Patient and Provider Experiences With a Digital App to Improve Compliance With Enhanced Recovery After Surgery (ERAS) Protocols: Mixed Methods Evaluation of a Canadian Experience.

BACKGROUND: Of all the care provided in health care systems, major surgical interventions are the costliest and can carry significant risks. Enhanced Recovery After Surgery (ERAS) is a bundle of interventions that help improve patient outcomes and experience along their surgical journey. However, given that patients can be overwhelmed by the multiple tasks that they are expected to follow, a digital application, the ERAS app, was developed to help improve the implementation of ERAS. OBJECTIVE: The objective of this work was to conduct a thorough assessment of patient and provider experiences using the ERAS app. METHODS: Patients undergoing colorectal or gynecological oncology surgery at 2 different hospitals in the province of Alberta, Canada, were invited to use the ERAS app and report on their experiences using it. Likewise, care providers were recruited to participate in this study to provide feedback on the performance of this app. Data were collected by an online survey and using qualitative interviews with participants. NVivo was used to analyze qualitative interview data, while quantitative data were analyzed using Excel and SPSS. RESULTS: Overall, patients found the app to be helpful in preparation for and recovery after surgery. Patients reported having access to reliable unbiased information regarding their surgery, and the app provided them with clarity of actions needed along their surgical journey and enhanced the self-management of their care. Clinicians found that the ERAS app was easy to navigate, was simple for older adults, and has the potential to decrease unnecessary visits and phone calls to care providers. Overall, this proof-of-concept study on the use of a digital health app to accompany patients during their health care journey has shown positive results. CONCLUSIONS: This is an important finding considering the massive investment and interest in promoting digital health in health care systems around the world.

Does the Type of Surgical Headwear Worn in the OR Matter? A Review of Evidence and Opinions.

Proper surgical attire is essential in decreasing surgical site infections; however, the effectiveness of the different types of headwear is a controversial topic. We conducted a narrative review based on studies identified through a focused literature search to summarize and critically assess evidence and opinions on the most appropriate type of headwear for OR personnel. We included 48 articles: 17 original research studies and 31 non-peer-reviewed articles of various types. Research published before 2014 mostly supports the complete coverage of all hair, which aligns with the 2015 AORN guidelines. However, more recent literature rebuts these guidelines and emphasizes the importance of clean headwear. Although earlier studies (published before 2017) lacked scientific rigor, later studies (published after 2017) have other various limitations, including missing data on compliance, surgery-related techniques, and surgical attire other than headwear. The findings from this review highlight the importance of solid evidence-based guidelines and expert collaboration.

A population-based assessment of avoidable hospitalizations and resource use of non-vaccinated patients with COVID-19.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has precipitated a prolonged public health crisis. Numerous public health protections were widely implemented. The availability of effective and safe vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presented an opportunity to resolve this crisis; however, vaccine uptake was slow and inconsistent. This study evaluated the potential for preventable hospitalizations and avoidable resource use among eligible non-vaccinated persons hospitalized for COVID-19 had these persons been vaccinated. METHODS: This was a retrospective, population-based cohort study. The population-at-risk were persons aged ≥ 12 years in Alberta (mid-year 2021 population ~ 4.4 million). The primary exposure was vaccination status. The primary outcome was hospitalization with confirmed SARS-CoV-2, and secondary outcomes included avoidable hospitalizations, avoidable hospital bed-days, and the potential cost avoidance related to COVID-19. The study inception period was 27 September 2021 to 25 January 2022. Data on COVID-19 hospitalizations, vaccination status, health services, and costs were obtained from the Government of Alberta and from the Discharge Abstract Database. RESULTS: Hospitalizations occurred in 3835, 1907, and 481 persons who were non-vaccinated, fully vaccinated, and boosted (risk of hospitalization/100,000 population: 886, 92, and 43), respectively. For non-vaccinated persons compared with fully vaccinated and boosted persons, the risk ratios (95%CI) of hospitalization were 9.7 (7.9-11.8) and 20.6 (17.9-23.6), respectively. For non-vaccinated persons, estimates of avoidable hospitalizations and bed-days used were 3439 and 36,331 if fully vaccinated and 3764 and 40,185 if boosted. Estimates of cost avoidance for non-vaccinated persons were $101.46 million if fully vaccinated and $110.24 million if boosted. CONCLUSION: Eligible non-vaccinated persons with COVID-19 had tenfold and 21-fold higher risks of hospitalization relative to whether they had been fully vaccinated or boosted, resulting in considerable avoidable hospital bed-days and costs.

