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OBJECTIVES: Recent advances have created options for first-line (1L) treatment of advanced/metastatic non--small cell lung cancer (aNSCLC). The study objectives were to describe the utilization of 3 classes of 1L treatment--chemotherapy (CT), immunotherapy (IO), and chemoimmunotherapy (IO+CT)--and the total, third-party payer, direct health care costs. STUDY DESIGN: Retrospective, administrative claims database analysis of patients with aNSCLC who initiated 1L treatment between January 1, 2017, and May 31, 2019, with IO, CT, or IO+CT. METHODS: Microcosting enumerated health care resource utilization, including antineoplastic drug costs, using standardized costs. Generalized linear models estimated per-patient per-month (PPPM) costs during 1L treatment, and adjusted cost differences in 1L among treatment cohorts were calculated using recycled predictions. RESULTS: A total of 1317 IO-, 5315 CT-, and 1522 IO+CTtreated patients were identified. Utilization of CT declined from 72.3% to 47.6% between 2017 and 2019, replaced by use of IO+CT, which increased from 1.8% to 29.8%. Total PPPM costs in 1L were highest with IO+CT at $32,436, compared with $19,000 and $17,763 in the CT and IO cohorts, respectively. Adjusted analyses showed that PPPM costs were $13,933 (95% CI, $11,760-$16,105) higher in the IO+CT vs IO cohort (P < .001) and IO costs were $1024 (95% CI, $67-$1980) lower than CT (P = .04). CONCLUSIONS: IO+CT accounts for almost one-third of 1L aNSCLC treatment modalities, coinciding with a reduction in treatment with CT. Costs for patients treated with IO were lower than those for patients treated with both IO+CT and CT alone, driven primarily by antineoplastic drug and associated medical costs. [ABSTRACT FROM AUTHOR]

Background. Haitian immigrant women residing in Little Haiti, a large ethnic enclave in Miami-Dade County, experience the highest cervical cancer incidence rates in South Florida. While this disparity primarily reflects lack of access to screening with cervical cytology, the burden of human papillomavirus (HPV) which causes virtually all cases of cervical cancer worldwide, varies by population and may contribute to excess rate of disease. Our study examined the prevalence of oncogenic and nononcogenic HPV types and risk factors for HPV infection in Little Haiti. Methods. As part of an ongoing community-based participatory research initiative, community health workers recruited study participants between 2007 and 2008, instructed women on self collecting cervicovaginal specimens, and collected socio demographic and healthcare access data. Results. Of the 242 women who contributed adequate specimens, the overall prevalence of HPV was 20.7%, with oncogenic HPV infections (13.2% of women) outnumbering nononcogenic infections (7.4%). Age-specific prevalence of oncogenic HPV was highest in women 18-30 years (38.9%) although the prevalence of oncogenic HPV does not appear to be elevated relative to the general U.S. population. The high prevalence of oncogenic types in women over 60 years may indicate a substantial number of persistent infections at high risk of progression to precancer. [ABSTRACT FROM AUTHOR]

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm with a prevalence of 4 to 6 per 100,000 people in the USA. Treatment recommendations are risk-adapted. This study was conducted to evaluate how physicians risk-stratify patients at the time of MF diagnosis, the accuracy of the risk stratification, and its effect on treatment selection. Medical charts were reviewed at US community hematology/oncology practices in the Cardinal Health Oncology Provider Extended Network; patient clinical characteristics, risk stratification, and treatment data were collected. Physician-assigned risk categorizations were compared with data-derived risk categorizations based on the International Prognostic Scoring System, the system recommended at diagnosis. A total of 491 patients diagnosed with MF between 2012 and 2016 (mean [SD] age at diagnosis, 65.4 [11.8] years; 54.8% male, 69.2% with primary MF) were included. Risk categorization was not assigned for 30.1% of patients. Of the patients with a physician-assigned risk categorization (n = 343), a scoring system was used in 49.9%. Compared with data-derived risk categorizations, 42.9% of physician-assigned risk categorizations were incorrect; 85.0% of incorrect physician-assigned risk categorizations were underestimations. Notably, 38.5% of patients with data-derived intermediate- or high-risk categorizations did not initiate treatment within 120 days of diagnosis. Among patients with data-derived intermediate risk, those with an underestimated physician-assigned risk categorization were significantly less likely to receive treatment within 120 days of diagnosis (51.6% with correct physician-assigned categorization vs 18.5% with underestimated risk categorization; P = 0.0023). These results highlight the gap in risk assessment and the importance of accurate risk stratification at diagnosis. [ABSTRACT FROM AUTHOR]

