In this report, we demonstrate that usnic acid causes

rapid and strong inhibition of RNA and DNA synthesis in Gram-positive bacteria, represented by Bacillus subtilis and Staphylococcus aureus, while it does not inhibit production of macromolecules (DNA, RNA, and proteins) in Escherichia coli, which is resistant to even high doses of this compound. However, we also observed slight inhibition of RNA synthesis in a Gram-negative XL184 bacterium, Vibrio harveyi. Inhibition of protein synthesis in B. subtilis and S. aureus was delayed, which suggest indirect action (possibly through impairment of transcription) of usnic acid on translation. Interestingly, DNA synthesis was halted rapidly in B. subtilis and S. aureus, suggesting interference of usnic acid with elongation of DNA replication. We propose that inhibition of RNA synthesis may be a general mechanism of antibacterial action of usnic acid, with additional direct mechanisms, such as impairment of DNA replication in B. subtilis and S. aureus. “
“The latest threat of multidrug-resistant Gram-negative bacteria corresponds to the emergence of carbapenemase NDM-1 (New Delhi metallo-β-lactamase) producers, mostly in Enterobacteriacae. Five blaNDM-1-positive plasmids of different incompatibility groups (IncL/M,

FII, A/C and two untypeable plasmids) from clinical Enterobacteriaceae were evaluated for conjugation properties and host specificity. Successful conjugative transfers were obtained using Neratinib all tested enterobacterial species as recipients (Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium and Proteus mirabilis) and all plasmid types. Conjugation frequencies varied from 1 × 10−4 to 6 × 10−8 transconjugants per donor. Higher conjugation rates were obtained for two plasmids at 30 °C compared with that observed at 25 and 37 °C. Carbapenems used as selector did not lead to higher conjugation frequencies. None of the five plasmids was transferable to Acinetobacter baumannii or Pseudomonas aeruginosa by conjugation. Isotretinoin This work underlines how efficient the spread of the carbapenemase blaNDM-1 gene could be among Enterobacteriaceae.

Carbapenem-hydrolysing β-lactamases identified in Enterobacteriaceae are the emerging threat for treating infected patients. New Delhi metallo-β-lactamase (NDM-1) confers resistance to all β-lactams except the monobactam aztreonam and is expressed in multidrug or pandrug-resistant isolates (Kumarasamy et al., 2010). The NDM-1 was identified first from Klebsiella pneumoniae and Escherichia coli isolates from a patient previously hospitalized in India (Yong et al., 2009) (hence its name). NDM-1 producers have been reported from all over the world except from South and Central America but mostly from the United Kingdom, India and Pakistan (Nordmann et al., 2011). It has been identified from Enterobacteriaceae and Acinetobacter baumannii isolates and recently from environmental Gram-negative rods (Nordmann et al., 2011; Walsh et al., 2011).

Approximately 21% of Switzerland’s 7.7 million population are less than 20 years of age, and 22% of Swiss residents are foreign-born. International travel has become increasingly popular worldwide. The number of families traveling with their children to and from tropical destinations has steadily increased over the last years providing potential exposures to tropical diseases. This is a global trend. Travel data of US residents from 2000 reported that 7% (1.9 million) of US international travelers were children.1 There learn more is little

published literature on the incidence and type of illness in Europe-based children who travel. The aims of this study are to characterize the profile of travel-associated illness occurring in children in Zürich, identify risk groups, and use this information as an evidence base to formulate pre-travel health advice. The Zürich

Centre of the GeoSentinel surveillance network (GeoSentinel, The Global Surveillance Network of the International Society of Travel Medicine and the Centers for Diseases Control and Prevention; www.geosentinel.org) provided clinician-based find more pediatric surveillance data for this analysis during an 18-month period. The Zürich site is a composite site of the University Hospital and the University of Zürich Children’s Hospital. For the purpose of our study, patients were included if they were younger than 16 years and had sought medical advice for a presumed travel-related illness at the Emergency Room of the University of Zürich Children’s Hospital, Switzerland,

