The Long-Term impact of Business Support? - Exploring the Role of Evaluation Timing using Micro Data

The original contribution of this work is threefold. Firstly, this thesis develops a critical perspective on current evaluation practice of business support, with focus on the timing of evaluation. The general time frame applied for business support policy evaluation is limited to one to two, seldom three years post intervention. This is despite calls for long-term impact studies by various authors, concerned about time lags before effects are fully realised. This desire for long-term evaluation opposes the requirements by policy-makers and funders, seeking quick results. Also, current ‘best practice’ frameworks do not refer to timing or its implications, and data availability affects the ability to undertake long-term evaluation. Secondly, this thesis provides methodological value for follow-up and similar studies by using data linking of scheme-beneficiary data with official performance datasets. Thus data availability problems are avoided through the use of secondary data. Thirdly, this thesis builds the evidence, through the application of a longitudinal impact study of small business support in England, covering seven years of post intervention data. This illustrates the variability of results for different evaluation periods, and the value in using multiple years of data for a robust understanding of support impact. For survival, impact of assistance is found to be immediate, but limited. Concerning growth, significant impact centres on a two to three year period post intervention for the linear selection and quantile regression models – positive for employment and turnover, negative for productivity. Attribution of impact may present a problem for subsequent periods. The results clearly support the argument for the use of longitudinal data and analysis, and a greater appreciation by evaluators of the factor time. This analysis recommends a time frame of four to five years post intervention for soft business support evaluation.

The long-term impact of business support? - Exploring the role of evaluation timing using micro data

The original contribution of this work is threefold. Firstly, this thesis develops a critical perspective on current evaluation practice of business support, with focus on the timing of evaluation. The general time frame applied for business support policy evaluation is limited to one to two, seldom three years post intervention. This is despite calls for long-term impact studies by various authors, concerned about time lags before effects are fully realised. This desire for long-term evaluation opposes the requirements by policy-makers and funders, seeking quick results. Also, current ‘best practice’ frameworks do not refer to timing or its implications, and data availability affects the ability to undertake long-term evaluation. Secondly, this thesis provides methodological value for follow-up and similar studies by using data linking of scheme-beneficiary data with official performance datasets. Thus data availability problems are avoided through the use of secondary data. Thirdly, this thesis builds the evidence, through the application of a longitudinal impact study of small business support in England, covering seven years of post intervention data. This illustrates the variability of results for different evaluation periods, and the value in using multiple years of data for a robust understanding of support impact. For survival, impact of assistance is found to be immediate, but limited. Concerning growth, significant impact centres on a two to three year period post intervention for the linear selection and quantile regression models – positive for employment and turnover, negative for productivity. Attribution of impact may present a problem for subsequent periods. The results clearly support the argument for the use of longitudinal data and analysis, and a greater appreciation by evaluators of the factor time. This analysis recommends a time frame of four to five years post intervention for soft business support evaluation.

Hypoxia induces dilated cardiomyopathy in the chick embryo:mechanism, intervention, and long-term consequences

Background - Intrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development in chick embryos. The aim of this study was to further characterize cardiac disease in hypoxic chick embryos. Methods - Chick embryos were exposed to hypoxia and cardiac structure was examined by histological methods one day prior to hatching (E20) and at adulthood. Cardiac function was assessed in vivo by echocardiography and ex vivo by contractility measurements in isolated heart muscle bundles and isolated cardiomyocytes. Chick embryos were exposed to vascular endothelial growth factor (VEGF) and its scavenger soluble VEGF receptor-1 (sFlt-1) to investigate the potential role of this hypoxia-regulated cytokine. Principal Findings - Growth restricted hypoxic chick embryos showed cardiomyopathy as evidenced by left ventricular (LV) dilatation, reduced ventricular wall mass and increased apoptosis. Hypoxic hearts displayed pump dysfunction with decreased LV ejection fractions, accompanied by signs of diastolic dysfunction. Cardiomyopathy caused by hypoxia persisted into adulthood. Hypoxic embryonic hearts showed increases in VEGF expression. Systemic administration of rhVEGF165 to normoxic chick embryos resulted in LV dilatation and a dose-dependent loss of LV wall mass. Lowering VEGF levels in hypoxic embryonic chick hearts by systemic administration of sFlt-1 yielded an almost complete normalization of the phenotype. Conclusions/Significance - Our data show that hypoxia causes a decreased cardiac performance and cardiomyopathy in chick embryos, involving a significant VEGF-mediated component. This cardiomyopathy persists into adulthood.

Long-term drivers of broadband traffic in next-generation networks

This paper is concerned with long-term (20+ years) forecasting of broadband traffic in next-generation networks. Such long-term approach requires going beyond extrapolations of past traffic data while facing high uncertainty in predicting the future developments and facing the fact that, in 20 years, the current network technologies and architectures will be obsolete. Thus, "order of magnitude" upper bounds of upstream and downstream traffic are deemed to be good enough to facilitate such long-term forecasting. These bounds can be obtained by evaluating the limits of human sighting and assuming that these limits will be achieved by future services or, alternatively, by considering the contents transferred by bandwidth-demanding applications such as those using embedded interactive 3D video streaming. The traffic upper bounds are a good indication of the peak values and, subsequently, also of the future network capacity demands. Furthermore, the main drivers of traffic growth including multimedia as well as non-multimedia applications are identified. New disruptive applications and services are explored that can make good use of the large bandwidth provided by next-generation networks. The results can be used to identify monetization opportunities of future services and to map potential revenues for network operators. © 2014 The Author(s).

