Clinical Performance of Direct RT-PCR Testing of Raw Saliva for Detection of SARS-CoV-2 in Symptomatic and Asymptomatic Individuals.

RT-PCR tests based on RNA extraction from nasopharyngeal swabs (NPS) are promoted as the "gold standard" for SARS-CoV-2 detection. However, the use of saliva samples offers noninvasive self-collection more suitable for high-throughput testing. This study evaluated performance of the TaqPath COVID-19 Fast PCR Combo kit 2.0 assay for detection of SARS-CoV-2 in raw saliva relative to a lab-developed direct RT-PCR test (SalivaDirect-based PCR, SDB-PCR) and an RT-PCR test based on RNA extraction from NPS. Saliva and NPS samples were collected from symptomatic and asymptomatic individuals (N = 615). Saliva samples were tested for SARS-CoV-2 using the TaqPath COVID-19 Fast PCR Combo kit 2.0 and the SDB-PCR, while NPS samples were tested by RT-PCR in RNA extracts according to the Irish national testing system. TaqPath COVID-19 Fast PCR Combo kit 2.0 detected SARS-CoV-2 in 52 saliva samples, of which 51 were also positive with the SDB-PCR. Compared to the NPS "gold standard" biospecimen method, 49 samples displayed concordant results, while three samples (35

Consumer-Led Screening for Atrial Fibrillation: Frontier Review of the AF-SCREEN International Collaboration.

The technological evolution and widespread availability of wearables and handheld ECG devices capable of screening for atrial fibrillation (AF), and their promotion directly to consumers, has focused attention of health care professionals and patient organizations on consumer-led AF screening. In this Frontiers review, members of the AF-SCREEN International Collaboration provide a critical appraisal of this rapidly evolving field to increase awareness of the complexities and uncertainties surrounding consumer-led AF screening. Although there are numerous commercially available devices directly marketed to consumers for AF monitoring and identification of unrecognized AF, health care professional-led randomized controlled studies using multiple ECG recordings or continuous ECG monitoring to detect AF have failed to demonstrate a significant reduction in stroke. Although it remains uncertain if consumer-led AF screening reduces stroke, it could increase early diagnosis of AF and facilitate an integrated approach, including appropriate anticoagulation, rate or rhythm management, and risk factor modification to reduce complications. Companies marketing AF screening devices should report the accuracy and performance of their products in high- and low-risk populations and avoid claims about clinical outcomes unless improvement is demonstrated in randomized clinical trials. Generally, the diagnostic yield of AF screening increases with the number, duration, and temporal dispersion of screening sessions, but the prognostic importance may be less than for AF detected by single-time point screening, which is largely permanent, persistent, or high-burden paroxysmal AF. Consumer-initiated ECG recordings suggesting possible AF always require confirmation by a health care professional experienced in ECG reading, whereas suspicion of AF on the basis of photoplethysmography must be confirmed with an ECG. Consumer-led AF screening is unlikely to be cost-effective for stroke prevention in the predominantly young, early adopters of this technology. Studies in older people at higher stroke risk are required to demonstrate both effectiveness and cost-effectiveness. The direct interaction between companies and consumers creates new regulatory gaps in relation to data privacy and the registration of consumer apps and devices. Although several barriers for optimal use of consumer-led screening exist, results of large, ongoing trials, powered to detect clinical outcomes, are required before health care professionals should support widespread adoption of consumer-led AF screening.

Atrial Fibrillation and Dementia: A Report From the AF-SCREEN International Collaboration.

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.

Paediatric management of a tuberculosis outbreak in an Irish Direct Provision Centre.

Direct Provision in Ireland provides basic needs of food and shelter to asylum seekers while their refugee status is processed. There are a number of issues associated with living conditions in these centres including overcrowding, nutrition and play facilities (1,2). This article outlines the protocol of contact tracing and management of latent tuberculosis infection in the paediatric setting after a confirmed adult case of tuberculosis within a Direct Provision centre in Ireland. This is a retrospective case series of 82 children living in the centre. Twenty-two children were deemed at risk of infection, all asymptomatic. Sixteen children (20%) were treated for possible latent tuberculosis infection with isoniazid for 6-9 months; compliance was good with no side effects reported. This article highlights the risk to vulnerable populations, especially children, when residing in Direct Provision facilities. Initial migrant screening on entry is essential, in addition to improving living conditions and time spent by families in this living environment.