between July 2007 and December 2008. Final diagnoses were assigned by a physician. Data were collected according to a standardized, anonymous questionnaire and entered into a Structured Query Language database. The questionnaire comprises demographic data (age, sex, country of birth, country of residence, current citizenship), travel history in the last 5 years, inpatient or outpatient status, major clinical complaint (more than one per patient is possible), reason for most recent travel, and patient classification. Final diagnoses were assigned a diagnostic code from a standardized list Silibinin of >500 diagnoses, which were also categorized into 21 broad syndrome groups. Patient diagnoses were defined as follows: “diarrhea” included gastroenteritis, acute diarrhea of parasitic, viral, bacterial or unknown origin, and chronic diarrhea of unknown origin; “dermatologic”; “febrile/systemic illness”; “other gastrointestinal and genitourinary” included abdominal pain, hepatitis, pyelonephritis, appendicitis, and urinary tract infection; “injury and musculoskeletal” included trauma, fracture, arthritis, nonspecific symptoms or findings, and vertigo; “ophthalmologic”; “oral and dental”; and “respiratory” included upper and lower respiratory infections, otitis, bronchitis, and asthma.

Presentation of stimuli and recording of participants’ responses were carried out using

Cogent (http://www.vislab.ucl.ac.uk/cogent_graphics.php) running in Matlab 6.5 (MathWorks™). In each of the six experimental sessions, a T2*-weighted, gradient-echo, echo-planar imaging sequence was used to acquire 164 40-slice (2 mm thickness and 1 mm gap; TE = 65 ms; α = 90 °) volumes covering the whole brain and cerebellum with an in-plane resolution of 3 × 3 mm (64 × 64 matrix, fov 192 × 192 × 144 mm3; TR = 2600 ms). A high-resolution (1 × 1 × 1 mm3) structural image (MPRAGE sequence) was also collected. fMRI TSA HDAC chemical structure data were analysed using SPM8 (http://www.fil.ion.ucl.ac.uk/spm) procedures, running in Matlab 7.6 (MathWorks™), after discarding the first four dummy volumes in each session to allow for T1 equilibrium effect. Slice timing correction was applied to correct for offsets of slice acquisition. EPI volumes were realigned to the first volume for each subject to correct for interscan movement, and unwarped for movement-induced inhomogeneities of the magnetic field using realignment CX-5461 mouse parameters (Andersson

et al., 2001). EPI volumes were stereotactically normalized into the standard space defined by the Montreal Neurological Institute (MNI) using a two-step procedure: the mean EPI image created during realignment was coregistered with the structural image, which was spatially normalized to the SPM T1 template using a 12-parameter affine and non-linear cosine basis function transformation, both transformations being subsequently applied to all EPI volumes. new Normalized images were smoothed using an 8-mm isometric Gaussian kernel to account for residual inter-subject differences in functional anatomy (Friston et al., 2007). Analysis of the functional imaging data entailed the creation

of statistical parametric maps representing a statistical assessment of hypothesized condition-specific effects (Friston et al., 1994). A random effect procedure was adopted for data analysis. Within individual subjects, the 20-s stimulations were modelled for the three types of stimuli (Control, Oldowan, Acheulean), the 5-s tasks were modelled for the three types of stimuli and two tasks (Imagine, Evaluate), and the motor responses were modelled as events (duration 0) irrespective of the experimental condition. Rest was modelled as a 12-s condition. Each condition was defined with a boxcar function convolved with SPM8 canonical haemodynamic response function to estimate condition-specific effects with the General Linear Model. Low-frequency drifts were removed by a high-pass filtering with a cut-off of 128 s.

, 2007), thereby permitting serum albumin entry into the brain (van Vliet et al., 2007), followed by astrocytic albumin uptake (Ivens et al., 2007); and activation of endothelial and leukocytes interactions (Fabene et al., 2008; Kleen & Holmes, 2008; Ransohoff, 2009).

