Assessing the effect of selective serotonin reuptake inhibitors in the prevention of post-acute sequelae of COVID-19.

Background: Post-acute sequelae of COVID-19 (PASC) produce significant morbidity, prompting evaluation of interventions that might lower risk. Selective serotonin reuptake inhibitors (SSRIs) potentially could modulate risk of PASC via their central, hypothesized immunomodulatory, and/or antiplatelet properties although clinical trial data are lacking. Materials and Methods: This retrospective study was conducted leveraging real-world clinical data within the National COVID Cohort Collaborative (N3C) to evaluate whether SSRIs with agonist activity at the sigma-1 receptor (S1R) lower the risk of PASC, since agonism at this receptor may serve as a mechanism by which SSRIs attenuate an inflammatory response. Additionally, determine whether the potential benefit could be traced to S1R agonism. Presumed PASC was defined based on a computable PASC phenotype trained on the U09.9 ICD-10 diagnosis code. Results: Of the 17,908 patients identified, 1521 were exposed at baseline to a S1R agonist SSRI, 1803 to a non-S1R agonist SSRI, and 14,584 to neither. Using inverse probability weighting and Poisson regression, relative risk (RR) of PASC was assessed.A 29% reduction in the RR of PASC (0.704 [95% CI, 0.58-0.85]; P = 4 ×10-4) was seen among patients who received an S1R agonist SSRI compared to SSRI unexposed patients and a 21% reduction in the RR of PASC was seen among those receiving an SSRI without S1R agonist activity (0.79 [95% CI, 0.67 - 0.93]; P = 0.005).Thus, SSRIs with and without reported agonist activity at the S1R were associated with a significant decrease in the risk of PASC.

The Burden of Wildfire Smoke on Respiratory Health in California at the Zip Code Level: Uncovering the Disproportionate Impacts of Differential Fine Particle Composition.

Wildfires constitute a growing source of extremely high levels of particulate matter that is less than 2.5 microns in diameter (PM2.5). Recently, toxicologic and epidemiologic studies have shown that PM2.5 generated from wildfires may have a greater health burden than PM2.5 generated from other pollutant sources. This study examined the impact of PM2.5 on hospitalizations for respiratory diseases in California between 2006 and 2019 using a health impact assessment approach that considers differential concentration-response functions (CRF) for PM2.5 from wildfire and non-wildfire sources of emissions. We quantified the burden of respiratory hospitalizations related to PM2.5 exposure at the zip code level through two different approaches: (a) naïve (considering the same CRF for all PM2.5 emissions) and (b) nuanced (considering different CRFs for PM2.5 from wildfires and from other sources). We conducted a Geographically Weighted Regression to analyze spatially varying relationships between the delta (i.e., the difference between the naïve and nuanced approaches) and the Centers for Disease Control and Prevention's Social Vulnerability Index (SVI). A higher attributable number of respiratory hospitalizations was found when accounting for the larger health burden of wildfire PM2.5. We found that, between 2006 and 2019, the number of hospitalizations attributable to PM2.5 may have been underestimated by approximately 13% as a result of not accounting for the higher CRF of wildfire-related PM2.5 throughout California. This underestimation was higher in northern California and areas with higher SVI rankings. The relationship between delta and SVI varied spatially across California. These findings can be useful for updating future air pollution guideline recommendations.

Paxlovid (nirmatrelvir/ritonavir) effectiveness against hospitalization and death in N3C: A target trial emulation study.

