Clinical and cost-effectiveness of individualised (early) patient-directed rehabilitation versus standard rehabilitation after surgical repair of the rotator cuff of the shoulder: protocol for a multicentre, randomised controlled trial with integrated Quintet Recruitment Intervention (RaCeR 2).

INTRODUCTION: Despite the high number of operations and surgical advancement, rehabilitation after rotator cuff repair has not progressed for over 20 years. The traditional cautious approach might be contributing to suboptimal outcomes. Our aim is to assess whether individualised (early) patient-directed rehabilitation results in less shoulder pain and disability at 12 weeks after surgical repair of full-thickness tears of the rotator cuff compared with current standard (delayed) rehabilitation. METHODS AND ANALYSIS: The rehabilitation after rotator cuff repair (RaCeR 2) study is a pragmatic multicentre, open-label, randomised controlled trial with internal pilot phase. It has a parallel group design with 1:1 allocation ratio, full health economic evaluation and quintet recruitment intervention. Adults awaiting arthroscopic surgical repair of a full-thickness tear are eligible to participate. On completion of surgery, 638 participants will be randomised. The intervention (individualised early patient-directed rehabilitation) includes advice to the patient to remove their sling as soon as they feel able, gradually begin using their arm as they feel able and a specific exercise programme. Sling removal and movement is progressed by the patient over time according to agreed goals and within their own pain and tolerance. The comparator (standard rehabilitation) includes advice to the patient to wear the sling for at least 4 weeks and only to remove while eating, washing, dressing or performing specific exercises. Progression is according to specific timeframes rather than as the patient feels able. The primary outcome measure is the Shoulder Pain and Disability Index total score at 12-week postrandomisation. The trial timeline is 56 months in total, from September 2022. TRIAL REGISTRATION NUMBER: ISRCTN11499185.

Clinical statistical analysis plan for the ACCURE trial: the effect of appendectomy on the clinical course of ulcerative colitis, a randomised international multicentre trial.

BACKGROUND: The primary treatment of ulcerative colitis (UC) is medical therapy using a standard step-up approach. An appendectomy might modulate the clinical course of UC, decreasing the incidence of relapses and reducing need for medication. The objective of the ACCURE trial is to assess the efficacy of laparoscopic appendectomy in addition to standard medical treatment in maintaining remission in UC patients. This article presents the statistical analysis plan to evaluate the outcomes of the ACCURE trial. DESIGN AND METHODS: The ACCURE trial was designed as a multicentre, randomised controlled trial. UC patients with a new diagnosis or a disease relapse within the past 12 months, treated with 5-ASA, corticosteroids, or immunomodulators until complete clinical and endoscopic remission (defined as total Mayo score < 3 with endoscopic subscore of 0 or 1), were counselled for inclusion. Also, patients previously treated with biologicals who had a washout period of at least 3 months were considered for inclusion. Patients were randomised (1:1) to laparoscopic appendectomy plus maintenance treatment or a control group (maintenance therapy only). The primary outcome is the 1-year UC relapse rate (defined as a total Mayo-score ≥ 5 with endoscopic subscore of 2 or 3, or clinically as an exacerbation of symptoms and rectal bleeding or FCP > 150 or intensified medical therapy other than 5-ASA therapy). Secondary outcomes include number of relapses per patient, time to first relapse, disease activity, number of colectomies, medication usage, and health-related quality of life. DISCUSSION: The ACCURE trial will provide comprehensive evidence whether adding an appendectomy to maintenance treatment is superior to maintenance treatment only in maintaining remission in UC patients. TRIAL REGISTRATION: Dutch Trial Register (NTR) NTR2883 . Registered May 3, 2011. ISRCTN, ISRCTN60945764 . Registered August 12, 2019.

The Acute VertEbRal AugmentaTion (AVERT) study: protocol for a randomised controlled, feasibility trial of spinal medial branch nerve block in hospitalised older patients with vertebral fragility fractures.