Bleomycin mouse However, despite this wealth of data, the mechanisms underlying enduring immune and inflammatory responses in temporal lobe epilepsy (TLE) remain largely elusive. As described in the current issue of EJN, Aronica et al. (2010) took an important step toward resolving this issue. They demonstrated the selective up-regulation of a proinflammatory signalling-associated microRNA (miRNA) in a rat model of TLE as well as in human TLE. MicroRNAs are genomically encoded small non-coding RNAs that influence the translation and stability of mRNAs (Zhao & Srivastava, 2007). Aronica et al. (2010) focused on miR-146a, a microRNA that is induced by pro-inflammatory stimuli, modulating innate immunity through regulation of Toll-like receptor signaling and cytokine responses (Taganov et al., 2006). miR-146a is also known to play a functional role in T lymphocyte-mediated immune responses (Curtale et al., 2010). In order to understand the regulation and function of miR-146a in epilepsy, Aronica

et al. (2010) investigated the dynamics of miR-146a expression during epileptogenesis in a rat model of TLE. Furthermore, they studied Trichostatin A cost the expression and cellular distribution of this microRNA in hippocampal tissue obtained from TLE patients with hippocampal sclerosis. The authors report an increase of miR-146a expression in the CA3 region of rats during latent and chronic phases of experimental epilepsy, as well as in the human tissue. It is important to note that miR-146a expression was evident not only in neurons, but most prominently in GFAP-positive reactive astrocytes, underscoring their key role for orchestrating inflammatory responses in epilepsy. The results of this study PI-1840 suggest new avenues toward the identification of cellular mechanisms underlying epileptogenesis and persistent functional alterations in chronic epilepsy.

Furthermore, these results indicate that miRNAs, linking astrocytes with inflammatory mechanisms, are potentially promising new cellular targets for the development of antiepileptic drugs. “
“Cell therapy for spinal cord injury (SCI) is a promising strategy for clinical application. Both bone marrow mesenchymal stromal cells (MSCs; also known as bone marrow-derived ‘mesenchymal stem cells’) and olfactory ensheathing cells (OECs) have demonstrated beneficial effects following transplantation in animal models of SCI. However, due to the large number of affecting parameters that determine the therapy success and the lack of methodological consensus, the comparison of different works is difficult. Therefore, we compared the effects of MSC and OEC transplants at early or delayed time after a spinal cord contusion injury in the rat.

P. T., B. G., M. L., and J. J. are current employees of GSK Biologicals; M. L. and J. J. also have stock Afatinib ownership at GSK Biologicals. “
“Ciguatera fish poisoning is a travel-related illness characterized by a combination of gastrointestinal and neurological symptoms in persons who eat ciguatoxic seafood in endemic areas. In 2009, an outbreak of the disease on a

refrigerator vessel in the port of Hamburg was investigated. The ship’s crew fell ill after they ate fish from a catch in the Caribbean 2 weeks earlier. All 15 sailors on board were examined by port medical officers. Samples of blood and stool specimens were taken from symptomatic sailors. The frozen fish was secured for the prevention of further disease spreading and additional diagnostic tests. All but one sailor ate the fish. The intoxication resulted in gastrointestinal or neurological symptoms in all 14 sailors who consumed the

fish and persisted in varying degrees in 93% of sailors over at least 14 days. No fatality occurred, but two seamen were “unfit for duty” on the ship due to severity of symptoms. The diagnosis was supported by the fact FG-4592 purchase that all seafarers who consumed the same reef fish, experienced typical signs, symptoms, and time course consistent with ciguatera fish poisoning. The fish from the catch in the Caribbean was identified as Caranx sexfasciatus (Bigeye Trevally) and Cephalopholis miniata (Red Grouper). An experimental assay later confirmed presence of the ciguatoxin in the fish. Sailors are an occupational group at risk for ciguatera fish poisoning due to potentially unsafe food sources selleckchem during international travel. Even if no fatality occurred, the disease affected

marine operations due to high attack rates and chronicity of symptoms. Medical doctors must be aware that ciguatera fish poisoning is a risk for seafarers traveling in tropical and subtropical areas. Stocking of food in affected ports from safe sources, adequate training of ship cooks, and informing sailors about the risk of fishing are needed to prevent disease occurrence in seafarers in international trade and traffic. Ciguatera fish poisoning is an illness characterized by a combination of gastrointestinal, neurological, and neuropsychiatric symptoms in people who eat seafood that contains the naturally occurring ciguatoxins. Most of the reported cases are related to the consumption of large reef fish in travelers to tropical and subtropical areas and to inhabitants of endemic areas. The global incidence of the disease was estimated to affect annually between 10,000 and 50,000 individuals; however, the accurate epidemiology is difficult to assess since reporting is a requirement in only a few countries.[1, 2] This article summarizes the investigation results in an outbreak on board a cargo ship under Bahamian flag that was docked in the Port of Hamburg in Germany for repair work.