Importance: COVID-19 has placed a monumental burden on the health care system globally. Although no longer a public health emergency, there is still a pressing need for effective treatments to prevent hospitalization and death. Paxlovid (nirmatrelvir/ritonavir) is a promising and potentially effective antiviral that has received emergency use authorization by the U.S. FDA. Objective: Determine real world effectiveness of Paxlovid nationwide and investigate disparities between treated and untreated eligible patients. Design/Setting/Participants: Population-based cohort study emulating a target trial, using inverse probability weighted models to balance treated and untreated groups on baseline confounders. Participants were patients with a SARS-CoV-2 positive test or diagnosis (index) date between December 2021 and February 2023 selected from the National COVID Cohort Collaborative (N3C) database who were eligible for Paxlovid treatment. Namely, adults with at least one risk factor for severe COVID-19 illness, no contraindicated medical conditions, not using one or more strictly contraindicated medications, and not hospitalized within three days of index. From this cohort we identified patients who were treated with Paxlovid within 5 days of positive test or diagnosis (n = 98,060) and patients who either did not receive Paxlovid or were treated outside the 5-day window (n = 913,079 never treated; n = 1,771 treated after 5 days). Exposures: Treatment with Paxlovid within 5 days of positive COVID-19 test or diagnosis. Main Outcomes and Measures: Hospitalization and death in the 28 days following COVID-19 index date. Results: A total of 1,012,910 COVID-19 positive patients at risk for severe COVID-19 were included, 9.7% of whom were treated with Paxlovid. Uptake varied widely by geographic region and timing, with top adoption areas near 50% and bottom near 0%. Adoption increased rapidly after EUA, reaching steady state by 6/2022. Participants who were treated with Paxlovid had a 26% (RR, 0.742; 95% CI, 0.689-0.812) reduction in hospitalization risk and 73% (RR, 0.269, 95% CI, 0.179-0.370) reduction in mortality risk in the 28 days following COVID-19 index date. Conclusions/Relevance: Paxlovid is effective in preventing hospitalization and death in at-risk COVID-19 patients. These results were robust to a large number of sensitivity considerations. Disclosure: The authors report no disclosures. Key points: Question: Is treatment with Paxlovid (nirmatrelvir/ritonavir) associated with a reduction in 28-day hospitalization and mortality in patients at risk for severe COVID-19? Findings: In this multi-institute retrospective cohort study of 1,012,910 patients, Paxlovid treatment within 5 days after COVID-19 diagnosis reduced 28-day hospitalization and mortality by 26% and 73% respectively, compared to no treatment with Paxlovid within 5 days. Paxlovid uptake was low overall (9.7%) and highly variable. Meaning: In Paxlovid-eligible patients, treatment was associated with decreased risk of hospitalization and death. Results align with prior randomized trials and observational studies, thus supporting the real-world effectiveness of Paxlovid.

Comparing the Use of DynaMed and UpToDate by Physician Trainees in Clinical Decision-Making: A Randomized Crossover Trial.

BACKGROUND: Costs vary substantially among electronic medical knowledge resources used for clinical decision support, warranting periodic assessment of institution-wide adoption. OBJECTIVES: To compare two medical knowledge resources, UpToDate and DynaMed Plus, regarding accuracy and time required to answer standardized clinical questions and user experience. METHODS: A crossover trial design was used, wherein physicians were randomized to first use one of the two medical knowledge resources to answer six standardized questions. Following use of each resource, they were surveyed regarding their user experience. The percentage of accurate answers and time required to answer each question were recorded. The surveys assessed ease of use, enjoyment using the resource, quality of information, and ability to assess level of evidence. Tests of carry-over effects were performed. Themes were identified within open-ended survey comments regarding overall user experience. RESULTS: Among 26 participating physicians, accuracy of answers differed by 4 percentage points or less. For all but one question, there were no significant differences in the time required for completion. Most participants felt both resources were easy to use, contained high quality of information, and enabled assessment of the level of evidence. A greater proportion of participants endorsed enjoyment of use with UpToDate (23/26, 88%) compared with DynaMed Plus (16/26, 62%). Themes from open-ended comments included interface/information presentation, coverage of clinical topics, search functions, and utility for clinical decision-making. The majority (59%) of open-ended comments expressed an overall preference for UpToDate, compared with 19% preferring DynaMed Plus. CONCLUSION: DynaMed Plus is noninferior to UpToDate with respect to ability to achieve accurate answers, time required for answering clinical questions, ease of use, quality of information, and ability to assess level of evidence. However, user experience was more positive with UpToDate. Future studies of electronic medical knowledge resources should continue to emphasize evaluation of usability and user experience.

Spatial variation in the joint effect of extreme heat events and ozone on respiratory hospitalizations in California.