INTRODUCTION: Vertebral fragility fractures (VFFs) are the most common type of osteoporotic fracture found in older people, resulting in increasing morbidity and excess mortality. These fractures can cause significant pain, requiring admission to hospital. Vertebroplasty (VP) is effective in reducing pain and allowing early mobilisation in hospitalised patients. However, it may be associated with complications such as cement leakage, infection, bleeding at the injection site and fracture of adjacent vertebrae. It is also costly and not readily accessible in many UK hospitals.A recent retrospective study reported that spinal medial branch nerve block (MBNB), typically used to treat facet arthropathy, had similar efficacy in terms of pain relief compared with VP for the treatment of painful VFF. However, to date, no study has prospectively compared MBNB to VP. We therefore propose a prospective feasibility randomised controlled trial (RCT) to compare the role of MBNB to VP, in hospitalised older patients. METHOD: A parallel, two-arm RCT with participants allocated on a 1:1 ratio to either standard care-VP or MBNB in hospitalised patients aged over 70 with acute osteoporotic vertebral fractures. Follow-up will be at weeks 1, 4 and 8 post intervention. The primary objective is to determine the feasibility and design of a future trial, including specific outcomes of recruitment, adherence to randomisation and safety. Embedded within the trial will be a health economic evaluation to understand resource utilisation and implications of the intervention and a qualitative study of the experiences and insights of trial participants and clinicians. Secondary outcomes will include pain scores, analgesia requirements, resource use and quality of life data. ETHICS AND DISSEMINATION: Ethical approval was granted by the Yorkshire & the Humber Research Ethics Committee (reference 21/YH/0065). AVERT (Acute VertEbRal AugmentaTion) has received approval by the Health Research Authority (reference IRAS 293210) and is sponsored by Nottingham University Hospitals NHS Trust (reference 21HC001). Recruitment is ongoing. Results will be presented at relevant conferences and submitted to appropriate journals for publication on completion. TRIAL REGISTRATION NUMBER: ISRCTN18334053.

Salbutamol for analgesia in renal colic: study protocol for a prospective, randomised, placebo-controlled phase II trial (SARC).

BACKGROUND: Renal colic is the pain experienced by a patient when a renal calculus (kidney stone) causes partial or complete obstruction of part of the renal outflow tract. The standard analgesic regimes for renal colic are often ineffective; in some studies, less than half of patients achieve complete pain relief, and a large proportion of patients require rescue analgesia within 4 h. Current analgesic regimes are also associated with significant side effects including nausea, vomiting, drowsiness and respiratory depression. It has been hypothesised that beta adrenoreceptor agonists, such as salbutamol, may reduce the pain of renal colic. They have been shown to impact a number of factors that target the physiological causes of pain in renal colic (ureteric spasm and increased peristalsis, increased pressure at the renal pelvis and prostaglandin release with inflammation). There is biological plausibility and a body of evidence sufficient to suggest that this novel treatment for the pain of renal colic should be taken to a phase II clinical trial. The aim of this trial is to test whether salbutamol is an efficacious analgesic adjunct when added to the standard analgesic regime for patients presenting to the ED with subsequently confirmed renal colic. METHODS: A phase II, randomised, placebo-controlled trial will be performed in an acute NHS Trust in the East Midlands. Patients presenting to the emergency department with pain requiring IV analgesia and working diagnosis of renal colic will be randomised to receive standard analgesia ± a single intravenous injection of Salbutamol. Secondary study objectives will explore the feasibility of conducting a larger, phase III trial. DISCUSSION: The trial will provide important information about the efficacy of salbutamol as an analgesic adjunct in renal colic. It will also guide the development of a definitive phase III trial to test the cost and clinical effectiveness of salbutamol as an analgesic adjunct in renal colic. Salbutamol benefits from widespread use across the health service for multiple indications, extensive staff familiarity and a good side effect profile; therefore, its potential use for pain relief may have significant benefits for patient care. TRIAL REGISTRATION: ISRCTN Registry ISRCTN14552440 . Registered on 22 July 2019.

Trends in emergency department litigation within the NHS: a retrospective database analysis.

The objectives of this study are to examine trends in litigation related to emergency department care within the NHS. The study is based on retrospective database analysis. NHS Resolution databases of litigation activity pertaining to Type I emergency departments within the NHS are used. The main outcome measures were number of claims, number of successful claims, costs associated with litigation and costs per claim, all in comparison to patterns of ED attendance numbers and inflation. The results showed that the annual cost of litigation relating to emergency department care within the NHS has increased from £25.5 million in 2005/6 to £161.9 million in 2017/18. Mean cost per claim has increased from £58,252 in 2005/6 to £168,966 in 2017/18. The number of claims received has increased significantly; the proportion of these which were successful has remained constant. Therefore, it was concluded that the costs of litigation are increasing disproportionately to inflation and attendance numbers. Multiple potential causes are discussed, with significant implications for clinical practice.