This measure is widely used to assess the detectability of an imperative stimulus in a manner independent of a given individual’s response criteria, or fluctuations therein. d-prime is computed by taking into account the probability of Pictilisib mw correctly responding to targets when a target is present and the probability of incorrectly initiating a response in the absence of a target (Green & Swets, 1966). To assess the time-course of oscillatory power changes in the alpha band during our cued-attention task, TSE waveforms were computed (Foxe et al., 1998). TSE waveforms provide a robust

measure of induced oscillatory power changes (i.e. changes in amplitude of rhythmic activity in which phase varies randomly from trial to trial). The computation of the TSE waveforms in the present study took the following course: (i) Individual trials were bandpass-filtered from 8 to 14 Hz (fourth-order digital Butterworth, zero-phase); (ii) the analytic representation of the bandpass-filtered trials were acquired

by applying the Hilbert transform; (iii) the absolute value of the analytic representation of each trial was taken as a measure of the instantaneous amplitude in the alpha band across the trial; and (iv) trials in each condition were averaged. RT and d-prime accuracy were analysed using a repeated-measures anova with Trial (switch vs. repeat) and Task Modality (visual vs. auditory) as within-subject factors. TSE measures were analysed using the mean amplitude across nine electrode sites over frontopolar (D4/D5/D6/D11/D12/D13/C28/C29/C30 in the Biosemi labeling convention) TGF-beta inhibitor and parieto-occipital (A15/A16/A17/A21/A22/A23/A28/A29/A30) scalp regions during an early (700–900 ms) and a late (1100–1300 ms) phase of anticipatory preparatory activity. As a first step, our analyses detailed the time-course and topographic distribution of oscillatory power changes in the alpha band associated with task-set reconfiguration. This was accomplished by a repeated-measures anova with factors Modality (visual vs. auditory),

Trial (switch vs. Leukotriene-A4 hydrolase repeat), Time (early vs. late) and Scalp Region (frontopolar vs. parieto-occipital). If a significant Modality × Trial interaction was found, our second step was to run two protected anovas, one testing task-set reconfiguration between and one within modalities in order to unpack the interaction. For the between-modalities anova, we tested the time-course and strength of alpha power deployment contrasting switch-auditory against switch-visual trials and repeat-auditory against repeat-visual trials. The between modalities anova considers alpha power deployment associated with task-set reconfiguration and differences therein between Switch and Repeat trials. For the within-modality anova we tested time-course and strength of alpha power deployment contrasting switch-auditory against repeat-auditory trials as well as switch-visual against repeat-visual trials.

1% ethanol), E2 or efavirenz in the presence or absence of the anti-oestrogen ICI Thiazovivin 182,780. The relative cell number after 4–6 days of growth was determined using crystal violet staining and WST cell proliferation staining (Roche Applied Science, Indianapolis, IN, USA) as described previously [21]. Fluorescence polarization-based competitive binding assays were performed to measure the relative binding affinity of efavirenz for ER-α using a commercially available kit

(P2698; Invitrogen, Carlsbad, CA, USA) according to the manufacturer’s specifications. We have previously described the use of this assay to evaluate the relative affinity of ligands for ER-α [19]. Reactions (100 μL) were carried out in black-wall, low-volume 96-well plates (6006270; PerkinElmer, Waltham, MA, USA). Following 2 hours of incubation at room temperature, fluorescence polarization values were obtained using a BMG PolarStar Omega plate reader (BMG Labtech, Durham, NC, USA). Student’s t-tests

were used to compare treatments with respective controls (sigmastat Version 3.5; Systat Software Inc., San Jose, CA, USA). Curve fitting and effective concentration for half-maximal growth (EC50) or binding (IC50) were determined using graphpad prism Version 4.03 (GraphPad selleck products Software, San Diego, CA, USA). Efavirenz (10 μM) induced growth of MCF-7 cells that was ∼1.2-fold greater than that induced by vehicle treatment (Fig. 1a; right, solid bar). This effect was blocked by the anti-oestrogen ICI 182,780 (Fig. 1a; right, chequered bar). As expected, E2 (10 nM) maximally stimulated growth (∼3.2-fold)

