Effects of dietary nitrate on the O2 cost of submaximal exercise: Accounting for "noise" in pulmonary gas exchange measurements.

Dietary nitrate (NO3-) supplementation can reduce the oxygen cost of submaximal exercise, but this has not been reported consistently. We hypothesised that the number of step transitions to moderate-intensity exercise, and corresponding effects on the signal-to-noise ratio for pulmonary V˙ O2, may be important in this regard. Twelve recreationally active participants were assigned in a randomised, double-blind, crossover design to supplement for 4 days in three conditions: 1) control (CON; water); 2); PL (NO3--depleted beetroot juice); and 3) BR (NO3--rich beetroot juice). On days 3 and 4, participants completed two 6-min step transitions to moderate-intensity cycle exercise. Breath-by-breath V˙ O2 data were collected and V˙ O2 kinetic responses were determined for a single transition and when the responses to 2, 3 and 4 transitions were ensemble-averaged. Steady-state V˙ O2 was not different between PL and BR when the V˙ O2 response to one-, two- or three-step transition was compared but was significantly lower in BR compared to PL when four-step transitions was considered (PL: 1.33 ± 0.34 vs. BR: 1.31 ± 0.34 L·min-1, P < 0.05). There were no differences in pulmonary V˙ O2 responses between CON and PL (P > 0.05). Multiple step transitions may be required to detect the influence of NO3- supplementation on steady-state V˙ O2.

Assessing the Content Validity of the EQ-5D Questionnaire Among Asians in Singapore: A Qualitative Study.

INTRODUCTION: Although the EQ-5D questionnaire is widely used to measure health status internationally, there is little evidence of its content validity in Asian populations. This qualitative study aimed to explore the content validity of the EQ-5D in Singapore. MATERIALS AND METHODS: Sixty Singaporeans (Chinese: 20; Malay: 20; Indian: 20) completed semi-structured interviews in which they were asked about health concepts which were important to them and the relevance and comprehensiveness of the EQ-5D descriptive system (DS). Thematic analysis employing open, focused and axial coding was used to identify the themes and subthemes from the interviews. RESULTS: A total of 70 health concepts were identified which fall into the broad categories of 'physical health', 'mental well-being', 'social relationships', 'medical conditions and treatment', and 'health promotion knowledge and behaviours'. The 5 dimensions in the EQ-5D DS were among the health concepts nominated by participants. Some participants suggested that content validity could be improved by adding social relationships, medical conditions and treatment, and health promotion knowledge and behaviours to the EQ-5D DS. CONCLUSIONS: This study confirmed that EQ-5D dimensions are important and relevant aspects of health to Asians in Singapore, although some dimensions that could be important to Singaporeans are absent.

A vision 'bolt-on' increases the responsiveness of EQ-5D: preliminary evidence from a study of cataract surgery.

OBJECTIVES: (1) To evaluate the effect of adding a vision dimension ('bolt-on') to the 5-level EQ-5D (EQ-5D-5L) and 3-level EQ-5D (EQ-5D-3L) on their responsiveness, and (2) to compare the responsiveness of a vision 'bolt-on' EQ-5D-3L (EQ-5D-3L + V) with SF-6D and Health Utilities Index Mark 3 (HUI3) to the benefit of cataract surgery. METHODS: Sixty-three patients were assessed before and after their cataract surgery using the EQ-5D-3L, EQ-5D-5L, SF-6D, HUI3, as well as a 3-level and a 5-level vision dimension. Preference-based indices were calculated using available value sets for EQ-5D-3L, EQ-5D-3L + V, EQ-5D-5L, SF-6D, and HUI3, and non-preference-based indices were calculated using the sum-score method for EQ-5D-5L and EQ-5D-5L + V (vision bolt-on EQ-5D-5L). Responsiveness was assessed using the standardized response mean (SRM) and F-statistic. RESULTS: Among preference-based indices, mean changes from pre to post-surgery in EQ-5D-3L + V and EQ-5D-3L indices were 0.031 and 0.018, respectively. The mean changes for EQ-5D-5L, SF-6D and HUI3 indices were 0.020, 0.012 and 0.105, respectively. The SRM (F-statistic) for EQ-5D-3L + V and EQ-5D-3L indices were 0.458 (13.2) and 0.098 (0.6), respectively. The responsiveness of EQ-5D-3L + V was better than EQ-5D-5L, SF-6D; the responsiveness of HUI3 was better than all other measures. Using non-preference-based indices, mean change for EQ-5D-5L + V and EQ-5D-5L were 0.067 and 0.017, respectively. The corresponding SRM (F-statistic) were 0.709 (31.7) and 0.295 (5.4). CONCLUSIONS: Preliminary evidence from our study suggests that a vision 'bolt-on' may increase the responsiveness of EQ-5D-3L and EQ-5D-5L to change in health outcomes experienced by patients undergoing cataract surgery. In absence of the preference-based vision bolt-on EQ-5D-5L index, HUI3 was the most responsive measure.

