Characteristics of alpha-1 antitrypsin deficiency related lung disease exacerbations using a daily symptom diary and urinary biomarkers.

BACKGROUND: Pulmonary exacerbations in alpha-1 antitrypsin deficiency (AATD) related lung disease are a significant contributor to disease burden, as with usual COPD. Separating the early stages of an exacerbation from the day-to-day variation in stable COPD is central to the concerns of both clinicians and patients and has been identified as a research priority by NIHR. Clinical tools that distinguish baseline symptoms from those of an exacerbation could allow early and appropriate treatment of AECOPD to reduce the impact and potentially may slow disease progression thereby improving survival and quality of life. Candidate tools include symptom diaries and biomarkers of infection and acute inflammation. Urinary biomarkers of AECOPD have yet to be explored in AATD related COPD. METHODS: 55 patients with AATD related lung disease with a history of 2 or more AECOPD in the preceding year were prospectively followed for 18 months. Each patient recorded symptom scores daily via an electronic symptom diary (eDiary) based on Bronkotest. Urinary biomarkers for AAT, NE, CRP, TIMP1 and desmosine were measured weekly using a home urinary lateral flow device. During self-reported AECOPD patients were asked to perform urine analysis on the first 7 consecutive days. RESULTS: Type I Anthonisen exacerbations and episodes occurring in autumn/winter lasted longer than Type II/III exacerbations and spring/summer episodes respectively. Median urinary CRP concentration across all study participants increased during Type I AECOPD. eDiary adherence was 68% over a median of 17.8 months (IQR 15.7 to 18.5). CONCLUSIONS: Use of an eDiary and urinary biomarkers to detect and characterise AECOPD remotely in AATD related lung disease is feasible over a prolonged period and paves the way for precision detection of exacerbations.

Effect of temporal frequency on habituation in migraine.

Individuals with migraine tend to experience discomfort when viewing flickering stimuli. It has been suggested that one of the characteristics of migraine is a lack of habituation to repetitive visual stimuli, although findings can be mixed. Previous work has typically used similar visual stimuli (chequerboard) and only one temporal frequency. This study systematically varied the spatial and temporal characteristics of the visual stimulus, using steady-state visual evoked potentials to assess the differences in amplitude between migraine and control group over consecutive blocks of stimulation. Twenty individuals with migraine and 18 control observers were asked to rate their visual discomfort after viewing sequences of flickering Gabor patches with a frequency of either 3 or 9 Hz across three different spatial frequencies (low 0.5 cpd; mid-range 3 cpd; high 12 cpd). Compared to the control group, the migraine group showed a reduction in SSVEP responses with increased exposure, suggesting habituation processes are intact at 3-Hz stimulation. However, at 9-Hz stimulation, there was evidence of increased responses with increasing exposure in the migraine group in particular, which might suggest a build-up of the response over repetitive presentations. Visual discomfort varied with spatial frequency, for both 3- and 9-Hz stimuli, the highest spatial frequencies were the least uncomfortable compared to the low- and mid-range spatial frequencies in both groups. This difference in SSVEP response behaviour, dependent on temporal frequency, is important to consider when researching the effects of repetitive visual stimulation in migraine and could give some indication of build-up of effects leading to aversion to visual stimuli.

Improvement in visual perception after high-frequency transcranial random noise stimulation (hf-tRNS) in those with migraine: An equivalent noise approach.

Migraine is a common neurological disorder with strong links to vision. Interictal migraine is thought to be characterised by internal noise in the brain, possibly due to increased variability in neural firing, which can be estimated using equivalent noise tasks. High-frequency transcranial random noise stimulation (hf-tRNS) can be used to modulate levels of internal noise in the brain, and so presents a possible therapy to redress noise levels in the migraine brain. This is a case-control study using a 2-alternative forced choice (2AFC) design. Hf-tRNS and Sham control stimulation were used alongside a global motion direction discrimination task and visually based equivalent noise tasks. The migraine group demonstrated increased baseline internal noise levels compared to the control group. Internal noise levels, and sampling, were reduced using hf-tRNS but not Sham stimulation. However, there were no differences in terms of coherence thresholds, slopes, and lapse rate for global motion discrimination between the two groups. This is the first demonstration of the possibility of decreasing internal noise levels in migraine using hf-tRNS. Future work could explore the possibility of neurostimulation as a therapy for migraine.

Improving the Quality of Dentistry (IQuaD): a cluster factorial randomised controlled trial comparing the effectiveness and cost-benefit of oral hygiene advice and/or periodontal instrumentation with routine care for the prevention and management of periodontal disease in dentate adults attending dental primary care.

