Cervico-Ocular Reflex in Normal Subjects and Patients with Unilateral Vestibular Hypofunction

Objective: To determine whether the cervico-ocular reflex contributes to gaze stability in patients with unilateral vestibular hypofunction. Study Design: Prospective study. Setting: Tertiary referral center. Patients: Patients with unilateral vestibular hypofunction (n = 3) before and after vestibular rehabilitation and healthy subjects (n = 7). Interventions: Vestibular rehabilitation. Main Outcome Measures: We measured the cervico-ocular reflex in patients with unilateral vestibular hypofunction before and after vestibular rehabilitation and in healthy subjects. To measure the cervico-ocular reflex, we recorded eye movements with a scleral search coil while the trunk moved at 0.3, 1.0, and 1.5 Hz beneath a stabilized head. To determine whether the head was truly stabilized, we measured head movement using a search coil. Results: We found no evidence of cervico-ocular reflex in any of the seven healthy subjects or in two of the patients with unilateral vestibular hypofunction. In one patient with chronic unilateral vestibular hypofunction, the cervico-ocular reflex was present before vestibular rehabilitation only for leftward trunk rotation (relative head rotation toward the intact side). After 5 weeks of placebo exercises, there was no change in the cervico-ocular reflex. After an additional 5 weeks that included vestibular exercises, cervico-ocular reflex gain for leftward trunk rotation had increased threefold. In addition, there was now evidence of a cervico-ocular reflex for rightward trunk rotation, potentially compensating for the vestibular deficit. Conclusion: The cervico-ocular reflex appears to be a highly inconsistent mechanism. The change of the cervico-ocular reflex in one patient after vestibular exercises suggests that the cervico-ocular reflex may be adaptable in some patients

Oculomotor Strategies and Their Effect on Reducing Gaze Position Error

Objective: Vestibular adaptation exercises have been shown to improve gaze stability during active head rotation in individuals with vestibular hypofunction. Little is known, however, of the types of eye movements used during passive head rotation and their effect on gaze stability in individuals with vestibular hypofunction. The primary purpose of this study was to determine differences in oculomotor strategies and their effect on stabilizing gaze during ipsilesional passive and active head rotations in vestibular hypofunction. Patients: Subjects with unilateral (n = 4) and bilateral (n = 3) vestibular hypofunction and healthy subjects (n = 4) based on bithermal caloric and rotational chair testing. Intervention: Diagnostic. Main Outcome Measure: Head and eye velocity and position data measured with scleral search coil. Results: Subjects with unilateral and bilateral vestibular hypofunction generated 3 types of gaze-stabilizing eye movements with ipsilesional head impulses: slow vestibular ocular reflex, compensatory, and corrective saccades. The types of eye movements generated during active and passive head impulses were highly individualized. Gaze position error was reduced when compensatory saccades were recruited as part of the gaze-stabilizing strategy. Conclusion: Rehabilitation for individuals with vestibular hypofunction should identify individuals' unique gaze stability preferences and attempt to facilitate compensatory saccades

Methods and representativeness of a European survey in children and adolescents: the KIDSCREEN study

Background: The objective of the present study was to compare three different sampling and questionnaire administration methods used in the international KIDSCREEN study in terms of participation, response rates, and external validity. Methods: Children and adolescents aged 8-18 years were surveyed in 13 European countries using either telephone sampling and mail administration, random sampling of school listings followed by classroom or mail administration, or multistage random sampling of communities and households with self-administration of the survey materials at home. Cooperation, completion, and response rates were compared across countries and survey methods. Data on non-respondents was collected in 8 countries. The population fraction (PF, respondents in each sex-age, or educational level category, divided by the population in the same category from Eurostat census data) and population fraction ratio (PFR, ratio of PF) and their corresponding 95% confidence intervals were used to analyze differences by country between the KIDSCREEN samples and a reference Eurostat population. Results: Response rates by country ranged from 18.9% to 91.2%. Response rates were highest in the school-based surveys (69.0%-91.2%). Sample proportions by age and gender were similar to the reference Eurostat population in most countries, although boys and adolescents were slightly underrepresented (PFR <1). Parents in lower educational categories were less likely to participate (PFR <1 in 5 countries). Parents in higher educational categories were overrepresented when the school and household sampling strategies were used (PFR = 1.78-2.97). Conclusion: School-based sampling achieved the highest overall response rates but also produced slightly more biased samples than the other methods. The results suggest that the samples were sufficiently representative to provide reference population values for the KIDSCREEN instrument

