A patient-centred and multi-stakeholder co-designed observational prospective study protocol: Example of the adolescent experience of treatment for X-linked hypophosphataemia (XLH).

The importance of patient centricity and keeping the patient at the heart of research design is now well recognised within the healthcare community. The involvement of patient, caregiver and clinician representatives in the study design process may help researchers to achieve this goal and to ensure robust and meaningful data generation. Real-world data collection allows for a more flexible and patient-centred research approach for gaining important insights into the experience of disease and treatments, which is acutely relevant for rare diseases where knowledge about the disease is more likely to be limited. Here, we describe a practical example of a patient-centric, multi-stakeholder approach that led to the co-design of a prospective observational study investigating the lived experience of adolescents with the rare disease, X-linked hypophosphataemia. Specifically, we describe how the knowledge and expertise of a diverse research team, which included expert physicians, research and technology specialists, patients and caregivers, were applied in order to identify the relevant research questions and to ensure the robustness of the study design and its appropriateness to the population of interest within the context of the current clinical landscape. We also demonstrate how a structured patient engagement exercise was key to informing the selection of appropriate outcome measures, data sources, timing of data collection, and to assessing the feasibility and acceptability of the proposed data collection approach.

Real-world tyrosine kinase inhibitor treatment pathways, monitoring patterns and responses in patients with chronic myeloid leukaemia in the United Kingdom: the UK TARGET CML study.

Management of chronic myeloid leukaemia (CML) has recently undergone dramatic changes, prompting the European LeukemiaNet (ELN) to issue recommendations in 2013; however, it remains unclear whether real-world CML management is consistent with these goals. We report results of UK TARGET CML, a retrospective observational study of 257 patients with chronic-phase CML who had been prescribed a first-line TKI between 2013 and 2017, most of whom received first-line imatinib (n = 203). Although 44% of patients required ≥1 change of TKI, these real-world data revealed that molecular assessments were frequently missed, 23% of patients with ELN-defined treatment failure did not switch TKI, and kinase domain mutation analysis was performed in only 49% of patients who switched TKI for resistance. Major molecular response (MMR; BCR-ABL1IS ≤0·1%) and deep molecular response (DMR; BCR-ABL1IS ≤0·01%) were observed in 50% and 29%, respectively, of patients treated with first-line imatinib, and 63% and 54%, respectively, receiving a second-generation TKI first line. MMR and DMR were also observed in 77% and 44% of evaluable patients with ≥13 months follow-up, receiving a second-generation TKI second line. We found little evidence that cardiovascular risk factors were considered during TKI management. These findings highlight key areas for improvement in providing optimal care to patients with CML.

Evidence-based policy making for health promotion to reduce the burden of non-communicable diseases in Moldova.

The Republic of Moldova faces several concurrent health challenges most notably an increase in chronic non-communicable diseases, spiralling health care costs and widening health inequalities. To accelerate progress in their resolution there is a need for new and innovative health promotion and behaviour change communication interventions. The Ministry of Health, Labour and Social Protection in collaboration with the newly created National Agency for Public Health held a conference on the occasion of the Moldovan National Day of Health Promotion on 14th March 2018 in which national and invited international experts exchanged their views on (1) best practice examples of behaviour change interventions, health promotion activities and lessons learned from the UK and elsewhere; and (2) possible ways forward for Moldova to implement cost-effective and evidence-based intersectoral health promotion programmes. The experts provided recommendations on implementing behaviour change interventions to reduce and prevent obesity; on the creation of a favourable tobacco control environment to reduce smoking prevalence; and on how physical activity programme design can benefit from health psychology research. All these strategies could foster health promotion activities and ultimately contribute to improving the health outcomes of the Moldovan population.

A retrospective observational study of early experiences of vedolizumab treatment for inflammatory bowel disease in the UK: The REVIVE study.

