Intravenous iron versus blood transfusion for postpartum anemia: a systematic review and meta-analysis.

BACKGROUND: Intravenous iron (IV-iron) is used as an alternative to, or alongside, red blood cell transfusion (RBC-T) to treat more severe postpartum anemia (PPA), although optimal treatment options remain unclear. No previous systematic reviews have examined IV-iron and RBC-T, including patient-reported outcomes and hematological responses. METHODS: A systematic review and meta-analysis of randomized trials comparing IV-iron and RBC-T with each other, oral iron, no treatment, and placebo for the treatment of PPA. Key inclusion criteria were PPA (hemoglobin < 12 g/dL) and IV-iron or RBC-T as interventions. Key exclusion criteria were antenatal IV-iron or RBC-T. Fatigue was the primary outcome. Secondary outcomes included hemoglobin and ferritin concentrations, and adverse events. From 27th August 2020 to 26th September 2022, databases, registries, and hand searches identified studies. A fixed-effect meta-analysis was undertaken using RevMan (5.4) software. The quality of the studies and the evidence was assessed using the Cochrane Risk of Bias table, and Grading of Recommendations, Assessment, Development, and Evaluation. This review is registered with the Prospective Register of Systematic Reviews (CRD42020201115). RESULTS: Twenty studies and 4196 participants were included: 1834 assigned IV-iron, 1771 assigned oral iron, 330 assigned RBC-T, and 261 assigned non-intervention. Six studies reported the primary outcome of fatigue (1251 participants). Only studies of IV-iron vs. oral iron (15 studies) were available for meta-analysis. Of these, three reported on fatigue using different scales; two were available for meta-analysis. There was a significant reduction in fatigue with IV-iron compared to oral iron (standardized mean difference - 0.40, 95% confidence interval (CI) - 0.62, - 0.18, I2 = 0%). The direction of effect also favored IV-iron for hemoglobin (mean difference (MD) 0.54 g/dL, 95% confidence interval (CI) 0.47, 0.61, I2 = 91%), ferritin, (MD 58.07 mcg/L, 95% CI 55.74, 60.41, I2 = 99%), and total adverse events (risk-ratio 0.63, 95% CI 0.52, 0.77, I2 = 84%). The overall quality of the evidence was low-moderate. DISCUSSION: For all outcomes, the evidence for RBC-T, compared to IV-iron, non-intervention, or dose effects of RBC-T is very limited. Further research is needed to determine whether RBC-T or IV-iron for the treatment of PPA is superior for fatigue and hematological outcomes.

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.

Outbreak of invasive Streptococcus pneumoniae among an inner-city population in Victoria, British Columbia, 2016-2017.

BACKGROUND: Invasive pneumococcal disease (IPD) is a significant cause of morbidity and mortality; however, outbreaks of IPD are relatively rare. Homelessness and substance use are known risk factors for IPD and have been associated with several outbreaks in Canada, despite national recommendations for routine childhood and targeted adult pneumococcal vaccination. OBJECTIVES: To describe the epidemiology and public health challenges related to an outbreak of novel serotype 4 IPD in a homeless and unstably housed population in Victoria, British Columbia during the autumn and winter of 2016-2017. RESULTS: Prospective, enhanced surveillance was initiated for laboratory confirmed cases reported to public health, including variables recording housing status and substance use. Thirty-three cases of serotype 4 IPD within the Victoria area were reported to public health between August 1, 2016 and September 1, 2017. Compared with other serotypes, these cases were more likely to be middle-aged, homeless or unstably housed, and to have a recent history of substance use. A targeted pneumococcal vaccination campaign was initiated in collaboration with external community organizations; however, these initiatives were challenged by incomplete data and staffing constraints. CONCLUSION: This report illustrates an outbreak of serotype 4 IPD among an inner-city population with multiple risk factors, including homelessness, unstable housing and substance use. Given the challenges controlling the outbreak, outreach capacity and pneumococcal vaccination coverage is needed among this marginalized population.

Systematic review and meta-analysis of interventions for depression and anxiety in persons with multiple sclerosis.

