Estimation of the serial interval and proportion of pre-symptomatic transmission events of COVID- 19 in Ireland using contact tracing data.

BACKGROUND: The serial interval is the period of time between the onset of symptoms in an infector and an infectee and is an important parameter which can impact on the estimation of the reproduction number. Whilst several parameters influencing infection transmission are expected to be consistent across populations, the serial interval can vary across and within populations over time. Therefore, local estimates are preferable for use in epidemiological models developed at a regional level. We used data collected as part of the national contact tracing process in Ireland to estimate the serial interval of SARS-CoV-2 infection in the Irish population, and to estimate the proportion of transmission events that occurred prior to the onset of symptoms. RESULTS: After data cleaning, the final dataset consisted of 471 infected close contacts from 471 primary cases. The median serial interval was 4 days, mean serial interval was 4.0 (95% confidence intervals 3.7, 4.3) days, whilst the 25th and 75th percentiles were 2 and 6 days respectively. We found that intervals were lower when the primary or secondary case were in the older age cohort (greater than 64 years). Simulating from an incubation period distribution from international literature, we estimated that 67% of transmission events had greater than 50% probability of occurring prior to the onset of symptoms in the infector. CONCLUSIONS: Whilst our analysis was based on a large sample size, data were collected for the primary purpose of interrupting transmission chains. Similar to other studies estimating the serial interval, our analysis is restricted to transmission pairs where the infector is known with some degree of certainty. Such pairs may represent more intense contacts with infected individuals than might occur in the overall population. It is therefore possible that our analysis is biased towards shorter serial intervals than the overall population.

Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project.

BACKGROUND: Genome-wide and clinical studies have linked the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with hypertension, whilst limited evidence shows that intervention with riboflavin (i.e. the MTHFR co-factor) can lower blood pressure (BP) in hypertensive patients with the variant MTHFR 677TT genotype. We investigated the impact of this common polymorphism on BP throughout adulthood and hypothesised that riboflavin status would modulate the genetic risk of hypertension. METHODS: Observational data on 6076 adults of 18-102 years were drawn from the Joint Irish Nutrigenomics Organisation project, comprising the Trinity-Ulster Department of Agriculture (TUDA; volunteer sample) and the National Adult Nutrition Survey (NANS; population-based sample) cohorts. Participants were recruited from the Republic of Ireland and Northern Ireland (UK) in 2008-2012 using standardised methods. RESULTS: The variant MTHFR 677TT genotype was identified in 12% of adults. From 18 to 70 years, this genotype was associated with an increased risk of hypertension (i.e. systolic BP ≥ 140 and/or a diastolic BP ≥ 90 mmHg): odds ratio (OR) 1.42, 95% confidence interval (CI) 1.07 to 1.90; P = 0.016, after adjustment for antihypertensive drug use and other significant factors, namely, age, male sex, BMI, alcohol and total cholesterol. Low or deficient biomarker status of riboflavin (observed in 30.2% and 30.0% of participants, respectively) exacerbated the genetic risk of hypertension, with a 3-fold increased risk for the TT genotype in combination with deficient riboflavin status (OR 3.00, 95% CI, 1.34-6.68; P = 0.007) relative to the CC genotype combined with normal riboflavin status. Up to 65 years, we observed poorer BP control rates on antihypertensive treatment in participants with the TT genotype (30%) compared to those without this variant, CT (37%) and CC (45%) genotypes (P < 0.027). CONCLUSIONS: The MTHFR 677TT genotype is associated with higher BP independently of homocysteine and predisposes adults to an increased risk of hypertension and poorer BP control with antihypertensive treatment, whilst better riboflavin status is associated with a reduced genetic risk. Riboflavin intervention may thus offer a personalised approach to prevent the onset of hypertension in adults with the TT genotype; however, this requires confirmation in a randomised trial in non-hypertensive adults.

A Common Polymorphism in HIBCH Influences Methylmalonic Acid Concentrations in Blood Independently of Cobalamin.

