Timing of the first vancomycin maintenance dose in an acute hospital setting - room for improvement?

Introduction Intravenous vancomycin therapy typically starts with a loading dose followed by a maintenance dose 12 to 24 hours later. In the acute hospital setting, this often results in doses being administered in the middle of the night, which is impractical for both patients and staff. This audit examined current practice and developed new guidelines to support greater flexibility in the timing of the first maintenance dose. Methods Data recording forms used by pharmacists to support the therapeutic drug monitoring of vancomycin were collected from two hospital sites over six weeks. Forms containing at least two vancomycin concentrations were selected and the time of administration of the first maintenance dose was recorded. Individual vancomycin pharmacokinetic parameter estimates were obtained using MAP Bayesian analysis then used to predict vancomycin concentrations 6, 8, 10, 12 and 14 hours after a banded loading dose and 20 mg/kg (capped at 3000 mg). Predicted concentrations were compared with a target range of 10 – 20 mg/L. Results Data were obtained from 49 patients with a mean (SD) age of 63.1 (16.7) years and weight 80.1 (27.6) kg. In all patients, creatinine clearance estimates were >40 mL/min and, according to current practice guidelines, all patients required 12 hourly maintenance dosing. The time recorded for the administration of the first maintenance dose was between 11 pm and 7 am in 30 (61%) of these patients. In 14 patients (29%), the first maintenance dose was administered >12 hours after loading. The target range was achieved with banded doses (20 mg/kg) in 65% (71%) of concentrations at 6 hours, 74% (84%) at 8 hours, 57% (67%) at 10 hours, 53% (55%) at 12 hours and 39% (43%) at 14 hours. Conclusions This audit has shown that current practice results in a high proportion of vancomycin maintenance doses being administered at impractical times. Allowing a more flexible time window of 6-12 hours after the loading dose for administration of the first vancomycin maintenance dose could help to alleviate this problem and reduce the risk of early subtherapeutic vancomycin trough concentrations

Amikacin use and therapeutic drug monitoring in adults : do dose regimens and drug exposures affect either outcome or adverse events? A systematic review

Objectives To identify the amikacin dosage regimens and drug concentrations consistent with good outcomes and to determine the drug exposures related to nephrotoxicity and ototoxicity. Methods A literature review was conducted in Medline, EMBASE and the Cochrane Central Register of Controlled Trials. Full journal articles of randomised controlled trials, controlled clinical trials, interrupted time series trials and controlled before and after studies involving amikacin TDM and dose adjustment were considered for inclusion. Results Seventeen included studies were identified, comprising 1677 participants. Amikacin doses ranged from 11-15 mg/kg/day with thirteen studies using 15 mg/kg/day. Studies were generally designed to compare different aminoglycosides rather than to assess concentration-effect relationships. Only eleven papers presented data on target concentrations, rate of clinical cure and toxicity. Target peak concentrations ranged from 15 – 40 mg/L and target troughs were typically <10 mg/L or <5 mg/L. It was not clear whether these targets were achieved. Measured peaks averaged 28 mg/L for twice daily dosing and 40-45 mg/L for once daily dosing; troughs averaged 5 mg/L and 1-2 mg/L, respectively. Fifteen of the included studies reported rates of nephrotoxicity; auditory and vestibular toxicities were reported in twelve and eight studies. Conclusions This systematic review found little published evidence to support an optimal dosage regimen or TDM targets for amikacin therapy. The use of alternative approaches, such as consensus opinion and a review of current practice, will be required to develop guidelines to maximise therapeutic outcomes and minimise toxicity with amikacin

Research is ‘a step into the unknown’: an exploration of pharmacists’ perceptions of factors impacting on research participation in the NHS

