Economic considerations for moving beyond the Kato-Katz technique for diagnosing intestinal parasites as we move towards elimination

While the need for more sensitive diagnostics for intestinal helminths is well known, the cost of developing and implementing new tests is considered relatively high compared to the Kato-Katz technique. Here, we review the reported costs of performing the Kato-Katz technique. We also outline several economic arguments we believe highlight the need for further investment in alternative diagnostics, and considerations that should be made when comparing their costs. In our opinion, we highlight that, without new diagnostic methods, it will be difficult for policy makers to make the most cost-effective decisions and that the potentially higher unit costs of new methods can be outweighed by the long-term programmatic benefits they have (such as the ability to detect the interruption of transmission)

An investigation into the potential of collaborative computer game-based learning in Higher Education

Advocates of game-based learning argue that computer games have the potential to transform university education, motivating and engaging a new generation of learners in a way that traditional education does not. The research described in this thesis, grounded in the fields of education, human-computer interaction and game design, questions this assumption and considers the case for computer game-based learning in Higher Education. Initial research found that positive motivation for games-based learning is by no means universal in adults, and that a propensity to play games recreationally does not imply an enthusiasm to use games for learning. However, even reluctant gamers were willing to try game-based learning if it was perceived to be an efficient way to learn. Criteria were developed for the design of effective educational games, based around theories of constructivist learning. These informed the development of two collaborative game-based activities with identical learning outcomes: an adventure game and an online version of a traditional teambuilding exercise. Questionnaires were developed to measure self-reported learning and engagement and 112 students participated in an experiment to compare educational effectiveness between two groups, one using the adventure game and the other the teambuilding activity. No significant difference was found between the two conditions, with the exception that those students who used the teambuilding game had a significantly greater perception of control than those who used the adventure game. This study challenges the assumption that games will revolutionise education because they lead to increased motivation and engagement. Instead, it argues that there is a potential for increased engagement through educational games, but this is because they embody the principles of interactive, collaborative and experiential learning. Overall, this research offers an insight of the nature of adult game playing, practical guidance for the development of educational games, a validated tool for measuring post-experiential engagement, a critical analysis of usability testing techniques for multi-user games, and a genuine rationale for the use of game-based learning.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

An investigation into the potential of collaborative computer game-based learning in Higher Education

Advocates of game-based learning argue that computer games have the potential to transform university education, motivating and engaging a new generation of learners in a way that traditional education does not. The research described in this thesis, grounded in the fields of education, human-computer interaction and game design, questions this assumption and considers the case for computer game-based learning in Higher Education.Initial research found that positive motivation for games-based learning is by no means universal in adults, and that a propensity to play games recreationally does not imply an enthusiasm to use games for learning. However, even reluctant gamers were willing to try game-based learning if it was perceived to be an efficient way to learn.Criteria were developed for the design of effective educational games, based around theories of constructivist learning. These informed the development of two collaborative game-based activities with identical learning outcomes: an adventure game and an online version of a traditional teambuilding exercise.Questionnaires were developed to measure self-reported learning and engagement and 112 students participated in an experiment to compare educational effectiveness between two groups, one using the adventure game and the other the teambuilding activity. No significant difference was found between the two conditions, with the exception that those students who used the teambuilding game had a significantly greater perception of control than those who used the adventure game.This study challenges the assumption that games will revolutionise education because they lead to increased motivation and engagement. Instead, it argues that there is a potential for increased engagement through educational games, but this is because they embody the principles of interactive, collaborative and experiential learning.Overall, this research offers an insight of the nature of adult game playing, practical guidance for the development of educational games, a validated tool for measuring post-experiential engagement, a critical analysis of usability testing techniques for multi-user games, and a genuine rationale for the use of game-based learning

Virtual care pathways for people living with HIV:A mixed‐methods systematic review