Methylmalonic acid (MMA) is a by-product of propionic acid metabolism through the vitamin B12 (cobalamin)-dependent enzyme methylmalonyl CoA mutase. Elevated MMA concentrations are a hallmark of several inborn errors of metabolism and indicators of cobalamin deficiency in older persons. In a genome-wide analysis of 2,210 healthy young Irish adults (median age 22 years) we identified a strong association of plasma MMA with SNPs in 3-hydroxyisobutyryl-CoA hydrolase (HIBCH, p = 8.42 × 10(-89)) and acyl-CoA synthetase family member 3 (ACSF3, p = 3.48 × 10(-19)). These loci accounted for 12% of the variance in MMA concentration. The most strongly associated SNP (HIBCH rs291466; c:2T>C) causes a missense change of the initiator methionine codon (minor-allele frequency = 0.43) to threonine. Surprisingly, the resulting variant, p.Met1?, is associated with increased expression of HIBCH mRNA and encoded protein. These homozygotes had, on average, 46% higher MMA concentrations than methionine-encoding homozygotes in young adults with generally low MMA concentrations (0.17 [0.14-0.21] µmol/L; median [25(th)-75(th) quartile]). The association between MMA levels and HIBCH rs291466 was highly significant in a replication cohort of 1,481 older individuals (median age 79 years) with elevated plasma MMA concentrations (0.34 [0.24-0.51] µmol/L; p = 4.0 × 10(-26)). In a longitudinal study of 185 pregnant women and their newborns, the association of this SNP remained significant across the gestational trimesters and in newborns. HIBCH is unique to valine catabolism. Studies evaluating flux through the valine catabolic pathway in humans should account for these variants. Furthermore, this SNP could help resolve equivocal clinical tests where plasma MMA values have been used to diagnose cobalamin deficiency.

The relationship between adiposity and cognitive function in a large community-dwelling population: data from the Trinity Ulster Department of Agriculture (TUDA) ageing cohort study.

Previous reports investigating adiposity and cognitive function in the population allude to a negative association, although the relationship in older adults is unclear. The aim of this study was to investigate the association of adiposity (BMI and waist:hip ratio (WHR)) with cognitive function in community-dwelling older adults (≥60 years). Participants included 5186 adults from the Trinity Ulster Department of Agriculture ageing cohort study. Neuropsychological assessment measures included the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Multi-variable linear regression models were used to assess the association between adiposity and cognitive function adjusting for insulin resistance, inflammation and cerebrovascular disease. The mean ages were 80·3 (sd 6·7), 71·0 (sd 7·3) and 70·2 (sd 6·3) years on the cognitive, bone and hypertensive cohorts, respectively. In the cognitive cohort, BMI was positively associated with immediate and delay memory, visuospatial/constructional ability, language and MMSE, and negatively with FAB (log-transformed), whereas WHR was negatively associated with attention. In the bone cohort, BMI was not associated with any cognitive domain, whereas WHR was negatively associated with visuospatial/constructional ability, attention and MMSE. In the hypertensive cohort, BMI was not associated with any cognitive domain, whereas WHR was negatively associated with immediate and delayed memory, visuospatial/constructional ability, language and MMSE and positively with FAB (log-transformed). In the cognitive and bone cohorts, the association of WHR and attention disappeared by further controlling for C-reactive protein and HbA1C. In this study of older adults, central adiposity was a stronger predictor of poor cognitive performance than BMI. Older adults could benefit from targeted public health strategies aimed at reducing obesity and obeseogenic risk factors to avoid/prevent/slow cognitive dysfunction.

Ambient UVB Dose and Sun Enjoyment Are Important Predictors of Vitamin D Status in an Older Population.