Methotrexate polyglutamates as a potential marker of adherence to long-term therapy in children with juvenile idiopathic arthritis and juvenile dermatomyositis:an observational, cross-sectional study

Introduction: Methotrexate (MTX) is a cornerstone of treatment in a wide variety of inflammatory conditions, including juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). However, owing to its narrow therapeutic index and the considerable interpatient variability in clinical response, monitoring of adherence to MTX is important. The present study demonstrates the feasibility of using methotrexate polyglutamates (MTXPGs) as a biomarker to measure adherence to MTX treatment in children with JIA and JDM. Methods: Data were collected prospectively from a cohort of 48 children (median age 11.5 years) who received oral or subcutaneous (SC) MTX therapy for JIA or JDM. Dried blood spot samples were obtained from children by finger pick at the clinic or via self- or parent-led sampling at home, and they were analysed to determine the variability in MTXPG concentrations and assess adherence to MTX therapy. Results: Wide fluctuations in MTXPG total concentrations (>2.0-fold variations) were found in 17 patients receiving stable weekly doses of MTX, which is indicative of nonadherence or partial adherence to MTX therapy. Age (P = 0.026) and route of administration (P = 0.005) were the most important predictors of nonadherence to MTX treatment. In addition, the study showed that MTX dose and route of administration were significantly associated with variations in the distribution of MTXPG subtypes. Higher doses and SC administration of MTX produced higher levels of total MTXPGs and selective accumulation of longer-chain MTXPGs (P < 0.001 and P < 0.0001, respectively). Conclusions: Nonadherence to MTX therapy is a significant problem in children with JIA and JDM. The present study suggests that patients with inadequate adherence and/or intolerance to oral MTX may benefit from SC administration of the drug. The clinical utility of MTXPG levels to monitor and optimise adherence to MTX in children has been demonstrated. Trial registration: ISRCTN Registry identifier: ISRCTN93945409. Registered 2 December 2011.

Medicines optimisation for young people with juvenile arthritis and other long-term conditions:system-level barriers to engagement

To explore the views of pharmacy and rheumatology stakeholders about system-related barriers to medicines optimisation activities with young people with long-term conditions. A three-phase consensus-building study comprising (1) focus groups with community and hospital pharmacists; (2) semi-structured telephone interviews with lay and professional adolescent rheumatology stakeholders and pharmacy policymakers, and (3) multidisciplinary discussion groups with community and hospital pharmacists and rheumatology staff. Qualitative verbatim transcripts from phases 1 and 2 were subjected to framework analysis. Themes from phase 1 underpinned a briefing for phase 2 interviewees. Themes from phases 1 and 2 generated elements of good pharmacy practice and current/future pharmacy roles for ranking in phase 3. Results from phase 3 prioritisation and ranking exercises were captured on self-completion data collection forms, entered into an Excel spreadsheet and subjected to descriptive statistical analysis. Institutional ethical approval was given by Aston University Health and Life Sciences Research Ethics Committee. Four focus groups were conducted with 18 pharmacists across England, Scotland and Wales (7 hospital, 10 community and 1 community/public health). Fifteen stakeholders took part in telephone interviews (3 pharmacist commissioners; 2 pharmacist policymakers; 2 pharmacy staff members (1 community and 1 hospital); 4 rheumatologists; 1 specialist nurse, and 3 lay juvenile arthritis advocates). Twenty-five participants took part in three discussion groups in adolescent rheumatology centres across England and Scotland (9 community pharmacists; 4 hospital pharmacists; 6 rheumatologists; 5 specialist nurses, and 1 physiotherapist). In all phases of the study, system-level issues were acknowledged as barriers to more engagement with young people and families. Community pharmacists in the focus groups reported that opportunities for engaging with young people were low if parents collected prescriptions alone, which was agreed by other stakeholders. Moreover, institutional/company prescription collection policies – an activity largely disallowed for a young person under 16 without an accompanying parent - were identified by hospital and community pharmacists as barriers to open discussion and engagement. Few community pharmacists reported using Medicines Use Review (England/Wales) or Chronic Medication Service (Scotland) as a medicines optimisation activity with young people; many were unsure about consent procedures. Despite these limitations, rheumatology stakeholders ranked highly the potential of pharmacists empowering young people with general health care skills, such as repeat prescription ordering. The pharmacy profession lacks vision for its role in the care of young people with long-term conditions. Pharmacists and rheumatology stakeholders identified system-level barriers to more engagement with young people who take medicines regularly. We acknowledge that the modest number of participants may have had a specific interest and thus bias for the topic, but this underscores their frank admission of the challenges. Professional guidance and policy, practice frameworks and institutional/company policies must promote flexibility for pharmacy staff to recognise and empower young people who are able to give consent and take responsibility for medicines activities. This will increase mutual confidence and trust, and foster pharmacy’s role in teaching general health care skills. In this way, pharmacists will be able to build long-term relationships with young people and families.

