the benzyl moiety adopting a conformation with respect to the nitro-gen atom of the phenanthridine segment.

The defining a model for antimicrobial stewardship-results from an international cross-sectional survey.

Background: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world.

Variations in Definitions and Outcome Measures in Gastroesophageal Reflux Disease: A Systematic Review.

Context: Gastroesophageal reflux (GER) is defined as GER disease (GERD) when it leads to troublesome symptoms and/or complications. We hypothesized that definitions and outcome measures in randomized controlled trials (RCTs) on pediatric GERD would be heterogeneous.

Objectives: Systematically assess definitions and outcome measures in RCTs in this population.

Antimicrobial resistance in the next 30 years, humankind, bugs and drugs: a visionary approach.

Purpose: To describe the current standards of care and major recent advances with regard to antimicrobial resistance (AMR) and to give a prospective overview for the next 30 years in this field.

Methods: Review of medical literature and expert opinion were used in the development of this review.

Results: There is undoubtedly a large clinical and public health burden associated with AMR in ICU, but it is challenging to quantify the associated excess morbidity and mortality.

Stepwise introduction of the 'Best Care Always' central-line-associated bloodstream infection prevention bundle in a network of South African hospitals.

Background: Healthcare-associated infection (HCAI) remains a major international problem.

Aim: The 'Best Care Always!' (BCA) campaign was launched in South Africa to reduce preventable HCAI, including central-line-associated bloodstream infection (CLABSI).

Methods: The intervention took place in 43 Netcare Private Hospitals, increasing later to 49 with 958 intensive care units (ICUs) and 439 high-care (HC) beds and 1207 ICUs and 493 HC beds, respectively.

Identification of GalNAc-Conjugated Antisense Oligonucleotide Metabolites Using an Untargeted and Generic Approach Based on High Resolution Mass Spectrometry.

Antisense oligonucleotides linked by phosphorothioates are an important class of therapeutics under investigation in various pharmaceutical companies. Antisense oligonucleotides may be coupled to high-affinity ligands (triantennary N-acetyl galactosamine = GalNAc) for hepatocyte-specific asialoglycoprotein receptors (ASGPR) to enhance uptake to hepatocytes and to increase potency. Since disposition and biotransformation of GalNAc-conjugated oligonucleotides is different from unconjugated oligonucleotides, appropriate analytical methods are required to identify main cleavage sites and degradation products of GalNAc conjugated and unconjugated oligonucleotides in target cells.

New leads for fragment-based design of rhenium/technetium radiopharmaceutical agents.

Multiple possibilities for the coordination of -[Re(CO)(HO)] to a protein have been determined and include binding to Asp, Glu, Arg and His amino-acid residues as well as to the C-terminal carboxylate in the vicinity of Leu and Pro. The large number of rhenium metal complex binding sites that have been identified on specific residues thereby allow increased target identification for the design of future radiopharmaceuticals. The core experimental concept involved the use of state-of-art tuneable synchrotron radiation at the Diamond Light Source to optimize the rhenium anomalous dispersion signal to a large value ('' of 12.

Dynamic assessment of visual neglect: The Mobility Assessment Course as a diagnostic tool.

Introduction: Visual neglect is a frequent disorder following stroke and is often diagnosed by neuropsychological assessment. However, paper-and-pencil tasks have low predictive value as they lack sensitivity to capture neglect in complex, dynamic situations, such as activities of daily living. Aims of the current study were to assess the feasibility of the Mobility Assessment Course (MAC), a visual search multitask, to assess neglect, and its relation with existing neglect tasks.

Structure-metabolism relationships in AOX: Chemical insights from a large database of aza-aromatic and amide compounds.

Aldehyde oxidase (AOX) is a metabolic enzyme catalyzing the oxidation of aldehyde and aza-aromatic compounds and the hydrolysis of amides, moieties frequently shared by the majority of drugs. Despite its key role in human metabolism, to date only fragmentary information about the chemical features responsible for AOX susceptibility are reported and only "very local" structure-metabolism relationships based on a small number of similar compounds have been developed. This study reports a more comprehensive coverage of the chemical space of structures with a high risk of AOX phase I metabolism in humans.

Application of Imaging Techniques to Cases of Drug-Induced Crystal Nephropathy in Preclinical Studies.

A number of drugs can cause precipitates within renal tubules leading to crystal nephropathy. Crystal nephropathy is usually an exposure-related finding and is not uncommon in preclinical studies, where high doses are tested. An understanding of the nature of precipitates is important for human risk assessment and further development.

Potential for thermochemical conversion of biomass residues from the integrated sugar-ethanol process - Fate of ash and ash-forming elements.

In this work, potential for thermochemical conversion of biomass residues from an integrated sugar-ethanol process and the fate of ash and ash-forming elements in the process are presented. Ash, ash-forming elements, and energy flows in the process were determined using mass balances and analyses of eight different biomass samples for ash contents, elemental compositions, and heating values. The results show that the ash content increases from the sugarcane to the final residue, vinasse.

Characteristics and health conditions of a group of nursing home patients with mental-physical multimorbidity - the MAPPING study.

Background: Long-term care facilities have partly taken over the traditional asylum function of psychiatric hospitals and house an increasing group of patients with mental-physical multimorbidity (MPM). Little is known about the characteristics, behavior, and care dependency of these patients. This paper aims to describe these aspects.

Pharmacological Treatment of Visuospatial Neglect: A Systematic Review.

Objectives: The aims of the current review were (1) to give an overview of human studies investigating pharmacotherapy to ameliorate visuospatial neglect and (2) to evaluate the quality of those studies.

Methods: A systematic literature search using PubMed, Scopus, and ResearchGate was conducted in regard to studies that evaluated pharmacological interventions aiming to ameliorate poststroke visuospatial neglect. The search was limited in the following features: species (human), adults (≥18 years of age), language (English), and type of neglect (visuospatial).

From guidelines to practice: a pharmacist-driven prospective audit and feedback improvement model for peri-operative antibiotic prophylaxis in 34 South African hospitals.

Background: Few data exist on the implementation of process measures to facilitate adherence to peri-operative antibiotic prophylaxis (PAP) guidelines in Africa.

Objectives: To implement an improvement model for PAP utilizing existing resources, in order to achieve a reduction in surgical site infections (SSIs) across a heterogeneous group of 34 urban and rural South African hospitals.

Methods: A pharmacist-driven, prospective audit and feedback strategy involving change management and improvement principles was utilized.