RéSUMé: OBJECTIF: La pandémie de maladie à coronavirus 2019 (COVID-19) a précipité une crise de santé publique prolongée. De nombreuses mesures de protection de la santé publique ont été appliquées à grande échelle. La disponibilité de vaccins sûrs et efficaces contre le coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) a présenté une occasion de résoudre la crise, mais l'acceptation de la vaccination a été lente et inégale. Dans cette étude, nous évaluons le potentiel d'hospitalisations évitables et d'utilisation évitable des ressources pour les personnes non vaccinées admissibles hospitalisées pour la COVID-19, si ces personnes avaient été vaccinées. MéTHODES: Il s'agissait d'une étude de cohorte populationnelle rétrospective. La population à risque était les personnes de ≥ 12 ans en Alberta (~ 4,4 millions au milieu de l'année 2021). Le principal risque était le statut vaccinal. Le principal résultat clinique était l'hospitalisation avec SRAS-CoV-2 confirmé, et les résultats cliniques secondaires étaient les hospitalisations évitables, les jours-lits à l'hôpital évitables et l'évitement potentiel des coûts liés à la COVID-19. La période initiale de l'étude s'est étendue du 27 septembre 2021 au 25 janvier 2022. Les données sur les hospitalisations pour la COVID-19, le statut vaccinal, les coûts et les services de santé provenaient du gouvernement de l'Alberta et de la Base de données sur les congés des patients. RéSULTATS: En tout, 3 835 personnes non vaccinées, 1 907 personnes ayant reçu tous leurs vaccins et 481 personnes ayant reçu des doses de rappel ont été hospitalisées (risque d'hospitalisation p. 100 000 personnes : 886, 92 et 43, respectivement). Pour les personnes non vaccinées, comparativement aux personnes ayant reçu tous leurs vaccins et/ou les doses de rappel, les risques relatifs d'hospitalisation (IC de 95%) étaient de 9,7 (7,9­11,8) et de 20,6 (17,9­23,6), respectivement. Selon nos estimations, les personnes non vaccinées auraient évité 3 439 hospitalisations et 36 331 jours-lits si elles avaient reçu tous leurs vaccins, et 3 764 hospitalisations et 40 185 jours-lits si elles avaient en plus reçu les doses de rappel. Nous avons aussi estimé que les personnes non vaccinées auraient évité des coûts de 101,46 millions de dollars si elles avaient reçu tous leurs vaccins et de 110,24 millions de dollars si elles avaient en plus reçu les doses de rappel. CONCLUSION: Les personnes non vaccinées admissibles ayant contracté la COVID-19 ont présenté un risque d'hospitalisation 10 fois plus élevé que si elles avaient reçu tous leurs vaccins et 21 fois plus élevé que si elles avaient en plus reçu les doses de rappel, ce qui représente des jours-lits à l'hôpital et des coûts évitables considérables.

Beyond guideline knowledge: a theory-based qualitative study of low-value preoperative testing.

BACKGROUND: Choosing Wisely Canada and most major anesthesia and preoperative guidelines recommend against obtaining preoperative tests before low-risk procedures. However, these recommendations alone have not reduced low-value test ordering. In this study, the theoretical domains framework (TDF) was used to understand the drivers of preoperative electrocardiogram (ECG) and chest X-ray (CXR) ordering for patients undergoing low-risk surgery ('low-value preoperative testing') among anesthesiologists, internal medicine specialists, nurses, and surgeons. METHODS: Using snowball sampling, preoperative clinicians working in a single health system in Canada were recruited for semi-structured interviews about low-value preoperative testing. The interview guide was developed using the TDF to identify the factors that influence preoperative ECG and CXR ordering. Interview content was deductively coded using TDF domains and specific beliefs were identified by grouping similar utterances. Domain relevance was established based on belief statement frequency, presence of conflicting beliefs, and perceived influence over preoperative test ordering practices. RESULTS: Sixteen clinicians (7 anesthesiologists, 4 internists, 1 nurse, and 4 surgeons) participated. Eight of the 12 TDF domains were identified as the drivers of preoperative test ordering. While most participants agreed that the guidelines were helpful, they also expressed distrust in the evidence behind them (knowledge). Both a lack of clarity about the responsibilities of the specialties involved in the preoperative process and the ease by which any clinician could order, but not cancel tests, were drivers of low-value preoperative test ordering (social/professional role and identity, social influences, belief about capabilities). Additionally, low-value tests could also be ordered by nurses or the surgeon and may be completed before the anesthesia or internal medicine preoperative assessment appointment (environmental context and resources, beliefs about capabilities). Finally, while participants agreed that they did not intend to routinely order low-value tests and understood that these would not benefit patient outcomes, they also reported ordering tests to prevent surgery cancellations and problems during surgery (motivation and goals, beliefs about consequences, social influences). CONCLUSIONS: We identified key factors that anesthesiologists, internists, nurses, and surgeons believe influence preoperative test ordering for patients undergoing low-risk surgeries. These beliefs highlight the need to shift away from knowledge-based interventions and focus instead on understanding local drivers of behaviour and target change at the individual, team, and institutional levels.

