N-of-1 (individual comparison) trials are a promising approach for comparing the effectiveness of 2 or more treatments for individual patients; yet, few studies have qualitatively examined how ...patients use and make sense of their own patient-generated health data (PGHD) in the context of N-of-1 trials.
The objective of our study was to explore chronic pain patients' perceptions about the PGHD they compiled while comparing 2 chronic pain treatments and tracking their symptoms using a smartphone N-of-1 app in collaboration with their clinicians.
Semistructured interviews were recorded with 33 patients, a consecutive subset of the intervention group in a primary study testing the feasibility and effectiveness of the Trialist N-of-1 app. Interviews were transcribed verbatim, and a descriptive thematic analysis was completed.
Patients were enthusiastic about recording and accessing their own data. They valued sharing data with clinicians but also used their data independently.
N-of-1 trials remain a promising approach to evidence-based decision making. Patients appear to value their roles as trial participants but place as much or more importance on the independent use of trial data as on comparative effectiveness results. Future efforts to design patient-centered N-of-1 trials might consider adaptable designs that maximize patient flexibility and autonomy while preserving a collaborative role with clinicians and researchers.
Some dioxins are carcinogenic, but few studies have investigated the relationship between ambient polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) and risk of breast cancer. We evaluated ...associations between proximity-based residential exposure to industrial emissions of PCDD/F and breast cancer risk in a large U.S. cohort. Sister Study participants at enrollment (2003–2009) were followed for incident breast cancer through September 2018. After restricting to participants with ≥10 years of residential history prior to enrollment (n = 35,908), we generated 10-year distance- and toxic equivalency quotient (TEQ)-weighted average emissions indices (AEI g TEQ/km2) within 3, 5, or 10 km of participants’ residences, overall and by facility type. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between AEI quartiles (vs. zero AEI) and risk of breast cancer invasive or ductal carcinoma in situ. There were 2670 incident breast cancer cases over 11 years (median) of follow-up. Breast cancer risk was increased for those in the highest quartile Q of AEI exposure within 3 km (HRQ4:1.18, 95% CI: 0.99,1.40, Ptrend = 0.03). The HR was higher for the 10-year AEI at 3 km from municipal solid waste facilities (HR ≥ median.vs.0:1.50, 95% CI: 0.98, 2.29; Ptrend = 0.07). Risk was higher among ever smokers (vs. never smokers) in the top quartile of the 3 km AEI (HRQ4:1.41, 95% CI:1.12,1.77, Ptrend = 0.003; Pinteraction = 0.03) and higher risk for ER negative tumors was suggested (HRQ4:1.47, 95% CI: 0.95, 2.28, Ptrend = 0.07, Pheterogeneity = 0.17). Our findings suggest that residential exposure to PCDD/F emissions may confer an increased risk of breast cancer.
•Dioxins are persistent organic pollutants, and some are known carcinogens.•Research on air emissions of dioxins and breast cancer risk is limited.•Airborne dioxins within 3 km were associated with increased breast cancer risk.•This association was strongest for emissions from municipal solid waste facilities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The vibrational spectra of a model phenol-amine proton transfer complex dissolved in CH3Cl solvent confined in a 12 Å radius spherical hydrophobic cavity were calculated using mixed quantum-classical ...molecular dynamics simulations. The reaction free energy of the proton transfer complex was varied in order to explore the contributions to the vibrational absorption band from product and reactant species. The vibrational spectra of the model proton transfer complex resulted in motionally narrowed spectral linewidths with two distinct peaks for products and reactants in cases where the system undergoes chemical exchange. It was found that the n = 1 and n = 2 vibrational excited states combine to form diabatic states such that the spectra have contributions from both n = 0 → n = 1 and n = 0 → n = 2 transitions. A strong relationship between the instantaneous vibrational frequency and a collective solvent coordinate was found that assists in understanding the origin of the spectral features.
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IJS, KILJ, NUK, PNG, UL, UM
Disinfection byproducts (DBPs) and
-nitroso compounds (NOC), formed endogenously after nitrate ingestion, are suspected endometrial carcinogens, but epidemiological studies are limited.
We ...investigated the relationship of these exposures with endometrial cancer risk in a large prospective cohort.
