Using specialist screening practitioners (SSPs) to increase uptake of bowel scope (flexible sigmoidoscopy) screening: results of a feasibility single-stage phase II randomised trial

Objective To determine the feasibility of specialist screening practitioners (SSPs) offering patient navigation (PN) to facilitate uptake of bowel scope screening (BSS) among patients who do not confirm or attend their appointment. Design A single-stage phase II trial. Setting South Tyneside District Hospital, Tyne and Wear, England, UK. Participants Individuals invited for BSS at South Tyneside District Hospital during the 6-month recruitment period were invited to participate in the study. Intervention Consenting individuals were randomly assigned to either the PN intervention or usual care group in a 4:1 ratio. The intervention involved BSS non-attenders receiving a phone call from an SSP to elicit their reasons for non-attendance and offer educational, practical and emotional support as required. If requested by the patient, another BSS appointment was then scheduled. Primary outcome measure The number of non-attenders in the intervention group who were navigated and then rebooked and attended their new BSS appointment. Secondary outcome measures Barriers to BSS attendance, patient-reported outcomes including informed choice and satisfaction with BSS and the PN intervention, reasons for study non-participation, SSPs’ evaluation of the PN process and a cost analysis. Results Of those invited to take part (n=1050), 152 (14.5%) were randomised into the study: PN intervention=109; usual care=43. Most participants attended their BSS appointment (PN: 79.8%; control: 79.1%) leaving 22 eligible for PN: only two were successfully contacted. SSPs were confident in delivering PN, but were concerned that low BSS awareness and information overload may have deterred patients from taking part in the study. Difficulty contacting patients was reported as a burden to their workload. Conclusions PN, as implemented, was not a feasible intervention to increase BSS uptake in South Tyneside. Interventions to increase BSS awareness may be better suited to this population

The economic costs of intrapartum care in Tower Hamlets: a comparison between the cost of birth in a freestanding midwifery unit and hospital for women at low risk of obstetric complications

Objective To compare the economic costs of intrapartum maternity care in an inner city area for ‘low risk’ women opting to give birth in a freestanding midwifery unit compared with those who chose birth in hospital. Design Micro-costing of health service resources used in the intrapartum care of mothers and their babies during the period between admission and discharge, data extracted from clinical notes Setting The Barkantine Birth Centre, a freestanding midwifery unit and the Royal London Hospital’s consultant-led obstetric unit, both run by the former Barts and the London NHS Trust in Tower Hamlets, a deprived inner city borough in east London, England, 2007-2010. Participants Maternity records of 333 women who were resident in Tower Hamlets and who satisfied the Trust’s eligibility criteria for using the Birth Centre. Of these, 167 women started their intrapartum care at the Birth Centre and 166 started care at the Royal London Hospital. Measurements and findings Women who planned their birth at the Birth Centre experienced continuous intrapartum midwifery care, higher rates of spontaneous vaginal delivery, greater use of a birth pool, lower rates of epidural use, higher rates of established breastfeeding and a longer post-natal stay, compared with those who planned for care in the hospital. The total average cost per mother-baby dyad for care where mothers started their intrapartum care at the Birth Centre was £1296.23, approximately £850 per patient less than the average cost per mother and baby who received all their care at the Royal London Hospital. These costs reflect intrapartum throughput using bottom up costing per patient, from admission to discharge, including transfer, but excluding occupancy rates and the related running costs of the units. Key conclusions and implications for practice The study showed that intrapartum throughput in the Birth Centre could be considered cost-minimising when compared to hospital. Modelling the financial viability of midwifery units at a local level is important because it can inform the appropriate provision of these services. This finding from this study contribute a local perspective and thus further weight to the evidence from the Birthplace Programme in support of freestanding midwifery unit care for women without obstetric complications

Thin-layer chromatography method for the simultaneous quantification and stability testing of alprazolam and mebeverine in their combined pharmaceutical dosage form

