Multiple lines of evidence point to pesticides as stressors affecting invertebrate communities in small streams in five United States regions.

Multistressor studies were performed in five regions of the United States to assess the role of pesticides as stressors affecting invertebrate communities in wadable streams. Pesticides and other chemical and physical stressors were measured in 75 to 99 streams per region for 4 weeks, after which invertebrate communities were surveyed (435 total sites). Pesticides were sampled weekly in filtered water, and once in bed sediment. The role of pesticides as a stressor to invertebrate communities was assessed by evaluating multiple lines of evidence: toxicity predictions based on measured pesticide concentrations, multivariate models and other statistical analyses, and previously published mesocosm experiments. Toxicity predictions using benchmarks and species sensitivity distributions and statistical correlations suggested that pesticides were present at high enough concentrations to adversely affect invertebrate communities at the regional scale. Two undirected techniques-boosted regression tree models and distance-based linear models-identified which pesticides were predictors of (respectively) invertebrate metrics and community composition. To put insecticides in context with known, influential covariates of invertebrate response, generalized additive models were used to identify which individual pesticide(s) were important predictors of invertebrate community condition in each region, after accounting for natural covariates. Four insecticides were identified as stressors to invertebrate communities at the regional scale: bifenthrin, chlordane, fipronil and its degradates, and imidacloprid. Fipronil was particularly important in the Southeast region, and imidacloprid, bifenthrin, and chlordane were important in multiple regions. For imidacloprid, bifenthrin, and fipronil, toxicity predictions were supported by mesocosm experiments that demonstrated adverse effects on naïve aquatic communities when dosed under controlled conditions. These multiple lines of evidence do not prove causality-which is challenging in the field under multistressor conditions-but they make a strong case for the role of insecticides as stressors adversely affecting invertebrate communities in streams within the five sampled regions.

Prevention and treatment of peripartum urinary incontinence-a survey of hospital-based maternity services in Ireland.

INTRODUCTION AND HYPOTHESIS: Considerable proportions of pregnant and postpartum women experience urinary incontinence, but to our knowledge, there are no national data on the preventative and treatment services available in Ireland's 19 maternity hospitals. METHODS: Ethical approval was granted. A national benchmarking survey on the range and type of services on prevention and treatment of urinary incontinence during pregnancy and postpartum was developed. Directors of Midwifery and Nursing in each hospital identified midwives and women's health physiotherapists to complete the survey. Data were analysed descriptively, and results presented as proportions. RESULTS: Responses were received from 17 hospitals. Women were asked about urinary incontinence during their first booking visit in 6 hospitals, during all antenatal visits in 2 and the onus was on women self-reporting symptoms in 9. Pelvic floor muscle exercises were taught in antenatal classes in 14 hospitals and management of urinary incontinence in 9. In hospital postpartum, midwives in 13 hospitals asked women about urinary incontinence. All women were seen by a physiotherapist in 7 hospitals and only those who were referred in 6. Women could access the hospital's physiotherapy services up to 6 weeks postpartum in 3 hospitals, up to 6 months or 1 year in 5 and beyond 1 year in 6. CONCLUSIONS: Geographical inequity exists in the services offered to pregnant and postpartum women nationally. This indicates that many pregnant and postpartum women, both continent and incontinent, cannot avail themselves of preventative and treatment services within the maternity hospital system and points to the need to review, reconfigure and resource services.

Trajectories of Postpartum Recovery: What is Known and Not Known.

Women's postpartum health is a public health issue that has lifelong consequences. Timely recognition and treatment of physical and mental health issues can have positive health consequences while lack of access to effective treatments or health care services can lead to long-term health problems. To advance knowledge of priority health symptoms and trajectories of postpartum recovery from women's health perspectives, we share findings from the Maternal health And Maternal Morbidity in Ireland (MAMMI) study. Data from 3047 first-time mothers recruited to a longitudinal maternal health study in Ireland from 2012 to 2017 reveal the trajectories of maternal health and health problems experienced up to 12 months postpartum. Morbidities explored include urinary incontinence, pelvic girdle pain, and sexual and mental health issues. Viewed together, and over time, the scale and persistent nature of many physical and mental health problems become apparent, yet considerable proportions of women were not asked directly about health problems by health care professionals. When women do not know what is and is not normal postpartum, they may suffer in silence and the consequence is that health problems/issues that are preventable, and treatable, are likely to become chronic. To make positive contributions to women's health, maternity care systems must be truly woman-centered and structured in ways that place emphasis on women's own health needs. In systems where women's voices and concerns are acknowledged and central, women are likely to thrive and flourish in motherhood.