BACKGROUND: Depression and anxiety are common in persons with multiple sclerosis (MS), and adversely affect fatigue, medication adherence, and quality of life. Though effective treatments for depression and anxiety exist in the general population, their applicability in the MS population has not been definitively established. OBJECTIVE: To determine the overall effect of psychological and pharmacological treatments for depression or anxiety in persons with MS. METHODS: We searched the Medline, EMBASE, PsycINFO, PsycARTICLES Full Text, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and Scopus databases using systematic review methodology from database inception until March 25, 2015. Two independent reviewers screened abstracts, extracted data, and assessed risk of bias and strength of evidence. We included controlled clinical trials reporting on the effect of pharmacological or psychological interventions for depression or anxiety in a sample of persons with MS. We calculated standardized mean differences (SMD) and pooled using random effects meta-analysis. RESULTS: Of 1753 abstracts screened, 21 articles reporting on 13 unique clinical trials met the inclusion criteria. Depression severity improved in nine psychological trials of depression treatment (N=307; SMD: -0.45 (95%CI: -0.74, -0.16)). The severity of depression also improved in three pharmacological trials of depression treatment (SMD: -0.63 (N=165; 95%CI: -1.07, -0.20)). For anxiety, only a single trial examined psychological therapy for injection phobia and reported no statistically significant improvement. CONCLUSION: Pharmacological and psychological treatments for depression were effective in reducing depressive symptoms in MS. The data are insufficient to determine the effectiveness of treatments for anxiety.

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.

Barriers and enablers to healthcare access and use among Arabic-speaking and Caucasian English-speaking patients with type 2 diabetes mellitus: a qualitative comparative study.

OBJECTIVE: The objective of this study was to explore the decision-making processes and associated barriers and enablers that determine access and use of healthcare services in Arabic-speaking and English-speaking Caucasian patients with diabetes in Australia. STUDY SETTING AND DESIGN: Face-to-face semistructured individual interviews and group interviews were conducted at various healthcare settings-diabetes outpatient clinics in 2 tertiary referral hospitals, 6 primary care practices and 10 community centres in Melbourne, Australia. PARTICIPANTS: A total of 100 participants with type 2 diabetes mellitus were recruited into 2 groups: 60 Arabic-speaking and 40 English-speaking Caucasian. DATA COLLECTION: Interviews were audio-taped, translated into English when necessary, transcribed and coded thematically. Sociodemographic and clinical information was gathered using a self-completed questionnaire and medical records. PRINCIPAL FINDINGS: Only Arabic-speaking migrants intentionally delayed access to healthcare services when obvious signs of diabetes were experienced, missing opportunities to detect diabetes at an early stage. Four major barriers and enablers to healthcare access and use were identified: influence of significant other(s), unique sociocultural and religious beliefs, experiences with healthcare providers and lack of knowledge about healthcare services. Compared with Arabic-speaking migrants, English-speaking participants had no reluctance to access and use medical services when signs of ill-health appeared; their treatment-seeking behaviours were straightforward. CONCLUSIONS: Arabic-speaking migrants appear to intentionally delay access to medical services even when symptomatic. Four barriers to health services access have been identified. Tailored interventions must be developed for Arabic-speaking migrants to improve access to available health services, facilitate timely diagnosis of diabetes and ultimately to improve glycaemic control.

Medicine-taking experiences and associated factors: comparison between Arabic-speaking and Caucasian English-speaking patients with Type 2 diabetes.

AIM: The aim of this study was to explore and compare medication-taking experiences and associated issues in Arabic-speaking and Caucasian English-speaking patients with Type 2 diabetes in Australia. METHODS: Various healthcare settings in metropolitan Melbourne, Australia, were purposefully selected to obtain a diverse group of participants with Type 2 diabetes. Recruitment occurred at diabetes outpatient clinics in two tertiary referral hospitals, six primary care practices and ten community centres. Face-to-face semi-structured individual interviews and group interviews were employed. All interviews were audiotaped, transcribed and coded thematically. Data collection continued until saturation was reached. RESULTS: In total, 100 participants were recruited into two groups: 60 were Arabic-speaking and 40 were Caucasian English-speaking. Both groups had similar demographic and clinical characteristics. Only 5% of the Arabic-speaking participants had well-controlled diabetes compared with 17.5% of the participants in the English-speaking group. Arabic-speaking participants actively changed medication regimens on their own without informing their healthcare professionals. Arabic-speaking patients had more knowledge gaps about their prescribed treatments, compared with the English-speaking group. Their use of diabetes medicines was heavily influenced by peers with diabetes and family members; conversely, they feared revealing their diagnosis within the wider Arabic community due to stigma and collective negative social labelling of diabetes. Confidence in non-Arabic-speaking healthcare providers was lacking. CONCLUSIONS: Findings yielded new insights into medication-taking practices and associated factors in Arabic-speaking patients with diabetes. It is vital that healthcare professionals working with Arabic-speaking patients adapt their treatment approaches to accommodate different beliefs and views about medicines.

MS incidence and prevalence in Africa, Asia, Australia and New Zealand: A systematic review.