A sensitive, selective and precise high-performance thin-layer chromatographic method was developed and validated for the simultaneous determination of alprazolam and mebeverine, both as bulk drugs and in formulations. The method employed HPTLC aluminium plates that had been pre-coated with silica gel 60F-254 as the stationary phase, while the solvent system was acetone:methanol:acetic acid (6:4:0.1, v/v/v). The Rf values of alprazolam and mebeverine were observed to be 0.80 ± 0.08 and 0.60 ± 0.05, respectively. The densitometric analysis was carried out in absorbance mode at 225 nm. The linear regression analysis for the calibration plots showed a good linear relationship for alprazolam and mebeverine over concentration ranges of 600 to 3600 ng/spot and 1000 to 6000 ng/spot, respectively. The limit of detection and the limit of quantification for alprazolam (mebeverine) were determined to be 63.97 (11.35) ng/spot and 193.85 (34.40) ng/spot, respectively. Alprazolam and mebeverine stock solutions were subjected to acid and alkali hydrolysis, chemical oxidation, dry heat degradation and photo-degradation. Both drugs were found to be susceptible to acid and alkali hydrolysis, chemical oxidation and photo-degradation, whereas both were found to be stable towards dry heat. The degraded product peaks were well resolved from the pure drug peak and displayed a significant difference in their Rf values. Stressed samples were assayed using the developed HPTLC method. The proposed method was validated with respect to linearity, accuracy, precision and robustness. The method was successfully applied to the estimation of alprazolam and mebeverine in marketed formulations. Statistical analysis showed that the method is repeatable, selective, and precise

A comparative phase 1 clinical trial to identify anti-infective mechanisms of vitamin D in people with HIV infection

Objectives:To determine if there is a biological mechanism that explains the association between HIV disease progression and increased mortality with low circulating vitamin D levels; specifically, to determine if restoring vitamin D levels induced T-cell functional changes important for antiviral immunity.Design:This was a pilot, open-label, three-arm prospective phase 1 study.Methods:We recruited 28 patients with low plasma vitamin D (<50nmol/l 25-hydroxyvitamin D3), comprising 17 HIV+ patients (11 on HAART, six treatment-naive) and 11 healthy controls, who received a single dose of 200000IU oral cholecalciferol. Advanced T-cell flow cytometry methods measured CD4(+) T-cell function associated with viral control in blood samples at baseline and 1-month after vitamin D supplementation.Results:One month of vitamin D supplementation restored plasma levels to sufficiency (>75nmol/l) in 27 of 28 patients, with no safety issues. The most striking change was in HIV+ HAART+ patients, where increased frequencies of antigen-specific T cells expressing macrophage inflammatory protein (MIP)-1 - an important anti-HIV blocking chemokine - were observed, with a concomitant increase in plasma MIP-1, both of which correlated significantly with vitamin D levels. In addition, plasma cathelicidin - a vitamin D response gene with broad antimicrobial activity - was enhanced.Conclusion:Vitamin D supplementation modulates disease-relevant T-cell functions in HIV-infected patients, and may represent a useful adjunct to HAART therapy. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved

Economic evaluation of policy initiatives in the organisation and delivery of healthcare: a case study of gastroenterology endoscopy services

BACKGROUND: Complex clinical interventions are increasingly subject to evaluation by randomised trial linked to economic evaluation. However evaluations of policy initiatives tend to eschew experimental designs in favour of interpretative perspectives which rarely allow the economic evaluation methods used in clinical trials. As evidence of the cost effectiveness of such initiatives is critical in informing policy, it is important to explore whether conventional economic evaluation methods apply to experimental evaluations of policy initiatives.METHODS: We used mixed methods based on a quasi-experimental design to evaluate a policy initiative whose aim was to expedite the modernisation of gastroenterology endoscopy services in England. We compared 10 sites which had received funding and support to modernise their endoscopy services with 10 controls. We collected data from five waves of patients undergoing endoscopy. The economic component of the study compared sites by levels of investment in modernisation and patients' use of health service resources, time off work and health related quality of life.RESULTS: We found no statistically significant difference between intervention and control sites in investment in modernisation or any patient outcome including health.CONCLUSIONS: This study highlights difficulties in applying the rigour of a randomised trial and associated technique of economic evaluation to a policy initiative. It nevertheless demonstrates the feasibility of using this approach although further work is needed to demonstrate its generalisability in other applications. The present application shows that the small incentives offered to intervention sites did not enhance modernisation of gastroenterology endoscopy services or improve patient outcomes

A systematic review of the clinical effectiveness and cost-effectiveness of sensory, psychological and behavioural interventions for managing agitation in older adults with dementia

