Jonathan Cooke

Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis

Abstract Objective: To evaluate efficacy of probiotics in prevention and treatment of diarrhoea associated with the use of antibiotics. Design: Meta-analysis; outcome data (proportion of patients not getting diarrhoea) were analysed, pooled, and compared to determine odds ratios in treated and control groups. Identification: Studies identified by searching Medline between 1966 and 2000 and the Cochrane Library. Studies reviewed Nine randomised, double blind, placebo controlled trials of probiotics. Results: Two of the nine studies investigated the effects of probiotics in children. Four trials used a yeast (Saccharomyces boulardii), four used lactobacilli, and one used a strain of enterococcus that produced lactic acid. Three trials used a combination of probiotic strains of bacteria. In all nine trials, the probiotics were given in combination with antibiotics and the control groups received placebo and antibiotics. The odds ratio in favour of active treatment over placebo in preventing diarrhoea associated with antibiotics was 0.39 (95% confidence interval 0.25 to 0.62; P<0.001) for the yeast and 0.34 (0.19 to 0.61; P<0.01 for lactobacilli. The combined odds ratio was 0.37 (0.26 to 0.53; P<0.001) in favour of active treatment over placebo. Conclusions: The meta-analysis suggests that probiotics can be used to prevent antibiotic associated diarrhoea and that S boulardii and lactobacilli have the potential to be used in this situation. The efficacy of probiotics in treating antibiotic associated diarrhoea remains to be proved. A further large trial in which probiotics are used as preventive agents should look at the costs of and need for routine use of these agents.

Causes of Medication Administration Errors in Hospitals: a Systematic Review of Quantitative and Qualitative Evidence

BackgroundUnderlying systems factors have been seen to be crucial contributors to the occurrence of medication errors. By understanding the causes of these errors, the most appropriate interventions can be designed and implemented to minimise their occurrence.ObjectiveThis study aimed to systematically review and appraise empirical evidence relating to the causes of medication administration errors (MAEs) in hospital settings.Data SourcesNine electronic databases (MEDLINE, EMBASE, International Pharmaceutical Abstracts, ASSIA, PsycINFO, British Nursing Index, CINAHL, Health Management Information Consortium and Social Science Citations Index) were searched between 1985 and May 2013.Study SelectionInclusion and exclusion criteria were applied to identify eligible publications through title analysis followed by abstract and then full text examination. English language publications reporting empirical data on causes of MAEs were included. Reference lists of included articles and relevant review papers were hand searched for additional studies. Studies were excluded if they did not report data on specific MAEs, used accounts from individuals not directly involved in the MAE concerned or were presented as conference abstracts with insufficient detail.Data Appraisal and Synthesis MethodsA total of 54 unique studies were included. Causes of MAEs were categorised according to Reason’s model of accident causation. Studies were assessed to determine relevance to the research question and how likely the results were to reflect the potential underlying causes of MAEs based on the method(s) used.ResultsSlips and lapses were the most commonly reported unsafe acts, followed by knowledge-based mistakes and deliberate violations. Error-provoking conditions influencing administration errors included inadequate written communication (prescriptions, documentation, transcription), problems with medicines supply and storage (pharmacy dispensing errors and ward stock management), high perceived workload, problems with ward-based equipment (access, functionality), patient factors (availability, acuity), staff health status (fatigue, stress) and interruptions/distractions during drug administration. Few studies sought to determine the causes of intravenous MAEs. A number of latent pathway conditions were less well explored, including local working culture and high-level managerial decisions. Causes were often described superficially; this may be related to the use of quantitative surveys and observation methods in many studies, limited use of established error causation frameworks to analyse data and a predominant focus on issues other than the causes of MAEs among studies.LimitationsAs only English language publications were included, some relevant studies may have been missed.ConclusionsLimited evidence from studies included in this systematic review suggests that MAEs are influenced by multiple systems factors, but if and how these arise and interconnect to lead to errors remains to be fully determined. Further research with a theoretical focus is needed to investigate the MAE causation pathway, with an emphasis on ensuring interventions designed to minimise MAEs target recognised underlying causes of errors to maximise their impact.