versus the vehicle treatment (Fig. 1a; left, solid bar). ICI 182,780 completely blocked E2-induced growth (Fig. 1a; left, chequered bar). Efavirenz induced a similar amount of growth in ZR-75-1 cells following 4 days of treatment (Fig. 1b), and this growth was blocked by ICI 182,780 (data not shown). However, efavirenz did not stimulate the growth of T47D cells following 6 days of treatment (Fig. 1b). The concentration–effect curve for efavirenz-induced growth in MCF-7 cells is shown in Fig. 1c. Efavirenz-induced cellular growth was concentration-dependent Phospholipase D1 up to 10 μM. Growth induced at any concentration was completely blocked by 1 μM ICI 182,780 (data not shown). Higher efavirenz concentrations (50 or 100 μM) were growth inhibitory to MCF-7, T47D and ZR-75-1 cells; this effect could not be blocked by ICI 182,780 (data not shown). Although this growth inhibition at high concentrations prevented full characterization of the concentration–effect relationship, we estimated an EC50 of approximately 15.7 μM using the data obtained for lower concentrations (1–10 μM). The affinity of efavirenz binding to the ER relative to that of E2 was determined using a competitive binding assay as described in ‘Materials and methods’ section.

Antecedent hypoglycaemia diminishes physiological responses, and impairs the ability to identify further episodes, leading to a vicious downwards spiral and a high risk of further severe hypoglycaemic episodes. Fully established hypoglycaemia unawareness is thankfully rare, but difficulty in recognising the onset of hypoglycaemia is common. Therefore effective treatments to reverse or prevent hypoglycaemia unawareness are urgently needed. This review

Metformin cost article examines the evidence around the pathophysiology of hypoglycaemia unawareness, and current therapeutic strategies. Copyright © 2011 John Wiley & Sons. “
“Important side effects and potential clinical hazards have emerged from long-term follow up in some drug classes used in type Crizotinib solubility dmso 2 diabetes treatment. Systematic phase 4 post-marketing data in early use of newer diabetes drugs may have a role in informing drug choice in practice and assist in pharmacoeconomic assessments of these drug choices. We carried out a comparison of the prevalence of drug withdrawals derived from both liraglutide registration trial data, and a systematic, prospective case-note review of all new liraglutide prescriptions (n=176) from a specialist diabetes clinic over the first 12 months of drug introduction. Trial data used for the marketing authorisation

application for liraglutide reported 7.0% withdrawal due to adverse events. Equal numbers of patients experienced mild, moderate and severe side effects. By contrast, data derived from a ‘real world’ clinical group describe 14.8% withdrawal due to adverse events, with withdrawal typically occurring early, by three months. Adverse events were more frequently responsible for treatment withdrawal at lower, compared to higher, doses

of liraglutide therapy. Systematic observations of withdrawals in early use of new drugs in current clinical practice are higher than reported in registration trial data. These data highlight that post-marketing surveillance should inform guideline recommendations and pharmacoeconomic evaluations. Copyright © 2012 John Wiley & Sons. “
“The aim of this research was to determine whether consumers PTK6 are able to read and understand food labels. A structured interview was conducted during September 2009 with 176 consumers from a cross section of the population. Consumers, from teenagers to pensioners, were interviewed in a variety of locations including a town centre, a cafe, a supermarket, a commercial workplace, a leisure centre and a fast food restaurant. The majority of respondents (n=155, 88%) try to lead a healthy lifestyle with 149 (85%) reporting that eating healthily is important to them. Over half of respondents (n=102, 58%) read food labels when purchasing food and drink.

Eur J Endocrinol 2006; 154: 899–906. 21. Malkin CJ, et al. The effect of testosterone replacement on endogenous inflammatory

cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab 2004; 89: 3313–8. 22. Bhasin S, et al. Testosterone therapy in adult men with androgen deficiency syndrome: An endocrine society clinical practice guideline. J Clin End Metab 2010; 91: 1995–2010. 23. Basaria S, et al. Adverse events associated with testosterone administration. N Eng J Med 2010; 363: 109–22. 24. Srinivas-Shankar U, et al. Effect of testosterone on muscle strength, physical function, ERK high throughput screening body composition, and quality of life in frail elderly men: a randomised, double-blind, placebo controlled study. J Clin End Metab 2010; 95: 639–50. 25. Jones TH. ‘What should I do with a 60-year old man with a slightly low serum total testosterone concentration and normal levels of serum gonadotrophins?’ Clin Endocrinol 2010; 72: 584–8. Dr Richard Quinton1 and Dr Arif Ullah21Consultant Endocrinologist, Royal Victoria Infirmary, and Senior Lecturer, Institute of Human Genetics, University of Newcastle-upon-Tyne, UK 2Specialist Trainee Registrar, Endocrinology and Diabetes, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK 1. Harman

