Exploring inequalities in child cognitive ability, psychological well-being and risky health behaviours

PhD ThesisThe aim of this thesis was to analyse household inequalities in child and adolescent outcomes. Using the National Child Development Study, British Cohort Study and Millennium Cohort Study, the first empirical chapter estimated the extent of socioeconomic inequality in child cognitive ability, investigated if the magnitude of these inequalities had changed significantly over time, and decomposed the inequality into its contributing factors. Results showed substantial socioeconomic inequalities in child cognitive ability. There was limited evidence that the magnitude of the relationship had changed over time. Income and parental occupational classification accounted for the majority of income related socioeconomic inequality, with smaller roles for maternal education and family size. The second empirical chapter estimated the impact of both family size and birth order on child cognitive ability and psychological well-being, using the Millennium Cohort Study. Ordinary Least Squares models indicated a negative conditional association between family size and psychological well-being, but not cognitive ability. Two Stage Least Squares models, using two separate identification strategies, showed no causal effect of family size. For birth order, both Ordinary Least Squares and Nearest Neighbour Matching models showed substantial later born advantages for the certain subscales of psychological well-being, with this relationship in general not shown for cognitive ability. The third empirical chapter estimated the impact of both maternal labour market supply and non-standard work schedules on adolescent risky health behaviour, using the UK Household Longitudinal Survey dataset. Using a variety of panel data models, there was evidence of a small conditional association between maternal working hours and adolescent drinking, with this relationship not shown for smoking. Two instrumental variable strategies implemented to identify a causal effect were shown to be inappropriate for the research question. For the incidence of non-standard work schedules, there was little evidence of a conditional association for either risky health behaviour.Health Foundatio

Exploration of the costs of accessing health services: data from a longitudinal study of young people in transition from paediatric to adult services.

BACKGROUND: Economic evaluations that include the patient perspective often base their estimates of patient time and travel costs on data collected at a single point in time. This, however, may be inaccurate if the costs of accessing care change substantially over time, as may be the case for young people in transition from paediatric to adult health services. AIMS: The aim of this study was to explore the differences in these time and travel costs between two data collection points for young individuals in transition between health care services, and thus to provide an insight of whether such costs should be collected more than once. METHODS: Descriptive statistics and regression modelling were used to estimate the average difference in costs between the two points of data collection, as well as the potential drivers of those cost differences. RESULTS: We found a small difference in costs between the two time points, equal to -£45.78 [95% CI: - 89.70 to - 1.86]. The results were largely driven by changes in the unit cost of visits and in the number of attendances. CONCLUSIONS: A simple and common assumption that patient costs could be collected at a single time point cannot be made in the context of our study. When deciding on the frequency of elicitation of patient costs, future studies should consider the relative impacts of additional data collection on the estimates of efficiency, inequalities and resource implications for collecting new data

Evaluating high-cost technologies - no need to throw the baby out with the bathwater

INTRODUCTION: Evidence generation for the health technology assessment (HTA) of a new technology is a long and expensive process with no guarantees that the health technology will be adopted and implemented into a health-care system. This would suggest that there is a greater risk of failure for a company developing a high-cost technology and therefore incentives (such as increasing the funding available for research or additional market exclusivity) may be needed to encourage development of such technologies as has been seen with many high-cost orphan drugs. AREAS COVERED: This paper discusses some of the key issues relating to the evaluation of high-cost technologies through the use of existing HTA processes and what the challenges will be going forward. EXPERT OPINION: We propose that while the current HTA process is robust, its evolution into accommodating the incorporation of real-world data and evidence alongside a life-cycle HTA approach should better enable developers to produce the evidence required on effectiveness and cost-effectiveness. This should lead to reduced decision uncertainty for HTA agencies to make adoption decisions in a more timely and efficient manner. Furthermore, budget impact analysis remains important in understanding the actual financial impact on health-care systems and budgets outside of the cost-effectiveness framework used to aid decision-making

The impact of New Labour’s English health inequalities strategy on geographical inequalities in infant mortality : a time trend analysis

