Treatment of influenza with neuraminidase inhibitors.

PURPOSE OF REVIEW: Seasonal and pandemic influenza are major causes of morbidity and mortality globally. Neuraminidase inhibitors (NAIs) are the only class of antiviral agent recommended for the treatment of currently circulating strains of influenza. There has previously been controversy over the level of evidence for patient benefit with NAIs. We review here the current evidence base for the clinical impact of treatment of influenza with NAIs. RECENT FINDINGS: Meta-analysis of pharma-sponsored studies (including previously unpublished data) shows that NAIs reduce the duration of illness in influenza-infected patients, and suggest a possible reduction in the rate of complications and hospitalization. Meta-analysis of observational studies examining oseltamivir use during the H1N1 2009 pandemic, suggest a reduction in hospitalization rate in community-dwelling patients and a reduction in mortality in hospitalized adults treated with NAIs. Current NAI use in the community and hospitals varies widely but in general they are underutilized. SUMMARY: Although there has been controversy over the level of evidence for patient benefit, a growing body of evidence suggests that treatment of influenza with NAIs is associated with improved outcomes for both patients in the community and more severely unwell patients in hospital. Clinical outcomes are optimal with earlier use and strategies to improve early widespread NAI utilization are needed.

A simple step to improve fat and energy delivery of human milk delivered via bottle-feeding pump, an experimental study.

BACKGROUND: Enteral feeding pump systems deliver decreased amounts of macronutrients in human milk to neonates. This study determined the macronutrient loss associated with a bottle-feeding pump system and the effect of manually mixing the human milk during extended feeds. METHODS: Macronutrient content from samples of donor human milk was analyzed after simulated extended feeds with a bottle-feeding pump system, using a human milk analyzer. Simulations were repeated using manual mixing of the bottle every 30 min during feeding. The percentage of the baseline was calculated, and one-sample t tests and analysis of variance compared the effect of manual mixing and the duration of feeding on macronutrient delivery. RESULTS: The delivery of fat and energy was lower over time, but manual mixing considerably improved retention. The length of feeding impacted fat delivery, with less fat delivered over time (P < 0.001). Manually mixing significantly increased fat delivery (P < 0.001). Similar results were found for energy, with a significant reduction in energy delivery over time (P < 0.001) and significantly more energy delivered with mixing (P < 0.001). Mixing and the duration of feeding had minimal effect on protein or carbohydrate delivery. CONCLUSIONS: Bottle-feeding pump systems are associated with a significant reduction in the delivery of fat and energy of donor human milk. The manual mixing of donor human milk during prolonged feeds is a simple way to improve fat and energy delivery to the neonate.

Metabolic bone disease of prematurity screening and individualized enteral mineral supplementation in high-risk neonates: a quality improvement initiative.

OBJECTIVE: Prompted by an alarmingly low screening rate for metabolic bone disease of prematurity (MBDP), we aimed to increase MBDP screening with serum calcium, phosphorous, and alkaline phosphatase at four to six weeks of life in infants born at <1500 g and <32 gestational weeks from a baseline of 27.37% to 90% within one year. STUDY DESIGN: We used the Institute for Healthcare Improvement's Model for Improvement as a framework. A key driver diagram informed the interventions which were carried out through four Plan-Do-Study-Act cycles. RESULTS: There were 129 and 130 neonates in the pre-intervention baseline group and post-intervention MBDP bundle group, respectively. MBDP bundled primary screening rates increased from 27.37% to 95.56% (p < 0.001). Furthermore, 20% of infants had an individualized change in their enteral mineral supplementation after the initiative. CONCLUSIONS: An interdisciplinary team-based quality improvement approach was effective in altering clinical practice to improve screening and subsequent treatment for MBDP.

Routine, molecular point-of-care testing for SARS-CoV-2 and other respiratory viruses within an acute oncology service improves patient care.