Implementation of a Perioperative Glycemic Management Quality Improvement Pathway in Gynecologic Oncology Patients: A Single-cohort Interrupted Time-series Analysis.

OBJECTIVE: We evaluated implementation and clinical outcomes of a perioperative glycemic management pathway in gynecologic oncology. METHODS: Interrupted time-series analysis was used to compare process, balancing and outcome measures and clinical outcomes from 18 months preimplementation to 18 months postimplementation. RESULTS: Compared with in the preimplementation period, the proportion of patients who underwent preoperative screening with glycated hemoglobin in the postimplementation period increased by 11.3% (95% confidence interval [CI], 5.0% to 17.7%; p=0.001). The proportion of patients with diabetes who had at least 1 blood glucose measurement after surgery increased by 15.3% (95% CI, -3.2% to 33.8%; p=0.10). There was no change in the proportion of patients who had any hyperglycemia or moderate or severe hyperglycemia. The median length of stay decreased by 0.42 days (95% CI, -0.91 to 0.07 days; p=0.09). There were major quality gaps in perioperative glycemic management that did not clearly improve after implementation of a multidisciplinary care pathway. CONCLUSION: Optimal strategies for improvement of perioperative glycemic management are not yet known.

The impact of delaying surgery during the COVID-19 pandemic in Alberta: a qualitative study.

BACKGROUND: The COVID-19 pandemic overwhelmed health care systems, leading many jurisdictions to reduce surgeries to create capacity (beds and staff) to care for the surge of patients with COVID-19; little is known about the impact of this on patients whose surgery was delayed. The objective of this study was to understand the patient and family/caregiver perspective of having a surgery delayed during the COVID-19 pandemic. METHODS: Using an interpretative descriptive approach, we conducted interviews between Sept. 20 and Oct. 8, 2021. Adult patients who had their surgery delayed or cancelled during the COVID-19 pandemic in Alberta, Canada, and their family/caregivers were eligible to participate. Trained interviewers conducted semistructured interviews, which were iteratively analyzed by 2 independent reviewers using an inductive approach to thematic content analysis. RESULTS: We conducted 16 interviews with 15 patients and 1 family member/caregiver, ranging from 27 to 75 years of age, with a variety of surgical procedures delayed. We identified 4 interconnected themes: individual-level impacts on physical and mental health, family and friends, work and quality of life; system-level factors related to health care resources, communication and perceived accountability within the system; unique issues related to COVID-19 (maintaining health and isolation); and uncertainty about health and timing of surgery. INTERPRETATION: Although the decision to delay nonurgent surgeries was made to manage the strain on health care systems, our study illustrates the consequences of these decisions, which were diffuse and consequential. The findings of this study highlight the need to develop and adopt strategies to mitigate the burden of waiting for surgery during and after the COVID-19 pandemic.

Excess deaths during the COVID-19 pandemic in Alberta, Canada.

