ABSTRACT
Consolidation of multi-domain risk management research is essential for strategies facilitating the concerted government (educational) and population-level (behavioural) actions required to reduce microbial private groundwater contamination. However, few studies to date have synthesised this literature or sought to ascertain the causal generality and extent of supply contamination and preventive responses. In light of the Republic of Ireland (ROI) and Ontario's high reliance and research focus on private wells and consequent utility for empirical comparison, a scoping review of pertinent literature (1990-2022) from both regions was undertaken. The SPICE (Setting, Perspective, Intervention, Comparison, Evaluation) method was employed to inform literature searches, with Scopus and Web of Science selected as primary databases for article identification. The review identified 65 relevant articles (Ontario = 34, ROI = 31), with those investigating well user actions (n = 22) and groundwater quality (n = 28) the most frequent. A markedly higher pooled proportion of private supplies in the ROI exhibited microbial contamination (38.3 % vs. 4.1 %), despite interregional similarities in contamination drivers (e.g., weather, physical supply characteristics). While Ontarian well users demonstrated higher rates of historical (≥ 1) and annual well testing (90.6 % vs. 71.1 %; 39.1 % vs. 8.6 %) and higher rates of historical well treatment (42.3 % vs. 24.3 %), interregional levels of general supply knowledge were analogous (70.7 % vs. 71.0 %). Financial cost, organoleptic properties and residence on property during supply construction emerged as predictors of cognition and behaviour in both regions. Review findings suggest broad interregional similarities in drivers of supply contamination and individual-level risk mitigation, indicating that divergence in contamination rates may be attributable to policy discrepancies - particularly well testing incentivisation. The paucity of identified intervention-oriented studies further highlights the importance of renewed research and policy agendas for improved, targeted well user outreach and incentivised, convenience-based services promoting routine supply maintenance.
Subject(s)
Groundwater , Water Supply , Risk Assessment , Risk Management , Ireland , Water WellsABSTRACT
Understanding patient progression from symptomatic COVID-19 infection to a severe outcome represents an important tool for improved diagnoses, surveillance, and triage. A series of models have been developed and validated to elucidate hospitalization, admission to an intensive care unit (ICU) and mortality in patients from the Republic of Ireland. This retrospective cohort study of patients with laboratory-confirmed symptomatic COVID-19 infection included data extracted from national COVID-19 surveillance forms (i.e., age, gender, underlying health conditions, occupation) and geographically-referenced potential predictors (i.e., urban/rural classification, socio-economic profile). Generalised linear models and recursive partitioning and regression trees were used to elucidate COVID-19 progression. The incidence of symptomatic infection over the study-period was 0.96% (n = 47,265), of whom 3781 (8%) required hospitalisation, 615 (1.3%) were admitted to ICU and 1326 (2.8%) died. Models demonstrated an increasingly efficacious fit for predicting hospitalization [AUC 0.816 (95% CI 0.809, 0.822)], admission to ICU [AUC 0.885 (95% CI 0.88 0.89)] and death [AUC of 0.955 (95% CI 0.951 0.959)]. Severe obesity (BMI ≥ 40) was identified as a risk factor across all prognostic models; severely obese patients were substantially more likely to receive ICU treatment [OR 19.630] or die [OR 10.802]. Rural living was associated with an increased risk of hospitalization (OR 1.200 (95% CI 1.143-1.261)]. Urban living was associated with ICU admission [OR 1.533 (95% CI 1.606-1.682)]. Models provide approaches for predicting COVID-19 prognoses, allowing for evidence-based decision-making pertaining to targeted non-pharmaceutical interventions, risk-based vaccination priorities and improved patient triage.