OBJECTIVES: COVID-19 has caused significant challenges for infection prevention measures and patient flow in hospital admission pathways. We aimed to assess the impact of replacing laboratory PCR with molecular point-of-care testing (mPOCT) for respiratory viruses including SARS-CoV-2, within an Acute Oncology Service (AOS). METHODS: This pre- and post-implementation study took place in the AOS of a large teaching hospital, in Southampton, UK. We collected data from two periods: November 25th, 2019 to November 24th, 2020, when respiratory virus testing utilised laboratory PCR, and December 1st, 2020 to May 31st, 2021 following the introduction of mPOCT. The primary outcome was the time to results. RESULTS: 2189 patients were tested in the pre-implementation period and 1540 in the post implementation period. Median (IQR) time to results was 5.8 h (4.2-10.6) pre-implementation and 1.9 h (1.5-3.0) post-implementation (difference -3.6 h [95%CI to -3.8 to -3.5]; p < 0.0001). Median time spent in assessment areas was 6.0 h (4.1-7.9) pre-implementation and 5.5 h (3.8-7.4) post-implementation (p < 0.0001). 20 (0.9%) patients admitted via AOS assessment unit developed hospital-acquired respiratory virus infection pre-implementation versus 0 (0%) post-implementation (p = 0.031). CONCLUSIONS: Routine mPOCT for respiratory viruses, including SARS-CoV-2, was associated with a reduced time to results, reduced time in assessment areas, and a reduction in the rates of hospital-acquired respiratory virus infection in an acute oncology assessment unit.

Clinical impact of syndromic molecular point-of-care testing for gastrointestinal pathogens in adults hospitalised with suspected gastroenteritis (GastroPOC): a pragmatic, open-label, randomised controlled trial.

BACKGROUND: Single-occupancy isolation rooms are a finite resource in UK hospitals but are crucial in preventing transmission of infection. Patients with suspected gastroenteritis are nursed in single-occupancy rooms, but delays in laboratory testing lead to non-infectious patients remaining isolated for prolonged periods unnecessarily. Rapid molecular test panels for gastrointestinal pathogens have a run time of around 1 h but their clinical impact is unknown. We aimed to evaluate the clinical impact of syndromic molecular point-of-care testing (mPOCT) for gastrointestinal pathogens in adult patients presenting to hospital with suspected gastroenteritis on single-occupancy room use and a range of other outcome measures. METHODS: In this pragmatic, open-label, randomised controlled trial, we enrolled adults hospitalised with suspected gastroenteritis in a large UK hospital. Patients were randomly allocated (1:1) to receive syndromic mPOCT of stool or rectal samples, or to routine clinical care (control) with laboratory testing. The primary outcome was the duration of time in single-occupancy rooms assessed on a modified intention-to-treat basis. Secondary outcomes included the time to results, time to de-isolation, antibiotic use, and safety outcomes. The study was registered with ISRCTN, ISRCTN88918395, and is complete. FINDINGS: Between March 20, 2017 and March 17, 2020, from 455 patients assessed for eligibility, we enrolled 278 patients, 138 assigned to mPOCT (one withdrawal) and 140 to the control group. The duration (geometric mean) of single-occupancy room isolation was 1·8 days (95% CI 1·5-2·2) in the mPOCT group compared with 2·6 days (2·2-3·0) in the control group (exponentiated coefficient 0·70 [95% CI 0·56 to 0·87]; p=0·0017). The median (IQR) time to results was 1·7 h (1·5-2·0) for mPOCT and 44·7 h (21·2-66·1) for the control group (p<0·0001). Time to de-isolation was 0·6 days (0·3-1·8) in the mPOCT group compared with 2·2 days (1·2-3·2) in the control group, (p<0·0001). Antibiotics were given in 89 (65%) of 137 in the mPOCT group and 66 (47%) of 140 in the control group (p=0·0028). There were no differences between groups in length of hospital stay, or in safety outcomes including mortality, intensive care unit admission, or readmission to hospital. INTERPRETATION: mPOCT for gastrointestinal pathogens in patients with suspected gastroenteritis returned results more rapidly than conventional testing and was associated with a reduction in single-occupancy room use. However, these benefits need to be balanced against a potential increase in antibiotic use. FUNDING: University Hospital Southampton NHS Foundation Trust.

Geosensor data representation using layered slope grids.

Environmental monitoring applications are designed for supplying derived and often integrated information by tracking and analyzing phenomena. To determine the condition of a target place, they employ a geosensor network to get the heterogeneous sensor data. To effectively handle a large volume of sensor data, applications need a data abstraction model, which supports the summarized data representation by encapsulating raw data. For faster data processing to answer a user's queries with representative attributes of an abstracted model, we propose such a data abstraction model, the Layered Slopes in Grid for Sensor Data Abstraction (LSGSA), which is based on the SGSA. In a single grid-based layer for each sensor type, collected data is represented by slope directional vectors in two layered slopes, such as height and surface. To answer a user query in a central monitoring server, LSGSA is used to reduce the time needed to extract event features from raw sensor data as a preprocessing step for interpreting the observed data. The extracted features are used to understand the current data trends and the progress of a detected phenomenon without accessing raw sensor data.