Background The English health inequalities strategy (1999-2010) aimed to reduce health inequalities between the most deprived local authorities and the rest of England. The multifaceted strategy included increased investment in healthcare, the early years, education and neighbourhood renewal. The objective of this study was to investigate whether the strategy was associated with a reduction in geographical inequalities in the infant mortality rate (IMR). Methods We used segmented regression analysis to measure inequalities in the IMR between the most deprived local authorities and the rest of England before, during and after the health inequalities strategy period. Results Before the strategy was implemented (1983-1998), absolute inequalities in the IMR increased between the most deprived local authorities and the rest of England at a rate of 0.034 annually (95% CI 0.001 to 0.067). Once the strategy had been implemented (1999-2010), absolute inequalities decreased at a rate of -0.116 annually (95% CI -0.178 to -0.053). After the strategy period ended (2011-2017), absolute inequalities increased at a rate of 0.042 annually (95% CI -0.042 to 0.125). Relative inequalities also marginally decreased during the strategy period. Conclusion The English health inequalities strategy period was associated with a decline in geographical inequalities in the IMR. This research adds to the evidence base suggesting that the English health inequalities strategy was at least partially effective in reducing health inequalities, and that current austerity policies may undermine these gains

Treatment of newly diagnosed glioblastoma in the elderly: a network meta-analysis

