The impact of a computerised decision support system on antibiotic usage in an English hospital.

Background Antimicrobial resistance is correlated with the inappropriate use of antibiotics. Computerised decision support systems may help practitioners to make evidence-based decisions when prescribing antibiotics. Objective This study aimed to evaluate the impact of computerized decision support systems on the volume of antibiotics used. Setting A very large 1200-bed teaching hospital in Birmingham, England. Main outcome measure The primary outcome measure was the defined daily doses/1000 occupied bed-days. Method A retrospective longitudinal study was conducted to examine the impact of computerised decision support systems on the volume of antibiotic use. The study compared two periods: one with computerised decision support systems, which lasted for 2 years versus one without which lasted for 2 years after the withdrawal of computerised decision support systems. Antibiotic use data from June 2012 to June 2016 were analysed (comprising 2 years with computerised decision support systems immediately followed by 2 years where computerised decision support systems had been withdrawn). Regression analysis was applied to assess the change in antibiotic consumption through the period of the study. Result From June 2012 to June 2016, total antibiotic usage increased by 13.1% from 1436 to 1625 defined daily doses/1000 bed-days: this trend of increased antibiotic prescribing was more pronounced following the withdrawal of structured prescribing (computerised decision support systems). There was a difference of means of - 110.14 defined daily doses/1000 bed days of the total usage of antibiotics in the period with and without structured prescribing, and this was statistically significant (p = 0.026). From June 2012 to June 2016, the dominant antibiotic class used was penicillins. The trends for the total consumption of all antibiotics demonstrated an increase of use for all antibiotic classes except for tetracyclines, quinolones, and anti-mycobacterial drugs, whereas aminoglycoside usage remained stable. Conclusion The implementation of computerised decision support systems appears to influence the use of antibiotics by reducing their consumption. Further research is required to determine the specific features of computerised decision support systems, which influence increased higher adoption and uptake of this technology.

Patient and public involvement in Paediatric Intensive Care research: considerations, challenges and facilitating factors.

PLAIN ENGLISH SUMMARY: Paediatric Intensive Care (PIC) provides care to extremely ill children. Research in this area can be difficult because children are often too sick to discuss being involved in a study and parents are too upset about their child to think about taking part. This makes it even more important that research is well designed. We conducted a review of the literature about involving patients and the public (PPI) in PIC research. We wanted to know what PPI has taken place, who had been consulted and how this was undertaken. We reviewed the titles and abstracts of 4717 papers but found only 4 relevant papers. Three of the papers had consulted with parents of children who had been on PIC but only one study had spoken directly to a child themselves. The studies had used a number of different methods to invite people to take part but there did not appear to be one solution. All of the studies thought PPI was good for the development of their research but none of them had tried to measure what had changed as a result. There are difficulties associated with carrying out PPI in the PIC setting. Researchers need to share more of their experiences, positive and negative, so we can try to identify the best ways of carrying out PPI in PIC studies. This will help ensure that research studies are designed which address the needs and concerns of children and their parents. ABSTRACT: Introduction Involving the public in health care research is reported to enhance the quality, appropriateness, acceptability and relevance to patients and the public (INVOLVE, Briefing notes for researchers, 2012; Staniszewska et al., Int J Technol Assess Health Care 274:391-9, 2011). Conducting research with children and young people is regarded as challenging and this makes it even more important that the research is well designed and understands the perspective of the child and family. We conducted a narrative literature review of the Patient and Public Involvement (PPI) literature, in the context of Paediatric Intensive Care (PIC). Our aims were to identify what PPI activity has taken place, with whom researchers engaged and what outcomes they reported. Method Electronic databases Medline, CINAHL and Embase (January 2000- June 2016) were searched using the search terms patient and public involvement and consultation. Participants were defined as child, parent, paediatric or pediatric and the context as intensive or critical care. Papers were excluded where activity reflected 'participants' as research subjects. Included papers were reviewed using the GRIPP checklist to appraise the quality of reporting. Results The search strategy identified 4717 abstracts. Seventeen papers were reviewed in full and four papers were included, all of which are case studies, describing a consultation approach. None of the papers described PPI as a multi-stage process. Only one study engaged with a former PIC patient and the majority of those consulted did not have any PIC experience. Activity was reported as being of benefit but there was no measurement of the impact of PPI. Conclusion There are numerous challenges associated with the conduct of research in PIC. It is therefore essential that the perspective of children, young people and their parents have been considered in the design of trials. However, there are few published accounts of PPI within the PIC context and the accounts that exist highlight issues about who to approach and when, and a lack of clarity about the best ways to engage with them. Research Ethics Committees and funding bodies expect to see evidence of PPI in research applications and we need to develop our understanding of what contributes towards successful PPI in this context.