BACKGROUND: Periodontal disease is preventable but remains the most common oral disease worldwide, with major health and economic implications. Stakeholders lack reliable evidence of the relative clinical effectiveness and cost-effectiveness of different types of oral hygiene advice (OHA) and the optimal frequency of periodontal instrumentation (PI). OBJECTIVES: To test clinical effectiveness and assess the economic value of the following strategies: personalised OHA versus routine OHA, 12-monthly PI (scale and polish) compared with 6-monthly PI, and no PI compared with 6-monthly PI. DESIGN: Multicentre, pragmatic split-plot, randomised open trial with a cluster factorial design and blinded outcome evaluation with 3 years' follow-up and a within-trial cost-benefit analysis. NHS and participant costs were combined with benefits [willingness to pay (WTP)] estimated from a discrete choice experiment (DCE). SETTING: UK dental practices. PARTICIPANTS: Adult dentate NHS patients, regular attenders, with Basic Periodontal Examination (BPE) scores of 0, 1, 2 or 3. INTERVENTION: Practices were randomised to provide routine or personalised OHA. Within each practice, participants were randomised to the following groups: no PI, 12-monthly PI or 6-monthly PI (current practice). MAIN OUTCOME MEASURES: Clinical - gingival inflammation/bleeding on probing at the gingival margin (3 years). Patient - oral hygiene self-efficacy (3 years). Economic - net benefits (mean WTP minus mean costs). RESULTS: A total of 63 dental practices and 1877 participants were recruited. The mean number of teeth and percentage of bleeding sites was 24 and 33%, respectively. Two-thirds of participants had BPE scores of ≤ 2. Under intention-to-treat analysis, there was no evidence of a difference in gingival inflammation/bleeding between the 6-monthly PI group and the no-PI group [difference 0.87%, 95% confidence interval (CI) -1.6% to 3.3%; p = 0.481] or between the 6-monthly PI group and the 12-monthly PI group (difference 0.11%, 95% CI -2.3% to 2.5%; p = 0.929). There was also no evidence of a difference between personalised and routine OHA (difference -2.5%, 95% CI -8.3% to 3.3%; p = 0.393). There was no evidence of a difference in self-efficacy between the 6-monthly PI group and the no-PI group (difference -0.028, 95% CI -0.119 to 0.063; p = 0.543) and no evidence of a clinically important difference between the 6-monthly PI group and the 12-monthly PI group (difference -0.097, 95% CI -0.188 to -0.006; p = 0.037). Compared with standard care, no PI with personalised OHA had the greatest cost savings: NHS perspective -£15 (95% CI -£34 to £4) and participant perspective -£64 (95% CI -£112 to -£16). The DCE shows that the general population value these services greatly. Personalised OHA with 6-monthly PI had the greatest incremental net benefit [£48 (95% CI £22 to £74)]. Sensitivity analyses did not change conclusions. LIMITATIONS: Being a pragmatic trial, we did not deny PIs to the no-PI group; there was clear separation in the mean number of PIs between groups. CONCLUSIONS: There was no additional benefit from scheduling 6-monthly or 12-monthly PIs over not providing this treatment unless desired or recommended, and no difference between OHA delivery for gingival inflammation/bleeding and patient-centred outcomes. However, participants valued, and were willing to pay for, both interventions, with greater financial value placed on PI than on OHA. FUTURE WORK: Assess the clinical effectiveness and cost-effectiveness of providing multifaceted periodontal care packages in primary dental care for those with periodontitis. TRIAL REGISTRATION: Current Controlled Trials ISRCTN56465715. 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. 22, No. 38. See the NIHR Journals Library website for further project information.

Investigating Head Movements Induced by 'Riloid' Patterns in Migraine and Control Groups Using a Virtual Reality Display.

Certain striped patterns can induce illusory motion, such as those used in op-art. The visual system and the vestibular system work together closely, and so it is possible that illusory motion from a visual stimulus can result in uncertainty in the vestibular system. This increased uncertainty may be measureable in terms of the magnitude of head movements. Head movements were measured using a head-mounted visual display. Results showed that stimuli associated with illusory motion also seem to induce greater head movements when compared to similar stimuli. Individuals with migraine are more susceptible to visual discomfort, and this includes illusory motion from striped stimuli. However, there was no evidence of increased effect of illusory motion on those with migraine compared to those without, suggesting that while motion illusions may affect discomfort judgements, this is not limited to only those with migraine.