Background: A glioblastoma is a fatal type of brain tumour for which the standard of care is maximum surgical resection followed by chemoradiotherapy, when possible. Age is an important consideration in this disease, as older age is associated with shorter survival and a higher risk of treatment‐related toxicity. Objectives: To determine the most effective and best‐tolerated approaches for the treatment of elderly people with newly diagnosed glioblastoma. To summarise current evidence for the incremental resource use, utilities, costs and cost‐effectiveness associated with these approaches. Search methods: We searched electronic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase to 3 April 2019, and the NHS Economic Evaluation Database (EED) up to database closure. We handsearched clinical trial registries and selected neuro‐oncology society conference proceedings from the past five years. Selection criteria: Randomised trials (RCTs) of treatments for glioblastoma in elderly people. We defined ‘elderly' as 70+ years but included studies defining ‘elderly' as over 65+ years if so reported. Data collection and analysis: We used standard Cochrane methods for study selection and data extraction. Where sufficient data were available, treatment options were compared in a network meta‐analysis (NMA) using Stata software (version 15.1). For outcomes with insufficient data for NMA, pairwise meta‐analysis were conducted in RevMan. The GRADE approach was used to grade the evidence. Main results: We included 12 RCTs involving approximately 1818 participants. Six were conducted exclusively among elderly people (either defined as 65 years or older or 70 years or older) with newly diagnosed glioblastoma, the other six reported data for an elderly subgroup among a broader age range of participants. Most participants were capable of self‐care. Study quality was commonly undermined by lack of outcome assessor blinding and attrition. NMA was only possible for overall survival; other analyses were pair‐wise meta‐analyses or narrative syntheses. Seven trials contributed to the NMA for overall survival, with interventions including supportive care only (one trial arm); hypofractionated radiotherapy (RT40; four trial arms); standard radiotherapy (RT60; five trial arms); temozolomide (TMZ; three trial arms); chemoradiotherapy (CRT; three trial arms); bevacizumab with chemoradiotherapy (BEV_CRT; one trial arm); and bevacizumab with radiotherapy (BEV_RT). Compared with supportive care only, NMA evidence suggested that all treatments apart from BEV_RT prolonged survival to some extent. Overall survival: High‐certainty evidence shows that CRT prolongs overall survival (OS) compared with RT40 (hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.56 to 0.80) and low‐certainty evidence suggests that CRT may prolong overall survival compared with TMZ (TMZ versus CRT: HR 1.42, 95% CI 1.01 to 1.98). Low‐certainty evidence also suggests that adding BEV to CRT may make little or no difference (BEV_CRT versus CRT: HR 0.83, 95% CrI 0.48 to 1.44). We could not compare the survival effects of CRT with different radiotherapy fractionation schedules (60 Gy/30 fractions and 40 Gy/15 fractions) due to a lack of data. When treatments were ranked according to their effects on OS, CRT ranked higher than TMZ, RT and supportive care only, with the latter ranked last. BEV plus RT was the only treatment for which there was no clear benefit in OS over supportive care only. One trial comparing tumour treating fields (TTF) plus adjuvant chemotherapy (TTF_AC) with adjuvant chemotherapy alone could not be included in the NMA as participants were randomised after receiving concomitant chemoradiotherapy, not before. Findings from the trial suggest that the intervention probably improves overall survival in this selected patient population. We were unable to perform NMA for other outcomes due to insufficient data. Pairwise analyses were conducted for the following. Quality of life: Moderate‐certainty narrative evidence suggests that overall, there may be little difference in QoL between TMZ and RT, except for discomfort from communication deficits, which are probably more common with RT (1 study, 306 participants, P = 0.002). Data on QoL for other comparisons were sparse, partly due to high dropout rates, and the certainty of the evidence tended to be low or very low. Progression‐free survival: High‐certainty evidence shows that CRT increases time to disease progression compared with RT40 (HR 0.50, 95% CI 0.41 to 0.61); moderate‐certainty evidence suggests that RT60 probably increases time to disease progression compared with supportive care only (HR 0.28, 95% CI 0.17 to 0.46), and that BEV_RT probably increases time to disease progression compared with RT40 alone (HR 0.46, 95% CI 0.27 to 0.78). Evidence for other treatment comparisons was of low‐ or very low‐certainty. Severe adverse events: Moderate‐certainty evidence suggests that TMZ probably increases the risk of grade 3+ thromboembolic events compared with RT60 (risk ratio (RR) 2.74, 95% CI 1.26 to 5.94; participants = 373; studies = 1) and also the risk of grade 3+ neutropenia, lymphopenia, and thrombocytopenia. Moderate‐certainty evidence also suggests that CRT probably increases the risk of grade 3+ neutropenia, leucopenia and thrombocytopenia compared with hypofractionated RT alone. Adding BEV to CRT probably increases the risk of thromboembolism (RR 16.63, 95% CI 1.00 to 275.42; moderate‐certainty evidence). Economic evidence: There is a paucity of economic evidence regarding the management of newly diagnosed glioblastoma in the elderly. Only one economic evaluation on two short course radiotherapy regimen (25 Gy versus 40 Gy) was identified and its findings were considered unreliable. Authors' conclusions: For elderly people with glioblastoma who are self‐caring, evidence suggests that CRT prolongs survival compared with RT and may prolong overall survival compared with TMZ alone. For those undergoing RT or TMZ therapy, there is probably little difference in QoL overall. Systemic anti‐cancer treatments TMZ and BEV carry a higher risk of severe haematological and thromboembolic events and CRT is probably associated with a higher risk of these events. Current evidence provides little justification for using BEV in elderly patients outside a clinical trial setting. Whilst the novel TTF device appears promising, evidence on QoL and tolerability is needed in an elderly population. QoL and economic assessments of CRT versus TMZ and RT are needed. More high‐quality economic evaluations are needed, in which a broader scope of costs (both direct and indirect) and outcomes should be included

Diagnostic accuracy of 1p/19q codeletion tests in oligodendroglioma:a comprehensive meta-analysis based on a Cochrane Systematic Review