Results from clinical trials show that vedolizumab is an efficacious treatment for inflammatory bowel disease, namely Crohn's disease (CD) and ulcerative colitis (UC). However, there is limited evidence from real-world clinical practice, especially on early clinical experiences in the UK.To describe real-world early experiences of vedolizumab to treat CD and UC in the UK.A retrospective, chart review study of patients with CD or UC treated with vedolizumab across 5 UK hospitals. All eligible adults (≥18 years at initiation) with a diagnosis of CD and ≥14 weeks of data or UC and ≥10 weeks of data available following vedolizumab initiation were included.Data were analyzed for 112 patients (CD: 66; UC: 46). Patients with CD had a median of 7.4 (interquartile range 5.7-9.4) months follow-up and patients with UC had a median of 7.4 (5.6-10.2) months follow-up post-vedolizumab initiation. Most patients, 80% (53/66) with CD and 89% (41/46) with UC, remained on vedolizumab treatment at the time of data collection. No new safety signals were identified during the study.These results add to the body of evidence supporting vedolizumab as an effective and well-tolerated treatment for CD and UC in real-world clinical practice.

Opportunities for antimicrobial stewardship in patients with acute bacterial skin and skin structure infections who are unsuitable for beta-lactam antibiotics: a multicenter prospective observational study.

PURPOSE: The objective of this prospective, observational study was to describe the treatment, severity assessment and healthcare resources required for management of patients with acute bacterial skin and skin structure infections who were unsuitable for beta-lactam antibiotic treatments. METHODS: Patients were enrolled across five secondary care National Health Service hospitals. Eligible patients had a diagnosis of acute bacterial skin and skin structure infection and were considered unsuitable for beta-lactam antibiotics (e.g. confirmed/suspected methicillin-resistant Staphylococcus aureus, beta-lactam allergy). Data regarding diagnosis, severity of the infection, antibiotic treatment and patient management were collected. RESULTS: 145 patients with acute bacterial skin and skin structure infection were included; 79% (n = 115) patients received greater than two antibiotic regimens; median length of the first antibiotic regimen was 2 days (interquartile range of 1-5); median time to switch from intravenous to oral antibiotics was 4 days (interquartile range of 3-8, n = 72/107); 25% (n = 10/40) patients with Eron class 1 infection had systemic inflammatory response syndrome, suggesting they were misclassified. A higher proportion of patients with systemic inflammatory response syndrome received treatment in an inpatient setting, and their length of stay was prolonged in comparison with patients without systemic inflammatory response syndrome. CONCLUSION: There exists an urgent need for more focused antimicrobial stewardship strategies and tools for standardised clinical assessment of acute bacterial skin and skin structure infection severity in patients who are unsuitable for beta-lactam antibiotics. This will lead to optimised antimicrobial treatment strategies and ensure effective healthcare resource utilisation.

Self-Monitoring Symptoms in Glaucoma: A Feasibility Study of a Web-Based Diary Tool.

Purpose. Glaucoma patients annually spend only a few hours in an eye clinic but spend more than 5000 waking hours engaged in everything else. We propose that patients could self-monitor changes in visual symptoms providing valuable between clinic information; we test the hypothesis that this is feasible using a web-based diary tool. Methods. Ten glaucoma patients with a range of visual field loss took part in an eight-week pilot study. After completing a series of baseline tests, volunteers were prompted to monitor symptoms every three days and complete a diary about their vision during daily life using a bespoke web-based diary tool. Response to an end of a study questionnaire about the usefulness of the exercise was a main outcome measure. Results. Eight of the 10 patients rated the monitoring scheme to be "valuable" or "very valuable." Completion rate to items was excellent (96%). Themes from a qualitative synthesis of the diary entries related to behavioural aspects of glaucoma. One patient concluded that a constant focus on monitoring symptoms led to negative feelings. Conclusions. A web-based diary tool for monitoring self-reported glaucoma symptoms is practically feasible. The tool must be carefully designed to ensure participants are benefitting, and it is not increasing anxiety.

'I didn't see that coming': simulated visual fields and driving hazard perception test performance.