Objectives: To determine if there was excess mortality in Alberta, Canada during the coronavirus disease 2019 (COVID-19) pandemic, to confirm if excess mortality affected all age groups equally, and to determine what proportions of excess deaths were directly related to COVID-19 and non-pharmaceutical drug poisoning. Methods: Weekly all-cause data used to estimate excess mortality were modelled against the pre-pandemic period (January 2015-February 2020). Age-adjusted weekly mortality rates for March 2020 to December 2021 were compared with the preceding 5 years. Results: From March 2020 to December 2021, there was an 11% excess mortality rate, corresponding to an average of 265 monthly excess deaths (maximum >30%). COVID-19-related deaths (n=3202) accounted for 54.9% of total excess deaths (n=5833) that occurred in the 22-month period. The increase in all-cause excess deaths was proportionately higher, and with significantly greater numbers, in younger age groups. Significant increases in monthly drug poisoning deaths occurred from March 2020 to April 2021, with a total of 1819 deaths. Eight hundred and 25 excess drug poisoning deaths, representing 25.4% of total all-cause excess deaths, occurred, mainly among those aged 25-60 years. Overall, 54.9% of all excess deaths were directly related to COVID-19 and 25.4% were related to drug poisoning. Conclusions: There was a significant increase in all-cause mortality during the COVID-19 pandemic. Although older adults are more likely to die of COVID-19, a massive increase in non-COVID-19-related mortality was observed among younger people. These factors should be considered in public policy decisions on epidemic/pandemic management.

Avoidable intensive care unit resource use and costs of unvaccinated patients with COVID-19: a historical population-based cohort study.

PURPOSE: SARS-CoV-2 vaccines have been proven effective at preventing poor outcomes from COVID-19; however, voluntary vaccination rates have been suboptimal. We assessed the potential avoidable intensive care unit (ICU) resource use and associated costs had unvaccinated or partially vaccinated patients hospitalized with COVID-19 been fully vaccinated. METHODS: We conducted a retrospective, population-based cohort study of persons aged 12 yr or greater in Alberta (2021 population ~ 4.4 million) admitted to any ICU with COVID-19 from 6 September 2021 to 4 January 2022. We used publicly available aggregate data on COVID-19 infections, vaccination status, and health services use. Intensive care unit admissions, bed-days, lengths of stay, and costs were estimated for patients with COVID-19 and stratified by vaccination status. RESULTS: In total, 1,053 patients admitted to the ICU with COVID-19 were unvaccinated, 42 were partially vaccinated, and 173 were fully vaccinated (cumulative incidence 230.6, 30.8, and 5.5 patients/100,000 population, respectively). Cumulative incidence rate ratios of ICU admission were 42.2 (95% confidence interval [CI], 39.7 to 44.9) for unvaccinated patients and 5.6 (95% CI, 4.1 to 7.6) for partially vaccinated patients when compared with fully vaccinated patients. During the study period, 1,028 avoidable ICU admissions and 13,015 bed-days were recorded for unvaccinated patients and the total avoidable costs were CAD 61.3 million. The largest opportunity to avoid ICU bed-days and costs was in unvaccinated patients aged 50 to 69 yr. CONCLUSIONS: Unvaccinated patients with COVID-19 had substantially greater rates of ICU admissions, ICU bed-days, and ICU-related costs than vaccinated patients did. This increased resource use would have been potentially avoidable had these unvaccinated patients been vaccinated against SARS-CoV-2.

RéSUMé: OBJECTIF: Les vaccins contre le SRAS-CoV-2 se sont avérés efficaces pour prévenir les devenirs défavorables associés à la COVID-19; toutefois, les taux de vaccination volontaire ont été sous-optimaux. Nous avons évalué l'utilisation potentiellement évitable des ressources des unités de soins intensifs (USI) et les coûts associés si les patients non vaccinés ou partiellement vaccinés qui ont dû être hospitalisés pour la COVID-19 avaient été complètement vaccinés. MéTHODE: Nous avons réalisé une étude de cohorte rétrospective basée sur la population de personnes âgées de 12 ans ou plus en Alberta (population de 2021 ~ 4,4 millions) admises dans une unité de soins intensifs et atteintes de COVID-19 du 6 septembre 2021 au 4 janvier 2022. Nous avons utilisé des données agrégées accessibles au public sur les infections à la COVID-19, le statut vaccinal et l'utilisation des services de santé. Les admissions aux soins intensifs, les journées-patients, les durées de séjour et les coûts ont été estimés pour les patients atteints de la COVID-19 et stratifiés selon le statut vaccinal. RéSULTATS: Au total, 1053 patients admis à l'USI souffrant de la COVID-19 n'étaient pas vaccinés, 42 étaient partiellement vaccinés et 173 étaient complètement vaccinés (incidence cumulative 230,6, 30,8 et 5,5 patients / 100 000 habitants, respectivement). Les taux d'incidence cumulés des admissions aux soins intensifs étaient de 42,2 (intervalle de confiance [IC] à 95 %, 39,7 à 44,9) pour les patients non vaccinés et de 5,6 (IC 95 %, 4,1 à 7,6) pour les patients partiellement vaccinés par rapport aux patients entièrement vaccinés. Au cours de la période à l'étude, 1028 admissions évitables aux soins intensifs et 13 015 journées-patients ont été enregistrées pour les patients non vaccinés, et les coûts totaux évitables étaient de 61,3 millions de dollars canadiens. L'économie potentielle la plus importante en matière de journées-patients et de coûts en soins intensifs touchait les patients non vaccinés âgés de 50 à 69 ans. CONCLUSION: Les patients non vaccinés atteints de COVID-19 ont affiché des taux beaucoup plus élevés d'admissions à l'USI, de journées-patients à l'USI et de coûts liés à l'USI que les patients vaccinés. Cette utilisation accrue des ressources aurait été potentiellement évitable si ces patients non vaccinés avaient été vaccinés contre le SRAS-CoV-2.