Is mammography screening an effective public health intervention? Evidence from a natural experiment.

Population-based breast screening programmes aim to improve clinical outcomes, alleviate health inequalities, and reduce healthcare costs. However, while screening can bring about immediate changes in mode of presentation and stage at diagnosis of breast cancer cases, the benefits and harms of these programmes can only be observed at a population level, and only over a long enough timeframe for the cascade of events triggered by screening to culminate in disease-specific mortality reductions. In this paper we exploit a natural experiment resulting from the phased geographic rollout of a national mammography screening programme to examine the impact of screening on breast cancer outcomes from both a patient cohort and a population perspective. Using data on 33,722 breast cancer cases over the period 1994-2011, we employ a difference-in-differences research design using ten-year follow-up data for cases diagnosed before and after the introduction of the programme in screened and unscreened regions. We conclude that although the programme produced the intended intermediate effects on breast cancer presentation and incidence, these failed to translate into significant decreases in overall population-level mortality, though screening may have helped to reduce socioeconomic disparities in late stage breast cancer incidence.

Oral pre-exposure prophylaxis (PrEP) to prevent HIV: a systematic review and meta-analysis of clinical effectiveness, safety, adherence and risk compensation in all populations.

OBJECTIVE: To conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) of the effectiveness and safety of oral pre-exposure prophylaxis (PrEP) to prevent HIV. METHODS: Databases (PubMed, Embase and the Cochrane Register of Controlled Trials) were searched up to 5 July 2020. Search terms for 'HIV' were combined with terms for 'PrEP' or 'tenofovir/emtricitabine'. RCTs were included that compared oral tenofovir-containing PrEP to placebo, no treatment or alternative medication/dosing schedule. The primary outcome was the rate ratio (RR) of HIV infection using a modified intention-to-treat analysis. Secondary outcomes included safety, adherence and risk compensation. All analyses were stratified a priori by population: men who have sex with men (MSM), serodiscordant couples, heterosexuals and people who inject drugs (PWIDs). The quality of individual studies was assessed using the Cochrane risk-of-bias tool, and the certainty of evidence was assessed using GRADE. RESULTS: Of 2803 unique records, 15 RCTs met our inclusion criteria. Over 25 000 participants were included, encompassing 38 289 person-years of follow-up data. PrEP was found to be effective in MSM (RR 0.25, 95% CI 0.1 to 0.61; absolute rate difference (RD) -0.03, 95% CI -0.01 to -0.05), serodiscordant couples (RR 0.25, 95% CI 0.14 to 0.46; RD -0.01, 95% CI -0.01 to -0.02) and PWID (RR 0.51, 95% CI 0.29 to 0.92; RD -0.00, 95% CI -0.00 to -0.01), but not in heterosexuals (RR 0.77, 95% CI 0.46 to 1.29). Efficacy was strongly associated with adherence (p<0.01). PrEP was found to be safe, but unrecognised HIV at enrolment increased the risk of viral drug resistance mutations. Evidence for behaviour change or an increase in sexually transmitted infections was not found. CONCLUSIONS: PrEP is safe and effective in MSM, serodiscordant couples and PWIDs. Additional research is needed prior to recommending PrEP in heterosexuals. No RCTs reported effectiveness or safety data for other high-risk groups, such as transgender women and sex workers. PROSPERO REGISTRATION NUMBER: CRD42017065937.

Ecological consequences of neonicotinoid mixtures in streams.