Treatment options for patients with acute myeloid leukemia (AML), who are unfit for induction chemotherapy are unsatisfactory. Overall survival (OS) superiority has not been demonstrated in randomized controlled trials (RCT) in this population, challenging the value of available therapies. We sought to assess the relative value of approved therapies using value-assessment tools. Clinical, safety, quality-of-life (QOL), supportive care, and resource utilization outcomes data were abstracted from RCTs and examined using value-assessment frameworks. Three RCTs, one each of azacitidine, decitabine, and low-dose cytarabine were identified. OS was not statistically significant and secondary outcomes including response rates, rates of transfusion independence, the frequency of hospitalizations and changes in QOL were reported differently across trials. Value-assessment tools considered OS as the primary efficacy endpoint without consideration to response rates. The NCCN Evidence BlocksTM were most successful in considering secondary endpoints. With the move toward value-based care, understanding how these value tools apply to AML patients is critical. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Real‐world data are critical to demonstrate the consistency of evidence and external generalizability of randomized controlled trials (RCTs). This study examined characteristics and outcomes of metastatic triple‐negative breast cancer (mTNBC) patients treated with eribulin mesylate at community oncology practices in the United States. Methods: Physicians identified mTNBC patients initiating eribulin between 1 January 2011 and 1 January 2014 and abstracted data into an electronic case report form (eCRF). Eribulin treatment in the metastatic setting was categorized as early use (EU, first‐/second‐line) and late use (LU, third‐line or later). Patient characteristics, overall survival (OS), disease response (per treating physician), and adverse events (AEs) rates in each group, respectively, are reported. Results: Overall 252 eCRFs were completed: 125 (49.6%) EU and 127 (50.4%) LU. The median age at metastatic diagnosis was 53 years and 42.1% were stage IV at their initial diagnosis. The median duration of follow‐up from the initiation of first‐line treatment was 24 months. Rates of disease response (complete or partial per treating physician) were 69.9% in the EU group and 48.8% in the LU group. The five most commonly reported adverse events during eribulin were as follows: fatigue (65.1%), weakness (40.1%), decreased appetite (32.5%), neutropenia (31.0%), and leukopenia (27.4%). Discontinuation of eribulin due to AE was observed in 4.0% of patients. Median OS from initiation of eribulin was 23.0 months (95% CI: 18.7‐27.3) among EU and 14.7 (95% CI: 12.6‐16.9) among LU. Conclusion: In the real‐world eribulin‐treated mTNBC, patients have more sites of metastatic disease and exposure to greater numbers of prior therapies compared to RCTs. The median OS of 14.7 months among LU patients is consistent with, and slightly longer than the 13.1 months and 14.4 months reported in the EMBRACE and Study 301 clinical trials, respectively. [ABSTRACT FROM AUTHOR]

Objective:Haitian women have the highest incidence of cervical cancer within the Western hemisphere. Intravaginal hygiene practices have been linked with human papilloma virus (HPV) infection and cervical dysplasia. These practices, known as ‘twalet deba’ in Haitian Creole, are common among Haitian women and are performed with various natural and synthetic agents. As part of a community-based participatory research initiative aimed at reducing cervical cancer disparities in rural Haiti, we explored the use of intravaginal agents and their associations with high-risk HPV infection. Design:Community Health Workers recruited 416 women for cervical self-sampling from two neighborhoods within Thomonde, Haiti. Participants were interviewed regarding intravaginal hygiene practices and completed a cervical self-sampling procedure. Cervical samples were analyzed for the presence of high-risk HPV infection. Associations between each intravaginal agent and high-risk HPV infection were examined via univariate logistic regression analyses, as well as via multivariate analyses controlling for sociodemographic factors and concurrent agent use. Results:Nearly all women (97.1%) performed twalet deba, using a variety of herbal and commercially produced intravaginal agents. Approximately 11% of the participants tested positive for high-risk HPV. Pigeon pea and lime juice were the only agents found to be associated with high-risk HPV in the univariate analyses, with women who used these agents being approximately twice as likely to have high-risk HPV as those who did not. Only pigeon pea remained significantly associated with high-risk HPV after controlling for sociodemographic factors and concurrent agent use. Conclusion:Two agents, pigeon pea and lime juice, may contribute to risk for HPV infection in this population. Results suggest that in addition to cervical cancer screening interventions, future preventive initiatives should focus on minimizing risk by advocating for the use of less-toxic twalet deba alternatives. [ABSTRACT FROM AUTHOR]