Understanding implementation context and social processes through integrating Normalization Process Theory (NPT) and the Consolidated Framework for Implementation Research (CFIR).

BACKGROUND: For successful implementation of an innovation within a complex adaptive system, we need to understand the ways that implementation processes and their contexts shape each other. To do this, we need to explore the work people do to make sense of an innovation and integrate it into their workflow and the contextual elements that impact implementation. Combining Normalization Process Theory (NPT) with the Consolidated Framework for Implementation Research (CFIR) offers an approach to achieve this. NPT is an implementation process theory that explains how changes in the way people think about and use an innovation occurs, while CFIR is a framework that categorizes and describes contextual determinants across five domains that influence implementation. We demonstrate through a case example from our prior research how we integrated NPT and CFIR to inform the development of the interview guide, coding manual, and analysis of the findings. METHODS: In collaboration with our stakeholders, we selected NPT and CFIR to study the implementation process and co-developed an interview guide to elicit responses that would illuminate concepts from both. We conducted, audio-recorded, and transcribed 28 interviews with various professionals involved with the implementation. Based on independent coding of select transcripts and team discussion comparing, clarifying, and crystallizing codes, we developed a coding manual integrating CFIR and NPT constructs. We applied the integrated codes to all interview transcripts. RESULTS: Our findings highlight how integrating CFIR domains with NPT mechanisms adds explanatory strength to the analysis of implementation processes, with particular implications for practical strategies to facilitate implementation. Multiple coding across both theoretical frames captured the entanglement of process and context. Integrating NPT and CFIR enriched understandings of how interactions between implementation processes and contextual determinants shaped each other during implementation. CONCLUSION: The integration of NPT and CFIR provides guidance to identify and explore complex entangled interactions between agents, processes, and contextual conditions within and beyond organizations to embed innovations into routine practices. Nuanced understandings gained through this approach moves understandings beyond descriptions of determinants to explain how change occurs or not during implementation. Mechanism-based explanations illuminate concrete practical strategies to support implementation.

What work is required to implement and sustain the National Surgical Quality Improvement Program (NSQIP)? A qualitative study of NSQIP implementation in Alberta, Canada.

OBJECTIVES: Hospitals introducing the National Surgical Quality Improvement Program (NSQIP) face implementation challenges. To understand the work of embedding NSQIP into routine practice, we explored interactions between contextual factors and the work among implementation teams at the individual, team and organisational level to illuminate how to support and sustain NSQIP implementation. DESIGN: Qualitative interpretative study using thematic analysis. SETTING: Five contextually diverse hospital sites in Alberta, Canada, for in-depth interviewing and four additional hospitals for observation of NSQIP meetings. PARTICIPANTS: 9 Surgeon and Anaesthesiologist Champions; 6 Surgical Clinical Reviewers; 4 Directors and 1 Surgical Site Manager; 3 Operating Room Managers; 3 Quality Improvement Consultants; 1 Surgeon and 1 Provincial NSQIP Lead. METHODS: To capture context, process and the dynamic interplay between the two, we integrated the Consolidated Framework for Implementation Research (CFIR) and Normalisation Process Theory (NPT) to guide data collection and analysis. 28 individual semi-structured interviews with key informants and observations with field notes of 10 NSQIP meetings were conducted. Data were coded deductively and inductively and analysed thematically. RESULTS: Key findings informed by CFIR describe the impact of Provincial Collaboratives, leadership support and resources to support NSQIP work. Key findings illuminated by NPT highlight how teams overcame mistrust in NSQIP through relationship building, creating formative spaces to inform collective understandings of NSQIP and inviting feedback from professional groups to cocreate quality improvement solutions. This approach led to increased engagement with NSQIP data and encouraged shifts in conversations within and between nursing and physician groups from problems to solutions based. CONCLUSIONS: The work the teams did to implement and sustain NSQIP highlights the need for time and resources to develop shared understandings of work processes, reorganise themselves to work together and understand how to help others in the surgical community interpret and value using NSQIP to improve care.