POSNOC-POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy: a randomised controlled trial of axillary treatment in women with early-stage breast cancer who have metastases in one or two sentinel nodes.

INTRODUCTION: ACOSOG-Z0011(Z11) trial showed that axillary node clearance (ANC) may be omitted in women with ≤2 positive nodes undergoing breast conserving surgery (BCS) and whole breast radiotherapy (RT). A confirmatory study is needed to clarify the role of axillary treatment in women with ≤2 macrometastases undergoing BCS and groups that were not included in Z11 for example, mastectomy and those with microscopic extranodal invasion. The primary objective of POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy (POSNOC) is to evaluate whether for women with breast cancer and 1 or 2 macrometastases, adjuvant therapy alone is non-inferior to adjuvant therapy plus axillary treatment, in terms of 5-year axillary recurrence. METHODS AND ANALYSIS: POSNOC is a pragmatic, multicentre, non-inferiority, international trial with participants randomised in a 1:1 ratio. Women are eligible if they have T1/T2, unifocal or multifocal invasive breast cancer, and 1 or 2 macrometastases at sentinel node biopsy, with or without extranodal extension. In the intervention group women receive adjuvant therapy alone, in the standard care group they receive ANC or axillary RT. In both groups women receive adjuvant therapy, according to local guidelines. This includes systemic therapy and, if indicated, RT to breast or chest wall. The UK Radiotherapy Trials Quality Assurance Group manages the in-built radiotherapy quality assurance programme. Primary endpoint is 5-year axillary recurrence. Secondary outcomes are arm morbidity assessed by Lymphoedema and Breast Cancer Questionnaire and QuickDASH questionnaires; quality of life and anxiety as assessed with FACT B+4 and State/Trait Anxiety Inventory questionnaires, respectively; other oncological outcomes; economic evaluation using EQ-5D-5L. Target sample size is 1900. Primary analysis is per protocol. Recruitment started on 1 August 2014 and as of 9 June 2021, 1866 participants have been randomised. ETHICS AND DISSEMINATION: Protocol was approved by the National Research Ethics Service Committee East Midlands-Nottingham 2 (REC reference: 13/EM/0459). Results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN54765244; NCT0240168Cite Now.

Can an ECG performed during emergency department triage and interpreted as normal by computer analysis safely wait for clinician review until the time of patient assessment? A pilot study.

INTRODUCTION: Electrocardiograms (ECGs) are frequently performed during patient triage in Emergency Departments (EDs). Emergency Physicians (EPs) are interrupted during other tasks to review ECGs. Critics believe this practice could lead to distraction with consequent medical error and decision fatigue. ECGs can be interpreted by computer software at the time of capture; some evidence exists to suggest that an ECG performed during ED triage with an immediate computer interpretation (ICI) of 'normal' will seldom contain information necessitating a change to triage management. MATERIAL AND METHODS: All ED triage ECGs performed in the Royal Derby Hospital between 13th July 2017 and 12th July 2018 in patients without chest pain and with an ICI of 'normal' were identified through a database search. Forty were randomly selected and reviewed by two EPs (blinded to patient details, ICI and outcome) who were asked to identify those that required a change to triage management. RESULTS: The study processes were feasible. At least one of the two EP reviewers felt that a change to triage management was required in 48% of cases (e.g. "review patient", "obtain blood gas", "review old ECGs"); they agreed on the need for change of management in 13% of cases. An ICI of normal had a NPV of 53% (95% CI 37-67%) for the need for a change to triage management based upon ECG findings. Inter-observer agreement was poor (kappa = 0.17). CONCLUSIONS: Based on these results, ED triage ECGs should still be presented to EPs for immediate review regardless of the ICI. Inter-observer agreement between EPs was poor. Further research is required to link triage ECG interpretation, need for intervention and patient outcome.