Subject(s)
COVID-19/epidemiology , Obesity, Morbid/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19/mortality , Comorbidity , Evidence-Based Medicine , Female , Hospital Mortality , Hospitalization , Humans , Incidence , Intensive Care Units , Ireland/epidemiology , Linear Models , Male , Middle Aged , Population Surveillance , Prognosis , Retrospective Studies , Rural Population/statistics & numerical data , Socioeconomic Factors , Urban Population/statistics & numerical dataABSTRACT
Extreme Weather Events (EWEs) impose a substantial health and socio-economic burden on exposed populations. Projected impacts on public health, based on increasing EWE frequencies since the 1950s, alongside evidence of human-mediated climatic change represents a growing concern. To date, the impacts of EWEs on mental health remain ambiguous, largely due to the inherent complexities in linking extreme weather phenomena with psychological status. This exploratory investigation provides a new empirical and global perspective on the psychological toll of EWEs by exclusively focusing on psychological morbidity among individuals exposed to such events. Morbidity data collated from a range of existing psychological and well-being measures have been integrated to develop a single ("holistic") metric, namely, psychological impairment. Morbidity, and impairment, were subsequently pooled for key disorders-, specifically PTSD, anxiety and depression. A "composite" (any impairment) post-exposure pooled-prevalence rate of 23% was estimated, with values of 24% calculated for depression and â17% for both PTSD and anxiety. Notably, calculated pooled odds ratios (pOR = 1.9) indicate a high likelihood of any negative psychological outcome (+90%) following EWE exposure. Pooled analyses of reported risk factors (p < 0.05) highlight the pronounced impacts of EWEs among individuals with higher levels of event exposure or experienced stressors (14.5%) and socio-demographic traits traditionally linked to vulnerable sub-populations, including female gender (10%), previous history (i.e., pre-event) of psychological impairment (5.5%), lower socio-economic status (5.5%), and a lower education level (5.2%). Inherent limitations associated with collating mental health data from populations exposed to EWEs, and key knowledge gaps in the field are highlighted. Study findings provide a robust evidence base for developing and implementing public health intervention strategies aimed at ameliorating the psychological impacts of extreme weather among exposed populations.
Subject(s)
Anxiety Disorders , Extreme Weather , Mental Health , Benchmarking , Climate Change , Humans , WeatherABSTRACT
BACKGROUND: Ireland frequently reports the highest annual Crude Incidence Rates (CIRs) of cryptosporidiosis in the EU, with national CIRs up to ten times the EU average. Accordingly, the current study sought to examine the spatiotemporal trends associated with this potentially severe protozoan infection. METHODS: Overall, 4509 cases of infection from January 2008 to December 2017 were geo-referenced to a Census Small Area (SA), with an ensemble of geo-statistical approaches including seasonal decomposition, Local Moran's I, and space-time scanning used to elucidate spatiotemporal patterns of infection. RESULTS: One or more confirmed cases were notified in 3413 of 18,641 Census SAs (18.3%), with highest case numbers occurring in the 0-5-year range (n = 2672, 59.3%). Sporadic cases were more likely male (OR 1.4) and rural (OR 2.4), with outbreak-related cases more likely female (OR 1.4) and urban (OR 1.5). Altogether, 55 space-time clusters (≥ 10 confirmed cases) of sporadic infection were detected, with three "high recurrence" regions identified; no large urban conurbations were present within recurrent clusters. CONCLUSIONS: Spatiotemporal analysis represents an important indicator of infection patterns, enabling targeted epidemiological intervention and surveillance. Presented results may also be used to further understand the sources, pathways, receptors, and thus mechanisms of cryptosporidiosis in Ireland.