BACKGROUND: Evidence is limited regarding specific types of visual field loss associated with unsafe driving. We use novel gaze-contingent software to examine the effect of simulated visual field loss on computer-based driving hazard detection with the specific aim of testing the impact of scotomata located to the right and left of fixation. METHODS: The 'hazard perception test' is a component of the UK driving licence examination, which measures speed of detecting 15 different hazards in a series of real-life driving films. We have developed a novel eye-tracking and computer set up capable of generating a realistic gaze-contingent scotoma simulation (GazeSS) overlaid on film content. Thirty drivers with healthy vision completed three versions of the hazard perception test in a repeated measures experiment. In two versions, GazeSS simulated a scotoma in the binocular field of view to the left or right of fixation. A third version was unmodified to establish baseline performance. RESULTS: Participants' mean baseline hazard perception test score was 51 ± 7 (out of 75). This reduced to 46 ± 9 and 46 ± 11 when completing the task with a binocular visual field defect located to the left and right of fixation, respectively. While the main effect of simulated visual field loss on performance was statistically significant (p = 0.007), there were no average differences in the experimental conditions where a scotoma was located in the binocular visual field to the right or left of fixation. CONCLUSION: Simulated visual field loss impairs driving hazard detection on a computer-based test. There was no statistically significant difference in average performance when the simulated scotoma was located to the right or left of fixation of the binocular visual field, but certain types of hazard caused more difficulties than others.

Living with glaucoma: a qualitative study of functional implications and patients' coping behaviours.

BACKGROUND: Sight loss from glaucoma can have a significant impact on functioning and performing everyday activities, but this varies between patients. The purpose of this study was to explore whether patients with glaucoma use different coping strategies in response to their vision loss. METHODS: Audio-recorded semi-structured interviews were conducted with 16 patients (median age: 71 [interquartile range [IQR]: 68 to 77 years]; 50 % female) about their experiences of living with glaucoma. Patients had their glaucoma diagnosis for at least 5 years (range: 6 to 29 years) and had a range of disease severities (median best eye Mean Deviation was -9.1 dB [IQR: -12.9 to -4.1 dB]). A framework approach to analysis was taken whereby data was indexed using manual and computer-assisted methods, with codes applied to depict areas of functioning perceived to be impacted by glaucoma and coping behaviours used in response to these difficulties. RESULTS: In order to maintain independence, some patients increased confidence by making practical changes such as adjusting lighting, using handrails and magnifying glasses, or actively changed aspects of their behaviour such as moving their head and eyes towards known areas of vision loss. Support from friends and family was often used, although some people worried about becoming a burden. Others imposed self-restrictions or gave up activities, thus compromising well-being and independence. Certain coping strategies were linked to time since diagnosis and location of vision loss. The type and quality of information received during clinical appointments, and the potential benefits of communication with other patients, emerged as other important themes. CONCLUSIONS: Results from this qualitative study suggest that the adoption of certain coping behaviours and techniques may help some glaucomatous patients to adapt to their condition. An awareness of coping and adaptive strategies, in addition to the usual clinical tests, may provide a better insight into the impact of disease and help inform future educational and management strategies for glaucoma.

Impact of superior and inferior visual field loss on hazard detection in a computer-based driving test.

PURPOSE: Binocular visual field (VF) loss is linked to driving impairment, guiding authorities to implement fitness to drive requirements for VFs. Yet, evidence is limited regarding the specific types of VF defect that impede driving. This study used a novel gaze-contingent display to test the hypothesis that superior VF loss impacts detection of driving hazards more than inferior loss. METHODS: The Hazard Perception Test (HPT) is a computer-based component of the UK examination for learner drivers. It measures the response rate for detecting hazards in a series of real-life driving films, yielding a score out of 75, calculated based on the efficiency of detecting 15 hazards. Thirty UK drivers with healthy vision completed three versions of the HPT in a random order. In two versions, a computer set-up incorporating an eye-tracker modified a simulated VF defect in the superior and inferior VFs, respectively, according to the users' real-time gaze as they completed the HPT. The other version was unmodified to measure the baseline performance. RESULTS: Participants' mean score at baseline was 49/75 (SD=9). Mean (SD) performance fell by 18% (40(11)) when viewing films with a superior defect and 12% with an inferior defect (43(10)). These average differences were statistically significant (p<0.001; 95% CI for mean difference=1-7) CONCLUSIONS: In this study, simulated VF defects impaired the ability to detect driving hazards relative to participants' normal performances, with superior defects having more impact than inferior defects. These results could help inform the design of fairer tests of the VF component for fitness to drive.