The effectiveness of a new dried human amnion derived membrane in addition to standard care in treating diabetic foot ulcers: A patient and assessor blind, randomised controlled pilot study.

Recent reviews suggest that amniotic membrane products may accelerate healing of diabetic foot ulcers. A new dried human amniotic membrane (dHAM) has been used for ocular ulcers but not for diabetic foot ulcers. This was a multi-centre, prospective, patient and observer blind, randomised controlled pilot trial, to investigate whether 2 weekly addition of the dHAM to standard care versus standard care alone increased the proportion of healed participants' index foot ulcers within 12 weeks. Thirty-one people (mean age 59.8 years, 81% male, 87% type 2 diabetes) were randomised (15 dHAM, 16 usual care). Within 12 weeks, healing occurred in 4 (27%) ulcers in the dHAM group versus 1 (6.3%) usual care group (P = .1). Percentage wound area reduction was higher in the dHAM versus control group. (P = .0057). There was no difference in AEs between the two groups. Six participants allocated to dHAM correctly identified their treatment group, although 5 in usual care incorrectly thought they were in the intervention arm. This pilot trial result is encouraging showing that this dHAM preparation is safe and promising treatment. These results will be used to design a statistically powered, definitive double blind randomised controlled trial.

Clinical investigation plan for the use of interactive binocular treatment (I-BiT) for the management of anisometropic, strabismic and mixed amblyopia in children aged 3.5-12 years: a randomised controlled trial.

BACKGROUND: Amblyopia (lazy eye) affects the vision of approximately 2% of all children. Traditional treatment consists of wearing a patch over their 'good' eye for a number of hours daily, over several months. This treatment is unpopular and compliance is often low. Therefore, results can be poor. I-BiT is a system, based on stereo technology using shutter glasses, designed to treat amblyopia using dichoptic stimulation. This trial uses a redesigned system for home use and includes eye-tracking capability. METHODS/DESIGN: This is a randomised controlled trial involving three groups of 40 patients each, aged between 3.5 and 12 years, with a diagnosis of (1) anisometropic amblyopia, (2) mixed or strabismic amblyopia prior to strabismic surgery and (3) mixed or strabismic amblyopia who have just undergone strabismus surgery. They will be randomised in a 1:1 ratio between I-BiT and control and will receive treatment, at home over a 6-week period. Their visual acuity will be assessed independently at baseline, mid-treatment (week 3), at the end of treatment (week 6) and, for those receiving the active I-BiT treatment, 4 weeks after completing treatment (week 10). The primary endpoint will be the change in visual acuity from baseline to the end of treatment. Secondary endpoints will be additional visual acuity measures, patient acceptability, compliance and the incidence of adverse events. DISCUSSION: This is a randomised controlled trial using the redesigned I-BiT™ system to determine if this is a feasible treatment strategy for the management of anisometropic, strabismic and mixed amblyopia. TRIAL REGISTRATION: ISRCTN Number/Clinical trials.gov, ID: NCT02810847 . Registered on 23 June 2016.

ß-Adrenoreceptor agonists in the management of pain associated with renal colic: a systematic review.

OBJECTIVES: To determine whether ß-adrenoreceptor agonists are effective analgesics for patients with renal colic through a systematic review of the literature. SETTING: Adult emergency departments or acute assessment units. PARTICIPANTS: Human participants with proven or suspected renal colic. INTERVENTIONS: ß-adrenoreceptor agonists. OUTCOME MEASURES: Primary: level of pain at 30 min following administration of the ß-agonist. Secondary: level of pain at various time points following ß-agonist administration; length of hospital stay; analgesic requirement; stone presence, size and position; degree of hydronephrosis. RESULTS: 256 records were screened and 4 identified for full-text review. No articles met the inclusion criteria. CONCLUSIONS AND IMPLICATIONS: There is no evidence to support or refute the proposed use of ß-agonists for analgesia in patients with renal colic. Given the biological plausibility and existing literature base, clinical trials investigating the use of ß-adrenoreceptor agonists in the acute setting for treatment of the pain associated with renal colic are recommended. TRIAL REGISTRATION NUMBER: CRD42015016266.

Randomised controlled trial of video clips and interactive games to improve vision in children with amblyopia using the I-BiT system.