Purpose: Most patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with a complement protein 5 (C5) inhibitor achieve full control of terminal complement activity and intravascular hemolysis. The minority remains anemic and transfusion dependent despite this control. Etiology for ongoing anemia is multifactorial and includes bone marrow failure, breakthrough hemolysis, extravascular hemolysis (EVH) and nutritional deficiencies. Patients and Methods: To evaluate the potential etiologies of hemoglobin levels < 10 g/dL despite receiving C5 inhibitor therapy, we performed a retrospective US chart review of adult patients with PNH and treated for at least 12 months with eculizumab (n=53), ravulizumab (n=32), or eculizumab followed by ravulizumab (n=15). Clinically evident EVH was defined as at least one transfusion, reticulocyte count ≥ 120× 109/L and hemoglobin level ≤ 9.5 g/dL. Safety data were not collected. Mean treatment duration was 26.5± 17.2 months. Results: Treatment with C5 inhibitors significantly improved hemoglobin, lactate dehydrogenase, and number of transfusions versus baseline. Among the patients with hemoglobin < 10 g/dL during the last 6 months of treatment (n=38), one patient (eculizumab) had clinically evident EVH, and 10 patients had active concomitant bone marrow failure. Bone marrow failure was a major contributor to hemoglobin < 10 g/dL and transfusion dependence; clinically evident EVH was uncommon. Conclusion: A range of hematologic causes need to be considered when evaluating anemia in the presence of treatment with a C5 inhibitor. [ABSTRACT FROM AUTHOR]

Ruxolitinib is an FDA-approved treatment of intermediate- and high-risk myelofibrosis. In the phase 3 COMFORT studies, ruxolitinib reduced spleen volume in patients with myelofibrosis, with a median time to response of 3 months. However, nearly 20% of patients discontinued by month 4 with few treatment options available following discontinuation of ruxolitinib treatment. In this study, 2 independent patient care data sources were queried (Cardinal Health Oncology Provider Extended Network [OPEN] and HealthCore Integrated Research Environment [HIRE®]), and a retrospective review of medical charts was conducted. Patients aged ≥18 years with a diagnosis of myelofibrosis (primary or secondary), use of ruxolitinib for myelofibrosis, and documented physician-directed ruxolitinib interruption were included. Among 26 included patients, pre-interruption median (interquartile range [IQR]) ruxolitinib treatment duration was 123 (57–391, OPEN) and 110 (37–148, HIRE) days. Half the patients interrupted treatment within 3 months, commonly for adverse events (42% and 71%, respectively). After restarting ruxolitinib, median (IQR) re-treatment duration was 196 (54–553) and 166 (108–262) days, respectively. Consistent with previous reports, symptoms and spleen size improved in (OPEN/HIRE) 45%/43% and 40%/33% of evaluable patients, respectively. Further studies investigating the management of dose modifications and interruptions are needed to optimize benefit from ruxolitinib therapy. [ABSTRACT FROM AUTHOR]

In January 2010, a massive earthquake struck Haiti resulting in unprecedented damage. Little attention, however, has focused on the earthquake's mental health impact in the Haitian diaspora community. As part of an established community-based participatory research initiative in Little Haiti, the predominately Haitian neighborhood in Miami, FL, USA, community health workers conducted surveys with neighborhood residents about earthquake-related losses, coping strategies, and depressive/traumatic symptomology. Findings reveal the earthquake strongly impacted the diaspora community and highlights prominent coping strategies. Following the earthquake, only a small percentage of participants self-reported engaging in any negative health behaviors. Instead, a majority relied on their social networks for support. This study contributes to the discourse on designing culturally-responsive mental health initiatives for the Haitian diaspora and the ability of existing community-academic partnerships to rapidly adapt to community needs. [ABSTRACT FROM AUTHOR]