Potential Application of SARS-CoV-2 Rapid Antigen Diagnostic Tests for the Detection of Infectious Individuals Attending Mass Gatherings - A Simulation Study.

Rapid Antigen Diagnostic Tests (RADTs) for the detection of SARS-CoV-2 offer advantages in that they are cheaper and faster than currently used PCR tests but have reduced sensitivity and specificity. One potential application of RADTs is to facilitate gatherings of individuals, through testing of attendees at the point of, or immediately prior to entry at a venue. Understanding the baseline risk in the tested population is of particular importance when evaluating the utility of applying diagnostic tests for screening purposes. We used incidence data from January and from July-August 2021, periods of relatively high and low levels of infection, to estimate the prevalence of infectious individuals in the community at particular time points and simulated mass gatherings by sampling from a series of age cohorts. Nine different illustrative scenarios were simulated, small (n = 100), medium (n = 1,000) and large (n = 10,000) gatherings each with 3 possible age constructs: mostly younger, mostly older or a gathering with equal numbers from each age cohort. For each scenario, we estimated the prevalence of infectious attendees, then simulated the likely number of positive and negative test results, the proportion of cases detected and the corresponding positive and negative predictive values, and the cost per case identified. Our findings suggest that for each reported case on a given day, there are likely to be 13.8 additional infectious individuals also present in the community. Prevalence ranged from 0.26% for "mostly older" events in July-August, to 2.6% for "mostly younger" events in January. For small events (100 attendees) the expected number of infectious attendees ranged from <1 across all age constructs of attendees in July-August, to 2.6 for "mostly younger" events in January. For large events (10,000 attendees) the expected number of infectious attendees ranged from 27 (95% confidence intervals 12 to 45) for mostly older events in July-August, to 267 (95% confidence intervals 134 to 436) infectious attendees for mostly younger attendees in January. Given rapid changes in SARS-CoV-2 incidence over time, we developed an RShiny app to allow users to run updated simulations for specific events.

Numbers of close contacts of individuals infected with SARS-CoV-2 and their association with government intervention strategies.

BACKGROUND: Contact tracing is conducted with the primary purpose of interrupting transmission from individuals who are likely to be infectious to others. Secondary analyses of data on the numbers of close contacts of confirmed cases could also: provide an early signal of increases in contact patterns that might precede larger than expected case numbers; evaluate the impact of government interventions on the number of contacts of confirmed cases; or provide data information on contact rates between age cohorts for the purpose of epidemiological modelling. We analysed data from 140,204 close contacts of 39,861 cases in Ireland from 1st May to 1st December 2020. RESULTS: Negative binomial regression models highlighted greater numbers of contacts within specific population demographics, after correcting for temporal associations. Separate segmented regression models of the number of cases over time and the average number of contacts per case indicated that a breakpoint indicating a rapid decrease in the number of contacts per case in October 2020 preceded a breakpoint indicating a reduction in the number of cases by 11 days. CONCLUSIONS: We found that the number of contacts per infected case was overdispersed, the mean varied considerable over time and was temporally associated with government interventions. Analysis of the reported number of contacts per individual in contact tracing data may be a useful early indicator of changes in behaviour in response to, or indeed despite, government restrictions. This study provides useful information for triangulating assumptions regarding the contact mixing rates between different age cohorts for epidemiological modelling.

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.

Identifying priorities for primary care investment in Ireland through a population-based analysis of avoidable hospital admissions for ambulatory care sensitive conditions (ACSC).