OBJECTIVES: Studies of multiple sclerosis (MS) incidence and prevalence from Africa, Asia, Australia and New Zealand are relatively scarce. We systematically reviewed MS incidence and prevalence in these regions including a standardized evaluation of study quality. METHODS: We searched MEDLINE and EMBASE databases for studies of MS prevalence or incidence in Africa, Asia, Australia and New Zealand published in English or French between January 1, 1985 and January 31, 2011. Study quality was assessed using a standardized tool. All steps of the review were performed in duplicate. RESULTS: Of 3925 citations identified, 28 studies met inclusion criteria and 21 of these were from Asia. Quality scores ranged from 1/8 to 8/8; the lowest scores were observed in studies from Asia (median 4/8, IQR 3,6). Prevalence was lowest in South African Blacks (0.22/100,000) and highest amongst Australian-born individuals in Australia (125/100,000). Prevalence increased over time in many countries. MS prevalence increased with increasing latitude only in some regions, and prevalence varied significantly with ethnicity. Eight studies reported incidence, which ranged from 0.67/100,000/year in Taiwan to 3.67/100,00/year in Australia. CONCLUSIONS: This comprehensive study provides an update of MS epidemiology in Africa, Asia, Australia, and New Zealand. Incidence and prevalence were lowest in Africa and Asia and highest in Australia, but many Asian studies were of poor quality. Use of consistent case ascertainment methods, standardized data collection tools, and similar outcomes would all improve study quality and comparability. The underlying basis of observed ethnic differences is an important area for future study.

Prospective observational study to evaluate NOTSS (Non-Technical Skills for Surgeons) for assessing trainees' non-technical performance in the operating theatre.

BACKGROUND: Most surgical assessment has been aimed at technical proficiency. However, non-technical skills also affect patient safety and clinical effectiveness. The NOTSS (Non-Technical Skills for Surgeons) assessment instrument was developed specifically to assess the non-technical skills of individual surgeons in the operating theatre. This study evaluated NOTSS as a real-world assessment, with a mix of minimally trained assessors. The evaluation criteria were feasibility, validity and psychometric reliability. METHODS: In a standard evaluation of NOTSS, 56 anaesthetists, 39 scrub nurses, two surgical care practitioners and three independent assessors provided 715 assessments of 404 surgical cases of 15 index procedures across six specialties performed by 85 surgical trainees. RESULTS: The assessment was feasible, but important implementation challenges were highlighted. Most respondents considered the method valid, but with reservations about assessing cognition. The factor structure of scores, and their positive relationships with other measures of experience and performance, supported validity. Trainees' non-technical skill scores were relatively procedure-independent and achieved good reliability (generalizability coefficient 0·8 or more) when six to eight assessors observed one case each. CONCLUSION: Minimally trained assessors, who are typically present in operating theatres, were sufficiently discriminating and consistent in their judgements of trainee surgeons' non-technical skills to provide reliable scores based on an achievable number of observations.

Assessing the surgical skills of trainees in the operating theatre: a prospective observational study of the methodology.