Extreme heat and ozone are co-occurring exposures that independently and synergistically increase the risk of respiratory disease. To our knowledge, no joint warning systems consider both risks; understanding their interactive effect can warrant use of comprehensive warning systems to reduce their burden. We examined heterogeneity in joint effects (on the additive scale) between heat and ozone at small geographical scales. A within-community matched design with a Bayesian hierarchical model was applied to study this association at the zip code level. Spatially varying relative risks due to interaction (RERI) were quantified to consider joint effects. Determinants of the spatial variability of effects were assessed using a random effects metaregression to consider the role of demographic/neighborhood characteristics that are known effect modifiers. A total of 817,354 unscheduled respiratory hospitalizations occurred in California from 2004 to 2013 in the May to September period. RERIs revealed no additive interaction when considering overall joint effects. However, when considering the zip code level, certain areas observed strong joint effects. A lower median income, higher percentage of unemployed residents, and exposure to other air pollutants within a zip code drove stronger joint effects; a higher percentage of commuters who walk/bicycle, a marker for neighborhood wealth, showed decreased effects. Results indicate the importance of going beyond average measures to consider spatial variation in the health burden of these exposures and predictors of joint effects. This information can be used to inform early warning systems that consider both heat and ozone to protect populations from these deleterious effects in identified areas.

Respiratory hospitalizations and wildfire smoke: a spatiotemporal analysis of an extreme firestorm in San Diego County, California.

Wildfire smoke adversely impacts respiratory health as fine particles can penetrate deeply into the lungs. Epidemiological studies of differential impacts typically target population subgroups in terms of vulnerability to wildfire smoke. Such information is useful to customize smoke warnings and mitigation actions for specific groups of individuals. In addition to individual vulnerability, it is also important to assess spatial patterns of health impacts to identify vulnerable communities and tailor public health actions during wildfire smoke events. METHODS: We assess the spatiotemporal variation in respiratory hospitalizations in San Diego County during a set of major wildfires in 2007, which led to a substantial public health burden. We propose a spatial within-community matched design analysis, adapted to the study of wildfire impacts, coupled with a Bayesian Hierarchical Model, that explicitly considers the spatial variation of respiratory health associated with smoke exposure, compared to reference periods before and after wildfires. We estimate the signal-to-noise ratio to ultimately gauge the precision of the Bayesian model output. RESULTS: We find the highest excess hospitalizations in areas covered by smoke, mainly ZIP codes contained by and immediately downwind of wildfire perimeters, and that excess hospitalizations tend to follow the distribution of smoke plumes across space (ZIP codes) and time (days). CONCLUSIONS: Analyzing the spatiotemporal evolution of exposure to wildfire smoke is necessary due to variations in smoke plume extent, particularly in this region where the most damaging wildfires are associated with strong wind conditions.

Understanding Aging in Bipolar Disorder by Integrating Archival Clinical Research Datasets.

OBJECTIVE: Although 25% of people with bipolar disorder (BD) are over age 60, there is a dearth of research on older age bipolar disorder (OABD). This report describes an initial effort to create an integrated OABD database using the U.S. National Institute of Mental Health Data Archive (NDA). Goals were to: 1) combine data from three BD studies in the United States that included overlapping data elements; 2) investigate research questions related to aims of the original studies; and 3) take an important first step toward combining existing datasets relevant to aging and BD. METHODS: Data were prepared and uploaded to the NDA, with a focus on data elements common to all studies. As appropriate, data were harmonized to select or collapse categories suitable for cross-walk analysis. Associations between age, BD symptoms, functioning, medication load, medication adherence, and medical comorbidities were assessed. The total sample comprised 451 individuals, mean age 57.7 (standard deviation: 13.1) years. RESULTS: Medical comorbidity was not significantly associated with either age or functioning and there did not appear to be an association between medication load, comorbidity, age, and adherence. Men and African-Americans were significantly more likely to have poor adherence. Both BD mania and depression symptoms were associated with functioning, but this differed across studies. CONCLUSION: Despite limitations including heterogeneity in study design and samples and cross-sectional methodology, integrated datasets represent an opportunity to better understand how aging may impact the presentation and evolution of chronic mental health disorders across the lifespan.

Using social determinants of health to link health workforce diversity, care quality and access, and health disparities to achieve health equity in nursing.

It is widely accepted that diversifying the nation's health-care workforce is a necessary strategy to increase access to quality health care for all populations, reduce health disparities, and achieve health equity. In this article, we present a conceptual model that utilizes the social determinants of health framework to link nursing workforce diversity and care quality and access to two critical population health indicators-health disparities and health equity. Our proposed model suggests that a diverse nursing workforce can provide increased access to quality health care and health resources for all populations, and is a necessary precursor to reduce health disparities and achieve health equity. With this conceptual model as a foundation, we aim to stimulate the conceptual and analytical work-both within and outside the nursing field-that is necessary to answer these important but largely unanswered questions.