Aspergillus fumigatus causing vertebral osteomyelitis in an immunocompetent patient: a case report and literature review.

Aspergillus vertebral osteomyelitis causing deformity in immunocompetent patients is uncommon. We describe a previously healthy 68-year-old male who was referred after 2 years of lower thoracic back pain and gibbus. His inflammatory markers and HIV test were normal. Imaging demonstrated bony destruction of T12/L1 and L2 with vertebral collapse. Following inconclusive CT-guided biopsy, he underwent reconstructive spinal surgery. Histopathology showed fungi and Aspergillus fumigatus was cultured. He was treated with isavuconazole 200 mg once daily for 12 months with a satisfactory clinical outcome. We present a summary of recently published cases of atraumatic Aspergillus vertebral osteomyelitis in immunocompetent patients without risk factors. Fungal infection should be considered in culture-negative spondylodiscitis, even in the absence of risk factors.

Combined RT-PCR and Host Response Point-of-Care Testing in Patients Hospitalised with Suspected COVID-19: A Prospective Diagnostic Accuracy Study.

INTRODUCTION: RT-PCR has suboptimal sensitivity for the diagnosis of COVID-19. A composite reference standard comprising RT-PCR plus radiological and clinical features has been recommended for diagnostic accuracy studies. The FebriDx finger prick point-of-care test detects an antiviral host response protein (MxA) in 10 min. We evaluated the diagnostic accuracy of FebriDx and RT-PCR compared to a composite reference standard. METHODS: Adults presenting to hospital with suspected COVID-19 were tested by FebriDx and RT-PCR. A composite reference standard was used to classify patients as having COVID-19 based on RT-PCR positivity, or RT-PCR negativity with COVID-19 radiological findings or other clinical criteria. Measures of accuracy were calculated for MxA alone, RT-PCR alone, and both combined. This study is registered with the ISRCTN (ISRCTN14966673) and has completed. RESULTS: A total of 478 patients were tested, with valid results in 475. Of these 475 patients, 222 (46.7%) were classified as having COVID-19; 192 (40.4%) were RT-PCR positive, and 30 (6.3%) were RT-PCR negative and diagnosed on radiological/clinical criteria. Sensitivity of FebriDx MxA vs the composite reference standard was 186/222 (83.8%, 95% CI 78.3-88.4) and was similar to the sensitivity of RT-PCR (192/222 (86.5%, 95% CI 81.3-90.7), (difference of 2.7%, 95% CI - 3.9 to 9.3, p = 0.42). The sensitivity of combined FebriDx and RT-PCR was 208/222 (93.7%) which was superior to both RT-PCR alone (difference of 9.9, 95% CI 4.1-15.9; p = 0.001) and FebriDx MxA alone (difference of 7.2, 95% CI 1.6-12.9; p = 0.011). CONCLUSION: Sensitivity of combined FebriDx and RT-PCR testing was superior to each alone for the detection of COVID-19 in hospital and may improve infection control and treatment decisions.

FebriDx host response point-of-care testing improves patient triage for coronavirus disease 2019 (COVID-19) in the emergency department.