Codeletion of chromosomal arms 1p and 19q, in conjunction with a mutation in the isocitrate dehydrogenase 1 or 2 gene, is the molecular diagnostic criterion for oligodendroglioma, IDH mutant and 1p/19q codeleted. 1p/19q codeletion is a diagnostic marker and allows prognostication and prediction of the best drug response within IDH‐mutant tumours. We performed a Cochrane review and simple economic analysis to establish the most sensitive, specific and cost‐effective techniques for determining 1p/19q codeletion status. Fluorescent in situ hybridisation (FISH) and polymerase chain reaction (PCR)‐based loss of heterozygosity (LOH) test methods were considered as reference standard. Most techniques (FISH, chromogenic in situ hybridisation [CISH], PCR, real‐time PCR, multiplex ligation‐dependent probe amplification [MLPA], single nucleotide polymorphism [SNP] array, comparative genomic hybridisation [CGH], array CGH, next‐generation sequencing [NGS], mass spectrometry and NanoString) showed good sensitivity (few false negatives) for detection of 1p/19q codeletions in glioma, irrespective of whether FISH or PCR‐based LOH was used as the reference standard. Both NGS and SNP array had a high specificity (fewer false positives) for 1p/19q codeletion when considered against FISH as the reference standard. Our findings suggest that G banding is not a suitable test for 1p/19q analysis. Within these limits, considering cost per diagnosis and using FISH as a reference, MLPA was marginally more cost‐effective than other tests, although these economic analyses were limited by the range of available parameters, time horizon and data from multiple healthcare organisations

Health for Wealth : Building a Healthier Northern Powerhouse for UK Productivity

There is a well-known productivity gap between the Northern Powerhouse and the rest of England of £4 perperson-per-hour. There is also a substantial health gap between the Northern Powerhouse and the rest of England, with average life expectancy 2 years lower in the North. Given that both health and productivity are lower in the Northern Powerhouse, the NHSA commissioned this report from six of its eight university members (Newcastle, Manchester, Lancaster, Liverpool, Sheeld and York) to understand the impact of poor health on productivity and to explore the opportunities for improving UK productivity by unlocking inclusive, green, regional growth through health improvement. Our report shows the importance of health and the NHS for productivity in the Northern Powerhouse. So, as it develops its post-Brexit industrial strategy, central government should pay particular attention to the importance of improving health in the Northern Powerhouse as a route to increased wealth

Analysis of high-molecular-weight fructan polymers in crude plant extracts by high-resolution LC-MS

The main water-soluble carbohydrates in temperate forage grasses are polymeric fructans. Fructans consist of fructose chains of various chain lengths attached to sucrose as a core molecule. In grasses, fructans are a complex mixture of a large number of isomeric oligomers with a degree of polymerisation ranging from 3 to >100. Accurate monitoring and unambiguous peak identification requires chromatographic separation coupled to mass spectrometry. The mass range of ion trap mass spectrometers is limited, and we show here how monitoring selected multiply charged ions can be used for the detection and quantification of individual isomers and oligomers of high mass, particularly those of high degree of polymerization (DP > 20) in complex plant extracts. Previously reported methods using linear ion traps with low mass resolution have been shown to be useful for the detection of fructans with a DP up to 49. Here, we report a method using high-resolution mass spectrometry (MS) using an Exactive Orbitrap MS which greatly improves the signal-to-noise ratio and allows the detection of fructans up to DP = 100. High-sugar (HS) Lolium perenne cultivars with high concentrations of these fructans have been shown to be of benefit to the pastoral agricultural industry because they improve rumen nitrogen use efficiency and reduce nitrous oxide emissions from pastures. We demonstrate with our method that these HS grasses not only contain increased amounts of fructans in leaf blades but also accumulate fructans with much higher DP compared to cultivars with normal sugar levels

Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: the LiTEFORM RCT.