Prevalence and Nature of Medication Administration Errors in Health Care Settings: A Systematic Review of Direct Observational Evidence:

OBJECTIVE: To systematically review empirical evidence on the prevalence and nature of medication administration errors (MAEs) in health care settings. DATA SOURCES: Ten electronic databases (MEDLINE, EMBASE, International Pharmaceutical Abstracts, Scopus, Applied Social Sciences Index and Abstracts, PsycINFO, Cochrane Reviews and Trials, British Nursing Index, Cumulative Index to Nursing and Allied Health Literature, and Health Management Information Consortium) were searched (1985-May 2012). STUDY SELECTION AND DATA EXTRACTION: English-language publications reporting MAE data using the direct observation method were included, providing an error rate could be determined. Reference lists of all included articles were screened for additional studies. DATA SYNTHESIS: In all, 91 unique studies were included. The median error rate (interquartile range) was 19.6% (8.6–28.3%) of total opportunities for error including wrong-time errors and 8.0% (5.1–10.9%) without timing errors, when each dose could be considered only correct or incorrect. The median rate of error when more than 1 error could be counted per dose was 25.6% (20.8–41.7%) and 20.7% (9.7–30.3%), excluding wrong-time errors. A higher median MAE rate was observed for the intravenous route (53.3% excluding timing errors (IQR 26.6–57.9%)) compared to when all administration routes were studied (20.1%; 9.0–24.6%), where each dose could accumulate more than one error. Studies consistently reported wrong time, omission, and wrong dosage among the 3 most common MAE subtypes. Common medication groups associated with MAEs were those affecting nutrition and blood, gastrointestinal system, cardiovascular system, central nervous system, and antiinfectives. Medication administration error rates varied greatly as a product of differing medication error definitions, data collection methods, and settings of included studies. Although MAEs remained a common occurrence in health care settings throughout the time covered by this review, potential targets for intervention to minimize MAEs were identified. CONCLUSIONS: Future research should attend to the wide methodological inconsistencies between studies to gain a greater measure of comparability to help guide any forthcoming interventions.

Estimation of central aortic pressure by SphygmoCor ® requires intra-arterial peripheral pressures

Central arterial pressure, measured close to the heart, may be of more patho-physiological importance than conventional non-invasive cuff blood pressure. The technique of applanation tonometry using SphygmoCor® has been proposed as a non-invasive method of estimating central pressure. This relies on mathematically derived generalized transfer functions, which have been previously validated using invasive peripheral pressure measurements. We compared simultaneous estimates of central aortic pressure using this technique with those measured directly during the routine diagnostic cardiac catheterization of 30 subjects (age range 27–84 years), half of whom were aged 65 years or more. This was done by applanating the left radial artery and recording the non-invasive brachial cuff blood pressure to generate a central aortic pressure estimate, using the SphygmoCor® radial transfer function. The comparative results were analysed using Bland—Altman plots of mean difference. SphygmoCor®, on average, underestimated systolic central arterial pressure by 13.3 mmHg and overestimated diastolic pressure by 11.5 mmHg. The results were similar in patients aged under and above 65 years. Furthermore, non-invasively measured brachial pressures were seen to give an overall closer estimate of the central arterial pressure than the SphygmoCor® system. The transfer function has been validated from invasively measured arterial pressures and the current use by the system of non-invasive measures may explain the discrepancies. However, age, drugs and arterial disease would also be expected to play a role.

Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process

Reactive oxygen species (ROS) play a pivotal role in the orchestration of the normal wound‐healing response. They act as secondary messengers to many immunocytes and non‐lymphoid cells, which are involved in the repair process, and appear to be important in coordinating the recruitment of lymphoid cells to the wound site and effective tissue repair. ROS also possess the ability to regulate the formation of blood vessels (angiogenesis) at the wound site and the optimal perfusion of blood into the wound‐healing area. ROS act in the hosts defence through phagocytes that induce an ROS burst onto the pathogens present in wounds, leading to their destruction, and during this period, excess ROS leakage into the surrounding environment has further bacteriostatic effects. In light of these important roles of ROS in wound healing and the continued quest for therapeutic strategies to treat wounds in general and chronic wounds, such as diabetic foot ulcers, venous and arterial leg ulcers and pressure ulcers in particular, the manipulation of ROS represents a promising avenue for improving wound‐healing responses when they are stalled. This article presents a review of the evidence supporting the critical role of ROS in wound healing and infection control at the wound site, and some of the new emerging concepts associated with ROS modulation and its potential in improving wound healing are discussed.

Terminal digit preference and single-number preference in the Syst-Eur trial: influence of quality control

BackgroundTerminal digit and single-number preference may produce inaccuracy and biased results when measuring blood pressure. We describe these preferences in the Syst-Eur randomized placebo-controlled trial of the treatment of isolated systolic hypertension and describe how we sought to eliminate these problems. MethodsThe Data Monitoring Committee of the trial conducted yearly quality control meetings in Belgium and visited the participating centres to check their adherence to the protocol. These meetings involved identifying terminal digit preference, improving blood pressure control and boosting recruitment. ResultsThe prevalence of use of terminal digit zero when measuring sitting systolic blood pressure (first readings) reduced from an average of 42.4% in the year prior to the date when a centre first randomized a patient to 31.5, 25, 22.3, 26.3, 23.2 and 22% in the subsequent 6 years. This trend was independent of the calendar year during which a centre entered the trial and supports the hypothesis that data-quality monitoring, including the feedback of digit preference to centres, led to a reduction in terminal digit zero preference. In addition, a higher than expected prevalence of the systolic blood pressure value of 148 mmHg was found in the active treatment groups in the double-blind phase. Selection for 148 mmHg persisted over time and constituted a single-number preference bias. This arose from the instruction to investigators to reduce systolic blood pressure to below 150 mmHg. ConclusionMonitoring and feedback of data quality should be undertaken to minimize digit and number preference. Automatic devices should ideally be employed to help to avoid these problems as long as the devices are fully validated and regularly serviced, and providing that readings are not rejected and repeated.

The antimicrobial activity of prototype modified honeys that generate reactive oxygen species (ROS) hydrogen peroxide

BackgroundAntimicrobial resistance continues to be a global issue in healthcare organisations. Honey has long been shown to possess wound healing and antimicrobial properties that are dependent on a number of physical and chemical properties of the honey. We tested the antimicrobial activity of a medicinal honey, Surgihoney® (SH) and two prototype modified honeys made by Apis mellifera (honeybee) against Staphylococcus aureus (NCIMB 9518). We also examined the modified honey prototypes for the ability to generate reactive oxygen species (ROS) by changing the level of production of hydrogen peroxide from the samples.MethodsSurgihoney® (SH) was compared with two modified honeys, Prototype 1 (PT1) and Prototype 2 (PT2) using a bioassay method against a standard strain of Staphylococcus aureus. Further work studied the rate of generation of ROS hydrogen peroxide from these preparations.ResultsSurgihoney® antimicrobial activity was shown to be largely due to ROS hydrogen peroxide production. By modification of Surgihoney®, two more potent honey prototypes were shown to generate between a two- and three-fold greater antibacterial activity and up to ten times greater ROS peroxide activity.ConclusionsSurgihoney® is a clinically available wound antiseptic dressing that shows good antimicrobial activity. Two further honey prototypes have been shown to have antimicrobial activity that is possible to be enhanced due to demonstrated increases in ROS peroxide activity.