BACKGROUND: Traditional treatment of amblyopia involves either wearing a patch or atropine penalisation of the better eye. A new treatment is being developed on the basis of virtual reality technology allowing either DVD footage or computer games which present a common background to both eyes and the foreground, containing the imagery of interest, only to the amblyopic eye. METHODS: A randomised control trial was performed on patients with amblyopia aged 4-8 years with three arms. All three arms had dichoptic stimulation using shutter glass technology. One arm had DVD footage shown to the amblyopic eye and common background to both, the second used a modified shooter game, Nux, with sprite and targets presented to the amblyopic eye (and background to both) while the third arm had both background and foreground presented to both eyes (non-interactive binocular treatment (non-I-BiT) games). RESULTS: Seventy-five patients were randomised; 67 were residual amblyopes and 70 had an associated strabismus. The visual acuity improved in all three arms by approximately 0.07 logMAR in the amblyopic eye at 6 weeks. There was no difference between I-BiT DVD and non-I-BiT games compared with I-BiT games (stated primary outcome) in terms of gain in vision. CONCLUSIONS: There was a modest vision improvement in all three arms. Treatment was well tolerated and safe. There was no difference between the three treatments in terms of primary stated outcomes but treatment duration was short and the high proportion of previously treated amblyopia and strabismic amblyopia disadvantaged dichoptic stimulation treatment. TRIAL REGISTRATION NUMBER: NCT01702727, results.

A prospective study of adverse drug reactions to antiepileptic drugs in children.

OBJECTIVES: To prospectively determine the nature and rate of adverse drug reactions (ADRs) in children on antiepileptic drugs (AEDs) and to prospectively evaluate the effect of AEDs on behaviour. SETTING: A single centre prospective observational study. PARTICIPANTS: Children (<18 years old) receiving one or more AEDs for epilepsy, at each clinically determined follow-up visit. PRIMARY AND SECONDARY OUTCOMES: Primary outcome was adverse reactions of AEDs. Behavioural and cognitive functions were secondary outcomes. RESULTS: 180 children were recruited. Sodium valproate and carbamazepine were the most frequently used AEDs. A total of 114 ADRs were recorded in 56 of these children (31%). 135 children (75%) were on monotherapy. 27 of the 45 children (60%) on polytherapy had ADRs; while 29 (21%) of those on monotherapy had ADRs. The risk of ADRs was significantly lower in patients receiving monotherapy than polytherapy (RR: 0.61, 95% CI 0.47 to 0.79, p<0.0001). Behavioural problems and somnolence were the most common ADRs. 23 children had to discontinue their AED due to an ADR. CONCLUSIONS: Behavioural problems and somnolence were the most common ADRs. Polytherapy significantly increases the likelihood of ADRs in children. TRAIL REGISTRATION NUMBER: EudraCT (2007-000565-37).

Hospitalization in Parkinson's disease: a survey of UK neurologists, geriatricians and Parkinson's disease nurse specialists.

INTRODUCTION: Care for people with Parkinson's admitted to hospital is often suboptimal and services for these patients vary. We conducted a national survey to document current service provision in the UK and to explore clinicians' views on standards of care and potential service improvements. METHOD: We used the mailing lists of British Geriatric Society Movement Disorder Section (BGS-MDS), British and Irish Neurologists' Movement Disorders Group (BRING-MD), and Parkinson's Disease Nurse Specialists Association (PDNSA) and invited participation by email with a link to an online survey (www.surveymonkey.com). The survey was posted in spring 2014 for six weeks. RESULTS: There were 93 respondents from at least 65 different hospitals. The estimated response rate was 19%. Respondents were: 35 consultant geriatricians; 21 consultant neurologists, 29 Parkinson's Disease Nurse Specialists (PDNS), 8 others. 81% respondents report their hospital has a PDNS. 79% have a geriatrician with an interest in Parkinson's. 54% have a Parkinson's clinical guideline, 16% a cohort/specialist ward for Parkinson's and 11% an electronic system for flagging Parkinson's admissions. 21% rated overall standard of care as poor. 61% were not confident that medications were given on time. Having a PDNS see all Parkinson's in-patients, flagging of Parkinson's admissions and having a Parkinson's outreach service were ranked most likely of 16 potential service developments to improve care. CONCLUSION: Care for Parkinson's in-patients is not highly rated by UK Parkinson's clinicians. Interventions to improve care need to be studied but wide variations in current service provision pose a challenge for future study design.