Background: The COVID-19 pandemic prompted an unprecedented surge in virtual services, necessitating a rapid shift to digital healthcare approaches. This review focuses on evaluating the evidence of virtual care (VC) in delivering HIV care, considering the complex nature of HIV and the need for tailored-approaches, especially for marginalized populations.Methods: A mixed-methods systematic review was performed with searches on five databases, covering studies from January 1946 to May 2022. Inclusion criteria involved two-way virtual consultations between healthcare workers and people living with HIV (PLHIV), with detailed descriptions and outcomes. Qualitative and quantitative studies were included, and the risk of bias was assessed using the Newcastle–Ottawa score and Stenfors' framework.Results: Among 4143 identified records, 26 studies met the criteria, with various models of care described. The majority of studies were observational, and videoconferencing was the primary mode of virtual consultation employed. Quantitative analysis revealed PLHIV generally accept VC, with high attendance rates (87%). Mean acceptability and satisfaction rates were 80% and 85%, respectively, while 87% achieved HIV viral suppression. The setting and models of VC implementation varied, with some introduced in response to COVID-19 while others were as part of trials.Conclusions: VC for PLHIV is deemed an acceptable and effective approach and is associated with good virological outcomes. Data on other health outcomes is lacking. The review underscores the importance of diverse models of care, patient choice and comprehensive training initiatives for both staff and patients. Establishing a ‘gold standard’ for VC models is crucial for ensuring appropriate and effective reviews of PLHIV in virtual settings.</div

Feasibility, double-blind, randomised, placebo-controlled, multi-centre trial of hand-held NB-UVB phototherapy for the treatment of vitiligo at home (HI-Light trial: Home Intervention of Light therapy)

BACKGROUND: Hand-held NB-UVB units are lightweight devices that may overcome the need to treat vitiligo in hospital-based phototherapy cabinets, allowing early treatment at home that may enhance the likelihood of successful repigmentation. The pilot Hi-Light trial examined the feasibility of conducting a large multi-centre randomised controlled trial (RCT) on the use of such devices by exploring recruitment, adherence, acceptability, and patient education. METHODS: This was a feasibility, double-blind, multi-centre, parallel group randomised placebo-controlled trial of hand-held NB-UVB phototherapy for the treatment of vitiligo at home. The overall duration of the trial was seven months; three months recruitment and four months treatment. Participants were randomly allocated to active or placebo groups (2:1 ratio). The primary outcome measure was the proportion of eligible participants who were willing to be randomised. The secondary outcomes included proportion of participants expressing interest in the trial and fulfilling eligibility criteria, withdrawal rates and missing data, proportion of participants adhering to and satisfied with the treatment, and incidence of NB-UVB short-term adverse events. RESULTS: Eighty-three percent (45/54) of vitiligo patients who expressed interest in the trial were willing to be randomised. Due to time and financial constraints, only 29/45 potential participants were booked to attend a baseline hospital visit. All 29 (100%) potential participants were confirmed as being eligible and were subsequently randomised. Willingness to participate in the study for General Practice (family physicians) surgeries and hospitals were 40% and 79%, respectively; 86% (25/29) of patients adhered to the treatment and 65% (7/11) of patients in the active group had some degree of repigmentation. Only one patient in the active group reported erythema grade 3 (3%). Both devices (Dermfix 1000 NB-UVB and Waldmann NB-UVB 109) were acceptable to participants. CONCLUSIONS: Hand-held NB-UVB devices need evaluation in a large, pragmatic RCT. This pilot trial has explored many of the uncertainties that need to be overcome before embarking on a full scale trial, including the development of a comprehensive training package and treatment protocol. The study has shown strong willingness of participants to be randomised, very good treatment adherence and repigmentation rates, and provided evidence of feasibility for a definitive trial. TRIAL REGISTRATION: NCT0147894

Evaluating the variation in the projected benefit of community-wide mass treatment for schistosomiasis: Implications for future economic evaluations

Background The majority of schistosomiasis control programmes focus on targeting school-aged children. Expanding the use of community-wide mass treatment to reach more adults is under consideration. However, it should be noted that this would require a further increase in programmatic resources, international aid, and commitment for the provision of praziquantel. Consequently, it is important to understand i) where a change of strategy would have the greatest benefit, and ii) how generalizable the conclusions of field trials and analytical studies based on mathematical models investigating the impact of community-wide mass treatment, are to a broad range of settings. Method In this paper, we employ a previously described deterministic fully age-structured schistosomiasis transmission model and evaluate the benefit of community-wide mass treatment both in terms of controlling morbidity and eliminating transmission for Schistosoma mansoni, across a wide range of epidemiological settings and programmatic scenarios. This included variation in the baseline relative worm pre-control burden in adults, the overall level of transmission in defined settings, choice of effectiveness metric (basing morbidity calculations on prevalence or intensity), the level of school enrolment and treatment compliance. Results Community-wide mass treatment was found to be more effective for controlling the transmission of schistosome parasites than using a school-based programme only targeting school-aged children. However, in the context of morbidity control, the potential benefit of switching to community-wide mass treatment was highly variable across the different scenarios analysed. In contrast, for areas where the goal is to eliminate transmission, the projected benefit of community-wide mass treatment was more consistent. Conclusion Whether community-wide mass treatment is appropriate will depend on the local epidemiological setting (i.e. the relative pre-control burden in adults, and transmission intensity), and whether the goal is morbidity control or eliminating transmission. This has important implications regarding the generalisability of cost-effectiveness analyses of schistosomiasis interventions. Our results indicate that areas with poor school-enrolment/coverage could benefit more from community-wide treatment of praziquantel and should potentially be prioritised for any change in strategy. This work highlights the importance of not over-generalising conclusions and policy in this area, but of basing decisions on high quality epidemiological data and quantitative analyses of the impact of interventions in a range of settings

Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial

BackgroundWhole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis.MethodsIn this randomised, controlled, phase 3 trial, adult patients (aged 18 years or older) from 48 institutions in the USA and Canada with one resected brain metastasis and a resection cavity less than 5·0 cm in maximal extent were randomly assigned (1:1) to either postoperative SRS (12-20 Gy single fraction with dose determined by surgical cavity volume) or WBRT (30 Gy in ten daily fractions or 37·5 Gy in 15 daily fractions of 2·5 Gy; fractionation schedule predetermined for all patients at treating centre). We randomised patients using a dynamic allocation strategy with stratification factors of age, duration of extracranial disease control, number of brain metastases, histology, maximal resection cavity diameter, and treatment centre. Patients and investigators were not masked to treatment allocation. The co-primary endpoints were cognitive-deterioration-free survival and overall survival, and analyses were done by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT01372774.FindingsBetween Nov 10, 2011, and Nov 16, 2015, 194 patients were enrolled and randomly assigned to SRS (98 patients) or WBRT (96 patients). Median follow-up was 11·1 months (IQR 5·1-18·0). Cognitive-deterioration-free survival was longer in patients assigned to SRS (median 3·7 months [95% CI 3·45-5·06], 93 events) than in patients assigned to WBRT (median 3·0 months [2·86-3·25], 93 events; hazard ratio [HR] 0·47 [95% CI 0·35-0·63]; p&lt;0·0001), and cognitive deterioration at 6 months was less frequent in patients who received SRS than those who received WBRT (28 [52%] of 54 evaluable patients assigned to SRS vs 41 [85%] of 48 evaluable patients assigned to WBRT; difference -33·6% [95% CI -45·3 to -21·8], p&lt;0·00031). Median overall survival was 12·2 months (95% CI 9·7-16·0, 69 deaths) for SRS and 11·6 months (9·9-18·0, 67 deaths) for WBRT (HR 1·07 [95% CI 0·76-1·50]; p=0·70). The most common grade 3 or 4 adverse events reported with a relative frequency greater than 4% were hearing impairment (three [3%] of 93 patients in the SRS group vs eight [9%] of 92 patients in the WBRT group) and cognitive disturbance (three [3%] vs five [5%]). There were no treatment-related deaths.InterpretationDecline in cognitive function was more frequent with WBRT than with SRS and there was no difference in overall survival between the treatment groups. After resection of a brain metastasis, SRS radiosurgery should be considered one of the standards of care as a less toxic alternative to WBRT for this patient population.FundingNational Cancer Institute

Association of Circulating Markers With Cognitive Decline After Radiation Therapy for Brain Metastasis

BACKGROUND: A recent phase III trial (NCT01372774) comparing use of stereotactic radiosurgery [SRS] versus whole-brain radiation therapy [WBRT] after surgical resection of a single brain metastasis revealed that declines in cognitive function were more common with WBRT than with SRS. A secondary endpoint in that trial, and the primary objective in this secondary analysis, was to identify baseline biomarkers associated with cognitive impairment after either form of radiotherapy for brain metastasis. Here we report our findings on APOE genotype and serum levels of associated proteins and their association with radiation-induced neurocognitive decline. METHODS: In this retrospective analysis of prospectively collected samples from a completed randomized clinical trial, patients provided blood samples every 3 months that were tested by genotyping and enzyme-linked immunosorbent assay, and results were analyzed in association with cognitive impairment. RESULTS: The APOE genotype was not associated with neurocognitive impairment at 3 months. However, low serum levels of ApoJ, ApoE, or ApoA protein (all P \u3c .01) and higher amyloid beta (Aβ 1-42) levels (P = .048) at baseline indicated a greater likelihood of neurocognitive decline at 3 months after SRS, whereas lower ApoJ levels were associated with decline after WBRT (P = .014). CONCLUSIONS: Patients with these pretreatment serum markers should be counseled about radiation-related neurocognitive decline