Subject(s)
Cryptosporidiosis , Cryptosporidiosis/epidemiology , Disease Outbreaks , Female , Humans , Incidence , Ireland/epidemiology , Male , Rural PopulationABSTRACT
Risk communication represents the optimal instrument for decreasing the incidence of private groundwater contamination and associated waterborne illnesses. However, despite attempts to promote voluntary well maintenance in high groundwater-reliant regions such as the Republic of Ireland, awareness levels of supply status (e.g. structural integrity) have remained low. As investigations of supply awareness are often thematically narrow and homogeneous with respect to sub-population, revised analyses of awareness among both current and future supply owners (i.e. adults of typical well owner and student age) are necessary. Accordingly, the current study utilised a national survey of well users and an age-based comparison of supply awareness. Awareness was measured among 560 Irish private well users using a multi-domain scoring framework and analysed in conjunction with experiential variables including experience of extreme weather events and previous household infections, and perceived self-efficacy in maintaining supply. Respondents displayed a median overall awareness score of 66.7%, with supply owners (n = 399) and students (n = 161) exhibiting median scores of 75% and 58.3%. Awareness among both combined respondent subsets and well owners was significantly related to gender, well use factors and self-perceived behavioural efficacy while awareness among students was not correlated with any independent variable. Cluster analysis identified three distinct respondent groups characterised by awareness score and gender in both current and future well owner subsets. Male well owners and students displayed higher perceived self-efficacy irrespective of awareness score while female well owners that demonstrated high awareness were significantly more likely to report postgraduate educational (p < 0.001). Findings suggest that recent experience of extreme weather events does not significantly influence supply awareness and mirror previously identified knowledge differences between well owners and young adults. Age, gender, supply use and perceived self-efficacy emerge as recurring focal points and accordingly merit consideration from groundwater and health communication practitioners for future risk interventions.
Subject(s)
Groundwater , Water Supply , Cluster Analysis , Cross-Sectional Studies , Female , Humans , Ireland , Male , Young AdultABSTRACT
Extreme weather events (EWEs) may significantly increase pathogenic contamination of private (unregulated) groundwater supplies. However, due to the paucity of protective guidance, private well users may be ill-equipped to undertake adaptive actions. With rising instances of waterborne illness documented in groundwater-dependent, developed regions such as the Republic of Ireland, a better understanding of well user risk perceptions pertaining to EWEs is required to establish appropriate educational interventions. To this end, the current study employed an online and physical questionnaire to identify current risk perceptions and correspondent predictors among Irish private well users concerning extreme weather. Respondents were elicited via purposive sampling, with 515 private well users elucidating perceived supply contamination risk in the wake of five EWEs between the years 2013-2018 including drought and pluvial flooding. A novel scoring protocol was devised to quantify overall risk perception (i.e. perceived likelihood, severity and consequences) of extreme weather impacts. Overall risk perception of EWEs was found to demonstrate a significant relationship with gender (p = 0.017) and event experience (p < 0.001), with female respondents and those reporting prior event experience exhibiting higher median risk perception scores. Risk perception was additionally mediated by perceived self-efficacy in undertaking supply maintenance (p = 0.001), as well users citing confidence in ability scored significantly lower than those citing no confidence. Two-step cluster analysis identified three distinct respondent subsets based on risk perception of EWEs (high, moderate and low perception), with female respondents and those with a third-level education significantly more likely to fall within the high perception cluster. Study findings affirm that certain demographic, experiential and cognitive factors exert a significant influence on private well user risk perceptions of EWE impacts and highlight potential focal points for future educational interventions seeking to reduce the risk of human infection associated with groundwater and extreme weather.
Subject(s)
Extreme Weather , Groundwater , Climate Change , Cognition , Demography , Humans , Ireland , Perception , Water SupplyABSTRACT
Verocytotoxin-producing E. coli (VTEC) are important agents of diarrhoeal disease in humans globally. As a noted waterborne disease, emphasis has been given to the study VTEC in surface waters, readily susceptible to microbial contamination. Conversely, the status of VTEC in potable groundwater sources, generally regarded as a "safe" drinking-water supply remains largely understudied. As such, this investigation presents the first scoping review seeking to determine the global prevalence of VTEC in groundwater supply sources intended for human consumption. Twenty-three peer-reviewed studies were identified and included for data extraction. Groundwater sample and supply detection rates (estimated 0.6 and 1.3%, respectively) indicate VTEC is infrequently present in domestic groundwater sources. However, where generic (fecal indicator) E. coli are present, the VTEC to E. coli ratio was found to be 9.9%, representing a latent health concern for groundwater consumers. Geographically, extracted data indicates higher VTEC detection rates in urban (5.4%) and periurban (4.9%) environments than in rural areas (0.9%); however, this finding is confounded by the predominance of research studies in lower income regions. Climate trends indicate local environments classified as 'temperate' (14/554; 2.5%) and 'cold' (8/392; 2%) accounted for a majority of supply sources with VTEC present, with similar detection rates encountered among supplies sampled during periods typically characterized by 'high' precipitation (15/649; 2.3%). Proposed prevalence figures may find application in preventive risk-based catchment and groundwater quality management including development of Quantitative Microbial Risk Assessments (QMRA). Notwithstanding, to an extent, a large geographical disparity in available investigations, lack of standardized reporting, and bias in source selection, restrict the transferability of research findings. Overall, the mechanisms responsible for VTEC transport and ingress into groundwater supplies remain ambiguous, representing a critical knowledge gap, and denoting a distinctive lack of integration between hydrogeological and public health research. Key recommendations and guidelines are provided for prospective studies directed at increasingly integrative and multi-disciplinary research.