Using eye tracking to assess reading performance in patients with glaucoma: a within-person study.

Reading is often cited as a demanding task for patients with glaucomatous visual field (VF) loss, yet reading speed varies widely between patients and does not appear to be predicted by standard visual function measures. This within-person study aimed to investigate reading duration and eye movements when reading short passages of text in a patient's worse eye (most VF damage) when compared to their better eye (least VF damage). Reading duration and saccade rate were significantly different on average in the worse eye when compared to the better eye (P < 0.001) in 14 patients with glaucoma that had median (interquartile range) between-eye difference in mean deviation (MD; a standard clinical measure for VF loss) of 9.8 (8.3 to 14.8) dB; differences were not related to the size of the difference in MD between eyes. Patients with a more pronounced effect of longer reading duration on their worse eye made a larger proportion of "regressions" (backward saccades) and "unknown" EMs (not adhering to expected reading patterns) when reading with the worse eye when compared to the better eye. A between-eye study in patients with asymmetric disease, coupled with eye tracking, provides a useful experimental design for exploring reading performance in glaucoma.

A qualitative investigation into patients' views on visual field testing for glaucoma monitoring.

OBJECTIVES: To investigate the views and experiences of patients regarding their glaucoma follow-up, particularly towards the type and frequency of visual field (VF) testing. DESIGN: A qualitative investigation using focus groups. The group discussion used broad open questions around the topics in a prompt guide relating to experiences of glaucoma follow-up, and in particular, VF monitoring. All the groups were taped, transcribed and coded using manual and computer-aided methods. SETTING: Three National Health Service (NHS) hospitals in England; two focus groups took place at each hospital. PARTICIPANTS: 28 patients (mean (SD) age: 74 (9) years; 54% women) diagnosed with glaucoma for at least 2 years. Each focus group consisted of 3-6 patients. PRIMARY AND SECONDARY OUTCOMES: (1) Attitudes and experiences of patients with glaucoma regarding VF testing. (2) Patients' opinions about successful follow-up in glaucoma. RESULTS: These patients did not enjoy the VF test but they recognised the importance of regular monitoring for preserving their vision. These patients would agree to more frequent VF testing on their clinician's recommendation. A number of themes recurred throughout the focus groups representing perceived barriers to follow-up care. The testing environment, waiting times, efficiency of appointment booking and travel to the clinic were all perceived to influence the general clinical experience and the quality of assessment data. Patients were also concerned about aspects of patient-doctor communication, and often received little to no feedback about their results. CONCLUSIONS: Patients trust the clinician to make the best decisions for their glaucoma follow-up. However, patients highlighted a number of issues that could compromise the effectiveness of VF testing. Addressing patient-perceived barriers could be an important step for devising optimal strategies for follow-up care.

Saccadic eye movements and face recognition performance in patients with central glaucomatous visual field defects.

Patients with more advanced glaucoma are likely to experience problems with everyday visual tasks such as face recognition. However, some patients still perform well at face recognition despite their visual field (VF) defects. This study investigated whether certain eye movement patterns are associated with better performance in the Cambridge Face Memory Test. For patients with bilateral VF defects in their central 10° of VF, making larger saccades appeared to be associated with better face recognition performance (rho=0.60, p=0.001). Associations were less apparent for the patients without significant 10° defects. There were no significant associations between saccade amplitude and task performance in people with healthy vision (rho=-0.24; p=0.13). These findings suggest that some patients with likely symptomatic glaucomatous damage manifest eye movements to adapt to VF loss during certain visual activities.

How does glaucoma look?: patient perception of visual field loss.