Among postmenopausal women in the Iowa Women's Health Study cohort, we evaluated two major classes of DBPs, total trihalomethanes (TTHM) and five haloacetic acids (HAA5), and nitrate-nitrogen (
) in public water supplies (PWS) in relation to incident primary endometrial cancer (1986-2014). For women using their PWS
at enrollment (
;
), we computed historical averages of annual concentrations; exposures were categorized into quantiles and when possible
percentile. We also computed years of PWS use above one-half the U.S. maximum contaminant level (
;
TTHM;
HAA5;
). Dietary nitrate/nitrite intakes were estimated from a food frequency questionnaire. We estimated hazard ratios (HR) and 95% confidence intervals (CI) via Cox models adjusted for age, endometrial cancer risk factors e.g., body mass index, hormone replacement therapy (HRT), and mutually adjusted for
. We evaluated associations for low-grade (
) vs. high-grade (
) type I tumors. We assessed interactions between exposures and endometrial cancer risk factors and dietary factors influencing NOC formation.
Higher average concentrations of DBPs (95th percentile: TTHM
, HAA5
) were associated with endometrial cancer risk (TTHM:
, 95% CI: 1.41, 3.40; HAA5:
, 95% CI: 1.19, 2.83;
). Associations were similarly observed for women greater than median years of PWS use with levels
, in comparison with zero years (TTHM:
, 95% CI: 1.18, 2.21; HAA5:
, 95% CI: 1.31, 2.62). Associations with DBPs appeared stronger for low-grade tumors (TTHM:
, 95% CI: 1.17, 3.83;
) than for high-grade tumors (TTHM:
, 95% CI: 0.80, 2.44;
), but differences were not statistically significant (
). Associations with TTHM were stronger among ever HRT users than non-HRT users (
). We observed no associations with
in drinking water or diet.
We report novel associations between the highest DBP levels and endometrial cancer for our Iowa cohort that warrant future evaluation. https://doi.org/10.1289/EHP10207.
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CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Global climate change has altered the timing of seasonal events (i.e., phenology) for a diverse range of biota. Within and among species, however, the degree to which alterations in phenology match ...climate variability differ substantially. To better understand factors driving these differences, we evaluated variation in timing of nesting of eight Arctic‐breeding shorebird species at 18 sites over a 23‐year period. We used the Normalized Difference Vegetation Index as a proxy to determine the start of spring (SOS) growing season and quantified relationships between SOS and nest initiation dates as a measure of phenological responsiveness. Among species, we tested four life history traits (migration distance, seasonal timing of breeding, female body mass, expected female reproductive effort) as species‐level predictors of responsiveness. For one species (Semipalmated Sandpiper), we also evaluated whether responsiveness varied across sites. Although no species in our study completely tracked annual variation in SOS, phenological responses were strongest for Western Sandpipers, Pectoral Sandpipers, and Red Phalaropes. Migration distance was the strongest additional predictor of responsiveness, with longer‐distance migrant species generally tracking variation in SOS more closely than species that migrate shorter distances. Semipalmated Sandpipers are a widely distributed species, but adjustments in timing of nesting relative to variability in SOS did not vary across sites, suggesting that different breeding populations of this species were equally responsive to climate cues despite differing migration strategies. Our results unexpectedly show that long‐distance migrants are more sensitive to local environmental conditions, which may help them to adapt to ongoing changes in climate.
Global climate change has altered the timing of seasonal events for many animals, including northern‐nesting birds, but it is not clear why in some species, changes in timing of nesting match variation in climate more closely than in others. We tested to see if differences in the species' ecology might help explain these differences. Adjustments to timing of nesting were most closely matched to climate variation in species migrating over long distances, which may help them adapt to climate change.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aim To examine time trends and deprivation gradients in fire-related deaths and injuries. Methods A cross-sectional study and time trend analysis using data on fire casualties in England between 1995 ...and 2004 obtained from the Department for Communities and Local Government. Injury rates were calculated assuming a Poisson distribution. Incidence rate ratios (IRRs) were calculated to compare changes in deprivation gradients over time. Results There were significant reductions in fatal and non-fatal fire injuries in children (fatal injuries IRR χ21 = 11.18, P < 0.001; non-fatal injuries IRR χ22 = 61.44, P < 0.001), adults (fatal injuries IRR χ21 = 15.99, P < 0.001; non-fatal injuries IRR χ22 = 183.25, P < 0.001) and older people (fatal injuries IRR χ21 = 56.88, P < 0.001; non-fatal injuries IRR χ22 = 54.09, P < 0.001) between 1995 and 2004. Adult and child fire deaths were most commonly caused by smokers' materials (e.g. cigarettes, cigars and tobacco), and cigarette lighters and matches, respectively. Cooking appliances caused most non-fatal fire injuries. Injury rates increased with increasing levels of deprivation and deprivation gradients did not change over 10 years. Conclusions Fire prevention interventions should promote the safe use of cooking and heating appliances and the responsible use of smokers' materials, lighters and matches, and should target those at greater risk of fire, including the socially disadvantaged.