Background: UVB-induced skin synthesis is considered the key source of vitamin D, yet exposure to UVB is poorly accounted for in epidemiological studies.Objectives: The aim of this study was to examine the association of serum 25-hydroxyvitamin D [25(OH)D] concentration with accurately measured ambient UVB dose, sun enjoyment, supplements, and other factors.Methods: An all-Irish cohort of community-dwelling participants aged >60 y [median age: 73; 67% female; median 25(OH)D: 54.5 nmol/L] was used. Participants from this large, cross-sectional study completed a questionnaire to provide information on demographic factors and lifestyle (including supplement use and sun enjoyment). The Tropospheric Emission Monitoring Internet Service database was used to extract the daily ambient UVB dose at wavelengths that could induce vitamin D synthesis (D-UVB) over Ireland (latitude: 51°N-55°N). Blood sampling occurred throughout the year. Ambient exposure at the place of residence was calculated for each participant individually. Associations between determinants and serum 25(OH)D concentration were examined in a multivariate model. Random forest analysis was used to establish prediction models of vitamin D deficiency, and area under the curve (AUC) is shown.Results: In total, 5138 individuals were included. Median D-UVB was 63 mJ/cm2, which varied between seasons and latitudes, despite the small latitude differential. Vitamin D supplementation (ß = 27.7; P < 10 × 10-10), D-UVB (ß = 1.58 per 1000 mJ/cm2; P < 10 × 10-10), and sun enjoyment (ß = 6.6; P < 0.001) were strongly positively associated with serum 25(OH)D. Those who avoided sunshine were largely at risk of deficiency (<40 nmol/L), whereas those who enjoyed sunshine tended to be vitamin D sufficient (≥50 nmol/L). D-UVB and sun enjoyment improved prediction of deficiency in non-supplement-taking individuals; the overall AUC improved by 3.5%.Conclusion: D-UVB and sun enjoyment are important predictors of vitamin D status, even in this elderly population at northern latitudes. Accurate estimation of ambient UVB can help to further clarify the role of other determinants of vitamin D status and inform sunshine recommendation guidelines.

The Frontal Assessment Battery: Normative Performance in a Large Sample of Older Community-Dwelling Hospital Outpatient or General Practitioner Attenders.

BACKGROUND: The Frontal Assessment Battery (FAB) is a short battery designed to assess frontal executive functioning, but data for interpretation of performance are limited. OBJECTIVES: The Trinity, Ulster, Department of Agriculture (TUDA) study provided the opportunity to derive performance data from a large sample of community-dwelling hospital outpatient or general practitioner (GP) attenders. METHODS: Normative analysis based on 2508 TUDA participants meeting these criteria: Mini-Mental State Examination (MMSE) >26/30, not depressed (Center for Epidemiologic Studies Depression <16) or anxious (Hospital Anxiety and Depression Scale <8), no history of stroke, or transient ischemic attack. Correlation and regression analyses were used to evaluate the effects of age, education, gender, and general cognition (MMSE). Norms for FAB were created stratified by age and education, using overlapping midpoint ranges of 10 years with a 3-year interval from age 60 to 97. RESULTS: Age and education accounted for 9.6% of variance in FAB score ( r2 = .096) with no significant effect of gender. The FAB and MMSE were modestly correlated ( r = .29, P < .01) with MMSE increasing the model's total explained variance in FAB score from 9.6% to 14%. CONCLUSION: This is the largest study to date to create normative data for the FAB. Age and education had the most significant impact on FAB performance, which was largely independent of global cognition (MMSE). These data may be of benefit in interpreting FAB performance in individuals with similar demographic/health status characteristics in hospital outpatient or GP settings.

Determinants of 25-hydroxyvitamin D in older Irish adults.

BACKGROUND: vitamin D deficiency is prevalent in older adults living in Northern Europe and is influenced by several factors which may vary significantly with age. OBJECTIVE: we aimed to investigate the determinants of 25-hydroxyvitamin D [25(OH)D] in older Irish adults and in particular to examine the effect of supplement use and surrogate markers of sun exposure. METHODS: subjects were non-institutionalised community dwelling Irish adults aged over 60 years who were participants of a large cross-sectional study comprising three disease defined cohorts. Serum 25(OH)D was measured by liquid chromatography mass spectroscopy. Associations between 25(OH)D and potential confounders were explored in forward regression models in each cohort. RESULTS: the three cohorts comprised 1895, 1233 and 1316 participants (respective mean ages 70.1, 71.0 and 80.4 years). Statistical models explained between a fifth to a third of the variation in 25(OH)D. Supplement use and global solar radiation were positive predictors of 25(OH)D in all cohorts whereas the only universal negative predictor was body mass index. Supplement use was associated with a mean increase in 25(OH)D of between 21.4 and 35.4 nmol/l. The other main predictors varied by cohort but included sun holiday travel, enjoyment of sunshine when outside, use of vitamin D fortified milk, smoking, oily fish and egg consumption and physical frailty. CONCLUSION: supplement use was the most important determinant of vitamin D status. Vitamin D fortified milk and spending time in the sun, even in the oldest old may also be useful strategies to improve 25(OH)D.