Critical evaluation of HPV16 gene copy number quantification by SYBR green PCR

Background: Human papilloma virus (HPV) load and physical status are considered useful parameters for clinical evaluation of cervical squamous cell neoplasia. However, the errors implicit in HPV gene quantification by PCR are not well documented. We have undertaken the first rigorous evaluation of the errors that can be expected when using SYBR green qPCR for quantification of HPV type 16 gene copy numbers. We assessed a modified method, in which external calibration curves were generated from a single construct containing HPV16 E2, HPV16 E6 and the host gene hydroxymethylbilane synthase in a 1: 1: 1 ratio.Results: When testing dilutions of mixed HPV/host DNA in replicate runs, we observed errors in quantifying E2 and E6 amplicons of 5 - 40%, with greatest error at the lowest DNA template concentration (3 ng/mu l). Errors in determining viral copy numbers per diploid genome were 13 - 53%. Nevertheless, in cervical keratinocyte cell lines we observed reasonable agreement between viral loads determined by qPCR and Southern blotting. The mean E2/E6 ratio in episome-only cells was 1.04, but with a range of 0.76 - 1.32. In three integrant-only lines the mean E2/E6 ratios were 0.20, 0.72 and 2.61 (values confirmed by gene-specific Southern blotting). When E2/E6 ratios in fourteen HPV16-positive cervical carcinomas were analysed, conclusions regarding viral physical state could only be made in three cases, where the E2/E6 ratio was <= 0.06.Conclusion: Run-to-run variation in SYBR green qPCR produces unavoidable inaccuracies that should be allowed for when quantifying HPV gene copy number. While E6 copy numbers can be considered to provide a useable indication of viral loads, the E2/E6 ratio is of limited value. Previous studies may have overestimated the frequency of mixed episomal/integrant HPV infections

Which multi-attribute utility instruments are recommended for use in cost-utility analysis? A review of national health technology assessment (HTA) guidelines.

Kennedy-Martin M, Slaap B, Herdman M, et al. Which multi-attribute utility instruments are recommended for use in cost-utility analysis? A review of national health technology assessment (HTA) guidelines. The European journal of health economics : HEPAC : health economics in prevention and care. 2020.BACKGROUND: Several multi-attribute utility instruments (MAUIs) are available from which utilities can be derived for use in cost-utility analysis (CUA). This study provides a review of recommendations from national health technology assessment (HTA) agencies regarding the choice of MAUIs.; METHODS: A list was compiled of HTA agencies that provide or refer to published official pharmacoeconomic (PE) guidelines for pricing, reimbursement or market access. The guidelines were reviewed for recommendations on the indirect calculation of utilities and categorized as: a preference for a specific MAUI; providing no MAUI preference, but providing examples of suitable MAUIs and/or recommending the use of national value sets; and recommending CUA, but not providing examples of MAUIs.; RESULTS: Thirty-four PE guidelines were included for review. MAUIs named for use in CUA: EQ-5D (n=29 guidelines), the SF-6D (n=11), HUI (n=10), QWB (n=3), AQoL (n=2), CHU9D (n=1). EQ-5D was a preferred MAUI in 15 guidelines. Alongside the EQ-5D, the HUI was a preferred MAUI in one guideline, with DALY disability weights mentioned in another. Fourteen guidelines expressed no preference for a specific MAUI, but provided examples: EQ-5D (n=14), SF-6D (n=11), HUI (n=9), QWB (n=3), AQoL (n=2), CHU9D (n=1). Of those that did not specify a particular MAUI, 12 preferred calculating utilities using national preference weights.; CONCLUSIONS: The EQ-5D, HUI, and SF-6D were the three MAUIs most frequently mentioned in guidelines. The most commonly cited MAUI (in 85% of PE guidelines) was EQ-5D, either as a preferred MAUI or as an example of a suitable MAUI for use in CUA in HTA

(CNRS URA 2172),

Genotyping of axenic and non-axenic isolates of the genus Prochlorococcus and the OMF-‘Synechococcus ’ clade by size, sequence analysis or RFLP of the Internal Transcribed Spacer of the ribosomal opero

Effect on Health-related Quality of Life of changes in mental health in children and adolescents

<p>Abstract</p> <p>Background</p> <p>The objective of the study was to assess the effect of changes in mental health status on health-related quality of life (HRQOL) in children and adolescents aged 8 - 18 years.</p> <p>Methods</p> <p>A representative sample of Spanish children and adolescents aged 8-18 years completed the self-administered KIDSCREEN-52 questionnaire at baseline and after 3 years. Mental health status was measured using the Strengths and Difficulties Questionnaire (SDQ). Changes on SDQ scores over time were used to classify respondents in one of 3 categories (improved, stable, worsened). Data was also collected on gender, undesirable life events, and family socio-economic status. Changes in HRQOL were evaluated using effect sizes (ES). A multivariate analysis was performed to identify predictors of poor HRQOL at follow-up.</p> <p>Results</p> <p>Response rate at follow-up was 54% (n = 454). HRQOL deteriorated in all groups on most KIDSCREEN dimensions. Respondents who worsened on the SDQ showed the greatest deterioration, particularly on Psychological well-being (ES = -0.81). Factors most strongly associated with a decrease in HRQOL scores were undesirable life events and worsening SDQ score.</p> <p>Conclusions</p> <p>Changes in mental health status affect children and adolescents' HRQOL. Improvements in mental health status protect against poorer HRQOL while a worsening in mental health status is a risk factor for poorer HRQOL.</p

