COVID-19 Vaccination for Frail Older Adults in Singapore - Rapid Evidence Summary and Delphi Consensus Statements.

OBJECTIVE: This study aimed to synthesize available evidence on the effectiveness and safety of COVID-19 vaccines for frail older adults through a rapid review, supplemented with geriatricians' consensus statements. METHODS: References were identified through MEDLINE and Web of Science on 1st February 2021 using relevant terms related to COVID-19, vaccine, and older adults. Searches were also conducted on reference lists of review articles and Google Scholar. The content was updated on 8th April via hand searching. We included studies on Phase III randomized controlled trials, and data from real world administration of vaccines. A two-round Delphi study was conducted with 15 geriatricians to elicit their thoughts and recommendations regarding COVID-19 vaccination for frail older adults. RESULTS: Five Phase III randomized controlled efficacy trials reported vaccine efficacy ranging from 66.7% to 95% among participants aged 16 to 95. The vaccine efficacy for participants aged 65 and above is 94.7% and 86.4% for Pfizer-BioNTech and Moderna respectively. Sputnik V reported a vaccine efficacy of 91.8% for participants 60 and above. Serious adverse events were reported by 0.27% to 1% of participants who received at least one dose of the four vaccines. For the Delphi study, 16 out of 24 statements achieved consensus. The Delphi panel opined that frail or very old adults, except those with limited life expectancy, should be vaccinated due to their vulnerability. They also agree that vaccination decisions should be made by patients when possible, with the involvement of next-of-kin should the frail older adult be unable to do so. Lastly, the panel thought that frail older adults should be included in future clinical trials. CONCLUSION: In early clinical trials, there is paucity of evidence on efficacy and safety of current COVID-19 vaccines among frail older adults. Geriatricians' consensus indicate that frail older adults should be vaccinated except where life expectancy is limited. Future trials assessing efficacy and safety should include frail older adults.

A Rapid Review of the Measurement of Intrinsic Capacity in Older Adults.

OBJECTIVES: This study aims to address the knowledge gap and summarise the measurement for intrinsic capacity for the five WHO domains across different populations. It specifically aims to identify measurement tools, methods used for computation of a composite intrinsic capacity index and factors associated with intrinsic capacity among older adults. METHODS: We performed literature review in Medline, including search terms "aged" or "elderly" and "intrinsic capacity" for articles published from 2000 - 2020 in English. Studies which assessed intrinsic capacity in the five WHO domains were included. Information pertaining to study setting, methods used for measuring the domains of intrinsic capacity, computation methods for composite intrinsic capacity index, and details on tool validation were extracted. RESULTS: Seven articles fulfilling the inclusion criteria were included in the review. Of these, the majority were conducted in community settings (n=5) and were retrospective studies (n=6). The most commonly used tools for assessing intrinsic capacity were gait speed test and chair stand test (locomotion); handgrip-strength and mini-nutritional assessment (vitality); Mini-Mental State Examination (cognition); Geriatric Depression Scale (GDS) and Center for Epidemiological Studies Depression Scale (CES-D) (psychological), and self-reported vision and health questionnaires (sensory). Among the tools used to operationalise the domains, we found variations and non-concordance, especially in the vitality and psychological domains, which make inter-study comparison difficult. Validated scales were less commonly used for vitality and sensory domains. Biomarkers were used for locomotion, vitality, and sensory domains. Self-reported measures were mostly used in the psychological and sensory domains. Three studies operationalised a global score for intrinsic capacity, whereby scores from the individual domains were used to create a composite intrinsic capacity index, using two approaches: a) Structural equation modelling, and b) Sub-scores for each domain which were combined either by arithmetic sum or average. CONCLUSION: We identified considerable variations in measurement instruments and processes which are used to assess intrinsic capacity, especially among the vitality and psychological domains. A standardized intrinsic capacity composite score for clinical or community settings has not been operationalised yet. Further validation via prospective studies of the intrinsic capacity concept and computation of composite score using validated scales are needed.