A questionnaire survey comparing the educational priorities of patients and medical students in the management of multiple sclerosis.

OBJECTIVE: To compare the educational priorities patients and students raise concerning the management of multiple sclerosis (MS). DESIGN/SETTING: A single-centre comparative questionnaire survey conducted in a foundation trust hospital which provides teaching for one UK medical school. PARTICIPANTS: A total of 255 people with multiple sclerosis (pwMS) and 125 final year medical students attending a mandatory module were invited to participate. MAIN OUTCOME MEASUREMENTS: Questionnaires were developed and piloted for this study and analysed on the basis of the International Classification of Functioning, Disability and Health terminology. RESULTS: Questionnaires were returned by 125 (50%) pwMS (age range 36-86 years; median 58) and 96 (77%) medical students (age range 22-37 years; median 23). The most commonly reported priority listed by people with MS and students concerned 'environmental contextual factors' (95.5% and 99%, respectively). PwMS focused primarily on the 'social and attitudinal aspects' of the environment (53.6%), while students expressed greater interest in the use of medications (91.7%) and investigations (14.6%) (p < 0.001). People with greater psychological or physical impact of the condition were more likely to prioritise 'health condition' topics. CONCLUSIONS: PwMS and medical students identify different topics when asked to list aspects of management of MS which they deem to be important for medical student teaching. These differences in educational priorities should be taken into consideration when teaching students about MS. The findings may also apply to other long-term neurological conditions and warrant further investigation.

Does a specialist unit improve outcomes for hospitalized patients with Parkinson's disease?

OBJECTIVE: Suboptimal management of Parkinson's disease (PD) medication in hospital may lead to avoidable complications. We introduced an in-patient PD unit for those admitted urgently with general medical problems. We explored the effect of the unit on medication management, length of stay and patient experience. METHODS: We conducted a single-center prospective feasibility study. The unit's core features were defined following consultation with patients and professionals: specially trained staff, ready availability of PD drugs, guidelines, and care led by a geriatrician with specialty PD training. Mandatory staff training comprised four 1 h sessions: PD symptoms; medications; therapy; communication and swallowing. Most medication was prescribed using an electronic Prescribing and Administration system (iSOFT) which provided accurate data on time of administration. We compared patient outcomes before and after introduction of the unit. RESULTS: The general ward care (n = 20) and the Specialist Parkinson's Unit care (n = 24) groups had similar baseline characteristics. On the specialist unit: less Parkinson's medication was omitted (13% vs 20%, p < 0.001); of the medication that was given, more was given on time (64% vs 50%, p < 0.001); median length of stay was shorter (9 days vs 13 days, p = 0.043) and patients' experience of care was better (p = 0.01). DISCUSSION: If replicated and generalizable to other hospitals, reductions in length of stay would lead to significant cost savings. The apparent improved outcomes with Parkinson's unit care merit further investigation. We hope to test the hypothesis that specialized units are cost-effective and improve patient care using a randomized controlled trial design.

Determinants of arterial stiffness in chronic kidney disease stage 3.