Universal masking during COVID-19 pandemic: Can textile engineering help public health? Narrative review of the evidence.

The Coronavirus Disease-2019 (COVID-19) pandemic caused by the virus SARS-CoV-2 is spreading very quickly around the world. In less than 7 months since it became known to the international community, the virus has infected 18 million in more than 180 countries and killing more than 700,000 people. Person-to-person transmission through infected respiratory droplets from patients with symptoms and asymptomatic carriers is the main mode of spread in the community. There is currently no standard agreed upon drug to treat the disease and the prospect of having a safe and efficacious vaccine might be years away. Thus, public health interventions such as social distancing and hand washing have been introduced and has, to some extent, slowed the progression of the pandemic. Universal masking as a public health intervention is currently mandatory in a vast majority of countries around the world. To avoid personal protective equipment (PPE) shortage crisis for medical staff and other frontline workers, health authorities are recommending the use cloth masks. Although in theory, cloth masks can be helpful to limit the spread of the COVID-19, serious consideration should be given to the choice of textile, the number of layers of cloth used, pre-treatment of the material with water repellent material and other compounds that can enhance the filtration efficiency of the masks without compromising their breathability. This review uses concepts of textile engineering and the theoretical principles of filtration to make suggestions and recommendations to improve the quality and safety of cloth masks for the general public.

Isomer-Specific Binding Affinity of Perfluorooctanesulfonate (PFOS) and Perfluorooctanoate (PFOA) to Serum Proteins.

Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are among the most prominent contaminants in human serum, and these were historically manufactured as technical mixtures of linear and branched isomers. The isomers display unique pharmacokinetics in humans and in animal models, but molecular mechanisms underlying isomer-specific PFOS and PFOA disposition have not previously been studied. Here, ultrafiltration devices were used to examine (i) the dissociation constants (Kd) of individual PFOS and PFOA isomers with human serum albumin (HSA) and (ii) relative binding affinity of isomers in technical mixtures spiked to whole calf serum and human serum. Measurement of HSA Kd's demonstrated that linear PFOS (Kd=8(±4)×10(-8) M) was much more tightly bound than branched PFOS isomers (Kd range from 8(±1)×10(-5) M to 4(±2)×10(-4) M). Similarly, linear PFOA (Kd=1(±0.9)×10(-4) M) was more strongly bound to HSA compared to branched PFOA isomers (Kd range from 4(±2)×10(-4) M to 3(±2)×10(-4) M). The higher binding affinities of linear PFOS and PFOA to total serum protein were confirmed when both calf serum and human serum were spiked with technical mixtures. Overall, these data provide a mechanistic explanation for the longer biological half-life of PFOS in humans, compared to PFOA, and for the higher transplacental transfer efficiencies and renal clearance of branched PFOS and PFOA isomers, compared to the respective linear isomer.

Temporal trends of perfluorooctanesulfonate isomer and enantiomer patterns in archived Swedish and American serum samples.

Human perfluorooctanesulfonate (PFOS) body burdens are attributable to both direct PFOS and indirect PFOS precursor (PreFOS) exposure. The relative importance of these two pathways has been estimated, but the relative temporal trajectory of exposure to PFOS and PreFOS has not been examined. Here, two hypothesized biomarkers of PreFOS exposure, PFOS isomer profiles (quantified as percent branched PFOS, %br-PFOS) and chiral 1m-PFOS enantiomer fractions (1m-PFOS EF) were analyzed in archived human serum samples of individual American adults (1974-2010) and pooled samples of Swedish primiparous women (1996-2010). After correcting for potential confounders, significant correlations between %br-PFOS and 1m-PFOS EFs were observed in American samples and in Swedish samples for the 1996-2000 period, supporting the hypothesis that both %br-PFOS and 1m-PFOS EF are biomarkers of PreFOS exposure. Significant trends of increasing %br-PFOS, from 2000 to 2010, and increasingly non-racemic 1m-PFOS EFs, from 1996 to 2000, were detected in Swedish samples. No statistically significant trend for %br-PFOS or 1m-PFOS EF was observed in American samples, but American males had significantly higher %br-PFOS and significantly lower 1m-PFOS EF (i.e. more non-racemic) than females, and a similar significant difference was shown in the older age group, relative to the younger age group. These temporal trends in %br-PFOS and 1m-PFOS EF are not easily explained and the results highlight uncertainties about how humans are exposed to PFOS.