Abstract: Due to global climate change, the world will, on average, experience a higher number of heat waves, and the intensity and length of these heat waves is projected to increase. Knowledge about the implications of heat exposure to human health is growing, with excess mortality and illness occurring during hot weather in diverse regions. Certain groups, including the elderly, the urban poor, and those with chronic health conditions, are at higher risk. Preventive actions include: establishing heat wave warning systems; making cool environments available (through air conditioning or other means); public education; planting trees and other vegetation; and modifying the built environment to provide proper ventilation and use materials and colors that reduce heat build-up and optimize thermal comfort. However, to inspire local prevention activities, easily understood information about the strategies’ benefits needs to be incorporated into decision tools. Integrating heat health information into a comprehensive adaptation planning process can alert local decision-makers to extreme heat risks and provide information necessary to choose strategies that yield the largest health improvements and cost savings. Tools to enable this include web-based programs that illustrate effective methods for including heat health in comprehensive local-level adaptation planning; calculate costs and benefits of several activities; maps showing zones of high potential heat exposure and vulnerable populations in a local area; and public awareness materials and training for implementing preventive activities. A new computer-based decision tool will enable local estimates of heat-related health effects and potential savings from implementing a range of prevention strategies. [Copyright &y& Elsevier]

Objectives: Real-world evidence (RWE) has gained increased attention in recent years as a complement to traditional clinical trials. The use of RWE to establish the efficacy of oncology drugs for Food and Drug Administration (FDA) approval has not been described. In this paper, we review 5 recent examples where RWE was submitted in support of the FDA approvals of original or supplementary indications for oncology drugs.Methods: To identify cases where RWE was used, we reviewed drug approval packages available at Drugs@FDA for oncology drugs approved between 2017 and 2019. Five cases were selected to present a broad overview of different types of RWE, different circumstances under which RWE has been used for regulatory approvals, and how FDA evaluated the data in each case. The type of RWE submitted, the indication, limitations identified by FDA reviewers, and the outcome of the submission are discussed.Results: RWE, particularly historical controls for rare or orphan indications, has been used to support both original and supplementary oncology drug approvals. Types of RWE included data from electronic health records, claims, post-marketing safety reports, retrospective medical record reviews, and expanded access studies. Small sample sizes, data quality, and methodological issues were among concerns cited by FDA reviewers.Conclusion: By bridging the gap between the constraints of the trial setting and the realities of clinical practice, RWE can add value to a regulatory submission. These early examples provide insight into how regulators evaluated RWE submitted as evidence of efficacy for oncology drugs. [ABSTRACT FROM AUTHOR]

Purpose The development of skeletal-related events (SREs) (pathologic fracture, need for surgery and/or radiation to bone, spinal cord compression, and hypercalcemia of malignancy) in metastatic prostate cancer (MPC) is associated with worsened pain and compromised quality of life. Opioids are frequently used throughout the course of SRE treatment. This study describes the treatment patterns and incremental use of opioids in MPC patients diagnosed with SREs. Methods PC patients with bone metastases newly diagnosed with an SRE between January 1, 2005, and September 30, 2014, were identified using MarketScan Commercial and Medicare databases. Included patients were aged ≥40 years, had medical/pharmacy benefits for ≥12 months before (preindex) and ≥6 months after (postindex) diagnosis, and were without evidence of other primary cancers. Patients were categorized as nonusers of opioids (<10 days), short-term users (≥10 and <60 days), or long-term users (≥60 days) and further by SRE type. Opioid type, proportion of time on opioids, morphine-equivalent dose, adjuvant medications, and radiation use before and after SRE diagnosis were evaluated. Findings A total of 1071 eligible patients were identified (mean age, 71 years; 10.8% had chronic pain at baseline). The most common SRE types present were radiation (60.2%), radiation and bone surgery (15.0%), pathologic fracture (7.2%), and bone surgery (6.5%). Opioid use increased from 49.9% preindex to 53.3% postindex ( P < 0.0001). The proportion of time on opioids doubled after SRE (pre, 0.3 vs post, 0.6; P < 0.0001). A greater percentage of patients used only opioids after an SRE (pre, 11.0%; post, 46.1% [ P < 0.0001]), while a lesser percentage of patients used only radiation after an SRE (pre, 36.0%; post, 4.7% [ P < 0.0001]). An increase was observed in patients using neither radiation nor opioids (pre, 14.5%; post, 42.0% [ P < 0.0001]). An increase of ~50% was noted in long-term opioid users (from 22.1% to 32.1%). The use of monotherapy with a short-acting opioid decreased (pre, 35.1%; post, 32.5% [ P < 0.0001]), while use of mixed opioids increased (pre, 13.7%; post, 19.1% [ P < 0.0001]). Mean morphine-equivalent dose increased from pre- to post-SRE (9.1 vs 13.1 mg). Bisphosphonate and NSAID users decreased from before to after an SRE diagnosis (bisphosphonates, 40.2% vs 8.6%; NSAIDs, 26.7% vs 17.5% [both, P < 0.0001]). Implications Long-term opioid use and dose were significantly increased after SRE development in MPC. The high percentage of patients not treated with an opioid or radiation potentially supports the need for additional treatment options for controlling pain if medically necessary and/or to prevent SREs. [ABSTRACT FROM AUTHOR]