Neonicotinoid mixtures are common in streams worldwide, but corresponding ecological responses are poorly understood. We combined experimental and observational studies to narrow this knowledge gap. The mesocosm experiment determined that concentrations of the neonicotinoids imidacloprid and clothianidin (range of exposures, 0 to 11.9 µg/liter) above the hazard concentration for 5% of species (0.017 and 0.010 µg/liter, respectively) caused a loss in taxa abundance and richness, disrupted adult emergence, and altered trophodynamics, while mixtures of the two neonicotinoids caused dose-dependent synergistic effects. In 85 Coastal California streams, neonicotinoids were commonly detected [59% of samples (n = 340), 72% of streams], frequently occurred as mixtures (56% of streams), and potential toxicity was dominated by imidacloprid (maximum = 1.92 µg/liter) and clothianidin (maximum = 2.51 µg/liter). Ecological responses in the field were consistent with the synergistic effects observed in the mesocosm experiment, indicating that neonicotinoid mixtures pose greater than expected risks to stream health.

Preliminary Classification of Selected Farmland Habitats in Ireland Using Deep Neural Networks.

Ireland has a wide variety of farmlands that includes arable fields, grassland, hedgerows, streams, lakes, rivers, and native woodlands. Traditional methods of habitat identification rely on field surveys, which are resource intensive, therefore there is a strong need for digital methods to improve the speed and efficiency of identification and differentiation of farmland habitats. This is challenging because of the large number of subcategories having nearly indistinguishable features within the habitat classes. Heterogeneity among sites within the same habitat class is another problem. Therefore, this research work presents a preliminary technique for accurate farmland classification using stacked ensemble deep convolutional neural networks (DNNs). The proposed approach has been validated on a high-resolution dataset collected using drones. The image samples were manually labelled by the experts in the area before providing them to the DNNs for training purposes. Three pre-trained DNNs customized using the transfer learning approach are used as the base learners. The predicted features derived from the base learners were then used to train a DNN based meta-learner to achieve high classification rates. We analyse the obtained results in terms of convergence rate, confusion matrices, and ROC curves. This is a preliminary work and further research is needed to establish a standard technique.

The characteristics and effectiveness of pregnancy yoga interventions: a systematic review and meta-analysis.

BACKGROUND: Yoga is a popular mind-body medicine frequently recommended to pregnant women. Gaps remain in our understanding of the core components of effective pregnancy yoga programmes. This systematic review and meta-analysis examined the characteristics and effectiveness of pregnancy yoga interventions, incorporating the FITT (frequency, intensity, time/duration and type) principle of exercise prescription. METHODS: Nine electronic databases were searched: MEDLINE, PsycINFO, EMBASE, CINAHL, WHOLiS, AMED, ScieLo, ASSIA and Web of Science. Randomised control trials and quasi-experimental studies examining pregnancy yoga interventions were eligible. Covidence was used to screen titles, abstracts, and full-text articles. Outcomes of interest were stress, anxiety, depression, quality of life, labour duration, pain management in labour and mode of birth. The Cochrane Collaboration's Risk of Bias Assessment tool was used to assess methodological quality of studies and GRADE criteria (GRADEpro) evaluated quality of the evidence. Meta-analysis was performed using RevMan 5.3. RESULTS: Of 862 citations retrieved, 31 studies met inclusion criteria. Twenty-nine studies with 2217 pregnant women were included for meta-analysis. Pregnancy yoga interventions reduced anxiety (SMD: -0.91; 95% CI: - 1.49 to - 0.33; p = 0.002), depression (SMD: -0.47; 95% CI: - 0.9 to - 0.04, P = 0.03) and perceived stress (SMD: -1.03; 95% CI: - 1.55 to - 0.52; p < 0.001). Yoga interventions also reduced duration of labour (MD = - 117.75; 95% CI - 153.80 to - 81.71, p < 0.001) and, increased odds of normal vaginal birth (OR 2.58; 95% CI 1.46-4.56, p < 0.001) and tolerance for pain. The quality of evidence (GRADE criteria) was low to very low for all outcomes. Twelve or more yoga sessions delivered weekly/bi-weekly had a statistically significant impact on mode of birth, while 12 or more yoga sessions of long duration (> 60 min) had a statistically significant impact on perceived stress. CONCLUSION: The evidence highlights positive effects of pregnancy yoga on anxiety, depression, perceived stress, mode of birth and duration of labour. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019119916. Registered on 11th January 2019.