Measurement Properties of Commonly Used Generic Preference-Based Measures in East and South-East Asia: A Systematic Review.

OBJECTIVES: Our aim was to systematically review published evidence on the construct validity, test-retest reliability and responsiveness of generic preference-based measures (PBMs) used in East and South-East Asia. METHODS: This systematic review was guided by the COSMIN guideline. A literature search on the MEDLINE, EMBASE, PsycINFO and PubMed databases up to August 2019 was conducted for measurement properties validation papers of the EuroQol-5 Dimensions (EQ-5D), Short Form-6 Dimensions (SF-6D), Health Utilities Index (HUI), Quality of Well-Being (QWB), 15-Dimensional (15D) and Assessment of Quality of Life (AQOL) in East and South-East Asian countries. Included papers were disaggregated into individual studies whose results and quality of design were rated separately. The population-specific measurement properties (construct validity, test-retest reliability and responsiveness) of each PBM were assessed separately using relevant studies. The overall methodological quality of the studies used in each of the assessments was also rated. RESULTS: A total of 79 papers containing 1504 studies were included in this systematic review. The methodological quality was 'very good' or 'adequate' for the majority of the construct validity studies (99%) and responsiveness studies (61%), but for only a small portion of the test-retest reliability studies (23%). EQ-5D was most widely assessed and was found to have 'sufficient' construct validity and responsiveness in many populations, while the SF-6D and EuroQol-Visual Analog Scale (EQ-VAS) exhibited 'inconsistent' construct validity in some populations. Scarce evidence was available on HUI and QWB, but current evidence supported the use of HUI. CONCLUSIONS: This systematic review provides a summary of the quality of existing generic PBMs in Asian populations. The current evidence supports the use of EQ-5D as the preferred choice when a generic PBM is needed, and continuous testing of all PBMs in the region.

Mobile Technology in Allergic Rhinitis: Evolution in Management or Revolution in Health and Care?

Smart devices and Internet-based applications (apps) are largely used in allergic rhinitis and may help to address some unmet needs. However, these new tools need to first of all be tested for privacy rules, acceptability, usability, and cost-effectiveness. Second, they should be evaluated in the frame of the digital transformation of health, their impact on health care delivery, and health outcomes. This review (1) summarizes some existing mobile health apps for allergic rhinitis and reviews those in which testing has been published, (2) discusses apps that include risk factors of allergic rhinitis, (3) examines the impact of mobile health apps in phenotype discovery, (4) provides real-world evidence for care pathways, and finally (5) discusses mobile health tools enabling the digital transformation of health and care, empowering citizens, and building a healthier society.

Von Economo Neurons in Behavioral Variant Frontotemporal Dementia with Underlying Alzheimer's Disease.

The selective loss of von Economo neurons has been linked to the behavioral deficits in behavioral variant frontotemporal dementia (bvFTD) but whether these neurons are affected in bvFTD patients with underlying Alzheimer's disease (AD) has yet to be established. The present study assesses the von Economo neurons in pathological AD cases clinically diagnosed with either AD or bvFTD. Our results demonstrate no significant loss of von Economo neurons in all pathological AD cases, irrespective of clinical diagnosis or co-existing Lewy body pathology. These results suggest that the behavioral deficits in patients with clinical bvFTD and underlying pathological AD are not driven by the loss of von Economo neurons.

EQ-5D-5L is More Responsive than EQ-5D-3L to Treatment Benefit of Cataract Surgery.