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BFBNIB, NMLJ, NUK, OILJ, PNG, UL, UM, UPUK, VSZLJ
Although theory strongly suggests that liberal democracies should perform better than autocracies on sustainability indicators, the empirical evidence is unclear. Using multivariate statistical ...techniques, political factors such as the stability of the system, public opinion, the nature of the party system and other institutional features such as presidentialism are considered. Liberal democracy is given qualified endorsement: it typically promotes weak sustainability, and stable core autocracies perform worse on strong sustainability measures than stable core democracies. Presidentialism generally is bad for sustainability. However, there is no compelling evidence that public opinion matters, even allowing for the intervening effects of the party system and institutional structure, which raises questions about the nature of the democratic process.
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BFBNIB, NUK, ODKLJ, PILJ, SAZU, UL, UM, UPUK
Several authors have suggested that it is safe to raise the health standard for nitrate in drinking water, and save money on measures associated with nitrate pollution of drinking water resources. ...The major argument has been that the epidemiologic evidence for acute and chronic health effects related to drinking water nitrate at concentrations near the health standard is inconclusive. With respect to the chronic effects, the argument was motivated by the absence of evidence for adverse health effects related to ingestion of nitrate from dietary sources. An interdisciplinary discussion of these arguments led to three important observations. First, there have been only a few well-designed epidemiologic studies that evaluated ingestion of nitrate in drinking water and risk of specific cancers or adverse reproductive outcomes among potentially susceptible subgroups likely to have elevated endogenous nitrosation. Positive associations have been observed for some but not all health outcomes evaluated. Second, the epidemiologic studies of cancer do not support an association between ingestion of dietary nitrate (vegetables) and an increased risk of cancer, because intake of dietary nitrate is associated with intake of antioxidants and other beneficial phytochemicals. Third, 2-3 % of the population in Western Europe and the US could be exposed to nitrate levels in drinking water exceeding the WHO standard of 50 mg/l nitrate, particularly those living in rural areas. The health losses due to this exposure cannot be estimated. Therefore, we conclude that it is not possible to weigh the costs and benefits from changing the nitrate standard for drinking water and groundwater resources by considering the potential consequences for human health and by considering the potential savings due to reduced costs for nitrate removal and prevention of nitrate pollution.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nitrate and nitrite are precursors in the formation of N-nitroso compounds. We recently found a 40% increased risk of NHL with higher dietary nitrite intake and significant increases in risk for ...follicular and T-cell lymphoma. It is possible that these compounds also affect NHL prognosis by enhancing cancer progression in addition to development by further impairing immune system function. To test the hypothesis that nitrate and nitrite intake affects NHL survival, we evaluated the association in study participants that have been followed post-disease diagnosis in a population-based case-control study among women in Connecticut. We did not observe a significant increasing trend of mortality for NHL overall or by subtype for nitrate or nitrite intake for deaths from NHL or death from any cause, although a borderline significant protective trend was observed for follicular lymphoma with increasing nitrate intake. We did not identify a difference in overall survival for nitrate (P = 0.39) or for nitrite (P = 0.66) or for NHL specific survival for nitrate (P = 0.96) or nitrite (P = 0.17). Thus, our null findings do not confer support for the possibility that dietary nitrate and nitrite intake impacts NHL survival by promoting immune unresponsiveness.
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DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Regulation of milk synthesis and secretion is controlled mostly through local (intramammary) mechanisms. To gain insight into the molecular pathways comprising this response, an analysis of mammary ...gene expression was conducted in 12 lactating cows shifted from twice daily to once daily milking. Tissues were sampled by biopsy from adjacent mammary quarters of these animals during the two milking frequencies, allowing changes in gene expression to be assessed within each animal. Using bovine-specific, oligonucleotide arrays representing 21,495 unique transcripts, a range of differentially expressed genes were found as a result of less frequent milk removal, constituting transcripts and pathways related to apoptotic signaling (NF-kappaB, JUN, ATF3, IGFBP5, TNFSF12A) mechanical stress and epithelial tight junction synthesis (CYR61, CTGF, THBS1, CLDN4, CLDN8), and downregulated milk synthesis (LALBA, B4GALT1, UGP2, CSN2, GPAM, LPL). Quantitative real-time PCR was used to assess the expression of 13 genes in the study, and all 13 of these were correlated (P < 0.05) with values derived from array analysis. It can be concluded that the physiological changes that occur in the bovine mammary gland as a result of reduced milk removal frequency likely comprise the earliest stages of the involution response and that mechano-signal transduction cascades associated with udder distension may play a role in triggering these events.
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