BACKGROUND: Early chronic kidney disease (CKD) is associated with increased cardiovascular (CV) risk but underlying mechanisms remain uncertain. Arterial stiffness (AS) is associated with increased CV risk in advanced CKD, but it is unclear whether AS is relevant to CV disease (CVD) in early CKD. STUDY DESIGN: Cross-sectional. SETTING AND PARTICIPANTS: 1717 patients with previous estimated glomerular filtration rate (eGFR) 59-30 mL/min/1.73 m(2); mean age 73±9y, were recruited from 32 general practices in primary care. OUTCOMES: Increased arterial stiffness. MEASUREMENTS: Medical history was obtained and participants underwent clinical assessment, urine and serum biochemistry testing. Carotid to femoral pulse wave velocity (PWV) was determined as a measure of AS, using a Vicorder™ device. RESULTS: Univariate analysis revealed significant correlations between PWV and risk factors for CVD including age (r = 0.456; p<0.001), mean arterial pressure (MAP) (r = 0.228; p<0.001), body mass index (r = -0.122; p<0.001), log urinary albumin to creatinine ratio (r = 0.124; p<0.001), Waist to Hip ratio (r = 0.124, p<0.001), eGFR (r = -0.074; p = 0.002), log high sensitivity c-reactive protein (r = 0.066; p = 0.006), HDL (r = -0.062; p = 0.01) and total cholesterol (r = -0.057; p = 0.02). PWV was higher in males (9.6 m/sec vs.10.3 m/sec; p<0.001), diabetics (9.8 m/sec vs. 10.3 m/sec; p<0.001), and those with previous CV events (CVE) (9.8 m/s vs. 10.3 m/sec; p<0.001). Multivariable analysis identified age, MAP and diabetes as strongest independent determinants of higher PWV (adjusted R²â€Š= 0.29). An interactive term indicated that PWV increased to a greater extent with age in males versus females. Albuminuria was a weaker determinant of PWV and eGFR did not enter the model. LIMITATIONS: Data derived from one study visit, with absence of normal controls. CONCLUSION: In this cohort, age and traditional CV risk factors were the strongest determinants of AS. Albuminuria was a relatively weak determinant of AS and eGFR was not an independent determinant. Long-term follow-up will investigate AS as an independent risk factor for CVE in this cohort.

Axillary treatment for patients with early breast cancer and lymph node metastasis: systematic review protocol.

BACKGROUND: For patients with early breast cancer and lymph node metastasis, axillary treatment is widely recommended. This is either surgical removal of the axillary lymph nodes, or axillary radiotherapy. The rationale for axillary treatment is that it will reduce the risk of recurrence in the axilla, and may improve survival. However, both treatments are associated with adverse effects, such as lymphedema, pain and sensory loss, and are costly to the health services and to patients. With improvements in adjuvant therapy, routine axillary treatment may no longer offer any overall advantage. OBJECTIVES: To assess the short and long term benefits and adverse effects of routine axillary treatment (axillary lymph node clearance or axillary radiotherapy) for patients with lymph node positive early-stage breast cancer. METHODS/DESIGN: Criteria for potentially eligibility for the study will be that the participants are men and women with early breast cancer and lymph nodes with metastasis. The study compares either axillary treatment with no axillary treatment, or axillary node clearance with axillary radiotherapy, and the study is a randomized trial. Primary outcomes are axillary recurrence, disease-free and overall survival. Secondary outcomes include breast or chest wall recurrence, distant metastasis, time to axillary recurrence, axillary recurrence-free survival, arm morbidity, quality of life and health economic costs. The search strategy will include the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and WHO International Clinical Trials Registry Platform (ICTRP) search portal. Two independent reviewers will assess studies for inclusion in the review, assess study quality and extract data. Characteristics of included studies will be described. Meta-analysis will be conducted using ReVman software. COMMENT: This review addresses an important clinical question, and results will inform clinical practice and health care policy.

Safety of fluconazole in paediatrics: a systematic review.

PURPOSE: To determine the safety of fluconazole in neonates and other paediatric age groups by identifying adverse events (AEs) and drug interactions associated with treatment. METHODS: A search of EMBASE (1950-January 2012), MEDLINE (1946-January 2012), the Cochrane database for systematic reviews and the Cumulative Index to Nursing and Allied Health Literature (1982-2012) for any clinical study about fluconazole use that involved at least one paediatric patient (≤17 years) was performed. Only articles with sufficient quality of safety reporting after patients' exposure to fluconazole were included. RESULTS: We identified 90 articles, reporting on 4,209 patients, which met our inclusion criteria. In total, 794 AEs from 35 studies were recorded, with hepatotoxicity accounting for 378 (47.6 %) of all AEs. When fluconazole was compared with placebo and other antifungals, the relative risk (RR) of hepatotoxicity was not statistically different [RR 1.36, 95 % confidence interval (CI) 0.87-2.14, P = 0.175 and RR 1.43, 95 % CI 0.67-3.03, P = 0.352, respectively]. Complete resolution of hepatoxicity was achieved by 84 % of patients with follow-up available. There was no statistical difference in the risk of gastrointestinal events of fluconazole compared with placebo and other antifungals (RR 0.81, 95 % CI 0.12-5.60, P = 0.831 and RR 1.23, 95 %CI 0.87-1.71, P = 0.235, respectively). There were 41 drug withdrawals, 17 (42 %) of which were due to elevated liver enzymes. Five reports of drug interactions occurred in children. CONCLUSION: Fluconazole is relatively safe for paediatric patients. Hepatotoxicity and gastrointestinal toxicity are the most common adverse events. It is important to be aware that drug interactions with fluconazole can result in significant toxicity.