Optimization of arylindenopyrimidines as potent adenosine A(2A)/A(1) antagonists.

Two reactive metabolites were identified in vivo for the dual A(2A)/A(1) receptor antagonist 1. Two strategies were implemented to successfully mitigate the metabolic liabilities associated with 1. Optimization of the arylindenopyrimidines led to a number of amide, ether, and amino analogs having comparable in vitro and in vivo activity.

Methylene amine substituted arylindenopyrimidines as potent adenosine A(2A)/A(1) antagonists.

A novel series of arylindenopyrimidines were identified as A(2A) and A(1) receptor antagonists. The series was optimized for in vitro activity by substituting the 8- and 9-positions with methylene amine substituents. The compounds show excellent activity in mouse models of Parkinson's disease when dosed orally.

Two-generation reproduction and cross-foster studies of perfluorooctanesulfonate (PFOS) in rats.

Perfluorooctanesulfonate (PFOS) is a persistent acid found widely distributed in wildlife and humans. To understand the potential reproductive and developmental effects of PFOS, a two-generation reproduction study was conducted in rats. Male and female rats were dosed via oral gavage at dose levels of 0, 0.1, 0.4, 1.6, and 3.2 mg/(kg day) for 6 weeks prior to mating, during mating, and, for females, through gestation and lactation, across two generations. Due to substantial F1 neonatal toxicity observed in the 1.6 and 3.2 mg/(kg day) groups, continuation into the second generation was limited to F1 pups from the 0, 0.1, and 0.4 mg/(kg day) groups. No adverse effects were observed in F0 females or their fetuses upon caesarean sectioning at gestation day 10. Statistically significant reductions in body-weight gain and feed consumption were observed in F0 generation males and females at dose levels of 0.4 mg/(kg day) and higher, but not in F1 adults. PFOS did not affect reproductive performance (mating, estrous cycling, and fertility); however, reproductive outcome, as demonstrated by decreased length of gestation, number of implantation sites, and increased numbers of dams with stillborn pups or with all pups dying on lactation days 1-4, was affected at 3.2 mg/(kg day) in F0 dams. These effects were not observed in F1 dams at the highest dose tested, 0.4 mg/(kg day). Neonatal toxicity in F1 pups, as demonstrated by reduced survival and body-weight gain through the end of lactation, occurred at a maternal dose of 1.6 mg/(kg day) and higher while not at dose levels of 0.1 or 0.4 mg/(kg day) or in F2 pups at the 0.1 or 0.4 mg/(kg day) dose levels tested. In addition to these adverse effects, slight yet statistically significant developmental delays occurred at 0.4 (eye opening) and 1.6 mg/(kg day) (eye opening, air righting, surface righting, and pinna unfolding) in F1 pups. Based on these data, the NOAELs were as follows: reproductive function: F0> or =3.2 and F1> or =0.4 mg/(kg day); reproductive outcome: F0=1.6 and F1> or =0.4 mg/(kg day); overall parental effects: F0=0.1 and F1> or =0.4 mg/(kg day); offspring effects: F0=0.4 and F1> or =0.4 mg/(kg day). To distinguish between maternal and pup influences contributing to the perinatal mortality observed in the two-generation study, a follow-up cross-foster study was performed. Results of this study indicated that in utero exposure to PFOS causally contributed to post-natal pup mortality, and that pre-natal and post-natal exposure to PFOS was additive with respect to the toxic effects observed in pups.

Neonatal mortality from in utero exposure to perfluorooctanesulfonate (PFOS) in Sprague-Dawley rats: dose-response, and biochemical and pharamacokinetic parameters.