OBJECTIVE: To explore patient perception of vision loss in glaucoma and, specifically, to test the hypothesis that patients do not recognize their impairment as a black tunnel effect or as black patches in their field of view. DESIGN: Clinic-based cross-sectional study. PARTICIPANTS: Fifty patients (age range, 52-82 years) with visual acuity better than 20/30 and with a range of glaucomatous visual field (VF) defects in both eyes, excluding those with very advanced disease (perimetrically blind). METHODS: Participants underwent monocular VF testing in both eyes using a Humphrey Field Analyzer (HFA; Carl Zeiss Meditec, Dublin, CA; 24-2 Swedish interactive threshold algorithm standard tests) and other tests of visual function. Participants took part in a recorded interview during which they were asked if they were aware of their VF loss; if so, there were encouraged to describe it in their own words. Participants were shown 6 images modified in a variety of ways on a computer monitor and were asked to select the image that most closely represented their perception of their VF loss. MAIN OUTCOME MEASURES: Forced choice of an image best representing glaucomatous vision impairment. RESULTS: Participants had a range of VF defect severity: average HFA mean deviation was -8.7 dB (standard deviation [SD], 5.8 dB) and -10.5 dB (SD, 7.1 dB) in the right and left eyes, respectively. Thirteen patients (26%; 95% confidence interval [CI], 15%-40%) reported being completely unaware of their vision loss. None of the patients chose the images with a distinct black tunnel effect or black patches. Only 2 patients (4%; 95% CI, 0%-14%) chose the image with a tunnel effect with blurred edges. An image depicting blurred patches and another with missing patches was chosen by 54% (95% CI, 39%-68%) and 16% (95% CI, 7%-29%) of the patients, respectively. Content analysis of the transcripts from the recorded interviews indicated a frequent use of descriptors of visual symptoms associated with reported blur and missing features. CONCLUSIONS: Patients with glaucoma do not perceive their vision loss as a black tunnel effect or as black patches masking their field of view. These findings are important in the context of depicting the effects of glaucomatous vision loss and raising awareness for glaucoma detection. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Eye movements in patients with glaucoma when viewing images of everyday scenes.

This study tests the hypothesis that patients with bilateral glaucoma exhibit different eye movements compared to normally-sighted people when viewing computer displayed photographs of everyday scenes. Thirty glaucomatous patients and 30 age-related controls with normal vision viewed images on a computer monitor whilst eye movements were simultaneously recorded using an eye tracking system. The patients demonstrated a significant reduction in the average number of saccades compared to controls (P = 0.02; mean reduction of 7% (95% confidence interval (CI): 3-11%)). There was no difference in average saccade amplitude between groups but there was between-person variability in patients. The average elliptical region scanned by the patients by a bivariate contour ellipse area (BCEA) analysis, was more restricted compared to controls (P = 0.004; mean reduction of 23% (95% (CI): 11-35%)). A novel analysis mapping areas of interest in the images indicated a weak association between severity of functional deficit and a tendency to not view regions typically viewed by the controls. In conclusion, some eye movements in some patients with bilateral glaucomatous defects differ from normal-sighted people of a similar age when viewing images of everyday scenes, providing evidence for a potential new window for looking into the functional consequences of the disease.

Eye movements during visual search in patients with glaucoma.

BACKGROUND: Glaucoma has been shown to lead to disability in many daily tasks including visual search. This study aims to determine whether the saccadic eye movements of people with glaucoma differ from those of people with normal vision, and to investigate the association between eye movements and impaired visual search. METHODS: Forty patients (mean age: 67 [SD: 9] years) with a range of glaucomatous visual field (VF) defects in both eyes (mean best eye mean deviation [MD]: -5.9 (SD: 5.4) dB) and 40 age-related people with normal vision (mean age: 66 [SD: 10] years) were timed as they searched for a series of target objects in computer displayed photographs of real world scenes. Eye movements were simultaneously recorded using an eye tracker. Average number of saccades per second, average saccade amplitude and average search duration across trials were recorded. These response variables were compared with measurements of VF and contrast sensitivity. RESULTS: The average rate of saccades made by the patient group was significantly smaller than the number made by controls during the visual search task (P = 0.02; mean reduction of 5.6% (95% CI: 0.1 to 10.4%). There was no difference in average saccade amplitude between the patients and the controls (P = 0.09). Average number of saccades was weakly correlated with aspects of visual function, with patients with worse contrast sensitivity (PR logCS; Spearman's rho: 0.42; P = 0.006) and more severe VF defects (best eye MD; Spearman's rho: 0.34; P = 0.037) tending to make less eye movements during the task. Average detection time in the search task was associated with the average rate of saccades in the patient group (Spearman's rho = -0.65; P < 0.001) but this was not apparent in the controls. CONCLUSIONS: The average rate of saccades made during visual search by this group of patients was fewer than those made by people with normal vision of a similar average age. There was wide variability in saccade rate in the patients but there was an association between an increase in this measure and better performance in the search task. Assessment of eye movements in individuals with glaucoma might provide insight into the functional deficits of the disease.