Professionals' awareness of operational antibiotic prescribing controls in UK NHS hospitals.

In recent years, there have been increasing recommendations for multidisciplinary collaboration between clinical pharmacists and medical microbiologists in an attempt to control the quality (and quantity) of antibiotic prescribing. A questionnaire addressing the utilization of antibiotic prescribing controls was sent to the chief pharmacist and medical microbiologist in UK NHS hospitals. Responses were received from both the chief pharmacist and the medical microbiologist employed in the same hospital from 83 hospitals (a 30% response rate from two independent studies). A high level of disagreement and poor awareness was identified between the interprofessional staff groups regarding the existence of antibiotic formulary (with disagreement between the two groups, or not known by one or both respondents, in 46% of the paired hospitals, N = 38) and guideline documents (13%, N = 11), performance of antibiotic prescribing audits (40%, N = 33), and whether pharmacists (52%, N = 43) and medical microbiologists (77%, N = 64) monitored physician compliance with antibiotic prescribing control documents. This study has identified poor knowledge of the existence of basic antibiotic prescribing control mechanisms and the role of professional colleagues. It is suggested that there is some way to go before 'Agenda for Change' principles of flexible and collaborative roles are met.

Documentation of antibiotic prescribing controls in UK NHS hospitals.

OBJECTIVES: To identify the types, prevalence and nature of antibiotic prescribing control documents within NHS hospitals in the UK. METHODS: A self-completion postal questionnaire was sent to each Chief Pharmacist at 465 NHS hospitals in 2001/2002. This contained questions covering hospital demographics, and hospital antibiotic prescribing control documentation, including format, dissemination, approval and review processes. RESULTS: In total, 253 (54%) completed questionnaires were returned. Of these, 168 respondents' hospitals had an antibiotic formulary, 107 had a policy for antibiotic prescribing and 216 had guidelines on antibiotic use. All three types of antibiotic prescribing documents were used by 82 hospitals but 18 did not have any documents; 44% of formularies, 45% of policies and 35% of guidelines were available electronically. The Drug and Therapeutics Committee was the most frequently cited body for document approval and approximately one-third of documents had been approved during the current year of the questionnaire. Only about one-half of responding hospitals had an annual review of documents. CONCLUSIONS: Despite publication of high-profile national guidance in response to growing concerns regarding antimicrobial resistance, there has been little increase in the use of antibiotic prescribing control documents in NHS hospitals over the past decade. It is clear that appropriate controls for antibiotic prescribing are not yet universally applied in the UK and recommendations for action have been proposed.

Adverse drug reaction teaching in UK undergraduate medical and pharmacy programmes.