Perfluorooctanesulfonate (PFOS) is a widely distributed, environmentally persistent acid found at low levels in human, wildlife, and environmental media samples. Neonatal mortality has been observed following PFOS exposure in a two-generation reproduction study in rats and after dosing pregnant rats and mice during gestation. Objectives of the current study were to better define the dose-response curve for neonatal mortality in rat pups born to PFOS-exposed dams and to investigate biochemical and pharmacokinetic parameters potentially related to the etiology of effects observed in neonatal rat pups. In the current study, additional doses of 0.8, 1.0, 1.2, and 2.0 mg/kg/day were included with original doses used in the two-generation study of 0.4 and 1.6 mg/kg/day in order to obtain data in the critical range of the dose-response curve. Biochemical parameters investigated in dams and litters included: (1) serum lipids, glucose, mevalonic acid, and thyroid hormones; (2) milk cholesterol; and (3) liver lipids. Pharmacokinetic parameters investigated included the interrelationship of administered oral dose of PFOS to maternal body burden of PFOS and the transfer of maternal body burden to the fetus in utero and pup during lactation, as these factors may affect neonatal toxicity. Dosing of dams occurred for 6 weeks prior to mating with untreated breeder males, through confirmed mating, gestation, and day four of lactation. Dose levels for the dose-response and etiological investigation were 0.0, 0.4, 0.8, 1.0, 1.2, 1.6, and 2.0 mg/kg/day PFOS. Statistically significant decreases in gestation length were observed in the 0.8 mg/kg and higher dose groups. Decreases in viability through lactation day 5 were observed in the 0.8 mg/kg and higher dose groups, becoming statistically significant in the 1.6 and 2.0 mg/kg dose groups. Reduced neonatal survival did not appear to be the result of reductions in lipids, glucose utilization, or thyroid hormones. The endpoints of gestation length and decreased viability were positively correlated, suggesting that late-stage fetal development may be affected in pups exposed to PFOS in utero and may contribute to the observed mortality. Benchmark dose (BMD) estimates for decreased gestation length, birth weight, pup weight on lactation day 5, pup weight gain through lactation day 5, and viability resulted in values ranging from 0.27 to 0.89mg/kg/day for the lower 95% confidence limit of the BMD5 (BMDL5). Results of analyses for PFOS in biological matrices indicate a linear proportionality of mean serum PFOS concentration to maternal administered dose prior to mating and through the first two trimesters of gestation. However, at 21 days of gestation, mean serum PFOS concentrations were notably reduced from values measured earlier in gestation. Urinary and fecal elimination was low as expected from prior observations in adult rats. Significant transfer of PFOS from dam to fetus in utero was confirmed, and results suggest that dam and corresponding fetal body burdens, as indicated by serum and liver PFOS levels, correlate with neonatal survival.

Historical comparison of perfluorooctanesulfonate, perfluorooctanoate, and other fluorochemicals in human blood.

The purpose of this investigation was to determine whether there has been a change in the human blood concentration of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and five other fluorochemicals since 1974. Blood samples were collected in 1974 (serum) and 1989 (plasma) from volunteer participants of a large community health study. The study included a total of 356 samples (178 from each time period). These samples were analyzed by high-pressure liquid chromatography/tandem mass spectrometry methods. The median 1974 and 1989 fluorochemical concentrations, respectively, were as follows: PFOS, 29.5 ng/mL vs. 34.7 ng/mL; PFOA, 2.3 ng/mL vs. 5.6 ng/mL; perfluorohexanesulfonate (PFHS), 1.6 ng/mL vs. 2.4 ng/mL; and N-ethyl perfluorooctanesulfonamidoacetate (PFOSAA), less than the lower limit of quantitation (LLOQ; 1.6 ng/mL, vs. 3.4 ng/mL). For N-methyl perfluorooctanesulfonamidoacetate (M570), perfluorooctanesulfonamide, and perfluorooctanesulfonamidoacetate, median serum concentrations in both years were less than the LLOQ values (1.0, 1.0, and 2.5 ng/mL, respectively). Statistical analysis of 58 paired samples indicated that serum concentrations of PFOS, PFOSAA, PFOA, PFHS, and M570 were significantly (p < 0.001) higher in 1989 than in 1974. The data from 1989 were then compared with geometric mean fluorochemical concentrations of serum samples collected in 2001 from 108 American Red Cross adult blood donors from the same region. Except for M570, there were no statistically significant (p < 0.05) geometric mean fluorochemical concentration differences between the 1989 and 2001 samples. In conclusion, based on this study population, PFOS and other serum fluorochemical concentrations have increased between 1974 and 1989. Comparison with other regional data collected in 2001 did not suggest a continued increase in concentrations since 1989.

Serum concentrations of perfluorooctanesulfonate and other fluorochemicals in an elderly population from Seattle, Washington.