OBJECTIVES: Patients presenting to hospital with suspected coronavirus disease 2019 (COVID-19), based on clinical symptoms, are routinely placed in a cohort together until polymerase chain reaction (PCR) test results are available. This procedure leads to delays in transfers to definitive areas and high nosocomial transmission rates. FebriDx is a finger-prick point-of-care test (PoCT) that detects an antiviral host response and has a high negative predictive value for COVID-19. We sought to determine the clinical impact of using FebriDx for COVID-19 triage in the emergency department (ED). DESIGN: We undertook a retrospective observational study evaluating the real-world clinical impact of FebriDx as part of an ED COVID-19 triage algorithm. SETTING: Emergency department of a university teaching hospital. PATIENTS: Patients presenting with symptoms suggestive of COVID-19, placed in a cohort in a 'high-risk' area, were tested using FebriDx. Patients without a detectable antiviral host response were then moved to a lower-risk area. RESULTS: Between September 22, 2020, and January 7, 2021, 1,321 patients were tested using FebriDx, and 1,104 (84%) did not have a detectable antiviral host response. Among 1,104 patients, 865 (78%) were moved to a lower-risk area within the ED. The median times spent in a high-risk area were 52 minutes (interquartile range [IQR], 34-92) for FebriDx-negative patients and 203 minutes (IQR, 142-255) for FebriDx-positive patients (difference of -134 minutes; 95% CI, -144 to -122; P < .0001). The negative predictive value of FebriDx for the identification of COVID-19 was 96% (661 of 690; 95% CI, 94%-97%). CONCLUSIONS: FebriDx improved the triage of patients with suspected COVID-19 and reduced the time that severe acute respiratory coronavirus virus 2 (SARS-CoV-2) PCR-negative patients spent in a high-risk area alongside SARS-CoV-2-positive patients.

Design of sensor data processing steps in an air pollution monitoring system.

Environmental monitoring is required to understand the effects of various kinds of phenomena such as a flood, a typhoon, or a forest fire. To detect the environmental conditions in remote places, monitoring applications employ the sensor networks to detect conditions, context models to understand phenomena, and computing technology to process the large volumes of data. In this paper, we present an air pollution monitoring system to provide alarm messages about potentially dangerous areas with sensor data analysis. We design the data analysis steps to understand the detected air pollution regions and levels. The analyzed data is used to track the pollution and to give an alarm. This implemented monitoring system is used to mitigate the damages caused by air pollution.

A comparison of prospective space-time scan statistics and spatiotemporal event sequence based clustering for COVID-19 surveillance.

The outbreak of the COVID-19 disease was first reported in Wuhan, China, in December 2019. Cases in the United States began appearing in late January. On March 11, the World Health Organization (WHO) declared a pandemic. By mid-March COVID-19 cases were spreading across the US with several hotspots appearing by April. Health officials point to the importance of surveillance of COVID-19 to better inform decision makers at various levels and efficiently manage distribution of human and technical resources to areas of need. The prospective space-time scan statistic has been used to help identify emerging COVID-19 disease clusters, but results from this approach can encounter strategic limitations imposed by constraints of the scanning window. This paper presents a different approach to COVID-19 surveillance based on a spatiotemporal event sequence (STES) similarity. In this STES based approach, adapted for this pandemic context we compute the similarity of evolving daily COVID-19 incidence rates by county and then cluster these sequences to identify counties with similarly trending COVID-19 case loads. We analyze four study periods and compare the sequence similarity-based clusters to prospective space-time scan statistic-based clusters. The sequence similarity-based clusters provide an alternate surveillance perspective by identifying locations that may not be spatially proximate but share a similar disease progression pattern. Results of the two approaches taken together can aid in tracking the progression of the pandemic to aid local or regional public health responses and policy actions taken to control or moderate the disease spread.

SARS-CoV-2 viral load at presentation to hospital is independently associated with the risk of death.

Objectives Previous studies have suggested that SARS-CoV-2 viral load, measured on upper respiratory tract samples at presentation to hospital using PCR Cycle threshold (Ct) value, has prognostic utility. However, these studies have not comprehensively adjusted for factors known to be intimately related to viral load. We aimed to evaluate the association between Ct value at admission and patient outcome whilst adjusting carefully for covariates. Methods We evaluated the association between Ct value at presentation and the outcomes of ICU admission and death, in patients hospitalised during the first wave of the pandemic in Southampton, UK. We adjusted for covariates including age, duration of illness and antibody sero-status, measured by neutralisation assay. Results 185 patients were analysed, with a median [IQR] Ct value of 27.9 [22.6-32.1]. On univariate analysis the Ct value at presentation was associated with the risk of both ICU admission and death. In addition, Ct value significantly differed according to age, the duration of illness at presentation and antibody sero-status. On multivariate analysis, Ct value was independently associated with risk of death (aOR 0.84, 95% CI 0.72-0.96; p = 0.011) but not ICU admission (aOR 1.04, 95% CI 0.93-1.16; p = 0.507). Neutralising antibody status at presentation was not associated with mortality or ICU admission (aOR 10.62, 95% CI 0.47-889; p = 0.199 and aOR 0.46, 95% CI 0.10-2.00; p = 0.302, respectively). Conclusions SARS-CoV-2 Ct value on admission to hospital was independently associated with mortality, when comprehensively adjusting for other factors and could be used for risk stratification.