OBJECTIVES: To assess the extent of teaching about the Committee on Safety of Medicine's Yellow Card scheme and adverse drug reactions within UK Schools of Medicine and Pharmacy. METHODS: A self-completed questionnaire sent to all heads of undergraduate schools of medicine and pharmacy within the UK. RESULTS: The majority of undergraduate syllabi feature the Yellow Card Scheme. Knowledge of the Yellow Card Scheme was assessed in 79% of pharmacy programmes and 57% of medical schools. Specialist speakers on the Yellow Card Scheme were infrequently used. Fewer than half of respondents provided students with a guide to reporting ADRs (43% pharmacy and 43% medical). There is some disagreement about the value of supplying students with printed material about the Yellow Card Scheme. Half of medical Schools did not think that supplying 'Current Problems In Pharmacovigilance' would be useful. CONCLUSIONS: It was found that in both medicine and pharmacy, courses differed substantially in teaching about the Yellow Card Scheme and adverse drug reactions (ADRs). There is scope for increased involvement of the Medicines and Healthcare products Regulatory Agency in undergraduate education, in line with recommendations from the National Audit Office.

An evaluation of quinolone prescribing in a group of acute hospitals: development of an objective measure of usage.

OBJECTIVES: To develop an objective measure to enable hospital Trusts to compare their use of antibiotics. DESIGN: Self-completion, postal questionnaire with telephone follow up. SAMPLE: 4 hospital trusts in the English Midlands. RESULTS: The survey showed that it was possible to collect data concerning the number of Defined Daily Doses (DDD's) of quinolone antibiotic dispensed per Finished Consultant Episode (FCE) in each Trust. In the 4 trusts studied the mean DDD/FCE was 0.197 (range 0.117 to 0.258). This indicates that based on a typical course length of 5 days, 3.9% of patient episodes resulted in the prescription of a quinolone antibiotic. Antibiotic prescribing control measures in each Trust were found to be comparable. CONCLUSION: The measure will enable Trusts to objectively compare their usage of quinolone antibiotics and use this information to carry out clinical audit should differences be recorded. This is likely to be applicable to other groups of antibiotics.

Are prostaglandins major mediators in perennial allergic rhinitis?

Certain prostaglandins acting as inflammatory mediators have been implicated in the aetiology of perennial allergic rhinitis (PAR). Inhibition of prostaglandin synthesis in the nasal mucosa might therefore influence the symptoms associated with PAR. A randomised, doubleblind, placebo-controlled cross-over trial using 0.1% Diclofenac eye-drops has been conducted to investigate this hypothesis. Diclofenac, a non-steroidal anti-inflammatory drug (NSAID), reduces prostaglandin synthesis through the inhibition of the cyclo-oxygenase pathway. Twenty-five patients with significant PAR and positive skin tests to relevant perennial allergens were recruited and two drops of the given preparation were administered bilaterally q.d.s.. Thirteen patients completed the study. Nasal symptom score (itch, rhinorrhoea, sneezing, and blockage), smell test score, saccharin transit time, total nasal airflow resistance, and nasal inspiratory peak flow measurements were obtained at each of three study visits. No significant treatment effects were found. The daily nasal symptom score over the entire study period showed no significant variation. Adverse effects such as local invitation, dry nose or throat were rare. No untoward changes in haematological, biochemical profiles and urinalysis occurred. In conclusion, topical 0.1% Diclofenac eye-drops applied nasally have no significant effect on PAR. Prostaglandins alone may not play a major role in mediation of symptoms in this condition.

The use of proprietary medicines by patients presenting with peptic ulcer haemorrhage.

1. Medication, social and symptom histories were compared in patients with severe haemorrhage from a peptic ulcer (n = 71) and matched control subjects. Self-medication with proprietary agents was catalogued in addition to therapy prescribed by general medical practitioners. 2. Prior to the bleed, only 4% of ulcer patients had been free of symptoms normally associated with peptic ulceration, whereas 76% of the control group had been asymptomatic. 3. Gastro-irritant proprietary medicines were used regularly by 23% of ulcer patients compared with only 4% of controls. However, proprietary antacids were used chronically by 46% of ulcer patients compared with only 7% of controls. Bicarbonate was the antacid of choice used by 13% of ulcer patients. The odds ratio for the association between development of bleeding peptic ulcer and the use of indigestion remedies was 11.5% (95% CI 1.1, 121). 4. Fifty-one percent of ulcer patients were prescribed agents known to cause gastro-intestinal damage, whereas only 25% of the control group were prescribed similar agents. Only 7% of the control group were prescribed anti-ulcer therapy compared with 37% of those with bleeding ulcer. 5. A large proportion of patients with haemorrhage from a peptic ulcer had had symptoms sufficient to warrant recourse to self-medication with antacids without medical knowledge. Exacerbation of peptic ulcer by self-medication with proprietary products is likely to be of lesser significance.