Perfluorooctanesulfonyl fluoride (POSF, C8F17SO2F) related-materials have been used as surfactants, paper and packaging treatments, and surface (e.g., carpet, textile, upholstery) protectants. A metabolite, perfluorooctanesulfonate (PFOS, C8F17SO3-), has been identified in the serum and liver of non-occupationally exposed humans and wildlife. Because of its persistence, an important question was whether elderly humans might have higher PFOS concentrations. From a prospective study designed to examine cognitive function in the Seattle (WA) metropolitan area, blood samples were collected from 238 dementia-free subjects (ages 65-96). High-pressure liquid chromatography-electrospray tandem mass spectrometry determined seven fluorochemicals: PFOS; N-ethyl perfluorooctanesulfonamidoacetate; N-methyl perfluorooctanesulfonamidoacetate; perfluorooctanesulfonamidoacetate; perfluorooctanesulfonamide; perfluorooctanoate; and perfluorohexanesulfonate. Serum PFOS concentrations ranged from less than the lower limit of quantitation (3.4 ppb) to 175.0 ppb (geometric mean 31.0 ppb; 95% CI 28.8-33.4). An estimate of the 95% tolerance limit was 84.1 ppb (upper 95% confidence limit 104.0 ppb). Serum PFOS concentrations were slightly lower among the most elderly. There were no significant differences by sex or years residence in Seattle. The distributions of the other fluorochemicals were approximately an order of magnitude lower. Similar to other reported findings of younger adults, the geometric mean serum PFOS concentration in non-occupational adult populations likely approximates 30-40 ppb with 95% of the population's serum PFOS concentrations below 100 ppb.

Perfluorooctanesulfonate and other fluorochemicals in the serum of American Red Cross adult blood donors.

Perfluorooctanesulfonyl fluoride-based products have included surfactants, paper and packaging treatments, and surface protectants (e.g., for carpet, upholstery, textile). Depending on the specific functional derivatization or degree of polymerization, such products may degrade or metabolize, to an undetermined degree, to perfluorooctanesulfonate (PFOS), a stable and persistent end product that has the potential to bioaccumulate. In this investigation, a total of 645 adult donor serum samples from six American Red Cross blood collection centers were analyzed for PFOS and six other fluorochemicals using HPLC-electrospray tandem mass spectrometry. PFOS concentrations ranged from the lower limit of quantitation of 4.1 ppb to 1656.0 ppb with a geometric mean of 34.9 ppb [95% confidence interval (CI), 33.3-36.5]. The geometric mean was higher among males (37.8 ppb; 95% CI, 35.5-40.3) than among females (31.3 ppb; 95% CI, 30.0-34.3). No substantial difference was observed with age. The estimate of the 95% tolerance limit of PFOS was 88.5 ppb (upper limit of 95% CI, 100.0 ppb). The measures of central tendency for the other fluorochemicals (N-ethyl perfluorooctanesulfonamidoacetate, N-methyl perfluorooctanesulfonamidoacetate, perfluorooctanesulfonamidoacetate, perfluorooctanesulfonamide, perfluorooctanoate, and perfluorohexanesulfonate) were approximately an order of magnitude lower than PFOS. Because serum PFOS concentrations correlate with cumulative human exposure, this information can be useful for risk characterization.

An occupational exposure assessment of a perfluorooctanesulfonyl fluoride production site: biomonitoring.

This investigation randomly sampled a fluorochemical manufacturing employee population to determine the distribution of serum fluorochemical levels according to employees' jobs and work areas. Previous analyses of medical surveillance data have not shown significant associations between fluorochemical production employees' clinical chemistry and hematology tests and their serum PFOS and perfluorooctanoate (PFOA, C(7)F(15)COO(-)) concentrations, but may have been subject to nonparticipation bias. A random sample of the on-site film plant employee population, where fluorochemicals are not produced, determined their serum concentrations also. Of the 232 employees randomly selected for serum sampling, 186 (80%) employees participated (n=126 chemical plant; n=60 film plant). Sera samples were extracted using an ion-pairing extraction procedure and were quantitatively analyzed for seven fluorochemicals using high-pressure liquid chromatography electrospray tandem mass spectrometry methods. Geometric means (in parts per million) and 95% confidence intervals (in parentheses) of the random sample of 126 chemical plant employees were: PFOS 0.941 (0.787-1.126); PFOA 0.899 (0.722-1.120); perfluorohexanesulfonate 0.180 (0.145-0.223); N-ethyl perfluorooctanesulfonamidoacetate 0.008 (0.006-0.011); N-methyl perfluorooctanesulfonamidoacetate 0.081 (0.067-0.098); perfluorooctanesulfonamide 0.013 (0.009-0.018); and perfluorooctanesulfonamidoacetate 0.022 (0.018-0.029). These geometric means were approximately one order of magnitude higher than those observed for the film plant employees.