A new understanding of oral and dental pathology of the equine cheek teeth.

Equine dental disease has a high prevalence. Because of developmental, functional, and anatomic differences, limited inference can be made from brachydont dental pathology to that of equine cheek teeth. This article reviews the pathology of equine cheek teeth and their associated oral tissues, with specific information on periodontitis, pulpitis, maxillary infundibular changes, dental fractures, dental overgrowths, mucosal ulceration, and the regenerative capacity of equine teeth.

Can Ingoing Contact Chains and other cattle movement network metrics help predict herd-level bovine tuberculosis in Irish cattle herds?

We used logistic regression to investigate whether the risk of an Irish cattle herd undergoing a bovine tuberculosis (bTB) breakdown increased with the size of the Ingoing Contact Chain (ICC) of previous herd to herd cattle movements, in a sequence up to eight moves back from the most recent, direct, movement into the herd. We further examined whether taking into account the bTB test history of each herd in the chain would improve model fit. We found that measures of cattle movements directly into the herd were risk factors for subsequent bTB restrictions, and the number of herds that animals were coming from was the most important of these. However, in contrast to a previous study in Great Britain, the ICC herd count at steps more remote than direct movements into the herd did not result in better fitting models than restricting the count to direct movements. Restricting the ICC counts to herds which had previously or would in the future test positive for bTB resulted in improved model fits, but this was not the case if only the previous test status was considered. This suggests that in many cases bTB infected animals are moving out of herds before being identified through testing, and that risk-based trading approaches should not rely solely on the previous test history of source herds as a proxy for future risk. Model fit was also improved by the inclusion of variables measuring bTB history of the herd, bTB in neighbouring herds, herd size, herd type, the movement network measures "in strength" and "betweenness", altitude, modelled badger abundance and county. Rainfall was not a good predictor. The most influential measures of bTB in nearby herds (a proxy for neighbourhood infection) were the proportion of herds with a history of bTB whose centroids were within 6 km, or whose boundaries were within 4 km, of the index herd. As well as informing national control and surveillance measures, our models can be used to identify areas where bTB rates are anomalously high, to prompt further investigation in these areas.

Bovine tuberculosis in youngstock cattle: A narrative review.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains a high-priority global pathogen of concern. The role of youngstock animals in the epidemiology of bTB has not been a focus of contemporary research. Here we have aimed to collate and summarize what is known about the susceptibility, diagnosis, transmission (infectiousness), and epidemiology to M. bovis in youngstock (up to 1-year of age). Youngstock are susceptible to M. bovis infection when exposed, with the capacity to develop typical bTB lesions. Calves can be exposed through similar routes as adults, via residual infection, contiguous neighborhood spread, wildlife spillback infection, and the buying-in of infected but undetected cattle. Dairy systems may lead to greater exposure risk to calves relative to other production systems, for example, via pooled milk. Given their young age, calves tend to have shorter bTB at-risk exposure periods than older cohorts. The detection of bTB varies with age when using a wide range of ante-mortem diagnostics, also with post-mortem examination and confirmation (histological and bacteriological) of infection. When recorded as positive by ante-mortem test, youngstock appear to have the highest probabilities of any age cohort for confirmation of infection post-mortem. They also appear to have the lowest false negative bTB detection risk. In some countries, many calves are moved to other herds for rearing, potentially increasing inter-herd transmission risk. Mathematical models suggest that calves may also experience lower force of infection (the rate that susceptible animals become infected). There are few modeling studies investigating the role of calves in the spread and maintenance of infection across herd networks. One study found that calves, without operating testing and control measures, can help to maintain infection and lengthen the time to outbreak eradication. Policies to reduce testing for youngstock could lead to infected calves remaining undetected and increasing onwards transmission. Further studies are required to assess the risk associated with changes to testing policy for youngstock in terms of the impact for within-herd disease control, and how this may affect the transmission and persistence of infection across a network of linked herds.

Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B12 status in the elderly.