Glaucoma and reading: exploring the effects of contrast lowering of text.

PURPOSE: Past research has not fully ascertained the extent to which people with glaucoma have difficulties with reading. This study measures change in reading speed when letter contrast is reduced, to test the hypothesis that patients with glaucoma are more sensitive to letter contrast than age-similar visually healthy people. METHODS: Fifty-three patients with glaucoma [mean age: 66 years (standard deviation: 9)] with bilateral visual field (VF) defects and 40 age-similar visually healthy control subjects [mean age: 69 (standard deviation: 8) years] had reading speeds measured using sets of fixed size, non-scrolling texts on a computer setup that incorporated an eye tracking device. All participants had visual acuity ≥6/9, and they underwent standard tests of visual function including Humphrey 24-2 and 10-2 VFs. Potential non-visual confounders were also tested, including cognitive ability (Middlesex Elderly Assessment of Mental Status Test) and general reading ability. Individual average raw reading speeds were calculated from 8 trials (different passages of text) at both 100% and 20% letter contrast. RESULTS: Patients had an average 24-2 VF MD of -6.5 (range: 0.7 to -17.3) dB in the better eye. The overall median reduction in reading speed due to decreasing the contrast of the text in the patients was 20%, but with considerable between-individual variation (interquartile range, 8%-44%). This reduction was significantly greater (p = 0.01) than the controls [median: 11% (interquartile range, 6%-17%)]. Patients and controls had similar average performance on Middlesex Elderly Assessment of Mental Status Test (p = 0.71), a modified Burt Reading ability test (p = 0.33), and a computer-based lexical decision task (p = 0.53) and had similar self-reported day-to-day reading frequency (p = 0.12). CONCLUSIONS: Average reduction in reading speed caused by a difference in letter contrast between 100% and 20% is significantly more apparent in patients with glaucoma when compared with visually healthy people with a similar age and similar cognitive/reading ability.

Do patients with glaucoma have difficulty recognizing faces?

PURPOSE: To compare face recognition performance of glaucomatous patients with age-similar visually healthy people. METHODS: Percentage of correctly identified faces in the Cambridge Face Memory Test was assessed in glaucomatous patients (n = 54; mean age = 69) with a range of visual field (VF) defects and visually healthy controls (n = 41; mean age = 67). All participants underwent cognitive and visual assessment (binocular visual acuity [BVA], contrast sensitivity [CS], and Humphrey VFs, both 10-2 and 24-2) and had BVA of at least 0.18 logMAR. Patients were classified as having "early," "moderate," or "advanced" VF defects using the Hodapp, Parrish and Anderson Method: Patients were also stratified by better-eye 10-2 mean deviation (MD) being better or worse than the 1% normative value. RESULTS: There were no significant differences in age (P = 0.25) or cognitive ability (P = 0.31) between groups; however, differences in BVA and CS were statistically significant (P < 0.05). Patients with advanced VF defects identified fewer faces on average (±SD) (66% ± 15%) than those with early (75% ± 11%) and moderate (75% ± 13%) defects and controls (75% ± 11%); P < 0.05. Patients with a best-eye 10-2 MD P < 1% identified fewer faces (67% ± 13%) than those with 10-2 MD P > 1% (77% ± 11%) and controls P < 0.01 (75% ± 11%). Multiple regression analysis revealed CS was important for face recognition. CONCLUSIONS: When compared with age-similar people with healthy vision, glaucomatous patients with advanced bilateral 24-2 VF loss, significant 10-2 VF loss, or poor CS are more likely to experience problems with face recognition.