Hybridization and range expansion in tamarisk beetles (Diorhabda spp.) introduced to North America for classical biological control.

With the global rise of human-mediated translocations and invasions, it is critical to understand the genomic consequences of hybridization and mechanisms of range expansion. Conventional wisdom is that high genetic drift and loss of genetic diversity due to repeated founder effects will constrain introduced species. However, reduced genetic variation can be countered by behavioral aspects and admixture with other distinct populations. As planned invasions, classical biological control (biocontrol) agents present important opportunities to understand the mechanisms of establishment and spread in a novel environment. The ability of biocontrol agents to spread and adapt, and their effects on local ecosystems, depends on genomic variation and the consequences of admixture in novel environments. Here, we use a biocontrol system to examine the genome-wide outcomes of introduction, spread, and hybridization in four cryptic species of a biocontrol agent, the tamarisk beetle (Diorhabda carinata, D. carinulata, D. elongata, and D. sublineata), introduced from six localities across Eurasia to control the invasive shrub tamarisk (Tamarix spp.) in western North America. We assembled a de novo draft reference genome and applied RADseq to over 500 individuals across laboratory cultures, the native ranges, and the introduced range. Despite evidence of a substantial genetic bottleneck among D. carinulata in N. America, populations continue to establish and spread, possibly due to aggregation behavior. We found that D. carinata, D. elongata, and D. sublineata hybridize in the field to varying extents, with D. carinata × D. sublineata hybrids being the most abundant. Genetic diversity was greater at sites with hybrids, highlighting potential for increased ability to adapt and expand. Our results demonstrate the complex patterns of genomic variation that can result from introduction of multiple ecotypes or species for biocontrol, and the importance of understanding them to predict and manage the effects of biocontrol agents in novel ecosystems.

Impact of Noninvasive Respiratory Support in Patients With COVID-19 Requiring V-V ECMO.

The impact of the duration of noninvasive respiratory support (RS) including high-flow nasal cannula and noninvasive ventilation before the initiation of extracorporeal membrane oxygenation (ECMO) is unknown. We reviewed data of patients with coronavirus disease 2019 (COVID-19) treated with V-V ECMO at two high-volume tertiary care centers. Survival analysis was used to compare the effect of duration of RS on liberation from ECMO. A total of 78 patients required ECMO and the median duration of RS and invasive mechanical ventilation (IMV) before ECMO was 2 days (interquartile range [IQR]: 0, 6) and 2.5 days (IQR: 1, 5), respectively. The median duration of ECMO support was 24 days (IQR: 11, 73) and 59.0% (N = 46) remained alive at the time of censure. Patients that received RS for ≥3 days were significantly less likely to be liberated from ECMO (HR: 0.46; 95% CI: 0.26-0.83), IMV (HR: 0.42; 95% CI: 0.20-0.89) or be discharged from the hospital (HR: 0.52; 95% CI: 0.27-0.99) compared to patients that received RS for <3 days. There was no difference in hospital mortality between the groups (HR: 1.12; 95% CI: 0.56-2.26). These relationships persisted after adjustment for age, gender, and duration of IMV. Prolonged duration of RS before ECMO may result in lung injury and worse subsequent outcomes.

Ejaculatory dysfunction following prostate artery embolization: A retrospective study utilizing the male sexual health questionnaire-ejaculation dysfunction questionnaire.