Subject(s)
Groundwater , Shiga-Toxigenic Escherichia coli , Waterborne Diseases , Humans , Prospective Studies , Water SupplyABSTRACT
Cryptosporidiosis is one of the leading causes of diarrhoeal illness and mortality induced by protozoan pathogens worldwide. As a largely waterborne disease, emphasis has been given to the study of Cryptosporidium spp. in surface waters, readily susceptible to pathogenic contamination. Conversely, the status of Cryptosporidium in potable groundwater sources, generally regarded as a pristine and "safe" drinking-water supply owing to (sub)-soil protection, remains largely unknown. As such, this investigation presents the first literature review aimed to ascertain the global prevalence of Cryptosporidium in groundwater supply sources intended for human consumption. Thirty-seven peer-reviewed studies were identified and included in the review. Groundwater sample and supply detection rates (estimated 10-20%) indicate Cryptosporidium is frequently present in domestic groundwater sources, representing a latent health concern for groundwater consumers. Specifically, sample (10.4%) and source (19.1%) detection rates deriving from comprehensive "temporal" investigations are put forward as representative of a contamination 'baseline' for Cryptosporidium in 'domestic' groundwater supplies. Proposed 'baseline' prevalence figures are largely applicable in preventive risk-based catchment and groundwater quality management including the formulation of Quantitative Microbial Risk Assessment (QMRA). Notwithstanding, a large geographical disparity in available investigations and lack of standardized reporting restrict the transferability of research findings. Overall, the mechanisms responsible for Cryptosporidium transport and ingress into groundwater supplies remain ambiguous, representing a critical knowledge gap, and denoting a distinctive lack of integration between groundwater and public-health sub-disciplines among investigations. Key recommendations and guidelines are provided for prospective studies directed at more integrative and multi-disciplinary research.
Subject(s)
Cryptosporidiosis , Cryptosporidium , Groundwater , Animals , Humans , Prevalence , Prospective Studies , Risk Factors , Water SupplyABSTRACT
Groundwater contamination constitutes a significant health risk for private well users residing in rural areas. As the responsibility to safeguard rural private domestic groundwater typically rests with non-expert homeowners, interventions promoting risk mitigation and awareness represent the most viable means of preventing supply contamination. However, no global review or pooled analyses of these interventions has been undertaken to date. The current study sought to identify and quantify the performance of private well interventions from 1990 to 2018 via a global systematised review and pooled analysis. The PICO (Population-Intervention-Comparison-Outcome) approach was employed for literature identification. Relevant studies were statistically analysed across two quantitative outcome (performance) types, namely knowledge and behaviour, controlling for intervention characteristics and country development status. Mean behavioural and knowledge attainment across interventions was 53% and 48%, respectively, with interventions in economically developed regions exhibiting higher behavioural outcomes (56% vs. 45%) than those in developing regions. Geographically, interventions were located in southern or southeast Asia (n = 23), North America (n = 15), Central America (n = 1) and Africa (n = 1), with none identified in Australia/Oceania, Europe, or South America. Behavioural outcomes were significantly associated with presence of educational/research coordinator (p = 0.023), with these interventions attaining higher levels of efficacy (+74%) than those implemented by other coordinator types. Findings indicate that instructor-led, practical interventions allied with both large- and local-scale awareness-raising campaigns represent an optimum approach for future private well risk interventions. Subsequent adoption of such interventions may lead to increased levels of private well maintenance and provide a point of reference for myriad water and health communication contexts.