This study documents the vicarious psychological impact of the 2010 earthquake in Haiti on Haitians living in the United States. The role of coping resources-family, religious, and community support-was explored. The results highlight the importance of family and community as coping strategies to manage such trauma. Este estudio documenta el impacto psicológico vicario que tuvo el terremoto de 2010 en Haití sobre los residentes haitianos que viven en Estados Unidos. Se explora el papel de los recursos de afrontamiento-apoyo familiar, religioso y comunitario. Lo resultados destacan la importancia de la familia y la comunidad como estrategias de afrontamiento para superar un trauma de esas characterísticas. [ABSTRACT FROM AUTHOR]

Reports of Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) detected in marine environments have occurred since the early 1990s. This investigation sought to isolate and characterize S. aureus from marine waters and sand at a subtropical recreational beach, with and without bathers present, in order to investigate possible sources and to identify the risks to bathers of exposure to these organisms. During 40 days over 17 months, 1,001 water and 36 intertidal sand samples were collected by either bathers or investigators at a subtropical recreational beach. Methicillin-sensitive S. aureus (MSSA) and MRSA were isolated and identified using selective growth media and an organism-specific molecular marker. Antimicrobial susceptibility, staphylococcal cassette chromosome mec (SCC mec) type, pulsed-field gel electrophoresis (PFGE) pattern, multi-locus sequence type (MLST), and staphylococcal protein A ( spa) type were characterized for all MRSA. S. aureus was isolated from 248 (37 %) bather nearby water samples at a concentration range of <2-780 colony forming units per ml, 102 (31 %) ambient water samples at a concentration range of <2-260 colony forming units per ml, and 9 (25 %) sand samples. Within the sand environment, S. aureus was isolated more often from above the intertidal zone than from intermittently wet or inundated sand. A total of 1334 MSSA were isolated from 37 sampling days and 22 MRSA were isolated from ten sampling days. Seventeen of the 22 MRSA were identified by PFGE as the community-associated MRSA USA300. MRSA isolates were all SCC mec type IVa, encompassed five spa types (t008, t064, t622, t688, and t723), two MLST types (ST8 and ST5), and 21 of 22 isolates carried the genes for Panton-Valentine leukocidin. There was a correlation ( r = 0.45; p = 0.05) between the daily average number of bathers and S. aureus in the water; however, no association between exposure to S. aureus in these waters and reported illness was found. This report supports the concept that humans are a potential direct source for S. aureus in marine waters. [ABSTRACT FROM AUTHOR]