Human donor liver and serum concentrations of perfluorooctanesulfonate and other perfluorochemicals.

Perfluorooctanesulfonate (PFOS, CaF17SO3-) has been identified in the serum of nonoccupationally exposed humans and in serum and liver tissue in wildlife. The purpose of this investigation was to determine whether PFOS liver concentrations in humans are comparable to the approximate 30 ng/mL average serum concentrations reported in nonoccupationally exposed subjects. Thirty-one donors (16 male and 15 female, age range 5-74) provided serum and/or liver samples for analysis of PFOS and three other fluorochemicals: perfluorosulfonamide (PFOSA, C8F17SO2NH2), perfluorooctanoate (PFOA, C7F15CO2-), and perfluorohexanesulfonate (PFHxS, C6F13SO3-). Both sera and liver samples were extracted by ion-pair extraction and quantitatively assayed using high-performance liquid chromatography electrospray tandem mass spectrometry. Liver PFOS concentrations ranged from <4.5 ng/g (limit of quantitation, LOQ)to 57.0 ng/g. Serum PFOS concentrations ranged from <6.1 ng/mL (LOQ) to 58.3 ng/mL. Among the 23 paired samples, the mean liver to serum ratio was 1.3:1 (95% confidence interval 0.9:1-1.7:1). This liver to serum ratio is comparable to that reported in a toxicological study of cynomolgus monkeys, which had liver and serum concentrations 2-3 orders of magnitude higher than observed in these human donors. This information may be useful in human risk characterization for PFOS. Liver to serum ratios were not estimated for PFOA, PFHxS, and PFOSA as 90% of the human donor liver samples were determined to be less than the LOQ.

Long-term psychological impact and perceived efficacy of pulsed-dye laser therapy for patients with port-wine stains.

BACKGROUND: The rationale for treatment of patients with port-wine stain (PWS) birthmarks has focused on the belief that eventual soft-tissue hypertrophy and negative psychological effects might be diminished or avoided. Pulsed-dye laser (PDL) therapy has become widely accepted as the treatment of choice for PWS, and a variety of studies have been conducted that evaluate its short-term efficacy. Long-term data regarding outcome and patient satisfaction are lacking. OBJECTIVE: Our objective was to evaluate the long-term efficacy of pulsed-dye laser therapy from the patient's perspective. METHODS: A survey was mailed to all patients or parents of minor patients whose last known laser treatment was performed between January 1, 1989, and January 1, 1996. Patients were asked to quantify changes in their PWS as well as their psychological well-being. A formal qualitative analysis was performed on their written comments as well. RESULTS: A total of 164 surveys were mailed to the most recent address available by the patient record. Fifty-two surveys were returned as undeliverable, and 55 evaluable surveys were returned, yielding a 49% overall return rate for patients who could be located. The mean age of respondents was 28.8 years, 96% of whom were white and 62% female. The mean number of years since last treatment was 7.04. The vast majority of patients noted little or no change in texture, height, or dimension of their PWS, whereas 62% noted color improvement. A majority or patients (60%) worried less about their appearance after treatment, whereas a similar number (61%) believed their ability to make friends or meet others was unaffected by treatment. Only 19% thought others looked at or treated them differently because of their PWS. Overall, 48% of patients indicated satisfaction with treatment, 24% dissatisfaction, and 28% neutral. On a 10-point scale indicating their likelihood of recommending treatment to someone similarly affected, the mean score was 7.42. Men were significantly and consistently less satisfied with treatment than women, despite rating the degree of color improvement similarly to women. Qualitative analysis of patient comments helped validate quantitative data and revealed gender differences in satisfaction, as well as correlations with adverse events from treatment, desire for additional treatment, and a trend toward more positive comments with the passage of time. CONCLUSION: The pulsed-dye laser improves the color of PWS over long periods of time in a majority of patients. Patients tended to worry less about their appearance after treatment, although most believed treatment did not substantially affect their relationship with others or others' view of them. Most patients were satisfied or neutral with regard to satisfaction with therapy and would recommend treatment to others. A minority of patients was dissatisfied with treatment, and men were more likely to be dissatisfied. Additional long-term and prospective studies will be helpful in assessing the physical and psychosocial impact of PDL for PWS.