Subject(s)
Groundwater , Humans , RiskABSTRACT
Extreme weather events (EWEs) are increasing in frequency, posing a greater risk of adverse human health effects. As such, developing sociological and psychological based interventions is paramount to empowering individuals and communities to actively protect their own health. Accordingly, this study compared the efficacy of two established social-cognitive models, namely the Health Beliefs Model (HBM) and Risks-Attitudes-Norms-Abilities-Self-regulation (RANAS) framework, in predicting health behaviours following EWEs. Surface water flooding was used as the exemplar EWE in the current study, due to the increasing incidence of these events in the Republic of Ireland over the past decade. Levels of prior experience with flooding were considered for analyses and comparative tools included a number of variables predicting health behaviours and intervention potential scores (i.e. measure of impact of targeting each model element). Results suggest that the RANAS model provides a robust foundation for designing interventions for any level of experience with an extreme weather event, however, use of the simpler HBM may be more cost-effective among participants unacquainted with an EWE and in relatively infrequent health threat scenarios. Results provide an evidence base for researchers and policymakers to appropriately engage with populations about such threats and successfully promote spatiotemporally appropriate health behaviours in a changing climate.
Subject(s)
Environmental Exposure/statistics & numerical data , Health Behavior , Models, Theoretical , Water Pollution/statistics & numerical data , Waterborne Diseases/epidemiology , Groundwater , Humans , Ireland/epidemiology , Water Supply/statistics & numerical dataABSTRACT
The performance of indwelling medical devices that depend on an interface with soft tissue is plagued by complex, unpredictable foreign body responses. Such devices-including breast implants, biosensors, and drug delivery devices-are often subject to a collection of biological host responses, including fibrosis, which can impair device functionality. This work describes a milliscale dynamic soft reservoir (DSR) that actively modulates the biomechanics of the biotic-abiotic interface by altering strain, fluid flow, and cellular activity in the peri-implant tissue. We performed cyclical actuation of the DSR in a preclinical rodent model. Evaluation of the resulting host response showed a significant reduction in fibrous capsule thickness (P = 0.0005) in the actuated DSR compared with non-actuated controls, whereas the collagen density and orientation were not changed. We also show a significant reduction in myofibroblasts (P = 0.0036) in the actuated group and propose that actuation-mediated strain reduces differentiation and proliferation of myofibroblasts and therefore extracellular matrix production. Computational models quantified the effect of actuation on the reservoir and surrounding fluid. By adding a porous membrane and a therapy reservoir to the DSR, we demonstrate that, with actuation, we could (i) increase transport of a therapy analog and (ii) enhance pharmacokinetics and time to functional effect of an inotropic agent. The dynamic reservoirs presented here may act as a versatile tool to further understand, and ultimately to ameliorate, the host response to implantable biomaterials.