BACKGROUND: Agitation is common, persistent and distressing in dementia and is linked with care breakdown. Psychotropic medication is often ineffective or harmful, but the evidence regarding non-pharmacological interventions is unclear. OBJECTIVES: We systematically reviewed and synthesised the evidence for clinical effectiveness and cost-effectiveness of non-pharmacological interventions for reducing agitation in dementia, considering dementia severity, the setting, the person with whom the intervention is implemented, whether the effects are immediate or longer term, and cost-effectiveness. DATA SOURCES: We searched twice using relevant search terms (9 August 2011 and 12 June 2012) in Web of Knowledge (incorporating MEDLINE); EMBASE; British Nursing Index; the Health Technology Assessment programme database; PsycINFO; NHS Evidence; System for Information on Grey Literature; The Stationery Office Official Documents website; The Stationery National Technical Information Service; Cumulative Index to Nursing and Allied Health Literature; and The Cochrane Library. We also searched Cochrane reviews of interventions for behaviour in dementia, included papers' references, and contacted authors about 'missed' studies. We included quantitative studies, evaluating non-pharmacological interventions for agitation in dementia, in all settings. REVIEW METHOD: We rated quality, prioritising higher-quality studies. We separated results by intervention type and agitation level. As we were unable to meta-analyse results except for light therapy, we present a qualitative evidence synthesis. In addition, we calculated standardised effect sizes (SESs) with available data, to compare heterogeneous interventions. In the health economic analysis, we reviewed economic studies, calculated the cost of effective interventions from the effectiveness review, calculated the incremental cost per unit improvement in agitation, used data from a cohort study to evaluate the relationship between health and social care costs and health-related quality of life (DEMQOL-Proxy-U scores) and developed a new cost-effectiveness model. RESULTS: We included 160 out of 1916 papers screened. Supervised person-centred care, communication skills (SES = -1.8 to -0.3) or modified dementia care mapping (DCM) with implementing plans (SES = -1.4 to -0.6) were all efficacious at reducing clinically significant agitation in care home residents, both immediately and up to 6 months afterwards. In care home residents, during interventions but not at follow-up, activities (SES = -0.8 to -0.6) and music therapy (SES = -0.8 to -0.5) by protocol reduced mean levels of agitation; sensory intervention (SES = -1.3 to -0.6) reduced mean and clinically significant symptoms. Advantages were not demonstrated with 'therapeutic touch' or individualised activity. Aromatherapy and light therapy did not show clinical effectiveness. Training family carers in behavioural or cognitive interventions did not decrease severe agitation. The few studies reporting activities of daily living or quality-of-life outcomes found no improvement, even when agitation had improved. We identified two health economic studies. Costs of interventions which significantly impacted on agitation were activities, £80-696; music therapy, £13-27; sensory interventions, £3-527; and training paid caregivers in person-centred care or communication skills with or without behavioural management training and DCM, £31-339. Among the 11 interventions that were evaluated using the Cohen-Mansfield Agitation Inventory (CMAI), the incremental cost per unit reduction in CMAI score ranged from £162 to £3480 for activities, £4 for music therapy, £24 to £143 for sensory interventions, and £6 to £62 for training paid caregivers in person-centred care or communication skills with or without behavioural management training and DCM. Health and social care costs ranged from around £7000 over 3 months in people without clinically significant agitation symptoms to around £15,000 at the most severe agitation levels. There is some evidence that DEMQOL-Proxy-U scores decline with Neuropsychiatric Inventory agitation scores. A multicomponent intervention in participants with mild to moderate dementia had a positive monetary net benefit and a 82.2% probability of being cost-effective at a maximum willingness to pay for a quality-adjusted life-year of £20,000 and a 83.18% probability at a value of £30,000. LIMITATIONS: Although there were some high-quality studies, there were only 33 reasonably sized (> 45 participants) randomised controlled trials, and lack of evidence means that we cannot comment on many interventions' effectiveness. There were no hospital studies and few studies in people's homes. More health economic data are needed. CONCLUSIONS: Person-centred care, communication skills and DCM (all with supervision), sensory therapy activities, and structured music therapies reduce agitation in care-home dementia residents. Future interventions should change care home culture through staff training and permanently implement evidence-based treatments and evaluate health economics. There is a need for further work on interventions for agitation in people with dementia living in their own homes. PROTOCOL REGISTRATION: The study was registered as PROSPERO no. CRD42011001370. FUNDING: The National Institute for Health Research Health Technology Assessment programme