Home-based narrowband UVB, topical corticosteroid or combination for children and adults with vitiligo: HI-Light Vitiligo three-arm RCT

BACKGROUND: Systematic reviews suggest that narrowband ultraviolet B light combined with treatments such as topical corticosteroids may be more effective than monotherapy for vitiligo. OBJECTIVE: To explore the clinical effectiveness and cost-effectiveness of topical corticosteroid monotherapy compared with (1) hand-held narrowband ultraviolet B light monotherapy and (2) hand-held narrowband ultraviolet B light/topical corticosteroid combination treatment for localised vitiligo. DESIGN: Pragmatic, three-arm, randomised controlled trial with 9 months of treatment and a 12-month follow-up. SETTING: Sixteen UK hospitals - participants were recruited from primary and secondary care and the community. PARTICIPANTS: Adults and children (aged ≥ 5 years) with active non-segmental vitiligo affecting ≤ 10% of their body area. INTERVENTIONS: Topical corticosteroids [mometasone furoate 0.1% (Elocon®, Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA) plus dummy narrowband ultraviolet B light]; narrowband ultraviolet B light (narrowband ultraviolet B light plus placebo topical corticosteroids); or combination (topical corticosteroids plus narrowband ultraviolet B light). Topical corticosteroids were applied once daily on alternate weeks and narrowband ultraviolet B light was administered every other day in escalating doses, with a dose adjustment for erythema. All treatments were home based. MAIN OUTCOME MEASURES: The primary outcome was self-assessed treatment success for a chosen target patch after 9 months of treatment ('a lot less noticeable' or 'no longer noticeable' on the Vitiligo Noticeability Scale). Secondary outcomes included blinded assessment of primary outcome and percentage repigmentation, onset and maintenance of treatment response, quality of life, side effects, treatment burden and cost-effectiveness (cost per additional successful treatment). RESULTS: In total, 517 participants were randomised (adults, n = 398; and children, n =  119; 52% male; 57% paler skin types I-III, 43% darker skin types IV-VI). At the end of 9 months of treatment, 370 (72%) participants provided primary outcome data. The median percentage of narrowband ultraviolet B light treatment-days (actual/allocated) was 81% for topical corticosteroids, 77% for narrowband ultraviolet B light and 74% for combination groups; and for ointment was 79% for topical corticosteroids, 83% for narrowband ultraviolet B light and 77% for combination. Target patch location was head and neck (31%), hands and feet (32%), and rest of the body (37%). Target patch treatment 'success' was 20 out of 119 (17%) for topical corticosteroids, 27 out of 123 (22%) for narrowband ultraviolet B light and 34 out of 128 (27%) for combination. Combination treatment was superior to topical corticosteroids (adjusted risk difference 10.9%, 95% confidence interval 1.0% to 20.9%; p = 0.032; number needed to treat = 10). Narrowband ultraviolet B light was not superior to topical corticosteroids (adjusted risk difference 5.2%, 95% confidence interval -4.4% to 14.9%; p = 0.290; number needed to treat = 19). The secondary outcomes supported the primary analysis. Quality of life did not differ between the groups. Participants who adhered to the interventions for > 75% of the expected treatment protocol were more likely to achieve treatment success. Over 40% of participants had lost treatment response after 1 year with no treatment. Grade 3 or 4 erythema was experienced by 62 participants (12%) (three of whom were using the dummy) and transient skin thinning by 13 participants (2.5%) (two of whom were using the placebo). We observed no serious adverse treatment effects. For combination treatment compared with topical corticosteroids, the unadjusted incremental cost-effectiveness ratio was £2328.56 (adjusted £1932) per additional successful treatment (from an NHS perspective). LIMITATIONS: Relatively high loss to follow-up limits the interpretation of the trial findings, especially during the post-intervention follow-up phase. CONCLUSION: Hand-held narrowband ultraviolet B light plus topical corticosteroid combination treatment is superior to topical corticosteroids alone for treatment of localised vitiligo. Combination treatment was relatively safe and well tolerated, but was effective in around one-quarter of participants only. Whether or not combination treatment is cost-effective depends on how much decision-makers are willing to pay for the benefits observed. FUTURE WORK: Development and testing of new vitiligo treatments with a greater treatment response and longer-lasting effects are needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN17160087. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 64. See the NIHR Journals Library website for further project information