ABSTRACT
BACKGROUND: In trials incorporating a health economic evaluation component, reliable validated measures for health-related quality of life (HRQOL) are essential. The EQ-5D is the preferred measure for cost-effectiveness analysis in UK trials. This paper presents a qualitative evaluation of the use of the EQ-5D-3L in a feasibility randomised control trial with participants who had a mild- to moderate learning disability and type 2 diabetes. METHODS: Researchers administered the EQ-5D-3L to 82 participants at baseline and 77 at follow-up. After each interview, researchers rated the ease of administering the EQ-5D-3L and made free-text entries on the administration experience. For a subset of 16 interviews, researchers audio-recorded more detailed journal entries. Ease of administration data were analysed using descriptive statistics. Free-text responses were subject to a basic content analysis. The EQ-5D-3L-related journal entries were transcribed, coded and analysed thematically. RESULTS: Over half of participants were perceived to experience difficulty answering some or all of the items in the EQ-5D-3L (60% at baseline; 54% at follow-up). Analysis of the free-text entries and audio journals identified four themes that question the use of the EQ-5D-3L in this population. The first theme is related to observations of participant intellectual ability and difficulties, for example, in understanding the wording of the measure. Theme 2 is related to the normalisation of adjustments for impairments, which rendered the measure less sensitive in this population. Theme 3 is related to researcher adaptation and non-standard administration. An overarching fourth theme was identified in that people with learning disabilities were viewed as 'unreliable witnesses' by both researchers and supporters. CONCLUSIONS: It is recommended that the EQ-5D-3L should not be used in isolation to assess health-related quality of life outcomes in trials research in adults with a learning disability. Further research is required to develop and evaluate a version of the EQ-5D appropriate for this population in trials research. It is unrealistic to expect that adjustments to the wording alone will deliver an appropriate measure: supporter or researcher involvement will almost always be required. This requirement needs to be factored into the development and administration guidelines of any new version of the EQ-5D for adults with a learning disability. TRIAL REGISTRATION: Current Controlled Trials ISRCTN41897033 [registered 21 January 2013].
ABSTRACT
AIMS: To undertake a feasibility randomized controlled trial of supported self-management vs treatment as usual in a population of adults with obesity, Type 2 diabetes and an intellectual disability. METHODS: We conducted an individually randomized feasibility trial. Participants were adults aged >18 years with a mild or moderate intellectual disability, living in the community with Type 2 diabetes, on any therapy other than insulin. Participants had mental capacity to consent to research and the intervention. Inclusion criteria included HbA1c > 48 mmol/mol (6.5%), BMI >25 kg/m2 , or self-reported physical activity below national guideline levels. The experimental intervention was standardized supported self-management delivered by diabetes specialist nurses plus treatment as usual, compared with treatment as usual alone. Feasibility outcomes included: recruitment and retention; intervention acceptability and feasibility; data collection and completeness for physiological state and values for candidate primary outcomes (HbA1c and BMI). RESULTS: A total of 82 participants (89% of those contacted and eligible) were randomized. All supported self-management sessions were completed by 35/41 participants (85%); only four completed no sessions. Data on the follow-up candidate primary outcomes HbA1c and BMI were obtained for 75/82 (91%) and 77/82 participants (94%), respectively. The mean baseline HbA1c was 56±16.5 mmol/mol (7.3±1.5%) and the mean BMI was 34±7.6 kg/m2 . CONCLUSIONS: Adherence to supported self-management and willingness to have blood taken for outcome measurement was good. A definitive randomized controlled trial is feasible in this population. (Trial registration: Current Controlled Trials ISRCTN41897033).
Subject(s)
Diabetes Mellitus, Type 2/nursing , Intellectual Disability/complications , Obesity/complications , Self-Management/methods , Affect , Blood Pressure/physiology , Body Mass Index , Diabetes Mellitus, Type 2/psychology , Feasibility Studies , Female , Glycated Hemoglobin/metabolism , House Calls/statistics & numerical data , Humans , Intellectual Disability/nursing , Male , Medication Adherence , Middle Aged , Obesity/nursing , Social Support , Surveys and QuestionnairesABSTRACT
Significant volumes of research over the past four decades has sought to elucidate the social, infrastructural, economic, and human health effects of climate change induced surface flooding. To date, epidemiological and public health studies of flooding events have focused on mental health effects, vector-borne diseases, and infectious enteric disease due to floodwater contact (i.e. typically low consumption rates). The inherent nature of groundwater (i.e. out of sight, out of mind) and the widely held belief that aquifers represent a pristine source of drinking water due to natural attenuation may represent the "perfect storm" causing direct consumption of relatively large volumes of surface flood-contaminated groundwater. Accordingly, the current study sought to systematically identify and synthesize all available peer-reviewed literature pertaining to the nexus between surface flooding, groundwater contamination and human gastroenteric outcomes. Just 14 relevant studies were found to have been published during the period 1980-2017, thus highlighting the fact that this potentially significant source of climate-related exposure to environmental infection has remained understudied to date. Studies differed significantly in terms of type and data reporting procedures, making it difficult to discern clear trends and patterns. Approximately 945 confirmed cases of flood-related enteric disease were examined across studies; these concurred with almost 10,000 suspected cases, equating to approximately 20 suspected cases per confirmed case. As such, no regional, national or global estimates are available for the human gastrointestinal health burden of flood-related groundwater contamination. In light of the demonstrable public health significance of the concurrent impacts of groundwater susceptibility and climate change exacerbation, strategies to increase awareness about potential sources of contamination and motivate precautionary behaviour (e.g. drinking water testing and treatment, supply interruptions) are necessary. Mainstreaming climate adaptation concerns into planning policies will also be necessary to reduce human exposure to waterborne sources of enteric infection.