BACKGROUND: It is not clear whether 5-level EQ-5D (EQ-5D-5L) utilities based on recently developed value sets are more responsive than 3-level EQ-5D (EQ-5D-3L) utilities. OBJECTIVES: The study aims were to compare (1) the responsiveness of EQ-5D-5L and EQ-5D-3L utilities and (2) the responsiveness of these utilities with the Short Form-6 Dimension (SF-6D) and Health Utilities Index Mark 3 (HUI3) utilities to the treatment benefit of cataract surgery. METHODS: A total of 148 patients were interviewed before and after their cataract surgery using EQ-5D-3L, EQ-5D-5L, SF-6D, and HUI3. Responsiveness was assessed for all measures using the mean change (post-treatment-pre-treatment), standardized effect size (SES), standardized response mean (SRM), and F-statistic. RESULTS: Using the Singapore value sets, mean change for EQ-5D-3L and EQ-5D-5L utilities was 0.016 and 0.028, SES was 0.097 and 0.199; SRM was 0.091 and 0.196; and F-statistic was 1.2 and 5.7, respectively. Similar trends were observed using the UK/England EQ-5D value sets, although the magnitude was slightly smaller. The mean change, SES, SRM and F-statistics for SF-6D (UK value set) were 0.020, 0.234, 0.249, and 9.2, respectively. The values of mean change, SES, SRM and F-statistics for HUI3 (Canada value set) were 0.080, 0.472, 0.474, and 33.3, respectively. CONCLUSIONS: The EQ-5D-5L utilities tend to be more responsive than the EQ-5D-3L utilities to treatment benefits of cataract surgery. The HUI3 utilities are more responsive than both the EQ-5D-5L and SF-6D, and SF-6D utilities may be slightly more responsive than the EQ-5D-5L for assessing patients undergoing cataract surgery.

Assessment of amyloid ß in pathologically confirmed frontotemporal dementia syndromes.

INTRODUCTION: The diagnostic utility of in vivo amyloid ß (Aß) imaging to aid in the clinical distinction between frontotemporal dementia (FTD) and Alzheimer's disease remains unclear without data on the prevalence and severity of Aß in pathologically confirmed FTD syndromes. METHODS: Aß was assessed in 98 autopsy-confirmed FTD and 36 control cases, and the pathological accuracy of 11C-Pittsburgh compound B (PiB)-positron emission tomography imaging was assessed in a subset of FTD cases (n = 15). RESULTS: Aß was identified in a similar proportion of FTD syndromes and age-matched controls and increases with age. Alzheimer's disease pathology was identified in all cases with high PiB retention and in one case with low PiB retention. We further demonstrate a strong regional correlation between volume fraction of histological Aß with PiB standard uptake value ratio scaled to the white matter. DISCUSSION: The present study provides a pathologic reference to assist in the interpretation of in vivo assessments in FTD syndromes.

von Economo Neuron Density and Thalamus Volumes in Behavioral Deficits in Frontotemporal Dementia Cases with and without a C9ORF72 Repeat Expansion.

BACKGROUND: The early and selective loss of von Economo neurons in the anterior cingulate cortex has been linked to behavioral deficits in frontotemporal dementia (FTD). Importantly, whether these neurons are also targeted in patients with the C9ORF72 repeat expansion has yet to be established. This is of particular interest given the recent evidence highlighting the thalamus rather than anterior cingulate cortex as a region of significant degeneration in patients with the C9ORF72 repeat expansion. OBJECTIVE: To assess the von Economo neuron density and thalamus volumes in behavioral variant FTD (bvFTD) cases with the C9ORF72 repeat expansion, sporadic bvFTD, sporadic ALS, and controls. METHODS: Volumetric and quantitative cell counting methods were employed to assess the von Economo neuron density and thalamus volumes in 37 pathologically-confirmed cases comprised of patients with bvFTD (n = 13) cases with the C9ORF72 repeat expansion (62% with psychosis), sporadic bvFTD (n = 8), sporadic amyotrophic lateral sclerosis (n = 7) and controls (n = 9). RESULTS: von Economo neuron density was significantly reduced in sporadic bvFTD cases only. Thalamus degeneration was identified only in bvFTD cases with the C9ORF72 repeat expansion, and to a similar extent in cases with and without psychosis. No significant difference in von Economo neuron density or thalamus degeneration was seen between bvFTD cases with or without the C9ORF72 repeat expansion. CONCLUSION: The present histological findings converge with neuroimaging results to corroborate the anterior cingulate cortex as a core region involved in sporadic bvFTD, and the thalamus as a major region targeted in patients with the C9ORF72 expansion.