A prospective study to assess the palatability of analgesic medicines in children.

AIM: This study examined children's opinions on the taste of three analgesic medicines: paracetamol, ibuprofen and codeine. BACKGROUND: Many medicines for children are unpleasant and unacceptable. Research has shown that children's taste preferences differ to adults, in whom palatability is often tested. Little British research exists on children's opinions on the palatability of medicines. This study aimed to address this gap in knowledge. DESIGN: Prospective observational study. METHODS: Between May-September 2008, hospital inpatients aged 5-16 years rated the taste of required analgesics on a 100-mm visual analogue scale. This incorporated a 5-point facial hedonic scale. They were also asked their favourite flavour and colour for a medicine. RESULTS: A total of 159 children took part. Eighty-five males (53·5%) and 74 females (46·5%). The median age was 8 years (Inter-quartile range 6-11). The taste of ibuprofen was significantly preferred to paracetamol or codeine. Significant differences were observed depending if the medicine rated was taken first or second (for example pre-medication with paracetamol and ibuprofen). Younger children (5-8 years) were more likely to choose the extremes of the scale when grading than older children were. Preferred flavours on questioning were strawberry 44% and banana 17%. Favourite colours were pink 25·8% and red 20·8%, with girls more likely to choose pink and boys blue. CONCLUSION: Ibuprofen was the most palatable analgesic medicine tested. Children reported they preferred fruit flavours and colour was sex dependent. Nurses when administering two medicines together should consider giving the least palatable first, for example paracetamol before ibuprofen for pre-medication.

Rationale and design of a multi-centre randomised controlled trial of individualised cooled dialysate to prevent left ventricular systolic dysfunction in haemodialysis patients.

BACKGROUND: The main hypothesis of this study is that patients having regular conventional haemodialysis (HD) will have a smaller decline in cardiac systolic function by using cooler dialysate. Cooler dialysate may also be beneficial for brain function. METHODS/DESIGN: The trial is a multicentre, prospective, randomised, un-blinded, controlled trial. Patients will be randomised 1:1 to use a dialysate temperature of 37°C for 12 months or an individualised cooled dialysate. The latter will be set at 0.5°C less than the patient's own temperature, determined from the mean of 6 prior treatment sessions with a tympanic thermometer, up to a maximum of 36°C. Protocol adherence will be regularly checked. Inclusion criteria are incident adult HD patients within 180 days of commencing in-centre treatment 3 times per week with capacity to consent for the trial and without contra-indications for magnetic resonance imaging. Exclusion criteria include not meeting inclusion criteria, inability to tolerate magnetic resonance imaging and New York Heart Association Grade IV heart failure. During the study period, resting cardiac and cerebral magnetic resonance imaging will be performed at baseline and 12 months on an inter-dialytic day. Cardiovascular performance during HD will also be assessed by continuous cardiac output monitors, intra-dialytic echocardiography and biomarkers at baseline and 12 months. The primary outcome measure is a 5% between-group difference in left ventricular ejection fraction measured by cardiac magnetic resonance imaging at 12 months compared to baseline. Analysis will be by intention-to-treat. Secondary outcome measures will include changes in cerebral microstructure and changes in cardiovascular performance during HD. A total of 73 patients have been recruited into the trial from four UK centres. The trial is funded by a Research for Patient Benefit Grant from the National Institute of Healthcare Research. AO is funded by a British Heart Foundation Clinical Research Training Fellowship Grant. The funders had no role in the design of the study. DISCUSSION: This investigator-initiated study has been designed to provide evidence to help nephrologists determine the optimal dialysate temperature for preserving cardiac and cerebral function in HD patients. TRIAL REGISTRATION: ISRCTN00206012 and UKCRN ID 7422.