Differential effects of hypoxia upon contractions evoked by potassium and noradrenaline in rabbit arteries in vitro.

1. A study has been made on isolated sections of rabbit femoral, renal and saphenous arteries of the effects of graded hypoxia (reducing bath PO2 from 110 mmHg, normoxia, to 55, 23 and 6 mmHg) upon contractile responses evoked by noradrenaline (NA) and KCl to 80% of maximum. 2. Potassium-evoked contractions were not affected by moderate hypoxia but were reduced in all vessels to 70-80% of the control response in normoxia, by exposure to either PO2 23 or 6 mmHg. Potassium-evoked contractions were virtually abolished by Ca2(+)-free Krebs solution and greatly reduced by verapamil (10 microM), indicating that they relied upon influx of extracellular Ca2+. 3. By contrast, NA-evoked contractions were reduced in a graded fashion in all vessels by exposure to graded levels of hypoxia and at PO2 6 mmHg they were significantly more reduced than K(+)-evoked contractions. Noradrenaline-evoked contractions of femoral arteries were most affected, being reduced to 80% of control at PO2 55 mmHg, and to 28% and 6% of control at PO2 23 and 6 mmHg respectively. Contractions in renal arteries were least affected, being reduced to only 47% of control at PO2 6 mmHg. 4. Noradrenaline-evoked contractions were reduced, but not abolished, in Ca2(+)-free Krebs solution. In normoxia, they reached 42%, 35% and 25% of control responses in the presence of Ca2+ in femoral, renal and saphenous arteries respectively. The Ca2(+)-free responses of the femoral and saphenous arteries were significantly different, indicating that the femoral arteries were least dependent and saphenous most dependent on influx of extracellular Ca2+ for contraction. 5. Contractions evoked by NA in Ca2(+)-free Krebs solution were not significantly affected by PO2 55 mmHg. Those evoked in saphenous arteries were not affected by more severe hypoxia, but in renal arteries they were significantly reduced at PO2 23 mmHg, while in femoral arteries they were significantly reduced both at PO2 23 and at PO2 6 mmHg. 6. Verapamil produced changes similar to Ca2+ withdrawal. Contractions evoked by NA in the presence of verapamil were affected by hypoxia in a similar way to those evoked in the absence of Ca2+. 7. These results indicate that the inhibition of contraction induced by hypoxia is not simply dependent upon inhibition of Ca2+ influx. Instead, we propose that receptor-operated rather than voltage-operated processes are particularly vulnerable, there being inhibition of the components of contraction which are dependent on receptor-operated Ca2+ influx and release of intracellular Ca2+.

Effects of hypoxia upon contractions evoked in isolated rabbit pulmonary artery by potassium and noradrenaline.