BackgroundOral mucositis is a debilitating and painful complication of head and neck cancer irradiation that is characterised by inflammation of the mucous membranes, erythema and ulceration. Oral mucositis affects 6000 head and neck cancer patients per year in England and Wales. Current treatments have not proven to be effective. International studies suggest that low-level laser therapy may be an effective treatment.ObjectivesTo assess the clinical effectiveness and cost-effectiveness of low-level laser therapy in the management of oral mucositis in head and neck cancer irradiation. To identify barriers to and facilitators of implementing low-level laser therapy in routine care.DesignPlacebo-controlled, individually randomised, multicentre Phase III superiority trial, with an internal pilot and health economic and qualitative process evaluations. The participants, outcome assessors and therapists were blinded.SettingNine NHS head and neck cancer sites in England and Wales.ParticipantsA total of 87 out of 380 participants were recruited who were aged ≥ 18 years and were undergoing head and neck cancer irradiation with ≥ 60 Gy.InterventionRandom allocation (1 : 1 ratio) to either low-level laser therapy or sham low-level laser therapy three times per week for the duration of irradiation. The diode laser had the following specifications: wavelength 660 nm, power output 75 mW, beam area 1.5 cm2, irradiance 50 mW/cm2, exposure time 60 seconds and fluence 3 J/cm2. There were 20-30 spots per session. Sham low-level laser therapy was delivered in an identical manner.Main outcome measureThe mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks following the start of irradiation. Higher scores indicate a worse outcome.ResultsA total of 231 patients were screened and, of these, 87 were randomised (low-level laser therapy arm, n = 44; sham arm, n = 43). The mean age was 59.4 years (standard deviation 8.8 years) and 69 participants (79%) were male. The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks was 33.2 (standard deviation 10) in the low-level laser therapy arm and 27.4 (standard deviation 13.8) in the sham arm.LimitationsThe trial lacked statistical power because it did not meet the recruitment target. Staff and patients willingly participated in the trial and worked hard to make the LiTEFORM trial succeed. However, the task of introducing, embedding and sustaining new low-level laser therapy services into a complex care pathway proved challenging. Sites could deliver low-level laser therapy to only a small number of patients at a time. The administration of low-level laser therapy was viewed as straightforward, but also time-consuming and sometimes uncomfortable for both patients and staff, particularly those staff who were not used to working in a patient's mouth.ConclusionsThis trial had a robust design but lacked power to be definitive. Low-level laser therapy is relatively inexpensive. In contrast with previous trials, some patients found low-level laser therapy sessions to be difficult. The duration of low-level laser therapy sessions is, therefore, an important consideration. Clinicians experienced in oral cavity work most readily adapt to delivering low-level laser therapy, although other allied health professionals can be trained. Blinding the clinicians delivering low-level laser therapy is feasible. There are important human resource, real estate and logistical considerations for those setting up low-level laser therapy services.Future workFurther well-designed randomised controlled trials investigating low-level laser therapy in head and neck cancer irradiation are needed, with similar powered recruitment targets but addressing the recruitment challenges and logistical findings from this research.Trial registrationThis trial is registered as ISRCTN14224600.FundingThis project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 46. See the NIHR Journals Library website for further project information

Incorporating economic methods into Cochrane systematic reviews: case studies in brain tumour research.

BACKGROUND: Cochrane systematic reviews have established methods for identifying and critically appraising empirical evidence in health. In addition to evidence regarding the clinical effectiveness of interventions, the resource implications of such interventions can have a huge impact on a decision maker's ability to adopt and implement them. In this paper, we present examples of the three approaches to include economic evidence in Cochrane reviews. METHODS: The Cochrane Handbook presents three different methods of integrating economic evidence into reviews: the Brief Economic Commentary (BEC), the Integrated Full Systematic Review of Economic Evaluations (IFSREE) and using an Economic Decision Model. Using the examples from three different systematic reviews in the field of brain cancer, we utilised each method to address three different research questions. A BEC was utilised in a review that evaluates the long-term side effects of radiotherapy (with or without chemotherapy). An IFSREE was utilised in a review comparing different treatment strategies for newly diagnosed glioblastoma in the elderly. Finally, an economic model was included in a review assessing diagnostic test accuracy for tests of codeletion of chromosomal arms in people with glioma. RESULTS: The BEC mirrored the results of the main review and found a paucity of quality evidence with regard to the side effects of radiotherapy in those with glioma. The IFSREE identified a single economic evaluation regarding glioblastoma in the elderly, but this study had a number of methodological issues. The economic model identified a number of potentially cost-effective strategies for tests for codeletion of chromosomal arms 1p and 19q in people with glioma. CONCLUSIONS: There are strengths and limitations of each approach for integrating economic evidence in Cochrane systematic reviews. The type of research question, resources available and study timeline should be considered when choosing which approach to use when integrating economic evidence