Subject(s)
Developed Countries , Floods , Groundwater/chemistry , Water Pollution/analysis , Water Supply/standards , Waterborne Diseases/epidemiology , Climate Change , Humans , Public Health , Water Pollution/adverse effectsABSTRACT
ARCTIC was a multicenter, randomized-controlled, open, phase IIB non-inferiority trial in previously untreated chronic lymphocytic leukemia (CLL). Conventional frontline therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). The trial hypothesized that including mitoxantrone with low-dose rituximab (FCM-miniR) would be non-inferior to FCR. A total of 200 patients were recruited to assess the primary end point of complete remission (CR) rates according to IWCLL criteria. Secondary end points were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity, safety and cost-effectiveness. The trial closed following a pre-planned interim analysis. At final analysis, CR rates were 76 FCR vs 55% FCM-miniR (adjusted odds ratio: 0.37; 95% confidence interval: 0.19-0.73). MRD-negativity rates were 54 FCR vs 44% FCM-miniR. More participants experienced serious adverse reactions with FCM-miniR (49%) compared to FCR (41%). There are no significant differences between the treatment groups for PFS and OS. FCM-miniR is not expected to be cost-effective over a lifetime horizon. In summary, FCM-miniR is less well tolerated than FCR with an inferior response and MRD-negativity rate and increased toxicity, and will not be taken forward into a confirmatory trial. The trial demonstrated that oral FCR yields high response rates compared to historical series with intravenous chemotherapy.
Subject(s)
Antineoplastic Agents/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Rituximab/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Antineoplastic Agents/economics , Costs and Cost Analysis , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Rituximab/adverse effects , Rituximab/economics , Survival AnalysisABSTRACT
Ireland reports the highest incidence of verotoxigenic Escherichia coli (VTEC) infection in Europe. This study investigated potential risk factors for confirmed sporadic and outbreak primary VTEC infections during 2008-2013. Overall, 989 VTEC infections including 521 serogroup O157 and 233 serogroup O26 were geo-referenced to 931 of 18 488 census enumeration areas. The geographical distribution of human population, livestock, unregulated groundwater sources, domestic wastewater treatment systems (DWWTS) and a deprivation index were examined relative to notification of VTEC events in 524 of 6242 rural areas. Multivariate modelling identified three spatially derived variables associated with VTEC notification: private well usage [odds ratio (OR) 6·896, P < 0·001], cattle density (OR 1·002, P < 0·001) and DWWTS density (OR 0·978, P = 0·002). Private well usage (OR 18·727, P < 0·001) and cattle density (OR 1·001, P = 0·007) were both associated with VTEC O157 infection, while DWWTS density (OR 0·987, P = 0·028) was significant within the VTEC O26 model. Findings indicate that VTEC infection in the Republic of Ireland is particularly associated with rural areas, which are associated with a ubiquity of pathogen sources (cattle) and pathways (unregulated groundwater supplies).