1. Comparisons have been made between rabbit thoracic aorta and main pulmonary artery of the effects of hypoxia upon contractions evoked by noradrenaline (NA) and KCl (K+). 2. Contractions were evoked in cylindrical sections of pulmonary artery and aorta, mounted for isometric recording of tension, by NA and K+ (at ED80) in normoxia (PO2 110 mmHg) and hypoxia (PO2 23 or 7 mmHg). Contractions were also evoked in Ca2(+)-free conditions with EGTA to prevent influx of extracellular Ca2+. All contractions are expressed as a percentage of normoxic response in the presence of Ca2+. 3. Potassium-evoked contractions of aorta and pulmonary artery were reduced to a similar extent by both levels of hypoxia, to 85 and 92% respectively. As expected K(+)-evoked contractions were virtually abolished by Ca2(+)-free conditions. It is proposed that hypoxia has a small inhibitory effect upon contraction mediated by Ca2+ influx via voltage-operated Ca2+ channels. 4. In the aorta in the presence of Ca2+, hypoxia reduced NA-evoked contractions to 84% at PO2 23 mmHg and 34% at PO2 7 mmHg. In the absence of Ca2+, NA-evoked contractions reached 73% in normoxia, but only 43 and 21% at PO2 23 and 7 mmHg respectively. These results suggest that hypoxia reduces the component of contraction that is mediated by release of intracellular Ca2+ and possibly that mediated by agonist-induced Ca2+ influx. 5. In the pulmonary artery also, NA-evoked responses in the absence of Ca2+ were reduced from 60% in normoxia, to 49 and 38% at PO2 23 and 7 mmHg. But, in the presence of Ca2+, hypoxia potentiated NA-evoked contractions to 113 and 111% at PO2 23 and 7 mmHg respectively. It is proposed that in the pulmonary artery, hypoxia reduces the component of contraction mediated by release of intracellular Ca2+, but facilitates that mediated by extracellular Ca2+. Possible mechanisms are discussed.

The effects of verapamil upon noradrenaline-induced contraction of the rat isolated aorta following acute and prolonged alterations in PO2.

1. Noradrenaline (NA;ED90) caused a contraction of the rat aorta which could be separated into two components, a rapid response mediated by release of intracellular Ca2+ and a more slowly developing contraction which relied principally upon Ca2+ influx. 2. Exposure to acute (30 min) hypoxia has been previously shown to reduce the NA-induced contraction (by 28.0 +/- 2.7%, n = 168) which recovered completely upon re-oxygenation (recovery response). In the present study, prolonged exposure to hypoxia (70 h) caused a more pronounced reduction (39.7 +/- 3.0%, n = 90) of the NA-induced contraction, but, re-oxygenation then produced incomplete recovery to 77.9 +/- 3.9% (n = 90) of the control response. 3. Prolonged exposure to 95% O2 caused a 36.5 +/- 3.1% (n = 42) reduction of NA-induced contractions, whereas prolonged exposure to 21% O2 only caused a small (12.6 +/- 3.4%, n = 6) depression of these responses. 4. The component of the NA-induced contraction mediated by release of intracellular Ca2+ is 39.8 +/- 1.3% (n = 83) of the NA contraction in Ca-containing Krebs solution and was previously found to be unaffected by acute hypoxia. However, following prolonged exposure to either hypoxia or 21% O2, this component only reached 30.7 +/- 2.2% (n = 32) or 28.3 +/- 0.9% (n = 6) of the control response, respectively. Prolonged exposure to 95% O2 caused a more pronounced reduction of this component of contraction which then reached 19.1 +/- 2.1% (n = 12) of the control response. 5. Verapamil (10nM-10 microM) produced similar concentration-dependent reductions of NA-induced contractions elicited during control conditions or acute hypoxia; under these conditions, 1 microM verapamil caused a 34.1 + 6.9% (n = 6) and a 41.8 + 2.9% (n = 18) reduction of these responses respectively. However, recovery responses caused by re-oxygenation of tissues exposed to acute hypoxia were more sensitive to verapamil which, at a concentration of 1 microM, caused a 59.2 + 2.7% (n = 18) reduction of these responses. Verapamil (10 nM-10 microM) also caused similar pronounced concentration-dependent reductions of contractions elicited during prolonged exposure to normoxia or hyperoxia and of recovery responses obtained following re-oxygenation of tissues exposed to prolonged hypoxia; 1 microM verapamil caused a 62.5 + 1.1% (n = 6), 77.2 + 3.8% (n = 12) and a 68.0 + 4.3% (n = 12) reduction of these responses respectively. In contrast, contractions elicited during prolonged hypoxia were less sensitive to verapamil which at a concentration of 1 microM only caused a 16.2 + 2.2% (n 12) reduction of these responses. 6. The present study indicates that prolonged exposure of the rat aorta to either hypoxic or oxygenated conditions causes attenuation of NA-induced contraction. However, these effects are also accompanied by changes in tissue Ca2+ handling which differ under each condition and might account for the observed modifications in tissue sensitivity to the calcium-entry blocker verapamil.