PURPOSE: The purpose of this study was to determine the rate of ejaculatory dysfunction that develops following prostate artery embolization (PAE) and identify predictive factors. MATERIALS AND METHODS: Thirty-nine men (mean age, 67.9 ± 8.1 ([SD)] years; range: 52-84 years) who underwent PAE were retrospectively asked to complete the male sexual health questionnaire-ejaculation dysfunction (MSHQ-EjD) short form. Pre-treatment, procedural, and post-treatment variables were also collected. RESULTS: A total of four patients (4/39, 10.3%) developed ejaculatory dysfunction following PAE, with one (1/4, 25%) reporting improvement in his ejaculatory dysfunction over time. When evaluating the group as a whole there was no significant difference between the pre and post-treatment answers of patients when asked about how often they ejaculate when having sexual activity (P = 0.77), strength of ejaculation (P = 0.86), or volume of ejaculation (P = 0.67). Similarly, the total MHSQ-EjD score was not different when evaluating the group as a whole pre (11.4 ± 5.3 [SD]; range: 1-15) and post-treatment (10.7 ± 5.3 [SD]; range: 1-15) (P = 0.54), nor was the degree of bother from ejaculatory difficulties significantly different (0.82 ± 1.1 [SD]; range: 0-5 vs. 1 ± 1.1 [SD]; range: 0-5; P = 0.9). When comparing those who did to those who did not develop ejaculatory dysfunction, univariable analysis demonstrated that post void residual volume was significantly greater in those who did develop dysfunction (median, 202 mL; IQR: 274; range: 40-588) than in those who did not (median, 58 mL; IQR: 124; range: 0-408) (P = 0.04). CONCLUSION: We found that 10.3% of patients undergoing PAE develop ejaculatory dysfunction and those with greater post void residual volume may be at increased risk. However, the data should be interpreted with caution given the small sample size and more, preferably prospective, data are needed to determine the true rates of ejaculatory dysfunction following PAE.

Is there an association between parity and urinary incontinence in women during pregnancy and the first year postpartum?: A systematic review and meta-analysis.

AIMS: To systematically review the literature on possible associations between parity and urinary incontinence (UI) during pregnancy and in the first year postpartum. METHODS: We searched the databases Pubmed, CINAHL, Embase, the Cochrane Library, PsycINFO, MIDIRS, ClinicalTrials.gov (inception-18 April 2020). One reviewer screened all titles. Two reviewers independently selected studies by abstract and full text. Risk of bias was assessed using the Quality In Prognosis Studies tool. Findings were synthesised in meta-analysis or narratively. We assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation Working Group approach adopted for prognostic studies. RESULTS: We identified 16 643 records and 39 were included. Thirty studies examined UI during pregnancy and 12 examined UI postpartum. Multiparity was associated with UI at any point in the last pregnancy (odds ratio [OR]: 1.59 [1.26-2.00], 5 studies, 1565 participants) and in the third trimester when measured by ICIQ-SF (OR: 2.67 [1.53-4.67], 4 studies, 1150 participants), but not when studies measured the UI point prevalence (OR: 2.48 [0.91-6.79], 4 studies, 52 976 participants), or if they measured the prevalence at one point in any trimester (OR: 1.09 (0.60-1.95), 3 studies, 872 participants). At 3 months postpartum, UI was associated with multiparity (OR: 2.03 [1.35-3.06], 4 studies, 6781 participants). CONCLUSIONS: Increased parity was associated with UI in the first year postpartum, but studies on UI during pregnancy had conflicting results. The evidence was (very) uncertain. Future studies should use comparable definitions and further explore UI sub-types.

The maternal health-related issues that matter most to women in Ireland as they transition to motherhood - A qualitative study.

BACKGROUND: Many studies on women's maternity care experiences reveal recurring issues that are poor or less than optimal. Women's opinions on the maternal health-related issues that matter most to them are essential if care and services are to be improved. AIMS: To identify the maternal health-related issues that matter most to women in Ireland, based on their own experiences of maternity care, services and motherhood. METHODS: A qualitative exploratory study with 24 women. Following university ethical approval, audio-recorded one-to-one telephone interviews were conducted and thematically analysed. FINDINGS: We identified two themes, each with four subthemes, connected to a central concept of the invisible woman. Pendulum of care, and subthemes Inconsistent services, All about the baby, Induced anxiety and Information seesaw, illustrated the extremes of care and services that women experienced. Magnitude of motherhood, and subthemes Weight of responsibility, Real-time reassurance, Change of identity and Growth into advocacy, depicted the intensity of their new role while transitioning to motherhood. DISCUSSION: Findings articulate the issues that mattered most to women in Ireland as they transitioned to motherhood. Some women identified specific research topics/areas, but all of the issues identified can be translated into researchable topics that seek to improve local care and service provision. CONCLUSION: Given the recurring nature of women's less than satisfactory experiences of aspects of maternity care in many countries, it is likely that conducting research on issues that matters most to women will have the greatest impact on their health, wellbeing and lives as they transition to motherhood.