Post discharge follow up of children on long term medication

Background: There have been no published studies observing what happens to children post hospital discharge and if medication discrepancies occurred between the hospital and General Practitioner (GP) interface.1 Objectives: To identify the type of discrepancies between hospital discharge prescription and the patient's medicines after their first GP prescription. Method: Over a 3 month period (March–June 2012) across two London NHS hospital sites, parents of children on long term medications aged 18 years and under, were approached and consented prior to discharge from the ward. The patients were followed up 21 days after discharge by telephone call or home visit depending on their preference. The parent was asked if they had contacted their GP for further medications during the follow up, and if not the follow up was rescheduled. The parents were interviewed to find out if there were any discrepancies that occurred post discharge by comparing the patient's hospital discharge letter and medication at follow up. All this information was captured on a data collection form. Results: Eighty-eight patients were consented and 60 patients (68%; 60/88) were followed up by telephone call 21 days post discharge. A total of 317 medications were ordered at discharge among the 60 patients. Of the 60 that were followed up, nine were lost to follow up, one died post discharge, one was excluded from the study, and 11 had not contacted the GP and were to be followed up at a later date. Of the 38 patients who were followed up, 254 medications were ordered. Of the 38 patients there were 12 (32%) patients who had discrepancies that occurred between the discharge letter and GP, 19 (50%) had no issues, and seven (18%) mentioned issues to do with post discharge that were not discrepancies. Of the 12 patients who had at least one medication discrepancy (total 34 medications, range 1–7 discrepancies per patient), six patients had GP discrepancies, four had discrepancies resulting from a hospital outpatient appointment, one related to the discharge letter order and one was a complex discrepancy. An example: a patient was discharged on amiodarone liquid 16.5 mg daily as opposed to 65 mg daily of amiodarone from the GP. Upon interview the parent used volume units to communicate dose as opposed to the actual dose itself and the strengths of liquid had changed. Conclusions: The preliminary results from the study have shown that discrepancies due to several causes occur when paediatric patients leave hospital.

Usual medical treatments or levonorgestrel-IUS for women with heavy menstrual bleeding:long-term randomised pragmatic trial in primary care

Background: Heavy menstrual bleeding (HMB) is a common, chronic problem affecting women and health services. However, long-term evidence on treatment in primary care is lacking. Aim: To assess the effectiveness of commencing the levonorgestrel-releasing intrauterine system (LNG-IUS) or usual medical treatments for women presenting with HMB in general practice. Design and setting: A pragmatic, multicentre, parallel, open-label, long term, randomised controlled trial in 63 primary care practices across the English Midlands. Method: In total, 571 women aged 25–50 years, with HMB were randomised to LNG-IUS or usual medical treatment (tranexamic/mefenamic acid, combined oestrogen–progestogen, or progesterone alone). The primary outcome was the patient reported Menorrhagia Multi-Attribute Scale (MMAS, measuring effect of HMB on practical difficulties, social life, psychological and physical health, and work and family life; scores from 0 to 100). Secondary outcomes included surgical intervention (endometrial ablation/hysterectomy), general quality of life, sexual activity, and safety. Results: At 5 years post-randomisation, 424 (74%) women provided data. While the difference between LNG-IUS and usual treatment groups was not significant (3.9 points; 95% confidence interval = −0.6 to 8.3; P = 0.09), MMAS scores improved significantly in both groups from baseline (mean increase, 44.9 and 43.4 points, respectively; P<0.001 for both comparisons). Rates of surgical intervention were low in both groups (surgery-free survival was 80% and 77%; hazard ratio 0.90; 95% CI = 0.62 to 1.31; P = 0.6). There was no difference in generic quality of life, sexual activity scores, or serious adverse events. Conclusion: Large improvements in symptom relief across both groups show treatment for HMB can be successfully initiated with long-term benefit and with only modest need for surgery.

Short-term and long-term changes in corneal power are not correlated with axial elongation of the eye induced by orthokeratology in children

PURPOSE: To assess the relationship between short-term and long-term changes in power at different corneal locations relative to the change in central corneal power and the 2-year change in axial elongation relative to baseline in children fitted with orthokeratology contact lenses (OK). METHODS: Thirty-one white European subjects 6 to 12 years of age and with myopia −0.75 to −4.00 DS and astigmatism ≤1.00 DC were fitted with OK. Differences in refractive power 3 and 24 months post-OK in comparison with baseline and relative to the change in central corneal power were determined from corneal topography data in eight different corneal regions (i.e., N[nasal]1, N2, T[temporal]1, T2, I[inferior]1, I2, S[superior]1, S2), and correlated with OK-induced axial length changes at two years relative to baseline. RESULTS: After 2 years of OK lens wear, axial length increased by 0.48±0.18 mm (P0.05). CONCLUSION: The reduction in central corneal power and relative increase in paracentral and pericentral power induced by OK over 2 years were not significantly correlated with concurrent changes in axial length of white European children.