OBJECTIVES: To compare user satisfaction and acceptability, reliability and validity of three different methods of assessing the surgical skills of trainees by direct observation in the operating theatre across a range of different surgical specialties and index procedures. DESIGN AND SETTING: A 2-year prospective, observational study in the operating theatres of three teaching hospitals in Sheffield. METHODS: The assessment methods were procedure-based assessment (PBA), Objective Structured Assessment of Technical Skills (OSATS) and Non-technical Skills for Surgeons (NOTSS). The specialties were obstetrics and gynaecology (O&G) and upper gastrointestinal, colorectal, cardiac, vascular and orthopaedic surgery. Two to four typical index procedures were selected from each specialty. Surgical trainees were directly observed performing typical index procedures and assessed using a combination of two of the three methods (OSATS or PBA and NOTSS for O&G, PBA and NOTSS for the other specialties) by the consultant clinical supervisor for the case and the anaesthetist and/or scrub nurse, as well as one or more independent assessors from the research team. OUTCOME MEASURES: Information on user satisfaction and acceptability of each assessment method from both assessor and trainee perspectives was obtained from structured questionnaires. The reliability of each method was measured using generalisability theory. Aspects of validity included the internal structure of each tool and correlation between tools, construct validity, predictive validity, interprocedural differences, the effect of assessor designation and the effect of assessment on performance. RESULTS: Of the 558 patients who were consented, a total of 437 (78%) cases were included in the study: 51 consultant clinical supervisors, 56 anaesthetists, 39 nurses, 2 surgical care practitioners and 4 independent assessors provided 1635 assessments on 85 trainees undertaking the 437 cases. A total of 749 PBAs, 695 NOTSS and 191 OSATSs were performed. Non-O&G clinical supervisors and trainees provided mixed, but predominantly positive, responses about a range of applications of PBA. Most felt that PBA was important in surgical education, and would use it again in the future and did not feel that it added time to the operating list. The overall satisfaction of O&G clinical supervisors and trainees with OSATS was not as high, and a majority of those who used both preferred PBA. A majority of anaesthetists and nurses felt that NOTSS allowed them to rate interpersonal skills (communication, teamwork and leadership) more easily than cognitive skills (situation awareness and decision-making), that it had formative value and that it was a valuable adjunct to the assessment of technical skills. PBA demonstrated high reliability (G > 0.8 for only three assessor judgements on the same index procedure). OSATS had lower reliability (G > 0.8 for five assessor judgements on the same index procedure). Both were less reliable on a mix of procedures because of strong procedure-specific factors. A direct comparison of PBA between O&G and non-O&G cases showed a striking difference in reliability. Within O&G, a good level of reliability (G > 0.8) could not be obtained using a feasible number of assessments. Conversely, the reliability within non-O&G cases was exceptionally high, with only two assessor judgements being required. The reasons for this difference probably include the more summative purpose of assessment in O&G and the much higher proportion of O&G trainees in this study with training concerns (42% vs 4%). The reliability of NOTSS was lower than that for PBA. Reliability for the same procedure (G > 0.8) required six assessor judgements. However, as procedure-specific factors exerted a lesser influence on NOTSS, reliability on a mix of procedures could be achieved using only eight assessor judgements. NOTSS also demonstrated a valid internal structure. The strongest correlations between NOTSS and PBA or OSATS were in the 'decision-making' domain. PBA and NOTSS showed better construct validity than OSATS, the year of training and the number of recent index procedures performed being significant independent predictors of performance. There was little variation in scoring between different procedures or different designations of assessor. CONCLUSIONS: The results suggest that PBA is a reliable and acceptable method of assessing surgical skills, with good construct validity. Specialties that use OSATS may wish to consider changing the design or switching to PBA. Whatever workplace-based assessment method is used, the purpose, timing and frequency of assessment require detailed guidance. NOTSS is a promising tool for the assessment of non-technical skills, and surgical specialties may wish to consider its inclusion in their assessment framework. Further research is required into the use of health-care professionals other than consultant surgeons to assess trainees, the relationship between performance and experience, the educational impact of assessment and the additional value of video recording.

Evaluation of procedure-based assessment for assessing trainees' skills in the operating theatre.

BACKGROUND: Procedure-based assessment (PBA) is used within most UK surgical training programmes for assessing trainees' procedural skills in the operating theatre. All postgraduate assessment methods require evidence to support their implementation. The aims were to evaluate the validity, reliability and acceptability of PBA. METHODS: Eighty-one trainees in six surgical specialties were assessed performing common procedures; 749 PBAs were provided across 348 operations by 57 clinical supervisors and four independent assessors. RESULTS: Construct validity was demonstrated by correlation of PBA scores with measures of surgical training and experience. Reliability (G exceeding 0·8) of the adjusted total item score and global summary score for a given procedure was achieved using four and three assessor judgements respectively; assessing a mix of procedures required more cases/assessors because performance is procedure specific. The acceptability of PBA for assessment and feedback within surgical training was predominantly positive among clinical supervisors and trainees. CONCLUSION: PBA demonstrated good overall validity and acceptability, and exceptionally high reliability. Trainees should be assessed adequately for each given procedure.

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.

Differential display polymerase chain reaction reveals increased expression of striatal rat glia-derived nexin following chronic clozapine treatment.

Clozapine is considered a prototype of the 'so-called' atypical antipsychotic drug class. It has affinity for a broad range of receptors and, in comparison to typical antipsychotic drugs, produces less extrapyramidal side effects. However, its mechanism of action remains unclear. Differential display polymerase chain reaction (ddPCR) was implemented in this study to contribute to the current understanding of this mechanism at the genetic level and to identify novel genes regulated by clozapine. This technique generated approximately 2400 gene sequences that were analyzed for differential gene expression following protracted clozapine treatment. One of these sequences, originally termed Clozapine Regulated Gene (CRG), was shown to be significantly upregulated following the treatment. Northern hybridization confirmation of this finding revealed that chronic clozapine administration caused a five-fold increase in CRG mRNA. Elongation of the 5'- and 3'-ends of CRG indicated that the fragment was in fact rat glia-derived nexin mRNA. Western blotting demonstrated that levels of the mRNA's associated protein also increased comparably (three-fold) following chronic treatment with the antipsychotic drug. This study presents a possible neuroprotective role of nexin in clozapine treatment, particularly in the prevention of neuronal proteolytic degradation, since nexin has been shown to be a protease inhibitor.