Clinical impact of a routine, molecular, point-of-care, test-and-treat strategy for influenza in adults admitted to hospital (FluPOC): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Diagnosis of influenza in patients admitted to hospital is delayed due to long turnaround times with laboratory testing, leading to inappropriate and late antiviral treatment and isolation facility use. Molecular point-of-care tests (mPOCTs) are highly accurate, easy to use, and generate results in less than 1 h, but high-quality evidence for their effect on management and clinical outcomes is needed. The aim of this study was to assess the clinical impact of an mPOCT on influenza detection, antiviral use, infection control measures, and clinical outcomes in adults admitted to hospital with acute respiratory illness. METHODS: In this multicentre, pragmatic, open-label, randomised controlled trial (FluPOC), we recruited adults admitted to hospital with acute respiratory illness during influenza seasons from two hospitals in Hampshire, UK. Eligible patients were aged 18 years and older, with acute respiratory illness of 10 days or fewer duration before admission to hospital, who were recruited within 16 h of admission to hospital. Participants were randomly assigned (1:1), using random permuted blocks of varying sizes (4, 6 and 8), to receive mPOCT for influenza or routine clinical care (control group). The primary outcome was the proportion of patients infected with influenza who were treated appropriately with antivirals (neuraminidase inhibitors) within 5 days of admission. Safety was assessed in all patients. Secondary outcomes included time to antivirals, isolation facility use, and clinical outcomes. This study is registered with the ISRCTN registry, ISRCTN17197293, and is now complete. FINDINGS: Between Dec 12, 2017, and May 3, 2019, over two influenza seasons, 613 patients were enrolled, of whom 307 were assigned to the mPOCT group and 306 to the control group, and all were analysed. Median age was 62 years (IQR 45-75) and 332 (54%) of 612 participants with data were female. 100 (33%) of 307 patients in the mPOCT group and 102 (33%) of 306 in the control group had influenza. 100 (100%) of 100 patients with influenza were diagnosed in the mPOCT group and 60 (59%) of 102 were diagnosed though routine clinical care in the control group (relative risk 1·7, 95% CI 1·7-1·7; p<0·0001). 99 (99%) of 100 patients with influenza in the mPOCT group were given antiviral treatment within 5 days of admission versus 63 (62%) 102 in the control group (relative risk 1·6, 95% CI 1·4-1·9; p<0·0001). Median time to antivirals was 1·0 h (IQR 0·0 to 2·0) in the mPOCT group versus 6·0 h (0·0 to 12·0) in the control group (difference of 5·0 h [95% CI 0·0-6·0; p=0·0039]). 70 (70%) of 100 patients with influenza in the mPOCT group were isolated to single-room accommodation versus 39 (38%) of 102 in the control group (relative risk 1·8 [95% CI 1·4-2·4; p<0·0001]). 19 adverse events occurred among patients with influenza in the mPOCT group compared with 34 events in the control group. No patients with influenza died in the mPOCT group and two (2%) died in the control group (p=0·16). INTERPRETATION: Routine mPOCT for influenza was associated with improved influenza detection and improvements in appropriate and timely antiviral and isolation facility use. Routine mPOCT should replace laboratory-based diagnostics for acute admissions to hospital during the influenza season. FUNDING: National Institute for Health Research.

Pragmatic multicentre randomised controlled trial evaluating the impact of a routine molecular point-of-care 'test-and-treat' strategy for influenza in adults hospitalised with acute respiratory illness (FluPOC): trial protocol.