BACKGROUND: In 2016, the Irish acute hospital system operated well above internationally recommended occupancy targets. Investment in primary care can prevent hospital admissions of ambulatory care sensitive conditions (ACSCs). OBJECTIVE: To measure the impact of ACSCs on acute hospital capacity in the Irish public system and identify specific care areas for enhanced primary care provision. DESIGN: National Hospital In-patient Enquiry System data were used to calculate 2011-2016 standardised bed day rates for selected ACSC conditions. A prioritisation exercise was undertaken to identify the most significant contributors to bed days within our hospital system. Poisson regression was used to determine change over time using incidence rate ratios (IRR). RESULTS: In 2016 ACSCs accounted for almost 20% of acute public hospital beds (n=871 328 bed days) with adults over 65 representing 69.1% (n=602 392) of these. Vaccine preventable conditions represented 39.1% of ACSCs. Influenza and pneumonia were responsible for 99.8% of these, increasing by 8.2% (IRR: 1.02; 95% CI 1.02 to 1.03) from 2011 to 2016. Pyelonephritis represented 47.6% of acute ACSC bed days, increasing by 46.5% (IRR: 1.07; 95% CI 1.06 to 1.08) over the 5 years examined. CONCLUSIONS: Prioritisation for targeted investment in integrated care programmes is enabled through analysis of ACSC's in terms of acute hospital bed days. This analysis demonstrates that primary care investment in integrated care programmes for respiratory ACSC's from prevention to rehabilitation at scale could assist with bed capacity in acute hospitals in Ireland. In adults 65 years and over, including chronic obstructive pulmonary disease patients, the current analysis supports targeting community based pulmonary rehabilitation including pneumococcal and influenza vaccination programmes in order to reduce the burden of infection and hospitalisations. Further exploration of pyelonephritis is necessary in order to ascertain patient profile and appropriateness of admissions.

Estimated stroke risk, yield, and number needed to screen for atrial fibrillation detected through single time screening: a multicountry patient-level meta-analysis of 141,220 screened individuals.

BACKGROUND: The precise age distribution and calculated stroke risk of screen-detected atrial fibrillation (AF) is not known. Therefore, it is not possible to determine the number needed to screen (NNS) to identify one treatable new AF case (NNS-Rx) (i.e., Class-1 oral anticoagulation [OAC] treatment recommendation) in each age stratum. If the NNS-Rx is known for each age stratum, precise cost-effectiveness and sensitivity simulations can be performed based on the age distribution of the population/region to be screened. Such calculations are required by national authorities and organisations responsible for health system budgets to determine the best age cutoffs for screening programs and decide whether programs of screening should be funded. Therefore, we aimed to determine the exact yield and calculated stroke-risk profile of screen-detected AF and NNS-Rx in 5-year age strata. METHODS AND FINDINGS: A systematic review of Medline, Pubmed, and Embase was performed (January 2007 to February 2018), and AF-SCREEN international collaboration members were contacted to identify additional studies. Twenty-four eligible studies were identified that performed a single time point screen for AF in a general ambulant population, including people ≥65 years. Authors from eligible studies were invited to collaborate and share patient-level data. Statistical analysis was performed using random effects logistic regression for AF detection rate, and Poisson regression modelling for CHA2DS2-VASc scores. Nineteen studies (14 countries from a mix of low- to middle- and high-income countries) collaborated, with 141,220 participants screened and 1,539 new AF cases. Pooled yield of screening was greater in males across all age strata. The age/sex-adjusted detection rate for screen-detected AF in ≥65-year-olds was 1.44% (95% CI, 1.13%-1.82%) and 0.41% (95% CI, 0.31%-0.53%) for <65-year-olds. New AF detection rate increased progressively with age from 0.34% (<60 years) to 2.73% (≥85 years). Neither the choice of screening methodology or device, the geographical region, nor the screening setting influenced the detection rate of AF. Mean CHA2DS2-VASc scores (n = 1,369) increased with age from 1.1 (<60 years) to 3.9 (≥85 years); 72% of ≥65 years had ≥1 additional stroke risk factor other than age/sex. All new AF ≥75 years and 66% between 65 and 74 years had a Class-1 OAC recommendation. The NNS-Rx is 83 for ≥65 years, 926 for 60-64 years; and 1,089 for <60 years. The main limitation of this study is there are insufficient data on sociodemographic variables of the populations and possible ascertainment biases to explain the variance in the samples. CONCLUSIONS: People with screen-detected AF are at elevated calculated stroke risk: above age 65, the majority have a Class-1 OAC recommendation for stroke prevention, and >70% have ≥1 additional stroke risk factor other than age/sex. Our data, based on the largest number of screen-detected AF collected to date, show the precise relationship between yield and estimated stroke risk profile with age, and strong dependence for NNS-RX on the age distribution of the population to be screened: essential information for precise cost-effectiveness calculations.

Cost-Effectiveness of a National Opportunistic Screening Program for Atrial Fibrillation in Ireland.