BACKGROUND: Vitamin B12 deficiency is common among the elderly, and early detection is clinically important. However, clinical signs and symptoms have limited diagnostic accuracy and there is no accepted reference test method. METHODS: In elderly subjects (n = 700; age range 63-97 years), we investigated the ability of serum cobalamin, holotranscobalamin (holoTC), total homocysteine (tHcy), methylmalonic acid (MMA), serum and erythrocyte folate, and other hematologic variables to discriminate cobalamin deficiency, defined as red blood cell cobalamin <33 pmol/L. RESULTS: Serum holoTC was the best predictor, with area under the ROC curve (95% CI) 0.90 (0.86-0.93), and this was significantly better (P ≤ 0.0002) than the next best predictors; serum cobalamin, 0.80 (0.75-0.85), and MMA, 0.78 (0.72-0.83). For these 3 analytes, we constructed a 3-zone partition of positive and negative zones and a deliberate indeterminate zone between. The boundaries were values of each test that resulted in a posttest probability of deficiency of 60% and a posttest probability of no deficiency of 98%. The proportion of indeterminate observations for holoTC, cobalamin, and MMA was 14%, 45%, and 50%, respectively. Within the holoTC indeterminate zone (defined as 20-30 pmol/L), discriminant analysis selected only erythrocyte folate, which correctly allocated 65% (58/89) of the observations. Renal dysfunction compromised the diagnostic accuracy of MMA but not holoTC or serum cobalamin. CONCLUSIONS: This study supports the use of holoTC as the first-line diagnostic procedure for vitamin B12 status.

Primary-care prescribing of anti-osteoporotic-type medications following hospitalisation for fractures.

PURPOSE: We examined the prescribing of antiosteoporotic medications pre- and post hospital admission in patients with fragility fractures as well as factors associated with prescribing of these treatments following admission. METHODS: We identified all patients aged ≥ 55 years at a large teaching hospital between 2005 and 2008 with a fracture using the Hospital In-Patient Enquiry (HIPE) system. These data were linked to prescribing data from the Health Service Executive Primary Care Reimbursement Services (HSE-PCRS) scheme before and after discharge (821 patients). Logistic regression analysis was used to examine the likelihood of prescription of antiosteoporotic medication pre- and post discharge in relation to year of discharge, age, gender, and type of fracture. RESULTS: Prescribing of antiosteoporotic treatment before fracture increased from 2.6% [95% confidence interval (CI) 2.23-2.93%] in 2005 to 10.6% (95% CI 9.32-11.86) by 2008, whereas post fracture prescribing increased from 11% (95% CI 9.64-12.36) to 47% (95% CI 43.6-50.3). In patients discharged from hospital in 2007, postfracture prescribing was 31.8% (95% CI 28.66-35.02) at 12 months, increasing to 50.3% (95% CI 46.6-53.9) at 24 months. The highest rate of prescribing was in the 65- to 69-year age group [odds ratio (OR) 8.51, 95% CI 1.75-41.35]. Patients discharged in 2008 were eight times more likely to be treated than patients discharged in 2005 (OR 8.01, 95% CI 4.55-14.09). CONCLUSION: The percentage of patients on antiosteoporotic treatment post fracture increased significantly from 2005 to 2008. This may be largely due to the introduction of the Osteoporosis Clinic to the hospital in 2005.

Seasonal variation of serum vitamin D and the effect of vitamin D supplementation in Irish community-dwelling older people.