Studies evaluating the relationship between microbes and human health at non-point source beaches are necessary for establishing criteria which would protect public health while minimizing economic burdens. The objective of this study was to evaluate water quality and daily cumulative health effects (gastrointestinal, skin, and respiratory illnesses) for bathers at a non-point source subtropical marine recreational beach in order to better understand the inter-relationships between these factors and hence improve monitoring and pollution prevention techniques. Daily composite samples were collected, during the Oceans and Human Health Beach Exposure Assessment and Characterization Health Epidemiologic Study conducted in Miami (Florida, USA)at a non-point source beach, and analyzed for several pathogens, microbial source tracking markers, indicator microbes, and environmental parameters. Analysis demonstrated that rainfall and tide were more influential, when compared to other environmental factors and source tracking markers, in determining the presence of both indicator microbes and pathogens. Antecedent rainfall and F+ coliphage detection in water should be further assessed to confirm their possible association with skin and gastrointestinal (GI) illness outcomes, respectively. The results of this research illustrate the potential complexity of beach systems characterized by non-point sources, and how more novel and comprehensive approaches are needed to assess beach water quality for the purpose of protecting bather health. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus including methicillin resistant S. aureus, MRSA, are human colonizing bacteria that commonly cause opportunistic infections primarily involving the skin in otherwise healthy individuals. These infections have been linked to close contact and sharing of common facilities such as locker rooms, schools and prisons Waterborne exposure and transmission routes have not been traditionally associated with S. aureus infections. Coastal marine waters and beaches used for recreation are potential locations for the combination of high numbers of people with close contact and therefore could contribute to the exposure to and infection by these organisms. The primary aim of this study was to evaluate the amount and characteristics of the shedding of methicillin sensitive S. aureus, MSSA and MRSA by human bathers in marine waters. Results: Nasal cultures were collected from bathers, and water samples were collected from two sets of pools designed to isolate and quantify MSSA and MRSA shed by adults and toddlers during exposure to marine water. A combination of selective growth media and biochemical and polymerase chain reaction analysis was used to identify and perform limited characterization of the S. aureus isolated from the water and the participants. Twelve of 15 MRSA isolates collected from the water had identical genetic characteristics as the organisms isolated from the participants exposed to that water while the remaining 3 MRSA were without matching nasal isolates from participants. The amount of S. aureus shed per person corresponded to 105 to 106 CFU per person per 15-minute bathing period, with 15 to 20% of this quantity testing positive for MRSA. Conclusions: This is the first report of a comparison of human colonizing organisms with bacteria from human exposed marine water attempting to confirm that participants shed their own colonizing MSSA and MRSA into their bathing milieu. These findings clearly demonstrate that adults and toddlers shed their colonizing organisms into marine waters and therefore can be sources of potentially pathogenic S. aureus and MRSA in recreational marine waters. Additional research is needed to evaluate recreational beaches and marine waters as potential exposure and transmission pathways for MRSA. [ABSTRACT FROM AUTHOR]

The objectives of this work were to compare enterococci (ENT) measurements based on the membrane filter, ENT(MF) with alternatives that can provide faster results including alternative enterococci methods (e.g., chromogenic substrate (CS), and quantitative polymerase chain reaction (qPCR)), and results from regression models based upon environmental parameters that can be measured in real-time. ENT(MF) were also compared to source tracking markers (Staphylococcus aureus, Bacteroidales human and dog markers, and Catellicoccus gull marker) in an effort to interpret the variability of the signal. Results showed that concentrations of enterococci based upon MF (<2 to 3320 CFU/100 mL) were significantly different from the CS and qPCR methods (p < 0.01). The correlations between MF and CS (r = 0.58, p < 0.01) were stronger than between MF and qPCR (r ≤ 0.36, p < 0.01). Enterococci levels by MF, CS, and qPCR methods were positively correlated with turbidity and tidal height. Enterococci by MF and CS were also inversely correlated with solar radiation but enterococci by qPCR was not. The regression model based on environmental variables provided fair qualitative predictions of enterococci by MF in real-time, for daily geometric mean levels, but not for individual samples. Overall, ENT(MF) was not significantly correlated with source tracking markers with the exception of samples collected during one storm event. The inability of the regression model to predict ENT(MF) levels for individual samples is likely due to the different sources of ENT impacting the beach at any given time, making it particularly difficult to to predict short-term variability of ENT(MF) for environmental parameters. [ABSTRACT FROM AUTHOR]

Background: Microbial water-quality indicators, in high concentrations in sewage, are used to determine whether water is safe for recreational purposes. Recently, the use of these indicators to regulate recreational water bodies, particularly in sub/tropical recreational marine waters without known sources of sewage, has been questioned. The objectives of this study were to evaluate the risk to humans from exposure to subtropical recreational marine waters with no known point source, and the possible relationship between microbe densities and reported symptoms in human subjects with random-exposure assignment and intensive individual microbial monitoring in this environment.Methods: A total of 1303 adult regular bathers were randomly assigned to bather and non-bather groups, with subsequent follow-up for reported illness, in conjunction with extensive environmental sampling of indicator organisms (enterococci).Results: Bathers were 1.76 times more likely to report gastrointestinal illness [95% confidence interval (CI) 0.94-3.30; P = 0.07]; 4.46 times more likely to report acute febrile respiratory illness (95% CI 0.99-20.90; P = 0.051) and 5.91 times more likely to report a skin illness (95% CI 2.76-12.63; P < 0.0001) relative to non-bathers. Evidence of a dose-response relationship was found between skin illnesses and increasing enterococci exposure among bathers [1.46 times (95% CI 0.97-2.21; P = 0.07) per increasing log(10) unit of enterococci exposure], but not for gastrointestinal or respiratory illnesses.Conclusions: This study indicated that bathers may be at increased risk of several illnesses relative to non-bathers, even in the absence of any known source of domestic sewage impacting the recreational marine waters. There was no dose-response relationship between gastroenteritis and increasing exposure to enterococci, even though many current water-monitoring standards use gastroenteritis as the major outcome illness. [ABSTRACT FROM AUTHOR]