Maternal exposure to bisphenol-A and fetal growth restriction: a case-referent study.

We conducted a case-referent study of the effect of exposure to bisphenol-A on fetal growth in utero in full-term, live-born singletons in Alberta, Canada. Newborns <10 percentile of expected weight for gestational age and sex were individually matched on sex, maternal smoking and maternal age to referents with weight appropriate to gestational age. Exposure of the fetus to bisphenol-A was estimated from maternal serum collected at 15-16 weeks of gestation. We pooled sera across subjects for exposure assessment, stratified on case-referent status and sex. Individual 1:1 matching was maintained in assembling 69 case and 69 referent pools created from 550 case-referent pairs. Matched pools had an equal number of aliquots from individual women. We used an analytical strategy conditioning on matched set and total pool-level values of covariates to estimate individual-level effects. Pools of cases and referents had identical geometric mean bisphenol-A concentrations (0.5 ng/mL) and similar geometric standard deviations (2.3-2.5). Mean difference in concentration between matched pools was 0 ng/mL, standard deviation: 1 ng/mL. Stratification by sex and control for confounding did not suggest bisphenol-A increased fetal growth restriction. Our analysis does not provide evidence to support the hypothesis that bisphenol-A contributes to fetal growth restriction in full-term singletons.

Biomonitoring and Elimination of Perfluorinated Compounds and Polychlorinated Biphenyls through Perspiration: Blood, Urine, and Sweat Study.

Perfluorinated compounds (PFCs) are man-made organofluorine chemicals manufactured and marketed for their stain-resistant properties. Polychlorinated biphenyls (PCBs) are anthropogenic organochlorine compounds previously used in various industrial and chemical applications prior to being banned in the Western world in the 1970s. Both PFCs and PCBs are persistent contaminants within the human organism and both have been linked to adverse health sequelae. Data is lacking on effective means to facilitate clearance of PFCs and PCBs from the body. Methods. Blood, urine, and sweat were collected from 20 individuals (10 healthy participants and 10 participants with assorted health problems) and analyzed for PFCs and PCBs using high performance liquid chromatography tandem mass spectrometry. Results. Some individual PCB congeners, but not all, were released into sweat at varying concentrations. None of the PFCs found in serum testing appeared to be excreted efficiently into perspiration. Conclusions. Induced perspiration may have some role in facilitating elimination of selected PCBs. Sweat analysis may be helpful in establishing the existence of some accrued PCBs in the human body. Sweating does not appear to facilitate clearance of accrued PFHxS (perfluorohexane sulfonate), PFOS (perfluorooctane sulfonate), or PFOA (perfluorooctanoic acid), the most common PFCs found in the human body.

Biomonitoring of perfluoroalkyl acids in human urine and estimates of biological half-life.

Perfluoroalkyl acids (PFAAs) are persistent and bioaccumulative compounds that have been associated with adverse health outcomes. In human blood, PFAAs exist as both linear and branched isomers, yet for most linear homologues, and for all branched isomers, elimination rates are unknown. Paired blood and urine samples (n = 86) were collected from adults in China. They were analyzed by a sensitive isomer-specific method that permitted the detection of many PFAAs in human urine for the first time. For all PFAAs except perfluoroundecanoate (PFUnA), levels in urine correlated positively with levels in blood. Perfluoroalkyl carboxylates (PFCAs) were excreted more efficiently than perfluoroalkane sulfonates (PFSAs) of the same carbon chain-length. In general, shorter PFCAs were excreted more efficiently than longer ones, but for PFSAs, perfluorooctanesulfonate (PFOS, a C8 compound) was excreted more efficiently than perfluorohexanesulfonate (PFHxS, a C6 compound). Among PFOS and perfluorooctanoate (PFOA) isomers, major branched isomers were more efficiently excreted than the corresponding linear isomer. A one-compartment model was used to estimate the biological elimination half-lives of PFAAs. Among all PFAAs, the estimated arithmetic mean elimination half-lives ranged from 0.5 ± 0.1 years (for one branched PFOA isomer, 5m-PFOA) to 90 ± 11 years (for one branched PFOS isomer, 1m-PFOS). Urinary excretion was the major elimination route for short PFCAs (C ≤ 8), but for longer PFCAs, PFOS and PFHxS, other routes of excretion likely contribute to overall elimination. Urinary concentrations are good biomarkers of the internal dose, and this less invasive strategy can therefore be used in future epidemiological and biomonitoring studies. The very long half-lives of long-chain PFCAs, PFHxS, and PFOS isomers in humans stress the importance of global and domestic exposure mitigation strategies.