The silence of the clams: Forestry registered pesticides as multiple stressors on soft-shell clams.

Contaminants are ubiquitous in the environment, often reaching aquatic systems. Combinations of forestry use pesticides have been detected in both water and aquatic organism tissue samples in coastal systems. Yet, most toxicological studies focus on the effects of these pesticides individually, at high doses, and over acute time periods, which, while key for establishing toxicity and safe limits, are rarely environmentally realistic. We examined chronic (90 days) exposure by the soft-shell clam, Mya arenaria, to environmentally relevant concentrations of four pesticides registered for use in forestry (atrazine, 5 µg/L; hexazinone, 0.3 µg/L; indaziflam, 5 µg/L; and bifenthrin, 1.5 µg/g organic carbon (OC)). Pesticides were tested individually and in combination, except bifenthrin, which was tested only in combination with the other three. We measured shell growth and condition index every 30 days, as well as feeding rates, mortality, and chemical concentrations in tissue from a subset of clams at the end of the experiment to measure contaminant uptake. Indaziflam caused a high mortality rate (max. 36%), followed by atrazine (max. 27%), both individually as well as in combination with other pesticides. Additionally, indaziflam concentrations in tissue (61.70-152.56 ng/g) were higher than those of atrazine (26.48-48.56 ng/g), despite equal dosing concentrations, indicating higher tissue accumulation. Furthermore, clams exposed to indaziflam and hexazinone experienced reduced condition index and clearance rates individually and in combination with other compounds; however, the two combined did not result in significant mortality. These two compounds, even at environmentally relevant concentrations, affected a non-target organism and, in the case of the herbicide indaziflam, accumulated in clam tissue and appeared more toxic than other tested pesticides. These findings underscore the need for more comprehensive studies combining multiple compounds at relevant concentrations to understand their impacts on aquatic ecosystems.

Multiple in-stream stressors degrade biological assemblages in five U.S. regions.

Biological assemblages in streams are affected by a wide variety of physical and chemical stressors associated with land-use development, yet the importance of combinations of different types of stressors is not well known. From 2013 to 2017, the U.S. Geological Survey completed multi-stressor/multi-assemblage stream ecological assessments in five regions of the United States (434 streams total). Diatom, invertebrate, and fish communities were enumerated, and five types of potential stressors were quantified: habitat disturbance, excess nutrients, high flows, basic water quality, and contaminants in water and sediment. Boosted regression tree (BRT) models for each biological assemblage and region generally included variables from all five stressor types and multiple stressors types in each model was the norm. Classification and regression tree (CART) models then were used to determine thresholds for each BRT model variable above which there appeared to be adverse effects (multi-metric index (MMI) models only). In every region and assemblage there was a significant inverse relation between the MMI and the number of stressors exerting potentially adverse effects. The number of elevated instream stressors often varied substantially for a given level of land-use development and the number of elevated stressors was a better predictor of biological condition than was development. Using the adverse effects-levels that were developed based on the BRT model results, 68% of the streams had two or more stressors with potentially adverse effects and 35% had four or more. Our results indicate that relatively small increases in the number of stressors of different types can have a large effect on a stream ecosystem.

Biology of an Adventive Population of the Armored Scale Rhizaspidiotus donacis, a Biological Control Agent of Arundo donax in California.