BACKGROUND: Ireland is at 53°N, and its population risk of vitamin D deficiency is high. Previous Irish studies suggested a significant seasonality of serum 25-hydroxyvitamin D [25(OH)D] and a beneficial effect of supplementation in raising 25(OH)D levels. However, in Irish older people, little is known about the magnitude of the supplementation effect and whether supplementation affects 25(OH)D seasonality. DESIGN: cross-sectional observational. SETTING: outpatient clinic. SUBJECTS: five hundred and forty-six community-dwelling subjects (mean age 73.0, SD 7.4; 68.5% females) were assessed between September 2007 and May 2009. METHODS: for supplemented and non-supplemented: 'cosinor' analysis (Pulse_XP®) of monthly 25(OH)D. Period global solar radiation (GSR) and solar elevation angle (SEA) data were collected as proxy markers of ultraviolet-B radiation exposure. Multivariate linear regression was conducted to investigate the independent effect of GSR and SEA on 25(OH)D, controlling for confounders. RESULTS: supplemented group (N = 183): 89.1% were on cholecalciferol 800 IU/day. Mean 25(OH)D = 64.1 (95% confidence interval: 52.2-75.8) nmol/l, with no significant seasonality; regression: neither GSR nor SEA predicted 25(OH)D. Non-supplemented group (N = 363): mean 25(OH)D = 40.3 (35.5-45.0) nmol/l, with significant seasonality (55.5% variance remaining), peak in August, amplitude = 6.0 (3.1-8.8) nmol/l; regression: both GSR (P = 0.002) and the interaction GSR * SEA (P = 0.018) predicted 25(OH)D. CONCLUSIONS: vitamin D supplementation was associated with a mean serum 25(OH)D increase of 23.8 nmol/l. Interestingly, supplementation seemed to blunt seasonality. In the supplemented group, 72.1% had individual 25(OH)D levels below the recommended 75 nmol/l. There is a case for universal supplementation in Irish older people, probably at a higher dose. Further research is needed to establish the optimum dose.

Progressive resistance training in a post-acute, older, inpatient setting: A randomised controlled feasibility study.

OBJECTIVES: Progressive resistance training can successfully target functional decline in healthy older community-dwelling adults. There are concerns about the safety and acceptance of its use in frail older populations. The aim of this study was to evaluate the feasibility of using progressive resistance training in an older, post-acute, inpatient setting. METHODS: A randomised controlled feasibility study was conducted. Appropriate older inpatients undergoing post-acute rehabilitation were recruited. Feasibility measures examined were safety, recruitment, outcome measurement, adherence and retention rates and satisfaction. A range of clinical measures were used to capture changes in body structure and function, activity and participation. Assessments were performed on admission to the study and six weeks later. RESULTS: A sample of 33 patients were included and randomised to the treatment group (n=16) or the control group (n=17). There were no serious adverse events, adherence rates were 63% and retention rates were 82%. While both groups improved between time 1 and 2, there were no significant differences in clinical measures between the groups. CONCLUSION: Progressive resistance training is a safe and acceptable intervention for use with this population. Further work on the effectiveness of progressive resistance training in this setting is now required.

Vitamin D and Hospital Admission in Older Adults: A Prospective Association.

The health effects of vitamin D are well documented, with increasing evidence of its roles beyond bone. There is, however, little evidence of the effects of vitamin D on hospitalisation among older adults. This study aimed to prospectively determine the relationship of vitamin D status in older adults with hospital admission and emergency department (ED) attendance. Trinity University of Ulster Department of Agriculture (TUDA) is a large cross-sectional study of older adults with a community population from three disease-defined cohorts (cognitive dysfunction, hypertension, and osteoporosis). Participants included in this analysis were recruited between 2008 and 2012. ED and hospital admission data were gathered from the date of TUDA participation until June 2013, with a mean follow up of 3.6 years. Of the 3093 participants, 1577 (50.9%) attended the ED during the period of follow-up. Attendees had lower mean serum 25(OH)D concentrations than non-attendees (59.1 vs. 70.6 nmol/L). Fully adjusted models showed an inverse association between vitamin D and ED attendance (Hazard Ratio (HR) 0.996; 95% Confidence Interval (CI) 0.995-0.998; p < 0.001). A total of 1269 participants (41%) were admitted to hospital during the follow-up. Those admitted had lower mean vitamin D concentrations (58.4 vs. 69.3 nmol/L, p < 0.001). In fully adjusted models, higher vitamin D was inversely associated with hospital admission (HR 0.996; 95% CI 0.994-0.998; p < 0.001) and length of stay (LOS) (ß = -0.95, p = 0.006). This study showed independent prospective associations between vitamin D deficiency and increased hospitalisation by older adults. The need for further evaluation of current recommendations in relation to vitamin D supplementation, with consideration beyond bone health, is warranted and should focus on randomised controlled trials.

Associations of atrophic gastritis and proton-pump inhibitor drug use with vitamin B-12 status, and the impact of fortified foods, in older adults.