Narrative review of primary care point-of-care testing (POCT) and antibacterial use in respiratory tract infection (RTI)

Antimicrobial resistance is a global problem and is being addressed through national strategies to improve diagnostics, develop new antimicrobials and promote antimicrobial stewardship. A narrative review of the literature was undertaken to ascertain the value of C reactive protein (CRP) and procalcitonin, measurements to guide antibacterial prescribing in adult patients presenting to GP practices with symptoms of respiratory tract infection (RTI). Studies that were included were randomised controlled trials, controlled before and after studies, cohort studies and economic evaluations. Many studies demonstrated that the use of CRP tests in patients presenting with RTI symptoms reduces antibiotic prescribing by 23.3% to 36.16%. Procalcitonin is not currently available as a point-of-care testing (POCT), but has shown value for patients with RTI admitted to hospital. GPs and patients report a good acceptability for a CRP POCT and economic evaluations show cost-effectiveness of CRP POCT over existing RTI management in primary care. POCTs increase diagnostic precision for GPs in the better management of patients with RTI. CRP POCT can better target antibacterial prescribing by GPs and contribute to national antimicrobial resistance strategies. Health services need to develop ways to ensure funding is transferred in order for POCT to be implemented.

Retrospective analysis of medication incidents reported using an on-line reporting system

ObjectiveTo examine the types of prescribing, administration and dispensing incidents reported to an on-line incident-reporting scheme and determine the types of healthcare professionals responsible for reporting such incidents.MethodRetrospective analysis of medication-related incidents reported to an on-line incident-reporting scheme in a large (1000-bed) teaching hospital in the UK.Main outcome measuresFrequency and type of incidents, the discipline of the health care professional who reported the incident and the stage in the medication use process (prescribing, dispensing, or administration) at which the incident occurred.ResultsOver a 26-month study period, there were 495 medication-related incidents reported, of which 38.6% (191) were classified to be a “near miss”. Medication-related incidents were reported most often at the stages of administration (230, 46.5%) and prescribing (192, 38.8%), whilst incidents involving dispensing or supply of medication were reported less often (73, 14.7%). Of all the incidents, pharmacists reported 51.9% (257), nursing staff reported 37.6% (186), and doctors reported 9.1% (45). Cardiovascular (149, 30.1%), central nervous system (106, 21.4%), and antibiotic/anti-infective medication (71, 14.3%) were the most common therapeutic categories associated with reports of medication-related incidents.ConclusionAn on-line reporting scheme can be used to monitor medication-related incidents at key stages in the medication-use process in secondary care. The types of incidents reported by health care professionals differ markedly, with fewer medication-related incidents being reported by doctors. Future research should explore the prevailing safety culture amongst the different health care disciplines, and examine the impact that information technology has on the willingness of health care professionals to report adverse incidents.

Engineered honey: In vitro antimicrobial activity of a novel topical wound care treatment

Surgihoney is a novel engineered organic honey product for wound care. Its antimicrobial activity can be controlled and adjusted by the engineering process, allowing preparation of three different potencies, labelled Surgihoney 1-3. Susceptibility testing of a range of wound and ulcer bacterial isolates to Surgihoney by the disc diffusion method, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) determination, and time-kill measurements by time suspension tests were performed. Surgihoney demonstrated highly potent inhibitory and cidal activity against a wide range of Gram-positive and Gram-negative bacteria and fungi. MICs/MBCs were significantly lower than concentrations likely to be achieved in topical clinical use. The topical concentration of Surgihoney in wounds was estimated at ca. 500g/L. MICs/MBCs for Staphylococcus aureus were 32/125g/L for Surgihoney 1 and 0.12/0.25g/L for Surgihoney 3. Cidal speed depended on potency, being 48h for Surgihoney 1 and 30min for Surgihoney 3. Maintenance of the Surgihoney inoculum preparation for up to a week demonstrated complete cidal activity and no bacterial persistence. Surgihoney has wide potential as a highly active topical treatment combining the effects of the healing properties of honey with the potent antimicrobial activity of the engineered product for skin lesions, wounds, ulcers and cavities. It is highly active against multidrug-resistant bacteria. It is more active than other honeys tested and is comparable with chemical antiseptics in antimicrobial activity.