Marker encoded fringe projection profilometry for efficient 3D model acquisition.

This paper presents a novel marker encoded fringe projection profilometry (FPP) scheme for efficient 3-dimensional (3D) model acquisition. Traditional FPP schemes can introduce large errors to the reconstructed 3D model when the target object has an abruptly changing height profile. For the proposed scheme, markers are encoded in the projected fringe pattern to resolve the ambiguities in the fringe images due to that problem. Using the analytic complex wavelet transform, the marker cue information can be extracted from the fringe image, and is used to restore the order of the fringes. A series of simulations and experiments have been carried out to verify the proposed scheme. They show that the proposed method can greatly improve the accuracy over the traditional FPP schemes when reconstructing the 3D model of objects with abruptly changing height profile. Since the scheme works directly in our recently proposed complex wavelet FPP framework, it enjoys the same properties that it can be used in real time applications for color objects.

Natural history of dilated cardiomyopathy due to lamin A/C gene mutations.

OBJECTIVES: We examined the prevalence, genotype-phenotype correlation, and natural history of lamin A/C gene (LMNA) mutations in subjects with dilated cardiomyopathy (DCM). BACKGROUND: Mutations in LMNA have been found in patients with DCM with familial conduction defects and muscular dystrophy, but the clinical spectrum, prognosis, and clinical relevance of laminopathies in DCM are unknown. BACKGROUND: A cohort of 49 nuclear families, 40 with familial DCM and 9 with sporadic DCM (269 subjects, 105 affected), was screened for mutations in LMNA using denaturing high-performance liquid chromatography and sequence analysis. Bivariate analysis of clinical predictors of LMNA mutation carrier status and Kaplan-Meier survival analysis were performed. RESULTS: Mutations in LMNA were detected in four families (8%), three with familial (R89L, 959delT, R377H) and one with sporadic DCM (S573L). There was significant phenotypic variability, but the presence of skeletal muscle involvement (p < 0.001), supraventricular arrhythmia (p = 0.003), conduction defects (p = 0.01), and "mildly" DCM (p = 0.006) were predictors of LMNA mutations. The LMNA mutation carriers had a significantly poorer cumulative survival compared with non-carrier DCM patients: event-free survival at the age of 45 years was 31% versus 75% in non-carriers. CONCLUSIONS: Mutations in LMNA cause a severe and progressive DCM in a relevant proportion of patients. Mutation screening should be considered in patients with DCM, in particular when clinical predictors of LMNA mutation are present, regardless of family history.

Optimized acquisition time and image sampling for dynamic SPECT of Tl-201.

With the recent development in scatter and attenuation correction algorithms, dynamic single photon emission computerized tomography (SPECT) can potentially yield physiological parameters, with tracers exhibiting suitable kinetics such as thallium-201 (Tl-201). A systematic way is proposed to investigate the minimum data acquisition times and sampling requirements for estimating physiological parameters with quantitative dynamic SPECT. Two different sampling schemes were investigated with Monte Carlo simulations: 1) Continuous data collection for total study duration ranging from 30-240 min. 2) Continuous data collection for first 10-45 min followed by a delayed study at approximately 3 h. Tissue time activity curves with realistic noise were generated from a mean plasma time activity curve and rate constants (K1 - k4) derived from Tl-201 kinetic studies in 16 dogs. Full dynamic sampling schedules (DynSS) were compared to optimum sampling schedules (OSS). We found that OSS can reliably estimate the blood flow related K1 and Vd comparable to DynSS. A 30-min continuous collection was sufficient if only K1 was of interest. A split session schedule of a 30-min dynamic followed by a static study at 3 h allowed reliable estimation of both K1 and Vd avoiding the need for a prolonged (>60-min) continuous dynamic acquisition. The methodology developed should also be applicable to optimizing sampling schedules for other SPECT tracers.