Objective This study explored National Health Service (NHS) pharmacists&rsquo; perceptions and experiences of pharmacist-led research in the workplace.&nbsp; Design Semistructured, face-to-face discussions continued until distinct clusters of opinion characteristics formed. Verbatim transcripts of audio-recordings were subjected to framework analysis.&nbsp; Setting Interviews were carried out with 54 pharmacists with diverse backgrounds and roles from general practices and secondary care in the UK's largest health authority.&nbsp; Results The purpose and potential of health services research (HSR) was understood and acknowledged to be worthwhile by participants, but a combination of individual and system-related themes tended to make participation difficult, except when this was part of formal postgraduate education leading to a qualification. Lack of prioritisation was routinely cited as the greatest barrier, with motivation, confidence and competence as additional impediments. System-related themes included lack of practical support and pharmacy professional issues. A minority of highly motivated individuals managed to embed research participation into routine activity.&nbsp; Conclusions Most pharmacists realised the desirability and necessity of research to underpin pharmacy service expansion, but a combination of individual and professional level changes is needed to increase activity. Our findings provide a starting point for better understanding the mindset of hospital-based and general practice-based pharmacists towards research, as well as their perceived barriers and supports

Discontinuation, persistence and adherence to subcutaneous biologics delivered via a homecare route to Scottish adults with rheumatic diseases: a retrospective study

ObjectivesTo understand patterns of subcutaneous (SC) biologics use over time in adults with inflammatory rheumatic musculoskeletal diseases receiving a homecare delivery service.DesignRetrospective cohort.SettingPatients in secondary care receiving SC biologics in the largest Scottish Health Board.ParticipantsA new bespoke cohort was created from routine data gathered as part of a health board Homecare Service Database. Patients over 18 years who received a supply of SC biologic from January 2012 to May 2015 with a diagnosis for rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) were included.Outcomes measuredA standardised framework was applied by measuring discontinuation rates, persistence using Kaplan-Meier analysis and Cox regression and adherence using medication refill adherence (MRA) and compliance rate (CR).Results751 patients were identified (AS: 105, PsA: 227, RA: 419) of whom 89.3% had more than one biologic delivery (median days’ follow-up: AS: 494; PsA: 544; RA: 529) and 83.2% did not switch biologic. For all conditions, approximately half were persistent on their index biologic (52% AS, 54% PsA, 48%RA). Of patients who discontinued treatment, the majority reinitiated with the same biologic (19% AS, 18% PsA and 21% RA). Overall adherence during the period of treatment was over 80% when calculated using MRA (median %MRA: AS: 84.0%, PsA: 85.0%, RA: 82.4%) or CR (median %CR: AS: 96.6%, PsA: 97%, RA: 96.6%).ConclusionUse of linked routine data is a sustainable pathway to enable ongoing evaluation of biologics use. A more consistent approach to studying use (discontinuation, persistence and adherence metrics) should be adopted to enable comparability of studies.</jats:sec

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

NHS Scotland Gentamicin and Vancomycin (GaV) Quality Improvement Programme (QIP) Report - January 2012

This is the first report from the gentamicin and vancomycin quality improvement programme (GaV QIP) commissioned in 2010 by the Healthcare Associated Infection (HAI) Task Force in collaboration with the Scottish Antimicrobial Prescribing Group (SAPG). This work has been delivered as a joint project between the University of Strathclyde and the SAPG Information workstream. The programme aims to assess the impact of implementing SAPG endorsed guidance on the use of gentamicin (following either the Hartford or the Greater Glasgow and Clyde [GGC] nomogram) and vancomycin across NHS Scotland

Development and evaluation of a national gentamicin and vancomycin quality improvement programme

Scottish Antimicrobial Prescribing Group (SAPG) recommendations to reduce broad-spectrum antimicrobial use led to an increase in gentamicin and vancomycin prescribing. In 2009, SAPG introduced national guidance to standardize dosage regimens, reduce calculation errors and improve the monitoring of these antibiotics. Studies conducted in 2010 and 2011 identified limitations in guideline implementation. To develop, implement and assess the long-term impact of quality improvement (QI) resources to support gentamicin and vancomycin prescribing, administration and monitoring. Methods: New resources, comprising revised guidelines, online and mobile app dose calculators, educational material and specialized prescribing and monitoring charts were developed in collaboration with antimicrobial specialists and implemented throughout Scotland during 2013-16. An online survey in 2017 evaluated the use of these resources and a before (2011) and after (2018) point prevalence study assessed their impact. Results: All 12 boards who responded to the survey (80%) were using the guidance, electronic calculators and gentamicin prescription chart; 8 used a vancomycin chart. The percentage of patients who received the recommended gentamicin dose increased from 44% to 89% (OR 10.99, 95% CI = 6.37-18.95) between 2011 and 2018. For vancomycin, the correct loading dose increased from 50% to 85% (OR = 5.69, CI = 2.76-11.71) and the correct maintenance dose from 55% to 90% (OR = 7.17, CI = 3.01-17.07). Conclusions: This study demonstrated improvements in the national prescribing of gentamicin and vancomycin through the development and coordinated implementation of a range of QI resources and engagement with local and national multidisciplinary teams