OBJECTIVES: To evaluate the cost-effectiveness of a national atrial fibrillation screening program in Ireland involving annual opportunistic pulse palpation of all those older than 65 years during general practitioner consultations, with an electrocardiogram being performed if an irregular pulse is detected. METHODS: A probabilistic Markov model was used to simulate costs and clinical outcomes in a hypothetical cohort of men and women with and without screening over the course of 25 years, using a societal perspective. RESULTS: Screening was associated with an incremental cost-effectiveness ratio of €23,004/quality-adjusted life-year compared with routine care. Nevertheless, if the relative risk of stroke and systematic embolism in screen-detected patients is more than 12% lower than that in patients with atrial fibrillation identified through routine practice, then screening would not be considered cost-effective at a willingness-to-pay threshold of €45,000/quality-adjusted life-year. An analysis comparing alternative combinations of start age and screening interval found that less frequent screening with a later start age may be more cost-effective than an annual screening from age 65 years. CONCLUSIONS: Annual opportunistic screening of men and women aged 65 years and older in primary care in Ireland is likely to be cost-effective using conventional willingness-to-pay thresholds, assuming that those detected through screening have a comparable stroke risk profile as those detected through routine practice. Raising the start age of screening or increasing the screening interval may improve the cost-effectiveness of a prospective screening program.

The farming population in Ireland: mortality trends during the 'Celtic Tiger' years.

BACKGROUND: Although the Irish farming population is a significant occupational group, analysis of their mortality patterns is limited. This study compared mortality trends with other occupational groups and assessed the impact of socio-economic factors. METHODS: Population and mortality data (2000-06) were obtained to calculate standardized mortality ratios (SMRs) by cause of death and matched with socio-economic data. The extent to which variation in mortality was explained by variations in the socio-economic data was determined using multiple regression. RESULTS: Farmers and agricultural workers experienced the highest levels of mortality for all causes of death (2000-06). Farmers are 5.14 times more likely and agricultural workers are 7.35 times more likely to die from any cause of death than the lowest risk group. Circulatory disease is a significant cause of mortality among farmers [SMR = 215.91, 95% confidence interval (CI) = 201.83-229.98]. Other significant causes include cancers (SMR = 156.60, CI = 146.73-166.48) and injuries and poisonings (SMR = 149.69, CI = 135.44-163.93). Agricultural workers have similar mortality trends: circulatory disease (SMR = 226.27; CI = 192.45-260.08), cancers (SMR = 221.44; CI = 193.88-249.00), and injuries and poisonings (SMR = 353.90; CI = 302.48-405.32). From 2000 to 2006, SMRs increased incrementally. Multiple regression identified farm size and income poverty risk as predictors of mortality. CONCLUSION: Irish farmers and agricultural workers have experienced a reversal of mortality trends compared to the 1980s and 1990 s. Policies should target them as a high-risk group.

Years of potential life lost among heroin addicts 33 years after treatment.

OBJECTIVE: To examine premature mortality in terms of years of potential life lost (YPLL) among a cohort of long-term heroin addicts. METHOD: This longitudinal, prospective study followed a cohort of 581 male heroin addicts in California for more than 33 years. In the latest follow-up conducted in 1996/97, 282 subjects (48.5%) were confirmed as deceased by death certificates. YPLL before age 65 years was calculated by causes of death. Ethnic differences in YPLL were assessed among Whites, Hispanics, and African Americans. RESULTS: On average, addicts in this cohort lost 18.3 years (SD=10.7) of potential life before age 65. Of the total YPLL for the cohort, 22.3% of the years lost was due to heroin overdose, 14.0% due to chronic liver disease, and 10.2% to accidents. The total YPLL and YPLL by death cause in addict cohort were significantly higher than that of US population. The YPLL among African Americans was significantly lower than that among Whites or Hispanics. CONCLUSION: The YPLL among addicts was much higher than that in the national population; within the cohort, premature mortality was higher among Whites and Hispanics compared to African American addicts.

Life expectancy and productivity loss among narcotics addicts thirty-three years after index treatment.

This study computed the life expectancy of a cohort of male narcotics addicts followed for 33 years and assessed the productivity lost as a result of premature mortality. The future life expectancy was constructed for the narcotics addicts and for a comparable cohort from the general U.S. population. The average future life expectancy of the cohort was 18.84 years compared to 33.48 years for comparable U.S. males (t = 49.49, p < .00001). As a result of this premature mortality, the estimated monetary value of lost productivity was greater than 174 million dollars. The lives of heroin addicts were severely truncated at productive ages resulting in a loss of potential productivity that increases social and economic burdens.