SM, et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J Clin Endocrinol Metab 2001; 86: 724–31. 2. Bhasin S, et click here al. Testosterone therapy in adult men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2006; 91: 1995–2010. 3. Turner HE, Wass JA. Gonadal function in men with chronic illness, Clin Endocrinol (Oxf) 1997; 47(4): 379–403. 4. Tajar A, et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: Evidence from the European Male Ageing Study. J Clin Endocrinol Metab 2010; 95: 1810–18. 5. Wu FC, et al., the European Male Aging Study Group. Hypothalamic-pituitary-testicular

axis disruptions tuclazepam in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab 2008; 93: 2737–45. 6. Prelevic GM, Jacobs HS. Menopause and post-menopause. Baillière’s Clin Endocrinol Metab 1997; 11: 311–40. 7. Stampfer MJ, Colditz GA. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev Med 1991; 20(1): 47–63. 8. Barrett-Connor E, Laakso M. Ischemic heart disease risk in postmenopausal women. Effects of estrogen use on glucose and insulin levels. Arterioscler Thromb Vasc Biol 1990; 10: 531–4. 9. Stampfer MJ, et al. Menopause and heart disease: a review. Ann N Y Acad Sci 1990; 592: 193–203. 10. Barrett-Connor E, Bush TL. Estrogen and coronary disease. JAMA 1991; 265: 1861–7. 11. Henderson BE, et al. Decreased mortality in users of estrogen replacement therapy. Arch Intern Med 1991; 151: 75–8. 12. Paganini-Hill A, et al.

The need for weight-based therapeutic interventions in children[97,99] and lack of readily available proprietary medicines in strengths suitable for paediatric dosing often necessitating titration have long

influenced medication safety in the paediatric setting. Moreover, the elderly and children use primary healthcare more than the rest of the population with implications for medication safety in the face of the ever-pressured healthcare system. There is therefore an urgent need for more research into medication safety among these patient populations. Previous researchers have identified the prescribing and administration stages as the most dangerous stages of the medicines management system.[15] Twenty-six of the 33 studies reviewed evaluated the prescribing stage MAPK inhibitor in keeping with this finding.

There is some suggestion in the existing literature that errors occur when patients take their medicines and that there is a need to prioritize processes at the patient end of the system for ERK inhibitor interventions.[8] This review showed that there is a shortage of studies at the ‘patient end of the system’ because of the obvious difficulties. Nonetheless, there is substantial evidence in practice that many patients may not be using their medicines as directed, resulting in therapeutic failure and hospital admissions.[100–102] Research and practice must therefore overcome the challenges of evaluating medication administration quality and safety in primary care to improve patient health outcomes. Although the use of varying error definitions by researchers in determining error rates has been previously identified,[8,36,37,103] this review has confirmed that this problem still exists. This is reflected in the wide range (<1–>90%) of error rates reported. Such variance in definitions and data capture could lead Avelestat (AZD9668) to erroneous evaluations of the system causes

of error. Attempts to develop common definitions for practice and research have been made,[36,56,99] and although more studies and practice in secondary care are adopting the use of these definitions,[104] there is still significant variation among the studies reviewed. One study[19] adapted a definition developed in secondary care for use in primary care but due to differences in the medication handling system between both settings, this approach may be burdensome, difficult to interpret and result in loss of important data. There is a need for a primary care practitioner-led definition of a prescribing error, where the highest error rates are recorded. This review has also demonstrated that error rates varied with the method of identification. For example, the highest error rate of 90.5% prescriptions[33] was recorded in Bahrain following the audit of paper prescriptions issued for paediatric patients from 20 primary healthcare centres.