Arundo donax (giant reed) is invasive in Mediterranean, sub-, and tropical riparian systems worldwide. The armored scale Rhizaspidiotus donacis is approved for biocontrol in North America, but an adventive population was recently discovered in southern California. We documented this population's distribution, phylogeny, phenology, potential host spillover to Phragmites spp., and potential for parasitism by a common biocontrol parasitoid of citrus scale. The adventive scale was found within a single watershed and is genetically closest to Iberian scale genotypes. Rhizaspidiotus donacis developed on Phragmites haplotypes but at much lower densities than Arundo. The adventive population is univoltine, producing crawlers from March-June. Aphytis melinus parasitoids exhibited sustained interest in R. donacis during choice and no-choice trials and oviposition resulted in a small second generation. Rhizaspidiotus donacis appears limited in distribution by its univoltinism and sessile adult females. This presents challenges for broad biocontrol implementation but allows for targeted application. The genetic differentiation between imported biocontrol samples and adventive populations presents an opportunity for exploring benefits of hybrids and/or alternative genotypes where establishment has been difficult. While unlikely to occur in situ, spillover to vulnerable endemic Phragmites or deleterious parasitoid effects on scale biocontrol agents warrants consideration when planning use of R. donacis.

Cost-Effectiveness Analysis of a National Pre-Exposure Prophylaxis (PrEP) Program in Ireland.

OBJECTIVES: To estimate the cost-effectiveness of introducing a publicly funded pre-exposure prophylaxis (PrEP) program in Ireland. METHODS: We constructed a state-transition Markov model. This was a cross-sectional population model that tracked all HIV-negative men who have sex with men (MSM) in Ireland over their lifetime. Access to a publicly funded PrEP program (medications + frequent monitoring) in high-risk MSM was compared with no PrEP. The primary outcome measure was the incremental cost-effectiveness ratio (ICER). RESULTS: In the base case, introducing a PrEP program was considered cost saving and provided significant health benefits to the population. Univariate sensitivity analysis demonstrated that PrEP efficacy and HIV incidence had the greatest impact on cost-effectiveness. Including an increase in sexually transmitted infections had a negligible impact on the results. Efficacy was a significant driver in the model. PrEP was cost saving at all efficacy values above 60%, and at the lowest reported efficacy in MSM (44% in the iPrEX trial), the ICER was €4711/QALY (highly cost-effective). Event-based dosing (administration during high-risk periods only) was associated with additional cost savings. We estimated that 1705 individuals (95% CI: 617-3452) would join the program in year 1. The incremental budget impact was €1.5m (95% CI: €0.5m to €3m) in the first year and €5.4m over 5 years (95% CI: €1.8m to €11.5m), with 173 cases of HIV averted over 5 years. CONCLUSION: We found that the introduction of a PrEP program would be considered cost saving in the first cost-effectiveness analysis of its kind in Ireland.

Is there an urban pesticide signature? Urban streams in five U.S. regions share common dissolved-phase pesticides but differ in predicted aquatic toxicity.

Pesticides occur in urban streams globally, but the relation of occurrence to urbanization can be obscured by regional differences. In studies of five regions of the United States, we investigated the effect of region and urbanization on the occurrence and potential toxicity of dissolved pesticide mixtures. We analyzed 225 pesticide compounds in weekly discrete water samples collected during 6-12 weeks from 271 wadable streams; development in these basins ranged from undeveloped to highly urbanized. Sixteen pesticides were consistently detected in 16 urban centers across the five regions-we propose that these pesticides comprise a suite of urban signature pesticides (USP) that are all common in small U.S. urban streams. These USPs accounted for the majority of summed maximum pesticide concentrations at urban sites within each urban center. USP concentrations, mixture complexity, and potential toxicity increased with the degree of urbanization in the basin. Basin urbanization explained the most variability in multivariate distance-based models of pesticide profiles, with region always secondary in importance. The USPs accounted for 83% of pesticides in the 20 most frequently occurring 2-compound unique mixtures at urban sites, with carbendazim+prometon the most common. Although USPs were consistently detected in all regions, detection frequencies and concentrations varied by region, conferring differences in potential aquatic toxicity. Potential toxicity was highest for invertebrates (benchmarks exceeded in 51% of urban streams), due most often to the neonicotinoid insecticide imidacloprid and secondarily to organophosphate insecticides and fipronil. Benchmarks were rarely exceeded in urban streams for plants (at 3% of sites) or fish (<1%). We propose that the USPs identified here would make logical core (nonexclusive) constituents for monitoring dissolved pesticides in U.S. urban streams, and that unique mixtures containing imidacloprid, fipronil, and carbendazim are priority candidates for mixtures toxicity testing.