BACKGROUND: Atrophic gastritis (AG) and use of proton pump inhibitors (PPIs) result in gastric acid suppression that can impair the absorption of vitamin B-12 from foods. The crystalline vitamin B-12 form, found in fortified foods, does not require gastric acid for its absorption and could thus be beneficial for older adults with hypochlorhydria, but evidence is lacking. OBJECTIVES: To investigate associations of AG and PPI use with vitamin B-12 status, and the potential protective role of fortified foods, in older adults. METHODS: Eligible participants (n = 3299) not using vitamin B-12 supplements were drawn from the Trinity-Ulster and Department of Agriculture cohort, a study of noninstitutionalized adults aged ≥60 y and recruited in 2008-2012. Vitamin B-12 status was measured using 4 biomarkers, and vitamin B-12 deficiency was defined as a combined indicator value < -0.5. A pepsinogen I:II ratio <3 was considered indicative of AG. RESULTS: AG was identified in 15% of participants and associated with significantly lower serum total vitamin B-12 (P < 0.001) and plasma holotranscobalamin (holoTC; P < 0.001), and higher prevalence of vitamin B-12 deficiency (38%), compared with PPI users (21%) and controls (without AG and nonusers of PPIs; 15%; P < 0.001). PPI drugs were used (≥6 mo) by 37% of participants and were associated with lower holoTC concentrations, but only in participants taking higher doses (≥30 mg/d). Regular, compared with nonregular, consumption of fortified foods (i.e., ≥5 and 0-4 portions/wk, respectively) was associated with higher vitamin B-12 biomarkers in all participants, but inadequate to restore normal vitamin B-12 status in those with AG. CONCLUSIONS: Older adults who have AG and/or use higher doses of PPIs are more likely to have indicators of vitamin B-12 deficiency. Fortified foods, if consumed regularly, were associated with enhanced vitamin B-12 status, but higher levels of added vitamin B-12 than currently provided could be warranted to optimize status in people with AG.

Statistical analysis of fat and muscle mass in osteoporosis in elderly population using total body DXA scans.

BACKGROUND: The magnitude of effects of lean mass and fat mass on bone health is controversial, and this study is a contribution to understand its effects on skeletal composition. AIM: We explored the relationship of body fat and muscle parameters with bone mineral density (BMD) and age and observed if it changed when matched with body mass index (BMI) of the same study subjects. METHODS: One-hundred sixty-four community dwelling, ambulatory elderly attending the osteoporosis services of a Dublin hospital was recruited. Out of these, 158 female patients had a total body DXA scan, and their body composition outcomes were included in this analysis. The relationship between body fat and muscle composition and BMD at all sites was determined and also matched by BMI. RESULTS: Total-Body BMD had a strong positive correlation with lean mass(r = 0.492, p 0.00) and fat mass(r = 0.414, p 0.00), though lean mass remained the strongest predictor of BMD at all sites. Increasing BMI categorically had a positive effect on both lean mass and fat mass. Increasing age was significantly associated with an increase in fat mass(r = 2.40, p 0.00) and a decrease in muscle mass(r = 0.478, p 0.01). CONCLUSION: Both lean mass and fat mass are significant predictors of BMD. To preserve BMD maintenance or increase of lean mass is more effective than fat mass. BMI correlates well with body composition; however, we recommend the use of direct measures of body fat and muscle to make this relation more interpretable. Total Body DXA is a readily available diagnostic tool which provides high-valued information about body composition.

Rapid review of available evidence on the serial interval and generation time of COVID-19.

The serial interval is the time between symptom onsets in an infector-infectee pair. The generation time, also known as the generation interval, is the time between infection events in an infector-infectee pair. The serial interval and the generation time are key parameters for assessing the dynamics of a disease. A number of scientific papers reported information pertaining to the serial interval and/or generation time for COVID-19. OBJECTIVE: Conduct a review of available evidence to advise on appropriate parameter values for serial interval and generation time in national COVID-19 transmission models for Ireland and on methodological issues relating to those parameters. METHODS: We conducted a rapid review of the literature covering the period 1 January 2020 and 21 August 2020, following predefined eligibility criteria. Forty scientific papers met our inclusion criteria and were included in the review. RESULTS: The mean of the serial interval ranged from 3.03 to 7.6 days, based on 38 estimates, and the median from 1.0 to 6.0 days (based on 15 estimates). Only three estimates were provided for the mean of the generation time. These ranged from 3.95 to 5.20 days. One estimate of 5.0 days was provided for the median of the generation time. DISCUSSION: Estimates of the serial interval and the generation time are very dependent on the specific factors that apply at the time that the data are collected, including the level of social contact. Consequently, the estimates may not be entirely relevant to other environments. Therefore, local estimates should be obtained as soon as possible. Careful consideration should be given to the methodology that is used. Real-time estimations of the serial interval/generation time, allowing for variations over time, may provide more accurate estimates of reproduction numbers than using conventionally fixed serial interval/generation time distributions.