A comparison of the effects of the calcium entry blockers, verapamil, diltiazem and flunarizine against contractions of the rat isolated aorta and portal vein.

1. The actions of the chemically distinct calcium entry blockers, verapamil (Ver), diltiazem (Dlz) and flunarizine (Flu) have been compared in rat isolated aorta and portal vein. 2. KCl-induced contractions of the rat aorta depend exclusively upon extracellular Ca2+, whereas, those induced by noradrenaline (NA) rely upon Ca2+ from intra- and extracellular sources. The NA-induced contraction was pharmacologically dissected under Ca2+-free conditions revealing a contraction dependent upon intracellular Ca2+ (EGTA-resistant response) or a low concentration of prazosin which left a contraction which was mediated by extracellular Ca2+ (prazosin-resistant response). 3. The portal vein produced spontaneous rhythmic contractions and a sustained contraction to NA and KCl; however, all responses appeared to depend exclusively upon extracellular Ca2+. 4. In the aorta, contractions which might be expected to depend upon Ca2+-entry through voltage-operated channels (KCl-induced contraction) showed similar sensitivities to Ver, Dlz and Flu whereas, marked differences in the sensitivity to these agents was noted against contractions which appear to depend upon Ca2+-entry through receptor-operated channels (prazosin-resistant response). Only Dlz reduced contractions mediated by intracellular Ca2+ (EGTA-resistant response). 5. In the portal vein, Ver and Dlz caused similar pronounced reductions of spontaneous and NA of KCl-induced contractions. In contrast, these contractions of the portal vein were unaffected by Flu except at a concentration of 10 microM. However, contractions induced by addition of Ca2+ (0-14 mM) to previously depolarized portal veins could be reduced by Flu (100 nM-10 microM). 6. The present study indicates that in the rat aorta, contractions mediated by intracellular Ca2+ and depolarization or receptor-activated Ca2+ entry can be pharmacologically dissected and that these processes show different sensitivities to calcium entry blockade. Of the agents tested, Ver displays the properties most commonly associated with an ideal calcium entry blocker. Ca2+-activation mechanisms in the portal vein differ from those in the aorta resulting in a different spectrum of selectivity of the calcium entry blockers studied.

An investigation of the actions of diltiazem on rat aorta exposed to acute hypoxia followed by re-oxygenation.

1 The effects of diltiazem and removal of extracellular Ca2+ were examined on contractions, of the rat isolated aorta, to noradrenaline (NA) and high K+, during exposure to oxygenated conditions and hypoxia followed by re-oxygenation. 2 Exposure to hypoxia caused a similar reduction of contractile responses to NA and KCl, while re-oxygenation restored contractile activity. 3 Ca2+-free conditions abolished responses to KCl but a transient response to NA remained which was resistant to hypoxia. 4 Diltiazem produced similar reductions of responses to NA during both oxygenated conditions and hypoxia, whereas during re-oxygenation the effects of diltiazem upon responses to NA were enhanced. 5 Diltiazem produced a more pronounced reduction of responses to KCl than of responses to NA. However, the reduction of responses to KCl by diltiazem was not modified by the changes in PO2 examined in the present study. 6 The present study indicates that contractions of the rat aorta mediated by intracellular Ca2+ are resistant to the hypoxic conditions studied in the present investigation, whereas those responses mediated by an influx of Ca2+ are reduced. The increase in the contractile response to NA following re-oxygenation may result from an increased influx of extracellular Ca2+ since such responses show an enhanced sensitivity to diltiazem.