A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis : childhood outcomes at 5 years

Objective We performed a randomised trial in very preterm, small for gestational age (SGA) babies to determine if prophylaxis with granulocyte macrophage colony stimulating factor (GM-CSF) improves outcomes (the PROGRAMS trial). GM-CSF was associated with improved neonatal neutrophil counts, but no change in other neonatal or 2-year outcomes. As subtle benefits in outcome may not be ascertainable until school age we performed an outcome study at 5 years. Patients and methods 280 babies born at 31 weeks of gestation or less and SGA were entered into the trial. Outcomes were assessed at 5 years to determine neurodevelopmental and general health status and educational attainment. Results We found no significant differences in cognitive, general health or educational outcomes between 83 of 106 (78%) surviving children in the GM-CSF arm compared with 81 of 110 (74%) in the control arm. Mean mental processing composite (equivalent to IQ) at 5 years were 94 (SD 16) compared with 95 (SD 15), respectively (difference in means −1 (95%CI −6 to 4), and similar proportions were in receipt of special educational needs support (41% vs 35%; risk ratio 1.2 (95% CI 0.8 to 1.9)). Performance on Kaufmann-ABC subscales and components of NEPSY were similar. The suggestion of worse respiratory outcomes in the GM-CSF group at 2 years was replicated at 5 years. Conclusions The administration of GM-CSF to very preterm SGA babies is not associated with improved or more adverse neurodevelopmental, general health or educational outcomes at 5 years

A Cross-Sectional Randomised Study of Fracture Risk in People with HIV Infection in the Probono 1 Study

OBJECTIVE:To determine comparative fracture risk in HIV patients compared with uninfected controls. DESIGN:A randomised cross-sectional study assessing bone mineral density (BMD), fracture history and risk factors in the 2 groups. SETTING:Hospital Outpatients. SUBBBJECTS:222 HIV infected patients and an equal number of age-matched controls. ASSESSMENTS:Fracture risk factors were assessed and biochemical, endocrine and bone markers measured. BMD was assessed at hip and spine. 10-year fracture probability (FRAX) and remaining lifetime fracture probability (RFLP) were calculated. MAIN OUTCOME MEASURES:BMD, and history of fractures. RESULTS:Reported fractures occurred more frequently in HIV than controls, (45 vs. 16; 20.3 vs. 7%; OR=3.27; p=0.0001), and unsurprisingly in this age range, non-fragility fractures in men substantially contributed to this increase. Osteoporosis was more prevalent in patients with HIV (17.6% vs. 3.6%, p<0.0001). BMD was most reduced, and predicted fracture rates most increased, at the spine. Low BMD was associated with antiretroviral therapy (ART), low body mass index and PTH. 10-year FRAX risk was <5% for all groups. RLFP was greater in patients with HIV (OR=1.22; p=0.003) and increased with ART (2.4 vs. 1.50; OR= 1.50; p=0.03). CONCLUSIONS:The increased fracture rate in HIV patients in our relatively youthful population is partly driven by fractures, including non-fragility fractures, in men. Nonetheless, these findings may herald a rise in osteoporotic fractures in HIV patients. An appropriate screening and management response is required to assess these risks and identify associated lifestyle factors that are also associated with other conditions such as cardiovascular disease and diabetes

Non-pharmacological interventions for agitation in dementia: systematic review of randomised controlled trials

Background Agitation in dementia is common, persistent and distressing and can lead to care breakdown. Medication is often ineffective and harmful. Aims To systematically review randomised controlled trial evidence regarding non-pharmacological interventions. Method We reviewed 33 studies fitting predetermined criteria, assessed their validity and calculated standardised effect sizes (SES). Results Person-centred care, communication skills training and adapted dementia care mapping decreased symptomatic and severe agitation in care homes immediately (SES range 0.3-1.8) and for up to 6 months afterwards (SES range 0.2-2.2). Activities and music therapy by protocol (SES range 0.5-0.6) decreased overall agitation and sensory intervention decreased clinically significant agitation immediately. Aromatherapy and light therapy did not demonstrate efficacy. Conclusions There are evidence-based strategies for care homes. Future interventions should focus on consistent and long-term implementation through staff training. Further research is needed for people living in their own homes