Isomers of perfluorooctanesulfonate and perfluorooctanoate and total perfluoroalkyl acids in human serum from two cities in North China.

The sources and pathways of human exposure to perfluoroalkyl acids (PFAAs) are not well characterized, particularly in China where many perfluorinated substances are now manufactured. Here, isomer-specific PFAA analysis was used for the first time to evaluate exposure sources for Chinese people, by applying the method to 129 serum samples collected in two typical cities (Shijiazhuang and Handan) in North China. Among all samples, total perfluorooctanesulfonate (∑PFOS, mean 33.3 ng/ml) was the predominant PFAA followed by perfluorohexanesulfonate (2.95 ng/ml), total perfluorooctanoate (∑PFOA, 2.38 ng/ml), and perfluorononanoate (0.51 ng/ml). The level of ∑PFOS was higher than in people from North America in recent years. The mean concentrations of ΣPFAAs in the participants living in urban Shijiazhuang (59.0 ng/ml) and urban Handan (35.6 ng/ml) were significantly higher (p<0.001 and p=0.041, respectively) than those living in the rural district of Shijiazhuang (24.3 ng/ml). The young female sub-population had the lowest ΣPFAA concentrations compared with older females and all males. On average, the proportion of linear PFOS (n-PFOS) was only 48.1% of ∑PFOS, which is much lower than what was present in technical PFOS from the major historical manufacturer (ca. 70% linear), and which is also lower than data reported from any other countries. Moreover, the proportion of n-PFOS decreased significantly with increasing ∑PFOS concentration in the serum samples (r=-0.694, p<0.001). Taken together, the data lend weight to previous suggestions that i) high branched PFOS content in serum is a biomarker of exposure to PFOS-precursors, and ii) that people with the highest ∑PFOS concentrations are exposed disproportionately to high concentrations of PFOS-precursors. On average, linear PFOA (n-PFOA) contributed 96.1% of ∑PFOA, significantly higher than in technical PFOA (ca. 75-80% linear), but lower than in Americans, suggesting higher exposure to electrochemically fluorinated PFOA than in other countries, including the United States.

Human elimination of phthalate compounds: blood, urine, and sweat (BUS) study.

BACKGROUND: Individual members of the phthalate family of chemical compounds are components of innumerable everyday consumer products, resulting in a high exposure scenario for some individuals and population groups. Multiple epidemiological studies have demonstrated statistically significant exposure-disease relationships involving phthalates and toxicological studies have shown estrogenic effects in vitro. Data is lacking in the medical literature, however, on effective means to facilitate phthalate excretion. METHODS: Blood, urine, and sweat were collected from 20 individuals (10 healthy participants and 10 participants with assorted health problems) and analyzed for parent phthalate compounds as well as phthalate metabolites using high performance liquid chromatography-tandem mass spectrometry. RESULTS: Some parent phthalates as well as their metabolites were excreted into sweat. All patients had MEHP (mono(2-ethylhexyl) phthalate) in their blood, sweat, and urine samples, suggesting widespread phthalate exposure. In several individuals, DEHP (di (2-ethylhexl) phthalate) was found in sweat but not in serum, suggesting the possibility of phthalate retention and bioaccumulation. On average, MEHP concentration in sweat was more than twice as high as urine levels. CONCLUSIONS: Induced perspiration may be useful to facilitate elimination of some potentially toxic phthalate compounds including DEHP and MEHP. Sweat analysis may be helpful in establishing the existence of accrued DEHP in the human body.