An exploratory, large-scale study of pain and quality of life outcomes in cancer patients with moderate or severe pain, and variables predicting improvement

Background There have been few large-scale, real world studies in Spain to assess change in pain and quality of life (QOL) outcomes in cancer patients with moderate to severe pain. This study aimed to assess changes on both outcomes after 3 months of usual care and to investigate factors associated with change in QoL. Patients and methods Large, multi-centre, observational study in patients with lung, head and neck, colorectal or breast cancer experiencing a first episode of moderate to severe pain while attending one of the participating centres. QoL was assessed using the EuroQol-5D questionnaire and pain using the Brief Pain Inventory (BPI). Instruments were administered at baseline and after 3 months of follow up. Multivariate analyses were used to assess the impact of treatment factors, demographic and clinical variables, pain and other symptoms on QoL scores. Results 1711 patients were included for analysis. After 3 months of usual care, a significant improvement was observed in pain and QoL in all four cancer groups (p<0.001). Effect sizes were medium to large on the BPI and EQ-5D Index and Visual Analogue Scale (VAS). Improvements were seen on the majority of EQ-5D dimensions in all patient groups, though breast cancer patients showed the largest gains. Poorer baseline performance status (ECOG) and the presence of anxiety/depression were associated with significantly poorer QOL outcomes. Improvements in BPI pain scores were associated with improved QoL. Conclusion In the four cancer types studied, pain and QoL outcomes improved considerably after 3 months of usual care. Improvements in pain made a substantial contribution to QoL gains whilst the presence of anxiety and depression and poor baseline performance status significantly constrained improvementFinancial support for this research was provided by Mundipharma Pharmaceuticals S.L

EQ-5D-Y-5L: developing a revised EQ-5D-Y with increased response categories.

Kreimeier S, Astrom M, Burstrom K, et al. EQ-5D-Y-5L: developing a revised EQ-5D-Y with increased response categories. Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation. 2019;28(7):1951-1961.PURPOSE: EQ-5D-Y is a generic measure of health status for children and adolescents aged 8-15 years. Originally, it has three levels of severity in each dimension (3L). This study aimed to develop a descriptive system of EQ-5D-Y with an increased number of severity levels and to test comprehensibility and feasibility. METHODS: The study was conducted in Germany, Spain, Sweden and the UK. In Phase 1, a review of existing instruments and focus group interviews were carried out to create a pool of possible labels for a modified severity classification. Participants aged 8-15 rated the severity of the identified labels in individual sorting and response scaling interviews. In Phase 2, preliminary 4L and 5L versions were constructed for further testing in cognitive interviews with healthy participants aged 8-15 years and children receiving treatment for a health condition. RESULTS: In Phase 1, a total of 233 labels was generated, ranging from 37 (UK) to 79 labels (Germany). Out of these, 7 to 16 possible labels for each dimension in the different languages were rated in 255 sorting and response scaling interviews. Labels covered an appropriate range of severity on the health continuum in all countries. In Phase 2, the 5L version was generally preferred (by 68-88% of the participants per country) over the 4L version. CONCLUSIONS: This multinational study has provided a version of the EQ-5D-Y with 5 severity levels in each dimension. This extended version (EQ-5D-Y-5L) requires testing its psychometric properties and its performance compared to that of the original EQ-5D-Y-3L

Reliability and validity of the Spanish version of the Child Health and Illness Profile (CHIP) Child-Edition, Parent Report Form (CHIP-CE/PRF)

<p>Abstract</p> <p>Background</p> <p>The objectives of the study were to assess the reliability, and the content, construct, and convergent validity of the Spanish version of the CHIP-CE/PRF, to analyze parent-child agreement, and compare the results with those of the original U.S. version.</p> <p>Methods</p> <p>Parents from a representative sample of children aged 6-12 years were selected from 9 primary schools in Barcelona. Test-retest reliability was assessed in a convenience subsample of parents from 2 schools. Parents completed the Spanish version of the CHIP-CE/PRF. The Achenbach Child Behavioural Checklist (CBCL) was administered to a convenience subsample.</p> <p>Results</p> <p>The overall response rate was 67% (n = 871). There was no floor effect. A ceiling effect was found in 4 subdomains. Reliability was acceptable at the domain level (internal consistency = 0.68-0.86; test-retest intraclass correlation coefficients = 0.69-0.85). Younger girls had better scores on Satisfaction and Achievement than older girls. Comfort domain score was lower (worse) in children with a probable mental health problem, with high effect size (ES = 1.45). The level of parent-child agreement was low (0.22-0.37).</p> <p>Conclusions</p> <p>The results of this study suggest that the parent version of the Spanish CHIP-CE has acceptable psychometric properties although further research is needed to check reliability at sub-domain level. The CHIP-CE parent report form provides a comprehensive, psychometrically sound measure of health for Spanish children 6 to 12 years old. It can be a complementary perspective to the self-reported measure or an alternative when the child is unable to complete the questionnaire. In general, the results are similar to the original U.S. version.</p