Spread of pathology in amyotrophic lateral sclerosis: assessment of phosphorylated TDP-43 along axonal pathways.

INTRODUCTION: The progression of amyotrophic lateral sclerosis (ALS) through the brain has recently been staged using independent neuropathological and neuroimaging modalities. The two schemes tie into the concept of pathological spread through corticofugal axonal transmission that stems from observation of oligodendrocyte pTDP-43 aggregates along with neuronal inclusions. Here, we aimed to assess evidence of transmission along axonal pathways by looking for pTDP-43 oligodendrocyte pathology in involved white matter tracts, and to present a first validation of the neuropathological staging scheme. pTDP-43 immunohistochemistry was performed in select white matter tracts and grey matter regions from the staging scheme in postmortem-confirmed ALS cases (N = 34). Double-labelling immunofluorescence was performed to confirm co-localisation of pTDP-43 immunoreactivity to oligodendrocytes. RESULTS: While pTDP-43 immunoreactive oligodendrocytes were frequent in the white matter under the motor and sensory cortices, similar assessment of the white matter along the corticospinal tract and in the corpus callosum and cingulum bundle of the same cases revealed no pTDP-43 pathology, questioning the involvement of oligodendrocytes in pathological propagation. The assessment of Betz cell loss revealed that the lack of deep white matter pTDP-43 oligodendrocyte pathology was not due to an absence of motor axons. Assessment of the propagation of pathology to different grey matter regions validated that all cases could be allocated to one of four neuropathological stages, although Stage 4 cases were found to differ significantly in age of onset (~10 years older) and disease duration (shorter duration than Stage 3 and similar to Stage 2). CONCLUSIONS: Four stages of ALS neuropathology can be consistently identified, although evidence of sequential clinical progression requires further assessment. As limited pTDP-43 oligodendrocyte pathology in deep corticospinal and other white matter tracts from the motor cortex was observed, the propagation of pathology between neurons may not involve oligodendrocytes and the interpretation of the changes observed on neuroimaging should be modified accordingly.

Economic analysis of endobronchial ultrasound (EBUS) as a tool in the diagnosis and staging of lung cancer in Singapore.

OBJECTIVES: Endobronchial ultrasound (EBUS), encompassing endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) and Endobronchial ultrasound transbronchial lung biopsy (EBUS-TBLB) has been proven to be a useful modality in the staging and diagnosis of lung cancer. However, there are limited publications on the cost-effectiveness of EBUS and no economic evaluations relevant to the Singapore setting. An economic evaluation using our hospital's data was used to assess the cost implications of EBUS substituting where clinically appropriate: transthoracic needle aspiration; (TTNA), fluoroscopy-guided transbronchial lung biopsy (TBLB), and mediastinoscopy in the diagnosis and staging of lung cancer. METHODS: Relationship between the clinical and economic implications of alternative modalities was modeled using data inputs that were relevant to the Singapore setting. Two decision analytic models were constructed to evaluate the cost of EBUS compared with TTNA, TBLB, and staging mediastinoscopy. Only direct costs were imputed. RESULTS: In the base-case analysis, TTNA was the most economical strategy (SGD3,335 = US$2,403) where clinically suitable for the diagnosis of lung cancer as compared to the other options: TBLB (SGD4,499) and EBUS-TBLB (SGD4,857). On the other hand, EBUS-TBNA resulted in expected cost savings of SGD1,214 per positive staging of lung cancer as compared to mediastinoscopy. CONCLUSIONS: The use of EBUS-TBNA could result in cost savings of SGD1,214 per positive staging of lung cancer as compared to mediastinoscopy. Whereas TTNA was the most economical intervention for the diagnosis of lung cancer as compared to the other options, its main limitation lies in its suitability only for peripheral lung lesions and high complication rate.