BACKGROUND: Influenza infections often remain undiagnosed in patients admitted to hospital due to lack of routine testing. When tested for, the diagnosis and treatment of influenza are often delayed due to the slow turnaround times of centralised laboratory PCR testing. Newer molecular systems, have comparable accuracy to laboratory PCR testing, and can generate a result in under 1 hour, making them potentially deployable as point-of-care tests (POCTs). High-quality evidence for the impact of routine POCT for influenza on clinical outcomes is, however, currently lacking. This large pragmatic multicentre randomised controlled trial aims to address this evidence gap. METHODS AND ANALYSIS: The FluPOC trial is a pragmatic, multicentre, randomised controlled trial evaluating adults admitted to a large teaching hospital and a district general hospital with an acute respiratory illness, during influenza season and defined by Public Health England. Up to 840 patients will be recruited over up to three influenza seasons, and randomised (1:1) to receive either POCT using the FilmArray respiratory panel, or routine clinical care. Clinical and infection control teams will be informed of the results in real time and where influenza is detected clinical teams will be encouraged to offer neuraminidase inhibitor (NAI) treatment in accordance with national guidelines. Those allocated to standard clinical care will have a swab taken for later analysis to allow assessment of missed diagnoses. The outcomes assessment will be by retrospective case note analysis. The outcome measures include the proportion of influenza-positive patients detected and appropriately treated with NAIs, isolation facility use, antibiotic use, length of hospital stay, complications and mortality. ETHICS AND DISSEMINATION: Prior to commencing the study, approval was obtained from the South Central Hampshire A Ethics Committee (reference 17/SC/0368, granted 7 September 2017). Results generated from this protocol will be published in peer-reviewed scientific journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN17197293.

Hospitalised adults with pneumonia are frequently misclassified as another diagnosis.

Using data from a large randomised controlled trial of adults hospitalised with acute respiratory illness, we examined the reliability of pneumonia diagnosis on discharge documentation. 50 (28.2%) of 177 patients with a pneumonia diagnosis had no radiological evidence of pneumonia. 67 (34.9%) of 192 patients with clinico-radiological evidence of pneumonia did not have a diagnosis of pneumonia listed; 'COPD exacerbation' or 'lower respiratory tract infection' was often listed instead. These patients more frequently had a respiratory comorbidity and lower oxygen saturations, CRP and temperature at presentation. Pneumonia diagnoses misclassification on discharge documentation may have clinical, financial, and research data implications.

Five winters of pneumococcal serotype replacement in UK carriage following PCV introduction.

The seven-valent pneumococcal conjugate vaccine (PCV7) was added to the UK national immunisation programme in September 2006. PCV13 replaced PCV7 in April 2010. As carriage precedes disease cases this study collected carried pneumococci from children each winter from 2006/7 to 2010/11 over PCV introduction. Conventional microbiology and whole genome sequencing were utilised to characterise pneumococcal strains. Overall prevalence of pneumococcal carriage remained stable. Vaccine serotypes (VT) decreased (p<0.0001) with concomitant increases in non-vaccine serotypes (NVT). In winter 2010/11 only one isolate of PCV7 VT was observed (6B). PCV13 unique VTs decreased between winters immediately preceding and following PCV13 introduction (p=0.04). Significant decreases for VTs 6B, 19F, 23F (PCV7) and 6A (PCV13) and increases for NVT 21, 23B, 33F and 35F were detected. The serotype replacement was accompanied by parallel changes in genotype prevalence for associated sequence types with clonal expansion contributing to replacement. By winter 2010/11, serotype coverage of PCV7 and PCV13 was 1% and 11% respectively. VT replacement was observed for PCV7 and PCV13 serotypes. Conjugate vaccine design and use requires continuous monitoring and revision.

Analyzing spatial and temporal (222)Rn trends in Maine.

Prolonged radon exposure has been linked to lung cancer. Cancer registry data indicates excess risk for age-adjusted lung cancer in Maine. Maine's mean residential radon activity exceeds the EPA maximum contaminant level (MCL). This paper describes the application of spatial autocorrelation methods to retrospective data as a means of analyzing radon activity in Maine. Retrospective air and well water radon activity data, sampled throughout Maine between 1993 and 2008, are standardized and geocoded for analysis. Three spatial autocorrelation algorithms-local Getis-Ord, local Moran, and spatial scan statistic-are used to identify spatial, temporal, and spatiotemporal radon activity clusters and/or outliers. Spatial clusters of high air- and well water-Rn activity are associated with Maine's Lucerne and Sebago granitic formations. Spatial clusters of low air- and well water-Rn activity are associated with Biddeford Granite and the metamorphic bedrock formation Silurian Ordovician Vassalboro. Space-time analysis indicates that most spatial clusters persist over the period of sampling. No significant temporal clusters are identified. Persistent spatial variations in radon may help to better understand and predict radon-related health risks associated with Maine residences.