Subject(s)
Escherichia coli Infections/epidemiology , Shiga-Toxigenic Escherichia coli/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Animal Husbandry , Animals , Cattle , Child , Child, Preschool , Drainage, Sanitary , Escherichia coli Infections/microbiology , Female , Humans , Infant , Infant, Newborn , Ireland/epidemiology , Male , Middle Aged , Retrospective Studies , Risk Factors , Rural Population , Young AdultABSTRACT
OBJECTIVE: The aim of this study was to assess the cost effectiveness of silicone and alginate impressions for complete dentures. METHODS: Cost effectiveness analyses were undertaken alongside a UK single centre, double blind, controlled, crossover clinical trial. Taking the perspective of the healthcare sector, effectiveness is measured using the EuroQol (EQ-5D-3L) which provides a single index value for health status that may be combined with time to produce quality adjusted life years (QALYs); and Oral Health Impact Profile (OHIP-EDENT). Incremental cost effectiveness ratios are presented representing the additional cost per one unit gained. RESULTS: Mean cost was higher in the silicone impression group (£388.57 vs. £363.18). Negligible between-group differences were observed in QALY gains; the silicone group had greater mean OHIP-EDENT gains. The additional cost using silicone was £3.41 per change of one point in the OHIP-EDENT. CONCLUSIONS: The silicone group was more costly, driven by the cost of materials. Changes in the EQ-5D and QALY gains over time and between arms were not statistically significant. Change in OHIP-EDENT score showed greater improvement in the silicone group and the difference between arms was statistically significant. Given negligible QALY gains and low level of resource use, results must be treated with caution. It is difficult to make robust claims about the comparative cost-effectiveness. CLINICAL SIGNIFICANCE: Silicone impressions for complete dentures improve patients' quality of life (OHIP-EDENT score). The extra cost of silicone impressions is £30 per patient. Dentists, patients and health care funders need to consider the clinical and financial value of silicone impressions. Different patients, different dentists, different health funders will have individual perceptions and judgements. ISRCTN01528038. NIHR-RfPB grant PB-PG-0408-16300. This article forms part of a project for which the author (TPH) won the Senior Clinical Unilever Hatton Award of the International Assocation for Dental Research, Capetown, South Africa, June 2014.
Subject(s)
Alginates/economics , Dental Impression Materials/economics , Denture Design/economics , Denture, Complete/economics , Silicone Elastomers/economics , Adult , Aged , Aged, 80 and over , Cost-Benefit Analysis , Cross-Over Studies , Dental Care/economics , Dental Care/statistics & numerical data , Double-Blind Method , Drug Costs , Female , Follow-Up Studies , Health Care Costs , Health Status , Humans , Male , Middle Aged , Oral Health , Prospective Studies , Quality of Life , Quality-Adjusted Life Years , State Dentistry/economics , Time Factors , United KingdomABSTRACT
BACKGROUND: Emergency department (ED) crowding caused by access block is an increasing public health issue and has been associated with impaired healthcare delivery, negative patient outcomes and increased staff workload. AIM: To investigate the impact of opening a new ED on patient and healthcare service outcomes. METHODS: A 24-month time series analysis was employed using deterministically linked data from the ambulance service and three ED and hospital admission databases in Queensland, Australia. RESULTS: Total volume of ED presentations increased 18%, while local population growth increased by 3%. Healthcare service and patient outcomes at the two pre-existing hospitals did not improve. These outcomes included ambulance offload time: (Hospital A PRE: 10 min, POST: 10 min, P < 0.001; Hospital B PRE: 10 min, POST: 15 min, P < 0.001); ED length of stay: (Hospital A PRE: 242 min, POST: 246 min, P < 0.001; Hospital B PRE: 182 min, POST: 210 min, P < 0.001); and access block: (Hospital A PRE: 41%, POST: 46%, P < 0.001; Hospital B PRE: 23%, POST: 40%, P < 0.001). Time series modelling indicated that the effect was worst at the hospital furthest away from the new ED. CONCLUSIONS: An additional ED within the region saw an increase in the total volume of presentations at a rate far greater than local population growth, suggesting it either provided an unmet need or a shifting of activity from one sector to another. Future studies should examine patient decision making regarding reasons for presenting to a new or pre-existing ED. There is an inherent need to take a 'whole of health service area' approach to solve crowding issues.