Abstract: The use of enterococci as the primary fecal indicator bacteria (FIB) for the determination of recreational water safety has been questioned, particularly in sub/tropical marine waters without known point sources of sewage. Alternative FIB (such as the Bacteroidales group) and alternative measurement methods (such as rapid molecular testing) have been proposed to supplement or replace current marine water quality testing methods which require culturing enterococci. Moreover, environmental parameters have also been proposed to supplement current monitoring programs. The objective of this study was to evaluate the health risks to humans from exposure to subtropical recreational marine waters with no known point source. The study reported symptoms between one set of human subjects randomly assigned to marine water exposure with intensive environmental monitoring compared with other subjects who did not have exposure. In addition, illness outcomes among the exposed bathers were compared to levels of traditional and alternative FIB (as measured by culture-based and molecular-based methods), and compared to easily measured environmental parameters. Results demonstrated an increase in self-reported gastrointestinal, respiratory and skin illnesses among bathers vs. non-bathers. Among the bathers, a dose–response relationship by logistic regression modeling was observed for skin illness, where illness was positively related to enterococci enumeration by membrane filtration (odds ratio = 1.46 [95% confidence interval = 0.97–2.21] per increasing log10 unit of enterococci exposure) and positively related to 24 h antecedent rain fall (1.04 [1.01–1.07] per increasing millimeters of rain). Acute febrile respiratory illness was inversely related to water temperature (0.74 [0.56–0.98] per increasing degree of water temperature). There were no significant dose–response relationships between report of human illness and any of the other FIB or environmental measures. Therefore, for non-point source subtropical recreational marine waters, this study suggests that humans may be at increased risk of reported illness, and that the currently recommended and investigational FIB may not track gastrointestinal illness under these conditions; the relationship between other human illness and environmental measures is less clear. [Copyright &y& Elsevier]

Abstract: Traditionally, the use of enterococci has been recommended as the fecal indicator bacteria of choice for testing marine recreational water quality, and prior studies have shown that bathers shed large numbers of enterococci into the water. The current study expands upon prior research by evaluating shedding from both toddlers and adults, and by the expansion of measurements to include enterococci shedding via three different methods (membrane filter (MF), chromogenic substrate (CS), and quantitative polymerase chain reaction (qPCR)) and shedding of alternative fecal indicator bacteria (Bacteroidales human markers UCD and HF8 via qPCR). Two sets of experiments were conducted. The first experiment consisted of two groups of 10 adults who bathed together in a large pool. The second study consisted of 14 toddlers who bathed individually in a small pool which allowed for sand recovery. Sand recovery was used to estimate the amount of sand transported on the bodies of toddlers and to estimate the number of fecal indicator bacteria released from this sand. The numbers of estimated enterococci shed per adult ranged from 1.8×104 to 2.8×106 CFU, from 1.9×103 to 4.5×106 MPN, and from 3.8×105 to 5.5×106 GEU based on the MF, CS, and qPCR methods, respectively. The estimated numbers of Bacteroidales human markers ranged from 1.8×104 to 1.3×106 for UCD, and ranged from the below detection limit to 1.6×105 for HF8. The estimated amount of sand transported per toddler (n =14) into the water column after sand exposure was 8±6g on average. When normalizing the numbers of enterococci shed from toddlers via sand by the 3.9 body surface area ratio, the differences between toddlers and adults were insignificant. Contributions of sands to the total enterococci (MF) shed per toddler was 3.7±4.4% on average. Although shedding via beach sand may contribute a small fraction of the microbial load during initial bathing, it may have a significant role if bathers go to water repetitively after sand exposure. [Copyright &y& Elsevier]