Development and application of a micro-capillary rheometer for in-vitro evaluation of parenteral injectability.

A micro-capillary rheometer was developed to determine the rheology and injectability of parenteral formulations. The rheometer consisted of a micro-capillary and a glass syringe attached to an Instron that drove the syringe plunger at predetermined speeds and measured resulting forces on the plunger. The cross-head speed and the measured force were used to calculate the shear rate and the shear stress respectively, according to the Hagen-Poiseuille equation. The resulting rheograms of several Newtonian standards showed excellent linearity over a broad range of about 10 x 10(3) to 160 x 10(3) s(-1) and produced accurate and reproducible viscosity determinations over the viscosity range of about 10 x 10(-3) to 100 x 10(-3) Pa.s. The developed methodology focussed primarily on the minimization of errors associated with the determination of the wall frictional force using both direct measurement and linear regression to determine this parameter from the data. The effect of micro-capillary diameter, syringe cross-sectional area and micro-capillary length was explored in an effort to increase the measured force so that wall frictional force errors could be minimized. The micro-capillary rheometer gave reproducible and accurate rheograms over a range of shear rates consistent with the shear rate range used in clinical practice, and showed that Newtonian and non-Newtonian rheological behaviours could be evaluated quantitatively.

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.

Angiogenesis inhibitors in cancer therapy.

The formation of new blood vessels is essential for tumor growth and progression. Angiogenesis inhibitors have been demonstrated to block tumor growth and/or metastasis. Although initial clinical data have been disappointing, new strategies to increase the efficacy of these drugs have ensured their ongoing clinical development. This review highlights the broad spectrum of angiogenesis inhibitors under investigation in both preclinical and clinical studies. From 'natural' inhibitors to thalidomide analogs, the number of compounds in development is extensive. Elucidating the mechanisms of action will enable their use in conjunction with existing/other novel therapies, thereby maximizing the potential efficacy of angiogenesis inhibitors to fulfill their promise in patients with cancer.

Thalidomide derived immunomodulatory drugs (IMiDs) as potential therapeutic agents.

Thalidomide is known to be effective in the treatment of a number of conditions, including leprosy and various cancers. The exact mechanisms of action remain unclear although these are known to include anti-tumour necrosis factor (TNF)-alpha, T cell costimulatory, anti-angiogenic and anti-tumour activities. However, thalidomide is being superceded by novel structural derivatives which have been designed to have improved immunomodulatory activity and side effect profiles. These are currently being characterised and some are entering the clinic in phase I/II studies. One novel group of structural analogues are classified as the Immunomodulatory Drugs (IMiDs). This review describes the emerging immunological, anti-angiogenic and direct anti-tumour properties of thalidomide and the characterisation and clinical application of its IMiD analogues. We describe the laboratory studies which have led to the characterisation and development of IMiDs into potentially clinically relevant drugs. Early trial data suggests that these compounds may themselves become established therapies, particularly in certain cancers. Furthermore, ongoing studies will determine how best to apply these compounds to the appropriate clinical settings. We will describe the various clinical studies of lead compounds that are in progress and speculate as to the potential and future development of these exciting compounds.

Thalidomide analogs as emerging anti-cancer drugs.

Recently, it has been demonstrated that a number of novel thalidomide analogs possess anti-cancer properties due to their T cell co-stimulatory, anti-angiogenic and/or anti-inflammatory effects. Based on such effects, a class of thalidomide analogs known as Immunomodulatory Drugs (IMiDs) have recently entered into phase I clinical trials for the treatment of a number of cancers. The lead IMiD CC-5013 (referred to clinically as REVIMID) is now entering phase III clinical trials for multiple myeloma and metastatic melanoma, while CC-4047 (ACTIMID) is currently under investigation in phase I/II and II trials for multiple myeloma and prostate cancer, respectively. The other group of compounds, classified as Selective Cytokine Inhibitory Drugs (SelCIDs), do not co-stimulate T cells, but have anti-inflammatory and anti-angiogenic properties. Moreover, a subset of SelCIDs has been found to possess direct anti-tumor activity both in vitro and in vivo. This minireview highlights the various mechanisms of action associated with these compounds and their subsequent clinical development. The enhanced efficacy and lower side-effect profiles of the analogs in comparison to thalidomide make the use of these agents very attractive as novel anti-cancer agents.