Adherence and persistence of subcutaneous biologics delivered through homecare services to a cohort of patients with rheumatoid arthritis

ABSTRACT Objectives Biologics are a class of medicines recommended by UK and international guidelines for treatment of patients with rheumatoid arthritis (RA) who are unresponsive, intolerant or who have contraindications to conventional therapies. Biologics are often supplied in the UK to patients in their home by external healthcare providers commissioned by the National Health Service (NHS). Patient adherence and persistence to biologics has not been assessed within NHS Scotland. The aim of this study was to evaluate adherence and persistence patterns of subcutaneous biologics delivered by homecare services to patients with rheumatoid arthritis in a Scottish NHS Board. Approach A population-based cohort study was conducted using records from patients receiving medication through healthcare delivery companies in the NHS Greater Glasgow and Clyde health board. RA patients with deliveries between 2012- 2015 were linked via their Community Health Index number to their prescriptions in primary care, hospital admissions and death records. For this study those with at least two deliveries of biologics and who did not switch biologic treatment were included. Length of therapy was determined from first delivery to last day treatment was covered. Adherence rate referring to the supply received for the whole study period was evaluated through Medication Refill Adherence (MRA). Persistence from first delivery to discontinuation was estimated using survival analysis and a drug–free interval of 90 days. Results A total of 434 patients with RA received a subcutaneous biologic. The mean age at first delivery was 54.7 (SD 13.4) years and 78% were female. From this cohort, 322 had at least 2 deliveries of the same biologic. The overall median length of treatment was 387.5 days (IQR 544.5); the longest for certolizumab pegol users with a median of 511.5 days (IQR 629.2) and the shortest for tocilizumab (median of 187 days, IQR 90.5). The adherence throughout the study had a mean MRA 79.73% (SD 29.95) and was similar across the different biologics. Persistence at follow-up decreased with time from 81% of the patients receiving a biologic at 6 months, to 67% after 1 year and 65% after two years. Adalimumab, certolizumab pegol, etanercept and golimumab users had higher persistence rates. Conclusion Length of treatment and persistence, but not adherence, are influenced by the type of subcutaneous biologic received by the RA patients in this cohort. Future research will gain a better insight into the factors influencing adherence and persistence to these medicines

Diagnostic Utility of High Sensitivity Troponins for Echocardiographic Markers of Structural Heart Disease

The conventional use of high-sensitivity troponins (hs-troponins) is for diagnosing myocardial infarction however they also have a role in chronic disease management. This pilot study assessed the relationship of hs-troponins with echocardiographic markers of left ventricular hypertrophy (LVH) and structural heart disease (SHD). Patients undergoing computer gomography (CT) coronary angiogram for low-intermediate risk chest pain and healthy volunteers were recruited. Hs-troponins Singulex I, Abbott I and Roche T and N-terminal pro-brain natriuretic peptide (NT-proBNP) were evaluated in relation to SHD parameters including left ventricular hypertrophy (LVHEcho) and left atrial enlargement (LAEEcho) on echocardiography. 78 subjects who underwent echocardiography were included in this study. C-statistics (95% confidence interval) of the four biomarkers for predicting LVHEcho were 0.84 (0.72–0.92), 0.84 (0.73–0.92), 0.75 (0.63–0.85) and 0.62 (0.49–0.74); for LAEEcho 0.74 (0.6–0.85), 0.78 (0.66–0.88), 0.55 (0.42–0.67) and 0.68 (0.62–0.85); and composite SHD 0.79 (0.66–0.88), 0.87 (0.75–0.94), 0.62 (0.49–0.73) and 0.74 (0.62–0.84) respectively. Optimal cut points for SHD were &gt;1.2 ng/L, &gt;1.6 ng/L, &gt;8 ng/L and &gt;18 pmol/L respectively. These results advocate the potential role of hs-troponins as screening tools for structural heart disease with theranostic implications