Incubation period of COVID-19: a rapid systematic review and meta-analysis of observational research.

OBJECTIVES: The aim of this study was to conduct a rapid systematic review and meta-analysis of estimates of the incubation period of COVID-19. DESIGN: Rapid systematic review and meta-analysis of observational research. SETTING: International studies on incubation period of COVID-19. PARTICIPANTS: Searches were carried out in PubMed, Google Scholar, Embase, Cochrane Library as well as the preprint servers MedRxiv and BioRxiv. Studies were selected for meta-analysis if they reported either the parameters and CIs of the distributions fit to the data, or sufficient information to facilitate calculation of those values. After initial eligibility screening, 24 studies were selected for initial review, nine of these were shortlisted for meta-analysis. Final estimates are from meta-analysis of eight studies. PRIMARY OUTCOME MEASURES: Parameters of a lognormal distribution of incubation periods. RESULTS: The incubation period distribution may be modelled with a lognormal distribution with pooled mu and sigma parameters (95% CIs) of 1.63 (95% CI 1.51 to 1.75) and 0.50 (95% CI 0.46 to 0.55), respectively. The corresponding mean (95% CIs) was 5.8 (95% CI 5.0 to 6.7) days. It should be noted that uncertainty increases towards the tail of the distribution: the pooled parameter estimates (95% CIs) resulted in a median incubation period of 5.1 (95% CI 4.5 to 5.8) days, whereas the 95th percentile was 11.7 (95% CI 9.7 to 14.2) days. CONCLUSIONS: The choice of which parameter values are adopted will depend on how the information is used, the associated risks and the perceived consequences of decisions to be taken. These recommendations will need to be revisited once further relevant information becomes available. Accordingly, we present an R Shiny app that facilitates updating these estimates as new data become available.

Inferred duration of infectious period of SARS-CoV-2: rapid scoping review and analysis of available evidence for asymptomatic and symptomatic COVID-19 cases.

OBJECTIVES: Our objective was to review the literature on the inferred duration of the infectious period of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and provide an overview of the variation depending on the methodological approach. DESIGN: Rapid scoping review. Literature review with fixed search terms, up to 1 April 2020. Central tendency and variation of the parameter estimates for infectious period in (A) asymptomatic and (B) symptomatic cases from (1) virological studies (repeated testing), (2) tracing studies and (3) modelling studies were gathered. Narrative review of viral dynamics. INFORMATION SOURCES: Search strategies developed and the following searched: PubMed, Google Scholar, MedRxiv and BioRxiv. Additionally, the Health Information Quality Authority (Ireland) viral load synthesis was used, which screened literature from PubMed, Embase, ScienceDirect, NHS evidence, Cochrane, medRxiv and bioRxiv, and HRB open databases. RESULTS: There was substantial variation in the estimates, and how infectious period was inferred. One study provided approximate median infectious period for asymptomatic cases of 6.5-9.5 days. Median presymptomatic infectious period across studies varied over <1-4 days. Estimated mean time from symptom onset to two negative RT-PCR tests was 13.4 days (95% CI 10.9 to 15.8) but was shorter when studies included children or less severe cases. Estimated mean duration from symptom onset to hospital discharge or death (potential maximal infectious period) was 18.1 days (95% CI 15.1 to 21.0); time to discharge was on average 4 days shorter than time to death. Viral dynamic data and model infectious parameters were often shorter than repeated diagnostic data. CONCLUSIONS: There are limitations of inferring infectiousness from repeated diagnosis, viral loads and viral replication data alone and also potential patient recall bias relevant to estimating exposure and symptom onset times. Despite this, available data provide a preliminary evidence base to inform models of central tendency for key parameters and variation for exploring parameter space and sensitivity analysis.